An ERP study of regular and irregular English past tense inflection.

PubMed

Newman, Aaron J; Ullman, Michael T; Pancheva, Roumyana; Waligura, Diane L; Neville, Helen J

2007-01-01

Compositionality is a critical and universal characteristic of human language. It is found at numerous levels, including the combination of morphemes into words and of words into phrases and sentences. These compositional patterns can generally be characterized by rules. For example, the past tense of most English verbs ("regulars") is formed by adding an -ed suffix. However, many complex linguistic forms have rather idiosyncratic mappings. For example, "irregular" English verbs have past tense forms that cannot be derived from their stems in a consistent manner. Whether regular and irregular forms depend on fundamentally distinct neurocognitive processes (rule-governed combination vs. lexical memorization), or whether a single processing system is sufficient to explain the phenomena, has engendered considerable investigation and debate. We recorded event-related potentials while participants read English sentences that were either correct or had violations of regular past tense inflection, irregular past tense inflection, syntactic phrase structure, or lexical semantics. Violations of regular past tense and phrase structure, but not of irregular past tense or lexical semantics, elicited left-lateralized anterior negativities (LANs). These seem to reflect neurocognitive substrates that underlie compositional processes across linguistic domains, including morphology and syntax. Regular, irregular, and phrase structure violations all elicited later positivities that were maximal over midline parietal sites (P600s), and seem to index aspects of controlled syntactic processing of both phrase structure and morphosyntax. The results suggest distinct neurocognitive substrates for processing regular and irregular past tense forms: regulars depending on compositional processing, and irregulars stored in lexical memory.

Optimal boundary regularity for a singular Monge-Ampère equation

NASA Astrophysics Data System (ADS)

Jian, Huaiyu; Li, You

2018-06-01

In this paper we study the optimal global regularity for a singular Monge-Ampère type equation which arises from a few geometric problems. We find that the global regularity does not depend on the smoothness of domain, but it does depend on the convexity of the domain. We introduce (a , η) type to describe the convexity. As a result, we show that the more convex is the domain, the better is the regularity of the solution. In particular, the regularity is the best near angular points.

SPH Numerical Modeling for the Wave-Thin Structure Interaction

NASA Astrophysics Data System (ADS)

Ren, Xi-feng; Sun, Zhao-chen; Wang, Xing-gang; Liang, Shu-xiu

2018-04-01

In this paper, a numerical model of 2D weakly compressible smoothed particle hydrodynamics (WCSPH) is developed to simulate the interaction between waves and thin structures. A new color domain particle (CDP) technique is proposed to overcome difficulties of applying the ghost particle method to thin structures in dealing with solid boundaries. The new technique can deal with zero-thickness structures. To apply this enforcing technique, the computational fluid domain is divided into sub domains, i.e., boundary domains and internal domains. A color value is assigned to each particle, and contains the information of the domains in which the particle belongs to and the particles can interact with. A particle, nearby a thin boundary, is prevented from interacting with particles, which should not interact with on the other side of the structure. It is possible to model thin structures, or the structures with the thickness negligible with this technique. The proposed WCSPH module is validated for a still water tank, divided by a thin plate at the middle section, with different water levels in the subdomains, and is applied to simulate the interaction between regular waves and a perforated vertical plate. Finally, the computation is carried out for waves and submerged twin-horizontal plate interaction. It is shown that the numerical results agree well with experimental data in terms of the pressure distribution, pressure time series and wave transmission.

Wavelet domain image restoration with adaptive edge-preserving regularization.

PubMed

Belge, M; Kilmer, M E; Miller, E L

2000-01-01

In this paper, we consider a wavelet based edge-preserving regularization scheme for use in linear image restoration problems. Our efforts build on a collection of mathematical results indicating that wavelets are especially useful for representing functions that contain discontinuities (i.e., edges in two dimensions or jumps in one dimension). We interpret the resulting theory in a statistical signal processing framework and obtain a highly flexible framework for adapting the degree of regularization to the local structure of the underlying image. In particular, we are able to adapt quite easily to scale-varying and orientation-varying features in the image while simultaneously retaining the edge preservation properties of the regularizer. We demonstrate a half-quadratic algorithm for obtaining the restorations from observed data.

High throughput profile-profile based fold recognition for the entire human proteome.

PubMed

McGuffin, Liam J; Smith, Richard T; Bryson, Kevin; Sørensen, Søren-Aksel; Jones, David T

2006-06-07

In order to maintain the most comprehensive structural annotation databases we must carry out regular updates for each proteome using the latest profile-profile fold recognition methods. The ability to carry out these updates on demand is necessary to keep pace with the regular updates of sequence and structure databases. Providing the highest quality structural models requires the most intensive profile-profile fold recognition methods running with the very latest available sequence databases and fold libraries. However, running these methods on such a regular basis for every sequenced proteome requires large amounts of processing power. In this paper we describe and benchmark the JYDE (Job Yield Distribution Environment) system, which is a meta-scheduler designed to work above cluster schedulers, such as Sun Grid Engine (SGE) or Condor. We demonstrate the ability of JYDE to distribute the load of genomic-scale fold recognition across multiple independent Grid domains. We use the most recent profile-profile version of our mGenTHREADER software in order to annotate the latest version of the Human proteome against the latest sequence and structure databases in as short a time as possible. We show that our JYDE system is able to scale to large numbers of intensive fold recognition jobs running across several independent computer clusters. Using our JYDE system we have been able to annotate 99.9% of the protein sequences within the Human proteome in less than 24 hours, by harnessing over 500 CPUs from 3 independent Grid domains. This study clearly demonstrates the feasibility of carrying out on demand high quality structural annotations for the proteomes of major eukaryotic organisms. Specifically, we have shown that it is now possible to provide complete regular updates of profile-profile based fold recognition models for entire eukaryotic proteomes, through the use of Grid middleware such as JYDE.

AN ERP STUDY OF REGULAR AND IRREGULAR ENGLISH PAST TENSE INFLECTION

PubMed Central

Newman, Aaron J.; Ullman, Michael T.; Pancheva, Roumyana; Waligura, Diane L.; Neville, Helen J.

2006-01-01

Compositionality is a critical and universal characteristic of human language. It is found at numerous levels, including the combination of morphemes into words and of words into phrases and sentences. These compositional patterns can generally be characterized by rules. For example, the past tense of most English verbs (“regulars”) is formed by adding an -ed suffix. However, many complex linguistic forms have rather idiosyncratic mappings. For example, “irregular” English verbs have past tense forms that cannot be derived from their stems in a consistent manner. Whether regular and irregular forms depend on fundamentally distinct neurocognitive processes (rule-governed combination vs. lexical memorization), or whether a single processing system is sufficient to explain the phenomena, has engendered considerable investigation and debate. We recorded event-related potentials while participants read English sentences that were either correct or had violations of regular past tense inflection, irregular past tense inflection, syntactic phrase structure, or lexical semantics. Violations of regular past tense and phrase structure, but not of irregular past tense or lexical semantics, elicited left-lateralized anterior negativities (LANs). These seem to reflect neurocognitive substrates that underlie compositional processes across linguistic domains, including morphology and syntax. Regular, irregular, and phrase structure violations all elicited later positivities that were maximal over right parietal sites (P600s), and which seem to index aspects of controlled syntactic processing of both phrase structure and morphosyntax. The results suggest distinct neurocognitive substrates for processing regular and irregular past tense forms: regulars depending on compositional processing, and irregulars stored in lexical memory. PMID:17070703

Comprehensive comparative analysis and identification of RNA-binding protein domains: multi-class classification and feature selection.

PubMed

Jahandideh, Samad; Srinivasasainagendra, Vinodh; Zhi, Degui

2012-11-07

RNA-protein interaction plays an important role in various cellular processes, such as protein synthesis, gene regulation, post-transcriptional gene regulation, alternative splicing, and infections by RNA viruses. In this study, using Gene Ontology Annotated (GOA) and Structural Classification of Proteins (SCOP) databases an automatic procedure was designed to capture structurally solved RNA-binding protein domains in different subclasses. Subsequently, we applied tuned multi-class SVM (TMCSVM), Random Forest (RF), and multi-class ℓ1/ℓq-regularized logistic regression (MCRLR) for analysis and classifying RNA-binding protein domains based on a comprehensive set of sequence and structural features. In this study, we compared prediction accuracy of three different state-of-the-art predictor methods. From our results, TMCSVM outperforms the other methods and suggests the potential of TMCSVM as a useful tool for facilitating the multi-class prediction of RNA-binding protein domains. On the other hand, MCRLR by elucidating importance of features for their contribution in predictive accuracy of RNA-binding protein domains subclasses, helps us to provide some biological insights into the roles of sequences and structures in protein-RNA interactions.

Direct Recordings of Pitch Responses from Human Auditory Cortex

PubMed Central

Griffiths, Timothy D.; Kumar, Sukhbinder; Sedley, William; Nourski, Kirill V.; Kawasaki, Hiroto; Oya, Hiroyuki; Patterson, Roy D.; Brugge, John F.; Howard, Matthew A.

2010-01-01

Summary Pitch is a fundamental percept with a complex relationship to the associated sound structure [1]. Pitch perception requires brain representation of both the structure of the stimulus and the pitch that is perceived. We describe direct recordings of local field potentials from human auditory cortex made while subjects perceived the transition between noise and a noise with a regular repetitive structure in the time domain at the millisecond level called regular-interval noise (RIN) [2]. RIN is perceived to have a pitch when the rate is above the lower limit of pitch [3], at approximately 30 Hz. Sustained time-locked responses are observed to be related to the temporal regularity of the stimulus, commonly emphasized as a relevant stimulus feature in models of pitch perception (e.g., [1]). Sustained oscillatory responses are also demonstrated in the high gamma range (80–120 Hz). The regularity responses occur irrespective of whether the response is associated with pitch perception. In contrast, the oscillatory responses only occur for pitch. Both responses occur in primary auditory cortex and adjacent nonprimary areas. The research suggests that two types of pitch-related activity occur in humans in early auditory cortex: time-locked neural correlates of stimulus regularity and an oscillatory response related to the pitch percept. PMID:20605456

Transitional properties of supersolitons in a two electron temperature warm multi-ion plasma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Varghese, Steffy S., E-mail: steffy13@iigs.iigm.res.in; Ghosh, S. S., E-mail: sukti@iigs.iigm.res.in

The existence domain of an ion acoustic supersoliton and its transition to a regular kind of solitary wave have been explored in detail using Sagdeev pseudopotential technique for a two electron temperature warm multi-ion plasma having two species of ions. It was found that both the cold to hot electron temperature ratio and their respective ambient densities play a deterministic role for the existence of a supersoliton, as well as its transitional processes to a regular solitary wave. Analogous to a double layer solution, which often marks the boundary of the existence domain of a regular solitary wave, a “curvemore » of inflection” determines the boundary of the existence domain of a supersoliton. The characteristics of the “curve of inflection,” in turn, depend on the respective concentrations of the two ion species. It is observed that the supersolitons are actually a subset of a more general kind of solutions which are characterized by a fluctuation in the corresponding charge separation which precedes their maximum amplitude. It is also observed that these novel kinds of solitary structures, including supersolitons, occur only for a very narrow range of parameters near constant amplitude beyond which the wave breaks.« less

Profiling of engineering hotspots identifies an allosteric CRISPR-Cas9 switch.

PubMed

Oakes, Benjamin L; Nadler, Dana C; Flamholz, Avi; Fellmann, Christof; Staahl, Brett T; Doudna, Jennifer A; Savage, David F

2016-06-01

The clustered, regularly interspaced, short palindromic repeats (CRISPR)-associated protein Cas9 from Streptococcus pyogenes is an RNA-guided DNA endonuclease with widespread utility for genome modification. However, the structural constraints limiting the engineering of Cas9 have not been determined. Here we experimentally profile Cas9 using randomized insertional mutagenesis and delineate hotspots in the structure capable of tolerating insertions of a PDZ domain without disruption of the enzyme's binding and cleavage functions. Orthogonal domains or combinations of domains can be inserted into the identified sites with minimal functional consequence. To illustrate the utility of the identified sites, we construct an allosterically regulated Cas9 by insertion of the estrogen receptor-α ligand-binding domain. This protein showed robust, ligand-dependent activation in prokaryotic and eukaryotic cells, establishing a versatile one-component system for inducible and reversible Cas9 activation. Thus, domain insertion profiling facilitates the rapid generation of new Cas9 functionalities and provides useful data for future engineering of Cas9.

Personal, interpersonal, and cultural predictors of stages of cigarette smoking among adolescents in Johannesburg, South Africa.

PubMed

Brook, J S; Morojele, N K; Brook, D W; Zhang, C; Whiteman, M

2006-06-01

This study examined the personal, parental, peer, and cultural predictors of stage of smoking among South African urban adolescents. A cross-sectional design was employed. A stratified random approach based on census data was used to obtain the sample. Analyses were conducted using logistic regression. The study took place in communities in and around Johannesburg, South Africa. Participants consisted of 731 adolescents in the age range of 12-17 years old. The sample was 47% male and 53% female, and contained four ethnic classifications: white, black, Indian, and "coloured" (a South African term for mixed ancestry). A structured, in-person interview was administered to each participant in private by a trained interviewer, after obtaining consent. The dependent variables consisted of three stages of smoking: non-smoking, experimental smoking, and regular smoking. The independent measures were drawn from four domains: personal attributes, parental, peer, and cultural influences. Factors in all four domains significantly predicted three different stages of smoking. Personal attributes (internalising and externalising) distinguished among the three stages. Parental factors (for example, affection) reduced the odds of being a regular smoker compared with an experimental smoker or non-smoker, but did not differentiate experimental smokers from non-smokers. Findings from the peer domain (for example, peer substance use) predicted an increase in the risk of being a regular smoker compared with an experimental smoker or non-smoker. In the cultural domain, ethnic identification predicted a decrease in the risk of being a regular smoker compared with an experimental smoker, whereas discrimination and victimisation predicted an increase in the risk of being an experimental smoker compared with a non-smoker. All the domains were important for all four ethnic groups. Four psychosocial domains are important in distinguishing among the three stages of smoking studied. Some predictors differentiated all stages of smoking, others between some of the stages of smoking. Therefore, intervention and prevention programmes which are culturally and linguistically sensitive and appropriate should consider the individual's stage of smoking.

Limited angle CT reconstruction by simultaneous spatial and Radon domain regularization based on TV and data-driven tight frame

NASA Astrophysics Data System (ADS)

Zhang, Wenkun; Zhang, Hanming; Wang, Linyuan; Cai, Ailong; Li, Lei; Yan, Bin

2018-02-01

Limited angle computed tomography (CT) reconstruction is widely performed in medical diagnosis and industrial testing because of the size of objects, engine/armor inspection requirements, and limited scan flexibility. Limited angle reconstruction necessitates usage of optimization-based methods that utilize additional sparse priors. However, most of conventional methods solely exploit sparsity priors of spatial domains. When CT projection suffers from serious data deficiency or various noises, obtaining reconstruction images that meet the requirement of quality becomes difficult and challenging. To solve this problem, this paper developed an adaptive reconstruction method for limited angle CT problem. The proposed method simultaneously uses spatial and Radon domain regularization model based on total variation (TV) and data-driven tight frame. Data-driven tight frame being derived from wavelet transformation aims at exploiting sparsity priors of sinogram in Radon domain. Unlike existing works that utilize pre-constructed sparse transformation, the framelets of the data-driven regularization model can be adaptively learned from the latest projection data in the process of iterative reconstruction to provide optimal sparse approximations for given sinogram. At the same time, an effective alternating direction method is designed to solve the simultaneous spatial and Radon domain regularization model. The experiments for both simulation and real data demonstrate that the proposed algorithm shows better performance in artifacts depression and details preservation than the algorithms solely using regularization model of spatial domain. Quantitative evaluations for the results also indicate that the proposed algorithm applying learning strategy performs better than the dual domains algorithms without learning regularization model

A generalized analysis of hydrophobic and loop clusters within globular protein sequences

PubMed Central

Eudes, Richard; Le Tuan, Khanh; Delettré, Jean; Mornon, Jean-Paul; Callebaut, Isabelle

2007-01-01

Background Hydrophobic Cluster Analysis (HCA) is an efficient way to compare highly divergent sequences through the implicit secondary structure information directly derived from hydrophobic clusters. However, its efficiency and application are currently limited by the need of user expertise. In order to help the analysis of HCA plots, we report here the structural preferences of hydrophobic cluster species, which are frequently encountered in globular domains of proteins. These species are characterized only by their hydrophobic/non-hydrophobic dichotomy. This analysis has been extended to loop-forming clusters, using an appropriate loop alphabet. Results The structural behavior of hydrophobic cluster species, which are typical of protein globular domains, was investigated within banks of experimental structures, considered at different levels of sequence redundancy. The 294 more frequent hydrophobic cluster species were analyzed with regard to their association with the different secondary structures (frequencies of association with secondary structures and secondary structure propensities). Hydrophobic cluster species are predominantly associated with regular secondary structures, and a large part (60 %) reveals preferences for α-helices or β-strands. Moreover, the analysis of the hydrophobic cluster amino acid composition generally allows for finer prediction of the regular secondary structure associated with the considered cluster within a cluster species. We also investigated the behavior of loop forming clusters, using a "PGDNS" alphabet. These loop clusters do not overlap with hydrophobic clusters and are highly associated with coils. Finally, the structural information contained in the hydrophobic structural words, as deduced from experimental structures, was compared to the PSI-PRED predictions, revealing that β-strands and especially α-helices are generally over-predicted within the limits of typical β and α hydrophobic clusters. Conclusion The dictionary of hydrophobic clusters described here can help the HCA user to interpret and compare the HCA plots of globular protein sequences, as well as provides an original fundamental insight into the structural bricks of protein folds. Moreover, the novel loop cluster analysis brings additional information for secondary structure prediction on the whole sequence through a generalized cluster analysis (GCA), and not only on regular secondary structures. Such information lays the foundations for developing a new and original tool for secondary structure prediction. PMID:17210072

Microscopy and microRaman study of periodically poled domains in deeply thinned lithium niobate wafers

NASA Astrophysics Data System (ADS)

Bullen, P. S.; Huang, H.-C.; Yang, H.; Dadap, J. I.; Kymissis, I.; Osgood, R. M.

2016-07-01

The domain structure of poled deeply thinned lithium niobate is investigated as a function of sample thickness. Free-standing samples of thickness from 25 to 500 μm are prepared by a multiple-cycle polish and annealing procedure and then periodically poled. Using these samples and employing micro-Raman scattering and scanning electron, atomic force, and optical microscopy together, the domain broadening and poling voltage are found to vary in a regular and significant manner. The poled domains show a reduction in width spreading of 38% as the sample thickness is reduced from 500 to 25 μm. Micro-Raman probe measurements verify the quality and the uniformity of the poled domains and provide insight into their thickness-dependent poling contrast.

Is there a domain-general cognitive structuring system? Evidence from structural priming across music, math, action descriptions, and language.

PubMed

Van de Cavey, Joris; Hartsuiker, Robert J

2016-01-01

Cognitive processing in many domains (e.g., sentence comprehension, music listening, and math solving) requires sequential information to be organized into an integrational structure. There appears to be some overlap in integrational processing across domains, as shown by cross-domain interference effects when for example linguistic and musical stimuli are jointly presented (Koelsch, Gunter, Wittfoth, & Sammler, 2005; Slevc, Rosenberg, & Patel, 2009). These findings support theories of overlapping resources for integrational processing across domains (cfr. SSIRH Patel, 2003; SWM, Kljajevic, 2010). However, there are some limitations to the studies mentioned above, such as the frequent use of unnaturalistic integrational difficulties. In recent years, the idea has risen that evidence for domain-generality in structural processing might also be yielded though priming paradigms (cfr. Scheepers, 2003). The rationale behind this is that integrational processing across domains regularly requires the processing of dependencies across short or long distances in the sequence, involving respectively less or more syntactic working memory resources (cfr. SWM, Kljajevic, 2010), and such processing decisions might persist over time. However, whereas recent studies have shown suggestive priming of integrational structure between language and arithmetics (though often dependent on arithmetic performance, cfr. Scheepers et al., 2011; Scheepers & Sturt, 2014), it remains to be investigated to what extent we can also find evidence for priming in other domains, such as music and action (cfr. SWM, Kljajevic, 2010). Experiment 1a showed structural priming from the processing of musical sequences onto the position in the sentence structure (early or late) to which a relative clause was attached in subsequent sentence completion. Importantly, Experiment 1b showed that a similar structural manipulation based on non-hierarchically ordered color sequences did not yield any priming effect, suggesting that the priming effect is not based on linear order, but integrational dependency. Finally, Experiment 2 presented primes in four domains (relative clause sentences, music, mathematics, and structured descriptions of actions), and consistently showed priming within and across domains. These findings provide clear evidence for domain-general structural processing mechanisms. Copyright © 2015 Elsevier B.V. All rights reserved.

Crystal structure of clustered regularly interspaced short palindromic repeats (CRISPR)-associated Csn2 protein revealed Ca2+-dependent double-stranded DNA binding activity.

PubMed

Nam, Ki Hyun; Kurinov, Igor; Ke, Ailong

2011-09-02

Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated protein genes (cas genes) are widespread in bacteria and archaea. They form a line of RNA-based immunity to eradicate invading bacteriophages and malicious plasmids. A key molecular event during this process is the acquisition of new spacers into the CRISPR loci to guide the selective degradation of the matching foreign genetic elements. Csn2 is a Nmeni subtype-specific cas gene required for new spacer acquisition. Here we characterize the Enterococcus faecalis Csn2 protein as a double-stranded (ds-) DNA-binding protein and report its 2.7 Å tetrameric ring structure. The inner circle of the Csn2 tetrameric ring is ∼26 Å wide and populated with conserved lysine residues poised for nonspecific interactions with ds-DNA. Each Csn2 protomer contains an α/β domain and an α-helical domain; significant hinge motion was observed between these two domains. Ca(2+) was located at strategic positions in the oligomerization interface. We further showed that removal of Ca(2+) ions altered the oligomerization state of Csn2, which in turn severely decreased its affinity for ds-DNA. In summary, our results provided the first insight into the function of the Csn2 protein in CRISPR adaptation by revealing that it is a ds-DNA-binding protein functioning at the quaternary structure level and regulated by Ca(2+) ions.

Crystal Structure of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated Csn2 Protein Revealed Ca[superscript 2+]-dependent Double-stranded DNA Binding Activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nam, Ki Hyun; Kurinov, Igor; Ke, Ailong

Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated protein genes (cas genes) are widespread in bacteria and archaea. They form a line of RNA-based immunity to eradicate invading bacteriophages and malicious plasmids. A key molecular event during this process is the acquisition of new spacers into the CRISPR loci to guide the selective degradation of the matching foreign genetic elements. Csn2 is a Nmeni subtype-specific cas gene required for new spacer acquisition. Here we characterize the Enterococcus faecalis Csn2 protein as a double-stranded (ds-) DNA-binding protein and report its 2.7 {angstrom} tetrameric ring structure. The inner circle ofmore » the Csn2 tetrameric ring is {approx}26 {angstrom} wide and populated with conserved lysine residues poised for nonspecific interactions with ds-DNA. Each Csn2 protomer contains an {alpha}/{beta} domain and an {alpha}-helical domain; significant hinge motion was observed between these two domains. Ca{sup 2+} was located at strategic positions in the oligomerization interface. We further showed that removal of Ca{sup 2+} ions altered the oligomerization state of Csn2, which in turn severely decreased its affinity for ds-DNA. In summary, our results provided the first insight into the function of the Csn2 protein in CRISPR adaptation by revealing that it is a ds-DNA-binding protein functioning at the quaternary structure level and regulated by Ca{sup 2+} ions.« less

Schnek: A C++ library for the development of parallel simulation codes on regular grids

NASA Astrophysics Data System (ADS)

Schmitz, Holger

2018-05-01

A large number of algorithms across the field of computational physics are formulated on grids with a regular topology. We present Schnek, a library that enables fast development of parallel simulations on regular grids. Schnek contains a number of easy-to-use modules that greatly reduce the amount of administrative code for large-scale simulation codes. The library provides an interface for reading simulation setup files with a hierarchical structure. The structure of the setup file is translated into a hierarchy of simulation modules that the developer can specify. The reader parses and evaluates mathematical expressions and initialises variables or grid data. This enables developers to write modular and flexible simulation codes with minimal effort. Regular grids of arbitrary dimension are defined as well as mechanisms for defining physical domain sizes, grid staggering, and ghost cells on these grids. Ghost cells can be exchanged between neighbouring processes using MPI with a simple interface. The grid data can easily be written into HDF5 files using serial or parallel I/O.

Graph Laplacian Regularization for Image Denoising: Analysis in the Continuous Domain.

PubMed

Pang, Jiahao; Cheung, Gene

2017-04-01

Inverse imaging problems are inherently underdetermined, and hence, it is important to employ appropriate image priors for regularization. One recent popular prior-the graph Laplacian regularizer-assumes that the target pixel patch is smooth with respect to an appropriately chosen graph. However, the mechanisms and implications of imposing the graph Laplacian regularizer on the original inverse problem are not well understood. To address this problem, in this paper, we interpret neighborhood graphs of pixel patches as discrete counterparts of Riemannian manifolds and perform analysis in the continuous domain, providing insights into several fundamental aspects of graph Laplacian regularization for image denoising. Specifically, we first show the convergence of the graph Laplacian regularizer to a continuous-domain functional, integrating a norm measured in a locally adaptive metric space. Focusing on image denoising, we derive an optimal metric space assuming non-local self-similarity of pixel patches, leading to an optimal graph Laplacian regularizer for denoising in the discrete domain. We then interpret graph Laplacian regularization as an anisotropic diffusion scheme to explain its behavior during iterations, e.g., its tendency to promote piecewise smooth signals under certain settings. To verify our analysis, an iterative image denoising algorithm is developed. Experimental results show that our algorithm performs competitively with state-of-the-art denoising methods, such as BM3D for natural images, and outperforms them significantly for piecewise smooth images.

Structure and stability of the ankyrin domain of the Drosophila Notch receptor.

PubMed

Zweifel, Mark E; Leahy, Daniel J; Hughson, Frederick M; Barrick, Doug

2003-11-01

The Notch receptor contains a conserved ankyrin repeat domain that is required for Notch-mediated signal transduction. The ankyrin domain of Drosophila Notch contains six ankyrin sequence repeats previously identified as closely matching the ankyrin repeat consensus sequence, and a putative seventh C-terminal sequence repeat that exhibits lower similarity to the consensus sequence. To better understand the role of the Notch ankyrin domain in Notch-mediated signaling and to examine how structure is distributed among the seven ankyrin sequence repeats, we have determined the crystal structure of this domain to 2.0 angstroms resolution. The seventh, C-terminal, ankyrin sequence repeat adopts a regular ankyrin fold, but the first, N-terminal ankyrin repeat, which contains a 15-residue insertion, appears to be largely disordered. The structure reveals a substantial interface between ankyrin polypeptides, showing a high degree of shape and charge complementarity, which may be related to homotypic interactions suggested from indirect studies. However, the Notch ankyrin domain remains largely monomeric in solution, demonstrating that this interface alone is not sufficient to promote tight association. Using the structure, we have classified reported mutations within the Notch ankyrin domain that are known to disrupt signaling into those that affect buried residues and those restricted to surface residues. We show that the buried substitutions greatly decrease protein stability, whereas the surface substitutions have only a marginal affect on stability. The surface substitutions are thus likely to interfere with Notch signaling by disrupting specific Notch-effector interactions and map the sites of these interactions.

Efficient integration method for fictitious domain approaches

NASA Astrophysics Data System (ADS)

Duczek, Sascha; Gabbert, Ulrich

2015-10-01

In the current article, we present an efficient and accurate numerical method for the integration of the system matrices in fictitious domain approaches such as the finite cell method (FCM). In the framework of the FCM, the physical domain is embedded in a geometrically larger domain of simple shape which is discretized using a regular Cartesian grid of cells. Therefore, a spacetree-based adaptive quadrature technique is normally deployed to resolve the geometry of the structure. Depending on the complexity of the structure under investigation this method accounts for most of the computational effort. To reduce the computational costs for computing the system matrices an efficient quadrature scheme based on the divergence theorem (Gauß-Ostrogradsky theorem) is proposed. Using this theorem the dimension of the integral is reduced by one, i.e. instead of solving the integral for the whole domain only its contour needs to be considered. In the current paper, we present the general principles of the integration method and its implementation. The results to several two-dimensional benchmark problems highlight its properties. The efficiency of the proposed method is compared to conventional spacetree-based integration techniques.

Solvability and Regularity for an Elliptic System Prescribing the Curl, Divergence, and Partial Trace of a Vector Field on Sobolev-Class Domains

NASA Astrophysics Data System (ADS)

Cheng, C. H. Arthur; Shkoller, Steve

2017-09-01

We provide a self-contained proof of the solvability and regularity of a Hodge-type elliptic system, wherein the divergence and curl of a vector field u are prescribed in an open, bounded, Sobolev-class domain {Ω \\subseteq R^n}, and either the normal component {{u} \\cdot {N}} or the tangential components of the vector field {{u} × {N}} are prescribed on the boundary {partial Ω}. For {k > n/2}, we prove that u is in the Sobolev space {H^k+1(Ω)} if {Ω} is an {H^k+1}-domain, and the divergence, curl, and either the normal or tangential trace of u has sufficient regularity. The proof is based on a regularity theory for vector elliptic equations set on Sobolev-class domains and with Sobolev-class coefficients, and with a rather general set of Dirichlet and Neumann boundary conditions. The resulting regularity theory for the vector u is fundamental in the analysis of free-boundary and moving interface problems in fluid dynamics.

Substructural Regularization With Data-Sensitive Granularity for Sequence Transfer Learning.

PubMed

Sun, Shichang; Liu, Hongbo; Meng, Jiana; Chen, C L Philip; Yang, Yu

2018-06-01

Sequence transfer learning is of interest in both academia and industry with the emergence of numerous new text domains from Twitter and other social media tools. In this paper, we put forward the data-sensitive granularity for transfer learning, and then, a novel substructural regularization transfer learning model (STLM) is proposed to preserve target domain features at substructural granularity in the light of the condition of labeled data set size. Our model is underpinned by hidden Markov model and regularization theory, where the substructural representation can be integrated as a penalty after measuring the dissimilarity of substructures between target domain and STLM with relative entropy. STLM can achieve the competing goals of preserving the target domain substructure and utilizing the observations from both the target and source domains simultaneously. The estimation of STLM is very efficient since an analytical solution can be derived as a necessary and sufficient condition. The relative usability of substructures to act as regularization parameters and the time complexity of STLM are also analyzed and discussed. Comprehensive experiments of part-of-speech tagging with both Brown and Twitter corpora fully justify that our model can make improvements on all the combinations of source and target domains.

New regularization scheme for blind color image deconvolution

NASA Astrophysics Data System (ADS)

Chen, Li; He, Yu; Yap, Kim-Hui

2011-01-01

This paper proposes a new regularization scheme to address blind color image deconvolution. Color images generally have a significant correlation among the red, green, and blue channels. Conventional blind monochromatic deconvolution algorithms handle each color image channels independently, thereby ignoring the interchannel correlation present in the color images. In view of this, a unified regularization scheme for image is developed to recover edges of color images and reduce color artifacts. In addition, by using the color image properties, a spectral-based regularization operator is adopted to impose constraints on the blurs. Further, this paper proposes a reinforcement regularization framework that integrates a soft parametric learning term in addressing blind color image deconvolution. A blur modeling scheme is developed to evaluate the relevance of manifold parametric blur structures, and the information is integrated into the deconvolution scheme. An optimization procedure called alternating minimization is then employed to iteratively minimize the image- and blur-domain cost functions. Experimental results show that the method is able to achieve satisfactory restored color images under different blurring conditions.

Numerical solution of the wave equation with variable wave speed on nonconforming domains by high-order difference potentials

NASA Astrophysics Data System (ADS)

Britt, S.; Tsynkov, S.; Turkel, E.

2018-02-01

We solve the wave equation with variable wave speed on nonconforming domains with fourth order accuracy in both space and time. This is accomplished using an implicit finite difference (FD) scheme for the wave equation and solving an elliptic (modified Helmholtz) equation at each time step with fourth order spatial accuracy by the method of difference potentials (MDP). High-order MDP utilizes compact FD schemes on regular structured grids to efficiently solve problems on nonconforming domains while maintaining the design convergence rate of the underlying FD scheme. Asymptotically, the computational complexity of high-order MDP scales the same as that for FD.

Second-Order Two-Sided Estimates in Nonlinear Elliptic Problems

NASA Astrophysics Data System (ADS)

Cianchi, Andrea; Maz'ya, Vladimir G.

2018-05-01

Best possible second-order regularity is established for solutions to p-Laplacian type equations with {p \\in (1, ∞)} and a square-integrable right-hand side. Our results provide a nonlinear counterpart of the classical L 2-coercivity theory for linear problems, which is missing in the existing literature. Both local and global estimates are obtained. The latter apply to solutions to either Dirichlet or Neumann boundary value problems. Minimal regularity on the boundary of the domain is required, although our conclusions are new even for smooth domains. If the domain is convex, no regularity of its boundary is needed at all.

Finsler Geometry of Nonlinear Elastic Solids with Internal Structure

DTIC Science & Technology

2017-01-01

should enable regularized numerical solutions with discretization -size independence for representation of materials demonstrating softening, e.g...additional possibility of a discrete larger void/cavity forming at the core of the sphere. In the second case, comparison with the classical...core of the domain. This hollow sphere physically represents a discrete cavity, while the constant field ξH physically represents a continuous

Childhood self-regulatory skills predict adolescent smoking behavior.

PubMed

deBlois, Madeleine E; Kubzansky, Laura D

2016-01-01

Cigarette smoking is the primary preventable cause of premature death. Better self-regulatory capacity is a key psychosocial factor that has been linked with reduced likelihood of tobacco use. Studies point to the importance of multiple forms of self-regulation, in the domains of emotion, attention, behavior, and social regulation, although no work has evaluated all of these domains in a single prospective study. Considering those four self-regulation domains separately and in combination, this study prospectively investigated whether greater self-regulation in childhood is associated with reduced likelihood of either trying cigarettes or becoming a regular smoker. Hypotheses were tested using longitudinal data from a cohort of 1709 US children participating in the Panel Study of Income Dynamics--Child Development Supplement. Self-regulation was assessed at study baseline when children ranged in age from 6 to 14 years, using parent-reported measures derived from the Behavior Problems Index and Positive Behavior Scale. Children ages 12-19 self-reported their cigarette smoking, defined in two ways: (1) trying and (2) regular use. Separate multiple logistic regression models were used to evaluate odds of trying or regularly using cigarettes, taking account of various potential confounders. Over an average of five years of follow-up, 34.5% of children ever tried cigarettes and 10.6% smoked regularly. Higher behavioral self-regulation was the only domain associated with reduced odds of trying cigarettes (odds ratio (OR) = .85, 95% confidence interval (CI) = .73-.99). Effective regulation in each of the domains was associated with reduced likelihood of regular smoking, although the association with social regulation was not statistically significant (ORs range .70-.85). For each additional domain in which a child was able to regulate successfully, the odds of becoming a regular smoker dropped by 18% (95% CI = .70-.97). These findings suggest that effective childhood self-regulatory skills across multiple domains may reduce future health risk behaviors.

Scattering effects and high-spatial-frequency nanostructures on ultrafast laser irradiated surfaces of zirconium metallic alloys with nano-scaled topographies.

PubMed

Li, Chen; Cheng, Guanghua; Sedao, Xxx; Zhang, Wei; Zhang, Hao; Faure, Nicolas; Jamon, Damien; Colombier, Jean-Philippe; Stoian, Razvan

2016-05-30

The origin of high-spatial-frequency laser-induced periodic surface structures (HSFL) driven by incident ultrafast laser fields, with their ability to achieve structure resolutions below λ/2, is often obscured by the overlap with regular ripples patterns at quasi-wavelength periodicities. We experimentally demonstrate here employing defined surface topographies that these structures are intrinsically related to surface roughness in the nano-scale domain. Using Zr-based bulk metallic glass (Zr-BMG) and its crystalline alloy (Zr-CA) counterpart formed by thermal annealing from its glassy precursor, we prepared surfaces showing either smooth appearances on thermoplastic BMG or high-density nano-protuberances from randomly distributed embedded nano-crystallites with average sizes below 200 nm on the recrystallized alloy. Upon ultrashort pulse irradiation employing linearly polarized 50 fs, 800 nm laser pulses, the surfaces show a range of nanoscale organized features. The change of topology was then followed under multiple pulse irradiation at fluences around and below the single pulse threshold. While the former material (Zr-BMG) shows a specific high quality arrangement of standard ripples around the laser wavelength, the latter (Zr-CA) demonstrates strong predisposition to form high spatial frequency rippled structures (HSFL). We discuss electromagnetic scenarios assisting their formation based on near-field interaction between particles and field-enhancement leading to structure linear growth. Finite-difference-time-domain simulations outline individual and collective effects of nanoparticles on electromagnetic energy modulation and the feedback processes in the formation of HSFL structures with correlation to regular ripples (LSFL).

Nodal domains of a non-separable problem—the right-angled isosceles triangle

NASA Astrophysics Data System (ADS)

Aronovitch, Amit; Band, Ram; Fajman, David; Gnutzmann, Sven

2012-03-01

We study the nodal set of eigenfunctions of the Laplace operator on the right-angled isosceles triangle. A local analysis of the nodal pattern provides an algorithm for computing the number νn of nodal domains for any eigenfunction. In addition, an exact recursive formula for the number of nodal domains is found to reproduce all existing data. Eventually, we use the recursion formula to analyse a large sequence of nodal counts statistically. Our analysis shows that the distribution of nodal counts for this triangular shape has a much richer structure than the known cases of regular separable shapes or completely irregular shapes. Furthermore, we demonstrate that the nodal count sequence contains information about the periodic orbits of the corresponding classical ray dynamics.

Spectral analysis of point-vortex dynamics: first application to vortex polygons in a circular domain

NASA Astrophysics Data System (ADS)

Speetjens, M. F. M.; Meleshko, V. V.; van Heijst, G. J. F.

2014-06-01

The present study addresses the classical problem of the dynamics and stability of a cluster of N-point vortices of equal strength arranged in a polygonal configuration (‘N-vortex polygons’). In unbounded domains, such N-vortex polygons are unconditionally stable for N\\leqslant 7. Confinement in a circular domain tightens the stability conditions to N\\leqslant 6 and a maximum polygon size relative to the domain radius. This work expands on existing studies on stability and integrability by a first giving an exploratory spectral analysis of the dynamics of N vortex polygons in circular domains. Key to this is that the spectral signature of the time evolution of vortex positions reflects their qualitative behaviour. Expressing vortex motion by a generic evolution operator (the so-called Koopman operator) provides a rigorous framework for such spectral analyses. This paves the way to further differentiation and classification of point-vortex behaviour beyond stability and integrability. The concept of Koopman-based spectral analysis is demonstrated for N-vortex polygons. This reveals that conditional stability can be seen as a local form of integrability and confirms an important generic link between spectrum and dynamics: discrete spectra imply regular (quasi-periodic) motion; continuous (sub-)spectra imply chaotic motion. Moreover, this exposes rich nonlinear dynamics as intermittency between regular and chaotic motion and quasi-coherent structures formed by chaotic vortices. Dedicated to the memory of Slava Meleshko, a dear friend and inspiring colleague.

Efficient Delaunay Tessellation through K-D Tree Decomposition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morozov, Dmitriy; Peterka, Tom

Delaunay tessellations are fundamental data structures in computational geometry. They are important in data analysis, where they can represent the geometry of a point set or approximate its density. The algorithms for computing these tessellations at scale perform poorly when the input data is unbalanced. We investigate the use of k-d trees to evenly distribute points among processes and compare two strategies for picking split points between domain regions. Because resulting point distributions no longer satisfy the assumptions of existing parallel Delaunay algorithms, we develop a new parallel algorithm that adapts to its input and prove its correctness. We evaluatemore » the new algorithm using two late-stage cosmology datasets. The new running times are up to 50 times faster using k-d tree compared with regular grid decomposition. Moreover, in the unbalanced data sets, decomposing the domain into a k-d tree is up to five times faster than decomposing it into a regular grid.« less

Model for the architecture of caveolae based on a flexible, net-like assembly of Cavin1 and Caveolin discs

PubMed Central

Stoeber, Miriam; Schellenberger, Pascale; Siebert, C. Alistair; Leyrat, Cedric; Helenius, Ari

2016-01-01

Caveolae are invaginated plasma membrane domains involved in mechanosensing, signaling, endocytosis, and membrane homeostasis. Oligomers of membrane-embedded caveolins and peripherally attached cavins form the caveolar coat whose structure has remained elusive. Here, purified Cavin1 60S complexes were analyzed structurally in solution and after liposome reconstitution by electron cryotomography. Cavin1 adopted a flexible, net-like protein mesh able to form polyhedral lattices on phosphatidylserine-containing vesicles. Mutating the two coiled-coil domains in Cavin1 revealed that they mediate distinct assembly steps during 60S complex formation. The organization of the cavin coat corresponded to a polyhedral nano-net held together by coiled-coil segments. Positive residues around the C-terminal coiled-coil domain were required for membrane binding. Purified caveolin 8S oligomers assumed disc-shaped arrangements of sizes that are consistent with the discs occupying the faces in the caveolar polyhedra. Polygonal caveolar membrane profiles were revealed in tomograms of native caveolae inside cells. We propose a model with a regular dodecahedron as structural basis for the caveolae architecture. PMID:27834731

Algorithm-Dependent Generalization Bounds for Multi-Task Learning.

PubMed

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.

Structural analyses of the CRISPR protein Csc2 reveal the RNA-binding interface of the type I-D Cas7 family.

PubMed

Hrle, Ajla; Maier, Lisa-Katharina; Sharma, Kundan; Ebert, Judith; Basquin, Claire; Urlaub, Henning; Marchfelder, Anita; Conti, Elena

2014-01-01

Upon pathogen invasion, bacteria and archaea activate an RNA-interference-like mechanism termed CRISPR (clustered regularly interspaced short palindromic repeats). A large family of Cas (CRISPR-associated) proteins mediates the different stages of this sophisticated immune response. Bioinformatic studies have classified the Cas proteins into families, according to their sequences and respective functions. These range from the insertion of the foreign genetic elements into the host genome to the activation of the interference machinery as well as target degradation upon attack. Cas7 family proteins are central to the type I and type III interference machineries as they constitute the backbone of the large interference complexes. Here we report the crystal structure of Thermofilum pendens Csc2, a Cas7 family protein of type I-D. We found that Csc2 forms a core RRM-like domain, flanked by three peripheral insertion domains: a lid domain, a Zinc-binding domain and a helical domain. Comparison with other Cas7 family proteins reveals a set of similar structural features both in the core and in the peripheral domains, despite the absence of significant sequence similarity. T. pendens Csc2 binds single-stranded RNA in vitro in a sequence-independent manner. Using a crosslinking - mass-spectrometry approach, we mapped the RNA-binding surface to a positively charged surface patch on T. pendens Csc2. Thus our analysis of the key structural and functional features of T. pendens Csc2 highlights recurring themes and evolutionary relationships in type I and type III Cas proteins.

The intrinsically disordered C-terminal domain of the measles virus nucleoprotein interacts with the C-terminal domain of the phosphoprotein via two distinct sites and remains predominantly unfolded

PubMed Central

Bourhis, Jean-Marie; Receveur-Bréchot, Véronique; Oglesbee, Michael; Zhang, Xinsheng; Buccellato, Matthew; Darbon, Hervé; Canard, Bruno; Finet, Stéphanie; Longhi, Sonia

2005-01-01

Measles virus is a negative-sense, single-stranded RNA virus within theMononegavirales order,which includes several human pathogens, including rabies, Ebola, Nipah, and Hendra viruses. Themeasles virus nucleoprotein consists of a structured N-terminal domain, and of an intrinsically disordered C-terminal domain, NTAIL (aa 401–525), which undergoes induced folding in the presence of the C-terminal domain (XD, aa 459–507) of the viral phosphoprotein. With in NTAIL, an α-helical molecular recognition element (α-MoRE, aa 488–499) involved in binding to P and in induced folding was identified and then observed in the crystal structure of XD. Using small-angle X-ray scattering, we have derived a low-resolution structural model of the complex between XD and NTAIL, which shows that most of NTAIL remains disordered in the complex despite P-induced folding within the α-MoRE. The model consists of an extended shape accommodating the multiple conformations adopted by the disordered N-terminal region of NTAIL, and of a bulky globular region, corresponding to XD and to the C terminus of NTAIL (aa 486–525). Using surface plasmon resonance, circular dichroism, fluorescence spectroscopy, and heteronuclear magnetic resonance, we show that NTAIL has an additional site (aa 517–525) involved in binding to XD but not in the unstructured-to-structured transition. This work provides evidence that intrinsically disordered domains can establish complex interactions with their partners, and can contact them through multiple sites that do not all necessarily gain regular secondary structure. PMID:16046624

An analytical method for the inverse Cauchy problem of Lame equation in a rectangle

NASA Astrophysics Data System (ADS)

Grigor’ev, Yu

2018-04-01

In this paper, we present an analytical computational method for the inverse Cauchy problem of Lame equation in the elasticity theory. A rectangular domain is frequently used in engineering structures and we only consider the analytical solution in a two-dimensional rectangle, wherein a missing boundary condition is recovered from the full measurement of stresses and displacements on an accessible boundary. The essence of the method consists in solving three independent Cauchy problems for the Laplace and Poisson equations. For each of them, the Fourier series is used to formulate a first-kind Fredholm integral equation for the unknown function of data. Then, we use a Lavrentiev regularization method, and the termwise separable property of kernel function allows us to obtain a closed-form regularized solution. As a result, for the displacement components, we obtain solutions in the form of a sum of series with three regularization parameters. The uniform convergence and error estimation of the regularized solutions are proved.

Membrane Sculpting by F-BAR Domains Studied by Molecular Dynamics Simulations

PubMed Central

Yu, Hang; Schulten, Klaus

2013-01-01

Interplay between cellular membranes and their peripheral proteins drives many processes in eukaryotic cells. Proteins of the Bin/Amphiphysin/Rvs (BAR) domain family, in particular, play a role in cellular morphogenesis, for example curving planar membranes into tubular membranes. However, it is still unclear how F-BAR domain proteins act on membranes. Electron microscopy revealed that, in vitro, F-BAR proteins form regular lattices on cylindrically deformed membrane surfaces. Using all-atom and coarse-grained (CG) molecular dynamics simulations, we show that such lattices, indeed, induce tubes of observed radii. A 250 ns all-atom simulation reveals that F-BAR domain curves membranes via the so-called scaffolding mechanism. Plasticity of the F-BAR domain permits conformational change in response to membrane interaction, via partial unwinding of the domains 3-helix bundle structure. A CG simulation covering more than 350 µs provides a dynamic picture of membrane tubulation by lattices of F-BAR domains. A series of CG simulations identified the optimal lattice type for membrane sculpting, which matches closely the lattices seen through cryo-electron microscopy. PMID:23382665

Flightin maintains myofilament lattice organization required for optimal flight power and courtship song quality in Drosophila.

PubMed

Chakravorty, Samya; Tanner, Bertrand C W; Foelber, Veronica Lee; Vu, Hien; Rosenthal, Matthew; Ruiz, Teresa; Vigoreaux, Jim O

2017-05-17

The indirect flight muscles (IFMs) of Drosophila and other insects with asynchronous flight muscles are characterized by a crystalline myofilament lattice structure. The high-order lattice regularity is considered an adaptation for enhanced power output, but supporting evidence for this claim is lacking. We show that IFMs from transgenic flies expressing flightin with a deletion of its poorly conserved N-terminal domain ( fln ΔN62 ) have reduced inter-thick filament spacing and a less regular lattice. This resulted in a decrease in flight ability by 33% and in skinned fibre oscillatory power output by 57%, but had no effect on wingbeat frequency or frequency of maximum power output, suggesting that the underlying actomyosin kinetics is not affected and that the flight impairment arises from deficits in force transmission. Moreover, we show that fln ΔN62 males produced an abnormal courtship song characterized by a higher sine song frequency and a pulse song with longer pulses and longer inter-pulse intervals (IPIs), the latter implicated in male reproductive success. When presented with a choice, wild-type females chose control males over mutant males in 92% of the competition events. These results demonstrate that flightin N-terminal domain is required for optimal myofilament lattice regularity and IFM activity, enabling powered flight and courtship song production. As the courtship song is subject to female choice, we propose that the low amino acid sequence conservation of the N-terminal domain reflects its role in fine-tuning species-specific courtship songs. © 2017 The Author(s).

How evolution learns to generalise: Using the principles of learning theory to understand the evolution of developmental organisation.

PubMed

Kouvaris, Kostas; Clune, Jeff; Kounios, Loizos; Brede, Markus; Watson, Richard A

2017-04-01

One of the most intriguing questions in evolution is how organisms exhibit suitable phenotypic variation to rapidly adapt in novel selective environments. Such variability is crucial for evolvability, but poorly understood. In particular, how can natural selection favour developmental organisations that facilitate adaptive evolution in previously unseen environments? Such a capacity suggests foresight that is incompatible with the short-sighted concept of natural selection. A potential resolution is provided by the idea that evolution may discover and exploit information not only about the particular phenotypes selected in the past, but their underlying structural regularities: new phenotypes, with the same underlying regularities, but novel particulars, may then be useful in new environments. If true, we still need to understand the conditions in which natural selection will discover such deep regularities rather than exploiting 'quick fixes' (i.e., fixes that provide adaptive phenotypes in the short term, but limit future evolvability). Here we argue that the ability of evolution to discover such regularities is formally analogous to learning principles, familiar in humans and machines, that enable generalisation from past experience. Conversely, natural selection that fails to enhance evolvability is directly analogous to the learning problem of over-fitting and the subsequent failure to generalise. We support the conclusion that evolving systems and learning systems are different instantiations of the same algorithmic principles by showing that existing results from the learning domain can be transferred to the evolution domain. Specifically, we show that conditions that alleviate over-fitting in learning systems successfully predict which biological conditions (e.g., environmental variation, regularity, noise or a pressure for developmental simplicity) enhance evolvability. This equivalence provides access to a well-developed theoretical framework from learning theory that enables a characterisation of the general conditions for the evolution of evolvability.

L1-norm locally linear representation regularization multi-source adaptation learning.

PubMed

Tao, Jianwen; Wen, Shiting; Hu, Wenjun

2015-09-01

In most supervised domain adaptation learning (DAL) tasks, one has access only to a small number of labeled examples from target domain. Therefore the success of supervised DAL in this "small sample" regime needs the effective utilization of the large amounts of unlabeled data to extract information that is useful for generalization. Toward this end, we here use the geometric intuition of manifold assumption to extend the established frameworks in existing model-based DAL methods for function learning by incorporating additional information about the target geometric structure of the marginal distribution. We would like to ensure that the solution is smooth with respect to both the ambient space and the target marginal distribution. In doing this, we propose a novel L1-norm locally linear representation regularization multi-source adaptation learning framework which exploits the geometry of the probability distribution, which has two techniques. Firstly, an L1-norm locally linear representation method is presented for robust graph construction by replacing the L2-norm reconstruction measure in LLE with L1-norm one, which is termed as L1-LLR for short. Secondly, considering the robust graph regularization, we replace traditional graph Laplacian regularization with our new L1-LLR graph Laplacian regularization and therefore construct new graph-based semi-supervised learning framework with multi-source adaptation constraint, which is coined as L1-MSAL method. Moreover, to deal with the nonlinear learning problem, we also generalize the L1-MSAL method by mapping the input data points from the input space to a high-dimensional reproducing kernel Hilbert space (RKHS) via a nonlinear mapping. Promising experimental results have been obtained on several real-world datasets such as face, visual video and object. Copyright © 2015 Elsevier Ltd. All rights reserved.

Domain structures and Prco antisite point defects in double-perovskite PrBaCo2O5+δ and PrBa0.8Ca0.2Co2O5+δ.

PubMed

Ding, Yong; Chen, Yu; Pradel, Ken C; Zhang, Weilin; Liu, Meilin; Wang, Zhong Lin

2018-06-15

Owing to the excellent mixed-ionic and electronic conductivity and fast oxygen kinetics at reduced temperature (<800 °C), double-perovskite oxides such as PrBaCo 2 O 5+δ exhibit excellent properties as an oxygen electrode for solid oxide fuel cells (SOFCs). Using transmission electron microscopy (TEM), we revealed high-density antiphase domain boundaries (APBs) and 90° domain walls in PrBaCo 2 O 5+δ grains. Besides the regular lamellar 90° domain walls in {021} planes, irregular fine 90° domains are attached to the curved APBs. Electron energy-loss spectroscopy (EELS) reveals the composition variation across some of the 90° domain walls. There are fewer Co and more Ba ions approaching the 90° domain walls, while the changes in Pr and O ions are not detectable. We assume that the extra Ba 2+ cations replace the Pr 3+ cations, while the Pr 3+ cations go to the Co site to form Pr Co antisite point defects and become Pr 4+ . In this case, the Pr 4+ cations will help to balance the local charges and have compatible ionic radius with that of Co 3+ . The local strain field around the 90° domain walls play a crucial role in the stabilization of such Pr Co antisite point defects. The antisite point defects have been observed in our high-resolution TEM images and aberration-corrected high-angle annular dark-field (HAADF) scanning TEM images. After Ca 2+ doped into PrBaCo 2 O 5+δ to improve the structure stability, we observed tweed structures in the PrBa 0.8 Ca 0.2 Co 2 O 5+δ grain. The tweed structure is composed of high-density intersected needle-shaped 90° domain walls, which is linked to a strong local strain field and composition variation. Even when the temperature is increased to 750 °C, the domain structures are still stable as revealed by our in situ TEM investigation. Therefore, the influence of the domain structures and the Pr Co antisite defects on the ionic and electric conductivities must be considered. Copyright © 2018. Published by Elsevier B.V.

Conservation of the Human Integrin-Type Beta-Propeller Domain in Bacteria

PubMed Central

Chouhan, Bhanupratap; Denesyuk, Alexander; Heino, Jyrki; Johnson, Mark S.; Denessiouk, Konstantin

2011-01-01

Integrins are heterodimeric cell-surface receptors with key functions in cell-cell and cell-matrix adhesion. Integrin α and β subunits are present throughout the metazoans, but it is unclear whether the subunits predate the origin of multicellular organisms. Several component domains have been detected in bacteria, one of which, a specific 7-bladed β-propeller domain, is a unique feature of the integrin α subunits. Here, we describe a structure-derived motif, which incorporates key features of each blade from the X-ray structures of human αIIbβ3 and αVβ3, includes elements of the FG-GAP/Cage and Ca2+-binding motifs, and is specific only for the metazoan integrin domains. Separately, we searched for the metazoan integrin type β-propeller domains among all available sequences from bacteria and unicellular eukaryotic organisms, which must incorporate seven repeats, corresponding to the seven blades of the β-propeller domain, and so that the newly found structure-derived motif would exist in every repeat. As the result, among 47 available genomes of unicellular eukaryotes we could not find a single instance of seven repeats with the motif. Several sequences contained three repeats, a predicted transmembrane segment, and a short cytoplasmic motif associated with some integrins, but otherwise differ from the metazoan integrin α subunits. Among the available bacterial sequences, we found five examples containing seven sequential metazoan integrin-specific motifs within the seven repeats. The motifs differ in having one Ca2+-binding site per repeat, whereas metazoan integrins have three or four sites. The bacterial sequences are more conserved in terms of motif conservation and loop length, suggesting that the structure is more regular and compact than those example structures from human integrins. Although the bacterial examples are not full-length integrins, the full-length metazoan-type 7-bladed β-propeller domains are present, and sometimes two tandem copies are found. PMID:22022374

Magnetic stripes and skyrmions with helicity reversals.

PubMed

Yu, Xiuzhen; Mostovoy, Maxim; Tokunaga, Yusuke; Zhang, Weizhu; Kimoto, Koji; Matsui, Yoshio; Kaneko, Yoshio; Nagaosa, Naoto; Tokura, Yoshinori

2012-06-05

It was recently realized that topological spin textures do not merely have mathematical beauty but can also give rise to unique functionalities of magnetic materials. An example is the skyrmion--a nano-sized bundle of noncoplanar spins--that by virtue of its nontrivial topology acts as a flux of magnetic field on spin-polarized electrons. Lorentz transmission electron microscopy recently emerged as a powerful tool for direct visualization of skyrmions in noncentrosymmetric helimagnets. Topologically, skyrmions are equivalent to magnetic bubbles (cylindrical domains) in ferromagnetic thin films, which were extensively explored in the 1970s for data storage applications. In this study we use Lorentz microscopy to image magnetic domain patterns in the prototypical magnetic oxide-M-type hexaferrite with a hint of scandium. Surprisingly, we find that the magnetic bubbles and stripes in the hexaferrite have a much more complex structure than the skyrmions and spirals in helimagnets, which we associate with the new degree of freedom--helicity (or vector spin chirality) describing the direction of spin rotation across the domain walls. We observe numerous random reversals of helicity in the stripe domain state. Random helicity of cylindrical domain walls coexists with the positional order of magnetic bubbles in a triangular lattice. Most unexpectedly, we observe regular helicity reversals inside skyrmions with an unusual multiple-ring structure.

Influence of initial seed distribution on the pattern formation of the phase field crystals

NASA Astrophysics Data System (ADS)

Starodumov, Ilya; Galenko, Peter; Kropotin, Nikolai; Alexandrov, Dmitri V.

2017-11-01

The process of crystal growth can be expressed as a transition of atomic structure to a finally stable state or to a metastable state. In the Phase Field Crystal Model (PFC-model) these states are described by regular distributions of the atomic density. Getting the system into any metastable condition may be caused by the peculiarities of the computational domain, initial and boundary conditions. However, an important factor in the formation of the crystal structure can be the initial disturbance. In the report we show how different types of initial disturbance can change the finally stable state of crystal structure in equilibrium.

Correlation between polymer architecture, mesoscale structure and photovoltaic performance in side-chain-modified PAE-PAV:fullerene bulk-heterojunction solar cells

NASA Astrophysics Data System (ADS)

Rathgeber, S.; Kuehnlenz, F.; Hoppe, H.; Egbe, D. A. M.; Tuerk, S.; Perlich, J.; Gehrke, R.

2012-02-01

A poly(arylene-ethynylene)-alt-poly(arylene-vinylene) statistical copolymer carrying linear and branched alkoxy side chains along the conjugated backbone in a random manner, yields, compared to its regular substituted counterparts, an improved performance in polymer:fullerene bulk-heterojunction solar cells. Results obtained from GiWAXS experiments show that the improved performance of the statistical copolymer may be attributed to the following structural characteristics: 1) Well, ordered stacked domains that promote backbone planarization and thus improve the ππ-overlap. 2) Partly face-on alignment of domains relative to the electrodes for an improved active layer electrode charge transfer. Branched side chains seem to promote face-on domain orientation. Most likely they can minimize their unfavorable contact with the interface by just bringing the CH3 groups of the branches into direct contact with the surface so that favorable phenylene-substrate interaction can promote face-on orientation. 3) A more isotropic domain orientation throughout the active layer to ensure that the backbone alignment direction has components perpendicular and parallel to the electrodes in order to compromise between light absorption and efficient intra-chain charge transport.

Early detection of skin cancer via terahertz spectral profiling and 3D imaging.

PubMed

Rahman, Anis; Rahman, Aunik K; Rao, Babar

2016-08-15

Terahertz scanning reflectometry, terahertz 3D imaging and terahertz time-domain spectroscopy have been used to identify features in human skin biopsy samples diagnosed for basal cell carcinoma (BCC) and compared with healthy skin samples. It was found from the 3D images that the healthy skin samples exhibit regular cellular pattern while the BCC skin samples indicate lack of regular cell pattern. The skin is a highly layered structure organ; this is evident from the thickness profile via a scan through the thickness of the healthy skin samples, where, the reflected intensity of the terahertz beam exhibits fluctuations originating from different skin layers. Compared to the healthy skin samples, the BCC samples' profiles exhibit significantly diminished layer definition; thus indicating a lack of cellular order. In addition, terahertz time-domain spectroscopy reveals significant and quantifiable differences between the healthy and BCC skin samples. Thus, a combination of three different terahertz techniques constitutes a conclusive route for detecting the BCC condition on a cellular level compared to the healthy skin. Copyright © 2016 Elsevier B.V. All rights reserved.

Irregular Wave Energy Extraction Analysis for a Slider Crank WEC Power Take-Off System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sang, Yuanrui; Karayaka, H. Bora; Yan, Yanjun

2015-09-02

Slider crank Wave Energy Converter (WEC) is a novel energy conversion device. It converts wave energy into electricity at a relatively high efficiency, and it features a simple structure. Past analysis on this WEC has been done under regular sinusoidal wave conditions, and a suboptimal energy could be achieved. This paper presents the analysis of the system under irregular wave conditions; a time-domain hydrodynamics model is adopted and the control methodology is modified to better serve the irregular wave conditions. Results from the simulations show that the performance of the system under irregular wave conditions is different from that undermore » regular sinusoidal wave conditions, but still a reasonable amount of energy can be extracted.« less

On a full Bayesian inference for force reconstruction problems

NASA Astrophysics Data System (ADS)

Aucejo, M.; De Smet, O.

2018-05-01

In a previous paper, the authors introduced a flexible methodology for reconstructing mechanical sources in the frequency domain from prior local information on both their nature and location over a linear and time invariant structure. The proposed approach was derived from Bayesian statistics, because of its ability in mathematically accounting for experimenter's prior knowledge. However, since only the Maximum a Posteriori estimate was computed, the posterior uncertainty about the regularized solution given the measured vibration field, the mechanical model and the regularization parameter was not assessed. To answer this legitimate question, this paper fully exploits the Bayesian framework to provide, from a Markov Chain Monte Carlo algorithm, credible intervals and other statistical measures (mean, median, mode) for all the parameters of the force reconstruction problem.

Delayed Acquisition of Non-Adjacent Vocalic Distributional Regularities

ERIC Educational Resources Information Center

Gonzalez-Gomez, Nayeli; Nazzi, Thierry

2016-01-01

The ability to compute non-adjacent regularities is key in the acquisition of a new language. In the domain of phonology/phonotactics, sensitivity to non-adjacent regularities between consonants has been found to appear between 7 and 10 months. The present study focuses on the emergence of a posterior-anterior (PA) bias, a regularity involving two…

Regularized Dual Averaging Image Reconstruction for Full-Wave Ultrasound Computed Tomography.

PubMed

Matthews, Thomas P; Wang, Kun; Li, Cuiping; Duric, Neb; Anastasio, Mark A

2017-05-01

Ultrasound computed tomography (USCT) holds great promise for breast cancer screening. Waveform inversion-based image reconstruction methods account for higher order diffraction effects and can produce high-resolution USCT images, but are computationally demanding. Recently, a source encoding technique has been combined with stochastic gradient descent (SGD) to greatly reduce image reconstruction times. However, this method bundles the stochastic data fidelity term with the deterministic regularization term. This limitation can be overcome by replacing SGD with a structured optimization method, such as the regularized dual averaging method, that exploits knowledge of the composition of the cost function. In this paper, the dual averaging method is combined with source encoding techniques to improve the effectiveness of regularization while maintaining the reduced reconstruction times afforded by source encoding. It is demonstrated that each iteration can be decomposed into a gradient descent step based on the data fidelity term and a proximal update step corresponding to the regularization term. Furthermore, the regularization term is never explicitly differentiated, allowing nonsmooth regularization penalties to be naturally incorporated. The wave equation is solved by the use of a time-domain method. The effectiveness of this approach is demonstrated through computer simulation and experimental studies. The results suggest that the dual averaging method can produce images with less noise and comparable resolution to those obtained by the use of SGD.

Beta-propellers: associated functions and their role in human diseases.

PubMed

Pons, Tirso; Gómez, Raú; Chinea, Glay; Valencia, Alfonso

2003-03-01

The beta-propeller fold appears as a very fascinating architecture based on four-stranded antiparallel and twisted beta-sheets, radially arranged around a central tunnel. Similar to the alpha/beta-barrel (TIM-barrel) fold, the beta-propeller has a wide range of different functions, and is gaining substantial attention. Some proteins containing beta-propeller domains have been implicated in the pathogenesis of a variety of diseases such as cancer, Alzheimer, Huntington, arthritis, familial hypercholesterolemia, retinitis pigmentosa, osteogenesis, hypertension, and microbial and viral infections. This article reviews some aspects of 3D structure, amino acids sequence regularities, and biological functions of the proteins containing beta-propeller domains. Major emphasis has been laid on beta-propellers whose functions are associated to human diseases. Recent research efforts reported in the fields of protein engineering, drug design, and protein structure-function relationship studies, concerning the beta-propeller architecture, have also been discussed.

Study on magnetic properties of magnetic minerals in the quartzofeldspathic schist by using magnetic force microscope

NASA Astrophysics Data System (ADS)

Ni, C. H.; Chen, Y. H.

2016-12-01

The pseudotachylyte generated from the fault sliding during an earthquake plays an important role in the geology. In general, the pseudotachylyte vein has a magnetic susceptibility which is higher than wall rocks attributed by the fine-grained magnetic minerals. In this study, the fault pseudotachylyte formed by frictional melting in quartzofeldspathic schist rocks from Alpine Fault, New Zealand, was investigated. The scanning electron microscopy (SEM) was used to obtain the morphology of magnetic minerals and magnetic force microscopy (MFM) was utilized to observe magnetic domain structures. We want to realize how the growth process of magnetic minerals affects magnetic structures and magnetic properties. It was observed exsoluted-titanomagnetite was especially around outer edge of pseudotachylyte. These titanomagnetite had a single domain (SD) and distributed paralleling to the direction of exsolution. In contrast, the magnetic minerals (magnetite) in the pseudotachylyte vein had two different magnetic structures: one is the detrital magnetite showed multiple domains (MD) without regular arrangement, which may be indicated the thermal remanent magnetization (TRM). One the other is neoformed fine-grained magnetite scattering in the matrix and showed SD to pseudo-single-domain (PSD) and their magnetic direction was perpendicular to the direction of pseudotachylyte veins, suggesting the chemical remanent magnetization (CRM). However, the macroscopic magnetic property, based on Day's plot, measured from superconducting quantum interference device (SQUID) was shown the sample belonged to MD structures. These results indicated that MFM is a more powerful and precise tool to figure out the magnetic structure. The related studies will be further investigated.

Switchable friction enabled by nanoscale self-assembly on graphene

DOE PAGES

Gallagher, Patrick; Lee, Menyoung; Amet, Francois; ...

2016-02-23

Graphene monolayers are known to display domains of anisotropic friction with twofold symmetry and anisotropy exceeding 200%. This anisotropy has been thought to originate from periodic nanoscale ripples in the graphene sheet, which enhance puckering around a sliding asperity to a degree determined by the sliding direction. Here we demonstrate that these frictional domains derive not from structural features in the graphene but from self-assembly of environmental adsorbates into a highly regular superlattice of stripes with period 4–6 nm. The stripes and resulting frictional domains appear on monolayer and multilayer graphene on a variety of substrates, as well as onmore » exfoliated flakes of hexagonal boron nitride. We show that the stripe-superlattices can be reproducibly and reversibly manipulated with submicrometre precision using a scanning probe microscope, allowing us to create arbitrary arrangements of frictional domains within a single flake. In conclusion, our results suggest a revised understanding of the anisotropic friction observed on graphene and bulk graphite in terms of adsorbates.« less

Chimeras in leaky integrate-and-fire neural networks: effects of reflecting connectivities

NASA Astrophysics Data System (ADS)

Tsigkri-DeSmedt, Nefeli Dimitra; Hizanidis, Johanne; Schöll, Eckehard; Hövel, Philipp; Provata, Astero

2017-07-01

The effects of attracting-nonlocal and reflecting connectivity are investigated in coupled Leaky Integrate-and-Fire (LIF) elements, which model the exchange of electrical signals between neurons. Earlier investigations have demonstrated that repulsive-nonlocal and hierarchical network connectivity can induce complex synchronization patterns and chimera states in systems of coupled oscillators. In the LIF system we show that if the elements are nonlocally linked with positive diffusive coupling on a ring network, the system splits into a number of alternating domains. Half of these domains contain elements whose potential stays near the threshold and they are interrupted by active domains where the elements perform regular LIF oscillations. The active domains travel along the ring with constant velocity, depending on the system parameters. When we introduce reflecting coupling in LIF networks unexpected complex spatio-temporal structures arise. For relatively extensive ranges of parameter values, the system splits into two coexisting domains: one where all elements stay near the threshold and one where incoherent states develop, characterized by multi-leveled mean phase velocity profiles.

Structural and Functional Adaptation of Vancomycin Resistance VanT Serine Racemases

PubMed Central

Meziane-Cherif, Djalal; Stogios, Peter J.; Evdokimova, Elena; Egorova, Olga

2015-01-01

ABSTRACT Vancomycin resistance in Gram-positive bacteria results from the replacement of the d-alanyl–d-alanine target of peptidoglycan precursors with d-alanyl–d-lactate or d-alanyl–d-serine (d-Ala-d-Ser), to which vancomycin has low binding affinity. VanT is one of the proteins required for the production of d-Ala-d-Ser-terminating precursors by converting l-Ser to d-Ser. VanT is composed of two domains, an N-terminal membrane-bound domain, likely involved in l-Ser uptake, and a C-terminal cytoplasmic catalytic domain which is related to bacterial alanine racemases. To gain insight into the molecular function of VanT, the crystal structure of the catalytic domain of VanTG from VanG-type resistant Enterococcus faecalis BM4518 was determined. The structure showed significant similarity to type III pyridoxal 5′-phosphate (PLP)-dependent alanine racemases, which are essential for peptidoglycan synthesis. Comparative structural analysis between VanTG and alanine racemases as well as site-directed mutagenesis identified three specific active site positions centered around Asn696 which are responsible for the l-amino acid specificity. This analysis also suggested that VanT racemases evolved from regular alanine racemases by acquiring additional selectivity toward serine while preserving that for alanine. The 4-fold-lower relative catalytic efficiency of VanTG against l-Ser versus l-Ala implied that this enzyme relies on its membrane-bound domain for l-Ser transport to increase the overall rate of d-Ser production. These findings illustrate how vancomycin pressure selected for molecular adaptation of a housekeeping enzyme to a bifunctional enzyme to allow for peptidoglycan remodeling, a strategy increasingly observed in antibiotic-resistant bacteria. PMID:26265719

Structural and functional adaptation of vancomycin resistance VanT serine racemases

DOE PAGES

Meziane-Cherif, Djalal; Stogios, Peter J.; Evdokimova, Elena; ...

2015-08-11

Vancomycin resistance in Gram-positive bacteria results from the replacement of the D-alanyl–D-alanine target of peptidoglycan precursors with D-alanyl–D-lactate or D-alanyl–D-serine (D-Ala-D-Ser), to which vancomycin has low binding affinity. VanT is one of the proteins required for the production of D-Ala-D-Ser-terminating precursors by converting L-Ser to D-Ser. VanT is composed of two domains, an N-terminal membrane-bound domain, likely involved in L-Ser uptake, and a C-terminal cytoplasmic catalytic domain which is related to bacterial alanine racemases. To gain insight into the molecular function of VanT, the crystal structure of the catalytic domain of VanT G from VanG-type resistant Enterococcus faecalis BM4518more » was determined. The structure showed significant similarity to type III pyridoxal 5'-phosphate (PLP)-dependent alanine racemases, which are essential for peptidoglycan synthesis. Comparative structural analysis between VanT G and alanine racemases as well as site-directed mutagenesis identified three specific active site positions centered around Asn 696 which are responsible for theL-amino acid specificity. This analysis also suggested that VanT racemases evolved from regular alanine racemases by acquiring additional selectivity toward serine while preserving that for alanine. The 4-fold-lower relative catalytic efficiency of VanT G against L-Ser versus L-Ala implied that this enzyme relies on its membrane-bound domain for L-Ser transport to increase the overall rate of D-Ser production. These findings illustrate how vancomycin pressure selected for molecular adaptation of a housekeeping enzyme to a bifunctional enzyme to allow for peptidoglycan remodeling, a strategy increasingly observed in antibiotic-resistant bacteria.« less

Spectral analysis based on fast Fourier transformation (FFT) of surveillance data: the case of scarlet fever in China.

PubMed

Zhang, T; Yang, M; Xiao, X; Feng, Z; Li, C; Zhou, Z; Ren, Q; Li, X

2014-03-01

Many infectious diseases exhibit repetitive or regular behaviour over time. Time-domain approaches, such as the seasonal autoregressive integrated moving average model, are often utilized to examine the cyclical behaviour of such diseases. The limitations for time-domain approaches include over-differencing and over-fitting; furthermore, the use of these approaches is inappropriate when the assumption of linearity may not hold. In this study, we implemented a simple and efficient procedure based on the fast Fourier transformation (FFT) approach to evaluate the epidemic dynamic of scarlet fever incidence (2004-2010) in China. This method demonstrated good internal and external validities and overcame some shortcomings of time-domain approaches. The procedure also elucidated the cycling behaviour in terms of environmental factors. We concluded that, under appropriate circumstances of data structure, spectral analysis based on the FFT approach may be applicable for the study of oscillating diseases.

Conservation and variability in the structure and function of the Cas5d endoribonuclease in the CRISPR-mediated microbial immune system.

PubMed

Koo, Yoon; Ka, Donghyun; Kim, Eun-Jin; Suh, Nayoung; Bae, Euiyoung

2013-10-23

Clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins form an RNA-mediated microbial immune system against invading foreign genetic elements. Cas5 proteins constitute one of the most prevalent Cas protein families in CRISPR-Cas systems and are predicted to have RNA recognition motif (RRM) domains. Cas5d is a subtype I-C-specific Cas5 protein that can be divided into two distinct subgroups, one of which has extra C-terminal residues while the other contains a longer insertion in the middle of its N-terminal RRM domain. Here, we report crystal structures of Cas5d from Streptococcus pyogenes and Xanthomonas oryzae, which respectively represent the two Cas5d subgroups. Despite a common domain architecture consisting of an N-terminal RRM domain and a C-terminal β-sheet domain, the structural differences between the two Cas5d proteins are highlighted by the presence of a unique extended helical region protruding from the N-terminal RRM domain of X. oryzae Cas5d. We also demonstrate that Cas5d proteins possess not only specific endoribonuclease activity for CRISPR RNAs but also nonspecific double-stranded DNA binding affinity. These findings suggest that Cas5d may play multiple roles in CRISPR-mediated immunity. Furthermore, the specific RNA processing was also observed between S. pyogenes Cas5d protein and X. oryzae CRISPR RNA and vice versa. This cross-species activity of Cas5d provides a special opportunity for elucidating conserved features of the CRISPR RNA processing event. Copyright © 2013 Elsevier Ltd. All rights reserved.

Six-dimensional regularization of chiral gauge theories

NASA Astrophysics Data System (ADS)

Fukaya, Hidenori; Onogi, Tetsuya; Yamamoto, Shota; Yamamura, Ryo

2017-03-01

We propose a regularization of four-dimensional chiral gauge theories using six-dimensional Dirac fermions. In our formulation, we consider two different mass terms having domain-wall profiles in the fifth and the sixth directions, respectively. A Weyl fermion appears as a localized mode at the junction of two different domain walls. One domain wall naturally exhibits the Stora-Zumino chain of the anomaly descent equations, starting from the axial U(1) anomaly in six dimensions to the gauge anomaly in four dimensions. Another domain wall implies a similar inflow of the global anomalies. The anomaly-free condition is equivalent to requiring that the axial U(1) anomaly and the parity anomaly are canceled among the six-dimensional Dirac fermions. Since our formulation is based on a massive vector-like fermion determinant, a nonperturbative regularization will be possible on a lattice. Putting the gauge field at the four-dimensional junction and extending it to the bulk using the Yang-Mills gradient flow, as recently proposed by Grabowska and Kaplan, we define the four-dimensional path integral of the target chiral gauge theory.

Regular Latin Dancing and Health Education may Improve Cognition of Late Middle-Aged and Older Latinos

PubMed Central

Marquez, David X.; Wilson, Robert; Aguiñaga, Susan; Vásquez, Priscilla; Fogg, Louis; Yang, Zhi; Wilbur, JoEllen; Hughes, Susan; Spanbauer, Charles

2017-01-01

Disparities exist between Latinos and non-Latino whites in cognitive function. Dance is culturally appropriate and challenges individuals physically and cognitively, yet the impact of regular dancing on cognitive function in older Latinos has not been examined. A two-group pilot trial was employed among inactive, older Latinos. Participants (N = 57) participated in the BAILAMOS© dance program or a health education program. Cognitive test scores were converted to z-scores and measures of global cognition and specific domains (executive function, episodic memory, working memory) were derived. Results revealed a group × time interaction for episodic memory (p<0.05), such that the dance group showed greater improvement in episodic memory than the health education group. A main effect for time for global cognition (p<0.05) was also demonstrated, with participants in both groups improving. Structured Latin dance programs can positively influence episodic memory; and participation in structured programs may improve overall cognition among older Latinos. PMID:28095105

Regular Latin Dancing and Health Education May Improve Cognition of Late Middle-Aged and Older Latinos.

PubMed

Marquez, David X; Wilson, Robert; Aguiñaga, Susan; Vásquez, Priscilla; Fogg, Louis; Yang, Zhi; Wilbur, JoEllen; Hughes, Susan; Spanbauer, Charles

2017-07-01

Disparities exist between Latinos and non-Latino Whites in cognitive function. Dance is culturally appropriate and challenges individuals physically and cognitively, yet the impact of regular dancing on cognitive function in older Latinos has not been examined. A two-group pilot trial was employed among inactive, older Latinos. Participants (N = 57) participated in the BAILAMOS © dance program or a health education program. Cognitive test scores were converted to z-scores and measures of global cognition and specific domains (executive function, episodic memory, working memory) were derived. Results revealed a group × time interaction for episodic memory (p < .05), such that the dance group showed greater improvement in episodic memory than the health education group. A main effect for time for global cognition (p < .05) was also demonstrated, with participants in both groups improving. Structured Latin dance programs can positively influence episodic memory, and participation in structured programs may improve overall cognition among older Latinos.

Energy Extraction from a Slider-Crank Wave Energy under Irregular Wave Conditions: Preprint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sang, Yuanrui; Karayaka, H. Bora; Yan, Yanjun

2015-08-24

A slider-crank wave energy converter (WEC) is a novel energy conversion device. It converts wave energy into electricity at a relatively high efficiency, and it features a simple structure. Past analysis on this particular WEC has been done under regular sinusoidal wave conditions, and suboptimal energy could be achieved. This paper presents the analysis of the system under irregular wave conditions; a time-domain hydrodynamics model is adopted and a rule-based control methodology is introduced to better serve the irregular wave conditions. Results from the simulations show that the performance of the system under irregular wave conditions is different from thatmore » under regular sinusoidal wave conditions, but a reasonable amount of energy can still be extracted.« less

Energy Extraction from a Slider-Crank Wave Energy Converter under Irregular Wave Conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sang, Yuanrui; Karayaka, H. Bora; Yan, Yanjun

2015-10-19

A slider-crank wave energy converter (WEC) is a novel energy conversion device. It converts wave energy into electricity at a relatively high efficiency, and it features a simple structure. Past analysis on this particular WEC has been done under regular sinusoidal wave conditions, and suboptimal energy could be achieved. This paper presents the analysis of the system under irregular wave conditions; a time-domain hydrodynamics model is adopted and a rule-based control methodology is introduced to better serve the irregular wave conditions. Results from the simulations show that the performance of the system under irregular wave conditions is different from thatmore » under regular sinusoidal wave conditions, but a reasonable amount of energy can still be extracted.« less

Low-dose 4D cone-beam CT via joint spatiotemporal regularization of tensor framelet and nonlocal total variation

NASA Astrophysics Data System (ADS)

Han, Hao; Gao, Hao; Xing, Lei

2017-08-01

Excessive radiation exposure is still a major concern in 4D cone-beam computed tomography (4D-CBCT) due to its prolonged scanning duration. Radiation dose can be effectively reduced by either under-sampling the x-ray projections or reducing the x-ray flux. However, 4D-CBCT reconstruction under such low-dose protocols is prone to image artifacts and noise. In this work, we propose a novel joint regularization-based iterative reconstruction method for low-dose 4D-CBCT. To tackle the under-sampling problem, we employ spatiotemporal tensor framelet (STF) regularization to take advantage of the spatiotemporal coherence of the patient anatomy in 4D images. To simultaneously suppress the image noise caused by photon starvation, we also incorporate spatiotemporal nonlocal total variation (SNTV) regularization to make use of the nonlocal self-recursiveness of anatomical structures in the spatial and temporal domains. Under the joint STF-SNTV regularization, the proposed iterative reconstruction approach is evaluated first using two digital phantoms and then using physical experiment data in the low-dose context of both under-sampled and noisy projections. Compared with existing approaches via either STF or SNTV regularization alone, the presented hybrid approach achieves improved image quality, and is particularly effective for the reconstruction of low-dose 4D-CBCT data that are not only sparse but noisy.

Solution properties of the archaeal CRISPR DNA repeat-binding homeodomain protein Cbp2

PubMed Central

Kenchappa, Chandra S.; Heidarsson, Pétur O.; Kragelund, Birthe B.; Garrett, Roger A.; Poulsen, Flemming M.

2013-01-01

Clustered regularly interspaced short palindromic repeats (CRISPR) form the basis of diverse adaptive immune systems directed primarily against invading genetic elements of archaea and bacteria. Cbp1 of the crenarchaeal thermoacidophilic order Sulfolobales, carrying three imperfect repeats, binds specifically to CRISPR DNA repeats and has been implicated in facilitating production of long transcripts from CRISPR loci. Here, a second related class of CRISPR DNA repeat-binding protein, denoted Cbp2, is characterized that contains two imperfect repeats and is found amongst members of the crenarchaeal thermoneutrophilic order Desulfurococcales. DNA repeat-binding properties of the Hyperthermus butylicus protein Cbp2Hb were characterized and its three-dimensional structure was determined by NMR spectroscopy. The two repeats generate helix-turn-helix structures separated by a basic linker that is implicated in facilitating high affinity DNA binding of Cbp2 by tethering the two domains. Structural studies on mutant proteins provide support for Cys7 and Cys28 enhancing high thermal stability of Cbp2Hb through disulphide bridge formation. Consistent with their proposed CRISPR transcriptional regulatory role, Cbp2Hb and, by inference, other Cbp1 and Cbp2 proteins are closely related in structure to homeodomain proteins with linked helix-turn-helix (HTH) domains, in particular the paired domain Pax and Myb family proteins that are involved in eukaryal transcriptional regulation. PMID:23325851

Investigating energy-based pool structure selection in the structure ensemble modeling with experimental distance constraints: The example from a multidomain protein Pub1.

PubMed

Zhu, Guanhua; Liu, Wei; Bao, Chenglong; Tong, Dudu; Ji, Hui; Shen, Zuowei; Yang, Daiwen; Lu, Lanyuan

2018-05-01

The structural variations of multidomain proteins with flexible parts mediate many biological processes, and a structure ensemble can be determined by selecting a weighted combination of representative structures from a simulated structure pool, producing the best fit to experimental constraints such as interatomic distance. In this study, a hybrid structure-based and physics-based atomistic force field with an efficient sampling strategy is adopted to simulate a model di-domain protein against experimental paramagnetic relaxation enhancement (PRE) data that correspond to distance constraints. The molecular dynamics simulations produce a wide range of conformations depicted on a protein energy landscape. Subsequently, a conformational ensemble recovered with low-energy structures and the minimum-size restraint is identified in good agreement with experimental PRE rates, and the result is also supported by chemical shift perturbations and small-angle X-ray scattering data. It is illustrated that the regularizations of energy and ensemble-size prevent an arbitrary interpretation of protein conformations. Moreover, energy is found to serve as a critical control to refine the structure pool and prevent data overfitting, because the absence of energy regularization exposes ensemble construction to the noise from high-energy structures and causes a more ambiguous representation of protein conformations. Finally, we perform structure-ensemble optimizations with a topology-based structure pool, to enhance the understanding on the ensemble results from different sources of pool candidates. © 2018 Wiley Periodicals, Inc.

Design optimization of space structures

NASA Technical Reports Server (NTRS)

Felippa, Carlos

1991-01-01

The topology-shape-size optimization of space structures is investigated through Kikuchi's homogenization method. The method starts from a 'design domain block,' which is a region of space into which the structure is to materialize. This domain is initially filled with a finite element mesh, typically regular. Force and displacement boundary conditions corresponding to applied loads and supports are applied at specific points in the domain. An optimal structure is to be 'carved out' of the design under two conditions: (1) a cost function is to be minimized, and (2) equality or inequality constraints are to be satisfied. The 'carving' process is accomplished by letting microstructure holes develop and grow in elements during the optimization process. These holes have a rectangular shape in two dimensions and a cubical shape in three dimensions, and may also rotate with respect to the reference axes. The properties of the perforated element are obtained through an homogenization procedure. Once a hole reaches the volume of the element, that element effectively disappears. The project has two phases. In the first phase the method was implemented as the combination of two computer programs: a finite element module, and an optimization driver. In the second part, focus is on the application of this technique to planetary structures. The finite element part of the method was programmed for the two-dimensional case using four-node quadrilateral elements to cover the design domain. An element homogenization technique different from that of Kikuchi and coworkers was implemented. The optimization driver is based on an augmented Lagrangian optimizer, with the volume constraint treated as a Courant penalty function. The optimizer has to be especially tuned to this type of optimization because the number of design variables can reach into the thousands. The driver is presently under development.

Structure of the C-terminal domain of the arginine repressor protein from Mycobacterium tuberculosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cherney, Leonid T.; Cherney, Maia M.; Garen, Craig R.

2008-09-01

The structure of the core domain of the arginine repressor protein from M. tuberculosis has been determined with (1.85 Å resolution) and without (2.15 Å resolution) the arginine corepressor bound. Three additional arginine molecules have been found to bind to the core domain hexamer at high (0.2 M) arginine concentration. The Mycobacterium tuberculosis (Mtb) gene product encoded by open reading frame Rv1657 is an arginine repressor (ArgR). All genes involved in the l-arginine (hereafter arginine) biosynthetic pathway are essential for optimal growth of the Mtb pathogen, thus making MtbArgR a potential target for drug design. The C-terminal domains of argininemore » repressors (CArgR) participate in oligomerization and arginine binding. Several crystal forms of CArgR from Mtb (MtbCArgR) have been obtained. The X-ray crystal structures of MtbCArgR were determined at 1.85 Å resolution with bound arginine and at 2.15 Å resolution in the unliganded form. These structures show that six molecules of MtbCArgR are arranged into a hexamer having approximate 32 point symmetry that is formed from two trimers. The trimers rotate relative to each other by about 11° upon binding arginine. All residues in MtbCArgR deemed to be important for hexamer formation and for arginine binding have been identified from the experimentally determined structures presented. The hexamer contains six regular sites in which the arginine molecules have one common binding mode and three sites in which the arginine molecules have two overlapping binding modes. The latter sites only bind the ligand at high (200 mM) arginine concentrations.« less

A New Pansharpening Method Based on Spatial and Spectral Sparsity Priors.

PubMed

He, Xiyan; Condat, Laurent; Bioucas-Diaz, Jose; Chanussot, Jocelyn; Xia, Junshi

2014-06-27

The development of multisensor systems in recent years has led to great increase in the amount of available remote sensing data. Image fusion techniques aim at inferring high quality images of a given area from degraded versions of the same area obtained by multiple sensors. This paper focuses on pansharpening, which is the inference of a high spatial resolution multispectral image from two degraded versions with complementary spectral and spatial resolution characteristics: a) a low spatial resolution multispectral image; and b) a high spatial resolution panchromatic image. We introduce a new variational model based on spatial and spectral sparsity priors for the fusion. In the spectral domain we encourage low-rank structure, whereas in the spatial domain we promote sparsity on the local differences. Given the fact that both panchromatic and multispectral images are integrations of the underlying continuous spectra using different channel responses, we propose to exploit appropriate regularizations based on both spatial and spectral links between panchromatic and the fused multispectral images. A weighted version of the vector Total Variation (TV) norm of the data matrix is employed to align the spatial information of the fused image with that of the panchromatic image. With regard to spectral information, two different types of regularization are proposed to promote a soft constraint on the linear dependence between the panchromatic and the fused multispectral images. The first one estimates directly the linear coefficients from the observed panchromatic and low resolution multispectral images by Linear Regression (LR) while the second one employs the Principal Component Pursuit (PCP) to obtain a robust recovery of the underlying low-rank structure. We also show that the two regularizers are strongly related. The basic idea of both regularizers is that the fused image should have low-rank and preserve edge locations. We use a variation of the recently proposed Split Augmented Lagrangian Shrinkage (SALSA) algorithm to effectively solve the proposed variational formulations. Experimental results on simulated and real remote sensing images show the effectiveness of the proposed pansharpening method compared to the state-of-the-art.

Instationary Generalized Stokes Equations in Partially Periodic Domains

NASA Astrophysics Data System (ADS)

Sauer, Jonas

2018-06-01

We consider an instationary generalized Stokes system with nonhomogeneous divergence data under a periodic condition in only some directions. The problem is set in the whole space, the half space or in (after an identification of the periodic directions with a torus) bounded domains with sufficiently regular boundary. We show unique solvability for all times in Muckenhoupt weighted Lebesgue spaces. The divergence condition is dealt with by analyzing the associated reduced Stokes system and in particular by showing maximal regularity of the partially periodic reduced Stokes operator.

[Development of a measurement of intellectual capital for hospital nursing organizations].

PubMed

Kim, Eun A; Jang, Keum Seong

2011-02-01

This study was done to develop an instrument for measuring intellectual capital and assess its validity and reliability in identifying the components, human capital, structure capital and customer capital of intellectual capital in hospital nursing organizations. The participants were 950 regular clinical nurses who had worked for over 13 months in 7 medical hospitals including 4 national university hospitals and 3 private university hospitals. The data were collected through a questionnaire survey done from July 2 to August 25, 2009. Data from 906 nurses were used for the final analysis. Data were analyzed using descriptive statistics, Cronbach's alpha coefficients, item analysis, factor analysis (principal component analysis, Varimax rotation) with the SPSS PC+ 17.0 for Windows program. Developing the instrument for measuring intellectual capital in hospital nursing organizations involved a literature review, development of preliminary items, and verification of validity and reliability. The final instrument was in a self-report form on a 5-point Likert scale. There were 29 items on human capital (5 domains), 21 items on customer capital (4 domains), 26 items on structure capital (4 domains). The results of this study may be useful to assess the levels of intellectual capital of hospital nursing organizations.

Total variation iterative constraint algorithm for limited-angle tomographic reconstruction of non-piecewise-constant structures

NASA Astrophysics Data System (ADS)

Krauze, W.; Makowski, P.; Kujawińska, M.

2015-06-01

Standard tomographic algorithms applied to optical limited-angle tomography result in the reconstructions that have highly anisotropic resolution and thus special algorithms are developed. State of the art approaches utilize the Total Variation (TV) minimization technique. These methods give very good results but are applicable to piecewise constant structures only. In this paper, we propose a novel algorithm for 3D limited-angle tomography - Total Variation Iterative Constraint method (TVIC) which enhances the applicability of the TV regularization to non-piecewise constant samples, like biological cells. This approach consists of two parts. First, the TV minimization is used as a strong regularizer to create a sharp-edged image converted to a 3D binary mask which is then iteratively applied in the tomographic reconstruction as a constraint in the object domain. In the present work we test the method on a synthetic object designed to mimic basic structures of a living cell. For simplicity, the test reconstructions were performed within the straight-line propagation model (SIRT3D solver from the ASTRA Tomography Toolbox), but the strategy is general enough to supplement any algorithm for tomographic reconstruction that supports arbitrary geometries of plane-wave projection acquisition. This includes optical diffraction tomography solvers. The obtained reconstructions present resolution uniformity and general shape accuracy expected from the TV regularization based solvers, but keeping the smooth internal structures of the object at the same time. Comparison between three different patterns of object illumination arrangement show very small impact of the projection acquisition geometry on the image quality.

Improving Employment Prospects for Soldiers Leaving the Regular Army

DTIC Science & Technology

2017-01-01

difficulties in the civilian job market . Furthermore, since 2012, the Army has been reducing its active component end strength; this has increased the number...Domains and Focus Domains (Number of Questions) Domain Focus Knowledge (33) Sets of facts and principles needed to address problems and issues that are part

Fractal analysis of time varying data

DOEpatents

Vo-Dinh, Tuan; Sadana, Ajit

2002-01-01

Characteristics of time varying data, such as an electrical signal, are analyzed by converting the data from a temporal domain into a spatial domain pattern. Fractal analysis is performed on the spatial domain pattern, thereby producing a fractal dimension D.sub.F. The fractal dimension indicates the regularity of the time varying data.

Numerical simulation of a shear-thinning fluid through packed spheres

NASA Astrophysics Data System (ADS)

Liu, Hai Long; Moon, Jong Sin; Hwang, Wook Ryol

2012-12-01

Flow behaviors of a non-Newtonian fluid in spherical microstructures have been studied by a direct numerical simulation. A shear-thinning (power-law) fluid through both regular and randomly packed spheres has been numerically investigated in a representative unit cell with the tri-periodic boundary condition, employing a rigorous three-dimensional finite-element scheme combined with fictitious-domain mortar-element methods. The present scheme has been validated for the classical spherical packing problems with literatures. The flow mobility of regular packing structures, including simple cubic (SC), body-centered cubic (BCC), face-centered cubic (FCC), as well as randomly packed spheres, has been investigated quantitatively by considering the amount of shear-thinning, the pressure gradient and the porosity as parameters. Furthermore, the mechanism leading to the main flow path in a highly shear-thinning fluid through randomly packed spheres has been discussed.

Frequency Domain Decomposition performed on the strain data obtained from the aluminium model of an offshore support structure

NASA Astrophysics Data System (ADS)

Mieloszyk, M.; Opoka, S.; Ostachowicz, W.

2015-07-01

This paper presents an application of Fibre Bragg Grating (FBG) sensors for Structural Health Monitoring (SHM) of offshore wind energy support structure model. The analysed structure is a tripod equipped with 16 FBG sensors. From a wide variety of Operational Modal Analysis (OMA) methods Frequency Domain Decomposition (FDD) technique is used in this paper under assumption that the input loading is similar to a white noise excitation. The FDD method can be applied using different sets of sensors, i.e. the one which contains all FBG sensors and the other set of sensors localised only on a particular tripod's leg. The cases considered during investigation were as follows: damaged and undamaged scenarios, different support conditions. The damage was simulated as an dismantled flange on an upper brace in one of the tripod legs. First the model was fixed to an antishaker table and investigated in the air under impulse excitations. Next the tripod was submerged into water basin in order to check the quality of the measurement set-up in different environmental condition. In this case the model was excited by regular waves.

Assignment of protein sequences to existing domain and family classification systems: Pfam and the PDB.

PubMed

Xu, Qifang; Dunbrack, Roland L

2012-11-01

Automating the assignment of existing domain and protein family classifications to new sets of sequences is an important task. Current methods often miss assignments because remote relationships fail to achieve statistical significance. Some assignments are not as long as the actual domain definitions because local alignment methods often cut alignments short. Long insertions in query sequences often erroneously result in two copies of the domain assigned to the query. Divergent repeat sequences in proteins are often missed. We have developed a multilevel procedure to produce nearly complete assignments of protein families of an existing classification system to a large set of sequences. We apply this to the task of assigning Pfam domains to sequences and structures in the Protein Data Bank (PDB). We found that HHsearch alignments frequently scored more remotely related Pfams in Pfam clans higher than closely related Pfams, thus, leading to erroneous assignment at the Pfam family level. A greedy algorithm allowing for partial overlaps was, thus, applied first to sequence/HMM alignments, then HMM-HMM alignments and then structure alignments, taking care to join partial alignments split by large insertions into single-domain assignments. Additional assignment of repeat Pfams with weaker E-values was allowed after stronger assignments of the repeat HMM. Our database of assignments, presented in a database called PDBfam, contains Pfams for 99.4% of chains >50 residues. The Pfam assignment data in PDBfam are available at http://dunbrack2.fccc.edu/ProtCid/PDBfam, which can be searched by PDB codes and Pfam identifiers. They will be updated regularly.

Directing self-assembly of gold nanoparticles in diblock copolymer scaffold

NASA Astrophysics Data System (ADS)

Li, Qifang; He, Jinbo; Glogowski, Elizabeth; Emrick, Todd; Russell, Thomas

2007-03-01

A versatile hierarchical approach for directing self -assembly of gold nanostructures with size 2-3nm in diblock copolymer scaffolds is found. Diblock copolymer polystyrene-b-poly(2-vinylpyridine) (PS-b-P2VP) is used to form a regular scaffold of highly anisotropic, stripe-like domains, and controlled differential wetting by dichloromethane and thermal annealing guides gold nanoparticles with half hydrophilic ligand to aggregate selectively along the scaffold, producing highly organized metal nanostructures. In as-cast block-copolymer and gold nanoparticles thin films, micelle structure and gold nanoparticles random distribution on scaffold are typically observed. However, samples annealed in dichloromethane exhibit well-defined short-range ordered nanostructure with gold nanoparticles located at the interface of PS and P2VP nanoscale domain. After annealing at 170 C, the gold nanoparticles at interface migrated into the middle of P2VP phase and exhibited long-range ordered hierarchical structures. Synergistic interactions between the gold nanoparticles and the PS-b-P2VP caused an orientation of the microdomains normal to the film surface.

Morphological and Structural Aspects of the Extremely Halophilic Archaeon Haloquadratum walsbyi

PubMed Central

Sublimi Saponetti, Matilde; Bobba, Fabrizio; Salerno, Grazia; Scarfato, Alessandro; Corcelli, Angela; Cucolo, Annamaria

2011-01-01

Ultrathin square cell Haloquadratum walsbyi from the Archaea domain are the most abundant microorganisms in the hypersaline water of coastal salterns and continental salt lakes. In this work, we explore the cell surface of these microorganisms using amplitude-modulation atomic-force microscopy in nearly physiological conditions. We demonstrate the presence of a regular corrugation with a periodicity of 16–20 nm attributed to the surface layer (S-layer) protein lattice, striped domains asymmetrically distributed on the cell faces and peculiar bulges correlated with the presence of intracellular granules. Besides, subsequent images of cell evolution during the drying process indicate the presence of an external capsule that might correspond to the giant protein halomucin, predicted by the genome but never before observed by other microscopy studies. PMID:21559517

Morphological and structural aspects of the extremely halophilic archaeon Haloquadratum walsbyi.

PubMed

Sublimi Saponetti, Matilde; Bobba, Fabrizio; Salerno, Grazia; Scarfato, Alessandro; Corcelli, Angela; Cucolo, Annamaria

2011-04-29

Ultrathin square cell Haloquadratum walsbyi from the Archaea domain are the most abundant microorganisms in the hypersaline water of coastal salterns and continental salt lakes. In this work, we explore the cell surface of these microorganisms using amplitude-modulation atomic-force microscopy in nearly physiological conditions. We demonstrate the presence of a regular corrugation with a periodicity of 16-20 nm attributed to the surface layer (S-layer) protein lattice, striped domains asymmetrically distributed on the cell faces and peculiar bulges correlated with the presence of intracellular granules. Besides, subsequent images of cell evolution during the drying process indicate the presence of an external capsule that might correspond to the giant protein halomucin, predicted by the genome but never before observed by other microscopy studies.

Description of waves in inhomogeneous domains using Heun's equation

NASA Astrophysics Data System (ADS)

Bednarik, M.; Cervenka, M.

2018-04-01

There are a number of model equations describing electromagnetic, acoustic or quantum waves in inhomogeneous domains and some of them are of the same type from the mathematical point of view. This isomorphism enables us to use a unified approach to solving the corresponding equations. In this paper, the inhomogeneity is represented by a trigonometric spatial distribution of a parameter determining the properties of an inhomogeneous domain. From the point of view of modeling, this trigonometric parameter function can be smoothly connected to neighboring constant-parameter regions. For this type of distribution, exact local solutions of the model equations are represented by the local Heun functions. As the interval for which the solution is sought includes two regular singular points. For this reason, a method is proposed which resolves this problem only based on the local Heun functions. Further, the transfer matrix for the considered inhomogeneous domain is determined by means of the proposed method. As an example of the applicability of the presented solutions the transmission coefficient is calculated for the locally periodic structure which is given by an array of asymmetric barriers.

Dynamics of meso and thermo citrate synthases with implicit solvation

NASA Astrophysics Data System (ADS)

Cordeiro, J. M. M.

The dynamics of hydration of meso and thermo citrate synthases has been investigated using the EEF1 methodology implemented with the CHARMM program. The native enzymes are composed of two identical subunits, each divided into a small and large domain. The dynamics behavior of both enzymes at 30°C and 60°C has been compared. The results of simulations show that during the hydration process, each subunit follows a different pathway of hydration, in spite of the identical sequence. The hydrated structures were compared with the crystalline structure, and the root mean square deviation (RMSD) of each residue along the trajectory was calculated. The regions with larger and smaller mobility were identified. In particular, helices belonging to the small domain are more mobile than those of the large domain. In contrast, the residues that constitute the active site show a much lower displacement compared with the crystalline structure. Hydration free energy calculations point out that Thermoplasma acidophilum citrate synthase (TCS) is more stable than chicken citrate synthase (CCS), at high temperatures. Such result has been ascribed to the higher number of superficial charges in the thermophilic homologue, which stabilizes the enzyme, while the mesophilic homologue denatures. These results are in accord with the experimental found that TCS keeps activity at temperatures farther apart from the catalysis regular temperature than the CCS.

A comparative molecular dynamics study of thermophilic and mesophilic β-fructosidase enzymes.

PubMed

Mazola, Yuliet; Guirola, Osmany; Palomares, Sucel; Chinea, Glay; Menéndez, Carmen; Hernández, Lázaro; Musacchio, Alexis

2015-09-01

Arabidopsis thaliana cell wall invertase 1 (AtcwINV1) and Thermotoga maritima β-fructosidase (BfrA) are among the best structurally studied members of the glycoside hydrolase family 32. Both enzymes hydrolyze sucrose as the main substrate but differ strongly in their thermal stability. Mesophilic AtcwINV1 and thermophilic BfrA have divergent sequence similarities in the N-terminal five bladed β-propeller catalytic domain (31 %) and the C-terminal β-sandwich domain (15 %) of unknown function. The two enzymes were subjected to 200 ns molecular dynamics simulations at 300 K (27 °C) and 353 K (80 °C). Regular secondary structure regions, but not loops, in AtcwINV1 and BfrA showed no significant fluctuation differences at both temperatures. BfrA was more rigid than AtcwINV1 at 300 K. The simulation at 353 K did not alter the structural stability of BfrA, but did increase the overall flexibility of AtcwINV1 exhibiting the most fluctuating regions in the β-propeller domain. The simulated heat treatment also increased the gyration radius and hydrophobic solvent accessible surface area of the plant enzyme, consistent with the initial steps of an unfolding process. The preservation of the conformational rigidity of BfrA at 353 K is linked to the shorter size of the protein loops. Shortening of BfrA loops appears to be a key mechanism for thermostability.

Can We Improve Structured Sequence Processing? Exploring the Direct and Indirect Effects of Computerized Training Using a Mediational Model

PubMed Central

Smith, Gretchen N. L.; Conway, Christopher M.; Bauernschmidt, Althea; Pisoni, David B.

2015-01-01

Recent research suggests that language acquisition may rely on domain-general learning abilities, such as structured sequence processing, which is the ability to extract, encode, and represent structured patterns in a temporal sequence. If structured sequence processing supports language, then it may be possible to improve language function by enhancing this foundational learning ability. The goal of the present study was to use a novel computerized training task as a means to better understand the relationship between structured sequence processing and language function. Participants first were assessed on pre-training tasks to provide baseline behavioral measures of structured sequence processing and language abilities. Participants were then quasi-randomly assigned to either a treatment group involving adaptive structured visuospatial sequence training, a treatment group involving adaptive non-structured visuospatial sequence training, or a control group. Following four days of sequence training, all participants were assessed with the same pre-training measures. Overall comparison of the post-training means revealed no group differences. However, in order to examine the potential relations between sequence training, structured sequence processing, and language ability, we used a mediation analysis that showed two competing effects. In the indirect effect, adaptive sequence training with structural regularities had a positive impact on structured sequence processing performance, which in turn had a positive impact on language processing. This finding not only identifies a potential novel intervention to treat language impairments but also may be the first demonstration that structured sequence processing can be improved and that this, in turn, has an impact on language processing. However, in the direct effect, adaptive sequence training with structural regularities had a direct negative impact on language processing. This unexpected finding suggests that adaptive training with structural regularities might potentially interfere with language processing. Taken together, these findings underscore the importance of pursuing designs that promote a better understanding of the mechanisms underlying training-related changes, so that regimens can be developed that help reduce these types of negative effects while simultaneously maximizing the benefits to outcome measures of interest. PMID:25946222

Can we improve structured sequence processing? Exploring the direct and indirect effects of computerized training using a mediational model.

PubMed

Smith, Gretchen N L; Conway, Christopher M; Bauernschmidt, Althea; Pisoni, David B

2015-01-01

Recent research suggests that language acquisition may rely on domain-general learning abilities, such as structured sequence processing, which is the ability to extract, encode, and represent structured patterns in a temporal sequence. If structured sequence processing supports language, then it may be possible to improve language function by enhancing this foundational learning ability. The goal of the present study was to use a novel computerized training task as a means to better understand the relationship between structured sequence processing and language function. Participants first were assessed on pre-training tasks to provide baseline behavioral measures of structured sequence processing and language abilities. Participants were then quasi-randomly assigned to either a treatment group involving adaptive structured visuospatial sequence training, a treatment group involving adaptive non-structured visuospatial sequence training, or a control group. Following four days of sequence training, all participants were assessed with the same pre-training measures. Overall comparison of the post-training means revealed no group differences. However, in order to examine the potential relations between sequence training, structured sequence processing, and language ability, we used a mediation analysis that showed two competing effects. In the indirect effect, adaptive sequence training with structural regularities had a positive impact on structured sequence processing performance, which in turn had a positive impact on language processing. This finding not only identifies a potential novel intervention to treat language impairments but also may be the first demonstration that structured sequence processing can be improved and that this, in turn, has an impact on language processing. However, in the direct effect, adaptive sequence training with structural regularities had a direct negative impact on language processing. This unexpected finding suggests that adaptive training with structural regularities might potentially interfere with language processing. Taken together, these findings underscore the importance of pursuing designs that promote a better understanding of the mechanisms underlying training-related changes, so that regimens can be developed that help reduce these types of negative effects while simultaneously maximizing the benefits to outcome measures of interest.

Infants with Williams syndrome detect statistical regularities in continuous speech.

PubMed

Cashon, Cara H; Ha, Oh-Ryeong; Graf Estes, Katharine; Saffran, Jenny R; Mervis, Carolyn B

2016-09-01

Williams syndrome (WS) is a rare genetic disorder associated with delays in language and cognitive development. The reasons for the language delay are unknown. Statistical learning is a domain-general mechanism recruited for early language acquisition. In the present study, we investigated whether infants with WS were able to detect the statistical structure in continuous speech. Eighteen 8- to 20-month-olds with WS were familiarized with 2min of a continuous stream of synthesized nonsense words; the statistical structure of the speech was the only cue to word boundaries. They were tested on their ability to discriminate statistically-defined "words" and "part-words" (which crossed word boundaries) in the artificial language. Despite significant cognitive and language delays, infants with WS were able to detect the statistical regularities in the speech stream. These findings suggest that an inability to track the statistical properties of speech is unlikely to be the primary basis for the delays in the onset of language observed in infants with WS. These results provide the first evidence of statistical learning by infants with developmental delays. Copyright © 2016 Elsevier B.V. All rights reserved.

Controlling the stereochemistry and regularity of butanethiol self-assembled monolayers on au(111).

PubMed

Yan, Jiawei; Ouyang, Runhai; Jensen, Palle S; Ascic, Erhad; Tanner, David; Mao, Bingwei; Zhang, Jingdong; Tang, Chunguang; Hush, Noel S; Ulstrup, Jens; Reimers, Jeffrey R

2014-12-10

The rich stereochemistry of the self-assembled monolayers (SAMs) of four butanethiols on Au(111) is described, the SAMs containing up to 12 individual C, S, or Au chiral centers per surface unit cell. This is facilitated by synthesis of enantiomerically pure 2-butanethiol (the smallest unsubstituted chiral alkanethiol), followed by in situ scanning tunneling microscopy (STM) imaging combined with density functional theory molecular dynamics STM image simulations. Even though butanethiol SAMs manifest strong headgroup interactions, steric interactions are shown to dominate SAM structure and chirality. Indeed, steric interactions are shown to dictate the nature of the headgroup itself, whether it takes on the adatom-bound motif RS(•)Au(0)S(•)R or involves direct binding of RS(•) to face-centered-cubic or hexagonal-close-packed sites. Binding as RS(•) produces large, organizationally chiral domains even when R is achiral, while adatom binding leads to rectangular plane groups that suppress long-range expression of chirality. Binding as RS(•) also inhibits the pitting intrinsically associated with adatom binding, desirably producing more regularly structured SAMs.

Derivation of regularized Grad's moment system from kinetic equations: modes, ghosts and non-Markov fluxes

NASA Astrophysics Data System (ADS)

Karlin, Ilya

2018-04-01

Derivation of the dynamic correction to Grad's moment system from kinetic equations (regularized Grad's 13 moment system, or R13) is revisited. The R13 distribution function is found as a superposition of eight modes. Three primary modes, known from the previous derivation (Karlin et al. 1998 Phys. Rev. E 57, 1668-1672. (doi:10.1103/PhysRevE.57.1668)), are extended into the nonlinear parameter domain. Three essentially nonlinear modes are identified, and two ghost modes which do not contribute to the R13 fluxes are revealed. The eight-mode structure of the R13 distribution function implies partition of R13 fluxes into two types of contributions: dissipative fluxes (both linear and nonlinear) and nonlinear streamline convective fluxes. Physical interpretation of the latter non-dissipative and non-local in time effect is discussed. A non-perturbative R13-type solution is demonstrated for a simple Lorentz scattering kinetic model. The results of this study clarify the intrinsic structure of the R13 system. This article is part of the theme issue `Hilbert's sixth problem'.

Structure-based classification and ontology in chemistry

PubMed Central

2012-01-01

Background Recent years have seen an explosion in the availability of data in the chemistry domain. With this information explosion, however, retrieving relevant results from the available information, and organising those results, become even harder problems. Computational processing is essential to filter and organise the available resources so as to better facilitate the work of scientists. Ontologies encode expert domain knowledge in a hierarchically organised machine-processable format. One such ontology for the chemical domain is ChEBI. ChEBI provides a classification of chemicals based on their structural features and a role or activity-based classification. An example of a structure-based class is 'pentacyclic compound' (compounds containing five-ring structures), while an example of a role-based class is 'analgesic', since many different chemicals can act as analgesics without sharing structural features. Structure-based classification in chemistry exploits elegant regularities and symmetries in the underlying chemical domain. As yet, there has been neither a systematic analysis of the types of structural classification in use in chemistry nor a comparison to the capabilities of available technologies. Results We analyze the different categories of structural classes in chemistry, presenting a list of patterns for features found in class definitions. We compare these patterns of class definition to tools which allow for automation of hierarchy construction within cheminformatics and within logic-based ontology technology, going into detail in the latter case with respect to the expressive capabilities of the Web Ontology Language and recent extensions for modelling structured objects. Finally we discuss the relationships and interactions between cheminformatics approaches and logic-based approaches. Conclusion Systems that perform intelligent reasoning tasks on chemistry data require a diverse set of underlying computational utilities including algorithmic, statistical and logic-based tools. For the task of automatic structure-based classification of chemical entities, essential to managing the vast swathes of chemical data being brought online, systems which are capable of hybrid reasoning combining several different approaches are crucial. We provide a thorough review of the available tools and methodologies, and identify areas of open research. PMID:22480202

Incomplete Multisource Transfer Learning.

PubMed

Ding, Zhengming; Shao, Ming; Fu, Yun

2018-02-01

Transfer learning is generally exploited to adapt well-established source knowledge for learning tasks in weakly labeled or unlabeled target domain. Nowadays, it is common to see multiple sources available for knowledge transfer, each of which, however, may not include complete classes information of the target domain. Naively merging multiple sources together would lead to inferior results due to the large divergence among multiple sources. In this paper, we attempt to utilize incomplete multiple sources for effective knowledge transfer to facilitate the learning task in target domain. To this end, we propose an incomplete multisource transfer learning through two directional knowledge transfer, i.e., cross-domain transfer from each source to target, and cross-source transfer. In particular, in cross-domain direction, we deploy latent low-rank transfer learning guided by iterative structure learning to transfer knowledge from each single source to target domain. This practice reinforces to compensate for any missing data in each source by the complete target data. While in cross-source direction, unsupervised manifold regularizer and effective multisource alignment are explored to jointly compensate for missing data from one portion of source to another. In this way, both marginal and conditional distribution discrepancy in two directions would be mitigated. Experimental results on standard cross-domain benchmarks and synthetic data sets demonstrate the effectiveness of our proposed model in knowledge transfer from incomplete multiple sources.

Boundary Regularity for the Porous Medium Equation

NASA Astrophysics Data System (ADS)

Björn, Anders; Björn, Jana; Gianazza, Ugo; Siljander, Juhana

2018-05-01

We study the boundary regularity of solutions to the porous medium equation {u_t = Δ u^m} in the degenerate range {m > 1} . In particular, we show that in cylinders the Dirichlet problem with positive continuous boundary data on the parabolic boundary has a solution which attains the boundary values, provided that the spatial domain satisfies the elliptic Wiener criterion. This condition is known to be optimal, and it is a consequence of our main theorem which establishes a barrier characterization of regular boundary points for general—not necessarily cylindrical—domains in {{R}^{n+1}} . One of our fundamental tools is a new strict comparison principle between sub- and superparabolic functions, which makes it essential for us to study both nonstrict and strict Perron solutions to be able to develop a fruitful boundary regularity theory. Several other comparison principles and pasting lemmas are also obtained. In the process we obtain a rather complete picture of the relation between sub/superparabolic functions and weak sub/supersolutions.

Self-Reported Obstacles to Regular Dental Care among Information Technology Professionals.

PubMed

Reddy, L Swetha; Doshi, Dolar; Reddy, B Srikanth; Kulkarni, Suhas; Reddy, M Padma; Satyanarayana, D; Baldava, Pavan

2016-10-01

Good oral health is important for an individual as well as social well-being. Occupational stress and work exhaustion in Information Technology (IT) professionals may influence the oral health and oral health related quality of life. To assess and compare self-reported obstacles for regular dental care and dental visits among IT professionals based on age, gender, dental insurance and working days per week. A cross-sectional study was conducted among 1,017 IT professionals to assess the self-reported obstacles to regular oral health care in Hyderabad city, Telangana, India. The Dental Rejection of Innovation Scale (DRI-S) was employed in this study. Comparison between means of DRI-S based on variables was done using t-test and ANOVA. The association between variables and DRI-S was determined using Chi-square test. A total of 1017 participants comprising of 574 (56%) males and 443 (44%) females participated in the study. As age increased, a significant increase in mean DRI-S scores was seen for total and individual domains except for the "Situational" domain wherein higher mean score (9.42±2.5; p=0.0006) was observed among 30-39 years age group. Even though females reported higher mean scores for total and individual domains when compared to males, nevertheless significant difference was seen only for total (p=0.03) and "Lack of Knowledge" (p=0.001) domain. Self-reported obstacles to regular dental care was more with increasing age, increased number of working days per week, irregular dental visits and absence of dental insurance facility.

Disordered configurations of the Glauber model in two-dimensional networks

NASA Astrophysics Data System (ADS)

Bačić, Iva; Franović, Igor; Perc, Matjaž

2017-12-01

We analyze the ordering efficiency and the structure of disordered configurations for the zero-temperature Glauber model on Watts-Strogatz networks obtained by rewiring 2D regular square lattices. In the small-world regime, the dynamics fails to reach the ordered state in the thermodynamic limit. Due to the interplay of the perturbed regular topology and the energy neutral stochastic state transitions, the stationary state consists of two intertwined domains, manifested as multiclustered states on the original lattice. Moreover, for intermediate rewiring probabilities, one finds an additional source of disorder due to the low connectivity degree, which gives rise to small isolated droplets of spins. We also examine the ordering process in paradigmatic two-layer networks with heterogeneous rewiring probabilities. Comparing the cases of a multiplex network and the corresponding network with random inter-layer connectivity, we demonstrate that the character of the final state qualitatively depends on the type of inter-layer connections.

Global gradient estimates for divergence-type elliptic problems involving general nonlinear operators

NASA Astrophysics Data System (ADS)

Cho, Yumi

2018-05-01

We study nonlinear elliptic problems with nonstandard growth and ellipticity related to an N-function. We establish global Calderón-Zygmund estimates of the weak solutions in the framework of Orlicz spaces over bounded non-smooth domains. Moreover, we prove a global regularity result for asymptotically regular problems which are getting close to the regular problems considered, when the gradient variable goes to infinity.

Structural and Functional Characterization of the Recombinant Death Domain from Death-Associated Protein Kinase

PubMed Central

Dioletis, Evangelos; Dingley, Andrew J.; Driscoll, Paul C.

2013-01-01

Death-associated protein kinase (DAPk) is a calcium/calmodulin-regulated Ser/Thr-protein kinase that functions at an important point of integration for cell death signaling pathways. DAPk has a structurally unique multi-domain architecture, including a C-terminally positioned death domain (DD) that is a positive regulator of DAPk activity. In this study, recombinant DAPk-DD was observed to aggregate readily and could not be prepared in sufficient yield for structural analysis. However, DAPk-DD could be obtained as a soluble protein in the form of a translational fusion protein with the B1 domain of streptococcal protein G. In contrast to other DDs that adopt the canonical six amphipathic α-helices arranged in a compact fold, the DAPk-DD was found to possess surprisingly low regular secondary structure content and an absence of a stable globular fold, as determined by circular dichroism (CD), NMR spectroscopy and a temperature-dependent fluorescence assay. Furthermore, we measured the in vitro interaction between extracellular-regulated kinase-2 (ERK2) and various recombinant DAPk-DD constructs. Despite the low level of structural order, the recombinant DAPk-DD retained the ability to interact with ERK2 in a 1∶1 ratio with a K d in the low micromolar range. Only the full-length DAPk-DD could bind ERK2, indicating that the apparent ‘D-motif’ located in the putative sixth helix of DAPk-DD is not sufficient for ERK2 recognition. CD analysis revealed that binding of DAPk-DD to ERK2 is not accompanied by a significant change in secondary structure. Taken together our data argue that the DAPk-DD, when expressed in isolation, does not adopt a classical DD fold, yet in this state retains the capacity to interact with at least one of its binding partners. The lack of a stable globular structure for the DAPk-DD may reflect either that its folding would be supported by interactions absent in our experimental set-up, or a limitation in the structural bioinformatics assignment of the three-dimensional structure. PMID:23922916

Structural and functional characterization of the recombinant death domain from death-associated protein kinase.

PubMed

Dioletis, Evangelos; Dingley, Andrew J; Driscoll, Paul C

2013-01-01

Death-associated protein kinase (DAPk) is a calcium/calmodulin-regulated Ser/Thr-protein kinase that functions at an important point of integration for cell death signaling pathways. DAPk has a structurally unique multi-domain architecture, including a C-terminally positioned death domain (DD) that is a positive regulator of DAPk activity. In this study, recombinant DAPk-DD was observed to aggregate readily and could not be prepared in sufficient yield for structural analysis. However, DAPk-DD could be obtained as a soluble protein in the form of a translational fusion protein with the B1 domain of streptococcal protein G. In contrast to other DDs that adopt the canonical six amphipathic α-helices arranged in a compact fold, the DAPk-DD was found to possess surprisingly low regular secondary structure content and an absence of a stable globular fold, as determined by circular dichroism (CD), NMR spectroscopy and a temperature-dependent fluorescence assay. Furthermore, we measured the in vitro interaction between extracellular-regulated kinase-2 (ERK2) and various recombinant DAPk-DD constructs. Despite the low level of structural order, the recombinant DAPk-DD retained the ability to interact with ERK2 in a 1∶1 ratio with a K d in the low micromolar range. Only the full-length DAPk-DD could bind ERK2, indicating that the apparent 'D-motif' located in the putative sixth helix of DAPk-DD is not sufficient for ERK2 recognition. CD analysis revealed that binding of DAPk-DD to ERK2 is not accompanied by a significant change in secondary structure. Taken together our data argue that the DAPk-DD, when expressed in isolation, does not adopt a classical DD fold, yet in this state retains the capacity to interact with at least one of its binding partners. The lack of a stable globular structure for the DAPk-DD may reflect either that its folding would be supported by interactions absent in our experimental set-up, or a limitation in the structural bioinformatics assignment of the three-dimensional structure.

Assignment of protein sequences to existing domain and family classification systems: Pfam and the PDB

PubMed Central

Dunbrack, Roland L.

2012-01-01

Motivation: Automating the assignment of existing domain and protein family classifications to new sets of sequences is an important task. Current methods often miss assignments because remote relationships fail to achieve statistical significance. Some assignments are not as long as the actual domain definitions because local alignment methods often cut alignments short. Long insertions in query sequences often erroneously result in two copies of the domain assigned to the query. Divergent repeat sequences in proteins are often missed. Results: We have developed a multilevel procedure to produce nearly complete assignments of protein families of an existing classification system to a large set of sequences. We apply this to the task of assigning Pfam domains to sequences and structures in the Protein Data Bank (PDB). We found that HHsearch alignments frequently scored more remotely related Pfams in Pfam clans higher than closely related Pfams, thus, leading to erroneous assignment at the Pfam family level. A greedy algorithm allowing for partial overlaps was, thus, applied first to sequence/HMM alignments, then HMM–HMM alignments and then structure alignments, taking care to join partial alignments split by large insertions into single-domain assignments. Additional assignment of repeat Pfams with weaker E-values was allowed after stronger assignments of the repeat HMM. Our database of assignments, presented in a database called PDBfam, contains Pfams for 99.4% of chains >50 residues. Availability: The Pfam assignment data in PDBfam are available at http://dunbrack2.fccc.edu/ProtCid/PDBfam, which can be searched by PDB codes and Pfam identifiers. They will be updated regularly. Contact: Roland.Dunbracks@fccc.edu PMID:22942020

A blind deconvolution method based on L1/L2 regularization prior in the gradient space

NASA Astrophysics Data System (ADS)

Cai, Ying; Shi, Yu; Hua, Xia

2018-02-01

In the process of image restoration, the result of image restoration is very different from the real image because of the existence of noise, in order to solve the ill posed problem in image restoration, a blind deconvolution method based on L1/L2 regularization prior to gradient domain is proposed. The method presented in this paper first adds a function to the prior knowledge, which is the ratio of the L1 norm to the L2 norm, and takes the function as the penalty term in the high frequency domain of the image. Then, the function is iteratively updated, and the iterative shrinkage threshold algorithm is applied to solve the high frequency image. In this paper, it is considered that the information in the gradient domain is better for the estimation of blur kernel, so the blur kernel is estimated in the gradient domain. This problem can be quickly implemented in the frequency domain by fast Fast Fourier Transform. In addition, in order to improve the effectiveness of the algorithm, we have added a multi-scale iterative optimization method. This paper proposes the blind deconvolution method based on L1/L2 regularization priors in the gradient space can obtain the unique and stable solution in the process of image restoration, which not only keeps the edges and details of the image, but also ensures the accuracy of the results.

Regularity of p(ṡ)-superharmonic functions, the Kellogg property and semiregular boundary points

NASA Astrophysics Data System (ADS)

Adamowicz, Tomasz; Björn, Anders; Björn, Jana

2014-11-01

We study various boundary and inner regularity questions for $p(\\cdot)$-(super)harmonic functions in Euclidean domains. In particular, we prove the Kellogg property and introduce a classification of boundary points for $p(\\cdot)$-harmonic functions into three disjoint classes: regular, semiregular and strongly irregular points. Regular and especially semiregular points are characterized in many ways. The discussion is illustrated by examples. Along the way, we present a removability result for bounded $p(\\cdot)$-harmonic functions and give some new characterizations of $W^{1, p(\\cdot)}_0$ spaces. We also show that $p(\\cdot)$-superharmonic functions are lower semicontinuously regularized, and characterize them in terms of lower semicontinuously regularized supersolutions.

A general natural-language text processor for clinical radiology.

PubMed Central

Friedman, C; Alderson, P O; Austin, J H; Cimino, J J; Johnson, S B

1994-01-01

OBJECTIVE: Development of a general natural-language processor that identifies clinical information in narrative reports and maps that information into a structured representation containing clinical terms. DESIGN: The natural-language processor provides three phases of processing, all of which are driven by different knowledge sources. The first phase performs the parsing. It identifies the structure of the text through use of a grammar that defines semantic patterns and a target form. The second phase, regularization, standardizes the terms in the initial target structure via a compositional mapping of multi-word phrases. The third phase, encoding, maps the terms to a controlled vocabulary. Radiology is the test domain for the processor and the target structure is a formal model for representing clinical information in that domain. MEASUREMENTS: The impression sections of 230 radiology reports were encoded by the processor. Results of an automated query of the resultant database for the occurrences of four diseases were compared with the analysis of a panel of three physicians to determine recall and precision. RESULTS: Without training specific to the four diseases, recall and precision of the system (combined effect of the processor and query generator) were 70% and 87%. Training of the query component increased recall to 85% without changing precision. PMID:7719797

Constraint Reasoning Over Strings

NASA Technical Reports Server (NTRS)

Koga, Dennis (Technical Monitor); Golden, Keith; Pang, Wanlin

2003-01-01

This paper discusses an approach to representing and reasoning about constraints over strings. We discuss how many string domains can often be concisely represented using regular languages, and how constraints over strings, and domain operations on sets of strings, can be carried out using this representation.

Sparse regularization for force identification using dictionaries

NASA Astrophysics Data System (ADS)

Qiao, Baijie; Zhang, Xingwu; Wang, Chenxi; Zhang, Hang; Chen, Xuefeng

2016-04-01

The classical function expansion method based on minimizing l2-norm of the response residual employs various basis functions to represent the unknown force. Its difficulty lies in determining the optimum number of basis functions. Considering the sparsity of force in the time domain or in other basis space, we develop a general sparse regularization method based on minimizing l1-norm of the coefficient vector of basis functions. The number of basis functions is adaptively determined by minimizing the number of nonzero components in the coefficient vector during the sparse regularization process. First, according to the profile of the unknown force, the dictionary composed of basis functions is determined. Second, a sparsity convex optimization model for force identification is constructed. Third, given the transfer function and the operational response, Sparse reconstruction by separable approximation (SpaRSA) is developed to solve the sparse regularization problem of force identification. Finally, experiments including identification of impact and harmonic forces are conducted on a cantilever thin plate structure to illustrate the effectiveness and applicability of SpaRSA. Besides the Dirac dictionary, other three sparse dictionaries including Db6 wavelets, Sym4 wavelets and cubic B-spline functions can also accurately identify both the single and double impact forces from highly noisy responses in a sparse representation frame. The discrete cosine functions can also successfully reconstruct the harmonic forces including the sinusoidal, square and triangular forces. Conversely, the traditional Tikhonov regularization method with the L-curve criterion fails to identify both the impact and harmonic forces in these cases.

Multimodal manifold-regularized transfer learning for MCI conversion prediction.

PubMed

Cheng, Bo; Liu, Mingxia; Suk, Heung-Il; Shen, Dinggang; Zhang, Daoqiang

2015-12-01

As the early stage of Alzheimer's disease (AD), mild cognitive impairment (MCI) has high chance to convert to AD. Effective prediction of such conversion from MCI to AD is of great importance for early diagnosis of AD and also for evaluating AD risk pre-symptomatically. Unlike most previous methods that used only the samples from a target domain to train a classifier, in this paper, we propose a novel multimodal manifold-regularized transfer learning (M2TL) method that jointly utilizes samples from another domain (e.g., AD vs. normal controls (NC)) as well as unlabeled samples to boost the performance of the MCI conversion prediction. Specifically, the proposed M2TL method includes two key components. The first one is a kernel-based maximum mean discrepancy criterion, which helps eliminate the potential negative effect induced by the distributional difference between the auxiliary domain (i.e., AD and NC) and the target domain (i.e., MCI converters (MCI-C) and MCI non-converters (MCI-NC)). The second one is a semi-supervised multimodal manifold-regularized least squares classification method, where the target-domain samples, the auxiliary-domain samples, and the unlabeled samples can be jointly used for training our classifier. Furthermore, with the integration of a group sparsity constraint into our objective function, the proposed M2TL has a capability of selecting the informative samples to build a robust classifier. Experimental results on the Alzheimer's Disease Neuroimaging Initiative (ADNI) database validate the effectiveness of the proposed method by significantly improving the classification accuracy of 80.1 % for MCI conversion prediction, and also outperforming the state-of-the-art methods.

Improved performance of HgCdTe infrared detector focal plane arrays by modulating light field based on photonic crystal structure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liang, Jian; Hu, Weida, E-mail: wdhu@mail.sitp.ac.cn; Ye, Zhenhua

2014-05-14

An HgCdTe long-wavelength infrared focal plane array photodetector is proposed by modulating light distributions based on the photonic crystal. It is shown that a promising prospect of improving performance is better light harvest and dark current limitation. To optimize the photon field distributions of the HgCdTe-based photonic crystal structure, a numerical method is built by combining the finite-element modeling and the finite-difference time-domain simulation. The optical and electrical characteristics of designed HgCdTe mid-wavelength and long-wavelength photon-trapping infrared detector focal plane arrays are obtained numerically. The results indicate that the photon crystal structure, which is entirely compatible with the large infraredmore » focal plane arrays, can significantly reduce the dark current without degrading the quantum efficiency compared to the regular mesa or planar structure.« less

Sub-domain decomposition methods and computational controls for multibody dynamical systems. [of spacecraft structures

NASA Technical Reports Server (NTRS)

Menon, R. G.; Kurdila, A. J.

1992-01-01

This paper presents a concurrent methodology to simulate the dynamics of flexible multibody systems with a large number of degrees of freedom. A general class of open-loop structures is treated and a redundant coordinate formulation is adopted. A range space method is used in which the constraint forces are calculated using a preconditioned conjugate gradient method. By using a preconditioner motivated by the regular ordering of the directed graph of the structures, it is shown that the method is order N in the total number of coordinates of the system. The overall formulation has the advantage that it permits fine parallelization and does not rely on system topology to induce concurrency. It can be efficiently implemented on the present generation of parallel computers with a large number of processors. Validation of the method is presented via numerical simulations of space structures incorporating large number of flexible degrees of freedom.

Structural and Functional Characterization of an Archaeal Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated Complex for Antiviral Defense (CASCADE)*

PubMed Central

Lintner, Nathanael G.; Kerou, Melina; Brumfield, Susan K.; Graham, Shirley; Liu, Huanting; Naismith, James H.; Sdano, Matthew; Peng, Nan; She, Qunxin; Copié, Valérie; Young, Mark J.; White, Malcolm F.; Lawrence, C. Martin

2011-01-01

In response to viral infection, many prokaryotes incorporate fragments of virus-derived DNA into loci called clustered regularly interspaced short palindromic repeats (CRISPRs). The loci are then transcribed, and the processed CRISPR transcripts are used to target invading viral DNA and RNA. The Escherichia coli “CRISPR-associated complex for antiviral defense” (CASCADE) is central in targeting invading DNA. Here we report the structural and functional characterization of an archaeal CASCADE (aCASCADE) from Sulfolobus solfataricus. Tagged Csa2 (Cas7) expressed in S. solfataricus co-purifies with Cas5a-, Cas6-, Csa5-, and Cas6-processed CRISPR-RNA (crRNA). Csa2, the dominant protein in aCASCADE, forms a stable complex with Cas5a. Transmission electron microscopy reveals a helical complex of variable length, perhaps due to substoichiometric amounts of other CASCADE components. A recombinant Csa2-Cas5a complex is sufficient to bind crRNA and complementary ssDNA. The structure of Csa2 reveals a crescent-shaped structure unexpectedly composed of a modified RNA-recognition motif and two additional domains present as insertions in the RNA-recognition motif. Conserved residues indicate potential crRNA- and target DNA-binding sites, and the H160A variant shows significantly reduced affinity for crRNA. We propose a general subunit architecture for CASCADE in other bacteria and Archaea. PMID:21507944

Structural and functional characterization of an archaeal clustered regularly interspaced short palindromic repeat (CRISPR)-associated complex for antiviral defense (CASCADE).

PubMed

Lintner, Nathanael G; Kerou, Melina; Brumfield, Susan K; Graham, Shirley; Liu, Huanting; Naismith, James H; Sdano, Matthew; Peng, Nan; She, Qunxin; Copié, Valérie; Young, Mark J; White, Malcolm F; Lawrence, C Martin

2011-06-17

In response to viral infection, many prokaryotes incorporate fragments of virus-derived DNA into loci called clustered regularly interspaced short palindromic repeats (CRISPRs). The loci are then transcribed, and the processed CRISPR transcripts are used to target invading viral DNA and RNA. The Escherichia coli "CRISPR-associated complex for antiviral defense" (CASCADE) is central in targeting invading DNA. Here we report the structural and functional characterization of an archaeal CASCADE (aCASCADE) from Sulfolobus solfataricus. Tagged Csa2 (Cas7) expressed in S. solfataricus co-purifies with Cas5a-, Cas6-, Csa5-, and Cas6-processed CRISPR-RNA (crRNA). Csa2, the dominant protein in aCASCADE, forms a stable complex with Cas5a. Transmission electron microscopy reveals a helical complex of variable length, perhaps due to substoichiometric amounts of other CASCADE components. A recombinant Csa2-Cas5a complex is sufficient to bind crRNA and complementary ssDNA. The structure of Csa2 reveals a crescent-shaped structure unexpectedly composed of a modified RNA-recognition motif and two additional domains present as insertions in the RNA-recognition motif. Conserved residues indicate potential crRNA- and target DNA-binding sites, and the H160A variant shows significantly reduced affinity for crRNA. We propose a general subunit architecture for CASCADE in other bacteria and Archaea.

Detection of superlattice domain formation in ternary lipid mixtures using fluorescence spectroscopy

NASA Astrophysics Data System (ADS)

Mutlu, Burcin; Lopez, Stephanie; Vaughn, Mark; Huang, Juyang; Cheng, K.

2011-10-01

Multicomponent lipid bilayers represent an important model system for studying the structures and functions of cell membranes. At present, the lateral organization of lipid components, particularly the formation of regular distribution, in lipid membranes containing charged lipid, e.g., phosphatidylserine, is not clear. Using a ternary phosphatidylcholine/phosphatidylserine/cholesterol lipid bilayer system, the presence of ordered domain formation was examined by measuring the fluorescence anisotropy of the embedded fluorescent probe, 22-(N-(7-nitrobenz-2-oxa-1,3-diazol- 4-yl)amino)-23,24-bisnor-5-cholen-3β- ol (NBD-CHOL), with structure similar to that of a cholesterol, as a function of phospatidylserine composition. The plot of the anisotropy vs. phosphatidylserine revealed abrupt changes at certain critical compositions of phosphatidylserine. Some of these critical compositions agree favorably with those predicted by the headgroup superlattice model suggesting that the charged phosphatidylserine lipid molecules adopt a superlattice-like distribution in the lipid bilayer at some predicted compositions. The ordered distribution of charged lipids may play an important role in the regulation of the composition of the biological membranes.

Exponential Family Functional data analysis via a low-rank model.

PubMed

Li, Gen; Huang, Jianhua Z; Shen, Haipeng

2018-05-08

In many applications, non-Gaussian data such as binary or count are observed over a continuous domain and there exists a smooth underlying structure for describing such data. We develop a new functional data method to deal with this kind of data when the data are regularly spaced on the continuous domain. Our method, referred to as Exponential Family Functional Principal Component Analysis (EFPCA), assumes the data are generated from an exponential family distribution, and the matrix of the canonical parameters has a low-rank structure. The proposed method flexibly accommodates not only the standard one-way functional data, but also two-way (or bivariate) functional data. In addition, we introduce a new cross validation method for estimating the latent rank of a generalized data matrix. We demonstrate the efficacy of the proposed methods using a comprehensive simulation study. The proposed method is also applied to a real application of the UK mortality study, where data are binomially distributed and two-way functional across age groups and calendar years. The results offer novel insights into the underlying mortality pattern. © 2018, The International Biometric Society.

Regularity estimates up to the boundary for elliptic systems of difference equations

NASA Technical Reports Server (NTRS)

Strikwerda, J. C.; Wade, B. A.; Bube, K. P.

1986-01-01

Regularity estimates up to the boundary for solutions of elliptic systems of finite difference equations were proved. The regularity estimates, obtained for boundary fitted coordinate systems on domains with smooth boundary, involve discrete Sobolev norms and are proved using pseudo-difference operators to treat systems with variable coefficients. The elliptic systems of difference equations and the boundary conditions which are considered are very general in form. The regularity of a regular elliptic system of difference equations was proved equivalent to the nonexistence of eigensolutions. The regularity estimates obtained are analogous to those in the theory of elliptic systems of partial differential equations, and to the results of Gustafsson, Kreiss, and Sundstrom (1972) and others for hyperbolic difference equations.

SERS detection of R6G based on a novel graphene oxide/silver nanoparticles/silicon pyramid arrays structure.

PubMed

Zhang, C; Jiang, S Z; Huo, Y Y; Liu, A H; Xu, S C; Liu, X Y; Sun, Z C; Xu, Y Y; Li, Z; Man, B Y

2015-09-21

We present a novel surface-enhanced Raman scattering (SERS) substrate based on graphene oxide/silver nanoparticles/silicon pyramid arrays structure (GO/Ag/PSi). The SERS behaviors are discussed and compared by the detection of R6G. Based on the contrast experiments with PSi, GO/PSi, Ag/PSi and GO/AgA/PSi as SERS substrate, the perfect bio-compatibility, good homogeneity and chemical stability were confirmed. We also calculated the electric field distributions using Finite-difference time-domain (FDTD) analysis to further understand the GO/Ag/PSi structure as a perfect SERS platform. These experimental and theoretical results imply that the GO/Ag/PSi with regular pyramids array is expected to be an effective substrate for label-free sensitive SERS detections in areas of medicine, food safety and biotechnology.

Firewall or smooth horizon?

NASA Astrophysics Data System (ADS)

Ori, Amos

2016-01-01

Almheiri, Marolf, Polchinski, and Sully pointed out that for a sufficiently old black hole (BH), the set of assumptions known as the complementarity postulates appears to be inconsistent with the assumption of local regularity at the horizon. They concluded that the horizon of an old BH is likely to be the locus of local irregularity, a "firewall". Here I point out that if one adopts a different assumption, namely that semiclassical physics holds throughout its anticipated domain of validity, then the inconsistency is avoided, and the horizon retains its regularity. In this alternative view-point, the vast portion of the original BH information remains trapped inside the BH throughout the semiclassical domain of evaporation, and possibly leaks out later on. This appears to be an inevitable outcome of semiclassical gravity (if assumed to apply throughout its anticipated domain of validity).

Controlled wavelet domain sparsity for x-ray tomography

NASA Astrophysics Data System (ADS)

Purisha, Zenith; Rimpeläinen, Juho; Bubba, Tatiana; Siltanen, Samuli

2018-01-01

Tomographic reconstruction is an ill-posed inverse problem that calls for regularization. One possibility is to require sparsity of the unknown in an orthonormal wavelet basis. This, in turn, can be achieved by variational regularization, where the penalty term is the sum of the absolute values of the wavelet coefficients. The primal-dual fixed point algorithm showed that the minimizer of the variational regularization functional can be computed iteratively using a soft-thresholding operation. Choosing the soft-thresholding parameter \

Adult Regularization of Inconsistent Input Depends on Pragmatic Factors

ERIC Educational Resources Information Center

Perfors, Amy

2016-01-01

In a variety of domains, adults who are given input that is only partially consistent do not discard the inconsistent portion (regularize) but rather maintain the probability of consistent and inconsistent portions in their behavior (probability match). This research investigates the possibility that adults probability match, at least in part,…

On the domain of the Nelson Hamiltonian

NASA Astrophysics Data System (ADS)

Griesemer, M.; Wünsch, A.

2018-04-01

The Nelson Hamiltonian is unitarily equivalent to a Hamiltonian defined through a closed, semibounded quadratic form, the unitary transformation being explicitly known and due to Gross. In this paper, we study the mapping properties of the Gross-transform in order to characterize the regularity properties of vectors in the form domain of the Nelson Hamiltonian. Since the operator domain is a subset of the form domain, our results apply to vectors in the domain of the Hamiltonian as well. This work is a continuation of our previous work on the Fröhlich Hamiltonian.

Indirect boundary force measurements in beam-like structures using a derivative estimator

NASA Astrophysics Data System (ADS)

Chesne, Simon

2014-12-01

This paper proposes a new method for the identification of boundary forces (shear force or bending moment) in a beam, based on displacement measurements. The problem is considered in terms of the determination of the boundary spatial derivatives of transverse displacements. By assuming the displacement fields to be approximated by Taylor expansions in a domain close to the boundaries, the spatial derivatives can be estimated using specific point-wise derivative estimators. This approach makes it possible to extract the derivatives using a weighted spatial integration of the displacement field. Following the theoretical description, numerical simulations made with exact and noisy data are used to determine the relationship between the size of the integration domain and the wavelength of the vibrations. The simulations also highlight the self-regularization of the technique. Experimental measurements demonstrate the feasibility and accuracy of the proposed method.

Ferroelectricity in CaTiO3 Single Crystal Surfaces and Thin Films and Probed by Nonlinear Optics and Raman Spectroscopy

NASA Astrophysics Data System (ADS)

Vlahos, Eftihia; Lummen, Tom; Haislmaier, Ryan; Denev, Sava; Brooks, Charles; Biegalski, Michael; Schlom, Darrell; Eklund, Carl-Johan; Rabe, Karin; Fennie, Craig; Gopalan, Venkatraman

2011-03-01

Bulk CaTi O3 has a centrosymmetric point group and is not polar or ferroelectric. However, we present surprising results that show highly regular polar domains in single crystals of CaTi O3 . Confocal Second Harmonic Generation (SHG) and Raman imaging studies were carried out on perovskite CaTi O3 crystal surfaces. They reveal large, crystallographic polar domains at room temperature, with in-plane polarization components delineated by twin walls. SHG analysis indicates that the highest symmetry of the polar surface is m (space group P c) with polarization in the m plane. In addition, we present results of the polar domain structure imaged before and after the application of an external electric field. Finally, we present the SHG studies of CaTi O3 thin films grown using reactive Molecular Beam Epitaxy (MBE); these films are predicted by theory to be ferroelectric and are shown experimentally, both with SHG and in-plane dielectric measurements, to be ferroelectric for temperatures less than ~ 150 K with group symmetry mm2.

Preserved Statistical Learning of Tonal and Linguistic Material in Congenital Amusia

PubMed Central

Omigie, Diana; Stewart, Lauren

2011-01-01

Congenital amusia is a lifelong disorder whereby individuals have pervasive difficulties in perceiving and producing music. In contrast, typical individuals display a sophisticated understanding of musical structure, even in the absence of musical training. Previous research has shown that they acquire this knowledge implicitly, through exposure to music's statistical regularities. The present study tested the hypothesis that congenital amusia may result from a failure to internalize statistical regularities – specifically, lower-order transitional probabilities. To explore the specificity of any potential deficits to the musical domain, learning was examined with both tonal and linguistic material. Participants were exposed to structured tonal and linguistic sequences and, in a subsequent test phase, were required to identify items which had been heard in the exposure phase, as distinct from foils comprising elements that had been present during exposure, but presented in a different temporal order. Amusic and control individuals showed comparable learning, for both tonal and linguistic material, even when the tonal stream included pitch intervals around one semitone. However analysis of binary confidence ratings revealed that amusic individuals have less confidence in their abilities and that their performance in learning tasks may not be contingent on explicit knowledge formation or level of awareness to the degree shown in typical individuals. The current findings suggest that the difficulties amusic individuals have with real-world music cannot be accounted for by an inability to internalize lower-order statistical regularities but may arise from other factors. PMID:21779263

Force-activatable coating enables high-resolution cellular force imaging directly on regular cell culture surfaces.

PubMed

Sarkar, Anwesha; Zhao, Yuanchang; Wang, Yongliang; Wang, Xuefeng

2018-06-25

Integrin-transmitted cellular forces are crucial mechanical signals regulating a vast range of cell functions. Although various methods have been developed to visualize and quantify cellular forces at the cell-matrix interface, a method with high performance and low technical barrier is still in demand. Here we developed a force-activatable coating (FAC), which can be simply coated on regular cell culture apparatus' surfaces by physical adsorption, and turn these surfaces to force reporting platforms that enable cellular force mapping directly by fluorescence imaging. The FAC molecule consists of an adhesive domain for surface coating and a force-reporting domain which can be activated to fluoresce by integrin molecular tension. The tension threshold required for FAC activation is tunable in 10-60 piconewton (pN), allowing the selective imaging of cellular force contributed by integrin tension at different force levels. We tested the performance of two FACs with tension thresholds of 12 and 54 pN (nominal values), respectively, on both glass and polystyrene surfaces. Cellular forces were successfully mapped by fluorescence imaging on all the surfaces. FAC-coated surfaces also enable co-imaging of cellular forces and cell structures in both live cells and immunostained cells, therefore opening a new avenue for the study of the interplay of force and structure. We demonstrated the co-imaging of integrin tension and talin clustering in live cells, and concluded that talin clustering always occurs before the generation of integrin tension above 54 pN, reinforcing the notion that talin is an important adaptor protein for integrin tension transmission. Overall, FAC provides a highly convenient approach that is accessible to general biological laboratories for the study of cellular forces with high sensitivity and resolution, thus holding the potential to greatly boost the research of cell mechanobiology.

The Numerical Simulation of Time Dependent Flow Structures Over a Natural Gravel Surface.

NASA Astrophysics Data System (ADS)

Hardy, R. J.; Lane, S. N.; Ferguson, R. I.; Parsons, D. R.

2004-05-01

Research undertaken over the last few years has demonstrated the importance of the structure of gravel river beds for understanding the interaction between fluid flow and sediment transport processes. This includes the observation of periodic high-speed fluid wedges interconnected by low-speed flow regions. Our understanding of these flows has been enhanced significantly through a series of laboratory experiments and supported by field observations. However, the potential of high resolution three dimensional Computational Fluid Dynamics (CFD) modeling has yet to be fully developed. This is largely the result of the problems of designing numerically stable meshes for use with complex bed topographies and that Reynolds averaged turbulence schemes are applied. This paper develops two novel techniques for dealing with these issues. The first is the development and validation of a method for representing the complex surface topography of gravel-bed rivers in high resolution three-dimensional computational fluid dynamic models. This is based upon a porosity treatment with a regular structured grid and the application of a porosity modification to the mass conservation equation in which: fully blocked cells are assigned a porosity of zero; fully unblocked cells are assigned a porosity of one; and partly blocked cells are assigned a porosity of between 0 and 1, according to the percentage of the cell volume that is blocked. The second is the application of Large Eddy Simulation (LES) which enables time dependent flow structures to be numerically predicted over the complex bed topographies. The regular structured grid with the embedded porosity algorithm maintains a constant grid cell size throughout the domain implying a constant filter scale for the LES simulation. This enables the prediction of coherent structures, repetitive quasi-cyclic large-scale turbulent motions, over the gravel surface which are of a similar magnitude and frequency to those previously observed in both flume and field studies. These structures are formed by topographic forcing within the domain and are scaled with the flow depth. Finally, this provides the numerical framework for the prediction of sediment transport within a time dependent framework. The turbulent motions make a significant contribution to the turbulent shear stress and the pressure fluctuations which significantly affect the forces acting on the bed and potentially control sediment motion.

Dynamical analysis of an orbiting three-rigid-body system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pagnozzi, Daniele, E-mail: daniele.pagnozzi@strath.ac.uk, E-mail: james.biggs@strath.ac.uk; Biggs, James D., E-mail: daniele.pagnozzi@strath.ac.uk, E-mail: james.biggs@strath.ac.uk

2014-12-10

The development of multi-joint-spacecraft mission concepts calls for a deeper understanding of their nonlinear dynamics to inform and enhance system design. This paper presents a study of a three-finite-shape rigid-body system under the action of an ideal central gravitational field. The aim of this paper is to gain an insight into the natural dynamics of this system. The Hamiltonian dynamics is derived and used to identify relative attitude equilibria of the system with respect to the orbital reference frame. Then a numerical investigation of the behaviour far from the equilibria is provided using tools from modern dynamical systems theory suchmore » as energy methods, phase portraits and Poincarè maps. Results reveal a complex structure of the dynamics as well as the existence of connections between some of the equilibria. Stable equilibrium configurations appear to be surrounded by very narrow regions of regular and quasi-regular motions. Trajectories evolve on chaotic motions in the rest of the domain.« less

A Novel Mechanism of Latency in Matrix Metalloproteinases*

PubMed Central

López-Pelegrín, Mar; Ksiazek, Miroslaw; Karim, Abdulkarim Y.; Guevara, Tibisay; Arolas, Joan L.; Potempa, Jan; Gomis-Rüth, F. Xavier

2015-01-01

The matrix metalloproteinases (MMPs) are a family of secreted soluble or membrane-anchored multimodular peptidases regularly found in several paralogous copies in animals and plants, where they have multiple functions. The minimal consensus domain architecture comprises a signal peptide, a 60–90-residue globular prodomain with a conserved sequence motif including a cysteine engaged in “cysteine-switch” or “Velcro” mediated latency, and a catalytic domain. Karilysin, from the human periodontopathogen Tannerella forsythia, is the only bacterial MMP to have been characterized biochemically to date. It shares with eukaryotic forms the catalytic domain but none of the flanking domains. Instead of the consensus MMP prodomain, it features a 14-residue propeptide, the shortest reported for a metallopeptidase, which lacks cysteines. Here we determined the structure of a prokarilysin fragment encompassing the propeptide and the catalytic domain, and found that the former runs across the cleft in the opposite direction to a bound substrate and inhibits the latter through an “aspartate-switch” mechanism. This finding is reminiscent of latency maintenance in the otherwise unrelated astacin and fragilysin metallopeptidase families. In addition, in vivo and biochemical assays showed that the propeptide contributes to protein folding and stability. Our analysis of prokarilysin reveals a novel mechanism of latency and activation in MMPs. Finally, our findings support the view that the karilysin catalytic domain was co-opted by competent bacteria through horizontal gene transfer from a eukaryotic source, and later evolved in a specific bacterial environment. PMID:25555916

Compaction and binding properties of the intrinsically disordered C-terminal domain of Henipavirus nucleoprotein as unveiled by deletion studies.

PubMed

Blocquel, David; Habchi, Johnny; Gruet, Antoine; Blangy, Stéphanie; Longhi, Sonia

2012-01-01

Henipaviruses are recently emerged severe human pathogens within the Paramyxoviridae family. Their genome is encapsidated by the nucleoprotein (N) within a helical nucleocapsid that recruits the polymerase complex via the phosphoprotein (P). We have previously shown that in Henipaviruses the N protein possesses an intrinsically disordered C-terminal domain, N(TAIL), which undergoes α-helical induced folding in the presence of the C-terminal domain (P(XD)) of the P protein. Using computational approaches, we previously identified within N(TAIL) four putative molecular recognition elements (MoREs) with different structural propensities, and proposed a structural model for the N(TAIL)-P(XD) complex where the MoRE encompassing residues 473-493 adopt an α-helical conformation at the P(XD) surface. In this work, for each N(TAIL) protein, we designed four deletion constructs bearing different combinations of the predicted MoREs. Following purification of the N(TAIL) truncated proteins from the soluble fraction of E. coli, we characterized them in terms of their conformational, spectroscopic and binding properties. These studies provided direct experimental evidence for the structural state of the four predicted MoREs, and showed that two of them have clear α-helical propensities, with the one spanning residues 473-493 being strictly required for binding to P(XD). We also showed that Henipavirus N(TAIL) and P(XD) form heterologous complexes, indicating that the P(XD) binding regions are functionally interchangeable between the two viruses. By combining spectroscopic and conformational analyses, we showed that the content in regular secondary structure is not a major determinant of protein compaction.

On the Regularities of the Polar Profiles of Proteins Related to Ebola Virus Infection and their Functional Domains.

PubMed

Polanco, Carlos; Samaniego Mendoza, José Lino; Buhse, Thomas; Uversky, Vladimir N; Bañuelos Chao, Ingrid Paola; Bañuelos Cedano, Marcela Angola; Tavera, Fernando Michel; Tavera, Daniel Michel; Falconi, Manuel; Ponce de León, Abelardo Vela

2018-03-06

The number of fatalities and economic losses caused by the Ebola virus infection across the planet culminated in the havoc that occurred between August and November 2014. However, little is known about the molecular protein profile of this devastating virus. This work represents a thorough bioinformatics analysis of the regularities of charge distribution (polar profiles) in two groups of proteins and their functional domains associated with Ebola virus disease: Ebola virus proteins and Human proteins interacting with Ebola virus. Our analysis reveals that a fragment exists in each of these proteins-one named the "functional domain"-with the polar profile similar to the polar profile of the protein that contains it. Each protein is formed by a group of short sub-sequences, where each fragment has a different and distinctive polar profile and where the polar profile between adjacent short sub-sequences changes orderly and gradually to coincide with the polar profile of the whole protein. When using the charge distribution as a metric, it was observed that it effectively discriminates the proteins from their functional domains. As a counterexample, the same test was applied to a set of synthetic proteins built for that purpose, revealing that any of the regularities reported here for the Ebola virus proteins and human proteins interacting with Ebola virus were not present in the synthetic proteins. Our results indicate that the polar profile of each protein studied and its corresponding functional domain are similar. Thus, when building each protein from its functional domai-adding one amino acid at a time and plotting each time its polar profile-it was observed that the resulting graphs can be divided into groups with similar polar profiles.

Centrality based Document Ranking

DTIC Science & Technology

2014-11-01

clinical domain and very uncommon elsewhere. A regular IR system may fail to rank documents from such a domain, dealing with symptoms, diagnosis and...description). We prepared a hand-crafted list of synonyms for each of the query types, viz. diagnosis , test and treatment. This list was used to expand the...Miller. Semantic search. In INTERNATIONAL WORLD WIDE WEB CONFERENCE, pages 700–709. ACM, 2003. 8. A. Hanbury and M. Lupu . Toward a Model of Domain

Integrating Moral and Social Development within Middle School Social Studies: A Social Cognitive Domain Approach

ERIC Educational Resources Information Center

Nucci, Larry; Creane, Michael W.; Powers, Deborah W.

2015-01-01

Eleven teachers and 254 urban middle-school students comprised the sample of this study examining the social and moral development outcomes of the integration of social cognitive domain theory within regular classroom instruction. Participating teachers were trained to construct and implement history lessons that stimulated students' moral…

Innovation from a Computational Social Science Perspective: Analyses and Models

ERIC Educational Resources Information Center

Casstevens, Randy M.

2013-01-01

Innovation processes are critical for preserving and improving our standard of living. While innovation has been studied by many disciplines, the focus has been on qualitative measures that are specific to a single technological domain. I adopt a quantitative approach to investigate underlying regularities that generalize across multiple domains.…

Integration of QUARK and I-TASSER for ab initio protein structure prediction in CASP11

PubMed Central

Zhang, Wenxuan; Yang, Jianyi; He, Baoji; Walker, Sara Elizabeth; Zhang, Hongjiu; Govindarajoo, Brandon; Virtanen, Jouko; Xue, Zhidong; Shen, Hong-Bin; Zhang, Yang

2015-01-01

We tested two pipelines developed for template-free protein structure prediction in the CASP11 experiment. First, the QUARK pipeline constructs structure models by reassembling fragments of continuously distributed lengths excised from unrelated proteins. Five free-modeling (FM) targets have the model successfully constructed by QUARK with a TM-score above 0.4, including the first model of T0837-D1, which has a TM-score=0.736 and RMSD=2.9 Å to the native. Detailed analysis showed that the success is partly attributed to the high-resolution contact map prediction derived from fragment-based distance-profiles, which are mainly located between regular secondary structure elements and loops/turns and help guide the orientation of secondary structure assembly. In the Zhang-Server pipeline, weakly scoring threading templates are re-ordered by the structural similarity to the ab initio folding models, which are then reassembled by I-TASSER based structure assembly simulations; 60% more domains with length up to 204 residues, compared to the QUARK pipeline, were successfully modeled by the I-TASSER pipeline with a TM-score above 0.4. The robustness of the I-TASSER pipeline can stem from the composite fragment-assembly simulations that combine structures from both ab initio folding and threading template refinements. Despite the promising cases, challenges still exist in long-range beta-strand folding, domain parsing, and the uncertainty of secondary structure prediction; the latter of which was found to affect nearly all aspects of FM structure predictions, from fragment identification, target classification, structure assembly, to final model selection. Significant efforts are needed to solve these problems before real progress on FM could be made. PMID:26370505

Integration of QUARK and I-TASSER for Ab Initio Protein Structure Prediction in CASP11.

PubMed

Zhang, Wenxuan; Yang, Jianyi; He, Baoji; Walker, Sara Elizabeth; Zhang, Hongjiu; Govindarajoo, Brandon; Virtanen, Jouko; Xue, Zhidong; Shen, Hong-Bin; Zhang, Yang

2016-09-01

We tested two pipelines developed for template-free protein structure prediction in the CASP11 experiment. First, the QUARK pipeline constructs structure models by reassembling fragments of continuously distributed lengths excised from unrelated proteins. Five free-modeling (FM) targets have the model successfully constructed by QUARK with a TM-score above 0.4, including the first model of T0837-D1, which has a TM-score = 0.736 and RMSD = 2.9 Å to the native. Detailed analysis showed that the success is partly attributed to the high-resolution contact map prediction derived from fragment-based distance-profiles, which are mainly located between regular secondary structure elements and loops/turns and help guide the orientation of secondary structure assembly. In the Zhang-Server pipeline, weakly scoring threading templates are re-ordered by the structural similarity to the ab initio folding models, which are then reassembled by I-TASSER based structure assembly simulations; 60% more domains with length up to 204 residues, compared to the QUARK pipeline, were successfully modeled by the I-TASSER pipeline with a TM-score above 0.4. The robustness of the I-TASSER pipeline can stem from the composite fragment-assembly simulations that combine structures from both ab initio folding and threading template refinements. Despite the promising cases, challenges still exist in long-range beta-strand folding, domain parsing, and the uncertainty of secondary structure prediction; the latter of which was found to affect nearly all aspects of FM structure predictions, from fragment identification, target classification, structure assembly, to final model selection. Significant efforts are needed to solve these problems before real progress on FM could be made. Proteins 2016; 84(Suppl 1):76-86. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

The Power of the Frame: Systems Transformation Framework for Health Care Leaders.

PubMed

Scott, Kathy A; Pringle, Janice

Health care leaders are responsible for oversight of multiple and competing change interventions. These interventions regularly fail to achieve the desired outcomes and/or sustainable results. This often occurs because of the mental models and approaches that are used to plan, design, implement, and evaluate the system. These do not account for inherent characteristics that determine the system's likely ability to innovate while maintaining operational effectiveness. Theories exist on how to assess a system's readiness to change, but the definitions, constructs, and assessments are diverse and often look at facets of systems in isolation. The Systems Transformation Framework prescriptively defines and characterizes system domains on the basis of complex adaptive systems theory so that domains can be assessed in tandem. As a result, strengths and challenges to implementation are recognized before implementation begins. The Systems Transformation Framework defines 8 major domains: vision, leadership, organizational culture, organizational behavior, organizational structure, performance measurements, internal learning, and external learning. Each domain has principles that are critical for creating the conditions that lead to successful organizational adaptation and change. The Systems Transformation Framework can serve as a guide for health care leaders at all levels of the organization to (1) create environments that are change ready and (2) plan, design, implement, and evaluate change within complex adaptive systems.

Statistical Learning Is Constrained to Less Abstract Patterns in Complex Sensory Input (but not the Least)

PubMed Central

Emberson, Lauren L.; Rubinstein, Dani

2016-01-01

The influence of statistical information on behavior (either through learning or adaptation) is quickly becoming foundational to many domains of cognitive psychology and cognitive neuroscience, from language comprehension to visual development. We investigate a central problem impacting these diverse fields: when encountering input with rich statistical information, are there any constraints on learning? This paper examines learning outcomes when adult learners are given statistical information across multiple levels of abstraction simultaneously: from abstract, semantic categories of everyday objects to individual viewpoints on these objects. After revealing statistical learning of abstract, semantic categories with scrambled individual exemplars (Exp. 1), participants viewed pictures where the categories as well as the individual objects predicted picture order (e.g., bird1—dog1, bird2—dog2). Our findings suggest that participants preferentially encode the relationships between the individual objects, even in the presence of statistical regularities linking semantic categories (Exps. 2 and 3). In a final experiment we investigate whether learners are biased towards learning object-level regularities or simply construct the most detailed model given the data (and therefore best able to predict the specifics of the upcoming stimulus) by investigating whether participants preferentially learn from the statistical regularities linking individual snapshots of objects or the relationship between the objects themselves (e.g., bird_picture1— dog_picture1, bird_picture2—dog_picture2). We find that participants fail to learn the relationships between individual snapshots, suggesting a bias towards object-level statistical regularities as opposed to merely constructing the most complete model of the input. This work moves beyond the previous existence proofs that statistical learning is possible at both very high and very low levels of abstraction (categories vs. individual objects) and suggests that, at least with the current categories and type of learner, there are biases to pick up on statistical regularities between individual objects even when robust statistical information is present at other levels of abstraction. These findings speak directly to emerging theories about how systems supporting statistical learning and prediction operate in our structure-rich environments. Moreover, the theoretical implications of the current work across multiple domains of study is already clear: statistical learning cannot be assumed to be unconstrained even if statistical learning has previously been established at a given level of abstraction when that information is presented in isolation. PMID:27139779

Object Recognition Under Semantic Impairment: The Effects of Conceptual Regularities on Perceptual Decisions.

ERIC Educational Resources Information Center

Rogers, Timothy T.; Hodges, John R.; Ralph, Matthew A. Lambon; Patterson, Karalyn

2003-01-01

Presents evidence that although patients with semantic deficits can sometimes show good performance on tests or object decisions, this pattern applies when nonsee-objects do not respect the regularities of the domain. Patients with semantic dementia viewed line drawings of a real and chimeric animals side-by-side and were asked to decide which was…

Joint Inversion of Body-Wave Arrival Times and Surface-Wave Dispersion Data in the Wavelet Domain Constrained by Sparsity Regularization

NASA Astrophysics Data System (ADS)

Zhang, H.; Fang, H.; Yao, H.; Maceira, M.; van der Hilst, R. D.

2014-12-01

Recently, Zhang et al. (2014, Pure and Appiled Geophysics) have developed a joint inversion code incorporating body-wave arrival times and surface-wave dispersion data. The joint inversion code was based on the regional-scale version of the double-difference tomography algorithm tomoDD. The surface-wave inversion part uses the propagator matrix solver in the algorithm DISPER80 (Saito, 1988) for forward calculation of dispersion curves from layered velocity models and the related sensitivities. The application of the joint inversion code to the SAFOD site in central California shows that the fault structure is better imaged in the new model, which is able to fit both the body-wave and surface-wave observations adequately. Here we present a new joint inversion method that solves the model in the wavelet domain constrained by sparsity regularization. Compared to the previous method, it has the following advantages: (1) The method is both data- and model-adaptive. For the velocity model, it can be represented by different wavelet coefficients at different scales, which are generally sparse. By constraining the model wavelet coefficients to be sparse, the inversion in the wavelet domain can inherently adapt to the data distribution so that the model has higher spatial resolution in the good data coverage zone. Fang and Zhang (2014, Geophysical Journal International) have showed the superior performance of the wavelet-based double-difference seismic tomography method compared to the conventional method. (2) For the surface wave inversion, the joint inversion code takes advantage of the recent development of direct inversion of surface wave dispersion data for 3-D variations of shear wave velocity without the intermediate step of phase or group velocity maps (Fang et al., 2014, Geophysical Journal International). A fast marching method is used to compute, at each period, surface wave traveltimes and ray paths between sources and receivers. We will test the new joint inversion code at the SAFOD site to compare its performance over the previous code. We will also select another fault zone such as the San Jacinto Fault Zone to better image its structure.

Recognition Memory for Novel Stimuli: The Structural Regularity Hypothesis

ERIC Educational Resources Information Center

Cleary, Anne M.; Morris, Alison L.; Langley, Moses M.

2007-01-01

Early studies of human memory suggest that adherence to a known structural regularity (e.g., orthographic regularity) benefits memory for an otherwise novel stimulus (e.g., G. A. Miller, 1958). However, a more recent study suggests that structural regularity can lead to an increase in false-positive responses on recognition memory tests (B. W. A.…

The right inferior frontal gyrus processes nested non-local dependencies in music.

PubMed

Cheung, Vincent K M; Meyer, Lars; Friederici, Angela D; Koelsch, Stefan

2018-02-28

Complex auditory sequences known as music have often been described as hierarchically structured. This permits the existence of non-local dependencies, which relate elements of a sequence beyond their temporal sequential order. Previous studies in music have reported differential activity in the inferior frontal gyrus (IFG) when comparing regular and irregular chord-transitions based on theories in Western tonal harmony. However, it is unclear if the observed activity reflects the interpretation of hierarchical structure as the effects are confounded by local irregularity. Using functional magnetic resonance imaging (fMRI), we found that violations to non-local dependencies in nested sequences of three-tone musical motifs in musicians elicited increased activity in the right IFG. This is in contrast to similar studies in language which typically report the left IFG in processing grammatical syntax. Effects of increasing auditory working demands are moreover reflected by distributed activity in frontal and parietal regions. Our study therefore demonstrates the role of the right IFG in processing non-local dependencies in music, and suggests that hierarchical processing in different cognitive domains relies on similar mechanisms that are subserved by domain-selective neuronal subpopulations.

Sensor fusion for structural tilt estimation using an acceleration-based tilt sensor and a gyroscope

NASA Astrophysics Data System (ADS)

Liu, Cheng; Park, Jong-Woong; Spencer, B. F., Jr.; Moon, Do-Soo; Fan, Jiansheng

2017-10-01

A tilt sensor can provide useful information regarding the health of structural systems. Most existing tilt sensors are gravity/acceleration based and can provide accurate measurements of static responses. However, for dynamic tilt, acceleration can dramatically affect the measured responses due to crosstalk. Thus, dynamic tilt measurement is still a challenging problem. One option is to integrate the output of a gyroscope sensor, which measures the angular velocity, to obtain the tilt; however, problems arise because the low-frequency sensitivity of the gyroscope is poor. This paper proposes a new approach to dynamic tilt measurements, fusing together information from a MEMS-based gyroscope and an acceleration-based tilt sensor. The gyroscope provides good estimates of the tilt at higher frequencies, whereas the acceleration measurements are used to estimate the tilt at lower frequencies. The Tikhonov regularization approach is employed to fuse these measurements together and overcome the ill-posed nature of the problem. The solution is carried out in the frequency domain and then implemented in the time domain using FIR filters to ensure stability. The proposed method is validated numerically and experimentally to show that it performs well in estimating both the pseudo-static and dynamic tilt measurements.

Functional group selective STM Imaging in self-assembled monolayers: Benzeneselenol on Au(111)

NASA Astrophysics Data System (ADS)

Azzam, Waleed; Zharnikov, Michael; Rohwerde, Michael; Bashir, Asif

2018-01-01

Benzeneselenol (PSe) self-assembled monolayers (SAMs) formed on Au(111) substrate by the immersion procedure with an immersion time of 24 h and 4 weeks were studied by high-resolution scanning tunneling microscopy (STM). The short molecular rows, which have been previously attributed to irregular translational domains, were found to be regularly repeated within a single domain in the SAMs fabricated upon the immersion for 4 weeks, forming adlayer structure with a very large unit cell. This structure could be assigned as a (27 × 5) superlattice (α phase) containing 36 molecules in the oblique unit cell. This phase coexisted with a different phase having a commensurate (8√{ 3 } × 4) superstructure (β phase) containing 28 protrusions per rectangular unit cell. Analysis of the STM images suggested that each PSe molecule in the β phase was imaged not as one but as a pair of protrusions, which were attributed to the benzene ring and the selenium headgroup of the PSe molecule. At the given molecular length, the spacing between the protrusions defined the molecular tilt, allowing us to derive the orientation of the SAM constituents directly from the STM image.

Design of a minimal protein oligomerization domain by a structural approach.

PubMed

Burkhard, P; Meier, M; Lustig, A

2000-12-01

Because of the simplicity and regularity of the alpha-helical coiled coil relative to other structural motifs, it can be conveniently used to clarify the molecular interactions responsible for protein folding and stability. Here we describe the de novo design and characterization of a two heptad-repeat peptide stabilized by a complex network of inter- and intrahelical salt bridges. Circular dichroism spectroscopy and analytical ultracentrifugation show that this peptide is highly alpha-helical and 100% dimeric tinder physiological buffer conditions. Interestingly, the peptide was shown to switch its oligomerization state from a dimer to a trimer upon increasing ionic strength. The correctness of the rational design principles used here is supported by details of the atomic structure of the peptide deduced from X-ray crystallography. The structure of the peptide shows that it is not a molten globule but assumes a unique, native-like conformation. This de novo peptide thus represents an attractive model system for the design of a molecular recognition system.

Design of a minimal protein oligomerization domain by a structural approach.

PubMed Central

Burkhard, P.; Meier, M.; Lustig, A.

2000-01-01

Because of the simplicity and regularity of the alpha-helical coiled coil relative to other structural motifs, it can be conveniently used to clarify the molecular interactions responsible for protein folding and stability. Here we describe the de novo design and characterization of a two heptad-repeat peptide stabilized by a complex network of inter- and intrahelical salt bridges. Circular dichroism spectroscopy and analytical ultracentrifugation show that this peptide is highly alpha-helical and 100% dimeric tinder physiological buffer conditions. Interestingly, the peptide was shown to switch its oligomerization state from a dimer to a trimer upon increasing ionic strength. The correctness of the rational design principles used here is supported by details of the atomic structure of the peptide deduced from X-ray crystallography. The structure of the peptide shows that it is not a molten globule but assumes a unique, native-like conformation. This de novo peptide thus represents an attractive model system for the design of a molecular recognition system. PMID:11206050

Control of the transition between regular and mach reflection of shock waves

NASA Astrophysics Data System (ADS)

Alekseev, A. K.

2012-06-01

A control problem was considered that makes it possible to switch the flow between stationary Mach and regular reflection of shock waves within the dual solution domain. The sensitivity of the flow was computed by solving adjoint equations. A control disturbance was sought by applying gradient optimization methods. According to the computational results, the transition from regular to Mach reflection can be executed by raising the temperature. The transition from Mach to regular reflection can be achieved by lowering the temperature at moderate Mach numbers and is impossible at large numbers. The reliability of the numerical results was confirmed by verifying them with the help of a posteriori analysis.

The Level of Satisfaction of Female Learning Disabilities' Parents with Their Kids' Integration in Regular Schools in Riyadh, Saudi Arabia

ERIC Educational Resources Information Center

Abahusain, Wedad A.

2016-01-01

This study aims at finding out the parents' level of satisfaction with the integration of their daughters with learning disabilities in regular schools in Riyadh, Saudi Arabia. The study sample consisted of 283 parents of female students. The instrument of data collection was a questionnaire consisting of 59 items for 10 domains. The study results…

Wavelet-promoted sparsity for non-invasive reconstruction of electrical activity of the heart.

PubMed

Cluitmans, Matthijs; Karel, Joël; Bonizzi, Pietro; Volders, Paul; Westra, Ronald; Peeters, Ralf

2018-05-12

We investigated a novel sparsity-based regularization method in the wavelet domain of the inverse problem of electrocardiography that aims at preserving the spatiotemporal characteristics of heart-surface potentials. In three normal, anesthetized dogs, electrodes were implanted around the epicardium and body-surface electrodes were attached to the torso. Potential recordings were obtained simultaneously on the body surface and on the epicardium. A CT scan was used to digitize a homogeneous geometry which consisted of the body-surface electrodes and the epicardial surface. A novel multitask elastic-net-based method was introduced to regularize the ill-posed inverse problem. The method simultaneously pursues a sparse wavelet representation in time-frequency and exploits correlations in space. Performance was assessed in terms of quality of reconstructed epicardial potentials, estimated activation and recovery time, and estimated locations of pacing, and compared with performance of Tikhonov zeroth-order regularization. Results in the wavelet domain obtained higher sparsity than those in the time domain. Epicardial potentials were non-invasively reconstructed with higher accuracy than with Tikhonov zeroth-order regularization (p < 0.05), and recovery times were improved (p < 0.05). No significant improvement was found in terms of activation times and localization of origin of pacing. Next to improved estimation of recovery isochrones, which is important when assessing substrate for cardiac arrhythmias, this novel technique opens potentially powerful opportunities for clinical application, by allowing to choose wavelet bases that are optimized for specific clinical questions. Graphical Abstract The inverse problem of electrocardiography is to reconstruct heart-surface potentials from recorded bodysurface electrocardiograms (ECGs) and a torso-heart geometry. However, it is ill-posed and solving it requires additional constraints for regularization. We introduce a regularization method that simultaneously pursues a sparse wavelet representation in time-frequency and exploits correlations in space. Our approach reconstructs epicardial (heart-surface) potentials with higher accuracy than common methods. It also improves the reconstruction of recovery isochrones, which is important when assessing substrate for cardiac arrhythmias. This novel technique opens potentially powerful opportunities for clinical application, by allowing to choose wavelet bases that are optimized for specific clinical questions.

Regularity of random attractors for fractional stochastic reaction-diffusion equations on Rn

NASA Astrophysics Data System (ADS)

Gu, Anhui; Li, Dingshi; Wang, Bixiang; Yang, Han

2018-06-01

We investigate the regularity of random attractors for the non-autonomous non-local fractional stochastic reaction-diffusion equations in Hs (Rn) with s ∈ (0 , 1). We prove the existence and uniqueness of the tempered random attractor that is compact in Hs (Rn) and attracts all tempered random subsets of L2 (Rn) with respect to the norm of Hs (Rn). The main difficulty is to show the pullback asymptotic compactness of solutions in Hs (Rn) due to the noncompactness of Sobolev embeddings on unbounded domains and the almost sure nondifferentiability of the sample paths of the Wiener process. We establish such compactness by the ideas of uniform tail-estimates and the spectral decomposition of solutions in bounded domains.

Real-space evidence of the equilibrium ordered bicontinuous double diamond structure of a diblock copolymer.

PubMed

Chu, C Y; Jiang, X; Jinnai, H; Pei, R Y; Lin, W F; Tsai, J C; Chen, H L

2015-03-14

The ordered bicontinuous double diamond (OBDD) structure has long been believed to be an unstable ordered network nanostructure, which is relative to the ordered bicontinuous double gyroid (OBDG) structure for diblock copolymers. Using electron tomography, we present the first real-space observation of the thermodynamically stable OBDD structure in a diblock copolymer composed of a stereoregular block, syndiotactic polypropylene-block-polystyrene (sPP-b-PS), in which the sPP tetrapods are interconnected via a bicontinuous network with Pn3̄m symmetry. The OBDD structure underwent a thermally reversible order-order transition (OOT) to OBDG upon heating, and the transition was accompanied with a slight reduction of domain spacing, as demonstrated both experimentally and theoretically. The thermodynamic stability of the OBDD structure was attributed to the ability of the configurationally regular sPP block to form helical segments, even above its melting point, as the reduction of internal energy associated with the helix formation may effectively compensate the greater packing frustration in OBDD relative to that in the tripods of OBDG.

Structural and Functional Adaptation of Vancomycin Resistance VanT Serine Racemases.

PubMed

Meziane-Cherif, Djalal; Stogios, Peter J; Evdokimova, Elena; Egorova, Olga; Savchenko, Alexei; Courvalin, Patrice

2015-08-11

Vancomycin resistance in Gram-positive bacteria results from the replacement of the D-alanyl-D-alanine target of peptidoglycan precursors with D-alanyl-D-lactate or D-alanyl-D-serine (D-Ala-D-Ser), to which vancomycin has low binding affinity. VanT is one of the proteins required for the production of D-Ala-D-Ser-terminating precursors by converting L-Ser to D-Ser. VanT is composed of two domains, an N-terminal membrane-bound domain, likely involved in L-Ser uptake, and a C-terminal cytoplasmic catalytic domain which is related to bacterial alanine racemases. To gain insight into the molecular function of VanT, the crystal structure of the catalytic domain of VanTG from VanG-type resistant Enterococcus faecalis BM4518 was determined. The structure showed significant similarity to type III pyridoxal 5'-phosphate (PLP)-dependent alanine racemases, which are essential for peptidoglycan synthesis. Comparative structural analysis between VanTG and alanine racemases as well as site-directed mutagenesis identified three specific active site positions centered around Asn696 which are responsible for the L-amino acid specificity. This analysis also suggested that VanT racemases evolved from regular alanine racemases by acquiring additional selectivity toward serine while preserving that for alanine. The 4-fold-lower relative catalytic efficiency of VanTG against L-Ser versus L-Ala implied that this enzyme relies on its membrane-bound domain for L-Ser transport to increase the overall rate of d-Ser production. These findings illustrate how vancomycin pressure selected for molecular adaptation of a housekeeping enzyme to a bifunctional enzyme to allow for peptidoglycan remodeling, a strategy increasingly observed in antibiotic-resistant bacteria. Vancomycin is one of the drugs of last resort against Gram-positive antibiotic-resistant pathogens. However, bacteria have evolved a sophisticated mechanism which remodels the drug target, the D-alanine ending precursors in cell wall synthesis, into precursors terminating with D-lactate or D-serine, to which vancomycin has less affinity. D-Ser is synthesized by VanT serine racemase, which has two unusual characteristics: (i) it is one of the few serine racemases identified in bacteria and (ii) it contains a membrane-bound domain involved in L-Ser uptake. The structure of the catalytic domain of VanTG showed high similarity to alanine racemases, and we identified three specific active site substitutions responsible for L-Ser specificity. The data provide the molecular basis for VanT evolution to a bifunctional enzyme coordinating both transport and racemization. Our findings also illustrate the evolution of the essential alanine racemase into a vancomycin resistance enzyme in response to antibiotic pressure. Copyright © 2015 Meziane-Cherif et al.

Pi-Pi contacts are an overlooked protein feature relevant to phase separation

PubMed Central

Vernon, Robert McCoy; Chong, Paul Andrew; Tsang, Brian; Kim, Tae Hun; Bah, Alaji; Farber, Patrick; Lin, Hong

2018-01-01

Protein phase separation is implicated in formation of membraneless organelles, signaling puncta and the nuclear pore. Multivalent interactions of modular binding domains and their target motifs can drive phase separation. However, forces promoting the more common phase separation of intrinsically disordered regions are less understood, with suggested roles for multivalent cation-pi, pi-pi, and charge interactions and the hydrophobic effect. Known phase-separating proteins are enriched in pi-orbital containing residues and thus we analyzed pi-interactions in folded proteins. We found that pi-pi interactions involving non-aromatic groups are widespread, underestimated by force-fields used in structure calculations and correlated with solvation and lack of regular secondary structure, properties associated with disordered regions. We present a phase separation predictive algorithm based on pi interaction frequency, highlighting proteins involved in biomaterials and RNA processing. PMID:29424691

Geometry-aware multiscale image registration via OBBTree-based polyaffine log-demons.

PubMed

Seiler, Christof; Pennec, Xavier; Reyes, Mauricio

2011-01-01

Non-linear image registration is an important tool in many areas of image analysis. For instance, in morphometric studies of a population of brains, free-form deformations between images are analyzed to describe the structural anatomical variability. Such a simple deformation model is justified by the absence of an easy expressible prior about the shape changes. Applying the same algorithms used in brain imaging to orthopedic images might not be optimal due to the difference in the underlying prior on the inter-subject deformations. In particular, using an un-informed deformation prior often leads to local minima far from the expected solution. To improve robustness and promote anatomically meaningful deformations, we propose a locally affine and geometry-aware registration algorithm that automatically adapts to the data. We build upon the log-domain demons algorithm and introduce a new type of OBBTree-based regularization in the registration with a natural multiscale structure. The regularization model is composed of a hierarchy of locally affine transformations via their logarithms. Experiments on mandibles show improved accuracy and robustness when used to initialize the demons, and even similar performance by direct comparison to the demons, with a significantly lower degree of freedom. This closes the gap between polyaffine and non-rigid registration and opens new ways to statistically analyze the registration results.

Parallel architectures for iterative methods on adaptive, block structured grids

NASA Technical Reports Server (NTRS)

Gannon, D.; Vanrosendale, J.

1983-01-01

A parallel computer architecture well suited to the solution of partial differential equations in complicated geometries is proposed. Algorithms for partial differential equations contain a great deal of parallelism. But this parallelism can be difficult to exploit, particularly on complex problems. One approach to extraction of this parallelism is the use of special purpose architectures tuned to a given problem class. The architecture proposed here is tuned to boundary value problems on complex domains. An adaptive elliptic algorithm which maps effectively onto the proposed architecture is considered in detail. Two levels of parallelism are exploited by the proposed architecture. First, by making use of the freedom one has in grid generation, one can construct grids which are locally regular, permitting a one to one mapping of grids to systolic style processor arrays, at least over small regions. All local parallelism can be extracted by this approach. Second, though there may be a regular global structure to the grids constructed, there will be parallelism at this level. One approach to finding and exploiting this parallelism is to use an architecture having a number of processor clusters connected by a switching network. The use of such a network creates a highly flexible architecture which automatically configures to the problem being solved.

Different polarization dynamic states in a vector Yb-doped fiber laser.

PubMed

Li, Xingliang; Zhang, Shumin; Han, Huiyun; Han, Mengmeng; Zhang, Huaxing; Zhao, Luming; Wen, Fang; Yang, Zhenjun

2015-04-20

Different polarization dynamic states in an unidirectional, vector, Yb-doped fiber ring laser have been observed. A rich variety of dynamic states, including group velocity locked polarization domains and their splitting into regularly distributed multiple domains, polarization locked square pulses and their harmonic mode locking counterparts, and dissipative soliton resonances have all been observed with different operating parameters. We have also shown experimentally details of the conditions under which polarization-domain-wall dark pulses and bright square pulses form.

Unraveling the nature of autism: finding order amid change

PubMed Central

Hellendoorn, Annika; Wijnroks, Lex; Leseman, Paul P. M.

2015-01-01

In this article, we hypothesize that individuals with autism spectrum disorder (ASD) are born with a deficit in invariance detection, which is a learning process whereby people and animals come to attend the relatively stable patterns or structural regularities in the changing stimulus array. This paper synthesizes a substantial body of research which suggests that a deficit in the domain-general perceptual learning process of invariant detection in ASD can lead to a cascade of consequences in different developmental domains. We will outline how this deficit in invariant detection can cause uncertainty, unpredictability, and a lack of control for individuals with ASD and how varying degrees of impairments in this learning process can account for the heterogeneity of the ASD phenotype. We also describe how differences in neural plasticity in ASD underlie the impairments in perceptual learning. The present account offers an alternative to prior theories and contributes to the challenge of understanding the developmental trajectories that result in the variety of autistic behaviors. PMID:25870581

Analysis of satellite and airborne wind measurements during the SEMAPHORE experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tournadre, J.; Hauser, D.

1994-12-31

During the SEMAPHORE experiment Intensive Observation Period (IOP), held in October and November 1993 in the Azores-Madeira region, two airplanes, instrumented for atmospheric research, and two oceanographic research vessels have conducted in situ measurements in a 500km x 500km domain. Within the framework of SEMAPHORE, the SOFIA program is dedicated to the study of the air-sea fluxes and interactions from local scale up to mesoscale. The analysis of the structure of the wind and wave fields and their relations to the surface fluxes (especially near oceanic fronts) and the validation of the satellite data are two of the main goalsmore » of the SOFIA program. During the IOP, the experiment domain was regularly overflown by the ERS-1 and Topex-Poseidon (TP) satellites. This study presents a preliminary analysis of the ERS-1 and TP altimeter wind and wave measurement and ERS-1 scatterometer wind fields. The data from the airborne RESSAC (a radar ocean wave spectrometer) are also presented.« less

Geometrical and topological issues in octree based automatic meshing

NASA Technical Reports Server (NTRS)

Saxena, Mukul; Perucchio, Renato

1987-01-01

Finite element meshes derived automatically from solid models through recursive spatial subdivision schemes (octrees) can be made to inherit the hierarchical structure and the spatial addressability intrinsic to the underlying grid. These two properties, together with the geometric regularity that can also be built into the mesh, make octree based meshes ideally suited for efficient analysis and self-adaptive remeshing and reanalysis. The element decomposition of the octal cells that intersect the boundary of the domain is discussed. The problem, central to octree based meshing, is solved by combining template mapping and element extraction into a procedure that utilizes both constructive solid geometry and boundary representation techniques. Boundary cells that are not intersected by the edge of the domain boundary are easily mapped to predefined element topology. Cells containing edges (and vertices) are first transformed into a planar polyhedron and then triangulated via element extractor. The modeling environments required for the derivation of planar polyhedra and for element extraction are analyzed.

Octree based automatic meshing from CSG models

NASA Technical Reports Server (NTRS)

Perucchio, Renato

1987-01-01

Finite element meshes derived automatically from solid models through recursive spatial subdivision schemes (octrees) can be made to inherit the hierarchical structure and the spatial addressability intrinsic to the underlying grid. These two properties, together with the geometric regularity that can also be built into the mesh, make octree based meshes ideally suited for efficient analysis and self-adaptive remeshing and reanalysis. The element decomposition of the octal cells that intersect the boundary of the domain is emphasized. The problem, central to octree based meshing, is solved by combining template mapping and element extraction into a procedure that utilizes both constructive solid geometry and boundary respresentation techniques. Boundary cells that are not intersected by the edge of the domain boundary are easily mapped to predefined element topology. Cells containing edges (and vertices) are first transformed into a planar polyhedron and then triangulated via element extractors. The modeling environments required for the derivation of planar polyhedra and for element extraction are analyzed.

Vector intensity reconstruction using the data completion method.

PubMed

Langrenne, Christophe; Garcia, Alexandre

2013-04-01

This paper presents an application of the data completion method (DCM) for vector intensity reconstructions. A mobile array of 36 pressure-pressure probes (72 microphones) is used to perform measurements near a planar surface. Nevertheless, since the proposed method is based on integral formulations, DCM can be applied with any kind of geometry. This method requires the knowledge of Cauchy data (pressure and velocity) on a part of the boundary of an empty domain in order to evaluate pressure and velocity on the remaining part of the boundary. Intensity vectors are calculated in the interior domain surrounded by the measurement array. This inverse acoustic problem requires the use of a regularization method to obtain a realistic solution. An experiment in a closed wooden car trunk mock-up excited by a shaker and two loudspeakers is presented. In this case, where the volume of the mock-up is small (0.61 m(3)), standing-waves and fluid structure interactions appear and show that DCM is a powerful tool to identify sources in a confined space.

Analogue modelling of inclined, brittle-ductile transpression: Testing analytical models through natural shear zones (external Betics)

NASA Astrophysics Data System (ADS)

Barcos, L.; Díaz-Azpiroz, M.; Balanyá, J. C.; Expósito, I.; Jiménez-Bonilla, A.; Faccenna, C.

2016-07-01

The combination of analytical and analogue models gives new opportunities to better understand the kinematic parameters controlling the evolution of transpression zones. In this work, we carried out a set of analogue models using the kinematic parameters of transpressional deformation obtained by applying a general triclinic transpression analytical model to a tabular-shaped shear zone in the external Betic Chain (Torcal de Antequera massif). According to the results of the analytical model, we used two oblique convergence angles to reproduce the main structural and kinematic features of structural domains observed within the Torcal de Antequera massif (α = 15° for the outer domains and α = 30° for the inner domain). Two parallel inclined backstops (one fixed and the other mobile) reproduce the geometry of the shear zone walls of the natural case. Additionally, we applied digital particle image velocimetry (PIV) method to calculate the velocity field of the incremental deformation. Our results suggest that the spatial distribution of the main structures observed in the Torcal de Antequera massif reflects different modes of strain partitioning and strain localization between two domain types, which are related to the variation in the oblique convergence angle and the presence of steep planar velocity - and rheological - discontinuities (the shear zone walls in the natural case). In the 15° model, strain partitioning is simple and strain localization is high: a single narrow shear zone is developed close and parallel to the fixed backstop, bounded by strike-slip faults and internally deformed by R and P shears. In the 30° model, strain partitioning is strong, generating regularly spaced oblique-to-the backstops thrusts and strike-slip faults. At final stages of the 30° experiment, deformation affects the entire model box. Our results show that the application of analytical modelling to natural transpressive zones related to upper crustal deformation facilitates to constrain the geometrical parameters of analogue models.

Development and Validation of the Scan of Postgraduate Educational Environment Domains (SPEED): A Brief Instrument to Assess the Educational Environment in Postgraduate Medical Education

PubMed Central

Schönrock-Adema, Johanna; Visscher, Maartje; Raat, A. N. Janet; Brand, Paul L. P.

2015-01-01

Introduction Current instruments to evaluate the postgraduate medical educational environment lack theoretical frameworks and are relatively long, which may reduce response rates. We aimed to develop and validate a brief instrument that, based on a solid theoretical framework for educational environments, solicits resident feedback to screen the postgraduate medical educational environment quality. Methods Stepwise, we developed a screening instrument, using existing instruments to assess educational environment quality and adopting a theoretical framework that defines three educational environment domains: content, atmosphere and organization. First, items from relevant existing instruments were collected and, after deleting duplicates and items not specifically addressing educational environment, grouped into the three domains. In a Delphi procedure, the item list was reduced to a set of items considered most important and comprehensively covering the three domains. These items were triangulated against the results of semi-structured interviews with 26 residents from three teaching hospitals to achieve face validity. This draft version of the Scan of Postgraduate Educational Environment Domains (SPEED) was administered to residents in a general and university hospital and further reduced and validated based on the data collected. Results Two hundred twenty-three residents completed the 43-item draft SPEED. We used half of the dataset for item reduction, and the other half for validating the resulting SPEED (15 items, 5 per domain). Internal consistencies were high. Correlations between domain scores in the draft and brief versions of SPEED were high (>0.85) and highly significant (p<0.001). Domain score variance of the draft instrument was explained for ≥80% by the items representing the domains in the final SPEED. Conclusions The SPEED comprehensively covers the three educational environment domains defined in the theoretical framework. Because of its validity and brevity, the SPEED is promising as useful and easily applicable tool to regularly screen educational environment quality in postgraduate medical education. PMID:26413836

The International Index of Erectile Function: development of an adapted tool for use in HIV-positive men who have sex with men.

PubMed

Coyne, Katherine; Mandalia, Sundhiya; McCullough, Sonya; Catalan, Jose; Noestlinger, Christiana; Colebunders, Robert; Asboe, David

2010-02-01

Erectile dysfunction is common in HIV-positive men who have sex with men (MSM). A standardized scale is needed to assess erectile function in clinical practice and research studies. The International Index of Erectile Function (IIEF) is a widely accepted tool for assessing erectile function designed for heterosexual men. We modified the tool for MSM. We present an analysis of internal consistency of the questionnaire in an HIV-positive cohort. The adapted questionnaire included modified questions within each of the five domains of the IIEF: (i) erectile function, (ii) intercourse satisfaction, (iii) orgasmic function, (iv) sexual desire, and (v) overall satisfaction with sex. MSM at seven European HIV treatment centers completed the questionnaire. Responses were analyzed for internal consistency using standardized Cronbach's alpha values within each of the five domains. A factor analysis was performed to confirm the domain structure of the questionnaire. Data from 486 MSM were analyzed. The factor analysis supported the domain structure described. Questions about erectile function, orgasmic function, and sexual desire performed well, with Cronbach's alpha values of 0.82, 0.83, and 0.89, respectively. Questions concerning intercourse satisfaction were less consistent (Cronbach's alpha 0.55) because frequency of attempts at sexual intercourse did not correlate with other responses. Responses about satisfaction with sex with a regular partner diverged from satisfaction with overall sex life. Frequency of morning erections diverged from other aspects of erectile function, whereas erections with masturbation correlated better. Internal consistency was high overall. This tool is suitable for HIV-positive MSM and can be used in screening, research, and monitoring treatment response.

Generalizations of Tikhonov's regularized method of least squares to non-Euclidean vector norms

NASA Astrophysics Data System (ADS)

Volkov, V. V.; Erokhin, V. I.; Kakaev, V. V.; Onufrei, A. Yu.

2017-09-01

Tikhonov's regularized method of least squares and its generalizations to non-Euclidean norms, including polyhedral, are considered. The regularized method of least squares is reduced to mathematical programming problems obtained by "instrumental" generalizations of the Tikhonov lemma on the minimal (in a certain norm) solution of a system of linear algebraic equations with respect to an unknown matrix. Further studies are needed for problems concerning the development of methods and algorithms for solving reduced mathematical programming problems in which the objective functions and admissible domains are constructed using polyhedral vector norms.

Structural studies on Pax-8 Prd domain/DNA complex.

PubMed

Campagnolo, M; Pesaresi, A; Zelezetsky, I; Geremia, S; Randaccio, L; Bisca, A; Tell, G

2007-04-01

Pax-8 is a member of the Pax family of transcription factors and is essential in the development of thyroid follicular cells. Pax-8 has two DNA-binding domains: the paired domain and the homeo domain. In this study, a preliminary X-ray diffraction analysis of the mammalian Pax-8 paired domain in complex with the C-site of the thyroglobulin promoter was achieved. The Pax-8 paired domain was crystallized by the hanging-drop vapor-diffusion method in complex with both a blunt-ended 26 bp DNA fragment and with a sticky-ended 24 bp DNA fragment with two additional overhanging bases. Crystallization experiments make clear that the growth of transparent crystals with large dimensions and regular shape is particularly influenced by ionic strength. The crystals of Pax-8 complex with blunt-ended and sticky-ended DNA, diffracted synchrotron radiation to 6.0 and 8.0 A resolution and belongs both to the C centered monoclinic system with cell dimensions: a = 89.88 A, b = 80.05 A, c = 67.73 A, and beta = 124.3 degrees and a = 256.56, b = 69.07, c = 99.32 A, and beta = 98.1 degrees , respectively. Fluorescence experiments suggest that the crystalline disorder, deduced by the poor diffraction, can be attributed to the low homogeneity of the protein-DNA sample. The theoretical comparative model of the Pax-8 paired domain complexed with the C-site of the thyroglobulin promoter shows the probable presence of some specific protein-DNA interactions already observed in other Pax proteins and the important role of the cysteine residues of PAI subdomain in the redox control of the DNA recognition.

5 CFR 532.203 - Structure of regular wage schedules.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Structure of regular wage schedules. 532.203 Section 532.203 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PREVAILING RATE SYSTEMS Prevailing Rate Determinations § 532.203 Structure of regular wage schedules. (a...

Small scale homelike special care units and traditional special care units: effects on cognition in dementia; a longitudinal controlled intervention study.

PubMed

Kok, Jeroen S; van Heuvelen, Marieke J G; Berg, Ina J; Scherder, Erik J A

2016-02-16

Evidence shows that living in small scale homelike Special Care Units (SCU) has positive effects on behavioural and psychological symptoms of patients with dementia. Effects on cognitive functioning in relation to care facilities, however, are scarcely investigated. The purpose of this study is to gain more insight into the effects of living in small scale homelike Special Care Units, compared to regular SCU's, on the course of cognitive functioning in dementia. A group of 67 patients with dementia who moved from a regular SCU to a small scale homelike SCU and a group of 48 patients with dementia who stayed in a regular SCU participated in the study. Cognitive and behavioural functioning was assessed by means of a neuropsychological test battery and observation scales one month before (baseline), as well as 3 (post) and 6 months (follow-up) after relocation. Comparing the post and follow-up measurement with the baseline measurement, no significant differences on separate measures of cognitive functioning between both groups were found. Additional analyses, however, on 'domain clusters' revealed that global cognitive functioning of the small scale homelike SCU group showed significantly less cognitive decline three months after the transfer (p < 0.05). Effect sizes (95% CI) show a tendency for better aspects of cognition in favour of the homelike small scaled SCU group, i.e., visual memory, picture recognition, cognitive decline as observed by representatives and the clustered domains episodic memory and global cognitive functioning. While there is no significant longitudinal effect on the progression of cognitive decline comparing small scaled homelike SCU's with regular SCU's for patients with dementia, analyses on the domain clusters and effect sizes cautiously suggest differences in favour of the small scaled homelike SCU for different aspects of cognition.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Itagaki, Masafumi; Miyoshi, Yoshinori; Hirose, Hideyuki

A procedure is presented for the determination of geometric buckling for regular polygons. A new computation technique, the multiple reciprocity boundary element method (MRBEM), has been applied to solve the one-group neutron diffusion equation. The main difficulty in applying the ordinary boundary element method (BEM) to neutron diffusion problems has been the need to compute a domain integral, resulting from the fission source. The MRBEM has been developed for transforming this type of domain integral into an equivalent boundary integral. The basic idea of the MRBEM is to apply repeatedly the reciprocity theorem (Green's second formula) using a sequence ofmore » higher order fundamental solutions. The MRBEM requires discretization of the boundary only rather than of the domain. This advantage is useful for extensive survey analyses of buckling for complex geometries. The results of survey analyses have indicated that the general form of geometric buckling is B[sub g][sup 2] = (a[sub n]/R[sub c])[sup 2], where R[sub c] represents the radius of the circumscribed circle of the regular polygon under consideration. The geometric constant A[sub n] depends on the type of regular polygon and takes the value of [pi] for a square and 2.405 for a circle, an extreme case that has an infinite number of sides. Values of a[sub n] for a triangle, pentagon, hexagon, and octagon have been calculated as 4.190, 2.281, 2.675, and 2.547, respectively.« less

An Evaluation of Recently Developed RANS-Based Turbulence Models for Flow Over a Two-Dimensional Block Subjected to Different Mesh Structures and Grid Resolutions

NASA Astrophysics Data System (ADS)

Kardan, Farshid; Cheng, Wai-Chi; Baverel, Olivier; Porté-Agel, Fernando

2016-04-01

Understanding, analyzing and predicting meteorological phenomena related to urban planning and built environment are becoming more essential than ever to architectural and urban projects. Recently, various version of RANS models have been established but more validation cases are required to confirm their capability for wind flows. In the present study, the performance of recently developed RANS models, including the RNG k-ɛ , SST BSL k-ω and SST ⪆mma-Reθ , have been evaluated for the flow past a single block (which represent the idealized architecture scale). For validation purposes, the velocity streamlines and the vertical profiles of the mean velocities and variances were compared with published LES and wind tunnel experiment results. Furthermore, other additional CFD simulations were performed to analyze the impact of regular/irregular mesh structures and grid resolutions based on selected turbulence model in order to analyze the grid independency. Three different grid resolutions (coarse, medium and fine) of Nx × Ny × Nz = 320 × 80 × 320, 160 × 40 × 160 and 80 × 20 × 80 for the computational domain and nx × nz = 26 × 32, 13 × 16 and 6 × 8, which correspond to number of grid points on the block edges, were chosen and tested. It can be concluded that among all simulated RANS models, the SST ⪆mma-Reθ model performed best and agreed fairly well to the LES simulation and experimental results. It can also be concluded that the SST ⪆mma-Reθ model provides a very satisfactory results in terms of grid dependency in the fine and medium grid resolutions in both regular and irregular structure meshes. On the other hand, despite a very good performance of the RNG k-ɛ model in the fine resolution and in the regular structure grids, a disappointing performance of this model in the coarse and medium grid resolutions indicates that the RNG k-ɛ model is highly dependent on grid structure and grid resolution. These quantitative validations are essential to access the accuracy of RANS models for the simulation of flow in urban environment.

On the Inequalities of Babu\\vska-Aziz, Friedrichs and Horgan-Payne

NASA Astrophysics Data System (ADS)

Costabel, Martin; Dauge, Monique

2015-09-01

The equivalence between the inequalities of Babu\\vska-Aziz and Friedrichs for sufficiently smooth bounded domains in the plane was shown by Horgan and Payne 30 years ago. We prove that this equivalence, and the equality between the associated constants, is true without any regularity condition on the domain. For the Horgan-Payne inequality, which is an upper bound of the Friedrichs constant for plane star-shaped domains in terms of a geometric quantity known as the Horgan-Payne angle, we show that it is true for some classes of domains, but not for all bounded star-shaped domains. We prove a weaker inequality that is true in all cases.

Magnetoresistance due to domain walls in an epitaxial microfabricated Fe wire

NASA Astrophysics Data System (ADS)

Rüdiger, U.; Yu, J.; Kent, A. D.; Parkin, S. S. P.

1998-08-01

The domain wall (DW) contribution to magnetoresistance has been investigated using an epitaxial microfabricated bcc (110) Fe wires of 2 μm linewidth. A strong in-plane uniaxial component to the magnetic anisotropy perpendicular to the wire axis causes a regular stripe domain pattern with closure domains. The stripe domain width in zero-applied magnetic field is strongly affected by the magnetic history and can be continuously varied from 0.45 to 1.8 μm. This enables a measurement of the resistivity as a function of DW density in a single wire. Clear evidence is presented that the resistivity is reduced in the presence of DWs at low temperatures.

Modal identification of structures by a novel approach based on FDD-wavelet method

NASA Astrophysics Data System (ADS)

Tarinejad, Reza; Damadipour, Majid

2014-02-01

An important application of system identification in structural dynamics is the determination of natural frequencies, mode shapes and damping ratios during operation which can then be used for calibrating numerical models. In this paper, the combination of two advanced methods of Operational Modal Analysis (OMA) called Frequency Domain Decomposition (FDD) and Continuous Wavelet Transform (CWT) based on novel cyclic averaging of correlation functions (CACF) technique are used for identification of dynamic properties. By using this technique, the autocorrelation of averaged correlation functions is used instead of original signals. Integration of FDD and CWT methods is used to overcome their deficiency and take advantage of the unique capabilities of these methods. The FDD method is able to accurately estimate the natural frequencies and mode shapes of structures in the frequency domain. On the other hand, the CWT method is in the time-frequency domain for decomposition of a signal at different frequencies and determines the damping coefficients. In this paper, a new formulation applied to the wavelet transform of the averaged correlation function of an ambient response is proposed. This application causes to accurate estimation of damping ratios from weak (noise) or strong (earthquake) vibrations and long or short duration record. For this purpose, the modified Morlet wavelet having two free parameters is used. The optimum values of these two parameters are obtained by employing a technique which minimizes the entropy of the wavelet coefficients matrix. The capabilities of the novel FDD-Wavelet method in the system identification of various dynamic systems with regular or irregular distribution of mass and stiffness are illustrated. This combined approach is superior to classic methods and yields results that agree well with the exact solutions of the numerical models.

Automated generation of individually customized visualizations of diagnosis-specific medical information using novel techniques of information extraction

NASA Astrophysics Data System (ADS)

Chen, Andrew A.; Meng, Frank; Morioka, Craig A.; Churchill, Bernard M.; Kangarloo, Hooshang

2005-04-01

Managing pediatric patients with neurogenic bladder (NGB) involves regular laboratory, imaging, and physiologic testing. Using input from domain experts and current literature, we identified specific data points from these tests to develop the concept of an electronic disease vector for NGB. An information extraction engine was used to extract the desired data elements from free-text and semi-structured documents retrieved from the patient"s medical record. Finally, a Java-based presentation engine created graphical visualizations of the extracted data. After precision, recall, and timing evaluation, we conclude that these tools may enable clinically useful, automatically generated, and diagnosis-specific visualizations of patient data, potentially improving compliance and ultimately, outcomes.

A new wavelet transform to sparsely represent cortical current densities for EEG/MEG inverse problems.

PubMed

Liao, Ke; Zhu, Min; Ding, Lei

2013-08-01

The present study investigated the use of transform sparseness of cortical current density on human brain surface to improve electroencephalography/magnetoencephalography (EEG/MEG) inverse solutions. Transform sparseness was assessed by evaluating compressibility of cortical current densities in transform domains. To do that, a structure compression method from computer graphics was first adopted to compress cortical surface structure, either regular or irregular, into hierarchical multi-resolution meshes. Then, a new face-based wavelet method based on generated multi-resolution meshes was proposed to compress current density functions defined on cortical surfaces. Twelve cortical surface models were built by three EEG/MEG softwares and their structural compressibility was evaluated and compared by the proposed method. Monte Carlo simulations were implemented to evaluate the performance of the proposed wavelet method in compressing various cortical current density distributions as compared to other two available vertex-based wavelet methods. The present results indicate that the face-based wavelet method can achieve higher transform sparseness than vertex-based wavelet methods. Furthermore, basis functions from the face-based wavelet method have lower coherence against typical EEG and MEG measurement systems than vertex-based wavelet methods. Both high transform sparseness and low coherent measurements suggest that the proposed face-based wavelet method can improve the performance of L1-norm regularized EEG/MEG inverse solutions, which was further demonstrated in simulations and experimental setups using MEG data. Thus, this new transform on complicated cortical structure is promising to significantly advance EEG/MEG inverse source imaging technologies. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

An Immersed Boundary method with divergence-free velocity interpolation and force spreading

NASA Astrophysics Data System (ADS)

Bao, Yuanxun; Donev, Aleksandar; Griffith, Boyce E.; McQueen, David M.; Peskin, Charles S.

2017-10-01

The Immersed Boundary (IB) method is a mathematical framework for constructing robust numerical methods to study fluid-structure interaction in problems involving an elastic structure immersed in a viscous fluid. The IB formulation uses an Eulerian representation of the fluid and a Lagrangian representation of the structure. The Lagrangian and Eulerian frames are coupled by integral transforms with delta function kernels. The discretized IB equations use approximations to these transforms with regularized delta function kernels to interpolate the fluid velocity to the structure, and to spread structural forces to the fluid. It is well-known that the conventional IB method can suffer from poor volume conservation since the interpolated Lagrangian velocity field is not generally divergence-free, and so this can cause spurious volume changes. In practice, the lack of volume conservation is especially pronounced for cases where there are large pressure differences across thin structural boundaries. The aim of this paper is to greatly reduce the volume error of the IB method by introducing velocity-interpolation and force-spreading schemes with the properties that the interpolated velocity field in which the structure moves is at least C1 and satisfies a continuous divergence-free condition, and that the force-spreading operator is the adjoint of the velocity-interpolation operator. We confirm through numerical experiments in two and three spatial dimensions that this new IB method is able to achieve substantial improvement in volume conservation compared to other existing IB methods, at the expense of a modest increase in the computational cost. Further, the new method provides smoother Lagrangian forces (tractions) than traditional IB methods. The method presented here is restricted to periodic computational domains. Its generalization to non-periodic domains is important future work.

Scalar self-force on eccentric geodesics in Schwarzschild spacetime: A time-domain computation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haas, Roland

2007-06-15

We calculate the self-force acting on a particle with scalar charge moving on a generic geodesic around a Schwarzschild black hole. This calculation requires an accurate computation of the retarded scalar field produced by the moving charge; this is done numerically with the help of a fourth-order convergent finite-difference scheme formulated in the time domain. The calculation also requires a regularization procedure, because the retarded field is singular on the particle's world line; this is handled mode-by-mode via the mode-sum regularization scheme first introduced by Barack and Ori. This paper presents the numerical method, various numerical tests, and a samplemore » of results for mildly eccentric orbits as well as ''zoom-whirl'' orbits.« less

Phase-Field Simulations of Topological Structures and Topological Phase Transitions in Ferroelectric Oxide Heterostructures

NASA Astrophysics Data System (ADS)

Zijian Hong

Ferroelectrics are materials that exhibit spontaneous electric polarization which can be switched between energy-degenerated states by external stimuli (e.g., mechanical force and electric field) that exceeds a critical value. They have wide potential applications in memories, capacitors, piezoelectric and pyroelectric sensors, and nanomechanical systems. Topological structures and topological phase transitions have been introduced to the condensed matter physics in the past few decades and have attracted broad attentions in various disciplines due to the rich physical insights and broad potential applications. Ferromagnetic topological structures such as vortex and skyrmion are known to be stabilized by the antisymmetric chiral interaction (e.g., Dzyaloshinskii-Moriya interaction). Without such interaction, ferroelectric topological structures (i.e., vortex, flux-closure, skyrmions, and merons) have been studied only recently with other designing strategies, such as reducing the dimension of the ferroelectrics. The overarching goal of this dissertation is to investigate the topological structures in ferroelectric oxide perovskites as well as the topological phase transitions under external applied forces. Pb(Zr,Ti)O3 (PZT) with morphotropic phase boundary is widely explored for high piezoelectric and dielectric properties. The domain structure of PZT tetragonal/rhombohedral (T/R) bilayer is investigated. Strong interfacial coupling is shown, with large polarization rotation to a lower symmetry phase near the T/R interface. Interlayer domain growth can also be captured, with T-domains in the R layer and R-domains in the T layer. For thin PZT bilayer with 5nm of T-layer and 20 nm of R-layer, the a1/a 2 twin domain structure is formed in the top T layer, which could be fully switched to R domains under applied bias. While a unique flux-closure pattern is observed both theoretically and experimentally in the thick bilayer film with 50 nm of thickness for both T and R layers. It is revealed that the bilayer system could facilitate the motion of the ferroelastic adomain in the top T-layer since the a-domain is not directly embedded in the substrate with high density of defects which can pin the domain wall. Excellent dielectric and piezoelectric responses are demonstrated due to the large polarization rotation and the highly mobile domain walls in both the thick and thin bilayer systems. density of defects which can pin the domain wall. Excellent dielectric and piezoelectric responses are demonstrated due to the large polarization rotation and the highly mobile domain walls in both the thick and thin bilayer systems. The long-range ordered polar vortex array is observed in the (PbTiO 3)n/(SrTiO3)n (PTOn/STOn with n=10˜20) superlattices with combined experimental and theoretical studies. Phase-field simulations reveal the three-dimensional textures of the polar vortex arrays. The neighboring vortices rotate in the opposite directions, which extended into tube-like vortex lines perpendicular to the vortex plane. The thickness-dependent phase diagram is predicted and verified by experimental observations. The energetics (the contributions from elastic, electrostatic, gradient and Landau chemical energies) accompanying the phase transitions are analyzed in details. The dominating depolarization energy at short periodicity (n<10) favors a1/ a2 twin domain, while the large elastic relaxation and Landau energy reduction at large periodicity (n>20) leads to the formation of flux-closure domain with both 90° a/c domain walls and 180° c+/c - domain walls, counterbalancing of the individual energies at intermediate periodicities (n=10˜20) gives rise to the formation of exotic vortex structure with continuous polarization rotation surrounding a singularity-like vortex core. Analytical calculations are performed, showing that the stability of the polar vortex structure is directly related to the length of Pi times bulk domain wall width, where vortex structure can be expected when the geometric length scale of the ferroelectrics is close to this value. The role of insulating STO is further revealed, which shows that a rich phase diagram can be formed by simply tuning the thickness of this layer. Wave-like polar spiral phase is simulated by substituting part of the PTO with BiFeO3 (BFO) in the PTO/STO superlattice (i.e., in a (PTO) 4/(BFO)4/(PTO)4/(STO)12 tricolor system) which has demonstrate ordered polar vortex lattice. This spiral phase is made up of semi-vortex cores that are floating up-down in the ferroelectric PTO layers, giving rise to a net in-plane polarization. An increase of Curie temperature and topological to regular domain transition temperature (over 200 K) is observed, due to the higher Curie temperature and larger spontaneous polarization in BFO layers. This unidirectional spiral state can be reversibly switched by experimentally feasible in-plane field, which evolves into a metastable vortex structure in-between two spiral phases with opposite in-plane directions. (Abstract shortened by ProQuest.).

Self-organization and positioning of bacterial protein clusters

NASA Astrophysics Data System (ADS)

Murray, Seán M.; Sourjik, Victor

2017-10-01

Many cellular processes require proteins to be precisely positioned within the cell. In some cases this can be attributed to passive mechanisms such as recruitment by other proteins in the cell or by exploiting the curvature of the membrane. However, in bacteria, active self-positioning is likely to play a role in multiple processes, including the positioning of the future site of cell division and cytoplasmic protein clusters. How can such dynamic clusters be formed and positioned? Here, we present a model for the self-organization and positioning of dynamic protein clusters into regularly repeating patterns based on a phase-locked Turing pattern. A single peak in the concentration is always positioned at the midpoint of the model cell, and two peaks are positioned at the midpoint of each half. Furthermore, domain growth results in peak splitting and pattern doubling. We argue that the model may explain the regular positioning of the highly conserved structural maintenance of chromosomes complexes on the bacterial nucleoid and that it provides an attractive mechanism for the self-positioning of dynamic protein clusters in other systems.

Wave chaos in a randomly inhomogeneous waveguide: spectral analysis of the finite-range evolution operator.

PubMed

Makarov, D V; Kon'kov, L E; Uleysky, M Yu; Petrov, P S

2013-01-01

The problem of sound propagation in a randomly inhomogeneous oceanic waveguide is considered. An underwater sound channel in the Sea of Japan is taken as an example. Our attention is concentrated on the domains of finite-range ray stability in phase space and their influence on wave dynamics. These domains can be found by means of the one-step Poincare map. To study manifestations of finite-range ray stability, we introduce the finite-range evolution operator (FREO) describing transformation of a wave field in the course of propagation along a finite segment of a waveguide. Carrying out statistical analysis of the FREO spectrum, we estimate the contribution of regular domains and explore their evanescence with increasing length of the segment. We utilize several methods of spectral analysis: analysis of eigenfunctions by expanding them over modes of the unperturbed waveguide, approximation of level-spacing statistics by means of the Berry-Robnik distribution, and the procedure used by A. Relano and coworkers [Relano et al., Phys. Rev. Lett. 89, 244102 (2002); Relano, Phys. Rev. Lett. 100, 224101 (2008)]. Comparing the results obtained with different methods, we find that the method based on the statistical analysis of FREO eigenfunctions is the most favorable for estimating the contribution of regular domains. It allows one to find directly the waveguide modes whose refraction is regular despite the random inhomogeneity. For example, it is found that near-axial sound propagation in the Sea of Japan preserves stability even over distances of hundreds of kilometers due to the presence of a shearless torus in the classical phase space. Increasing the acoustic wavelength degrades scattering, resulting in recovery of eigenfunction localization near periodic orbits of the one-step Poincaré map.

Self-organization of a self-assembled supramolecular rectangle, square, and three-dimensional cage on Au111 surfaces.

PubMed

Yuan, Qun-Hui; Wan, Li-Jun; Jude, Hershel; Stang, Peter J

2005-11-23

The structure and conformation of three self-assembled supramolecular species, a rectangle, a square, and a three-dimensional cage, on Au111 surfaces were investigated by scanning tunneling microscopy. These supramolecular assemblies adsorb on Au111 surfaces and self-organize to form highly ordered adlayers with distinct conformations that are consistent with their chemical structures. The faces of the supramolecular rectangle and square lie flat on the surface, preserving their rectangle and square conformations, respectively. The three-dimensional cage also forms well-ordered adlayers on the gold surface, forming regular molecular rows of assemblies. When the rectangle and cage were mixed together, the assemblies separated into individual domains, and no mixed adlayers were observed. These results provide direct evidence of the noncrystalline solid-state structures of these assemblies and information about how they self-organize on Au111 surfaces, which is of importance in the potential manufacturing of functional nanostructures and devices.

Numerical and Experimental Study on Hydrodynamic Performance of A Novel Semi-Submersible Concept

NASA Astrophysics Data System (ADS)

Gao, Song; Tao, Long-bin; Kou, Yu-feng; Lu, Chao; Sun, Jiang-long

2018-04-01

Multiple Column Platform (MCP) semi-submersible is a newly proposed concept, which differs from the conventional semi-submersibles, featuring centre column and middle pontoon. It is paramount to ensure its structural reliability and safe operation at sea, and a rigorous investigation is conducted to examine the hydrodynamic and structural performance for the novel structure concept. In this paper, the numerical and experimental studies on the hydrodynamic performance of MCP are performed. Numerical simulations are conducted in both the frequency and time domains based on 3D potential theory. The numerical models are validated by experimental measurements obtained from extensive sets of model tests under both regular wave and irregular wave conditions. Moreover, a comparative study on MCP and two conventional semi-submersibles are carried out using numerical simulation. Specifically, the hydrodynamic characteristics, including hydrodynamic coefficients, natural periods and motion response amplitude operators (RAOs), mooring line tension are fully examined. The present study proves the feasibility of the novel MCP and demonstrates the potential possibility of optimization in the future study.

Packing Regularities in Biological Structures Relate to Their Dynamics

PubMed Central

Jernigan, Robert L.; Kloczkowski, Andrzej

2007-01-01

The high packing density inside proteins leads to certain geometric regularities and also is one of the most important contributors to the high extent of cooperativity manifested by proteins in their cohesive domain motions. The orientations between neighboring non-bonded residues in proteins substantially follow the similar geometric regularities, regardless of whether the residues are on the surface or buried - a direct result of hydrophobicity forces. These orientations are relatively fixed and correspond closely to small deformations from those of the face-centered cubic lattice, which is the way in which identical spheres pack at the highest density. Packing density also is related to the extent of conservation of residues, and we show this relationship for residue packing densities by averaging over a large sample or residue packings. There are three regimes: 1) over a broad range of packing densities the relationship between sequence entropy and inverse packing density is nearly linear, 2) over a limited range of low packing densities the sequence entropy is nearly constant, and 3) at extremely low packing densities the sequence entropy is highly variable. These packing results provide important justification for the simple elastic network models that have been shown for a large number of proteins to represent protein dynamics so successfully, even when the models are extremely coarse-grained. Elastic network models for polymeric chains are simple and could be combined with these protein elastic networks to represent partially denatured parts of proteins. Finally, we show results of applications of the elastic network model to study the functional motions of the ribosome, based on its known structure. These results indicate expected correlations among its components for the step-wise processing steps in protein synthesis, and suggest ways to use these elastic network models to develop more detailed mechanisms - an important possibility, since most experiments yield only static structures. PMID:16957327

Electrophysiological evidence for a specific neural correlate of musical violation expectation in primary-school children.

PubMed

James, Clara E; Cereghetti, Donato M; Roullet Tribes, Elodie; Oechslin, Mathias S

2015-01-01

The majority of studies on music processing in children used simple musical stimuli. Here, primary schoolchildren judged the appropriateness of musical closure in expressive polyphone music, while high-density electroencephalography was recorded. Stimuli ended either regularly or contained refined in-key harmonic transgressions at closure. The children discriminated the transgressions well above chance. Regular and transgressed endings evoked opposite scalp voltage configurations peaking around 400ms after stimulus onset with bilateral frontal negativity for regular and centro-posterior negativity (CPN) for transgressed endings. A positive correlation could be established between strength of the CPN response and rater sensitivity (d-prime). We also investigated whether the capacity to discriminate the transgressions was supported by auditory domain specific or general cognitive mechanisms, and found that working memory capacity predicted transgression discrimination. Latency and distribution of the CPN are reminiscent of the N400, typically observed in response to semantic incongruities in language. Therefore our observation is intriguing, as the CPN occurred here within an intra-musical context, without any symbols referring to the external world. Moreover, the harmonic in-key transgressions that we implemented may be considered syntactical as they transgress structural rules. Such structural incongruities in music are typically followed by an early right anterior negativity (ERAN) and an N5, but not so here. Putative contributive sources of the CPN were localized in left pre-motor, mid-posterior cingulate and superior parietal regions of the brain that can be linked to integration processing. These results suggest that, at least in children, processing of syntax and meaning may coincide in complex intra-musical contexts. Copyright © 2014 Elsevier Inc. All rights reserved.

Healable supramolecular polymers as organic metals.

PubMed

Armao, Joseph J; Maaloum, Mounir; Ellis, Thomas; Fuks, Gad; Rawiso, Michel; Moulin, Emilie; Giuseppone, Nicolas

2014-08-13

Organic materials exhibiting metallic behavior are promising for numerous applications ranging from printed nanocircuits to large area electronics. However, the optimization of electronic conduction in organic metals such as charge-transfer salts or doped conjugated polymers requires high crystallinity, which is detrimental to their processability. To overcome this problem, the combination of the electronic properties of metal-like materials with the mechanical properties of soft self-assembled systems is attractive but necessitates the absence of structural defects in a regular lattice. Here we describe a one-dimensional supramolecular polymer in which photoinduced through-space charge-transfer complexes lead to highly coherent domains with delocalized electronic states displaying metallic behavior. We also reveal that diffusion of supramolecular polarons in the nanowires repairs structural defects thereby improving their conduction. The ability to access metallic properties from mendable self-assemblies extends the current understanding of both fields and opens a wide range of processing techniques for applications in organic electronics.

Pi-Pi contacts are an overlooked protein feature relevant to phase separation.

PubMed

Vernon, Robert McCoy; Chong, Paul Andrew; Tsang, Brian; Kim, Tae Hun; Bah, Alaji; Farber, Patrick; Lin, Hong; Forman-Kay, Julie Deborah

2018-02-09

Protein phase separation is implicated in formation of membraneless organelles, signaling puncta and the nuclear pore. Multivalent interactions of modular binding domains and their target motifs can drive phase separation. However, forces promoting the more common phase separation of intrinsically disordered regions are less understood, with suggested roles for multivalent cation-pi, pi-pi, and charge interactions and the hydrophobic effect. Known phase-separating proteins are enriched in pi-orbital containing residues and thus we analyzed pi-interactions in folded proteins. We found that pi-pi interactions involving non-aromatic groups are widespread, underestimated by force-fields used in structure calculations and correlated with solvation and lack of regular secondary structure, properties associated with disordered regions. We present a phase separation predictive algorithm based on pi interaction frequency, highlighting proteins involved in biomaterials and RNA processing. © 2018, Vernon et al.

Stability Results, Almost Global Generalized Beltrami Fields and Applications to Vortex Structures in the Euler Equations

NASA Astrophysics Data System (ADS)

Enciso, Alberto; Poyato, David; Soler, Juan

2018-05-01

Strong Beltrami fields, that is, vector fields in three dimensions whose curl is the product of the field itself by a constant factor, have long played a key role in fluid mechanics and magnetohydrodynamics. In particular, they are the kind of stationary solutions of the Euler equations where one has been able to show the existence of vortex structures (vortex tubes and vortex lines) of arbitrarily complicated topology. On the contrary, there are very few results about the existence of generalized Beltrami fields, that is, divergence-free fields whose curl is the field times a non-constant function. In fact, generalized Beltrami fields (which are also stationary solutions to the Euler equations) have been recently shown to be rare, in the sense that for "most" proportionality factors there are no nontrivial Beltrami fields of high enough regularity (e.g., of class {C^{6,α}}), not even locally. Our objective in this work is to show that, nevertheless, there are "many" Beltrami fields with non-constant factor, even realizing arbitrarily complicated vortex structures. This fact is relevant in the study of turbulent configurations. The core results are an "almost global" stability theorem for strong Beltrami fields, which ensures that a global strong Beltrami field with suitable decay at infinity can be perturbed to get "many" Beltrami fields with non-constant factor of arbitrarily high regularity and defined in the exterior of an arbitrarily small ball, and a "local" stability theorem for generalized Beltrami fields, which is an analogous perturbative result which is valid for any kind of Beltrami field (not just with a constant factor) but only applies to small enough domains. The proof relies on an iterative scheme of Grad-Rubin type. For this purpose, we study the Neumann problem for the inhomogeneous Beltrami equation in exterior domains via a boundary integral equation method and we obtain Hölder estimates, a sharp decay at infinity and some compactness properties for these sequences of approximate solutions. Some of the parts of the proof are of independent interest.

An Exemplar-Based Multi-View Domain Generalization Framework for Visual Recognition.

PubMed

Niu, Li; Li, Wen; Xu, Dong; Cai, Jianfei

2018-02-01

In this paper, we propose a new exemplar-based multi-view domain generalization (EMVDG) framework for visual recognition by learning robust classifier that are able to generalize well to arbitrary target domain based on the training samples with multiple types of features (i.e., multi-view features). In this framework, we aim to address two issues simultaneously. First, the distribution of training samples (i.e., the source domain) is often considerably different from that of testing samples (i.e., the target domain), so the performance of the classifiers learnt on the source domain may drop significantly on the target domain. Moreover, the testing data are often unseen during the training procedure. Second, when the training data are associated with multi-view features, the recognition performance can be further improved by exploiting the relation among multiple types of features. To address the first issue, considering that it has been shown that fusing multiple SVM classifiers can enhance the domain generalization ability, we build our EMVDG framework upon exemplar SVMs (ESVMs), in which a set of ESVM classifiers are learnt with each one trained based on one positive training sample and all the negative training samples. When the source domain contains multiple latent domains, the learnt ESVM classifiers are expected to be grouped into multiple clusters. To address the second issue, we propose two approaches under the EMVDG framework based on the consensus principle and the complementary principle, respectively. Specifically, we propose an EMVDG_CO method by adding a co-regularizer to enforce the cluster structures of ESVM classifiers on different views to be consistent based on the consensus principle. Inspired by multiple kernel learning, we also propose another EMVDG_MK method by fusing the ESVM classifiers from different views based on the complementary principle. In addition, we further extend our EMVDG framework to exemplar-based multi-view domain adaptation (EMVDA) framework when the unlabeled target domain data are available during the training procedure. The effectiveness of our EMVDG and EMVDA frameworks for visual recognition is clearly demonstrated by comprehensive experiments on three benchmark data sets.

Higher order total variation regularization for EIT reconstruction.

PubMed

Gong, Bo; Schullcke, Benjamin; Krueger-Ziolek, Sabine; Zhang, Fan; Mueller-Lisse, Ullrich; Moeller, Knut

2018-01-08

Electrical impedance tomography (EIT) attempts to reveal the conductivity distribution of a domain based on the electrical boundary condition. This is an ill-posed inverse problem; its solution is very unstable. Total variation (TV) regularization is one of the techniques commonly employed to stabilize reconstructions. However, it is well known that TV regularization induces staircase effects, which are not realistic in clinical applications. To reduce such artifacts, modified TV regularization terms considering a higher order differential operator were developed in several previous studies. One of them is called total generalized variation (TGV) regularization. TGV regularization has been successively applied in image processing in a regular grid context. In this study, we adapted TGV regularization to the finite element model (FEM) framework for EIT reconstruction. Reconstructions using simulation and clinical data were performed. First results indicate that, in comparison to TV regularization, TGV regularization promotes more realistic images. Graphical abstract Reconstructed conductivity changes located on selected vertical lines. For each of the reconstructed images as well as the ground truth image, conductivity changes located along the selected left and right vertical lines are plotted. In these plots, the notation GT in the legend stands for ground truth, TV stands for total variation method, and TGV stands for total generalized variation method. Reconstructed conductivity distributions from the GREIT algorithm are also demonstrated.

Neurocognitive consequences of cigarette smoking in young adults--a comparison with pre-drug performance.

PubMed

Fried, P A; Watkinson, B; Gray, R

2006-01-01

The present study examined effects of current and past regular cigarette smoking in young adult subjects. One hundred and twelve 17-21-year-old subjects, assessed since infancy, were evaluated using a battery of neurocognitive tests for which commensurate measures were obtained at 9-12 years of age, prior to the initiation of regular smoking. Smokers, determined by urinalysis and self-report, were categorized as heavy (>9 cigarettes per day) and light (<9 cigarettes per day) current smokers and former smokers, the latter having smoked cigarettes regularly in the past but not for at least 6 months. A third of the subjects were currently smoking cigarettes regularly with half of these being heavy smokers. Among former smokers, the average duration of smoking was slightly less than 2 years. Overall IQ, memory, processing speed, vocabulary, attention and abstract reasoning were the primary outcomes with comparisons being made between each of the three user groups and a control group who never smoked regularly. After accounting for potentially confounding factors including clinical assessment, marihuana use and pre-drug performance in the relevant cognitive domain, current regular smokers did significantly worse than non-smokers in a variety of cognitive areas predicated upon verbal/auditory competence including receptive and expressive vocabulary, oral arithmetic, and auditory memory. This impact of current smoking appears to behave in a dose-response and duration-related fashion. In contrast, former smokers differed from the non-smokers only in the arithmetic task. These results suggest that regular smoking during early adulthood is associated with cognitive impairments in selected domains and that these deficits may be reversed upon cessation. Together, the findings add to the body of evidence to be used in persuading adolescents and young adults against the initiation of smoking and, if currently smoking, the advantages of stopping.

Sample entropy and regularity dimension in complexity analysis of cortical surface structure in early Alzheimer's disease and aging.

PubMed

Chen, Ying; Pham, Tuan D

2013-05-15

We apply for the first time the sample entropy (SampEn) and regularity dimension model for measuring signal complexity to quantify the structural complexity of the brain on MRI. The concept of the regularity dimension is based on the theory of chaos for studying nonlinear dynamical systems, where power laws and entropy measure are adopted to develop the regularity dimension for modeling a mathematical relationship between the frequencies with which information about signal regularity changes in various scales. The sample entropy and regularity dimension of MRI-based brain structural complexity are computed for early Alzheimer's disease (AD) elder adults and age and gender-matched non-demented controls, as well as for a wide range of ages from young people to elder adults. A significantly higher global cortical structure complexity is detected in AD individuals (p<0.001). The increase of SampEn and the regularity dimension are also found to be accompanied with aging which might indicate an age-related exacerbation of cortical structural irregularity. The provided model can be potentially used as an imaging bio-marker for early prediction of AD and age-related cognitive decline. Copyright © 2013 Elsevier B.V. All rights reserved.

FAST TRACK COMMUNICATION: Regularized Kerr-Newman solution as a gravitating soliton

NASA Astrophysics Data System (ADS)

Burinskii, Alexander

2010-10-01

The charged, spinning and gravitating soliton is realized as a regular solution of the Kerr-Newman (KN) field coupled with a chiral Higgs model. A regular core of the solution is formed by a domain wall bubble interpolating between the external KN solution and a flat superconducting interior. An internal electromagnetic (em) field is expelled to the boundary of the bubble by the Higgs field. The solution reveals two new peculiarities: (i) the Higgs field is oscillating, similar to the known oscillon models; (ii) the em field forms on the edge of the bubble a Wilson loop, resulting in quantization of the total angular momentum.

Molecular dynamics simulations on discoidal HDL particles suggest a mechanism for rotation in the apo A-I belt model.

PubMed

Klon, Anthony E; Segrest, Jere P; Harvey, Stephen C

2002-12-06

Apolipoprotein A-I (apo A-I) is the major protein component of high-density lipoprotein (HDL) particles. Elevated levels of HDL in the bloodstream have been shown to correlate strongly with a reduced risk factor for atherosclerosis. Molecular dynamics simulations have been carried out on three separate model discoidal high-density lipoprotein particles (HDL) containing two monomers of apo A-I and 160 molecules of palmitoyloleoylphosphatidylcholine (POPC), to a time-scale of 1ns. The starting structures were on the basis of previously published molecular belt models of HDL consisting of the lipid-binding C-terminal domain (residues 44-243) wrapped around the circumference of a discoidal HDL particle. Subtle changes between two of the starting structures resulted in significantly different behavior during the course of the simulation. The results provide support for the hypothesis of Segrest et al. that helical registration in the molecular belt model of apo A-I is modulated by intermolecular salt bridges. In addition, we propose an explanation for the presence of proline punctuation in the molecular belt model, and for the presence of two 11-mer helical repeats interrupting the otherwise regular pattern of 22-mer helical repeats in the lipid-binding domain of apo A-I.

Three-Way Analysis of Spectrospatial Electromyography Data: Classification and Interpretation

PubMed Central

Kauppi, Jukka-Pekka; Hahne, Janne; Müller, Klaus-Robert; Hyvärinen, Aapo

2015-01-01

Classifying multivariate electromyography (EMG) data is an important problem in prosthesis control as well as in neurophysiological studies and diagnosis. With modern high-density EMG sensor technology, it is possible to capture the rich spectrospatial structure of the myoelectric activity. We hypothesize that multi-way machine learning methods can efficiently utilize this structure in classification as well as reveal interesting patterns in it. To this end, we investigate the suitability of existing three-way classification methods to EMG-based hand movement classification in spectrospatial domain, as well as extend these methods by sparsification and regularization. We propose to use Fourier-domain independent component analysis as preprocessing to improve classification and interpretability of the results. In high-density EMG experiments on hand movements across 10 subjects, three-way classification yielded higher average performance compared with state-of-the art classification based on temporal features, suggesting that the three-way analysis approach can efficiently utilize detailed spectrospatial information of high-density EMG. Phase and amplitude patterns of features selected by the classifier in finger-movement data were found to be consistent with known physiology. Thus, our approach can accurately resolve hand and finger movements on the basis of detailed spectrospatial information, and at the same time allows for physiological interpretation of the results. PMID:26039100

The persistence of the attentional bias to regularities in a changing environment.

PubMed

Yu, Ru Qi; Zhao, Jiaying

2015-10-01

The environment often is stable, but some aspects may change over time. The challenge for the visual system is to discover and flexibly adapt to the changes. We examined how attention is shifted in the presence of changes in the underlying structure of the environment. In six experiments, observers viewed four simultaneous streams of objects while performing a visual search task. In the first half of each experiment, the stream in the structured location contained regularities, the shapes in the random location were randomized, and gray squares appeared in two neutral locations. In the second half, the stream in the structured or the random location may change. In the first half of all experiments, visual search was facilitated in the structured location, suggesting that attention was consistently biased toward regularities. In the second half, this bias persisted in the structured location when no change occurred (Experiment 1), when the regularities were removed (Experiment 2), or when new regularities embedded in the original or novel stimuli emerged in the previously random location (Experiments 3 and 6). However, visual search was numerically but no longer reliably faster in the structured location when the initial regularities were removed and new regularities were introduced in the previously random location (Experiment 4), or when novel random stimuli appeared in the random location (Experiment 5). This suggests that the attentional bias was weakened. Overall, the results demonstrate that the attentional bias to regularities was persistent but also sensitive to changes in the environment.

The full Keller-Segel model is well-posed on nonsmooth domains

NASA Astrophysics Data System (ADS)

Horstmann, D.; Meinlschmidt, H.; Rehberg, J.

2018-04-01

In this paper we prove that the full Keller-Segel system, a quasilinear strongly coupled reaction-crossdiffusion system of four parabolic equations, is well-posed in the sense that it always admits an unique local-in-time solution in an adequate function space, provided that the initial values are suitably regular. The proof is done via an abstract solution theorem for nonlocal quasilinear equations by Amann and is carried out for general source terms. It is fundamentally based on recent nontrivial elliptic and parabolic regularity results which hold true even on rather general nonsmooth spatial domains. For space dimensions 2 and 3, this enables us to work in a nonsmooth setting which is not available in classical parabolic systems theory. Apparently, there exists no comparable existence result for the full Keller-Segel system up to now. Due to the large class of possibly nonsmooth domains admitted, we also obtain new results for the ‘standard’ Keller-Segel system consisting of only two equations as a special case. This work is dedicated to Prof Willi Jäger.

Domainal cleavage as an Anisotropic Reaction-diffusion Process

NASA Astrophysics Data System (ADS)

Mulchrone, Kieran; Meere, Patrick

2017-04-01

Domainal cleavage comprises zones dominated by quartz and feldspar (QF-domains) and zones dominated by Mica (M-domains) which form at low metamorphic grades. The protolith is typically fairly homogeneous mudstone, siltstone, sandstone or limestone. Wet diffusion or pressure solution along grain boundaries is a key mechanism in the development of domanial cleavage. However, this does not explain why M-domains become sub-regularly spaced, visually evident in coarser-grained rocks, and take on an anastomising morphology. The ratio of M to QF-domains by volume can range from 1 to 0.1 and lower i.e. in extreme cases M-domains are intermittent but regularly spaced. It is suggested here that an anisotropic reaction-diffusion process model can explain these features. The imposed stress field instantaneously leads to anisotropy of diffusion by narrowing intergranular channels perpendicular to the principal stress. This leads to a preferred diffusion of chemicals parallel to the principal stress direction and lower diffusion rates in the normal direction. Combining this with the chemical reaction of pressure solution produces an anisotropic reaction-diffusion system. Both isotropic and anistropic reaction diffusion systems lead to pattern formation as discovered by Alan Turing on the 1950's as an explanation for patterns found in animal skins such as spots and stripes. Thus domanial cleavage is a striped pattern induced by diffusion anisotropy combined with a chemical reaction. Furthermore, rates of chemical reaction in intergranular fluids is likely to be many orders of magnitude greater that rates of deformation. Therefore we expect domanial cleavage to form relatively rapidly. As deformation progresses the M-domains behave less competently and may be the site of enhanced shearing. An example from Co. Cork, Ireland demonstrates shear folding in low-grade metasedimentary rocks with reverse shear along M-domains at a high angle to the maximum compressive stress.

Social isolation in mental health: a conceptual and methodological review.

PubMed

Wang, Jingyi; Lloyd-Evans, Brynmor; Giacco, Domenico; Forsyth, Rebecca; Nebo, Cynthia; Mann, Farhana; Johnson, Sonia

2017-12-01

Social isolation and related concepts have been discussed increasingly in the field of mental health. Despite this, there is a lack of conceptual clarity and consistency in the definition and operationalisation of these terms. This review aimed to provide a clear framework for social isolation and related concepts, and to identify well-established measures in the field of mental health for each conceptual domain discussed. We used an iterative strategy of expert consultation and literature searching. A multi-disciplinary group of senior academics was consulted both before and after the literature searching to identify relevant terms, conceptual papers, or recommended measures. Our conceptual framework was also validated through expert consultation. We searched the Web of Science database using terms suggested by experts and subsequently identified further relevant studies through review articles and by reading full texts and reference lists of included studies. A narrative synthesis was conducted. We developed a model with five domains incorporating all the concepts relevant to social isolation in regular use in the mental health research literature. These five domains are: social network-quantity; social network-structure; social network-quality; appraisal of relationships-emotional; and appraisal of relationships-resources. We also identified well-developed measures suitable for assessing each of the five conceptual domains or covering multi-domains. Our review proposes a conceptual model to encompass and differentiate all terms relating to social isolation. Potential uses are in allowing researchers and intervention developers to identify precisely the intended outcomes of interventions, and to choose the most appropriate measures to use in mental health settings.

Nanofabrication and coloration study of artificial Morpho butterfly wings with aligned lamellae layers

PubMed Central

Zhang, Sichao; Chen, Yifang

2015-01-01

The bright and iridescent blue color from Morpho butterfly wings has attracted worldwide attentions to explore its mysterious nature for long time. Although the physics of structural color by the nanophotonic structures built on the wing scales has been well established, replications of the wing structure by standard top-down lithography still remains a challenge. This paper reports a technical breakthrough to mimic the blue color of Morpho butterfly wings, by developing a novel nanofabrication process, based on electron beam lithography combined with alternate PMMA/LOR development/dissolution, for photonic structures with aligned lamellae multilayers in colorless polymers. The relationship between the coloration and geometric dimensions as well as shapes is systematically analyzed by solving Maxwell’s Equations with a finite domain time difference simulator. Careful characterization of the mimicked blue by spectral measurements under both normal and oblique angles are carried out. Structural color in blue reflected by the fabricated wing scales, is demonstrated and further extended to green as an application exercise of the new technique. The effects of the regularity in the replicas on coloration are analyzed. In principle, this approach establishes a starting point for mimicking structural colors beyond the blue in Morpho butterfly wings. PMID:26577813

The spatial distributions of large gap-like structure on Fe(Se,Te) single crystals observed by STM/STS

NASA Astrophysics Data System (ADS)

Sugimoto, Akira; Sakai, Yuta; Nagasaka, Kouhei; Ekino, Toshikazu

2015-11-01

The nanoscale spatial distributions of large gap-like structure on superconducting FeSe1-xTex were investigated by scanning tunneling microscopy/spectroscopy (STM/STS). The STM topography shows regular atomic lattice arrangements with the lattice spacing ∼0.38 nm, together with the randomly distributed large spots due to the excess Fe atoms. From the STS measurements, the small gap structures of Δ ∼ 7 meV were partly observed. On the other hand, the high-bias dI/dV curves exhibit the broad peak structures at the negative biases of VPG = -200 to -400 mV in the measured whole surface area. The average of these large gaps is |VPGave| ∼ 305 mV with the standard deviation of σ ∼ 48 mV. The spatial distributions of the VPG exhibit the domain structures consisting of the relatively smaller gaps (<250 meV), which correspond to the excess Fe positions. The small gap Δ ∼ 7 meV is also observed at those positions, suggesting that the excess Fe affects the electronic structures of FeSe1-xTex.

Nanofabrication and coloration study of artificial Morpho butterfly wings with aligned lamellae layers.

PubMed

Zhang, Sichao; Chen, Yifang

2015-11-18

The bright and iridescent blue color from Morpho butterfly wings has attracted worldwide attentions to explore its mysterious nature for long time. Although the physics of structural color by the nanophotonic structures built on the wing scales has been well established, replications of the wing structure by standard top-down lithography still remains a challenge. This paper reports a technical breakthrough to mimic the blue color of Morpho butterfly wings, by developing a novel nanofabrication process, based on electron beam lithography combined with alternate PMMA/LOR development/dissolution, for photonic structures with aligned lamellae multilayers in colorless polymers. The relationship between the coloration and geometric dimensions as well as shapes is systematically analyzed by solving Maxwell's Equations with a finite domain time difference simulator. Careful characterization of the mimicked blue by spectral measurements under both normal and oblique angles are carried out. Structural color in blue reflected by the fabricated wing scales, is demonstrated and further extended to green as an application exercise of the new technique. The effects of the regularity in the replicas on coloration are analyzed. In principle, this approach establishes a starting point for mimicking structural colors beyond the blue in Morpho butterfly wings.

Nanofabrication and coloration study of artificial Morpho butterfly wings with aligned lamellae layers

NASA Astrophysics Data System (ADS)

Zhang, Sichao; Chen, Yifang

2015-11-01

The bright and iridescent blue color from Morpho butterfly wings has attracted worldwide attentions to explore its mysterious nature for long time. Although the physics of structural color by the nanophotonic structures built on the wing scales has been well established, replications of the wing structure by standard top-down lithography still remains a challenge. This paper reports a technical breakthrough to mimic the blue color of Morpho butterfly wings, by developing a novel nanofabrication process, based on electron beam lithography combined with alternate PMMA/LOR development/dissolution, for photonic structures with aligned lamellae multilayers in colorless polymers. The relationship between the coloration and geometric dimensions as well as shapes is systematically analyzed by solving Maxwell’s Equations with a finite domain time difference simulator. Careful characterization of the mimicked blue by spectral measurements under both normal and oblique angles are carried out. Structural color in blue reflected by the fabricated wing scales, is demonstrated and further extended to green as an application exercise of the new technique. The effects of the regularity in the replicas on coloration are analyzed. In principle, this approach establishes a starting point for mimicking structural colors beyond the blue in Morpho butterfly wings.

Predicting Health Care Utilization in Marginalized Populations: Black, Female, Street-based Sex Workers

PubMed Central

Varga, Leah M.; Surratt, Hilary L.

2014-01-01

Background Patterns of social and structural factors experienced by vulnerable populations may negatively affect willingness and ability to seek out health care services, and ultimately, their health. Methods The outcome variable was utilization of health care services in the previous 12 months. Using Andersen’s Behavioral Model for Vulnerable Populations, we examined self-reported data on utilization of health care services among a sample of 546 Black, street-based female sex workers in Miami, Florida. To evaluate the impact of each domain of the model on predicting health care utilization, domains were included in the logistic regression analysis by blocks using the traditional variables first and then adding the vulnerable domain variables. Findings The most consistent variables predicting health care utilization were having a regular source of care and self-rated health. The model that included only enabling variables was the most efficient model in predicting health care utilization. Conclusions Any type of resource, link, or connection to or with an institution, or any consistent point of care contributes significantly to health care utilization behaviors. A consistent and reliable source for health care may increase health care utilization and subsequently decrease health disparities among vulnerable and marginalized populations, as well as contribute to public health efforts that encourage preventive health. PMID:24657047

Comparison of level discrimination, increment detection, and comodulation masking release in the audio- and envelope-frequency domains

PubMed Central

Nelson, Paul C.; Ewert, Stephan D.; Carney, Laurel H.; Dau, Torsten

2008-01-01

In general, the temporal structure of stimuli must be considered to account for certain observations made in detection and masking experiments in the audio-frequency domain. Two such phenomena are (1) a heightened sensitivity to amplitude increments with a temporal fringe compared to gated level discrimination performance and (2) lower tone-in-noise detection thresholds using a modulated masker compared to those using an unmodulated masker. In the current study, translations of these two experiments were carried out to test the hypothesis that analogous cues might be used in the envelope-frequency domain. Pure-tone carrier amplitude-modulation (AM) depth-discrimination thresholds were found to be similar using both traditional gated stimuli and using a temporally modulated fringe for a fixed standard depth (ms=0.25) and a range of AM frequencies (4-64 Hz). In a second experiment, masked sinusoidal AM detection thresholds were compared in conditions with and without slow and regular fluctuations imposed on the instantaneous masker AM depth. Release from masking was obtained only for very slow masker fluctuations (less than 2 Hz). A physiologically motivated model that effectively acts as a first-order envelope change detector accounted for several, but not all, of the key aspects of the data. PMID:17471731

The respective roles of polar/nonpolar binary patterns and amino acid composition in protein regular secondary structures explored exhaustively using hydrophobic cluster analysis.

PubMed

Rebehmed, Joseph; Quintus, Flavien; Mornon, Jean-Paul; Callebaut, Isabelle

2016-05-01

Several studies have highlighted the leading role of the sequence periodicity of polar and nonpolar amino acids (binary patterns) in the formation of regular secondary structures (RSS). However, these were based on the analysis of only a few simple cases, with no direct mean to correlate binary patterns with the limits of RSS. Here, HCA-derived hydrophobic clusters (HC) which are conditioned binary patterns whose positions fit well those of RSS, were considered. All the HC types, defined by unique binary patterns, which were commonly observed in three-dimensional (3D) structures of globular domains, were analyzed. The 180 HC types with preferences for either α-helices or β-strands distinctly contain basic binary units typical of these RSS. Therefore a general trend supporting the "binary pattern preference" assumption was observed. HC for which observed RSS are in disagreement with their expected behavior (discordant HC) were also examined. They were separated in HC types with moderate preferences for RSS, having "weak" binary patterns and versatile RSS and HC types with high preferences for RSS, having "strong" binary patterns and then displaying nonpolar amino acids at the protein surface. It was shown that in both cases, discordant HC could be distinguished from concordant ones by well-differentiated amino acid compositions. The obtained results could, thus, help to complement the currently available methods for the accurate prediction of secondary structures in proteins from the only information of a single amino acid sequence. This can be especially useful for characterizing orphan sequences and for assisting protein engineering and design. © 2016 Wiley Periodicals, Inc.

Zinc Fingers, TALEs, and CRISPR Systems: A Comparison of Tools for Epigenome Editing.

PubMed

Waryah, Charlene Babra; Moses, Colette; Arooj, Mahira; Blancafort, Pilar

2018-01-01

The completion of genome, epigenome, and transcriptome mapping in multiple cell types has created a demand for precision biomolecular tools that allow researchers to functionally manipulate DNA, reconfigure chromatin structure, and ultimately reshape gene expression patterns. Epigenetic editing tools provide the ability to interrogate the relationship between epigenetic modifications and gene expression. Importantly, this information can be exploited to reprogram cell fate for both basic research and therapeutic applications. Three different molecular platforms for epigenetic editing have been developed: zinc finger proteins (ZFs), transcription activator-like effectors (TALEs), and the system of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated (Cas) proteins. These platforms serve as custom DNA-binding domains (DBDs), which are fused to epigenetic modifying domains to manipulate epigenetic marks at specific sites in the genome. The addition and/or removal of epigenetic modifications reconfigures local chromatin structure, with the potential to provoke long-lasting changes in gene transcription. Here we summarize the molecular structure and mechanism of action of ZF, TALE, and CRISPR platforms and describe their applications for the locus-specific manipulation of the epigenome. The advantages and disadvantages of each platform will be discussed with regard to genomic specificity, potency in regulating gene expression, and reprogramming cell phenotypes, as well as ease of design, construction, and delivery. Finally, we outline potential applications for these tools in molecular biology and biomedicine and identify possible barriers to their future clinical implementation.

The Cognitive Advantages of Counting Specifically: A Representational Analysis of Verbal Numeration Systems in Oceanic Languages.

PubMed

Bender, Andrea; Schlimm, Dirk; Beller, Sieghard

2015-10-01

The domain of numbers provides a paradigmatic case for investigating interactions of culture, language, and cognition: Numerical competencies are considered a core domain of knowledge, and yet the development of specifically human abilities presupposes cultural and linguistic input by way of counting sequences. These sequences constitute systems with distinct structural properties, the cross-linguistic variability of which has implications for number representation and processing. Such representational effects are scrutinized for two types of verbal numeration systems-general and object-specific ones-that were in parallel use in several Oceanic languages (English with its general system is included for comparison). The analysis indicates that the object-specific systems outperform the general systems with respect to counting and mental arithmetic, largely due to their regular and more compact representation. What these findings reveal on cognitive diversity, how the conjectures involved speak to more general issues in cognitive science, and how the approach taken here might help to bridge the gap between anthropology and other cognitive sciences is discussed in the conclusion. Copyright © 2015 Cognitive Science Society, Inc.

High-Frequency Subband Compressed Sensing MRI Using Quadruplet Sampling

PubMed Central

Sung, Kyunghyun; Hargreaves, Brian A

2013-01-01

Purpose To presents and validates a new method that formalizes a direct link between k-space and wavelet domains to apply separate undersampling and reconstruction for high- and low-spatial-frequency k-space data. Theory and Methods High- and low-spatial-frequency regions are defined in k-space based on the separation of wavelet subbands, and the conventional compressed sensing (CS) problem is transformed into one of localized k-space estimation. To better exploit wavelet-domain sparsity, CS can be used for high-spatial-frequency regions while parallel imaging can be used for low-spatial-frequency regions. Fourier undersampling is also customized to better accommodate each reconstruction method: random undersampling for CS and regular undersampling for parallel imaging. Results Examples using the proposed method demonstrate successful reconstruction of both low-spatial-frequency content and fine structures in high-resolution 3D breast imaging with a net acceleration of 11 to 12. Conclusion The proposed method improves the reconstruction accuracy of high-spatial-frequency signal content and avoids incoherent artifacts in low-spatial-frequency regions. This new formulation also reduces the reconstruction time due to the smaller problem size. PMID:23280540

Protein domain assignment from the recurrence of locally similar structures

PubMed Central

Tai, Chin-Hsien; Sam, Vichetra; Gibrat, Jean-Francois; Garnier, Jean; Munson, Peter J.

2010-01-01

Domains are basic units of protein structure and essential for exploring protein fold space and structure evolution. With the structural genomics initiative, the number of protein structures in the Protein Databank (PDB) is increasing dramatically and domain assignments need to be done automatically. Most existing structural domain assignment programs define domains using the compactness of the domains and/or the number and strength of intra-domain versus inter-domain contacts. Here we present a different approach based on the recurrence of locally similar structural pieces (LSSPs) found by one-against-all structure comparisons with a dataset of 6,373 protein chains from the PDB. Residues of the query protein are clustered using LSSPs via three different procedures to define domains. This approach gives results that are comparable to several existing programs that use geometrical and other structural information explicitly. Remarkably, most of the proteins that contribute the LSSPs defining a domain do not themselves contain the domain of interest. This study shows that domains can be defined by a collection of relatively small locally similar structural pieces containing, on average, four secondary structure elements. In addition, it indicates that domains are indeed made of recurrent small structural pieces that are used to build protein structures of many different folds as suggested by recent studies. PMID:21287617

MODBASE, a database of annotated comparative protein structure models

PubMed Central

Pieper, Ursula; Eswar, Narayanan; Stuart, Ashley C.; Ilyin, Valentin A.; Sali, Andrej

2002-01-01

MODBASE (http://guitar.rockefeller.edu/modbase) is a relational database of annotated comparative protein structure models for all available protein sequences matched to at least one known protein structure. The models are calculated by MODPIPE, an automated modeling pipeline that relies on PSI-BLAST, IMPALA and MODELLER. MODBASE uses the MySQL relational database management system for flexible and efficient querying, and the MODVIEW Netscape plugin for viewing and manipulating multiple sequences and structures. It is updated regularly to reflect the growth of the protein sequence and structure databases, as well as improvements in the software for calculating the models. For ease of access, MODBASE is organized into different datasets. The largest dataset contains models for domains in 304 517 out of 539 171 unique protein sequences in the complete TrEMBL database (23 March 2001); only models based on significant alignments (PSI-BLAST E-value < 10–4) and models assessed to have the correct fold are included. Other datasets include models for target selection and structure-based annotation by the New York Structural Genomics Research Consortium, models for prediction of genes in the Drosophila melanogaster genome, models for structure determination of several ribosomal particles and models calculated by the MODWEB comparative modeling web server. PMID:11752309

Downscaling Satellite Precipitation with Emphasis on Extremes: A Variational ℓ1-Norm Regularization in the Derivative Domain

NASA Astrophysics Data System (ADS)

Foufoula-Georgiou, E.; Ebtehaj, A. M.; Zhang, S. Q.; Hou, A. Y.

2014-05-01

The increasing availability of precipitation observations from space, e.g., from the Tropical Rainfall Measuring Mission (TRMM) and the forthcoming Global Precipitation Measuring (GPM) Mission, has fueled renewed interest in developing frameworks for downscaling and multi-sensor data fusion that can handle large data sets in computationally efficient ways while optimally reproducing desired properties of the underlying rainfall fields. Of special interest is the reproduction of extreme precipitation intensities and gradients, as these are directly relevant to hazard prediction. In this paper, we present a new formalism for downscaling satellite precipitation observations, which explicitly allows for the preservation of some key geometrical and statistical properties of spatial precipitation. These include sharp intensity gradients (due to high-intensity regions embedded within lower-intensity areas), coherent spatial structures (due to regions of slowly varying rainfall), and thicker-than-Gaussian tails of precipitation gradients and intensities. Specifically, we pose the downscaling problem as a discrete inverse problem and solve it via a regularized variational approach (variational downscaling) where the regularization term is selected to impose the desired smoothness in the solution while allowing for some steep gradients (called ℓ1-norm or total variation regularization). We demonstrate the duality between this geometrically inspired solution and its Bayesian statistical interpretation, which is equivalent to assuming a Laplace prior distribution for the precipitation intensities in the derivative (wavelet) space. When the observation operator is not known, we discuss the effect of its misspecification and explore a previously proposed dictionary-based sparse inverse downscaling methodology to indirectly learn the observation operator from a data base of coincidental high- and low-resolution observations. The proposed method and ideas are illustrated in case studies featuring the downscaling of a hurricane precipitation field.

Downscaling Satellite Precipitation with Emphasis on Extremes: A Variational 1-Norm Regularization in the Derivative Domain

NASA Technical Reports Server (NTRS)

Foufoula-Georgiou, E.; Ebtehaj, A. M.; Zhang, S. Q.; Hou, A. Y.

2013-01-01

The increasing availability of precipitation observations from space, e.g., from the Tropical Rainfall Measuring Mission (TRMM) and the forthcoming Global Precipitation Measuring (GPM) Mission, has fueled renewed interest in developing frameworks for downscaling and multi-sensor data fusion that can handle large data sets in computationally efficient ways while optimally reproducing desired properties of the underlying rainfall fields. Of special interest is the reproduction of extreme precipitation intensities and gradients, as these are directly relevant to hazard prediction. In this paper, we present a new formalism for downscaling satellite precipitation observations, which explicitly allows for the preservation of some key geometrical and statistical properties of spatial precipitation. These include sharp intensity gradients (due to high-intensity regions embedded within lower-intensity areas), coherent spatial structures (due to regions of slowly varying rainfall),and thicker-than-Gaussian tails of precipitation gradients and intensities. Specifically, we pose the downscaling problem as a discrete inverse problem and solve it via a regularized variational approach (variational downscaling) where the regularization term is selected to impose the desired smoothness in the solution while allowing for some steep gradients(called 1-norm or total variation regularization). We demonstrate the duality between this geometrically inspired solution and its Bayesian statistical interpretation, which is equivalent to assuming a Laplace prior distribution for the precipitation intensities in the derivative (wavelet) space. When the observation operator is not known, we discuss the effect of its misspecification and explore a previously proposed dictionary-based sparse inverse downscaling methodology to indirectly learn the observation operator from a database of coincidental high- and low-resolution observations. The proposed method and ideas are illustrated in case studies featuring the downscaling of a hurricane precipitation field.

Adaptive eigenspace method for inverse scattering problems in the frequency domain

NASA Astrophysics Data System (ADS)

Grote, Marcus J.; Kray, Marie; Nahum, Uri

2017-02-01

A nonlinear optimization method is proposed for the solution of inverse scattering problems in the frequency domain, when the scattered field is governed by the Helmholtz equation. The time-harmonic inverse medium problem is formulated as a PDE-constrained optimization problem and solved by an inexact truncated Newton-type iteration. Instead of a grid-based discrete representation, the unknown wave speed is projected to a particular finite-dimensional basis of eigenfunctions, which is iteratively adapted during the optimization. Truncating the adaptive eigenspace (AE) basis at a (small and slowly increasing) finite number of eigenfunctions effectively introduces regularization into the inversion and thus avoids the need for standard Tikhonov-type regularization. Both analytical and numerical evidence underpins the accuracy of the AE representation. Numerical experiments demonstrate the efficiency and robustness to missing or noisy data of the resulting adaptive eigenspace inversion method.

Production of Supra-regular Spatial Sequences by Macaque Monkeys.

PubMed

Jiang, Xinjian; Long, Tenghai; Cao, Weicong; Li, Junru; Dehaene, Stanislas; Wang, Liping

2018-06-18

Understanding and producing embedded sequences in language, music, or mathematics, is a central characteristic of our species. These domains are hypothesized to involve a human-specific competence for supra-regular grammars, which can generate embedded sequences that go beyond the regular sequences engendered by finite-state automata. However, is this capacity truly unique to humans? Using a production task, we show that macaque monkeys can be trained to produce time-symmetrical embedded spatial sequences whose formal description requires supra-regular grammars or, equivalently, a push-down stack automaton. Monkeys spontaneously generalized the learned grammar to novel sequences, including longer ones, and could generate hierarchical sequences formed by an embedding of two levels of abstract rules. Compared to monkeys, however, preschool children learned the grammars much faster using a chunking strategy. While supra-regular grammars are accessible to nonhuman primates through extensive training, human uniqueness may lie in the speed and learning strategy with which they are acquired. Copyright © 2018 Elsevier Ltd. All rights reserved.

Identifing Atmospheric Pollutant Sources Using Artificial Neural Networks

NASA Astrophysics Data System (ADS)

Paes, F. F.; Campos, H. F.; Luz, E. P.; Carvalho, A. R.

2008-05-01

The estimation of the area source pollutant strength is a relevant issue for atmospheric environment. This characterizes an inverse problem in the atmospheric pollution dispersion. In the inverse analysis, an area source domain is considered, where the strength of such area source term is assumed unknown. The inverse problem is solved by using a supervised artificial neural network: multi-layer perceptron. The conection weights of the neural network are computed from delta rule - learning process. The neural network inversion is compared with results from standard inverse analysis (regularized inverse solution). In the regularization method, the inverse problem is formulated as a non-linear optimization approach, whose the objective function is given by the square difference between the measured pollutant concentration and the mathematical models, associated with a regularization operator. In our numerical experiments, the forward problem is addressed by a source-receptor scheme, where a regressive Lagrangian model is applied to compute the transition matrix. The second order maximum entropy regularization is used, and the regularization parameter is calculated by the L-curve technique. The objective function is minimized employing a deterministic scheme (a quasi-Newton algorithm) [1] and a stochastic technique (PSO: particle swarm optimization) [2]. The inverse problem methodology is tested with synthetic observational data, from six measurement points in the physical domain. The best inverse solutions were obtained with neural networks. References: [1] D. R. Roberti, D. Anfossi, H. F. Campos Velho, G. A. Degrazia (2005): Estimating Emission Rate and Pollutant Source Location, Ciencia e Natura, p. 131-134. [2] E.F.P. da Luz, H.F. de Campos Velho, J.C. Becceneri, D.R. Roberti (2007): Estimating Atmospheric Area Source Strength Through Particle Swarm Optimization. Inverse Problems, Desing and Optimization Symposium IPDO-2007, April 16-18, Miami (FL), USA, vol 1, p. 354-359.

A comprehensive numerical analysis of background phase correction with V-SHARP.

PubMed

Özbay, Pinar Senay; Deistung, Andreas; Feng, Xiang; Nanz, Daniel; Reichenbach, Jürgen Rainer; Schweser, Ferdinand

2017-04-01

Sophisticated harmonic artifact reduction for phase data (SHARP) is a method to remove background field contributions in MRI phase images, which is an essential processing step for quantitative susceptibility mapping (QSM). To perform SHARP, a spherical kernel radius and a regularization parameter need to be defined. In this study, we carried out an extensive analysis of the effect of these two parameters on the corrected phase images and on the reconstructed susceptibility maps. As a result of the dependence of the parameters on acquisition and processing characteristics, we propose a new SHARP scheme with generalized parameters. The new SHARP scheme uses a high-pass filtering approach to define the regularization parameter. We employed the variable-kernel SHARP (V-SHARP) approach, using different maximum radii (R m ) between 1 and 15 mm and varying regularization parameters (f) in a numerical brain model. The local root-mean-square error (RMSE) between the ground-truth, background-corrected field map and the results from SHARP decreased towards the center of the brain. RMSE of susceptibility maps calculated with a spatial domain algorithm was smallest for R m between 6 and 10 mm and f between 0 and 0.01 mm -1 , and for maps calculated with a Fourier domain algorithm for R m between 10 and 15 mm and f between 0 and 0.0091 mm -1 . We demonstrated and confirmed the new parameter scheme in vivo. The novel regularization scheme allows the use of the same regularization parameter irrespective of other imaging parameters, such as image resolution. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

A physical model describing the interaction of nuclear transport receptors with FG nucleoporin domain assemblies.

PubMed

Zahn, Raphael; Osmanović, Dino; Ehret, Severin; Araya Callis, Carolina; Frey, Steffen; Stewart, Murray; You, Changjiang; Görlich, Dirk; Hoogenboom, Bart W; Richter, Ralf P

2016-04-08

The permeability barrier of nuclear pore complexes (NPCs) controls bulk nucleocytoplasmic exchange. It consists of nucleoporin domains rich in phenylalanine-glycine motifs (FG domains). As a bottom-up nanoscale model for the permeability barrier, we have used planar films produced with three different end-grafted FG domains, and quantitatively analyzed the binding of two different nuclear transport receptors (NTRs), NTF2 and Importin β, together with the concomitant film thickness changes. NTR binding caused only moderate changes in film thickness; the binding isotherms showed negative cooperativity and could all be mapped onto a single master curve. This universal NTR binding behavior - a key element for the transport selectivity of the NPC - was quantitatively reproduced by a physical model that treats FG domains as regular, flexible polymers, and NTRs as spherical colloids with a homogeneous surface, ignoring the detailed arrangement of interaction sites along FG domains and on the NTR surface.

Physical Activity and Cognitive Development: A Meta-Analysis.

PubMed

Jackson, William M; Davis, Nicholas; Sands, Stephen A; Whittington, Robert A; Sun, Lena S

2016-10-01

Is there an association between regular exercise, defined as a structured program of increased physical activity at least 1 month in duration, and improvements in measures of executive functions compared with children who engage in their normal daily activities? The association between increased physical activity and changes in performance on tasks of executive functions have not been well elucidated in children. Executive functioning is important to intellectual development and academic success in children, and inexpensive, nonpharmacological methods for the treatment of executive dysfunction represent an attractive interventional target. To estimate the effect of a structured regular exercise program on neuropsychological domains of executive function in children ages 7 to 12. We performed a systematic review of English and non-English articles using Cochrane Library, EBSCO CINAHL, Ovid MEDLINE, PSYCInfo, Pubmed, and Web of Science, including all years allowed by each individual search engine. The search string used was "(exercise OR phys*) AND (cognit* OR executive) AND (child* OR preadolesc*)." The authors of the studies selected for review were contacted for any unpublished data. Randomized controlled trials, which enrolled children between the ages of 7 and 12, with randomization to either normal activity or a structured physical activity intervention consisting of scheduled aerobic exercise, at least once per week, for a period of at least 1 month. Eligible studies must have included a neuropsychological battery of tests that measured at least 1 executive function both before and after the intervention was completed. Two independent reviewers examined the screened studies in detail for potential inclusion. The results of the individual examinations were compared; if any discrepancies were present, a third party analyzed the study to determine if it should be included in the meta-analysis. A total of 18 studies were identified by abstract as candidates for inclusion. From these 18 studies, 8 were independently selected by 2 authors for inclusion in the final analysis; there were no selection discrepancies between authors with regard to the studies to be included. In all, 770 subjects were included, 339 in the control group and 431 in the intervention group. All 8 studies contained a measure of inhibitory control; no other domain of executive function was measured frequently enough to perform meta-analysis, so only measures of inhibitory control were pooled and analyzed. A Cohen d effect size was calculated for each measure using the method of Morris for controlled pre-post control measurement studies. The studies were then combined in a random effects model using Comprehensive Meta Analysis software (Biostat, Englewood, NJ) for Windows (Microsoft, Redmond, WA). All studies showed a positive effect of regular exercise with improvements in measures of inhibitory control, but none were statistically significant for this measure. When pooled, the model revealed a combined Cohen d effect size of 0.2 (95% confidence interval, 0.03-0.37; P=0.021), indicating a small improvement of inhibitory control with long-term physical activity. Heterogeneity was very low (I=0). Many studies used different neuropsychological tests to assess inhibitory control, which may have introduced unforeseen confounders. Other domains of executive functions were not measured frequently enough to perform meta-analysis. Despite attempts to gather unpublished data, positive results were observed in all of the included studies, raising the possibility of publication bias. Increased regular physical activity is associated with a small and measurable, improvement in neuropsychological tests of executive functions, specifically inhibitory control. Executive functions play an important role in complex behavior, and may contribute to academic and career achievement as well as success in social interaction. This finding provides support for the important interaction between exercise and cognitive functioning.

What can we learn about beat perception by comparing brain signals and stimulus envelopes?

PubMed

Henry, Molly J; Herrmann, Björn; Grahn, Jessica A

2017-01-01

Entrainment of neural oscillations on multiple time scales is important for the perception of speech. Musical rhythms, and in particular the perception of a regular beat in musical rhythms, is also likely to rely on entrainment of neural oscillations. One recently proposed approach to studying beat perception in the context of neural entrainment and resonance (the "frequency-tagging" approach) has received an enthusiastic response from the scientific community. A specific version of the approach involves comparing frequency-domain representations of acoustic rhythm stimuli to the frequency-domain representations of neural responses to those rhythms (measured by electroencephalography, EEG). The relative amplitudes at specific EEG frequencies are compared to the relative amplitudes at the same stimulus frequencies, and enhancements at beat-related frequencies in the EEG signal are interpreted as reflecting an internal representation of the beat. Here, we show that frequency-domain representations of rhythms are sensitive to the acoustic features of the tones making up the rhythms (tone duration, onset/offset ramp duration); in fact, relative amplitudes at beat-related frequencies can be completely reversed by manipulating tone acoustics. Crucially, we show that changes to these acoustic tone features, and in turn changes to the frequency-domain representations of rhythms, do not affect beat perception. Instead, beat perception depends on the pattern of onsets (i.e., whether a rhythm has a simple or complex metrical structure). Moreover, we show that beat perception can differ for rhythms that have numerically identical frequency-domain representations. Thus, frequency-domain representations of rhythms are dissociable from beat perception. For this reason, we suggest caution in interpreting direct comparisons of rhythms and brain signals in the frequency domain. Instead, we suggest that combining EEG measurements of neural signals with creative behavioral paradigms is of more benefit to our understanding of beat perception.

On the persistence of spatiotemporal oscillations generated by invasion

NASA Astrophysics Data System (ADS)

Kay, A. L.; Sherratt, J. A.

1999-10-01

Many systems in biology and chemistry are oscillatory, with a stable, spatially homogeneous steady state which consists of periodic temporal oscillations in the interacting species, and such systems have been extensively studied on infinite or semi-infinite spatial domains. We consider the effect of a finite domain, with zero-flux boundary conditions, on the behaviour of solutions to oscillatory reaction-diffusion equations after invasion. We begin by considering numerical simulations of various oscillatory predatory-prey systems. We conclude that when regular spatiotemporal oscillations are left in the wake of invasion, these die out, beginning with a decrease in the spatial frequency of the oscillations at one boundary, which then propagates across the domain. The long-time solution in this case is purely temporal oscillations, corresponding to the limit cycle of the kinetics. Contrastingly, when irregular spatiotemporal oscillations are left in the wake of invasion, they persist, even in very long time simulations. To study this phenomenon in more detail, we consider the {lambda}-{omega} class of reaction-diffusion systems. Numerical simulations show that these systems also exhibit die-out of regular spatiotemporal oscillations and persistence of irregular spatiotemporal oscillations. Exploiting the mathematical simplicity of the {lambda}-{omega} form, we derive analytically an approximation to the transition fronts in r and {theta}x which occur during the die-out of the regular oscillations. We then use this approximation to describe how the die-out occurs, and to derive a measure of its rate, as a function of parameter values. We discuss applications of our results to ecology, calcium signalling and chemistry.

Nonlinear dynamics of skin blood flow response to mechanical and thermal stresses in the plantar foot of diabetics with peripheral neuropathy.

PubMed

Liao, Fuyuan; Jan, Yih-Kuen

2017-01-01

Diabetic foot ulcers (DFU) are a major complication in diabetics. Impaired microvascular reactivity is a major contributor to the development of DFU and has been traditionally quantified by time-domain or frequency-domain measures of skin blood flow (SBF). These measures, however, are unable to characterize the changes of nonlinear dynamics of SBF associated with diabetes and peripheral neuropathy. The objective of this study was to investigate altered nonlinear dynamics of skin blood flow in the plantar foot of diabetics with peripheral neuropathy. 18 type 2 diabetics with peripheral neuropathy and 8 healthy controls were recruited. SBF at the first metatarsal head in response to a loading pressure of 300 mmHg and a local heating was measured using laser Doppler flowmetry. A sample entropy approach was used to quantify the degree of regularity of SBF. Our results showed that the regularity degree of SBF in the diabetic foot underwent only small changes during post-occlusive reactive hyperemia and thermally induced biphasic response compared to non-diabetics. SBF of the diabetic foot has higher degree of irregularity during reactive hyperemia because of attenuated myogenic activity, and demonstrated higher regularity during the biphasic response largely due to significantly enhanced cardiac activities. This study suggests that the regularity degree of SBF at the first metatarsal head could be used to assess impaired microvascular reactivity and thus may be used to assess the risk for DFU in diabetics with peripheralneuropathy.

Image volume analysis of omnidirectional parallax regular-polyhedron three-dimensional displays.

PubMed

Kim, Hwi; Hahn, Joonku; Lee, Byoungho

2009-04-13

Three-dimensional (3D) displays having regular-polyhedron structures are proposed and their imaging characteristics are analyzed. Four types of conceptual regular-polyhedron 3D displays, i.e., hexahedron, octahedron, dodecahedron, and icosahedrons, are considered. In principle, regular-polyhedron 3D display can present omnidirectional full parallax 3D images. Design conditions of structural factors such as viewing angle of facet panel and observation distance for 3D display with omnidirectional full parallax are studied. As a main issue, image volumes containing virtual 3D objects represented by the four types of regular-polyhedron displays are comparatively analyzed.

3D image restoration for confocal microscopy: toward a wavelet deconvolution for the study of complex biological structures

NASA Astrophysics Data System (ADS)

Boutet de Monvel, Jacques; Le Calvez, Sophie; Ulfendahl, Mats

2000-05-01

Image restoration algorithms provide efficient tools for recovering part of the information lost in the imaging process of a microscope. We describe recent progress in the application of deconvolution to confocal microscopy. The point spread function of a Biorad-MRC1024 confocal microscope was measured under various imaging conditions, and used to process 3D-confocal images acquired in an intact preparation of the inner ear developed at Karolinska Institutet. Using these experiments we investigate the application of denoising methods based on wavelet analysis as a natural regularization of the deconvolution process. Within the Bayesian approach to image restoration, we compare wavelet denoising with the use of a maximum entropy constraint as another natural regularization method. Numerical experiments performed with test images show a clear advantage of the wavelet denoising approach, allowing to `cool down' the image with respect to the signal, while suppressing much of the fine-scale artifacts appearing during deconvolution due to the presence of noise, incomplete knowledge of the point spread function, or undersampling problems. We further describe a natural development of this approach, which consists of performing the Bayesian inference directly in the wavelet domain.

The Solaris-Panoptes Global Network of Robotic Telescopes and the Borowiec Satellite Laser Ranging System for SST: A Progress Report

NASA Astrophysics Data System (ADS)

Konacki, M.; Lejba, P.; Sybilski, P.; Pawłaszek, R.; Kozłowski, S.; Suchodolski, T.; Słonina, M.; Litwicki, M.; Sybilska, A.; Rogowska, B.; Kolb, U.; Burwitz, V.; Baader, J.; Groot, P.; Bloemen, S.; Ratajczak, M.; Hełminiak, K.; Borek, R.; Chodosiewicz, P.; Chimicz, A.

We present an update on the preparation of our assets that consists of a robotic network of eight optical telescopes and a laser ranging station for regular services in the SST domain. We report the development of new optical assets that include a double telescope system, Panoptes-1AB, and a new astrograph on our Solaris-3 telescope at the Siding Spring Observatory, Australia. Progress in the software development necessary for smooth SST operation includes a web based portal and an XML Azure Queue scheduling for the network giving easy access to our sensors. Astrometry24.net our new prototype cloud service for fast astrometry, streak detection and measurement with precision and performance results is also described. In the laser domain, for more than a year, Space Research Centre Borowiec laser station has regularly tracked space debris cooperative and uncooperative targets. The efforts of the stations’ staff have been focused on the tracking of typical rocket bodies from the LEO regime. Additionally, a second independent laser system fully dedicated to SST activities is under development. It will allow for an increased pace of operation of our consortium in the global SST laser domain.

Accurate mask-based spatially regularized correlation filter for visual tracking

NASA Astrophysics Data System (ADS)

Gu, Xiaodong; Xu, Xinping

2017-01-01

Recently, discriminative correlation filter (DCF)-based trackers have achieved extremely successful results in many competitions and benchmarks. These methods utilize a periodic assumption of the training samples to efficiently learn a classifier. However, this assumption will produce unwanted boundary effects, which severely degrade the tracking performance. Correlation filters with limited boundaries and spatially regularized DCFs were proposed to reduce boundary effects. However, their methods used the fixed mask or predesigned weights function, respectively, which was unsuitable for large appearance variation. We propose an accurate mask-based spatially regularized correlation filter for visual tracking. Our augmented objective can reduce the boundary effect even in large appearance variation. In our algorithm, the masking matrix is converted into the regularized function that acts on the correlation filter in frequency domain, which makes the algorithm fast convergence. Our online tracking algorithm performs favorably against state-of-the-art trackers on OTB-2015 Benchmark in terms of efficiency, accuracy, and robustness.

Accurate reconstruction of the optical parameter distribution in participating medium based on the frequency-domain radiative transfer equation

NASA Astrophysics Data System (ADS)

Qiao, Yao-Bin; Qi, Hong; Zhao, Fang-Zhou; Ruan, Li-Ming

2016-12-01

Reconstructing the distribution of optical parameters in the participating medium based on the frequency-domain radiative transfer equation (FD-RTE) to probe the internal structure of the medium is investigated in the present work. The forward model of FD-RTE is solved via the finite volume method (FVM). The regularization term formatted by the generalized Gaussian Markov random field model is used in the objective function to overcome the ill-posed nature of the inverse problem. The multi-start conjugate gradient (MCG) method is employed to search the minimum of the objective function and increase the efficiency of convergence. A modified adjoint differentiation technique using the collimated radiative intensity is developed to calculate the gradient of the objective function with respect to the optical parameters. All simulation results show that the proposed reconstruction algorithm based on FD-RTE can obtain the accurate distributions of absorption and scattering coefficients. The reconstructed images of the scattering coefficient have less errors than those of the absorption coefficient, which indicates the former are more suitable to probing the inner structure. Project supported by the National Natural Science Foundation of China (Grant No. 51476043), the Major National Scientific Instruments and Equipment Development Special Foundation of China (Grant No. 51327803), and the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (Grant No. 51121004).

Domain atrophy creates rare cases of functional partial protein domains.

PubMed

Prakash, Ananth; Bateman, Alex

2015-04-30

Protein domains display a range of structural diversity, with numerous additions and deletions of secondary structural elements between related domains. We have observed a small number of cases of surprising large-scale deletions of core elements of structural domains. We propose a new concept called domain atrophy, where protein domains lose a significant number of core structural elements. Here, we implement a new pipeline to systematically identify new cases of domain atrophy across all known protein sequences. The output of this pipeline was carefully checked by hand, which filtered out partial domain instances that were unlikely to represent true domain atrophy due to misannotations or un-annotated sequence fragments. We identify 75 cases of domain atrophy, of which eight cases are found in a three-dimensional protein structure and 67 cases have been inferred based on mapping to a known homologous structure. Domains with structural variations include ancient folds such as the TIM-barrel and Rossmann folds. Most of these domains are observed to show structural loss that does not affect their functional sites. Our analysis has significantly increased the known cases of domain atrophy. We discuss specific instances of domain atrophy and see that there has often been a compensatory mechanism that helps to maintain the stability of the partial domain. Our study indicates that although domain atrophy is an extremely rare phenomenon, protein domains under certain circumstances can tolerate extreme mutations giving rise to partial, but functional, domains.

Identification of spatially-localized initial conditions via sparse PCA

NASA Astrophysics Data System (ADS)

Dwivedi, Anubhav; Jovanovic, Mihailo

2017-11-01

Principal Component Analysis involves maximization of a quadratic form subject to a quadratic constraint on the initial flow perturbations and it is routinely used to identify the most energetic flow structures. For general flow configurations, principal components can be efficiently computed via power iteration of the forward and adjoint governing equations. However, the resulting flow structures typically have a large spatial support leading to a question of physical realizability. To obtain spatially-localized structures, we modify the quadratic constraint on the initial condition to include a convex combination with an additional regularization term which promotes sparsity in the physical domain. We formulate this constrained optimization problem as a nonlinear eigenvalue problem and employ an inverse power-iteration-based method to solve it. The resulting solution is guaranteed to converge to a nonlinear eigenvector which becomes increasingly localized as our emphasis on sparsity increases. We use several fluids examples to demonstrate that our method indeed identifies the most energetic initial perturbations that are spatially compact. This work was supported by Office of Naval Research through Grant Number N00014-15-1-2522.

Jazz drummers recruit language-specific areas for the processing of rhythmic structure.

PubMed

Herdener, Marcus; Humbel, Thierry; Esposito, Fabrizio; Habermeyer, Benedikt; Cattapan-Ludewig, Katja; Seifritz, Erich

2014-03-01

Rhythm is a central characteristic of music and speech, the most important domains of human communication using acoustic signals. Here, we investigated how rhythmical patterns in music are processed in the human brain, and, in addition, evaluated the impact of musical training on rhythm processing. Using fMRI, we found that deviations from a rule-based regular rhythmic structure activated the left planum temporale together with Broca's area and its right-hemispheric homolog across subjects, that is, a network also crucially involved in the processing of harmonic structure in music and the syntactic analysis of language. Comparing the BOLD responses to rhythmic variations between professional jazz drummers and musical laypersons, we found that only highly trained rhythmic experts show additional activity in left-hemispheric supramarginal gyrus, a higher-order region involved in processing of linguistic syntax. This suggests an additional functional recruitment of brain areas usually dedicated to complex linguistic syntax processing for the analysis of rhythmical patterns only in professional jazz drummers, who are especially trained to use rhythmical cues for communication.

Revealing molecular-level surface structure of amyloid fibrils in liquid by means of frequency modulation atomic force microscopy

NASA Astrophysics Data System (ADS)

Fukuma, Takeshi; Mostaert, Anika S.; Serpell, Louise C.; Jarvis, Suzanne P.

2008-09-01

We have investigated the surface structure of islet amyloid polypeptide (IAPP) fibrils and α-synuclein protofibrils in liquid by means of frequency modulation atomic force microscopy (FM-AFM). Ångström-resolution FM-AFM imaging of isolated macromolecules in liquid is demonstrated for the first time. Individual β-strands aligned perpendicular to the fibril axis with a spacing of 0.5 nm are resolved in FM-AFM images, which confirms cross-β structure of IAPP fibrils in real space. FM-AFM images also reveal the existence of 4 nm periodic domains along the axis of IAPP fibrils. Stripe features with 0.5 nm spacing are also found in images of α-synuclein protofibrils. However, in contrast to the case for IAPP fibrils, the stripes are oriented 30° from the axis, suggesting the possibility of β-strand alignment in protofibrils different from that in mature fibrils or the regular arrangement of thioflavin T molecules present during the fibril preparation aligned at the surface of the protofibrils.

High-resolution seismic data regularization and wavefield separation

NASA Astrophysics Data System (ADS)

Cao, Aimin; Stump, Brian; DeShon, Heather

2018-04-01

We present a new algorithm, non-equispaced fast antileakage Fourier transform (NFALFT), for irregularly sampled seismic data regularization. Synthetic tests from 1-D to 5-D show that the algorithm may efficiently remove leaked energy in the frequency wavenumber domain, and its corresponding regularization process is accurate and fast. Taking advantage of the NFALFT algorithm, we suggest a new method (wavefield separation) for the detection of the Earth's inner core shear wave with irregularly distributed seismic arrays or networks. All interfering seismic phases that propagate along the minor arc are removed from the time window around the PKJKP arrival. The NFALFT algorithm is developed for seismic data, but may also be used for other irregularly sampled temporal or spatial data processing.

Regularity gradient estimates for weak solutions of singular quasi-linear parabolic equations

NASA Astrophysics Data System (ADS)

Phan, Tuoc

2017-12-01

This paper studies the Sobolev regularity for weak solutions of a class of singular quasi-linear parabolic problems of the form ut -div [ A (x , t , u , ∇u) ] =div [ F ] with homogeneous Dirichlet boundary conditions over bounded spatial domains. Our main focus is on the case that the vector coefficients A are discontinuous and singular in (x , t)-variables, and dependent on the solution u. Global and interior weighted W 1 , p (ΩT , ω)-regularity estimates are established for weak solutions of these equations, where ω is a weight function in some Muckenhoupt class of weights. The results obtained are even new for linear equations, and for ω = 1, because of the singularity of the coefficients in (x , t)-variables.

Striking Plasticity of CRISPR-Cas9 and Key Role of Non-target DNA, as Revealed by Molecular Simulations.

PubMed

Palermo, Giulia; Miao, Yinglong; Walker, Ross C; Jinek, Martin; McCammon, J Andrew

2016-10-26

The CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 system recently emerged as a transformative genome-editing technology that is innovating basic bioscience and applied medicine and biotechnology. The endonuclease Cas9 associates with a guide RNA to match and cleave complementary sequences in double stranded DNA, forming an RNA:DNA hybrid and a displaced non-target DNA strand. Although extensive structural studies are ongoing, the conformational dynamics of Cas9 and its interplay with the nucleic acids during association and DNA cleavage are largely unclear. Here, by employing multi-microsecond time scale molecular dynamics, we reveal the conformational plasticity of Cas9 and identify key determinants that allow its large-scale conformational changes during nucleic acid binding and processing. We show how the "closure" of the protein, which accompanies nucleic acid binding, fundamentally relies on highly coupled and specific motions of the protein domains, collectively initiating the prominent conformational changes needed for nucleic acid association. We further reveal a key role of the non-target DNA during the process of activation of the nuclease HNH domain, showing how the nontarget DNA positioning triggers local conformational changes that favor the formation of a catalytically competent Cas9. Finally, a remarkable conformational plasticity is identified as an intrinsic property of the HNH domain, constituting a necessary element that allows for the HNH repositioning. These novel findings constitute a reference for future experimental studies aimed at a full characterization of the dynamic features of the CRISPR-Cas9 system, and-more importantly-call for novel structure engineering efforts that are of fundamental importance for the rational design of new genome-engineering applications.

Selection of regularization parameter for l1-regularized damage detection

NASA Astrophysics Data System (ADS)

Hou, Rongrong; Xia, Yong; Bao, Yuequan; Zhou, Xiaoqing

2018-06-01

The l1 regularization technique has been developed for structural health monitoring and damage detection through employing the sparsity condition of structural damage. The regularization parameter, which controls the trade-off between data fidelity and solution size of the regularization problem, exerts a crucial effect on the solution. However, the l1 regularization problem has no closed-form solution, and the regularization parameter is usually selected by experience. This study proposes two strategies of selecting the regularization parameter for the l1-regularized damage detection problem. The first method utilizes the residual and solution norms of the optimization problem and ensures that they are both small. The other method is based on the discrepancy principle, which requires that the variance of the discrepancy between the calculated and measured responses is close to the variance of the measurement noise. The two methods are applied to a cantilever beam and a three-story frame. A range of the regularization parameter, rather than one single value, can be determined. When the regularization parameter in this range is selected, the damage can be accurately identified even for multiple damage scenarios. This range also indicates the sensitivity degree of the damage identification problem to the regularization parameter.

Electromagnetically induced transparency in sinusoidal modulated ring resonator

NASA Astrophysics Data System (ADS)

Malik, Jagannath; Oruganti, Sai Kiran; Song, Seongkyu; Ko, Nak Young; Bien, Franklin

2018-06-01

In the present work, we demonstrate controlling the excitation of bright mode (continuum mode) resonance and dark mode (discrete mode) resonance in a planar metasurface made of sinusoidal modulation inside a closed rectangular metallic ring placed over a dielectric substrate. Unlike asymmetrical breaking of a meta-atom (often referred to as the unit cell) to achieve the dark mode response in regular metamaterials, in the present structure, the bright or dark mode resonance is achieved using even or odd half cycle modulation. The achieved dark-mode shows a sharp resonance for a particular polarization of the incident electric field, which results in an electromagnetically induced transparency like spectrum. The electromagnetic behavior of the proposed meta-atom has been investigated in the frequency domain using commercially available software and validated through experiments in the gigahertz regime.

Time-Gating Processes in Intra-Cavity Mode-Locking Devices Like Saturable Absorbers and Kerr Cells

NASA Technical Reports Server (NTRS)

Prasad, Narasimha; Roychoudhuri, Chandrasekhar

2010-01-01

Photons are non-interacting entities. Light beams do not interfere by themselves. Light beams constituting different laser modes (frequencies) are not capable of re-arranging their energies from extended time-domain to ultra-short time-domain by themselves without the aid of light-matter interactions with suitable intra-cavity devices. In this paper we will discuss the time-gating properties of intra-cavity "mode-locking" devices that actually help generate a regular train of high energy wave packets.

Interactive Cohort Identification of Sleep Disorder Patients Using Natural Language Processing and i2b2.

PubMed

Chen, W; Kowatch, R; Lin, S; Splaingard, M; Huang, Y

2015-01-01

Nationwide Children's Hospital established an i2b2 (Informatics for Integrating Biology & the Bedside) application for sleep disorder cohort identification. Discrete data were gleaned from semistructured sleep study reports. The system showed to work more efficiently than the traditional manual chart review method, and it also enabled searching capabilities that were previously not possible. We report on the development and implementation of the sleep disorder i2b2 cohort identification system using natural language processing of semi-structured documents. We developed a natural language processing approach to automatically parse concepts and their values from semi-structured sleep study documents. Two parsers were developed: a regular expression parser for extracting numeric concepts and a NLP based tree parser for extracting textual concepts. Concepts were further organized into i2b2 ontologies based on document structures and in-domain knowledge. 26,550 concepts were extracted with 99% being textual concepts. 1.01 million facts were extracted from sleep study documents such as demographic information, sleep study lab results, medications, procedures, diagnoses, among others. The average accuracy of terminology parsing was over 83% when comparing against those by experts. The system is capable of capturing both standard and non-standard terminologies. The time for cohort identification has been reduced significantly from a few weeks to a few seconds. Natural language processing was shown to be powerful for quickly converting large amount of semi-structured or unstructured clinical data into discrete concepts, which in combination of intuitive domain specific ontologies, allows fast and effective interactive cohort identification through the i2b2 platform for research and clinical use.

Magnetic structure of Basse-Terre volcanic island (Guadeloupe, Lesser Antilles) inferred from 3D inversion of aeromagnetic data

NASA Astrophysics Data System (ADS)

Barnoud, Anne; Bouligand, Claire; Coutant, Olivier; Carlut, Julie

2017-12-01

We interpret aeromagnetic data to constrain the magnetic structure of the island of Basse-Terre, Guadeloupe, Lesser Antilles. Aeromagnetic data are inverted in the spatial domain with a Bayesian formulation to retrieve the 3D distribution of rock magnetization intensity and polarity. The inversion is regularized using a correlation length and standard deviation for magnetization chosen to be consistent with results from paleomagnetic measurements on lava flow samples from Basse-Terre. The resulting 3D model of magnetization is consistent at the surface with observed polarities and at depth with a 2D model obtained from a Parker and Huestis (1974) inversion in the Fourier domain. The inferred magnetic structure is compared with the available geological information deduced from published geological, geomorphological and geochronological studies. In the southern part of the island, very low magnetization is observed around the Soufrière lava dome, last activity of the Grande-Découverte-Carmichaël-Soufrière composite volcano, in relation with a high level of hydrothermal alteration. High-magnetizations in the South-East might reflect the presence of massive lava flows and lava domes from the Madeleine vents and Monts Caraïbes. Medium magnetizations in the South-West coincide with the location of debris avalanche deposits associated with the collapse of the former Carmichaël volcano and might reflect less massive lava structure at depth. Using the volume of normal polarity in the South part of Basse-Terre recovered in our 3D model of rock magnetization, we estimate an average construction rate of ∼ 9.4 ×10-4 km3/yr during the Brunhes chron which provides new insights on the volcanic activity of La Soufrière volcano.

Interactive Cohort Identification of Sleep Disorder Patients Using Natural Language Processing and i2b2

PubMed Central

Chen, W.; Kowatch, R.; Lin, S.; Splaingard, M.

2015-01-01

Summary Nationwide Children’s Hospital established an i2b2 (Informatics for Integrating Biology & the Bedside) application for sleep disorder cohort identification. Discrete data were gleaned from semistructured sleep study reports. The system showed to work more efficiently than the traditional manual chart review method, and it also enabled searching capabilities that were previously not possible. Objective We report on the development and implementation of the sleep disorder i2b2 cohort identification system using natural language processing of semi-structured documents. Methods We developed a natural language processing approach to automatically parse concepts and their values from semi-structured sleep study documents. Two parsers were developed: a regular expression parser for extracting numeric concepts and a NLP based tree parser for extracting textual concepts. Concepts were further organized into i2b2 ontologies based on document structures and in-domain knowledge. Results 26,550 concepts were extracted with 99% being textual concepts. 1.01 million facts were extracted from sleep study documents such as demographic information, sleep study lab results, medications, procedures, diagnoses, among others. The average accuracy of terminology parsing was over 83% when comparing against those by experts. The system is capable of capturing both standard and non-standard terminologies. The time for cohort identification has been reduced significantly from a few weeks to a few seconds. Conclusion Natural language processing was shown to be powerful for quickly converting large amount of semi-structured or unstructured clinical data into discrete concepts, which in combination of intuitive domain specific ontologies, allows fast and effective interactive cohort identification through the i2b2 platform for research and clinical use. PMID:26171080

Rewritable ferroelectric vortex pairs in BiFeO3

NASA Astrophysics Data System (ADS)

Li, Yang; Jin, Yaming; Lu, Xiaomei; Yang, Jan-Chi; Chu, Ying-Hao; Huang, Fengzhen; Zhu, Jinsong; Cheong, Sang-Wook

2017-08-01

Ferroelectric vortex in multiferroic materials has been considered as a promising alternative to current memory cells for the merit of high storage density. However, the formation of regular natural ferroelectric vortex is difficult, restricting the achievement of vortex memory device. Here, we demonstrated the creation of ferroelectric vortex-antivortex pairs in BiFeO3 thin films by using local electric field. The evolution of the polar vortex structure is studied by piezoresponse force microscopy at nanoscale. The results reveal that the patterns and stability of vortex structures are sensitive to the poling position. Consecutive writing and erasing processes cause no influence on the original domain configuration. The Z4 proper coloring vortex-antivortex network is then analyzed by graph theory, which verifies the rationality of artificial vortex-antivortex pairs. This study paves a foundation for artificial regulation of vortex, which provides a possible pathway for the design and realization of non-volatile vortex memory devices and logical devices.

CRF: detection of CRISPR arrays using random forest.

PubMed

Wang, Kai; Liang, Chun

2017-01-01

CRISPRs (clustered regularly interspaced short palindromic repeats) are particular repeat sequences found in wide range of bacteria and archaea genomes. Several tools are available for detecting CRISPR arrays in the genomes of both domains. Here we developed a new web-based CRISPR detection tool named CRF (CRISPR Finder by Random Forest). Different from other CRISPR detection tools, a random forest classifier was used in CRF to filter out invalid CRISPR arrays from all putative candidates and accordingly enhanced detection accuracy. In CRF, particularly, triplet elements that combine both sequence content and structure information were extracted from CRISPR repeats for classifier training. The classifier achieved high accuracy and sensitivity. Moreover, CRF offers a highly interactive web interface for robust data visualization that is not available among other CRISPR detection tools. After detection, the query sequence, CRISPR array architecture, and the sequences and secondary structures of CRISPR repeats and spacers can be visualized for visual examination and validation. CRF is freely available at http://bioinfolab.miamioh.edu/crf/home.php.

Structure and activity of the Cas3 HD nuclease MJ0384, an effector enzyme of the CRISPR interference

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beloglazova, Natalia; Petit, Pierre; Flick, Robert

Clustered regularly interspaced short palindromic repeats (CRISPRs) and Cas proteins represent an adaptive microbial immunity system against viruses and plasmids. Cas3 proteins have been proposed to play a key role in the CRISPR mechanism through the direct cleavage of invasive DNA. Here, we show that the Cas3 HD domain protein MJ0384 from Methanocaldococcus jannaschii cleaves endonucleolytically and exonucleolytically (3'-5') single-stranded DNAs and RNAs, as well as 3'-flaps, splayed arms, and R-loops. The degradation of branched DNA substrates by MJ0384 is stimulated by the Cas3 helicase MJ0383 and ATP. The crystal structure of MJ0384 revealed the active site with two boundmore » metal cations and together with site-directed mutagenesis suggested a catalytic mechanism. Our studies suggest that the Cas3 HD nucleases working together with the Cas3 helicases can completely degrade invasive DNAs through the combination of endo- and exonuclease activities.« less

Structural model of homogeneous As–S glasses derived from Raman spectroscopy and high-resolution XPS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Golovchak, R.; Shpotyuk, O.; Mccloy, J. S.

2010-11-28

The structure of homogeneous bulk As x S 100- x (25 ≤ x ≤ 42) glasses, prepared by the conventional rocking–melting–quenching method, was investigated using high-resolution X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy. It is shown that the main building blocks of their glass networks are regular AsS 3/2 pyramids and sulfur chains. In the S-rich domain, the existence of quasi-tetrahedral (QT) S = As(S 1/2) 3 units is deduced from XPS data, but with a concentration not exceeding ~3–5% of total atomic sites. Therefore, QT units do not appear as primary building blocks of the glass backbone in thesemore » materials, and an optimally-constrained network may not be an appropriate description for glasses when x < 40. Finally, it is shown that, in contrast to Se-based glasses, the ‘chain-crossing’ model is only partially applicable to sulfide glasses.« less

Predicting health care utilization in marginalized populations: Black, female, street-based sex workers.

PubMed

Varga, Leah M; Surratt, Hilary L

2014-01-01

Patterns of social and structural factors experienced by vulnerable populations may negatively affect willingness and ability to seek out health care services, and ultimately, their health. The outcome variable was utilization of health care services in the previous 12 months. Using Andersen's Behavioral Model for Vulnerable Populations, we examined self-reported data on utilization of health care services among a sample of 546 Black, street-based, female sex workers in Miami, Florida. To evaluate the impact of each domain of the model on predicting health care utilization, domains were included in the logistic regression analysis by blocks using the traditional variables first and then adding the vulnerable domain variables. The most consistent variables predicting health care utilization were having a regular source of care and self-rated health. The model that included only enabling variables was the most efficient model in predicting health care utilization. Any type of resource, link, or connection to or with an institution, or any consistent point of care, contributes significantly to health care utilization behaviors. A consistent and reliable source for health care may increase health care utilization and subsequently decrease health disparities among vulnerable and marginalized populations, as well as contribute to public health efforts that encourage preventive health. Copyright © 2014 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

Infants Prefer the Musical Meter of Their Own Culture: A Cross-Cultural Comparison

ERIC Educational Resources Information Center

Soley, Gaye; Hannon, Erin E.

2010-01-01

Infants prefer native structures such as familiar faces and languages. Music is a universal human activity containing structures that vary cross-culturally. For example, Western music has temporally regular metric structures, whereas music of the Balkans (e.g., Bulgaria, Macedonia, Turkey) can have both regular and irregular structures. We…

High-speed manufacturing of highly regular femtosecond laser-induced periodic surface structures: physical origin of regularity.

PubMed

Gnilitskyi, Iaroslav; Derrien, Thibault J-Y; Levy, Yoann; Bulgakova, Nadezhda M; Mocek, Tomáš; Orazi, Leonardo

2017-08-16

Highly regular laser-induced periodic surface structures (HR-LIPSS) have been fabricated on surfaces of Mo, steel alloy and Ti at a record processing speed on large areas and with a record regularity in the obtained sub-wavelength structures. The physical mechanisms governing LIPSS regularity are identified and linked with the decay length (i.e. the mean free path) of the excited surface electromagnetic waves (SEWs). The dispersion of the LIPSS orientation angle well correlates with the SEWs decay length: the shorter this length, the more regular are the LIPSS. A material dependent criterion for obtaining HR-LIPSS is proposed for a large variety of metallic materials. It has been found that decreasing the spot size close to the SEW decay length is a key for covering several cm 2 of material surface by HR-LIPSS in a few seconds. Theoretical predictions suggest that reducing the laser wavelength can provide the possibility of HR-LIPSS production on principally any metal. This new achievement in the unprecedented level of control over the laser-induced periodic structure formation makes this laser-writing technology to be flexible, robust and, hence, highly competitive for advanced industrial applications based on surface nanostructuring.

Three-dimensional magnetotelluric inversion in practice—the electrical conductivity structure of the San Andreas Fault in Central California

NASA Astrophysics Data System (ADS)

Tietze, Kristina; Ritter, Oliver

2013-10-01

3-D inversion techniques have become a widely used tool in magnetotelluric (MT) data interpretation. However, with real data sets, many of the controlling factors for the outcome of 3-D inversion are little explored, such as alignment of the coordinate system, handling and influence of data errors and model regularization. Here we present 3-D inversion results of 169 MT sites from the central San Andreas Fault in California. Previous extensive 2-D inversion and 3-D forward modelling of the data set revealed significant along-strike variation of the electrical conductivity structure. 3-D inversion can recover these features but only if the inversion parameters are tuned in accordance with the particularities of the data set. Based on synthetic 3-D data we explore the model space and test the impacts of a wide range of inversion settings. The tests showed that the recovery of a pronounced regional 2-D structure in inversion of the complete impedance tensor depends on the coordinate system. As interdependencies between data components are not considered in standard 3-D MT inversion codes, 2-D subsurface structures can vanish if data are not aligned with the regional strike direction. A priori models and data weighting, that is, how strongly individual components of the impedance tensor and/or vertical magnetic field transfer functions dominate the solution, are crucial controls for the outcome of 3-D inversion. If deviations from a prior model are heavily penalized, regularization is prone to result in erroneous and misleading 3-D inversion models, particularly in the presence of strong conductivity contrasts. A `good' overall rms misfit is often meaningless or misleading as a huge range of 3-D inversion results exist, all with similarly `acceptable' misfits but producing significantly differing images of the conductivity structures. Reliable and meaningful 3-D inversion models can only be recovered if data misfit is assessed systematically in the frequency-space domain.

Language and Recursion

NASA Astrophysics Data System (ADS)

Lowenthal, Francis

2010-11-01

This paper examines whether the recursive structure imbedded in some exercises used in the Non Verbal Communication Device (NVCD) approach is actually the factor that enables this approach to favor language acquisition and reacquisition in the case of children with cerebral lesions. For that a definition of the principle of recursion as it is used by logicians is presented. The two opposing approaches to the problem of language development are explained. For many authors such as Chomsky [1] the faculty of language is innate. This is known as the Standard Theory; the other researchers in this field, e.g. Bates and Elman [2], claim that language is entirely constructed by the young child: they thus speak of Language Acquisition. It is also shown that in both cases, a version of the principle of recursion is relevant for human language. The NVCD approach is defined and the results obtained in the domain of language while using this approach are presented: young subjects using this approach acquire a richer language structure or re-acquire such a structure in the case of cerebral lesions. Finally it is shown that exercises used in this framework imply the manipulation of recursive structures leading to regular grammars. It is thus hypothesized that language development could be favored using recursive structures with the young child. It could also be the case that the NVCD like exercises used with children lead to the elaboration of a regular language, as defined by Chomsky [3], which could be sufficient for language development but would not require full recursion. This double claim could reconcile Chomsky's approach with psychological observations made by adherents of the Language Acquisition approach, if it is confirmed by researches combining the use of NVCDs, psychometric methods and the use of Neural Networks. This paper thus suggests that a research group oriented towards this problematic should be organized.

Functional analysis of alternative transcripts of the soybean Rj2 gene that restricts nodulation with specific rhizobial strains.

PubMed

Tang, F; Yang, S; Zhu, H

2016-05-01

The Rj2 gene is a TIR-NBS-LRR-type resistance gene in soybean (Glycine max) that restricts root nodule symbiosis with a group of Bradyrhizobium japonicum strains including USDA122. Rj2 generates two distinct transcript variants in its expression profile through alternative splicing. Alternative splicing of Rj2 is caused by the retention of the 86-bp intron 4. Inclusion of intron 4 in mature mRNA introduces an in-frame stop codon; as such, the alternative transcript is predicted to encode a truncated protein consisting of the entire portion of the TIR, NBS and LRR domains but missing the C-terminal domain of the full-length Rj2 protein encoded by the regular transcript. Since alternative splicing has been shown to be essential for full activity of several plant R genes, we attempted to test whether the alternative splicing is required for Rj2-mediated nodulation restriction. Here we demonstrated that the Rj2-mediated nodulation restriction does not require the combined presence of the regular and alternative transcripts, and the expression of the regular transcript alone is sufficient to confer nodulation restriction. © 2016 German Botanical Society and The Royal Botanical Society of the Netherlands.

Temporal sparsity exploiting nonlocal regularization for 4D computed tomography reconstruction

PubMed Central

Kazantsev, Daniil; Guo, Enyu; Kaestner, Anders; Lionheart, William R. B.; Bent, Julian; Withers, Philip J.; Lee, Peter D.

2016-01-01

X-ray imaging applications in medical and material sciences are frequently limited by the number of tomographic projections collected. The inversion of the limited projection data is an ill-posed problem and needs regularization. Traditional spatial regularization is not well adapted to the dynamic nature of time-lapse tomography since it discards the redundancy of the temporal information. In this paper, we propose a novel iterative reconstruction algorithm with a nonlocal regularization term to account for time-evolving datasets. The aim of the proposed nonlocal penalty is to collect the maximum relevant information in the spatial and temporal domains. With the proposed sparsity seeking approach in the temporal space, the computational complexity of the classical nonlocal regularizer is substantially reduced (at least by one order of magnitude). The presented reconstruction method can be directly applied to various big data 4D (x, y, z+time) tomographic experiments in many fields. We apply the proposed technique to modelled data and to real dynamic X-ray microtomography (XMT) data of high resolution. Compared to the classical spatio-temporal nonlocal regularization approach, the proposed method delivers reconstructed images of improved resolution and higher contrast while remaining significantly less computationally demanding. PMID:27002902

Evaluation of uncertainty for regularized deconvolution: A case study in hydrophone measurements.

PubMed

Eichstädt, S; Wilkens, V

2017-06-01

An estimation of the measurand in dynamic metrology usually requires a deconvolution based on a dynamic calibration of the measuring system. Since deconvolution is, mathematically speaking, an ill-posed inverse problem, some kind of regularization is required to render the problem stable and obtain usable results. Many approaches to regularized deconvolution exist in the literature, but the corresponding evaluation of measurement uncertainties is, in general, an unsolved issue. In particular, the uncertainty contribution of the regularization itself is a topic of great importance, because it has a significant impact on the estimation result. Here, a versatile approach is proposed to express prior knowledge about the measurand based on a flexible, low-dimensional modeling of an upper bound on the magnitude spectrum of the measurand. This upper bound allows the derivation of an uncertainty associated with the regularization method in line with the guidelines in metrology. As a case study for the proposed method, hydrophone measurements in medical ultrasound with an acoustic working frequency of up to 7.5 MHz are considered, but the approach is applicable for all kinds of estimation methods in dynamic metrology, where regularization is required and which can be expressed as a multiplication in the frequency domain.

Characterizing Novel Archaeal Lineages in Salton Sea Sediments

NASA Astrophysics Data System (ADS)

Tarn, J.; Valentine, D. L.

2016-12-01

Biological communities in extreme environments are often dominated by microorganisms of the domain Archaea. Abundant microbial assemblages of this group are found in the hottest, saltiest, and most thermodynamically-limited ecosystems on earth. These taxing surroundings are thought to impose a state of chronic energy stress on resident organisms due to high costs of cellular maintenance relative to resource availability. Even in more temperate settings, Archaea are regularly associated with low-nutrient lifestyles, reflecting their adaptation to extreme, biologically-limiting conditions, which may be an ancestral, domain-wide trait. In this study, we seek to characterize the Archaeal community of the Salton Sea, where members of this domain are novel and highly abundant. Previous work by Swan et al. in 2010 showed that gradients in salinity, sulfate, carbon and nitrogen across sediment horizons of the Salton Sea are linked to changes in Archaeal dominance and community structure. In light of recent taxonomic revisions of the domain, I reclassified the 107 published small subunit rRNA Archaeal sequences from the 2010 study using updated reference databases. The majority of these Euryarchaeal sequences were reassigned to the so-called DPANN superphylum, with Pacearchaeota-related sequences being very abundant in shallow, organic-rich sediments. In deeper, energy-limited strata, several groups of Bathyarchaeota and one divergent DPANN clade were dominant. Ongoing metagenomic work on these sediment communities is being used to assemble genomes of these novel Archaeal groups. These results will help define genomic adaptations of Salton Sea Archaea to varying levels of energy stress as well as inform future cultivation efforts.

A Kernel-free Boundary Integral Method for Elliptic Boundary Value Problems ⋆

PubMed Central

Ying, Wenjun; Henriquez, Craig S.

2013-01-01

This paper presents a class of kernel-free boundary integral (KFBI) methods for general elliptic boundary value problems (BVPs). The boundary integral equations reformulated from the BVPs are solved iteratively with the GMRES method. During the iteration, the boundary and volume integrals involving Green's functions are approximated by structured grid-based numerical solutions, which avoids the need to know the analytical expressions of Green's functions. The KFBI method assumes that the larger regular domain, which embeds the original complex domain, can be easily partitioned into a hierarchy of structured grids so that fast elliptic solvers such as the fast Fourier transform (FFT) based Poisson/Helmholtz solvers or those based on geometric multigrid iterations are applicable. The structured grid-based solutions are obtained with standard finite difference method (FDM) or finite element method (FEM), where the right hand side of the resulting linear system is appropriately modified at irregular grid nodes to recover the formal accuracy of the underlying numerical scheme. Numerical results demonstrating the efficiency and accuracy of the KFBI methods are presented. It is observed that the number of GM-RES iterations used by the method for solving isotropic and moderately anisotropic BVPs is independent of the sizes of the grids that are employed to approximate the boundary and volume integrals. With the standard second-order FEMs and FDMs, the KFBI method shows a second-order convergence rate in accuracy for all of the tested Dirichlet/Neumann BVPs when the anisotropy of the diffusion tensor is not too strong. PMID:23519600

Yeast mitochondrial threonyl-tRNA synthetase recognizes tRNA isoacceptors by distinct mechanisms and promotes CUN codon reassignment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ling, Jiqiang; Peterson, Kaitlyn M.; Simonovic, Ivana

2014-03-12

Aminoacyl-tRNA synthetases (aaRSs) ensure faithful translation of mRNA into protein by coupling an amino acid to a set of tRNAs with conserved anticodon sequences. Here, we show that in mitochondria of Saccharomyces cerevisiae, a single aaRS (MST1) recognizes and aminoacylates two natural tRNAs that contain anticodon loops of different size and sequence. Besides a regular ?? with a threonine (Thr) anticodon, MST1 also recognizes an unusual ??, which contains an enlarged anticodon loop and an anticodon triplet that reassigns the CUN codons from leucine to threonine. Our data show that MST1 recognizes the anticodon loop in both tRNAs, but employsmore » distinct recognition mechanisms. The size but not the sequence of the anticodon loop is critical for ?? recognition, whereas the anticodon sequence is essential for aminoacylation of ??. The crystal structure of MST1 reveals that, while lacking the N-terminal editing domain, the enzyme closely resembles the bacterial threonyl-tRNA synthetase (ThrRS). A detailed structural comparison with Escherichia coli ThrRS, which is unable to aminoacylate ??, reveals differences in the anticodon-binding domain that probably allow recognition of the distinct anticodon loops. Finally, our mutational and modeling analyses identify the structural elements in MST1 (e.g., helix {alpha}11) that define tRNA selectivity. Thus, MTS1 exemplifies that a single aaRS can recognize completely divergent anticodon loops of natural isoacceptor tRNAs and that in doing so it facilitates the reassignment of the genetic code in yeast mitochondria.« less

Fingerprinting the type of line edge roughness

NASA Astrophysics Data System (ADS)

Fernández Herrero, A.; Pflüger, M.; Scholze, F.; Soltwisch, V.

2017-06-01

Lamellar gratings are widely used diffractive optical elements and are prototypes of structural elements in integrated electronic circuits. EUV scatterometry is very sensitive to structure details and imperfections, which makes it suitable for the characterization of nanostructured surfaces. As compared to X-ray methods, EUV scattering allows for steeper angles of incidence, which is highly preferable for the investigation of small measurement fields on semiconductor wafers. For the control of the lithographic manufacturing process, a rapid in-line characterization of nanostructures is indispensable. Numerous studies on the determination of regular geometry parameters of lamellar gratings from optical and Extreme Ultraviolet (EUV) scattering also investigated the impact of roughness on the respective results. The challenge is to appropriately model the influence of structure roughness on the diffraction intensities used for the reconstruction of the surface profile. The impact of roughness was already studied analytically but for gratings with a periodic pseudoroughness, because of practical restrictions of the computational domain. Our investigation aims at a better understanding of the scattering caused by line roughness. We designed a set of nine lamellar Si-gratings to be studied by EUV scatterometry. It includes one reference grating with no artificial roughness added, four gratings with a periodic roughness distribution, two with a prevailing line edge roughness (LER) and another two with line width roughness (LWR), and four gratings with a stochastic roughness distribution (two with LER and two with LWR). We show that the type of line roughness has a strong impact on the diffuse scatter angular distribution. Our experimental results are not described well by the present modelling approach based on small, periodically repeated domains.

Impact of an irregular friction formulation on dynamics of a minimal model for brake squeal

NASA Astrophysics Data System (ADS)

Stender, Merten; Tiedemann, Merten; Hoffmann, Norbert; Oberst, Sebastian

2018-07-01

Friction-induced vibrations are of major concern in the design of reliable, efficient and comfortable technical systems. Well-known examples for systems susceptible to self-excitation can be found in fluid structure interaction, disk brake squeal, rotor dynamics, hip implants noise and many more. While damping elements and amplitude reduction are well-understood in linear systems, nonlinear systems and especially self-excited dynamics still constitute a challenge for damping element design. Additionally, complex dynamical systems exhibit deterministic chaotic cores which add severe sensitivity to initial conditions to the system response. Especially the complex friction interface dynamics remain a challenging task for measurements and modeling. Today, mostly simple and regular friction models are investigated in the field of self-excited brake system vibrations. This work aims at investigating the effect of high-frequency irregular interface dynamics on the nonlinear dynamical response of a self-excited structure. Special focus is put on the characterization of the system response time series. A low-dimensional minimal model is studied which features self-excitation, gyroscopic effects and friction-induced damping. Additionally, the employed friction formulation exhibits temperature as inner variable and superposed chaotic fluctuations governed by a Lorenz attractor. The time scale of the irregular fluctuations is chosen one order smaller than the overall system dynamics. The influence of those fluctuations on the structural response is studied in various ways, i.e. in time domain and by means of recurrence analysis. The separate time scales are studied in detail and regimes of dynamic interactions are identified. The results of the irregular friction formulation indicate dynamic interactions on multiple time scales, which trigger larger vibration amplitudes as compared to regular friction formulations conventionally studied in the field of friction-induced vibrations.

Self-assembly of a binodal metal-organic framework exhibiting a demi-regular lattice.

PubMed

Yan, Linghao; Kuang, Guowen; Zhang, Qiushi; Shang, Xuesong; Liu, Pei Nian; Lin, Nian

2017-10-26

Designing metal-organic frameworks with new topologies is a long-standing quest because new topologies often accompany new properties and functions. Here we report that 1,3,5-tris[4-(pyridin-4-yl)phenyl]benzene molecules coordinate with Cu atoms to form a two-dimensional framework in which Cu adatoms form a nanometer-scale demi-regular lattice. The lattice is articulated by perfectly arranged twofold and threefold pyridyl-Cu coordination motifs in a ratio of 1 : 6 and features local dodecagonal symmetry. This structure is thermodynamically robust and emerges solely when the molecular density is at a critical value. In comparison, we present three framework structures that consist of semi-regular and regular lattices of Cu atoms self-assembled out of 1,3,5-tris[4-(pyridin-4-yl)phenyl]benzene and trispyridylbenzene molecules. Thus a family of regular, semi-regular and demi-regular lattices can be achieved by Cu-pyridyl coordination.

Twistor interpretation of slice regular functions

NASA Astrophysics Data System (ADS)

Altavilla, Amedeo

2018-01-01

Given a slice regular function f : Ω ⊂ H → H, with Ω ∩ R ≠ ∅, it is possible to lift it to surfaces in the twistor space CP3 of S4 ≃ H ∪ { ∞ } (see Gentili et al., 2014). In this paper we show that the same result is true if one removes the hypothesis Ω ∩ R ≠ ∅ on the domain of the function f. Moreover we find that if a surface S ⊂CP3 contains the image of the twistor lift of a slice regular function, then S has to be ruled by lines. Starting from these results we find all the projective classes of algebraic surfaces up to degree 3 in CP3 that contain the lift of a slice regular function. In addition we extend and further explore the so-called twistor transform, that is a curve in Gr2(C4) which, given a slice regular function, returns the arrangement of lines whose lift carries on. With the explicit expression of the twistor lift and of the twistor transform of a slice regular function we exhibit the set of slice regular functions whose twistor transform describes a rational line inside Gr2(C4) , showing the role of slice regular functions not defined on R. At the end we study the twistor lift of a particular slice regular function not defined over the reals. This example shows the effectiveness of our approach and opens some questions.

The structure and dynamics of tandem WW domains in a negative regulator of notch signaling, Suppressor of deltex.

PubMed

Fedoroff, Oleg Y; Townson, Sharon A; Golovanov, Alexander P; Baron, Martin; Avis, Johanna M

2004-08-13

WW domains mediate protein recognition, usually though binding to proline-rich sequences. In many proteins, WW domains occur in tandem arrays. Whether or how individual domains within such arrays cooperate to recognize biological partners is, as yet, poorly characterized. An important question is whether functional diversity of different WW domain proteins is reflected in the structural organization and ligand interaction mechanisms of their multiple domains. We have determined the solution structure and dynamics of a pair of WW domains (WW3-4) from a Drosophila Nedd4 family protein called Suppressor of deltex (Su(dx)), a regulator of Notch receptor signaling. We find that the binding of a type 1 PPPY ligand to WW3 stabilizes the structure with effects propagating to the WW4 domain, a domain that is not active for ligand binding. Both WW domains adopt the characteristic triple-stranded beta-sheet structure, and significantly, this is the first example of a WW domain structure to include a domain (WW4) lacking the second conserved Trp (replaced by Phe). The domains are connected by a flexible linker, which allows a hinge-like motion of domains that may be important for the recognition of functionally relevant targets. Our results contrast markedly with those of the only previously determined three-dimensional structure of tandem WW domains, that of the rigidly oriented WW domain pair from the RNA-splicing factor Prp40. Our data illustrate that arrays of WW domains can exhibit a variety of higher order structures and ligand interaction mechanisms.

Factors associated with regular marijuana use among high school students: a long-term follow-up study.

PubMed

Griffin, Kenneth W; Botvin, Gilbert J; Scheier, Lawrence M; Nichols, Tracy R

2002-01-01

The present study investigated whether several behavioral and psychosocial factors measured during early adolescence predicted regular marijuana use 6 years later in a sample of high school students. As part of a school-based survey. 7th-grade students (N = 1,132) reported levels of alcohol, tobacco, and marijuana use, and were assessed on several domains of psychosocial functioning potentially relevant in the etiology of marijuana use. When students were followed-up in the 12th-grade, 14% smoked marijuana on a regular basis (once or more per month). Findings indicated that early cigarette smoking, alcohol use, and alcohol intoxication predicted later regular marijuana use. For boys, early marijuana use increased the odds for later regular marijuana use. Cigarette smoking by friends and siblings during early adolescence also increased the likelihood of later monthly marijuana use. The findings suggest that early prevention programs for adolescent alcohol, tobacco, and/or other drug use may have important preventive effects in terms of potentially more serious levels of marijuana involvement later in adolescence and early adulthood.

Predicting PDZ domain mediated protein interactions from structure

PubMed Central

2013-01-01

Background PDZ domains are structural protein domains that recognize simple linear amino acid motifs, often at protein C-termini, and mediate protein-protein interactions (PPIs) in important biological processes, such as ion channel regulation, cell polarity and neural development. PDZ domain-peptide interaction predictors have been developed based on domain and peptide sequence information. Since domain structure is known to influence binding specificity, we hypothesized that structural information could be used to predict new interactions compared to sequence-based predictors. Results We developed a novel computational predictor of PDZ domain and C-terminal peptide interactions using a support vector machine trained with PDZ domain structure and peptide sequence information. Performance was estimated using extensive cross validation testing. We used the structure-based predictor to scan the human proteome for ligands of 218 PDZ domains and show that the predictions correspond to known PDZ domain-peptide interactions and PPIs in curated databases. The structure-based predictor is complementary to the sequence-based predictor, finding unique known and novel PPIs, and is less dependent on training–testing domain sequence similarity. We used a functional enrichment analysis of our hits to create a predicted map of PDZ domain biology. This map highlights PDZ domain involvement in diverse biological processes, some only found by the structure-based predictor. Based on this analysis, we predict novel PDZ domain involvement in xenobiotic metabolism and suggest new interactions for other processes including wound healing and Wnt signalling. Conclusions We built a structure-based predictor of PDZ domain-peptide interactions, which can be used to scan C-terminal proteomes for PDZ interactions. We also show that the structure-based predictor finds many known PDZ mediated PPIs in human that were not found by our previous sequence-based predictor and is less dependent on training–testing domain sequence similarity. Using both predictors, we defined a functional map of human PDZ domain biology and predict novel PDZ domain function. Users may access our structure-based and previous sequence-based predictors at http://webservice.baderlab.org/domains/POW. PMID:23336252

Endemic infections are always possible on regular networks

NASA Astrophysics Data System (ADS)

Del Genio, Charo I.; House, Thomas

2013-10-01

We study the dependence of the largest component in regular networks on the clustering coefficient, showing that its size changes smoothly without undergoing a phase transition. We explain this behavior via an analytical approach based on the network structure, and provide an exact equation describing the numerical results. Our work indicates that intrinsic structural properties always allow the spread of epidemics on regular networks.

Implementing Access to Data Distributed on Many Processors

NASA Technical Reports Server (NTRS)

James, Mark

2006-01-01

A reference architecture is defined for an object-oriented implementation of domains, arrays, and distributions written in the programming language Chapel. This technology primarily addresses domains that contain arrays that have regular index sets with the low-level implementation details being beyond the scope of this discussion. What is defined is a complete set of object-oriented operators that allows one to perform data distributions for domain arrays involving regular arithmetic index sets. What is unique is that these operators allow for the arbitrary regions of the arrays to be fragmented and distributed across multiple processors with a single point of access giving the programmer the illusion that all the elements are collocated on a single processor. Today's massively parallel High Productivity Computing Systems (HPCS) are characterized by a modular structure, with a large number of processing and memory units connected by a high-speed network. Locality of access as well as load balancing are primary concerns in these systems that are typically used for high-performance scientific computation. Data distributions address these issues by providing a range of methods for spreading large data sets across the components of a system. Over the past two decades, many languages, systems, tools, and libraries have been developed for the support of distributions. Since the performance of data parallel applications is directly influenced by the distribution strategy, users often resort to low-level programming models that allow fine-tuning of the distribution aspects affecting performance, but, at the same time, are tedious and error-prone. This technology presents a reusable design of a data-distribution framework for data parallel high-performance applications. Distributions are a means to express locality in systems composed of large numbers of processor and memory components connected by a network. Since distributions have a great effect on the performance of applications, it is important that the distribution strategy is flexible, so its behavior can change depending on the needs of the application. At the same time, high productivity concerns require that the user be shielded from error-prone, tedious details such as communication and synchronization.

Electron Microscopy Structural Insights into CPAP Oligomeric Behavior: A Plausible Assembly Process of a Supramolecular Scaffold of the Centrosome

PubMed Central

Alvarez-Cabrera, Ana L.; Delgado, Sandra; Gil-Carton, David; Mortuza, Gulnahar B.; Montoya, Guillermo; Sorzano, Carlos O. S.; Tang, Tang K.; Carazo, Jose M.

2017-01-01

Centrosomal P4.1-associated protein (CPAP) is a cell cycle regulated protein fundamental for centrosome assembly and centriole elongation. In humans, the region between residues 897–1338 of CPAP mediates interactions with other proteins and includes a homodimerization domain. CPAP mutations cause primary autosomal recessive microcephaly and Seckel syndrome. Despite of the biological/clinical relevance of CPAP, its mechanistic behavior remains unclear and its C-terminus (the G-box/TCP domain) is the only part whose structure has been solved. This situation is perhaps due in part to the challenges that represent obtaining the protein in a soluble, homogeneous state for structural studies. Our work constitutes a systematic structural analysis on multiple oligomers of HsCPAP897−1338, using single-particle electron microscopy (EM) of negatively stained (NS) samples. Based on image classification into clearly different regular 3D maps (putatively corresponding to dimers and tetramers) and direct observation of individual images representing other complexes of HsCPAP897−1338 (i.e., putative flexible monomers and higher-order multimers), we report a dynamic oligomeric behavior of this protein, where different homo-oligomers coexist in variable proportions. We propose that dimerization of the putative homodimer forms a putative tetramer which could be the structural unit for the scaffold that either tethers the pericentriolar material to centrioles or promotes procentriole elongation. A coarse fitting of atomic models into the NS 3D maps at resolutions around 20 Å is performed only to complement our experimental data, allowing us to hypothesize on the oligomeric composition of the different complexes. In this way, the current EM work represents an initial step toward the structural characterization of different oligomers of CPAP, suggesting further insights to understand how this protein works, contributing to the elucidation of control mechanisms for centriole biogenesis. PMID:28396859

Framing Effects: Dynamics and Task Domains

PubMed

Wang

1996-11-01

The author examines the mechanisms and dynamics of framing effects in risky choices across three distinct task domains (i.e., life-death, public property, and personal money). The choice outcomes of the problems presented in each of the three task domains had a binary structure of a sure thing vs a gamble of equal expected value; the outcomes differed in their framing conditions and the expected values, raging from 6000, 600, 60, to 6, numerically. It was hypothesized that subjects would become more risk seeking, if the sure outcome was below their aspiration level (the minimum requirement). As predicted, more subjects preferred the gamble when facing the life-death choice problems than facing the counterpart problems presented in the other two task domains. Subjects' risk preference varied categorically along the group size dimension in the life-death domain but changed more linearly over the expected value dimension in the monetary domain. Framing effects were observed in 7 of 13 pairs of problems, showing a positive frame-risk aversion and negative frame-risk seeking relationship. In addition, two types of framing effects were theoretically defined and empirically identified. A bidirectional framing effect involves a reversal in risk preference, and occurs when a decision maker's risk preference is ambiguous or weak. Four bidirectional effects were observed; in each case a majority of subjects preferred the sure outcome under a positive frame but the gamble under a negative frame. In contrast, a unidirectional framing effect refers to a preference shift due to the framing of choice outcomes: A majority of subjects preferred one choice outcome (either the sure thing or the gamble) under both framing conditions, with positive frame augmented the preference for the sure thing and negative frame augmented the preference for the gamble. These findings revealed some dynamic regularities of framing effects and posed implications for developing predictive and testable models of human decision making.

Regularized Generalized Structured Component Analysis

ERIC Educational Resources Information Center

Hwang, Heungsun

2009-01-01

Generalized structured component analysis (GSCA) has been proposed as a component-based approach to structural equation modeling. In practice, GSCA may suffer from multi-collinearity, i.e., high correlations among exogenous variables. GSCA has yet no remedy for this problem. Thus, a regularized extension of GSCA is proposed that integrates a ridge…

Structure of PA1221, a nonribosomal peptide synthetase containing adenylation and peptidyl carrier protein domains.

PubMed

Mitchell, Carter A; Shi, Ce; Aldrich, Courtney C; Gulick, Andrew M

2012-04-17

Many bacteria use large modular enzymes for the synthesis of polyketide and peptide natural products. These multidomain enzymes contain integrated carrier domains that deliver bound substrates to multiple catalytic domains, requiring coordination of these chemical steps. Nonribosomal peptide synthetases (NRPSs) load amino acids onto carrier domains through the activity of an upstream adenylation domain. Our lab recently determined the structure of an engineered two-domain NRPS containing fused adenylation and carrier domains. This structure adopted a domain-swapped dimer that illustrated the interface between these two domains. To continue our investigation, we now examine PA1221, a natural two-domain protein from Pseudomonas aeruginosa. We have determined the amino acid specificity of this new enzyme and used domain specific mutations to demonstrate that loading the downstream carrier domain within a single protein molecule occurs more quickly than loading of a nonfused carrier domain intermolecularly. Finally, we have determined crystal structures of both apo- and holo-PA1221 proteins, the latter using a valine-adenosine vinylsulfonamide inhibitor that traps the adenylation domain-carrier domain interaction. The protein adopts an interface similar to that seen with the prior adenylation domain-carrier protein construct. A comparison of these structures with previous structures of multidomain NRPSs suggests that a large conformational change within the NRPS adenylation domains guides the carrier domain into the active site for thioester formation.

A physical model describing the interaction of nuclear transport receptors with FG nucleoporin domain assemblies

PubMed Central

Zahn, Raphael; Osmanović, Dino; Ehret, Severin; Araya Callis, Carolina; Frey, Steffen; Stewart, Murray; You, Changjiang; Görlich, Dirk; Hoogenboom, Bart W; Richter, Ralf P

2016-01-01

The permeability barrier of nuclear pore complexes (NPCs) controls bulk nucleocytoplasmic exchange. It consists of nucleoporin domains rich in phenylalanine-glycine motifs (FG domains). As a bottom-up nanoscale model for the permeability barrier, we have used planar films produced with three different end-grafted FG domains, and quantitatively analyzed the binding of two different nuclear transport receptors (NTRs), NTF2 and Importin β, together with the concomitant film thickness changes. NTR binding caused only moderate changes in film thickness; the binding isotherms showed negative cooperativity and could all be mapped onto a single master curve. This universal NTR binding behavior – a key element for the transport selectivity of the NPC – was quantitatively reproduced by a physical model that treats FG domains as regular, flexible polymers, and NTRs as spherical colloids with a homogeneous surface, ignoring the detailed arrangement of interaction sites along FG domains and on the NTR surface. DOI: http://dx.doi.org/10.7554/eLife.14119.001 PMID:27058170

Crystal structure of the N domain of human somatic angiotensin I-converting enzyme provides a structural basis for domain-specific inhibitor design.

PubMed

Corradi, Hazel R; Schwager, Sylva L U; Nchinda, Aloysius T; Sturrock, Edward D; Acharya, K Ravi

2006-03-31

Human somatic angiotensin I-converting enzyme (sACE) is a key regulator of blood pressure and an important drug target for combating cardiovascular and renal disease. sACE comprises two homologous metallopeptidase domains, N and C, joined by an inter-domain linker. Both domains are capable of cleaving the two hemoregulatory peptides angiotensin I and bradykinin, but differ in their affinities for a range of other substrates and inhibitors. Previously we determined the structure of testis ACE (C domain); here we present the crystal structure of the N domain of sACE (both in the presence and absence of the antihypertensive drug lisinopril) in order to aid the understanding of how these two domains differ in specificity and function. In addition, the structure of most of the inter-domain linker allows us to propose relative domain positions for sACE that may contribute to the domain cooperativity. The structure now provides a platform for the design of "domain-specific" second-generation ACE inhibitors.

Employing temporal self-similarity across the entire time domain in computed tomography reconstruction

PubMed Central

Kazantsev, D.; Van Eyndhoven, G.; Lionheart, W. R. B.; Withers, P. J.; Dobson, K. J.; McDonald, S. A.; Atwood, R.; Lee, P. D.

2015-01-01

There are many cases where one needs to limit the X-ray dose, or the number of projections, or both, for high frame rate (fast) imaging. Normally, it improves temporal resolution but reduces the spatial resolution of the reconstructed data. Fortunately, the redundancy of information in the temporal domain can be employed to improve spatial resolution. In this paper, we propose a novel regularizer for iterative reconstruction of time-lapse computed tomography. The non-local penalty term is driven by the available prior information and employs all available temporal data to improve the spatial resolution of each individual time frame. A high-resolution prior image from the same or a different imaging modality is used to enhance edges which remain stationary throughout the acquisition time while dynamic features tend to be regularized spatially. Effective computational performance together with robust improvement in spatial and temporal resolution makes the proposed method a competitive tool to state-of-the-art techniques. PMID:25939621

Supra-domains: evolutionary units larger than single protein domains.

PubMed

Vogel, Christine; Berzuini, Carlo; Bashton, Matthew; Gough, Julian; Teichmann, Sarah A

2004-02-20

Domains are the evolutionary units that comprise proteins, and most proteins are built from more than one domain. Domains can be shuffled by recombination to create proteins with new arrangements of domains. Using structural domain assignments, we examined the combinations of domains in the proteins of 131 completely sequenced organisms. We found two-domain and three-domain combinations that recur in different protein contexts with different partner domains. The domains within these combinations have a particular functional and spatial relationship. These units are larger than individual domains and we term them "supra-domains". Amongst the supra-domains, we identified some 1400 (1203 two-domain and 166 three-domain) combinations that are statistically significantly over-represented relative to the occurrence and versatility of the individual component domains. Over one-third of all structurally assigned multi-domain proteins contain these over-represented supra-domains. This means that investigation of the structural and functional relationships of the domains forming these popular combinations would be particularly useful for an understanding of multi-domain protein function and evolution as well as for genome annotation. These and other supra-domains were analysed for their versatility, duplication, their distribution across the three kingdoms of life and their functional classes. By examining the three-dimensional structures of several examples of supra-domains in different biological processes, we identify two basic types of spatial relationships between the component domains: the combined function of the two domains is such that either the geometry of the two domains is crucial and there is a tight constraint on the interface, or the precise orientation of the domains is less important and they are spatially separate. Frequently, the role of the supra-domain becomes clear only once the three-dimensional structure is known. Since this is the case for only a quarter of the supra-domains, we provide a list of the most important unknown supra-domains as potential targets for structural genomics projects.

[Knocking-out extra domain A alternative splice fragment of fibronectin using a clustered regularly interspaced short palindromic repeats/associated proteins 9 system].

PubMed

Yang, Yue; Wang, Haicheng; Xu, Shuyu; Peng, Jing; Jiang, Jiuhui; Li, Cuiying

2015-08-01

To investigate the effect of the fibronectin extra domain A on the aggressiveness of salivary adenoid cystic carcinoma (SACC) cells, via the clustered regularly interspaced short palindromic repeats (CRISPR)/ associated proteins (Cas) system. One sgRNA was designed to target the upstream of the genome sequences of extra domain A(EDA) exon and the downstream. Then the sgRNA was linked into plasmid PX-330 and transfected into SACC-83 cells. PCR and DNA sequence were used to testify the knockout cells, and the monoclones of EDA absent SACC cells were selected (A+C-2, A+C-6, B+C-10). CCK-8 cell proliferation and invasion was then tested in control group and the experimental group. The sgRNA was successfully linked into PX-330 plasmid. Part of adenoid cystic carcinoma cells' SACC-83 genomic EDA exon was knocked out, and the knockdown efficiency was above 70%, but the total amount of fibronectin did not change significantly. Three monoclones of EDA absent SACC- 83 cells were successfully selected with diminished migration and proliferation. The CRISPR/Cas9 system was a simplified system with relatively high knockout efficiency and EDA knockout could inhibiting SACC cell's mobility and invasiveness.

Solution structure of leptospiral LigA4 Big domain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mei, Song; Zhang, Jiahai; Zhang, Xuecheng

Pathogenic Leptospiraspecies express immunoglobulin-like proteins which serve as adhesins to bind to the extracellular matrices of host cells. Leptospiral immunoglobulin-like protein A (LigA), a surface exposed protein containing tandem repeats of bacterial immunoglobulin-like (Big) domains, has been proved to be involved in the interaction of pathogenic Leptospira with mammalian host. In this study, the solution structure of the fourth Big domain of LigA (LigA4 Big domain) from Leptospira interrogans was solved by nuclear magnetic resonance (NMR). The structure of LigA4 Big domain displays a similar bacterial immunoglobulin-like fold compared with other Big domains, implying some common structural aspects of Bigmore » domain family. On the other hand, it displays some structural characteristics significantly different from classic Ig-like domain. Furthermore, Stains-all assay and NMR chemical shift perturbation revealed the Ca{sup 2+} binding property of LigA4 Big domain. - Highlights: • Determining the solution structure of a bacterial immunoglobulin-like domain from a surface protein of Leptospira. • The solution structure shows some structural characteristics significantly different from the classic Ig-like domains. • A potential Ca{sup 2+}-binding site was identified by strains-all and NMR chemical shift perturbation.« less

Chinese Children's Statistical Learning of Orthographic Regularities: Positional Constraints and Character Structure

ERIC Educational Resources Information Center

Tong, Xiuli; McBride, Catherine

2014-01-01

This study examined how Chinese children acquire the untaught positional constraints of stroke patterns that are embedded in left-right structured and top-bottom structured characters. Using an orthographic regularity pattern elicitation paradigm, 536 Hong Kong Chinese children at different levels of reading (kindergarten, 2nd, and 5th grades)…

What's in a domain: Understanding how students approach questioning in history and science

NASA Astrophysics Data System (ADS)

Portnoy, Lindsay Blau

During their education, students are presented with information across a variety of academic domains. How students ask questions as they learn has implications for understanding, retention, and problem solving. The current research investigates the influence of age and prior knowledge on the ways students approach questioning across history and science content. In two studies, students read history and science passages and then generated questions they would ask to make sense of the content. Nine categories of questions were identified to discern patterns of inquiry across both domains. Results indicate that while age and prior knowledge may play a role in the way students ask questions by domain there are persistent main effects of domain across both studies. Specifically, across both studies students ask questions regarding the purpose or function of ideas in science passages, whereas history passage are more regularly met with questions for supplemental information to complete a student's understanding. In contrast to extant research on developmental status or experience within a content area, current work suggests that domains themselves hold unique properties, which may influence how students approach questioning across domains.

Domain-Invariant Partial-Least-Squares Regression.

PubMed

Nikzad-Langerodi, Ramin; Zellinger, Werner; Lughofer, Edwin; Saminger-Platz, Susanne

2018-05-11

Multivariate calibration models often fail to extrapolate beyond the calibration samples because of changes associated with the instrumental response, environmental condition, or sample matrix. Most of the current methods used to adapt a source calibration model to a target domain exclusively apply to calibration transfer between similar analytical devices, while generic methods for calibration-model adaptation are largely missing. To fill this gap, we here introduce domain-invariant partial-least-squares (di-PLS) regression, which extends ordinary PLS by a domain regularizer in order to align the source and target distributions in the latent-variable space. We show that a domain-invariant weight vector can be derived in closed form, which allows the integration of (partially) labeled data from the source and target domains as well as entirely unlabeled data from the latter. We test our approach on a simulated data set where the aim is to desensitize a source calibration model to an unknown interfering agent in the target domain (i.e., unsupervised model adaptation). In addition, we demonstrate unsupervised, semisupervised, and supervised model adaptation by di-PLS on two real-world near-infrared (NIR) spectroscopic data sets.

Assessment of First- and Second-Order Wave-Excitation Load Models for Cylindrical Substructures: Preprint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pereyra, Brandon; Wendt, Fabian; Robertson, Amy

2017-03-09

The hydrodynamic loads on an offshore wind turbine's support structure present unique engineering challenges for offshore wind. Two typical approaches used for modeling these hydrodynamic loads are potential flow (PF) and strip theory (ST), the latter via Morison's equation. This study examines the first- and second-order wave-excitation surge forces on a fixed cylinder in regular waves computed by the PF and ST approaches to (1) verify their numerical implementations in HydroDyn and (2) understand when the ST approach breaks down. The numerical implementation of PF and ST in HydroDyn, a hydrodynamic time-domain solver implemented as a module in the FASTmore » wind turbine engineering tool, was verified by showing the consistency in the first- and second-order force output between the two methods across a range of wave frequencies. ST is known to be invalid at high frequencies, and this study investigates where the ST solution diverges from the PF solution. Regular waves across a range of frequencies were run in HydroDyn for a monopile substructure. As expected, the solutions for the first-order (linear) wave-excitation loads resulting from these regular waves are similar for PF and ST when the diameter of the cylinder is small compared to the length of the waves (generally when the diameter-to-wavelength ratio is less than 0.2). The same finding applies to the solutions for second-order wave-excitation loads, but for much smaller diameter-to-wavelength ratios (based on wavelengths of first-order waves).« less

Assessment of First- and Second-Order Wave-Excitation Load Models for Cylindrical Substructures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pereyra, Brandon; Wendt, Fabian; Robertson, Amy

2016-07-01

The hydrodynamic loads on an offshore wind turbine's support structure present unique engineering challenges for offshore wind. Two typical approaches used for modeling these hydrodynamic loads are potential flow (PF) and strip theory (ST), the latter via Morison's equation. This study examines the first- and second-order wave-excitation surge forces on a fixed cylinder in regular waves computed by the PF and ST approaches to (1) verify their numerical implementations in HydroDyn and (2) understand when the ST approach breaks down. The numerical implementation of PF and ST in HydroDyn, a hydrodynamic time-domain solver implemented as a module in the FASTmore » wind turbine engineering tool, was verified by showing the consistency in the first- and second-order force output between the two methods across a range of wave frequencies. ST is known to be invalid at high frequencies, and this study investigates where the ST solution diverges from the PF solution. Regular waves across a range of frequencies were run in HydroDyn for a monopile substructure. As expected, the solutions for the first-order (linear) wave-excitation loads resulting from these regular waves are similar for PF and ST when the diameter of the cylinder is small compared to the length of the waves (generally when the diameter-to-wavelength ratio is less than 0.2). The same finding applies to the solutions for second-order wave-excitation loads, but for much smaller diameter-to-wavelength ratios (based on wavelengths of first-order waves).« less

Regularization techniques for backward--in--time evolutionary PDE problems

NASA Astrophysics Data System (ADS)

Gustafsson, Jonathan; Protas, Bartosz

2007-11-01

Backward--in--time evolutionary PDE problems have applications in the recently--proposed retrograde data assimilation. We consider the terminal value problem for the Kuramoto--Sivashinsky equation (KSE) in a 1D periodic domain as our model system. The KSE, proposed as a model for interfacial and combustion phenomena, is also often adopted as a toy model for hydrodynamic turbulence because of its multiscale and chaotic dynamics. Backward--in--time problems are typical examples of ill-posed problem, where disturbances are amplified exponentially during the backward march. Regularization is required to solve such problems efficiently and we consider approaches in which the original ill--posed problem is approximated with a less ill--posed problem obtained by adding a regularization term to the original equation. While such techniques are relatively well--understood for linear problems, they less understood in the present nonlinear setting. We consider regularization terms with fixed magnitudes and also explore a novel approach in which these magnitudes are adapted dynamically using simple concepts from the Control Theory.

Regularity theory for general stable operators

NASA Astrophysics Data System (ADS)

Ros-Oton, Xavier; Serra, Joaquim

2016-06-01

We establish sharp regularity estimates for solutions to Lu = f in Ω ⊂Rn, L being the generator of any stable and symmetric Lévy process. Such nonlocal operators L depend on a finite measure on S n - 1, called the spectral measure. First, we study the interior regularity of solutions to Lu = f in B1. We prove that if f is Cα then u belong to C α + 2 s whenever α + 2 s is not an integer. In case f ∈L∞, we show that the solution u is C2s when s ≠ 1 / 2, and C 2 s - ɛ for all ɛ > 0 when s = 1 / 2. Then, we study the boundary regularity of solutions to Lu = f in Ω, u = 0 in Rn ∖ Ω, in C 1 , 1 domains Ω. We show that solutions u satisfy u /ds ∈C s - ɛ (Ω ‾) for all ɛ > 0, where d is the distance to ∂Ω. Finally, we show that our results are sharp by constructing two counterexamples.

Structure of the Response Regulator PhoP from Mycobacterium tuberculosis Reveals a Dimer Through the Receiver Domain

DOE Office of Scientific and Technical Information (OSTI.GOV)

S Menon; S Wang

The PhoP protein from Mycobacterium tuberculosis is a response regulator of the OmpR/PhoB subfamily, whose structure consists of an N-terminal receiver domain and a C-terminal DNA-binding domain. How the DNA-binding activities are regulated by phosphorylation of the receiver domain remains unclear due to a lack of structural information on the full-length proteins. Here we report the crystal structure of the full-length PhoP of M. tuberculosis. Unlike other known structures of full-length proteins of the same subfamily, PhoP forms a dimer through its receiver domain with the dimer interface involving {alpha}4-{beta}5-{alpha}5, a common interface for activated receiver domain dimers. However, themore » switch residues, Thr99 and Tyr118, are in a conformation resembling those of nonactivated receiver domains. The Tyr118 side chain is involved in the dimer interface interactions. The receiver domain is tethered to the DNA-binding domain through a flexible linker and does not impose structural constraints on the DNA-binding domain. This structure suggests that phosphorylation likely facilitates/stabilizes receiver domain dimerization, bringing the DNA-binding domains to close proximity, thereby increasing their binding affinity for direct repeat DNA sequences.« less

Crystal structure studies of NADP{sup +} dependent isocitrate dehydrogenase from Thermus thermophilus exhibiting a novel terminal domain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, S.M.; Pampa, K.J.; Manjula, M.

2014-06-20

Highlights: • We determined the structure of isocitrate dehydrogenase with citrate and cofactor. • The structure reveals a unique novel terminal domain involved in dimerization. • Clasp domain shows significant difference, and catalytic residues are conserved. • Oligomerization of the enzyme is quantized with subunit-subunit interactions. • Novel domain of this enzyme is classified as subfamily of the type IV. - Abstract: NADP{sup +} dependent isocitrate dehydrogenase (IDH) is an enzyme catalyzing oxidative decarboxylation of isocitrate into oxalosuccinate (intermediate) and finally the product α-ketoglutarate. The crystal structure of Thermus thermophilus isocitrate dehydrogenase (TtIDH) ternary complex with citrate and cofactor NADP{supmore » +} was determined using X-ray diffraction method to a resolution of 1.80 Å. The overall fold of this protein was resolved into large domain, small domain and a clasp domain. The monomeric structure reveals a novel terminal domain involved in dimerization, very unique and novel domain when compared to other IDH’s. And, small domain and clasp domain showing significant differences when compared to other IDH’s of the same sub-family. The structure of TtIDH reveals the absence of helix at the clasp domain, which is mainly involved in oligomerization in other IDH’s. Also, helices/beta sheets are absent in the small domain, when compared to other IDH’s of the same sub family. The overall TtIDH structure exhibits closed conformation with catalytic triad residues, Tyr144-Asp248-Lys191 are conserved. Oligomerization of the protein is quantized using interface area and subunit–subunit interactions between protomers. Overall, the TtIDH structure with novel terminal domain may be categorized as a first structure of subfamily of type IV.« less

Annealing a magnetic cactus into phyllotaxis

NASA Astrophysics Data System (ADS)

Nisoli, Cristiano; Gabor, Nathaniel M.; Lammert, Paul E.; Maynard, J. D.; Crespi, Vincent H.

2010-04-01

The appearance of mathematical regularities in the disposition of leaves on a stem, scales on a pine-cone, and spines on a cactus has puzzled scholars for millennia; similar so-called phyllotactic patterns are seen in self-organized growth, polypeptides, convection, magnetic flux lattices and ion beams. Levitov showed that a cylindrical lattice of repulsive particles can reproduce phyllotaxis under the (unproved) assumption that minimum of energy would be achieved by two-dimensional Bravais lattices. Here we provide experimental and numerical evidence that the Phyllotactic lattice is actually a ground state. When mechanically annealed, our experimental “magnetic cactus” precisely reproduces botanical phyllotaxis, along with domain boundaries (called transitions in Botany) between different phyllotactic patterns. We employ a structural genetic algorithm to explore the more general axially unconstrained case, which reveals multijugate (multiple spirals) as well as monojugate (single-spiral) phyllotaxis.

Thermal transport across high-pressure semiconductor-metal transition in Si and Si 0.991 Ge 0.009

DOE PAGES

Hohensee, Gregory T.; Fellinger, Michael R.; Trinkle, Dallas R.; ...

2015-05-07

Time-domain thermoreflectance (TDTR) can be applied to metallic samples at high pressures in the diamond anvil cell (DAC) and provide non-contact measurements of thermal transport properties. We have performed regular and beam-offset TDTR to establish the thermal conductivities of Si and Si 0.991Ge 0.009 across the semiconductor-metal phase transition and up to 45 GPa. The thermal conductivities of metallic Si and Si(Ge) are comparable to aluminum and indicative of predominantly electronic heat carriers. Metallic Si and Si(Ge) have an anisotropy of approximately 1.4, similar to that of beryllium, due to the primitive hexagonal crystal structure. Furthermore, we used the Wiedemann-Franzmore » law to derive the associated electrical resistivity, and found it consistent with the Bloch-Gruneisen model.« less

Periodic measure for the stochastic equation of the barotropic viscous gas in a discretized one-dimensional domain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benseghir, Rym, E-mail: benseghirrym@ymail.com, E-mail: benseghirrym@ymail.com; Benchettah, Azzedine, E-mail: abenchettah@hotmail.com; Raynaud de Fitte, Paul, E-mail: prf@univ-rouen.fr

2015-11-30

A stochastic equation system corresponding to the description of the motion of a barotropic viscous gas in a discretized one-dimensional domain with a weight regularizing the density is considered. In [2], the existence of an invariant measure was established for this discretized problem in the stationary case. In this paper, applying a slightly modified version of Khas’minskii’s theorem [5], we generalize this result in the periodic case by proving the existence of a periodic measure for this problem.

Avoiding "greedy reductionism" in personality theory. Comment on "Personality from a cognitive-biological perspective" by Y. Neuman

NASA Astrophysics Data System (ADS)

Smillie, Luke D.; Zhao, Kun; Barford, Kate A.

2014-12-01

Personality traits - i.e., broad descriptions of regularities in behaviour and experience - can be parsimoniously organised in terms of five trait 'domains' [8]. This is demonstrated by Neuman's [12] observation of the overlap between these 'Big Five' domains and traits derived from Panksepp's Affective Neuroscience framework [13]. This overlap reflects the fact that the Big Five - which can be recovered from factor analyses of questionnaires designed to measure other trait systems [2,10] - represent the major dimensions of covariation among all personality traits [5].

Autotransporter structure reveals intra-barrel cleavage followed by conformational changes.

PubMed

Barnard, Travis J; Dautin, Nathalie; Lukacik, Petra; Bernstein, Harris D; Buchanan, Susan K

2007-12-01

Autotransporters are virulence factors produced by Gram-negative bacteria. They consist of two domains, an N-terminal 'passenger' domain and a C-terminal beta-domain. beta-domains form beta-barrel structures in the outer membrane while passenger domains are translocated into the extracellular space. In some autotransporters, the two domains are separated by proteolytic cleavage. Using X-ray crystallography, we solved the 2.7-A structure of the post-cleavage state of the beta-domain of EspP, an autotransporter produced by Escherichia coli strain O157:H7. The structure consists of a 12-stranded beta-barrel with the passenger domain-beta-domain cleavage junction located inside the barrel pore, approximately midway between the extracellular and periplasmic surfaces of the outer membrane. The structure reveals an unprecedented intra-barrel cleavage mechanism and suggests that two conformational changes occur in the beta-domain after cleavage, one conferring increased stability on the beta-domain and another restricting access to the barrel pore.

Effective Moment Feature Vectors for Protein Domain Structures

PubMed Central

Shi, Jian-Yu; Yiu, Siu-Ming; Zhang, Yan-Ning; Chin, Francis Yuk-Lun

2013-01-01

Imaging processing techniques have been shown to be useful in studying protein domain structures. The idea is to represent the pairwise distances of any two residues of the structure in a 2D distance matrix (DM). Features and/or submatrices are extracted from this DM to represent a domain. Existing approaches, however, may involve a large number of features (100–400) or complicated mathematical operations. Finding fewer but more effective features is always desirable. In this paper, based on some key observations on DMs, we are able to decompose a DM image into four basic binary images, each representing the structural characteristics of a fundamental secondary structure element (SSE) or a motif in the domain. Using the concept of moments in image processing, we further derive 45 structural features based on the four binary images. Together with 4 features extracted from the basic images, we represent the structure of a domain using 49 features. We show that our feature vectors can represent domain structures effectively in terms of the following. (1) We show a higher accuracy for domain classification. (2) We show a clear and consistent distribution of domains using our proposed structural vector space. (3) We are able to cluster the domains according to our moment features and demonstrate a relationship between structural variation and functional diversity. PMID:24391828

Multimaterial topology optimization of contact problems using phase field regularization

NASA Astrophysics Data System (ADS)

Myśliński, Andrzej

2018-01-01

The numerical method to solve multimaterial topology optimization problems for elastic bodies in unilateral contact with Tresca friction is developed in the paper. The displacement of the elastic body in contact is governed by elliptic equation with inequality boundary conditions. The body is assumed to consists from more than two distinct isotropic elastic materials. The materials distribution function is chosen as the design variable. Since high contact stress appears during the contact phenomenon the aim of the structural optimization problem is to find such topology of the domain occupied by the body that the normal contact stress along the boundary of the body is minimized. The original cost functional is regularized using the multiphase volume constrained Ginzburg-Landau energy functional rather than the perimeter functional. The first order necessary optimality condition is recalled and used to formulate the generalized gradient flow equations of Allen-Cahn type. The optimal topology is obtained as the steady state of the phase transition governed by the generalized Allen-Cahn equation. As the interface width parameter tends to zero the transition of the phase field model to the level set model is studied. The optimization problem is solved numerically using the operator splitting approach combined with the projection gradient method. Numerical examples confirming the applicability of the proposed method are provided and discussed.

Consistent Partial Least Squares Path Modeling via Regularization.

PubMed

Jung, Sunho; Park, JaeHong

2018-01-01

Partial least squares (PLS) path modeling is a component-based structural equation modeling that has been adopted in social and psychological research due to its data-analytic capability and flexibility. A recent methodological advance is consistent PLS (PLSc), designed to produce consistent estimates of path coefficients in structural models involving common factors. In practice, however, PLSc may frequently encounter multicollinearity in part because it takes a strategy of estimating path coefficients based on consistent correlations among independent latent variables. PLSc has yet no remedy for this multicollinearity problem, which can cause loss of statistical power and accuracy in parameter estimation. Thus, a ridge type of regularization is incorporated into PLSc, creating a new technique called regularized PLSc. A comprehensive simulation study is conducted to evaluate the performance of regularized PLSc as compared to its non-regularized counterpart in terms of power and accuracy. The results show that our regularized PLSc is recommended for use when serious multicollinearity is present.

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

PubMed

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.

Conformational changes in the expression domain of the Escherichia coli thiM riboswitch

PubMed Central

Rentmeister, Andrea; Mayer, Günter; Kuhn, Nicole; Famulok, Michael

2007-01-01

The thiM riboswitch contains an aptamer domain that adaptively binds the coenzyme thiamine pyrophosphate (TPP). The binding of TPP to the aptamer domain induces structural rearrangements that are relayed to a second domain, the so-called expression domain, thereby interfering with gene expression. The recently solved crystal structures of the aptamer domains of the thiM riboswitches in complex with TPP revealed how TPP stabilizes secondary and tertiary structures in the RNA ligand complex. To understand the global modes of reorganization between the two domains upon metabolite binding the structure of the entire riboswitch in presence and absence of TPP needs to be determined. Here we report the secondary structure of the entire thiM riboswitch from Escherichia coli in its TPP-free form and its transition into the TPP-bound variant, thereby depicting domains of the riboswitch that serve as communication links between the aptamer and the expression domain. Furthermore, structural probing provides an explanation for the lack of genetic control exerted by a riboswitch variant with mutations in the expression domain that still binds TPP. PMID:17517779

Domain structure of the ribozyme from eubacterial ribonuclease P.

PubMed Central

Loria, A; Pan, T

1996-01-01

Large RNAs can be composed of discrete domains that fold independently. One such "folding domain" has been identified previously in the ribozyme from Bacillus subtilis ribonuclease P (denoted P RNA). This domain contains roughly one-third of all residues. Folding of an RNA construct consisting of the remaining two-thirds of B. subtilis P RNA was examined by Fe(II)-EDTA hydroxyl radical protection. This molecule folds into the proper higher-order structure under identical conditions as the full-length P RNA, suggesting the presence of a second folding domain in B. subtilis P RNA. Folding analysis of the Escherichia coli P RNA by hydroxyl radical protection shows that this P RNA is completely folded at 5-6 mM Mg2+. In order to analyze the structural organization of folding domains in E. coli P RNA, constructs were designed based on the domain structure of B. subtilis P RNA. Fe(II)-EDTA protection indicates that E. coli P RNA also contains two folding domains. Despite the significant differences at the secondary structure level, both P RNAs appear to converge structurally at the folding domain level. The pre-tRNA substrate, localized in previous studies, may bind across the folding domains with the acceptor stem/3'CCA contacting the domain including the active site and the T stem-loop contacting the other. Because all eubacterial P RNAs share considerable homology in secondary structure to either B. subtilis or E. coli P RNA, these results suggest that this domain structure may be applicable for most, if not all, eubacterial P RNAs. Identification of folding domains should be valuable in dissecting structure-function relationship of large RNAs. PMID:8718684

Molecular Structures and Functional Relationships in Clostridial Neurotoxins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swaminathan S.

2011-12-01

The seven serotypes of Clostridium botulinum neurotoxins (A-G) are the deadliest poison known to humans. They share significant sequence homology and hence possess similar structure-function relationships. Botulinum neurotoxins (BoNT) act via a four-step mechanism, viz., binding and internalization to neuronal cells, translocation of the catalytic domain into the cytosol and finally cleavage of one of the three soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) causing blockage of neurotransmitter release leading to flaccid paralysis. Crystal structures of three holotoxins, BoNT/A, B and E, are available to date. Although the individual domains are remarkably similar, their domain organization is different. These structuresmore » have helped in correlating the structural and functional domains. This has led to the determination of structures of individual domains and combinations of them. Crystal structures of catalytic domains of all serotypes and several binding domains are now available. The catalytic domains are zinc endopeptidases and share significant sequence and structural homology. The active site architecture and the catalytic mechanism are similar although the binding mode of individual substrates may be different, dictating substrate specificity and peptide cleavage selectivity. Crystal structures of catalytic domains with substrate peptides provide clues to specificity and selectivity unique to BoNTs. Crystal structures of the receptor domain in complex with ganglioside or the protein receptor have provided information about the binding of botulinum neurotoxin to the neuronal cell. An overview of the structure-function relationship correlating the 3D structures with biochemical and biophysical data and how they can be used for structure-based drug discovery is presented here.« less

Identification of N-Terminal Lobe Motifs that Determine the Kinase Activity of the Catalytic Domains and Regulatory Strategies of Src and Csk Protein Tyrosine Kinases†

PubMed Central

Huang, Kezhen; Wang, Yue-Hao; Brown, Alex; Sun, Gongqin

2009-01-01

Csk and Src protein tyrosine kinases are structurally homologous, but use opposite regulatory strategies. The isolated catalytic domain of Csk is intrinsically inactive and is activated by interactions with the regulatory SH3 and SH2 domains, while the isolated catalytic domain of Src is intrinsically active and is suppressed by interactions with the regulatory SH3 and SH2 domains. The structural basis for why one isolated catalytic domain is intrinsically active while the other is inactive is not clear. In this current study, we identify the structural elements in the N-terminal lobe of the catalytic domain that render the Src catalytic domain active. These structural elements include the α-helix C region, a β-turn between the β-4 and β-5 strands, and an Arg residue at the beginning of the catalytic domain. These three motifs interact with each other to activate the Src catalytic domain, but the equivalent motifs in Csk directly interact with the regulatory domains that are important for Csk activation. The Src motifs can be grafted to the Csk catalytic domain to obtain an active Csk catalytic domain. These results, together with available Src and Csk tertiary structures, reveal an important structural switch that determines the kinase activity of a catalytic domain and dictates the regulatory strategy of a kinase. PMID:19244618

Combining observations in the reflective solar and thermal domains for improved mapping of carbon, water and energy fluxes

USDA-ARS?s Scientific Manuscript database

The REGularized canopy reFLECtance (REGFLEC) modeling tool integrates leaf optics, canopy reflectance, and atmospheric radiative transfer model components, facilitating accurate retrieval of leaf area index (LAI) and leaf chlorophyll content (Cab) directly from at-sensor radiances in green, red and ...

Minimizing Wide-Area Performance Disruptions in Inter-Domain Routing

DTIC Science & Technology

2011-09-01

Servers As another example, we saw the average round-trip time double for an ISP in Malaysia . The RTT increase was caused by a traffic shift to different... censorship , conduct wiretapping, or offer poor performance. This is achieved by applying regular expressions to the AS-PATH to assign lower preference

Pronounced microheterogeneity in a sorbitol-water mixture observed through variable temperature neutron scattering.

PubMed

Chou, Shin G; Soper, Alan K; Khodadadi, Sheila; Curtis, Joseph E; Krueger, Susan; Cicerone, Marcus T; Fitch, Andrew N; Shalaev, Evgenyi Y

2012-04-19

In this study, the structure of concentrated d-sorbitol-water mixtures is studied by wide- and small-angle neutron scattering (WANS and SANS) as a function of temperature. The mixtures are prepared using both deuterated and regular sorbitol and water at a molar fraction of sorbitol of 0.19 (equivalent to 70% by weight of regular sorbitol in water). Retention of an amorphous structure (i.e., absence of crystallinity) is confirmed for this system over the entire temperature range, 100-298 K. The glass transition temperature, Tg, is found from differential scanning calorimetry to be approximately 200 K. WANS data are analyzed using empirical potential structure refinement, to obtain the site-site radial distribution functions (RDFs) and coordination numbers. This analysis reveals the presence of nanoscaled water clusters surrounded by (and interacting with) sorbitol molecules. The water clusters appear more structured compared to bulk water and, especially at the lowest temperatures, resemble the structure of low-density amorphous ice (LDA). Upon cooling to 100 K the peaks in the water RDFs become markedly sharper, with increased coordination number, indicating enhanced local (nanometer-scale) ordering, with changes taking place both above and well below the Tg. On the mesoscopic (submicrometer) scale, although there are no changes between 298 and 213 K, cooling the sample to 100 K results in a significant increase in the SANS signal, which is indicative of pronounced inhomogeneities. This increase in the scattering is partly reversed during heating, although some hysteresis is observed. Furthermore, a power law analysis of the SANS data indicates the existence of domains with well-defined interfaces on the submicrometer length scale, probably as a result of the appearance and growth of microscopic voids in the glassy matrix. Because of the unusual combination of small and wide scattering data used here, the present results provide new physical insight into the structure of aqueous glasses over a broad temperature and length scale, leading to an improved understanding of the mechanisms of temperature- and water-induced (de)stabilization of various systems, including proteins, pharmaceuticals, and biological objects.

Human action recognition with group lasso regularized-support vector machine

NASA Astrophysics Data System (ADS)

Luo, Huiwu; Lu, Huanzhang; Wu, Yabei; Zhao, Fei

2016-05-01

The bag-of-visual-words (BOVW) and Fisher kernel are two popular models in human action recognition, and support vector machine (SVM) is the most commonly used classifier for the two models. We show two kinds of group structures in the feature representation constructed by BOVW and Fisher kernel, respectively, since the structural information of feature representation can be seen as a prior for the classifier and can improve the performance of the classifier, which has been verified in several areas. However, the standard SVM employs L2-norm regularization in its learning procedure, which penalizes each variable individually and cannot express the structural information of feature representation. We replace the L2-norm regularization with group lasso regularization in standard SVM, and a group lasso regularized-support vector machine (GLRSVM) is proposed. Then, we embed the group structural information of feature representation into GLRSVM. Finally, we introduce an algorithm to solve the optimization problem of GLRSVM by alternating directions method of multipliers. The experiments evaluated on KTH, YouTube, and Hollywood2 datasets show that our method achieves promising results and improves the state-of-the-art methods on KTH and YouTube datasets.

The cost of uniqueness in groundwater model calibration

NASA Astrophysics Data System (ADS)

Moore, Catherine; Doherty, John

2006-04-01

Calibration of a groundwater model requires that hydraulic properties be estimated throughout a model domain. This generally constitutes an underdetermined inverse problem, for which a solution can only be found when some kind of regularization device is included in the inversion process. Inclusion of regularization in the calibration process can be implicit, for example through the use of zones of constant parameter value, or explicit, for example through solution of a constrained minimization problem in which parameters are made to respect preferred values, or preferred relationships, to the degree necessary for a unique solution to be obtained. The "cost of uniqueness" is this: no matter which regularization methodology is employed, the inevitable consequence of its use is a loss of detail in the calibrated field. This, in turn, can lead to erroneous predictions made by a model that is ostensibly "well calibrated". Information made available as a by-product of the regularized inversion process allows the reasons for this loss of detail to be better understood. In particular, it is easily demonstrated that the estimated value for an hydraulic property at any point within a model domain is, in fact, a weighted average of the true hydraulic property over a much larger area. This averaging process causes loss of resolution in the estimated field. Where hydraulic conductivity is the hydraulic property being estimated, high averaging weights exist in areas that are strategically disposed with respect to measurement wells, while other areas may contribute very little to the estimated hydraulic conductivity at any point within the model domain, this possibly making the detection of hydraulic conductivity anomalies in these latter areas almost impossible. A study of the post-calibration parameter field covariance matrix allows further insights into the loss of system detail incurred through the calibration process to be gained. A comparison of pre- and post-calibration parameter covariance matrices shows that the latter often possess a much smaller spectral bandwidth than the former. It is also demonstrated that, as an inevitable consequence of the fact that a calibrated model cannot replicate every detail of the true system, model-to-measurement residuals can show a high degree of spatial correlation, a fact which must be taken into account when assessing these residuals either qualitatively, or quantitatively in the exploration of model predictive uncertainty. These principles are demonstrated using a synthetic case in which spatial parameter definition is based on pilot points, and calibration is implemented using both zones of piecewise constancy and constrained minimization regularization.

Evaluation and application of the ROMS 1-way embedding procedure to the central california upwelling system

NASA Astrophysics Data System (ADS)

Penven, Pierrick; Debreu, Laurent; Marchesiello, Patrick; McWilliams, James C.

What most clearly distinguishes near-shore and off-shore currents is their dominant spatial scale, O (1-30) km near-shore and O (30-1000) km off-shore. In practice, these phenomena are usually both measured and modeled with separate methods. In particular, it is infeasible for any regular computational grid to be large enough to simultaneously resolve well both types of currents. In order to obtain local solutions at high resolution while preserving the regional-scale circulation at an affordable computational cost, a 1-way grid embedding capability has been integrated into the Regional Oceanic Modeling System (ROMS). It takes advantage of the AGRIF (Adaptive Grid Refinement in Fortran) Fortran 90 package based on the use of pointers. After a first evaluation in a baroclinic vortex test case, the embedding procedure has been applied to a domain that covers the central upwelling region off California, around Monterey Bay, embedded in a domain that spans the continental U.S. Pacific Coast. Long-term simulations (10 years) have been conducted to obtain mean-seasonal statistical equilibria. The final solution shows few discontinuities at the parent-child domain boundary and a valid representation of the local upwelling structure, at a CPU cost only slightly greater than for the inner region alone. The solution is assessed by comparison with solutions for the whole US Pacific Coast at both low and high resolutions and to solutions for only the inner region at high resolution with mean-seasonal boundary conditions.

Motivational Pathways to Unique Types of Alcohol Consequences

PubMed Central

Merrill, Jennifer E.; Read, Jennifer P.

2010-01-01

Individuals consume alcohol for a variety of reasons (motives), and these reasons may be differentially associated with the types of drinking outcomes that result. The present study examined whether specific affect-relevant motivations for alcohol use (i.e., coping, enhancement) are associated with distinct types of consequences, and whether such associations occur directly, or only as a function of increased alcohol use. It was hypothesized that enhancement motives would be associated with distinct problem types only through alcohol use, whereas coping motives would be linked directly to hypothesized problem types. Regularly drinking undergraduates (N= 192, 93 female) completed self-report measures of drinking motives and alcohol involvement. Using structural equation modeling, we tested direct associations between Coping motives and indirect associations between Enhancement motives and eight unique alcohol problem domains: Risky Behaviors, Blackout Drinking, Physiological Dependence, Academic/Occupational problems, Poor Self-care, Diminished Self-perception, Social/Interpersonal problems, and Impaired Control. We observed direct effects of Coping motives on three unique problem domains (Academic/Occupational problems, Risky Behaviors, and Poor Self-care). Both Coping and Enhancement motives were indirectly associated (through Use) with several problem types. Unhypothesized associations between Conformity motives and unique consequence types also were observed. Findings suggest specificity in the consequences experienced by individuals who drink to cope with negative affect versus to enhance positive affect, and may have intervention implications. Findings depict the coping motivated student as one who is struggling across multiple domains, regardless of levels of drinking. Such students may need to be prioritized for interventions. PMID:20822194

Distribution and prediction of catalytic domains in 2-oxoglutarate dependent dioxygenases

PubMed Central

2012-01-01

Background The 2-oxoglutarate dependent superfamily is a diverse group of non-haem dioxygenases, and is present in prokaryotes, eukaryotes, and archaea. The enzymes differ in substrate preference and reaction chemistry, a factor that precludes their classification by homology studies and electronic annotation schemes alone. In this work, I propose and explore the rationale of using substrates to classify structurally similar alpha-ketoglutarate dependent enzymes. Findings Differential catalysis in phylogenetic clades of 2-OG dependent enzymes, is determined by the interactions of a subset of active-site amino acids. Identifying these with existing computational methods is challenging and not feasible for all proteins. A clustering protocol based on validated mechanisms of catalysis of known molecules, in tandem with group specific hidden markov model profiles is able to differentiate and sequester these enzymes. Access to this repository is by a web server that compares user defined unknown sequences to these pre-defined profiles and outputs a list of predicted catalytic domains. The server is free and is accessible at the following URL ( http://comp-biol.theacms.in/H2OGpred.html). Conclusions The proposed stratification is a novel attempt at classifying and predicting 2-oxoglutarate dependent function. In addition, the server will provide researchers with a tool to compare their data to a comprehensive list of HMM profiles of catalytic domains. This work, will aid efforts by investigators to screen and characterize putative 2-OG dependent sequences. The profile database will be updated at regular intervals. PMID:22862831

High-pressure phase transition and phase diagram of gallium arsenide

NASA Astrophysics Data System (ADS)

Besson, J. M.; Itié, J. P.; Polian, A.; Weill, G.; Mansot, J. L.; Gonzalez, J.

1991-09-01

Under hydrostatic pressure, cubic GaAs-I undergoes phase transitions to at least two orthorhombic structures. The initial phase transition to GaAs-II has been investigated by optical-transmittance measurements, Raman scattering, and x-ray absorption. The structure of pressurized samples, which are retrieved at ambient, has been studied by x-ray diffraction and high-resolution diffraction microscopy. Various criteria that define the domain of stability of GaAs-I are examined, such as the occurrence of crystalline defects, the local variation in atomic coordination number, or the actual change in crystal structure. These are shown not to occur at the same pressure at 300 K, the latter being observable only several GPa above the actual thermodynamic instability pressure of GaAs-I. Comparison of the evolution of these parameters on increasing and decreasing pressure locates the thermodynamic transition region GaAs-I-->GaAs-II at 12+/-1.5 GPa and at 300 K that is lower than generally reported. The use of thermodynamic relations around the triple point, and of regularities in the properties of isoelectronic and isostructural III-V compounds, yields a phase diagram for GaAs which is consistent with this value.

Regularized matrix regression

PubMed Central

Zhou, Hua; Li, Lexin

2014-01-01

Summary Modern technologies are producing a wealth of data with complex structures. For instance, in two-dimensional digital imaging, flow cytometry and electroencephalography, matrix-type covariates frequently arise when measurements are obtained for each combination of two underlying variables. To address scientific questions arising from those data, new regression methods that take matrices as covariates are needed, and sparsity or other forms of regularization are crucial owing to the ultrahigh dimensionality and complex structure of the matrix data. The popular lasso and related regularization methods hinge on the sparsity of the true signal in terms of the number of its non-zero coefficients. However, for the matrix data, the true signal is often of, or can be well approximated by, a low rank structure. As such, the sparsity is frequently in the form of low rank of the matrix parameters, which may seriously violate the assumption of the classical lasso. We propose a class of regularized matrix regression methods based on spectral regularization. A highly efficient and scalable estimation algorithm is developed, and a degrees-of-freedom formula is derived to facilitate model selection along the regularization path. Superior performance of the method proposed is demonstrated on both synthetic and real examples. PMID:24648830

An ambiguity principle for assigning protein structural domains.

PubMed

Postic, Guillaume; Ghouzam, Yassine; Chebrek, Romain; Gelly, Jean-Christophe

2017-01-01

Ambiguity is the quality of being open to several interpretations. For an image, it arises when the contained elements can be delimited in two or more distinct ways, which may cause confusion. We postulate that it also applies to the analysis of protein three-dimensional structure, which consists in dividing the molecule into subunits called domains. Because different definitions of what constitutes a domain can be used to partition a given structure, the same protein may have different but equally valid domain annotations. However, knowledge and experience generally displace our ability to accept more than one way to decompose the structure of an object-in this case, a protein. This human bias in structure analysis is particularly harmful because it leads to ignoring potential avenues of research. We present an automated method capable of producing multiple alternative decompositions of protein structure (web server and source code available at www.dsimb.inserm.fr/sword/). Our innovative algorithm assigns structural domains through the hierarchical merging of protein units, which are evolutionarily preserved substructures that describe protein architecture at an intermediate level, between domain and secondary structure. To validate the use of these protein units for decomposing protein structures into domains, we set up an extensive benchmark made of expert annotations of structural domains and including state-of-the-art domain parsing algorithms. The relevance of our "multipartitioning" approach is shown through numerous examples of applications covering protein function, evolution, folding, and structure prediction. Finally, we introduce a measure for the structural ambiguity of protein molecules.

Molecular structures and functional relationships in clostridial neurotoxins.

PubMed

Swaminathan, Subramanyam

2011-12-01

The seven serotypes of Clostridium botulinum neurotoxins (A-G) are the deadliest poison known to humans. They share significant sequence homology and hence possess similar structure-function relationships. Botulinum neurotoxins (BoNT) act via a four-step mechanism, viz., binding and internalization to neuronal cells, translocation of the catalytic domain into the cytosol and finally cleavage of one of the three soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) causing blockage of neurotransmitter release leading to flaccid paralysis. Crystal structures of three holotoxins, BoNT/A, B and E, are available to date. Although the individual domains are remarkably similar, their domain organization is different. These structures have helped in correlating the structural and functional domains. This has led to the determination of structures of individual domains and combinations of them. Crystal structures of catalytic domains of all serotypes and several binding domains are now available. The catalytic domains are zinc endopeptidases and share significant sequence and structural homology. The active site architecture and the catalytic mechanism are similar although the binding mode of individual substrates may be different, dictating substrate specificity and peptide cleavage selectivity. Crystal structures of catalytic domains with substrate peptides provide clues to specificity and selectivity unique to BoNTs. Crystal structures of the receptor domain in complex with ganglioside or the protein receptor have provided information about the binding of botulinum neurotoxin to the neuronal cell. An overview of the structure-function relationship correlating the 3D structures with biochemical and biophysical data and how they can be used for structure-based drug discovery is presented here. Journal compilation © 2011 FEBS. No claim to original US government works.

Bulk magnetic domain structures visualized by neutron dark-field imaging

NASA Astrophysics Data System (ADS)

Grünzweig, C.; David, C.; Bunk, O.; Dierolf, M.; Frei, G.; Kühne, G.; Schäfer, R.; Pofahl, S.; Rønnow, H. M. R.; Pfeiffer, F.

2008-09-01

We report on how a neutron grating interferometer can yield projection images of the internal domain structure in bulk ferromagnetic samples. The image contrast relies on the ultrasmall angle scattering of unpolarized neutrons at domain wall structures in the specimen. The results show the basic domains of (110)-oriented sheets in an FeSi test sample. The obtained domain structures could be correlated with surface sensitive magneto-optical Kerr effect micrographs.

Oral impacts on quality of life and problem-oriented attendance among South East London adults.

PubMed

Gaewkhiew, Piyada; Bernabé, Eduardo; Gallagher, Jennifer E; Klass, Charlotte; Delgado-Angulo, Elsa K

2017-04-26

Dental care seeking behaviour is often driven by symptoms. The value of oral health related quality of life (OHRQoL) measures to predict utilisation of dental services is unknown. This study aims to explore the association between OHRQoL and problem-oriented dental attendance among adults. We analysed cross-sectional data for 705 adults, aged 16 years and above, living in three boroughs of Inner South East London. Data were collected during structured interviews at home. The short form of the Oral Health Impact Profile (OHIP-14) was used to assess the frequency of oral impacts on daily life in the last year. Problem-oriented attendance was defined based on time elapsed since last visit (last 6 months) and reason for that visit (trouble with teeth). The association between OHIP-14 (total and domain) scores and problem-oriented attendance was tested in logistic regression models adjusting for participants' sociodemographic characteristics. Problem-oriented attenders had a higher OHIP-14 total score than regular attenders (6.73 and 3.73, respectively). In regression models, there was a positive association between OHIP-14 total score and problem-oriented attendance. The odds of visiting the dentist for trouble with teeth were 1.07 greater (95% Confidence Interval: 1.04-1.10) per unit increase in the OHIP-14 total score, after adjustment for participants' sociodemographic characteristics. In subsequent analysis by OHIP-14 domains, greater scores in all domains but handicap were significantly associated with problem-oriented attendance. This study shows that oral impacts on quality of life are associated with recent problem-oriented dental attendance among London adults. Six of the seven domains in the OHIP-14 questionnaire were also associated with dental visits for trouble with teeth.

On the function of chitin synthase extracellular domains in biomineralization.

PubMed

Weiss, Ingrid M; Lüke, Florian; Eichner, Norbert; Guth, Christina; Clausen-Schaumann, Hauke

2013-08-01

Molluscs with various shell architectures evolved around 542-525 million years ago, as part of a larger phenomenon related to the diversification of metazoan phyla. Molluscs deposit minerals in a chitin matrix. The mollusc chitin is synthesized by transmembrane enzymes that contain several unique extracellular domains. Here we investigate the assembly mechanism of the chitin synthase Ar-CS1 via its extracellular domain ArCS1_E22. The corresponding transmembrane protein ArCS1_E22TM accumulates in membrane fractions of the expression host Dictyostelium discoideum. Soluble recombinant ArCS1_E22 proteins can be purified as monomers only at basic pH. According to confocal fluorescence microscopy experiments, immunolabeled ArCS1_E22 proteins adsorb preferably to aragonitic nacre platelets at pH 7.75. At pH 8.2 or pH 9.0 the fluorescence signal is less intense, indicating that protein-mineral interaction is reduced with increasing pH. Furthermore, ArCS1_E22 forms regular nanostructures on cationic substrates as revealed by atomic force microscopy (AFM) experiments on modified mica cleavage planes. These experiments suggest that the extracellular domain ArCS1_E22 is involved in regulating the multiple enzyme activities of Ar-CS1 such as chitin synthesis and myosin movements by interaction with mineral surfaces and eventually by protein assembly. The protein complexes could locally probe the status of mineralization according to pH unless ions and pCO2 are balanced with suitable buffer substances. Taking into account that the intact enzyme could act as a force sensor, the results presented here provide further evidence that shell formation is coordinated physiologically with precise adjustment of cellular activities to the structure, topography and stiffness at the mineralizing interface. Copyright © 2013 Elsevier Inc. All rights reserved.

ADMET Evaluation in Drug Discovery. 18. Reliable Prediction of Chemical-Induced Urinary Tract Toxicity by Boosting Machine Learning Approaches.

PubMed

Lei, Tailong; Sun, Huiyong; Kang, Yu; Zhu, Feng; Liu, Hui; Zhou, Wenfang; Wang, Zhe; Li, Dan; Li, Youyong; Hou, Tingjun

2017-11-06

Xenobiotic chemicals and their metabolites are mainly excreted out of our bodies by the urinary tract through the urine. Chemical-induced urinary tract toxicity is one of the main reasons that cause failure during drug development, and it is a common adverse event for medications, natural supplements, and environmental chemicals. Despite its importance, there are only a few in silico models for assessing urinary tract toxicity for a large number of compounds with diverse chemical structures. Here, we developed a series of qualitative and quantitative structure-activity relationship (QSAR) models for predicting urinary tract toxicity. In our study, the recursive feature elimination method incorporated with random forests (RFE-RF) was used for dimension reduction, and then eight machine learning approaches were used for QSAR modeling, i.e., relevance vector machine (RVM), support vector machine (SVM), regularized random forest (RRF), C5.0 trees, eXtreme gradient boosting (XGBoost), AdaBoost.M1, SVM boosting (SVMBoost), and RVM boosting (RVMBoost). For building classification models, the synthetic minority oversampling technique was used to handle the imbalance data set problem. Among all the machine learning approaches, SVMBoost based on the RBF kernel achieves both the best quantitative (q ext 2 = 0.845) and qualitative predictions for the test set (MCC of 0.787, AUC of 0.893, sensitivity of 89.6%, specificity of 94.1%, and global accuracy of 90.8%). The application domains were then analyzed, and all of the tested chemicals fall within the application domain coverage. We also examined the structure features of the chemicals with large prediction errors. In brief, both the regression and classification models developed by the SVMBoost approach have reliable prediction capability for assessing chemical-induced urinary tract toxicity.

Donor cycle and donor segmentation: new tools for improving blood donor management.

PubMed

Veldhuizen, I; Folléa, G; de Kort, W

2013-07-01

An adequate donor population is of key importance for the entire blood transfusion chain. For good donor management, a detailed overview of the donor database is therefore imperative. This study offers a new description of the donor cycle related to the donor management process. It also presents the outcomes of a European Project, Donor Management IN Europe (DOMAINE), regarding the segmentation of the donor population into donor types. Blood establishments (BEs) from 18 European countries, the Thalassaemia International Federation and a representative from the South-Eastern Europe Health Network joined forces in DOMAINE. A questionnaire assessed blood donor management practices and the composition of the donor population using the newly proposed DOMAINE donor segmentation. 48 BEs in 34 European countries were invited to participate. The response rate was high (88%). However, only 14 BEs could deliver data on the composition of their donor population. The data showed large variations and major imbalances in the donor population. In 79% of the countries, inactive donors formed the dominant donor type. Only in 21%, regular donors were the largest subgroup, and in 29%, the proportion of first-time donors was higher than the proportion of regular donors. Good donor management depends on a thorough insight into the flow of donors through their donor career. Segmentation of the donor database is an essential tool to understand the influx and efflux of donors. The DOMAINE donor segmentation helps BEs in understanding their donor database and to adapt their donor recruitment and retention practices accordingly. Ways to use this new tool are proposed. © 2013 International Society of Blood Transfusion.

Regularity and dimensional salience in temporal grouping.

PubMed

Prince, Jon B; Rice, Tim

2018-04-30

How do pitch and duration accents combine to influence the perceived grouping of musical sequences? Sequence context influences the relative importance of these accents; for example, the presence of learned structure in pitch exaggerates the effect of pitch accents at the expense of duration accents despite being irrelevant to the task and not attributable to attention (Prince, 2014b). In the current study, two experiments examined whether the presence of temporal structure has the opposite effect. Experiment 1 tested baseline conditions, in which participants (N = 30) heard sequences with various sizes of either pitch or duration accents, which implied either duple or triple groupings (accent every two or three notes, respectively). Sequences either had regular temporal structure (isochronous) or not (irregular, via using random interonset intervals). Regularity enhanced the effect of duration accents but had negligible influence on pitch accents. The accent sizes that gave the most equivalent ratings across dimension and regularity levels were used in Experiment 2 (N = 33), in which sequences contained both pitch and duration accents that suggested either duple, triple, or neutral groupings. Despite controlling for the baseline effect of regularity by selecting equally effective accent sizes, regularity had additional effects on duration accents, but only for duple groupings. Regularity did not influence the effectiveness of pitch accents when combined with duration accents. These findings offer some support for a dimensional salience hypothesis, which proposes that the presence of temporal structure should foster duration accent effectiveness at the expense of pitch accents. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Structure-Based Low-Rank Model With Graph Nuclear Norm Regularization for Noise Removal.

PubMed

Ge, Qi; Jing, Xiao-Yuan; Wu, Fei; Wei, Zhi-Hui; Xiao, Liang; Shao, Wen-Ze; Yue, Dong; Li, Hai-Bo

2017-07-01

Nonlocal image representation methods, including group-based sparse coding and block-matching 3-D filtering, have shown their great performance in application to low-level tasks. The nonlocal prior is extracted from each group consisting of patches with similar intensities. Grouping patches based on intensity similarity, however, gives rise to disturbance and inaccuracy in estimation of the true images. To address this problem, we propose a structure-based low-rank model with graph nuclear norm regularization. We exploit the local manifold structure inside a patch and group the patches by the distance metric of manifold structure. With the manifold structure information, a graph nuclear norm regularization is established and incorporated into a low-rank approximation model. We then prove that the graph-based regularization is equivalent to a weighted nuclear norm and the proposed model can be solved by a weighted singular-value thresholding algorithm. Extensive experiments on additive white Gaussian noise removal and mixed noise removal demonstrate that the proposed method achieves a better performance than several state-of-the-art algorithms.

Novel functions of CCM1 delimit the relationship of PTB/PH domains.

PubMed

Zhang, Jun; Dubey, Pallavi; Padarti, Akhil; Zhang, Aileen; Patel, Rinkal; Patel, Vipulkumar; Cistola, David; Badr, Ahmed

2017-10-01

Three NPXY motifs and one FERM domain in CCM1 makes it a versatile scaffold protein for tethering the signaling components together within the CCM signaling complex (CSC). The cellular role of CCM1 protein remains inadequately expounded. Both phosphotyrosine binding (PTB) and pleckstrin homology (PH) domains were recognized as structurally related but functionally distinct domains. By utilizing molecular cloning, protein binding assays and RT-qPCR to identify novel cellular partners of CCM1 and its cellular expression patterns; by screening candidate PTB/PH proteins and subsequently structurally simulation in combining with current X-ray crystallography and NMR data to defined the essential structure of PTB/PH domain for NPXY-binding and the relationship among PTB, PH and FERM domain(s). We identified a group of 28 novel cellular partners of CCM1, all of which contain either PTB or PH domain(s), and developed a novel classification system for these PTB/PH proteins based on their relationship with different NPXY motifs of CCM1. Our results demonstrated that CCM1 has a wide spectrum of binding to different PTB/PH proteins and perpetuates their specificity to interact with certain PTB/PH domains through selective combination of three NPXY motifs. We also demonstrated that CCM1 can be assembled into oligomers through intermolecular interaction between its F3 lobe in FERM domain and one of the three NPXY motifs. Despite being embedded in FERM domain as F3 lobe, F3 module acts as a fully functional PH domain to interact with NPXY motif. The most salient feature of the study was that both PTB and PH domains are structurally and functionally comparable, suggesting that PTB domain is likely evolved from PH domain with polymorphic structural additions at its N-terminus. A new β1A-strand of the PTB domain was discovered and new minimum structural requirement of PTB/PH domain for NPXY motif-binding was determined. Based on our data, a novel theory of structure, function and relationship of PTB, PH and FERM domains has been proposed, which extends the importance of the NPXY-PTB/PH interaction on the CSC signaling and/or other cell receptors with great potential pointing to new therapeutic strategies. The study provides new insight into the structural characteristics of PTB/PH domains, essential structural elements of PTB/PH domain required for NPXY motif-binding, and function and relationship among PTB, PH and FERM domains. Copyright © 2017 Elsevier B.V. All rights reserved.

Domain walls in single-chain magnets

NASA Astrophysics Data System (ADS)

Pianet, Vivien; Urdampilleta, Matias; Colin, Thierry; Clérac, Rodolphe; Coulon, Claude

2017-12-01

The topology and creation energy of domain walls in different magnetic chains (called Single-Chain Magnets or SCMs) are discussed. As these domain walls, that can be seen as "defects", are known to control both static and dynamic properties of these one-dimensional systems, their study and understanding are necessary first steps before a deeper discussion of the SCM properties at finite temperature. The starting point of the paper is the simple regular ferromagnetic chain for which the characteristics of the domain walls are well known. Then two cases will be discussed (i) the "mixed chains" in which isotropic and anisotropic classical spins alternate, and (ii) the so-called "canted chains" where two different easy axis directions are present. In particular, we show that "strictly narrow" domain walls no longer exist in these more complex cases, while a cascade of phase transitions is found for canted chains as the canting angle approaches 45∘. The consequence for thermodynamic properties is briefly discussed in the last part of the paper.

AIDA: ab initio domain assembly for automated multi-domain protein structure prediction and domain–domain interaction prediction

PubMed Central

Xu, Dong; Jaroszewski, Lukasz; Li, Zhanwen; Godzik, Adam

2015-01-01

Motivation: Most proteins consist of multiple domains, independent structural and evolutionary units that are often reshuffled in genomic rearrangements to form new protein architectures. Template-based modeling methods can often detect homologous templates for individual domains, but templates that could be used to model the entire query protein are often not available. Results: We have developed a fast docking algorithm ab initio domain assembly (AIDA) for assembling multi-domain protein structures, guided by the ab initio folding potential. This approach can be extended to discontinuous domains (i.e. domains with ‘inserted’ domains). When tested on experimentally solved structures of multi-domain proteins, the relative domain positions were accurately found among top 5000 models in 86% of cases. AIDA server can use domain assignments provided by the user or predict them from the provided sequence. The latter approach is particularly useful for automated protein structure prediction servers. The blind test consisting of 95 CASP10 targets shows that domain boundaries could be successfully determined for 97% of targets. Availability and implementation: The AIDA package as well as the benchmark sets used here are available for download at http://ffas.burnham.org/AIDA/. Contact: adam@sanfordburnham.org Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25701568

PAT: predictor for structured units and its application for the optimization of target molecules for the generation of synthetic antibodies.

PubMed

Jeon, Jouhyun; Arnold, Roland; Singh, Fateh; Teyra, Joan; Braun, Tatjana; Kim, Philip M

2016-04-01

The identification of structured units in a protein sequence is an important first step for most biochemical studies. Importantly for this study, the identification of stable structured region is a crucial first step to generate novel synthetic antibodies. While many approaches to find domains or predict structured regions exist, important limitations remain, such as the optimization of domain boundaries and the lack of identification of non-domain structured units. Moreover, no integrated tool exists to find and optimize structural domains within protein sequences. Here, we describe a new tool, PAT ( http://www.kimlab.org/software/pat ) that can efficiently identify both domains (with optimized boundaries) and non-domain putative structured units. PAT automatically analyzes various structural properties, evaluates the folding stability, and reports possible structural domains in a given protein sequence. For reliability evaluation of PAT, we applied PAT to identify antibody target molecules based on the notion that soluble and well-defined protein secondary and tertiary structures are appropriate target molecules for synthetic antibodies. PAT is an efficient and sensitive tool to identify structured units. A performance analysis shows that PAT can characterize structurally well-defined regions in a given sequence and outperforms other efforts to define reliable boundaries of domains. Specially, PAT successfully identifies experimentally confirmed target molecules for antibody generation. PAT also offers the pre-calculated results of 20,210 human proteins to accelerate common queries. PAT can therefore help to investigate large-scale structured domains and improve the success rate for synthetic antibody generation.

Structure and DNA-Binding Sites of the SWI1 AT-rich Interaction Domain (ARID) Suggest Determinants for Sequence-Specific DNA Recognition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Suhkmann; Zhang, Ziming; Upchurch, Sean

2004-04-16

2 ARID is a homologous family of DNA-binding domains that occur in DNA binding proteins from a wide variety of species, ranging from yeast to nematodes, insects, mammals and plants. SWI1, a member of the SWI/SNF protein complex that is involved in chromatin remodeling during transcription, contains the ARID motif. The ARID domain of human SWI1 (also known as p270) does not select for a specific DNA sequence from a random sequence pool. The lack of sequence specificity shown by the SWI1 ARID domain stands in contrast to the other characterized ARID domains, which recognize specific AT-rich sequences. We havemore » solved the three-dimensional structure of human SWI1 ARID using solution NMR methods. In addition, we have characterized non-specific DNA-binding by the SWI1 ARID domain. Results from this study indicate that a flexible long internal loop in ARID motif is likely to be important for sequence specific DNA-recognition. The structure of human SWI1 ARID domain also represents a distinct structural subfamily. Studies of ARID indicate that boundary of the DNA binding structural and functional domains can extend beyond the sequence homologous region in a homologous family of proteins. Structural studies of homologous domains such as ARID family of DNA-binding domains should provide information to better predict the boundary of structural and functional domains in structural genomic studies. Key Words: ARID, SWI1, NMR, structural genomics, protein-DNA interaction.« less

Beta-propeller crystal structure of Psathyrella velutina lectin: an integrin-like fungal protein interacting with monosaccharides and calcium.

PubMed

Cioci, Gianluca; Mitchell, Edward P; Chazalet, Valerie; Debray, Henri; Oscarson, Stefan; Lahmann, Martina; Gautier, Catherine; Breton, Christelle; Perez, Serge; Imberty, Anne

2006-04-14

The lectin from the mushroom Psathyrella velutina recognises specifically N-acetylglucosamine and N-acetylneuraminic acid containing glycans. The crystal structure of the 401 amino acid residue lectin shows that it adopts a very regular seven-bladed beta-propeller fold with the N-terminal region tucked into the central cavity around the pseudo 7-fold axis. In the complex with N-acetylglucosamine, six monosaccharides are bound in pockets located between two consecutive propeller blades. Due to the repeats shown by the sequence the binding sites are very similar. Five hydrogen bonds between the protein and the sugar hydroxyl and N-acetyl groups stabilize the complex, together with the hydrophobic interactions with a conserved tyrosine and histidine. The complex with N-acetylneuraminic acid shows molecular mimicry with the same hydrogen bond network, but with different orientations of the carbohydrate ring in the binding site. The beta-hairpin loops connecting the two inner beta-strands of each blade are metal binding sites and two to three calcium ions were located in the structure. The multispecificity and high multivalency of this mushroom lectin, combined with its similarity to the extracellular domain of an important class of cell adhesion molecules, integrins, are another example of the outstanding success of beta-propeller structures as molecular binding machines in nature.

Structural Study of Liquid Lithium Niobate by Neutron Diffraction Role of the Li Atom in the Clustering Near Solidification

NASA Astrophysics Data System (ADS)

Andonov, P.; Fischer, H. E.; Palleau, P.; Kimura, S.

2001-05-01

The structure of liquid LiNbO3 has been investigated by neutron diffraction using samples with different isotopic composition of lithium. The intensity scattered by these samples has been measured for momentum transfers 0.4 Å-1 T> 1500 K, which include the undercooling domain. From an analysis of the correlation functions Gij(r) of the atomic pairs Li-Li, Li-Nb, Li-O and their structural evolutions, given by Δ Gi-j (r) = Gi-j(r)1500 -Gi-j(r)1550 made with reference to the crystalline LiNbO3 ferroelectric structure, it was possible to confirm a local ordering similar to that of the crystal. The presence of clusters (groupings of NbO3 octahedra) is confirmed. Both regular and irregular N b06 octahedra are observed in the liquid near solidification. With its high mobil­ity in the melt, the Li atom plays an important role in the clustering: the Li-O and Li-Nb bonds make possible the staking of four octahedra groups into clusters of eight octahedra or more. The Li-Li bonds join these groups. The diameter of the clusters is a least 22 Å in the undercooling regime.

Numerical Modeling of Sub-Wavelength Anti-Reflective Structures for Solar Module Applications

PubMed Central

Han, Katherine; Chang, Chih-Hung

2014-01-01

This paper reviews the current progress in mathematical modeling of anti-reflective subwavelength structures. Methods covered include effective medium theory (EMT), finite-difference time-domain (FDTD), transfer matrix method (TMM), the Fourier modal method (FMM)/rigorous coupled-wave analysis (RCWA) and the finite element method (FEM). Time-based solutions to Maxwell’s equations, such as FDTD, have the benefits of calculating reflectance for multiple wavelengths of light per simulation, but are computationally intensive. Space-discretized methods such as FDTD and FEM output field strength results over the whole geometry and are capable of modeling arbitrary shapes. Frequency-based solutions such as RCWA/FMM and FEM model one wavelength per simulation and are thus able to handle dispersion for regular geometries. Analytical approaches such as TMM are appropriate for very simple thin films. Initial disadvantages such as neglect of dispersion (FDTD), inaccuracy in TM polarization (RCWA), inability to model aperiodic gratings (RCWA), and inaccuracy with metallic materials (FDTD) have been overcome by most modern software. All rigorous numerical methods have accurately predicted the broadband reflection of ideal, graded-index anti-reflective subwavelength structures; ideal structures are tapered nanostructures with periods smaller than the wavelengths of light of interest and lengths that are at least a large portion of the wavelengths considered. PMID:28348287

Functional Properties at Domain Walls in BiFeO3: Electrical, Magnetic, and Structural investigations

NASA Astrophysics Data System (ADS)

He, Qing; Yang, C.-H.; Yu, P.; Gajek, M.; Seidel, J.; Ramesh, R.; Wang, F.; Chu, Y.-H.; Martin, L. W.; Spaldin, N.; Rother, A.

2009-03-01

BiFeO3 (BFO) is a widely studied robust ferroelectric, antiferromagnetic multiferroic. Conducting-atomic force microscopy studies reveal the presence of enhanced conductivity at certain types of domain walls in BFO. We have completed detailed TEM studies of the physical structure at these domain walls as well as in-depth DFT calculations of the evolution of electronic structure at these domain walls. These studies reveal two major contributions to the observed conduction: the formation of an electrostatic potential at the domain walls as well as a structurally-driven change in the electronic structure (i.e., a lower band gap locally) at the domain walls. We will discuss the use of optical characterization techniques as a way of probing this change in electronic structure at domain walls as well as detailed IV characterization both in atmospheric and UHV environments. Finally, the evolution of magnetism at these domain walls has been studied through the use of photoemission measurements. Initial findings point to a significant change in the magnetic order at these domain walls in BFO.

Fictitious domain method for fully resolved reacting gas-solid flow simulation

NASA Astrophysics Data System (ADS)

Zhang, Longhui; Liu, Kai; You, Changfu

2015-10-01

Fully resolved simulation (FRS) for gas-solid multiphase flow considers solid objects as finite sized regions in flow fields and their behaviours are predicted by solving equations in both fluid and solid regions directly. Fixed mesh numerical methods, such as fictitious domain method, are preferred in solving FRS problems and have been widely researched. However, for reacting gas-solid flows no suitable fictitious domain numerical method has been developed. This work presents a new fictitious domain finite element method for FRS of reacting particulate flows. Low Mach number reacting flow governing equations are solved sequentially on a regular background mesh. Particles are immersed in the mesh and driven by their surface forces and torques integrated on immersed interfaces. Additional treatments on energy and surface reactions are developed. Several numerical test cases validated the method and a burning carbon particles array falling simulation proved the capability for solving moving reacting particle cluster problems.

Extensions of PDZ domains as important structural and functional elements.

PubMed

Wang, Conan K; Pan, Lifeng; Chen, Jia; Zhang, Mingjie

2010-08-01

'Divide and conquer' has been the guiding strategy for the study of protein structure and function. Proteins are divided into domains with each domain having a canonical structural definition depending on its type. In this review, we push forward with the interesting observation that many domains have regions outside of their canonical definition that affect their structure and function; we call these regions 'extensions'. We focus on the highly abundant PDZ (PSD-95, DLG1 and ZO-1) domain. Using bioinformatics, we find that many PDZ domains have potential extensions and we developed an openly-accessible website to display our results ( http://bcz102.ust.hk/pdzex/ ). We propose, using well-studied PDZ domains as illustrative examples, that the roles of PDZ extensions can be classified into at least four categories: 1) protein dynamics-based modulation of target binding affinity, 2) provision of binding sites for macro-molecular assembly, 3) structural integration of multi-domain modules, and 4) expansion of the target ligand-binding pocket. Our review highlights the potential structural and functional importance of domain extensions, highlighting the significance of looking beyond the canonical boundaries of protein domains in general.

Theoretical Methods of Domain Structures in Ultrathin Ferroelectric Films: A Review

PubMed Central

Liu, Jianyi; Chen, Weijin; Wang, Biao; Zheng, Yue

2014-01-01

This review covers methods and recent developments of the theoretical study of domain structures in ultrathin ferroelectric films. The review begins with an introduction to some basic concepts and theories (e.g., polarization and its modern theory, ferroelectric phase transition, domain formation, and finite size effects, etc.) that are relevant to the study of domain structures in ultrathin ferroelectric films. Basic techniques and recent progress of a variety of important approaches for domain structure simulation, including first-principles calculation, molecular dynamics, Monte Carlo simulation, effective Hamiltonian approach and phase field modeling, as well as multiscale simulation are then elaborated. For each approach, its important features and relative merits over other approaches for modeling domain structures in ultrathin ferroelectric films are discussed. Finally, we review recent theoretical studies on some important issues of domain structures in ultrathin ferroelectric films, with an emphasis on the effects of interfacial electrostatics, boundary conditions and external loads. PMID:28788198

Geostatistical regularization operators for geophysical inverse problems on irregular meshes

NASA Astrophysics Data System (ADS)

Jordi, C.; Doetsch, J.; Günther, T.; Schmelzbach, C.; Robertsson, J. OA

2018-05-01

Irregular meshes allow to include complicated subsurface structures into geophysical modelling and inverse problems. The non-uniqueness of these inverse problems requires appropriate regularization that can incorporate a priori information. However, defining regularization operators for irregular discretizations is not trivial. Different schemes for calculating smoothness operators on irregular meshes have been proposed. In contrast to classical regularization constraints that are only defined using the nearest neighbours of a cell, geostatistical operators include a larger neighbourhood around a particular cell. A correlation model defines the extent of the neighbourhood and allows to incorporate information about geological structures. We propose an approach to calculate geostatistical operators for inverse problems on irregular meshes by eigendecomposition of a covariance matrix that contains the a priori geological information. Using our approach, the calculation of the operator matrix becomes tractable for 3-D inverse problems on irregular meshes. We tested the performance of the geostatistical regularization operators and compared them against the results of anisotropic smoothing in inversions of 2-D surface synthetic electrical resistivity tomography (ERT) data as well as in the inversion of a realistic 3-D cross-well synthetic ERT scenario. The inversions of 2-D ERT and seismic traveltime field data with geostatistical regularization provide results that are in good accordance with the expected geology and thus facilitate their interpretation. In particular, for layered structures the geostatistical regularization provides geologically more plausible results compared to the anisotropic smoothness constraints.

A structural portrait of the PDZ domain family.

PubMed

Ernst, Andreas; Appleton, Brent A; Ivarsson, Ylva; Zhang, Yingnan; Gfeller, David; Wiesmann, Christian; Sidhu, Sachdev S

2014-10-23

PDZ (PSD-95/Discs-large/ZO1) domains are interaction modules that typically bind to specific C-terminal sequences of partner proteins and assemble signaling complexes in multicellular organisms. We have analyzed the existing database of PDZ domain structures in the context of a specificity tree based on binding specificities defined by peptide-phage binding selections. We have identified 16 structures of PDZ domains in complex with high-affinity ligands and have elucidated four additional structures to assemble a structural database that covers most of the branches of the PDZ specificity tree. A detailed comparison of the structures reveals features that are responsible for the diverse specificities across the PDZ domain family. Specificity differences can be explained by differences in PDZ residues that are in contact with the peptide ligands, but these contacts involve both side-chain and main-chain interactions. Most PDZ domains bind peptides in a canonical conformation in which the ligand main chain adopts an extended β-strand conformation by interacting in an antiparallel fashion with a PDZ β-strand. However, a subset of PDZ domains bind peptides with a bent main-chain conformation and the specificities of these non-canonical domains could not be explained based on canonical structures. Our analysis provides a structural portrait of the PDZ domain family, which serves as a guide in understanding the structural basis for the diverse specificities across the family. Copyright © 2014 Elsevier Ltd. All rights reserved.

Structural classification of small, disulfide-rich protein domains.

PubMed

Cheek, Sara; Krishna, S Sri; Grishin, Nick V

2006-05-26

Disulfide-rich domains are small protein domains whose global folds are stabilized primarily by the formation of disulfide bonds and, to a much lesser extent, by secondary structure and hydrophobic interactions. Disulfide-rich domains perform a wide variety of roles functioning as growth factors, toxins, enzyme inhibitors, hormones, pheromones, allergens, etc. These domains are commonly found both as independent (single-domain) proteins and as domains within larger polypeptides. Here, we present a comprehensive structural classification of approximately 3000 small, disulfide-rich protein domains. We find that these domains can be arranged into 41 fold groups on the basis of structural similarity. Our fold groups, which describe broader structural relationships than existing groupings of these domains, bring together representatives with previously unacknowledged similarities; 18 of the 41 fold groups include domains from several SCOP folds. Within the fold groups, the domains are assembled into families of homologs. We define 98 families of disulfide-rich domains, some of which include newly detected homologs, particularly among knottin-like domains. On the basis of this classification, we have examined cases of convergent and divergent evolution of functions performed by disulfide-rich proteins. Disulfide bonding patterns in these domains are also evaluated. Reducible disulfide bonding patterns are much less frequent, while symmetric disulfide bonding patterns are more common than expected from random considerations. Examples of variations in disulfide bonding patterns found within families and fold groups are discussed.

An ambiguity principle for assigning protein structural domains

PubMed Central

Postic, Guillaume; Ghouzam, Yassine; Chebrek, Romain; Gelly, Jean-Christophe

2017-01-01

Ambiguity is the quality of being open to several interpretations. For an image, it arises when the contained elements can be delimited in two or more distinct ways, which may cause confusion. We postulate that it also applies to the analysis of protein three-dimensional structure, which consists in dividing the molecule into subunits called domains. Because different definitions of what constitutes a domain can be used to partition a given structure, the same protein may have different but equally valid domain annotations. However, knowledge and experience generally displace our ability to accept more than one way to decompose the structure of an object—in this case, a protein. This human bias in structure analysis is particularly harmful because it leads to ignoring potential avenues of research. We present an automated method capable of producing multiple alternative decompositions of protein structure (web server and source code available at www.dsimb.inserm.fr/sword/). Our innovative algorithm assigns structural domains through the hierarchical merging of protein units, which are evolutionarily preserved substructures that describe protein architecture at an intermediate level, between domain and secondary structure. To validate the use of these protein units for decomposing protein structures into domains, we set up an extensive benchmark made of expert annotations of structural domains and including state-of-the-art domain parsing algorithms. The relevance of our “multipartitioning” approach is shown through numerous examples of applications covering protein function, evolution, folding, and structure prediction. Finally, we introduce a measure for the structural ambiguity of protein molecules. PMID:28097215

Structure of the cytoplasmic domain of Yersinia pestis YscD, an essential component of the type III secretion system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lountos, George T.; Tropea, Joseph E.; Waugh, David S.

2012-09-17

The Yersinia pestis YscD protein is an essential component of the type III secretion system. YscD consists of an N-terminal cytoplasmic domain (residues 1-121), a transmembrane linker (122-142) and a large periplasmic domain (143-419). Both the cytoplasmic and the periplasmic domains are required for the assembly of the type III secretion system. Here, the structure of the YscD cytoplasmic domain solved by SAD phasing is presented. Although the three-dimensional structure is similar to those of forkhead-associated (FHA) domains, comparison with the structures of canonical FHA domains revealed that the cytoplasmic domain of YscD lacks the conserved residues that are requiredmore » for binding phosphothreonine and is therefore unlikely to function as a true FHA domain.« less

Solution structure of Syrian hamster prion protein rPrP(90-231).

PubMed

Liu, H; Farr-Jones, S; Ulyanov, N B; Llinas, M; Marqusee, S; Groth, D; Cohen, F E; Prusiner, S B; James, T L

1999-04-27

NMR has been used to refine the structure of Syrian hamster (SHa) prion protein rPrP(90-231), which is commensurate with the infectious protease-resistant core of the scrapie prion protein PrPSc. The structure of rPrP(90-231), refolded to resemble the normal cellular isoform PrPC spectroscopically and immunologically, has been studied using multidimensional NMR; initial results were published [James et al. (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 10086-10091]. We now report refinement with better definition revealing important structural and dynamic features which can be related to biological observations pertinent to prion diseases. Structure refinement was based on 2778 unambiguously assigned nuclear Overhauser effect (NOE) connectivities, 297 ambiguous NOE restraints, and 63 scalar coupling constants (3JHNHa). The structure is represented by an ensemble of 25 best-scoring structures from 100 structures calculated using ARIA/X-PLOR and further refined with restrained molecular dynamics using the AMBER 4.1 force field with an explicit shell of water molecules. The rPrP(90-231) structure features a core domain (residues 125-228), with a backbone atomic root-mean-square deviation (RMSD) of 0.67 A, consisting of three alpha-helices (residues 144-154, 172-193, and 200-227) and two short antiparallel beta-strands (residues 129-131 and 161-163). The N-terminus (residues 90-119) is largely unstructured despite some sparse and weak medium-range NOEs implying the existence of bends or turns. The transition region between the core domain and flexible N-terminus, i.e., residues 113-128, consists of hydrophobic residues or glycines and does not adopt any regular secondary structure in aqueous solution. There are about 30 medium- and long-range NOEs within this hydrophobic cluster, so it clearly manifests structure. Multiple discrete conformations are evident, implying the possible existence of one or more metastable states, which may feature in conversion of PrPC to PrPSc. To obtain a more comprehensive picture of rPrP(90-231), dynamics have been studied using amide hydrogen-deuterium exchange and 15N NMR relaxation times (T1 and T2) and 15N{1H} NOE measurements. Comparison of the structure with previous reports suggests sequence-dependent features that may be reflected in a species barrier to prion disease transmission.

Thermal depth profiling of vascular lesions: automated regularization of reconstruction algorithms

NASA Astrophysics Data System (ADS)

Verkruysse, Wim; Choi, Bernard; Zhang, Jenny R.; Kim, Jeehyun; Nelson, J. Stuart

2008-03-01

Pulsed photo-thermal radiometry (PPTR) is a non-invasive, non-contact diagnostic technique used to locate cutaneous chromophores such as melanin (epidermis) and hemoglobin (vascular structures). Clinical utility of PPTR is limited because it typically requires trained user intervention to regularize the inversion solution. Herein, the feasibility of automated regularization was studied. A second objective of this study was to depart from modeling port wine stain PWS, a vascular skin lesion frequently studied with PPTR, as strictly layered structures since this may influence conclusions regarding PPTR reconstruction quality. Average blood vessel depths, diameters and densities derived from histology of 30 PWS patients were used to generate 15 randomized lesion geometries for which we simulated PPTR signals. Reconstruction accuracy for subjective regularization was compared with that for automated regularization methods. The objective regularization approach performed better. However, the average difference was much smaller than the variation between the 15 simulated profiles. Reconstruction quality depended more on the actual profile to be reconstructed than on the reconstruction algorithm or regularization method. Similar, or better, accuracy reconstructions can be achieved with an automated regularization procedure which enhances prospects for user friendly implementation of PPTR to optimize laser therapy on an individual patient basis.

Correlation-based regularization and gradient operators for (joint) inversion on unstructured meshes

NASA Astrophysics Data System (ADS)

Jordi, Claudio; Doetsch, Joseph; Günther, Thomas; Schmelzbach, Cedric; Robertsson, Johan

2017-04-01

When working with unstructured meshes for geophysical inversions, special attention should be paid to the design of the operators that are used for regularizing the inverse problem and coupling of different property models in joint inversions. Regularization constraints for inversions on unstructured meshes are often defined in a rather ad-hoc manner and usually only involve the cell to which the operator is applied and its direct neighbours. Similarly, most structural coupling operators for joint inversion, such as the popular cross-gradients operator, are only defined in the direct neighbourhood of a cell. As a result, the regularization and coupling length scales and strength of these operators depend on the discretization as well as cell sizes and shape. Especially for unstructured meshes, where the cell sizes vary throughout the model domain, the dependency of the operator on the discretization may lead to artefacts. Designing operators that are based on a spatial correlation model allows to define correlation length scales over which an operator acts (called footprint), reducing the dependency on the discretization and the effects of variable cell sizes. Moreover, correlation-based operators can accommodate for expected anisotropy by using different length scales in horizontal and vertical directions. Correlation-based regularization operators also known as stochastic regularization operators have already been successfully applied to inversions on regular grids. Here, we formulate stochastic operators for unstructured meshes and apply them in 2D surface and 3D cross-well electrical resistivity tomography data inversion examples of layered media. Especially for the synthetic cross-well example, improved inversion results are achieved when stochastic regularization is used instead of a classical smoothness constraint. For the case of cross-gradients operators for joint inversion, the correlation model is used to define the footprint of the operator and weigh the contributions of the property values that are used to calculate the cross-gradients. In a first series of synthetic-data tests, we examined the mesh dependency of the cross-gradients operators. Compared to operators that are only defined in the direct neighbourhood of a cell, the dependency on the cell size of the cross-gradients calculation is markedly reduced when using operators with larger footprints. A second test with synthetic models focussed on the effect of small-scale variabilities of the parameter value on the cross-gradients calculation. Small-scale variabilities that are superimposed on a global trend of the property value can potentially degrade the cross-gradients calculation and destabilize joint inversion. We observe that the cross-gradients from operators with footprints larger than the length scale of the variabilities are less affected compared to operators with a small footprint. In joint inversions on unstructured meshes, we thus expect the correlation-based coupling operators to ensure robust coupling on a physically meaningful scale.

The costa of trichomonads: A complex macromolecular cytoskeleton structure made of uncommon proteins.

PubMed

de Andrade Rosa, Ivone; Caruso, Marjolly Brigido; de Oliveira Santos, Eidy; Gonzaga, Luiz; Zingali, Russolina Benedeta; de Vasconcelos, Ana Tereza R; de Souza, Wanderley; Benchimol, Marlene

2017-06-01

The costa is a prominent striated fibre that is found in protozoa of the Trichomonadidae family that present an undulating membrane. It is composed primarily of proteins that have not yet been explored. In this study, we used cell fractionation to obtain a highly enriched costa fraction whose structure and composition was further analysed by electron microscopy and mass spectrometry. Electron microscopy of negatively stained samples revealed that the costa, which is a periodic structure with alternating electron-dense and electron-lucent bands, displays three distinct regions, named the head, neck and body. Fourier transform analysis showed that the electron-lucent bands present sub-bands with a regular pattern. An analysis of the costa fraction via one- and two-dimensional electrophoresis and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) allowed the identification of 54 hypothetical proteins. Fourteen of those proteins were considered to be major components of the fraction. The costa of T. foetus is a complex and organised cytoskeleton structure made of a large number of proteins which is assembled into filamentous structures. Some of these proteins exhibit uncharacterised domains and no function related according to gene ontology, suggesting that the costa structure may be formed by a new class of proteins that differ from those previously described in other organisms. Seven of these proteins contain prefoldin domains displaying coiled-coil regions. This propriety is shared with proteins of the striated fibres of other protozoan as well as in intermediate filaments. Our observations suggest the presence of a new class of the cytoskeleton filaments in T. foetus. We believe that our data could auxiliate in determining the specific locations of these proteins in the distinct regions that compose the costa, as well as to define the functional roles of each component. Therefore, our study will help in the better understanding of the organisation and function of this structure in unicellular organisms. © 2017 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

Structure of Dimeric and Tetrameric Complexes of the BAR Domain Protein PICK1 Determined by Small-Angle X-Ray Scattering.

PubMed

Karlsen, Morten L; Thorsen, Thor S; Johner, Niklaus; Ammendrup-Johnsen, Ina; Erlendsson, Simon; Tian, Xinsheng; Simonsen, Jens B; Høiberg-Nielsen, Rasmus; Christensen, Nikolaj M; Khelashvili, George; Streicher, Werner; Teilum, Kaare; Vestergaard, Bente; Weinstein, Harel; Gether, Ulrik; Arleth, Lise; Madsen, Kenneth L

2015-07-07

PICK1 is a neuronal scaffolding protein containing a PDZ domain and an auto-inhibited BAR domain. BAR domains are membrane-sculpting protein modules generating membrane curvature and promoting membrane fission. Previous data suggest that BAR domains are organized in lattice-like arrangements when stabilizing membranes but little is known about structural organization of BAR domains in solution. Through a small-angle X-ray scattering (SAXS) analysis, we determine the structure of dimeric and tetrameric complexes of PICK1 in solution. SAXS and biochemical data reveal a strong propensity of PICK1 to form higher-order structures, and SAXS analysis suggests an offset, parallel mode of BAR-BAR oligomerization. Furthermore, unlike accessory domains in other BAR domain proteins, the positioning of the PDZ domains is flexible, enabling PICK1 to perform long-range, dynamic scaffolding of membrane-associated proteins. Together with functional data, these structural findings are compatible with a model in which oligomerization governs auto-inhibition of BAR domain function. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effective field theory dimensional regularization

NASA Astrophysics Data System (ADS)

Lehmann, Dirk; Prézeau, Gary

2002-01-01

A Lorentz-covariant regularization scheme for effective field theories with an arbitrary number of propagating heavy and light particles is given. This regularization scheme leaves the low-energy analytic structure of Greens functions intact and preserves all the symmetries of the underlying Lagrangian. The power divergences of regularized loop integrals are controlled by the low-energy kinematic variables. Simple diagrammatic rules are derived for the regularization of arbitrary one-loop graphs and the generalization to higher loops is discussed.

A localized interaction surface for voltage-sensing domains on the pore domain of a K+ channel.

PubMed

Li-Smerin, Y; Hackos, D H; Swartz, K J

2000-02-01

Voltage-gated K+ channels contain a central pore domain and four surrounding voltage-sensing domains. How and where changes in the structure of the voltage-sensing domains couple to the pore domain so as to gate ion conduction is not understood. The crystal structure of KcsA, a bacterial K+ channel homologous to the pore domain of voltage-gated K+ channels, provides a starting point for addressing this question. Guided by this structure, we used tryptophan-scanning mutagenesis on the transmembrane shell of the pore domain in the Shaker voltage-gated K+ channel to localize potential protein-protein and protein-lipid interfaces. Some mutants cause only minor changes in gating and when mapped onto the KcsA structure cluster away from the interface between pore domain subunits. In contrast, mutants producing large changes in gating tend to cluster near this interface. These results imply that voltage-sensing domains interact with localized regions near the interface between adjacent pore domain subunits.

Structural characterization of the packings of granular regular polygons.

PubMed

Wang, Chuncheng; Dong, Kejun; Yu, Aibing

2015-12-01

By using a recently developed method for discrete modeling of nonspherical particles, we simulate the random packings of granular regular polygons with three to 11 edges under gravity. The effects of shape and friction on the packing structures are investigated by various structural parameters, including packing fraction, the radial distribution function, coordination number, Voronoi tessellation, and bond-orientational order. We find that packing fraction is generally higher for geometrically nonfrustrated regular polygons, and can be increased by the increase of edge number and decrease of friction. The changes of packing fraction are linked with those of the microstructures, such as the variations of the translational and orientational orders and local configurations. In particular, the free areas of Voronoi tessellations (which are related to local packing fractions) can be described by log-normal distributions for all polygons. The quantitative analyses establish a clearer picture for the packings of regular polygons.

Microphase separation in random multiblock copolymers

NASA Astrophysics Data System (ADS)

Govorun, E. N.; Chertovich, A. V.

2017-01-01

Microphase separation in random multiblock copolymers is studied with the mean-field theory assuming that long blocks of a copolymer are strongly segregated, whereas short blocks are able to penetrate into "alien" domains and exchange between the domains and interfacial layer. A bidisperse copolymer with blocks of only two sizes (long and short) is considered as a model of multiblock copolymers with high polydispersity in the block size. Short blocks of the copolymer play an important role in the microphase separation. First, their penetration into the "alien" domains leads to the formation of joint long blocks in their own domains. Second, short blocks localized at the interface considerably change the interfacial tension. The possibility of penetration of short blocks into the "alien" domains is controlled by the product χ Nsh (χ is the Flory-Huggins interaction parameter and Nsh is the short block length). At not very large χ Nsh , the domain size is larger than that for a regular copolymer consisting of the same long blocks as in the considered random copolymer. At a fixed mean block size, the domain size grows with an increase in the block size dispersity, the rate of the growth being dependent of the more detailed parameters of the block size distribution.

Systems-based accident analysis in the led outdoor activity domain: application and evaluation of a risk management framework.

PubMed

Salmon, P; Williamson, A; Lenné, M; Mitsopoulos-Rubens, E; Rudin-Brown, C M

2010-08-01

Safety-compromising accidents occur regularly in the led outdoor activity domain. Formal accident analysis is an accepted means of understanding such events and improving safety. Despite this, there remains no universally accepted framework for collecting and analysing accident data in the led outdoor activity domain. This article presents an application of Rasmussen's risk management framework to the analysis of the Lyme Bay sea canoeing incident. This involved the development of an Accimap, the outputs of which were used to evaluate seven predictions made by the framework. The Accimap output was also compared to an analysis using an existing model from the led outdoor activity domain. In conclusion, the Accimap output was found to be more comprehensive and supported all seven of the risk management framework's predictions, suggesting that it shows promise as a theoretically underpinned approach for analysing, and learning from, accidents in the led outdoor activity domain. STATEMENT OF RELEVANCE: Accidents represent a significant problem within the led outdoor activity domain. This article presents an evaluation of a risk management framework that can be used to understand such accidents and to inform the development of accident countermeasures and mitigation strategies for the led outdoor activity domain.

A Deliberate Practice Account of Typing Proficiency in Everyday Typists

ERIC Educational Resources Information Center

Keith, Nina; Ericsson, K. Anders

2007-01-01

The concept of deliberate practice was introduced to explain exceptional performance in domains such as music and chess. We apply deliberate practice theory to intermediate-level performance in typing, an activity that many people pursue on a regular basis. Sixty university students with several years typing experience participated in laboratory…

College Students' Understanding of the Domain and Range of Functions on Graphs

ERIC Educational Resources Information Center

Cho, Young Doo

2013-01-01

The mathematical concept of function has been revisited and further developed with regularity since its introduction in ancient Babylonia (Kleiner, 1989). The difficulty of the concept of a function contributes to complications when students learn of functions and their graphs (Leinhardt, Zaslavsky, & Stein, 1990). To understand the concept of…

Social Contexts of Regular Smoking in Adolescence: Towards a Multidimensional Ecological Model

ERIC Educational Resources Information Center

Wen, Ming; Van Duker, Heather; Olson, Lenora M.

2009-01-01

Using data from the Add Health, this study examined multilevel factors of adolescent smoking after controlling for the baseline smoking behavior and individual characteristics. Results showed that peer, family and school were all important life domains contextually influencing subsequent smoking behavior among adolescents. Time spent with peers,…

The Role of Gender, Embedded Questions, and Domain Specific Readings with Learners of Spanish

ERIC Educational Resources Information Center

Brantmeier, Cindy; Callender, Aimee; McDaniel, Mark

2013-01-01

The present study utilizes readings taken from texts in social psychology to examine the effects by gender of embedded "what" questions and elaborative "why" questions on reading comprehension. During regular class time, 97 advanced second language (L2) learners of Spanish read two different vignettes, either with or without…

Parent Identification of the Talents of Gifted Students.

ERIC Educational Resources Information Center

Jin, Suk-un; Feldhusen, John F.

2000-01-01

A survey of 204 parents of gifted students (ages 3-14) found a majority reported their child showed high potential in more than two talent domains. Twenty-seven percent of parents reported that their child's school offers services for special talents and 60 percent reported their child participates regularly in sports activities. (Contains five…

On the Hodge-type decomposition and cohomology groups of k-Cauchy-Fueter complexes over domains in the quaternionic space

NASA Astrophysics Data System (ADS)

Chang, Der-Chen; Markina, Irina; Wang, Wei

2016-09-01

The k-Cauchy-Fueter operator D0(k) on one dimensional quaternionic space H is the Euclidean version of spin k / 2 massless field operator on the Minkowski space in physics. The k-Cauchy-Fueter equation for k ≥ 2 is overdetermined and its compatibility condition is given by the k-Cauchy-Fueter complex. In quaternionic analysis, these complexes play the role of Dolbeault complex in several complex variables. We prove that a natural boundary value problem associated to this complex is regular. Then by using the theory of regular boundary value problems, we show the Hodge-type orthogonal decomposition, and the fact that the non-homogeneous k-Cauchy-Fueter equation D0(k) u = f on a smooth domain Ω in H is solvable if and only if f satisfies the compatibility condition and is orthogonal to the set ℋ(k)1 (Ω) of Hodge-type elements. This set is isomorphic to the first cohomology group of the k-Cauchy-Fueter complex over Ω, which is finite dimensional, while the second cohomology group is always trivial.

Conductance and amantadine binding of a pore formed by a lysine-flanked transmembrane domain of SARS coronavirus envelope protein

PubMed Central

Torres, Jaume; Maheswari, Uma; Parthasarathy, Krupakar; Ng, Lifang; Liu, Ding Xiang; Gong, Xiandi

2007-01-01

The coronavirus responsible for the severe acute respiratory syndrome (SARS-CoV) contains a small envelope protein, E, with putative involvement in host cell apoptosis and virus morphogenesis. It has been suggested that E protein can form a membrane destabilizing transmembrane (TM) hairpin, or homooligomerize to form a regular TM α-helical bundle. We have shown previously that the topology of the α-helical putative TM domain of E protein (ETM), flanked by two lysine residues at C and N termini to improve solubility, is consistent with a regular TM α-helix, with orientational parameters in lipid bilayers that are consistent with a homopentameric model. Herein, we show that this peptide, reconstituted in lipid bilayers, shows sodium conductance. Channel activity is inhibited by the anti-influenza drug amantadine, which was found to bind our preparation with moderate affinity. Results obtained from single or double mutants indicate that the organization of the transmembrane pore is consistent with our previously reported pentameric α-helical bundle model. PMID:17766393

Statistical learning using real-world scenes: extracting categorical regularities without conscious intent.

PubMed

Brady, Timothy F; Oliva, Aude

2008-07-01

Recent work has shown that observers can parse streams of syllables, tones, or visual shapes and learn statistical regularities in them without conscious intent (e.g., learn that A is always followed by B). Here, we demonstrate that these statistical-learning mechanisms can operate at an abstract, conceptual level. In Experiments 1 and 2, observers incidentally learned which semantic categories of natural scenes covaried (e.g., kitchen scenes were always followed by forest scenes). In Experiments 3 and 4, category learning with images of scenes transferred to words that represented the categories. In each experiment, the category of the scenes was irrelevant to the task. Together, these results suggest that statistical-learning mechanisms can operate at a categorical level, enabling generalization of learned regularities using existing conceptual knowledge. Such mechanisms may guide learning in domains as disparate as the acquisition of causal knowledge and the development of cognitive maps from environmental exploration.

Accuracy of AFM force distance curves via direct solution of the Euler-Bernoulli equation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eppell, Steven J., E-mail: steven.eppell@case.edu; Liu, Yehe; Zypman, Fredy R.

2016-03-15

In an effort to improve the accuracy of force-separation curves obtained from atomic force microscope data, we compare force-separation curves computed using two methods to solve the Euler-Bernoulli equation. A recently introduced method using a direct sequential forward solution, Causal Time-Domain Analysis, is compared against a previously introduced Tikhonov Regularization method. Using the direct solution as a benchmark, it is found that the regularization technique is unable to reproduce accurate curve shapes. Using L-curve analysis and adjusting the regularization parameter, λ, to match either the depth or the full width at half maximum of the force curves, the two techniquesmore » are contrasted. Matched depths result in full width at half maxima that are off by an average of 27% and matched full width at half maxima produce depths that are off by an average of 109%.« less

Consistent Partial Least Squares Path Modeling via Regularization

PubMed Central

Jung, Sunho; Park, JaeHong

2018-01-01

Partial least squares (PLS) path modeling is a component-based structural equation modeling that has been adopted in social and psychological research due to its data-analytic capability and flexibility. A recent methodological advance is consistent PLS (PLSc), designed to produce consistent estimates of path coefficients in structural models involving common factors. In practice, however, PLSc may frequently encounter multicollinearity in part because it takes a strategy of estimating path coefficients based on consistent correlations among independent latent variables. PLSc has yet no remedy for this multicollinearity problem, which can cause loss of statistical power and accuracy in parameter estimation. Thus, a ridge type of regularization is incorporated into PLSc, creating a new technique called regularized PLSc. A comprehensive simulation study is conducted to evaluate the performance of regularized PLSc as compared to its non-regularized counterpart in terms of power and accuracy. The results show that our regularized PLSc is recommended for use when serious multicollinearity is present. PMID:29515491

A composite likelihood approach for spatially correlated survival data

PubMed Central

Paik, Jane; Ying, Zhiliang

2013-01-01

The aim of this paper is to provide a composite likelihood approach to handle spatially correlated survival data using pairwise joint distributions. With e-commerce data, a recent question of interest in marketing research has been to describe spatially clustered purchasing behavior and to assess whether geographic distance is the appropriate metric to describe purchasing dependence. We present a model for the dependence structure of time-to-event data subject to spatial dependence to characterize purchasing behavior from the motivating example from e-commerce data. We assume the Farlie-Gumbel-Morgenstern (FGM) distribution and then model the dependence parameter as a function of geographic and demographic pairwise distances. For estimation of the dependence parameters, we present pairwise composite likelihood equations. We prove that the resulting estimators exhibit key properties of consistency and asymptotic normality under certain regularity conditions in the increasing-domain framework of spatial asymptotic theory. PMID:24223450

A composite likelihood approach for spatially correlated survival data.

PubMed

Paik, Jane; Ying, Zhiliang

2013-01-01

The aim of this paper is to provide a composite likelihood approach to handle spatially correlated survival data using pairwise joint distributions. With e-commerce data, a recent question of interest in marketing research has been to describe spatially clustered purchasing behavior and to assess whether geographic distance is the appropriate metric to describe purchasing dependence. We present a model for the dependence structure of time-to-event data subject to spatial dependence to characterize purchasing behavior from the motivating example from e-commerce data. We assume the Farlie-Gumbel-Morgenstern (FGM) distribution and then model the dependence parameter as a function of geographic and demographic pairwise distances. For estimation of the dependence parameters, we present pairwise composite likelihood equations. We prove that the resulting estimators exhibit key properties of consistency and asymptotic normality under certain regularity conditions in the increasing-domain framework of spatial asymptotic theory.

Correlation between spin structure oscillations and domain wall velocities

PubMed Central

Bisig, André; Stärk, Martin; Mawass, Mohamad-Assaad; Moutafis, Christoforos; Rhensius, Jan; Heidler, Jakoba; Büttner, Felix; Noske, Matthias; Weigand, Markus; Eisebitt, Stefan; Tyliszczak, Tolek; Van Waeyenberge, Bartel; Stoll, Hermann; Schütz, Gisela; Kläui, Mathias

2013-01-01

Magnetic sensing and logic devices based on the motion of magnetic domain walls rely on the precise and deterministic control of the position and the velocity of individual magnetic domain walls in curved nanowires. Varying domain wall velocities have been predicted to result from intrinsic effects such as oscillating domain wall spin structure transformations and extrinsic pinning due to imperfections. Here we use direct dynamic imaging of the nanoscale spin structure that allows us for the first time to directly check these predictions. We find a new regime of oscillating domain wall motion even below the Walker breakdown correlated with periodic spin structure changes. We show that the extrinsic pinning from imperfections in the nanowire only affects slow domain walls and we identify the magnetostatic energy, which scales with the domain wall velocity, as the energy reservoir for the domain wall to overcome the local pinning potential landscape. PMID:23978905

ExDom: an integrated database for comparative analysis of the exon–intron structures of protein domains in eukaryotes

PubMed Central

Bhasi, Ashwini; Philip, Philge; Manikandan, Vinu; Senapathy, Periannan

2009-01-01

We have developed ExDom, a unique database for the comparative analysis of the exon–intron structures of 96 680 protein domains from seven eukaryotic organisms (Homo sapiens, Mus musculus, Bos taurus, Rattus norvegicus, Danio rerio, Gallus gallus and Arabidopsis thaliana). ExDom provides integrated access to exon-domain data through a sophisticated web interface which has the following analytical capabilities: (i) intergenomic and intragenomic comparative analysis of exon–intron structure of domains; (ii) color-coded graphical display of the domain architecture of proteins correlated with their corresponding exon-intron structures; (iii) graphical analysis of multiple sequence alignments of amino acid and coding nucleotide sequences of homologous protein domains from seven organisms; (iv) comparative graphical display of exon distributions within the tertiary structures of protein domains; and (v) visualization of exon–intron structures of alternative transcripts of a gene correlated to variations in the domain architecture of corresponding protein isoforms. These novel analytical features are highly suited for detailed investigations on the exon–intron structure of domains and make ExDom a powerful tool for exploring several key questions concerning the function, origin and evolution of genes and proteins. ExDom database is freely accessible at: http://66.170.16.154/ExDom/. PMID:18984624

Structure of the N-terminal domain of the protein Expansion: an ‘Expansion’ to the Smad MH2 fold

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beich-Frandsen, Mads; Aragón, Eric; Llimargas, Marta

2015-04-01

Expansion is a modular protein that is conserved in protostomes. The first structure of the N-terminal domain of Expansion has been determined at 1.6 Å resolution and the new Nα-MH2 domain was found to belong to the Smad/FHA superfamily of structures. Gene-expression changes observed in Drosophila embryos after inducing the transcription factor Tramtrack led to the identification of the protein Expansion. Expansion contains an N-terminal domain similar in sequence to the MH2 domain characteristic of Smad proteins, which are the central mediators of the effects of the TGF-β signalling pathway. Apart from Smads and Expansion, no other type of proteinmore » belonging to the known kingdoms of life contains MH2 domains. To compare the Expansion and Smad MH2 domains, the crystal structure of the Expansion domain was determined at 1.6 Å resolution, the first structure of a non-Smad MH2 domain to be characterized to date. The structure displays the main features of the canonical MH2 fold with two main differences: the addition of an α-helical region and the remodelling of a protein-interaction site that is conserved in the MH2 domain of Smads. Owing to these differences, to the new domain was referred to as Nα-MH2. Despite the presence of the Nα-MH2 domain, Expansion does not participate in TGF-β signalling; instead, it is required for other activities specific to the protostome phyla. Based on the structural similarities to the MH2 fold, it is proposed that the Nα-MH2 domain should be classified as a new member of the Smad/FHA superfamily.« less

Structure of the two-domain hexameric APS kinase from Thiobacillus denitrificans: structural basis for the absence of ATP sulfurylase activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gay, Sean C.; Segel, Irwin H.; Fisher, Andrew J., E-mail: fisher@chem.ucdavis.edu

2009-10-01

APS kinase from Thiobacillus denitrificans contains an inactive N-terminal ATP sulfurylase domain. The structure presented unveils the first hexameric assembly for an APS kinase, and reveals that structural changes in the N-terminal domain disrupt the ATP sulfurylase active site thus prohibiting activity. The Tbd-0210 gene of the chemolithotrophic bacterium Thiobacillus denitrificans is annotated to encode a 60.5 kDa bifunctional enzyme with ATP sulfurylase and APS kinase activity. This putative bifunctional enzyme was cloned, expressed and structurally characterized. The 2.95 Å resolution X-ray crystal structure reported here revealed a hexameric assembly with D{sub 3} symmetry. Each subunit contains a large N-terminalmore » sulfurylase-like domain and a C-terminal APS kinase domain reminiscent of the two-domain fungal ATP sulfurylases of Penicillium chrysogenum and Saccharomyces cerevisiae, which also exhibit a hexameric assembly. However, the T. denitrificans enzyme exhibits numerous structural and sequence differences in the N-terminal domain that render it inactive with respect to ATP sulfurylase activity. Surprisingly, the C-terminal domain does indeed display APS kinase activity, indicating that this gene product is a true APS kinase. Therefore, these results provide the first structural insights into a unique hexameric APS kinase that contains a nonfunctional ATP sulfurylase-like domain of unknown function.« less

Full waveform inversion in the frequency domain using classified time-domain residual wavefields

NASA Astrophysics Data System (ADS)

Son, Woohyun; Koo, Nam-Hyung; Kim, Byoung-Yeop; Lee, Ho-Young; Joo, Yonghwan

2017-04-01

We perform the acoustic full waveform inversion in the frequency domain using residual wavefields that have been separated in the time domain. We sort the residual wavefields in the time domain according to the order of absolute amplitudes. Then, the residual wavefields are separated into several groups in the time domain. To analyze the characteristics of the residual wavefields, we compare the residual wavefields of conventional method with those of our residual separation method. From the residual analysis, the amplitude spectrum obtained from the trace before separation appears to have little energy at the lower frequency bands. However, the amplitude spectrum obtained from our strategy is regularized by the separation process, which means that the low-frequency components are emphasized. Therefore, our method helps to emphasize low-frequency components of residual wavefields. Then, we generate the frequency-domain residual wavefields by taking the Fourier transform of the separated time-domain residual wavefields. With these wavefields, we perform the gradient-based full waveform inversion in the frequency domain using back-propagation technique. Through a comparison of gradient directions, we confirm that our separation method can better describe the sub-salt image than the conventional approach. The proposed method is tested on the SEG/EAGE salt-dome model. The inversion results show that our algorithm is better than the conventional gradient based waveform inversion in the frequency domain, especially for deeper parts of the velocity model.

Single-domain epitaxial silicene on diboride thin films

DOE PAGES

Fleurence, A.; Gill, T. G.; Friedlein, R.; ...

2016-04-12

Epitaxial silicene, which forms spontaneously on ZrB 2(0001) thin films grown on Si(111) wafers, has a periodic stripe domain structure. By adsorbing additional Si atoms on this surface, we find that the domain boundaries vanish, and a single-domain silicene sheet can be prepared without altering its buckled honeycomb structure. The amount of Si required to induce this change suggests that the domain boundaries are made of a local distortion of the silicene honeycomb lattice. LastlThe realization of a single domain sheet with structural and electronic properties close to those of the original striped state demonstrates the high structural flexibility ofmore » silicene.« less

Single-domain epitaxial silicene on diboride thin films

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fleurence, A., E-mail: antoine@jaist.ac.jp; Friedlein, R.; Aoyagi, K.

2016-04-11

Epitaxial silicene, which forms spontaneously on ZrB{sub 2}(0001) thin films grown on Si(111) wafers, has a periodic stripe domain structure. By adsorbing additional Si atoms on this surface, we find that the domain boundaries vanish, and a single-domain silicene sheet can be prepared without altering its buckled honeycomb structure. The amount of Si required to induce this change suggests that the domain boundaries are made of a local distortion of the silicene honeycomb lattice. The realization of a single domain sheet with structural and electronic properties close to those of the original striped state demonstrates the high structural flexibility ofmore » silicene.« less

Structure of a double-domain phosphagen kinase reveals an asymmetric arrangement of the tandem domains.

PubMed

Wang, Zhiming; Qiao, Zhu; Ye, Sheng; Zhang, Rongguang

2015-04-01

Tandem duplications and fusions of single genes have led to magnificent expansions in the divergence of protein structures and functions over evolutionary timescales. One of the possible results is polydomain enzymes with interdomain cooperativities, few examples of which have been structurally characterized at the full-length level to explore their innate synergistic mechanisms. This work reports the crystal structures of a double-domain phosphagen kinase in both apo and ligand-bound states, revealing a novel asymmetric L-shaped arrangement of the two domains. Unexpectedly, the interdomain connections are not based on a flexible hinge linker but on a rigid secondary-structure element: a long α-helix that tethers the tandem domains in relatively fixed positions. Besides the connective helix, the two domains also contact each other directly and form an interdomain interface in which hydrogen bonds and hydrophobic interactions further stabilize the L-shaped domain arrangement. Molecular-dynamics simulations show that the interface is generally stable, suggesting that the asymmetric domain arrangement crystallographically observed in the present study is not a conformational state simply restrained by crystal-packing forces. It is possible that the asymmetrically arranged tandem domains could provide a structural basis for further studies of the interdomain synergy.

Structural Biology of Non-Ribosomal Peptide Synthetases

PubMed Central

Miller, Bradley R.; Gulick, Andrew M.

2016-01-01

Summary The non-ribosomal peptide synthetases are modular enzymes that catalyze synthesis of important peptide products from a variety of standard and non-proteinogenic amino acid substrates. Within a single module are multiple catalytic domains that are responsible for incorporation of a single residue. After the amino acid is activated and covalently attached to an integrated carrier protein domain, the substrates and intermediates are delivered to neighboring catalytic domains for peptide bond formation or, in some modules, chemical modification. In the final module, the peptide is delivered to a terminal thioesterase domain that catalyzes release of the peptide product. This multi-domain modular architecture raises questions about the structural features that enable this assembly line synthesis in an efficient manner. The structures of the core component domains have been determined and demonstrate insights into the catalytic activity. More recently, multi-domain structures have been determined and are providing clues to the features of these enzyme systems that govern the functional interaction between multiple domains. This chapter describes the structures of NRPS proteins and the strategies that are being used to assist structural studies of these dynamic proteins, including careful consideration of domain boundaries for generation of truncated proteins and the use of mechanism-based inhibitors that trap interactions between the catalytic and carrier protein domains. PMID:26831698

Structural diversity of domain superfamilies in the CATH database.

PubMed

Reeves, Gabrielle A; Dallman, Timothy J; Redfern, Oliver C; Akpor, Adrian; Orengo, Christine A

2006-07-14

The CATH database of domain structures has been used to explore the structural variation of homologous domains in 294 well populated domain structure superfamilies, each containing at least three sequence diverse relatives. Our analyses confirm some previously detected trends relating sequence divergence to structural variation but for a much larger dataset and in some superfamilies the new data reveal exceptional structural variation. Use of a new algorithm (2DSEC) to analyse variability in secondary structure compositions across a superfamily sheds new light on how structures evolve. 2DSEC detects inserted secondary structures that embellish the core of conserved secondary structures found throughout the superfamily. Analysis showed that for 56% of highly populated superfamilies (>9 sequence diverse relatives), there are twofold or more increases in the numbers of secondary structures in some relatives. In some families fivefold increases occur, sometimes modifying the fold of the domain. Manual inspection of secondary structure insertions or embellishments in 48 particularly variable superfamilies revealed that although these insertions were usually discontiguous in the sequence they were often co-located in 3D resulting in a larger structural motif that often modified the geometry of the active site or the surface conformation promoting diverse domain partnerships and protein interactions. These observations, supported by automatic analysis of all well populated CATH families, suggest that accretion of small secondary structure insertions may provide a simple mechanism for evolving new functions in diverse relatives. Some layered domain architectures (e.g. mainly-beta and alpha-beta sandwiches) that recur highly in the genomes more frequently exploit these types of embellishments to modify function. In these architectures, aggregation occurs most often at the edges, top or bottom of the beta-sheets. Information on structural variability across domain superfamilies has been made available through the CATH Dictionary of Homologous Structures (DHS).

Structural and Histone Binding Ability Characterizations of Human PWWP Domains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Hong; Zeng, Hong; Lam, Robert

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,more » 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.« less

Network structure exploration in networks with node attributes

NASA Astrophysics Data System (ADS)

Chen, Yi; Wang, Xiaolong; Bu, Junzhao; Tang, Buzhou; Xiang, Xin

2016-05-01

Complex networks provide a powerful way to represent complex systems and have been widely studied during the past several years. One of the most important tasks of network analysis is to detect structures (also called structural regularities) embedded in networks by determining group number and group partition. Most of network structure exploration models only consider network links. However, in real world networks, nodes may have attributes that are useful for network structure exploration. In this paper, we propose a novel Bayesian nonparametric (BNP) model to explore structural regularities in networks with node attributes, called Bayesian nonparametric attribute (BNPA) model. This model does not only take full advantage of both links between nodes and node attributes for group partition via shared hidden variables, but also determine group number automatically via the Bayesian nonparametric theory. Experiments conducted on a number of real and synthetic networks show that our BNPA model is able to automatically explore structural regularities in networks with node attributes and is competitive with other state-of-the-art models.

Structural genomics reveals EVE as a new ASCH/PUA-related domain

PubMed Central

Bertonati, Claudia; Punta, Marco; Fischer, Markus; Yachdav, Guy; Forouhar, Farhad; Zhou, Weihong; Kuzin, Alexander P.; Seetharaman, Jayaraman; Abashidze, Mariam; Ramelot, Theresa A.; Kennedy, Michael A.; Cort, John R.; Belachew, Adam; Hunt, John F.; Tong, Liang; Montelione, Gaetano T.; Rost, Burkhard

2014-01-01

Summary We report on several proteins recently solved by structural genomics consortia, in particular by the Northeast Structural Genomics consortium (NESG). The proteins considered in this study differ substantially in their sequences but they share a similar structural core, characterized by a pseudobarrel five-stranded beta sheet. This core corresponds to the PUA domain-like architecture in the SCOP database. By connecting sequence information with structural knowledge, we characterize a new subgroup of these proteins that we propose to be distinctly different from previously described PUA domain-like domains such as PUA proper or ASCH. We refer to these newly defined domains as EVE. Although EVE may have retained the ability of PUA domains to bind RNA, the available experimental and computational data suggests that both the details of its molecular function and its cellular function differ from those of other PUA domain-like domains. This study of EVE and its relatives illustrates how the combination of structure and genomics creates new insights by connecting a cornucopia of structures that map to the same evolutionary potential. Primary sequence information alone would have not been sufficient to reveal these evolutionary links. PMID:19191354

Structural Genomics Reveals EVE as a New ASCH/PUA-Related Domain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bertonati, C.; Punta, M; Fischer, M

2008-01-01

We report on several proteins recently solved by structural genomics consortia, in particular by the Northeast Structural Genomics consortium (NESG). The proteins considered in this study differ substantially in their sequences but they share a similar structural core, characterized by a pseudobarrel five-stranded beta sheet. This core corresponds to the PUA domain-like architecture in the SCOP database. By connecting sequence information with structural knowledge, we characterize a new subgroup of these proteins that we propose to be distinctly different from previously described PUA domain-like domains such as PUA proper or ASCH. We refer to these newly defined domains as EVE.more » Although EVE may have retained the ability of PUA domains to bind RNA, the available experimental and computational data suggests that both the details of its molecular function and its cellular function differ from those of other PUA domain-like domains. This study of EVE and its relatives illustrates how the combination of structure and genomics creates new insights by connecting a cornucopia of structures that map to the same evolutionary potential. Primary sequence information alone would have not been sufficient to reveal these evolutionary links.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Niu, T; Dong, X; Petrongolo, M

Purpose: Dual energy CT (DECT) imaging plays an important role in advanced imaging applications due to its material decomposition capability. Direct decomposition via matrix inversion suffers from significant degradation of image signal-to-noise ratios, which reduces clinical value. Existing de-noising algorithms achieve suboptimal performance since they suppress image noise either before or after the decomposition and do not fully explore the noise statistical properties of the decomposition process. We propose an iterative image-domain decomposition method for noise suppression in DECT, using the full variance-covariance matrix of the decomposed images. Methods: The proposed algorithm is formulated in the form of least-square estimationmore » with smoothness regularization. It includes the inverse of the estimated variance-covariance matrix of the decomposed images as the penalty weight in the least-square term. Performance is evaluated using an evaluation phantom (Catphan 600) and an anthropomorphic head phantom. Results are compared to those generated using direct matrix inversion with no noise suppression, a de-noising method applied on the decomposed images, and an existing algorithm with similar formulation but with an edge-preserving regularization term. Results: On the Catphan phantom, our method retains the same spatial resolution as the CT images before decomposition while reducing the noise standard deviation of decomposed images by over 98%. The other methods either degrade spatial resolution or achieve less low-contrast detectability. Also, our method yields lower electron density measurement error than direct matrix inversion and reduces error variation by over 97%. On the head phantom, it reduces the noise standard deviation of decomposed images by over 97% without blurring the sinus structures. Conclusion: We propose an iterative image-domain decomposition method for DECT. The method combines noise suppression and material decomposition into an iterative process and achieves both goals simultaneously. The proposed algorithm shows superior performance on noise suppression with high image spatial resolution and low-contrast detectability. This work is supported by a Varian MRA grant.« less

A comparison of VLSI architectures for time and transform domain decoding of Reed-Solomon codes

NASA Technical Reports Server (NTRS)

Hsu, I. S.; Truong, T. K.; Deutsch, L. J.; Satorius, E. H.; Reed, I. S.

1988-01-01

It is well known that the Euclidean algorithm or its equivalent, continued fractions, can be used to find the error locator polynomial needed to decode a Reed-Solomon (RS) code. It is shown that this algorithm can be used for both time and transform domain decoding by replacing its initial conditions with the Forney syndromes and the erasure locator polynomial. By this means both the errata locator polynomial and the errate evaluator polynomial can be obtained with the Euclidean algorithm. With these ideas, both time and transform domain Reed-Solomon decoders for correcting errors and erasures are simplified and compared. As a consequence, the architectures of Reed-Solomon decoders for correcting both errors and erasures can be made more modular, regular, simple, and naturally suitable for VLSI implementation.

Structure-function analysis of the auxilin J-domain reveals an extended Hsc70 interaction interface.

PubMed

Jiang, Jianwen; Taylor, Alexander B; Prasad, Kondury; Ishikawa-Brush, Yumiko; Hart, P John; Lafer, Eileen M; Sousa, Rui

2003-05-20

J-domains are widespread protein interaction modules involved in recruiting and stimulating the activity of Hsp70 family chaperones. We have determined the crystal structure of the J-domain of auxilin, a protein which is involved in uncoating clathrin-coated vesicles. Comparison to the known structures of J-domains from four other proteins reveals that the auxilin J-domain is the most divergent of all J-domain structures described to date. In addition to the canonical J-domain features described previously, the auxilin J-domain contains an extra N-terminal helix and a long loop inserted between helices I and II. The latter loop extends the positively charged surface which forms the Hsc70 binding site, and is shown by directed mutagenesis and surface plasmon resonance to contain side chains important for binding to Hsc70.

Structural Studies of Geosmin Synthase, a Bifunctional Sesquiterpene Synthase with Alpha-Alpha Domain Architecture that Catalyzes a Unique Cyclization-Fragmentation Reaction Sequence

PubMed Central

Harris, Golda G.; Lombardi, Patrick M.; Pemberton, Travis A.; Matsui, Tsutomu; Weiss, Thomas M.; Cole, Kathryn E.; Köksal, Mustafa; Murphy, Frank V.; Vedula, L. Sangeetha; Chou, Wayne K.W.; Cane, David E.; Christianson, David W.

2015-01-01

Geosmin synthase from Streptomyces coelicolor (ScGS) catalyzes an unusual, metal-dependent terpenoid cyclization and fragmentation reaction sequence. Two distinct active sites are required for catalysis: the N-terminal domain catalyzes the ionization and cyclization of farnesyl diphosphate to form germacradienol and inorganic pyrophosphate (PPi), and the C-terminal domain catalyzes the protonation, cyclization, and fragmentation of germacradienol to form geosmin and acetone through a retro-Prins reaction. A unique αα domain architecture is predicted for ScGS based on amino acid sequence: each domain contains the metal-binding motifs typical of a class I terpenoid cyclase, and each domain requires Mg2+ for catalysis. Here, we report the X-ray crystal structure of the unliganded N-terminal domain of ScGS and the structure of its complex with 3 Mg2+ ions and alendronate. These structures highlight conformational changes required for active site closure and catalysis. Although neither full-length ScGS nor constructs of the C-terminal domain could be crystallized, homology models of the C-terminal domain were constructed based on ~36% sequence identity with the N-terminal domain. Small-angle X-ray scattering experiments yield low resolution molecular envelopes into which the N-terminal domain crystal structure and the C-terminal domain homology model were fit, suggesting possible αα domain architectures as frameworks for bifunctional catalysis. PMID:26598179

Self-consistent field theory simulations of polymers on arbitrary domains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ouaknin, Gaddiel, E-mail: gaddielouaknin@umail.ucsb.edu; Laachi, Nabil; Delaney, Kris

2016-12-15

We introduce a framework for simulating the mesoscale self-assembly of block copolymers in arbitrary confined geometries subject to Neumann boundary conditions. We employ a hybrid finite difference/volume approach to discretize the mean-field equations on an irregular domain represented implicitly by a level-set function. The numerical treatment of the Neumann boundary conditions is sharp, i.e. it avoids an artificial smearing in the irregular domain boundary. This strategy enables the study of self-assembly in confined domains and enables the computation of physically meaningful quantities at the domain interface. In addition, we employ adaptive grids encoded with Quad-/Oc-trees in parallel to automatically refinemore » the grid where the statistical fields vary rapidly as well as at the boundary of the confined domain. This approach results in a significant reduction in the number of degrees of freedom and makes the simulations in arbitrary domains using effective boundary conditions computationally efficient in terms of both speed and memory requirement. Finally, in the case of regular periodic domains, where pseudo-spectral approaches are superior to finite differences in terms of CPU time and accuracy, we use the adaptive strategy to store chain propagators, reducing the memory footprint without loss of accuracy in computed physical observables.« less

Practice of preventive dentistry for nursing staff in primary care.

PubMed

Jiménez-Báez, María Valeria; Acuña-Reyes, Raquel; Cigarroa-Martínez, Didier; Ureña-Bogarín, Enrique; Orgaz-Fernández, Jose David

2014-01-01

Determine the domain of preventive dentistry in nursing personnel assigned to a primary care unit. Prospective descriptive study, questionnaire validation, and prevalence study. In the first stage, the questionnaire for the practice of preventive dentistry (CPEP, for the term in Spanish) was validated; consistency and reliability were measured by Cronbach's alpha, Pearson's correlation, factor analysis with intra-class correlation coefficient (ICC). In the second stage, the domain in preventive dental nurses was explored. The overall internal consistency of CPEP is α= 0.66, ICC= 0.64, CI95%: 0.29-0.87 (p >0.01). Twenty-one subjects in the study, average age 43, 81.0% female, average seniority of 12.5 were included. A total of 71.5% showed weak domain, 28.5% regular domain, and there was no questionnaire with good domain result. The older the subjects were, the smaller the domain; female nurses showed greater mastery of preventive dentistry (29%, CI95%: 0.1-15.1) than male nurses. Public health nurses showed greater mastery with respect to other categories (50%, CI95%: 0.56-2.8). The CDEP has enough consistency to explore the domain of preventive dentistry in health-care staff. The domain of preventive dentistry in primary care nursing is poor, required to strengthen to provide education in preventive dentistry to the insured population.

Structural Determination of Functional Domains in Early B-cell Factor (EBF) Family of Transcription Factors Reveals Similarities to Rel DNA-binding Proteins and a Novel Dimerization Motif*

PubMed Central

Siponen, Marina I.; Wisniewska, Magdalena; Lehtiö, Lari; Johansson, Ida; Svensson, Linda; Raszewski, Grzegorz; Nilsson, Lennart; Sigvardsson, Mikael; Berglund, Helena

2010-01-01

The early B-cell factor (EBF) transcription factors are central regulators of development in several organs and tissues. This protein family shows low sequence similarity to other protein families, which is why structural information for the functional domains of these proteins is crucial to understand their biochemical features. We have used a modular approach to determine the crystal structures of the structured domains in the EBF family. The DNA binding domain reveals a striking resemblance to the DNA binding domains of the Rel homology superfamily of transcription factors but contains a unique zinc binding structure, termed zinc knuckle. Further the EBF proteins contain an IPT/TIG domain and an atypical helix-loop-helix domain with a novel type of dimerization motif. The data presented here provide insights into unique structural features of the EBF proteins and open possibilities for detailed molecular investigations of this important transcription factor family. PMID:20592035

Structure of the SANT domain from the Xenopus chromatin remodeling factor ISWI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Horton, John R.; Elgar, Stuart J.; Khan, Seema I.

2008-09-17

The SANT (Swi3, Ada2, N-Cor, and TFIIIB) module was first described as a putative DNA-binding domain with strong similarity to the helix-turn-helix DNA binding domain of Myb-related proteins. The X-ray structure of the C-terminal one third portion of the ATPase ISWI of Drosophila melangoaster, containing both SANT and SLIDE (SANT-Like ISWI Domain), confirmed the overall helix-turn-helix structural architecture of SANT as well as SLIDE. However, the DNA-contacting residues in Myb are not conserved in SANT and the structurally corresponding residues in the ISWI SANT domain are acidic, and therefore incompatible with DNA interaction. Recent studies suggested that SANT domains mightmore » be a histone-tail-binding module, including the DNA binding SANT domain of c-Myb. Here they present the X-ray structure of Xenopus laevis ISWI SANT domain, derived from limited proteolysis of a C-terminal fragment of ISWI protein.« less

Imaging and engineering the nanoscale-domain structure of a Sr0.61Ba0.39Nb2O6 crystal using a scanning force microscope

NASA Astrophysics Data System (ADS)

Terabe, K.; Takekawa, S.; Nakamura, M.; Kitamura, K.; Higuchi, S.; Gotoh, Y.; Gruverman, A.

2002-09-01

We have investigated the ferroelectric domain structure formed in a Sr0.61Ba0.39Nb2O6 single crystal by cooling the crystal through the Curie point. Imaging the etched surface structure using a scanning force microscope (SFM) in both the topographic mode and the piezoresponse mode revealed that a multidomain structure of nanoscale islandlike domains was formed. The islandlike domains could be inverted by applying an appropriate voltage using a conductive SFM tip. Furthermore, a nanoscale periodically inverted-domain structure was artificially fabricated using the crystal which underwent poling treatment.

Marginal turbulent state of viscoelastic fluids: A polymer drag reduction perspective.

PubMed

Xi, Li; Bai, Xue

2016-04-01

The laminar-turbulent (LT) transition of dilute polymer solutions is of great interest not only for the complex transition dynamics itself, but also for its potential link to the maximum drag reduction (MDR) phenomenon. We present an in-depth investigation of the edge state (ES), an asymptotic solution on the LT boundary, in viscoelastic channel flow. For given Re and simulation domain size, mean flow statistics of the ES do not vary with the introduction of polymers, proving that there is a region of turbulent states not susceptible to polymer drag reduction effects. The dynamics of the ES features low-frequency fluctuations and in the longer domains we studied it is nearly periodic with regular bursts of turbulent activities separated by extended quiescent periods. Its flow field is dominated by elongated vortices and streaks, with very weak extensional and rotational flow motions. Polymer stretching is almost exclusively contributed by the mean shear and polymer-turbulence interaction is minimal. Flow structures and the kinematics of the ES match hibernating turbulence, an MDR-like phase intermittently occurring in turbulent dynamics. Its observation now seems to result from recurrent visits to certain parts of the ES. The ES offers explanations for the existence and universality of MDR, the quantitative magnitude of which, however, still remains unsolved.

Marginal turbulent state of viscoelastic fluids: A polymer drag reduction perspective

NASA Astrophysics Data System (ADS)

Xi, Li; Bai, Xue

2016-04-01

The laminar-turbulent (LT) transition of dilute polymer solutions is of great interest not only for the complex transition dynamics itself, but also for its potential link to the maximum drag reduction (MDR) phenomenon. We present an in-depth investigation of the edge state (ES), an asymptotic solution on the LT boundary, in viscoelastic channel flow. For given Re and simulation domain size, mean flow statistics of the ES do not vary with the introduction of polymers, proving that there is a region of turbulent states not susceptible to polymer drag reduction effects. The dynamics of the ES features low-frequency fluctuations and in the longer domains we studied it is nearly periodic with regular bursts of turbulent activities separated by extended quiescent periods. Its flow field is dominated by elongated vortices and streaks, with very weak extensional and rotational flow motions. Polymer stretching is almost exclusively contributed by the mean shear and polymer-turbulence interaction is minimal. Flow structures and the kinematics of the ES match hibernating turbulence, an MDR-like phase intermittently occurring in turbulent dynamics. Its observation now seems to result from recurrent visits to certain parts of the ES. The ES offers explanations for the existence and universality of MDR, the quantitative magnitude of which, however, still remains unsolved.

Structure of the SPRY domain of the human RNA helicase DDX1, a putative interaction platform within a DEAD-box protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kellner, Julian N.; Meinhart, Anton, E-mail: anton.meinhart@mpimf-heidelberg.mpg.de

The structure of the SPRY domain of the human RNA helicase DDX1 was determined at 2.0 Å resolution. The SPRY domain provides a putative protein–protein interaction platform within DDX1 that differs from other SPRY domains in its structure and conserved regions. The human RNA helicase DDX1 in the DEAD-box family plays an important role in RNA processing and has been associated with HIV-1 replication and tumour progression. Whereas previously described DEAD-box proteins have a structurally conserved core, DDX1 shows a unique structural feature: a large SPRY-domain insertion in its RecA-like consensus fold. SPRY domains are known to function as protein–proteinmore » interaction platforms. Here, the crystal structure of the SPRY domain of human DDX1 (hDSPRY) is reported at 2.0 Å resolution. The structure reveals two layers of concave, antiparallel β-sheets that stack onto each other and a third β-sheet beneath the β-sandwich. A comparison with SPRY-domain structures from other eukaryotic proteins showed that the general β-sandwich fold is conserved; however, differences were detected in the loop regions, which were identified in other SPRY domains to be essential for interaction with cognate partners. In contrast, in hDSPRY these loop regions are not strictly conserved across species. Interestingly, though, a conserved patch of positive surface charge is found that may replace the connecting loops as a protein–protein interaction surface. The data presented here comprise the first structural information on DDX1 and provide insights into the unique domain architecture of this DEAD-box protein. By providing the structure of a putative interaction domain of DDX1, this work will serve as a basis for further studies of the interaction network within the hetero-oligomeric complexes of DDX1 and of its recruitment to the HIV-1 Rev protein as a viral replication factor.« less

Protein domain definition should allow for conditional disorder

PubMed Central

Yegambaram, Kavestri; Bulloch, Esther MM; Kingston, Richard L

2013-01-01

Abstract: Proteins are often classified in a binary fashion as either structured or disordered. However this approach has several deficits. Firstly, protein folding is always conditional on the physiochemical environment. A protein which is structured in some circumstances will be disordered in others. Secondly, it hides a fundamental asymmetry in behavior. While all structured proteins can be unfolded through a change in environment, not all disordered proteins have the capacity for folding. Failure to accommodate these complexities confuses the definition of both protein structural domains and intrinsically disordered regions. We illustrate these points with an experimental study of a family of small binding domains, drawn from the RNA polymerase of mumps virus and its closest relatives. Assessed at face value the domains fall on a structural continuum, with folded, partially folded, and near unstructured members. Yet the disorder present in the family is conditional, and these closely related polypeptides can access the same folded state under appropriate conditions. Any heuristic definition of the protein domain emphasizing conformational stability divides this domain family in two, in a way that makes no biological sense. Structural domains would be better defined by their ability to adopt a specific tertiary structure: a structure that may or may not be realized, dependent on the circumstances. This explicitly allows for the conditional nature of protein folding, and more clearly demarcates structural domains from intrinsically disordered regions that may function without folding. PMID:23963781

On the regularized fermionic projector of the vacuum

NASA Astrophysics Data System (ADS)

Finster, Felix

2008-03-01

We construct families of fermionic projectors with spherically symmetric regularization, which satisfy the condition of a distributional MP-product. The method is to analyze regularization tails with a power law or logarithmic scaling in composite expressions in the fermionic projector. The resulting regularizations break the Lorentz symmetry and give rise to a multilayer structure of the fermionic projector near the light cone. Furthermore, we construct regularizations which go beyond the distributional MP-product in that they yield additional distributional contributions supported at the origin. The remaining freedom for the regularization parameters and the consequences for the normalization of the fermionic states are discussed.

Traveling in the dark: the legibility of a regular and predictable structure of the environment extends beyond its borders.

PubMed

Yaski, Osnat; Portugali, Juval; Eilam, David

2012-04-01

The physical structure of the surrounding environment shapes the paths of progression, which in turn reflect the structure of the environment and the way that it shapes behavior. A regular and coherent physical structure results in paths that extend over the entire environment. In contrast, irregular structure results in traveling over a confined sector of the area. In this study, rats were tested in a dark arena in which half the area contained eight objects in a regular grid layout, and the other half contained eight objects in an irregular layout. In subsequent trials, a salient landmark was placed first within the irregular half, and then within the grid. We hypothesized that rats would favor travel in the area with regular order, but found that activity in the area with irregular object layout did not differ from activity in the area with grid layout, even when the irregular half included a salient landmark. Thus, the grid impact in one arena half extended to the other half and overshadowed the presumed impact of the salient landmark. This could be explained by mechanisms that control spatial behavior, such as grid cells and odometry. However, when objects were spaced irregularly over the entire arena, the salient landmark became dominant and the paths converged upon it, especially from objects with direct access to the salient landmark. Altogether, three environmental properties: (i) regular and predictable structure; (ii) salience of landmarks; and (iii) accessibility, hierarchically shape the paths of progression in a dark environment. Copyright © 2012 Elsevier B.V. All rights reserved.

A theoretical prediction of the paradoxical surface free energy for FCC metallic nanosolids

NASA Astrophysics Data System (ADS)

Abdul-Hafidh, Esam H.; Aïssa, Brahim

2016-08-01

We report on the development of an efficient and simple method to calculate the surface free energy (surface tension) of a general-shaped metallic nanosolid. Both nanoparticles and nanostructures that account for the crystal structure and size were considered. The surface free energy of a face-centered cubic structure of a metallic nanoparticles was found to decrease as the size decreases, for a shape factor equal to 1.0 (i.e., spherical). However, when the shape factor exceeds this value, which includes disk-like, regular tetrahedral, regular hexahedral, regular octahedral, nanorod, and regular quadrangular structures, the behavior of the surface free energy was found to reverse, especially for small nanoparticles and then increases as the size decreases. Moreover, this behavior was systematically recorded for large nanoparticles when the mechanical distortion was appreciable. As a matter of fact, this model was also applied to the noble transition metals, including gold and silver nanoparticles. This work is a clear step forward establishing a systematic mechanism for controlling the mechanical properties of nanoscale particles by controlling the shape, size and structure.

Multistep modeling (MSM) of biomolecular structure application to the A-G mispair in the B-DNA environment

NASA Technical Reports Server (NTRS)

Srinivasan, S.; Raghunathan, G.; Shibata, M.; Rein, R.

1986-01-01

A multistep modeling procedure has been evolved to study the structural changes introduced by lesions in DNA. We report here the change in the structure of regular B-DNA geometry due to the incorporation of Ganti-Aanti mispair in place of a regular G-C pair, preserving the helix continuity. The energetics of the structure so obtained is compared with the Ganti-Asyn configuration under similar constrained conditions. We present the methodology adopted and discuss the results.

Structural mapping of the coiled-coil domain of a bacterial condensin and comparative analyses across all domains of life suggest conserved features of SMC proteins.

PubMed

Waldman, Vincent M; Stanage, Tyler H; Mims, Alexandra; Norden, Ian S; Oakley, Martha G

2015-06-01

The structural maintenance of chromosomes (SMC) proteins form the cores of multisubunit complexes that are required for the segregation and global organization of chromosomes in all domains of life. These proteins share a common domain structure in which N- and C- terminal regions pack against one another to form a globular ATPase domain. This "head" domain is connected to a central, globular, "hinge" or dimerization domain by a long, antiparallel coiled coil. To date, most efforts for structural characterization of SMC proteins have focused on the globular domains. Recently, however, we developed a method to map interstrand interactions in the 50-nm coiled-coil domain of MukB, the divergent SMC protein found in γ-proteobacteria. Here, we apply that technique to map the structure of the Bacillus subtilis SMC (BsSMC) coiled-coil domain. We find that, in contrast to the relatively complicated coiled-coil domain of MukB, the BsSMC domain is nearly continuous, with only two detectable coiled-coil interruptions. Near the middle of the domain is a break in coiled-coil structure in which there are three more residues on the C-terminal strand than on the N-terminal strand. Close to the head domain, there is a second break with a significantly longer insertion on the same strand. These results provide an experience base that allows an informed interpretation of the output of coiled-coil prediction algorithms for this family of proteins. A comparison of such predictions suggests that these coiled-coil deviations are highly conserved across SMC types in a wide variety of organisms, including humans. © 2015 Wiley Periodicals, Inc.

Computational modeling of Repeat1 region of INI1/hSNF5: An evolutionary link with ubiquitin

PubMed Central

Bhutoria, Savita

2016-01-01

Abstract The structure of a protein can be very informative of its function. However, determining protein structures experimentally can often be very challenging. Computational methods have been used successfully in modeling structures with sufficient accuracy. Here we have used computational tools to predict the structure of an evolutionarily conserved and functionally significant domain of Integrase interactor (INI)1/hSNF5 protein. INI1 is a component of the chromatin remodeling SWI/SNF complex, a tumor suppressor and is involved in many protein‐protein interactions. It belongs to SNF5 family of proteins that contain two conserved repeat (Rpt) domains. Rpt1 domain of INI1 binds to HIV‐1 Integrase, and acts as a dominant negative mutant to inhibit viral replication. Rpt1 domain also interacts with oncogene c‐MYC and modulates its transcriptional activity. We carried out an ab initio modeling of a segment of INI1 protein containing the Rpt1 domain. The structural model suggested the presence of a compact and well defined ββαα topology as core structure in the Rpt1 domain of INI1. This topology in Rpt1 was similar to PFU domain of Phospholipase A2 Activating Protein, PLAA. Interestingly, PFU domain shares similarity with Ubiquitin and has ubiquitin binding activity. Because of the structural similarity between Rpt1 domain of INI1 and PFU domain of PLAA, we propose that Rpt1 domain of INI1 may participate in ubiquitin recognition or binding with ubiquitin or ubiquitin related proteins. This modeling study may shed light on the mode of interactions of Rpt1 domain of INI1 and is likely to facilitate future functional studies of INI1. PMID:27261671

Computational modeling of Repeat1 region of INI1/hSNF5: An evolutionary link with ubiquitin.

PubMed

Bhutoria, Savita; Kalpana, Ganjam V; Acharya, Seetharama A

2016-09-01

The structure of a protein can be very informative of its function. However, determining protein structures experimentally can often be very challenging. Computational methods have been used successfully in modeling structures with sufficient accuracy. Here we have used computational tools to predict the structure of an evolutionarily conserved and functionally significant domain of Integrase interactor (INI)1/hSNF5 protein. INI1 is a component of the chromatin remodeling SWI/SNF complex, a tumor suppressor and is involved in many protein-protein interactions. It belongs to SNF5 family of proteins that contain two conserved repeat (Rpt) domains. Rpt1 domain of INI1 binds to HIV-1 Integrase, and acts as a dominant negative mutant to inhibit viral replication. Rpt1 domain also interacts with oncogene c-MYC and modulates its transcriptional activity. We carried out an ab initio modeling of a segment of INI1 protein containing the Rpt1 domain. The structural model suggested the presence of a compact and well defined ββαα topology as core structure in the Rpt1 domain of INI1. This topology in Rpt1 was similar to PFU domain of Phospholipase A2 Activating Protein, PLAA. Interestingly, PFU domain shares similarity with Ubiquitin and has ubiquitin binding activity. Because of the structural similarity between Rpt1 domain of INI1 and PFU domain of PLAA, we propose that Rpt1 domain of INI1 may participate in ubiquitin recognition or binding with ubiquitin or ubiquitin related proteins. This modeling study may shed light on the mode of interactions of Rpt1 domain of INI1 and is likely to facilitate future functional studies of INI1. © 2016 The Protein Society.

Library of electrocatalytic sites in nano-structured domains: electrocatalysis of hydrogen peroxide.

PubMed

Pandey, Prem C; Singh, Bhupendra

2008-12-01

Electrochemical detection of hydrogen peroxide at eight types of ormosil-modified electrodes, referred as hexacyanoferrate-system; Prussian blue systems (PB-1, PB-2, and PB-3), palladium (Pd-) system, graphite (Gr-) system, gold nanoparticle (AuNPs) system and palladium-gold nanoparticle (Pd-AuNPs) system were studied. The results on electrochemical detection suggested that hydrogen peroxide does not undergo homogeneous electrochemical mediation; however, the presence of redox mediator within nano-structured domains facilitates the electro-analysis of the same via redox electrocatalysis. Four approaches causing manipulation in nano-structured domains are described: (a) increase in the molecular size of the components generating nano-structured domains; (b) modulation via chemical reactivity; (c) modulation by non-reactive moieties and known nanoparticles; and (d) modulation by mixed approaches (a-c), all leading to decrease in a nano-structured domains. The results demonstrated that an increase in the size of nano-structured domains or decrease in micro-porous geometry increases the efficiency of electrocatalysis. The basic reaction protocol adopted in generating nano-structured domains, followed by manipulation protocols, supported the introduction of a library for creating electrocatalytic sites with varying electrocatalytic efficiency within the same basic nano-structured platform.

Frequency-domain algorithm for the Lorenz-gauge gravitational self-force

NASA Astrophysics Data System (ADS)

Akcay, Sarp; Warburton, Niels; Barack, Leor

2013-11-01

State-of-the-art computations of the gravitational self-force (GSF) on massive particles in black hole spacetimes involve numerical evolution of the metric perturbation equations in the time domain, which is computationally very costly. We present here a new strategy based on a frequency-domain treatment of the perturbation equations, which offers considerable computational saving. The essential ingredients of our method are (i) a Fourier-harmonic decomposition of the Lorenz-gauge metric perturbation equations and a numerical solution of the resulting coupled set of ordinary equations with suitable boundary conditions; (ii) a generalized version of the method of extended homogeneous solutions [L. Barack, A. Ori, and N. Sago, Phys. Rev. D 78, 084021 (2008)] used to circumvent the Gibbs phenomenon that would otherwise hamper the convergence of the Fourier mode sum at the particle’s location; (iii) standard mode-sum regularization, which finally yields the physical GSF as a sum over regularized modal contributions. We present a working code that implements this strategy to calculate the Lorenz-gauge GSF along eccentric geodesic orbits around a Schwarzschild black hole. The code is far more efficient than existing time-domain methods; the gain in computation speed (at a given precision) is about an order of magnitude at an eccentricity of 0.2, and up to 3 orders of magnitude for circular or nearly circular orbits. This increased efficiency was crucial in enabling the recently reported calculation of the long-term orbital evolution of an extreme mass ratio inspiral [N. Warburton, S. Akcay, L. Barack, J. R. Gair, and N. Sago, Phys. Rev. D 85, 061501(R) (2012)]. Here we provide full technical details of our method to complement the above report.

Benefits of Matching Domain Structure for Planning Software: The Right Stuff

NASA Technical Reports Server (NTRS)

Billman, Dorrit Owen; Arsintescu, Lucica; Feary, Michael S.; Lee, Jessica Chia-Rong; Smith, Asha Halima; Tiwary, Rachna

2011-01-01

We investigated the role of domain structure in software design. We compared 2 planning applications, for a Mission Control group (International Space Station), and measured users speed and accuracy. Based on our needs analysis, we identified domain structure and used this to develop new prototype software that matched domain structure better than the legacy system. We took a high-fidelity analog of the natural task into the laboratory and found (large) periformance differences, favoring the system that matched domain structure. Our task design enabled us to attribute better periormance to better match of domain structure. We ran through the whole development cycle, in miniature, from needs analysis through design, development, and evaluation. Doing so enabled inferences not just about the particular systems compared, but also provided evidence for the viability of the design process (particularly needs analysis) that we are exploring.

Experimental verification, and domain definition, of structural alerts for protein binding: epoxides, lactones, nitroso, nitros, aldehydes and ketones.

PubMed

Nelms, M D; Cronin, M T D; Schultz, T W; Enoch, S J

2013-01-01

This study outlines how a combination of in chemico and Tetrahymena pyriformis data can be used to define the applicability domain of selected structural alerts within the profilers of the OECD QSAR Toolbox. Thirty-three chemicals were profiled using the OECD and OASIS profilers, enabling the applicability domain of six structural alerts to be defined, the alerts being: epoxides, lactones, nitrosos, nitros, aldehydes and ketones. Analysis of the experimental data showed the applicability domains for the epoxide, nitroso, aldehyde and ketone structural alerts to be well defined. In contrast, the data showed the applicability domains for the lactone and nitro structural alerts needed modifying. The accurate definition of the applicability domain for structural alerts within in silico profilers is important due to their use in the chemical category in predictive and regulatory toxicology. This study highlights the importance of utilizing multiple profilers in category formation.

F4 , E6 and G2 exceptional gauge groups in the vacuum domain structure model

NASA Astrophysics Data System (ADS)

Shahlaei, Amir; Rafibakhsh, Shahnoosh

2018-03-01

Using a vacuum domain structure model, we calculate trivial static potentials in various representations of F4 , E6, and G2 exceptional groups by means of the unit center element. Due to the absence of the nontrivial center elements, the potential of every representation is screened at far distances. However, the linear part is observed at intermediate quark separations and is investigated by the decomposition of the exceptional group to its maximal subgroups. Comparing the group factor of the supergroup with the corresponding one obtained from the nontrivial center elements of S U (3 ) subgroup shows that S U (3 ) is not the direct cause of temporary confinement in any of the exceptional groups. However, the trivial potential obtained from the group decomposition into the S U (3 ) subgroup is the same as the potential of the supergroup itself. In addition, any regular or singular decomposition into the S U (2 ) subgroup that produces the Cartan generator with the same elements as h1, in any exceptional group, leads to the linear intermediate potential of the exceptional gauge groups. The other S U (2 ) decompositions with the Cartan generator different from h1 are still able to describe the linear potential if the number of S U (2 ) nontrivial center elements that emerge in the decompositions is the same. As a result, it is the center vortices quantized in terms of nontrivial center elements of the S U (2 ) subgroup that give rise to the intermediate confinement in the static potentials.

Irreversible transformation of ferromagnetic ordered stripe domains in single-shot infrared-pump/resonant-x-ray-scattering-probe experiments

NASA Astrophysics Data System (ADS)

Bergeard, Nicolas; Schaffert, Stefan; López-Flores, Víctor; Jaouen, Nicolas; Geilhufe, Jan; Günther, Christian M.; Schneider, Michael; Graves, Catherine; Wang, Tianhan; Wu, Benny; Scherz, Andreas; Baumier, Cédric; Delaunay, Renaud; Fortuna, Franck; Tortarolo, Marina; Tudu, Bharati; Krupin, Oleg; Minitti, Michael P.; Robinson, Joe; Schlotter, William F.; Turner, Joshua J.; Lüning, Jan; Eisebitt, Stefan; Boeglin, Christine

2015-02-01

The evolution of a magnetic domain structure upon excitation by an intense, femtosecond infrared (IR) laser pulse has been investigated using single-shot based time-resolved resonant x-ray scattering at the x-ray free electron laser LCLS. A well-ordered stripe domain pattern as present in a thin CoPd alloy film has been used as a prototype magnetic domain structure for this study. The fluence of the IR laser pump pulse was sufficient to lead to an almost complete quenching of the magnetization within the ultrafast demagnetization process taking place within the first few hundreds of femtoseconds following the IR laser pump pulse excitation. On longer time scales this excitation gave rise to subsequent irreversible transformations of the magnetic domain structure. Under our specific experimental conditions, it took about 2 ns before the magnetization started to recover. After about 5 ns the previously ordered stripe domain structure had evolved into a disordered labyrinth domain structure. Surprisingly, we observe after about 7 ns the occurrence of a partially ordered stripe domain structure reoriented into a novel direction. It is this domain structure in which the sample's magnetization stabilizes as revealed by scattering patterns recorded long after the initial pump-probe cycle. Using micromagnetic simulations we can explain this observation based on changes of the magnetic anisotropy going along with heat dissipation in the film.

Crystal structure of a multi-domain human smoothened receptor in complex with a super stabilizing ligand

NASA Astrophysics Data System (ADS)

Zhang, Xianjun; Zhao, Fei; Wu, Yiran; Yang, Jun; Han, Gye Won; Zhao, Suwen; Ishchenko, Andrii; Ye, Lintao; Lin, Xi; Ding, Kang; Dharmarajan, Venkatasubramanian; Griffin, Patrick R.; Gati, Cornelius; Nelson, Garrett; Hunter, Mark S.; Hanson, Michael A.; Cherezov, Vadim; Stevens, Raymond C.; Tan, Wenfu; Tao, Houchao; Xu, Fei

2017-05-01

The Smoothened receptor (SMO) belongs to the Class Frizzled of the G protein-coupled receptor (GPCR) superfamily, constituting a key component of the Hedgehog signalling pathway. Here we report the crystal structure of the multi-domain human SMO, bound and stabilized by a designed tool ligand TC114, using an X-ray free-electron laser source at 2.9 Å. The structure reveals a precise arrangement of three distinct domains: a seven-transmembrane helices domain (TMD), a hinge domain (HD) and an intact extracellular cysteine-rich domain (CRD). This architecture enables allosteric interactions between the domains that are important for ligand recognition and receptor activation. By combining the structural data, molecular dynamics simulation, and hydrogen-deuterium-exchange analysis, we demonstrate that transmembrane helix VI, extracellular loop 3 and the HD play a central role in transmitting the signal employing a unique GPCR activation mechanism, distinct from other multi-domain GPCRs.

Structure-Processing Relationships in Solution Processable Polymer Thin Film Transistors and Small Molecule Bulk Heterojunction Solar Cells

NASA Astrophysics Data System (ADS)

Perez, Louis A.

A regio-regular (RR) conjugated copolymer based on cyclopenta[2,1-b:3,4- b]dithiophene (CDT) and pyridal[2,1,3]thiadiazole (PT) structural units was prepared by using polymerization reactions involving reactants specifically designed to avoid random orientation of the asymmetric PT heterocycle. Compared to its regio-irregular (RI) counterpart, the RR polymer exhibits a two orders of magnitude increase in hole mobility from 0.005 to 0.6 cm2V -1s-1. To probe the reason for this difference in mobility, we examined the crystalline structure and its orientation in thin films of both copolymers as a function of depth via grazing incidence wide angle X-ray scattering (GIWAXS). In the RI film, the pi-pi stacking direction of the crystallites is mainly perpendicular to the substrate normal (edge-on orientation) while in the RR film the crystallites adopt a mixed pi-pi stacking orientation in the center of the film as well as near the interface between the polymer and the dielectric layer. These results demonstrate that control of backbone regularity is another important design criterion to consider in the synthesis and optimization of new conjugated copolymers with asymmetric structural units. Solution processed organic photovoltaic devices (OPVs) have emerged as a promising sustainable energy technology due to their ease of fabrication, potential to enable low-cost manufacturing, and ability to be incorporated onto light-weight flexible substrates. To date, the most efficacious OPV device architecture, the bulk heterojunction (BHJ), consists of a blend of a light-harvesting conjugated organic electron donating molecule and a strong electron-accepting compound (usually a soluble fullerene derivative e.g. [6,6]-phenyl C71 butyric acid methyl ester (PC71BM). BHJ layer morphology, which has been shown to be highly dependent on processing, has a significant effect on OPV performance. It is postulated that optimal BHJ morphologies consist of discrete bicontinuous nanoscale domains of each moiety, on the order of the exciton diffusion length, which extend vertically from each electrode, thereby increasing the surface area of the domains and forming continuous conducting pathways for efficient charge extraction and transfer. An optimal morphology, however, is seldom achieved during film formation; therefore, a number of processing techniques, such as thermal and sol vent annealing, and the addition of solvent additives to the casting solution have been explored to control the morphology in order to attain the multiple structural requirements. Solvent additive processing, a technique that is used in most record performing polymer:fullerene BHJ solar cell devices, involves the addition of small volumes of a high boiling point liquid to the BHJ casting solu- tion. Solvent additive processing, with 1,8-diiodooctane (DIO) as the additive, has recently been employed in solution processable small molecule (SPSM) BHJ systems, showing similar drastic effects on several device metrics and ultimately the power conversion efficiency (PCE). A recent SPSM study delineates how the volume of solvent additive used affects device performance: when 0.4 v/v% of DIO was used, the PCE increased from 1.8 to 7%, while a deterioration in the PCE to less than 1% occurred when only 1 v/v% of DIO was used. Several structural characterization techniques, such as grazing incidence wide and small-angle X-ray scattering (GIWAXS and GISAXS), and energy filtered transmission electron microscopy (EF-TEM), were used to investigate structure-processing-property relationships in additive-treated SPSM BHJ films and were correlated to device performance. Scattering experiments showed that the use of additives had several effects on the structure of the BHJ at multiple length scales: e.g. the number and orientation of SPSM crystallites, different pi-pi stacking distances, and the nano-scale domain size. Additionally, EF-TEM further verified the effect of additives on the domain size and was complemented with tomographic reconstructions to provide a 3D representation of the BHJ morphology due to solvent additive processing. Finally, in situ GIWAXS was also performed to investigate the kinetics of crystallite formation during and shortly after spin-casting. The additive was shown to induce a complex structural evolution effect on the microstructure of SPSMs by inciting the formation of a metastable polymorph and enhanced crystalline quality of the SPSM during and shortly after casting, whereas the non-additive treated SPSM structure was static after initial crystallite formation. The results from this study have important implications for future optimization and design of solvent additive processed SPSM BHJ blends for OPV devices.

A BAR domain in the N terminus of the Arf GAP ASAP1 affects membrane structure and trafficking of epidermal growth factor receptor.

PubMed

Nie, Zhongzhen; Hirsch, Dianne S; Luo, Ruibai; Jian, Xiaoying; Stauffer, Stacey; Cremesti, Aida; Andrade, Josefa; Lebowitz, Jacob; Marino, Michael; Ahvazi, Bijan; Hinshaw, Jenny E; Randazzo, Paul A

2006-01-24

Arf GAPs are multidomain proteins that function in membrane traffic by inactivating the GTP binding protein Arf1. Numerous Arf GAPs contain a BAR domain, a protein structural element that contributes to membrane traffic by either inducing or sensing membrane curvature. We have examined the role of a putative BAR domain in the function of the Arf GAP ASAP1. ASAP1's N terminus, containing the putative BAR domain together with a PH domain, dimerized to form an extended structure that bound to large unilamellar vesicles containing acidic phospholipids, properties that define a BAR domain. A recombinant protein containing the BAR domain of ASAP1, together with the PH and Arf GAP domains, efficiently bent the surface of large unilamellar vesicles, resulting in the formation of tubular structures. This activity was regulated by Arf1*GTP binding to the Arf GAP domain. In vivo, the tubular structures induced by ASAP1 mutants contained epidermal growth factor receptor (EGFR) and Rab11, and ASAP1 colocalized in tubular structures with EGFR during recycling of receptor. Expression of ASAP1 accelerated EGFR trafficking and slowed cell spreading. An ASAP1 mutant lacking the BAR domain had no effect. The N-terminal BAR domain of ASAP1 mediates membrane bending and is necessary for ASAP1 function. The Arf dependence of the bending activity is consistent with ASAP1 functioning as an Arf effector.

Wavelet-based 3-D inversion for frequency-domain airborne EM data

NASA Astrophysics Data System (ADS)

Liu, Yunhe; Farquharson, Colin G.; Yin, Changchun; Baranwal, Vikas C.

2018-04-01

In this paper, we propose a new wavelet-based 3-D inversion method for frequency-domain airborne electromagnetic (FDAEM) data. Instead of inverting the model in the space domain using a smoothing constraint, this new method recovers the model in the wavelet domain based on a sparsity constraint. In the wavelet domain, the model is represented by two types of coefficients, which contain both large- and fine-scale informations of the model, meaning the wavelet-domain inversion has inherent multiresolution. In order to accomplish a sparsity constraint, we minimize an L1-norm measure in the wavelet domain that mostly gives a sparse solution. The final inversion system is solved by an iteratively reweighted least-squares method. We investigate different orders of Daubechies wavelets to accomplish our inversion algorithm, and test them on synthetic frequency-domain AEM data set. The results show that higher order wavelets having larger vanishing moments and regularity can deliver a more stable inversion process and give better local resolution, while the lower order wavelets are simpler and less smooth, and thus capable of recovering sharp discontinuities if the model is simple. At last, we test this new inversion algorithm on a frequency-domain helicopter EM (HEM) field data set acquired in Byneset, Norway. Wavelet-based 3-D inversion of HEM data is compared to L2-norm-based 3-D inversion's result to further investigate the features of the new method.

Iterative image-domain decomposition for dual-energy CT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Niu, Tianye; Dong, Xue; Petrongolo, Michael

2014-04-15

Purpose: Dual energy CT (DECT) imaging plays an important role in advanced imaging applications due to its capability of material decomposition. Direct decomposition via matrix inversion suffers from significant degradation of image signal-to-noise ratios, which reduces clinical values of DECT. Existing denoising algorithms achieve suboptimal performance since they suppress image noise either before or after the decomposition and do not fully explore the noise statistical properties of the decomposition process. In this work, the authors propose an iterative image-domain decomposition method for noise suppression in DECT, using the full variance-covariance matrix of the decomposed images. Methods: The proposed algorithm ismore » formulated in the form of least-square estimation with smoothness regularization. Based on the design principles of a best linear unbiased estimator, the authors include the inverse of the estimated variance-covariance matrix of the decomposed images as the penalty weight in the least-square term. The regularization term enforces the image smoothness by calculating the square sum of neighboring pixel value differences. To retain the boundary sharpness of the decomposed images, the authors detect the edges in the CT images before decomposition. These edge pixels have small weights in the calculation of the regularization term. Distinct from the existing denoising algorithms applied on the images before or after decomposition, the method has an iterative process for noise suppression, with decomposition performed in each iteration. The authors implement the proposed algorithm using a standard conjugate gradient algorithm. The method performance is evaluated using an evaluation phantom (Catphan©600) and an anthropomorphic head phantom. The results are compared with those generated using direct matrix inversion with no noise suppression, a denoising method applied on the decomposed images, and an existing algorithm with similar formulation as the proposed method but with an edge-preserving regularization term. Results: On the Catphan phantom, the method maintains the same spatial resolution on the decomposed images as that of the CT images before decomposition (8 pairs/cm) while significantly reducing their noise standard deviation. Compared to that obtained by the direct matrix inversion, the noise standard deviation in the images decomposed by the proposed algorithm is reduced by over 98%. Without considering the noise correlation properties in the formulation, the denoising scheme degrades the spatial resolution to 6 pairs/cm for the same level of noise suppression. Compared to the edge-preserving algorithm, the method achieves better low-contrast detectability. A quantitative study is performed on the contrast-rod slice of Catphan phantom. The proposed method achieves lower electron density measurement error as compared to that by the direct matrix inversion, and significantly reduces the error variation by over 97%. On the head phantom, the method reduces the noise standard deviation of decomposed images by over 97% without blurring the sinus structures. Conclusions: The authors propose an iterative image-domain decomposition method for DECT. The method combines noise suppression and material decomposition into an iterative process and achieves both goals simultaneously. By exploring the full variance-covariance properties of the decomposed images and utilizing the edge predetection, the proposed algorithm shows superior performance on noise suppression with high image spatial resolution and low-contrast detectability.« less

Reciprocal Influence of Protein Domains in the Cold-Adapted Acyl Aminoacyl Peptidase from Sporosarcina psychrophila

PubMed Central

Parravicini, Federica; Natalello, Antonino; Papaleo, Elena; De Gioia, Luca; Doglia, Silvia Maria; Lotti, Marina; Brocca, Stefania

2013-01-01

Acyl aminoacyl peptidases are two-domain proteins composed by a C-terminal catalytic α/β-hydrolase domain and by an N-terminal β-propeller domain connected through a structural element that is at the N-terminus in sequence but participates in the 3D structure of the C-domain. We investigated about the structural and functional interplay between the two domains and the bridge structure (in this case a single helix named α1-helix) in the cold-adapted enzyme from Sporosarcina psychrophila (SpAAP) using both protein variants in which entire domains were deleted and proteins carrying substitutions in the α1-helix. We found that in this enzyme the inter-domain connection dramatically affects the stability of both the whole enzyme and the β-propeller. The α1-helix is required for the stability of the intact protein, as in other enzymes of the same family; however in this psychrophilic enzyme only, it destabilizes the isolated β-propeller. A single charged residue (E10) in the α1-helix plays a major role for the stability of the whole structure. Overall, a strict interaction of the SpAAP domains seems to be mandatory for the preservation of their reciprocal structural integrity and may witness their co-evolution. PMID:23457536

Reciprocal influence of protein domains in the cold-adapted acyl aminoacyl peptidase from Sporosarcina psychrophila.

PubMed

Parravicini, Federica; Natalello, Antonino; Papaleo, Elena; De Gioia, Luca; Doglia, Silvia Maria; Lotti, Marina; Brocca, Stefania

2013-01-01

Acyl aminoacyl peptidases are two-domain proteins composed by a C-terminal catalytic α/β-hydrolase domain and by an N-terminal β-propeller domain connected through a structural element that is at the N-terminus in sequence but participates in the 3D structure of the C-domain. We investigated about the structural and functional interplay between the two domains and the bridge structure (in this case a single helix named α1-helix) in the cold-adapted enzyme from Sporosarcina psychrophila (SpAAP) using both protein variants in which entire domains were deleted and proteins carrying substitutions in the α1-helix. We found that in this enzyme the inter-domain connection dramatically affects the stability of both the whole enzyme and the β-propeller. The α1-helix is required for the stability of the intact protein, as in other enzymes of the same family; however in this psychrophilic enzyme only, it destabilizes the isolated β-propeller. A single charged residue (E10) in the α1-helix plays a major role for the stability of the whole structure. Overall, a strict interaction of the SpAAP domains seems to be mandatory for the preservation of their reciprocal structural integrity and may witness their co-evolution.

Structural basis of redox-dependent substrate binding of protein disulfide isomerase

PubMed Central

Yagi-Utsumi, Maho; Satoh, Tadashi; Kato, Koichi

2015-01-01

Protein disulfide isomerase (PDI) is a multidomain enzyme, operating as an essential folding catalyst, in which the b′ and a′ domains provide substrate binding sites and undergo an open–closed domain rearrangement depending on the redox states of the a′ domain. Despite the long research history of this enzyme, three-dimensional structural data remain unavailable for its ligand-binding mode. Here we characterize PDI substrate recognition using α-synuclein (αSN) as the model ligand. Our nuclear magnetic resonance (NMR) data revealed that the substrate-binding domains of PDI captured the αSN segment Val37–Val40 only in the oxidized form. Furthermore, we determined the crystal structure of an oxidized form of the b′–a′ domains in complex with an undecapeptide corresponding to this segment. The peptide-binding mode observed in the crystal structure with NMR validation, was characterized by hydrophobic interactions on the b′ domain in an open conformation. Comparison with the previously reported crystal structure indicates that the a′ domain partially masks the binding surface of the b′ domain, causing steric hindrance against the peptide in the reduced form of the b′–a′ domains that exhibits a closed conformation. These findings provide a structural basis for the mechanism underlying the redox-dependent substrate binding of PDI. PMID:26350503

Online Activities and Writing Practices of Urban Malaysian Adolescents

ERIC Educational Resources Information Center

Tan, Kok Eng; Ng, Melissa L. Y.; Saw, Kim Guan

2010-01-01

Among a number of urban adolescents in Malaysia, going online is a much valued practice. They are regularly drawn to the Internet to engage in activities across school, nonschool, mainstream and alternative domains. The aim of this study is to know more about what these adolescents do online. Data on the online activities were collected from 535…

On a Parabolic-Elliptic system with chemotaxis and logistic type growth

NASA Astrophysics Data System (ADS)

Galakhov, Evgeny; Salieva, Olga; Tello, J. Ignacio

2016-10-01

We consider a nonlinear PDEs system of two equations of Parabolic-Elliptic type with chemotactic terms. The system models the movement of a biological population ;u; towards a higher concentration of a chemical agent ;w; in a bounded and regular domain Ω ⊂RN for arbitrary N ∈ N. After normalization, the system is as follows

Efficacy of a Classroom Integrated Intervention of Phonological Awareness and Word Recognition in "Double-Deficit Children" Learning a Regular Orthography

ERIC Educational Resources Information Center

Mayer, Andreas; Motsch, Hans-Joachim

2015-01-01

This study analysed the effects of a classroom intervention focusing on phonological awareness and/or automatized word recognition in children with a deficit in the domains of phonological awareness and rapid automatized naming ("double deficit"). According to the double-deficit hypothesis (Wolf & Bowers, 1999), these children belong…

Validity of the Student Risk Screening Scale: Evidence of Predictive Validity in a Diverse, Suburban Elementary Setting

ERIC Educational Resources Information Center

Menzies, Holly M.; Lane, Kathleen Lynne

2012-01-01

In this study the authors examined the psychometric properties of the "Student Risk Screening Scale" (SRSS), including predictive validity in terms of student outcomes in behavioral and academic domains. The school, a diverse, suburban school in Southern California, administered the SRSS at three time points as part of regular school…

Adding Statistical Machine Translation Adaptation to Computer-Assisted Translation

DTIC Science & Technology

2013-09-01

are automatically searched and used to suggest possible translations; (2) spell-checkers; (3) glossaries; (4) dictionaries ; (5) alignment and...matching against TMs to propose translations; spell-checking, glossary, and dictionary look-up; support for multiple file formats; regular expressions...on Telecommunications. Tehran, 2012, 822–826. Bertoldi, N.; Federico, M. Domain Adaptation for Statistical Machine Translation with Monolingual

Physical and Structural Studies on the Cryo-cooling of Insulin Crystals

NASA Technical Reports Server (NTRS)

Lovelace, J.; Bellamy, H.; Snell, E. H.; Borgstahl, G.

2003-01-01

Reflection profiles were analyzed from microgravity-(mg) and earth-grown insulin crystals to measure mosaicity (h) and to reveal mosaic domain structure and composition. The effects of cryocooling on single and multi-domain crystals were compared. The effects of cryocooling on insulin structure were also re-examined. Microgravity crystals were larger, more homogeneous, and more perfect than earth crystals. Several mg crystals contained primarily a single mosaic domain with havg of 0.005deg. The earth crystals varied in quality and all contained multiple domains with havg of 0.031deg. Cryocooling caused a 43-fold increase in h for mg crystals (havg=0.217deg) and an %fold increase for earth crystals (havg=0.246deg). These results indicate that very well-ordered crystals are not completely protected from the stresses associated with cryocooling, especially when structural perturbations occur. However, there were differences in the reflection profiles. For multi-mosaic domain crystals, each domain individually broadened and separated from the other domains upon cryo-cooling. Cryo-cooling did not cause an increase in the number of domains. A crystal composed of a single domain retained this domain structure and the reflection profiles simply broadened. Therefore, an improved signal-to-noise ratio for each reflection was measured from cryo-cooled single domain crystals relative to cryo-cooled multi-domain crystals. This improved signal, along with the increase in crystal size, facilitated the measurement of the weaker high- resolution reflections. The observed broadening of reflection profiles indicates increased variation in unit cell dimensions which may be linked to cryo-cooling-associated structural changes and disorder.

Oxyanion Induced Variations in Domain Structure for Amorphous Cobalt Oxide Oxygen Evolving Catalysts, Resolved by X-ray Pair Distribution Function Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kwon, Gihan; Kokhan, Oleksandr; Han, Ali

Amorphous thin film oxygen evolving catalysts, OECs, of first-row transition metals show promise to serve as self-assembling photoanode materials in solar-driven, photoelectrochemical `artificial leaf' devices. This report demonstrates the ability to use high-energy X-ray scattering and atomic pair distribution function analysis, PDF, to resolve structure in amorphous metal oxide catalyst films. The analysis is applied here to resolve domain structure differences induced by oxyanion substitution during the electrochemical assembly of amorphous cobalt oxide catalyst films, Co-OEC. PDF patterns for Co-OEC films formed using phosphate, Pi, methylphosphate, MPi, and borate, Bi, electrolyte buffers show that the resulting domains vary in sizemore » following the sequence Pi < MPi < Bi. The increases in domain size for CoMPi and CoBi were found to be correlated with increases in the contributions from bilayer and trilayer stacked domains having structures intermediate between those of the LiCoOO and CoO(OH) mineral forms. The lattice structures and offset stacking of adjacent layers in the partially stacked CoMPi and CoBi domains were best matched to those in the LiCoOO layered structure. The results demonstrate the ability of PDF analysis to elucidate features of domain size, structure, defect content and mesoscale organization for amorphous metal oxide catalysts that are not readily accessed by other X-ray techniques. Finally, PDF structure analysis is shown to provide a way to characterize domain structures in different forms of amorphous oxide catalysts, and hence provide an opportunity to investigate correlations between domain structure and catalytic activity.« less

Oxyanion Induced Variations in Domain Structure for Amorphous Cobalt Oxide Oxygen Evolving Catalysts, Resolved by X-ray Pair Distribution Function Analysis

DOE PAGES

Kwon, Gihan; Kokhan, Oleksandr; Han, Ali; ...

2015-12-01

Amorphous thin film oxygen evolving catalysts, OECs, of first-row transition metals show promise to serve as self-assembling photoanode materials in solar-driven, photoelectrochemical `artificial leaf' devices. This report demonstrates the ability to use high-energy X-ray scattering and atomic pair distribution function analysis, PDF, to resolve structure in amorphous metal oxide catalyst films. The analysis is applied here to resolve domain structure differences induced by oxyanion substitution during the electrochemical assembly of amorphous cobalt oxide catalyst films, Co-OEC. PDF patterns for Co-OEC films formed using phosphate, Pi, methylphosphate, MPi, and borate, Bi, electrolyte buffers show that the resulting domains vary in sizemore » following the sequence Pi < MPi < Bi. The increases in domain size for CoMPi and CoBi were found to be correlated with increases in the contributions from bilayer and trilayer stacked domains having structures intermediate between those of the LiCoOO and CoO(OH) mineral forms. The lattice structures and offset stacking of adjacent layers in the partially stacked CoMPi and CoBi domains were best matched to those in the LiCoOO layered structure. The results demonstrate the ability of PDF analysis to elucidate features of domain size, structure, defect content and mesoscale organization for amorphous metal oxide catalysts that are not readily accessed by other X-ray techniques. Finally, PDF structure analysis is shown to provide a way to characterize domain structures in different forms of amorphous oxide catalysts, and hence provide an opportunity to investigate correlations between domain structure and catalytic activity.« less

Same but not alike: Structure, flexibility and energetics of domains in multi-domain proteins are influenced by the presence of other domains

PubMed Central

Vishwanath, Sneha

2018-01-01

The majority of the proteins encoded in the genomes of eukaryotes contain more than one domain. Reasons for high prevalence of multi-domain proteins in various organisms have been attributed to higher stability and functional and folding advantages over single-domain proteins. Despite these advantages, many proteins are composed of only one domain while their homologous domains are part of multi-domain proteins. In the study presented here, differences in the properties of protein domains in single-domain and multi-domain systems and their influence on functions are discussed. We studied 20 pairs of identical protein domains, which were crystallized in two forms (a) tethered to other proteins domains and (b) tethered to fewer protein domains than (a) or not tethered to any protein domain. Results suggest that tethering of domains in multi-domain proteins influences the structural, dynamic and energetic properties of the constituent protein domains. 50% of the protein domain pairs show significant structural deviations while 90% of the protein domain pairs show differences in dynamics and 12% of the residues show differences in the energetics. To gain further insights on the influence of tethering on the function of the domains, 4 pairs of homologous protein domains, where one of them is a full-length single-domain protein and the other protein domain is a part of a multi-domain protein, were studied. Analyses showed that identical and structurally equivalent functional residues show differential dynamics in homologous protein domains; though comparable dynamics between in-silico generated chimera protein and multi-domain proteins were observed. From these observations, the differences observed in the functions of homologous proteins could be attributed to the presence of tethered domain. Overall, we conclude that tethered domains in multi-domain proteins not only provide stability or folding advantages but also influence pathways resulting in differences in function or regulatory properties. PMID:29432415

Same but not alike: Structure, flexibility and energetics of domains in multi-domain proteins are influenced by the presence of other domains.

PubMed

Vishwanath, Sneha; de Brevern, Alexandre G; Srinivasan, Narayanaswamy

2018-02-01

The majority of the proteins encoded in the genomes of eukaryotes contain more than one domain. Reasons for high prevalence of multi-domain proteins in various organisms have been attributed to higher stability and functional and folding advantages over single-domain proteins. Despite these advantages, many proteins are composed of only one domain while their homologous domains are part of multi-domain proteins. In the study presented here, differences in the properties of protein domains in single-domain and multi-domain systems and their influence on functions are discussed. We studied 20 pairs of identical protein domains, which were crystallized in two forms (a) tethered to other proteins domains and (b) tethered to fewer protein domains than (a) or not tethered to any protein domain. Results suggest that tethering of domains in multi-domain proteins influences the structural, dynamic and energetic properties of the constituent protein domains. 50% of the protein domain pairs show significant structural deviations while 90% of the protein domain pairs show differences in dynamics and 12% of the residues show differences in the energetics. To gain further insights on the influence of tethering on the function of the domains, 4 pairs of homologous protein domains, where one of them is a full-length single-domain protein and the other protein domain is a part of a multi-domain protein, were studied. Analyses showed that identical and structurally equivalent functional residues show differential dynamics in homologous protein domains; though comparable dynamics between in-silico generated chimera protein and multi-domain proteins were observed. From these observations, the differences observed in the functions of homologous proteins could be attributed to the presence of tethered domain. Overall, we conclude that tethered domains in multi-domain proteins not only provide stability or folding advantages but also influence pathways resulting in differences in function or regulatory properties.

Crystal structure of Pseudomonas aeruginosa bacteriophytochrome: Photoconversion and signal transduction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Xiaojing; Kuk, Jane; Moffat, Keith

2008-11-12

Phytochromes are red-light photoreceptors that regulate light responses in plants, fungi, and bacteria via reversible photoconversion between red (Pr) and far-red (Pfr) light-absorbing states. Here we report the crystal structure at 2.9 {angstrom} resolution of a bacteriophytochrome from Pseudomonas aeruginosa with an intact, fully photoactive photosensory core domain in its dark-adapted Pfr state. This structure reveals how unusual interdomain interactions, including a knot and an 'arm' structure near the chromophore site, bring together the PAS (Per-ARNT-Sim), GAF (cGMP phosphodiesterase/adenyl cyclase/FhlA), and PHY (phytochrome) domains to achieve Pr/Pfr photoconversion. The PAS, GAF, and PHY domains have topologic elements in common andmore » may have a single evolutionary origin. We identify key interactions that stabilize the chromophore in the Pfr state and provide structural and mutational evidence to support the essential role of the PHY domain in efficient Pr/Pfr photoconversion. We also identify a pair of conserved residues that may undergo concerted conformational changes during photoconversion. Modeling of the full-length bacteriophytochrome structure, including its output histidine kinase domain, suggests how local structural changes originating in the photosensory domain modulate interactions between long, cross-domain signaling helices at the dimer interface and are transmitted to the spatially distant effector domain, thereby regulating its histidine kinase activity.« less

Electric field driven evolution of topological domain structure in hexagonal manganites

NASA Astrophysics Data System (ADS)

Yang, K. L.; Zhang, Y.; Zheng, S. H.; Lin, L.; Yan, Z. B.; Liu, J.-M.; Cheong, S.-W.

2017-10-01

Controlling and manipulating the topological state represents an important topic in condensed matters for both fundamental researches and applications. In this work, we focus on the evolution of a real-space topological domain structure in hexagonal manganites driven by electric field, using the analytical and numerical calculations based on the Ginzburg-Landau theory. It is revealed that the electric field drives a transition of the topological domain structure from the type-I pattern to the type-II one. In particular, it is identified that a high electric field can enforce the two antiphase-plus-ferroelectric (AP +FE ) domain walls with Δ Φ =π /3 to approach each other and to merge into one domain wall with Δ Φ = 2 π /3 eventually if the electric field is sufficiently high, where Δ Φ is the difference in the trimerization phase between two neighboring domains. Our simulations also reveal that the vortex cores of the topological structure can be disabled at a sufficiently high critical electric field by suppressing the structural trimerization therein, beyond which the vortex core region is replaced by a single ferroelectric domain without structural trimerization (Q = 0 ). Our results provide a stimulating reference for understanding the manipulation of real-space topological domain structure in hexagonal manganites.

Health monitoring of unmanned aerial vehicle based on optical fiber sensor array

NASA Astrophysics Data System (ADS)

Luo, Yuxiang; Shen, Jingshi; Shao, Fei; Guo, Chunhui; Yang, Ning; Zhang, Jiande

2017-10-01

The unmanned aerial vehicle (UAV) in flight needs to face the complicated environment, especially to withstand harsh weather conditions, such as the temperature and pressure. Compared with conventional sensors, fiber Bragg grating (FBG) sensor has the advantages of small size, light weight, high reliability, high precision, anti-electromagnetic interference, long lift-span, moistureproof and good resistance to causticity. It's easy to be embedded in composite structural components of UAVs. In the paper, over 1000 FBG sensors distribute regularly on a wide range of UAVs body, combining wavelength division multiplexing (WDM), time division multiplexing (TDM) and multichannel parallel architecture. WDM has the advantage of high spatial resolution. TDM has the advantage of large capacity and wide range. It is worthful to constitute a sensor network by different technologies. For the signal demodulation of FBG sensor array, WDM works by means of wavelength scanning light sources and F-P etalon. TDM adopts the technology of optical time-domain reflectometry. In order to demodulate efficiently, the most proper sensor multiplex number with some reflectivity is given by the curves fitting. Due to the regular array arrangement of FBG sensors on the UAVs, we can acquire the health state of UAVs in the form of 3D visualization. It is helpful to master the information of health status rapidly and give a real-time health evaluation.

Insights into Strand Exchange in BTB Domain Dimers from the Crystal Structures of FAZF and Miz1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stogios, Peter J.; Cuesta-Seijo, Jose Antonio; Chen, Lu

2010-09-22

The BTB domain is a widely distributed protein-protein interaction motif that is often found at the N-terminus of zinc finger transcription factors. Previous crystal structures of BTB domains have revealed tightly interwound homodimers, with the N-terminus from one chain forming a two-stranded anti-parallel {beta}-sheet with a strand from the other chain. We have solved the crystal structures of the BTB domains from Fanconi anemia zinc finger (FAZF) and Miz1 (Myc-interacting zinc finger 1) to resolutions of 2.0 {angstrom} and 2.6 {angstrom}, respectively. Unlike previous examples of BTB domain structures, the FAZF BTB domain is a nonswapped dimer, with each N-terminalmore » {beta}-strand associated with its own chain. As a result, the dimerization interface in the FAZF BTB domain is about half as large as in the domain-swapped dimers. The Miz1 BTB domain resembles a typical swapped BTB dimer, although it has a shorter N-terminus that is not able to form the interchain sheet. Using cysteine cross-linking, we confirmed that the promyelocytic leukemia zinc finger (PLZF) BTB dimer is strand exchanged in solution, while the FAZF BTB dimer is not. A phylogenic tree of the BTB fold based on both sequence and structural features shows that the common ancestor of the BTB domain in BTB-ZF (bric a brac, tramtrack, broad-complex zinc finger) proteins was a domain-swapped dimer. The differences in the N-termini seen in the FAZF and Miz1 BTB domains appear to be more recent developments in the structural evolution of the domain.« less

Heart rate variability indexes as a marker of chronic adaptation in athletes: a systematic review.

PubMed

da Silva, Vanessa Pereira; de Oliveira, Natacha Alves; Silveira, Heitor; Mello, Roger Gomes Tavares; Deslandes, Andrea Camaz

2015-03-01

Regular exercise promotes functional and structural changes in the central and peripheral mechanisms of the cardiovascular system. Heart rate variability (HRV) measurement provides a sensitive indicator of the autonomic balance. However, because of the diversity of methods and variables used, the results are difficult to compare in the sports sciences. Since the protocol (supine, sitting, or standing position) and measure (time or frequency domain) are not well defined, the aim of this study is to investigate the HRV measures that better indicates the chronic adaptations of physical exercise in athletes. PubMed (MEDLINE), Web of Science, SciELO (Scientific Electronic Library), and Scopus databases were consulted. Original complete articles in English with short-term signals evaluating young and adult athletes, between 17 and 40 years old, with a control group, published up to 2013 were included. Selected 19 of 1369 studies, for a total sample pool of 333 male and female athletes who practice different sports. The main protocols observed were the supine or standing positions in free or controlled breathing conditions. The main statistical results found in this study were the higher mean RR, standard deviation of RR intervals, and high frequency in athletes group. In addition, the analyses of Cohen's effect size showed that factors as modality of sport, protocol used and unit of measure selected could influence this expected results. Our findings indicate that time domain measures are more consistent than frequency domain to describe the chronic cardiovascular autonomic adaptations in athletes. © 2014 Wiley Periodicals, Inc.

Evolutionary Design of Controlled Structures

NASA Technical Reports Server (NTRS)

Masters, Brett P.; Crawley, Edward F.

1997-01-01

Basic physical concepts of structural delay and transmissibility are provided for simple rod and beam structures. Investigations show the sensitivity of these concepts to differing controlled-structures variables, and to rational system modeling effects. An evolutionary controls/structures design method is developed. The basis of the method is an accurate model formulation for dynamic compensator optimization and Genetic Algorithm based updating of sensor/actuator placement and structural attributes. One and three dimensional examples from the literature are used to validate the method. Frequency domain interpretation of these controlled structure systems provide physical insight as to how the objective is optimized and consequently what is important in the objective. Several disturbance rejection type controls-structures systems are optimized for a stellar interferometer spacecraft application. The interferometric designs include closed loop tracking optics. Designs are generated for differing structural aspect ratios, differing disturbance attributes, and differing sensor selections. Physical limitations in achieving performance are given in terms of average system transfer function gains and system phase loss. A spacecraft-like optical interferometry system is investigated experimentally over several different optimized controlled structures configurations. Configurations represent common and not-so-common approaches to mitigating pathlength errors induced by disturbances of two different spectra. Results show that an optimized controlled structure for low frequency broadband disturbances achieves modest performance gains over a mass equivalent regular structure, while an optimized structure for high frequency narrow band disturbances is four times better in terms of root-mean-square pathlength. These results are predictable given the nature of the physical system and the optimization design variables. Fundamental limits on controlled performance are discussed based on the measured and fit average system transfer function gains and system phase loss.

The PYRIN domain: A member of the death domain-fold superfamily

PubMed Central

Fairbrother, Wayne J.; Gordon, Nathaniel C.; Humke, Eric W.; O'Rourke, Karen M.; Starovasnik, Melissa A.; Yin, Jian-Ping; Dixit, Vishva M.

2001-01-01

PYRIN domains were identified recently as putative protein–protein interaction domains at the N-termini of several proteins thought to function in apoptotic and inflammatory signaling pathways. The ∼95 residue PYRIN domains have no statistically significant sequence homology to proteins with known three-dimensional structure. Using secondary structure prediction and potential-based fold recognition methods, however, the PYRIN domain is predicted to be a member of the six-helix bundle death domain-fold superfamily that includes death domains (DDs), death effector domains (DEDs), and caspase recruitment domains (CARDs). Members of the death domain-fold superfamily are well established mediators of protein–protein interactions found in many proteins involved in apoptosis and inflammation, indicating further that the PYRIN domains serve a similar function. An homology model of the PYRIN domain of CARD7/DEFCAP/NAC/NALP1, a member of the Apaf-1/Ced-4 family of proteins, was constructed using the three-dimensional structures of the FADD and p75 neurotrophin receptor DDs, and of the Apaf-1 and caspase-9 CARDs, as templates. Validation of the model using a variety of computational techniques indicates that the fold prediction is consistent with the sequence. Comparison of a circular dichroism spectrum of the PYRIN domain of CARD7/DEFCAP/NAC/NALP1 with spectra of several proteins known to adopt the death domain-fold provides experimental support for the structure prediction. PMID:11514682

A Method to Examine Content Domain Structures

ERIC Educational Resources Information Center

D'Agostino, Jerome; Karpinski, Aryn; Welsh, Megan

2011-01-01

After a test is developed, most content validation analyses shift from ascertaining domain definition to studying domain representation and relevance because the domain is assumed to be set once a test exists. We present an approach that allows for the examination of alternative domain structures based on extant test items. In our example based on…

Solution structure of the Big domain from Streptococcus pneumoniae reveals a novel Ca2+-binding module

PubMed Central

Wang, Tao; Zhang, Jiahai; Zhang, Xuecheng; Xu, Chao; Tu, Xiaoming

2013-01-01

Streptococcus pneumoniae is a pathogen causing acute respiratory infection, otitis media and some other severe diseases in human. In this study, the solution structure of a bacterial immunoglobulin-like (Big) domain from a putative S. pneumoniae surface protein SP0498 was determined by NMR spectroscopy. SP0498 Big domain adopts an eight-β-strand barrel-like fold, which is different in some aspects from the two-sheet sandwich-like fold of the canonical Ig-like domains. Intriguingly, we identified that the SP0498 Big domain was a Ca2+ binding domain. The structure of the Big domain is different from those of the well known Ca2+ binding domains, therefore revealing a novel Ca2+-binding module. Furthermore, we identified the critical residues responsible for the binding to Ca2+. We are the first to report the interactions between the Big domain and Ca2+ in terms of structure, suggesting an important role of the Big domain in many essential calcium-dependent cellular processes such as pathogenesis. PMID:23326635

Domain organization and crystal structure of the catalytic domain of E.coli RluF, a pseudouridine synthase that acts on 23S rRNA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sunita,S.; Zhenxing, H.; Swaathi, J.

2006-01-01

Pseudouridine synthases catalyze the isomerization of uridine to pseudouridine ({psi}) in rRNA and tRNA. The pseudouridine synthase RluF from Escherichia coli (E.C. 4.2.1.70) modifies U2604 in 23S rRNA, and belongs to a large family of pseudouridine synthases present in all kingdoms of life. Here we report the domain architecture and crystal structure of the catalytic domain of E. coli RluF at 2.6 Angstroms resolution. Limited proteolysis, mass spectrometry and N-terminal sequencing indicate that RluF has a distinct domain architecture, with the catalytic domain flanked at the N and C termini by additional domains connected to it by flexible linkers. Themore » structure of the catalytic domain of RluF is similar to those of RsuA and TruB. RluF is a member of the RsuA sequence family of {psi}-synthases, along with RluB and RluE. Structural comparison of RluF with its closest structural homologues, RsuA and TruB, suggests possible functional roles for the N-terminal and C-terminal domains of RluF.« less

The Evolution of Frequency Distributions: Relating Regularization to Inductive Biases through Iterated Learning

ERIC Educational Resources Information Center

Reali, Florencia; Griffiths, Thomas L.

2009-01-01

The regularization of linguistic structures by learners has played a key role in arguments for strong innate constraints on language acquisition, and has important implications for language evolution. However, relating the inductive biases of learners to regularization behavior in laboratory tasks can be challenging without a formal model. In this…

Structures of a Nonribosomal Peptide Synthetase Module Bound to MbtH-like Proteins Support a Highly Dynamic Domain Architecture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, Bradley R.; Drake, Eric J.; Shi, Ce

Nonribosomal peptide synthetases (NRPSs) produce a wide variety of peptide natural products. During synthesis, the multidomain NRPSs act as an assembly line, passing the growing product from one module to the next. Each module generally consists of an integrated peptidyl carrier protein, an amino acid-loading adenylation domain, and a condensation domain that catalyzes peptide bond formation. Some adenylation domains interact with small partner proteins called MbtH-like proteins (MLPs) that enhance solubility or activity. A structure of an MLP bound to an adenylation domain has been previously reported using a truncated adenylation domain, precluding any insight that might be derived frommore » understanding the influence of the MLP on the intact adenylation domain or on the dynamics of the entire NRPS module. Here, we present the structures of the full-length NRPS EntF bound to the MLPs from Escherichia coli and Pseudomonas aeruginosa. These new structures, along with biochemical and bioinformatics support, further elaborate the residues that define the MLP-adenylation domain interface. Additionally, the structures highlight the dynamic behavior of NRPS modules, including the module core formed by the adenylation and condensation domains as well as the orientation of the mobile thioesterase domain.« less

Structures of a Nonribosomal Peptide Synthetase Module Bound to MbtH-like Proteins Support a Highly Dynamic Domain Architecture*

PubMed Central

Miller, Bradley R.; Drake, Eric J.; Shi, Ce; Aldrich, Courtney C.; Gulick, Andrew M.

2016-01-01

Nonribosomal peptide synthetases (NRPSs) produce a wide variety of peptide natural products. During synthesis, the multidomain NRPSs act as an assembly line, passing the growing product from one module to the next. Each module generally consists of an integrated peptidyl carrier protein, an amino acid-loading adenylation domain, and a condensation domain that catalyzes peptide bond formation. Some adenylation domains interact with small partner proteins called MbtH-like proteins (MLPs) that enhance solubility or activity. A structure of an MLP bound to an adenylation domain has been previously reported using a truncated adenylation domain, precluding any insight that might be derived from understanding the influence of the MLP on the intact adenylation domain or on the dynamics of the entire NRPS module. Here, we present the structures of the full-length NRPS EntF bound to the MLPs from Escherichia coli and Pseudomonas aeruginosa. These new structures, along with biochemical and bioinformatics support, further elaborate the residues that define the MLP-adenylation domain interface. Additionally, the structures highlight the dynamic behavior of NRPS modules, including the module core formed by the adenylation and condensation domains as well as the orientation of the mobile thioesterase domain. PMID:27597544

Structures of a Nonribosomal Peptide Synthetase Module Bound to MbtH-like Proteins Support a Highly Dynamic Domain Architecture.

PubMed

Miller, Bradley R; Drake, Eric J; Shi, Ce; Aldrich, Courtney C; Gulick, Andrew M

2016-10-21

Nonribosomal peptide synthetases (NRPSs) produce a wide variety of peptide natural products. During synthesis, the multidomain NRPSs act as an assembly line, passing the growing product from one module to the next. Each module generally consists of an integrated peptidyl carrier protein, an amino acid-loading adenylation domain, and a condensation domain that catalyzes peptide bond formation. Some adenylation domains interact with small partner proteins called MbtH-like proteins (MLPs) that enhance solubility or activity. A structure of an MLP bound to an adenylation domain has been previously reported using a truncated adenylation domain, precluding any insight that might be derived from understanding the influence of the MLP on the intact adenylation domain or on the dynamics of the entire NRPS module. Here, we present the structures of the full-length NRPS EntF bound to the MLPs from Escherichia coli and Pseudomonas aeruginosa These new structures, along with biochemical and bioinformatics support, further elaborate the residues that define the MLP-adenylation domain interface. Additionally, the structures highlight the dynamic behavior of NRPS modules, including the module core formed by the adenylation and condensation domains as well as the orientation of the mobile thioesterase domain. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

A structural analysis of the AAA+ domains in Saccharomyces cerevisiae cytoplasmic dynein

PubMed Central

Gleave, Emma S.; Schmidt, Helgo; Carter, Andrew P.

2014-01-01

Dyneins are large protein complexes that act as microtubule based molecular motors. The dynein heavy chain contains a motor domain which is a member of the AAA+ protein family (ATPases Associated with diverse cellular Activities). Proteins of the AAA+ family show a diverse range of functionalities, but share a related core AAA+ domain, which often assembles into hexameric rings. Dynein is unusual because it has all six AAA+ domains linked together, in one long polypeptide. The dynein motor domain generates movement by coupling ATP driven conformational changes in the AAA+ ring to the swing of a motile element called the linker. Dynein binds to its microtubule track via a long antiparallel coiled-coil stalk that emanates from the AAA+ ring. Recently the first high resolution structures of the dynein motor domain were published. Here we provide a detailed structural analysis of the six AAA+ domains using our Saccharomycescerevisiae crystal structure. We describe how structural similarities in the dynein AAA+ domains suggest they share a common evolutionary origin. We analyse how the different AAA+ domains have diverged from each other. We discuss how this is related to the function of dynein as a motor protein and how the AAA+ domains of dynein compare to those of other AAA+ proteins. PMID:24680784

Solution structure of a DNA mimicking motif of an RNA aptamer against transcription factor AML1 Runt domain.

PubMed

Nomura, Yusuke; Tanaka, Yoichiro; Fukunaga, Jun-ichi; Fujiwara, Kazuya; Chiba, Manabu; Iibuchi, Hiroaki; Tanaka, Taku; Nakamura, Yoshikazu; Kawai, Gota; Kozu, Tomoko; Sakamoto, Taiichi

2013-12-01

AML1/RUNX1 is an essential transcription factor involved in the differentiation of hematopoietic cells. AML1 binds to the Runt-binding double-stranded DNA element (RDE) of target genes through its N-terminal Runt domain. In a previous study, we obtained RNA aptamers against the AML1 Runt domain by systematic evolution of ligands by exponential enrichment and revealed that RNA aptamers exhibit higher affinity for the Runt domain than that for RDE and possess the 5'-GCGMGNN-3' and 5'-N'N'CCAC-3' conserved motif (M: A or C; N and N' form Watson-Crick base pairs) that is important for Runt domain binding. In this study, to understand the structural basis of recognition of the Runt domain by the aptamer motif, the solution structure of a 22-mer RNA was determined using nuclear magnetic resonance. The motif contains the AH(+)-C mismatch and base triple and adopts an unusual backbone structure. Structural analysis of the aptamer motif indicated that the aptamer binds to the Runt domain by mimicking the RDE sequence and structure. Our data should enhance the understanding of the structural basis of DNA mimicry by RNA molecules.

Botulinum neurotoxin structure, engineering, and novel cellular trafficking and targeting.

PubMed

Singh, B R

2006-04-01

Botulinum neurotoxins are multifaceted molecules, which are truly unique not only in their mode of action, but also their utility as a drug carrier either across the gut wall or to the nerve terminals. The molecule is divided in clear functional domains that can operate independently. This feature can be used to employ them as cargo carrier by linking other drugs or vaccines with the binding and translocation domains of BoNT. While the domain structures are largely independent of each other, the dynamic structure of these domains, especially that of the enzymatic domain (L chain), is quite different from the reported crystal structures for several BoNT serotypes and their enzymatic domain. This review discusses the comparative structures of BoNT in crystal and solution for their relevance to the molecular mechanism of BoNT action, especially in view of our recent discovery that the enzymatically active structure of the BoNT exists as a molten-globule and that of the endopeptidase domain as a novel PRIME conformation. Finally, a non-exhaustive discussion has been included to explain the long-lasting biological effects of certain serotypes of BoNT, based on the current knowledge of the structure-function of different serotypes of botulinum neurotoxins.

Factor Structure of the Quality of Life Scale for Mental Disorders in Patients With Schizophrenia.

PubMed

Chiu, En-Chi; Lee, Shu-Chun

2018-06-01

The Quality of Life for Mental Disorders (QOLMD) scale was designed to measure health-related quality of life (HRQOL) in patients with mental illness, especially schizophrenia. The QOLMD contains 45 items, which are divided into eight domains. However, the factor structure of the QOLMD has not been evaluated, which restricts the interpretations of the results of this scale. The purpose of this study was to evaluate the factor structures (i.e., unidimensionality, eight-factor structure, and second-order model) of the QOLMD in patients with schizophrenia. Two hundred thirty-eight outpatients with schizophrenia participated. We first conducted confirmatory factor analysis to evaluate the unidimensionality of each domain. After the unidimensionality of the eight individual domains was supported, we examined the eight-factor structure and second-order model. The results of unidimensionality showed sufficient model fit in all of the domains with the exception of the autonomy domain. A good model fit was confirmed for the autonomy domain after deleting two of the original items. The eight-factor structure for the 43-item QOLMD showed an acceptable model fit, although the second-order model showed poor model fit. Our results supported the unidimensionality and eight-factor structure of the 43-item QOLMD. The sum score for each of the domains may be used to reflect its domain-specific function. We recommend using the 43-item QOLMD to capture the multiple domains of HRQOL. However, the second-order model showed an unsatisfactory model fit. Furthermore, caution is advised when interpreting overall HRQOL using the total score for the eight domains.

Structural and evolutionary relationships of "AT-less" type I polyketide synthase ketosynthases.

PubMed

Lohman, Jeremy R; Ma, Ming; Osipiuk, Jerzy; Nocek, Boguslaw; Kim, Youngchang; Chang, Changsoo; Cuff, Marianne; Mack, Jamey; Bigelow, Lance; Li, Hui; Endres, Michael; Babnigg, Gyorgy; Joachimiak, Andrzej; Phillips, George N; Shen, Ben

2015-10-13

Acyltransferase (AT)-less type I polyketide synthases (PKSs) break the type I PKS paradigm. They lack the integrated AT domains within their modules and instead use a discrete AT that acts in trans, whereas a type I PKS module minimally contains AT, acyl carrier protein (ACP), and ketosynthase (KS) domains. Structures of canonical type I PKS KS-AT didomains reveal structured linkers that connect the two domains. AT-less type I PKS KSs have remnants of these linkers, which have been hypothesized to be AT docking domains. Natural products produced by AT-less type I PKSs are very complex because of an increased representation of unique modifying domains. AT-less type I PKS KSs possess substrate specificity and fall into phylogenetic clades that correlate with their substrates, whereas canonical type I PKS KSs are monophyletic. We have solved crystal structures of seven AT-less type I PKS KS domains that represent various sequence clusters, revealing insight into the large structural and subtle amino acid residue differences that lead to unique active site topologies and substrate specificities. One set of structures represents a larger group of KS domains from both canonical and AT-less type I PKSs that accept amino acid-containing substrates. One structure has a partial AT-domain, revealing the structural consequences of a type I PKS KS evolving into an AT-less type I PKS KS. These structures highlight the structural diversity within the AT-less type I PKS KS family, and most important, provide a unique opportunity to study the molecular evolution of substrate specificity within the type I PKSs.

Structural and evolutionary relationships of “AT-less” type I polyketide synthase ketosynthases

PubMed Central

Lohman, Jeremy R.; Ma, Ming; Osipiuk, Jerzy; Nocek, Boguslaw; Kim, Youngchang; Chang, Changsoo; Cuff, Marianne; Mack, Jamey; Bigelow, Lance; Li, Hui; Endres, Michael; Babnigg, Gyorgy; Joachimiak, Andrzej; Phillips, George N.; Shen, Ben

2015-01-01

Acyltransferase (AT)-less type I polyketide synthases (PKSs) break the type I PKS paradigm. They lack the integrated AT domains within their modules and instead use a discrete AT that acts in trans, whereas a type I PKS module minimally contains AT, acyl carrier protein (ACP), and ketosynthase (KS) domains. Structures of canonical type I PKS KS-AT didomains reveal structured linkers that connect the two domains. AT-less type I PKS KSs have remnants of these linkers, which have been hypothesized to be AT docking domains. Natural products produced by AT-less type I PKSs are very complex because of an increased representation of unique modifying domains. AT-less type I PKS KSs possess substrate specificity and fall into phylogenetic clades that correlate with their substrates, whereas canonical type I PKS KSs are monophyletic. We have solved crystal structures of seven AT-less type I PKS KS domains that represent various sequence clusters, revealing insight into the large structural and subtle amino acid residue differences that lead to unique active site topologies and substrate specificities. One set of structures represents a larger group of KS domains from both canonical and AT-less type I PKSs that accept amino acid-containing substrates. One structure has a partial AT-domain, revealing the structural consequences of a type I PKS KS evolving into an AT-less type I PKS KS. These structures highlight the structural diversity within the AT-less type I PKS KS family, and most important, provide a unique opportunity to study the molecular evolution of substrate specificity within the type I PKSs. PMID:26420866

Determination of bulk domain structure and magnetization processes in bcc ferromagnetic alloys: Analysis of magnetostriction in F e83G a17

NASA Astrophysics Data System (ADS)

He, Yangkun; Coey, J. M. D.; Schaefer, Rudolf; Jiang, Chengbao

2018-01-01

The ground state of macroscopic samples of magnetically ordered materials is a domain state because of magnetostatic energy or entropy, yet we have limited experimental means for imaging the bulk domain structure and the magnetization process directly. The common methods available reveal the domains at the surface or in electron- or x-ray transparent lamellae, not those in the bulk. The magnetization curve just reflects the vector sum of the moments of all the domains in the sample, but magnetostriction curves are more informative. They are strongly influenced by the domain structure in the unmagnetized state and its evolution during the magnetization process in an applied field. Here we report a method of determining the bulk domain structure in a cubic magnetostrictive material by combining magneto-optic Kerr microscopy with magnetostriction and magnetization measurements on single crystals as a function of applied field. We analyze the magnetostriction of F e83G a17 crystals in terms of a domain structure that is greatly influenced by sample shape and heat treatment. Saturation magnetostriction measurements are used to determine the fraction of domains orientated along the three 〈100 〉 axes in the initial state. Domain wall motion and rotation process have characteristic signatures in the magnetostriction curves, including those associated with the Δ E effect and domain rotation through a 〈110 〉 auxetic direction.

Structural analysis of an oxygen-regulated diguanylate cyclase.

PubMed

Tarnawski, Miroslaw; Barends, Thomas R M; Schlichting, Ilme

2015-11-01

Cyclic di-GMP is a bacterial second messenger that is involved in switching between motile and sessile lifestyles. Given the medical importance of biofilm formation, there has been increasing interest in understanding the synthesis and degradation of cyclic di-GMPs and their regulation in various bacterial pathogens. Environmental cues are detected by sensing domains coupled to GGDEF and EAL or HD-GYP domains that have diguanylate cyclase and phosphodiesterase activities, respectively, producing and degrading cyclic di-GMP. The Escherichia coli protein DosC (also known as YddV) consists of an oxygen-sensing domain belonging to the class of globin sensors that is coupled to a C-terminal GGDEF domain via a previously uncharacterized middle domain. DosC is one of the most strongly expressed GGDEF proteins in E. coli, but to date structural information on this and related proteins is scarce. Here, the high-resolution structural characterization of the oxygen-sensing globin domain, the middle domain and the catalytic GGDEF domain in apo and substrate-bound forms is described. The structural changes between the iron(III) and iron(II) forms of the sensor globin domain suggest a mechanism for oxygen-dependent regulation. The structural information on the individual domains is combined into a model of the dimeric DosC holoprotein. These findings have direct implications for the oxygen-dependent regulation of the activity of the cyclase domain.

Crystal structure of caspase recruiting domain (CARD) of apoptosis repressor with CARD (ARC) and its implication in inhibition of apoptosis

PubMed Central

Jang, Tae-ho; Kim, Seong Hyun; Jeong, Jae-Hee; Kim, Sunghwan; Kim, Yeun Gil; Park, Hyun Ho

2015-01-01

Apoptosis repressor with caspase recruiting domain (ARC) is a multifunctional inhibitor of apoptosis that is unusually over-expressed or activated in various cancers and in the state of the pulmonary hypertension. Therefore, ARC might be an optimal target for therapeutic intervention. Human ARC is composed of two distinct domains, N-terminal caspase recruiting domain (CARD) and C-terminal P/E (proline and glutamic acid) rich domain. ARC inhibits the extrinsic apoptosis pathway by interfering with DISC formation. ARC CARD directly interacts with the death domains (DDs) of Fas and FADD, as well as with the death effector domains (DEDs) of procaspase-8. Here, we report the first crystal structure of the CARD domain of ARC at a resolution of 2.4 Å. Our structure was a dimer with novel homo-dimerization interfaces that might be critical to its inhibitory function. Interestingly, ARC did not exhibit a typical death domain fold. The sixth helix (H6), which was detected at the typical death domain fold, was not detected in the structure of ARC, indicating that H6 may be dispensable for the function of the death domain superfamily. PMID:26038885

C-terminal domains of bacterial proteases: structure, function and the biotechnological applications.

PubMed

Huang, J; Wu, C; Liu, D; Yang, X; Wu, R; Zhang, J; Ma, C; He, H

2017-01-01

C-terminal domains widely exist in the C-terminal region of multidomain proteases. As a β-sandwich domain in multidomain protease, the C-terminal domain plays an important role in proteolysis including regulation of the secretory process, anchoring and swelling the substrate molecule, presenting as an inhibitor for the preprotease and adapting the protein structural flexibility and stability. In this review, the diversity, structural characteristics and biological function of C-terminal protease domains are described. Furthermore, the application prospects of C-terminal domains, including polycystic kidney disease, prepeptidase C-terminal and collagen-binding domain, in the area of medicine and biological artificial materials are also discussed. © 2016 The Society for Applied Microbiology.

In situ visualization of domain structure evolution during field cooling in 0.67PMN-0.33PT single crystal

NASA Astrophysics Data System (ADS)

Ushakov, A. D.; Esin, A. A.; Chezganov, D. S.; Turygin, A. P.; Akhmatkhanov, A. R.; Hu, Q.; Sun, L.; Wei, X.; Shur, V. Ya

2017-10-01

The evolution of the domain structure during in-field cooling was in situ studied in [001]-cut single crystals of relaxor ferroelectric (1-x)Pb(Mg1/3Nb2/3)O3-xPbTiO3 (PMN-PT) with x = 0.33 with maximum of dielectric permittivity at 150°C. The main stages of domain evolution have been separated. The visualization of the static as-grown and polarized domain structures with high spatial resolution by piezoresponse force microscopy and scanning electron microscopy allowed measuring the characteristic features of maze and needle-like domain structures.

Domain-wall guided nucleation of superconductivity in hybrid ferromagnet-superconductor-ferromagnet layered structures.

PubMed

Gillijns, W; Aladyshkin, A Yu; Lange, M; Van Bael, M J; Moshchalkov, V V

2005-11-25

Domain-wall superconductivity is studied in a superconducting Nb film placed between two ferromagnetic Co/Pd multilayers with perpendicular magnetization. The parameters of top and bottom ferromagnetic films are chosen to provide different coercive fields, so that the magnetic domain structure of the ferromagnets can be selectively controlled. From the dependence of the critical temperature Tc on the applied magnetic field H, we have found evidence for domain-wall superconductivity in this three-layered F/S/F structure for different magnetic domain patterns. The phase boundary, calculated numerically for this structure from the linearized Ginzburg-Landau equation, is in good agreement with the experimental data.

Convergence of Spectral Discretizations of the Vlasov--Poisson System

DOE PAGES

Manzini, G.; Funaro, D.; Delzanno, G. L.

2017-09-26

Here we prove the convergence of a spectral discretization of the Vlasov-Poisson system. The velocity term of the Vlasov equation is discretized using either Hermite functions on the infinite domain or Legendre polynomials on a bounded domain. The spatial term of the Vlasov and Poisson equations is discretized using periodic Fourier expansions. Boundary conditions are treated in weak form through a penalty type term that can be applied also in the Hermite case. As a matter of fact, stability properties of the approximated scheme descend from this added term. The convergence analysis is carried out in detail for the 1D-1Vmore » case, but results can be generalized to multidimensional domains, obtained as Cartesian product, in both space and velocity. The error estimates show the spectral convergence under suitable regularity assumptions on the exact solution.« less

Pair correlation functions for identifying spatial correlation in discrete domains

NASA Astrophysics Data System (ADS)

Gavagnin, Enrico; Owen, Jennifer P.; Yates, Christian A.

2018-06-01

Identifying and quantifying spatial correlation are important aspects of studying the collective behavior of multiagent systems. Pair correlation functions (PCFs) are powerful statistical tools that can provide qualitative and quantitative information about correlation between pairs of agents. Despite the numerous PCFs defined for off-lattice domains, only a few recent studies have considered a PCF for discrete domains. Our work extends the study of spatial correlation in discrete domains by defining a new set of PCFs using two natural and intuitive definitions of distance for a square lattice: the taxicab and uniform metric. We show how these PCFs improve upon previous attempts and compare between the quantitative data acquired. We also extend our definitions of the PCF to other types of regular tessellation that have not been studied before, including hexagonal, triangular, and cuboidal. Finally, we provide a comprehensive PCF for any tessellation and metric, allowing investigation of spatial correlation in irregular lattices for which recognizing correlation is less intuitive.

A thermodynamic definition of protein domains.

PubMed

Porter, Lauren L; Rose, George D

2012-06-12

Protein domains are conspicuous structural units in globular proteins, and their identification has been a topic of intense biochemical interest dating back to the earliest crystal structures. Numerous disparate domain identification algorithms have been proposed, all involving some combination of visual intuition and/or structure-based decomposition. Instead, we present a rigorous, thermodynamically-based approach that redefines domains as cooperative chain segments. In greater detail, most small proteins fold with high cooperativity, meaning that the equilibrium population is dominated by completely folded and completely unfolded molecules, with a negligible subpopulation of partially folded intermediates. Here, we redefine structural domains in thermodynamic terms as cooperative folding units, based on m-values, which measure the cooperativity of a protein or its substructures. In our analysis, a domain is equated to a contiguous segment of the folded protein whose m-value is largely unaffected when that segment is excised from its parent structure. Defined in this way, a domain is a self-contained cooperative unit; i.e., its cooperativity depends primarily upon intrasegment interactions, not intersegment interactions. Implementing this concept computationally, the domains in a large representative set of proteins were identified; all exhibit consistency with experimental findings. Specifically, our domain divisions correspond to the experimentally determined equilibrium folding intermediates in a set of nine proteins. The approach was also proofed against a representative set of 71 additional proteins, again with confirmatory results. Our reframed interpretation of a protein domain transforms an indeterminate structural phenomenon into a quantifiable molecular property grounded in solution thermodynamics.

A comparative analysis of the foamy and ortho virus capsid structures reveals an ancient domain duplication.

PubMed

Taylor, William R; Stoye, Jonathan P; Taylor, Ian A

2017-04-04

The Spumaretrovirinae (foamy viruses) and the Orthoretrovirinae (e.g. HIV) share many similarities both in genome structure and the sequences of the core viral encoded proteins, such as the aspartyl protease and reverse transcriptase. Similarity in the gag region of the genome is less obvious at the sequence level but has been illuminated by the recent solution of the foamy virus capsid (CA) structure. This revealed a clear structural similarity to the orthoretrovirus capsids but with marked differences that left uncertainty in the relationship between the two domains that comprise the structure. We have applied protein structure comparison methods in order to try and resolve this ambiguous relationship. These included both the DALI method and the SAP method, with rigorous statistical tests applied to the results of both methods. For this, we employed collections of artificial fold 'decoys' (generated from the pair of native structures being compared) to provide a customised background distribution for each comparison, thus allowing significance levels to be estimated. We have shown that the relationship of the two domains conforms to a simple linear correspondence rather than a domain transposition. These similarities suggest that the origin of both viral capsids was a common ancestor with a double domain structure. In addition, we show that there is also a significant structural similarity between the amino and carboxy domains in both the foamy and ortho viruses. These results indicate that, as well as the duplication of the double domain capsid, there may have been an even more ancient gene-duplication that preceded the double domain structure. In addition, our structure comparison methodology demonstrates a general approach to problems where the components have a high intrinsic level of similarity.

Functional Implications of Domain Organization Within Prokaryotic Rhomboid Proteases.

PubMed

Panigrahi, Rashmi; Lemieux, M Joanne

2015-01-01

Intramembrane proteases are membrane embedded enzymes that cleave transmembrane substrates. This interesting class of enzyme and its water mediated substrate cleavage mechanism occurring within the hydrophobic lipid bilayer has drawn the attention of researchers. Rhomboids are a family of ubiquitous serine intramembrane proteases. Bacterial forms of rhomboid proteases are mainly composed of six transmembrane helices that are preceded by a soluble N-terminal domain. Several crystal structures of the membrane domain of the E. coli rhomboid protease ecGlpG have been solved. Independently, the ecGlpG N-terminal cytoplasmic domain structure was solved using both NMR and protein crystallography. Despite these structures, we still do not know the structure of the full-length protein, nor do we know the functional role of these domains in the cell. This chapter will review the structural and functional roles of the different domains associated with prokaryotic rhomboid proteases. Lastly, we will address questions remaining in the field.

Ideal regularization for learning kernels from labels.

PubMed

Pan, Binbin; Lai, Jianhuang; Shen, Lixin

2014-08-01

In this paper, we propose a new form of regularization that is able to utilize the label information of a data set for learning kernels. The proposed regularization, referred to as ideal regularization, is a linear function of the kernel matrix to be learned. The ideal regularization allows us to develop efficient algorithms to exploit labels. Three applications of the ideal regularization are considered. Firstly, we use the ideal regularization to incorporate the labels into a standard kernel, making the resulting kernel more appropriate for learning tasks. Next, we employ the ideal regularization to learn a data-dependent kernel matrix from an initial kernel matrix (which contains prior similarity information, geometric structures, and labels of the data). Finally, we incorporate the ideal regularization to some state-of-the-art kernel learning problems. With this regularization, these learning problems can be formulated as simpler ones which permit more efficient solvers. Empirical results show that the ideal regularization exploits the labels effectively and efficiently. Copyright © 2014 Elsevier Ltd. All rights reserved.

A multiplicative regularization for force reconstruction

NASA Astrophysics Data System (ADS)

Aucejo, M.; De Smet, O.

2017-02-01

Additive regularizations, such as Tikhonov-like approaches, are certainly the most popular methods for reconstructing forces acting on a structure. These approaches require, however, the knowledge of a regularization parameter, that can be numerically computed using specific procedures. Unfortunately, these procedures are generally computationally intensive. For this particular reason, it could be of primary interest to propose a method able to proceed without defining any regularization parameter beforehand. In this paper, a multiplicative regularization is introduced for this purpose. By construction, the regularized solution has to be calculated in an iterative manner. In doing so, the amount of regularization is automatically adjusted throughout the resolution process. Validations using synthetic and experimental data highlight the ability of the proposed approach in providing consistent reconstructions.

Crystal Structure of the Arginine Repressor Protein in Complex With the DNA Operator From Mycobacterium Tuberculosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cherney, L.T.; Cherney, M.M.; Garen, C.R.

2009-05-12

The Mycobacterium tuberculosis (Mtb) gene product encoded by open reading frame Rv1657 is an arginine repressor (ArgR). All genes involved in the L-arginine (hereafter arginine) biosynthetic pathway are essential for optimal growth of the Mtb pathogen, thus making MtbArgR a potential target for drug design. The C-terminal domains of arginine repressors (CArgR) participate in oligomerization and arginine binding. Several crystal forms of CArgR from Mtb (MtbCArgR) have been obtained. The X-ray crystal structures of MtbCArgR were determined at 1.85 {angstrom} resolution with bound arginine and at 2.15 {angstrom} resolution in the unliganded form. These structures show that six molecules ofmore » MtbCArgR are arranged into a hexamer having approximate 32 point symmetry that is formed from two trimers. The trimers rotate relative to each other by about 11{sup o} upon binding arginine. All residues in MtbCArgR deemed to be important for hexamer formation and for arginine binding have been identified from the experimentally determined structures presented. The hexamer contains six regular sites in which the arginine molecules have one common binding mode and three sites in which the arginine molecules have two overlapping binding modes. The latter sites only bind the ligand at high (200 mM) arginine concentrations.« less

From Structure to Function: A Comprehensive Compendium of Tools to Unveil Protein Domains and Understand Their Role in Cytokinesis.

PubMed

Rincon, Sergio A; Paoletti, Anne

2016-01-01

Unveiling the function of a novel protein is a challenging task that requires careful experimental design. Yeast cytokinesis is a conserved process that involves modular structural and regulatory proteins. For such proteins, an important step is to identify their domains and structural organization. Here we briefly discuss a collection of methods commonly used for sequence alignment and prediction of protein structure that represent powerful tools for the identification homologous domains and design of structure-function approaches to test experimentally the function of multi-domain proteins such as those implicated in yeast cytokinesis.

Crystal structure of the motor domain of a class-I myosin

PubMed Central

Kollmar, Martin; Dürrwang, Ulrike; Kliche, Werner; Manstein, Dietmar J.; Kull, F.Jon

2002-01-01

The crystal structure of the motor domain of Dictyostelium discoideum myosin-IE, a monomeric unconventional myosin, was determined. The crystallographic asymmetric unit contains four independently resolved molecules, highlighting regions that undergo large conformational changes. Differences are particularly pronounced in the actin binding region and the converter domain. The changes in position of the converter domain reflect movements both parallel to and perpendicular to the actin axis. The orientation of the converter domain is ∼30° further up than in other myosin structures, indicating that MyoE can produce a larger power stroke by rotating its lever arm through a larger angle. The role of extended loops near the actin-binding site is discussed in the context of cellular localization. The core regions of the motor domain are similar, and the structure reveals how that core is stabilized in the absence of an N-terminal SH3-like domain. PMID:12032065

Seeking Temporal Predictability in Speech: Comparing Statistical Approaches on 18 World Languages.

PubMed

Jadoul, Yannick; Ravignani, Andrea; Thompson, Bill; Filippi, Piera; de Boer, Bart

2016-01-01

Temporal regularities in speech, such as interdependencies in the timing of speech events, are thought to scaffold early acquisition of the building blocks in speech. By providing on-line clues to the location and duration of upcoming syllables, temporal structure may aid segmentation and clustering of continuous speech into separable units. This hypothesis tacitly assumes that learners exploit predictability in the temporal structure of speech. Existing measures of speech timing tend to focus on first-order regularities among adjacent units, and are overly sensitive to idiosyncrasies in the data they describe. Here, we compare several statistical methods on a sample of 18 languages, testing whether syllable occurrence is predictable over time. Rather than looking for differences between languages, we aim to find across languages (using clearly defined acoustic, rather than orthographic, measures), temporal predictability in the speech signal which could be exploited by a language learner. First, we analyse distributional regularities using two novel techniques: a Bayesian ideal learner analysis, and a simple distributional measure. Second, we model higher-order temporal structure-regularities arising in an ordered series of syllable timings-testing the hypothesis that non-adjacent temporal structures may explain the gap between subjectively-perceived temporal regularities, and the absence of universally-accepted lower-order objective measures. Together, our analyses provide limited evidence for predictability at different time scales, though higher-order predictability is difficult to reliably infer. We conclude that temporal predictability in speech may well arise from a combination of individually weak perceptual cues at multiple structural levels, but is challenging to pinpoint.

Crystal structure of a multi-domain human smoothened receptor in complex with a super stabilizing ligand

DOE PAGES

Zhang, Xianjun; Zhao, Fei; Wu, Yiran; ...

2017-05-17

Here, the Smoothened receptor (SMO) belongs to the Class Frizzled of the G protein-coupled receptor (GPCR) superfamily, constituting a key component of the Hedgehog signalling pathway. Here we report the crystal structure of the multi-domain human SMO, bound and stabilized by a designed tool ligand TC114, using an X-ray free-electron laser source at 2.9 Å. The structure reveals a precise arrangement of three distinct domains: a seven-transmembrane helices domain (TMD), a hinge domain (HD) and an intact extracellular cysteine-rich domain (CRD). This architecture enables allosteric interactions between the domains that are important for ligand recognition and receptor activation. By combiningmore » the structural data, molecular dynamics simulation, and hydrogen-deuterium-exchange analysis, we demonstrate that transmembrane helix VI, extracellular loop 3 and the HD play a central role in transmitting the signal employing a unique GPCR activation mechanism, distinct from other multi-domain GPCRs.« less

A Constructive Approach to Regularity of Lagrangian Trajectories for Incompressible Euler Flow in a Bounded Domain

NASA Astrophysics Data System (ADS)

Besse, Nicolas; Frisch, Uriel

2017-04-01

The 3D incompressible Euler equations are an important research topic in the mathematical study of fluid dynamics. Not only is the global regularity for smooth initial data an open issue, but the behaviour may also depend on the presence or absence of boundaries. For a good understanding, it is crucial to carry out, besides mathematical studies, high-accuracy and well-resolved numerical exploration. Such studies can be very demanding in computational resources, but recently it has been shown that very substantial gains can be achieved first, by using Cauchy's Lagrangian formulation of the Euler equations and second, by taking advantage of analyticity results of the Lagrangian trajectories for flows whose initial vorticity is Hölder-continuous. The latter has been known for about 20 years (Serfati in J Math Pures Appl 74:95-104, 1995), but the combination of the two, which makes use of recursion relations among time-Taylor coefficients to obtain constructively the time-Taylor series of the Lagrangian map, has been achieved only recently (Frisch and Zheligovsky in Commun Math Phys 326:499-505, 2014; Podvigina et al. in J Comput Phys 306:320-342, 2016 and references therein). Here we extend this methodology to incompressible Euler flow in an impermeable bounded domain whose boundary may be either analytic or have a regularity between indefinite differentiability and analyticity. Non-constructive regularity results for these cases have already been obtained by Glass et al. (Ann Sci Éc Norm Sup 45:1-51, 2012). Using the invariance of the boundary under the Lagrangian flow, we establish novel recursion relations that include contributions from the boundary. This leads to a constructive proof of time-analyticity of the Lagrangian trajectories with analytic boundaries, which can then be used subsequently for the design of a very high-order Cauchy-Lagrangian method.

l0 regularization based on a prior image incorporated non-local means for limited-angle X-ray CT reconstruction.

PubMed

Zhang, Lingli; Zeng, Li; Guo, Yumeng

2018-01-01

Restricted by the scanning environment in some CT imaging modalities, the acquired projection data are usually incomplete, which may lead to a limited-angle reconstruction problem. Thus, image quality usually suffers from the slope artifacts. The objective of this study is to first investigate the distorted domains of the reconstructed images which encounter the slope artifacts and then present a new iterative reconstruction method to address the limited-angle X-ray CT reconstruction problem. The presented framework of new method exploits the structural similarity between the prior image and the reconstructed image aiming to compensate the distorted edges. Specifically, the new method utilizes l0 regularization and wavelet tight framelets to suppress the slope artifacts and pursue the sparsity. New method includes following 4 steps to (1) address the data fidelity using SART; (2) compensate for the slope artifacts due to the missed projection data using the prior image and modified nonlocal means (PNLM); (3) utilize l0 regularization to suppress the slope artifacts and pursue the sparsity of wavelet coefficients of the transformed image by using iterative hard thresholding (l0W); and (4) apply an inverse wavelet transform to reconstruct image. In summary, this method is referred to as "l0W-PNLM". Numerical implementations showed that the presented l0W-PNLM was superior to suppress the slope artifacts while preserving the edges of some features as compared to the commercial and other popular investigative algorithms. When the image to be reconstructed is inconsistent with the prior image, the new method can avoid or minimize the distorted edges in the reconstructed images. Quantitative assessments also showed that applying the new method obtained the highest image quality comparing to the existing algorithms. This study demonstrated that the presented l0W-PNLM yielded higher image quality due to a number of unique characteristics, which include that (1) it utilizes the structural similarity between the reconstructed image and prior image to modify the distorted edges by slope artifacts; (2) it adopts wavelet tight frames to obtain the first and high derivative in several directions and levels; and (3) it takes advantage of l0 regularization to promote the sparsity of wavelet coefficients, which is effective for the inhibition of the slope artifacts. Therefore, the new method can address the limited-angle CT reconstruction problem effectively and have practical significance.

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

DOE PAGES

Upadhyay, Amit A.; Fleetwood, Aaron D.; Adebali, Ogun; ...

2016-04-06

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Upadhyay, Amit A.; Fleetwood, Aaron D.; Adebali, Ogun

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

Exploring the limits of sequence and structure in a variant βγ-crystallin domain of the protein absent in melanoma-1 (AIM1)

PubMed Central

Aravind, Penmatsa; Wistow, Graeme; Sharma, Yogendra; Sankaranarayanan, Rajan

2008-01-01

βγ-Crystallins belong to a superfamily of proteins in prokaryotes and eukaryotes that are based on duplications of a characteristic, highly conserved Greek Key motif. Most members of the superfamily in vertebrates are structural proteins of the eye lens that contain four motifs arranged as two structural domains. Absent in melanoma-1 (AIM1), an unusual member of the superfamily whose expression is associated with suppression of malignancy in melanoma, contains 12 βγ-crystallin motifs in six domains. Some of these motifs diverge considerably from the canonical motif sequence. AIM1g1, the first βγ-crystallin domain of AIM1, is the most variant of βγ-crystallin domains currently known. In order to understand the limits of sequence variation on the structure, we report the crystal structure of AIM1g1 at 1.9Å resolution. In spite of having changes in key residues, the domain retains the overall βγ-crystallin fold. The domain also contains an unusual extended surface loop that significantly alters the shape of the domain and its charge profile. This structure illustrates the resilience of the βγ fold to considerable sequence changes and its remarkable ability to adapt for novel functions. PMID:18582473

Seismic structure and activity of the north-central Lesser Antilles subduction zone from an integrated approach: Similarities with the Tohoku forearc

NASA Astrophysics Data System (ADS)

Laigle, M.; Hirn, A.; Sapin, M.; Bécel, A.; Charvis, P.; Flueh, E.; Diaz, J.; Lebrun, J.-F.; Gesret, A.; Raffaele, R.; Galvé, A.; Evain, M.; Ruiz, M.; Kopp, H.; Bayrakci, G.; Weinzierl, W.; Hello, Y.; Lépine, J.-C.; Viodé, J.-P.; Sachpazi, M.; Gallart, J.; Kissling, E.; Nicolich, R.

2013-09-01

The 300-km-long north-central segment of the Lesser Antilles subduction zone, including Martinique and Guadeloupe islands has been the target of a specific approach to the seismic structure and activity by a cluster of active and passive offshore-onshore seismic experiments. The top of the subducting plate can be followed under the wide accretionary wedge by multichannel reflection seismics. This reveals the hidden updip limit of the contact of the upper plate crustal backstop onto the slab. Two OBS refraction seismic profiles from the volcanic arc throughout the forearc domain constrain a 26-km-large crustal thickness all along. In the common assumption that the upper plate Moho contact on the slab is a proxy of its downdip limit these new observations imply a three times larger width of the potential interplate seismogenic zone under the marine domain of the Caribbean plate with respect to a regular intra-oceanic subduction zone. Towards larger depth under the mantle corner, the top of the slab imaged from the conversions of teleseismic body-waves and the locations of earthquakes appears with kinks which increase the dip to 10-20° under the forearc domain, and then to 60° from 70 km depth. At 145 km depth under the volcanic arc just north of Martinique, the 2007 M 7.4 earthquake, largest for half a century in the region, allows to document a deep slab deformation consistent with segmentation into slab panels. In relation with this occurrence, an increased seismic activity over the whole depth range provides a new focussed image thanks to the OBS and land deployments. A double-planed dipping slab seismicity is thus now resolved, as originally discovered in Tohoku (NE Japan) and since in other subduction zones. Two other types of seismic activity uniquely observed in Tohoku, are now resolved here: "supraslab" earthquakes with normal-faulting focal mechanisms reliably located in the mantle corner and "deep flat-thrust" earthquakes at 45 km depth on the interplate fault under the Caribbean plate forearc mantle. None such types of seismicity should occur under the paradigm of a regular peridotitic mantle of the upper plate which is expected to be serpentinized by the fluids provided from the dehydrating slab beneath. This process is commonly considered as limiting the downward extent of the interplate coupling. Interpretations are not readily available either for the large crustal thickness of this shallow water marine upper plate, except when remarking its likeness to oceanic plateaus formed above hotspots. The Caribbean Oceanic Plateau of the upper plate has been formed earlier by the material advection from a mantle plume. It could then be underlain by a correspondingly modified, heterogeneous mantle, which may include pyroxenitic material among peridotites. Such heterogeneity in the mantle corner of the present subduction zone may account for the notable peculiarities in seismic structure and activity and impose regions of stick-slip behavior on the interplate among stable-gliding areas.

Genetic Testing Registry

MedlinePlus

... Splign Vector Alignment Search Tool (VAST) All Data & Software Resources... Domains & Structures BioSystems Cn3D Conserved Domain Database (CDD) Conserved Domain Search Service (CD Search) Structure (Molecular Modeling Database) Vector Alignment ...

Crystal Structure of the Passenger Domain of the Escherichia coli Autotransporter EspP

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khan, Shekeb; Mian, Hira S.; Sandercock, Linda E.

2013-03-07

Autotransporters represent a large superfamily of known and putative virulence factors produced by Gram-negative bacteria. They consist of an N-terminal 'passenger domain' responsible for the specific effector functions of the molecule and a C-terminal '{beta}-domain' responsible for translocation of the passenger across the bacterial outer membrane. Here, we present the 2.5-{angstrom} crystal structure of the passenger domain of the extracellular serine protease EspP, produced by the pathogen Escherichia coli O157:H7 and a member of the serine protease autotransporters of Enterobacteriaceae (SPATEs). Like the previously structurally characterized SPATE passenger domains, the EspP passenger domain contains an extended right-handed parallel {beta}-helix precededmore » by an N-terminal globular domain housing the catalytic function of the protease. Of note, however, is the absence of a second globular domain protruding from this {beta}-helix. We describe the structure of the EspP passenger domain in the context of previous results and provide an alternative hypothesis for the function of the {beta}-helix within SPATEs.« less

Practice of preventive dentistry for nursing staff in primary care

PubMed Central

Acuña-Reyes, Raquel; Cigarroa-Martínez, Didier; Ureña-Bogarín, Enrique; Orgaz-Fernández, Jose David

2014-01-01

Objectives: Determine the domain of preventive dentistry in nursing personnel assigned to a primary care unit. Methods: Prospective descriptive study, questionnaire validation, and prevalence study. In the first stage, the questionnaire for the practice of preventive dentistry (CPEP, for the term in Spanish) was validated; consistency and reliability were measured by Cronbach's alpha, Pearson's correlation, factor analysis with intra-class correlation coefficient (ICC). In the second stage, the domain in preventive dental nurses was explored. Results: The overall internal consistency of CPEP is α= 0.66, ICC= 0.64, CI95%: 0.29-0.87 (p >0.01). Twenty-one subjects in the study, average age 43, 81.0% female, average seniority of 12.5 were included. A total of 71.5% showed weak domain, 28.5% regular domain, and there was no questionnaire with good domain result. The older the subjects were, the smaller the domain; female nurses showed greater mastery of preventive dentistry (29%, CI95%: 0.1-15.1) than male nurses. Public health nurses showed greater mastery with respect to other categories (50%, CI95%: 0.56-2.8). Conclusions: The CDEP has enough consistency to explore the domain of preventive dentistry in health-care staff. The domain of preventive dentistry in primary care nursing is poor, required to strengthen to provide education in preventive dentistry to the insured population. PMID:25386037

Work Integration of People with Disabilities in the Regular Labour Market: What Can We Do to Improve These Processes?

ERIC Educational Resources Information Center

Vila, Montserrat; Pallisera, Maria; Fullana, Judit

2007-01-01

Background: It is important to ensure that regular processes of labour market integration are available for all citizens. Method: Thematic content analysis techniques, using semi-structured group interviews, were used to identify the principal elements contributing to the processes of integrating people with disabilities into the regular labour…

Shape regularized active contour based on dynamic programming for anatomical structure segmentation

NASA Astrophysics Data System (ADS)

Yu, Tianli; Luo, Jiebo; Singhal, Amit; Ahuja, Narendra

2005-04-01

We present a method to incorporate nonlinear shape prior constraints into segmenting different anatomical structures in medical images. Kernel space density estimation (KSDE) is used to derive the nonlinear shape statistics and enable building a single model for a class of objects with nonlinearly varying shapes. The object contour is coerced by image-based energy into the correct shape sub-distribution (e.g., left or right lung), without the need for model selection. In contrast to an earlier algorithm that uses a local gradient-descent search (susceptible to local minima), we propose an algorithm that iterates between dynamic programming (DP) and shape regularization. DP is capable of finding an optimal contour in the search space that maximizes a cost function related to the difference between the interior and exterior of the object. To enforce the nonlinear shape prior, we propose two shape regularization methods, global and local regularization. Global regularization is applied after each DP search to move the entire shape vector in the shape space in a gradient descent fashion to the position of probable shapes learned from training. The regularized shape is used as the starting shape for the next iteration. Local regularization is accomplished through modifying the search space of the DP. The modified search space only allows a certain amount of deformation of the local shape from the starting shape. Both regularization methods ensure the consistency between the resulted shape with the training shapes, while still preserving DP"s ability to search over a large range and avoid local minima. Our algorithm was applied to two different segmentation tasks for radiographic images: lung field and clavicle segmentation. Both applications have shown that our method is effective and versatile in segmenting various anatomical structures under prior shape constraints; and it is robust to noise and local minima caused by clutter (e.g., blood vessels) and other similar structures (e.g., ribs). We believe that the proposed algorithm represents a major step in the paradigm shift to object segmentation under nonlinear shape constraints.

Structure of a Burkholderia pseudomallei Trimeric Autotransporter Adhesin Head

PubMed Central

Edwards, Thomas E.; Phan, Isabelle; Abendroth, Jan; Dieterich, Shellie H.; Masoudi, Amir; Guo, Wenjin; Hewitt, Stephen N.; Kelley, Angela; Leibly, David; Brittnacher, Mitch J.; Staker, Bart L.; Miller, Samuel I.; Van Voorhis, Wesley C.; Myler, Peter J.; Stewart, Lance J.

2010-01-01

Background Pathogenic bacteria adhere to the host cell surface using a family of outer membrane proteins called Trimeric Autotransporter Adhesins (TAAs). Although TAAs are highly divergent in sequence and domain structure, they are all conceptually comprised of a C-terminal membrane anchoring domain and an N-terminal passenger domain. Passenger domains consist of a secretion sequence, a head region that facilitates binding to the host cell surface, and a stalk region. Methodology/Principal Findings Pathogenic species of Burkholderia contain an overabundance of TAAs, some of which have been shown to elicit an immune response in the host. To understand the structural basis for host cell adhesion, we solved a 1.35 Å resolution crystal structure of a BpaA TAA head domain from Burkholderia pseudomallei, the pathogen that causes melioidosis. The structure reveals a novel fold of an intricately intertwined trimer. The BpaA head is composed of structural elements that have been observed in other TAA head structures as well as several elements of previously unknown structure predicted from low sequence homology between TAAs. These elements are typically up to 40 amino acids long and are not domains, but rather modular structural elements that may be duplicated or omitted through evolution, creating molecular diversity among TAAs. Conclusions/Significance The modular nature of BpaA, as demonstrated by its head domain crystal structure, and of TAAs in general provides insights into evolution of pathogen-host adhesion and may provide an avenue for diagnostics. PMID:20862217

The Influence of Type and Token Frequency on the Acquisition of Affixation Patterns: Implications for Language Processing

ERIC Educational Resources Information Center

Endress, Ansgar D.; Hauser, Marc D.

2011-01-01

Rules, and exceptions to such rules, are ubiquitous in many domains, including language. Here we used simple artificial grammars to investigate the influence of 2 factors on the acquisition of rules and their exceptions, namely type frequency (the relative numbers of different exceptions to different regular items) and token frequency (the number…

Using New Models to Analyze Complex Regularities of the World: Commentary on Musso et al. (2013)

ERIC Educational Resources Information Center

Nokelainen, Petri; Silander, Tomi

2014-01-01

This commentary to the recent article by Musso et al. (2013) discusses issues related to model fitting, comparison of classification accuracy of generative and discriminative models, and two (or more) cultures of data modeling. We start by questioning the extremely high classification accuracy with an empirical data from a complex domain. There is…

Identification of structural domains in proteins by a graph heuristic.

PubMed

Wernisch, L; Hunting, M; Wodak, S J

1999-05-15

A novel automatic procedure for identifying domains from protein atomic coordinates is presented. The procedure, termed STRUDL (STRUctural Domain Limits), does not take into account information on secondary structures and handles any number of domains made up of contiguous or non-contiguous chain segments. The core algorithm uses the Kernighan-Lin graph heuristic to partition the protein into residue sets which display minimum interactions between them. These interactions are deduced from the weighted Voronoi diagram. The generated partitions are accepted or rejected on the basis of optimized criteria, representing basic expected physical properties of structural domains. The graph heuristic approach is shown to be very effective, it approximates closely the exact solution provided by a branch and bound algorithm for a number of test proteins. In addition, the overall performance of STRUDL is assessed on a set of 787 representative proteins from the Protein Data Bank by comparison to domain definitions in the CATH protein classification. The domains assigned by STRUDL agree with the CATH assignments in at least 81% of the tested proteins. This result is comparable to that obtained previously using PUU (Holm and Sander, Proteins 1994;9:256-268), the only other available algorithm designed to identify domains with any number of non-contiguous chain segments. A detailed discussion of the structures for which our assignments differ from those in CATH brings to light some clear inconsistencies between the concept of structural domains based on minimizing inter-domain interactions and that of delimiting structural motifs that represent acceptable folding topologies or architectures. Considering both concepts as complementary and combining them in a layered approach might be the way forward.

Perspectives for the use of structural information and chemical genetics to develop inhibitors of Janus kinases

PubMed Central

Haan, Claude; Behrmann, Iris; Haan, Serge

2010-01-01

Abstract Gain-of-function mutations in the genes encoding Janus kinases have been discovered in various haematologic diseases. Jaks are composed of a FERM domain, an SH2 domain, a pseudokinase domain and a kinase domain, and a complex interplay of the Jak domains is involved in regulation of catalytic activity and association to cytokine receptors. Most activating mutations are found in the pseudokinase domain. Here we present recently discovered mutations in the context of our structural models of the respective domains. We describe two structural hotspots in the pseudokinase domain of Jak2 that seem to be associated either to myeloproliferation or to lymphoblastic leukaemia, pointing at the involvement of distinct signalling complexes in these disease settings. The different domains of Jaks are discussed as potential drug targets. We present currently available inhibitors targeting Jaks and indicate structural differences in the kinase domains of the different Jaks that may be exploited in the development of specific inhibitors. Moreover, we discuss recent chemical genetic approaches which can be applied to Jaks to better understand the role of these kinases in their biological settings and as drug targets. PMID:20132407

Fast Poisson noise removal by biorthogonal Haar domain hypothesis testing

NASA Astrophysics Data System (ADS)

Zhang, B.; Fadili, M. J.; Starck, J.-L.; Digel, S. W.

2008-07-01

Methods based on hypothesis tests (HTs) in the Haar domain are widely used to denoise Poisson count data. Facing large datasets or real-time applications, Haar-based denoisers have to use the decimated transform to meet limited-memory or computation-time constraints. Unfortunately, for regular underlying intensities, decimation yields discontinuous estimates and strong “staircase” artifacts. In this paper, we propose to combine the HT framework with the decimated biorthogonal Haar (Bi-Haar) transform instead of the classical Haar. The Bi-Haar filter bank is normalized such that the p-values of Bi-Haar coefficients (p) provide good approximation to those of Haar (pH) for high-intensity settings or large scales; for low-intensity settings and small scales, we show that p are essentially upper-bounded by pH. Thus, we may apply the Haar-based HTs to Bi-Haar coefficients to control a prefixed false positive rate. By doing so, we benefit from the regular Bi-Haar filter bank to gain a smooth estimate while always maintaining a low computational complexity. A Fisher-approximation-based threshold implementing the HTs is also established. The efficiency of this method is illustrated on an example of hyperspectral-source-flux estimation.

A finite element method with overlapping meshes for free-boundary axisymmetric plasma equilibria in realistic geometries

NASA Astrophysics Data System (ADS)

Heumann, Holger; Rapetti, Francesca

2017-04-01

Existing finite element implementations for the computation of free-boundary axisymmetric plasma equilibria approximate the unknown poloidal flux function by standard lowest order continuous finite elements with discontinuous gradients. As a consequence, the location of critical points of the poloidal flux, that are of paramount importance in tokamak engineering, is constrained to nodes of the mesh leading to undesired jumps in transient problems. Moreover, recent numerical results for the self-consistent coupling of equilibrium with resistive diffusion and transport suggest the necessity of higher regularity when approximating the flux map. In this work we propose a mortar element method that employs two overlapping meshes. One mesh with Cartesian quadrilaterals covers the vacuum chamber domain accessible by the plasma and one mesh with triangles discretizes the region outside. The two meshes overlap in a narrow region. This approach gives the flexibility to achieve easily and at low cost higher order regularity for the approximation of the flux function in the domain covered by the plasma, while preserving accurate meshing of the geometric details outside this region. The continuity of the numerical solution in the region of overlap is weakly enforced by a mortar-like mapping.

Exploring equivalence domain in nonlinear inverse problems using Covariance Matrix Adaption Evolution Strategy (CMAES) and random sampling

NASA Astrophysics Data System (ADS)

Grayver, Alexander V.; Kuvshinov, Alexey V.

2016-05-01

This paper presents a methodology to sample equivalence domain (ED) in nonlinear partial differential equation (PDE)-constrained inverse problems. For this purpose, we first applied state-of-the-art stochastic optimization algorithm called Covariance Matrix Adaptation Evolution Strategy (CMAES) to identify low-misfit regions of the model space. These regions were then randomly sampled to create an ensemble of equivalent models and quantify uncertainty. CMAES is aimed at exploring model space globally and is robust on very ill-conditioned problems. We show that the number of iterations required to converge grows at a moderate rate with respect to number of unknowns and the algorithm is embarrassingly parallel. We formulated the problem by using the generalized Gaussian distribution. This enabled us to seamlessly use arbitrary norms for residual and regularization terms. We show that various regularization norms facilitate studying different classes of equivalent solutions. We further show how performance of the standard Metropolis-Hastings Markov chain Monte Carlo algorithm can be substantially improved by using information CMAES provides. This methodology was tested by using individual and joint inversions of magneotelluric, controlled-source electromagnetic (EM) and global EM induction data.

Block matching sparsity regularization-based image reconstruction for incomplete projection data in computed tomography

NASA Astrophysics Data System (ADS)

Cai, Ailong; Li, Lei; Zheng, Zhizhong; Zhang, Hanming; Wang, Linyuan; Hu, Guoen; Yan, Bin

2018-02-01

In medical imaging many conventional regularization methods, such as total variation or total generalized variation, impose strong prior assumptions which can only account for very limited classes of images. A more reasonable sparse representation frame for images is still badly needed. Visually understandable images contain meaningful patterns, and combinations or collections of these patterns can be utilized to form some sparse and redundant representations which promise to facilitate image reconstructions. In this work, we propose and study block matching sparsity regularization (BMSR) and devise an optimization program using BMSR for computed tomography (CT) image reconstruction for an incomplete projection set. The program is built as a constrained optimization, minimizing the L1-norm of the coefficients of the image in the transformed domain subject to data observation and positivity of the image itself. To solve the program efficiently, a practical method based on the proximal point algorithm is developed and analyzed. In order to accelerate the convergence rate, a practical strategy for tuning the BMSR parameter is proposed and applied. The experimental results for various settings, including real CT scanning, have verified the proposed reconstruction method showing promising capabilities over conventional regularization.

Crystal structure of the second fibronectin type III (FN3) domain from human collagen α1 type XX.

PubMed

Zhao, Jingfeng; Ren, Jixia; Wang, Nan; Cheng, Zhong; Yang, Runmei; Lin, Gen; Guo, Yi; Cai, Dayong; Xie, Yong; Zhao, Xiaohong

2017-12-01

Collagen α1 type XX, which contains fibronectin type III (FN3) repeats involving six FN3 domains (referred to as the FN#1-FN#6 domains), is an unusual member of the fibril-associated collagens with interrupted triple helices (FACIT) subfamily of collagens. The results of standard protein BLAST suggest that the FN3 repeats might contribute to collagen α1 type XX acting as a cytokine receptor. To date, solution NMR structures of the FN#3, FN#4 and FN#6 domains have been determined. To obtain further structural evidence to understand the relationship between the structure and function of the FN3 repeats from collagen α1 type XX, the crystal structure of the FN#2 domain from human collagen α1 type XX (residues Pro386-Pro466; referred to as FN2-HCXX) was solved at 2.5 Å resolution. The crystal structure of FN2-HCXX shows an immunoglobulin-like fold containing a β-sandwich structure, which is formed by a three-stranded β-sheet (β1, β2 and β5) packed onto a four-stranded β-sheet (β3, β4, β6 and β7). Two consensus domains, tencon and fibcon, are structural analogues of FN2-HCXX. Fn8, an FN3 domain from human oncofoetal fibronectin, is the closest structural analogue of FN2-HCXX derived from a naturally occurring sequence. Based solely on the structural similarity of FN2-HCXX to other FN3 domains, the detailed functions of FN2-HCXX and the FN3 repeats in collagen α1 type XX cannot be identified.

An Extended Structure of the APOBEC3G Catalytic Domain Suggests a Unique Holoenzyme Model

PubMed Central

Harjes, Elena; Gross, Phillip J.; Chen, Kuan-Ming; Lu, Yongjian; Shindo, Keisuke; Nowarski, Roni; Gross, John D.; Kotler, Moshe; Harris, Reuben S.; Matsuo, Hiroshi

2009-01-01

Summary Human APOBEC3G (A3G) belongs to a family of polynucleotide cytidine deaminases. This family includes APOBEC1 and AID, which edit APOB mRNA and antibody gene DNA, respectively. A3G deaminates cytidines to uridines in single-strand DNA and inhibits the replication of HIV-1, other retroviruses and retrotransposons. Although the mechanism of A3G-catalyzed DNA deamination has been investigated genetically and biochemically, atomic details are just starting to emerge. Here, we compare the DNA cytidine deaminase activities and NMR structures of two A3G catalytic domain constructs. The longer A3G191-384 protein is considerably more active than the shorter A3G198-384 variant. The longer structure has an α1 helix (residues 201–206) that was not apparent in the shorter protein and it contributes to catalytic activity through interactions with hydrophobic core structures (β1, β3, α5 and α6). Both A3G catalytic domain solution structures have a discontinuous β2 region that is clearly different than the continuous β2 strand of another family member APOBEC2. In addition, the longer A3G191-384 structure revealed part of the N-terminal pseudo-catalytic domain including the inter-domain linker and some of the last α-helix. These structured residues (191–196) enabled a novel full-length A3G model by providing physical overlap between the N-terminal pseudo-catalytic domain and the new C-terminal catalytic domain structure. Contrary to predictions, this structurally constrained model suggested that the two domains are tethered by structured residues and that the N- and C-terminal β2 regions are too distant from one another to participate in this interaction. PMID:19389408

Structural and evolutionary relationships of "AT-less" type I polyketide synthase ketosynthases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lohman, Jeremy; Ma, Ming; Osipiuk, Jerzy

2015-10-13

Acyltransferase (AT)-less type I polyketide synthases (PKSs) break the type I PKS paradigm. They lack the integrated AT domains within their modules and instead use a discrete AT that acts in trans, whereas a type I PKS module minimally contains AT, acyl carrier protein (ACP), and ketosynthase (KS) domains. Structures of canonical type I PKS KS-AT didomains reveal structured linkers that connect the two domains. AT-less type I PKS KSs have remnants of these linkers, which have been hypothesized to be AT docking domains. Natural products produced by AT-less type I PKSs are very complex because of an increased representationmore » of unique modifying domains. AT-less type I PKS KSs possess substrate specificity and fall into phylogenetic clades that correlate with their substrates, whereas canonical type I PKS KSs are monophyletic. We have solved crystal structures of seven AT-less type I PKS KS domains that represent various sequence clusters, revealing insight into the large structural and subtle amino acid residue differences that lead to unique active site topologies and substrate specificities. One set of structures represents a larger group of KS domains from both canonical and AT-less type I PKSs that accept amino acid-containing substrates. One structure has a partial AT-domain, revealing the structural consequences of a type I PKS KS evolving into an AT-less type I PKS KS. These structures highlight the structural diversity within the AT-less type I PKS KS family, and most important, provide a unique opportunity to study the molecular evolution of substrate specificity within the type I PKSs.« less

Epitope mapping of the domains of human angiotensin converting enzyme.

PubMed

Kugaevskaya, Elena V; Kolesanova, Ekaterina F; Kozin, Sergey A; Veselovsky, Alexander V; Dedinsky, Ilya R; Elisseeva, Yulia E

2006-06-01

Somatic angiotensin converting enzyme (sACE), contains in its single chain two homologous domains (called N- and C-domains), each bearing a functional zinc-dependent active site. The present study aims to define the differences between two sACE domains and to localize experimentally revealed antigenic determinants (B-epitopes) in the recently determined three-dimensional structure of testicular tACE. The predicted linear antigenic determinants of human sACE were determined by peptide scanning ("PEPSCAN") approach. Essential difference was demonstrated between locations of the epitopes in the N- and C-domains. Comparison of arrangement of epitopes in the human domains with the corresponding sequences of some mammalian sACEs enabled to classify the revealed antigenic determinants as variable or conserved areas. The location of antigenic determinants with respect to various structural elements and to functionally important sites of the human sACE C-domain was estimated. The majority of antigenic sites of the C-domain were located at the irregular elements and at the boundaries of secondary structure elements. The data show structural differences between the sACE domains. The experimentally revealed antigenic determinants were in agreement with the recently determined crystal tACE structure. New potential applications are open to successfully produce mono-specific and group-specific antipeptide antibodies.

A structural analysis of the AAA+ domains in Saccharomyces cerevisiae cytoplasmic dynein.

PubMed

Gleave, Emma S; Schmidt, Helgo; Carter, Andrew P

2014-06-01

Dyneins are large protein complexes that act as microtubule based molecular motors. The dynein heavy chain contains a motor domain which is a member of the AAA+ protein family (ATPases Associated with diverse cellular Activities). Proteins of the AAA+ family show a diverse range of functionalities, but share a related core AAA+ domain, which often assembles into hexameric rings. Dynein is unusual because it has all six AAA+ domains linked together, in one long polypeptide. The dynein motor domain generates movement by coupling ATP driven conformational changes in the AAA+ ring to the swing of a motile element called the linker. Dynein binds to its microtubule track via a long antiparallel coiled-coil stalk that emanates from the AAA+ ring. Recently the first high resolution structures of the dynein motor domain were published. Here we provide a detailed structural analysis of the six AAA+ domains using our Saccharomycescerevisiae crystal structure. We describe how structural similarities in the dynein AAA+ domains suggest they share a common evolutionary origin. We analyse how the different AAA+ domains have diverged from each other. We discuss how this is related to the function of dynein as a motor protein and how the AAA+ domains of dynein compare to those of other AAA+ proteins. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Crystal Structure of the Ubiquitin-associated (UBA) Domain of p62 and Its Interaction with Ubiquitin*

PubMed Central

Isogai, Shin; Morimoto, Daichi; Arita, Kyohei; Unzai, Satoru; Tenno, Takeshi; Hasegawa, Jun; Sou, Yu-shin; Komatsu, Masaaki; Tanaka, Keiji; Shirakawa, Masahiro; Tochio, Hidehito

2011-01-01

p62/SQSTM1/A170 is a multimodular protein that is found in ubiquitin-positive inclusions associated with neurodegenerative diseases. Recent findings indicate that p62 mediates the interaction between ubiquitinated proteins and autophagosomes, leading these proteins to be degraded via the autophagy-lysosomal pathway. This ubiquitin-mediated selective autophagy is thought to begin with recognition of the ubiquitinated proteins by the C-terminal ubiquitin-associated (UBA) domain of p62. We present here the crystal structure of the UBA domain of mouse p62 and the solution structure of its ubiquitin-bound form. The p62 UBA domain adopts a novel dimeric structure in crystals, which is distinctive from those of other UBA domains. NMR analyses reveal that in solution the domain exists in equilibrium between the dimer and monomer forms, and binding ubiquitin shifts the equilibrium toward the monomer to form a 1:1 complex between the UBA domain and ubiquitin. The dimer-to-monomer transition is associated with a structural change of the very C-terminal end of the p62 UBA domain, although the UBA fold itself is essentially maintained. Our data illustrate that dimerization and ubiquitin binding of the p62 UBA domain are incompatible with each other. These observations reveal an autoinhibitory mechanism in the p62 UBA domain and suggest that autoinhibition plays a role in the function of p62. PMID:21715324

Regularization of the Perturbed Spatial Restricted Three-Body Problem by L-Transformations

NASA Astrophysics Data System (ADS)

Poleshchikov, S. M.

2018-03-01

Equations of motion for the perturbed circular restricted three-body problem have been regularized in canonical variables in a moving coordinate system. Two different L-matrices of the fourth order are used in the regularization. Conditions for generalized symplecticity of the constructed transform have been checked. In the unperturbed case, the regular equations have a polynomial structure. The regular equations have been numerically integrated using the Runge-Kutta-Fehlberg method. The results of numerical experiments are given for the Earth-Moon system parameters taking into account the perturbation of the Sun for different L-matrices.

Slice regular functions of several Clifford variables

NASA Astrophysics Data System (ADS)

Ghiloni, R.; Perotti, A.

2012-11-01

We introduce a class of slice regular functions of several Clifford variables. Our approach to the definition of slice functions is based on the concept of stem functions of several variables and on the introduction on real Clifford algebras of a family of commuting complex structures. The class of slice regular functions include, in particular, the family of (ordered) polynomials in several Clifford variables. We prove some basic properties of slice and slice regular functions and give examples to illustrate this function theory. In particular, we give integral representation formulas for slice regular functions and a Hartogs type extension result.

The structure of the exopolyphsophatase (PPX) from Escherchia coli O157:H7 suggests a binding mode for long polyphosphate chains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rangarajan,E.; Nadeau, G.; Li, Y.

2006-01-01

Polyphosphate (polyP) is a linear polymer consisting of tens to hundreds of phosphate molecules joined together by high-energy anhydride bonds. These polymers are found in virtually all prokaryotic and eukaryotic cells and perform many functions; prominent among them are the responses to many stresses. Polyphosphate is synthesized by polyP kinase (PPK), using the terminal phosphate of ATP as the substrate, and degraded to inorganic phosphate by both endo- and exopolyphosphatases. Here we report the crystal structure and analysis of the polyphosphate phosphatase PPX from Escherichia coli O157:H7 refined at 2.2 Angstroms resolution. PPX is made of four domains. Domains Imore » and II display structural similarity with one another and share the ribonuclease-H-like fold. Domain III bears structural similarity to the N-terminal, HD domain of SpoT. Domain IV, the smallest domain, has structural counterparts in cold-shock associated RNA-binding proteins but is of unknown function in PPX. The putative PPX active site is located at the interface between domains I and II. In the crystal structure of PPX these two domains are close together and represent the 'closed' state. Comparison with the crystal structure of PPX/GPPA from Aquifex aeolicus reveals close structural similarity between domains I and II of the two enzymes, with the PPX/GPPA representing an 'open' state. A striking feature of the dimer is a deep S-shaped canyon extending along the dimer interface and lined with positively charged residues. The active site region opens to this canyon. We postulate that this is a likely site of polyP binding.« less

Broadband Structural Dynamics: Understanding the Impulse-Response of Structures Across Multiple Length and Time Scales

DTIC Science & Technology

2010-08-18

Spectral domain response calculated • Time domain response obtained through inverse transform Approach 4: WASABI Wavelet Analysis of Structural Anomalies...differences at unity scale! Time Function Transform Apply Spectral Domain Transfer Function Time Function Inverse Transform Transform Transform  mtP

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wong, Jaslyn E. M. M.; Midtgaard, Søren Roi; Gysel, Kira

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 themore » 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.« less

Micro-heterogeneity versus clustering in binary mixtures of ethanol with water or alkanes.

PubMed

Požar, Martina; Lovrinčević, Bernarda; Zoranić, Larisa; Primorać, Tomislav; Sokolić, Franjo; Perera, Aurélien

2016-08-24

Ethanol is a hydrogen bonding liquid. When mixed in small concentrations with water or alkanes, it forms aggregate structures reminiscent of, respectively, the direct and inverse micellar aggregates found in emulsions, albeit at much smaller sizes. At higher concentrations, micro-heterogeneous mixing with segregated domains is found. We examine how different statistical methods, namely correlation function analysis, structure factor analysis and cluster distribution analysis, can describe efficiently these morphological changes in these mixtures. In particular, we explain how the neat alcohol pre-peak of the structure factor evolves into the domain pre-peak under mixing conditions, and how this evolution differs whether the co-solvent is water or alkane. This study clearly establishes the heuristic superiority of the correlation function/structure factor analysis to study the micro-heterogeneity, since cluster distribution analysis is insensitive to domain segregation. Correlation functions detect the domains, with a clear structure factor pre-peak signature, while the cluster techniques detect the cluster hierarchy within domains. The main conclusion is that, in micro-segregated mixtures, the domain structure is a more fundamental statistical entity than the underlying cluster structures. These findings could help better understand comparatively the radiation scattering experiments, which are sensitive to domains, versus the spectroscopy-NMR experiments, which are sensitive to clusters.

National Center for Biotechnology Information

MedlinePlus

... Splign Vector Alignment Search Tool (VAST) All Data & Software Resources... Domains & Structures BioSystems Cn3D Conserved Domain Database (CDD) Conserved Domain Search Service (CD Search) Structure (Molecular Modeling Database) Vector Alignment ...

Structural Characterization of the Predominant Family of Histidine Kinase Sensor Domains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Z.; Hendrickson, W

2010-01-01

Histidine kinase (HK) receptors are used ubiquitously by bacteria to monitor environmental changes, and they are also prevalent in plants, fungi, and other protists. Typical HK receptors have an extracellular sensor portion that detects a signal, usually a chemical ligand, and an intracellular transmitter portion that includes both the kinase domain itself and the site for histidine phosphorylation. While kinase domains are highly conserved, sensor domains are diverse. HK receptors function as dimers, but the molecular mechanism for signal transduction across cell membranes remains obscure. In this study, eight crystal structures were determined from five sensor domains representative of themore » most populated family, family HK1, found in a bioinformatic analysis of predicted sensor domains from transmembrane HKs. Each structure contains an inserted repeat of PhoQ/DcuS/CitA (PDC) domains, and similarity between sequence and structure is correlated across these and other double-PDC sensor proteins. Three of the five sensors crystallize as dimers that appear to be physiologically relevant, and comparisons between ligated structures and apo-state structures provide insights into signal transmission. Some HK1 family proteins prove to be sensors for chemotaxis proteins or diguanylate cyclase receptors, implying a combinatorial molecular evolution.« less

The Vibrio cholerae Colonization Factor GbpA Possesses a Modular Structure that Governs Binding to Different Host Surfaces

PubMed Central

Wong, Edmond; Vaaje-Kolstad, Gustav; Ghosh, Avishek; Hurtado-Guerrero, Ramon; Konarev, Peter V.; Ibrahim, Adel F. M.; Svergun, Dmitri I.; Eijsink, Vincent G. H.; Chatterjee, Nabendu S.; van Aalten, Daan M. F.

2012-01-01

Vibrio cholerae is a bacterial pathogen that colonizes the chitinous exoskeleton of zooplankton as well as the human gastrointestinal tract. Colonization of these different niches involves an N-acetylglucosamine binding protein (GbpA) that has been reported to mediate bacterial attachment to both marine chitin and mammalian intestinal mucin through an unknown molecular mechanism. We report structural studies that reveal that GbpA possesses an unusual, elongated, four-domain structure, with domains 1 and 4 showing structural homology to chitin binding domains. A glycan screen revealed that GbpA binds to GlcNAc oligosaccharides. Structure-guided GbpA truncation mutants show that domains 1 and 4 of GbpA interact with chitin in vitro, whereas in vivo complementation studies reveal that domain 1 is also crucial for mucin binding and intestinal colonization. Bacterial binding studies show that domains 2 and 3 bind to the V. cholerae surface. Finally, mouse virulence assays show that only the first three domains of GbpA are required for colonization. These results explain how GbpA provides structural/functional modular interactions between V. cholerae, intestinal epithelium and chitinous exoskeletons. PMID:22253590

An oscillating wave energy converter with nonlinear snap-through Power-Take-Off systems in regular waves

NASA Astrophysics Data System (ADS)

Zhang, Xian-tao; Yang, Jian-min; Xiao, Long-fei

2016-07-01

Floating oscillating bodies constitute a large class of wave energy converters, especially for offshore deployment. Usually the Power-Take-Off (PTO) system is a directly linear electric generator or a hydraulic motor that drives an electric generator. The PTO system is simplified as a linear spring and a linear damper. However the conversion is less powerful with wave periods off resonance. Thus, a nonlinear snap-through mechanism with two symmetrically oblique springs and a linear damper is applied in the PTO system. The nonlinear snap-through mechanism is characteristics of negative stiffness and double-well potential. An important nonlinear parameter γ is defined as the ratio of half of the horizontal distance between the two springs to the original length of both springs. Time domain method is applied to the dynamics of wave energy converter in regular waves. And the state space model is used to replace the convolution terms in the time domain equation. The results show that the energy harvested by the nonlinear PTO system is larger than that by linear system for low frequency input. While the power captured by nonlinear converters is slightly smaller than that by linear converters for high frequency input. The wave amplitude, damping coefficient of PTO systems and the nonlinear parameter γ affect power capture performance of nonlinear converters. The oscillation of nonlinear wave energy converters may be local or periodically inter well for certain values of the incident wave frequency and the nonlinear parameter γ, which is different from linear converters characteristics of sinusoidal response in regular waves.

Structural and functional aspects of the nonribosomal peptide synthetase condensation domain superfamily: discovery, dissection and diversity.

PubMed

Bloudoff, Kristjan; Schmeing, T Martin

2017-11-01

Nonribosomal peptide synthetases (NRPSs) are incredible macromolecular machines that produce a wide range of biologically- and therapeutically-relevant molecules. During synthesis, peptide elongation is performed by the condensation (C) domain, as it catalyzes amide bond formation between the nascent peptide and the amino acid it adds to the chain. Since their discovery more than two decades ago, C domains have been subject to extensive biochemical, bioinformatic, mutagenic, and structural analyses. They are composed of two lobes, each with homology to chloramphenicol acetyltransferase, have two binding sites for their two peptidyl carrier protein-bound ligands, and have an active site with conserved motif HHxxxDG located between the two lobes. This review discusses some of the important insights into the structure, catalytic mechanism, specificity, and gatekeeping functions of C domains revealed since their discovery. In addition, C domains are the archetypal members of the C domain superfamily, which includes several other members that also function as NRPS domains. The other family members can replace the C domain in NRP synthesis, can work in concert with a C domain, or can fulfill diverse and novel functions. These domains include the epimerization (E) domain, the heterocyclization (Cy) domain, the ester-bond forming C domain, the fungal NRPS terminal C domain (C T ), the β-lactam ring forming C domain, and the X domain. We also discuss structural and function insight into C, E, Cy, C T and X domains, to present a holistic overview of historical and current knowledge of the C domain superfamily. This article is part of a Special Issue entitled: Biophysics in Canada, edited by Lewis Kay, John Baenziger, Albert Berghuis and Peter Tieleman. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.