Deriving Lifetime Maps in the Time/Frequency Domain of Coherent Structures in the Turbulent Boundary Layer

NASA Technical Reports Server (NTRS)

Palumbo, Dan

2008-01-01

The lifetimes of coherent structures are derived from data correlated over a 3 sensor array sampling streamwise sidewall pressure at high Reynolds number (> 10(exp 8)). The data were acquired at subsonic, transonic and supersonic speeds aboard a Tupolev Tu-144. The lifetimes are computed from a variant of the correlation length termed the lifelength. Characteristic lifelengths are estimated by fitting a Gaussian distribution to the sensors cross spectra and are shown to compare favorably with Efimtsov s prediction of correlation space scales. Lifelength distributions are computed in the time/frequency domain using an interval correlation technique on the continuous wavelet transform of the original time data. The median values of the lifelength distributions are found to be very close to the frequency averaged result. The interval correlation technique is shown to allow the retrieval and inspection of the original time data of each event in the lifelength distributions, thus providing a means to locate and study the nature of the coherent structure in the turbulent boundary layer. The lifelength data are converted to lifetimes using the convection velocity. The lifetime of events in the time/frequency domain are displayed in Lifetime Maps. The primary purpose of the paper is to validate these new analysis techniques so that they can be used with confidence to further characterize the behavior of coherent structures in the turbulent boundary layer.

Models for randomly distributed nanoscopic domains on spherical vesicles

NASA Astrophysics Data System (ADS)

Anghel, Vinicius N. P.; Bolmatov, Dima; Katsaras, John

2018-06-01

The existence of lipid domains in the plasma membrane of biological systems has proven controversial, primarily due to their nanoscopic size—a length scale difficult to interrogate with most commonly used experimental techniques. Scattering techniques have recently proven capable of studying nanoscopic lipid domains populating spherical vesicles. However, the development of analytical methods able of predicting and analyzing domain pair correlations from such experiments has not kept pace. Here, we developed models for the random distribution of monodisperse, circular nanoscopic domains averaged on the surface of a spherical vesicle. Specifically, the models take into account (i) intradomain correlations corresponding to form factors and interdomain correlations corresponding to pair distribution functions, and (ii) the analytical computation of interdomain correlations for cases of two and three domains on a spherical vesicle. In the case of more than three domains, these correlations are treated either by Monte Carlo simulations or by spherical analogs of the Ornstein-Zernike and Percus-Yevick (PY) equations. Importantly, the spherical analog of the PY equation works best in the case of nanoscopic size domains, a length scale that is mostly inaccessible by experimental approaches such as, for example, fluorescent techniques and optical microscopies. The analytical form factors and structure factors of nanoscopic domains populating a spherical vesicle provide a new and important framework for the quantitative analysis of experimental data from commonly studied phase-separated vesicles used in a wide range of biophysical studies.

Angular correlations of photons from solution diffraction at a free-electron laser encode molecular structure

DOE PAGES

Mendez, Derek; Watkins, Herschel; Qiao, Shenglan; ...

2016-09-26

During X-ray exposure of a molecular solution, photons scattered from the same molecule are correlated. If molecular motion is insignificant during exposure, then differences in momentum transfer between correlated photons are direct measurements of the molecular structure. In conventional small- and wide-angle solution scattering, photon correlations are ignored. This report presents advances in a new biomolecular structural analysis technique, correlated X-ray scattering (CXS), which uses angular intensity correlations to recover hidden structural details from molecules in solution. Due to its intense rapid pulses, an X-ray free electron laser (XFEL) is an excellent tool for CXS experiments. A protocol is outlinedmore » for analysis of a CXS data set comprising a total of half a million X-ray exposures of solutions of small gold nanoparticles recorded at the Spring-8 Ångström Compact XFEL facility (SACLA). From the scattered intensities and their correlations, two populations of nanoparticle domains within the solution are distinguished: small twinned, and large probably non-twinned domains. Finally, it is shown analytically how, in a solution measurement, twinning information is only accessible via intensity correlations, demonstrating how CXS reveals atomic-level information from a disordered solution of like molecules.« less

Distributed strain measurement and possible breakage detection of optical-fiber-embedded composite structure using slope-assisted Brillouin optical correlation-domain reflectometry

NASA Astrophysics Data System (ADS)

Lee, Heeyoung; Ochi, Yutaka; Matsui, Takahiro; Matsumoto, Yukihiro; Tanaka, Yosuke; Nakamura, Hitoshi; Mizuno, Yosuke; Nakamura, Kentaro

2018-07-01

Slope-assisted Brillouin optical correlation-domain reflectometry (SA-BOCDR) is a recently developed structural health monitoring technique for measurements of strain, temperature, and loss distributions along optical fibers. Although the basic operational principle of this method has been clarified, no measurements using optical fibers embedded in actual structures have been reported. As a first step towards such practical applications, in this study, we present an example of an SA-BOCDR-based diagnosis using a composite structure with carbon fiber-reinforced plastics. The system’s output agrees well with the actual strain distributions. We were also able to detect the breakage of the embedded fiber, thus demonstrating the promise of SA-BOCDR for practical applications.

Regulation of adhesion behavior of murine macrophage using supported lipid membranes displaying tunable mannose domains

NASA Astrophysics Data System (ADS)

Kaindl, T.; Oelke, J.; Pasc, A.; Kaufmann, S.; Konovalov, O. V.; Funari, S. S.; Engel, U.; Wixforth, A.; Tanaka, M.

2010-07-01

Highly uniform, strongly correlated domains of synthetically designed lipids can be incorporated into supported lipid membranes. The systematic characterization of membranes displaying a variety of domains revealed that the equilibrium size of domains significantly depends on the length of fluorocarbon chains, which can be quantitatively interpreted within the framework of an equivalent dipole model. A mono-dispersive, narrow size distribution of the domains enables us to treat the inter-domain correlations as two-dimensional colloidal crystallization and calculate the potentials of mean force. The obtained results demonstrated that both size and inter-domain correlation can precisely be controlled by the molecular structures. By coupling α-D-mannose to lipid head groups, we studied the adhesion behavior of the murine macrophage (J774A.1) on supported membranes. Specific adhesion and spreading of macrophages showed a clear dependence on the density of functional lipids. The obtained results suggest that such synthetic lipid domains can be used as a defined platform to study how cells sense the size and distribution of functional molecules during adhesion and spreading.

Functional CAR models for large spatially correlated functional datasets.

PubMed

Zhang, Lin; Baladandayuthapani, Veerabhadran; Zhu, Hongxiao; Baggerly, Keith A; Majewski, Tadeusz; Czerniak, Bogdan A; Morris, Jeffrey S

2016-01-01

We develop a functional conditional autoregressive (CAR) model for spatially correlated data for which functions are collected on areal units of a lattice. Our model performs functional response regression while accounting for spatial correlations with potentially nonseparable and nonstationary covariance structure, in both the space and functional domains. We show theoretically that our construction leads to a CAR model at each functional location, with spatial covariance parameters varying and borrowing strength across the functional domain. Using basis transformation strategies, the nonseparable spatial-functional model is computationally scalable to enormous functional datasets, generalizable to different basis functions, and can be used on functions defined on higher dimensional domains such as images. Through simulation studies, we demonstrate that accounting for the spatial correlation in our modeling leads to improved functional regression performance. Applied to a high-throughput spatially correlated copy number dataset, the model identifies genetic markers not identified by comparable methods that ignore spatial correlations.

Spontaneous Unfolding-Refolding of Fibronectin Type III Domains Assayed by Thiol Exchange

PubMed Central

Shah, Riddhi; Ohashi, Tomoo; Erickson, Harold P.; Oas, Terrence G.

2017-01-01

Globular proteins are not permanently folded but spontaneously unfold and refold on time scales that can span orders of magnitude for different proteins. A longstanding debate in the protein-folding field is whether unfolding rates or folding rates correlate to the stability of a protein. In the present study, we have determined the unfolding and folding kinetics of 10 FNIII domains. FNIII domains are one of the most common protein folds and are present in 2% of animal proteins. FNIII domains are ideal for this study because they have an identical seven-strand β-sandwich structure, but they vary widely in sequence and thermodynamic stability. We assayed thermodynamic stability of each domain by equilibrium denaturation in urea. We then assayed the kinetics of domain opening and closing by a technique known as thiol exchange. For this we introduced a buried Cys at the identical location in each FNIII domain and measured the kinetics of labeling with DTNB over a range of urea concentrations. A global fit of the kinetics data gave the kinetics of spontaneous unfolding and refolding in zero urea. We found that the folding rates were relatively similar, ∼0.1–1 s−1, for the different domains. The unfolding rates varied widely and correlated with thermodynamic stability. Our study is the first to address this question using a set of domains that are structurally homologous but evolved with widely varying sequence identity and thermodynamic stability. These data add new evidence that thermodynamic stability correlates primarily with unfolding rate rather than folding rate. The study also has implications for the question of whether opening of FNIII domains contributes to the stretching of fibronectin matrix fibrils. PMID:27909052

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

Visualization and manipulation of magnetic domains in the quasi-two-dimensional material F e3GeT e2

NASA Astrophysics Data System (ADS)

Nguyen, Giang D.; Lee, Jinhwan; Berlijn, Tom; Zou, Qiang; Hus, Saban M.; Park, Jewook; Gai, Zheng; Lee, Changgu; Li, An-Ping

2018-01-01

The magnetic domains in two-dimensional layered material F e3GeT e2 are studied by using a variable-temperature scanning tunneling microscope with a magnetic tip after in situ cleaving of single crystals. A stripy domain structure is revealed in a zero-field-cooled sample below the ferromagnetic transition temperature of 205 K, which is replaced by separate double-walled domains and bubble domains when cooling the sample under a magnetic field of a ferromagnetic Ni tip. The Ni tip can further convert the double-walled domain to a bubble domain pattern as well as move the Neel-type chiral bubble in submicrometer distance. The temperature-dependent evolutions of both zero-field-cooled and field-cooled domain structures correlate well with the bulk magnetization from magnetometry measurements. Atomic resolution scanning tunneling images and spectroscopy are acquired to understand the atomic and electronic structures of the material, which are further corroborated by first-principles calculations.

Long-range interaction between heterogeneously charged membranes.

PubMed

Jho, Y S; Brewster, R; Safran, S A; Pincus, P A

2011-04-19

Despite their neutrality, surfaces or membranes with equal amounts of positive and negative charge can exhibit long-range electrostatic interactions if the surface charge is heterogeneous; this can happen when the surface charges form finite-size domain structures. These domains can be formed in lipid membranes where the balance of the different ranges of strong but short-ranged hydrophobic interactions and longer-ranged electrostatic repulsion result in a finite, stable domain size. If the domain size is large enough, oppositely charged domains in two opposing surfaces or membranes can be strongly correlated by the electrostatic interactions; these correlations give rise to an attractive interaction of the two membranes or surfaces over separations on the order of the domain size. We use numerical simulations to demonstrate the existence of strong attractions at separations of tens of nanometers. Large line tensions result in larger domains but also increase the charge density within the domain. This promotes correlations and, as a result, increases the intermembrane attraction. On the other hand, increasing the salt concentration increases both the domain size and degree of domain anticorrelation, but the interactions are ultimately reduced due to increased screening. The result is a decrease in the net attraction as salt concentration is increased. © 2011 American Chemical Society

Wavelet analysis of polarization maps of polycrystalline biological fluids networks

NASA Astrophysics Data System (ADS)

Ushenko, Y. A.

2011-12-01

The optical model of human joints synovial fluid is proposed. The statistic (statistic moments), correlation (autocorrelation function) and self-similar (Log-Log dependencies of power spectrum) structure of polarization two-dimensional distributions (polarization maps) of synovial fluid has been analyzed. It has been shown that differentiation of polarization maps of joint synovial fluid with different physiological state samples is expected of scale-discriminative analysis. To mark out of small-scale domain structure of synovial fluid polarization maps, the wavelet analysis has been used. The set of parameters, which characterize statistic, correlation and self-similar structure of wavelet coefficients' distributions of different scales of polarization domains for diagnostics and differentiation of polycrystalline network transformation connected with the pathological processes, has been determined.

Validation of the LupusPRO version 1.8: an update to a disease-specific patient-reported outcome tool for systemic lupus erythematosus.

PubMed

Azizoddin, D R; Weinberg, S; Gandhi, N; Arora, S; Block, J A; Sequeira, W; Jolly, M

2018-04-01

Objectives LupusPRO has shown good measurement properties as a disease-specific patient-reported outcome tool in systemic lupus erythematosus (SLE). For the purpose of clinical trials, the version 1.7 (v1.7) domain of Pain-Vitality was separated into distinct Pain, Vitality and Sleep domains in v1.8, and the psychometric properties examined. Methods A total of 131 consecutive SLE patients were self-administered surveys assessing fatigue (FACIT, SF-36), pain (Pain Inventory, SF-36), insomnia (Insomnia Severity Index), emotional health (PHQ-9, SF-36) and quality of life (SF-36, LupusPRO) at routine care visits. Internal consistency reliability (ICR) for each domain was obtained using Cronbach's alpha. The convergent construct validity of LupusPRO domains with corresponding SF-36 domains or tools were tested using Spearman correlation. Varimax rotations were conducted to assess factor structures of the LupusPRO v1.8. Results Mean (SD) age was 40.04 (14.10) years. Scores from the LupusPRO-Sleep domain strongly correlated with insomnia scores, while LupusPRO-Vitality correlated strongly with fatigue (FACIT) and SF-36 vitality. The LupusPRO-Pain domain correlated strongly with pain (SF36 Bodily-Pain, Pain Inventory) scores. Similarly, the LupusPRO domains of Physical and Emotional Health had significant correlations with corresponding SF-36 domains. The ICR for HRQoL and non-HRQoL were 0.96 and 0.81. LupusPRO (domains HRQoL and QoL) scores correlated with disease activity. Principal component analysis included seven factor loadings presenting for the HRQOL subscales (combined Sleep, Vitality, and Pain), and three factors for the NHRQoL (Combined Coping and Social Support). Conclusions LupusPRO v1.8 (including its Sleep, Vitality, and Pain domains) has acceptable reliability and validity. Use of LupusPRO as an outcome measure in clinical trials would facilitate responsiveness assessment.

Correlative live and super-resolution imaging reveals the dynamic structure of replication domains.

PubMed

Xiang, Wanqing; Roberti, M Julia; Hériché, Jean-Karim; Huet, Sébastien; Alexander, Stephanie; Ellenberg, Jan

2018-06-04

Chromosome organization in higher eukaryotes controls gene expression, DNA replication, and DNA repair. Genome mapping has revealed the functional units of chromatin at the submegabase scale as self-interacting regions called topologically associating domains (TADs) and showed they correspond to replication domains (RDs). A quantitative structural and dynamic description of RD behavior in the nucleus is, however, missing because visualization of dynamic subdiffraction-sized RDs remains challenging. Using fluorescence labeling of RDs combined with correlative live and super-resolution microscopy in situ, we determined biophysical parameters to characterize the internal organization, spacing, and mechanical coupling of RDs. We found that RDs are typically 150 nm in size and contain four co-replicating regions spaced 60 nm apart. Spatially neighboring RDs are spaced 300 nm apart and connected by highly flexible linker regions that couple their motion only <550 nm. Our pipeline allows a robust quantitative characterization of chromosome structure in situ and provides important biophysical parameters to understand general principles of chromatin organization. © 2018 Xiang et al.

Exploring the Roles of Proline in Three-Dimensional Domain Swapping from Structure Analysis and Molecular Dynamics Simulations.

PubMed

Huang, Yongqi; Gao, Meng; Su, Zhengding

2018-02-01

Three-dimensional (3D) domain swapping is a mechanism to form protein oligomers. It has been proposed that several factors, including proline residues in the hinge region, may affect the occurrence of 3D domain swapping. Although introducing prolines into the hinge region has been found to promote domain swapping for some proteins, the opposite effect has also been observed in several studies. So far, how proline affects 3D domain swapping remains elusive. In this work, based on a large set of 3D domain-swapped structures, we performed a systematic analysis to explore the correlation between the presence of proline in the hinge region and the occurrence of 3D domain swapping. We further analyzed the conformations of proline and pre-proline residues to investigate the roles of proline in 3D domain swapping. We found that more than 40% of the domain-swapped structures contained proline residues in the hinge region. Unexpectedly, conformational transitions of proline residues were rarely observed upon domain swapping. Our analyses showed that hinge regions containing proline residues preferred more extended conformations, which may be beneficial for the occurrence of domain swapping by facilitating opening of the exchanged segments.

Protein structure recognition: From eigenvector analysis to structural threading method

NASA Astrophysics Data System (ADS)

Cao, Haibo

In this work, we try to understand the protein folding problem using pair-wise hydrophobic interaction as the dominant interaction for the protein folding process. We found a strong correlation between amino acid sequence and the corresponding native structure of the protein. Some applications of this correlation were discussed in this dissertation include the domain partition and a new structural threading method as well as the performance of this method in the CASP5 competition. In the first part, we give a brief introduction to the protein folding problem. Some essential knowledge and progress from other research groups was discussed. This part include discussions of interactions among amino acids residues, lattice HP model, and the designablity principle. In the second part, we try to establish the correlation between amino acid sequence and the corresponding native structure of the protein. This correlation was observed in our eigenvector study of protein contact matrix. We believe the correlation is universal, thus it can be used in automatic partition of protein structures into folding domains. In the third part, we discuss a threading method based on the correlation between amino acid sequence and ominant eigenvector of the structure contact-matrix. A mathematically straightforward iteration scheme provides a self-consistent optimum global sequence-structure alignment. The computational efficiency of this method makes it possible to search whole protein structure databases for structural homology without relying on sequence similarity. The sensitivity and specificity of this method is discussed, along with a case of blind test prediction. In the appendix, we list the overall performance of this threading method in CASP5 blind test in comparison with other existing approaches.

Homology modeling of a Class A GPCR in the inactive conformation: A quantitative analysis of the correlation between model/template sequence identity and model accuracy.

PubMed

Costanzi, Stefano; Skorski, Matthew; Deplano, Alessandro; Habermehl, Brett; Mendoza, Mary; Wang, Keyun; Biederman, Michelle; Dawson, Jessica; Gao, Jia

2016-11-01

With the present work we quantitatively studied the modellability of the inactive state of Class A G protein-coupled receptors (GPCRs). Specifically, we constructed models of one of the Class A GPCRs for which structures solved in the inactive state are available, namely the β 2 AR, using as templates each of the other class members for which structures solved in the inactive state are also available. Our results showed a detectable linear correlation between model accuracy and model/template sequence identity. This suggests that the likely accuracy of the homology models that can be built for a given receptor can be generally forecasted on the basis of the available templates. We also probed whether sequence alignments that allow for the presence of gaps within the transmembrane domains to account for structural irregularities afford better models than the classical alignment procedures that do not allow for the presence of gaps within such domains. As our results indicated, although the overall differences are very subtle, the inclusion of internal gaps within the transmembrane domains has a noticeable a beneficial effect on the local structural accuracy of the domain in question. Copyright © 2016 Elsevier Inc. All rights reserved.

Bacterial natural product biosynthetic domain composition in soil correlates with changes in latitude on a continent-wide scale.

PubMed

Lemetre, Christophe; Maniko, Jeffrey; Charlop-Powers, Zachary; Sparrow, Ben; Lowe, Andrew J; Brady, Sean F

2017-10-31

Although bacterial bioactive metabolites have been one of the most prolific sources of lead structures for the development of small-molecule therapeutics, very little is known about the environmental factors associated with changes in secondary metabolism across natural environments. Large-scale sequencing of environmental microbiomes has the potential to shed light on the richness of bacterial biosynthetic diversity hidden in the environment, how it varies from one environment to the next, and what environmental factors correlate with changes in biosynthetic diversity. In this study, the sequencing of PCR amplicons generated using primers targeting either ketosynthase domains from polyketide biosynthesis or adenylation domains from nonribosomal peptide biosynthesis was used to assess biosynthetic domain composition and richness in soils collected across the Australian continent. Using environmental variables collected at each soil site, we looked for environmental factors that correlated with either high overall domain richness or changes in the domain composition. Among the environmental variables we measured, changes in biosynthetic domain composition correlate most closely with changes in latitude and to a lesser extent changes in pH. Although it is unclear at this time the exact mix of factors that may drive the relationship between biosynthetic domain composition and latitude, from a practical perspective the identification of a latitudinal basis for differences in soil metagenome biosynthetic domain compositions should help guide future natural product discovery efforts. Published under the PNAS license.

Investigating the structure of the restricted, repetitive behaviours and interests domain of autism.

PubMed

Szatmari, Peter; Georgiades, Stelios; Bryson, Susan; Zwaigenbaum, Lonnie; Roberts, Wendy; Mahoney, William; Goldberg, Jeremy; Tuff, Lawrence

2006-06-01

The Restricted, Repetitive Behaviours and Interests (RRBIs) are represented in the DSM-IV and measured by the Autism Diagnostic Interview-Revised (ADI-R) as one of the three homogeneous symptom categories of Pervasive Developmental Disorders. Although this conceptualisation is well accepted in the field, the grouping of symptoms is based primarily on clinical judgment rather than on empirical evidence. The objective of this study was to examine the factor structure of the RRBI domain of autism. Eleven items from this domain of the ADI-R were used in a Principal Components Analysis (PCA). Our sample consisted of 339 individuals with a Best Estimate diagnosis of Pervasive Developmental Disorder (PDD). Findings indicate that the RRBI domain is composed of two distinct factors or dimensions: Insistence on Sameness (IS) and Repetitive Sensory and Motor Behaviours (RSMB). RSMB is negatively correlated with adaptive skills; that is, lower functioning individuals tend to have higher levels of repetitive sensory and motor behaviours. On the other hand, IS is positively correlated with autistic symptoms in the communication and language domain. Further analyses suggest moderate familial aggregation among affected sibling pairs within the IS but not the RSMB factor. These results provide evidence for the heterogeneity of the RRBI domain of the ADI-R in terms of both clinical presentation and other correlates. In addition, the IS factor seems to be under familial (presumably genetic) control, while RSMB appears to simply reflect variation in developmental level.

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

Macroscopic inhomogeneous deformation behavior arising in single crystal Ni-Mn-Ga foils under tensile loading

NASA Astrophysics Data System (ADS)

Murasawa, Go; Yeduru, Srinivasa R.; Kohl, Manfred

2016-12-01

This study investigated macroscopic inhomogeneous deformation occurring in single-crystal Ni-Mn-Ga foils under uniaxial tensile loading. Two types of single-crystal Ni-Mn-Ga foil samples were examined as-received and after thermo-mechanical training. Local strain and the strain field were measured under tensile loading using laser speckle and digital image correlation. The as-received sample showed a strongly inhomogeneous strain field with intermittence under progressive deformation, but the trained sample result showed strain field homogeneity throughout the specimen surface. The as-received sample is a mainly polycrystalline-like state composed of the domain structure. The sample contains many domain boundaries and large domain structures in the body. Its structure would cause large local strain band nucleation with intermittence. However, the trained one is an ideal single-crystalline state with a transformation preferential orientation of variants after almost all domain boundary and large domain structures vanish during thermo-mechanical training. As a result, macroscopic homogeneous deformation occurs on the trained sample surface during deformation.

Light control of orbital domains: case of the prototypical manganite La0.5Sr1.5MnO4

NASA Astrophysics Data System (ADS)

Miller, Timothy; Gensch, Michael; Wall, Simon

2016-12-01

Control of electronic and structural ordering in correlated materials on the ultrafast timescale with light is a new and emerging approach to disentangle the complex interplay of the charge, spin, orbital and structural degree of freedom. In this paper we present an overview of how orbital order and orbital domains can be controlled by near IR and THz radiation in the layered manganite La0.5Sr1.5MnO4. We show how near-IR pumping can efficiently and rapidly melt orbital ordering. However, the nanoscale domain structure recovers unchanged demonstrating the importance of structural defects for the orbital domain formation. On the contrary, we show that pulsed THz fields can be used to effectively orientate the domains. In this case the alignment depends on the in-plane electric field polarisation and is induced by an energy penalty that arises from THz field induced hopping of the localised charges.

DIMA 3.0: Domain Interaction Map.

PubMed

Luo, Qibin; Pagel, Philipp; Vilne, Baiba; Frishman, Dmitrij

2011-01-01

Domain Interaction MAp (DIMA, available at http://webclu.bio.wzw.tum.de/dima) is a database of predicted and known interactions between protein domains. It integrates 5807 structurally known interactions imported from the iPfam and 3did databases and 46,900 domain interactions predicted by four computational methods: domain phylogenetic profiling, domain pair exclusion algorithm correlated mutations and domain interaction prediction in a discriminative way. Additionally predictions are filtered to exclude those domain pairs that are reported as non-interacting by the Negatome database. The DIMA Web site allows to calculate domain interaction networks either for a domain of interest or for entire organisms, and to explore them interactively using the Flash-based Cytoscape Web software.

Calculation of smooth potential energy surfaces using local electron correlation methods

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

Mata, Ricardo A.; Werner, Hans-Joachim

2006-11-14

The geometry dependence of excitation domains in local correlation methods can lead to noncontinuous potential energy surfaces. We propose a simple domain merging procedure which eliminates this problem in many situations. The method is applied to heterolytic bond dissociations of ketene and propadienone, to SN2 reactions of Cl{sup -} with alkylchlorides, and in a quantum mechanical/molecular mechanical study of the chorismate mutase enzyme. It is demonstrated that smooth potentials are obtained in all cases. Furthermore, basis set superposition error effects are reduced in local calculations, and it is found that this leads to better basis set convergence when computing barriermore » heights or weak interactions. When the electronic structure strongly changes between reactants or products and the transition state, the domain merging procedure leads to a balanced description of all structures and accurate barrier heights.« less

Infrared scanning laser ophthalmoscope imaging of the macula and its correlation with functional loss and structural changes in patients with stargardt disease.

PubMed

Anastasakis, Anastasios; Fishman, Gerald A; Lindeman, Martin; Genead, Mohamed A; Zhou, Wensheng

2011-05-01

To correlate the degree of functional loss with structural changes in patients with Stargardt disease. Eighteen eyes of 10 patients with Stargardt disease were studied. Scanning laser ophthalmoscope infrared images were compared with corresponding spectral-domain optical coherence tomography scans. Additionally, scanning laser ophthalmoscope microperimetry was performed, and results were superimposed on scanning laser ophthalmoscope infrared images and in selected cases on fundus autofluorescence images. Seventeen of 18 eyes showed a distinct hyporeflective foveal and/or perifoveal area with distinct borders on scanning laser ophthalmoscope infrared images, which was less evident on funduscopy and incompletely depicted in fundus autofluorescence images. This hyporeflective zone corresponded to areas of significantly elevated psychophysical thresholds on microperimetry testing, in addition to thinning of the retinal pigment epithelium and disorganization or loss of the photoreceptor cell inner segment-outer segment junction and external-limiting membrane on spectral-domain optical coherence tomography. Scanning laser ophthalmoscope infrared fundus images are useful for depicting retinal structural changes in patients with Stargardt disease. A spectral-domain optical coherence tomography/scanning laser ophthalmoscope microperimetry device allows for a direct correlation of structural abnormalities with functional defects that will likely be applicable for the determination of retinal areas for potential improvement of retinal function in these patients during future clinical trials and for the monitoring of the diseases' natural history.

Separate but correlated: The latent structure of space and mathematics across development.

PubMed

Mix, Kelly S; Levine, Susan C; Cheng, Yi-Ling; Young, Chris; Hambrick, D Zachary; Ping, Raedy; Konstantopoulos, Spyros

2016-09-01

The relations among various spatial and mathematics skills were assessed in a cross-sectional study of 854 children from kindergarten, third, and sixth grades (i.e., 5 to 13 years of age). Children completed a battery of spatial mathematics tests and their scores were submitted to exploratory factor analyses both within and across domains. In the within domain analyses, all of the measures formed single factors at each age, suggesting consistent, unitary structures across this age range. Yet, as in previous work, the 2 domains were highly correlated, both in terms of overall composite score and pairwise comparisons of individual tasks. When both spatial and mathematics scores were submitted to the same factor analysis, the 2 domain specific factors again emerged, but there also were significant cross-domain factor loadings that varied with age. Multivariate regressions replicated the factor analysis and further revealed that mental rotation was the best predictor of mathematical performance in kindergarten, and visual-spatial working memory was the best predictor of mathematical performance in sixth grade. The mathematical tasks that predicted the most variance in spatial skill were place value (K, 3rd, 6th), word problems (3rd, 6th), calculation (K), fraction concepts (3rd), and algebra (6th). Thus, although spatial skill and mathematics each have strong internal structures, they also share significant overlap, and have particularly strong cross-domain relations for certain tasks. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Structure-function relationships using spectral-domain optical coherence tomography: comparison with scanning laser polarimetry.

PubMed

Aptel, Florent; Sayous, Romain; Fortoul, Vincent; Beccat, Sylvain; Denis, Philippe

2010-12-01

To evaluate and compare the regional relationships between visual field sensitivity and retinal nerve fiber layer (RNFL) thickness as measured by spectral-domain optical coherence tomography (OCT) and scanning laser polarimetry. Prospective cross-sectional study. One hundred and twenty eyes of 120 patients (40 with healthy eyes, 40 with suspected glaucoma, and 40 with glaucoma) were tested on Cirrus-OCT, GDx VCC, and standard automated perimetry. Raw data on RNFL thickness were extracted for 256 peripapillary sectors of 1.40625 degrees each for the OCT measurement ellipse and 64 peripapillary sectors of 5.625 degrees each for the GDx VCC measurement ellipse. Correlations between peripapillary RNFL thickness in 6 sectors and visual field sensitivity in the 6 corresponding areas were evaluated using linear and logarithmic regression analysis. Receiver operating curve areas were calculated for each instrument. With spectral-domain OCT, the correlations (r(2)) between RNFL thickness and visual field sensitivity ranged from 0.082 (nasal RNFL and corresponding visual field area, linear regression) to 0.726 (supratemporal RNFL and corresponding visual field area, logarithmic regression). By comparison, with GDx-VCC, the correlations ranged from 0.062 (temporal RNFL and corresponding visual field area, linear regression) to 0.362 (supratemporal RNFL and corresponding visual field area, logarithmic regression). In pairwise comparisons, these structure-function correlations were generally stronger with spectral-domain OCT than with GDx VCC and with logarithmic regression than with linear regression. The largest areas under the receiver operating curve were seen for OCT superior thickness (0.963 ± 0.022; P < .001) in eyes with glaucoma and for OCT average thickness (0.888 ± 0.072; P < .001) in eyes with suspected glaucoma. The structure-function relationship was significantly stronger with spectral-domain OCT than with scanning laser polarimetry, and was better expressed logarithmically than linearly. Measurements with these 2 instruments should not be considered to be interchangeable. Copyright © 2010 Elsevier Inc. All rights reserved.

Structure-function correlations in glaucoma using matrix and standard automated perimetry versus time-domain and spectral-domain OCT devices.

PubMed

Pinto, Luciano Moreira; Costa, Elaine Fiod; Melo, Luiz Alberto S; Gross, Paula Blasco; Sato, Eduardo Toshio; Almeida, Andrea Pereira; Maia, Andre; Paranhos, Augusto

2014-04-10

We examined the structure-function relationship between two perimetric tests, the frequency doubling technology (FDT) matrix and standard automated perimetry (SAP), and two optical coherence tomography (OCT) devices (time-domain and spectral-domain). This cross-sectional study included 97 eyes from 29 healthy individuals, and 68 individuals with early, moderate, or advanced primary open-angle glaucoma. The correlations between overall and sectorial parameters of retinal nerve fiber layer thickness (RNFL) measured with Stratus and Spectralis OCT, and the visual field sensitivity obtained with FDT matrix and SAP were assessed. The relationship also was evaluated using a previously described linear model. The correlation coefficients for the threshold sensitivity measured with SAP and Stratus OCT ranged from 0.44 to 0.79, and those for Spectralis OCT ranged from 0.30 to 0.75. Regarding FDT matrix, the correlation ranged from 0.40 to 0.79 with Stratus OCT and from 0.39 to 0.79 with Spectralis OCT. Stronger correlations were found in the overall measurements and the arcuate sectors for both visual fields and OCT devices. A linear relationship was observed between FDT matrix sensitivity and the OCT devices. The previously described linear model fit the data from SAP and the OCT devices well, particularly in the inferotemporal sector. The FDT matrix and SAP visual sensitivities were related strongly to the RNFL thickness measured with the Stratus and Spectralis OCT devices, particularly in the overall and arcuate sectors. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

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

Crystal Structure of the HEAT Domain from the Pre-mRNA Processing Factor Symplekin

PubMed Central

Kennedy, Sarah A.; Frazier, Monica L.; Steiniger, Mindy; Mast, Ann M.; Marzluff, William F.; Redinbo, Matthew R.

2009-01-01

The majority of eukaryotic pre-mRNAs are processed by 3′-end cleavage and polyadenylation, although in metazoa the replication-dependant histone mRNAs are processed by 3′-end cleavage but not polyadenylation. The macromolecular complex responsible for processing both canonical and histone pre-mRNAs contains the ~1,160-residue protein Symplekin. Secondary structural prediction algorithms identified putative HEAT domains in the 300 N-terminal residues of all Symplekins of known sequence. The structure and dynamics of this domain were investigated to begin elucidating the role Symplekin plays in mRNA maturation. The crystal structure of the Drosophila melanogaster Symplekin HEAT domain was determined to 2.4 Å resolution using SAD phasing methods. The structure exhibits 5 canonical HEAT repeats along with an extended 31 amino acid loop (loop 8) between the fourth and fifth repeat that is conserved within closely related Symplekin sequences. Molecular dynamics simulations of this domain show that the presence of loop 8 dampens correlated and anticorrelated motion in the HEAT domain, therefore providing a neutral surface for potential protein-protein interactions. HEAT domains are often employed for such macromolecular contacts. The Symplekin HEAT region not only structurally aligns with several established scaffolding proteins, but also has been reported to contact proteins essential for regulating 3′-end processing. Taken together, these data support the conclusion that the Symplekin HEAT domain serves as a scaffold for protein-protein interactions essential to the mRNA maturation process. PMID:19576221

Correlative Microscopy of Vitreous Sections Provides Insights into BAR-Domain Organization In Situ.

PubMed

Bharat, Tanmay A M; Hoffmann, Patrick C; Kukulski, Wanda

2018-04-10

Electron microscopy imaging of macromolecular complexes in their native cellular context is limited by the inherent difficulty to acquire high-resolution tomographic data from thick cells and to specifically identify elusive structures within crowded cellular environments. Here, we combined cryo-fluorescence microscopy with electron cryo-tomography of vitreous sections into a coherent correlative microscopy workflow, ideal for detection and structural analysis of elusive protein assemblies in situ. We used this workflow to address an open question on BAR-domain coating of yeast plasma membrane compartments known as eisosomes. BAR domains can sense or induce membrane curvature, and form scaffold-like membrane coats in vitro. Our results demonstrate that in cells, the BAR protein Pil1 localizes to eisosomes of varying membrane curvature. Sub-tomogram analysis revealed a dense protein coat on curved eisosomes, which was not present on shallow eisosomes, indicating that while BAR domains can assemble at shallow membranes in vivo, scaffold formation is tightly coupled to curvature generation. Copyright © 2018 MRC Laboratory of Molecular Biology. Published by Elsevier Ltd.. All rights reserved.

Intrinsic motions in the N-terminal domain of an ionotropic glutamate receptor detected by fluorescence correlation spectroscopy.

PubMed

Jensen, Mette H; Sukumaran, Madhav; Johnson, Christopher M; Greger, Ingo H; Neuweiler, Hannes

2011-11-18

Ionotropic glutamate receptors (iGluRs) mediate excitatory neurotransmission in the central nervous system and play key roles in brain development and disease. iGluRs have two distinct extracellular domains, but the functional role of the distal N-terminal domain (NTD) is poorly understood. Crystal structures of the NTD from some non-N-methyl-d-aspartate (NMDA) iGluRs are consistent with a rigid body that facilitates receptor assembly but suggest an additional dynamic role that could modulate signaling. Here, we moved beyond spatial and temporal limitations of conventional protein single-molecule spectroscopy by employing correlation analysis of extrinsic oxazine fluorescence fluctuations. We observed nanosecond (ns)-to-microsecond (μs) motions of loop segments and helices within a region of an AMPA-type iGluR NTD, which has been identified previously to be structurally variable. Our data reveal that the AMPA receptor NTD undergoes rapid conformational fluctuations, suggesting an inherent allosteric capacity for this domain in addition to its established assembly function. Copyright © 2011 Elsevier Ltd. All rights reserved.

Conduction at domain walls in oxide multiferroics

NASA Astrophysics Data System (ADS)

Seidel, J.; Martin, L. W.; He, Q.; Zhan, Q.; Chu, Y.-H.; Rother, A.; Hawkridge, M. E.; Maksymovych, P.; Yu, P.; Gajek, M.; Balke, N.; Kalinin, S. V.; Gemming, S.; Wang, F.; Catalan, G.; Scott, J. F.; Spaldin, N. A.; Orenstein, J.; Ramesh, R.

2009-03-01

Domain walls may play an important role in future electronic devices, given their small size as well as the fact that their location can be controlled. Here, we report the observation of room-temperature electronic conductivity at ferroelectric domain walls in the insulating multiferroic BiFeO3. The origin and nature of the observed conductivity are probed using a combination of conductive atomic force microscopy, high-resolution transmission electron microscopy and first-principles density functional computations. Our analyses indicate that the conductivity correlates with structurally driven changes in both the electrostatic potential and the local electronic structure, which shows a decrease in the bandgap at the domain wall. Additionally, we demonstrate the potential for device applications of such conducting nanoscale features.

Conduction at domain walls in oxide multiferroics.

PubMed

Seidel, J; Martin, L W; He, Q; Zhan, Q; Chu, Y-H; Rother, A; Hawkridge, M E; Maksymovych, P; Yu, P; Gajek, M; Balke, N; Kalinin, S V; Gemming, S; Wang, F; Catalan, G; Scott, J F; Spaldin, N A; Orenstein, J; Ramesh, R

2009-03-01

Domain walls may play an important role in future electronic devices, given their small size as well as the fact that their location can be controlled. Here, we report the observation of room-temperature electronic conductivity at ferroelectric domain walls in the insulating multiferroic BiFeO(3). The origin and nature of the observed conductivity are probed using a combination of conductive atomic force microscopy, high-resolution transmission electron microscopy and first-principles density functional computations. Our analyses indicate that the conductivity correlates with structurally driven changes in both the electrostatic potential and the local electronic structure, which shows a decrease in the bandgap at the domain wall. Additionally, we demonstrate the potential for device applications of such conducting nanoscale features.

A new method for the assessment of patient safety competencies during a medical school clerkship using an objective structured clinical examination

PubMed Central

Daud-Gallotti, Renata Mahfuz; Morinaga, Christian Valle; Arlindo-Rodrigues, Marcelo; Velasco, Irineu Tadeu; Arruda Martins, Milton; Tiberio, Iolanda Calvo

2011-01-01

INTRODUCTION: Patient safety is seldom assessed using objective evaluations during undergraduate medical education. OBJECTIVE: To evaluate the performance of fifth-year medical students using an objective structured clinical examination focused on patient safety after implementation of an interactive program based on adverse events recognition and disclosure. METHODS: In 2007, a patient safety program was implemented in the internal medicine clerkship of our hospital. The program focused on human error theory, epidemiology of incidents, adverse events, and disclosure. Upon completion of the program, students completed an objective structured clinical examination with five stations and standardized patients. One station focused on patient safety issues, including medical error recognition/disclosure, the patient-physician relationship and humanism issues. A standardized checklist was completed by each standardized patient to assess the performance of each student. The student's global performance at each station and performance in the domains of medical error, the patient-physician relationship and humanism were determined. The correlations between the student performances in these three domains were calculated. RESULTS: A total of 95 students participated in the objective structured clinical examination. The mean global score at the patient safety station was 87.59±1.24 points. Students' performance in the medical error domain was significantly lower than their performance on patient-physician relationship and humanistic issues. Less than 60% of students (n = 54) offered the simulated patient an apology after a medical error occurred. A significant correlation was found between scores obtained in the medical error domains and scores related to both the patient-physician relationship and humanistic domains. CONCLUSIONS: An objective structured clinical examination is a useful tool to evaluate patient safety competencies during the medical student clerkship. PMID:21876976

Topologically-associating domains are stable units of replication-timing regulation

PubMed Central

Pope, Benjamin D.; Ryba, Tyrone; Dileep, Vishnu; Yue, Feng; Wu, Weisheng; Denas, Olgert; Vera, Daniel L.; Wang, Yanli; Hansen, R. Scott; Canfield, Theresa K.; Thurman, Robert E.; Cheng, Yong; Gülsoy, Günhan; Dennis, Jonathan H.; Snyder, Michael P.; Stamatoyannopoulos, John A.; Taylor, James; Hardison, Ross C.; Kahveci, Tamer; Ren, Bing; Gilbert, David M.

2014-01-01

Summary Eukaryotic chromosomes replicate in a temporal order known as the replication-timing program1. During mammalian development, at least half the genome changes replication timing, primarily in units of 400–800 kb (“replication domains”; RDs), whose positions are preserved in different cell types, conserved between species, and appear to confine long-range effects of chromosome rearrangements2–7. Early and late replication correlate strongly with open and closed chromatin compartments identified by high-resolution chromosome conformation capture (Hi-C), and, to a lesser extent, lamina-associated domains (LADs)4,5,8,9. Recent Hi-C mapping has unveiled a substructure of topologically-associating domains (TADs) that are largely conserved in their positions between cell types and are similar in size to RDs8,10. However, TADs can be further sub-stratified into smaller domains, challenging the significance of structures at any particular scale11,12. Moreover, attempts to reconcile TADs and LADs to replication-timing data have not revealed a common, underlying domain structure8,9,13. Here, we localize boundaries of RDs to the early-replicating border of replication-timing transitions and map their positions in 18 human and 13 mouse cell types. We demonstrate that, collectively, RD boundaries share a near one-to-one correlation with TAD boundaries, whereas within a cell type, adjacent TADs that replicate at similar times obscure RD boundaries, largely accounting for the previously reported lack of alignment. Moreover, cell-type specific replication timing of TADs partitions the genome into two large-scale sub-nuclear compartments revealing that replication-timing transitions are indistinguishable from late-replicating regions in chromatin composition and lamina association and accounting for the reduced correlation of replication timing to LADs and heterochromatin. Our results reconcile cell type specific sub-nuclear compartmentalization with developmentally stable chromosome domains and offer a unified model for large-scale chromosome structure and function. PMID:25409831

Recent advances in MeCP2 structure and function1

PubMed Central

Hite, Kristopher C.; Adams, Valerie H.; Hansen, Jeffrey C.

2010-01-01

Mutations in methyl DNA binding protein 2 (MeCP2) cause the neurodevelopmental disorder Rett syndrome (RTT). The mechanism(s) by which the native MeCP2 protein operates in the cell are not well understood. Historically, MeCP2 has been characterized as a proximal gene silencer with 2 functional domains: a methyl DNA binding domain and a transcription repression domain. However, several lines of new data indicate that MeCP2 structure and function relationships are more complex. In this review, we first discuss recent studies that have advanced understanding of the basic structural biochemistry of MeCP2. This is followed by an analysis of cell-based experiments suggesting MeCP2 is a regulator, rather than a strict silencer, of transcription. The new data establish MeCP2 as a multifunctional nuclear protein, with potentially important roles in chromatin architecture, regulation of RNA splicing, and active transcription. We conclude by discussing clinical correlations between domain-specific mutations and RTT pathology to stress that all structural domains of MeCP2 are required to properly mediate cellular function of the intact protein. PMID:19234536

Investigation of the nanodomain structure formation by piezoelectric force microscopy and Raman confocal microscopy in LiNbO3 and LiTaO3 crystals

NASA Astrophysics Data System (ADS)

Shur, V. Ya.; Zelenovskiy, P. S.; Nebogatikov, M. S.; Alikin, D. O.; Sarmanova, M. F.; Ievlev, A. V.; Mingaliev, E. A.; Kuznetsov, D. K.

2011-09-01

Piezoelectric force microscopy (PFM) and Raman confocal microscopy have been used for studying the nanodomain structures in congruent LiNbO3 and LiTaO3 crystals. The high-resolution nanodomain images at the surface were observed via PFM. Raman confocal microscopy has been used for the visualization of the nanodomain structures in the bulk via layer-by-layer scanning at various depths. It has been shown experimentally that the nanodomain images obtained at different depths correspond to domain images at the polar surface obtained at different moments: the deeper the nanodomain, the earlier the moment. Such a correlation was applied for the reconstruction of the evolution of the domain structures with charged domain walls. The studied domain structures were obtained in highly non-equilibrium switching conditions realized in LiNbO3 and LiTaO3 via pulse laser irradiation and the electric field poling of LiNbO3, with the surface layer modified by ion implantation. The revealed main stages of the domain structure evolution allow the authors to demonstrate that all geometrically different nanodomain structures observed in LiNbO3 and LiTaO3 appeared as a result of discrete switching.

Collagenolytic Matrix Metalloproteinase Structure-Function Relationships: Insights From Molecular Dynamics Studies.

PubMed

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

2017-01-01

Several members of the zinc-dependent matrix metalloproteinase (MMP) family catalyze collagen degradation. Experimental data reveal a collaboration between different MMP domains in order to achieve efficient collagenolysis. Molecular dynamics (MD) simulations have been utilized to provide atomistic details of the collagenolytic process. The triple-helical structure of collagen exhibits local regions of flexibility, with modulation of interchain salt bridges and water bridges contributing to accessibility of individual chains by the enzyme. In turn, the hemopexin-like (HPX) domain of the MMP initially binds the triple helix and facilitates the presentation of individual strands to active site in the catalytic (CAT) domain. Extensive positive and negative correlated motions are observed between the CAT and HPX domains when collagen is bound. Ultimately, the MD simulation studies have complemented structural (NMR spectroscopy, X-ray crystallography) and kinetic analyses to provide a more detailed mechanistic view of MMP-catalyzed collagenolysis. © 2017 Elsevier Inc. All rights reserved.

Ketide Synthase (KS) Domain Prediction and Analysis of Iterative Type II PKS Gene in Marine Sponge-Associated Actinobacteria Producing Biosurfactants and Antimicrobial Agents

PubMed Central

Selvin, Joseph; Sathiyanarayanan, Ganesan; Lipton, Anuj N.; Al-Dhabi, Naif Abdullah; Valan Arasu, Mariadhas; Kiran, George S.

2016-01-01

The important biological macromolecules, such as lipopeptide and glycolipid biosurfactant producing marine actinobacteria were analyzed and their potential linkage between type II polyketide synthase (PKS) genes was explored. A unique feature of type II PKS genes is their high amino acid (AA) sequence homology and conserved gene organization. These enzymes mediate the biosynthesis of polyketide natural products with enormous structural complexity and chemical nature by combinatorial use of various domains. Therefore, deciphering the order of AA sequence encoded by PKS domains tailored the chemical structure of polyketide analogs still remains a great challenge. The present work deals with an in vitro and in silico analysis of PKS type II genes from five actinobacterial species to correlate KS domain architecture and structural features. Our present analysis reveals the unique protein domain organization of iterative type II PKS and KS domain of marine actinobacteria. The findings of this study would have implications in metabolic pathway reconstruction and design of semi-synthetic genomes to achieve rational design of novel natural products. PMID:26903957

Mathematical correlation of modal parameter identification methods via system realization theory

NASA Technical Reports Server (NTRS)

Juang, J. N.

1986-01-01

A unified approach is introduced using system realization theory to derive and correlate modal parameter identification methods for flexible structures. Several different time-domain and frequency-domain methods are analyzed and treated. A basic mathematical foundation is presented which provides insight into the field of modal parameter identification for comparison and evaluation. The relation among various existing methods is established and discussed. This report serves as a starting point to stimulate additional research towards the unification of the many possible approaches for modal parameter identification.

Characteristic Lifelength of Coherent Structure in the Turbulent Boundary Layer

NASA Technical Reports Server (NTRS)

Palumbo, Daniel L.

2006-01-01

A characteristic lifelength is defined by which a Gaussian distribution is fit to data correlated over a 3 sensor array sampling streamwise sidewall pressure. The data were acquired at subsonic, transonic and supersonic speeds aboard a Tu-144. Lifelengths are estimated using the cross spectrum and are shown to compare favorably with Efimtsov's prediction of correlation space scales. Lifelength distributions are computed in the time/frequency domain using an interval correlation technique on the continuous wavelet transform of the original time data. The median values of the lifelength distributions are found to be very close to the frequency averaged result. The interval correlation technique is shown to allow the retrieval and inspection of the original time data of each event in the lifelength distribution, thus providing a means to locate and study the nature of the coherent structure in the turbulent boundary layer. The lifelength data can be converted to lifetimes using the convection velocity. The lifetime of events in the time/frequency domain are displayed in Lifetime Maps. The primary purpose of the paper is to validate these new analysis techniques so that they can be used with confidence to further characterize coherent structure in the turbulent boundary layer.

[Correlation between quality of life and morbidity of the caregivers of elderly stroke patients].

PubMed

Santos, Nilce Maria de Freitas; Tavares, Darlene Mara Dos Santos

2012-08-01

The objective of this study was to describe the sociodemographic characteristics and the quality of life of the caregivers of elderly individuals with a stroke history, and correlate morbidity with the caregivers' quality of life scores. This is a cross-sectional household survey that interviewed the caregivers of elderly individuals using the following tools: a semi-structured instrument; the World Health Organization Quality of life-BREF; and the Brazilian Multidimensional Functional Assessment Questionnaire. Descriptive analysis and Pearson's correlation (p<0.05) were performed. Most participants were female (93.5%), with a mean age of 55.4±14.17 years, married or living with a partner (58.7%), with four to eight years of education (28.3%), and an income equivalent to one minimum wage salary (34.8%). The highest quality of life score was in the social relations domain (67.57) and the lowest was in the environmental domain (54.82). The highest number of caregiver morbidities correlated with the lowest scores in all quality of life domains.

Comparative Reliability of Structured Versus Unstructured Interviews in the Admission Process of a Residency Program

PubMed Central

Blouin, Danielle; Day, Andrew G.; Pavlov, Andrey

2011-01-01

Background Although never directly compared, structured interviews are reported as being more reliable than unstructured interviews. This study compared the reliability of both types of interview when applied to a common pool of applicants for positions in an emergency medicine residency program. Methods In 2008, one structured interview was added to the two unstructured interviews traditionally used in our resident selection process. A formal job analysis using the critical incident technique guided the development of the structured interview tool. This tool consisted of 7 scenarios assessing 4 of the domains deemed essential for success as a resident in this program. The traditional interview tool assessed 5 general criteria. In addition to these criteria, the unstructured panel members were asked to rate each candidate on the same 4 essential domains rated by the structured panel members. All 3 panels interviewed all candidates. Main outcomes were the overall, interitem, and interrater reliabilities, the correlations between interview panels, and the dimensionality of each interview tool. Results Thirty candidates were interviewed. The overall reliability reached 0.43 for the structured interview, and 0.81 and 0.71 for the unstructured interviews. Analyses of the variance components showed a high interrater, low interitem reliability for the structured interview, and a high interrater, high interitem reliability for the unstructured interviews. The summary measures from the 2 unstructured interviews were significantly correlated, but neither was correlated with the structured interview. Only the structured interview was multidimensional. Conclusions A structured interview did not yield a higher overall reliability than both unstructured interviews. The lower reliability is explained by a lower interitem reliability, which in turn is due to the multidimensionality of the interview tool. Both unstructured panels consistently rated a single dimension, even when prompted to assess the 4 specific domains established as essential to succeed in this residency program. PMID:23205201

Comparative reliability of structured versus unstructured interviews in the admission process of a residency program.

PubMed

Blouin, Danielle; Day, Andrew G; Pavlov, Andrey

2011-12-01

Although never directly compared, structured interviews are reported as being more reliable than unstructured interviews. This study compared the reliability of both types of interview when applied to a common pool of applicants for positions in an emergency medicine residency program. In 2008, one structured interview was added to the two unstructured interviews traditionally used in our resident selection process. A formal job analysis using the critical incident technique guided the development of the structured interview tool. This tool consisted of 7 scenarios assessing 4 of the domains deemed essential for success as a resident in this program. The traditional interview tool assessed 5 general criteria. In addition to these criteria, the unstructured panel members were asked to rate each candidate on the same 4 essential domains rated by the structured panel members. All 3 panels interviewed all candidates. Main outcomes were the overall, interitem, and interrater reliabilities, the correlations between interview panels, and the dimensionality of each interview tool. Thirty candidates were interviewed. The overall reliability reached 0.43 for the structured interview, and 0.81 and 0.71 for the unstructured interviews. Analyses of the variance components showed a high interrater, low interitem reliability for the structured interview, and a high interrater, high interitem reliability for the unstructured interviews. The summary measures from the 2 unstructured interviews were significantly correlated, but neither was correlated with the structured interview. Only the structured interview was multidimensional. A structured interview did not yield a higher overall reliability than both unstructured interviews. The lower reliability is explained by a lower interitem reliability, which in turn is due to the multidimensionality of the interview tool. Both unstructured panels consistently rated a single dimension, even when prompted to assess the 4 specific domains established as essential to succeed in this residency program.

Pattern, growth, and aging in aggregation kinetics of a Vicsek-like active matter model

NASA Astrophysics Data System (ADS)

Das, Subir K.

2017-01-01

Via molecular dynamics simulations, we study kinetics in a Vicsek-like phase-separating active matter model. Quantitative results, for isotropic bicontinuous pattern, are presented on the structure, growth, and aging. These are obtained via the two-point equal-time density-density correlation function, the average domain length, and the two-time density autocorrelation function. Both the correlation functions exhibit basic scaling properties, implying self-similarity in the pattern dynamics, for which the average domain size exhibits a power-law growth in time. The equal-time correlation has a short distance behavior that provides reasonable agreement between the corresponding structure factor tail and the Porod law. The autocorrelation decay is a power-law in the average domain size. Apart from these basic similarities, the overall quantitative behavior of the above-mentioned observables is found to be vastly different from those of the corresponding passive limit of the model which also undergoes phase separation. The functional forms of these have been quantified. An exceptionally rapid growth in the active system occurs due to fast coherent motion of the particles, mean-squared-displacements of which exhibit multiple scaling regimes, including a long time ballistic one.

Molecular dynamics simulations of domain motions of substrate-free S-adenosyl- L-homocysteine hydrolase in solution.

PubMed

Hu, Chen; Fang, Jianwen; Borchardt, Ronald T; Schowen, Richard L; Kuczera, Krzysztof

2008-04-01

S-Adenosyl-L-homocysteine hydrolase (SAHH) is an enzyme regulating intracellular methylation reactions. The homotetrameric SAHH exists in an open conformation in absence of substrate, while enzyme:inhibitor complexes crystallize in the closed conformation, in which the ligands are engulfed by the protein due to an 18 degrees domain reorientation within each of the four subunits. We present a microscopic description of the structure and dynamics of the substrate-free, NAD(+)-bound SAHH in solution, based on a 15-ns molecular dynamics simulation in explicit solvent. In the trajectory, the four cofactor-binding domains formed a relatively rigid core with structure very similar to the crystal conformation. The four substrate-binding domains, located at the protein exterior, also retained internal structures similar to the crystal, while undergoing large amplitude rigid-body reorientations. The trajectory domain motions exhibited two interesting properties. First, within each subunit the domains fluctuated between open and closed conformations, while at the tetramer level 80% of the domain motions were perpendicular to the direction of the open-to-closed structural transition. Second, the domain reorientations in solution could be represented as a sum of two components, faster, with 20-50 ps correlation time and 3-4 degrees amplitude, and slower, with 8-23 ns correlation time and amplitude of 14-22 degrees . The faster motion is similar to the 1.5 cm(-1) frequency hinge-bending vibrations found in our recent normal mode analysis (Wang et al., Biochemistry 2005;44:7228-7239). The slower motion agrees with fluorescence anisotropy decay measurements, which detected a 10-20 ns domain reorientation of ca. 26 degrees amplitude in the substrate-free enzyme (Wang et al., Biochemistry 2006;45:7778-7786). Our simulations are thus in excellent agreement with experimental data. The simulations allow us to assign the observed nanosecond fluorescence anisotropy signal to fluctuations in domain orientations, and indicate that the microscopic mechanism of the motion involves rotational diffusion within a cone of 10-20 degrees . Overall, our simulation results complement the existing experimental data and provide important new insights into SAHH domain motions in solution, which play a crucial role in the catalytic mechanism of SAHH. (c) 2007 Wiley-Liss, Inc.

Microstructure changes of on the extruded high-amylose bionanocomposites as affected by moisture content via synchrotron radiation studies

NASA Astrophysics Data System (ADS)

Liu, Huihua; Chaudhary, Deeptangshu

2014-08-01

The crystalline domain changes and lamellar structure observations of sorbitol-plasticized starch nanocomposite had been investigated via synchrotron. Strong interactions were found between amylose-sorbitol, resulting in reduced inter-helix spacing of the starch polymer. Achievable dspacing of nanoclay was confirmed to be correlated to the moisture content (mc) within the nanocomposites. SAXS diffraction patterns changed from circular (high mc samples) to elliptical (low mc samples), indicating the formation of long periodic structure and increased heterogeneities of the electron density within the samples. Two different domains sized at around 90 Å and 350 Å were found for the low mc samples. However, only the ~90 Å domain was observed in high mc samples. Formation of the 380 Å domain is attributed to the retrogradation behaviour in the absence of water molecules. Meanwhile, the nucleation effect of nanoclay is another factor leading to the emergence of the larger crystalline domain.

Latitudinal concordance between biogeographic regionalization, community structure, and richness patterns: a study on the reptiles of China

NASA Astrophysics Data System (ADS)

Chen, Youhua; Srivastava, Diane S.

2015-02-01

Latitudinal patterns in species richness may be affected by both continuous variations in macroecological factors as well as discrete change between biogeographic regions. We examined whether latitudinal reptilian richness and community structure in China were best explained by three macroecological patterns (mid-domain effects, Rapoport's rule effects, or environmental correlates) within or across the ranges of biogeographic realms. The results showed that (1) there was a weak mid-domain effect within the Oriental Realm. However, the mid-domain effect was detected neither at the overall regional scale nor in the Palaearctic Realm. (2) Rapoport's rule was only weakly supported for reptilian fauna in China at lower latitudinal areas. (3) Environmental variables were more strongly correlated with species' latitudinal community structure and richness patterns at the scale of biogeographic realms. Based on the faunal similarity of reptilian community across latitudinal bands, we proposed a latitudinal delineation scheme at 34° N for dividing East Asia into Oriental and Palaearctic biogeographic realms. At last, at the functional group level, we also evaluated the relevant ecological patterns for lizard and snake species across different latitudinal bins, showing that the distributions of lizards presented strong mid-domain effects at the latitudinal ranges within the Oriental Realm and over the whole range but did not support Rapoport's rule. In comparison, snake species supported Rapoport's rule at low latitudinal zones but did not present any remarkable mid-domain effects at any spatial extents. In conclusion, biogeographic realms are an appropriate scale for studying macroecological patterns. Reptilian latitudinal richness patterns of China were explained by a combination of environmental factors and geometric constraints, while the latitudinal community structure patterns were greatly affected by environmental gradients. Functional guilds present differentiated macroecological patterns along the latitudinal gradients.

The structure of psychological life satisfaction: insights from farmers and a general community sample in Australia

PubMed Central

2012-01-01

Background Psychological life satisfaction is a robust predictor of wellbeing. Public health measures to improve wellbeing would benefit from an understanding of how overall life satisfaction varies as a function of satisfaction with multiple life domains, an area that has been little explored. We examine a sample of drought-affected Australian farmers and a general community sample of Australians to investigate how domain satisfaction combines to form psychological satisfaction. In particular, we introduce a way of statistically testing for the presence of “supra-domains” of satisfaction to propose a novel way of examining the composition of psychological life satisfaction to gain insights for health promotion and policy. Methods Covariance between different perceptions of life domain satisfaction was identified by conducting correlation, regression, and exploratory factor analyses on responses to the Personal Wellbeing Index. Structural equations modelling was then used to (a) validate satisfaction supra-domain constructs emerging from different perceptions of life domain satisfaction, and (b) model relationships between supra-domains and an explicit measure of psychological life satisfaction. Results Perceived satisfaction with eight different life domains loaded onto a single unitary satisfaction construct adequately in each sample. However, in both samples, different domains better loaded onto two separate but correlated constructs (‘supra-domains’): “satisfaction with connectedness” and “satisfaction with efficacy”. Modelling reciprocal pathways between these supra-domains and an explicit measure of psychological life satisfaction revealed that efficacy mediated the link between connectedness and psychological satisfaction. Conclusions If satisfaction with connectedness underlies satisfaction with efficacy (and thus psychological satisfaction), a novel insight for health policy emerges: psychological life satisfaction, a vital part of wellbeing, can potentially be enhanced by strengthening individuals’ connectedness to community. This may be particularly important and efficacious for vulnerable populations. PMID:23148533

Mapping and Engineering Functional Domains of the Assembly Activating Protein of Adeno-Associated Viruses.

PubMed

Tse, Longping V; Moller-Tank, Sven; Meganck, Rita M; Asokan, Aravind

2018-04-25

Adeno-associated viruses (AAV) encode a unique assembly activating protein (AAP) within their genome that is essential for capsid assembly. Studies to date have focused on establishing the role of AAP as a chaperone that mediates stability, nucleolar transport, and assembly of AAV capsid proteins. Here, we map structure-function correlates of AAP using secondary structure analysis followed by deletion and substitutional mutagenesis of specific domains, namely, the hydrophobic N-terminal domain (HR), conserved core (CC), proline-rich region (PRR), threonine/serine rich region (T/S) and basic region (BR). First, we establish that the centrally located PRR and T/S regions are flexible linker domains that can either be deleted completely or replaced by heterologous functional domains that enable ancillary functions such as fluorescent imaging or increased AAP stability. We also demonstrate that the C-terminal BR domains can be substituted with heterologous nuclear or nucleolar localization sequences that display varying ability to support AAV capsid assembly. Further, by replacing the BR domain with immunoglobulin (IgG) Fc domains, we assessed AAP complexation with AAV capsid subunits and demonstrate that the hydrophobic region (HR) and the conserved core (CC) in the AAP N-terminus are the sole determinants for viral protein (VP) recognition. However, VP recognition alone is not sufficient for capsid assembly. Our study sheds light on the modular structure-function correlates of AAP and provides multiple approaches to engineer AAP that might prove useful towards understanding and controlling AAV capsid assembly. Importance: Adeno-associated viruses (AAV) encode a unique assembly activating protein (AAP) within their genome that is essential for capsid assembly. Understanding how AAP acts as a chaperone for viral assembly could help improve efficiency and potentially control this process. Our studies reveal that AAP has a modular architecture, with each module playing a distinct role and can be engineered for carrying out new functions. Copyright © 2018 American Society for Microbiology.

Correlating structure and function during the evolution of fibrinogen-related domains

PubMed Central

Doolittle, Russell F; McNamara, Kyle; Lin, Kevin

2012-01-01

Fibrinogen-related domains (FReDs) are found in a variety of animal proteins with widely different functions, ranging from non-self recognition to clot formation. All appear to have a common surface where binding of one sort or other occurs. An examination of 19 completed animal genomes—including a sponge and sea anemone, six protostomes, and 11 deuterostomes—has allowed phylogenies to be constructed that show where various types of FReP (proteins containing FReDs) first made their appearance. Comparisons of sequences and structures also reveal particular features that correlate with function, including the influence of neighbor-domains. A particular set of insertions in the carboxyl-terminal subdomain was involved in the transition from structures known to bind sugars to those known to bind amino-terminal peptides. Perhaps not unexpectedly, FReDs with different functions have changed at different rates, with ficolins by far the fastest changing group. Significantly, the greatest amount of change in ficolin FReDs occurs in the third subdomain (“P domain”), the very opposite of the situation in most other vertebrate FReDs. The unbalanced style of change was also observed in FReDs from non-chordates, many of which have been implicated in innate immunity. PMID:23076991

Domain walls and ferroelectric reversal in corundum derivatives

NASA Astrophysics Data System (ADS)

Ye, Meng; Vanderbilt, David

2017-01-01

Domain walls are the topological defects that mediate polarization reversal in ferroelectrics, and they may exhibit quite different geometric and electronic structures compared to the bulk. Therefore, a detailed atomic-scale understanding of the static and dynamic properties of domain walls is of pressing interest. In this work, we use first-principles methods to study the structures of 180∘ domain walls, both in their relaxed state and along the ferroelectric reversal pathway, in ferroelectrics belonging to the family of corundum derivatives. Our calculations predict their orientation, formation energy, and migration energy and also identify important couplings between polarization, magnetization, and chirality at the domain walls. Finally, we point out a strong empirical correlation between the height of the domain-wall-mediated polarization reversal barrier and the local bonding environment of the mobile A cations as measured by bond-valence sums. Our results thus provide both theoretical and empirical guidance for future searches for ferroelectric candidates in materials of the corundum derivative family.

Domain walls and ferroelectric reversal in corundum derivatives

NASA Astrophysics Data System (ADS)

Ye, Meng; Vanderbilt, David

Domain walls are the topological defects that mediate polarization reversal in ferroelectrics, and they may exhibit quite different geometric and electronic structures compared to the bulk. Therefore, a detailed atomic-scale understanding of the static and dynamic properties of domain walls is of pressing interest. In this work, we use first-principles methods to study the structures of 180° domain walls, both in their relaxed state and along the ferroelectric reversal pathway, in ferroelectrics belonging to the family of corundum derivatives. Our calculations predict their orientation, formation energy, and migration energy, and also identify important couplings between polarization, magnetization, and chirality at the domain walls. Finally, we point out a strong empirical correlation between the height of the domain-wall mediated polarization reversal barrier and the local bonding environment of the mobile A cations as measured by bond valence sums. Our results thus provide both theoretical and empirical guidance to further search for ferroelectric candidates in materials of the corundum derivative family. The work is supported by ONR Grant N00014-12-1-1035.

Structure of Methylobacterium extorquens malyl-CoA lyase: CoA-substrate binding correlates with domain shift

DOE PAGES

Gonzalez, Javier M.; Marti-Arbona, Ricardo; Chen, Julian C. -H.; ...

2017-01-27

Malyl-CoA lyase (MCL) is an Mg 2+-dependent enzyme that catalyzes the reversible cleavage of (2 S)-4-malyl-CoA to yield acetyl-CoA and glyoxylate. MCL enzymes, which are found in a variety of bacteria, are members of the citrate lyase-like family and are involved in the assimilation of one- and two-carbon compounds. Here, the 1.56 Å resolution X-ray crystal structure of MCL from Methylobacterium extorquens AM1 with bound Mg 2+is presented. Structural alignment with the closely related Rhodobacter sphaeroides malyl-CoA lyase complexed with Mg 2+, oxalate and CoA allows a detailed analysis of the domain motion of the enzyme caused by substrate binding.more » Alignment of the structures shows that a simple hinge motion centered on the conserved residues Phe268 and Thr269 moves the C-terminal domain by about 30° relative to the rest of the molecule. Furthermore, this domain motion positions a conserved aspartate residue located in the C-terminal domain in the active site of the adjacent monomer, which may serve as a general acid/base in the catalytic mechanism.« less

Structure of Methylobacterium extorquens malyl-CoA lyase: CoA-substrate binding correlates with domain shift

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

Gonzalez, Javier M.; Marti-Arbona, Ricardo; Chen, Julian C. -H.

Malyl-CoA lyase (MCL) is an Mg 2+-dependent enzyme that catalyzes the reversible cleavage of (2 S)-4-malyl-CoA to yield acetyl-CoA and glyoxylate. MCL enzymes, which are found in a variety of bacteria, are members of the citrate lyase-like family and are involved in the assimilation of one- and two-carbon compounds. Here, the 1.56 Å resolution X-ray crystal structure of MCL from Methylobacterium extorquens AM1 with bound Mg 2+is presented. Structural alignment with the closely related Rhodobacter sphaeroides malyl-CoA lyase complexed with Mg 2+, oxalate and CoA allows a detailed analysis of the domain motion of the enzyme caused by substrate binding.more » Alignment of the structures shows that a simple hinge motion centered on the conserved residues Phe268 and Thr269 moves the C-terminal domain by about 30° relative to the rest of the molecule. Furthermore, this domain motion positions a conserved aspartate residue located in the C-terminal domain in the active site of the adjacent monomer, which may serve as a general acid/base in the catalytic mechanism.« less

High-resolution high-sensitivity and truly distributed optical frequency domain reflectometry for structural crack detection

NASA Astrophysics Data System (ADS)

Li, Wenhai; Bao, Xiaoyi; Chen, Liang

2014-05-01

Optical Frequency Domain Reflectometry (OFDR) with the use of polarization maintaining fiber (PMF) is capable of distinguishing strain and temperature, which is critical for successful field applications such as structural health monitoring (SHM) and smart material. Location-dependent measurement sensitivities along PMF are compensated by cross- and auto-correlations measurements of the spectra form a distributed parameter matrix. Simultaneous temperature and strain measurement accuracy of 1μstrain and 0.1°C is achieved with 2.5mm spatial resolution in over 180m range.

Interaction of the p85 subunit of PI 3-kinase and its N-terminal SH2 domain with a PDGF receptor phosphorylation site: structural features and analysis of conformational changes.

PubMed Central

Panayotou, G; Bax, B; Gout, I; Federwisch, M; Wroblowski, B; Dhand, R; Fry, M J; Blundell, T L; Wollmer, A; Waterfield, M D

1992-01-01

Circular dichroism and fluorescence spectroscopy were used to investigate the structure of the p85 alpha subunit of the PI 3-kinase, a closely related p85 beta protein, and a recombinant SH2 domain-containing fragment of p85 alpha. Significant spectral changes, indicative of a conformational change, were observed on formation of a complex with a 17 residue peptide containing a phosphorylated tyrosine residue. The sequence of this peptide is identical to the sequence surrounding Tyr751 in the kinase-insert region of the platelet-derived growth factor beta-receptor (beta PDGFR). The rotational correlation times measured by fluorescence anisotropy decay indicated that phosphopeptide binding changed the shape of the SH2 domain-containing fragment. The CD and fluorescence spectroscopy data support the secondary structure prediction based on sequence analysis and provide evidence for flexible linker regions between the various domains of the p85 proteins. The significance of these results for SH2 domain-containing proteins is discussed. Images PMID:1330535

Donabedian's structure-process-outcome quality of care model: Validation in an integrated trauma system.

PubMed

Moore, Lynne; Lavoie, André; Bourgeois, Gilles; Lapointe, Jean

2015-06-01

According to Donabedian's health care quality model, improvements in the structure of care should lead to improvements in clinical processes that should in turn improve patient outcome. This model has been widely adopted by the trauma community but has not yet been validated in a trauma system. The objective of this study was to assess the performance of an integrated trauma system in terms of structure, process, and outcome and evaluate the correlation between quality domains. Quality of care was evaluated for patients treated in a Canadian provincial trauma system (2005-2010; 57 centers, n = 63,971) using quality indicators (QIs) developed and validated previously. Structural performance was measured by transposing on-site accreditation visit reports onto an evaluation grid according to American College of Surgeons criteria. The composite process QI was calculated as the average sum of proportions of conformity to 15 process QIs derived from literature review and expert opinion. Outcome performance was measured using risk-adjusted rates of mortality, complications, and readmission as well as hospital length of stay (LOS). Correlation was assessed with Pearson's correlation coefficients. Statistically significant correlations were observed between structure and process QIs (r = 0.33), and process and outcome QIs (r = -0.33 for readmission, r = -0.27 for LOS). Significant positive correlations were also observed between outcome QIs (r = 0.37 for mortality-readmission; r = 0.39 for mortality-LOS and readmission-LOS; r = 0.45 for mortality-complications; r = 0.34 for readmission-complications; 0.63 for complications-LOS). Significant correlations between quality domains observed in this study suggest that Donabedian's structure-process-outcome model is a valid model for evaluating trauma care. Trauma centers that perform well in terms of structure also tend to perform well in terms of clinical processes, which in turn has a favorable influence on patient outcomes. Prognostic study, level III.

Transcription factor-based biosensors enlightened by the analyte

PubMed Central

Fernandez-López, Raul; Ruiz, Raul; de la Cruz, Fernando; Moncalián, Gabriel

2015-01-01

Whole cell biosensors (WCBs) have multiple applications for environmental monitoring, detecting a wide range of pollutants. WCBs depend critically on the sensitivity and specificity of the transcription factor (TF) used to detect the analyte. We describe the mechanism of regulation and the structural and biochemical properties of TF families that are used, or could be used, for the development of environmental WCBs. Focusing on the chemical nature of the analyte, we review TFs that respond to aromatic compounds (XylS-AraC, XylR-NtrC, and LysR), metal ions (MerR, ArsR, DtxR, Fur, and NikR) or antibiotics (TetR and MarR). Analyzing the structural domains involved in DNA recognition, we highlight the similitudes in the DNA binding domains (DBDs) of these TF families. Opposite to DBDs, the wide range of analytes detected by TFs results in a diversity of structures at the effector binding domain. The modular architecture of TFs opens the possibility of engineering TFs with hybrid DNA and effector specificities. Yet, the lack of a crisp correlation between structural domains and specific functions makes this a challenging task. PMID:26191047

Transcription factor-based biosensors enlightened by the analyte.

PubMed

Fernandez-López, Raul; Ruiz, Raul; de la Cruz, Fernando; Moncalián, Gabriel

2015-01-01

Whole cell biosensors (WCBs) have multiple applications for environmental monitoring, detecting a wide range of pollutants. WCBs depend critically on the sensitivity and specificity of the transcription factor (TF) used to detect the analyte. We describe the mechanism of regulation and the structural and biochemical properties of TF families that are used, or could be used, for the development of environmental WCBs. Focusing on the chemical nature of the analyte, we review TFs that respond to aromatic compounds (XylS-AraC, XylR-NtrC, and LysR), metal ions (MerR, ArsR, DtxR, Fur, and NikR) or antibiotics (TetR and MarR). Analyzing the structural domains involved in DNA recognition, we highlight the similitudes in the DNA binding domains (DBDs) of these TF families. Opposite to DBDs, the wide range of analytes detected by TFs results in a diversity of structures at the effector binding domain. The modular architecture of TFs opens the possibility of engineering TFs with hybrid DNA and effector specificities. Yet, the lack of a crisp correlation between structural domains and specific functions makes this a challenging task.

Design and Nuclear Magnetic Resonance (NMR) Structure Determination of the Second Extracellular Immunoglobulin Tyrosine Kinase A (TrkAIg2) Domain Construct for Binding Site Elucidation in Drug Discovery

PubMed Central

2014-01-01

The tyrosine kinase A (TrkA) receptor is a validated therapeutic intervention point for a wide range of conditions. TrkA activation by nerve growth factor (NGF) binding the second extracellular immunoglobulin (TrkAIg2) domain triggers intracellular signaling cascades. In the periphery, this promotes the pain phenotype and, in the brain, cell survival or differentiation. Reproducible structural information and detailed validation of protein–ligand interactions aid drug discovery. However, the isolated TrkAIg2 domain crystallizes as a β-strand-swapped dimer in the absence of NGF, occluding the binding surface. Here we report the design and structural validation by nuclear magnetic resonance spectroscopy of the first stable, biologically active construct of the TrkAIg2 domain for binding site confirmation. Our structure closely mimics the wild-type fold of TrkAIg2 in complex with NGF (1WWW.pdb), and the 1H–15N correlation spectra confirm that both NGF and a competing small molecule interact at the known binding interface in solution. PMID:25454499

Mechanism of mRNA-STAR domain interaction: Molecular dynamics simulations of Mammalian Quaking STAR protein.

PubMed

Sharma, Monika; Anirudh, C R

2017-10-03

STAR proteins are evolutionary conserved mRNA-binding proteins that post-transcriptionally regulate gene expression at all stages of RNA metabolism. These proteins possess conserved STAR domain that recognizes identical RNA regulatory elements as YUAAY. Recently reported crystal structures show that STAR domain is composed of N-terminal QUA1, K-homology domain (KH) and C-terminal QUA2, and mRNA binding is mediated by KH-QUA2 domain. Here, we present simulation studies done to investigate binding of mRNA to STAR protein, mammalian Quaking protein (QKI). We carried out conventional MD simulations of STAR domain in presence and absence of mRNA, and studied the impact of mRNA on the stability, dynamics and underlying allosteric mechanism of STAR domain. Our unbiased simulations results show that presence of mRNA stabilizes the overall STAR domain by reducing the structural deviations, correlating the 'within-domain' motions, and maintaining the native contacts information. Absence of mRNA not only influenced the essential modes of motion of STAR domain, but also affected the connectivity of networks within STAR domain. We further explored the dissociation of mRNA from STAR domain using umbrella sampling simulations, and the results suggest that mRNA binding to STAR domain occurs in multi-step: first conformational selection of mRNA backbone conformations, followed by induced fit mechanism as nucleobases interact with STAR domain.

Brazilian Portuguese version of the Revised Fibromyalgia Impact Questionnaire (FIQR-Br): cross-cultural validation, reliability, and construct and structural validation.

PubMed

Lupi, Jaqueline Basilio; Carvalho de Abreu, Daniela Cristina; Ferreira, Mariana Candido; Oliveira, Renê Donizeti Ribeiro de; Chaves, Thais Cristina

2017-08-01

This study aimed to culturally adapt and validate the Revised Fibromyalgia Impact Questionnaire (FIQR) to Brazilian Portuguese, by the use of analysis of internal consistency, reliability, and construct and structural validity. A total of 100 female patients with fibromyalgia participated in the validation process of the Brazilian Portuguese version of the FIQR (FIQR-Br).The intraclass correlation coefficient (ICC) was used for statistical analysis of reliability (test-retest), Cronbach's alpha for internal consistency, Pearson's rank correlation for construct validity, and confirmatory factor analysis (CFA) for structural validity. It was verified excellent levels of reliability, with ICC greater than 0.75 for all questions and domains of the FIQR-Br. For internal consistency, alpha values greater than 0.70 for the items and domains of the questionnaire were observed. Moderate (0.40 < r < 0.70) and strong (r > 0.70) correlations were observed for the scores of domains and total score between the FIQR-Br and FIQ-Br. The structure of the three domains of the FIQR-Br was confirmed by CFA. The results of this study suggest that that the FIQR-Br is a reliable and valid instrument for assessing fibromyalgia-related impact, and supports its use in clinical settings and research. The structure of the three domains of the FIQR-Br was also confirmed. Implications for Rehabilitation Fibromyalgia is a chronic musculoskeletal disorder characterized by widespread and diffuse pain, fatigue, sleep disturbances, and depression. The disease significantly impairs patients' quality of life and can be highly disabling. To be used in multicenter research efforts, the Revised Fibromyalgia Impact Questionnaire (FIQR) must be cross-culturally validated and psychometrically tested. This paper will make available a new version of the FIQR-Br since another version already exists, but there are concerns about its measurement properties. The availability of an instrument adapted to and validated for Brazilian Portuguese may make it possible to reliably verify the effects of rehabilitation programs on disability from fibromyalgia. The FIQR-Br showed results comparable with other versions of the FIQR in other languages, thereby enabling comparison of effects of rehabilitation interventions on disability from fibromyalgia conducted in Brazil with results of studies carried out in other parts of the world.

Brillouin Optical Correlation Domain Analysis in Composite Material Beams

PubMed Central

Stern, Yonatan; London, Yosef; Preter, Eyal; Antman, Yair; Diamandi, Hilel Hagai; Silbiger, Maayan; Adler, Gadi; Shalev, Doron; Zadok, Avi

2017-01-01

Structural health monitoring is a critical requirement in many composites. Numerous monitoring strategies rely on measurements of temperature or strain (or both), however these are often restricted to point-sensing or to the coverage of small areas. Spatially-continuous data can be obtained with optical fiber sensors. In this work, we report high-resolution distributed Brillouin sensing over standard fibers that are embedded in composite structures. A phase-coded, Brillouin optical correlation domain analysis (B-OCDA) protocol was employed, with spatial resolution of 2 cm and sensitivity of 1 °K or 20 micro-strain. A portable measurement setup was designed and assembled on the premises of a composite structures manufacturer. The setup was successfully utilized in several structural health monitoring scenarios: (a) monitoring the production and curing of a composite beam over 60 h; (b) estimating the stiffness and Young’s modulus of a composite beam; and (c) distributed strain measurements across the surfaces of a model wing of an unmanned aerial vehicle. The measurements are supported by the predictions of structural analysis calculations. The results illustrate the potential added values of high-resolution, distributed Brillouin sensing in the structural health monitoring of composites. PMID:28974041

Brillouin Optical Correlation Domain Analysis in Composite Material Beams.

PubMed

Stern, Yonatan; London, Yosef; Preter, Eyal; Antman, Yair; Diamandi, Hilel Hagai; Silbiger, Maayan; Adler, Gadi; Levenberg, Eyal; Shalev, Doron; Zadok, Avi

2017-10-02

Structural health monitoring is a critical requirement in many composites. Numerous monitoring strategies rely on measurements of temperature or strain (or both), however these are often restricted to point-sensing or to the coverage of small areas. Spatially-continuous data can be obtained with optical fiber sensors. In this work, we report high-resolution distributed Brillouin sensing over standard fibers that are embedded in composite structures. A phase-coded, Brillouin optical correlation domain analysis (B-OCDA) protocol was employed, with spatial resolution of 2 cm and sensitivity of 1 °K or 20 micro-strain. A portable measurement setup was designed and assembled on the premises of a composite structures manufacturer. The setup was successfully utilized in several structural health monitoring scenarios: (a) monitoring the production and curing of a composite beam over 60 h; (b) estimating the stiffness and Young's modulus of a composite beam; and (c) distributed strain measurements across the surfaces of a model wing of an unmanned aerial vehicle. The measurements are supported by the predictions of structural analysis calculations. The results illustrate the potential added values of high-resolution, distributed Brillouin sensing in the structural health monitoring of composites.

The Scientific Competitiveness of Nations.

PubMed

Cimini, Giulio; Gabrielli, Andrea; Sylos Labini, Francesco

2014-01-01

We use citation data of scientific articles produced by individual nations in different scientific domains to determine the structure and efficiency of national research systems. We characterize the scientific fitness of each nation-that is, the competitiveness of its research system-and the complexity of each scientific domain by means of a non-linear iterative algorithm able to assess quantitatively the advantage of scientific diversification. We find that technological leading nations, beyond having the largest production of scientific papers and the largest number of citations, do not specialize in a few scientific domains. Rather, they diversify as much as possible their research system. On the other side, less developed nations are competitive only in scientific domains where also many other nations are present. Diversification thus represents the key element that correlates with scientific and technological competitiveness. A remarkable implication of this structure of the scientific competition is that the scientific domains playing the role of "markers" of national scientific competitiveness are those not necessarily of high technological requirements, but rather addressing the most "sophisticated" needs of the society.

Dielectric and structural characterisation of chalcogenide glasses via terahertz time-domain spectroscopy

NASA Astrophysics Data System (ADS)

Ravagli, A.; Naftaly, M.; Craig, C.; Weatherby, E.; Hewak, D. W.

2017-07-01

Terahertz time-domain spectroscopy (THz TDS) was used to investigate a series of chalcogenide glasses. In particular, the dielectric properties at terahertz frequencies were determined and correlated with the glass composition. The experimental results showed a strong relationship between the dielectric properties and the polarizability of the glasses studied. A new explanation based on the coordination number of the metallic cations was proposed to understand these observations.

Structures of the Porphyromonas gingivalis OxyR regulatory domain explain differences in expression of the OxyR regulon in Escherichia coli and P. gingivalis

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

Svintradze, David V.; Virginia Commonwealth University, Richmond, VA 23219-1540; Peterson, Darrell L.

Differences in OxyR regulated expression of oxidative stress genes between Escherichia coli and Porphyromonas gingivalis are explained by very minor differences in structure and amino-acid sequence of the respective oxidized and reduced OxyR regulatory domains. These differences affect OxyR quaternary structures and are predicted from model building of full length OxyR–DNA complexes to confer distinct modes of DNA binding on this transcriptional regulator. OxyR transcriptionally regulates Escherichia coli oxidative stress response genes through a reversibly reducible cysteine disulfide biosensor of cellular redox status. Structural changes induced by redox changes in these cysteines are conformationally transmitted to the dimer subunit interfaces,more » which alters dimer and tetramer interactions with DNA. In contrast to E. coli OxyR regulatory-domain structures, crystal structures of Porphyromonas gingivalis OxyR regulatory domains show minimal differences in dimer configuration on changes in cysteine disulfide redox status. This locked configuration of the P. gingivalis OxyR regulatory-domain dimer closely resembles the oxidized (activating) form of the E. coli OxyR regulatory-domain dimer. It correlates with the observed constitutive activation of some oxidative stress genes in P. gingivalis and is attributable to a single amino-acid insertion in P. gingivalis OxyR relative to E. coli OxyR. Modelling of full-length P. gingivalis, E. coli and Neisseria meningitidis OxyR–DNA complexes predicts different modes of DNA binding for the reduced and oxidized forms of each.« less

Phylogenetic profiles reveal structural/functional determinants of TRPC3 signal-sensing antennae

PubMed Central

Ko, Kyung Dae; Bhardwaj, Gaurav; Hong, Yoojin; Chang, Gue Su; Kiselyov, Kirill

2009-01-01

Biochemical assessment of channel structure/function is incredibly challenging. Developing computational tools that provide these data would enable translational research, accelerating mechanistic experimentation for the bench scientist studying ion channels. Starting with the premise that protein sequence encodes information about structure, function and evolution (SF&E), we developed a unified framework for inferring SF&E from sequence information using a knowledge-based approach. The Gestalt Domain Detection Algorithm-Basic Local Alignment Tool (GDDA-BLAST) provides phylogenetic profiles that can model, ab initio, SF&E relationships of biological sequences at the whole protein, single domain and single-amino acid level.1,2 In our recent paper,4 we have applied GDDA-BLAST analysis to study canonical TRP (TRPC) channels1 and empirically validated predicted lipid-binding and trafficking activities contained within the TRPC3 TRP_2 domain of unknown function. Overall, our in silico, in vitro, and in vivo experiments support a model in which TRPC3 has signal-sensing antennae which are adorned with lipid-binding, trafficking and calmodulin regulatory domains. In this Addendum, we correlate our functional domain analysis with the cryo-EM structure of TRPC3.3 In addition, we synthesize recent studies with our new findings to provide a refined model on the mechanism(s) of TRPC3 activation/deactivation. PMID:19704910

DNA methylation pathways and their crosstalk with histone methylation

PubMed Central

Du, Jiamu; Johnson, Lianna M.; Jacobsen, Steven E.; Patel, Dinshaw J.

2015-01-01

Methylation of DNA and of histone 3 at Lys 9 (H3K9) are highly correlated with gene silencing in eukaryotes from fungi to humans. Both of these epigenetic marks need to be established at specific regions of the genome and then maintained at these sites through cell division. Protein structural domains that specifically recognize methylated DNA and methylated histones are key for targeting enzymes that catalyse these marks to appropriate genome sites. Genetic, genomic, structural and biochemical data reveal connections between these two epigenetic marks, and these domains mediate much of the crosstalk. PMID:26296162

Nonequilibrium Phase Precursors during a Photoexcited Insulator-to-Metal Transition in V2O3

NASA Astrophysics Data System (ADS)

Singer, Andrej; Ramirez, Juan Gabriel; Valmianski, Ilya; Cela, Devin; Hua, Nelson; Kukreja, Roopali; Wingert, James; Kovalchuk, Olesya; Glownia, James M.; Sikorski, Marcin; Chollet, Matthieu; Holt, Martin; Schuller, Ivan K.; Shpyrko, Oleg G.

2018-05-01

Here, we photoinduce and directly observe with x-ray scattering an ultrafast enhancement of the structural long-range order in the archetypal Mott system V2O3 . Despite the ultrafast increase in crystal symmetry, the change of unit cell volume occurs an order of magnitude slower and coincides with the insulator-to-metal transition. The decoupling between the two structural responses in the time domain highlights the existence of a transient photoinduced precursor phase, which is distinct from the two structural phases present in equilibrium. X-ray nanoscopy reveals that acoustic phonons trapped in nanoscale twin domains govern the dynamics of the ultrafast transition into the precursor phase, while nucleation and growth of metallic domains dictate the duration of the slower transition into the metallic phase. The enhancement of the long-range order before completion of the electronic transition demonstrates the critical role the nonequilibrium structural phases play during electronic phase transitions in correlated electrons systems.

[Acquired Brain Injury: impacts on labor activity of individuals of working age and their relatives].

PubMed

Ponte, Aline Sarturi; Fedosse, Elenir

2016-10-01

This study correlated the impact of Acquired Brain Injury (ABI) on the labor activity of individuals of working age on their quality of life (QOL) and that of their relatives/caregivers. It involved qualitative (content analysis) and quantitative (descriptive) research. Forty-eight individuals with ABI and 27 relatives/caregivers were interviewed. The correlation of the International Classification of Functioning, Disability and Health (ICF) and the World Health Organization Quality of Life WHOQOL-BREF (52.1% men; mean age 48.7 years at the time of the injury; low schooling; 18,7% domestic) revealed that the Mental Functions compromised by ABI interfered in the four domains of QOL; Heart Functions and Blood Pressure compromised the social domain; Cerebral injury interfered with the Psychological and Environmental domains. With respect to relatives/caregivers (77.7% women; 96.3%, primary caregivers; mean age 52.6 years, and low schooling), we observed changes in the work routine and family structure (85.2%). The onset of ABI disrupts the injured individuals and their families, affecting QOL in all domains, especially in the physical, psychological and environmental domains of individuals with ABI and the physical and environmental domains of relatives/caregivers.

Dual-aspect monism à la Pauli and Jung perforates the completeness of physics

NASA Astrophysics Data System (ADS)

Atmanspacher, Harald

2012-12-01

In the mid 19th century, the physicist Wolfgang Pauli and the psychologist Carl Gustav Jung developed a philosophical position for the mind-matter problem that is today called dual-aspect monism. They conjectured a picture in which the mental and the material arise as two complementary aspects of one underlying psychophysically neutral reality to which they cannot be reduced and to which direct empirical access is impossible. This picture suggests structural, persistent,re-producible mind-matter correlations by splitting the underlying reality into aspects. In addition, it suggests induced, occasional, evasive mind-matter correlations above and below, respectively, those stable baseline correlations. These correlations, and the way they arise, suggest that the domain of the physical is not completely independent of the domain of the mental, and both are not independent from the assumed reality underlying them. Some ideas are presented of how these relationships might be conceived.

PDZ Binding Domains, Structural Disorder and Phosphorylation: A Menage-a-trois Tailing Dcp2 mRNA Decapping Enzymes.

PubMed

Gunawardana, Dilantha

2016-01-01

Diverse cellular activities are mediated through the interaction of protein domains and their binding partners. One such protein domain widely distributed in the higher metazoan world is the PDZ domain, which facilitates abundant protein-protein interactions. The PDZ domain-PDZ binding domain interaction has been implicated in several pathologies including Alzheimer's disease, Parkinson's disease and Down syndrome. PDZ domains bind to C-terminal peptides/proteins which have either of the following combinations: S/T-X-hydrophobic-COOH for type I, hydrophobic-Xhydrophobic- COOH for type II, and D/E-X-hydrophobic-COOH for type III, although hydrophobicity in the termini form the key characteristic of the PDZ-binding domains. We identified and characterized a Dcp2 type mRNA decapping enzyme from Arabidopsis thaliana, a protein containing a putative PDZ-binding domain using mutagenesis and protein biochemistry. Now we are using bioinformatics to study the Cterminal end of mRNA decapping enzymes from complex metazoans with the aim of (1) identifying putative PDZ-binding domains (2) Correlating structural disorder with PDZ binding domains and (3) Demonstrating the presence of phosphorylation sites in C-terminal extremities of Dcp2 type mRNA decapping enzymes. It is proposed here that the trinity of PDZbinding domains, structural disorder and phosphorylation-susceptible sites are a feature of the Dcp2 family of decapping enzymes and perhaps is a wider trick in protein evolution where scaffolding/tethering is a requirement for localization and function. It is critical though laboratory-based supporting evidence is sought to back-up this bioinformatics exploration into tail regions of mRNA decapping enzymes.

Structural consequences of metallothionein dimerization: solution structure of the isolated Cd4-alpha-domain and comparison with the holoprotein dimer.

PubMed

Ejnik, John W; Muñoz, Amalia; DeRose, Eugene; Shaw, C Frank; Petering, David H

2003-07-22

The NMR determination of the structure of Cd(7)-metallothionein was done previously using a relatively large protein concentration that favors dimer formation. The reactivity of the protein is also affected under this condition. To examine the influence of protein concentration on metallothionein conformation, the isolated Cd(4)-alpha-domain was prepared from rabbit metallothionein-2 (MT 2), and its three-dimensional structure was determined by heteronuclear, (1)H-(111)Cd, and homonuclear, (1)H-(1)H NMR, correlation experiments. The three-dimensional structure was refined using distance and angle constraints derived from these two-dimensional NMR data sets and a distance geometry/simulated annealing protocol. The backbone superposition of the alpha-domain from rabbit holoprotein Cd(7)-MT 2 and the isolated rabbit Cd(4)-alpha was measured at a RMSD of 2.0 A. Nevertheless, the conformations of the two Cd-thiolate clusters were distinctly different at two of the cadmium centers. In addition, solvent access to the sulfhydryl ligands of the isolated Cd(4)-alpha cluster was 130% larger due to this small change in cluster geometry. To probe whether these differences were an artifact of the structure calculation, the Cd(4)-alpha-domain structure in rabbit Cd(7)-MT 2 was redetermined, using the previously defined set of NOEs and the present calculation protocol. All calculations employed the same ionic radius for Cd(2+) and same cadmium-thiolate bond distance. The newly calculated structure matched the original with an RMSD of 1.24 A. It is hypothesized that differences in the two alpha-domain structures result from a perturbation of the holoprotein structure because of head-to-tail dimerization under the conditions of the NMR experiments.

Conditional random fields for pattern recognition applied to structured data

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

Burr, Tom; Skurikhin, Alexei

In order to predict labels from an output domain, Y, pattern recognition is used to gather measurements from an input domain, X. Image analysis is one setting where one might want to infer whether a pixel patch contains an object that is “manmade” (such as a building) or “natural” (such as a tree). Suppose the label for a pixel patch is “manmade”; if the label for a nearby pixel patch is then more likely to be “manmade” there is structure in the output domain that can be exploited to improve pattern recognition performance. Modeling P(X) is difficult because features betweenmore » parts of the model are often correlated. Thus, conditional random fields (CRFs) model structured data using the conditional distribution P(Y|X = x), without specifying a model for P(X), and are well suited for applications with dependent features. Our paper has two parts. First, we overview CRFs and their application to pattern recognition in structured problems. Our primary examples are image analysis applications in which there is dependence among samples (pixel patches) in the output domain. Second, we identify research topics and present numerical examples.« less

Conditional random fields for pattern recognition applied to structured data

DOE PAGES

Burr, Tom; Skurikhin, Alexei

2015-07-14

In order to predict labels from an output domain, Y, pattern recognition is used to gather measurements from an input domain, X. Image analysis is one setting where one might want to infer whether a pixel patch contains an object that is “manmade” (such as a building) or “natural” (such as a tree). Suppose the label for a pixel patch is “manmade”; if the label for a nearby pixel patch is then more likely to be “manmade” there is structure in the output domain that can be exploited to improve pattern recognition performance. Modeling P(X) is difficult because features betweenmore » parts of the model are often correlated. Thus, conditional random fields (CRFs) model structured data using the conditional distribution P(Y|X = x), without specifying a model for P(X), and are well suited for applications with dependent features. Our paper has two parts. First, we overview CRFs and their application to pattern recognition in structured problems. Our primary examples are image analysis applications in which there is dependence among samples (pixel patches) in the output domain. Second, we identify research topics and present numerical examples.« less

Slowing Translation between Protein Domains by Increasing Affinity between mRNAs and the Ribosomal Anti-Shine-Dalgarno Sequence Improves Solubility.

PubMed

Vasquez, Kevin A; Hatridge, Taylor A; Curtis, Nicholas C; Contreras, Lydia M

2016-02-19

Recent studies have demonstrated that effective protein production requires coordination of multiple cotranslational cellular processes, which are heavily affected by translation timing. Until recently, protein engineering has focused on codon optimization to maximize protein production rates, mostly considering the effect of tRNA abundance. However, as it relates to complex multidomain proteins, it has been hypothesized that strategic translational pauses between domains and between distinct individual structural motifs can prevent interactions between nascent chain fragments that generate kinetically trapped misfolded peptides and thereby enhance protein yields. In this study, we introduce synthetic transient pauses between structural domains in a heterologous model protein based on designed patterns of affinity between the mRNA and the anti-Shine-Dalgarno (aSD) sequence on the ribosome. We demonstrate that optimizing translation attenuation at domain boundaries can predictably affect solubility patterns in bacteria. Exploration of the affinity space showed that modifying less than 1% of the nucleotides (on a small 12 amino acid linker) can vary soluble protein yields up to ∼7-fold without altering the primary sequence of the protein. In the context of longer linkers, where a larger number of distinct structural motifs can fold outside the ribosome, optimal synonymous codon variations resulted in an additional 2.1-fold increase in solubility, relative to that of nonoptimized linkers of the same length. While rational construction of 54 linkers of various affinities showed a significant correlation between protein solubility and predicted affinity, only weaker correlations were observed between tRNA abundance and protein solubility. We also demonstrate that naturally occurring high-affinity clusters are present between structural domains of β-galactosidase, one of Escherichia coli's largest native proteins. Interdomain ribosomal affinity is an important factor that has not previously been explored in the context of protein engineering.

A thermophilic mini-chaperonin contains a conserved polypeptide-binding surface: combined crystallographic and NMR studies of the GroEL Apical Domain with implications for substrate interactions

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

Hua, Q. X. H.; Dementieva, I. S. D.; Walsh, M. A. W.

2001-02-23

A homologue of the Escherichia coli GroEL apical domain was obtained from thermophilic eubacterium Thermus thermophilus. The domains share 70 % sequence identity (101 out of 145 residues). The thermal stability of the T. thermophilus apical domain (T{sub m}>100{sup o}C as evaluated by circular dichroism) is at least 35{sup o}C greater than that of the E. coli apical domain (T{sub m}=65{sup o}C). The crystal structure of a selenomethione-substituted apical domain from T. thermophilus was determined to a resolution of 1.78 {angstrom} using multiwavelength-anomalous-diffraction phasing. The structure is similar to that of the E. coli apical domain (root-mean-square deviation 0.45 {angstrom}more » based on main-chain atoms). The thermophilic structure contains seven additional salt bridges of which four contain charge-stabilized hydrogen bonds. Only one of the additional salt bridges would face the 'Anfinsen cage' in GroEL. High temperatures were exploited to map sites of interactions between the apical domain and molten globules. NMR footprints of apical domain-protein complexes were obtained at elevated temperature using {sup 15}N-{sup 1}H correlation spectra of {sup 15}N-labeled apical domain. Footprints employing two polypeptides unrelated in sequence or structure (an insulin monomer and the SRY high-mobility-group box, each partially unfolded at 50{sup o}C) are essentially the same and consistent with the peptide-binding surface previously defined in E. coli GroEL and its apical domain-peptide complexes. An additional part of this surface comprising a short N-terminal {alpha}-helix is observed. The extended footprint rationalizes mutagenesis studies of intact GroEL in which point mutations affecting substrate binding were found outside the 'classical' peptide-binding site. Our results demonstrate structural conservation of the apical domain among GroEL homologues and conservation of an extended non-polar surface recognizing diverse polypeptides.« less

Information Technology (IT) Strategic Alignment: A Correlational Study between the Impact of IT Governance Structures and IT Strategic Alignment

ERIC Educational Resources Information Center

Asante, Keith K.

2010-01-01

This dissertation explored the extent to which Information Technology (IT) strategic alignment are impacted by IT governance structures. The study discusses several strategic alignment and IT governance literature that presents a gap in the literature domain. Subsequent studies researched issues surrounding why organizations are not able to align…

Matrix metalloproteinases: structures, evolution, and diversification.

PubMed

Massova, I; Kotra, L P; Fridman, R; Mobashery, S

1998-09-01

A comprehensive sequence alignment of 64 members of the family of matrix metalloproteinases (MMPs) for the entire sequences, and subsequently the catalytic and the hemopexin-like domains, have been performed. The 64 MMPs were selected from plants, invertebrates, and vertebrates. The analyses disclosed that as many as 23 distinct subfamilies of these proteins are known to exist. Information from the sequence alignments was correlated with structures, both crystallographic as well as computational, of the catalytic domains for the 23 representative members of the MMP family. A survey of the metal binding sites and two loops containing variable sequences of amino acids, which are important for substrate interactions, are discussed. The collective data support the proposal that the assembly of the domains into multidomain enzymes was likely to be an early evolutionary event. This was followed by diversification, perhaps in parallel among the MMPs, in a subsequent evolutionary time scale. Analysis indicates that a retrograde structure simplification may have accounted for the evolution of MMPs with simple domain constituents, such as matrilysin, from the larger and more elaborate enzymes.

Personality Inventory for DSM-5-Short Form (PID-5-SF): Reliability, Factorial Structure, and Relationship With Functional Impairment in Dual Diagnosis Patients.

PubMed

Díaz-Batanero, Carmen; Ramírez-López, Juan; Domínguez-Salas, Sara; Fernández-Calderón, Fermín; Lozano, Óscar M

2017-11-01

Section III of the Diagnostic and Statistical Manual of Mental Disorders-Fifth edition ( DSM-5) has generated a personality paradigm consisting of 25 personality facets identified in five domains. The developed assessment instrument Personality Inventory for DSM-5 (PID-5) has showed good psychometric properties, but the potential for certain improvements still remain. In this article, a sample of 282 dual diagnosis patients is used to provide evidence of the psychometric properties of the PID-5-Short Form. The mean value of Cronbach's alpha coefficients reached .73 on the facets and .84 for domains and test-retest values ranged between .57 to .83 for facets and .70 to .87 for the domains. Confirmatory factor analyses conducted showed good fit on both models tested: the five correlated factor structure and hierarchical structure of personality traits. The WHODAS 2.0 domains of understanding and communicating, and participating in society, appear to show the strongest relationship with personality facets. In general, the PID-5-Short Form shows adequate psychometric properties for use in dual diagnosis patients.

Tracking of large-scale structures in turbulent channel with direct numerical simulation of low Prandtl number passive scalar

NASA Astrophysics Data System (ADS)

Tiselj, Iztok

2014-12-01

Channel flow DNS (Direct Numerical Simulation) at friction Reynolds number 180 and with passive scalars of Prandtl numbers 1 and 0.01 was performed in various computational domains. The "normal" size domain was ˜2300 wall units long and ˜750 wall units wide; size taken from the similar DNS of Moser et al. The "large" computational domain, which is supposed to be sufficient to describe the largest structures of the turbulent flows was 3 times longer and 3 times wider than the "normal" domain. The "very large" domain was 6 times longer and 6 times wider than the "normal" domain. All simulations were performed with the same spatial and temporal resolution. Comparison of the standard and large computational domains shows the velocity field statistics (mean velocity, root-mean-square (RMS) fluctuations, and turbulent Reynolds stresses) that are within 1%-2%. Similar agreement is observed for Pr = 1 temperature fields and can be observed also for the mean temperature profiles at Pr = 0.01. These differences can be attributed to the statistical uncertainties of the DNS. However, second-order moments, i.e., RMS temperature fluctuations of standard and large computational domains at Pr = 0.01 show significant differences of up to 20%. Stronger temperature fluctuations in the "large" and "very large" domains confirm the existence of the large-scale structures. Their influence is more or less invisible in the main velocity field statistics or in the statistics of the temperature fields at Prandtl numbers around 1. However, these structures play visible role in the temperature fluctuations at low Prandtl number, where high temperature diffusivity effectively smears the small-scale structures in the thermal field and enhances the relative contribution of large-scales. These large thermal structures represent some kind of an echo of the large scale velocity structures: the highest temperature-velocity correlations are not observed between the instantaneous temperatures and instantaneous streamwise velocities, but between the instantaneous temperatures and velocities averaged over certain time interval.

Assessing infertility-related stress: the factor structure of the Fertility Problem Inventory in Italian couples undergoing infertility treatment.

PubMed

Donarelli, Zaira; Gullo, Salvatore; Lo Coco, Gianluca; Marino, Angelo; Scaglione, Piero; Volpes, Aldo; Allegra, Adolfo

2015-01-01

The factor structure of the Fertility Problem Inventory (FPI) and its invariance across gender were examined in Italian couples undergoing infertility treatment. About 1000 subjects (both partners of 500 couples) completed two questionnaires prior to commencing infertility treatment at a private Clinic in Palermo, Italy. Confirmatory Factor Analysis demonstrated that the original factor structure of the FPI was partially confirmed. Two correlated factors (Infertility Life Domains and Importance of Parenthood) were obtained via a post hoc Exploratory Factor Analysis. Finally, the invariance of this factor structure across gender was confirmed. The study supported the relevance of two interrelated factors specific to infertility stress which could help clinicians to focus on the core infertility-related stress domains of infertile couples.

The need for supportive care among head and neck cancer patients: psychometric assessment of the Dutch version of the Supportive Care Needs Survey Short-Form (SCNS-SF34) and the newly developed head and neck cancer module (SCNS-HNC).

PubMed

Jansen, Femke; Witte, Birgit I; van Uden-Kraan, Cornelia F; Braspenning, Anna M; Leemans, C René; Verdonck-de Leeuw, Irma M

2016-11-01

The purpose of this study is to assess the psychometric properties of the Dutch version of the 34-item Short-Form Supportive Care Needs Survey (SCNS-SF34) and the newly developed module for head and neck cancer (HNC) patients (SCNS-HNC). HNC patients were included from two cross-sectional studies. Content validity of the SCNS-HNC was analysed by examining redundancy and completeness of items. Factor structure was assessed using confirmatory and exploratory factor analyses. Cronbach's alpha, Spearman's correlation, Mann-Whitney U test, Kruskall-Wallis and intraclass correlation coefficients (ICC) were used to assess internal consistency, construct validity and test-retest reliability. Content validity of the SCNS-HNC was good, although some HNC topics were missing. For the SCNS-SF34, a four-factor structure was found, namely physical and daily living, psychological, sexuality and health system and information and patient support (alpha = .79 to .95). For the SCNS-HNC, a two-factor structure was found, namely HNC-specific functioning and lifestyle (alpha = .89 and .60). Respectively, 96 and 89 % of the hypothesised correlations between the SCNS-SF34 or SCNS-HNC and other patient-reported outcome measures were found; 57 and 67 % also showed the hypothesised magnitude of correlation. The SCNS-SF34 domains discriminated between treatment procedure (physical and daily living p = .02 and psychological p = .01) and time since treatment (health system, information and patient support p = .02). Test-retest reliability of SCNS-SF34 domains and HNC-specific functioning domain was above .70 (ICC = .74 to .83), and ICC = .67 for the lifestyle domain. Floor effects ranged from 21.1 to 70.9 %. The SCNS-SF34 and SCNS-HNC are valid and reliable instruments to evaluate the need for supportive care among (Dutch) HNC patients.

Behavioral and cognitive outcomes for clinical trials in children with neurofibromatosis type 1.

PubMed

van der Vaart, Thijs; Rietman, André B; Plasschaert, Ellen; Legius, Eric; Elgersma, Ype; Moll, Henriëtte A

2016-01-12

To evaluate the appropriateness of cognitive and behavioral outcome measures in clinical trials in neurofibromatosis type 1 (NF1) by analyzing the degree of deficits compared to reference groups, test-retest reliability, and how scores correlate between outcome measures. Data were analyzed from the Simvastatin for cognitive deficits and behavioral problems in patients with neurofibromatosis type 1 (NF1-SIMCODA) trial, a randomized placebo-controlled trial of simvastatin for cognitive deficits and behavioral problems in children with NF1. Outcome measures were compared with age-specific reference groups to identify domains of dysfunction. Pearson r was computed for before and after measurements within the placebo group to assess test-retest reliability. Principal component analysis was used to identify the internal structure in the outcome data. Strongest mean score deviations from the reference groups were observed for full-scale intelligence (-1.1 SD), Rey Complex Figure Test delayed recall (-2.0 SD), attention problems (-1.2 SD), and social problems (-1.1 SD). Long-term test-retest reliability were excellent for Wechsler scales (r > 0.88), but poor to moderate for other neuropsychological tests (r range 0.52-0.81) and Child Behavioral Checklist subscales (r range 0.40-0.79). The correlation structure revealed 2 strong components in the outcome measures behavior and cognition, with no correlation between these components. Scores on psychosocial quality of life correlate strongly with behavioral problems and less with cognitive deficits. Children with NF1 show distinct deficits in multiple domains. Many outcome measures showed weak test-retest correlations over the 1-year trial period. Cognitive and behavioral outcomes are complementary. This analysis demonstrates the need to include reliable outcome measures on a variety of cognitive and behavioral domains in clinical trials for NF1. © 2015 American Academy of Neurology.

Structural basis of sterol recognition and nonvesicular transport by lipid transfer proteins anchored at membrane contact sites.

PubMed

Tong, Junsen; Manik, Mohammad Kawsar; Im, Young Jun

2018-01-30

Membrane contact sites (MCSs) in eukaryotic cells are hotspots for lipid exchange, which is essential for many biological functions, including regulation of membrane properties and protein trafficking. Lipid transfer proteins anchored at membrane contact sites (LAMs) contain sterol-specific lipid transfer domains [StARkin domain (SD)] and multiple targeting modules to specific membrane organelles. Elucidating the structural mechanisms of targeting and ligand recognition by LAMs is important for understanding the interorganelle communication and exchange at MCSs. Here, we determined the crystal structures of the yeast Lam6 pleckstrin homology (PH)-like domain and the SDs of Lam2 and Lam4 in the apo form and in complex with ergosterol. The Lam6 PH-like domain displays a unique PH domain fold with a conserved N-terminal α-helix. The Lam6 PH-like domain lacks the basic surface for phosphoinositide binding, but contains hydrophobic patches on its surface, which are critical for targeting to endoplasmic reticulum (ER)-mitochondrial contacts. Structures of the LAM SDs display a helix-grip fold with a hydrophobic cavity and a flexible Ω1-loop as a lid. Ergosterol is bound to the pocket in a head-down orientation, with its hydrophobic acyl group located in the tunnel entrance. The Ω1-loop in an open conformation is essential for ergosterol binding by direct hydrophobic interaction. Structural comparison suggested that the sterol binding mode of the Lam2 SD2 is likely conserved among the sterol transfer proteins of the StARkin superfamily. Structural models of full-length Lam2 correlated with the sterol transport function at the membrane contact sites.

Conserved intron positions in FGFR genes reflect the modular structure of FGFR and reveal stepwise addition of domains to an already complex ancestral FGFR.

PubMed

Rebscher, Nicole; Deichmann, Christina; Sudhop, Stefanie; Fritzenwanker, Jens Holger; Green, Stephen; Hassel, Monika

2009-10-01

We have analyzed the evolution of fibroblast growth factor receptor (FGFR) tyrosine kinase genes throughout a wide range of animal phyla. No evidence for an FGFR gene was found in Porifera, but we tentatively identified an FGFR gene in the placozoan Trichoplax adhaerens. The gene encodes a protein with three immunoglobulin-like domains, a single-pass transmembrane, and a split tyrosine kinase domain. By superimposing intron positions of 20 FGFR genes from Placozoa, Cnidaria, Protostomia, and Deuterostomia over the respective protein domain structure, we identified ten ancestral introns and three conserved intron groups. Our analysis shows (1) that the position of ancestral introns correlates to the modular structure of FGFRs, (2) that the acidic domain very likely evolved in the last common ancestor of triploblasts, (3) that splicing of IgIII was enabled by a triploblast-specific insertion, and (4) that IgI is subject to substantial loss or duplication particularly in quickly evolving genomes. Moreover, intron positions in the catalytic domain of FGFRs map to the borders of protein subdomains highly conserved in other serine/threonine kinases. Nevertheless, these introns were introduced in metazoan receptor tyrosine kinases exclusively. Our data support the view that protein evolution dating back to the Cambrian explosion took place in such a short time window that only subtle changes in the domain structure are detectable in extant representatives of animal phyla. We propose that the first multidomain FGFR originated in the last common ancestor of Placozoa, Cnidaria, and Bilateria. Additional domains were introduced mainly in the ancestor of triploblasts and in the Ecdysozoa.

Correlation between hierarchical structure of crystal networks and macroscopic performance of mesoscopic soft materials and engineering principles.

PubMed

Lin, Naibo; Liu, Xiang Yang

2015-11-07

This review examines how the concepts and ideas of crystallization can be extended further and applied to the field of mesoscopic soft materials. It concerns the structural characteristics vs. the macroscopic performance, and the formation mechanism of crystal networks. Although this subject can be discussed in a broad sense across the area of mesoscopic soft materials, our main focus is on supramolecular materials, spider and silkworm silks, and biominerals. First, the occurrence of a hierarchical structure, i.e. crystal network and domain network structures, will facilitate the formation kinetics of mesoscopic phases and boost up the macroscopic performance of materials in some cases (i.e. spider silk fibres). Second, the structure and performance of materials can be correlated in some way by the four factors: topology, correlation length, symmetry/ordering, and strength of association of crystal networks. Moreover, four different kinetic paths of crystal network formation are identified, namely, one-step process of assembly, two-step process of assembly, mixed mode of assembly and foreign molecule mediated assembly. Based on the basic mechanisms of crystal nucleation and growth, the formation of crystal networks, such as crystallographic mismatch (or noncrystallographic) branching (tip branching and fibre side branching) and fibre/polymeric side merging, are reviewed. This facilitates the rational design and construction of crystal networks in supramolecular materials. In this context, the (re-)construction of a hierarchical crystal network structure can be implemented by thermal, precipitate, chemical, and sonication stimuli. As another important class of soft materials, the unusual mechanical performance of spider and silkworm silk fibres are reviewed in comparison with the regenerated silk protein derivatives. It follows that the considerably larger breaking stress and unusual breaking strain of spider silk fibres vs. silkworm silk fibres can be interpreted according to the synergistically correlated hierarchical structures of the domain and crystal networks, which can be quantified by the hierarchical structural correlation and the four structural parameters. Based on the concept of crystal networks, the new understanding acquired will transfer the research and engineering of mesoscopic materials, particularly, soft functional materials, to a new phase.

Molecular emulsions: from charge order to domain order.

PubMed

Perera, Aurélien

2017-10-25

Aqueous mixtures of small molecules, such as lower n-alkanols for example, are known to be micro-segregated, with domains in the nano-meter range. One consequence of this micro-segregation would be the existence of long range domain-domain oscillatory correlations in the various atom-atom pair correlation functions, and subsequent pre-peaks in the corresponding atom-atom structure factors, in the q-vector range corresponding to nano-sized domains. However, no such pre-peak have ever been observed in the large corpus of radiation scattering data published so far on aqueous mixtures of small n-alkanols. By using large scale simulations of aqueous-1propanol mixtures, it is shown herein that the origin for the absence of scattering pre-peak resides in the exact cancellation of the contributions of the various atom-atom correlation pre-peaks to the total scattered intensity. The mechanism for this cancellation is due to the differences in the long range oscillatory behaviour of the correlations (beyond 1 nm), which are exactly out-of-phase between same species and cross species. This is similar to the charge order observed in ionic melts, but differs from room temperature ionic liquids, where the segregation is between charged and neutral groups, instead of species segregation. The consequences of such cancellation in the experimental scattering data are examined, in relation to the possibility of detecting micro-segregation through such methods. In the particular case of aqueous-1propanol mixtures, it is shown the X-ray scattering leads an exact cancellation, while this cancellation in neutron scattering is seen to depend on the deuteration ratio between solvent and solute.

Reliability and validity of the 12-item WHODAS 2.0 in patients with Kashin-Beck disease.

PubMed

Younus, Mohammad Imran; Wang, Di-Miao; Yu, Fang-Fang; Fang, Hua; Guo, Xiong

2017-09-01

The purpose of this study was to check the reliability and validity of the 12-item Chinese version of the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) for the assessment of disability in patients with Kashin-Beck disease (KBD). We recruited 219 patients with KBD from the high-risk KBD area in the Shaanxi province, using stratified multistage random sampling. We assessed each patient using the Chinese version of the 12-item WHODAS 2.0 and the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC). Statistical evaluations of the instruments consisted of Cronbach's alpha, intraclass correlation coefficient (ICC), confirmatory factor analysis (CFA), and Pearson's correlation coefficient. Cronbach's alpha and ICC for the six domains ranged from 0.704 to 0.906 and 0.690 to 0.852, respectively. A six-factor structure fits the data well (CFI = 0.967, TLI = 0.944, RMSEA = 0.08). Regarding convergent validity, the four domains of the 12-item WHODAS 2.0 (getting around, self-care, life activity, and participation) showed moderate-to-strong correlation for all three domains of the WOMAC (0.428 < |r| < 0.804). Regarding divergent validity, the two domains of the 12-item WHODAS 2.0 (understanding and communication, and getting along with people) showed weak correlation for the three domains of WOMAC (0.182 < |r| < 0.295). The Chinese version of 12-item WHODAS 2.0 questionnaire is a reliable and valid instrument when administered to KBD patients.

Extracting the mass dependence and quantum numbers of short-range correlated pairs from A ( e , e ' p ) and A ( e , e ' p p ) scattering

DOE PAGES

Colle, C.; Hen, O.; Cosyn, W.; ...

2015-08-06

Tmore » he addition of Molybdenum was used to modify the nanostructure and enhance coercivity of rare-earth-free Zr 2Co 11-based nanocrystalline permanent magnets. he effect of Mo addition on magnetic domain structures of melt spun nanocrystalline Zr 16Co 84-xMo x( x = 0 , 0.5, 1, 1.5, and 2.0) ribbons has been investigated. It was found that magnetic properties and local domain structures are strongly influenced by Mo doping. he coercivity of the samples increases with the increase in Mo content ( x ≤ 1.5 ). he maximum energy product ( B H ) max increases with increasing x from 0.5 MGOe for x = 0 to a maximum value of 4.2 MGOe for x = 1.5 . he smallest domain size with a relatively short magnetic correlation length of 128 nm and largest root-mean-square phase shift Φ rms value of 0.66° are observed for the x = 1.5 . he optimal Mo addition promotes magnetic domain structure refinement and thus leads to a significant increase in coercivity and energy product in this sample. MDH is primarily a dimer in solution, although an oligomeric species with a molecular mass of ~450–560 kDa forms at higher protein concentrations. A new measurement of the rare, doubly radiative decay eta->pi 0 γγ was conducted with the Crystal Ball and APS multiphoton spectrometers together with the photon tagging facility at the Mainz Microtron MAMI.« less

Extracting the mass dependence and quantum numbers of short-range correlated pairs from A ( e , e ' p ) and A ( e , e ' p p ) scattering

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

Colle, C.; Hen, O.; Cosyn, W.

Tmore » he addition of Molybdenum was used to modify the nanostructure and enhance coercivity of rare-earth-free Zr 2Co 11-based nanocrystalline permanent magnets. he effect of Mo addition on magnetic domain structures of melt spun nanocrystalline Zr 16Co 84-xMo x( x = 0 , 0.5, 1, 1.5, and 2.0) ribbons has been investigated. It was found that magnetic properties and local domain structures are strongly influenced by Mo doping. he coercivity of the samples increases with the increase in Mo content ( x ≤ 1.5 ). he maximum energy product ( B H ) max increases with increasing x from 0.5 MGOe for x = 0 to a maximum value of 4.2 MGOe for x = 1.5 . he smallest domain size with a relatively short magnetic correlation length of 128 nm and largest root-mean-square phase shift Φ rms value of 0.66° are observed for the x = 1.5 . he optimal Mo addition promotes magnetic domain structure refinement and thus leads to a significant increase in coercivity and energy product in this sample. MDH is primarily a dimer in solution, although an oligomeric species with a molecular mass of ~450–560 kDa forms at higher protein concentrations. A new measurement of the rare, doubly radiative decay eta->pi 0 γγ was conducted with the Crystal Ball and APS multiphoton spectrometers together with the photon tagging facility at the Mainz Microtron MAMI.« less

Combining protein sequence, structure, and dynamics: A novel approach for functional evolution analysis of PAS domain superfamily.

PubMed

Dong, Zheng; Zhou, Hongyu; Tao, Peng

2018-02-01

PAS domains are widespread in archaea, bacteria, and eukaryota, and play important roles in various functions. In this study, we aim to explore functional evolutionary relationship among proteins in the PAS domain superfamily in view of the sequence-structure-dynamics-function relationship. We collected protein sequences and crystal structure data from RCSB Protein Data Bank of the PAS domain superfamily belonging to three biological functions (nucleotide binding, photoreceptor activity, and transferase activity). Protein sequences were aligned and then used to select sequence-conserved residues and build phylogenetic tree. Three-dimensional structure alignment was also applied to obtain structure-conserved residues. The protein dynamics were analyzed using elastic network model (ENM) and validated by molecular dynamics (MD) simulation. The result showed that the proteins with same function could be grouped by sequence similarity, and proteins in different functional groups displayed statistically significant difference in their vibrational patterns. Interestingly, in all three functional groups, conserved amino acid residues identified by sequence and structure conservation analysis generally have a lower fluctuation than other residues. In addition, the fluctuation of conserved residues in each biological function group was strongly correlated with the corresponding biological function. This research suggested a direct connection in which the protein sequences were related to various functions through structural dynamics. This is a new attempt to delineate functional evolution of proteins using the integrated information of sequence, structure, and dynamics. © 2017 The Protein Society.

Structure-based multiscale approach for identification of interaction partners of PDZ domains.

PubMed

Tiwari, Garima; Mohanty, Debasisa

2014-04-28

PDZ domains are peptide recognition modules which mediate specific protein-protein interactions and are known to have a complex specificity landscape. We have developed a novel structure-based multiscale approach which identifies crucial specificity determining residues (SDRs) of PDZ domains from explicit solvent molecular dynamics (MD) simulations on PDZ-peptide complexes and uses these SDRs in combination with knowledge-based scoring functions for proteomewide identification of their interaction partners. Multiple explicit solvent simulations ranging from 5 to 50 ns duration have been carried out on 28 PDZ-peptide complexes with known binding affinities. MM/PBSA binding energy values calculated from these simulations show a correlation coefficient of 0.755 with the experimental binding affinities. On the basis of the SDRs of PDZ domains identified by MD simulations, we have developed a simple scoring scheme for evaluating binding energies for PDZ-peptide complexes using residue based statistical pair potentials. This multiscale approach has been benchmarked on a mouse PDZ proteome array data set by calculating the binding energies for 217 different substrate peptides in binding pockets of 64 different mouse PDZ domains. Receiver operating characteristic (ROC) curve analysis indicates that, the area under curve (AUC) values for binder vs nonbinder classification by our structure based method is 0.780. Our structure based method does not require experimental PDZ-peptide binding data for training.

Role of Altered Sialylation of the I-Like Domain of β1 Integrin in the Binding of Fibronectin to β1 Integrin: Thermodynamics and Conformational Analyses

PubMed Central

Pan, Di; Song, Yuhua

2010-01-01

Abstract N-glycosylation of the I-like domain of β1 integrin plays an essential role in integrin structure and function, and the altered sialylation of β1 integrin regulates β1 integrin binding to fibronectin. However, the structural basis underlying the effect of altered sialylation of the β1 I-like domain on β1 integrin binding to fibronectin remains largely unknown. In this study, we used a combination of molecular dynamics simulations and binding free energy analyses to investigate changes in binding thermodynamics and in conformation of the glycosylated β1 I-like domain-FN-III9-10 complex caused by altered sialylation of the β1 I-like domain. Binding free energy analyses showed that desialylation of β1 I-like domain increased β1 integrin binding to fibronectin, consistent with experimental results. Interaction analyses showed that altered sialylation of the β1 I-like domain resulted in significant changes in the interaction of the N-glycans of the I-like domain with both the I-like domain and fibronectin, and these changes could directly affect the allosteric regulation of the interaction between the I-like domain and fibronectin. Altered sialylation of the β1 I-like domain caused significant conformational changes in key functional sites of both the β1 I-like domain and fibronectin. In addition, altered sialylation of the β1 I-like domain resulted in changes in the degree of correlated motions between residues in the I-like domain and residues in fibronectin, and in the degree of motion changes in fibronectin, which could affect β1 integrin binding to fibronectin. We believe results from this study provide thermodynamic and structural evidence for a role of altered sialylation of β1 integrin in regulating β1 integrin binding to fibronectin and it's induced cellular activities. PMID:20655849

The Scientific Competitiveness of Nations

PubMed Central

Cimini, Giulio; Gabrielli, Andrea; Sylos Labini, Francesco

2014-01-01

We use citation data of scientific articles produced by individual nations in different scientific domains to determine the structure and efficiency of national research systems. We characterize the scientific fitness of each nation—that is, the competitiveness of its research system—and the complexity of each scientific domain by means of a non-linear iterative algorithm able to assess quantitatively the advantage of scientific diversification. We find that technological leading nations, beyond having the largest production of scientific papers and the largest number of citations, do not specialize in a few scientific domains. Rather, they diversify as much as possible their research system. On the other side, less developed nations are competitive only in scientific domains where also many other nations are present. Diversification thus represents the key element that correlates with scientific and technological competitiveness. A remarkable implication of this structure of the scientific competition is that the scientific domains playing the role of “markers” of national scientific competitiveness are those not necessarily of high technological requirements, but rather addressing the most “sophisticated” needs of the society. PMID:25493626

Control of the structural landscape and neuronal proteotoxicity of mutant Huntingtin by domains flanking the polyQ tract

PubMed Central

Shen, Koning; Calamini, Barbara; Fauerbach, Jonathan A; Ma, Boxue; Shahmoradian, Sarah H; Serrano Lachapel, Ivana L; Chiu, Wah; Lo, Donald C; Frydman, Judith

2016-01-01

Many neurodegenerative diseases are linked to amyloid aggregation. In Huntington’s disease (HD), neurotoxicity correlates with an increased aggregation propensity of a polyglutamine (polyQ) expansion in exon 1 of mutant huntingtin protein (mHtt). Here we establish how the domains flanking the polyQ tract shape the mHtt conformational landscape in vitro and in neurons. In vitro, the flanking domains have opposing effects on the conformation and stabilities of oligomers and amyloid fibrils. The N-terminal N17 promotes amyloid fibril formation, while the C-terminal Proline Rich Domain destabilizes fibrils and enhances oligomer formation. However, in neurons both domains act synergistically to engage protective chaperone and degradation pathways promoting mHtt proteostasis. Surprisingly, when proteotoxicity was assessed in rat corticostriatal brain slices, either flanking region alone sufficed to generate a neurotoxic conformation, while the polyQ tract alone exhibited minimal toxicity. Linking mHtt structural properties to its neuronal proteostasis should inform new strategies for neuroprotection in polyQ-expansion diseases. DOI: http://dx.doi.org/10.7554/eLife.18065.001 PMID:27751235

HiTAD: detecting the structural and functional hierarchies of topologically associating domains from chromatin interactions

PubMed Central

Wang, Xiao-Tao; Cui, Wang

2017-01-01

Abstract A current question in the high-order organization of chromatin is whether topologically associating domains (TADs) are distinct from other hierarchical chromatin domains. However, due to the unclear TAD definition in tradition, the structural and functional uniqueness of TAD is not well studied. In this work, we refined TAD definition by further constraining TADs to the optimal separation on global intra-chromosomal interactions. Inspired by this constraint, we developed a novel method, called HiTAD, to detect hierarchical TADs from Hi-C chromatin interactions. HiTAD performs well in domain sensitivity, replicate reproducibility and inter cell-type conservation. With a novel domain-based alignment proposed by us, we defined several types of hierarchical TAD changes which were not systematically studied previously, and subsequently used them to reveal that TADs and sub-TADs differed statistically in correlating chromosomal compartment, replication timing and gene transcription. Finally, our work also has the implication that the refinement of TAD definition could be achieved by only utilizing chromatin interactions, at least in part. HiTAD is freely available online. PMID:28977529

Slush-like polar structures in single-crystal relaxors

NASA Astrophysics Data System (ADS)

Takenaka, Hiroyuki; Grinberg, Ilya; Liu, Shi; Rappe, Andrew M.

2017-06-01

Despite more than 50 years of investigation, it is still unclear how the underlying structure of relaxor ferroelectrics gives rise to their defining properties, such as ultrahigh piezoelectric coefficients, high permittivity over a broad temperature range, diffuse phase transitions, strong frequency dependence in dielectric response, and phonon anomalies. The model of polar nanoregions inside a non-polar matrix has been widely used to describe the structure of relaxor ferroelectrics. However, the lack of precise knowledge about the shapes, growth and dipole patterns of polar nanoregions has led to the characterization of relaxors as “hopeless messes”, and no predictive model for relaxor behaviour is currently available. Here we use molecular dynamics simulations of the prototypical Pb(Mg1/3,Nb2/3)O3-PbTiO3 relaxor material to examine its structure and the spatial and temporal polarization correlations. Our simulations show that the unusual properties of relaxors stem from the presence of a multi-domain state with extremely small domain sizes (2-10 nanometres), and no non-polar matrix, owing to the local dynamics. We find that polar structures in the multi-domain state in relaxors are analogous to those of the slush state of water. The multi-domain structure of relaxors that is revealed by our molecular dynamics simulations is consistent with recent experimental diffuse scattering results and indicates that relaxors have a high density of low-angle domain walls. This insight explains the recently discovered classes of relaxors that cannot be described by the polar nanoregion model, and provides guidance for the design and synthesis of new relaxor materials.

Molecular dynamics simulations of site point mutations in the TPR domain of cyclophilin 40 identify conformational states with distinct dynamic and enzymatic properties

NASA Astrophysics Data System (ADS)

Gur, Mert; Blackburn, Elizabeth A.; Ning, Jia; Narayan, Vikram; Ball, Kathryn L.; Walkinshaw, Malcolm D.; Erman, Burak

2018-04-01

Cyclophilin 40 (Cyp40) is a member of the immunophilin family that acts as a peptidyl-prolyl-isomerase enzyme and binds to the heat shock protein 90 (Hsp90). Its structure comprises an N-terminal cyclophilin domain and a C-terminal tetratricopeptide (TPR) domain. Cyp40 is overexpressed in prostate cancer and certain T-cell lymphomas. The groove for Hsp90 binding on the TPR domain includes residues Lys227 and Lys308, referred to as the carboxylate clamp, and is essential for Cyp40-Hsp90 binding. In this study, the effect of two mutations, K227A and K308A, and their combinative mutant was investigated by performing a total of 5.76 μs of all-atom molecular dynamics (MD) simulations in explicit solvent. All simulations, except the K308A mutant, were found to adopt two distinct (extended or compact) conformers defined by different cyclophilin-TPR interdomain distances. The K308A mutant was only observed in the extended form which is observed in the Cyp40 X-ray structure. The wild-type, K227A, and combined mutant also showed bimodal distributions. The experimental melting temperature, Tm, values of the mutants correlate with the degree of compactness with the K308A extended mutant having a marginally lower melting temperature. Another novel measure of compactness determined from the MD data, the "coordination shell volume," also shows a direct correlation with Tm. In addition, the MD simulations show an allosteric effect with the mutations in the remote TPR domain having a pronounced effect on the molecular motions of the enzymatic cyclophilin domain which helps rationalise the experimentally observed increase in enzyme activity measured for all three mutations.

Structural consequences of disease-causing mutations in the ATRX-DNMT3-DNMT3L (ADD) domain of the chromatin-associated protein ATRX.

PubMed

Argentaro, Anthony; Yang, Ji-Chun; Chapman, Lynda; Kowalczyk, Monika S; Gibbons, Richard J; Higgs, Douglas R; Neuhaus, David; Rhodes, Daniela

2007-07-17

The chromatin-associated protein ATRX was originally identified because mutations in the ATRX gene cause a severe form of syndromal X-linked mental retardation associated with alpha-thalassemia. Half of all of the disease-associated missense mutations cluster in a cysteine-rich region in the N terminus of ATRX. This region was named the ATRX-DNMT3-DNMT3L (ADD) domain, based on sequence homology with a family of DNA methyltransferases. Here, we report the solution structure of the ADD domain of ATRX, which consists of an N-terminal GATA-like zinc finger, a plant homeodomain finger, and a long C-terminal alpha-helix that pack together to form a single globular domain. Interestingly, the alpha-helix of the GATA-like finger is exposed and highly basic, suggesting a DNA-binding function for ATRX. The disease-causing mutations fall into two groups: the majority affect buried residues and hence affect the structural integrity of the ADD domain; another group affects a cluster of surface residues, and these are likely to perturb a potential protein interaction site. The effects of individual point mutations on the folding state and stability of the ADD domain correlate well with the levels of mutant ATRX protein in patients, providing insights into the molecular pathophysiology of ATR-X syndrome.

Cognitive representation of "musical fractals": Processing hierarchy and recursion in the auditory domain.

PubMed

Martins, Mauricio Dias; Gingras, Bruno; Puig-Waldmueller, Estela; Fitch, W Tecumseh

2017-04-01

The human ability to process hierarchical structures has been a longstanding research topic. However, the nature of the cognitive machinery underlying this faculty remains controversial. Recursion, the ability to embed structures within structures of the same kind, has been proposed as a key component of our ability to parse and generate complex hierarchies. Here, we investigated the cognitive representation of both recursive and iterative processes in the auditory domain. The experiment used a two-alternative forced-choice paradigm: participants were exposed to three-step processes in which pure-tone sequences were built either through recursive or iterative processes, and had to choose the correct completion. Foils were constructed according to generative processes that did not match the previous steps. Both musicians and non-musicians were able to represent recursion in the auditory domain, although musicians performed better. We also observed that general 'musical' aptitudes played a role in both recursion and iteration, although the influence of musical training was somehow independent from melodic memory. Moreover, unlike iteration, recursion in audition was well correlated with its non-auditory (recursive) analogues in the visual and action sequencing domains. These results suggest that the cognitive machinery involved in establishing recursive representations is domain-general, even though this machinery requires access to information resulting from domain-specific processes. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Effect of defects, magnetocrystalline anisotropy, and shape anisotropy on magnetic structure of iron thin films by magnetic force microscopy

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

Xu, Ke; Schreiber, Daniel K.; Li, Yulan

Microstructures of magnetic materials, including defects and crystallographic orientations, are known to strongly influence magnetic domain structures. Measurement techniques such as magnetic force microscopy (MFM) thus allow study of correlations between microstructural and magnetic properties. The present work probes effects of anisotropy and artificial defects on the evolution of domain structure with applied field. Single crystal iron thin films on MgO substrates were milled by Focused Ion Beam (FIB) to create different magnetically isolated squares and rectangles in [110] crystallographic orientations, having their easy axis 45° from the sample edge. To investigate domain wall response on encountering non-magnetic defects, amore » 150 nm diameter hole was created in the center of some samples. By simultaneously varying crystal orientation and shape, both magnetocrystalline anisotropy and shape anisotropy, as well as their interaction, could be studied. Shape anisotropy was found to be important primarily for the longer edge of rectangular samples, which exaggerated the FIB edge effects and provided nucleation sites for spike domains in non-easy axis oriented samples. Center holes acted as pinning sites for domain walls until large applied magnetic fields. The present studies are aimed at deepening the understanding of the propagation of different types of domain walls in the presence of defects and different crystal orientations.« less

Effect of defects, magnetocrystalline anisotropy, and shape anisotropy on magnetic structure of iron thin films by magnetic force microscopy

DOE PAGES

Xu, Ke; Schreiber, Daniel K.; Li, Yulan; ...

2017-02-10

Microstructures of magnetic materials, including defects and crystallographic orientations, are known to strongly influence magnetic domain structures. Measurement techniques such as magnetic force microscopy (MFM) thus allow study of correlations between microstructural and magnetic properties. The present work probes effects of anisotropy and artificial defects on the evolution of domain structure with applied field. Single crystal iron thin films on MgO substrates were milled by Focused Ion Beam (FIB) to create different magnetically isolated squares and rectangles in [110] crystallographic orientations, having their easy axis 45° from the sample edge. To investigate domain wall response on encountering non-magnetic defects, amore » 150 nm diameter hole was created in the center of some samples. By simultaneously varying crystal orientation and shape, both magnetocrystalline anisotropy and shape anisotropy, as well as their interaction, could be studied. Shape anisotropy was found to be important primarily for the longer edge of rectangular samples, which exaggerated the FIB edge effects and provided nucleation sites for spike domains in non-easy axis oriented samples. Center holes acted as pinning sites for domain walls until large applied magnetic fields. The present studies are aimed at deepening the understanding of the propagation of different types of domain walls in the presence of defects and different crystal orientations.« less

Transformed PANSS Factors Intended to Reduce Pseudospecificity Among Symptom Domains and Enhance Understanding of Symptom Change in Antipsychotic-Treated Patients With Schizophrenia

PubMed Central

Hopkins, Seth C; Ogirala, Ajay; Loebel, Antony; Koblan, Kenneth S

2018-01-01

Abstract Positive and Negative Syndrome Scale (PANSS) total score is the standard primary efficacy measure in acute treatment studies of schizophrenia. However, PANSS factors that have been derived from factor analytic approaches over the past several decades have uncertain clinical and regulatory status as they are, to varying degrees, intercorrelated. As a consequence of cross-factor correlations, the apparent improvement in key clinical domains (eg, negative symptoms, disorganized thinking/behavior) may largely be attributable to improvement in a related clinical domain, such as positive symptoms, a problem often referred to as pseudospecificity. Here, we analyzed correlations among PANSS items, at baseline and change post-baseline, in a pooled sample of 5 placebo-controlled clinical trials (N = 1710 patients), using clustering and factor analysis to identify an uncorrelated PANSS score matrix (UPSM) that minimized the degree of correlation between each resulting transformed PANSS factor. The transformed PANSS factors corresponded well with discrete symptom domains described by prior factor analyses, but between-factor change-scores correlations were markedly lower. We then used the UPSM to transform PANSS in data from 4657 unique schizophrenia patients included in 12 additional lurasidone clinical trials. The results confirmed that transformed PANSS factors retained a high degree of specificity, thus validating that low between-factor correlations are a reliable property of the USPM when transforming PANSS data from a variety of clinical trial data sets. These results provide a more robust understanding of the structure of symptom change in schizophrenia and suggest a means to evaluate the specificity of antipsychotic treatment effects. PMID:28981857

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

Wang, Liwei; Yang, Jin Kuk; Kabaleeswaran, Venkataraman

The death-inducing signaling complex (DISC) formed by the death receptor Fas, the adaptor protein FADD and caspase-8 mediates the extrinsic apoptotic program. Mutations in Fas that disrupt the DISC cause autoimmune lymphoproliferative syndrome (ALPS). Here we show that the Fas-FADD death domain (DD) complex forms an asymmetric oligomeric structure composed of 5-7 Fas DD and 5 FADD DD, whose interfaces harbor ALPS-associated mutations. Structure-based mutations disrupt the Fas-FADD interaction in vitro and in living cells; the severity of a mutation correlates with the number of occurrences of a particular interaction in the structure. The highly oligomeric structure explains the requirementmore » for hexameric or membrane-bound FasL in Fas signaling. It also predicts strong dominant negative effects from Fas mutations, which are confirmed by signaling assays. The structure optimally positions the FADD death effector domain (DED) to interact with the caspase-8 DED for caspase recruitment and higher-order aggregation.« less

Threading structural model of the manganese-stabilizing protein PsbO reveals presence of two possible beta-sandwich domains.

PubMed

Pazos, F; Heredia, P; Valencia, A; de las Rivas, J

2001-12-01

The manganese-stabilizing protein (PsbO) is an essential component of photosystem II (PSII) and is present in all oxyphotosynthetic organisms. PsbO allows correct water splitting and oxygen evolution by stabilizing the reactions driven by the manganese cluster. Despite its important role, its structure and detailed functional mechanism are still unknown. In this article we propose a structural model based on fold recognition and molecular modeling. This model has additional support from a study of the distribution of characteristics of the PsbO sequence family, such as the distribution of conserved, apolar, tree-determinants, and correlated positions. Our threading results consistently showed PsbO as an all-beta (beta) protein, with two homologous beta domains of approximately 120 amino acids linked by a flexible Proline-Glycine-Glycine (PGG) motif. These features are compatible with a general elongated and flexible architecture, in which the two domains form a sandwich-type structure with Greek key topology. The first domain is predicted to include 8 to 9 beta-strands, the second domain 6 to 7 beta-strands. An Ig-like beta-sandwich structure was selected as a template to build the 3-D model. The second domain has, between the strands, long-loops rich in Pro and Gly that are difficult to model. One of these long loops includes a highly conserved region (between P148 and P174) and a short alpha-helix (between E181 and N188)). These regions are characteristic parts of PsbO and show that the second domain is not so similar to the template. Overall, the model was able to account for much of the experimental data reported by several authors, and it would allow the detection of key residues and regions that are proposed in this article as essential for the structure and function of PsbO. Copyright 2001 Wiley-Liss, Inc.

Human acid sphingomyelinase structures provide insight to molecular basis of Niemann–Pick disease

PubMed Central

Zhou, Yan-Feng; Metcalf, Matthew C.; Garman, Scott C.; Edmunds, Tim; Qiu, Huawei; Wei, Ronnie R.

2016-01-01

Acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to ceramide and phosphocholine, essential components of myelin in neurons. Genetic alterations in ASM lead to ASM deficiency (ASMD) and have been linked to Niemann–Pick disease types A and B. Olipudase alfa, a recombinant form of human ASM, is being developed as enzyme replacement therapy to treat the non-neurological manifestations of ASMD. Here we present the human ASM holoenzyme and product bound structures encompassing all of the functional domains. The catalytic domain has a metallophosphatase fold, and two zinc ions and one reaction product phosphocholine are identified in a histidine-rich active site. The structures reveal the underlying catalytic mechanism, in which two zinc ions activate a water molecule for nucleophilic attack of the phosphodiester bond. Docking of sphingomyelin provides a model that allows insight into the selectivity of the enzyme and how the ASM domains collaborate to complete hydrolysis. Mapping of known mutations provides a basic understanding on correlations between enzyme dysfunction and phenotypes observed in ASMD patients. PMID:27725636

Molecular dynamics simulation of the Escherichia coli NikR protein: Equilibrium conformational fluctuations reveal inter-domain allosteric communication pathways

PubMed Central

Bradley, Michael J.; Chivers, Peter T.; Baker, Nathan A.

2008-01-01

Summary E. coliNikR is a homotetrameric Ni2+- and DNA-binding protein that functions as a transcriptional repressor of the NikABCDE nickel permease. The protein is composed of 2 distinct domains. The N-terminal fifty amino acids of each chain forms part of the dimeric ribbon-helix-helix (RHH) domains, a well-studied DNA-binding fold. The eighty-three residue C-terminal nickel-binding domain forms an ACT-fold and contains the tetrameric interface. In this study, we have utilized an equilibrium molecular dynamics (MD) simulation in order to explore the conformational dynamics of the NikR tetramer and determine important residue interactions within and between the RHH and ACT domains to gain insight into the effects of Ni on DNA-binding activity. The molecular simulation data was analyzed using two different correlation measures based on fluctuations in atomic position and non-covalent contacts, together with a clustering algorithm to define groups of residues with similar correlation patterns for both types of correlation measure. Based on these analyses, we have defined a series of residue interrelationships that describe an allosteric communication pathway between the Ni2+ and DNA binding sites, which are separated by 40 Å. Several of the residues identified by our analyses have been previously shown experimentally to be important for NikR function. An additional subset of the identified residues structurally connects the experimentally implicated residues and may help coordinate the allosteric communication between the ACT and RHH domains. PMID:18433769

Backbone dynamics in an intramolecular prolylpeptide-SH3 complex from the diphtheria toxin repressor, DtxR

PubMed Central

Bhattacharya, Nilakshee; Yi, Myunggi; Zhou, Huan-Xiang; Logan, Timothy M.

2008-01-01

Summary The diphtheria toxin repressor contains an SH3-like domain that forms an intramolecular complex with a proline-rich (Pr) peptide segment and stabilizes the inactive state of the repressor. Upon activation of DtxR by transition metals, this intramolecular complex must dissociate as the SH3 domain and Pr segment form different interactions in the active repressor. In this study we investigate the dynamics of this intramolecular complex using backbone amide nuclear spin relaxation rates determined using NMR spectroscopy and molecular dynamics trajectories. The SH3 domain in the unbound and bound states showed typical dynamics in that the secondary structures were fairly ordered with high generalized order parameters and low effective correlation times while residues in the loops connecting β-strands exhibited reduced generalized order parameters and required additional motional terms to adequately model the relaxation rates. Residues forming the Pr segment exhibited low order parameters with internal rotational correlation times on the order of 0.6 – 1 ns. Further analysis showed that the SH3 domain was rich in millisecond timescale motions while the Pr segment was rich in motions on the 100s μs timescale. Molecular dynamics simultations indicated structural rearrangements that may contribute to the observed relaxation rates and, together with the observed relaxation rate data, suggested that the Pr segment exhibits a binding ↔ unbinding equilibrium. The results of this study provide new insights into the nature of the intramolecular complex and provide a better understanding of the biological role of the SH3 domain in regulating DtxR activity. PMID:17976643

The genetic architecture of pediatric cognitive abilities in the Philadelphia Neurodevelopmental Cohort

PubMed Central

Robinson, Elise B.; Kirby, Andrew; Ruparel, Kosha; Yang, Jian; McGrath, Lauren; Anttila, Verneri; Neale, Benjamin M.; Merikangas, Kathleen; Lehner, Thomas; Sleiman, Patrick M.A.; Daly, Mark J.; Gur, Ruben; Gur, Raquel; Hakonarson, Hakon

2014-01-01

The objective of this analysis was to examine the genetic architecture of diverse cognitive abilities in children and adolescents, including the magnitude of common genetic effects and patterns of shared and unique genetic influences. Subjects included 3,689 members of the Philadelphia Neurodevelopmental Cohort, a general population sample of ages 8-21 years who completed an extensive battery of cognitive tests. We used genome-wide complex trait analysis (GCTA) to estimate the SNP-based heritability of each domain, as well as the genetic correlation between all domains that showed significant genetic influence. Several of the individual domains suggested strong influence of common genetic variants (e.g. reading ability, h2g=0.43, p=4e-06; emotion identification, h2g=0.36, p=1e-05; verbal memory, h2g=0.24, p=0.005). The genetic correlations highlighted trait domains that are candidates for joint interrogation in future genetic studies (e.g. language reasoning and spatial reasoning, r(g)=0.72, p=0.007). These results can be used to structure future genetic and neuropsychiatric investigations of diverse cognitive abilities. PMID:25023143

Spectral identification of topological domains

PubMed Central

Chen, Jie; Hero, Alfred O.; Rajapakse, Indika

2016-01-01

Motivation: Topological domains have been proposed as the backbone of interphase chromosome structure. They are regions of high local contact frequency separated by sharp boundaries. Genes within a domain often have correlated transcription. In this paper, we present a computational efficient spectral algorithm to identify topological domains from chromosome conformation data (Hi-C data). We consider the genome as a weighted graph with vertices defined by loci on a chromosome and the edge weights given by interaction frequency between two loci. Laplacian-based graph segmentation is then applied iteratively to obtain the domains at the given compactness level. Comparison with algorithms in the literature shows the advantage of the proposed strategy. Results: An efficient algorithm is presented to identify topological domains from the Hi-C matrix. Availability and Implementation: The Matlab source code and illustrative examples are available at http://bionetworks.ccmb.med.umich.edu/ Contact: indikar@med.umich.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27153657

Structural correlates of carrier protein recognition in tetanus toxoid-conjugated bacterial polysaccharide vaccines.

PubMed

Lockyer, Kay; Gao, Fang; Derrick, Jeremy P; Bolgiano, Barbara

2015-03-10

An analysis of structure-antibody recognition relationships in nine licenced polysaccharide-tetanus toxoid (TT) conjugate vaccines was performed. The panel of conjugates used included vaccine components to protect against disease caused by Haemophilus influenzae type b, Neisseria meningitidis groups A, C, W and Y and Streptococcus pneumoniae serotype 18C. Conformation and structural analysis included size exclusion chromatography with multi-angle light scattering to determine size, and intrinsic fluorescence spectroscopy and fluorescence quenching to evaluate the protein folding and exposure of Trp residues. A capture ELISA measured the recognition of TT epitopes in the conjugates, using four rat monoclonal antibodies: 2 localised to the HC domain, and 2 of which were holotoxoid conformation-dependent. The conjugates had a wide range of average molecular masses ranging from 1.8×10(6) g/mol to larger than 20×10(6) g/mol. The panel of conjugates were found to be well folded, and did not have spectral features typical of aggregated TT. A partial correlation was found between molecular mass and epitope recognition. Recognition of the epitopes either on the HC domain or the whole toxoid was not necessarily hampered by the size of the molecule. Correlation was also found between the accessibility of Trp side chains and polysaccharide loading, suggesting also that a higher level of conjugated PS does not necessarily interfere with toxoid accessibility. There were different levels of carrier protein Trp side-chain and epitope accessibility that were localised to the HC domain; these were related to the saccharide type, despite the conjugates being independently manufactured. These findings extend our understanding of the molecular basis for carrier protein recognition in TT conjugate vaccines. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Structural correlates of carrier protein recognition in tetanus toxoid-conjugated bacterial polysaccharide vaccines

PubMed Central

Lockyer, Kay; Gao, Fang; Derrick, Jeremy P.; Bolgiano, Barbara

2015-01-01

An analysis of structure-antibody recognition relationships in nine licenced polysaccharide-tetanus toxoid (TT) conjugate vaccines was performed. The panel of conjugates used included vaccine components to protect against disease caused by Haemophilus influenzae type b, Neisseria meningitidis groups A, C, W and Y and Streptococcus pneumoniae serotype 18C. Conformation and structural analysis included size exclusion chromatography with multi-angle light scattering to determine size, and intrinsic fluorescence spectroscopy and fluorescence quenching to evaluate the protein folding and exposure of Trp residues. A capture ELISA measured the recognition of TT epitopes in the conjugates, using four rat monoclonal antibodies: 2 localised to the HC domain, and 2 of which were holotoxoid conformation-dependent. The conjugates had a wide range of average molecular masses ranging from 1.8 × 106 g/mol to larger than 20 × 106 g/mol. The panel of conjugates were found to be well folded, and did not have spectral features typical of aggregated TT. A partial correlation was found between molecular mass and epitope recognition. Recognition of the epitopes either on the HC domain or the whole toxoid was not necessarily hampered by the size of the molecule. Correlation was also found between the accessibility of Trp side chains and polysaccharide loading, suggesting also that a higher level of conjugated PS does not necessarily interfere with toxoid accessibility. There were different levels of carrier protein Trp side-chain and epitope accessibility that were localised to the HC domain; these were related to the saccharide type, despite the conjugates being independently manufactured. These findings extend our understanding of the molecular basis for carrier protein recognition in TT conjugate vaccines. PMID:25640334

Cross-cultural adaptation, reliability and construct validity of the Tampa scale for kinesiophobia for temporomandibular disorders (TSK/TMD-Br) into Brazilian Portuguese.

PubMed

Aguiar, A S; Bataglion, C; Visscher, C M; Bevilaqua Grossi, D; Chaves, T C

2017-07-01

Fear of movement (kinesiophobia) seems to play an important role in the development of chronic pain. However, for temporomandibular disorders (TMD), there is a scarcity of studies about this topic. The Tampa Scale for Kinesiophobia for TMD (TSK/TMD) is the most widely used instrument to measure fear of movement and it is not available in Brazilian Portuguese. The purpose of this study was to culturally adapt the TSK/TMD to Brazilian Portuguese and to assess its psychometric properties regarding internal consistency, reliability, and construct and structural validity. A total of 100 female patients with chronic TMD participated in the validation process of the TSK/TMD-Br. The intraclass correlation coefficient (ICC) was used for statistical analysis of reliability (test-retest), Cronbach's alpha for internal consistency, Spearman's rank correlation for construct validity and confirmatory factor analysis (CFA) for structural validity. CFA endorsed the pre-specified model with two domains and 12-items (Activity Avoidance - AA/Somatic Focus - SF) and all items obtained a loading factor greater than 0·4. Acceptable levels of reliability were found (ICC > 0·75) for all questions and domains of the TSK/TMD-Br. For internal consistency, Cronbach's α of 0·78 for both domains were found. Moderate correlations (0·40 < r < 0.60) were observed for 84% of the analyses conducted between TSK/TMD-Br scores versus catastrophising, depression and jaw functional limitation. TSK/TMD-Br 12 items and two-factor demonstrated sound psychometric properties (transcultural validity, reliability, internal consistency and structural validity). In such a way, the instrument can be used in clinical settings and for research purposes. © 2017 John Wiley & Sons Ltd.

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.

Psychometric Characteristics of a Public-Domain Self-Report Measure of Vocational Interests: The Oregon Vocational Interest Scales

PubMed Central

Pozzebon, Julie A.; Visser, Beth A.; Ashton, Michael C.; Lee, Kibeom; Goldberg, Lewis R.

2009-01-01

We investigated the psychometric properties of the Oregon Vocational Interest Scales (ORVIS), a brief public-domain alternative to commercial inventories, in a large community sample and in a college sample. In both samples, we examined the factor structure, scale intercorrelations, and personality correlates of the ORVIS, and in the community sample we also examined the correlations of the ORVIS scales with cognitive abilities and with the scales of a longer, proprietary interest survey. In both samples, all eight scales—Leadership, Organization, Altruism, Creativity, Analysis, Producing, Adventuring, and Erudition—showed wide variation in scores, high internal-consistency reliabilities, and a pattern of high convergent and low discriminant correlations with the scales of the proprietary interest survey. Overall, the results support the construct validity of the scales, which are recommended for use in research on vocational interests and other individual differences. PMID:20155566

Psychometric characteristics of a public-domain self-report measure of vocational interests: the Oregon Vocational Interest Scales.

PubMed

Pozzebon, Julie A; Visser, Beth A; Ashton, Michael C; Lee, Kibeom; Goldberg, Lewis R

2010-03-01

We investigated the psychometric properties of the Oregon Vocational Interest Scales (ORVIS), a brief public-domain alternative to commercial inventories, in a large community sample and in a college sample. In both samples, we examined the factor structure, scale intercorrelations, and personality correlates of the ORVIS, and in the community sample, we also examined the correlations of the ORVIS scales with cognitive abilities and with the scales of a longer, proprietary interest survey. In both samples, all 8 scales-Leadership, Organization, Altruism, Creativity, Analysis, Producing, Adventuring, and Erudition-showed wide variation in scores, high internal-consistency reliabilities, and a pattern of high convergent and low discriminant correlations with the scales of the proprietary interest survey. Overall, the results support the construct validity of the scales, which are recommended for use in research on vocational interests and other individual differences.

Correlation of AH-1G airframe flight vibration data with a coupled rotor-fuselage analysis

NASA Technical Reports Server (NTRS)

Sangha, K.; Shamie, J.

1990-01-01

The formulation and features of the Rotor-Airframe Comprehensive Analysis Program (RACAP) is described. The analysis employs a frequency domain, transfer matrix approach for the blade structural model, a time domain wake or momentum theory aerodynamic model, and impedance matching for rotor-fuselage coupling. The analysis is applied to the AH-1G helicopter, and a correlation study is conducted on fuselage vibration predictions. The purpose of the study is to evaluate the state-of-the-art in helicopter fuselage vibration prediction technology. The fuselage vibration predicted using RACAP are fairly good in the vertical direction and somewhat deficient in the lateral/longitudinal directions. Some of these deficiencies are traced to the fuselage finite element model.

Structure-Function Relationship between Flicker-Defined Form Perimetry and Spectral-Domain Optical Coherence Tomography in Glaucoma Suspects.

PubMed

Reznicek, Lukas; Muth, Daniel; Vogel, Michaela; Hirneiß, Christoph

2017-03-01

To evaluate the relationship between functional parameters of repeated flicker-defined form perimetry (FDF) and structural parameters of spectral-domain optical coherence tomography (SD-OCT) in glaucoma suspects with normal findings in achromatic standard automated perimetry (SAP). Patients with optic nerve heads (ONH) clinically suspicious for glaucoma and normal SAP findings were enrolled in this prospective study. Each participant underwent visual field (VF) testing with FDF perimetry, using the Heidelberg Edge Perimeter (HEP, Heidelberg Engineering, Heidelberg, Germany) at two consecutive visits. Peripapillary RNFL thickness was obtained by SD-OCT (Spectralis, Heidelberg Engineering, Heidelberg, Germany). Correlations and regression analyses of global and sectoral peripapillary RNFL thickness with corresponding global and regional VF sensitivities were investigated. A consecutive series of 65 study eyes of 36 patients were prospectively included. The second FDF test (HEP II) was used for analysis. Cluster-point based suspicious VF defects were found in 34 eyes (52%). Significant correlations were observed between mean global MD (PSD) of HEP II and SD-OCT-based global peripapillary RNFL thickness (r = 0.380, p = 0.003 for MD and r = -0.516, p < 0.001 for PSD) and RNFL classification scores (R 2 = 0.157, p = 0.002 for MD and R 2 = 0.172, p = 0.001 for PSD). Correlations between mean global MD and PSD of HEP II and sectoral peripapillary RNFL thickness and classification scores showed highest correlations between function and structure for the temporal superior and temporal inferior sectors whereas sectoral MD and PSD correlated weaker with sectoral RNFL thickness. Correlations between linear RNFL values and untransformed logarithmic MD values for each segment were less significant than correlations between logarithmic MD values and RNFL thickness. In glaucoma suspects with normal SAP, global and sectoral peripapillary RNFL thickness is correlated with sensitivity and VF defects in FDF perimetry.

Magnetic Force Microscopy Study of Zr 2 Co 11 -Based Nanocrystalline Materials: Effect of Mo Addition

DOE PAGES

Yue, Lanping; Jin, Yunlong; Zhang, Wenyong; ...

2015-01-01

Tmore » he addition of Molybdenum was used to modify the nanostructure and enhance coercivity of rare-earth-free Zr 2Co 11-based nanocrystalline permanent magnets. he effect of Mo addition on magnetic domain structures of melt spun nanocrystalline Zr 16Co 84-xMo x( x = 0 , 0.5, 1, 1.5, and 2.0) ribbons has been investigated. It was found that magnetic properties and local domain structures are strongly influenced by Mo doping. he coercivity of the samples increases with the increase in Mo content ( x ≤ 1.5 ). he maximum energy product ( B H ) max increases with increasing x from 0.5 MGOe for x = 0 to a maximum value of 4.2 MGOe for x = 1.5 . he smallest domain size with a relatively short magnetic correlation length of 128 nm and largest root-mean-square phase shift Φ rms value of 0.66° are observed for the x = 1.5 . he optimal Mo addition promotes magnetic domain structure refinement and thus leads to a significant increase in coercivity and energy product in this sample.« less

Magnetic Force Microscopy Study of Zr 2 Co 11 -Based Nanocrystalline Materials: Effect of Mo Addition

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

Yue, Lanping; Jin, Yunlong; Zhang, Wenyong

Tmore » he addition of Molybdenum was used to modify the nanostructure and enhance coercivity of rare-earth-free Zr 2Co 11-based nanocrystalline permanent magnets. he effect of Mo addition on magnetic domain structures of melt spun nanocrystalline Zr 16Co 84-xMo x( x = 0 , 0.5, 1, 1.5, and 2.0) ribbons has been investigated. It was found that magnetic properties and local domain structures are strongly influenced by Mo doping. he coercivity of the samples increases with the increase in Mo content ( x ≤ 1.5 ). he maximum energy product ( B H ) max increases with increasing x from 0.5 MGOe for x = 0 to a maximum value of 4.2 MGOe for x = 1.5 . he smallest domain size with a relatively short magnetic correlation length of 128 nm and largest root-mean-square phase shift Φ rms value of 0.66° are observed for the x = 1.5 . he optimal Mo addition promotes magnetic domain structure refinement and thus leads to a significant increase in coercivity and energy product in this sample.« less

Linking Mechanics and Statistics in Epidermal Tissues

NASA Astrophysics Data System (ADS)

Kim, Sangwoo; Hilgenfeldt, Sascha

2015-03-01

Disordered cellular structures, such as foams, polycrystals, or living tissues, can be characterized by quantitative measurements of domain size and topology. In recent work, we showed that correlations between size and topology in 2D systems are sensitive to the shape (eccentricity) of the individual domains: From a local model of neighbor relations, we derived an analytical justification for the famous empirical Lewis law, confirming the theory with experimental data from cucumber epidermal tissue. Here, we go beyond this purely geometrical model and identify mechanical properties of the tissue as the root cause for the domain eccentricity and thus the statistics of tissue structure. The simple model approach is based on the minimization of an interfacial energy functional. Simulations with Surface Evolver show that the domain statistics depend on a single mechanical parameter, while parameter fluctuations from cell to cell play an important role in simultaneously explaining the shape distribution of cells. The simulations are in excellent agreement with experiments and analytical theory, and establish a general link between the mechanical properties of a tissue and its structure. The model is relevant to diagnostic applications in a variety of animal and plant tissues.

Phase-detected Brillouin optical correlation-domain reflectometry

NASA Astrophysics Data System (ADS)

Mizuno, Yosuke; Hayashi, Neisei; Fukuda, Hideyuki; Nakamura, Kentaro

2018-05-01

Optical fiber sensing techniques based on Brillouin scattering have been extensively studied for structural health monitoring owing to their capability of distributed strain and temperature measurement. Although a higher signal-to-noise ratio (leading to high spatial resolution and high-speed measurement) is generally obtained for two-end-access systems, they reduce the degree of freedom in embedding the sensors into structures, and render the measurement no longer feasible when extremely high loss or breakage occurs at a point of the sensing fiber. To overcome these drawbacks, a one-end-access sensing technique called Brillouin optical correlation-domain reflectometry (BOCDR) has been developed. BOCDR has a high spatial resolution and cost efficiency, but its conventional configuration suffered from relatively low-speed operation. In this paper, we review the recently developed high-speed configurations of BOCDR, including phase-detected BOCDR, with which we demonstrate real-time distributed measurement by tracking a propagating mechanical wave. We also demonstrate breakage detection with a wide strain dynamic range.

Phase-detected Brillouin optical correlation-domain reflectometry

NASA Astrophysics Data System (ADS)

Mizuno, Yosuke; Hayashi, Neisei; Fukuda, Hideyuki; Nakamura, Kentaro

2018-06-01

Optical fiber sensing techniques based on Brillouin scattering have been extensively studied for structural health monitoring owing to their capability of distributed strain and temperature measurement. Although a higher signal-to-noise ratio (leading to high spatial resolution and high-speed measurement) is generally obtained for two-end-access systems, they reduce the degree of freedom in embedding the sensors into structures, and render the measurement no longer feasible when extremely high loss or breakage occurs at a point of the sensing fiber. To overcome these drawbacks, a one-end-access sensing technique called Brillouin optical correlation-domain reflectometry (BOCDR) has been developed. BOCDR has a high spatial resolution and cost efficiency, but its conventional configuration suffered from relatively low-speed operation. In this paper, we review the recently developed high-speed configurations of BOCDR, including phase-detected BOCDR, with which we demonstrate real-time distributed measurement by tracking a propagating mechanical wave. We also demonstrate breakage detection with a wide strain dynamic range.

Evidence for the requirement of ITAM domains but not SLP-76/Gads interaction for integrin signaling in hematopoietic cells.

PubMed

Abtahian, Farhad; Bezman, Natalie; Clemens, Regina; Sebzda, Eric; Cheng, Lan; Shattil, Sanford J; Kahn, Mark L; Koretzky, Gary A

2006-09-01

Syk tyrosine kinase and Src homology 2 (SH2) domain-containing leukocyte-specific phosphoprotein of 76 kDa (SLP-76) are signaling mediators activated downstream of immunoreceptor tyrosine-based activation motif (ITAM)-containing immunoreceptors and integrins. While the signaling cascades descending from integrins are similar to immunoreceptors, the mechanism of Syk activation and SLP-76 recruitment remains unclear. We used an in vivo structure-function approach to study the requirements for the domains of Syk and SLP-76 in immunoreceptor and integrin signaling. We found that both SH2 domains and the kinase domain of Syk are required for immunoreceptor-dependent signaling and cellular response via integrins. While the Gads-binding domain of SLP-76 is needed for immunoreceptor signaling, it appears dispensable for integrin signaling. Syk and SLP-76 also are required for initiating and/or maintaining separation between the blood and lymphatic vasculature. Therefore, we correlated the signaling requirement of the various domains of Syk and SLP-76 to their requirement in regulating vascular separation. Our data suggest ITAMs are required in Syk-dependent integrin signaling, demonstrate the separation of the structural features of SLP-76 to selectively support immunoreceptor versus integrin signaling, and provide evidence that the essential domains of SLP-76 for ITAM signals are those which most efficiently support separation between lymphatic and blood vessels.

Order statistics inference for describing topological coupling and mechanical symmetry breaking in multidomain proteins

NASA Astrophysics Data System (ADS)

Kononova, Olga; Jones, Lee; Barsegov, V.

2013-09-01

Cooperativity is a hallmark of proteins, many of which show a modular architecture comprising discrete structural domains. Detecting and describing dynamic couplings between structural regions is difficult in view of the many-body nature of protein-protein interactions. By utilizing the GPU-based computational acceleration, we carried out simulations of the protein forced unfolding for the dimer WW - WW of the all-β-sheet WW domains used as a model multidomain protein. We found that while the physically non-interacting identical protein domains (WW) show nearly symmetric mechanical properties at low tension, reflected, e.g., in the similarity of their distributions of unfolding times, these properties become distinctly different when tension is increased. Moreover, the uncorrelated unfolding transitions at a low pulling force become increasingly more correlated (dependent) at higher forces. Hence, the applied force not only breaks "the mechanical symmetry" but also couples the physically non-interacting protein domains forming a multi-domain protein. We call this effect "the topological coupling." We developed a new theory, inspired by order statistics, to characterize protein-protein interactions in multi-domain proteins. The method utilizes the squared-Gaussian model, but it can also be used in conjunction with other parametric models for the distribution of unfolding times. The formalism can be taken to the single-molecule experimental lab to probe mechanical cooperativity and domain communication in multi-domain proteins.

Kinematic measures for upper limb robot-assisted therapy following stroke and correlations with clinical outcome measures: A review.

PubMed

Tran, Vi Do; Dario, Paolo; Mazzoleni, Stefano

2018-03-01

This review classifies the kinematic measures used to evaluate post-stroke motor impairment following upper limb robot-assisted rehabilitation and investigates their correlations with clinical outcome measures. An online literature search was carried out in PubMed, MEDLINE, Scopus and IEEE-Xplore databases. Kinematic parameters mentioned in the studies included were categorized into the International Classification of Functioning, Disability and Health (ICF) domains. The correlations between these parameters and the clinical scales were summarized. Forty-nine kinematic parameters were identified from 67 articles involving 1750 patients. The most frequently used parameters were: movement speed, movement accuracy, peak speed, number of speed peaks, and movement distance and duration. According to the ICF domains, 44 kinematic parameters were categorized into Body Functions and Structure, 5 into Activities and no parameters were categorized into Participation and Personal and Environmental Factors. Thirteen articles investigated the correlations between kinematic parameters and clinical outcome measures. Some kinematic measures showed a significant correlation coefficient with clinical scores, but most were weak or moderate. The proposed classification of kinematic measures into ICF domains and their correlations with clinical scales could contribute to identifying the most relevant ones for an integrated assessment of upper limb robot-assisted rehabilitation treatments following stroke. Increasing the assessment frequency by means of kinematic parameters could optimize clinical assessment procedures and enhance the effectiveness of rehabilitation treatments. Copyright © 2018 IPEM. Published by Elsevier Ltd. All rights reserved.

A novel iris patterns matching algorithm of weighted polar frequency correlation

NASA Astrophysics Data System (ADS)

Zhao, Weijie; Jiang, Linhua

2014-11-01

Iris recognition is recognized as one of the most accurate techniques for biometric authentication. In this paper, we present a novel correlation method - Weighted Polar Frequency Correlation(WPFC) - to match and evaluate two iris images, actually it can also be used for evaluating the similarity of any two images. The WPFC method is a novel matching and evaluating method for iris image matching, which is complete different from the conventional methods. For instance, the classical John Daugman's method of iris recognition uses 2D Gabor wavelets to extract features of iris image into a compact bit stream, and then matching two bit streams with hamming distance. Our new method is based on the correlation in the polar coordinate system in frequency domain with regulated weights. The new method is motivated by the observation that the pattern of iris that contains far more information for recognition is fine structure at high frequency other than the gross shapes of iris images. Therefore, we transform iris images into frequency domain and set different weights to frequencies. Then calculate the correlation of two iris images in frequency domain. We evaluate the iris images by summing the discrete correlation values with regulated weights, comparing the value with preset threshold to tell whether these two iris images are captured from the same person or not. Experiments are carried out on both CASIA database and self-obtained images. The results show that our method is functional and reliable. Our method provides a new prospect for iris recognition system.

Pipelined digital SAR azimuth correlator using hybrid FFT-transversal filter

NASA Technical Reports Server (NTRS)

Wu, C.; Liu, K. Y. (Inventor)

1984-01-01

A synthetic aperture radar system (SAR) having a range correlator is provided with a hybrid azimuth correlator which utilizes a block-pipe-lined fast Fourier transform (FFT). The correlator has a predetermined FFT transform size with delay elements for delaying SAR range correlated data so as to embed in the Fourier transform operation a corner-turning function as the range correlated SAR data is converted from the time domain to a frequency domain. The azimuth correlator is comprised of a transversal filter to receive the SAR data in the frequency domain, a generator for range migration compensation and azimuth reference functions, and an azimuth reference multiplier for correlation of the SAR data. Following the transversal filter is a block-pipelined inverse FFT used to restore azimuth correlated data in the frequency domain to the time domain for imaging.

Mapping the neuropsychological profile of temporal lobe epilepsy using cognitive network topology and graph theory.

PubMed

Kellermann, Tanja S; Bonilha, Leonardo; Eskandari, Ramin; Garcia-Ramos, Camille; Lin, Jack J; Hermann, Bruce P

2016-10-01

Normal cognitive function is defined by harmonious interaction among multiple neuropsychological domains. Epilepsy has a disruptive effect on cognition, but how diverse cognitive abilities differentially interact with one another compared with healthy controls (HC) is unclear. This study used graph theory to analyze the community structure of cognitive networks in adults with temporal lobe epilepsy (TLE) compared with that in HC. Neuropsychological assessment was performed in 100 patients with TLE and 82 HC. For each group, an adjacency matrix was constructed representing pair-wise correlation coefficients between raw scores obtained in each possible test combination. For each cognitive network, each node corresponded to a cognitive test; each link corresponded to the correlation coefficient between tests. Global network structure, community structure, and node-wise graph theory properties were qualitatively assessed. The community structure in patients with TLE was composed of fewer, larger, more mixed modules, characterizing three main modules representing close relationships between the following: 1) aspects of executive function (EF), verbal and visual memory, 2) speed and fluency, and 3) speed, EF, perception, language, intelligence, and nonverbal memory. Conversely, controls exhibited a relative division between cognitive functions, segregating into more numerous, smaller modules consisting of the following: 1) verbal memory, 2) language, perception, and intelligence, 3) speed and fluency, and 4) visual memory and EF. Overall node-wise clustering coefficient and efficiency were increased in TLE. Adults with TLE demonstrate a less clear and poorly structured segregation between multiple cognitive domains. This panorama suggests a higher degree of interdependency across multiple cognitive domains in TLE, possibly indicating compensatory mechanisms to overcome functional impairments. Copyright © 2016 Elsevier Inc. All rights reserved.

Monoclonal Antibodies to the V2 Domain of MN-rgp120: Fine Mapping of Epitopes and Inhibition of α4β7 Binding

PubMed Central

Nakamura, Gerald R.; Fonseca, Dora P. A. J.; O'Rourke, Sara M.; Vollrath, Aaron L.; Berman, Phillip W.

2012-01-01

Background Recombinant gp120 (MN-rgp120) was a major component of the AIDSVAX B/E vaccine used in the RV144 trial. This was the first clinical trial to show that vaccination could prevent HIV infection in humans. A recent RV144 correlates of protection study found that protection correlated with the presence of antibodies to the V2 domain. It has been proposed that antibodies to the α4β7 binding site in the V2 domain might prevent HIV-1 infection by blocking the ability of virions to recognize α4β7 on activated T-cells. In this study we investigated the specificity of monoclonal antibodies (MAbs) to the V2 domain of MN-rgp120 and examined the possibility that these antibodies could inhibit the binding of MN-rgp120 to the α4β7 integrin. Methodology/Principal Findings Nine MAbs to the V2 domain were isolated from mice immunized with recombinant envelope proteins. The ability of these MAbs to inhibit HIV infection, block the binding of gp120 to CD4, and block the binding of MN-rgp120 to the α4β7 integrin was measured. Mutational analysis showed that eight of the MAbs recognized two immunodominant clusters of amino acids (166–168 and 178–183) located at either end of the C strand within the four-strand anti-parallel sheet structure comprising the V1/V2 domain. Conclusions/Significance These studies showed that the antigenic structure of the V2 domain is exceedingly complex and that MAbs isolated from mice immunized with MN-rgp120 exhibited a high level of strain specificity compared to MAbs to the V2 domain isolated from HIV-infected humans. We found that immunization with MN-rgp120 readily elicits antibodies to the V2 domain and some of these were able to block the binding of MN-rgp120 to the α4β7 integrin. PMID:22720026

Evolutionary versatility of eukaryotic protein domains revealed by their bigram networks

PubMed Central

2011-01-01

Background Protein domains are globular structures of independently folded polypeptides that exert catalytic or binding activities. Their sequences are recognized as evolutionary units that, through genome recombination, constitute protein repertoires of linkage patterns. Via mutations, domains acquire modified functions that contribute to the fitness of cells and organisms. Recent studies have addressed the evolutionary selection that may have shaped the functions of individual domains and the emergence of particular domain combinations, which led to new cellular functions in multi-cellular animals. This study focuses on modeling domain linkage globally and investigates evolutionary implications that may be revealed by novel computational analysis. Results A survey of 77 completely sequenced eukaryotic genomes implies a potential hierarchical and modular organization of biological functions in most living organisms. Domains in a genome or multiple genomes are modeled as a network of hetero-duplex covalent linkages, termed bigrams. A novel computational technique is introduced to decompose such networks, whereby the notion of domain "networking versatility" is derived and measured. The most and least "versatile" domains (termed "core domains" and "peripheral domains" respectively) are examined both computationally via sequence conservation measures and experimentally using selected domains. Our study suggests that such a versatility measure extracted from the bigram networks correlates with the adaptivity of domains during evolution, where the network core domains are highly adaptive, significantly contrasting the network peripheral domains. Conclusions Domain recombination has played a major part in the evolution of eukaryotes attributing to genome complexity. From a system point of view, as the results of selection and constant refinement, networks of domain linkage are structured in a hierarchical modular fashion. Domains with high degree of networking versatility appear to be evolutionary adaptive, potentially through functional innovations. Domain bigram networks are informative as a model of biological functions. The networking versatility indices extracted from such networks for individual domains reflect the strength of evolutionary selection that the domains have experienced. PMID:21849086

Evolutionary versatility of eukaryotic protein domains revealed by their bigram networks.

PubMed

Xie, Xueying; Jin, Jing; Mao, Yongyi

2011-08-18

Protein domains are globular structures of independently folded polypeptides that exert catalytic or binding activities. Their sequences are recognized as evolutionary units that, through genome recombination, constitute protein repertoires of linkage patterns. Via mutations, domains acquire modified functions that contribute to the fitness of cells and organisms. Recent studies have addressed the evolutionary selection that may have shaped the functions of individual domains and the emergence of particular domain combinations, which led to new cellular functions in multi-cellular animals. This study focuses on modeling domain linkage globally and investigates evolutionary implications that may be revealed by novel computational analysis. A survey of 77 completely sequenced eukaryotic genomes implies a potential hierarchical and modular organization of biological functions in most living organisms. Domains in a genome or multiple genomes are modeled as a network of hetero-duplex covalent linkages, termed bigrams. A novel computational technique is introduced to decompose such networks, whereby the notion of domain "networking versatility" is derived and measured. The most and least "versatile" domains (termed "core domains" and "peripheral domains" respectively) are examined both computationally via sequence conservation measures and experimentally using selected domains. Our study suggests that such a versatility measure extracted from the bigram networks correlates with the adaptivity of domains during evolution, where the network core domains are highly adaptive, significantly contrasting the network peripheral domains. Domain recombination has played a major part in the evolution of eukaryotes attributing to genome complexity. From a system point of view, as the results of selection and constant refinement, networks of domain linkage are structured in a hierarchical modular fashion. Domains with high degree of networking versatility appear to be evolutionary adaptive, potentially through functional innovations. Domain bigram networks are informative as a model of biological functions. The networking versatility indices extracted from such networks for individual domains reflect the strength of evolutionary selection that the domains have experienced.

The isolated voltage sensing domain of the Shaker potassium channel forms a voltage-gated cation channel.

PubMed

Zhao, Juan; Blunck, Rikard

2016-10-06

Domains in macromolecular complexes are often considered structurally and functionally conserved while energetically coupled to each other. In the modular voltage-gated ion channels the central ion-conducting pore is surrounded by four voltage sensing domains (VSDs). Here, the energetic coupling is mediated by interactions between the S4-S5 linker, covalently linking the domains, and the proximal C-terminus. In order to characterize the intrinsic gating of the voltage sensing domain in the absence of the pore domain, the Shaker Kv channel was truncated after the fourth transmembrane helix S4 (Shaker-iVSD). Shaker-iVSD showed significantly altered gating kinetics and formed a cation-selective ion channel with a strong preference for protons. Ion conduction in Shaker-iVSD developed despite identical primary sequence, indicating an allosteric influence of the pore domain. Shaker-iVSD also displays pronounced 'relaxation'. Closing of the pore correlates with entry into relaxation suggesting that the two processes are energetically related.

Quantitative Subsurface Atomic Structure Fingerprint for 2D Materials and Heterostructures by First-Principles-Calibrated Contact-Resonance Atomic Force Microscopy.

PubMed

Tu, Qing; Lange, Björn; Parlak, Zehra; Lopes, Joao Marcelo J; Blum, Volker; Zauscher, Stefan

2016-07-26

Interfaces and subsurface layers are critical for the performance of devices made of 2D materials and heterostructures. Facile, nondestructive, and quantitative ways to characterize the structure of atomically thin, layered materials are thus essential to ensure control of the resultant properties. Here, we show that contact-resonance atomic force microscopy-which is exquisitely sensitive to stiffness changes that arise from even a single atomic layer of a van der Waals-adhered material-is a powerful experimental tool to address this challenge. A combined density functional theory and continuum modeling approach is introduced that yields sub-surface-sensitive, nanomechanical fingerprints associated with specific, well-defined structure models of individual surface domains. Where such models are known, this information can be correlated with experimentally obtained contact-resonance frequency maps to reveal the (sub)surface structure of different domains on the sample.

Globular, Sponge-like to Layer-like Morphological Transition in 1-n-Alkyl-3-methylimidazolium Octylsulfate Ionic Liquid Homologous Series.

PubMed

Kapoor, Utkarsh; Shah, Jindal K

2018-01-11

Segregation of polar and nonpolar domains in ionic liquids for which either the cation or anion is responsible for inducing nonpolar domains is well understood. On the other hand, information regarding the nanoscale heterogeneities originating due to the presence of nonpolar content on both the ions is rudimentary at this point. The present contribution is aimed at addressing this question and focuses on a molecular dynamics simulation study to probe nanoscale structural and aggregation features of the 1-n-alkyl-3-methylimidazolium [C n mim] octylsulfate [C 8 SO 4 ] ionic liquid homologous series (n = 2, 4, 6, 8, 10, and 12). The objective of this work is to determine the effect of increasing alkyl chain length in the cation on nonpolar domain formation, especially when the alkyl chain lengths from both the ions participate in defining such domains. The results indicate that all the ionic liquids form nonpolar domains, morphology of which gradually changes from globular, sponge-like to layer-like structure with increase in the cationic alkyl chain length. The length of the nonpolar domains calculated from the total structure factor for [C 10 mim][C 8 SO 4 ] is considerably higher than that reported for other imidazolium-based ionic liquid containing smaller anions. The structure factor for [C 12 mim][C 8 SO 4 ] ionic liquid contains multiple intermediate peaks separating the charge alternation peak and pre-peak, which points to nonpolar domains of varying lengths, an observation that remains to be validated. Analysis of the heterogeneous order parameters and orientational correlation functions of the alkyl chains further suggests an increase in the spatial heterogeneity and long-range order along the homologous series. The origin of rich diversity of structures obtained by introducing nonpolar content on both the ions is discussed.

Measuring single constructs by single items: Constructing an even shorter version of the “Short Five” personality inventory

PubMed Central

Konstabel, Kenn; Lönnqvist, Jan-Erik; Leikas, Sointu; García Velázquez, Regina; Qin, Hiaying; Verkasalo, Markku; Walkowitz, Gari

2017-01-01

The aim of this study was to construct a short, 30-item personality questionnaire that would be, in terms of content and meaning of the scores, as comparable as possible with longer, well-established inventories such as NEO PI-R and its clones. To do this, we shortened the formerly constructed 60-item “Short Five” (S5) by half so that each subscale would be represented by a single item. We compared all possibilities of selecting 30 items (preserving balanced keying within each domain of the five-factor model) in terms of correlations with well-established scales, self-peer correlations, and clarity of meaning, and selected an optimal combination for each domain. The resulting shortened questionnaire, XS5, was compared to the original S5 using data from student samples in 6 different countries (Estonia, Finland, UK, Germany, Spain, and China), and a representative Finnish sample. The correlations between XS5 domain scales and their longer counterparts from well-established scales ranged from 0.74 to 0.84; the difference from the equivalent correlations for full version of S5 or from meta-analytic short-term dependability coefficients of NEO PI-R was not large. In terms of prediction of external criteria (emotional experience and self-reported behaviours), there were no important differences between XS5, S5, and the longer well-established scales. Controlling for acquiescence did not improve the prediction of criteria, self-peer correlations, or correlations with longer scales, but it did improve internal reliability and, in some analyses, comparability of the principal component structure. XS5 can be recommended as an economic measure of the five-factor model of personality at the level of domain scales; it has reasonable psychometric properties, fair correlations with longer well-established scales, and it can predict emotional experience and self-reported behaviours no worse than S5. When subscales are essential, we would still recommend using the full version of S5. PMID:28800630

Measuring single constructs by single items: Constructing an even shorter version of the "Short Five" personality inventory.

PubMed

Konstabel, Kenn; Lönnqvist, Jan-Erik; Leikas, Sointu; García Velázquez, Regina; Qin, Hiaying; Verkasalo, Markku; Walkowitz, Gari

2017-01-01

The aim of this study was to construct a short, 30-item personality questionnaire that would be, in terms of content and meaning of the scores, as comparable as possible with longer, well-established inventories such as NEO PI-R and its clones. To do this, we shortened the formerly constructed 60-item "Short Five" (S5) by half so that each subscale would be represented by a single item. We compared all possibilities of selecting 30 items (preserving balanced keying within each domain of the five-factor model) in terms of correlations with well-established scales, self-peer correlations, and clarity of meaning, and selected an optimal combination for each domain. The resulting shortened questionnaire, XS5, was compared to the original S5 using data from student samples in 6 different countries (Estonia, Finland, UK, Germany, Spain, and China), and a representative Finnish sample. The correlations between XS5 domain scales and their longer counterparts from well-established scales ranged from 0.74 to 0.84; the difference from the equivalent correlations for full version of S5 or from meta-analytic short-term dependability coefficients of NEO PI-R was not large. In terms of prediction of external criteria (emotional experience and self-reported behaviours), there were no important differences between XS5, S5, and the longer well-established scales. Controlling for acquiescence did not improve the prediction of criteria, self-peer correlations, or correlations with longer scales, but it did improve internal reliability and, in some analyses, comparability of the principal component structure. XS5 can be recommended as an economic measure of the five-factor model of personality at the level of domain scales; it has reasonable psychometric properties, fair correlations with longer well-established scales, and it can predict emotional experience and self-reported behaviours no worse than S5. When subscales are essential, we would still recommend using the full version of S5.

Explaining the Substantial Inter-Domain and Over-Time Correlations in Student Achievement: The Importance of Stable Student Attributes

ERIC Educational Resources Information Center

Marks, Gary N.

2016-01-01

Multi-domain and longitudinal studies of student achievement routinely find moderate to strong correlations across achievement domains and even stronger within-domain correlations over time. The purpose of this study is to examine the sources of these patterns analysing student achievement in 5 domains across Years 3, 5 and 7. The analysis is of…

Phosphorylation-induced changes in the energetic frustration in human Tank binding kinase 1.

PubMed

Husain, Shahrukh; Kumar, Vijay; Hassan, Md Imtaiyaz

2018-07-14

Tank binding kinase 1 (TBK-1) plays an important role in immunity, inflammation, autophagy, cell growth and proliferation. Nevertheless, a key molecular and structural detail of TBK-1 phosphorylation and activation has been largely unknown. Here we investigated the energy landscape of phosphorylated (active) and unphosphorylated (inactive) forms of human TBK-1 to characterize the interplay between phosphorylation and local frustration. By employing the algorithm equipped with energy function and implemented in Frustratometer web-server (http://www.frustratometer.tk), we quantify the role of frustration in the activation of TBK-1. Accordingly, the conformational changes were observed in phosphoregulated active and inactive TBK-1. Substantial changes in frustration, flexibility and interatomic motions were observed among different forms of TBK-1. Structurally rigid kinase domain constitutes a minimally frustrated hub in the core of the catalytic domain, and highly frustrated clusters mainly at the C-lobe might enable the conformational transitions during activation. Also, a large network of highly frustrated interactions is found in the SDD domain of TBK-1 involved in protein-protein interactions and dimerization. The contact maps of the activation loop and α-C helix of kinase domain showed significant changes upon phosphorylation. Cross correlation analysis indicate that both intra and inter subunit correlated motions increases with phosphorylation of TBK-1. Phosphorylation thus introduces subtle changes in long-range contacts that might lead to significant conformational change of TBK-1. Copyright © 2018 Elsevier Ltd. All rights reserved.

Diversification of HP1-like Chromo Domain Proteins in Tetrahymena thermophila.

PubMed

Wiley, Emily A; Horrell, Scott; Yoshino, Alyssa; Schornak, Cara C; Bagnani, Claire; Chalker, Douglas L

2018-01-01

Proteins that possess a chromo domain are well-known for their roles in heterochromatin assembly and maintenance. The Heterochromatin Protein 1 (HP1) family, with a chromo domain and carboxy-terminal chromo shadow domain, targets heterochromatin through interaction with histone H3 methylated on lysine 9 (H3K9me2/3). The structural and functional diversity of these proteins observed in both fission yeast and metazoans correlate with chromatin specialization. To expand these studies, we examined chromo domain proteins in the ciliate Tetrahymena thermophila, which has functionally diverse and developmentally regulated heterochromatin domains. We identified thirteen proteins similar to HP1. Together they possess only a fraction of the possible chromo domain subtypes and most lack a recognizable chromo shadow domain. Using fluorescence microscopy to track chromatin localization of tagged proteins through the life cycle, we show evidence that in T. thermophila this family has diversified with biological roles in RNAi-directed DNA elimination, germline genome structure, and somatic heterochromatin. Those proteins with H3K27me3 binding sequence characteristics localize to chromatin in mature nuclei, whereas those with H3K9me2/3 binding characteristics localize to developing nuclei undergoing DNA elimination. Findings point to an expanded and diversified family of chromo domain proteins that parallels heterochromatin diversity in ciliates. © 2017 The Authors. Journal of Eukaryotic Microbiology published by Wiley Periodicals, Inc. on behalf of International Society of Protistologists.

Psychometric properties of the Chinese version of the Menopause-Specific Quality-of-Life questionnaire.

PubMed

Nie, Guangning; Yang, Hongyan; Liu, Jian; Zhao, ChunMei; Wang, Xiaoyun

2017-05-01

The Menopause-Specific Quality-of-Life (MENQOL) questionnaire was developed as a specific tool to measure the health-related quality-of-life of postmenopausal women. Thus far, the Chinese version questionnaire has not been subjected to psychometric assessment with a large sample. This study aims to evaluate the validity and reliability of the Chinese version of the MENQOL specific to postmenopausal women in China. A total of 1,137 menopausal symptomatic and 491 menopausal asymptomatic women from eight cities in China were recruited using a convenience sampling method. Psychometric properties were evaluated by descriptive statistics, validity, and reliability. Reliability was assessed for each subscale of the MENQOL through internal consistency reliability with Cronbach's α and intersubscale correlations. Item-domain correlations, principal components analysis (PCA), and confirmatory factor analysis were performed to determine construct validity. t tests were used to compare the differences between the menopausal symptomatic and asymptomatic women and to evaluate the discriminate validity. Pearson correlation coefficients were calculated between MENQOL scores and the Kupperman index to assess criterion-related validity. The most common symptoms in Chinese menopausal symptomatic women were "experiencing poor memory" (94.4%), "feeling tired or worn out" (93.8%), "aching in muscle and joints" (89.4%), "low backache" (86.9%), "decrease in physical strength" (86.6%), "aches in back of neck or head" (86.2%), "difficulty sleeping" (83.6%), "accomplishing less than I used to" (83.4%), "feeling a lack of energy" (83.3%), "change in your sexual desire" (81%), and "hot flash" (80.7%) among others. The symptoms of "increased facial hair" were rarely seen (9.9%). The vasomotor domain, as well as psychosocial, physical, and sexual domains showed high reliability (Cronbach's α 0.84, 0.87, 0.89, and 0.86, respectively). Item-domain correlation analysis showed that all items correlated more strongly with their own domains than with other domains. In the PCA, after deleting the "increased facial hair" item, items in the vasomotor, sexual, and psychosocial subscales loaded on their respective domains by and large, and items in the physical subscale divided into two factors. The PCA revealed a latent structure of the Chinese version of MENQOL nearly identical to the original MENQOL domains. The confirmatory factor analysis demonstrated that the questionnaire fits well with a four-domain model. The MENQOL can discriminate between menopausal symptomatic women with asymptomatic women as it showed good discriminate validity. Criterion-related validity was confirmed by a significant correlation between MENQOL scores and the Kupperman index. This study showed that Chinese version of MENQOL has good psychometric properties and would be suitable to measure the health-related quality-of-life of Chinese menopausal women except for item 21 (increased facial hair).

Analysis of correlated domain motions in IgG light chain reveals possible mechanisms of immunological signal transduction.

PubMed

Król, Marcin; Roterman, Irena; Piekarska, Barbara; Konieczny, Leszek; Rybarska, Janina; Stopa, Barbara; Spólnik, Paweł

2005-05-15

It was shown experimentally that binding of a micelle composed of Congo red molecules to immunological complexes leads to the enhanced stability of the latter, and simultaneously prevents binding of a complement molecule (C1q). The dye binds in a cavity created by the removal of N-terminal polypeptide chain, as observed experimentally in a model system-immunoglobulin G (IgG) light chain dimer. Molecular Dynamics (MD) simulations of three forms of IgG light chain dimer, with and without the dye, were performed to investigate the role of N-terminal fragment and self-assembled ligand in coupling between V and C domains. Root-mean-square distance (RMSD) time profiles show that removal of N-terminal fragment leads to destabilization of V domain. A micelle composed of four self-assembled dye molecules stabilizes and fixes the domain. Analysis of root-mean-square fluctuation (RMSF) values and dynamic cross-correlation matrices (DCCM) reveals that removal of N-terminal fragment results in complete decoupling between V and C domains. Binding of self-assembled Congo red molecules improves the coupling, albeit slightly. The disruption of a small beta-sheet composed of N- and C-terminal fragments of the domain (NC sheet) is the most likely reason for the decoupling. Self-assembled ligand, bound in the place originally occupied by N-terminal fragment, is not able to take over the function of the beta-sheet. Lack of correlation of motions between residues in V and C domains denotes that light chain-Congo red complexes have hampered ability to transmit conformational changes between domains. This is a likely explanation of the lack of complement binding by immunological complexes, which bind Congo red, and supports the idea that the NC sheet is the key structural fragment taking part in immunological signal transduction. Copyright 2005 Wiley-Liss, Inc.

Reexamining the Validity and Dimensionality of the Moorong Self-Efficacy Scale: Improving Its Clinical Utility.

PubMed

Middleton, James W; Tran, Yvonne; Lo, Charles; Craig, Ashley

2016-12-01

To improve the clinical utility of the Moorong Self-Efficacy Scale (MSES) by reexamining its factor structure and comparing its performance against a measure of general self-efficacy in persons with spinal cord injury (SCI). Cross-sectional survey design. Community. Adults with SCI (N=161; 118 men and 43 women) recruited from Australia (n=82) and the United States (n=79), including 86 with paraplegia and 75 with tetraplegia. None. Confirmatory factor analysis deriving fit indices on reported 1-, 2-, and 3-factor structures for the MSES. Exploratory factor analysis of MSES using principal component analysis with promax oblique rotation and structure validation, with correlations and multiple regression using cross-sectional data from the Sherer General Self-Efficacy Scale and Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). The MSES was confirmed to have a 3-factor structure, explaining 61% of variance. Two of the factors, labeled social function self-efficacy and personal function self-efficacy, were SCI condition-specific, whereas the other factor (accounting for 9.7% of variance) represented general self-efficacy, correlating most strongly with the Sherer General Self-Efficacy Scale. Correlations and multiple regression analyses between MSES factors, Sherer General Self-Efficacy Scale total score, SF-36 Physical and Mental Component Summary scores, and SF-36 domain scores support validity of this MSES factor structure. No significant cross-cultural differences existed between Australia and the United States in total MSES or factor scores. The findings support a 3-factor structure encompassing general and SCI domain-specific self-efficacy beliefs and better position the MSES to assist SCI rehabilitation assessment, planning, and research. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Differential Dynamic Engagement within 24 SH3 Domain: Peptide Complexes Revealed by Co-Linear Chemical Shift Perturbation Analysis

PubMed Central

Stollar, Elliott J.; Lin, Hong; Davidson, Alan R.; Forman-Kay, Julie D.

2012-01-01

There is increasing evidence for the functional importance of multiple dynamically populated states within single proteins. However, peptide binding by protein-protein interaction domains, such as the SH3 domain, has generally been considered to involve the full engagement of peptide to the binding surface with minimal dynamics and simple methods to determine dynamics at the binding surface for multiple related complexes have not been described. We have used NMR spectroscopy combined with isothermal titration calorimetry to comprehensively examine the extent of engagement to the yeast Abp1p SH3 domain for 24 different peptides. Over one quarter of the domain residues display co-linear chemical shift perturbation (CCSP) behavior, in which the position of a given chemical shift in a complex is co-linear with the same chemical shift in the other complexes, providing evidence that each complex exists as a unique dynamic rapidly inter-converting ensemble. The extent the specificity determining sub-surface of AbpSH3 is engaged as judged by CCSP analysis correlates with structural and thermodynamic measurements as well as with functional data, revealing the basis for significant structural and functional diversity amongst the related complexes. Thus, CCSP analysis can distinguish peptide complexes that may appear identical in terms of general structure and percent peptide occupancy but have significant local binding differences across the interface, affecting their ability to transmit conformational change across the domain and resulting in functional differences. PMID:23251481

Correlation of porous and functional properties of food materials by NMR relaxometry and multivariate analysis.

PubMed

Haiduc, Adrian Marius; van Duynhoven, John

2005-02-01

The porous properties of food materials are known to determine important macroscopic parameters such as water-holding capacity and texture. In conventional approaches, understanding is built from a long process of establishing macrostructure-property relations in a rational manner. Only recently, multivariate approaches were introduced for the same purpose. The model systems used here are oil-in-water emulsions, stabilised by protein, and form complex structures, consisting of fat droplets dispersed in a porous protein phase. NMR time-domain decay curves were recorded for emulsions with varied levels of fat, protein and water. Hardness, dry matter content and water drainage were determined by classical means and analysed for correlation with the NMR data with multivariate techniques. Partial least squares can calibrate and predict these properties directly from the continuous NMR exponential decays and yields regression coefficients higher than 82%. However, the calibration coefficients themselves belong to the continuous exponential domain and do little to explain the connection between NMR data and emulsion properties. Transformation of the NMR decays into a discreet domain with non-negative least squares permits the use of multilinear regression (MLR) on the resulting amplitudes as predictors and hardness or water drainage as responses. The MLR coefficients show that hardness is highly correlated with the components that have T2 distributions of about 20 and 200 ms whereas water drainage is correlated with components that have T2 distributions around 400 and 1800 ms. These T2 distributions very likely correlate with water populations present in pores with different sizes and/or wall mobility. The results for the emulsions studied demonstrate that NMR time-domain decays can be employed to predict properties and to provide insight in the underlying microstructural features.

Correlations of phase structure and thermal stability for Alnico 8 alloys

NASA Astrophysics Data System (ADS)

Zhao, J. T.; Sun, Y. L.; Liu, L.; Lee, D.; Liu, Z.; Feng, X. C.; Yan, A. R.

2017-11-01

The correlations of phase structure and thermal stability for Alnico 8 alloys is analyzed by three-step aging at 650 °C, 600 °C and 550 °C gradually in this paper. After three-step aging the a1 phase is a chess-like structure in transverse direction and a bamboo-like structure in longitudinal direction. Meanwhile the magnetic energy product ((BH)m) increases from 9.17 MGOe to 10.59 MGOe, and the remanence temperature coefficient a(RT-180 °C) reduces from -2.31 %%/°C to -1.25 %%/°C. The MPMS and VSM measurements indicate that three-step aging makes the a1 phase be single domain particles and dispersed distribution, which plays an important role in optimizing the thermal stability of Alnico alloys.

Mechanism of Protein Denaturation: Partial Unfolding of the P22 Coat Protein I-Domain by Urea Binding

PubMed Central

Newcomer, Rebecca L.; Fraser, LaTasha C.R.; Teschke, Carolyn M.; Alexandrescu, Andrei T.

2015-01-01

The I-domain is an insertion domain of the bacteriophage P22 coat protein that drives rapid folding and accounts for over half of the stability of the full-length protein. We sought to determine the role of hydrogen bonds (H-bonds) in the unfolding of the I-domain by examining 3JNC’ couplings transmitted through H-bonds, the temperature and urea-concentration dependence of 1HN and 15N chemical shifts, and native-state hydrogen exchange at urea concentrations where the domain is predominantly folded. The native-state hydrogen-exchange data suggest that the six-stranded β-barrel core of the I-domain is more stable against unfolding than a smaller subdomain comprised of a short α-helix and three-stranded β-sheet. H-bonds, separately determined from solvent protection and 3JNC’ H-bond couplings, are identified with an accuracy of 90% by 1HN temperature coefficients. The accuracy is improved to 95% when 15N temperature coefficients are also included. In contrast, the urea dependence of 1HN and 15N chemical shifts is unrelated to H-bonding. The protein segments with the largest chemical-shift changes in the presence of urea show curved or sigmoidal titration curves suggestive of direct urea binding. Nuclear Overhauser effects to urea for these segments are also consistent with specific urea-binding sites in the I-domain. Taken together, the results support a mechanism of urea unfolding in which denaturant binds to distinct sites in the I-domain. Disordered segments bind urea more readily than regions in stable secondary structure. The locations of the putative urea-binding sites correlate with the lower stability of the structure against solvent exchange, suggesting that partial unfolding of the structure is related to urea accessibility. PMID:26682823

Phenotypic Characteristics of a French Cohort of Patients with X-Linked Retinoschisis.

PubMed

Orès, Raphaëlle; Mohand-Said, Saddek; Dhaenens, Claire-Marie; Antonio, Aline; Zeitz, Christina; Augstburger, Edouard; Andrieu, Camille; Sahel, José-Alain; Audo, Isabelle

2018-05-05

To analyze the retinal structure in patients with X-linked retinoschisis (XLRS) using spectral-domain OCT and to correlate the morphologic findings with visual acuity, electroretinographic results, and patient age. Retrospective, observational study. Data from 52 consecutive male patients with molecularly confirmed XLRS were collected retrospectively. Complete clinical evaluation included best-corrected visual acuity, full-field electroretinography, fundus photography, spectral-domain OCT, and fundus autofluorescence. Spectral-domain OCT images were analyzed to determine full thickness of the retina and tomographic structural changes. Relationships between age, OCT, and visual acuity were assessed. One hundred four eyes of 52 patients were included. The mean age at inclusion was 24±15 years (range, 3-57 years). The best-corrected visual acuity ranged from no light perception to 0.1 logarithm of the minimum angle of resolution (mean, 0.6±0.38 logarithm of the minimum angle of resolution). Macular schisis was found in 88% of eyes and macular atrophy was found in 11% of eyes, whereas peripheral schisis was present in 30% of eyes. A spoke-wheel pattern of high and low intensity was the most frequently observed fundus autofluorescence abnormality (51/94 eyes [54%]). The b-to-a amplitude ratio on bright-flash dark-adapted electroretinography was reduced significantly in 45 of 64 eyes (70%). Spectral-domain OCT was available for 97 eyes and showed foveoschisis in 76 of 97 eyes (78%), parafoveal schisis in 10 of 97 eyes (10%), and foveal atrophy in 11 of 97 eyes (11%). Mean central macular thickness (CMT) was of 373.6±140 μm. Cystoid changes were localized mainly in the inner nuclear layer (85/97 eyes [88%]). Qualitative defects in photoreceptor structures were found in most eyes (79/97 eyes [81%]), and the most frequent abnormality was an interruption of the photoreceptor cell outer segment tips (79/79 eyes [100%]). Older age correlated well with lower CMT (correlation coefficient [CC], -0.44; P < 0.001) and with lower photoreceptor outer segment (PROS) length (CC, -0.42; P < 0.001). Lower visual acuity correlated strongly with lower PROS length (CC, -0.53; P < 0.001). This study underlined the wide variety of clinical features of XLRS. It highlighted the correlation between visual acuity, patient age, and OCT features, emphasizing the relevance of the latter as potential outcome measure in clinical trials. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Dynamic coupling between the LID and NMP domain motions in the catalytic conversion of ATP and AMP to ADP by adenylate kinase

NASA Astrophysics Data System (ADS)

Jana, Biman; Adkar, Bharat V.; Biswas, Rajib; Bagchi, Biman

2011-01-01

The catalytic conversion of adenosine triphosphate (ATP) and adenosine monophosphate (AMP) to adenosine diphosphate (ADP) by adenylate kinase (ADK) involves large amplitude, ligand induced domain motions, involving the opening and the closing of ATP binding domain (LID) and AMP binding domain (NMP) domains, during the repeated catalytic cycle. We discover and analyze an interesting dynamical coupling between the motion of the two domains during the opening, using large scale atomistic molecular dynamics trajectory analysis, covariance analysis, and multidimensional free energy calculations with explicit water. Initially, the LID domain must open by a certain amount before the NMP domain can begin to open. Dynamical correlation map shows interesting cross-peak between LID and NMP domain which suggests the presence of correlated motion between them. This is also reflected in our calculated two-dimensional free energy surface contour diagram which has an interesting elliptic shape, revealing a strong correlation between the opening of the LID domain and that of the NMP domain. Our free energy surface of the LID domain motion is rugged due to interaction with water and the signature of ruggedness is evident in the observed root mean square deviation variation and its fluctuation time correlation functions. We develop a correlated dynamical disorder-type theoretical model to explain the observed dynamic coupling between the motion of the two domains in ADK. Our model correctly reproduces several features of the cross-correlation observed in simulations.

Separation and Classification of Lipids Using Differential Ion Mobility Spectrometry

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

Shvartsburg, Alexandre A.; Isaac, Georgis; Leveque, Nathalie

2011-04-12

Correlations between the dimensions of a 2-D separation create trend lines that normally depend on structural or functional characteristics of the compound class and thus facilitate classification of unknowns. This broadly applies to conventional ion mobility spectrometry (IMS)/mass spectrometry (MS), where the major biomolecular classes (e.g., lipids, peptides, nucleotides) occupy different trend line domains. However, strong correlation between the IMS and MS separations for ions of same charge has impeded finer distinctions. Differential IMS (or FAIMS) is generally much less correlated to MS and thus should better separate the trend lines and associated domains. We report the first observation ofmore » chemical class separation by trend lines using FAIMS, here for lipids. For all lipids, FAIMS is indeed more independent of MS than conventional IMS, and subclasses (such as phospho-, glycero-, or sphingolipids) form distinct, often non-overlapping domains. Even finer categories with different functional groups or degrees of unsaturation are often separated. As expected, resolution improves in He-rich gases: at ~70% He, glycerolipid isomers with different positions of fatty acid attachment can be resolved. These results open the door for lipidomics application of FAIMS, particularly shotgun lipidomics and targeted analyses of bioactive lipids.« less

Controlled Terahertz Birefringence in Stretched Poly(lactic acid) Films Investigated by Terahertz Time-Domain Spectroscopy and Wide-Angle X-ray Scattering.

PubMed

Iwasaki, Hotsumi; Nakamura, Madoka; Komatsubara, Nozomu; Okano, Makoto; Nakasako, Masayoshi; Sato, Harumi; Watanabe, Shinichi

2017-07-20

We report a correlation between the dielectric property and structure of stretched poly(lactic acid) (PLA) films, revealed by polarization-sensitive terahertz time-domain spectroscopy and two-dimensional (2D) wide-angle X-ray scattering (WAXS). The experiments evidence that the dielectric function of the PLA film becomes more anisotropic with increasing draw ratio (DR). This behavior is explained by a classical Lorentz oscillator model assuming polarization-dependent absorption. The birefringence can be systematically altered from 0 to 0.13 by controlling DR. The combination of terahertz spectroscopy and 2D WAXS measurement reveals a clear correlation between the birefringence in the terahertz frequency domain and the degree of orientation of the PLA molecular chains. These findings imply that the birefringence is a result of the orientation of the PLA chains with anisotropic macromolecular vibration modes. Because of a good controllability of the birefringence, polymer-based materials will provide an attractive materials system for phase retarders in the terahertz frequency range.

Multimodal Retinal Imaging in Incontinentia Pigmenti Including Optical Coherence Tomography Angiography: Findings From an Older Cohort With Mild Phenotype.

PubMed

Liu, Tin Yan Alvin; Han, Ian C; Goldberg, Morton F; Linz, Marguerite O; Chen, Connie J; Scott, Adrienne W

2018-05-01

Incontinentia pigmenti (IP) is a rare, X-linked dominant disease with potentially severe ocular complications that predominantly affect the peripheral retina. However, little is known about its effects on the macula. To describe the structural and vascular abnormalities observed in the maculas of patients with IP and to correlate these findings with peripheral pathologies. Prospective, cross-sectional study at Wilmer Eye Institute, Johns Hopkins University. Five participants with a clinical diagnosis of IP were included and underwent multimodal imaging with ultra-wide-field fluorescein angiography (FA), spectral-domain optical coherence tomography (OCT), and OCT angiography. The structural and vascular abnormalities observed on spectral-domain OCT and OCT angiography and their correlation with peripheral pathologies seen on ultra-wide-field FA. A total of 9 eyes from 5 patients (median age, 20.5 years; range, 8.4-54.2 years) were included. Median Snellen visual acuity was 20/32 (range, 20/16 to 20/63). ultra-wide-field FA-identified retinal vascular abnormalities in all 7 eyes in which FA was obtained. These abnormalities included microaneurysms, areas of nonperfusion, and vascular anastomoses, most of which were peripheral to the standard view of 30° FA with peripheral sweeps. Structural abnormalities were observed in 6 eyes on spectral-domain OCT, including inner retinal thinning and irregularities in the outer plexiform layer. Optical coherence tomography angiography abnormalities were noted in all 9 eyes, including decreased vascular density, abnormal vascular loops, and flow loss in the superficial and deep plexuses, which corresponded to areas of retinal thinning on spectral-domain OCT. Although our study is limited by the small sample size, the findings suggest that multimodal imaging is useful for detecting structural and vascular abnormalities that may not be apparent on ophthalmoscopy in patients with IP. Macular pathologies, especially a decrease in vascular density on OCT angiography, are common. Further studies are needed to characterize further the association between macular and peripheral abnormalities in patients with IP.

High-throughput search for new permanent magnet materials.

PubMed

Goll, D; Loeffler, R; Herbst, J; Karimi, R; Schneider, G

2014-02-12

The currently highest-performance Fe-Nd-B magnets show limited cost-effectiveness and lifetime due to their rare-earth (RE) content. The demand for novel hard magnetic phases with more widely available RE metals, reduced RE content or, even better, completely free of RE metals is therefore tremendous. The chances are that such materials still exist given the large number of as yet unexplored alloy systems. To discover such phases, an elaborate concept is necessary which can restrict and prioritize the search field while making use of efficient synthesis and analysis methods. It is shown that an efficient synthesis of new phases using heterogeneous non-equilibrium diffusion couples and reaction sintering is possible. Quantitative microstructure analysis of the domain pattern of the hard magnetic phases can be used to estimate the intrinsic magnetic parameters (saturation polarization from the domain contrast, anisotropy constant from the domain width, Curie temperature from the temperature dependence of the domain contrast). The probability of detecting TM-rich phases for a given system is high, therefore the approach enables one to scan through even higher component systems with one single sample. The visualization of newly occurring hard magnetic phases via their typical domain structure and the correlation existing between domain structure and intrinsic magnetic properties allows an evaluation of the industrial relevance of these novel phases.

Comparison between the Correlations of Retinal Nerve Fiber Layer Thickness Measured by Spectral Domain Optical Coherence Tomography and Visual Field Defects in Standard Automated White-on-White Perimetry versus Pulsar Perimetry.

PubMed

Alnawaiseh, Maged; Hömberg, Lisann; Eter, Nicole; Prokosch, Verena

2017-01-01

To compare the structure-function relationships between retinal nerve fiber layer thickness (RNFLT) and visual field defects measured either by standard automated perimetry (SAP) or by Pulsar perimetry (PP). 263 eyes of 143 patients were prospectively included. Depending on the RNFLT, patients were assigned to the glaucoma group (group A: RNFL score 3-6) or the control group (group B: RNFL score 0-2). Structure-function relationships between RNFLT and mean sensitivity (MS) measured by SAP and PP were analyzed. Throughout the entire group, the MS assessed by PP and SAP correlated significantly with RNFLT in all sectors. In the glaucoma group, there was no significant difference between the correlations RNFL-SAP and RNFL-PP, whereas a significant difference was found in the control group. In the control group, the correlation between structure and function based on the PP data was significantly stronger than that based on SAP.

A novel fractal image compression scheme with block classification and sorting based on Pearson's correlation coefficient.

PubMed

Wang, Jianji; Zheng, Nanning

2013-09-01

Fractal image compression (FIC) is an image coding technology based on the local similarity of image structure. It is widely used in many fields such as image retrieval, image denoising, image authentication, and encryption. FIC, however, suffers from the high computational complexity in encoding. Although many schemes are published to speed up encoding, they do not easily satisfy the encoding time or the reconstructed image quality requirements. In this paper, a new FIC scheme is proposed based on the fact that the affine similarity between two blocks in FIC is equivalent to the absolute value of Pearson's correlation coefficient (APCC) between them. First, all blocks in the range and domain pools are chosen and classified using an APCC-based block classification method to increase the matching probability. Second, by sorting the domain blocks with respect to APCCs between these domain blocks and a preset block in each class, the matching domain block for a range block can be searched in the selected domain set in which these APCCs are closer to APCC between the range block and the preset block. Experimental results show that the proposed scheme can significantly speed up the encoding process in FIC while preserving the reconstructed image quality well.

Physical heterogeneity control on effective mineral dissolution rates

NASA Astrophysics Data System (ADS)

Jung, Heewon; Navarre-Sitchler, Alexis

2018-04-01

Hydrologic heterogeneity may be an important factor contributing to the discrepancy in laboratory and field measured dissolution rates, but the governing factors influencing mineral dissolution rates among various representations of physical heterogeneity remain poorly understood. Here, we present multiple reactive transport simulations of anorthite dissolution in 2D latticed random permeability fields and link the information from local grid scale (1 cm or 4 m) dissolution rates to domain-scale (1m or 400 m) effective dissolution rates measured by the flux-weighted average of an ensemble of flow paths. We compare results of homogeneous models to heterogeneous models with different structure and layered permeability distributions within the model domain. Chemistry is simplified to a single dissolving primary mineral (anorthite) distributed homogeneously throughout the domain and a single secondary mineral (kaolinite) that is allowed to dissolve or precipitate. Results show that increasing size in correlation structure (i.e. long integral scales) and high variance in permeability distribution are two important factors inducing a reduction in effective mineral dissolution rates compared to homogeneous permeability domains. Larger correlation structures produce larger zones of low permeability where diffusion is an important transport mechanism. Due to the increased residence time under slow diffusive transport, the saturation state of a solute with respect to a reacting mineral approaches equilibrium and reduces the reaction rate. High variance in permeability distribution favorably develops large low permeability zones that intensifies the reduction in mixing and effective dissolution rate. However, the degree of reduction in effective dissolution rate observed in 1 m × 1 m domains is too small (<1% reduction from the corresponding homogeneous case) to explain several orders of magnitude reduction observed in many field studies. When multimodality in permeability distribution is approximated by high permeability variance in 400 m × 400 m domains, the reduction in effective dissolution rate increases due to the effect of long diffusion length scales through zones with very slow reaction rates. The observed scale dependence becomes complicated when pH dependent kinetics are compared to the results from pH independent rate constants. In small domains where the entire domain is reactive, faster anorthite dissolution rates and slower kaolinite precipitation rates relative to pH independent rates at far-from-equilibrium conditions reduce the effective dissolution rate by increasing the saturation state. However, in large domains where less- or non-reactive zones develop, higher kaolinite precipitation rates in less reactive zones increase the effective anorthite dissolution rates relative to the rates observed in pH independent cases.

Using Common Spatial Distributions of Atoms to Relate Functionally Divergent Influenza Virus N10 and N11 Protein Structures to Functionally Characterized Neuraminidase Structures, Toxin Cell Entry Domains, and Non-Influenza Virus Cell Entry Domains

PubMed Central

Weininger, Arthur; Weininger, Susan

2015-01-01

The ability to identify the functional correlates of structural and sequence variation in proteins is a critical capability. We related structures of influenza A N10 and N11 proteins that have no established function to structures of proteins with known function by identifying spatially conserved atoms. We identified atoms with common distributed spatial occupancy in PDB structures of N10 protein, N11 protein, an influenza A neuraminidase, an influenza B neuraminidase, and a bacterial neuraminidase. By superposing these spatially conserved atoms, we aligned the structures and associated molecules. We report spatially and sequence invariant residues in the aligned structures. Spatially invariant residues in the N6 and influenza B neuraminidase active sites were found in previously unidentified spatially equivalent sites in the N10 and N11 proteins. We found the corresponding secondary and tertiary structures of the aligned proteins to be largely identical despite significant sequence divergence. We found structural precedent in known non-neuraminidase structures for residues exhibiting structural and sequence divergence in the aligned structures. In N10 protein, we identified staphylococcal enterotoxin I-like domains. In N11 protein, we identified hepatitis E E2S-like domains, SARS spike protein-like domains, and toxin components shared by alpha-bungarotoxin, staphylococcal enterotoxin I, anthrax lethal factor, clostridium botulinum neurotoxin, and clostridium tetanus toxin. The presence of active site components common to the N6, influenza B, and S. pneumoniae neuraminidases in the N10 and N11 proteins, combined with the absence of apparent neuraminidase function, suggests that the role of neuraminidases in H17N10 and H18N11 emerging influenza A viruses may have changed. The presentation of E2S-like, SARS spike protein-like, or toxin-like domains by the N10 and N11 proteins in these emerging viruses may indicate that H17N10 and H18N11 sialidase-facilitated cell entry has been supplemented or replaced by sialidase-independent receptor binding to an expanded cell population that may include neurons and T-cells. PMID:25706124

Local conductance: A means to extract polarization and depolarizing fields near domain walls in ferroelectrics

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

Douglas, A. M.; Kumar, A.; Gregg, J. M.

Conducting atomic force microscopy images of bulk semiconducting BaTiO{sub 3} surfaces show clear stripe domain contrast. High local conductance correlates with strong out-of-plane polarization (mapped independently using piezoresponse force microscopy), and current-voltage characteristics are consistent with dipole-induced alterations in Schottky barriers at the metallic tip-ferroelectric interface. Indeed, analyzing current-voltage data in terms of established Schottky barrier models allows relative variations in the surface polarization, and hence the local domain structure, to be determined. Fitting also reveals the signature of surface-related depolarizing fields concentrated near domain walls. Domain information obtained from mapping local conductance appears to be more surface-sensitive than thatmore » from piezoresponse force microscopy. In the right materials systems, local current mapping could therefore represent a useful complementary technique for evaluating polarization and local electric fields with nanoscale resolution.« less

Personal and Contextual Factors Associated with Students' Cheating in Science

ERIC Educational Resources Information Center

Tas, Yasemin; Tekkaya, Ceren

2010-01-01

The authors conducted a correlational study to investigate the relations among seventh-grade Turkish students' cheating behavior, academic self-efficacy beliefs, usage of self-handicapping strategies, personal goal orientations, and classroom goal structures specific to the science domain. The Patterns of Adaptive Learning Scales was administered…

White Matter Fractional Anisotrophy Differences and Correlates of Diagnostic Symptoms in Autism

ERIC Educational Resources Information Center

Cheung, C.; Chua, S. E.; Cheung, V.; Khong, P. L.; Tai, K. S.; Wong, T. K. W.; Ho, T. P.; McAlonan, G. M.

2009-01-01

Background: Individuals with autism have impairments in 3 domains: communication, social interaction and repetitive behaviours. Our previous work suggested early structural and connectivity abnormalities in prefrontal-striato-temporal-cerebellar networks but it is not clear how these are linked to diagnostic indices. Method: Children with autism…

Correlation between the ripple phase and stripe domains in membranes.

PubMed

Bernchou, Uffe; Midtiby, Henrik; Ipsen, John Hjort; Simonsen, Adam Cohen

2011-12-01

We investigate the relationship between stripe domains and the ripple phase in membranes. These have previously been observed separately without being linked explicitly. Past results have demonstrated that solid and ripple phases exhibit rich textural patterns related to the orientational order of tilted lipids and the orientation of ripple corrugations. Here we reveal a highly complex network pattern of ripple and solid domains in DLPC, DPPC bilayers with structures covering length scales from 10 nm to 100 μm. Using spincoated double supported membranes we investigate domains by correlated AFM and fluorescence microscopy. Cooling experiments demonstrate the mode of nucleation and growth of stripe domains enriched in the fluorescent probe. Concurrent AFM imaging reveals that these stripe domains have a one-to-one correspondence with a rippled morphology running parallel to the stripe direction. Both thin and thick stripe domains are observed having ripple periods of 13.5±0.2 nm and 27.4±0.6 nm respectively. These are equivalent to previously observed asymmetric/equilibrium and symmetric/metastable ripple phases, respectively. Thin stripes grow from small solid domains and grow predominantly in length with a speed of ~3 times that of the thick stripes. Thick stripes grow by templating on the sides of thinner stripes or can emerge directly from the fluid phase. Bending and branching angles of stripes are in accordance with an underlying six fold lattice. We discuss mechanisms for the nucleation and growth of ripples and discuss a generic phase diagram that may partly rationalize the coexistence of metastable and stable phases. Copyright © 2011 Elsevier B.V. All rights reserved.

Measuring achievement goal motivation, mindsets and cognitive load: validation of three instruments' scores.

PubMed

Cook, David A; Castillo, Richmond M; Gas, Becca; Artino, Anthony R

2017-10-01

Measurement of motivation and cognitive load has potential value in health professions education. Our objective was to evaluate the validity of scores from Dweck's Implicit Theories of Intelligence Scale (ITIS), Elliot's Achievement Goal Questionnaire-Revised (AGQ-R) and Leppink's cognitive load index (CLI). This was a validity study evaluating internal structure using reliability and factor analysis, and relationships with other variables using the multitrait-multimethod matrix. Two hundred and thirty-two secondary school students participated in a medical simulation-based training activity at an academic medical center. Pre-activity ITIS (implicit theory [mindset] domains: incremental, entity) and AGQ-R (achievement goal domains: mastery-approach, mastery-avoidance, performance-approach, performance-avoidance), post-activity CLI (cognitive load domains: intrinsic, extrinsic, germane) and task persistence (self-directed repetitions on a laparoscopic surgery task) were measured. Internal consistency reliability (Cronbach's alpha) was > 0.70 for all domain scores except AGQ-R performance-avoidance (alpha 0.68) and CLI extrinsic load (alpha 0.64). Confirmatory factor analysis of ITIS and CLI scores demonstrated acceptable model fit. Confirmatory factor analysis of AGQ-R scores demonstrated borderline fit, and exploratory factor analysis suggested a three-domain model for achievement goals (mastery-approach, performance and avoidance). Correlations among scores from conceptually-related domains generally aligned with expectations, as follows: ITIS incremental and entity, r = -0.52; AGQ-R mastery-avoidance and performance-avoidance, r = 0.71; mastery-approach and performance-approach, r = 0.55; performance-approach and performance-avoidance, r = 0.43; mastery-approach and mastery-avoidance, r = 0.36; CLI germane and extrinsic, r = -0.35; ITIS incremental and AGQ-R mastery-approach, r = 0.34; ITIS incremental and CLI germane, r = 0.44; AGQ-R mastery-approach and CLI germane, r = 0.48 (all p < 0.001). We found no correlation between the number of task repetitions (i.e. persistence) and mastery-approach scores, r = -0.01. ITIS and CLI scores had appropriate internal structures and relationships with other variables. AGQ-R scores fit a three-factor (not four-factor) model that collapsed avoidance into one domain, although relationships of other variables with the original four domain scores generally aligned with expectations. Mastery goals are positively correlated with germane cognitive load. © 2017 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

In silico molecular docking analysis of the human Argonaute 2 PAZ domain reveals insights into RNA interference.

PubMed

Kandeel, Mahmoud; Kitade, Yukio

2013-07-01

RNA interference (RNAi) is a critical cellular pathway activated by double stranded RNA and regulates the gene expression of target mRNA. During RNAi, the 3' end of siRNA binds with the PAZ domain, followed by release and rebinding in a cyclic manner, which deemed essential for proper gene silencing. Recently, we provided the forces underlying the recognition of small interfering RNA by PAZ in a computational study based on the structure of Drosophila Argonaute 2 (Ago2) PAZ domain. We have now reanalyzed these data within the view of the new available structures from human Argonauts. While the parameters of weak binding are correlated with higher (RNAi) in the Drosophila model, a different profile is predicted with the human Ago2 PAZ domain. On the basis of the human Ago2 PAZ models, the indicators of stronger binding as the total binding energy and the free energy were associated with better RNAi efficacy. This discrepancy might be attributable to differences in the binding site topology and the difference in the conformation of the bound nucleotides.

Navigating the conformational landscape of G protein-coupled receptor kinases during allosteric activation.

PubMed

Yao, Xin-Qiu; Cato, M Claire; Labudde, Emily; Beyett, Tyler S; Tesmer, John J G; Grant, Barry J

2017-09-29

G protein-coupled receptors (GPCRs) are essential for transferring extracellular signals into carefully choreographed intracellular responses controlling diverse aspects of cell physiology. The duration of GPCR-mediated signaling is primarily regulated via GPCR kinase (GRK)-mediated phosphorylation of activated receptors. Although many GRK structures have been reported, the mechanisms underlying GRK activation are not well-understood, in part because it is unknown how these structures map to the conformational landscape available to this enzyme family. Unlike most other AGC kinases, GRKs rely on their interaction with GPCRs for activation and not phosphorylation. Here, we used principal component analysis of available GRK and protein kinase A crystal structures to identify their dominant domain motions and to provide a framework that helps evaluate how close each GRK structure is to being a catalytically competent state. Our results indicated that disruption of an interface formed between the large lobe of the kinase domain and the regulator of G protein signaling homology domain (RHD) is highly correlated with establishment of the active conformation. By introducing point mutations in the GRK5 RHD-kinase domain interface, we show with both in silico and in vitro experiments that perturbation of this interface leads to higher phosphorylation activity. Navigation of the conformational landscape defined by this bioinformatics-based study is likely common to all GPCR-activated GRKs. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

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

Heo, Yooun; Lee, Jin Hong; Xie, Lin

Enhanced properties in modern functional materials can often be found at structural transition regions, such as morphotropic phase boundaries (MPB), owing to the coexistence of multiple phases with nearly equivalent energies. Strain-engineered MPBs have emerged in epitaxially grown BiFeO 3 (BFO) thin films by precisely tailoring a compressive misfit strain, leading to numerous intriguing phenomena, such as a massive piezoelectric response, magnetoelectric coupling, interfacial magnetism and electronic conduction. Recently, an orthorhombic–rhombohedral (O–R) phase boundary has also been found in tensile-strained BFO. In this study, we characterise the crystal structure and electronic properties of the two competing O and R phasesmore » using X-ray diffraction, scanning probe microscope and scanning transmission electron microscopy (STEM). We observe the temperature evolution of R and O domains and find that the domain boundaries are highly conductive. Temperature-dependent measurements reveal that the conductivity is thermally activated for R–O boundaries. STEM observations point to structurally wide boundaries, significantly wider than in other systems. Furthermore, we reveal a strong correlation between the highly conductive domain boundaries and structural material properties. These findings provide a pathway to use phase boundaries in this system for novel nanoelectronic applications.« less

Epitaxial structure and electronic property of β-Ga2O3 films grown on MgO (100) substrates by pulsed-laser deposition

NASA Astrophysics Data System (ADS)

Wakabayashi, Ryo; Yoshimatsu, Kohei; Hattori, Mai; Ohtomo, Akira

2017-10-01

We investigated heteroepitaxial growth of Si-doped Ga2O3 films on MgO (100) substrates by pulsed-laser deposition as a function of growth temperature (Tg) to find a strong correlation between the structural and electronic properties. The films were found to contain cubic γ-phase and monoclinic β-phase, the latter of which indicated rotational twin domains when grown at higher Tg. The formation of the metastable γ-phase and twin-domain structure in the stable β-phase are discussed in terms of the in-plane epitaxial relationships with a square MgO lattice, while crystallinity of the β-phase degraded monotonically with decreasing Tg. The room-temperature conductivity indicated a maximum at the middle of Tg, where the β-Ga2O3 layer was relatively highly crystalline and free from the twin-domain structure. Moreover, both crystallinity and conductivity of β-Ga2O3 films on the MgO substrates were found superior to those on α-Al2O3 (0001) substrates. A ratio of the conductivity, attained to the highest quantity on each substrate, was almost three orders of magnitude.

Molecular dynamics simulation of the Escherichia coli NikR protein: equilibrium conformational fluctuations reveal interdomain allosteric communication pathways.

PubMed

Bradley, Michael J; Chivers, Peter T; Baker, Nathan A

2008-05-16

Escherichia coli NikR is a homotetrameric Ni(2+)- and DNA-binding protein that functions as a transcriptional repressor of the NikABCDE nickel permease. The protein is composed of two distinct domains. The N-terminal 50 amino acids of each chain forms part of the dimeric ribbon-helix-helix (RHH) domains, a well-studied DNA-binding fold. The 83-residue C-terminal nickel-binding domain forms an ACT (aspartokinase, chorismate mutase, and TyrA) fold and contains the tetrameric interface. In this study, we have utilized an equilibrium molecular dynamics simulation in order to explore the conformational dynamics of the NikR tetramer and determine important residue interactions within and between the RHH and ACT domains to gain insight into the effects of Ni(2+) on DNA-binding activity. The molecular simulation data were analyzed using two different correlation measures based on fluctuations in atomic position and noncovalent contacts together with a clustering algorithm to define groups of residues with similar correlation patterns for both types of correlation measure. Based on these analyses, we have defined a series of residue interrelationships that describe an allosteric communication pathway between the Ni(2+)- and DNA-binding sites, which are separated by 40 A. Several of the residues identified by our analyses have been previously shown experimentally to be important for NikR function. An additional subset of the identified residues structurally connects the experimentally implicated residues and may help coordinate the allosteric communication between the ACT and RHH domains.

Comparable contributions of structural-functional constraints and expression level to the rate of protein sequence evolution

PubMed Central

Wolf, Maxim Y; Wolf, Yuri I; Koonin, Eugene V

2008-01-01

Background Proteins show a broad range of evolutionary rates. Understanding the factors that are responsible for the characteristic rate of evolution of a given protein arguably is one of the major goals of evolutionary biology. A long-standing general assumption used to be that the evolution rate is, primarily, determined by the specific functional constraints that affect the given protein. These constrains were traditionally thought to depend both on the specific features of the protein's structure and its biological role. The advent of systems biology brought about new types of data, such as expression level and protein-protein interactions, and unexpectedly, a variety of correlations between protein evolution rate and these variables have been observed. The strongest connections by far were repeatedly seen between protein sequence evolution rate and the expression level of the respective gene. It has been hypothesized that this link is due to the selection for the robustness of the protein structure to mistranslation-induced misfolding that is particularly important for highly expressed proteins and is the dominant determinant of the sequence evolution rate. Results This work is an attempt to assess the relative contributions of protein domain structure and function, on the one hand, and expression level on the other hand, to the rate of sequence evolution. To this end, we performed a genome-wide analysis of the effect of the fusion of a pair of domains in multidomain proteins on the difference in the domain-specific evolutionary rates. The mistranslation-induced misfolding hypothesis would predict that, within multidomain proteins, fused domains, on average, should evolve at substantially closer rates than the same domains in different proteins because, within a mutlidomain protein, all domains are translated at the same rate. We performed a comprehensive comparison of the evolutionary rates of mammalian and plant protein domains that are either joined in multidomain proteins or contained in distinct proteins. Substantial homogenization of evolutionary rates in multidomain proteins was, indeed, observed in both animals and plants, although highly significant differences between domain-specific rates remained. The contributions of the translation rate, as determined by the effect of the fusion of a pair of domains within a multidomain protein, and intrinsic, domain-specific structural-functional constraints appear to be comparable in magnitude. Conclusion Fusion of domains in a multidomain protein results in substantial homogenization of the domain-specific evolutionary rates but significant differences between domain-specific evolution rates remain. Thus, the rate of translation and intrinsic structural-functional constraints both exert sizable and comparable effects on sequence evolution. Reviewers This article was reviewed by Sergei Maslov, Dennis Vitkup, Claus Wilke (nominated by Orly Alter), and Allan Drummond (nominated by Joel Bader). For the full reviews, please go to the Reviewers' Reports section. PMID:18840284

Solvothermally Synthesized Sb2Te3 Platelets Show Unexpected Optical Contrasts in Mid-Infrared Near-Field Scanning Microscopy.

PubMed

Hauer, Benedikt; Saltzmann, Tobias; Simon, Ulrich; Taubner, Thomas

2015-05-13

We report nanoscale-resolved optical investigations on the local material properties of Sb2Te3 hexagonal platelets grown by solvothermal synthesis. Using mid-infrared near-field microscopy, we find a highly symmetric pattern, which is correlated to a growth spiral and which extends over the entire platelet. As the origin of the optical contrast, we identify domains with different densities of charge carriers. On Sb2Te3 samples grown by other means, we did not find a comparable domain structure.

Time-resolved experiments in the frequency domain using synchrotron radiation (invited)

NASA Astrophysics Data System (ADS)

De Stasio, Gelsomina; Giusti, A. M.; Parasassi, T.; Ravagnan, G.; Sapora, O.

1992-01-01

PLASTIQUE is the only synchrotron radiation beam line in the world that performs time-resolved fluorescence experiments in frequency domain. These experiments are extremely valuable sources of information on the structure and the dynamics of molecules. This technique measures fluorescence lifetimes with picosecond resolution in the near UV spectral range. Such accurate measurements are rendered possible by taking phase and modulation data, and by the advantages of the cross-correlation technique. A successful experiment demonstrated the radiation damage induced by low doses of radiation on rabbit blood cell membranes.

Domain ordering of strained 5 ML SrTiO3 films on Si(001)

NASA Astrophysics Data System (ADS)

Ryan, P.; Wermeille, D.; Kim, J. W.; Woicik, J. C.; Hellberg, C. S.; Li, H.

2007-05-01

High resolution x-ray diffraction data indicate ordered square shaped coherent domains, ˜1200Å in length, coexisting with longer, ˜9500Å correlated regions in highly strained 5 ML SrTiO3 films grown on Si(001). These long range film structures are due to the Si substrate terraces defined by the surface step morphology. The silicon surface "step pattern" is comprised of an "intrinsic" terrace length from strain relaxation and a longer "extrinsic" interstep distance due to the surface miscut.

Crystal structure of arrestin-3 reveals the basis of the difference in receptor binding between two non-visual subtypes

PubMed Central

Zhan, Xuanzhi; Gimenez, Luis E.; Gurevich, Vsevolod V.; Spiller, Benjamin W.

2011-01-01

Arrestins are multi-functional proteins that regulate signaling and trafficking of the majority of G protein-coupled receptors (GPCRs), as well as sub-cellular localization and activity of many other signaling proteins. Here we report the first crystal structure of arrestin-3, solved at 3.0Å. Arrestin-3 is an elongated two-domain molecule with the overall fold and key inter-domain interactions that hold free protein in the basal conformation similar to the other subtypes. Arrestin-3 is the least selective member of the family, binding wide variety of GPCRs with high affinity and demonstrating lower preference for active phosphorylated forms of the receptors. In contrast to the other three arrestins, part of the receptor-binding surface in the arrestin-3 C-domain does not form a contiguous β-sheet, consistent with increased flexibility. By swapping the corresponding elements between arrestin-2 and -3 we show that the presence of this loose structure correlates with reduced arrestin selectivity for activated receptor, consistent with a conformational change in this β-sheet upon receptor binding. PMID:21215759

Graphene Visualizes the Ion Distribution on Air-Cleaved Mica.

PubMed

Bampoulis, Pantelis; Sotthewes, Kai; Siekman, Martin H; Zandvliet, Harold J W; Poelsema, Bene

2017-03-06

The distribution of potassium (K + ) ions on air-cleaved mica is important in many interfacial phenomena such as crystal growth, self-assembly and charge transfer on mica. However, due to experimental limitations to nondestructively probe single ions and ionic domains, their exact lateral organization is yet unknown. We show, by the use of graphene as an ultra-thin protective coating and scanning probe microscopies, that single potassium ions form ordered structures that are covered by an ice layer. The K + ions prefer to minimize the number of nearest neighbour K + ions by forming row-like structures as well as small domains. This trend is a result of repulsive ionic forces between adjacent ions, weakened due to screening by the surrounding water molecules. Using high resolution conductive atomic force microscopy maps, the local conductance of the graphene is measured, revealing a direct correlation between the K + distribution and the structure of the ice layer. Our results shed light on the local distribution of ions on the air-cleaved mica, solving a long-standing enigma. They also provide a detailed understanding of charge transfer from the ionic domains towards graphene.

Human acid sphingomyelinase structures provide insight to molecular basis of Niemann–Pick disease

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

Zhou, Yan-Feng; Metcalf, Matthew C.; Garman, Scott C.

Acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to ceramide and phosphocholine, essential components of myelin in neurons. Genetic alterations in ASM lead to ASM deficiency (ASMD) and have been linked to Niemann–Pick disease types A and B. Olipudase alfa, a recombinant form of human ASM, is being developed as enzyme replacement therapy to treat the non-neurological manifestations of ASMD. Here we present the human ASM holoenzyme and product bound structures encompassing all of the functional domains. The catalytic domain has a metallophosphatase fold, and two zinc ions and one reaction product phosphocholine are identified in a histidine-rich active site. The structures revealmore » the underlying catalytic mechanism, in which two zinc ions activate a water molecule for nucleophilic attack of the phosphodiester bond. Docking of sphingomyelin provides a model that allows insight into the selectivity of the enzyme and how the ASM domains collaborate to complete hydrolysis. Mapping of known mutations provides a basic understanding on correlations between enzyme dysfunction and phenotypes observed in ASMD patients.« less

Infrared photoconductivity and photovoltaic response from nanoscale domains of PbS alloyed with thorium and oxygen

NASA Astrophysics Data System (ADS)

Arad-Vosk, N.; Beach, R.; Ron, A.; Templeman, T.; Golan, Y.; Sarusi, G.; Sa'ar, A.

2018-03-01

Thin films of lead sulfide alloyed with thorium and oxygen were deposited on GaAs substrates and processed to produce a photo-diode structure. Structural, optical and electrical characterizations indicate the presence of small nanoscale domains (NDs) that are characterized by dense packaging, high quality interfaces and a blue-shift of the energy bandgap toward the short wavelength infrared range of the spectrum. Photocurrent spectroscopy revealed a considerable photoconductivity that is correlated with excitation of carriers in the NDs of lead sulfide alloyed with thorium and oxygen. Furthermore, the appearance of a photovoltaic effect under near infrared illumination indicates a quasi-type II band alignment at the interface of the GaAs and the film of NDs.

Infrared photoconductivity and photovoltaic response from nanoscale domains of PbS alloyed with thorium and oxygen.

PubMed

Arad-Vosk, N; Beach, R; Ron, A; Templeman, T; Golan, Y; Sarusi, G; Sa'ar, A

2018-03-16

Thin films of lead sulfide alloyed with thorium and oxygen were deposited on GaAs substrates and processed to produce a photo-diode structure. Structural, optical and electrical characterizations indicate the presence of small nanoscale domains (NDs) that are characterized by dense packaging, high quality interfaces and a blue-shift of the energy bandgap toward the short wavelength infrared range of the spectrum. Photocurrent spectroscopy revealed a considerable photoconductivity that is correlated with excitation of carriers in the NDs of lead sulfide alloyed with thorium and oxygen. Furthermore, the appearance of a photovoltaic effect under near infrared illumination indicates a quasi-type II band alignment at the interface of the GaAs and the film of NDs.

New Possibilities of Substance Identification Based on THz Time Domain Spectroscopy Using a Cascade Mechanism of High Energy Level Excitation

PubMed Central

Trofimov, Vyacheslav A.; Varentsova, Svetlana A.; Zakharova, Irina G.; Zagursky, Dmitry Yu.

2017-01-01

Using an experiment with thin paper layers and computer simulation, we demonstrate the principal limitations of standard Time Domain Spectroscopy (TDS) based on using a broadband THz pulse for the detection and identification of a substance placed inside a disordered structure. We demonstrate the spectrum broadening of both transmitted and reflected pulses due to the cascade mechanism of the high energy level excitation considering, for example, a three-energy level medium. The pulse spectrum in the range of high frequencies remains undisturbed in the presence of a disordered structure. To avoid false absorption frequencies detection, we apply the spectral dynamics analysis method (SDA-method) together with certain integral correlation criteria (ICC). PMID:29186849

The reliability and validity of the English version of the Evaluation of Daily Activity Questionnaire for people with rheumatoid arthritis

PubMed Central

Tennant, Alan; Tyson, Sarah F.; Nordenskiöld, Ulla; Hawkins, Ruth; Prior, Yeliz

2015-01-01

Objectives. The Evaluation of Daily Activity Questionnaire (EDAQ) includes 138 items in 14 domains identified as important by people with RA. The aim of this study was to test the validity and reliability of the English EDAQ. Methods. A total of 502 participants completed two questionnaires 3 weeks apart. The first consisted of the EDAQ, HAQ, RA Quality of Life (RAQoL) and the Medical Outcomes Scale (MOS) 36-item Short-Form Health Survey (SF-36v2), and the second consisted of the EDAQ only. The 14 EDAQ domains were tested for: unidimensionality—using confirmatory factor analysis; fit, response dependency, invariance across groups (differential item functioning)—using Rasch analysis; internal consistency [Person Separation Index (PSI)]; concurrent validity—by correlations with the HAQ, SF-36v2 and RAQoL; and test–retest reliability (Spearman’s correlations). Results. Confirmatory factor analysis of the 14 EDAQ domains indicated unidimensionality, after adjustment for local dependency in each domain. All domains achieved a root mean square error of approximation <0.10 and satisfied Rasch model expectations for local dependency. DIF by age, gender and employment status was largely absent. The PSI was consistent with individual use (PSI = 0.94 for all 14 domains). For all domains, except Caring, concurrent validity was good: HAQ (rs = 0.72–0.91), RAQoL (rs = 0.67–0.82) and SF36v2 Physical Function scale (rs = −0.60 to −0.84) and test–retest reliability was good (rs = 0.70–0.89). Conclusion. Analysis supported a 14-domain, two-component structure (Self care and Mobility) of the EDAQ, where each domain, and both components, satisfied Rasch model requirements, and have robust reliability and validity. PMID:25863045

Protein Domain-Level Landscape of Cancer-Type-Specific Somatic Mutations

PubMed Central

Yang, Fan; Petsalaki, Evangelia; Rolland, Thomas; Hill, David E.; Vidal, Marc; Roth, Frederick P.

2015-01-01

Identifying driver mutations and their functional consequences is critical to our understanding of cancer. Towards this goal, and because domains are the functional units of a protein, we explored the protein domain-level landscape of cancer-type-specific somatic mutations. Specifically, we systematically examined tumor genomes from 21 cancer types to identify domains with high mutational density in specific tissues, the positions of mutational hotspots within these domains, and the functional and structural context where possible. While hotspots corresponding to specific gain-of-function mutations are expected for oncoproteins, we found that tumor suppressor proteins also exhibit strong biases toward being mutated in particular domains. Within domains, however, we observed the expected patterns of mutation, with recurrently mutated positions for oncogenes and evenly distributed mutations for tumor suppressors. For example, we identified both known and new endometrial cancer hotspots in the tyrosine kinase domain of the FGFR2 protein, one of which is also a hotspot in breast cancer, and found new two hotspots in the Immunoglobulin I-set domain in colon cancer. Thus, to prioritize cancer mutations for further functional studies aimed at more precise cancer treatments, we have systematically correlated mutations and cancer types at the protein domain level. PMID:25794154

Quantitative Determination of Technological Improvement from Patent Data

PubMed Central

2015-01-01

The results in this paper establish that information contained in patents in a technological domain is strongly correlated with the rate of technological progress in that domain. The importance of patents in a domain, the recency of patents in a domain and the immediacy of patents in a domain are all strongly correlated with increases in the rate of performance improvement in the domain of interest. A patent metric that combines both importance and immediacy is not only highly correlated (r = 0.76, p = 2.6*10-6) with the performance improvement rate but the correlation is also very robust to domain selection and appears to have good predictive power for more than ten years into the future. Linear regressions with all three causal concepts indicate realistic value in practical use to estimate the important performance improvement rate of a technological domain. PMID:25874447

Multisite stochastic simulation of daily precipitation from copula modeling with a gamma marginal distribution

NASA Astrophysics Data System (ADS)

Lee, Taesam

2018-05-01

Multisite stochastic simulations of daily precipitation have been widely employed in hydrologic analyses for climate change assessment and agricultural model inputs. Recently, a copula model with a gamma marginal distribution has become one of the common approaches for simulating precipitation at multiple sites. Here, we tested the correlation structure of the copula modeling. The results indicate that there is a significant underestimation of the correlation in the simulated data compared to the observed data. Therefore, we proposed an indirect method for estimating the cross-correlations when simulating precipitation at multiple stations. We used the full relationship between the correlation of the observed data and the normally transformed data. Although this indirect method offers certain improvements in preserving the cross-correlations between sites in the original domain, the method was not reliable in application. Therefore, we further improved a simulation-based method (SBM) that was developed to model the multisite precipitation occurrence. The SBM preserved well the cross-correlations of the original domain. The SBM method provides around 0.2 better cross-correlation than the direct method and around 0.1 degree better than the indirect method. The three models were applied to the stations in the Nakdong River basin, and the SBM was the best alternative for reproducing the historical cross-correlation. The direct method significantly underestimates the correlations among the observed data, and the indirect method appeared to be unreliable.

Taxonomic distribution, repeats, and functions of the S1 domain-containing proteins as members of the OB-fold family.

PubMed

Deryusheva, Evgeniia I; Machulin, Andrey V; Selivanova, Olga M; Galzitskaya, Oxana V

2017-04-01

Proteins of the nucleic acid-binding proteins superfamily perform such functions as processing, transport, storage, stretching, translation, and degradation of RNA. It is one of the 16 superfamilies containing the OB-fold in protein structures. Here, we have analyzed the superfamily of nucleic acid-binding proteins (the number of sequences exceeds 200,000) and obtained that this superfamily prevalently consists of proteins containing the cold shock DNA-binding domain (ca. 131,000 protein sequences). Proteins containing the S1 domain compose 57% from the cold shock DNA-binding domain family. Furthermore, we have found that the S1 domain was identified mainly in the bacterial proteins (ca. 83%) compared to the eukaryotic and archaeal proteins, which are available in the UniProt database. We have found that the number of multiple repeats of S1 domain in the S1 domain-containing proteins depends on the taxonomic affiliation. All archaeal proteins contain one copy of the S1 domain, while the number of repeats in the eukaryotic proteins varies between 1 and 15 and correlates with the protein size. In the bacterial proteins, the number of repeats is no more than 6, regardless of the protein size. The large variation of the repeat number of S1 domain as one of the structural variants of the OB-fold is a distinctive feature of S1 domain-containing proteins. Proteins from the other families and superfamilies have either one OB-fold or change slightly the repeat numbers. On the whole, it can be supposed that the repeat number is a vital for multifunctional activity of the S1 domain-containing proteins. Proteins 2017; 85:602-613. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Finite-Difference Time-Domain Analysis of Tapered Photonic Crystal Fiber

NASA Astrophysics Data System (ADS)

Ali, M. I. Md; Sanusidin, S. N.; Yusof, M. H. M.

2018-03-01

This paper brief about the simulation of tapered photonic crystal fiber (PCF) LMA-8 single-mode type based on correlation of scattering pattern at wavelength of 1.55 μm, analyzation of transmission spectrum at wavelength over the range of 1.0 until 2.5 μm and correlation of transmission spectrum with the refractive index change in photonic crystal holes with respect to taper size of 0.1 until 1.0 using Optiwave simulation software. The main objective is to simulate using Finite-Difference Time-Domain (FDTD) technique of tapered LMA-8 PCF and for sensing application by improving the capabilities of PCF without collapsing the crystal holes. The types of FDTD techniques used are scattering pattern and transverse transmission and principal component analysis (PCA) used as a mathematical tool to model the data obtained by MathCad software. The simulation results showed that there is no obvious correlation of scattering pattern at a wavelength of 1.55 μm, a correlation obtained between taper sizes with a transverse transmission and there is a parabolic relationship between the refractive index changes inside the crystal structure.

Source Reconstruction of Brain Potentials Using Bayesian Model Averaging to Analyze Face Intra-Domain vs. Face-Occupation Cross-Domain Processing.

PubMed

Olivares, Ela I; Lage-Castellanos, Agustín; Bobes, María A; Iglesias, Jaime

2018-01-01

We investigated the neural correlates of the access to and retrieval of face structure information in contrast to those concerning the access to and retrieval of person-related verbal information, triggered by faces. We experimentally induced stimulus familiarity via a systematic learning procedure including faces with and without associated verbal information. Then, we recorded event-related potentials (ERPs) in both intra-domain (face-feature) and cross-domain (face-occupation) matching tasks while N400-like responses were elicited by incorrect eyes-eyebrows completions and occupations, respectively. A novel Bayesian source reconstruction approach plus conjunction analysis of group effects revealed that in both cases the generated N170s were of similar amplitude but had different neural origin. Thus, whereas the N170 of faces was associated predominantly to right fusiform and occipital regions (the so-called "Fusiform Face Area", "FFA" and "Occipital Face Area", "OFA", respectively), the N170 of occupations was associated to a bilateral very posterior activity, suggestive of basic perceptual processes. Importantly, the right-sided perceptual P200 and the face-related N250 were evoked exclusively in the intra-domain task, with sources in OFA and extensively in the fusiform region, respectively. Regarding later latencies, the intra-domain N400 seemed to be generated in right posterior brain regions encompassing mainly OFA and, to some extent, the FFA, likely reflecting neural operations triggered by structural incongruities. In turn, the cross-domain N400 was related to more anterior left-sided fusiform and temporal inferior sources, paralleling those described previously for the classic verbal N400. These results support the existence of differentiated neural streams for face structure and person-related verbal processing triggered by faces, which can be activated differentially according to specific task demands.

Correlation of electron backscatter diffraction and piezoresponse force microscopy for the nanoscale characterization of ferroelectric domains in polycrystalline lead zirconate titanate

NASA Astrophysics Data System (ADS)

Burnett, T. L.; Weaver, P. M.; Blackburn, J. F.; Stewart, M.; Cain, M. G.

2010-08-01

The functional properties of ferroelectric ceramic bulk or thin film materials are strongly influenced by their nanostructure, crystallographic orientation, and structural geometry. In this paper, we show how, by combining textural analysis, through electron backscattered diffraction, with piezoresponse force microscopy, quantitative measurements of the piezoelectric properties can be made at a scale of 25 nm, smaller than the domain size. The combined technique is used to obtain data on the domain-resolved effective single crystal piezoelectric response of individual crystallites in Pb(Zr0.4Ti0.6)O3 ceramics. The results offer insight into the science of domain engineering and provide a tool for the future development of new nanostructured ferroelectric materials for memory, nanoactuators, and sensors based on magnetoelectric multiferroics.

Testing the factor structure of the Family Quality of Life Survey - 2006.

PubMed

Isaacs, B; Wang, M; Samuel, P; Ajuwon, P; Baum, N; Edwards, M; Rillotta, F

2012-01-01

Although the Family Quality of Life Survey - 2006 (FQOLS-2006) is being used in research, there is little evidence to support its hypothesised domain structure. The purpose of this study was to test the domain structure of the survey using confirmatory factor analysis. Samples from Australia, Canada, Nigeria and the USA were analysed using structural equation modelling. The data from Australia, Canada and the USA were combined on the assumption that these countries are similar, at least to some degree, in economic development, language and culture. The Nigerian data were analysed on its own. The analysis was undertaken in two phases. First, the hypothesis that each of nine domains of the FQOLS-2006 is a unidimensional construct that can reliably measure the dimensions Importance, Stability, Opportunities, Attainment, Stability and Satisfaction was tested. Second, the hypothesis that family quality of life (FQoL) is a single latent construct represented by the nine domains measured in the FQOLS-2006 was tested. In the first phase of the analysis, the Importance dimension was dropped because of skewness and lack of variance. The Stability dimension did not fit well within the individual domain model in both the Nigerian and the combined three countries' data. When Importance and Stability were excluded, the individual domain models showede good or acceptable fit when error variances of some dimensions were allowed to correlate. In the second phase of the analysis, the overall model, FQoL, represented by the nine domains of the FQOLS-2006 showed good fit in both data sets. The conceptual model of the FQOLS-2006 was supported with some qualifications. Each domain on the survey can be reliably measured by four dimensions Opportunities, Initiative, Attainment and Satisfaction. The dimensions of Importance and Stability, however, did not fit. Data reported on these dimensions from past and current studies should be interpreted with caution. The construct of FQoL is also reliably measured by the domains of the FQOLS-2006. Further research into the psychometric properties of the survey, particularly from a cross-cultural perspective, is needed. © 2011 The Authors. Journal of Intellectual Disability Research © 2011 Blackwell Publishing Ltd.

Mathematical correlation of modal-parameter-identification methods via system-realization theory

NASA Technical Reports Server (NTRS)

Juang, Jer-Nan

1987-01-01

A unified approach is introduced using system-realization theory to derive and correlate modal-parameter-identification methods for flexible structures. Several different time-domain methods are analyzed and treated. A basic mathematical foundation is presented which provides insight into the field of modal-parameter identification for comparison and evaluation. The relation among various existing methods is established and discussed. This report serves as a starting point to stimulate additional research toward the unification of the many possible approaches for modal-parameter identification.

Both Epistasis and Diversifying Selection Drive the Structural Evolution of the Ebola Virus Glycoprotein Mucin-Like Domain.

PubMed

Ibeh, Neke; Nshogozabahizi, Jean Claude; Aris-Brosou, Stéphane

2016-06-01

Throughout the last 3 decades, Ebola virus (EBOV) outbreaks have been confined to isolated areas within Central Africa; however, the 2014 variant reached unprecedented transmission and mortality rates. While the outbreak was still under way, it was reported that the variant leading up to this outbreak evolved faster than previous EBOV variants, but evidence for diversifying selection was undetermined. Here, we test this selection hypothesis and show that while previous EBOV outbreaks were preceded by bursts of diversification, evidence for site-specific diversifying selection during the emergence of the 2014 EBOV clade is weak. However, we show strong evidence supporting an interplay between selection and correlated evolution (epistasis), particularly in the mucin-like domain (MLD) of the EBOV glycoprotein. By reconstructing ancestral structures of the MLD, we further propose a structural mechanism explaining how the substitutions that accumulated between 1918 and 1969 distorted the MLD, while more recent epistatic substitutions restored part of the structure, with the most recent substitution being adaptive. We suggest that it is this complex interplay between weak selection, epistasis, and structural constraints that has shaped the evolution of the 2014 EBOV variant. The role that selection plays in the emergence of viral epidemics remains debated, particularly in the context of the 2014 EBOV outbreak. Most critically, should such evidence exist, it is generally unclear how this relates to function and increased virulence. Here, we show that the viral lineage leading up to the 2014 outbreak underwent a complex interplay between selection and correlated evolution (epistasis) in a protein region that is critical for immune evasion. We then reconstructed the three-dimensional structure of this domain and showed that the initial mutations in this lineage deformed the structure, while subsequent mutations restored part of the structure. Along this mutational path, the first and last mutations were adaptive, while the intervening ones were epistatic. Altogether, we provide a mechanistic model that explains how selection and epistasis acted on the structural constraints that materialized during the 2014 EBOV outbreak. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

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

PubMed

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

2017-01-01

The U-MICS is a self-report questionnaire designed to assess the identity dimensions from a domain-specific perspective. The present study reports on the development of a short-form version for the domains of job and romantic relationship in young adults from Germany and extends this scale to include the domain of region (n Sample1  = 95, 84% female, mean age 22.45 years; n Sample2  = 1,795, 71% female, mean age 24.53 years). We found the short form to possess adequate psychometric properties and to demonstrate a factor structure congruent to the long-form version. Regarding validity, the small correlations across domains within dimensions support a domain-specific approach to identity. The associations between the different identity domains with personality traits are similar, indicating a consistent pattern of convergent validity for all domains. We conclude that "region" provides a valuable complement to the established domains that can all be reliably assessed with the U-MICS-Short Form. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Psychometric properties of the Chinese version of the Menopause-Specific Quality-of-Life questionnaire

PubMed Central

Nie, Guangning; Yang, Hongyan; Liu, Jian; Zhao, ChunMei; Wang, Xiaoyun

2017-01-01

Abstract Objective: The Menopause-Specific Quality-of-Life (MENQOL) questionnaire was developed as a specific tool to measure the health-related quality-of-life of postmenopausal women. Thus far, the Chinese version questionnaire has not been subjected to psychometric assessment with a large sample. This study aims to evaluate the validity and reliability of the Chinese version of the MENQOL specific to postmenopausal women in China. Methods: A total of 1,137 menopausal symptomatic and 491 menopausal asymptomatic women from eight cities in China were recruited using a convenience sampling method. Psychometric properties were evaluated by descriptive statistics, validity, and reliability. Reliability was assessed for each subscale of the MENQOL through internal consistency reliability with Cronbach's α and intersubscale correlations. Item-domain correlations, principal components analysis (PCA), and confirmatory factor analysis were performed to determine construct validity. t tests were used to compare the differences between the menopausal symptomatic and asymptomatic women and to evaluate the discriminate validity. Pearson correlation coefficients were calculated between MENQOL scores and the Kupperman index to assess criterion-related validity. Results: The most common symptoms in Chinese menopausal symptomatic women were “experiencing poor memory” (94.4%), “feeling tired or worn out” (93.8%), “aching in muscle and joints” (89.4%), “low backache” (86.9%), “decrease in physical strength” (86.6%), “aches in back of neck or head” (86.2%), “difficulty sleeping” (83.6%), “accomplishing less than I used to” (83.4%), “feeling a lack of energy” (83.3%), “change in your sexual desire” (81%), and “hot flash” (80.7%) among others. The symptoms of “increased facial hair” were rarely seen (9.9%). The vasomotor domain, as well as psychosocial, physical, and sexual domains showed high reliability (Cronbach's α 0.84, 0.87, 0.89, and 0.86, respectively). Item-domain correlation analysis showed that all items correlated more strongly with their own domains than with other domains. In the PCA, after deleting the “increased facial hair” item, items in the vasomotor, sexual, and psychosocial subscales loaded on their respective domains by and large, and items in the physical subscale divided into two factors. The PCA revealed a latent structure of the Chinese version of MENQOL nearly identical to the original MENQOL domains. The confirmatory factor analysis demonstrated that the questionnaire fits well with a four-domain model. The MENQOL can discriminate between menopausal symptomatic women with asymptomatic women as it showed good discriminate validity. Criterion-related validity was confirmed by a significant correlation between MENQOL scores and the Kupperman index. Conclusions: This study showed that Chinese version of MENQOL has good psychometric properties and would be suitable to measure the health-related quality-of-life of Chinese menopausal women except for item 21 (increased facial hair). PMID:27922934

The isolated voltage sensing domain of the Shaker potassium channel forms a voltage-gated cation channel

PubMed Central

Zhao, Juan; Blunck, Rikard

2016-01-01

Domains in macromolecular complexes are often considered structurally and functionally conserved while energetically coupled to each other. In the modular voltage-gated ion channels the central ion-conducting pore is surrounded by four voltage sensing domains (VSDs). Here, the energetic coupling is mediated by interactions between the S4-S5 linker, covalently linking the domains, and the proximal C-terminus. In order to characterize the intrinsic gating of the voltage sensing domain in the absence of the pore domain, the Shaker Kv channel was truncated after the fourth transmembrane helix S4 (Shaker-iVSD). Shaker-iVSD showed significantly altered gating kinetics and formed a cation-selective ion channel with a strong preference for protons. Ion conduction in Shaker-iVSD developed despite identical primary sequence, indicating an allosteric influence of the pore domain. Shaker-iVSD also displays pronounced 'relaxation'. Closing of the pore correlates with entry into relaxation suggesting that the two processes are energetically related. DOI: http://dx.doi.org/10.7554/eLife.18130.001 PMID:27710769

Bilingualism tunes the anterior cingulate cortex for conflict monitoring.

PubMed

Abutalebi, Jubin; Della Rosa, Pasquale Anthony; Green, David W; Hernandez, Mireia; Scifo, Paola; Keim, Roland; Cappa, Stefano F; Costa, Albert

2012-09-01

Monitoring and controlling 2 language systems is fundamental to language use in bilinguals. Here, we reveal in a combined functional (event-related functional magnetic resonance imaging) and structural neuroimaging (voxel-based morphometry) study that dorsal anterior cingulate cortex (ACC), a structure tightly bound to domain-general executive control functions, is a common locus for language control and resolving nonverbal conflict. We also show an experience-dependent effect in the same region: Bilinguals use this structure more efficiently than monolinguals to monitor nonlinguistic cognitive conflicts. They adapted better to conflicting situations showing less ACC activity while outperforming monolinguals. Importantly, for bilinguals, brain activity in the ACC, as well as behavioral measures, also correlated positively with local gray matter volume. These results suggest that early learning and lifelong practice of 2 languages exert a strong impact upon human neocortical development. The bilingual brain adapts better to resolve cognitive conflicts in domain-general cognitive tasks.

Time domain simulation of novel photovoltaic materials

NASA Astrophysics Data System (ADS)

Chung, Haejun

Thin-film silicon-based solar cells have operated far from the Shockley- Queisser limit in all experiments to date. Novel light-trapping structures, however, may help address this limitation. Finite-difference time domain simulation methods offer the potential to accurately determine the light-trapping potential of arbitrary dielectric structures, but suffer from materials modeling problems. In this thesis, existing dispersion models for novel photovoltaic materials will be reviewed, and a novel dispersion model, known as the quadratic complex rational function (QCRF), will be proposed. It has the advantage of accurately fitting experimental semiconductor dielectric values over a wide bandwidth in a numerically stable fashion. Applying the proposed dispersion model, a statistically correlated surface texturing method will be suggested, and light absorption rates of it will be explained. In future work, these designs will be combined with other structures and optimized to help guide future experiments.

The structural coupling between ATPase activation and recovery stroke in the myosin II motor

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

Koppole, Sampath; Smith, Jeremy C; Fischer, S.

2007-07-01

Before the myosin motor head can perform the next power stroke, it undergoes a large conformational transition in which the converter domain, bearing the lever arm, rotates {approx} 65{sup o}. Simultaneous with this 'recovery stroke', myosin activates its ATPase function by closing the Switch-2 loop over the bound ATP. This coupling between the motions of the converter domain and of the 40 {angstrom}-distant Switch-2 loop is essential to avoid unproductive ATP hydrolysis. The coupling mechanism is determined here by finding a series of optimized intermediates between crystallographic end structures of the recovery stroke (Dictyostelium discoideum), yielding movies of the transitionmore » at atomic detail. The successive formation of two hydrogen bonds by the Switch-2 loop is correlated with the successive see-saw motions of the relay and SH1 helices that hold the converter domain. SH1 helix and Switch-2 loop communicate via a highly conserved loop that wedges against the SH1-helix upon Switch-2 closing.« less

The structural coupling between ATPase activation and recovery stroke in the myosin II motor.

PubMed

Koppole, Sampath; Smith, Jeremy C; Fischer, Stefan

2007-07-01

Before the myosin motor head can perform the next power stroke, it undergoes a large conformational transition in which the converter domain, bearing the lever arm, rotates approximately 65 degrees . Simultaneous with this "recovery stroke," myosin activates its ATPase function by closing the Switch-2 loop over the bound ATP. This coupling between the motions of the converter domain and of the 40 A-distant Switch-2 loop is essential to avoid unproductive ATP hydrolysis. The coupling mechanism is determined here by finding a series of optimized intermediates between crystallographic end structures of the recovery stroke (Dictyostelium discoideum), yielding movies of the transition at atomic detail. The successive formation of two hydrogen bonds by the Switch-2 loop is correlated with the successive see-saw motions of the relay and SH1 helices that hold the converter domain. SH1 helix and Switch-2 loop communicate via a highly conserved loop that wedges against the SH1-helix upon Switch-2 closing.

Structure of highly asymmetric hard-sphere mixtures: an efficient closure of the Ornstein-Zernike equations.

PubMed

Amokrane, S; Ayadim, A; Malherbe, J G

2005-11-01

A simple modification of the reference hypernetted chain (RHNC) closure of the multicomponent Ornstein-Zernike equations with bridge functions taken from Rosenfeld's hard-sphere bridge functional is proposed. Its main effect is to remedy the major limitation of the RHNC closure in the case of highly asymmetric mixtures--the wide domain of packing fractions in which it has no solution. The modified closure is also much faster, while being of similar complexity. This is achieved with a limited loss of accuracy, mainly for the contact value of the big sphere correlation functions. Comparison with simulation shows that inside the RHNC no-solution domain, it provides a good description of the structure, while being clearly superior to all the other closures used so far to study highly asymmetric mixtures. The generic nature of this closure and its good accuracy combined with a reduced no-solution domain open up the possibility to study the phase diagram of complex fluids beyond the hard-sphere model.

Functional rotation induced by alternating protonation states in the multidrug transporter AcrB: all-atom molecular dynamics simulations.

PubMed

Yamane, Tsutomu; Murakami, Satoshi; Ikeguchi, Mitsunori

2013-10-29

The multidrug transporter AcrB actively exports a wide variety of noxious compounds using proton-motive force as an energy source in Gram-negative bacteria. AcrB adopts an asymmetric structure comprising three protomers with different conformations that are sequentially converted during drug export; these cyclic conformational changes during drug export are referred to as functional rotation. To investigate functional rotation driven by proton-motive force, all-atom molecular dynamics simulations were performed. Using different protonation states for the titratable residues in the middle of the transmembrane domain, our simulations revealed the correlation between the specific protonation states and the side-chain configurations. Changing the protonation state for Asp408 induced a spontaneous structural transition, which suggests that the proton translocation stoichiometry may be one proton per functional rotation cycle. Furthermore, our simulations demonstrate that alternating the protonation states in the transmembrane domain induces functional rotation in the porter domain, which is primarily responsible for drug transport.

Conformational dynamics and ligand binding in the multi-domain protein PDC109.

PubMed

Kim, Hyun Jin; Choi, Moo Young; Kim, Hyung J; Llinás, Miguel

2010-02-18

PDC109 is a modular multi-domain protein with two fibronectin type II (Fn2) repeats joined by a linker. It plays a major role in bull sperm binding to the oviductal epithelium through its interactions with phosphorylcholines (PhCs), a head group of sperm cell membrane lipids. The crystal structure of the PDC109-PhC complex shows that each PhC binds to the corresponding Fn2 domain, while the two domains are on the same face of the protein. Long timescale explicit solvent molecular dynamics (MD) simulations of PDC109, in the presence and absence of PhC, suggest that PhC binding strongly correlates with the relative orientation of choline-phospholipid binding sites of the two Fn2 domains; unless the two domains tightly bind PhCs, they tend to change their relative orientation by deforming the flexible linker. The effective PDC109-PhC association constant of 28 M(-1), estimated from their potential of mean force is consistent with the experimental result. Principal component analysis of the long timescale MD simulations was compared to the significantly less expensive normal mode analysis of minimized structures. The comparison indicates that difference between relative domain motions of PDC109 with bound and unbound PhC is captured by the first principal component in the principal component analysis as well as the three lowest normal modes in the normal mode analysis. The present study illustrates the use of detailed MD simulations to clarify the energetics of specific ligand-domain interactions revealed by a static crystallographic model, as well as their influence on relative domain motions in a multi-domain protein.

Uranium nitride: a cubic antiferromagnet with anisotropic critical behavior

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

Buyers, W J.L.; Holden, T M; Svensson, E C

1977-11-01

Highly anisotropic critical scattering associated with the transition at T/sub N/ = 49.5 K to the type-I antiferromagnetic structure has been observed in uranium nitride. The transverse susceptibility is found to be unobservably small. The longitudinal susceptibility diverges at T/sub N/ and its anisotropy shows that the spins within the (001) ferromagnetic sheets of the (001) domain are much more highly correlated than they are with the spins lying in adjacent (001) sheets. The correlation range within the sheets is much greater than that expected for a Heisenberg system with the same T/sub N/. The rod-like scattering extended along themore » spin and domain direction is reminiscent of two-dimensional behavior. The results are inconsistent with a simple localized model and may reflect the itinerant nature of the 5f electrons.« less

Ternary blend polymer solar cells with self-assembled structure for enhancing power conversion efficiency

NASA Astrophysics Data System (ADS)

Yang, Zhenhua; Li, Hongfei; Nam, Chang-Yong; Kisslinger, Kim; Satija, Sushil; Rafailovich, Miriam

Bulk heterojunction (BHJ) polymer solar cells are an area of intense interest due to their advantages such as mechanical flexibility. The active layer is typically spin coated from the solution of polythiophene derivatives (donor) and fullerenes (acceptor) and interconnected domains are formed because of phase separation. However, the power conversion efficiency (PCE) of BHJ solar cell is restricted by the disordered inner structures in the active layer, donor or acceptor domains isolated from electrodes. Here we report a self-assembled columnar structure formed by phase separation between (PCDTBT) and polystyrene (PS) for the active layer morphology optimization. The BHJ solar cell device based on this structure is promising for exhibiting higher performance due to the shorter carrier transportation pathway and larger interfacial area between donor and acceptor. The surface morphology is investigated with atomic force microscopy (AFM) and the columnar structure is studied by investigation of cross-section of the blend thin film of PCDTBT and PS under the transmission electron microscopy (TEM). The different morphological structures formed via phase segregation are correlated with the performance of the BHJ solar cells.

Structural Basis for Iloprost as a Dual Peroxisome Proliferator-activated Receptor [alpha/delta] Agonist

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

Jin, Lihua; Lin, Shengchen; Rong, Hui

2012-03-15

Iloprost is a prostacyclin analog that has been used to treat many vascular conditions. Peroxisome proliferator-activated receptors (PPARs) are ligand-regulated transcription factors with various important biological effects such as metabolic and cardiovascular physiology. Here, we report the crystal structures of the PPAR{alpha} ligand-binding domain and PPAR{delta} ligand-binding domain bound to iloprost, thus providing unambiguous evidence for the direct interaction between iloprost and PPARs and a structural basis for the recognition of PPAR{alpha}/{delta} by this prostacyclin analog. In addition to conserved contacts for all PPAR{alpha} ligands, iloprost also initiates several specific interactions with PPARs using its unique structural groups. Structural andmore » functional studies of receptor-ligand interactions reveal strong functional correlations of the iloprost-PPAR{alpha}/{delta} interactions as well as the molecular basis of PPAR subtype selectivity toward iloprost ligand. As such, the structural mechanism may provide a more rational template for designing novel compounds targeting PPARs with more favorable pharmacologic impact based on existing iloprost drugs.« less

Three-Axis Distributed Fiber Optic Strain Measurement in 3D Woven Composite Structures

NASA Technical Reports Server (NTRS)

Castellucci, Matt; Klute, Sandra; Lally, Evan M.; Froggatt, Mark E.; Lowry, David

2013-01-01

Recent advancements in composite materials technologies have broken further from traditional designs and require advanced instrumentation and analysis capabilities. Success or failure is highly dependent on design analysis and manufacturing processes. By monitoring smart structures throughout manufacturing and service life, residual and operational stresses can be assessed and structural integrity maintained. Composite smart structures can be manufactured by integrating fiber optic sensors into existing composite materials processes such as ply layup, filament winding and three-dimensional weaving. In this work optical fiber was integrated into 3D woven composite parts at a commercial woven products manufacturing facility. The fiber was then used to monitor the structures during a VARTM manufacturing process, and subsequent static and dynamic testing. Low cost telecommunications-grade optical fiber acts as the sensor using a high resolution commercial Optical Frequency Domain Reflectometer (OFDR) system providing distributed strain measurement at spatial resolutions as low as 2mm. Strain measurements using the optical fiber sensors are correlated to resistive strain gage measurements during static structural loading. Keywords: fiber optic, distributed strain sensing, Rayleigh scatter, optical frequency domain reflectometry

Predicting chromatin architecture from models of polymer physics.

PubMed

Bianco, Simona; Chiariello, Andrea M; Annunziatella, Carlo; Esposito, Andrea; Nicodemi, Mario

2017-03-01

We review the picture of chromatin large-scale 3D organization emerging from the analysis of Hi-C data and polymer modeling. In higher mammals, Hi-C contact maps reveal a complex higher-order organization, extending from the sub-Mb to chromosomal scales, hierarchically folded in a structure of domains-within-domains (metaTADs). The domain folding hierarchy is partially conserved throughout differentiation, and deeply correlated to epigenomic features. Rearrangements in the metaTAD topology relate to gene expression modifications: in particular, in neuronal differentiation models, topologically associated domains (TADs) tend to have coherent expression changes within architecturally conserved metaTAD niches. To identify the nature of architectural domains and their molecular determinants within a principled approach, we discuss models based on polymer physics. We show that basic concepts of interacting polymer physics explain chromatin spatial organization across chromosomal scales and cell types. The 3D structure of genomic loci can be derived with high accuracy and its molecular determinants identified by crossing information with epigenomic databases. In particular, we illustrate the case of the Sox9 locus, linked to human congenital disorders. The model in-silico predictions on the effects of genomic rearrangements are confirmed by available 5C data. That can help establishing new diagnostic tools for diseases linked to chromatin mis-folding, such as congenital disorders and cancer.

Multivariate statistical characterization of charged and uncharged domain walls in multiferroic hexagonal YMnO3 single crystal visualized by a spherical aberration-corrected STEM.

PubMed

Matsumoto, Takao; Ishikawa, Ryo; Tohei, Tetsuya; Kimura, Hideo; Yao, Qiwen; Zhao, Hongyang; Wang, Xiaolin; Chen, Dapeng; Cheng, Zhenxiang; Shibata, Naoya; Ikuhara, Yuichi

2013-10-09

A state-of-the-art spherical aberration-corrected STEM was fully utilized to directly visualize the multiferroic domain structure in a hexagonal YMnO3 single crystal at atomic scale. With the aid of multivariate statistical analysis (MSA), we obtained unbiased and quantitative maps of ferroelectric domain structures with atomic resolution. Such a statistical image analysis of the transition region between opposite polarizations has confirmed atomically sharp transitions of ferroelectric polarization both in antiparallel (uncharged) and tail-to-tail 180° (charged) domain boundaries. Through the analysis, a correlated subatomic image shift of Mn-O layers with that of Y layers, exhibiting a double-arc shape of reversed curvatures, have been elucidated. The amount of image shift in Mn-O layers along the c-axis is statistically significant as small as 0.016 nm, roughly one-third of the evident image shift of 0.048 nm in Y layers. Interestingly, a careful analysis has shown that such a subatomic image shift in Mn-O layers vanishes at the tail-to-tail 180° domain boundaries. Furthermore, taking advantage of the annular bright field (ABF) imaging technique combined with MSA, the tilting of MnO5 bipyramids, the very core mechanism of multiferroicity of the material, is evaluated.

Estimating free-body modal parameters from tests of a constrained structure

NASA Technical Reports Server (NTRS)

Cooley, Victor M.

1993-01-01

Hardware advances in suspension technology for ground tests of large space structures provide near on-orbit boundary conditions for modal testing. Further advances in determining free-body modal properties of constrained large space structures have been made, on the analysis side, by using time domain parameter estimation and perturbing the stiffness of the constraints over multiple sub-tests. In this manner, passive suspension constraint forces, which are fully correlated and therefore not usable for spectral averaging techniques, are made effectively uncorrelated. The technique is demonstrated with simulated test data.

Gravity anomalies, plate tectonics and the lateral growth of Precambrian North America

NASA Technical Reports Server (NTRS)

Thomas, M. D.; Grieve, R. A. F.; Sharpton, V. L.

1988-01-01

The widespread gravity coverage of North America provides a picture of the gross structural fabric of the continent via the trends of gravity anomalies. The structural picture so obtained reveals a mosaic of gravity trend domains, many of which correlate closely with structural provinces and orogenic terranes. The gravity trend map, interpreted in the light of plate-tectonic theory, thus provides a new perspective for examining the mode of assembly and growth of North America. Suture zones, palaeosubduction directions, and perhaps, contrasting tectonic histories may be identified using gravity patterns.

The RDoC initiative and the structure of psychopathology.

PubMed

Krueger, Robert F; DeYoung, Colin G

2016-03-01

The NIMH Research Domain Criteria (RDoC) project represents a welcome effort to circumvent the limitations of psychiatric categories as phenotypes for psychopathology research. Here, we describe the hierarchical and dimensional structure of phenotypic psychopathology and illustrate how this structure provides phenotypes suitable for RDoC research on neural correlates of psychopathology. A hierarchical and dimensional approach to psychopathology phenotypes holds great promise for delineating connections between neuroscience constructs and the patterns of affect, cognition, and behavior that constitute manifest psychopathology. © 2016 Society for Psychophysiological Research.

Translation and validation of the Rhinosinusitis Disability Index for use in Nigeria.

PubMed

Asoegwu, C N; Nwawolo, C C; Okubadejo, N U

2017-07-01

The Rhinosinusitis Disability Index (RSDI) is a validated and reliable measure of severity of chronic rhinosinusitis. The objective of this study was to translate and validate the instrument for use in Nigeria. This is a methodological study. 71 patients with chronic rhinosinusitis attending two Otolaryngology clinics in Lagos, Nigeria. Using standardized methods and trained translators, the RSDI was translated to vernacular (Yoruba language) and back-translated to culturally appropriate English. Data analysis comprised of assessment of the item quality, content validity and internal consistency of the back-translated Rhinosinusitis Disability Index (bRSDI), and correlation to the original RSDI. Content validity (floor and ceiling effects) showed 0% floor and ceiling effects for the total scores, 0% ceiling effects for all domains and floor effect for physical domain, and 9.9 and 8.5% floor effects for functional and emotional domains, respectively. The mean item-own correlation for physical domain was 0.54 ± 0.08, 0.72 ± 0.08 for functional domain and 0.74 ± 0.07 for emotional domain. All domain item-own correlations were higher than item-other domain correlations. The total Cronbach's alpha was 0.936 and was higher than 0.70 for all the domains representing good internal consistency. Pearson correlation analysis showed strong correlation of RSDI to bRSDI (total score 0.881; p = 0.000, and domain subscores-physical: 0.788; p = 0.000, functional: 0.830; p = 0.000, and emotional: 0.888; p = 0.000). The back-translated Rhinosinusitis Disability Index shows good face and content validity with good internal consistency while correlating linearly and significantly with the original Rhinosinusitis Disability Index and is recommended for use in Nigeria.

Can Retinal Ganglion Cell Dipoles Seed Iso-Orientation Domains in the Visual Cortex?

PubMed Central

Schottdorf, Manuel; Eglen, Stephen J.; Wolf, Fred; Keil, Wolfgang

2014-01-01

It has been argued that the emergence of roughly periodic orientation preference maps (OPMs) in the primary visual cortex (V1) of carnivores and primates can be explained by a so-called statistical connectivity model. This model assumes that input to V1 neurons is dominated by feed-forward projections originating from a small set of retinal ganglion cells (RGCs). The typical spacing between adjacent cortical orientation columns preferring the same orientation then arises via Moiré-Interference between hexagonal ON/OFF RGC mosaics. While this Moiré-Interference critically depends on long-range hexagonal order within the RGC mosaics, a recent statistical analysis of RGC receptive field positions found no evidence for such long-range positional order. Hexagonal order may be only one of several ways to obtain spatially repetitive OPMs in the statistical connectivity model. Here, we investigate a more general requirement on the spatial structure of RGC mosaics that can seed the emergence of spatially repetitive cortical OPMs, namely that angular correlations between so-called RGC dipoles exhibit a spatial structure similar to that of OPM autocorrelation functions. Both in cat beta cell mosaics as well as primate parasol receptive field mosaics we find that RGC dipole angles are spatially uncorrelated. To help assess the level of these correlations, we introduce a novel point process that generates mosaics with realistic nearest neighbor statistics and a tunable degree of spatial correlations of dipole angles. Using this process, we show that given the size of available data sets, the presence of even weak angular correlations in the data is very unlikely. We conclude that the layout of ON/OFF ganglion cell mosaics lacks the spatial structure necessary to seed iso-orientation domains in the primary visual cortex. PMID:24475081

Can retinal ganglion cell dipoles seed iso-orientation domains in the visual cortex?

PubMed

Schottdorf, Manuel; Eglen, Stephen J; Wolf, Fred; Keil, Wolfgang

2014-01-01

It has been argued that the emergence of roughly periodic orientation preference maps (OPMs) in the primary visual cortex (V1) of carnivores and primates can be explained by a so-called statistical connectivity model. This model assumes that input to V1 neurons is dominated by feed-forward projections originating from a small set of retinal ganglion cells (RGCs). The typical spacing between adjacent cortical orientation columns preferring the same orientation then arises via Moiré-Interference between hexagonal ON/OFF RGC mosaics. While this Moiré-Interference critically depends on long-range hexagonal order within the RGC mosaics, a recent statistical analysis of RGC receptive field positions found no evidence for such long-range positional order. Hexagonal order may be only one of several ways to obtain spatially repetitive OPMs in the statistical connectivity model. Here, we investigate a more general requirement on the spatial structure of RGC mosaics that can seed the emergence of spatially repetitive cortical OPMs, namely that angular correlations between so-called RGC dipoles exhibit a spatial structure similar to that of OPM autocorrelation functions. Both in cat beta cell mosaics as well as primate parasol receptive field mosaics we find that RGC dipole angles are spatially uncorrelated. To help assess the level of these correlations, we introduce a novel point process that generates mosaics with realistic nearest neighbor statistics and a tunable degree of spatial correlations of dipole angles. Using this process, we show that given the size of available data sets, the presence of even weak angular correlations in the data is very unlikely. We conclude that the layout of ON/OFF ganglion cell mosaics lacks the spatial structure necessary to seed iso-orientation domains in the primary visual cortex.

Simultaneous prediction of binding free energy and specificity for PDZ domain-peptide interactions

NASA Astrophysics Data System (ADS)

Crivelli, Joseph J.; Lemmon, Gordon; Kaufmann, Kristian W.; Meiler, Jens

2013-12-01

Interactions between protein domains and linear peptides underlie many biological processes. Among these interactions, the recognition of C-terminal peptides by PDZ domains is one of the most ubiquitous. In this work, we present a mathematical model for PDZ domain-peptide interactions capable of predicting both affinity and specificity of binding based on X-ray crystal structures and comparative modeling with R osetta. We developed our mathematical model using a large phage display dataset describing binding specificity for a wild type PDZ domain and 91 single mutants, as well as binding affinity data for a wild type PDZ domain binding to 28 different peptides. Structural refinement was carried out through several R osetta protocols, the most accurate of which included flexible peptide docking and several iterations of side chain repacking and backbone minimization. Our findings emphasize the importance of backbone flexibility and the energetic contributions of side chain-side chain hydrogen bonds in accurately predicting interactions. We also determined that predicting PDZ domain-peptide interactions became increasingly challenging as the length of the peptide increased in the N-terminal direction. In the training dataset, predicted binding energies correlated with those derived through calorimetry and specificity switches introduced through single mutations at interface positions were recapitulated. In independent tests, our best performing protocol was capable of predicting dissociation constants well within one order of magnitude of the experimental values and specificity profiles at the level of accuracy of previous studies. To our knowledge, this approach represents the first integrated protocol for predicting both affinity and specificity for PDZ domain-peptide interactions.

Cross-cultural adaptation of the korean version of the minneapolis-manchester quality of life instrument-adolescent form.

PubMed

Park, Hyeon Jin; Yang, Hyung Kook; Shin, Dong Wook; Kim, Yoon Yi; Kim, Young Ae; Yun, Young Ho; Nam, Byung Ho; Bhatia, Smita; Park, Byung Kiu; Ghim, Thad T; Kang, Hyoung Jin; Park, Kyung Duk; Shin, Hee Young; Ahn, Hyo Seop

2013-12-01

We verified the reliability and validity of the Korean version of the Minneapolis-Manchester Quality of Life Instrument-Adolescent Form (KMMQL-AF) among Korean childhood cancer survivors. A total of 107 childhood cancer patients undergoing cancer treatment and 98 childhood cancer survivors who completed cancer treatment were recruited. To assess the internal structure of the KMMQL-AF, we performed multi-trait scaling analyses and exploratory factor analysis. Additionally, we compared each domains of the KMMQL-AF with those of the Karnofsky Performance Status Scale and the Revised Children's Manifest Anxiety Scale (RCMAS). Internal consistency of the KMMQL-AF was sufficient (Cronbach's alpha: 0.78-0.92). In multi-trait scaling analyses, the KMMQL-AF showed sufficient construct validity. The "physical functioning" domain showed moderate correlation with Karnofsky scores and the "psychological functioning" domain showed moderate-to-high correlation with the RCMAS. The KMMQL-AF discriminated between subgroups of different adolescent cancer survivors depending on treatment completion. The KMMQL-AF is a sufficiently reliable and valid instrument for measuring quality of life among Korean childhood cancer survivors.

Comparison between the Correlations of Retinal Nerve Fiber Layer Thickness Measured by Spectral Domain Optical Coherence Tomography and Visual Field Defects in Standard Automated White-on-White Perimetry versus Pulsar Perimetry

PubMed Central

Hömberg, Lisann; Eter, Nicole

2017-01-01

Purpose To compare the structure-function relationships between retinal nerve fiber layer thickness (RNFLT) and visual field defects measured either by standard automated perimetry (SAP) or by Pulsar perimetry (PP). Materials and Methods 263 eyes of 143 patients were prospectively included. Depending on the RNFLT, patients were assigned to the glaucoma group (group A: RNFL score 3–6) or the control group (group B: RNFL score 0–2). Structure-function relationships between RNFLT and mean sensitivity (MS) measured by SAP and PP were analyzed. Results Throughout the entire group, the MS assessed by PP and SAP correlated significantly with RNFLT in all sectors. In the glaucoma group, there was no significant difference between the correlations RNFL-SAP and RNFL-PP, whereas a significant difference was found in the control group. Conclusions In the control group, the correlation between structure and function based on the PP data was significantly stronger than that based on SAP. PMID:29119021

Structural damage identification using damping: a compendium of uses and features

NASA Astrophysics Data System (ADS)

Cao, M. S.; Sha, G. G.; Gao, Y. F.; Ostachowicz, W.

2017-04-01

The vibration responses of structures under controlled or ambient excitation can be used to detect structural damage by correlating changes in structural dynamic properties extracted from responses with damage. Typical dynamic properties refer to modal parameters: natural frequencies, mode shapes, and damping. Among these parameters, natural frequencies and mode shapes have been investigated extensively for their use in damage characterization by associating damage with reduction in local stiffness of structures. In contrast, the use of damping as a dynamic property to represent structural damage has not been comprehensively elucidated, primarily due to the complexities of damping measurement and analysis. With advances in measurement technologies and analysis tools, the use of damping to identify damage is becoming a focus of increasing attention in the damage detection community. Recently, a number of studies have demonstrated that damping has greater sensitivity for characterizing damage than natural frequencies and mode shapes in various applications, but damping-based damage identification is still a research direction ‘in progress’ and is not yet well resolved. This situation calls for an overall survey of the state-of-the-art and the state-of-the-practice of using damping to detect structural damage. To this end, this study aims to provide a comprehensive survey of uses and features of applying damping in structural damage detection. First, we present various methods for damping estimation in different domains including the time domain, the frequency domain, and the time-frequency domain. Second, we investigate the features and applications of damping-based damage detection methods on the basis of two predominant infrastructure elements, reinforced concrete structures and fiber-reinforced composites. Third, we clarify the influential factors that can impair the capability of damping to characterize damage. Finally, we recommend future research directions for advancing damping-based damage detection. This work holds the promise of (a) helping researchers identify crucial components in damping-based damage detection theories, methods, and technologies, and (b) leading practitioners to better implement damping-based structural damage identification.

Giant Permittivity in Epitaxial Ferroelectric Heterostructures

NASA Astrophysics Data System (ADS)

Erbil, A.; Kim, Y.; Gerhardt, R. A.

1996-08-01

A giant permittivity associated with the motion of domain walls is reported in epitaxial hetero- structures having alternating layers of ferroelectric and nonferroelectric oxides. At low frequencies, permittivities as high as 420 000 are found. Real and imaginary parts of the dielectric constant show large dispersion at high frequencies. In dc measurements, a nonlinear resistance is observed with a well-defined threshold field correlated with the dc bias-field dependence of ac permittivities. We interpret the observations as a result of the motion of a pinned domain wall lattice at low electric fields and sliding-mode motion at high electric fields.

Porous media flux sensitivity to pore-scale geostatistics: A bottom-up approach

NASA Astrophysics Data System (ADS)

Di Palma, P. R.; Guyennon, N.; Heße, F.; Romano, E.

2017-04-01

Macroscopic properties of flow through porous media can be directly computed by solving the Navier-Stokes equations at the scales related to the actual flow processes, while considering the porous structures in an explicit way. The aim of this paper is to investigate the effects of the pore-scale spatial distribution on seepage velocity through numerical simulations of 3D fluid flow performed by the lattice Boltzmann method. To this end, we generate multiple random Gaussian fields whose spatial correlation follows an assigned semi-variogram function. The Exponential and Gaussian semi-variograms are chosen as extreme-cases of correlation for short distances and statistical properties of the resulting porous media (indicator field) are described using the Matèrn covariance model, with characteristic lengths of spatial autocorrelation (pore size) varying from 2% to 13% of the linear domain. To consider the sensitivity of the modeling results to the geostatistical representativeness of the domain as well as to the adopted resolution, porous media have been generated repetitively with re-initialized random seeds and three different resolutions have been tested for each resulting realization. The main difference among results is observed between the two adopted semi-variograms, indicating that the roughness (short distances autocorrelation) is the property mainly affecting the flux. However, computed seepage velocities show additionally a wide variability (about three orders of magnitude) for each semi-variogram model in relation to the assigned correlation length, corresponding to pore sizes. The spatial resolution affects more the results for short correlation lengths (i.e., small pore sizes), resulting in an increasing underestimation of the seepage velocity with the decreasing correlation length. On the other hand, results show an increasing uncertainty as the correlation length approaches the domain size.

The formation of topological defects in phase transitions

NASA Technical Reports Server (NTRS)

Hodges, Hardy M.

1989-01-01

It was argued, and fought through numerical work that the results of non-dynamical Monte Carlo computer simulations cannot be applied to describe the formation of topological defects when the correlation length at the Ginzburg temperature is significantly smaller than the horizon size. To test the current hypothesis that infinite strings at formation are essentially described by Brownian walks of size the correlation length at the Ginzburg temperature, fields at the Ginzburg temperature were equilibrated. Infinite structure do not exist in equilibrium for reasonable definitions of the Ginzburg temperature, and horizons must be included in a proper treatment. A phase transition, from small-scale to large-scale string or domain wall structure, is found to occur very close to the Ginzburg temperature, in agreement with recent work. The formation process of domain walls and global strings were investigated through the breaking of initially ordered states. To mimic conditions in the early Universe, cooling times are chosen so that horizons exist in the sample volume when topological structure formation occurs. The classical fields are evolved in real-time by the numerical solution of Langevin equations of motion on a three dimensional spatial lattice. The results indicate that it is possible for most of the string energy to be in small loops, rather than in long strings, at formation.

Spanwise vorticity and wall normal velocity structure in the inertial region of turbulent boundary layers

NASA Astrophysics Data System (ADS)

Cuevas Bautista, Juan Carlos; Morrill-Winter, Caleb; White, Christopher; Chini, Gregory; Klewicki, Joseph

2017-11-01

The Reynolds shear stress gradient is a leading order mechanism on the inertial domain of turbulent wall-flows. This quantity can be described relative to the sum of two velocity-vorticity correlations, vωz and wωy . Recent studies suggest that the first of these correlates with the step-like structure of the instantaneous streamwise velocity profile on the inertial layer. This structure is comprised of large zones of uniform momentum segregated by slender regions of concentrated vorticity. In this talk we study the contributions of the v and ωz motions to the vorticity transport (vωz) mechanism through the use of experimental data at large friction Reynolds numbers, δ+. The primary contributions to v and ωz were estimated by identifying the peak wavelengths of their streamwise spectra. The magnitudes of these peaks are of the same order, and are shown to exhibit a weak δ+ dependence. The peak wavelengths of v, however, exhibit a strong wall-distance (y) dependence, while the peak wavelengths of ωz show only a weak y dependence, and remain almost O (√{δ+}) in size throughout the inertial domain. This research was partially supported by the National Science Foundation and partially supported by the Australian Research Council.

Modes of Interaction of Pleckstrin Homology Domains with Membranes: Toward a Computational Biochemistry of Membrane Recognition.

PubMed

Naughton, Fiona B; Kalli, Antreas C; Sansom, Mark S P

2018-02-02

Pleckstrin homology (PH) domains mediate protein-membrane interactions by binding to phosphatidylinositol phosphate (PIP) molecules. The structural and energetic basis of selective PH-PIP interactions is central to understanding many cellular processes, yet the molecular complexities of the PH-PIP interactions are largely unknown. Molecular dynamics simulations using a coarse-grained model enables estimation of free-energy landscapes for the interactions of 12 different PH domains with membranes containing PIP 2 or PIP 3 , allowing us to obtain a detailed molecular energetic understanding of the complexities of the interactions of the PH domains with PIP molecules in membranes. Distinct binding modes, corresponding to different distributions of cationic residues on the PH domain, were observed, involving PIP interactions at either the "canonical" (C) and/or "alternate" (A) sites. PH domains can be grouped by the relative strength of their C- and A-site interactions, revealing that a higher affinity correlates with increased C-site interactions. These simulations demonstrate that simultaneous binding of multiple PIP molecules by PH domains contributes to high-affinity membrane interactions, informing our understanding of membrane recognition by PH domains in vivo. Copyright © 2017. Published by Elsevier Ltd.

Interplay between membrane curvature and protein conformational equilibrium investigated by solid-state NMR.

PubMed

Liao, Shu Y; Lee, Myungwoon; Hong, Mei

2018-03-01

Many membrane proteins sense and induce membrane curvature for function, but structural information about how proteins modulate their structures to cause membrane curvature is sparse. We review our recent solid-state NMR studies of two virus membrane proteins whose conformational equilibrium is tightly coupled to membrane curvature. The influenza M2 proton channel has a drug-binding site in the transmembrane (TM) pore. Previous chemical shift data indicated that this pore-binding site is lost in an M2 construct that contains the TM domain and a curvature-inducing amphipathic helix. We have now obtained chemical shift perturbation, protein-drug proximity, and drug orientation data that indicate that the pore-binding site is restored when the full cytoplasmic domain is present. This finding indicates that the curvature-inducing amphipathic helix distorts the TM structure to interfere with drug binding, while the cytoplasmic tail attenuates this effect. In the second example, we review our studies of a parainfluenza virus fusion protein that merges the cell membrane and the virus envelope during virus entry. Chemical shifts of two hydrophobic domains of the protein indicate that both domains have membrane-dependent backbone conformations, with the β-strand structure dominating in negative-curvature phosphatidylethanolamine (PE) membranes. 31 P NMR spectra and 1 H- 31 P correlation spectra indicate that the β-strand-rich conformation induces saddle-splay curvature to PE membranes and dehydrates them, thus stabilizing the hemifusion state. These results highlight the indispensable role of solid-state NMR to simultaneously determine membrane protein structures and characterize the membrane curvature in which these protein structures exist. Copyright © 2018 Elsevier Inc. All rights reserved.

Local Conformational Stability of HIV-1 gp120 in Unliganded and CD4-Bound States as Defined by Amide Hydrogen/Deuterium Exchange▿ †

PubMed Central

Kong, Leopold; Huang, Chih-chin; Coales, Stephen J.; Molnar, Kathleen S.; Skinner, Jeff; Hamuro, Yoshitomo; Kwong, Peter D.

2010-01-01

The binding reaction of the HIV-1 gp120 envelope glycoprotein to the CD4 receptor involves exceptional changes in enthalpy and entropy. Crystal structures of gp120 in unliganded and various ligand-bound states, meanwhile, reveal an inner domain able to fold into diverse conformations, a structurally invariant outer domain, and, in the CD4-bound state, a bridging sheet minidomain. These studies, however, provide only hints as to the flexibility of each state. Here we use amide hydrogen/deuterium exchange coupled to mass spectrometry to provide quantifications of local conformational stability for HIV-1 gp120 in unliganded and CD4-bound states. On average, unliganded core gp120 displayed >10,000-fold slower exchange of backbone-amide hydrogens than a theoretically unstructured protein of the same composition, with binding by CD4 reducing the rate of gp120 amide exchange a further 10-fold. For the structurally constant CD4, alterations in exchange correlated well with alterations in binding surface (P value = 0.0004). For the structurally variable gp120, however, reductions in flexibility extended outside the binding surface, and regions of expected high structural diversity (inner domain/bridging sheet) displayed roughly 20-fold more rapid exchange in the unliganded state than regions of low diversity (outer domain). Thus, despite an extraordinary reduction in entropy, neither unliganded gp120 nor free CD4 was substantially unstructured, suggesting that most of the diverse conformations that make up the gp120 unliganded state are reasonably ordered. The results provide a framework for understanding how local conformational stability influences entropic change, conformational diversity, and structural rearrangements in the gp120-CD4 binding reaction. PMID:20660185

The IMPACT-III (HR) questionnaire: a valid measure of health-related quality of life in Croatian children with inflammatory bowel disease.

PubMed

Abdovic, Slaven; Mocic Pavic, Ana; Milosevic, Milan; Persic, Mladen; Senecic-Cala, Irena; Kolacek, Sanja

2013-12-01

To assess the reliability and validity of IMPACT-III (HR), a disease-specific, health-related quality of life instrument in Croatian children with inflammatory bowel disease. In a multicenter study, 104 children participated in a validation study of IMPACT-III (HR) cross-culturally adapted for Croatia. Factor analysis was used to determine optimal domain structure for this cohort, analysis of Cronbach's alpha coefficients to test internal reliability, ANOVA to assess discriminant validity, and correlation with Pediatric Quality of Life Inventory, Version 4.0 (PedsQL) using Pearson correlation coefficients to assess concurrent validity. Cronbach's alpha for the IMPACT-III (HR) total score was 0.92. The most robust factor solution was a 5-domain structure: Symptoms, Concerns, Socializing, Body Image, and Worry about Stool, all of which demonstrated good internal reliability (α=0.60-0.89), but two items were dropped to achieve this. Discriminant validity was demonstrated by significant differences (P<0.001) in mean IMPACT-III (HR) scores between quiescent and mild or moderate-severe disease activity groups for total (148 vs. 139 or 125) and following factor scores: Symptoms (84 vs. 71 or 61), Socializing (91 vs. 83 or 76), and Worry about Stool (significant only between quiescent and moderate-severe groups, 90 vs. 62, respectively). Concurrent validity of IMPACT-III (HR) with PedsQL showed significant correlation, which was strongest when similar domains were compared. IMPACT-III (HR) appears to be useful tool to measure health-related quality of life in Croatian children with Crohn's disease and ulcerative colitis. Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Validation of an instrument to measure quality of life in British children with inflammatory bowel disease.

PubMed

Ogden, C A; Akobeng, A K; Abbott, J; Aggett, P; Sood, M R; Thomas, A G

2011-09-01

To validate IMPACT-III (UK), a health-related quality of life (HRQoL) instrument, in British children with inflammatory bowel disease (IBD). One hundred six children and parents were invited to participate. IMPACT-III (UK) was validated by inspection by health professionals and children to assess face and content validity, factor analysis to determine optimum domain structure, use of Cronbach alpha coefficients to test internal reliability, ANOVA to assess discriminant validity, correlation with the Child Health Questionnaire to assess concurrent validity, and use of intraclass correlation coefficients to assess test-retest reliability. The independent samples t test was used to measure differences between sexes and age groups, and between paper and computerised versions of IMPACT-III (UK). IMPACT-III (UK) had good face and content validity. The most robust factor solution was a 5-domain structure: body image, embarrassment, energy, IBD symptoms, and worries/concerns about IBD, all of which demonstrated good internal reliability (α = 0.74-0.88). Discriminant validity was demonstrated by significant (P  < 0.05, P < 0.01) differences in HRQoL scores between the severe, moderate, and inactive/mild symptom severity groups for the embarrassment scale (63.7 vs 81.0 vs 81.2), IBD symptom scale (45.0 vs 64.2 vs 80.6), and the energy scale (46.4 vs 62.1 vs 77.7). Concurrent validity of IMPACT-III (UK) with comparable domains of the Child Health Questionnaire was confirmed. Test-retest reliability was confirmed with good intraclass correlation coefficients of 0.66 to 0.84. Paper and computer versions of IMPACT-III (UK) collected comparable scores, and there were no differences between the sexes and age groups. IMPACT-III (UK) appears to be a useful tool to measure HRQoL in British children with IBD.

Magneto-optical imaging technique for hostile environments: The ghost imaging approach

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

Meda, A.; Caprile, A.; Avella, A.

2015-06-29

In this paper, we develop an approach to magneto optical imaging (MOI), applying a ghost imaging (GI) protocol to perform Faraday microscopy. MOI is of the utmost importance for the investigation of magnetic properties of material samples, through Weiss domains shape, dimension and dynamics analysis. Nevertheless, in some extreme conditions such as cryogenic temperatures or high magnetic field applications, there exists a lack of domain images due to the difficulty in creating an efficient imaging system in such environments. Here, we present an innovative MOI technique that separates the imaging optical path from the one illuminating the object. The techniquemore » is based on thermal light GI and exploits correlations between light beams to retrieve the image of magnetic domains. As a proof of principle, the proposed technique is applied to the Faraday magneto-optical observation of the remanence domain structure of an yttrium iron garnet sample.« less

Conformational Flexibility of Metazoan Fatty Acid Synthase Enables Catalysis

PubMed Central

Brignole, Edward J.; Smith, Stuart; Asturias, Francisco J.

2008-01-01

The metazoan cytosolic fatty acid synthase (FAS) contains all of the enzymes required for de novo fatty acid biosynthesis covalently linked around two reaction chambers. While the 3D architecture of FAS has been mostly defined, it is unclear how reaction intermediates can transfer between distant catalytic domains. Using single-particle electron microscopy we have identified a near continuum of conformations consistent with remarkable flexibility of FAS. The distribution of conformations was influenced by the presence of substrates and altered by different catalytic mutations suggesting a direct correlation between conformation and specific enzymatic activities. 3D reconstructions were interpreted by docking high-resolution structures of individual domains and illustrate that the substrate loading and condensation domains dramatically swing and swivel to access substrates within either reaction chamber. Concomitant rearrangement of the β-carbon processing domains synchronizes acyl-chain reduction in one chamber with acyl-chain elongation in the other. PMID:19151726

Enhanced conductivity at orthorhombic–rhombohedral phase boundaries in BiFeO 3 thin films

DOE PAGES

Heo, Yooun; Lee, Jin Hong; Xie, Lin; ...

2016-08-26

Enhanced properties in modern functional materials can often be found at structural transition regions, such as morphotropic phase boundaries (MPB), owing to the coexistence of multiple phases with nearly equivalent energies. Strain-engineered MPBs have emerged in epitaxially grown BiFeO 3 (BFO) thin films by precisely tailoring a compressive misfit strain, leading to numerous intriguing phenomena, such as a massive piezoelectric response, magnetoelectric coupling, interfacial magnetism and electronic conduction. Recently, an orthorhombic–rhombohedral (O–R) phase boundary has also been found in tensile-strained BFO. In this study, we characterise the crystal structure and electronic properties of the two competing O and R phasesmore » using X-ray diffraction, scanning probe microscope and scanning transmission electron microscopy (STEM). We observe the temperature evolution of R and O domains and find that the domain boundaries are highly conductive. Temperature-dependent measurements reveal that the conductivity is thermally activated for R–O boundaries. STEM observations point to structurally wide boundaries, significantly wider than in other systems. Furthermore, we reveal a strong correlation between the highly conductive domain boundaries and structural material properties. These findings provide a pathway to use phase boundaries in this system for novel nanoelectronic applications.« less

ABC Transporters Involved in Export of Cell Surface Glycoconjugates

PubMed Central

Cuthbertson, Leslie; Kos, Veronica; Whitfield, Chris

2010-01-01

Summary: Complex glycoconjugates play critical roles in the biology of microorganisms. Despite the remarkable diversity in glycan structures and the bacteria that produce them, conserved themes are evident in the biosynthesis-export pathways. One of the primary pathways involves representatives of the ATP-binding cassette (ABC) transporter superfamily. These proteins are responsible for the export of a wide variety of cell surface oligo- and polysaccharides in both Gram-positive and Gram-negative bacteria. Recent investigations of the structure and function of ABC transporters involved in the export of lipopolysaccharide O antigens have revealed two fundamentally different strategies for coupling glycan polymerization to export. These mechanisms are distinguished by the presence (or absence) of characteristic nonreducing terminal modifications on the export substrates, which serve as chain termination and/or export signals, and by the presence (or absence) of a discrete substrate-binding domain in the nucleotide-binding domain polypeptide of the ABC transporter. A bioinformatic survey examining ABC exporters from known oligo- and polysaccharide biosynthesis loci identifies conserved nucleotide-binding domain protein families that correlate well with themes in the structures and assembly of glycans. The familial relationships among the ABC exporters generate hypotheses concerning the biosynthesis of structurally diverse oligo- and polysaccharides, which play important roles in the biology of bacteria with different lifestyles. PMID:20805402

The AvrM Effector from Flax Rust Has a Structured C-Terminal Domain and Interacts Directly with the M Resistance Protein

PubMed Central

Catanzariti, Ann-Maree; Dodds, Peter N.; Ve, Thomas; Kobe, Bostjan; Ellis, Jeffrey G.; Staskawicz, Brian J.

2011-01-01

In plant immunity, recognition of pathogen effectors by plant resistance proteins leads to the activation of plant defenses and a localized cell death response. The AvrM effector from flax rust is a small secreted protein that is recognized by the M resistance protein in flax. Here, we investigate the mechanism of M–AvrM recognition and show that these two proteins directly interact in a yeast two-hybrid assay, and that this interaction correlates with the recognition specificity observed for each of the different AvrM variants. We further characterize this interaction by demonstrating that the C-terminal domain of AvrM is required for M-dependent cell death, and show that this domain also interacts with the M protein in yeast. We investigate the role of C-terminal differences among the different AvrM proteins for their involvement in this interaction and establish that M recognition is hindered by an additional 34 amino acids present at the C terminus of several AvrM variants. Structural characterization of recombinant AvrM-A protein revealed a globular C-terminal domain that dimerizes. PMID:19958138

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.

Assessment of personality functioning: validity of the operationalized psychodynamic diagnosis axis IV (structure).

PubMed

Doering, Stephan; Burgmer, Markus; Heuft, Gereon; Menke, Dina; Bäumer, Brigitta; Lübking, Margit; Feldmann, Marcus; Schneider, Gudrun

2014-01-01

The assessment of personality functioning has recently become a focus of psychiatric diagnostics. The interview-based Operationalized Psychodynamic Diagnosis (OPD-2) provides a 'structure axis' for the assessment of personality functioning. One hundred twenty-four psychiatric patients were diagnosed by means of the Structured Clinical Interviews for DSM-IV (SCID-I and SCID-II), underwent OPD-2 interviews, and completed 9 questionnaires. The OPD-2 structure axis shows good interrater reliability (intraclass correlation = 0.793). Correlations between the OPD-2 structure axis domains and a priori selected questionnaire scales were of medium size and significant. Patients with a personality disorder (PD) showed significantly worse personality functioning than those without. In cluster B PD, personality functioning was more severely impaired than in cluster C PD. The OPD-2 structure axis shows good reliability as well as concurrent and discriminant validity and can be recommended for clinical use and research purposes. © 2013 S. Karger AG, Basel.

Thermodynamic study of the native and phosphorylated regulatory domain of the CFTR

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

Marasini, Carlotta, E-mail: marasini@ge.ibf.cnr.it; Galeno, Lauretta; Moran, Oscar

2012-07-06

Highlights: Black-Right-Pointing-Pointer CFTR mutations produce cystic fibrosis. Black-Right-Pointing-Pointer Chloride transport depends on the regulatory domain phosphorylation. Black-Right-Pointing-Pointer Regulatory domain is intrinsically disordered. Black-Right-Pointing-Pointer Secondary structure and protein stability change upon phosphorylation. -- Abstract: The regulatory domain (RD) of the cystic fibrosis transmembrane conductance regulator (CFTR), the defective protein in cystic fibrosis, is the region of the channel that regulates the CFTR activity with multiple phosphorylation sites. This domain is an intrinsically disordered protein, characterized by lack of stable or unique tertiary structure. The disordered character of a protein is directly correlated with its function. The flexibility of RD may bemore » important for its regulatory role: the continuous conformational change may be necessary for the progressive phosphorylation, and thus activation, of the channel. However, the lack of a defined and stable structure results in a considerable limitation when trying to in build a unique molecular model for the RD. Moreover, several evidences indicate significant structural differences between the native, non-phosphorylated state, and the multiple phosphorylated state of the protein. The aim of our work is to provide data to describe the conformations and the thermodynamic properties in these two functional states of RD. We have done the circular dichroism (CD) spectra in samples with a different degree of phosphorylation, from the non-phosphorylated state to a bona fide completely phosphorylated state. Analysis of CD spectra showed that the random coil and {beta}-sheets secondary structure decreased with the polypeptide phosphorylation, at expenses of an increase of {alpha}-helix. This observation lead to interpret phosphorylation as a mechanism favoring a more structured state. We also studied the thermal denaturation curves of the protein in the two conditions, monitoring the changes of the mean residue ellipticity measured at 222 nm as a function of temperature, between 20 and 95 Degree-Sign C. The thermodynamic analysis of the denaturation curves shows that phosphorylation of the protein induces a state of lower stability of R domain, characterized by a lower transition temperature, and by a smaller Gibbs free energy difference between the native and the unfolded states.« less

Mechanism of Protein Denaturation: Partial Unfolding of the P22 Coat Protein I-Domain by Urea Binding.

PubMed

Newcomer, Rebecca L; Fraser, LaTasha C R; Teschke, Carolyn M; Alexandrescu, Andrei T

2015-12-15

The I-domain is an insertion domain of the bacteriophage P22 coat protein that drives rapid folding and accounts for over half of the stability of the full-length protein. We sought to determine the role of hydrogen bonds (H-bonds) in the unfolding of the I-domain by examining (3)JNC' couplings transmitted through H-bonds, the temperature and urea-concentration dependence of (1)HN and (15)N chemical shifts, and native-state hydrogen exchange at urea concentrations where the domain is predominantly folded. The native-state hydrogen-exchange data suggest that the six-stranded β-barrel core of the I-domain is more stable against unfolding than a smaller subdomain comprised of a short α-helix and three-stranded β-sheet. H-bonds, separately determined from solvent protection and (3)JNC' H-bond couplings, are identified with an accuracy of 90% by (1)HN temperature coefficients. The accuracy is improved to 95% when (15)N temperature coefficients are also included. In contrast, the urea dependence of (1)HN and (15)N chemical shifts is unrelated to H-bonding. The protein segments with the largest chemical-shift changes in the presence of urea show curved or sigmoidal titration curves suggestive of direct urea binding. Nuclear Overhauser effects to urea for these segments are also consistent with specific urea-binding sites in the I-domain. Taken together, the results support a mechanism of urea unfolding in which denaturant binds to distinct sites in the I-domain. Disordered segments bind urea more readily than regions in stable secondary structure. The locations of the putative urea-binding sites correlate with the lower stability of the structure against solvent exchange, suggesting that partial unfolding of the structure is related to urea accessibility. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Synthesis of correlation filters: a generalized space-domain approach for improved filter characteristics

NASA Astrophysics Data System (ADS)

Sudharsanan, Subramania I.; Mahalanobis, Abhijit; Sundareshan, Malur K.

1990-12-01

Discrete frequency domain design of Minimum Average Correlation Energy filters for optical pattern recognition introduces an implementational limitation of circular correlation. An alternative methodology which uses space domain computations to overcome this problem is presented. The technique is generalized to construct an improved synthetic discriminant function which satisfies the conflicting requirements of reduced noise variance and sharp correlation peaks to facilitate ease of detection. A quantitative evaluation of the performance characteristics of the new filter is conducted and is shown to compare favorably with the well known Minimum Variance Synthetic Discriminant Function and the space domain Minimum Average Correlation Energy filter, which are special cases of the present design.

The Construct of Creativity: Structural Model for Self-Reported Creativity Ratings

ERIC Educational Resources Information Center

Kaufman, James C.; Cole, Jason C.; Baer, John

2009-01-01

Several thousand subjects completed self-report questionnaires about their own creativity in 56 discrete domains. This sample was then randomly divided into three subsamples that were subject to factor analyses that compared an oblique model (with a set of correlated factors) and a hierarchical model (with a single second-order, or hierarchical,…

Exploring Structural Dynamics within and between Sensory and Intellectual Functioning in Old and Very Old Age: Longitudinal Evidence from the Berlin Aging Study

ERIC Educational Resources Information Center

Ghisletta, Paolo; Lindenberger, Ulman

2005-01-01

Cross-sectional and longitudinal analyses of age-heterogeneous samples have revealed correlational links between and within intellectual, sensory, and sensorimotor domains. Due to basic limitations of cross-sectional designs and a reluctance to disentangle antecedent-consequent relations in longitudinal designs, the functional significance and…

Analysis of the structure and dynamics of human serum albumin.

PubMed

Guizado, T R Cuya

2014-10-01

Human serum albumin (HSA) is a biologically relevant protein that binds a variety of drugs and other small molecules. No less than 50 structures are deposited in the RCSB Protein Data Bank (PDB). Based on these structures, we first performed a clustering analysis. Despite the diversity of ligands, only two well defined conformations are detected, with a deviation of 0.46 nm between the average structures of the two clusters, while deviations within each cluster are smaller than 0.08 nm. Those two conformations are representative of the apoprotein and the HSA-myristate complex already identified in previous literature. Considering the structures within each cluster as a representative sample of the dynamical states of the corresponding conformation, we scrutinize the structural and dynamical differences between both conformations. Analysis of the fluctuations within each cluster set reveals that domain II is the most rigid one and better matches both structures. Then, taking this domain as reference, we show that the structural difference between both conformations can be expressed in terms of twist and hinge motions of domains I and III, respectively. We also characterize the dynamical difference between conformations by computing correlations and principal components for each set of dynamical states. The two conformations display different collective motions. The results are compared with those obtained from the trajectories of short molecular dynamics simulations, giving consistent outcomes. Let us remark that, beyond the relevance of the results for the structural and dynamical characterization of HAS conformations, the present methodology could be extended to other proteins in the PDB archive.

Structural organization of G-protein-coupled receptors

NASA Astrophysics Data System (ADS)

Lomize, Andrei L.; Pogozheva, Irina D.; Mosberg, Henry I.

1999-07-01

Atomic-resolution structures of the transmembrane 7-α-helical domains of 26 G-protein-coupled receptors (GPCRs) (including opsins, cationic amine, melatonin, purine, chemokine, opioid, and glycoprotein hormone receptors and two related proteins, retinochrome and Duffy erythrocyte antigen) were calculated by distance geometry using interhelical hydrogen bonds formed by various proteins from the family and collectively applied as distance constraints, as described previously [Pogozheva et al., Biophys. J., 70 (1997) 1963]. The main structural features of the calculated GPCR models are described and illustrated by examples. Some of the features reflect physical interactions that are responsible for the structural stability of the transmembrane α-bundle: the formation of extensive networks of interhelical H-bonds and sulfur-aromatic clusters that are spatially organized as 'polarity gradients' the close packing of side-chains throughout the transmembrane domain; and the formation of interhelical disulfide bonds in some receptors and a plausible Zn2+ binding center in retinochrome. Other features of the models are related to biological function and evolution of GPCRs: the formation of a common 'minicore' of 43 evolutionarily conserved residues; a multitude of correlated replacements throughout the transmembrane domain; an Na+-binding site in some receptors, and excellent complementarity of receptor binding pockets to many structurally dissimilar, conformationally constrained ligands, such as retinal, cyclic opioid peptides, and cationic amine ligands. The calculated models are in good agreement with numerous experimental data.

Development of quality of life instrument for urban poor in the northeast of Thailand.

PubMed

Surit, Phrutthinun; Laohasiriwong, Wongsa; Sanchaisuriya, Pattara; Schelp, Frank Perter

2008-09-01

Measuring the quality of life is important for evaluation and prediction of life and social care needs. To evaluate Quality of Life (QOL) in an urban poor population in northeast of Thailand, the Urban Poor Quality of Life (UPQOL) instrument was developed To develop an initial instrument to measure urban poor QOL. The development was started with literature review and investigated in urban poor communities. The results were transformed into the items required to build a structured questionnaire. Five hundred twenty three subjects, representatives of urban poor, were selected to test this instrument. Descriptive statistics described feature of items and the samples, exploratory factor analysis conducted the items score, and confirmatory factor analysis conducted the construct validity. The result found that the UPQOL instrument consisted of nine domains (education, income and employment, environment, health, infrastructure, security and safety, shelter and housing, civil society and political, and human rights domains) with egien value rank from 1.5 to 4.2 and 61 items with the factor loading rank from 0.41 to 0.82. The internal consistency was 0.92. The correlation between items to domain ranged from 0.30 to 0.72 and domains to overall QOL ranged from 0.27 to 0.84. Confirmatory factor analysis showed that the structure fit all domains well. Domains and overall structure were good with CFI (> 0.95). The internal consistency value ranged from 0.73-0.93. UPQOL scores were able to discriminate groups of subjects with differences levels of QOL. The UPQOL instrument is conceptually valid. The results support good validity and reliability. It forms the basis for future testing and application in other settings.

Gene polymorphism linked to increased asthma and IBD risk alters gasdermin-B structure, a sulfatide and phosphoinositide binding protein.

PubMed

Chao, Kinlin L; Kulakova, Liudmila; Herzberg, Osnat

2017-02-14

The exact function of human gasdermin-B (GSDMB), which regulates differentiation and growth of epithelial cells, is yet to be elucidated. In human epidermal growth factor receptor 2 (HER2)-positive breast cancer, GSDMB gene amplification and protein overexpression indicate a poor response to HER2-targeted therapy. Genome-wide association studies revealed a correlation between GSDMB SNPs and an increased susceptibility to Crohn's disease, ulcerative colitis, and asthma. The N- and C-terminal domains of all gasdermins possess lipid-binding and regulatory activities, respectively. Inflammatory caspases cleave gasdermin-D in the interdomain linker but not GSDMB. The cleaved N-terminal domain binds phosphoinositides and cardiolipin, forms membrane-disrupting pores, and executes pyroptosis. We show that both full-length GSDMB and the N-terminal domain bind to nitrocellulose membranes immobilized with phosphoinositides or sulfatide, but not with cardiolipin. In addition, the GSDMB N-terminal domain binds liposomes containing sulfatide. The crystal structure of the GSDMB C-terminal domain reveals the structural impact of the amino acids encoded by SNPs that are linked to asthma and inflammatory bowel disease (IBD). A loop that carries the polymorphism amino acids corresponding to healthy individuals (Gly299:Pro306) exhibits high conformational flexibility, whereas the loop carrying amino acids found in individuals with increased disease risk (Arg299:Ser306) exhibits a well-defined conformation and higher positive surface charge. Apoptotic executioner caspase-3, -6, and -7, but not the inflammatory caspases, cleave GSDMB at 88 DNVD 91 within the N-terminal domain. Selective sulfatide binding may indicate possible function for GSDMB in the cellular sulfatide transport.

Gene polymorphism linked to increased asthma and IBD risk alters gasdermin-B structure, a sulfatide and phosphoinositide binding protein

PubMed Central

Chao, Kinlin L.; Kulakova, Liudmila; Herzberg, Osnat

2017-01-01

The exact function of human gasdermin-B (GSDMB), which regulates differentiation and growth of epithelial cells, is yet to be elucidated. In human epidermal growth factor receptor 2 (HER2)-positive breast cancer, GSDMB gene amplification and protein overexpression indicate a poor response to HER2-targeted therapy. Genome-wide association studies revealed a correlation between GSDMB SNPs and an increased susceptibility to Crohn’s disease, ulcerative colitis, and asthma. The N- and C-terminal domains of all gasdermins possess lipid-binding and regulatory activities, respectively. Inflammatory caspases cleave gasdermin-D in the interdomain linker but not GSDMB. The cleaved N-terminal domain binds phosphoinositides and cardiolipin, forms membrane-disrupting pores, and executes pyroptosis. We show that both full-length GSDMB and the N-terminal domain bind to nitrocellulose membranes immobilized with phosphoinositides or sulfatide, but not with cardiolipin. In addition, the GSDMB N-terminal domain binds liposomes containing sulfatide. The crystal structure of the GSDMB C-terminal domain reveals the structural impact of the amino acids encoded by SNPs that are linked to asthma and inflammatory bowel disease (IBD). A loop that carries the polymorphism amino acids corresponding to healthy individuals (Gly299:Pro306) exhibits high conformational flexibility, whereas the loop carrying amino acids found in individuals with increased disease risk (Arg299:Ser306) exhibits a well-defined conformation and higher positive surface charge. Apoptotic executioner caspase-3, -6, and -7, but not the inflammatory caspases, cleave GSDMB at 88DNVD91 within the N-terminal domain. Selective sulfatide binding may indicate possible function for GSDMB in the cellular sulfatide transport. PMID:28154144

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

PubMed

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

2014-09-01

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

Predicting protein crystallization propensity from protein sequence

PubMed Central

2011-01-01

The high-throughput structure determination pipelines developed by structural genomics programs offer a unique opportunity for data mining. One important question is how protein properties derived from a primary sequence correlate with the protein’s propensity to yield X-ray quality crystals (crystallizability) and 3D X-ray structures. A set of protein properties were computed for over 1,300 proteins that expressed well but were insoluble, and for ~720 unique proteins that resulted in X-ray structures. The correlation of the protein’s iso-electric point and grand average hydropathy (GRAVY) with crystallizability was analyzed for full length and domain constructs of protein targets. In a second step, several additional properties that can be calculated from the protein sequence were added and evaluated. Using statistical analyses we have identified a set of the attributes correlating with a protein’s propensity to crystallize and implemented a Support Vector Machine (SVM) classifier based on these. We have created applications to analyze and provide optimal boundary information for query sequences and to visualize the data. These tools are available via the web site http://bioinformatics.anl.gov/cgi-bin/tools/pdpredictor. PMID:20177794

Psychometric properties of the World Health Organization quality of life assessment – brief in methadone patients: a validation study in northern Taiwan

PubMed Central

2013-01-01

Background Quality of life (QOL) is an important outcome measure in the treatment of heroin addiction. The Taiwan version of the World Health Organization Quality of Life assessment (WHOQOL-BREF [TW]) has been developed and studied in various groups, but not specifically in a population of injection drug users. The aim of this study was to analyze the psychometric properties of the WHOQOL-BREF (TW) in a sample of injection drug users undergoing methadone maintenance treatment. Methods A total of 553 participants were interviewed and completed the instrument. Item-response distributions, internal consistency, corrected item-domain correlation, criterion-related validity, and construct validity through confirmatory factor analysis were evaluated. Results The frequency distribution of the 4 domains of the WHOQOL-BREF (TW) showed no floor or ceiling effects. The instrument demonstrated adequate internal consistency (Cronbach’s alpha coefficients were higher than 0.7 across the 4 domains) and all items had acceptable correlation with the corresponding domain scores (r = 0.32-0.73). Correlations (p < 0.01) of the 4 domains with the 2 benchmark items assessing overall QOL and general health were supportive of criterion-related validity. Confirmatory factor analysis yielded marginal goodness-of-fit between the 4-domain model and the sample data. Conclusions The hypothesized WHOQOL-BREF measurement model was appropriate for the injection drug users after some adjustments. Despite different patterns found in the confirmatory factor analysis, the findings overall suggest that the WHOQOL-BREF (TW) is a reliable and valid measure of QOL among injection drug users and can be utilized in future treatment outcome studies. The factor structure provided by the study also helps to understand the QOL characteristics of the injection drug users in Taiwan. However, more research is needed to examine its test-retest reliability and sensitivity to changes due to treatment. PMID:24325611

Hum-mPLoc 3.0: prediction enhancement of human protein subcellular localization through modeling the hidden correlations of gene ontology and functional domain features.

PubMed

Zhou, Hang; Yang, Yang; Shen, Hong-Bin

2017-03-15

Protein subcellular localization prediction has been an important research topic in computational biology over the last decade. Various automatic methods have been proposed to predict locations for large scale protein datasets, where statistical machine learning algorithms are widely used for model construction. A key step in these predictors is encoding the amino acid sequences into feature vectors. Many studies have shown that features extracted from biological domains, such as gene ontology and functional domains, can be very useful for improving the prediction accuracy. However, domain knowledge usually results in redundant features and high-dimensional feature spaces, which may degenerate the performance of machine learning models. In this paper, we propose a new amino acid sequence-based human protein subcellular location prediction approach Hum-mPLoc 3.0, which covers 12 human subcellular localizations. The sequences are represented by multi-view complementary features, i.e. context vocabulary annotation-based gene ontology (GO) terms, peptide-based functional domains, and residue-based statistical features. To systematically reflect the structural hierarchy of the domain knowledge bases, we propose a novel feature representation protocol denoted as HCM (Hidden Correlation Modeling), which will create more compact and discriminative feature vectors by modeling the hidden correlations between annotation terms. Experimental results on four benchmark datasets show that HCM improves prediction accuracy by 5-11% and F 1 by 8-19% compared with conventional GO-based methods. A large-scale application of Hum-mPLoc 3.0 on the whole human proteome reveals proteins co-localization preferences in the cell. www.csbio.sjtu.edu.cn/bioinf/Hum-mPLoc3/. hbshen@sjtu.edu.cn. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Validation of the facial dysfunction domain of the Penn Acoustic Neuroma Quality-of-Life (PANQOL) Scale.

PubMed

Lodder, Wouter L; Adan, Guleed H; Chean, Chung S; Lesser, Tristram H; Leong, Samuel C

2017-06-01

The objective of this study is to evaluate the strength of content validity within the facial dysfunction domain of the Penn Acoustic Neuroma Quality-of-Life (PANQOL) Scale and to compare how it correlates with a facial dysfunction-specific QOL instrument (Facial Clinimetric Evaluation, FaCE). The study design is online questionnaire survey. Members of the British Acoustic Neuroma Association received both PANQOL questionnaires and the FaCE scale. 158 respondents with self-identified facial paralysis or dysfunction had completed PANQOL and FaCE data sets for analysis. The mean composite PANQOL score was 53.5 (range 19.2-93.5), whilst the mean total FaCE score was 50.9 (range 10-95). The total scores of the PANQOL and FaCE correlated moderate (r = 0.48). Strong correlation (r = 0.63) was observed between the PANQOL's facial dysfunction domain and the FaCE total score. Of all the FaCE domains, social function was strongly correlated with the PANQOL facial dysfunction domain (r = 0.66), whilst there was very weak-to-moderate correlation (range 0.01-0.43) to the other FaCE domains. The current study has demonstrated a strong correlation between the facial dysfunction domains of PANQOL with a facial paralysis-specific QOL instrument.

Correlation of Late Precambrian and Paleozoic events in the East European platform and the adjacent paleooceanic domains

NASA Astrophysics Data System (ADS)

Kheraskova, T. N.; Volozh, Yu. A.; Antipov, M. P.; Bykadorov, V. A.; Sapozhnikov, R. B.

2015-01-01

The correlation of geological events and structure-forming processes occurring contemporaneously in the inner parts of cratons and the adjacent paleooceanic basins is discussed in order to understand the effects of these processes on sedimentation and structural rearrangements. For this purpose, a series of paleodynamic reconstructions of the Riphean, Vendian, and Paleozoic epicontinental basins of the East European Platform and zones of their transition to marginal basins of the same age once situated in the Ural, Timan, Caucasus, Scandinavian fold regions and in the Scythian-Turan Plate have been performed on the basis of the available original and published data combined with interpretation of seismic profiles. As a result, a set of structural-facies maps of this territory have been compiled for several time intervals from the Late Riphean to Early Permian.

Dynamic characteristics of a wind turbine blade using 3D digital image correlation

NASA Astrophysics Data System (ADS)

Baqersad, Javad; Carr, Jennifer; Lundstrom, Troy; Niezrecki, Christopher; Avitabile, Peter; Slattery, Micheal

2012-04-01

Digital image correlation (DIC) has been becoming increasingly popular as a means to perform structural health monitoring because of its full-field, non-contacting measurement ability. In this paper, 3D DIC techniques are used to identify the mode shapes of a wind turbine blade. The blade containing a handful of optical targets is excited at different frequencies using a shaker as well as a pluck test. The response is recorded using two PHOTRON™ high speed cameras. Time domain data is transferred to the frequency domain to extract mode shapes and natural frequencies using an Operational Modal Approach. A finite element model of the blade is also used to compare the mode shapes. Furthermore, a modal hammer impact test is performed using a more conventional approach with an accelerometer. A comparison of mode shapes from the photogrammetric, finite element, and impact test approaches are presented to show the accuracy of the DIC measurement approach.

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.

Impact of O-glycosylation on the molecular and cellular adhesion properties of the Escherichia coli autotransporter protein Ag43.

PubMed

Reidl, Sebastian; Lehmann, Annika; Schiller, Roswitha; Salam Khan, A; Dobrindt, Ulrich

2009-08-01

Antigen 43 (Ag43) represents an entire family of closely related autotransporter proteins in Escherichia coli and has been described to confer aggregation and fluffing of cells, to promote biofilm formation, uptake and survival in macrophages as well as long-term persistence of uropathogenic E. coli in the murine urinary tract. Furthermore, it has been reported that glycosylation of the Ag43 passenger domain (alpha(43)) stabilizes its conformation and increases adhesion to Hep-2 cells. We characterized the role of Ag43 as an adhesin and the impact of O-glycosylation on the function of Ag43. To analyze whether structural variations in the alpha(43) domain correlate with different functional properties, we cloned 5 different agn43 alleles from different E. coli subtypes and tested them for autoaggregation, biofilm formation, adhesion to different eukaryotic cell lines as well as to purified components of the extracellular matrix. These experiments were performed with nonglycosylated and O-glycosylated Ag43 variants. We show for the first time that Ag43 mediates bacterial adhesion in a cell line-specific manner and that structural variations of the alpha(43) domain correlate with increased adhesive properties to proteins of the extracellular matrix such as collagen and laminin. Whereas O-glycosylation of many alpha(43) domains led to impaired autoaggregation and a significantly reduced adhesion to eukaryotic cell lines, their interaction with collagen was significantly increased. These data demonstrate that O-glycosylation is not a prerequisite for Ag43 function and that the different traits mediated by Ag43, i.e., biofilm formation, autoaggregation, adhesion to eukaryotic cells and extracellular matrix proteins, rely on distinct mechanisms.

Cyclophilin40 isomerase activity is regulated by a temperature-dependent allosteric interaction with Hsp90.

PubMed

Blackburn, Elizabeth A; Wear, Martin A; Landré, Vivian; Narayan, Vikram; Ning, Jia; Erman, Burak; Ball, Kathryn L; Walkinshaw, Malcolm D

2015-09-01

Cyclophilin 40 (Cyp40) comprises an N-terminal cyclophilin domain with peptidyl-prolyl isomerase (PPIase) activity and a C-terminal tetratricopeptide repeat (TPR) domain that binds to the C-terminal-EEVD sequence common to both heat shock protein 70 (Hsp70) and Hsp90. We show in the present study that binding of peptides containing the MEEVD motif reduces the PPIase activity by ∼30%. CD and fluorescence assays show that the TPR domain is less stable than the cyclophilin domain and is stabilized by peptide binding. Isothermal titration calorimetry (ITC) shows that the affinity for the-MEEVD peptide is temperature sensitive in the physiological temperature range. Results from these biophysical studies fit with the MD simulations of the apo and holo (peptide-bound) structures which show a significant reduction in root mean square (RMS) fluctuation in both TPR and cyclophilin domains when-MEEVD is bound. The MD simulations of the apo-protein also highlight strong anti-correlated motions between residues around the PPIase-active site and a band of residues running across four of the seven helices in the TPR domain. Peptide binding leads to a distortion in the shape of the active site and a significant reduction in these strongly anti-correlated motions, providing an explanation for the allosteric effect of ligand binding and loss of PPIase activity. Together the experimental and MD results suggest that on heat shock, dissociation of Cyp40 from complexes mediated by the TPR domain leads to an increased pool of free Cyp40 capable of acting as an isomerase/chaperone in conditions of cellular stress. © 2015 Authors.

Cyclophilin40 isomerase activity is regulated by a temperature-dependent allosteric interaction with Hsp90

PubMed Central

Blackburn, Elizabeth A.; Wear, Martin A.; Landré, Vivian; Narayan, Vikram; Ning, Jia; Erman, Burak; Ball, Kathryn L.; Walkinshaw, Malcolm D.

2015-01-01

Cyclophilin 40 (Cyp40) comprises an N-terminal cyclophilin domain with peptidyl-prolyl isomerase (PPIase) activity and a C-terminal tetratricopeptide repeat (TPR) domain that binds to the C-terminal–EEVD sequence common to both heat shock protein 70 (Hsp70) and Hsp90. We show in the present study that binding of peptides containing the MEEVD motif reduces the PPIase activity by ∼30%. CD and fluorescence assays show that the TPR domain is less stable than the cyclophilin domain and is stabilized by peptide binding. Isothermal titration calorimetry (ITC) shows that the affinity for the–MEEVD peptide is temperature sensitive in the physiological temperature range. Results from these biophysical studies fit with the MD simulations of the apo and holo (peptide-bound) structures which show a significant reduction in root mean square (RMS) fluctuation in both TPR and cyclophilin domains when–MEEVD is bound. The MD simulations of the apo-protein also highlight strong anti-correlated motions between residues around the PPIase-active site and a band of residues running across four of the seven helices in the TPR domain. Peptide binding leads to a distortion in the shape of the active site and a significant reduction in these strongly anti-correlated motions, providing an explanation for the allosteric effect of ligand binding and loss of PPIase activity. Together the experimental and MD results suggest that on heat shock, dissociation of Cyp40 from complexes mediated by the TPR domain leads to an increased pool of free Cyp40 capable of acting as an isomerase/chaperone in conditions of cellular stress. PMID:26330616

Hidden Structural Codes in Protein Intrinsic Disorder.

PubMed

Borkosky, Silvia S; Camporeale, Gabriela; Chemes, Lucía B; Risso, Marikena; Noval, María Gabriela; Sánchez, Ignacio E; Alonso, Leonardo G; de Prat Gay, Gonzalo

2017-10-17

Intrinsic disorder is a major structural category in biology, accounting for more than 30% of coding regions across the domains of life, yet consists of conformational ensembles in equilibrium, a major challenge in protein chemistry. Anciently evolved papillomavirus genomes constitute an unparalleled case for sequence to structure-function correlation in cases in which there are no folded structures. E7, the major transforming oncoprotein of human papillomaviruses, is a paradigmatic example among the intrinsically disordered proteins. Analysis of a large number of sequences of the same viral protein allowed for the identification of a handful of residues with absolute conservation, scattered along the sequence of its N-terminal intrinsically disordered domain, which intriguingly are mostly leucine residues. Mutation of these led to a pronounced increase in both α-helix and β-sheet structural content, reflected by drastic effects on equilibrium propensities and oligomerization kinetics, and uncovers the existence of local structural elements that oppose canonical folding. These folding relays suggest the existence of yet undefined hidden structural codes behind intrinsic disorder in this model protein. Thus, evolution pinpoints conformational hot spots that could have not been identified by direct experimental methods for analyzing or perturbing the equilibrium of an intrinsically disordered protein ensemble.

General and Domain-Specific Contributions to Creative Ideation and Creative Performance

PubMed Central

An, Donggun; Runco, Mark A.

2016-01-01

The general objective of this study was to reexamine two views of creativity, one positing that there is a general creative capacity or talent and the other that creativity is domain-specific. These two views were compared by (a) testing correlations among measures of domain-general and domain-specific creativity and (b) examining how the general and the specific measures was each related to indices of knowledge, motivation, and personality. Participants were 147 college students enrolled in a foreign language course. Data were collected on participants’ domain knowledge, motivation, and creative personality, as well as four measures representing “General or Domain-Specific Creative Ideation” or “Creative Performance and Activity”. Results indicated that the four measures of creativity were correlated with one another, except for “General Performance and Activity” and “Domain-Specific Ideation.” A canonical correlation indicated that knowledge, motivation, and personality were significantly correlated with the four creativity measures (Rc = .49, p < .01). Multiple regressions uncovered particular relationships consistent with the view that creativity has both general and domain-specific contributions. Limitations, such as the focus on one domain, and future directions are discussed. PMID:27872664

Examining the social context in the caregiving experience: correlates of global self-esteem among adult daughter caregivers to an older parent with cancer.

PubMed

Bachner, Yaacov G; Karus, Daniel G; Raveis, Victoria H

2009-10-01

To examine the associations between various patient, disease, situation, and caregiver characteristics (organized by five conceptual domains) and global self-esteem among caregiver daughters to parents with cancer. Dyads comprised of 237 cancer outpatients and their adult caregiving daughter completed structured telephone interviews. Two of the five domains of potential correlates significantly predicted caregiving daughters' global self-esteem-daughters' sociodemographics and constraints on/facilitators of caregiving. Daughters' overall sense of self-worth was directly correlated with their household income and inversely correlated with greater depressive affect and the number of patient needs for which someone else provided assistance. It was also correlated with the daughters' other role obligations. A higher sense of self-worth was associated with either being employed or having to care for a child/grandchild; a lower sense of self-worth was associated with having a spouse/partner. The present analysis documents the complexity of social connectedness, demonstrating that various role obligations contribute to caregiving daughters' global self-esteem in different ways. In the context of assuming cancer careprovision, daughters' existing repertoire of social roles may possibly mediate the stress associated with their care involvement or serve as a buffer against the strain of the caregiving experience.

Structural basis of empathy and the domain general region in the anterior insular cortex

PubMed Central

Mutschler, Isabella; Reinbold, Céline; Wankerl, Johanna; Seifritz, Erich; Ball, Tonio

2013-01-01

Empathy is key for healthy social functioning and individual differences in empathy have strong implications for manifold domains of social behavior. Empathy comprises of emotional and cognitive components and may also be closely linked to sensorimotor processes, which go along with the motivation and behavior to respond compassionately to another person's feelings. There is growing evidence for local plastic change in the structure of the healthy adult human brain in response to environmental demands or intrinsic factors. Here we have investigated changes in brain structure resulting from or predisposing to empathy. Structural MRI data of 101 healthy adult females was analyzed. Empathy in fictitious as well as real-life situations was assessed using a validated self-evaluation measure. Furthermore, empathy-related structural effects were also put into the context of a functional map of the anterior insular cortex (AIC) determined by activation likelihood estimate (ALE) meta-analysis of previous functional imaging studies. We found that gray matter (GM) density in the left dorsal AIC correlates with empathy and that this area overlaps with the domain general region (DGR) of the anterior insula that is situated in-between functional systems involved in emotion–cognition, pain, and motor tasks as determined by our meta-analysis. Thus, we propose that this insular region where we find structural differences depending on individual empathy may play a crucial role in modulating the efficiency of neural integration underlying emotional, cognitive, and sensorimotor information which is essential for global empathy. PMID:23675334

TIR-domain-containing adapter-inducing interferon-β (TRIF) forms filamentous structures, whose pro-apoptotic signalling is terminated by autophagy.

PubMed

Gentle, Ian E; McHenry, Kevin T; Weber, Arnim; Metz, Arlena; Kretz, Oliver; Porter, Dale; Häcker, Georg

2017-07-01

The formation of amyloid-like protein structures has recently emerged as a feature in signal transduction, particularly in innate immunity. These structures appear to depend on defined domains for their formation but likely also require dedicated ways to terminate signalling. We, here, define the innate immunity protein/Toll-like receptor adaptor TIR-domain-containing adapter-inducing interferon-β (TRIF) as a novel platform of fibril formation and probe signal initiation through TRIF as well as its termination in Toll-like receptor 3 (TLR3)-stimulated melanoma cells. A main signalling pathway triggered by TLR3 caused apoptosis, which was controlled by inhibitor of apoptosis proteins and was dependent on RIPK1 and independent of TNF. Using correlative electron/fluorescence microscopy, we visualised fibrillar structures formed through both Toll/interleukin-1 receptor and RIP homotypic interacting motif regions of TRIF. We provide evidence that these fibrillary structures are active signalling platforms whose activity is terminated by autophagy. TRIF-signalling enhanced autophagy, and fibrillary structures were partly contained within autophagosomes. Inhibition of autophagy increased levels of pro-apoptotic TRIF complexes, leading to the accumulation of active caspase-8 and enhanced apoptosis while stimulation of autophagy reduced TRIF-dependent death. We conclude that pro-death signals through TRIF are regulated by autophagy and propose that pro-apoptotic signalling through TRIF/RIPK1/caspase-8 occurs in fibrillary platforms. © 2017 Federation of European Biochemical Societies.

Micromagnetism in a planar system with a random magnetic anisotropy and two-dimensional magnetic correlations

NASA Astrophysics Data System (ADS)

Komogortsev, S. V.; Fel'k, V. A.; Iskhakov, R. S.; Shadrina, G. V.

2017-08-01

The hysteresis loops and the micromagnetic structure of a ferromagnetic nanolayer with a randomly oriented local easy magnetization axis and two-dimensional magnetization correlations are studied using a micromagnetic simulation. The properties and the micromagnetic structure of the nanolayer are determined by the competition between the anisotropy and exchange energies and by the dipole-dipole interaction energy. The magnetic microstructure can be described as an ensemble of stochastic magnetic domains and topological magnetization defects. Dipole-dipole interaction suppresses the formation of topological magnetization defects. The topological defects in the magnetic microstructure can cause a sharper change in the coercive force with the crystallite size than that predicted by the random magnetic anisotropy model.

Effect of Finite Computational Domain on Turbulence Scaling Law in Both Physical and Spectral Spaces

NASA Technical Reports Server (NTRS)

Hou, Thomas Y.; Wu, Xiao-Hui; Chen, Shiyi; Zhou, Ye

1998-01-01

The well-known translation between the power law of energy spectrum and that of the correlation function or the second order structure function has been widely used in analyzing random data. Here, we show that the translation is valid only in proper scaling regimes. The regimes of valid translation are different for the correlation function and the structure function. Indeed, they do not overlap. Furthermore, in practice, the power laws exist only for a finite range of scales. We show that this finite range makes the translation inexact even in the proper scaling regime. The error depends on the scaling exponent. The current findings are applicable to data analysis in fluid turbulence and other stochastic systems.

1H, 13C, and 15N resonance assignments of an enzymatically active domain from the catalytic component (CDTa, residues 216-420) of a binary toxin from Clostridium difficile.

PubMed

Roth, Braden M; Godoy-Ruiz, Raquel; Varney, Kristen M; Rustandi, Richard R; Weber, David J

2016-04-01

Clostridium difficile is a bacterial pathogen and is the most commonly reported source of nosocomial infection in industrialized nations. Symptoms of C. difficile infection (CDI) include antibiotic-associated diarrhea, pseudomembranous colitis, sepsis and death. Over the last decade, rates and severity of hospital infections in North America and Europe have increased dramatically and correlate with the emergence of a hypervirulent strain of C. difficile characterized by the presence of a binary toxin, CDT (C. difficile toxin). The binary toxin consists of an enzymatic component (CDTa) and a cellular binding component (CDTb) that together form the active binary toxin complex. CDTa harbors a pair of structurally similar but functionally distinct domains, an N-terminal domain (residues 1-215; (1-215)CDTa) that interacts with CDTb and a C-terminal domain (residues 216-420; (216-420)CDTa) that harbors the intact ADP-ribosyltransferase (ART) active site. Reported here are the (1)H, (13)C, and (15)N backbone resonance assignments of the 23 kDa, 205 amino acid C-terminal enzymatic domain of CDTa, termed (216-420)CDTa. These NMR resonance assignments for (216-420)CDTa represent the first for a family of ART binary toxins and provide the framework for detailed characterization of the solution-state protein structure determination, dynamic studies of this domain, as well as NMR-based drug discovery efforts.

Relationship between exercise capacity and quality of life in adolescents with asthma *

PubMed Central

Basso, Renata Pedrolongo; Jamami, Mauricio; Labadessa, Ivana Gonçalves; Regueiro, Eloisa Maria Gatti; Pessoa, Bruna Varanda; de Oliveira, Antônio Delfino; Lorenzo, Valéria Amorim Pires Di; Costa, Dirceu

2013-01-01

OBJECTIVE: To determine whether the quality of life of adolescents with asthma correlates with parameters obtained prior to and after the six-minute step test (6MST); spirometric results after the 6MST; and level of physical activity. METHODS: Nineteen adolescents with asthma, ranging from 11-15 years of age, were assessed with spirometry, 6MST, the International Physical Activity Questionnaire (IPAQ), the Pediatric Asthma Quality of Life Questionnaire (PAQLQ), and the 10-point Borg category-ratio scale. RESULTS: Sensation of dyspnea correlated negatively with the total PAQLQ score (r = −0.54) and with the scores of its activity limitation (AL) and symptoms domains (r = −0.64 and r = −0.63, respectively), leg fatigue also correlating negatively with those same domains (r = −0.49 and r = −0.56, respectively). The total IPAQ score correlated with the total PAQLQ score (r = 0.47) and with the PAQLQ AL domain (r = 0.51); IPAQ time spent walking correlated with the PAQLQ symptoms domain (r = 0.45); and IPAQ time spent in vigorous activity correlated with the AL domain (r = 0.50). In the regression analysis, only sensation of dyspnea remained significantly correlated with the total PAQLQ score and the PAQLQ AL domain; leg fatigue remained significantly correlated with the symptoms domain. CONCLUSIONS: Higher levels of physical activity indicate better quality of life, as do lower perception of dyspnea and less leg fatigue. The 6MST proved to be a viable option for evaluating exercise capacity in adolescents with asthma, because it reflects the discomfort that asthma causes during activities of daily living. PMID:23670496

Thermal fluctuations of ferroelectric nanodomains in a ferroelectric-dielectric PbTiO 3 / SrTiO 3 superlattice

DOE PAGES

Zhang, Qingteng; Dufresne, Eric M.; Chen, Pice; ...

2017-02-27

Ferroelectric-dielectric superlattices consisting of alternating layers of ferroelectric PbTiO 3 and dielectric SrTiO 3 exhibit a disordered striped nanodomain pattern, with characteristic length scales of 6 nm for the domain periodicity and 30 nm for the in-plane coherence of the domain pattern. Spatial disorder in the domain pattern gives rise to coherent hard x-ray scattering patterns exhibiting intensity speckles. We show here using variable-temperature Bragg-geometry x-ray photon correlation spectroscopy that x-ray scattering patterns from the disordered domains exhibit a continuous temporal decorrelation due to spontaneous domain fluctuations. The temporal decorrelation can be described using a compressed exponential function, consistent withmore » what has been observed in other systems with arrested dynamics. The fluctuation speeds up at higher temperatures and the thermal activation energy estimated from the Arrhenius model is 0.35±0.21 eV. As a result, the magnitude of the energy barrier implies that the complicated energy landscape of the domain structures is induced by pinning mechanisms and domain patterns fluctuate via the generation and annihilation of topological defects similar to soft materials such as block copolymers.« less

Bonding in Heavier Group 14 Zero-Valent Complexes-A Combined Maximum Probability Domain and Valence Bond Theory Approach.

PubMed

Turek, Jan; Braïda, Benoît; De Proft, Frank

2017-10-17

The bonding in heavier Group 14 zero-valent complexes of a general formula L 2 E (E=Si-Pb; L=phosphine, N-heterocyclic and acyclic carbene, cyclic tetrylene and carbon monoxide) is probed by combining valence bond (VB) theory and maximum probability domain (MPD) approaches. All studied complexes are initially evaluated on the basis of the structural parameters and the shape of frontier orbitals revealing a bent structural motif and the presence of two lone pairs at the central E atom. For the VB calculations three resonance structures are suggested, representing the "ylidone", "ylidene" and "bent allene" structures, respectively. The influence of both ligands and central atoms on the bonding situation is clearly expressed in different weights of the resonance structures for the particular complexes. In general, the bonding in the studied E 0 compounds, the tetrylones, is best described as a resonating combination of "ylidone" and "ylidene" structures with a minor contribution of the "bent allene" structure. Moreover, the VB calculations allow for a straightforward assessment of the π-backbonding (E→L) stabilization energy. The validity of the suggested resonance model is further confirmed by the complementary MPD calculations focusing on the E lone pair region as well as the E-L bonding region. Likewise, the MPD method reveals a strong influence of the σ-donating and π-accepting properties of the ligand. In particular, either one single domain or two symmetrical domains are found in the lone pair region of the central atom, supporting the predominance of either the "ylidene" or "ylidone" structures having one or two lone pairs at the central atom, respectively. Furthermore, the calculated average populations in the lone pair MPDs correlate very well with the natural bond orbital (NBO) populations, and can be related to the average number of electrons that is backdonated to the ligands. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

How children perceive fractals: Hierarchical self-similarity and cognitive development

PubMed Central

Martins, Maurício Dias; Laaha, Sabine; Freiberger, Eva Maria; Choi, Soonja; Fitch, W. Tecumseh

2014-01-01

The ability to understand and generate hierarchical structures is a crucial component of human cognition, available in language, music, mathematics and problem solving. Recursion is a particularly useful mechanism for generating complex hierarchies by means of self-embedding rules. In the visual domain, fractals are recursive structures in which simple transformation rules generate hierarchies of infinite depth. Research on how children acquire these rules can provide valuable insight into the cognitive requirements and learning constraints of recursion. Here, we used fractals to investigate the acquisition of recursion in the visual domain, and probed for correlations with grammar comprehension and general intelligence. We compared second (n = 26) and fourth graders (n = 26) in their ability to represent two types of rules for generating hierarchical structures: Recursive rules, on the one hand, which generate new hierarchical levels; and iterative rules, on the other hand, which merely insert items within hierarchies without generating new levels. We found that the majority of fourth graders, but not second graders, were able to represent both recursive and iterative rules. This difference was partially accounted by second graders’ impairment in detecting hierarchical mistakes, and correlated with between-grade differences in grammar comprehension tasks. Empirically, recursion and iteration also differed in at least one crucial aspect: While the ability to learn recursive rules seemed to depend on the previous acquisition of simple iterative representations, the opposite was not true, i.e., children were able to acquire iterative rules before they acquired recursive representations. These results suggest that the acquisition of recursion in vision follows learning constraints similar to the acquisition of recursion in language, and that both domains share cognitive resources involved in hierarchical processing. PMID:24955884

Age, distribution and style of deformation in Alaska north of 60°N: Implications for assembly of Alaska

USGS Publications Warehouse

Moore, Thomas; Box, Stephen E.

2016-01-01

The structural architecture of Alaska is the product of a complex history of deformation along both the Cordilleran and Arctic margins of North America involving oceanic plates, subduction zones and strike-slip faults and with continental elements of Laurentia, Baltica, and Siberia. We use geological constraints to assign regions of deformation to 14 time intervals and to map their distributions in Alaska. Alaska can be divided into three domains with differing deformational histories. Each domain includes a crustal fragment that originated near Early Paleozoic Baltica. The Northern domain experienced the Early Cretaceous Brookian orogeny, an oceanic arc-continent collision, followed by mid-Cretaceous extension. Early Cretaceous opening of the oceanic Canada Basin rifted the orogen from the Canadian Arctic margin, producing the bent trends of the orogen. The second (Southern) domain consists of Neoproterozoic and younger crust of the amalgamated Peninsular-Wrangellia-Alexander arc terrane and its paired Mesozoic accretionary prism facing the Pacific Ocean basin. The third (Interior) domain, situated between the first two domains and roughly bounded by the Cenozoic dextral Denali and Tintina faults, includes the large continental Yukon Composite and Farewell terranes having different Permian deformational episodes. Although a shared deformation that might mark their juxtaposition by collisional processes is unrecognized, sedimentary linkage between the two terranes and depositional overlap of the boundary with the Northern domain occurred by early Late Cretaceous. Late Late Cretaceous deformation is the first deformation shared by all three domains and correlates temporally with emplacement of the Southern domain against the remainder of Alaska. Early Cenozoic shortening is mild across interior Alaska but is significant in the Brooks Range, and correlates in time with dextral faulting, ridge subduction and counter-clockwise rotation of southern Alaska. Late Cenozoic shortening is significant in southern Alaska inboard of the underthrusting Yakutat terrane at the Pacific margin and in northeastern Alaska.

Structural stability of purified human CFTR is systematically improved by mutations in nucleotide binding domain 1.

PubMed

Yang, Zhengrong; Hildebrandt, Ellen; Jiang, Fan; Aleksandrov, Andrei A; Khazanov, Netaly; Zhou, Qingxian; An, Jianli; Mezzell, Andrew T; Xavier, Bala M; Ding, Haitao; Riordan, John R; Senderowitz, Hanoch; Kappes, John C; Brouillette, Christie G; Urbatsch, Ina L

2018-05-01

The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is an ABC transporter containing two transmembrane domains forming a chloride ion channel, and two nucleotide binding domains (NBD1 and NBD2). CFTR has presented a formidable challenge to obtain monodisperse, biophysically stable protein. Here we report a comprehensive study comparing effects of single and multiple NBD1 mutations on stability of both the NBD1 domain alone and on purified full length human CFTR. Single mutations S492P, A534P, I539T acted additively, and when combined with M470V, S495P, and R555K cumulatively yielded an NBD1 with highly improved structural stability. Strategic combinations of these mutations strongly stabilized the domain to attain a calorimetric T m  > 70 °C. Replica exchange molecular dynamics simulations on the most stable 6SS-NBD1 variant implicated fluctuations, electrostatic interactions and side chain packing as potential contributors to improved stability. Progressive stabilization of NBD1 directly correlated with enhanced structural stability of full-length CFTR protein. Thermal unfolding of the stabilized CFTR mutants, monitored by changes in intrinsic fluorescence, demonstrated that Tm could be shifted as high as 67.4 °C in 6SS-CFTR, more than 20 °C higher than wild-type. H1402S, an NBD2 mutation, conferred CFTR with additional thermal stability, possibly by stabilizing an NBD-dimerized conformation. CFTR variants with NBD1-stabilizing mutations were expressed at the cell surface in mammalian cells, exhibited ATPase and channel activity, and retained these functions to higher temperatures. The capability to produce enzymatically active CFTR with improved structural stability amenable to biophysical and structural studies will advance mechanistic investigations and future cystic fibrosis drug development. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

Miniature protein ligands for EVH1 domains: Interplay between affinity, specificity, and cell motility⊥

PubMed Central

Holtzman, Jennifer H.; Woronowicz, Kamil; Golemi-Kotra, Dasantila; Schepartz, Alanna

2008-01-01

Dynamic rearrangements of the actin cytoskeleton power cell motility in contexts ranging from intracellular microbial pathogenesis to axon guidance. The Ena/VASP family proteins--Mena, VASP, and Evl--are believed to control cell motility by serving as a direct link between signaling events and the actin cytoskeleton. Our lab has previously reported a novel miniature protein, pGolemi, which binds with high affinity to the EVH1 domain of Mena (Mena1-112) but not to those of VASP (VASP1-115) or Evl (Evl1-115) and also causes an unusual defect in actin-driven L. monocytogenes motility. Here, we use scanning mutagenesis to examine the effects of single amino acid changes within pGolemi on EVH1 domain affinity and specificity, miniature protein secondary structure, and L. monocytogenes motility. The data suggest that pGolemi contains the expected aPP-like fold and binds Mena1-112 in a manner highly analogous to the proline-rich repeat region of L. monocytogenes ActA protein. Residues throughout pGolemi contribute to both EVH1 domain affinity and paralog specificity. Moreover, the affinities of pGolemi variants for Mena1-112 correlate with selectivity against the EVH1 domains of VASP and Evl. In L. monocytogenes motility assays, speed and speed variability correlate strongly with EVH1 paralog specificity, suggesting that the Ena/VASP paralogs do not play equivalent roles in the process of L. monocytogenes actin tail maturation. PMID:17973491

Academic Difficulties in Children with Prenatal Alcohol Exposure: Presence, Profile, and Neural Correlates.

PubMed

Glass, Leila; Moore, Eileen M; Akshoomoff, Natacha; Jones, Kenneth Lyons; Riley, Edward P; Mattson, Sarah N

2017-05-01

Academic achievement was evaluated in children with heavy prenatal alcohol exposure to determine potential strengths and weaknesses, evaluate the utility of different definitions for identifying low academic performance, and explore the neural correlates that may underlie academic performance. Children (8 to 16 years) were assessed using the WIAT-II. Patterns of performance were examined in 2 subject groups: children with heavy prenatal alcohol exposure (n = 67) and controls (n = 61). A repeated-measures MANCOVA examining group differences on academic domain (reading, spelling, math) scores was conducted. Post hoc comparisons examined within-group profiles. Numbers and percentage of children with low achievement were calculated using several criteria. In a subsample (n = 42), neural correlates were analyzed using FreeSurfer v5.3 to examine relations between cortical structure (thickness and surface area) and performance. The alcohol-exposed group performed worse than controls on all domains and had a unique academic profile, supported by a significant group × academic domain interaction (p < 0.001). For the alcohol-exposed group, math reasoning was significantly lower than numerical operations, which was significantly lower than spelling and word reading. Over half of the alcohol-exposed group (58.2%) demonstrated low achievement on 1 or more academic domains. The number and percentage of children meeting criteria for low achievement varied based on the domain and definition used. The imaging analysis identified several surface area clusters that were differentially related to math (L superior parietal and R lateral/middle occipital) and spelling (bilateral inferior and medial temporal) performance by group, with no relations for the other academic domains. Generally, scores improved as surface area decreased in controls, whereas no relation or a positive relation was observed in the alcohol-exposed group. Alcohol-exposed children demonstrated deficits in academic performance across domains and definitions, with a relative weakness in math functioning. Atypical brain development may contribute to these impairments in academic achievement. Understanding academic difficulties can assist in advocating effectively for alcohol-exposed children. Copyright © 2017 by the Research Society on Alcoholism.

Scalable hierarchical PDE sampler for generating spatially correlated random fields using nonmatching meshes: Scalable hierarchical PDE sampler using nonmatching meshes

DOE PAGES

Osborn, Sarah; Zulian, Patrick; Benson, Thomas; ...

2018-01-30

This work describes a domain embedding technique between two nonmatching meshes used for generating realizations of spatially correlated random fields with applications to large-scale sampling-based uncertainty quantification. The goal is to apply the multilevel Monte Carlo (MLMC) method for the quantification of output uncertainties of PDEs with random input coefficients on general and unstructured computational domains. We propose a highly scalable, hierarchical sampling method to generate realizations of a Gaussian random field on a given unstructured mesh by solving a reaction–diffusion PDE with a stochastic right-hand side. The stochastic PDE is discretized using the mixed finite element method on anmore » embedded domain with a structured mesh, and then, the solution is projected onto the unstructured mesh. This work describes implementation details on how to efficiently transfer data from the structured and unstructured meshes at coarse levels, assuming that this can be done efficiently on the finest level. We investigate the efficiency and parallel scalability of the technique for the scalable generation of Gaussian random fields in three dimensions. An application of the MLMC method is presented for quantifying uncertainties of subsurface flow problems. Here, we demonstrate the scalability of the sampling method with nonmatching mesh embedding, coupled with a parallel forward model problem solver, for large-scale 3D MLMC simulations with up to 1.9·109 unknowns.« less

Scalable hierarchical PDE sampler for generating spatially correlated random fields using nonmatching meshes: Scalable hierarchical PDE sampler using nonmatching meshes

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

Osborn, Sarah; Zulian, Patrick; Benson, Thomas

This work describes a domain embedding technique between two nonmatching meshes used for generating realizations of spatially correlated random fields with applications to large-scale sampling-based uncertainty quantification. The goal is to apply the multilevel Monte Carlo (MLMC) method for the quantification of output uncertainties of PDEs with random input coefficients on general and unstructured computational domains. We propose a highly scalable, hierarchical sampling method to generate realizations of a Gaussian random field on a given unstructured mesh by solving a reaction–diffusion PDE with a stochastic right-hand side. The stochastic PDE is discretized using the mixed finite element method on anmore » embedded domain with a structured mesh, and then, the solution is projected onto the unstructured mesh. This work describes implementation details on how to efficiently transfer data from the structured and unstructured meshes at coarse levels, assuming that this can be done efficiently on the finest level. We investigate the efficiency and parallel scalability of the technique for the scalable generation of Gaussian random fields in three dimensions. An application of the MLMC method is presented for quantifying uncertainties of subsurface flow problems. Here, we demonstrate the scalability of the sampling method with nonmatching mesh embedding, coupled with a parallel forward model problem solver, for large-scale 3D MLMC simulations with up to 1.9·109 unknowns.« less

Natural single amino acid polymorphism (F19Y) in human galectin-8: detection of structural alterations and increased growth-regulatory activity on tumor cells.

PubMed

Ruiz, Federico M; Scholz, Barbara A; Buzamet, Eliza; Kopitz, Jürgen; André, Sabine; Menéndez, Margarita; Romero, Antonio; Solís, Dolores; Gabius, Hans-Joachim

2014-03-01

Natural amino acid substitution by single-site nucleotide polymorphism can become a valuable tool for structure-activity correlations, especially if evidence for association to disease parameters exists. Focusing on the F19Y change in human galectin-8, connected clinically to rheumatoid arthritis, we here initiate the study of consequences of a single-site substitution in the carbohydrate recognition domain of this family of cellular effectors. We apply a strategically combined set of structural and cell biological techniques for comparing properties of the wild-type and variant proteins. The overall hydrodynamic behavior of the full-length protein and of the separate N-domain is not noticeably altered, but displacements in the F0 β-strand of the β-sandwich fold in the N-domain are induced, as evidenced by protein crystallography. Analysis of thermal stability by circular dichroism spectroscopy revealed perceptible differences for the full-length proteins, pointing to an impact of the substitution beyond the N-domain. In addition, small differences in thermodynamic parameters of carbohydrate binding are detected. On the level of two types of tumor cells, characteristics of binding appeared rather similar. In further comparison of the influence on proliferation, the variant proved to be more active as growth regulator in the six tested lines of neuroblastoma, erythroleukemia and colon adenocarcinoma. The seemingly subtle structural change identified here thus has functional implications in vitro, encouraging further analysis in autoimmune regulation and, in a broad context, in work with other natural single-site variants, using the documented combined strategy. The atomic coordinates and structure factors (codes 4BMB, 4BME) have been deposited in the Protein Data Bank. © 2014 FEBS.

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

Structural requirements of oleosin domains for subcellular targeting to the oil body.

PubMed Central

van Rooijen, G J; Moloney, M M

1995-01-01

We have investigated the protein domains responsible for the correct subcellular targeting of plant seed oleosins. We have attempted to study this targeting in vivo using "tagged" oleosins in transgenic plants. Different constructs were prepared lacking gene sequences encoding one of three structural domains of natural oleosins. Each was fused in frame to the Escherichia coli uid A gene encoding beta-glucuronidase (GUS). These constructs were introduced into Brassica napus using Agrobacterium-mediated transformation. GUS activity was measured in washed oil bodies and in the soluble protein fraction of the transgenic seeds. It was found that complete Arabidopsis oleosin-GUS fusions undergo correct subcellular targeting in transgenic Brassica seeds. Removal of the C-terminal domain of the Arabidopsis oleosin comprising the last 48 amino acids had no effect on overall subcellular targeting. In contrast, loss of the first 47 amino acids (N terminus) or amino acids 48 to 113 (which make up a lipophilic core) resulted in impaired targeting of the fusion protein to the oil bodies and greatly reduced accumulation of the fusion protein. Northern blotting revealed that this reduction is not due to differences in mRNA accumulation. Results from these measurements indicated that both the N-terminal and central oleosin domain are important for targeting to the oil body and show that there is a direct correlation between the inability to target to the oil body and protein stability. PMID:8539295

Separate but Correlated: The Latent Structure of Space and Mathematics across Development

ERIC Educational Resources Information Center

Mix, Kelly S.; Levine, Susan C.; Cheng, Yi-Ling; Young, Chris; Hambrick, D. Zachary; Ping, Raedy

2016-01-01

The relations among various spatial and mathematics skills were assessed in a cross-sectional study of 854 children from kindergarten, third, and sixth grades (i.e., 5 to 13 years of age). Children completed a battery of spatial mathematics tests and their scores were submitted to exploratory factor analyses both within and across domains. In the…

Sensitivity of visual evoked potentials and spectral domain optical coherence tomography in early relapsing remitting multiple sclerosis.

PubMed

Behbehani, Raed; Ahmed, Samar; Al-Hashel, Jasem; Rousseff, Rossen T; Alroughani, Raed

2017-02-01

Visual evoked potentials and spectral-domain optical coherence tomography are common ancillary studies that assess the visual pathways from a functional and structural aspect, respectively. To compare prevalence of abnormalities of Visual evoked potentials (VEP) and spectral-domain optical coherence tomography (SDOCT) in patients with relapsing remitting multiple sclerosis (RRMS). A cross-sectional study of 100 eyes with disease duration of less than 5 years since the diagnosis. Correlation between retinal nerve fiber layer and ganglion-cell/inner plexiform layer with pattern-reversal visual evoked potentials amplitude and latency and contrast sensitivity was performed. The prevalence of abnormalities in pattern-reversal visual VEP was 56% while that of SOCT was 48% in all eyes. There was significant negative correlations between the average RNFL (r=-0.34, p=0.001) and GCIPL (r=-0.39, p<0.001) with VEP latency. In eyes with prior optic neuritis, a significant negative correlation was seen between average RNFL (r=-0.33, p=0.037) and GCIPL (r=-0.40, p=0.010) with VEP latency. We have found higher prevalence of VEP abnormalities than SCOCT in early relapsing-remitting multiple sclerosis. This suggests that VEP has a higher sensitivity for detecting lesions of the visual pathway in patients with early RRMS. Copyright © 2016 Elsevier B.V. All rights reserved.

Construct validity of the PROMIS® sexual function and satisfaction measures in patients with cancer

PubMed Central

2013-01-01

Background With data from a diverse sample of patients either in treatment for cancer or post-treatment for cancer, we examine inter-domain and cross-domain correlations among the core domains of the Patient-Reported Outcomes Measurement Information System Sexual Function and Satisfaction measures (PROMIS® SexFS) and the corresponding domains from conceptually-similar measures of sexual function, the International Index of Erectile Function and the Female Sexual Function Index. Findings Men (N=389) and women (N=430) were recruited from a tumor registry, oncology clinics, and an internet panel. The PROMIS SexFS, International Index of Erectile Function, and Female Sexual Function Index were used to collect participants’ self-reported sexual function. The domains shared among the measures include desire/interest in sexual activity, lubrication and vaginal discomfort/pain (women), erectile function (men), orgasm, and satisfaction. We examined correlations among different domains within the same instrument (discriminant validity) and correlations among similar domains measured by different instruments (convergent validity). Correlations demonstrating discriminant validity ranged from 0.38 to 0.73 for men and 0.48 to 0.74 for women, while correlations demonstrating convergent validity ranged from 0.62 to 0.83 for men and 0.71 to 0.92 for women. As expected, correlations demonstrating convergent validity were higher than correlations demonstrating discriminant validity, with one exception (orgasm for men). Conclusions Construct validity was supported by convergent and discriminant validity in a diverse sample of patients with cancer. For patients with cancer who may or may not have sexual dysfunction, the PROMIS SexFS measures provide a comprehensive assessment of key domains of sexual function and satisfaction. PMID:23497200

Source Reconstruction of Brain Potentials Using Bayesian Model Averaging to Analyze Face Intra-Domain vs. Face-Occupation Cross-Domain Processing

PubMed Central

Olivares, Ela I.; Lage-Castellanos, Agustín; Bobes, María A.; Iglesias, Jaime

2018-01-01

We investigated the neural correlates of the access to and retrieval of face structure information in contrast to those concerning the access to and retrieval of person-related verbal information, triggered by faces. We experimentally induced stimulus familiarity via a systematic learning procedure including faces with and without associated verbal information. Then, we recorded event-related potentials (ERPs) in both intra-domain (face-feature) and cross-domain (face-occupation) matching tasks while N400-like responses were elicited by incorrect eyes-eyebrows completions and occupations, respectively. A novel Bayesian source reconstruction approach plus conjunction analysis of group effects revealed that in both cases the generated N170s were of similar amplitude but had different neural origin. Thus, whereas the N170 of faces was associated predominantly to right fusiform and occipital regions (the so-called “Fusiform Face Area”, “FFA” and “Occipital Face Area”, “OFA”, respectively), the N170 of occupations was associated to a bilateral very posterior activity, suggestive of basic perceptual processes. Importantly, the right-sided perceptual P200 and the face-related N250 were evoked exclusively in the intra-domain task, with sources in OFA and extensively in the fusiform region, respectively. Regarding later latencies, the intra-domain N400 seemed to be generated in right posterior brain regions encompassing mainly OFA and, to some extent, the FFA, likely reflecting neural operations triggered by structural incongruities. In turn, the cross-domain N400 was related to more anterior left-sided fusiform and temporal inferior sources, paralleling those described previously for the classic verbal N400. These results support the existence of differentiated neural streams for face structure and person-related verbal processing triggered by faces, which can be activated differentially according to specific task demands. PMID:29628877

Mapping flexible protein domains at subnanometer resolution with the atomic force microscope.

PubMed

Müller, D J; Fotiadis, D; Engel, A

1998-06-23

The mapping of flexible protein domains with the atomic force microscope is reviewed. Examples discussed are the bacteriorhodopsin from Halobacterium salinarum, the head-tail-connector from phage phi29, and the hexagonally packed intermediate layer from Deinococcus radiodurans which all were recorded in physiological buffer solution. All three proteins undergo reversible structural changes that are reflected in standard deviation maps calculated from aligned topographs of individual protein complexes. Depending on the lateral resolution (up to 0.8 nm) flexible surface regions can ultimately be correlated with individual polypeptide loops. In addition, multivariate statistical classification revealed the major conformations of the protein surface.

Magnetoelectric control of spin-chiral ferroelectric domains in a triangular lattice antiferromagnet

NASA Astrophysics Data System (ADS)

Kimura, Kenta; Nakamura, Hiroyuki; Ohgushi, Kenya; Kimura, Tsuyoshi

2008-10-01

We have grown single crystals of a triangular lattice antiferromagnet (TLA), CuCrO2 , and investigated the correlation between magnetic and dielectric properties. Two magnetic phase transitions are observed at TN2≈24.2K and TN1≈23.6K . It was found that ferroelectric polarization along the triangular lattice plane develops at TN1 , suggesting that the system undergoes a transition into an out-of-plane 120° spin-chiral phase at TN1 . The TLA provides an opportunity for unique magnetoelectric control of spin-chiral ferroelectric domain structures by means of electric and/or magnetic fields.

Structural predictions for Correlated Electron Materials Using the Functional Dynamical Mean Field Theory Approach

NASA Astrophysics Data System (ADS)

Haule, Kristjan

2018-04-01

The Dynamical Mean Field Theory (DMFT) in combination with the band structure methods has been able to address reach physics of correlated materials, such as the fluctuating local moments, spin and orbital fluctuations, atomic multiplet physics and band formation on equal footing. Recently it is getting increasingly recognized that more predictive ab-initio theory of correlated systems needs to also address the feedback effect of the correlated electronic structure on the ionic positions, as the metal-insulator transition is almost always accompanied with considerable structural distortions. We will review recently developed extension of merger between the Density Functional Theory (DFT) and DMFT method, dubbed DFT+ embedded DMFT (DFT+eDMFT), whichsuccessfully addresses this challenge. It is based on the stationary Luttinger-Ward functional to minimize the numerical error, it subtracts the exact double-counting of DFT and DMFT, and implements self-consistent forces on all atoms in the unit cell. In a few examples, we will also show how the method elucidated the important feedback effect of correlations on crystal structure in rare earth nickelates to explain the mechanism of the metal-insulator transition. The method showed that such feedback effect is also essential to understand the dynamic stability of the high-temperature body-centered cubic phase of elemental iron, and in particular it predicted strong enhancement of the electron-phonon coupling over DFT values in FeSe, which was very recently verified by pioneering time-domain experiment.

Macular Thickness Assessment in Patients with Glaucoma and Its Correlation with Visual Fields

PubMed Central

Vaz, Fernando T; Ramalho, Mário; Pedrosa, Catarina; Lisboa, Maria; Kaku, Paulo; Esperancinha, Florindo

2016-01-01

Aim To determine the relationship between macular thickness (MT) and visual field (VF) parameters, as well as with changes in the retinal nerve fiber layer (RNFL) thickness in patients with glaucoma and ocular hypertension (OH). Materials and methods Cross-sectional statistical analysis of spectral domain optical coherence tomography (SD-OCT) compared with several VF parameters (mean defect - MD and loss variance - LV), in a nonrandom sample of 70 eyes from patients with glaucoma or OH. Statistical analysis was performed using Statistical Package for Social Sciences®. The correlation coefficient used was determined by Spearman correlation and the value of p < 0.05 was considered statistically significant. Results A significant correlation was seen between VF parameters and decrease in MT (MD: r = –0.363, p = 0.002; LV: r=–0.378, p = 0.001). The results were more significant when we compared the LV in the group with average MT 270 to 300 μm (r = –0.413, p = 0.015). Asymmetry between the superior macula and inferior macula correlated with LV (r = 0.432, p = 0.019) in the group with MT < 270 μm. There was also a significant correlation between thinning of superior-temporal and inferior-temporal RNFL and the decrease of the superior and inferior MT respectively (p < 0.001). Conclusion Spectral domain optical coherence tomography measurements of retinal thickness in the macula correlate with VF parameters and RNFL parameters in glaucoma patients. This relationship was first demonstrated with static computerized perimetry made with Octopus 101®. These results can be a valuable aid for evaluating and monitoring of glaucoma patients, establishing a correlation between structure and function. Measurements of retinal thickness in the macula may be an additional instrument for early detection of structural changes and its correlation with functional defects. How to cite this article Mota M, Vaz FT, Ramalho M, Pedrosa C, Lisboa M, Kaku P, Esperancinha F. Macular Thickness Assessment in Patients with Glaucoma and Its Correlation with Visual Fields. J Curr Glaucoma Pract 2016;10(3):85-90. PMID:27857487

Ares I-X In-Flight Modal Identification

NASA Technical Reports Server (NTRS)

Bartkowicz, Theodore J.; James, George H., III

2011-01-01

Operational modal analysis is a procedure that allows the extraction of modal parameters of a structure in its operating environment. It is based on the idealized premise that input to the structure is white noise. In some cases, when free decay responses are corrupted by unmeasured random disturbances, the response data can be processed into cross-correlation functions that approximate free decay responses. Modal parameters can be computed from these functions by time domain identification methods such as the Eigenvalue Realization Algorithm (ERA). The extracted modal parameters have the same characteristics as impulse response functions of the original system. Operational modal analysis is performed on Ares I-X in-flight data. Since the dynamic system is not stationary due to propellant mass loss, modal identification is only possible by analyzing the system as a series of linearized models over short periods of time via a sliding time-window of short time intervals. A time-domain zooming technique was also employed to enhance the modal parameter extraction. Results of this study demonstrate that free-decay time domain modal identification methods can be successfully employed for in-flight launch vehicle modal extraction.

Experimental validation of solid rocket motor damping models

NASA Astrophysics Data System (ADS)

Riso, Cristina; Fransen, Sebastiaan; Mastroddi, Franco; Coppotelli, Giuliano; Trequattrini, Francesco; De Vivo, Alessio

2017-12-01

In design and certification of spacecraft, payload/launcher coupled load analyses are performed to simulate the satellite dynamic environment. To obtain accurate predictions, the system damping properties must be properly taken into account in the finite element model used for coupled load analysis. This is typically done using a structural damping characterization in the frequency domain, which is not applicable in the time domain. Therefore, the structural damping matrix of the system must be converted into an equivalent viscous damping matrix when a transient coupled load analysis is performed. This paper focuses on the validation of equivalent viscous damping methods for dynamically condensed finite element models via correlation with experimental data for a realistic structure representative of a slender launch vehicle with solid rocket motors. A second scope of the paper is to investigate how to conveniently choose a single combination of Young's modulus and structural damping coefficient—complex Young's modulus—to approximate the viscoelastic behavior of a solid propellant material in the frequency band of interest for coupled load analysis. A scaled-down test article inspired to the Z9-ignition Vega launcher configuration is designed, manufactured, and experimentally tested to obtain data for validation of the equivalent viscous damping methods. The Z9-like component of the test article is filled with a viscoelastic material representative of the Z9 solid propellant that is also preliminarily tested to investigate the dependency of the complex Young's modulus on the excitation frequency and provide data for the test article finite element model. Experimental results from seismic and shock tests performed on the test configuration are correlated with numerical results from frequency and time domain analyses carried out on its dynamically condensed finite element model to assess the applicability of different equivalent viscous damping methods to describe damping properties of slender launch vehicles in payload/launcher coupled load analysis.

Experimental validation of solid rocket motor damping models

NASA Astrophysics Data System (ADS)

Riso, Cristina; Fransen, Sebastiaan; Mastroddi, Franco; Coppotelli, Giuliano; Trequattrini, Francesco; De Vivo, Alessio

2018-06-01

In design and certification of spacecraft, payload/launcher coupled load analyses are performed to simulate the satellite dynamic environment. To obtain accurate predictions, the system damping properties must be properly taken into account in the finite element model used for coupled load analysis. This is typically done using a structural damping characterization in the frequency domain, which is not applicable in the time domain. Therefore, the structural damping matrix of the system must be converted into an equivalent viscous damping matrix when a transient coupled load analysis is performed. This paper focuses on the validation of equivalent viscous damping methods for dynamically condensed finite element models via correlation with experimental data for a realistic structure representative of a slender launch vehicle with solid rocket motors. A second scope of the paper is to investigate how to conveniently choose a single combination of Young's modulus and structural damping coefficient—complex Young's modulus—to approximate the viscoelastic behavior of a solid propellant material in the frequency band of interest for coupled load analysis. A scaled-down test article inspired to the Z9-ignition Vega launcher configuration is designed, manufactured, and experimentally tested to obtain data for validation of the equivalent viscous damping methods. The Z9-like component of the test article is filled with a viscoelastic material representative of the Z9 solid propellant that is also preliminarily tested to investigate the dependency of the complex Young's modulus on the excitation frequency and provide data for the test article finite element model. Experimental results from seismic and shock tests performed on the test configuration are correlated with numerical results from frequency and time domain analyses carried out on its dynamically condensed finite element model to assess the applicability of different equivalent viscous damping methods to describe damping properties of slender launch vehicles in payload/launcher coupled load analysis.

Distinct structural transitions of chromatin topological domains correlate with coordinated hormone-induced gene regulation

PubMed Central

Le Dily, François; Baù, Davide; Pohl, Andy; Vicent, Guillermo P.; Serra, François; Soronellas, Daniel; Castellano, Giancarlo; Wright, Roni H.G.; Ballare, Cecilia; Filion, Guillaume; Marti-Renom, Marc A.

2014-01-01

The human genome is segmented into topologically associating domains (TADs), but the role of this conserved organization during transient changes in gene expression is not known. Here we describe the distribution of progestin-induced chromatin modifications and changes in transcriptional activity over TADs in T47D breast cancer cells. Using ChIP-seq (chromatin immunoprecipitation combined with high-throughput sequencing), Hi-C (chromosome capture followed by high-throughput sequencing), and three-dimensional (3D) modeling techniques, we found that the borders of the ∼2000 TADs in these cells are largely maintained after hormone treatment and that up to 20% of the TADs could be considered as discrete regulatory units where the majority of the genes are either transcriptionally activated or repressed in a coordinated fashion. The epigenetic signatures of the TADs are homogeneously modified by hormones in correlation with the transcriptional changes. Hormone-induced changes in gene activity and chromatin remodeling are accompanied by differential structural changes for activated and repressed TADs, as reflected by specific and opposite changes in the strength of intra-TAD interactions within responsive TADs. Indeed, 3D modeling of the Hi-C data suggested that the structure of TADs was modified upon treatment. The differential responses of TADs to progestins and estrogens suggest that TADs could function as “regulons” to enable spatially proximal genes to be coordinately transcribed in response to hormones. PMID:25274727

Dynamics of water around the complex structures formed between the KH domains of far upstream element binding protein and single-stranded DNA molecules

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

Chakraborty, Kaushik; Bandyopadhyay, Sanjoy, E-mail: sanjoy@chem.iitkgp.ernet.in

2015-07-28

Single-stranded DNA (ss-DNA) binding proteins specifically bind to the single-stranded regions of the DNA and protect it from premature annealing, thereby stabilizing the DNA structure. We have carried out atomistic molecular dynamics simulations of the aqueous solutions of two DNA binding K homology (KH) domains (KH3 and KH4) of the far upstream element binding protein complexed with two short ss-DNA segments. Attempts have been made to explore the influence of the formation of such complex structures on the microscopic dynamics and hydrogen bond properties of the interfacial water molecules. It is found that the water molecules involved in bridging themore » ss-DNA segments and the protein domains form a highly constrained thin layer with extremely retarded mobility. These water molecules play important roles in freezing the conformational oscillations of the ss-DNA oligomers and thereby forming rigid complex structures. Further, it is demonstrated that the effect of complexation on the slow long-time relaxations of hydrogen bonds at the interface is correlated with hindered motions of the surrounding water molecules. Importantly, it is observed that the highly restricted motions of the water molecules bridging the protein and the DNA components in the complexed forms originate from more frequent hydrogen bond reformations.« less

Structure and inference in annotated networks

PubMed Central

Newman, M. E. J.; Clauset, Aaron

2016-01-01

For many networks of scientific interest we know both the connections of the network and information about the network nodes, such as the age or gender of individuals in a social network. Here we demonstrate how this ‘metadata' can be used to improve our understanding of network structure. We focus in particular on the problem of community detection in networks and develop a mathematically principled approach that combines a network and its metadata to detect communities more accurately than can be done with either alone. Crucially, the method does not assume that the metadata are correlated with the communities we are trying to find. Instead, the method learns whether a correlation exists and correctly uses or ignores the metadata depending on whether they contain useful information. We demonstrate our method on synthetic networks with known structure and on real-world networks, large and small, drawn from social, biological and technological domains. PMID:27306566

Structure and inference in annotated networks

NASA Astrophysics Data System (ADS)

Newman, M. E. J.; Clauset, Aaron

2016-06-01

For many networks of scientific interest we know both the connections of the network and information about the network nodes, such as the age or gender of individuals in a social network. Here we demonstrate how this `metadata' can be used to improve our understanding of network structure. We focus in particular on the problem of community detection in networks and develop a mathematically principled approach that combines a network and its metadata to detect communities more accurately than can be done with either alone. Crucially, the method does not assume that the metadata are correlated with the communities we are trying to find. Instead, the method learns whether a correlation exists and correctly uses or ignores the metadata depending on whether they contain useful information. We demonstrate our method on synthetic networks with known structure and on real-world networks, large and small, drawn from social, biological and technological domains.

Modeling metabolic syndrome and its association with cognition: the Northern Manhattan study.

PubMed

Levin, Bonnie E; Llabre, Maria M; Dong, Chuanhui; Elkind, Mitchell S V; Stern, Yaakov; Rundek, Tatjana; Sacco, Ralph L; Wright, Clinton B

2014-11-01

Metabolic syndrome (MetS) is a clustering of vascular risk factors and is associated with increased risk of cardiovascular disease. Less is known about the relationship between MetS and cognition. We examined component vascular risk factors of MetS as correlates of different cognitive domains. The Northern Manhattan Study (NOMAS) includes 1290 stroke-free participants from a largely Hispanic multi-ethnic urban community. We used structural equation modeling (SEM) to model latent variables of MetS, assessed at baseline and an average of 10 years later, at which time participants also underwent a full cognitive battery. The two four-factor models, of the metabolic syndrome (blood pressure, lipid levels, obesity, and fasting glucose) and of cognition (language, executive function, psychomotor, and memory), were each well supported (CFI=0.97 and CFI=0.95, respectively). When the two models were combined, the correlation between metabolic syndrome and cognition was -.31. Among the metabolic syndrome components, only blood pressure uniquely predicted all four cognitive domains. After adjusting for age, gender, race/ethnicity, education, smoking, alcohol, and risk factor treatment variables, blood pressure remained a significant correlate of all domains except memory. In this stroke-free race/ethnically diverse community-based cohort, MetS was associated with cognitive function suggesting that MetS and its components may be important predictors of cognitive outcomes. After adjusting for sociodemographic and vascular risk factors, blood pressure was the strongest correlate of cognitive performance. Findings suggest MetS, and in particular blood pressure, may represent markers of vascular or neurodegenerative damage in aging populations.

Psychometric properties of the Iranian interview-administered version of the World Health Organization's Quality of Life Questionnaire (WHOQOL-BREF): a population-based study.

PubMed

Nedjat, Saharnaz; Montazeri, Ali; Holakouie, Kourosh; Mohammad, Kazem; Majdzadeh, Reza

2008-03-21

The objective of the current study was to translate and validate the Iranian version of the WHOQOL-BREF. A forward-backward translation procedure was followed to develop the Iranian version of the questionnaire. A stratified random sample of individuals aged 18 and over completed the questionnaire in Tehran, Iran. Psychometric properties of the instrument including reliability (internal consistency, and test-retest analysis), validity (known groups' comparison and convergent validity), and items' correlation with their hypothesized domains were assessed. In all 1164 individuals entered into the study. The mean age of the participants was 36.6 (SD = 13.2) years, and the mean years of their formal education was 10.7 (SD = 4.4). In general the questionnaire received well and all domains met the minimum reliability standards (Cronbach's alpha and intra-class correlation > 0.7), except for social relationships (alpha = 0.55). Performing known groups' comparison analysis, the results indicated that the questionnaire discriminated well between subgroups of the study samples differing in their health status. Since the WHOQOL-BREF demonstrated statistically significant correlation with the Iranian version of the SF-36 as expected, the convergent validity of the questionnaire was found to be desirable. Correlation matrix also showed satisfactory results in all domains except for social relationships. This study has provided some preliminary evidence of the reliability and validity of the WHOQOL-BREF to be used in Iran, though further research is required to challenge the problems of reliability in one of the dimensions and the instrument's factor structure.

Relating surface roughness and magnetic domain structure to giant magneto-impedance of Co-rich melt-extracted microwires

DOE PAGES

Jiang, S. D.; Eggers, T.; Thiabgoh, O.; ...

2017-04-11

Understanding the relationship between the surface conditions and giant magneto-impedance (GMI) in Co-rich melt-extracted microwires is key to optimizing their magnetic responses for magnetic sensor applications. The surface magnetic domain structure (SMDS) parameters of ~45 μm diameter Co 69.25Fe 4.25Si 13B 13.5-xZr x (x = 0, 1, 2, 3) microwires, including the magnetic domain period (d) and surface roughness (Rq) as extracted from the magnetic force microscopy (MFM) images, have been correlated with GMI in the range 1–1000 MHz. It was found that substitution of B with 1 at. % Zr increased d of the base alloy from 729 tomore » 740 nm while retaining Rq from ~1 nm to ~3 nm. A tremendous impact on the GMI ratio was found, increasing the ratio from ~360% to ~490% at an operating frequency of 40 MHz. Further substitution with Zr decreased the high frequency GMI ratio, which can be understood by the significant increase in surface roughness evident by force microscopy. Lastly, this study demonstrates the application of the domain period and surface roughness found by force microscopy to the interpretation of the GMI in Co-rich microwires.« less

Structural pathway of regulated substrate transfer and threading through an Hsp100 disaggregase.

PubMed

Deville, Célia; Carroni, Marta; Franke, Kamila B; Topf, Maya; Bukau, Bernd; Mogk, Axel; Saibil, Helen R

2017-08-01

Refolding aggregated proteins is essential in combating cellular proteotoxic stress. Together with Hsp70, Hsp100 chaperones, including Escherichia coli ClpB, form a powerful disaggregation machine that threads aggregated polypeptides through the central pore of tandem adenosine triphosphatase (ATPase) rings. To visualize protein disaggregation, we determined cryo-electron microscopy structures of inactive and substrate-bound ClpB in the presence of adenosine 5'- O -(3-thiotriphosphate), revealing closed AAA+ rings with a pronounced seam. In the substrate-free state, a marked gradient of resolution, likely corresponding to mobility, spans across the AAA+ rings with a dynamic hotspot at the seam. On the seam side, the coiled-coil regulatory domains are locked in a horizontal, inactive orientation. On the opposite side, the regulatory domains are accessible for Hsp70 binding, substrate targeting, and activation. In the presence of the model substrate casein, the polypeptide threads through the entire pore channel and increased nucleotide occupancy correlates with higher ATPase activity. Substrate-induced domain displacements indicate a pathway of regulated substrate transfer from Hsp70 to the ClpB pore, inside which a spiral of loops contacts the substrate. The seam pore loops undergo marked displacements, along with ordering of the regulatory domains. These asymmetric movements suggest a mechanism for ATPase activation and substrate threading during disaggregation.

Spatially Restricted and Developmentally Dynamic Expression of Engrailed Genes in Multiple Cerebellar Cell Types

PubMed Central

Wilson, Sandra L.; Kalinovsky, Anna; Orvis, Grant D.

2011-01-01

The cerebellum is a highly organized structure partitioned into lobules along the anterior–posterior (A-P) axis and into striped molecular domains along the medial–lateral (M-L) axis. The Engrailed (En) homeobox genes are required for patterning the morphological and molecular domains along both axes, as well as for the establishment of the normal afferent topography required to generate a fully functional cerebellum. As a means to understand how the En genes regulate multiple levels of cerebellum construction, we characterized En1 and En2 expression around birth and at postnatal day (P)21 during the period when the cerebellum undergoes a remarkable transformation from a smooth ovoid structure to a highly foliated structure. We show that both En1 and En2 are expressed in many neuronal cell types in the cerebellum, and expression persists until at least P21. En1 and En2 expression, however, undergoes profound changes in their cellular and spatial distributions between embryonic stages and P21, and their expression domains become largely distinct. Comparison of the distribution of En-expressing Purkinje cells relative to early- and late-onset Purkinje cell M-L stripe proteins revealed that although En1- and En2-expressing Purkinje cell domains do not strictly align with those of ZEBRINII at P21, a clear pattern exists that is most evident at E17.5 by an inverse correlation between the level of En2 expression and PLCβ4 and EPHA4. PMID:21431469

Aggression in toddlers: associations with parenting and marital relations.

PubMed

Brook, J S; Zheng, L; Whiteman, M; Brook, D W

2001-06-01

This study examined the relation among parenting factors, marital relations, and toddler aggression. A structured questionnaire was administered to both parents of 254 2-year-olds. The authors used correlation and hierarchical multiple regression analyses to assess the extent to which certain personality traits, drug use, parenting style, and marital conflicts were related to the toddlers' aggressive behavior. Results showed that the maternal child-rearing and parental aggression domains had a direct effect on toddler aggression. The domain of maternal child rearing also served as a mediator for the domains of marital relations, paternal child rearing, parental aggression, and parental drug use. The findings indicated that maternal child-rearing practices, personality attributes, and drug use were more important than paternal attributes in relation to toddler aggression. Implications for prevention among families at risk are discussed.

Improving the resolution for Lamb wave testing via a smoothed Capon algorithm

NASA Astrophysics Data System (ADS)

Cao, Xuwei; Zeng, Liang; Lin, Jing; Hua, Jiadong

2018-04-01

Lamb wave testing is promising for damage detection and evaluation in large-area structures. The dispersion of Lamb waves is often unavoidable, restricting testing resolution and making the signal hard to interpret. A smoothed Capon algorithm is proposed in this paper to estimate the accurate path length of each wave packet. In the algorithm, frequency domain whitening is firstly used to obtain the transfer function in the bandwidth of the excitation pulse. Subsequently, wavenumber domain smoothing is employed to reduce the correlation between wave packets. Finally, the path lengths are determined by distance domain searching based on the Capon algorithm. Simulations are applied to optimize the number of smoothing times. Experiments are performed on an aluminum plate consisting of two simulated defects. The results demonstrate that spatial resolution is improved significantly by the proposed algorithm.

Automated Processing Workflow for Ambient Seismic Recordings

NASA Astrophysics Data System (ADS)

Girard, A. J.; Shragge, J.

2017-12-01

Structural imaging using body-wave energy present in ambient seismic data remains a challenging task, largely because these wave modes are commonly much weaker than surface wave energy. In a number of situations body-wave energy has been extracted successfully; however, (nearly) all successful body-wave extraction and imaging approaches have focused on cross-correlation processing. While this is useful for interferometric purposes, it can also lead to the inclusion of unwanted noise events that dominate the resulting stack, leaving body-wave energy overpowered by the coherent noise. Conversely, wave-equation imaging can be applied directly on non-correlated ambient data that has been preprocessed to mitigate unwanted energy (i.e., surface waves, burst-like and electromechanical noise) to enhance body-wave arrivals. Following this approach, though, requires a significant preprocessing effort on often Terabytes of ambient seismic data, which is expensive and requires automation to be a feasible approach. In this work we outline an automated processing workflow designed to optimize body wave energy from an ambient seismic data set acquired on a large-N array at a mine site near Lalor Lake, Manitoba, Canada. We show that processing ambient seismic data in the recording domain, rather than the cross-correlation domain, allows us to mitigate energy that is inappropriate for body-wave imaging. We first develop a method for window selection that automatically identifies and removes data contaminated by coherent high-energy bursts. We then apply time- and frequency-domain debursting techniques to mitigate the effects of remaining strong amplitude and/or monochromatic energy without severely degrading the overall waveforms. After each processing step we implement a QC check to investigate improvements in the convergence rates - and the emergence of reflection events - in the cross-correlation plus stack waveforms over hour-long windows. Overall, the QC analyses suggest that automated preprocessing of ambient seismic recordings in the recording domain successfully mitigates unwanted coherent noise events in both the time and frequency domain. Accordingly, we assert that this method is beneficial for direct wave-equation imaging with ambient seismic recordings.

Structure and Correlates of Cognitive Aging in a Narrow Age Cohort

PubMed Central

2014-01-01

Aging-related changes occur for multiple domains of cognitive functioning. An accumulating body of research indicates that, rather than representing statistically independent phenomena, aging-related cognitive changes are moderately to strongly correlated across domains. However, previous studies have typically been conducted in age-heterogeneous samples over longitudinal time lags of 6 or more years, and have failed to consider whether results are robust to a comprehensive set of controls. Capitalizing on 3-year longitudinal data from the Lothian Birth Cohort of 1936, we took a longitudinal narrow age cohort approach to examine cross-domain cognitive change interrelations from ages 70 to 73 years. We fit multivariate latent difference score models to factors representing visuospatial ability, processing speed, memory, and crystallized ability. Changes were moderately interrelated, with a general factor of change accounting for 47% of the variance in changes across domains. Change interrelations persisted at close to full strength after controlling for a comprehensive set of demographic, physical, and medical factors including educational attainment, childhood intelligence, physical function, APOE genotype, smoking status, diagnosis of hypertension, diagnosis of cardiovascular disease, and diagnosis of diabetes. Thus, the positive manifold of aging-related cognitive changes is highly robust in that it can be detected in a narrow age cohort followed over a relatively brief longitudinal period, and persists even after controlling for many potential confounders. PMID:24955992

Structure and correlates of cognitive aging in a narrow age cohort.

PubMed

Tucker-Drob, Elliot M; Briley, Daniel A; Starr, John M; Deary, Ian J

2014-06-01

Aging-related changes occur for multiple domains of cognitive functioning. An accumulating body of research indicates that, rather than representing statistically independent phenomena, aging-related cognitive changes are moderately to strongly correlated across domains. However, previous studies have typically been conducted in age-heterogeneous samples over longitudinal time lags of 6 or more years, and have failed to consider whether results are robust to a comprehensive set of controls. Capitalizing on 3-year longitudinal data from the Lothian Birth Cohort of 1936, we took a longitudinal narrow age cohort approach to examine cross-domain cognitive change interrelations from ages 70 to 73 years. We fit multivariate latent difference score models to factors representing visuospatial ability, processing speed, memory, and crystallized ability. Changes were moderately interrelated, with a general factor of change accounting for 47% of the variance in changes across domains. Change interrelations persisted at close to full strength after controlling for a comprehensive set of demographic, physical, and medical factors including educational attainment, childhood intelligence, physical function, APOE genotype, smoking status, diagnosis of hypertension, diagnosis of cardiovascular disease, and diagnosis of diabetes. Thus, the positive manifold of aging-related cognitive changes is highly robust in that it can be detected in a narrow age cohort followed over a relatively brief longitudinal period, and persists even after controlling for many potential confounders. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Dynamic oligomeric conversions of the cytoplasmic RCK domains mediate MthK potassium channel activity.

PubMed

Kuo, Mario Meng-Chiang; Baker, Kent A; Wong, Lee; Choe, Senyon

2007-02-13

The crystal structure of the RCK-containing MthK provides a molecular framework for understanding the ligand gating mechanisms of K+ channels. Here we examined the macroscopic currents of MthK in enlarged Escherichia coli membrane by patch clamp and rapid perfusion techniques and showed that the channel undergoes desensitization in seconds after activation by Ca2+ or Cd2+. Additionally, MthK is inactivated by slightly acidic pH only from the cytoplasmic side. Examinations of isolated RCK domain by size-exclusion chromatography, static light scattering, analytical sedimentation, and stopped-flow spectroscopy show that Ca2+ rapidly converts isolated RCK monomers to multimers at alkaline pH. In contrast, the RCK domain at acidic pH remains firmly dimeric regardless of Ca2+ but restores predominantly to multimer or monomer at basic pH with or without Ca2+, respectively. These functional and biochemical analyses correlate the four functional states of the MthK channel with distinct oligomeric states of its RCK domains and indicate that the RCK domains undergo oligomeric conversions in modulating MthK activities.

Estimation of pH effect on the structure and stability of kinase domain of human integrin-linked kinase.

PubMed

Syed, Sunayana Begum; Shahbaaz, Mohd; Khan, Sabab Hassan; Srivastava, Saurabha; Islam, Asimul; Ahmad, Faizan; Hassan, Md Imtaiyaz

2018-01-07

Integrin-linked kinase (ILK) is an evolutionarily conserved Ser/Thr protein kinase, involved in many physiological functions such as signal transduction, actin rearrangement, cell proliferation, migration, polarisation, angiogenesis and apoptosis. An increased expression of ILK is associated with different cancers and thus considered as an attractive target for cancer therapy. We have successfully cloned, expressed and purified the kinase domain (193-446 residues) of ILK. To see the effect of pH on the structure and conformation, we performed circular diachroism, fluorescence and absorbance measurements in a wide range of pH conditions. We observed that within the range of pH 7.5-11.0, ILK 193-446 maintains its both secondary and tertiary structures. While visible aggregates were observed under the acidic pH 2.0-5.5 conditions, in order to complement these observations, we have performed molecular dynamics simulations of this kinase domain by mimicking diverse pH conditions which enabled us to see conformational preferences of the protein under such conditions. A significant correlation between the spectroscopic and molecular dynamics simulation was observed. These findings are useful to understand the conformation of ILK protein under certain pH condition which may be further implicated in the drug design and discovery.

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.

Membrane-Surface Anchoring of Charged Diacylglycerol-Lactones Correlates with Biological Activities | Center for Cancer Research

Cancer.gov

The inside cover picture shows the molecular structure of a DAG lactone derivative on top of the inner leaflet of a DMPC bilayer. The confocal microscopy image illustrates DAG-lactone-stimulated membrane localization of PKCδ-ECFP in living cells, while the space-filling model shows the surface of the C1B domain of PKCδ, the target of the lactone.

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

Becker, Verena; Sengupta, D; Ketteler, Robin

The formation of signal-promoting dimeric or oligomeric receptor complexes at the cell surface is modulated by self-interaction of their transmembrane (TM) domains. To address the importance of TM domain packing density for receptor functionality, we examined a set of asparagine mutants in the TM domain of the erythropoietin receptor (EpoR). We identified EpoR-T242N as a receptor variant that is present at the cell surface similar to wild-type EpoR but lacks visible localization in vesicle-like structures and is impaired in efficient activation of specific signaling cascades. Analysis by a molecular modeling approach indicated an increased interhelical distance for the EpoR-T242N TMmore » dimer. By employing the model, we designed additional mutants with increased or decreased packing volume and confirmed a correlation between packing volume and biological responsiveness. These results propose that the packing density of the TM domain provides a novel layer for fine-tuned regulation of signal transduction and cellular decisions.« less

Mechanical design of proteins studied by single-molecule force spectroscopy and protein engineering.

PubMed

Carrion-Vazquez, M; Oberhauser, A F; Fisher, T E; Marszalek, P E; Li, H; Fernandez, J M

2000-01-01

Mechanical unfolding and refolding may regulate the molecular elasticity of modular proteins with mechanical functions. The development of the atomic force microscopy (AFM) has recently enabled the dynamic measurement of these processes at the single-molecule level. Protein engineering techniques allow the construction of homomeric polyproteins for the precise analysis of the mechanical unfolding of single domains. alpha-Helical domains are mechanically compliant, whereas beta-sandwich domains, particularly those that resist unfolding with backbone hydrogen bonds between strands perpendicular to the applied force, are more stable and appear frequently in proteins subject to mechanical forces. The mechanical stability of a domain seems to be determined by its hydrogen bonding pattern and is correlated with its kinetic stability rather than its thermodynamic stability. Force spectroscopy using AFM promises to elucidate the dynamic mechanical properties of a wide variety of proteins at the single molecule level and provide an important complement to other structural and dynamic techniques (e.g., X-ray crystallography, NMR spectroscopy, patch-clamp).

Academic emotions from a social-cognitive perspective: antecedents and domain specificity of students' affect in the context of Latin instruction.

PubMed

Goetz, Thomas; Pekrun, Reinhard; Hall, Nathan; Haag, Ludwig

2006-06-01

This study concentrates on two assumptions of a social-cognitive model outlining the development of academic emotions (emotions directly linked to learning, classroom instruction, and achievement), namely on their antecedents and domain-specific organization. Our sample consisted of 200 students from Grades 7 to 10. Proposed relationships concerning the antecedents of academic emotions were tested in the context of Latin language instruction. Correlational analyses substantiated our assumptions concerning the relationships between academic emotions, students' cognitions, and aspects of the social environment. The mediating mechanisms proposed in the model were also confirmed using linear structural equation modelling. Subjective control- and value-related cognitions were found to mediate the relationship between aspects of the social environment and students' emotional experience. Our results further suggest that academic emotions are largely organized along domain-specific lines, with the degree of domain specificity varying according to the emotion in question. Implications for research and practice are discussed.

Differences between time domain and Fourier domain optical coherence tomography in imaging tissues.

PubMed

Gao, W; Wu, X

2017-11-01

It has been numerously demonstrated that both time domain and Fourier domain optical coherence tomography (OCT) can generate high-resolution depth-resolved images of living tissues and cells. In this work, we compare the common points and differences between two methods when the continuous and random properties of live tissue are taken into account. It is found that when relationships that exist between the scattered light and tissue structures are taken into account, spectral interference measurements in Fourier domain OCT (FDOCT) is more advantageous than interference fringe envelope measurements in time domain OCT (TDOCT) in the cases where continuous property of tissue is taken into account. It is also demonstrated that when random property of tissue is taken into account FDOCT measures the Fourier transform of the spatial correlation function of the refractive index and speckle phenomena will limit the effective limiting imaging resolution in both TDOCT and FDOCT. Finally, the effective limiting resolution of both TDOCT and FDOCT are given which can be used to estimate the effective limiting resolution in various practical applications. © 2017 The Authors Journal of Microscopy © 2017 Royal Microscopical Society.

The Conformational Change in Elongation Factor Tu Involves Separation of Its Domains

DOE PAGES

Lai, Jonathan; Ghaemi, Zhaleh; Luthey-Schulten, Zaida

2017-10-18

Elongation factor Tu (EF-Tu) is a highly conserved GTPase that is responsible for supplying the aminoacylated tRNA to the ribosome. Upon binding to the ribosome, EF-Tu undergoes GTP hydrolysis, which drives a major conformational change, triggering the release of aminoacylated tRNA to the ribosome. Using a combination of molecular simulation techniques, we studied the transition between the pre- and post-hydrolysis structures through two distinct pathways. Here, we show that the transition free energy is minimal along a non-intuitive pathway that involves “separation” of the GTP binding domain (domain 1) from the OB folds (domains 2 and 3), followed by domainmore » 1 rotation, and, eventually, locking the EF-Tu conformation in the post-hydrolysis state. The domain separation also leads to a slight extension of the linker connecting domain 1 to domain 2. Using docking tools and correlation-based analysis, we identified and characterized the EF-Tu conformations that release the tRNA. These calculations suggest that EF-Tu can release the tRNA before the domains separate and after domain 1 rotates by 25°. Lastly, we also examined the EF-Tu conformations in the context of the ribosome. Given the high degrees of sequence similarity with other translational GTPases, we predict a similar separation mechanism is followed.« less

Design and isolation of ribozyme-substrate pairs using RNase P-based ribozymes containing altered substrate binding sites.

PubMed Central

Mobley, E M; Pan, T

1999-01-01

Substrate recognition and cleavage by the bacterial RNase P RNA requires two domains, a specificity domain, or S-domain, and a catalytic domain, or C-domain. The S-domain binds the T stem-loop region in a pre-tRNA substrate to confer specificity for tRNA substrates. In this work, the entire S-domain of the Bacillus subtilis RNase P RNA is replaced with an artificial substrate binding module. New RNA substrates are isolated by in vitro selection using two libraries containing random regions of 60 nt. At the end of the selection, the cleavage rates of the substrate library are approximately 0.7 min(-1)in 10 mM MgCl(2)at 37 degrees C, approximately 4-fold better than the cleavage of a pre-tRNA substrate by the wild-type RNase P RNA under the same conditions. The contribution of the S-domain replacement to the catalytic efficiency is from 6- to 22 000-fold. Chemical and nuclease mapping of two ribozyme-product complexes shows that this contribution correlates with direct interactions between the S-domain replacement and the selected substrate. These results demonstrate the feasibility of design and isolation of RNase P-based, matching ribozyme-substrate pairs without prior knowledge of the sequence or structure of the interactive modules in the ribozyme or substrate. PMID:10518624

The Conformational Change in Elongation Factor Tu Involves Separation of Its Domains

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

Lai, Jonathan; Ghaemi, Zhaleh; Luthey-Schulten, Zaida

Elongation factor Tu (EF-Tu) is a highly conserved GTPase that is responsible for supplying the aminoacylated tRNA to the ribosome. Upon binding to the ribosome, EF-Tu undergoes GTP hydrolysis, which drives a major conformational change, triggering the release of aminoacylated tRNA to the ribosome. Using a combination of molecular simulation techniques, we studied the transition between the pre- and post-hydrolysis structures through two distinct pathways. Here, we show that the transition free energy is minimal along a non-intuitive pathway that involves “separation” of the GTP binding domain (domain 1) from the OB folds (domains 2 and 3), followed by domainmore » 1 rotation, and, eventually, locking the EF-Tu conformation in the post-hydrolysis state. The domain separation also leads to a slight extension of the linker connecting domain 1 to domain 2. Using docking tools and correlation-based analysis, we identified and characterized the EF-Tu conformations that release the tRNA. These calculations suggest that EF-Tu can release the tRNA before the domains separate and after domain 1 rotates by 25°. Lastly, we also examined the EF-Tu conformations in the context of the ribosome. Given the high degrees of sequence similarity with other translational GTPases, we predict a similar separation mechanism is followed.« less

Room temperature ferroelectricity in continuous croconic acid thin films

NASA Astrophysics Data System (ADS)

Jiang, Xuanyuan; Lu, Haidong; Yin, Yuewei; Zhang, Xiaozhe; Wang, Xiao; Yu, Le; Ahmadi, Zahra; Costa, Paulo S.; DiChiara, Anthony D.; Cheng, Xuemei; Gruverman, Alexei; Enders, Axel; Xu, Xiaoshan

2016-09-01

Ferroelectricity at room temperature has been demonstrated in nanometer-thin quasi 2D croconic acid thin films, by the polarization hysteresis loop measurements in macroscopic capacitor geometry, along with observation and manipulation of the nanoscale domain structure by piezoresponse force microscopy. The fabrication of continuous thin films of the hydrogen-bonded croconic acid was achieved by the suppression of the thermal decomposition using low evaporation temperatures in high vacuum, combined with growth conditions far from thermal equilibrium. For nominal coverages ≥20 nm, quasi 2D and polycrystalline films, with an average grain size of 50-100 nm and 3.5 nm roughness, can be obtained. Spontaneous ferroelectric domain structures of the thin films have been observed and appear to correlate with the grain patterns. The application of this solvent-free growth protocol may be a key to the development of flexible organic ferroelectric thin films for electronic applications.

Close correlation between magnetic properties and the soft phonon mode of the structural transition in BaFe 2 As 2 and SrFe 2 As 2

DOE PAGES

Parshall, D.; Pintschovius, L.; Niedziela, Jennifer L.; ...

2015-04-27

Pmore » arent compounds of Fe-based superconductors undergo a structural phase transition from a tetragonal to an orthorhombic structure. We investigated the temperature dependence of the frequencies of TA phonons that extrapolate to the shear vibrational mode at the zone center, which corresponds to the orthorhombic deformation of the crystal structure at low temperatures in BaFe 2 As 2 and SrFe 2 As 2 . We found that acoustic phonons at small wave vectors soften gradually towards the transition from high temperatures, tracking the increase of the size of slowly fluctuating magnetic domains. On cooling below the transition to base temperature the phonons harden, following the square of the magnetic moment (which we find is proportional to the anisotropy gap). Finally, our results provide evidence for close correlation between magnetic and phonon properties in Fe-based superconductors.« less

Oxide Thermoelectric Materials: A Structure-Property Relationship

NASA Astrophysics Data System (ADS)

Nag, Abanti; Shubha, V.

2014-04-01

Recent demand for thermoelectric materials for power harvesting from automobile and industrial waste heat requires oxide materials because of their potential advantages over intermetallic alloys in terms of chemical and thermal stability at high temperatures. Achievement of thermoelectric figure of merit equivalent to unity ( ZT ≈ 1) for transition-metal oxides necessitates a second look at the fundamental theory on the basis of the structure-property relationship giving rise to electron correlation accompanied by spin fluctuation. Promising transition-metal oxides based on wide-bandgap semiconductors, perovskite and layered oxides have been studied as potential candidate n- and p-type materials. This paper reviews the correlation between the crystal structure and thermoelectric properties of transition-metal oxides. The crystal-site-dependent electronic configuration and spin degeneracy to control the thermopower and electron-phonon interaction leading to polaron hopping to control electrical conductivity is discussed. Crystal structure tailoring leading to phonon scattering at interfaces and nanograin domains to achieve low thermal conductivity is also highlighted.

The static structure and dynamics of cadmium sulfide nanoparticles within poly(styrene- block-isoprene) diblock copolymer melts

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

Jang, Woo -Sik; Koo, Peter; Bryson, Kyle

Here, the static structure and dynamic behavior of cadmium sulfide nanoparticles suspended in block copolymer matrix are investigated using transmission electron microscopy, small-angle X-ray scattering, and X-ray photon correlation spectroscopy. The transmission electron micro- scopy study shows that cadmium sulfide nanoparticles are preferentially segregated within the polyisoprene domain of a poly(styrene- block-isoprene) diblock copolymer. For the dynamics study, X-ray photon correlation spectroscopy captures the relaxation process of cadmium sulfide nanoparticles. The measured characteristic relaxation time reveals that the observed dynamics are hyperdiffusive. The characteristic velocity and corresponding activation energy, which are hallmarks of a hyperdiffusive system, are determined from themore » relationship between the characteristic relaxation time and the wavevector.« less

The static structure and dynamics of cadmium sulfide nanoparticles within poly(styrene- block-isoprene) diblock copolymer melts

DOE PAGES

Jang, Woo -Sik; Koo, Peter; Bryson, Kyle; ...

2015-12-20

Here, the static structure and dynamic behavior of cadmium sulfide nanoparticles suspended in block copolymer matrix are investigated using transmission electron microscopy, small-angle X-ray scattering, and X-ray photon correlation spectroscopy. The transmission electron micro- scopy study shows that cadmium sulfide nanoparticles are preferentially segregated within the polyisoprene domain of a poly(styrene- block-isoprene) diblock copolymer. For the dynamics study, X-ray photon correlation spectroscopy captures the relaxation process of cadmium sulfide nanoparticles. The measured characteristic relaxation time reveals that the observed dynamics are hyperdiffusive. The characteristic velocity and corresponding activation energy, which are hallmarks of a hyperdiffusive system, are determined from themore » relationship between the characteristic relaxation time and the wavevector.« less

A class of covariate-dependent spatiotemporal covariance functions

PubMed Central

Reich, Brian J; Eidsvik, Jo; Guindani, Michele; Nail, Amy J; Schmidt, Alexandra M.

2014-01-01

In geostatistics, it is common to model spatially distributed phenomena through an underlying stationary and isotropic spatial process. However, these assumptions are often untenable in practice because of the influence of local effects in the correlation structure. Therefore, it has been of prolonged interest in the literature to provide flexible and effective ways to model non-stationarity in the spatial effects. Arguably, due to the local nature of the problem, we might envision that the correlation structure would be highly dependent on local characteristics of the domain of study, namely the latitude, longitude and altitude of the observation sites, as well as other locally defined covariate information. In this work, we provide a flexible and computationally feasible way for allowing the correlation structure of the underlying processes to depend on local covariate information. We discuss the properties of the induced covariance functions and discuss methods to assess its dependence on local covariate information by means of a simulation study and the analysis of data observed at ozone-monitoring stations in the Southeast United States. PMID:24772199

Depression and anxiety among elderly earthquake survivors in China.

PubMed

Liang, Ying

2017-12-01

This study investigated depression and anxiety among Chinese elderly earthquake survivors, addressing relevant correlations. We sampled one earthquake-prone city, utilising the Geriatric Depression Scale and Beck Anxiety Inventory. In addition, explorative factor analysis and structural equation model methods were used. Results indicated elderly earthquake survivors exhibited symptoms of moderate depression and anxiety; depression and anxiety are highly positively correlated. The overlap between these two psychological problems may be due to subjective fear and motoric dimensions; subjective fear and motoric dimensions of Beck Anxiety Inventory are more strongly related to Geriatric Depression Scale domains. The two scales exhibit high reliability and validity.

Hazard-to-Risk: High-Performance Computing Simulations of Large Earthquake Ground Motions and Building Damage in the Near-Fault Region

NASA Astrophysics Data System (ADS)

Miah, M.; Rodgers, A. J.; McCallen, D.; Petersson, N. A.; Pitarka, A.

2017-12-01

We are running high-performance computing (HPC) simulations of ground motions for large (magnitude, M=6.5-7.0) earthquakes in the near-fault region (< 50 km) to 5 Hz and higher. Ground motions are then used as forcing functions for canonical steel moment frame buildings throughout the near-fault domain. For ground motions, we are using SW4, a fourth order summation-by-parts finite difference time-domain code running on 10,000-100,000's of cores. Earthquake ruptures are generated using the Graves and Pitarka (2017) method. We validated ground motion intensity measurements against Ground Motion Prediction Equations. We considered two events (M=6.5 and 7.0) for vertical strike-slip ruptures with three-dimensional (3D) basin structures, including stochastic heterogeneity. We have also considered M7.0 scenarios for a Hayward Fault rupture scenario which effects the San Francisco Bay Area and northern California using both 1D and 3D earth structure. Dynamic, inelastic response of canonical buildings is computed with the NEVADA, a nonlinear, finite-deformation finite element code. Canonical buildings include 3-, 9-, 20- and 40-story steel moment frame buildings. Damage potential is tracked by the peak inter-story drift (PID) ratio, which measures the maximum displacement between adjacent floors of the building and is strongly correlated with damage. PID ratios greater 1.0 generally indicate non-linear response and permanent deformation of the structure. We also track roof displacement to identify permanent deformation. PID (damage) for a given earthquake scenario (M, slip distribution, hypocenter) is spatially mapped throughout the SW4 domain with 1-2 km resolution. Results show that in the near fault region building damage is correlated with peak ground velocity (PGV), while farther away (> 20 km) it is better correlated with peak ground acceleration (PGA). We also show how simulated ground motions have peaks in the response spectra that shift to longer periods for larger magnitude events and for locations of forward directivity, as has been reported by Sommerville (2003). These advanced numerical simulation capabilities provide a detailed look at the regional distribution of ground motions and allow us to quantify how ground motion hazard translate to risk for specific structures on a regional scale.

The development of 'Quality of Life Instrument for Indian Diabetes patients (QOLID): a validation and reliability study in middle and higher income groups.

PubMed

Nagpal, Jitender; Kumar, Arvind; Kakar, Sonia; Bhartia, Abhishek

2010-05-01

To develop a reliable and valid quality of life questionnaire for Indian patients with diabetes. A draft of 75 questions was prepared on the basis of expert opinion, focus group discussions, review of existing literature and detailed semi-structured interviews of patients with diabetes with the intention of including all aspects of diabetes-specific and quality of life considered relevant by patients and care providers to enable constrict validity. A Stage 2 questionnaire was then prepared with 13 domains and 54 items (questions) after expert panel review for obvious irrelevance and duplication of issues. It was administered to 150 participants visiting a diabetes center at New Delhi. Factor analysis was done using principal component method with varimax rotation. Reliability analysis was done by calculating Cronbach's Alpha. For evaluating concordant validity the questionnaire was co-administered with DQL-CTQ to 30 participants. The discriminant validity of the questionnaire was tested using 't' test for metabolic control, co-morbidities, insulin use and gender. Using principal component method 8 domains were identified on the basis of an apriori hypothesis and the scree plot. These 8 domains explained 49.9% of the total variation. 34 items (questions) were selected to represent these domains on the basis of extraction communality, factor loading, inter-item and item-total correlations. The final questionnaire has an Overall Cronbach's Alpha value of 0.894 (subscale- 0.55 to 0.85) showing high internal consistency. The questionnaire showed good concordance (product moment correlation 0.724; p = 0.001; subscale correlation - 0.457 to 0.779) with the DQL-CTQ. The overall standardized questionnaire score showed good responsiveness to metabolic control and co-morbidities establishing discriminant validity. The final version of questionnaire with 8 domains and 34 items is a reliable and valid tool for assessment of quality of life of Indian patients with diabetes.

Organizational and safety culture in Canadian intensive care units: relationship to size of intensive care unit and physician management model.

PubMed

Dodek, Peter M; Wong, Hubert; Jaswal, Danny; Heyland, Daren K; Cook, Deborah J; Rocker, Graeme M; Kutsogiannis, Demetrios J; Dale, Craig; Fowler, Robert; Ayas, Najib T

2012-02-01

The objectives of this study are to describe organizational and safety culture in Canadian intensive care units (ICUs), to correlate culture with the number of beds and physician management model in each ICU, and to correlate organizational culture and safety culture. In this cross-sectional study, surveys of organizational and safety culture were administered to 2374 clinical staff in 23 Canadian tertiary care and community ICUs. For the 1285 completed surveys, scores were calculated for each of 34 domains. Average domain scores for each ICU were correlated with number of ICU beds and with intensivist vs nonintensivist management model. Domain scores for organizational culture were correlated with domain scores for safety culture. Culture domain scores were generally favorable in all ICUs. There were moderately strong positive correlations between number of ICU beds and perceived effectiveness at recruiting/retaining physicians (r = 0.58; P < .01), relative technical quality of care (r = 0.66; P < .01), and medical director budgeting authority (r = 0.46; P = .03), and moderately strong negative correlations with frequency of events reported (r = -0.46; P = .03), and teamwork across hospital units (r = -0.51; P = .01). There were similar patterns for relationships with intensivist management. For most pairs of domains, there were weak correlations between organizational and safety culture. Differences in perceptions between staff in larger and smaller ICUs highlight the importance of teamwork across units in larger ICUs. Copyright © 2012 Elsevier Inc. All rights reserved.

Correlation between the Voice Handicap and Swallowing Quality of Life in patients with laryngeal cancer submitted to chemoradiotherapy.

PubMed

Rosa, Maria Eduarda da; Mituuti, Cláudia Tiemi; Ghirardi, Ana Carolina de Assis Moura

2018-01-01

Purpose To verify the correlation between the voice handicap and swallowing quality of life in individuals submitted to chemoradiotherapy for laryngeal cancer treatment. Methods Cross-sectional, observational and quantitative study. Fourteen male individuals diagnosed with laryngeal cancer were submitted to exclusive chemoradiotherapy treatment. The individuals completed the Voice Handicap Index (VHI) and the Swallowing Quality of Life (SWAL-QOL) questionnaires. Data were submitted to descriptive and inferential analysis using Spearman's Correlation Test to verify possible correlations among the scores of these instruments. Values of p ≤ 0.05 were considered statistically significant. Results No significant correlation was found between the total VHI and overall SWAL-QOL scores. However, there was significant correlation between the domain Functional of the VHI and the domains Fatigue and Social of the SWAL-QOL, between the domain Organic in the VHI and the SWAL-QOL domain Social, and total VHI score and SWAL-QOL domain Swallowing as a burden. Furthermore, chemoradiotherapy treatment had a greater impact on the voice than on the swallowing for the studied individuals. Conclusion The data showed a significant correlation between voice handicap and the impact of quality of life involving swallowing in individuals with laryngeal cancer submitted to chemoradiotherapy. This may affect individuals' emotional and social aspects, impacting their overall quality of life.

Contrasting two models of academic self-efficacy--domain-specific versus cross-domain--in children receiving and not receiving special instruction in mathematics.

PubMed

Jungert, Tomas; Hesser, Hugo; Träff, Ulf

2014-10-01

In social cognitive theory, self-efficacy is domain-specific. An alternative model, the cross-domain influence model, would predict that self-efficacy beliefs in one domain might influence performance in other domains. Research has also found that children who receive special instruction are not good at estimating their performance. The aim was to test two models of how self-efficacy beliefs influence achievement, and to contrast children receiving special instruction in mathematics with normally-achieving children. The participants were 73 fifth-grade children who receive special instruction and 70 children who do not receive any special instruction. In year four and five, the children's skills in mathematics and reading were assessed by national curriculum tests, and in their fifth year, self-efficacy in mathematics and reading were measured. Structural equation modeling showed that in domains where children do not receive special instruction in mathematics, self-efficacy is a mediating variable between earlier and later achievement in the same domain. Achievement in mathematics was not mediated by self-efficacy in mathematics for children who receive special instruction. For normal achieving children, earlier achievement in the language domain had an influence on later self-efficacy in the mathematics domain, and self-efficacy beliefs in different domains were correlated. Self-efficacy is mostly domain specific, but may play a different role in academic performance depending on whether children receive special instruction. The results of the present study provided some support of the Cross-Domain Influence Model for normal achieving children. © 2014 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Social Cognition in Psychosis: Multidimensional Structure, Clinical Correlates, and Relationship With Functional Outcome

PubMed Central

Mancuso, Francesco; Horan, William P.; Kern, Robert S.; Green, Michael F.

2010-01-01

Social cognitive impairments are common, detectable across a wide range of tasks, and appear to play a key role in explaining poor outcome in schizophrenia and related psychotic disorders. However, little is known about the underlying factor structure of social cognition in people with psychotic disorders due to a lack of exploratory factor analyses using a relatively comprehensive social cognitive assessment battery. In a sample of 85 outpatients with psychosis, we examined the factor structure and clinical/functional correlates of eight indexes derived from five social cognition tasks that span the domains of emotional processing, social perception, attributional style, and Theory of Mind. Exploratory factor analysis revealed three factors with relatively low inter-correlations that explained a total of 54% of the variance: (1) Hostile attributional style, (2) Lower-level social cue detection, and (3) Higher-level inferential and regulatory processes. None of the factors showed significant correlations with negative symptoms. Factor 1 significantly correlated with clinical symptoms (positive, depression-anxiety, agitation) but not functional outcome, whereas Factors 2 and 3 significantly correlated with functional outcome (functional capacity and real-world social and work functioning) but not clinical symptoms. Furthermore, Factor 2 accounted for unique incremental variance in functional capacity, above and beyond non-social neurocognition (measured with MATRICS Consensus Cognitive Battery) and negative symptoms. Results suggest that multiple separable dimensions of social cognition can be identified in psychosis, and these factors show distinct patterns of correlation with clinical features and functional outcome. PMID:21112743

Structural considerations for functional anti-EGFR × anti-CD3 bispecific diabodies in light of domain order and binding affinity.

PubMed

Asano, Ryutaro; Nagai, Keisuke; Makabe, Koki; Takahashi, Kento; Kumagai, Takashi; Kawaguchi, Hiroko; Ogata, Hiromi; Arai, Kyoko; Umetsu, Mitsuo; Kumagai, Izumi

2018-03-02

We previously reported a functional humanized bispecific diabody (bsDb) that targeted EGFR and CD3 (hEx3-Db) and enhancement of its cytotoxicity by rearranging the domain order in the V domain. Here, we further dissected the effect of domain order in bsDbs on their cross-linking ability and binding kinetics to elucidate general rules regarding the design of functional bsDbs. Using Ex3-Db as a model system, we first classified the four possible domain orders as anti-parallel (where both chimeric single-chain components are variable heavy domain (VH)-variable light domain (VL) or VL-VH order) and parallel types (both chimeric single-chain components are mixed with VH-VL and VL-VH order). Although anti-parallel Ex3-Dbs could cross-link the soluble target antigens, their cross-linking ability between soluble targets had no correlation with their growth inhibitory effects. In contrast, the binding affinity of one of the two constructs with a parallel-arrangement V domain was particularly low, and structural modeling supported this phenomenon. Similar results were observed with E2x3-Dbs, in which the V region of the anti-EGFR antibody clone in hEx3 was replaced with that of another anti-EGFR clone. Only anti-parallel types showed affinity-dependent cancer inhibitory effects in each molecule, and E2x3-LH (both components in VL-VH order) showed the most intense anti-tumor activity in vitro and in vivo . Our results showed that, in addition to rearranging the domain order of bsDbs, increasing their binding affinity may be an ideal strategy for enhancing the cytotoxicity of anti-parallel constructs and that E2x3-LH is particularly attractive as a candidate next-generation anti-cancer drug.

Velocity-vorticity correlation structures (VVCS) in spatially developing compressible turbulent boundary layer

NASA Astrophysics Data System (ADS)

Li, Shi-Yao; She, Zhen-Su; Chen, Jun

2017-11-01

A velocity-vorticity correlation structure (VVCS) analysis is applied to the direct numerical simulation (DNS) of compressible turbulent boundary layer (CTBL) at Mach numbers, Ma = 2.25 , 4.50 and 6.0 . It is shown that the VVCS analysis captures the geometry variation in the streamwise direction during the transition and in the wall-normal direction in the fully developed regime. Specifically, before transition, the VVCS captures the instability wave number, while in the transition region it displays a distinct scaling change of the dimensions. The fully developed turbulence regime is characterized by a nearly constant spatial extension of the VVCS. Particularly, after turbulence is well developed, a multi-layer structure in the wall normal direction is observed in the maximum correlation coefficient and in the length scales of the VVCS, as expected from a recent symmetry-based theory, the ensemble structure dynamics (SED). The most interesting outcome is an observed linear dependence of the length scale of the VVCS from y+ 50 to 200, which is a direct support to Townsend's attached-eddy theory. In conclusion, the VVCS analysis quantifies the geometrical characteristics of the coherent structures in turbulent compressible shear flows throughout the whole domain. Supported by NSFC (11172006, 11221062, 11452002) and by MOST (China) 973 project (2009CB724100).

Stability and Sugar Recognition Ability of Ricin-Like Carbohydrate Binding Domains

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

Yao, Jianzhuang; Nellas, Ricky B; Glover, Mary M

2011-01-01

Lectins are a class of proteins known for their novel binding to saccharides. Understanding this sugar recognition process can be crucial in creating structure-based designs of proteins with various biological roles. We focus on the sugar binding of a particular lectin, ricin, which has two -trefoil carbohydrate-binding domains (CRDs) found in several plant protein toxins. The binding ability of possible sites of ricin-like CRD has been puzzling. The apo and various (multiple) ligand-bound forms of the sugar-binding domains of ricin were studied by molecular dynamics simulations. By evaluating structural stability, hydrogen bond dynamics, flexibility, and binding energy, we obtained amore » detailed picture of the sugar recognition of the ricin-like CRD. Unlike what was previously believed, we found that the binding abilities of the two known sites are not independent of each other. The binding ability of one site is positively affected by the other site. While the mean positions of different binding scenarios are not altered significantly, the flexibility of the binding pockets visibly decreases upon multiple ligand binding. This change in flexibility seems to be the origin of the binding cooperativity. All the hydrogen bonds that are strong in the monoligand state are also strong in the double-ligand complex, although the stability is much higher in the latter form due to cooperativity. These strong hydrogen bonds in a monoligand state are deemed to be the essential hydrogen bonds. Furthermore, by examining the structural correlation matrix, the two domains are structurally one entity. Galactose hydroxyl groups, OH4 and OH3, are the most critical parts in both site 1 and site 2 recognition.« less

Measuring Client Experiences in Maternity Care under Change: Development of a Questionnaire Based on the WHO Responsiveness Model

PubMed Central

Scheerhagen, Marisja; van Stel, Henk F.; Birnie, Erwin; Franx, Arie; Bonsel, Gouke J.

2015-01-01

Background Maternity care is an integrated care process, which consists of different services, involves different professionals and covers different time windows. To measure performance of maternity care based on clients' experiences, we developed and validated a questionnaire. Methods and Findings We used the 8-domain WHO Responsiveness model, and previous materials to develop a self-report questionnaire. A dual study design was used for development and validation. Content validity of the ReproQ-version-0 was determined through structured interviews with 11 pregnant women (≥28 weeks), 10 women who recently had given birth (≤12 weeks), and 19 maternity care professionals. Structured interviews established the domain relevance to the women; all items were separately commented on. All Responsiveness domains were judged relevant, with Dignity and Communication ranking highest. Main missing topic was the assigned expertise of the health professional. After first adaptation, construct validity of the ReproQ-version-1 was determined through a web-based survey. Respondents were approached by maternity care organizations with different levels of integration of services of midwives and obstetricians. We sent questionnaires to 605 third trimester pregnant women (response 65%), and 810 women 6 weeks after delivery (response 55%). Construct validity was based on: response patterns; exploratory factor analysis; association of the overall score with a Visual Analogue Scale (VAS), known group comparisons. Median overall ReproQ score was 3.70 (range 1–4) showing good responsiveness. The exploratory factor analysis supported the assumed domain structure and suggested several adaptations. Correlation of the VAS rating and overall ReproQ score (antepartum, postpartum) supported validity (r = 0.56; 0.59, p<0.001 Spearman's correlation coefficient). Pre-stated group comparisons confirmed the expected difference following a good vs. adverse birth outcome. Fully integrated organizations performed slightly better (median = 3.78) than less integrated organizations (median = 3.63; p<0.001). Participation rate of women with a low educational level and/or a non-western origin was low. Conclusions The ReproQ appears suitable for assessing quality of maternity care from the clients' perspective. Recruitment of disadvantaged groups requires additional non-digital approaches. PMID:25671310

Spatiotemporal mapping of diffusion dynamics and organization in plasma membranes

NASA Astrophysics Data System (ADS)

Bag, Nirmalya; Ng, Xue Wen; Sankaran, Jagadish; Wohland, Thorsten

2016-09-01

Imaging fluorescence correlation spectroscopy (FCS) and the related FCS diffusion law have been applied in recent years to investigate the diffusion modes of lipids and proteins in membranes. These efforts have provided new insights into the membrane structure below the optical diffraction limit, new information on the existence of lipid domains, and on the influence of the cytoskeleton on membrane dynamics. However, there has been no systematic study to evaluate how domain size, domain density, and the probe partition coefficient affect the resulting imaging FCS diffusion law parameters. Here, we characterize the effects of these factors on the FCS diffusion law through simulations and experiments on lipid bilayers and live cells. By segmenting images into smaller 7  ×  7 pixel areas, we can evaluate the FCS diffusion law on areas smaller than 2 µm and thus provide detailed maps of information on the membrane structure and heterogeneity at this length scale. We support and extend this analysis by deriving a mathematical expression to calculate the mean squared displacement (MSDACF) from the autocorrelation function of imaging FCS, and demonstrate that the MSDACF plots depend on the existence of nanoscopic domains. Based on the results, we derive limits for the detection of domains depending on their size, density, and relative viscosity in comparison to the surroundings. Finally, we apply these measurements to bilayers and live cells using imaging total internal reflection FCS and single plane illumination microscopy FCS.

Optimized signal detection and analysis methods for in vivo photoacoustic flow cytometry

NASA Astrophysics Data System (ADS)

Wang, Qiyan; Zhou, Quanyu; Yang, Ping; Wang, Xiaoling; Niu, Zhenyu; Suo, Yuanzhen; He, Hao; Gao, Wenyuan; Tang, Shuo; Wei, Xunbin

2017-02-01

Melanoma is known as a malignant tumor of melanocytes, which usually appear in the blood circulation at the metastasis stage of cancer. Thus the detection of circulating melanoma cells is useful for early diagnosis and therapy of cancer. Here we have developed an in vivo photoacoustic flow cytometry (PAFC) based on the photoacoustic effect to detect melanoma cells. However, the raw signals we obtain from the target cells contain noises such as environmental sonic noises and electronic noises. Therefore we apply correlation comparison and feature separation methods to the detection and verification of the in vivo signals. Due to similar shape and structure of cells, the photoacoustic signals usually have similar vibration mode. By analyzing the correlations and the signal features in time domain and frequency domain, we are able to provide a method for separating photoacoustic signals generated by target cells from background noises. The method introduced here has proved to optimize the signal acquisition and signal processing, which can improve the detection accuracy in PAFC.

A cosmic superfluid phase

NASA Technical Reports Server (NTRS)

Gradwohl, Ben-Ami

1991-01-01

The universe may have undergone a superfluid-like phase during its evolution, resulting from the injection of nontopological charge into the spontaneously broken vacuum. In the presence of vortices this charge is identified with angular momentum. This leads to turbulent domains on the scale of the correlation length. By restoring the symmetry at low temperatures, the vortices dissociate and push the charges to the boundaries of these domains. The model can be scaled (phenomenologically) to very low energies, it can be incorporated in a late time phase transition and form large scale structure in the boundary layers of the correlation volumes. The novel feature of the model lies in the fact that the dark matter is endowed with coherent motion. The possibilities of identifying this flow around superfluid vortices with the observed large scale bulk motion is discussed. If this identification is possible, then the definite prediction can be made that a more extended map of peculiar velocities would have to reveal large scale circulations in the flow pattern.

Validation of the 36-item version of the WHO Disability Assessment Schedule 2.0 (WHODAS 2.0) for assessing women's disability and functioning associated with maternal morbidity.

PubMed

Silveira, Carla; Parpinelli, Mary Angela; Pacagnella, Rodolfo Carvalho; Andreucci, Carla Betina; Angelini, Carina Robles; Ferreira, Elton Carlos; Cecatti, José Guilherme

2017-02-01

Objective  To validate the translation and adaptation to Brazilian Portuguese of 36 items from the World Health Organizaton Disability Assessment Schedule 2.0 (WHODAS 2.0), regarding their content and structure (construct), in a female population after pregnancy. Methods  This is a validation of an instrument for the evaluation of disability and functioning and an assessment of its psychometric properties, performed in a tertiary maternity and a referral center specialized in high-risk pregnancies in Brazil. A sample of 638 women in different postpartum periods who had either a normal or a complicated pregnancy was included. The structure was evaluated by exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), while the content and relationships among the domains were assessed through Pearson's correlation coefficient. The sociodemographic characteristics were identified, and the mean scores with their standard deviations for the 36 questions of the WHODAS 2.0 were calculated. The internal consistency was evaluated byCronbach's α. Results  Cronbach's α was higher than 0.79 for both sets of questons of the questionnaire. The EFA and CFA for the main 32 questions exhibited a total variance of 54.7% (Kaiser-Meyer-Olkin [KMO] measure of sampling adequacy =  0.934; p  < 0.001) and 53.47% (KMO = 0.934; p  < 0.001) respectively. There was a significant correlation among the 6 domains (r = 0.571-0.876), and a moderate correlation among all domains (r = 0.476-0.694). Conclusion  The version of the WHODAS 2.0 instrument adapted to Brazilian Portuguese showed good psychometric properties in this sample, and therefore could be applied to populations of women regarding their reproductive history. Thieme-Revinter Publicações Ltda Rio de Janeiro, Brazil.

Reductive evolution and the loss of PDC/PAS domains from the genus Staphylococcus

PubMed Central

2013-01-01

Background The Per-Arnt-Sim (PAS) domain represents a ubiquitous structural fold that is involved in bacterial sensing and adaptation systems, including several virulence related functions. Although PAS domains and the subclass of PhoQ-DcuS-CitA (PDC) domains have a common structure, there is limited amino acid sequence similarity. To gain greater insight into the evolution of PDC/PAS domains present in the bacterial kingdom and staphylococci in specific, the PDC/PAS domains from the genomic sequences of 48 bacteria, representing 5 phyla, were identified using the sensitive search method based on HMM-to-HMM comparisons (HHblits). Results A total of 1,007 PAS domains and 686 PDC domains distributed over 1,174 proteins were identified. For 28 Gram-positive bacteria, the distribution, organization, and molecular evolution of PDC/PAS domains were analyzed in greater detail, with a special emphasis on the genus Staphylococcus. Compared to other bacteria the staphylococci have relatively fewer proteins (6–9) containing PDC/PAS domains. As a general rule, the staphylococcal genomes examined in this study contain a core group of seven PDC/PAS domain-containing proteins consisting of WalK, SrrB, PhoR, ArlS, HssS, NreB, and GdpP. The exceptions to this rule are: 1) S. saprophyticus lacks the core NreB protein; 2) S. carnosus has two additional PAS domain containing proteins; 3) S. epidermidis, S. aureus, and S. pseudintermedius have an additional protein with two PDC domains that is predicted to code for a sensor histidine kinase; 4) S. lugdunensis has an additional PDC containing protein predicted to be a sensor histidine kinase. Conclusions This comprehensive analysis demonstrates that variation in PDC/PAS domains among bacteria has limited correlations to the genome size or pathogenicity; however, our analysis established that bacteria having a motile phase in their life cycle have significantly more PDC/PAS-containing proteins. In addition, our analysis revealed a tremendous amount of variation in the number of PDC/PAS-containing proteins within genera. This variation extended to the Staphylococcus genus, which had between 6 and 9 PDC/PAS proteins and some of these appear to be previously undescribed signaling proteins. This latter point is important because most staphylococcal proteins that contain PDC/PAS domains regulate virulence factor synthesis or antibiotic resistance. PMID:23902280

Reductive evolution and the loss of PDC/PAS domains from the genus Staphylococcus.

PubMed

Shah, Neethu; Gaupp, Rosmarie; Moriyama, Hideaki; Eskridge, Kent M; Moriyama, Etsuko N; Somerville, Greg A

2013-07-31

The Per-Arnt-Sim (PAS) domain represents a ubiquitous structural fold that is involved in bacterial sensing and adaptation systems, including several virulence related functions. Although PAS domains and the subclass of PhoQ-DcuS-CitA (PDC) domains have a common structure, there is limited amino acid sequence similarity. To gain greater insight into the evolution of PDC/PAS domains present in the bacterial kingdom and staphylococci in specific, the PDC/PAS domains from the genomic sequences of 48 bacteria, representing 5 phyla, were identified using the sensitive search method based on HMM-to-HMM comparisons (HHblits). A total of 1,007 PAS domains and 686 PDC domains distributed over 1,174 proteins were identified. For 28 Gram-positive bacteria, the distribution, organization, and molecular evolution of PDC/PAS domains were analyzed in greater detail, with a special emphasis on the genus Staphylococcus. Compared to other bacteria the staphylococci have relatively fewer proteins (6-9) containing PDC/PAS domains. As a general rule, the staphylococcal genomes examined in this study contain a core group of seven PDC/PAS domain-containing proteins consisting of WalK, SrrB, PhoR, ArlS, HssS, NreB, and GdpP. The exceptions to this rule are: 1) S. saprophyticus lacks the core NreB protein; 2) S. carnosus has two additional PAS domain containing proteins; 3) S. epidermidis, S. aureus, and S. pseudintermedius have an additional protein with two PDC domains that is predicted to code for a sensor histidine kinase; 4) S. lugdunensis has an additional PDC containing protein predicted to be a sensor histidine kinase. This comprehensive analysis demonstrates that variation in PDC/PAS domains among bacteria has limited correlations to the genome size or pathogenicity; however, our analysis established that bacteria having a motile phase in their life cycle have significantly more PDC/PAS-containing proteins. In addition, our analysis revealed a tremendous amount of variation in the number of PDC/PAS-containing proteins within genera. This variation extended to the Staphylococcus genus, which had between 6 and 9 PDC/PAS proteins and some of these appear to be previously undescribed signaling proteins. This latter point is important because most staphylococcal proteins that contain PDC/PAS domains regulate virulence factor synthesis or antibiotic resistance.

1H, 13C, and 15N backbone assignment and secondary structure of the receptor-binding domain of vascular endothelial growth factor.

PubMed Central

Fairbrother, W. J.; Champe, M. A.; Christinger, H. W.; Keyt, B. A.; Starovasnik, M. A.

1997-01-01

Nearly complete sequence-specific 1H, 13C, and 15N resonance assignments are reported for the backbone atoms of the receptor-binding domain of vascular endothelial growth factor (VEGF), a 23-kDa homodimeric protein that is a major regulator of both normal and pathological angiogenesis. The assignment strategy relied on the use of seven 3D triple-resonance experiments [HN(CO)CA, HNCA, HNCO, (HCA)CONH, HN(COCA)HA, HN(CA)HA, and CBCA-(CO)NH] and a 3D 15N-TOCSY-HSQC experiment recorded on a 0.5 mM (12 mg/mL) sample at 500 MHz, pH 7.0, 45 degrees C. Under these conditions, 15N relaxation data show that the protein has a rotational correlation time of 15.0 ns. Despite this unusually long correlation time, assignments were obtained for 94 of the 99 residues; 8 residues lack amide 1H and 15N assignments, presumably due to rapid exchange of the amide 1H with solvent under the experimental conditions used. The secondary structure of the protein was deduced from the chemical shift indices of the 1H alpha, 13C alpha, 13C beta, and 13CO nuclei, and from analysis of backbone NOEs observed in a 3D 15N-NOESY-HSQC spectrum. Two helices and a significant amount of beta-sheet structure were identified, in general agreement with the secondary structure found in a recently determined crystal structure of a similar VEGF construct [Muller YA et al., 1997, Proc Natl Acad Sci USA 94:7192-7197]. PMID:9336848

Comment on "Pulsating Auroras Produced by Interactions of Electrons and Time Domain Structures" by Mozer Et Al.

NASA Astrophysics Data System (ADS)

Nishimura, Y.; Bortnik, J.; Li, W.; Angelopoulos, V.; Donovan, E. F.; Spanswick, E. L.

2018-03-01

Mozer et al. (2017, https://doi.org/10.1002/2017JA024223) suggested that time domain structures (TDSs) drive pulsating aurora (with additional contributions by kinetic Alfvén waves (KAWs)) and that chorus waves have negligible effects. In this comment, we point out that electrons scattered by TDS or KAW (dominantly at 0.1-3 keV, <1 s modulation) cannot explain key features of pulsating aurora, which require precipitation above a few keV with a couple of tens of second modulation. Their study did not conduct quantitative evaluations of wave-aurora correlation. The use of short burst mode data ( <10 s) may only cover a single pulse of pulsating aurora and is not suitable for examining connections to pulsating aurora. "Field-aligned" electrons do not necessarily represent loss cone population, and their characteristic energy (hundreds of eV) is much lower than typical precipitation over pulsating aurora. By reexamining the events studied by Mozer et al., we quantitatively demonstrate that TDS and KAW are uncorrelated with pulsating aurora and that only chorus waves showed high correlations with pulsating aurora. Occasional simultaneous occurrence of TDS/KAW and pulsating aurora is found to be coincidental, because the correlation over a time scale of minutes is poor. Several auroral features analyzed in that paper are not pulsating aurora but other types of aurora. We also show that the chorus-pulsating aurora correlation can last for 2 h or longer and can be used to highlight dynamic changes in magnetic field mapping. Chorus waves can resonate with electrons above a few keV and are in agreement with pulsating auroral properties.

Comparison of diagnostic capability of macular ganglion cell complex and retinal nerve fiber layer among primary open angle glaucoma, ocular hypertension, and normal population using Fourier-domain optical coherence tomography and determining their functional correlation in Indian population

PubMed Central

Barua, Nabanita; Sitaraman, Chitra; Goel, Sonu; Chakraborti, Chandana; Mukherjee, Sonai; Parashar, Hemandra

2016-01-01

Context: Analysis of diagnostic ability of macular ganglionic cell complex and retinal nerve fiber layer (RNFL) in glaucoma. Aim: To correlate functional and structural parameters and comparing predictive value of each of the structural parameters using Fourier-domain (FD) optical coherence tomography (OCT) among primary open angle glaucoma (POAG) and ocular hypertension (OHT) versus normal population. Setting and Design: Single centric, cross-sectional study done in 234 eyes. Materials and Methods: Patients were enrolled in three groups: POAG, ocular hypertensive and normal (40 patients in each group). After comprehensive ophthalmological examination, patients underwent standard automated perimetry and FD-OCT scan in optic nerve head and ganglion cell mode. The relationship was assessed by correlating ganglion cell complex (GCC) parameters with mean deviation. Results were compared with RNFL parameters. Statistical Analysis: Data were analyzed with SPSS, analysis of variance, t-test, Pearson's coefficient, and receiver operating curve. Results: All parameters showed strong correlation with visual field (P < 0.001). Inferior GCC had highest area under curve (AUC) for detecting glaucoma (0.827) in POAG from normal population. However, the difference was not statistically significant (P > 0.5) when compared with other parameters. None of the parameters showed significant diagnostic capability to detect OHT from normal population. In diagnosing early glaucoma from OHT and normal population, only inferior GCC had statistically significant AUC value (0.715). Conclusion: In this study, GCC and RNFL parameters showed equal predictive capability in perimetric versus normal group. In early stage, inferior GCC was the best parameter. In OHT population, single day cross-sectional imaging was not valuable. PMID:27221682

Spectral Domain Optical Coherence Tomography in Glaucoma: Qualitative and Quantitative Analysis of the Optic Nerve Head and Retinal Nerve Fiber Layer (An AOS Thesis)

PubMed Central

Chen, Teresa C.

2009-01-01

Purpose: To demonstrate that video-rate spectral domain optical coherence tomography (SDOCT) can qualitatively and quantitatively evaluate optic nerve head (ONH) and retinal nerve fiber layer (RNFL) glaucomatous structural changes. To correlate quantitative SDOCT parameters with disc photography and visual fields. Methods: SDOCT images from 4 glaucoma eyes (4 patients) with varying stages of open-angle glaucoma (ie, early, moderate, late) were qualitatively contrasted with 2 age-matched normal eyes (2 patients). Of 61 other consecutive patients recruited in an institutional setting, 53 eyes (33 patients) met inclusion/exclusion criteria for quantitative studies. Images were obtained using two experimental SDOCT systems, one utilizing a superluminescent diode and the other a titanium:sapphire laser source, with axial resolutions of about 6 μm and 3 μm, respectively. Results: Classic glaucomatous ONH and RNFL structural changes were seen in SDOCT images. An SDOCT reference plane 139 μm above the retinal pigment epithelium yielded cup-disc ratios that best correlated with masked physician disc photography cup-disc ratio assessments. The minimum distance band, a novel SDOCT neuroretinal rim parameter, showed good correlation with physician cup-disc ratio assessments, visual field mean deviation, and pattern standard deviation (P values range, .0003–.024). RNFL and retinal thickness maps correlated well with disc photography and visual field testing. Conclusions: To our knowledge, this thesis presents the first comprehensive qualitative and quantitative evaluation of SDOCT images of the ONH and RNFL in glaucoma. This pilot study provides basis for developing more automated quantitative SDOCT-specific glaucoma algorithms needed for future prospective multicenter national trials. PMID:20126502

Comparison and correlation of binding mode of ATP in the kinase domains of Hexokinase family

PubMed Central

Kumar, Yellapu Nanda; Kumar, Pasupuleti Santhosh; Sowjenya, Gopal; Rao, Valasani Koteswara; Yeswanth, Sthanikam; Prasad, Uppu Venkateswara; Pradeepkiran, Jangampalli Adi; Sarma, PVGK; Bhaskar, Matcha

2012-01-01

Hexokinases (HKs) are the enzymes that catalyses the ATP dependent phosphorylation of Hexose sugars to Hexose-6-Phosphate (Hex-6-P). There exist four different forms of HKs namely HK-I, HK-II, HK-III and HK-IV and all of them share a common ATP binding site core surrounded by more variable sequence that determine substrate affinities. Although they share a common binding site but they differ in their kinetic functions, hence the present study is aimed to analyze the binding mode of ATP. The analysis revealed that the four ATP binding domains are showing 13 identical, 7 similar and 6 dissimilar residues with similar structural conformation. Molecular docking of ATP into the kinase domains using Molecular Operating Environment (MOE) soft ware tool clearly showed the variation in the binding mode of ATP with variable docking scores. This probably explains the variable phosphorylation rates among hexokinases family. PMID:22829728

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.

Upscaling anomalous reactive kinetics (A+B-->C) from pore scale Lagrangian velocity analysis

NASA Astrophysics Data System (ADS)

De Anna, P.; Tartakovsky, A. M.; Le Borgne, T.; Dentz, M.

2011-12-01

Natural flow fields in porous media display a complex spatio-temporal organization due to heterogeneous geological structures at different scales. This multiscale disorder implies anomalous dispersion, mixing and reaction kinetics (Berkowitz et al. RG 2006, Tartakovsky PRE 2010). Here, we focus on the upscaling of anomalous kinetics arising from pore scale, non Gaussian and correlated, velocity distributions. We consider reactive front simulations, where a component A displaces a component B that saturates initially the porous domain. The reactive component C is produced at the dispersive front located at interface between the A and B domains. The simulations are performed with the SPH method. As the mixing zone grows, the total mass of C produced increases with time. The scaling of this evolution with time is different from that which would be obtained from the homogeneous advection dispersion reaction equation. This anomalous kinetics property is related to spatial structure of the reactive mixture, and its evolution with time under the combined action of advective and diffusive processes. We discuss the different scaling regimes arising depending on the dominant process that governs mixing. In order to upscale these processes, we analyze the Lagrangian velocity properties, which are characterized by the non Gaussian distributions and long range temporal correlation. The main origin of these properties is the existence of very low velocity regions where solute particles can remain trapped for a long time. Another source of strong correlation is the channeling of flow in localized high velocity regions, which created finger-like structures in the concentration field. We show the spatial Markovian, and temporal non Markovian, nature of the Lagrangian velocity field. Therefore, an upscaled model can be defined as a correlated Continuous Time Random Walk (Le Borgne et al. PRL 2008). A key feature of this model is the definition of a transition probability density for Lagrangian velocities across a characteristic correlation distance. We quantify this transition probability density from pore scale simulations and use it in the effective stochastic model. In this framework, we investigate the ability of this effective model to represent correctly dispersion and mixing.

Parameter motivated mutual correlation analysis: Application to the study of currency exchange rates based on intermittency parameter and Hurst exponent

NASA Astrophysics Data System (ADS)

Cristescu, Constantin P.; Stan, Cristina; Scarlat, Eugen I.; Minea, Teofil; Cristescu, Cristina M.

2012-04-01

We present a novel method for the parameter oriented analysis of mutual correlation between independent time series or between equivalent structures such as ordered data sets. The proposed method is based on the sliding window technique, defines a new type of correlation measure and can be applied to time series from all domains of science and technology, experimental or simulated. A specific parameter that can characterize the time series is computed for each window and a cross correlation analysis is carried out on the set of values obtained for the time series under investigation. We apply this method to the study of some currency daily exchange rates from the point of view of the Hurst exponent and the intermittency parameter. Interesting correlation relationships are revealed and a tentative crisis prediction is presented.

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

Self-rating of daily time management in children: psychometric properties of the Time-S.

PubMed

Sköld, Annika; Janeslätt, Gunnel Kristina

2017-05-01

Impaired ability to manage time has been shown in several diagnoses common in childhood. Impaired ability involves activities and participation domain (daily time management, DTM) and body function and structure domain (time-processing ability, TPA). DTM needs to be evaluated from an individual's own perspective. To date, there has been a lack of self-rating instruments for children that focus on DTM. The aim of this study is to describe psychometric properties of Time-S when used in children aged 10-17 years with a diagnosis of ADHD, Autism, CP or mild ID. Further, to test whether TPA correlates with self-rated DTM. Eighty-three children aged 10-17 years participated in the study. Rasch analysis was used to assess psychometric properties. Correlation analysis was performed between Time-S and a measure of TPA. The 21 items of the Time-S questionnaire fit into a unitary construct measuring self-perceived daily management of an individual's time. A non-significant, small correlation was found between TPA and DTM. The results indicate good psychometric properties for the questionnaire. The questionnaire is potentially useful in intervention planning and evaluation.

[Validation of the Schizophrenia Quality Of Life Scale (SQLS) to Measure Quality of Life in Patients Diagnosed With Schizophrenia in Colombia].

PubMed

Suárez, María Fernanda; Sánchez, Ricardo; Calvo, José Manuel

2013-09-01

To validate the SQLS scale in Colombian patients diagnosed with schizophrenia. The self-report scale was applied to 251 patients. Measures of test-retest reliability, internal consistency and correlation inter-scales with the SF-12 were made by applying the scale 2 days later in 28 patients, and 30 days later in 38; 50 patients filled-out the SF-12 scale to determine the concurrent validity. Three domains were found with all of them having Cronbach's alphas >0.7. The three factors model did not show adequate fit indexes. Test-retest evaluation showed satisfactory correlation values (>0.86). Sensitivity to change did not shown significant differences between the repeated measures. As regards concurrent validity, acceptable correlation values were found only in SF-12 domains related to mental health and functioning. The SQLS has a factorial structure consistent with previous reports, adequate internal consistency and temporal stability. However, a more detailed examination of some of these items is required, considering that the measurement of the construct does not appear to be adequate. Copyright © 2013 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Electronic self-organization in the single-layer manganite $$\\rm Pr_{1-x}Ca_{1+x}MnO4$$

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

Ye, Feng; Chi, Songxue; Fernandez-Baca, Jaime A

We use neutron scattering to investigate the doping evolution of the magnetic correlations in the single-layer manganitemore » $$\\rm Pr_{\\it 1-x}Ca_{\\it 1+x}MnO_4$$, away from the $x=0.5$ composition where the CE-type commensurate antiferromagnetic (AF) structure is stable. We find that short-range incommensurate spin correlations develop as the system is electron doped ($x<0.5$), which coexist with the CE-type AF order. This suggests that electron doping in this system induces an inhomogeneous electronic self-organization, where commensurate AF patches with $x=0.5$ are separated by electron-rich domain walls with short range magnetic correlations. This behavior is strikingly different than for the three-dimensional $$\\rm Pr_{\\it 1-x}Ca_{\\it x}MnO_3$$, where the long-range CE-type commensurate AF structure is stable over a wide range of electron or hole doping around $x=0.5$.« less

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.

White matter correlates of cognitive domains in normal aging with diffusion tensor imaging.

PubMed

Sasson, Efrat; Doniger, Glen M; Pasternak, Ofer; Tarrasch, Ricardo; Assaf, Yaniv

2013-01-01

The ability to perform complex as well as simple cognitive tasks engages a network of brain regions that is mediated by the white matter fiber bundles connecting them. Different cognitive tasks employ distinctive white matter fiber bundles. The temporal lobe and its projections subserve a variety of key functions known to deteriorate during aging. In a cohort of 52 healthy subjects (ages 25-82 years), we performed voxel-wise regression analysis correlating performance in higher-order cognitive domains (executive function, information processing speed, and memory) with white matter integrity, as measured by diffusion tensor imaging (DTI) fiber tracking in the temporal lobe projections [uncinate fasciculus (UF), fornix, cingulum, inferior longitudinal fasciculus (ILF), and superior longitudinal fasciculus (SLF)]. The fiber tracts were spatially registered and statistical parametric maps were produced to spatially localize the significant correlations. Results showed that performance in the executive function domain is correlated with DTI parameters in the left SLF and right UF; performance in the information processing speed domain is correlated with fractional anisotropy (FA) in the left cingulum, left fornix, right and left ILF and SLF; and the memory domain shows significant correlations with DTI parameters in the right fornix, right cingulum, left ILF, left SLF and right UF. These findings suggest that DTI tractography enables anatomical definition of region of interest (ROI) for correlation of behavioral parameters with diffusion indices, and functionality can be correlated with white matter integrity.

Fe65-PTB2 Dimerization Mimics Fe65-APP Interaction.

PubMed

Feilen, Lukas P; Haubrich, Kevin; Strecker, Paul; Probst, Sabine; Eggert, Simone; Stier, Gunter; Sinning, Irmgard; Konietzko, Uwe; Kins, Stefan; Simon, Bernd; Wild, Klemens

2017-01-01

Physiological function and pathology of the Alzheimer's disease causing amyloid precursor protein (APP) are correlated with its cytosolic adaptor Fe65 encompassing a WW and two phosphotyrosine-binding domains (PTBs). The C-terminal Fe65-PTB2 binds a large portion of the APP intracellular domain (AICD) including the GYENPTY internalization sequence fingerprint. AICD binding to Fe65-PTB2 opens an intra-molecular interaction causing a structural change and altering Fe65 activity. Here we show that in the absence of the AICD, Fe65-PTB2 forms a homodimer in solution and determine its crystal structure at 2.6 Å resolution. Dimerization involves the unwinding of a C-terminal α-helix that mimics binding of the AICD internalization sequence, thus shielding the hydrophobic binding pocket. Specific dimer formation is validated by nuclear magnetic resonance (NMR) techniques and cell-based analyses reveal that Fe65-PTB2 together with the WW domain are necessary and sufficient for dimerization. Together, our data demonstrate that Fe65 dimerizes via its APP interaction site, suggesting that besides intra- also intermolecular interactions between Fe65 molecules contribute to homeostatic regulation of APP mediated signaling.

Exploring dangerous neighborhoods: Latent Semantic Analysis and computing beyond the bounds of the familiar

PubMed Central

Cohen, Trevor; Blatter, Brett; Patel, Vimla

2005-01-01

Certain applications require computer systems to approximate intended human meaning. This is achievable in constrained domains with a finite number of concepts. Areas such as psychiatry, however, draw on concepts from the world-at-large. A knowledge structure with broad scope is required to comprehend such domains. Latent Semantic Analysis (LSA) is an unsupervised corpus-based statistical method that derives quantitative estimates of the similarity between words and documents from their contextual usage statistics. The aim of this research was to evaluate the ability of LSA to derive meaningful associations between concepts relevant to the assessment of dangerousness in psychiatry. An expert reference model of dangerousness was used to guide the construction of a relevant corpus. Derived associations between words in the corpus were evaluated qualitatively. A similarity-based scoring function was used to assign dangerousness categories to discharge summaries. LSA was shown to derive intuitive relationships between concepts and correlated significantly better than random with human categorization of psychiatric discharge summaries according to dangerousness. The use of LSA to derive a simulated knowledge structure can extend the scope of computer systems beyond the boundaries of constrained conceptual domains. PMID:16779020

Fe65-PTB2 Dimerization Mimics Fe65-APP Interaction

PubMed Central

Feilen, Lukas P.; Haubrich, Kevin; Strecker, Paul; Probst, Sabine; Eggert, Simone; Stier, Gunter; Sinning, Irmgard; Konietzko, Uwe; Kins, Stefan; Simon, Bernd; Wild, Klemens

2017-01-01

Physiological function and pathology of the Alzheimer’s disease causing amyloid precursor protein (APP) are correlated with its cytosolic adaptor Fe65 encompassing a WW and two phosphotyrosine-binding domains (PTBs). The C-terminal Fe65-PTB2 binds a large portion of the APP intracellular domain (AICD) including the GYENPTY internalization sequence fingerprint. AICD binding to Fe65-PTB2 opens an intra-molecular interaction causing a structural change and altering Fe65 activity. Here we show that in the absence of the AICD, Fe65-PTB2 forms a homodimer in solution and determine its crystal structure at 2.6 Å resolution. Dimerization involves the unwinding of a C-terminal α-helix that mimics binding of the AICD internalization sequence, thus shielding the hydrophobic binding pocket. Specific dimer formation is validated by nuclear magnetic resonance (NMR) techniques and cell-based analyses reveal that Fe65-PTB2 together with the WW domain are necessary and sufficient for dimerization. Together, our data demonstrate that Fe65 dimerizes via its APP interaction site, suggesting that besides intra- also intermolecular interactions between Fe65 molecules contribute to homeostatic regulation of APP mediated signaling. PMID:28553201

Specific intermolecular interactions of conserved water molecules with amino acids in the Galectin-1 carbohydrate recognition domain

NASA Astrophysics Data System (ADS)

Di Lella, Santiago; Petruk, Ariel A.; Armiño, Diego J. Alonso de; Álvarez, Rosa M. S.

2010-08-01

Water molecules, rigidly associated to protein surfaces, play a key role in stabilizing biomolecules and participating in their biological functions. Recent studies on the solvation properties of the carbohydrate recognition domain of Galectin-1 by means of molecular dynamic simulations have revealed the existence of several water sites which were well correlated to both the bound water molecules observed in the crystal structure of the protein in the free state and to some of the hydroxyl groups of the carbohydrate ligand observed in the crystal structure of the complexed protein. In this work, we present a study using quantum mechanical methods (B3LYP/6-311++G(3df,3dp)//B3LYP/6-31+G(d)) to determine the energy involved in the binding of these water molecules to specific amino acids in the carbohydrate recognition domain of the protein. By modeling the hydroxyl groups of the carbohydrate by methanol, the energies associated to the local interactions between the ligand and the protein have been evaluated by replacing specific water molecules with methanol. The values of the binding energies have been compared to those previously obtained by the molecular dynamic method.

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.

Needlet estimation of cross-correlation between CMB lensing maps and LSS

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

Bianchini, Federico; Renzi, Alessandro; Marinucci, Domenico, E-mail: fbianchini@sissa.it, E-mail: renzi@mat.uniroma2.it, E-mail: marinucc@mat.uniroma2.it

In this paper we develop a novel needlet-based estimator to investigate the cross-correlation between cosmic microwave background (CMB) lensing maps and large-scale structure (LSS) data. We compare this estimator with its harmonic counterpart and, in particular, we analyze the bias effects of different forms of masking. In order to address this bias, we also implement a MASTER-like technique in the needlet case. The resulting estimator turns out to have an extremely good signal-to-noise performance. Our analysis aims at expanding and optimizing the operating domains in CMB-LSS cross-correlation studies, similarly to CMB needlet data analysis. It is motivated especially by nextmore » generation experiments (such as Euclid) which will allow us to derive much tighter constraints on cosmological and astrophysical parameters through cross-correlation measurements between CMB and LSS.« less

Reliability, convergent validity and factor structure of the DASS-21 in a sample of Vietnamese adolescents.

PubMed

Le, Minh Thi Hong; Tran, Thach Duc; Holton, Sara; Nguyen, Huong Thanh; Wolfe, Rory; Fisher, Jane

2017-01-01

To assess the internal consistency, latent structure and convergent validity of the Depression, Anxiety and Stress Scale-21 (DASS-21) among adolescents in Vietnam. An anonymous, self-completed questionnaire was conducted among 1,745 high school students in Hanoi, Vietnam between October, 2013 and January, 2014. Confirmatory factor analyses were performed to assess the latent structure of the DASS-21. Factorial invariance between girls and boys was examined. Cronbach alphas and correlation coefficients between DASS-21 factor scores and the domain scores of the Duke Health Profile Adolescent Vietnamese validated version (ADHP-V) were calculated to assess DASS-21 internal consistency and convergent validity. A total of 1,606/ 1,745 (92.6%) students returned the questionnaire. Of those, 1,387 students provided complete DASS-21 data. The scale demonstrated adequate internal consistency (Cronbach α: 0.761 to 0.906). A four-factor model showed the best fit to the data. Items loaded significantly on a common general distress factor, the depression, and the anxiety factors, but few on the stress factor (p<0.05). DASS-21 convergent validity was confirmed with moderate correlation coefficients (-0.47 to -0.66) between its factor scores and the ADHP-V mental health related domains. The DASS-21 is reliable and suitable for use to assess symptoms of common mental health problems, especially depression and anxiety among Vietnamese adolescents. However, its ability in detecting stress among these adolescents may be limited. Further research is warrant to explore these results.

Metal-Induced Stabilization and Activation of Plasmid Replication Initiator RepB

PubMed Central

Ruiz-Masó, José A.; Bordanaba-Ruiseco, Lorena; Sanz, Marta; Menéndez, Margarita; del Solar, Gloria

2016-01-01

Initiation of plasmid rolling circle replication (RCR) is catalyzed by a plasmid-encoded Rep protein that performs a Tyr- and metal-dependent site-specific cleavage of one DNA strand within the double-strand origin (dso) of replication. The crystal structure of RepB, the initiator protein of the streptococcal plasmid pMV158, constitutes the first example of a Rep protein structure from RCR plasmids. It forms a toroidal homohexameric ring where each RepB protomer consists of two domains: the C-terminal domain involved in oligomerization and the N-terminal domain containing the DNA-binding and endonuclease activities. Binding of Mn2+ to the active site is essential for the catalytic activity of RepB. In this work, we have studied the effects of metal binding on the structure and thermostability of full-length hexameric RepB and each of its separate domains by using different biophysical approaches. The analysis of the temperature-induced changes in RepB shows that the first thermal transition, which occurs at a range of temperatures physiologically relevant for the pMV158 pneumococcal host, represents an irreversible conformational change that affects the secondary and tertiary structure of the protein, which becomes prone to self-associate. This transition, which is also shown to result in loss of DNA binding capacity and catalytic activity of RepB, is confined to its N-terminal domain. Mn2+ protects the protein from undergoing this detrimental conformational change and the observed protection correlates well with the high-affinity binding of the cation to the active site, as substituting one of the metal-ligands at this site impairs both the protein affinity for Mn2+and the Mn2+-driven thermostabilization effect. The level of catalytic activity of the protein, especially in the case of full-length RepB, cannot be explained based only on the high-affinity binding of Mn2+ at the active site and suggests the existence of additional, lower-affinity metal binding site(s), missing in the separate catalytic domain, that must also be saturated for maximal activity. The molecular bases of the thermostabilizing effect of Mn2+ on the N-terminal domain of the protein as well as the potential location of additional metal binding sites in the entire RepB are discussed. PMID:27709114

Ionogels Based on Poly(methyl methacrylate) and Metal-Containing Ionic Liquids: Correlation between Structure and Mechanical and Electrical Properties.

PubMed

Zehbe, Kerstin; Kollosche, Matthias; Lardong, Sebastian; Kelling, Alexandra; Schilde, Uwe; Taubert, Andreas

2016-03-16

Ionogels (IGs) based on poly(methyl methacrylate) (PMMA) and the metal-containing ionic liquids (ILs) bis-1-butyl-3-methlimidazolium tetrachloridocuprate(II), tetrachloride cobaltate(II), and tetrachlorido manganate(II) have been synthesized and their mechanical and electrical properties have been correlated with their microstructure. Unlike many previous examples, the current IGs show a decreasing stability in stress-strain experiments on increasing IL fractions. The conductivities of the current IGs are lower than those observed in similar examples in the literature. Both effects are caused by a two-phase structure with micrometer-sized IL-rich domains homogeneously dispersed an IL-deficient continuous PMMA phase. This study demonstrates that the IL-polymer miscibility and the morphology of the IGs are key parameters to control the (macroscopic) properties of IGs.

Ionogels Based on Poly(methyl methacrylate) and Metal-Containing Ionic Liquids: Correlation between Structure and Mechanical and Electrical Properties

PubMed Central

Zehbe, Kerstin; Kollosche, Matthias; Lardong, Sebastian; Kelling, Alexandra; Schilde, Uwe; Taubert, Andreas

2016-01-01

Ionogels (IGs) based on poly(methyl methacrylate) (PMMA) and the metal-containing ionic liquids (ILs) bis-1-butyl-3-methlimidazolium tetrachloridocuprate(II), tetrachloride cobaltate(II), and tetrachlorido manganate(II) have been synthesized and their mechanical and electrical properties have been correlated with their microstructure. Unlike many previous examples, the current IGs show a decreasing stability in stress-strain experiments on increasing IL fractions. The conductivities of the current IGs are lower than those observed in similar examples in the literature. Both effects are caused by a two-phase structure with micrometer-sized IL-rich domains homogeneously dispersed an IL-deficient continuous PMMA phase. This study demonstrates that the IL-polymer miscibility and the morphology of the IGs are key parameters to control the (macroscopic) properties of IGs. PMID:26999112

Drainage - Structure Correlation in tectonically active Regions: Case studies in the Bolivian and Colombian Andes

NASA Astrophysics Data System (ADS)

Zeilinger, Gerold; Parra, Mauricio; Kober, Florian

2017-04-01

It is widely accepted, that drainage patterns are often controlled by tectonics/climate and geology/rheology. Classical drainage patterns can be found 1) in fault-and-thrust belt, where rives follow the valleys parallel or cut perpendicular to strike trough the ridges, forming a trellis pattern, 2) at dome structures where the drainage form a radial pattern or 3) rectangular patterns in strongly fractured regions. In this study, we focus on fault-and-thrust belts, that undergone different phases of tectonic activity. According to classical models, the deformation is propagating into the foreland, hence being youngest at the frontal part and getting successively older towards the axis of the orogen. Drainage patterns in the more interior parts of the orogenic wedge should be then less influenced by the direction of structures, as landscape evolution is changing to a tectonic passive stage. This relationship might represent the transience and maturity of drainage pattern evolution. Here we study drainage patterns of the Bolivian and the eastern Colombian Andes by comparing the relative orientation of the drainage network with the orogen structural grain. The drainage is extracted from Digital Elevation Models (SRTM 30 m) and indexed by their Strahler Order. Order 1 channels have an upstream area of 1 km2. The direction of all segments is analyzed by linear directional mean function that results in the mean orientation of input channels with approx. 500 m average length. The orientation of structures for different structural domains is calculated using the same function on digitized faults and fold-axis. Rose diagrams show the length-weighted directional distribution of structures, of higher (>= 4) and of lower order (<= 3) channels. The structural trend in the Bolivian Andes is controlled by the orocline, where a predominant NW-SE trend turns into an N-S trend at 18°S and where the eastern orogen comprise from west to east, the Eastern Cordillera (EC), the Interandean Zone and the Subandean Zone (SA), exhibiting a catchment relief of up to 5000 m. While the structural trend in the EC is predominately NW-SE with a uniform (no preferred orientation) distribution of lower order fluvial channels, it changes in the SA into a distinct N-S trend with a pronounced E-W orientation of lower order fluvial channels. A similar pattern is recognized in the Eastern Andes of Colombia, where the structural trend is NE-SW. The Eastern Cordillera comprise a frontal thin-skinned Neogene and Paleogene domain (FR) and the more interior lower Cretaceous an Upper Paleozoic thick-skinned region (IR). The trend of higher order channels is, as expected, parallel to the structures in the interior parts and perpendicular in the frontal part. However, the trend of lower order channels reveal no directional correlation to the structural trend in the interior, but a significant correlation to the structures in the frontal range that suffered relatively to the interior domains younger deformation phases. We therefore postulate a dependency of the directional evolution of drainage patterns on the relative timing of tectonic activity. The only weakly preferred orientation of drainages in the interior parts (EC and IR) suggests a balance between structural control and drainage occupation, and higher maturity of the landscape. In contrast, the distinct pattern of drainages oblique to the structural grain in the frontal ranges (SA and FR) highlights the alignment of tributaries and suggests an ongoing tectonic control on drainage orientation. We test the hypothesis whether the correlation between the direction of small order rivers and the direction of structures can be used as a proxy for relative tectonic activity, which might be relevant in questions on 1) dominance of tectonics over climate, 2) dynamics of deformation propagation in fault-and-thrust-belts and 3) occurrence of higher erosion rates despite "limited" relief or threshold slopes. Ongoing efforts will investigate the possibility to quantify or compare relative tectonic activity across sites.

The Reliability and Validity of the Japanese Version of the Stroke Impact Scale Version 3.0.

PubMed

Ochi, Mitsuhiro; Ohashi, Hiroshi; Hachisuka, Kenji; Saeki, Satoru

It is important to evaluate body functions and structures, activity, and participation in stroke rehabilitation. The Stroke Impact Scale (SIS), a new stroke-specific self-report measure that was developed by Duncan et al, is widely used to measure multidimensional consequences about health-related quality of life. The SIS version 3.0 includes 9 domains (strength, hand function, activity of daily living and instrumental activity of daily living, mobility, communication, emotion, memory and thinking, participation, and recovery). Patients are asked to make a percentage rating of their recovery since their stroke on a visual analog scale of 0 to 100 for the stroke recovery domain. Each item in the 8 domains other than stroke recovery are scored in a range of 1 to 5 as a raw score and calculated using the manual to a final score. We developed a Japanese version of the SIS version 3.0 and assessed its reliability and validity in 32 chronic stroke survivors. The internal consistency (Cronbach's α < 0.70) was satisfactory. The test-retest reliability (ICC, 0.86 to 0.96) was also satisfactory. Regarding convergent validity, a significant correlation (Spearman's correlation coefficient, P < 0.05) was found between the SIS physical domain score and Brunnstrom stage (r, 0.49 to 0.53) and short form 8 (r = 0.82). The Japanese version of the SIS version 3.0 is valid, reliable, and clinically useful for stroke survivors.

Evolution of electrical properties and domain configuration of Mn modified Pb(In1/2Nb1/2)O3-PbTiO3 single crystals

NASA Astrophysics Data System (ADS)

Qiao, Huimin; He, Chao; Yuan, Feifei; Wang, Zujian; Li, Xiuzhi; Liu, Ying; Guo, Haiyan; Long, Xifa

2018-04-01

The acceptor doped relaxor-based ferroelectric materials are useful for high power applications such as probes in ultrasound-guided high intensity focused ultrasound therapy. In addition, a high Curie temperature is desired because of wider temperature usage and improved temperature stability. Previous investigations have focused on Pb(Mg1/3Nb2/3)O3-PbTiO3 and Pb(Zn1/3Nb2/3)O3-PbTiO3 systems, which have a ultrahigh piezoelectric coefficient and dielectric constant, but a relatively low Curie temperature. It is desirable to study the binary relaxor-based system with a high Curie temperature. Therefore, Pb(In1/2Nb1/2)O3-PbTiO3 (PINT) single crystals were chosen to study the Mn-doped influence on their electrical properties and domain configuration. The evolution of ferroelectric hysteresis loops for doped and virgin samples exhibit the pinning effect in Mn-doped PINT crystals. The relaxation behaviors of doped and virgin samples are studied by fit of the modified Curie-Weiss law and Volgel-Fucher relation. In addition, a short-range correlation length was fitted to study the behavior of polar nanoregions based on the domain configuration obtained by piezoresponse force microscopy. Complex domain structures and smaller short-range correlation lengths (100-150 nm for Mn-doped PINT and >400 nm for pure PINT) were obtained in the Mn-doped PINT single crystals.

Reversal modes in FeCoNi nanowire arrays: Correlation between magnetostatic interactions and nanowires length

NASA Astrophysics Data System (ADS)

Samanifar, S.; Almasi Kashi, M.; Ramazani, A.; Alikhani, M.

2015-03-01

FeCoNi nanowire arrays (175 nm in diameter and lengths ranging from 5 to 40 μm) were fabricated into nanopores of hard-anodized aluminum oxide templates using pulsed ac electrodeposition technique. Increasing the length had no considerable effect on the composition and crystalline characteristics of Fe47Co38Ni15 nanowires (NWs). By eliminating the dendrites formed at the bottom of the pores, we report a careful investigation on the effect of magnetostatic interactions on magnetic properties and the effect of nanowire length on reversal modes. Hysteresis loop measurements indicated that increasing the length decreases coercivity and squareness values. On the other hand, first-order reversal curve measurements show a linear correlation between the magnetostatic interactions and length of NWs. Comparing reversal modes of the NWs both experimentally and theoretically using angular dependence of coercivity, we find that when L≤22 μm, a vortex domain wall mode is only occurred. When L>22 μm, a non-monotonic behavior indicates a transition from the vortex to transverse domain wall propagation. As a result, a critical length was found above which the transition between the reversal modes is occurred due the enhanced interactions. The transition angle also shifts toward a lower angle as the length increases. Moreover, with increasing length from 22 to 31 μm, the single domain structure of NWs changes to a pseudo single domain state. A multidomain-like behavior is also found for the longest NWs length.

Detecting Coevolution in and among Protein Domains

PubMed Central

Yeang, Chen-Hsiang; Haussler, David

2007-01-01

Correlated changes of nucleic or amino acids have provided strong information about the structures and interactions of molecules. Despite the rich literature in coevolutionary sequence analysis, previous methods often have to trade off between generality, simplicity, phylogenetic information, and specific knowledge about interactions. Furthermore, despite the evidence of coevolution in selected protein families, a comprehensive screening of coevolution among all protein domains is still lacking. We propose an augmented continuous-time Markov process model for sequence coevolution. The model can handle different types of interactions, incorporate phylogenetic information and sequence substitution, has only one extra free parameter, and requires no knowledge about interaction rules. We employ this model to large-scale screenings on the entire protein domain database (Pfam). Strikingly, with 0.1 trillion tests executed, the majority of the inferred coevolving protein domains are functionally related, and the coevolving amino acid residues are spatially coupled. Moreover, many of the coevolving positions are located at functionally important sites of proteins/protein complexes, such as the subunit linkers of superoxide dismutase, the tRNA binding sites of ribosomes, the DNA binding region of RNA polymerase, and the active and ligand binding sites of various enzymes. The results suggest sequence coevolution manifests structural and functional constraints of proteins. The intricate relations between sequence coevolution and various selective constraints are worth pursuing at a deeper level. PMID:17983264

Respiratory-phase domain analysis of heart rate variability can accurately estimate cardiac vagal activity during a mental arithmetic task.

PubMed

Kotani, Kiyoshi; Takamasu, Kiyoshi; Tachibana, Makoto

2007-01-01

The objectives of this paper were to present a method to extract the amplitude of RSA in the respiratory-phase domain, to compare that with subjective or objective indices of the MWL (mental workload), and to compare that with a conventional frequency analysis in terms of its accuracy during a mental arithmetic task. HRV (heart rate variability), ILV (instantaneous lung volume), and motion of the throat were measured under a mental arithmetic experiment and subjective and objective indices were also obtained. The amplitude of RSA was extracted in the respiratory-phase domain, and its correlation with the load level was compared with the results of the frequency domain analysis, which is the standard analysis of the HRV. The subjective and objective indices decreased as the load level increased, showing that the experimental protocol was appropriate. Then, the amplitude of RSA in the respiratory-phase domain also decreased with the increase in the load level. The results of the correlation analysis showed that the respiratory-phase domain analysis has higher negative correlations, -0.84 and -0.82, with the load level as determined by simple correlation and rank correlation, respectively, than does frequency analysis, for which the correlations were found to be -0.54 and -0.63, respectively. In addition, it was demonstrated that the proposed method could be applied to the short-term extraction of RSA amplitude. We proposed a simple and effective method to extract the amplitude of the respiratory sinus arrhythmia (RSA) in the respiratory-phase domain and the results show that this method can estimate cardiac vagal activity more accurately than frequency analysis.

Structural basis of the interaction between integrin α6β4 and plectin at the hemidesmosomes

PubMed Central

de Pereda, José M; Lillo, M Pilar; Sonnenberg, Arnoud

2009-01-01

The interaction between the integrin α6β4 and plectin is essential for the assembly and stability of hemidesmosomes, which are junctional adhesion complexes that anchor epithelial cells to the basement membrane. We describe the crystal structure at 2.75 Å resolution of the primary α6β4–plectin complex, formed by the first pair of fibronectin type III domains and the N-terminal region of the connecting segment of β4 and the actin-binding domain of plectin. Two missense mutations in β4 (R1225H and R1281W) linked to nonlethal forms of epidermolysis bullosa prevent essential intermolecular contacts. We also present two structures at 1.75 and 2.05 Å resolution of the β4 moiety in the absence of plectin, which reveal a major rearrangement of the connecting segment of β4 on binding to plectin. This conformational switch is correlated with the way α6β4 promotes stable adhesion or cell migration and suggests an allosteric control of the integrin. PMID:19242489

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.

Ligand-induced perturbation of the HIF-2α:ARNT dimer dynamics

PubMed Central

Motta, Stefano

2018-01-01

Hypoxia inducible factors (HIFs) are transcription factors belonging to the basic helix−loop−helix PER-ARNT-SIM (bHLH-PAS) protein family with a role in sensing oxygen levels in the cell. Under hypoxia, the HIF-α degradation pathway is blocked and dimerization with the aryl hydrocarbon receptor nuclear translocator (ARNT) makes HIF-α transcriptionally active. Due to the common hypoxic environment of tumors, inhibition of this mechanism by destabilization of HIF-α:ARNT dimerization has been proposed as a promising therapeutic strategy. Following the discovery of a druggable cavity within the PAS-B domain of HIF-2α, research efforts have been directed to identify artificial ligands that can impair heterodimerization. Although the crystallographic structures of the HIF-2α:ARNT complex have elucidated the dimer architecture and the 0X3-inhibitor placement within the HIF-2α PAS-B, unveiling the inhibition mechanism requires investigation of how ligand-induced perturbations could dynamically propagate through the structure and affect dimerization. To this end, we compared evolutionary features, intrinsic dynamics and energetic properties of the dimerization interfaces of HIF-2α:ARNT in both the apo and holo forms. Residue conservation analysis highlighted inter-domain connecting elements that have a role in dimerization. Analysis of domain contributions to the dimerization energy demonstrated the importance of bHLH and PAS-A of both partners and of HIF-2α PAS-B domain in dimer stabilization. Among quaternary structure oscillations revealed by Molecular Dynamics simulations, the hinge-bending motion of the ARNT PAS-B domain around the flexible PAS-A/PAS-B linker supports a general model for ARNT dimerization in different heterodimers. Comparison of the HIF-2α:ARNT dynamics in the apo and 0X3-bound forms indicated a model of inhibition where the HIF-2α-PAS-B interfaces are destabilised as a result of water-bridged ligand-protein interactions and these local effects allosterically propagate to perturb the correlated motions of the domains and inter-domain communication. These findings will guide the design of improved inhibitors to contrast cell survival in tumor masses. PMID:29489822

Substituting Tyr138 in the active site loop of human phenylalanine hydroxylase affects catalysis and substrate activation.

PubMed

Leandro, João; Stokka, Anne J; Teigen, Knut; Andersen, Ole A; Flatmark, Torgeir

2017-07-01

Mammalian phenylalanine hydroxylase (PAH) is a key enzyme in l-phenylalanine (l-Phe) metabolism and is active as a homotetramer. Biochemical and biophysical work has demonstrated that it cycles between two states with a variably low and a high activity, and that the substrate l-Phe is the key player in this transition. X-ray structures of the catalytic domain have shown mobility of a partially intrinsically disordered Tyr 138 -loop to the active site in the presence of l-Phe. The mechanism by which the loop dynamics are coupled to substrate binding at the active site in tetrameric PAH is not fully understood. We have here conducted functional studies of four Tyr 138 point mutants. A high linear correlation ( r 2 = 0.99) was observed between their effects on the catalytic efficiency of the catalytic domain dimers and the corresponding effect on the catalytic efficiency of substrate-activated full-length tetramers. In the tetramers, a correlation ( r 2 = 0.96) was also observed between the increase in catalytic efficiency (activation) and the global conformational change (surface plasmon resonance signal response) at the same l-Phe concentration. The new data support a similar functional importance of the Tyr 138 -loop in the catalytic domain and the full-length enzyme homotetramer.

1H-detected MAS solid-state NMR experiments enable the simultaneous mapping of rigid and dynamic domains of membrane proteins

NASA Astrophysics Data System (ADS)

Gopinath, T.; Nelson, Sarah E. D.; Veglia, Gianluigi

2017-12-01

Magic angle spinning (MAS) solid-state NMR (ssNMR) spectroscopy is emerging as a unique method for the atomic resolution structure determination of native membrane proteins in lipid bilayers. Although 13C-detected ssNMR experiments continue to play a major role, recent technological developments have made it possible to carry out 1H-detected experiments, boosting both sensitivity and resolution. Here, we describe a new set of 1H-detected hybrid pulse sequences that combine through-bond and through-space correlation elements into single experiments, enabling the simultaneous detection of rigid and dynamic domains of membrane proteins. As proof-of-principle, we applied these new pulse sequences to the membrane protein phospholamban (PLN) reconstituted in lipid bilayers under moderate MAS conditions. The cross-polarization (CP) based elements enabled the detection of the relatively immobile residues of PLN in the transmembrane domain using through-space correlations; whereas the most dynamic region, which is in equilibrium between folded and unfolded states, was mapped by through-bond INEPT-based elements. These new 1H-detected experiments will enable one to detect not only the most populated (ground) states of biomacromolecules, but also sparsely populated high-energy (excited) states for a complete characterization of protein free energy landscapes.

Spanish translation and validation of the Preschool Activity Card Sort.

PubMed

Stoffel, Ashley; Berg, Christine

2008-05-01

Few standardized assessments exist for children living in the United States who are Hispanic/Latino. This study reports the Spanish translation process for the Preschool Activity Card Sort (PACS), which is a measure of participation in preschool children, and examines content, construct, and concurrent validity. Methods of verifying accuracy of translation included expert review and back translation and supported content validity of the Tarjetas de Actividades Preescolares (TAP). Subsequently, a sample of 37 parents of children between 3 and 6 years of age completed the PACS/TAP by structured interview. Twenty-six parents were Spanish speaking, and 11 were English speaking. A comparison of reported participation by Spanish- and English-speaking children provides initial construct validity of the TAP. Results indicate that the TAP differentiates among children of recent immigrants as compared to preschoolers who were born in the United States on domains of self-care, high and low demand leisure, and educational activities. Results emphasize the importance of considering sociocultural influences when assessing participation. PACS/TAP scores were moderately correlated with Pediatric Evaluation of Disability Inventory scores for the self-care domain, but did not correlate with the mobility or social function domains. The PACS/TAP appears to provide a useful means of understanding preschoolers' participation. Future research is needed to further establish the validity of this assessment.

Retinal thickness changes after phacoemulsification

PubMed Central

Pardianto, Gede; Moeloek, Nila; Reveny, Julia; Wage, Sutarman; Satari, Imsyah; Sembiring, Rosita; Srisamran, Nuttamon

2013-01-01

Purpose To determine the effect of phacoemulsification on macular volume and thickness using spectral domain optical coherence tomography examinations. Methods Twenty-seven eyes of 27 subjects who underwent phacoemulsification were studied. All nine areas of the macula were examined by spectral domain optical coherence tomography preoperatively and 2 months postoperatively. Effective phacoemulsification time and absolute phacoemulsification time were also recorded. Results There were statistically significant differences in macular thickness between preoperative and postoperative spectral domain optical coherence tomography examinations in nine areas including macular volume. In the paracentral macular area, the thickness of three quadrants significantly increased (superior P=0.015; temporal P=0.001; and nasal P=0.023). Peripheral macular thickness also increased significantly in the superior (P=0.05) and temporal macular areas (P<0.001). The macular volume increased significantly after phacoemulsification (P<0.001). There were no correlations between absolute/effective phacoemulsification time and macular cellular structures (P>0.05), but a significant correlation (P=0.011) was found between absolute phacoemulsification time and change in macular volume. Conclusion Macular thickness changes in the nasal, superior, and temporal quadrants of the paracentral area and the superior and temporal quadrants of the peripheral area, as well as macular volume, may be used as detailed biomarkers to measure the effects of intraocular pressure fluctuations and maneuvers in phacoemulsification intraocular surgeries. PMID:24235812

The organization of domains in proteins obeys Menzerath-Altmann's law of language.

PubMed

Shahzad, Khuram; Mittenthal, Jay E; Caetano-Anollés, Gustavo

2015-08-11

The combination of domains in multidomain proteins enhances their function and structure but lengthens the molecules and increases their cost at cellular level. The dependence of domain length on the number of domains a protein holds was surveyed for a set of 60 proteomes representing free-living organisms from all kingdoms of life. Distributions were fitted using non-linear functions and fitted parameters interpreted with a formulation of decreasing returns. We find that domain length decreases with increasing number of domains in proteins, following the Menzerath-Altmann (MA) law of language. Highly significant negative correlations exist for the set of proteomes examined. Mathematically, the MA law expresses as a power law relationship that unfolds when molecular persistence P is a function of domain accretion. P holds two terms, one reflecting the matter-energy cost of adding domains and extending their length, the other reflecting how domain length and number impinges on information and biophysics. The pattern of diminishing returns can therefore be explained as a frustrated interplay between the strategies of economy, flexibility and robustness, matching previously observed trade-offs in the domain makeup of proteomes. Proteomes of Archaea, Fungi and to a lesser degree Plants show the largest push towards molecular economy, each at their own economic stratum. Fungi increase domain size in single domain proteins while reinforcing the pattern of diminishing returns. In contrast, Metazoa, and to lesser degrees Protista and Bacteria, relax economy. Metazoa achieves maximum flexibility and robustness by harboring compact molecules and complex domain organization, offering a new functional vocabulary for molecular biology. The tendency of parts to decrease their size when systems enlarge is universal for language and music, and now for parts of macromolecules, extending the MA law to natural systems.

Application of Cross-Correlation Greens Function Along With FDTD for Fast Computation of Envelope Correlation Coefficient Over Wideband for MIMO Antennas

NASA Astrophysics Data System (ADS)

Sarkar, Debdeep; Srivastava, Kumar Vaibhav

2017-02-01

In this paper, the concept of cross-correlation Green's functions (CGF) is used in conjunction with the finite difference time domain (FDTD) technique for calculation of envelope correlation coefficient (ECC) of any arbitrary MIMO antenna system over wide frequency band. Both frequency-domain (FD) and time-domain (TD) post-processing techniques are proposed for possible application with this FDTD-CGF scheme. The FDTD-CGF time-domain (FDTD-CGF-TD) scheme utilizes time-domain signal processing methods and exhibits significant reduction in ECC computation time as compared to the FDTD-CGF frequency domain (FDTD-CGF-FD) scheme, for high frequency-resolution requirements. The proposed FDTD-CGF based schemes can be applied for accurate and fast prediction of wideband ECC response, instead of the conventional scattering parameter based techniques which have several limitations. Numerical examples of the proposed FDTD-CGF techniques are provided for two-element MIMO systems involving thin-wire half-wavelength dipoles in parallel side-by-side as well as orthogonal arrangements. The results obtained from the FDTD-CGF techniques are compared with results from commercial electromagnetic solver Ansys HFSS, to verify the validity of proposed approach.

Insight into structural rearrangements and interdomain interactions related to electron transfer between flavin mononucleotide and heme in nitric oxide synthase: A molecular dynamics study.

PubMed

Sheng, Yinghong; Zhong, Linghao; Guo, Dahai; Lau, Gavin; Feng, Changjian

2015-12-01

Calmodulin (CaM) binding to nitric oxide synthase (NOS) enables a conformational change, in which the FMN domain shuttles between the FAD and heme domains to deliver electrons to the active site heme center. A clear understanding of this large conformational change is critical, since this step is the rate-limiting in NOS catalysis. Herein molecular dynamics simulations were conducted on a model of an oxygenase/FMN (oxyFMN) construct of human inducible NOS (iNOS). This is to investigate the structural rearrangements and the domain interactions related to the FMN-heme interdomain electron transfer (IET). We carried out simulations on the iNOS oxyFMN·CaM complex models in [Fe(III)][FMNH(-)] and [Fe(II)][FMNH] oxidation states, the pre- and post-IET states. The comparison of the dynamics and conformations of the iNOS construct at the two oxidation states has allowed us to identify key factors related to facilitating the FMN-heme IET process. The computational results demonstrated, for the first time, that the conformational change is redox-dependent. Predictions of the key interacting sites in optimal interdomain FMN/heme docking are well supported by experimental data in the literature. An intra-subunit pivot region is predicted to modulate the FMN domain motion and correlate with existence of a bottleneck in the conformational sampling that leads to the electron transfer-competent state. Interactions of the residues identified in this work are proposed to ensure that the FMN domain moves with appropriate degrees of freedom and docks to proper positions at the heme domain, resulting in efficient IET and nitric oxide production. Copyright © 2015 Elsevier Inc. All rights reserved.

The four-domain structure model of a depression scale for medical students: A cross-sectional study in Haiphong, Vietnam.

PubMed

Nguyen, Thao Thi Thu; Nguyen, Ngoc Thi Minh; Pham, Manh Van; Pham, Han Van; Nakamura, Hiroyuki

2018-01-01

Depression is a common mental health problem with a higher prevalence in medical students than in the general population. This study aims to investigate the association between depressive symptoms, particularly those in each domain of the Center for Epidemiological Studies Depression (CES-D) Scale, and related factors. A cross-sectional study was conducted with a random sample of 1319 medical students at Haiphong University of Medicine and Pharmacy in 2016. The CES-D scale and a self-reported questionnaire were used to identify the prevalence of depressive symptoms and related risk factors. Univariate and multivariate logistic regression were performed to assess the risk factors associated with depressive symptoms and the score for each structure factor. Depressive symptoms were observed in 514 (39%) students, including more males than females (44.2% vs 36.9%, p = 0.015). Students whose mothers' highest education level was primary school had a higher prevalence of depressive symptoms than students whose mothers had higher education levels (p = 0.038). There was a significant relationship between depressive symptoms and stressful life events, especially a decline in personal health. A higher correlation was found between the somatic complaints and depressive affect domains. The impacts of risk factors differed for each domain of the depression scale. Only the factor of achieving excellence showed no statistically significant associations with depressive symptoms and the scores on the four domains considered in this study. The high prevalence of depressive symptoms among medical students with risk factors and the impact of these risk factors on each domain of depression scale need further clarification to alleviate depression in students during their medical training.

Genome-wide analysis of putative peroxiredoxin in unicellular and filamentous cyanobacteria.

PubMed

Cui, Hongli; Wang, Yipeng; Wang, Yinchu; Qin, Song

2012-11-16

Cyanobacteria are photoautotrophic prokaryotes with wide variations in genome sizes and ecological habitats. Peroxiredoxin (PRX) is an important protein that plays essential roles in protecting own cells against reactive oxygen species (ROS). PRXs have been identified from mammals, fungi and higher plants. However, knowledge on cyanobacterial PRXs still remains obscure. With the availability of 37 sequenced cyanobacterial genomes, we performed a comprehensive comparative analysis of PRXs and explored their diversity, distribution, domain structure and evolution. Overall 244 putative prx genes were identified, which were abundant in filamentous diazotrophic cyanobacteria, Acaryochloris marina MBIC 11017, and unicellular cyanobacteria inhabiting freshwater and hot-springs, while poor in all Prochlorococcus and marine Synechococcus strains. Among these putative genes, 25 open reading frames (ORFs) encoding hypothetical proteins were identified as prx gene family members and the others were already annotated as prx genes. All 244 putative PRXs were classified into five major subfamilies (1-Cys, 2-Cys, BCP, PRX5_like, and PRX-like) according to their domain structures. The catalytic motifs of the cyanobacterial PRXs were similar to those of eukaryotic PRXs and highly conserved in all but the PRX-like subfamily. Classical motif (CXXC) of thioredoxin was detected in protein sequences from the PRX-like subfamily. Phylogenetic tree constructed of catalytic domains coincided well with the domain structures of PRXs and the phylogenies based on 16s rRNA. The distribution of genes encoding PRXs in different unicellular and filamentous cyanobacteria especially those sub-families like PRX-like or 1-Cys PRX correlate with the genome size, eco-physiology, and physiological properties of the organisms. Cyanobacterial and eukaryotic PRXs share similar conserved motifs, indicating that cyanobacteria adopt similar catalytic mechanisms as eukaryotes. All cyanobacterial PRX proteins share highly similar structures, implying that these genes may originate from a common ancestor. In this study, a general framework of the sequence-structure-function connections of the PRXs was revealed, which may facilitate functional investigations of PRXs in various organisms.

Genome-wide analysis of putative peroxiredoxin in unicellular and filamentous cyanobacteria

PubMed Central

2012-01-01

Background Cyanobacteria are photoautotrophic prokaryotes with wide variations in genome sizes and ecological habitats. Peroxiredoxin (PRX) is an important protein that plays essential roles in protecting own cells against reactive oxygen species (ROS). PRXs have been identified from mammals, fungi and higher plants. However, knowledge on cyanobacterial PRXs still remains obscure. With the availability of 37 sequenced cyanobacterial genomes, we performed a comprehensive comparative analysis of PRXs and explored their diversity, distribution, domain structure and evolution. Results Overall 244 putative prx genes were identified, which were abundant in filamentous diazotrophic cyanobacteria, Acaryochloris marina MBIC 11017, and unicellular cyanobacteria inhabiting freshwater and hot-springs, while poor in all Prochlorococcus and marine Synechococcus strains. Among these putative genes, 25 open reading frames (ORFs) encoding hypothetical proteins were identified as prx gene family members and the others were already annotated as prx genes. All 244 putative PRXs were classified into five major subfamilies (1-Cys, 2-Cys, BCP, PRX5_like, and PRX-like) according to their domain structures. The catalytic motifs of the cyanobacterial PRXs were similar to those of eukaryotic PRXs and highly conserved in all but the PRX-like subfamily. Classical motif (CXXC) of thioredoxin was detected in protein sequences from the PRX-like subfamily. Phylogenetic tree constructed of catalytic domains coincided well with the domain structures of PRXs and the phylogenies based on 16s rRNA. Conclusions The distribution of genes encoding PRXs in different unicellular and filamentous cyanobacteria especially those sub-families like PRX-like or 1-Cys PRX correlate with the genome size, eco-physiology, and physiological properties of the organisms. Cyanobacterial and eukaryotic PRXs share similar conserved motifs, indicating that cyanobacteria adopt similar catalytic mechanisms as eukaryotes. All cyanobacterial PRX proteins share highly similar structures, implying that these genes may originate from a common ancestor. In this study, a general framework of the sequence-structure-function connections of the PRXs was revealed, which may facilitate functional investigations of PRXs in various organisms. PMID:23157370

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

Sequence stratigraphy, structural style, and age of deformation of the Malaita accretionary prism (Solomon arc-Ontong Java Plateau convergent zone)

NASA Astrophysics Data System (ADS)

Phinney, Eric J.; Mann, Paul; Coffin, Millard F.; Shipley, Thomas H.

2004-10-01

Possibilities for the fate of oceanic plateaus at subduction zones range from complete subduction of the plateau beneath the arc to complete plateau-arc accretion and resulting collisional orogenesis. Deep penetration, multi-channel seismic reflection (MCS) data from the northern flank of the Solomon Islands reveal the sequence stratigraphy, structural style, and age of deformation of an accretionary prism formed during late Neogene (5-0 Ma) convergence between the ˜33-km-thick crust of the Ontong Java oceanic plateau and the ˜15-km-thick Solomon island arc. Correlation of MCS data with the satellite-derived, free-air gravity field defines the tectonic boundaries and internal structure of the 800-km-long, 140-km-wide accretionary prism. We name this prism the "Malaita accretionary prism" or "MAP" after Malaita, the largest and best-studied island exposure of the accretionary prism in the Solomon Islands. MCS data, gravity data, and stratigraphic correlations to islands and ODP sites on the Ontong Java Plateau (OJP) reveal that the offshore MAP is composed of folded and thrust faulted sedimentary rocks and upper crystalline crust offscraped from the Solomon the subducting Ontong Java Plateau (Pacific plate) and transferred to the Solomon arc. With the exception of an upper, sequence of Quaternary? island-derived terrigenous sediments, the deformed stratigraphy of the MAP is identical to that of the incoming Ontong Java Plateau in the North Solomon trench. We divide the MAP into four distinct, folded and thrust fault-bounded structural domains interpreted to have formed by diachronous, southeast-to-northwest, and highly oblique entry of the Ontong Java Plateau into a former trench now marked by the Kia-Kaipito-Korigole (KKK) left-lateral strike-slip fault zone along the suture between the Solomon arc and the MAP. The structural style within each of the four structural domains consists of a parallel series of three to four fault propagation folds formed by the seaward propagation of thrust faults roughly parallel to sub-horizontal layering in the upper crystalline part of the OJP. Thrust fault offsets, spacing between thrusts, and the amplitude of related fault propagation folds progressively decrease to the west in the youngest zone of active MAP accretion (Choiseul structural domain). Surficial faulting and folding in the most recently deformed, northwestern domain show active accretion of greater than 1 km of sedimentary rock and 6 km, or about 20%, of the upper crystalline part of the OJP. The eastern MAP (Malaita and Ulawa domains) underwent an earlier, similar style of partial plateau accretion. A pre-late Pliocene age of accretion (˜3.4 Ma) is constrained by an onshore and offshore major angular unconformity separating Pliocene reefal limestone and conglomerate from folded and faulted pelagic limestone of Cretaceous to Miocene age. The lower 80% of the Ontong Java Plateau crust beneath the MAP thrust decollement appears unfaulted and unfolded and is continuous with a southwestward-dipping subducted slab of presumably denser plateau material beneath most of the MAP, and is traceable to depths >200 km in the mantle beneath the Solomon Islands.

Psychometric properties of the WHOQOL-BREF in an Iranian adult sample.

PubMed

Yousefy, A R; Usefy, A R; Ghassemi, Gh R; Sarrafzadegan, N; Mallik, S; Baghaei, A M; Rabiei, K

2010-04-01

To evaluate discriminant validity, reliability, internal consistency, and dimensional structure of the World Health Organization Quality of Life-BREF (WHOQOL-BREF) in a heterogeneous Iranian population. A clustered randomized sample of 2,956 healthy with 2,936 unhealthy rural and urban inhabitants aged 30 and above from two dissimilar Iranian provinces during 2006 completed the Persian version of the WHOQOL-BREF. We performed descriptive and analytical analysis including t-student, correlation matrix, Cronbach's Alpha, and factor analysis with principal components method and Varimax rotation with SPSS.15. The mean age of the participants was 42.2 +/- 12.1 years and the mean years of education was 9.3 +/- 3.8. The Iranian version of the WHOQOL-BREF domain scores demonstrated good internal consistency, criterion validity, and discriminant validity. The physical health domain contributed most in overall quality of life, while the environment domain made the least contribution. Factor analysis provided evidence for construct validity for four-factor model of the instrument. The scores of all domains discriminated between healthy persons and the patients. The WHOQOL-BREF has adequate psychometric properties and is, therefore, an adequate measure for assessing quality of life at the domain level in an adult Iranian population.

Development of the Complex General Linear Model in the Fourier Domain: Application to fMRI Multiple Input-Output Evoked Responses for Single Subjects

PubMed Central

Rio, Daniel E.; Rawlings, Robert R.; Woltz, Lawrence A.; Gilman, Jodi; Hommer, Daniel W.

2013-01-01

A linear time-invariant model based on statistical time series analysis in the Fourier domain for single subjects is further developed and applied to functional MRI (fMRI) blood-oxygen level-dependent (BOLD) multivariate data. This methodology was originally developed to analyze multiple stimulus input evoked response BOLD data. However, to analyze clinical data generated using a repeated measures experimental design, the model has been extended to handle multivariate time series data and demonstrated on control and alcoholic subjects taken from data previously analyzed in the temporal domain. Analysis of BOLD data is typically carried out in the time domain where the data has a high temporal correlation. These analyses generally employ parametric models of the hemodynamic response function (HRF) where prewhitening of the data is attempted using autoregressive (AR) models for the noise. However, this data can be analyzed in the Fourier domain. Here, assumptions made on the noise structure are less restrictive, and hypothesis tests can be constructed based on voxel-specific nonparametric estimates of the hemodynamic transfer function (HRF in the Fourier domain). This is especially important for experimental designs involving multiple states (either stimulus or drug induced) that may alter the form of the response function. PMID:23840281

Development of the complex general linear model in the Fourier domain: application to fMRI multiple input-output evoked responses for single subjects.

PubMed

Rio, Daniel E; Rawlings, Robert R; Woltz, Lawrence A; Gilman, Jodi; Hommer, Daniel W

2013-01-01

A linear time-invariant model based on statistical time series analysis in the Fourier domain for single subjects is further developed and applied to functional MRI (fMRI) blood-oxygen level-dependent (BOLD) multivariate data. This methodology was originally developed to analyze multiple stimulus input evoked response BOLD data. However, to analyze clinical data generated using a repeated measures experimental design, the model has been extended to handle multivariate time series data and demonstrated on control and alcoholic subjects taken from data previously analyzed in the temporal domain. Analysis of BOLD data is typically carried out in the time domain where the data has a high temporal correlation. These analyses generally employ parametric models of the hemodynamic response function (HRF) where prewhitening of the data is attempted using autoregressive (AR) models for the noise. However, this data can be analyzed in the Fourier domain. Here, assumptions made on the noise structure are less restrictive, and hypothesis tests can be constructed based on voxel-specific nonparametric estimates of the hemodynamic transfer function (HRF in the Fourier domain). This is especially important for experimental designs involving multiple states (either stimulus or drug induced) that may alter the form of the response function.

Full waveform inversion using envelope-based global correlation norm

NASA Astrophysics Data System (ADS)

Oh, Ju-Won; Alkhalifah, Tariq

2018-05-01

To increase the feasibility of full waveform inversion on real data, we suggest a new objective function, which is defined as the global correlation of the envelopes of modelled and observed data. The envelope-based global correlation norm has the advantage of the envelope inversion that generates artificial low-frequency information, which provides the possibility to recover long-wavelength structure in an early stage. In addition, the envelope-based global correlation norm maintains the advantage of the global correlation norm, which reduces the sensitivity of the misfit to amplitude errors so that the performance of inversion on real data can be enhanced when the exact source wavelet is not available and more complex physics are ignored. Through the synthetic example for 2-D SEG/EAGE overthrust model with inaccurate source wavelet, we compare the performance of four different approaches, which are the least-squares waveform inversion, least-squares envelope inversion, global correlation norm and envelope-based global correlation norm. Finally, we apply the envelope-based global correlation norm on the 3-D Ocean Bottom Cable (OBC) data from the North Sea. The envelope-based global correlation norm captures the strong reflections from the high-velocity caprock and generates artificial low-frequency reflection energy that helps us recover long-wavelength structure of the model domain in the early stages. From this long-wavelength model, the conventional global correlation norm is sequentially applied to invert for higher-resolution features of the model.

Extending the half-life of a fab fragment through generation of a humanized anti-human serum albumin Fv domain: An investigation into the correlation between affinity and serum half-life.

PubMed

Adams, Ralph; Griffin, Laura; Compson, Joanne E; Jairaj, Mark; Baker, Terry; Ceska, Tom; West, Shauna; Zaccheo, Oliver; Davé, Emma; Lawson, Alastair Dg; Humphreys, David P; Heywood, Sam

2016-10-01

We generated an anti-albumin antibody, CA645, to link its Fv domain to an antigen-binding fragment (Fab), thereby extending the serum half-life of the Fab. CA645 was demonstrated to bind human, cynomolgus, and mouse serum albumin with similar affinity (1-7 nM), and to bind human serum albumin (HSA) when it is in complex with common known ligands. Importantly for half-life extension, CA645 binds HSA with similar affinity within the physiologically relevant range of pH 5.0 - pH 7.4, and does not have a deleterious effect on the binding of HSA to neonatal Fc receptor (FcRn). A crystal structure of humanized CA645 Fab in complex with HSA was solved and showed that CA645 Fab binds to domain II of HSA. Superimposition with the crystal structure of FcRn bound to HSA confirmed that CA645 does not block HSA binding to FcRn. In mice, the serum half-life of humanized CA645 Fab is 84.2 h. This is a significant extension in comparison with < 1 h for a non-HSA binding CA645 Fab variant. The Fab-HSA structure was used to design a series of mutants with reduced affinity to investigate the correlation between the affinity for albumin and serum half-life. Reduction in the affinity for MSA by 144-fold from 2.2 nM to 316 nM had no effect on serum half-life. Strikingly, despite a reduction in affinity to 62 µM, an extension in serum half-life of 26.4 h was still obtained. CA645 Fab and the CA645 Fab-HSA complex have been deposited in the Protein Data Bank (PDB) with accession codes, 5FUZ and 5FUO, respectively.

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

The auto-inhibitory state of Rho guanine nucleotide exchange factor ARHGEF5/TIM can be relieved by targeting its SH3 domain with rationally designed peptide aptamers.

PubMed

He, Ping; Tan, De-Li; Liu, Hong-Xiang; Lv, Feng-Lin; Wu, Wei

2015-04-01

The short isoform of Rho guanine nucleotide exchange factor ARHGEF5 is known as TIM, which plays diverse roles in, for example, tumorigenesis, neuronal development and Src-induced podosome formation through the activation of its substrates, the Rho family of GTPases. The activation is auto-inhibited by a putative helix N-terminal to the DH domain of TIM, which is stabilized by the intramolecular interaction of C-terminal SH3 domain with a poly-proline sequence between the putative helix and the DH domain. In this study, we systematically investigated the structural basis, energetic landscape and biological implication underlying TIM auto-inhibition by using atomistic molecular dynamics simulations and binding free energy analysis. The computational study revealed that the binding of SH3 domain to poly-proline sequence is the prerequisite for the stabilization of TIM auto-inhibition. Thus, it is suggested that targeting SH3 domain with competitors of the poly-proline sequence would be a promising strategy to relieve the auto-inhibitory state of TIM. In this consideration, we rationally designed a number of peptide aptamers for competitively inhibiting the SH3 domain based on modeled TIM structure and computationally generated data. Peptide binding test and guanine nucleotide exchange analysis solidified that these designed peptides can both bind to the SH3 domain potently and activate TIM-catalyzed RhoA exchange reaction effectively. Interestingly, a positive correlation between the peptide affinity and induced exchange activity was observed. In addition, separate mutation of three conserved residues Pro49, Pro52 and Lys54 - they are required for peptide recognition by SH3 domain -- in a designed peptide to Ala would completely abolish the capability of this peptide activating TIM. All these come together to suggest an intrinsic relationship between peptide binding to SH3 domain and the activation of TIM. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

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

Interferometry theory for the block 2 processor

NASA Technical Reports Server (NTRS)

Thomas, J. B.

1987-01-01

Presented is the interferometry theory for the Block 2 processor, including a high-level functional description and a discussion of data structure. The analysis covers the major processing steps: cross-correlation, fringe counter-rotation, transformation to the frequency domain, phase calibration, bandwidth synthesis, and extraction of the observables of amplitude, phase, phase rate, and delay. Also included are analyses for fractional bitshift correction, station clock error, ionosphere correction, and effective frequencies for the observables.

Logo recognition using alpha-rooted phase correlation in the radon transform domain

NASA Astrophysics Data System (ADS)

DelMarco, Stephen

2009-08-01

Alpha-rooted phase correlation (ARPC) is a recently-developed variant of classical phase correlation that includes a Fourier domain image enhancement operation. ARPC combines classical phase correlation with alpha-rooting to provide tunable image enhancement. The alpha-rooting parameters may be adjusted to provide a tradeoff between height and width of the ARPC main lobe. A high narrow main lobe peak provides high matching accuracy for aligned images, but reduced matching performance for misaligned logos. A lower, wider peak trades matching accuracy on aligned logos, for improved matching performance on misaligned imagery. Previously, we developed ARPC and used it in the spatial domain for logo recognition as part of an overall automated document analysis problem. However, spatial domain ARPC performance can be sensitive to logo misalignments, including rotational misalignment. In this paper we use ARPC as a match metric in the radon transform domain for logo recognition. In the radon transform domain, rotational misalignments correspond to translations in the radon transform angle parameter. These translations are captured by ARPC, thereby producing rotation-invariant logo matching. In the paper, we first present an overview of ARPC, and then describe the logo matching algorithm. We present numerical performance results demonstrating matching tolerance to rotational misalignments. We demonstrate robustness of the radon transform domain rotation estimation to noise. We present logo verification and recognition performance results using the proposed approach on a public domain logo database. We compare performance results to performance obtained using spatial domain ARPC, and state-of-the-art SURF features, for logos in salt-and-pepper noise.

Development of five digits is controlled by a bipartite long-range cis-regulator.

PubMed

Lettice, Laura A; Williamson, Iain; Devenney, Paul S; Kilanowski, Fiona; Dorin, Julia; Hill, Robert E

2014-04-01

Conservation within intergenic DNA often highlights regulatory elements that control gene expression from a long range. How conservation within a single element relates to regulatory information and how internal composition relates to function is unknown. Here, we examine the structural features of the highly conserved ZRS (also called MFCS1) cis-regulator responsible for the spatiotemporal control of Shh in the limb bud. By systematically dissecting the ZRS, both in transgenic assays and within in the endogenous locus, we show that the ZRS is, in effect, composed of two distinct domains of activity: one domain directs spatiotemporal activity but functions predominantly from a short range, whereas a second domain is required to promote long-range activity. We show further that these two domains encode activities that are highly integrated and that the second domain is crucial in promoting the chromosomal conformational changes correlated with gene activity. During limb bud development, these activities encoded by the ZRS are interpreted differently by the fore limbs and the hind limbs; in the absence of the second domain there is no Shh activity in the fore limb, and in the hind limb low levels of Shh lead to a variant digit pattern ranging from two to four digits. Hence, in the embryo, the second domain stabilises the developmental programme providing a buffer for SHH morphogen activity and this ensures that five digits form in both sets of limbs.

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

Portuguese-language version of the Chronic Respiratory Questionnaire: a validity and reproducibility study.

PubMed

Moreira, Graciane Laender; Pitta, Fábio; Ramos, Dionei; Nascimento, Cinthia Sousa Carvalho; Barzon, Danielle; Kovelis, Demétria; Colange, Ana Lúcia; Brunetto, Antonio Fernando; Ramos, Ercy Mara Cipulo

2009-08-01

To determine the validity and reproducibility of a Portuguese-language version of the Chronic Respiratory Questionnaire (CRQ) in patients with COPD. A Portuguese-language version of the CRQ (provided by McMaster University, the holder of the questionnaire copyright) was applied to 50 patients with COPD (70 +/- 8 years of age; 32 males; FEV1 = 47 +/- 18% of predicted) on two occasions, one week apart. The CRQ has four domains (dyspnea, fatigue, emotional function, and mastery) and was applied as an interviewer-administered instrument. The Saint George's Respiratory Questionnaire (SGRQ), already validated for use in Brazil, was used as the criterion for validation. Spirometry and the six-minute walk test (6MWT) were performed to analyze the correlations with the CRQ scores. There were no significant CRQ test-retest differences (p > 0.05 for all domains). The test-retest intraclass correlation coefficient was 0.98, 0.97, 0.98 and 0.95 for the dyspnea, fatigue, emotional function and mastery domains, respectively. The Cronbach's alpha coefficient was 0.91. The CRQ domains correlated significantly with the SGRQ domains (-0.30 < r < -0.67; p < 0.05). There were no significant correlations between spirometric variables and the CRQ domains or between the CRQ domains and the 6MWT, with the exception of the fatigue domain (r = 0.30; p = 0.04). The Portuguese-language version of the CRQ proved to be reproducible and valid for use in Brazilian patients with COPD.

The Ebola Virus VP30-NP Interaction Is a Regulator of Viral RNA Synthesis

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

Kirchdoerfer, Robert N.; Moyer, Crystal L.; Abelson, Dafna M.

Filoviruses are capable of causing deadly hemorrhagic fevers. All nonsegmented negative-sense RNA-virus nucleocapsids are composed of a nucleoprotein (NP), a phosphoprotein (VP35) and a polymerase (L). However, the VP30 RNA-synthesis co-factor is unique to the filoviruses. The assembly, structure, and function of the filovirus RNA replication complex remain unclear. Here, we have characterized the interactions of Ebola, Sudan and Marburg virus VP30 with NP using in vitro biochemistry, structural biology and cell-based mini-replicon assays. We have found that the VP30 C-terminal domain interacts with a short peptide in the C-terminal region of NP. Further, we have solved crystal structures ofmore » the VP30-NP complex for both Ebola and Marburg viruses. These structures reveal that a conserved, proline-rich NP peptide binds a shallow hydrophobic cleft on the VP30 C-terminal domain. Structure-guided Ebola virus VP30 mutants have altered affinities for the NP peptide. Correlation of these VP30-NP affinities with the activity for each of these mutants in a cell-based mini-replicon assay suggests that the VP30-NP interaction plays both essential and inhibitory roles in Ebola virus RNA synthesis.« less

Low-temperature thermal reduction of graphene oxide: In situ correlative structural, thermal desorption, and electrical transport measurements

NASA Astrophysics Data System (ADS)

Lipatov, Alexey; Guinel, Maxime J.-F.; Muratov, Dmitry S.; Vanyushin, Vladislav O.; Wilson, Peter M.; Kolmakov, Andrei; Sinitskii, Alexander

2018-01-01

Elucidation of the structural transformations in graphene oxide (GO) upon reduction remains an active and important area of research. We report the results of in situ heating experiments, during which electrical, mass spectrometry, X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and transmission electron microscopy (TEM) measurements were carried out correlatively. The simultaneous electrical and temperature programmed desorption measurements allowed us to correlate the onset of the increase in the electrical conductivity of GO by five orders of magnitude at about 150 °C with the maxima of the rates of desorption of H2O, CO, and CO2. Interestingly, this large conductivity change happens at an intermediate level of the reduction of GO, which likely corresponds to the point when the graphitic domains become large enough to enable percolative electronic transport. We demonstrate that the gas desorption is intimately related to (i) the changes in the chemical structure of GO detected by XPS and Raman spectroscopy and (ii) the formation of nanoscopic holes in GO sheets revealed by TEM. These in situ observations provide a better understanding of the mechanism of the GO thermal reduction.

Domain-Specific and Domain-General Learning Factors are Expressed in Genetically Heterogeneous CD-1 mice

PubMed Central

Kolata, Stefan; Light, Kenneth; Matzel, Louis D.

2008-01-01

It has been established that both domain-specific (e.g. spatial) as well as domain-general (general intelligence) factors influence human cognition. However, the separation of these processes has rarely been attempted in studies using laboratory animals. Previously, we have found that the performances of outbred mice across a wide range of learning tasks correlate in such a way that a single factor can explain 30– 44% of the variance between animals. This general learning factor is in some ways qualitatively and quantitatively analogous to general intelligence in humans. The complete structure of cognition in mice, however, has not been explored due to the limited sample sizes of our previous analyses. Here we report a combined analysis from 241 CD-1 mice tested in five primary learning tasks, and a subset of mice tested in two additional learning tasks. At least two (possibly three) of the seven learning tasks placed explicit demands on spatial and/or hippocampus-dependent processing abilities. Consistent with previous findings, we report a robust general factor influencing learning in mice that accounted for 38% of the variance across tasks. In addition, a domain-specific factor was found to account for performance on that subset of tasks that shared a dependence on hippocampal and/or spatial processing. These results provide further evidence for a general learning/cognitive factor in genetically heterogeneous mice. Furthermore (and similar to human cognitive performance), these results suggest a hierarchical structure to cognitive processes in this genetically heterogeneous species. PMID:19129932

Unc-45 Mutations in Caenorhabditis elegans Implicate a CRO1/She4p-like Domain in Myosin Assembly

PubMed Central

Barral, José M.; Bauer, Christopher C.; Ortiz, Irving; Epstein, Henry F.

1998-01-01

The Caenorhabditis elegans unc-45 locus has been proposed to encode a protein machine for myosin assembly. The UNC-45 protein is predicted to contain an NH2-terminal domain with three tetratricopeptide repeat motifs, a unique central region, and a COOH-terminal domain homologous to CRO1 and She4p. CRO1 and She4p are fungal proteins required for the segregation of other molecules in budding, endocytosis, and septation. Three mutations that lead to temperature-sensitive (ts) alleles have been localized to conserved residues within the CRO1/She4p-like domain, and two lethal alleles were found to result from stop codon mutations in the central region that would prevent translation of the COOH-terminal domain. Electron microscopy shows that thick filament accumulation in vivo is decreased by ∼50% in the CB286 ts mutant grown at the restrictive temperature. The thick filaments that assemble have abnormal structure. Immunofluorescence and immunoelectron microscopy show that myosins A and B are scrambled, in contrast to their assembly into distinct regions at the permissive temperature and in wild type. This abnormal structure correlates with the high degree of instability of the filaments in vitro as reflected by their extremely low yields and shortened lengths upon isolation. These results implicate the UNC-45 CRO1/She4p-like region in the assembly of myosin isoforms in C. elegans and suggest a possible common mechanism for the function of this UCS (UNC-45/CRO1/She4p) protein family. PMID:9832550

Measuring family needs of people living with cancer. Portuguese validation and descriptive studies of the Family Inventory of Needs.

PubMed

Areia, Neide P; Major, Sofia; Relvas, Ana P

2017-10-01

The aim of this study was to validate the Portuguese version of the Family Inventory of Needs (FIN). The FIN aims to measure important family needs and their fulfilment by a healthcare team. This cross-sectional study involved a sample of 364 family members of cancer patients, recruited from three medical institutions and through online recruitment. Three instruments were used: a socio-demographic questionnaire, the FIN and the Brief Symptom Inventory - 18 (BSI-18). Construct validity and reliability were considered regarding the FIN's psychometric properties. The method used to determine construct validity was factor structure analysis (confirmatory factor analysis), inter-factor correlations (Spearman's rank correlation) and convergent validity (Spearman's rank correlation). To assess scale reliability, the FIN's internal consistency was evaluated (Cronbach's alpha coefficient). Descriptive and frequency statistics and tests to compare means were used to assess important needs and to what extent they were met. The four-factor structure of the FIN was confirmed. Thus, the FIN has four domains: Basic Information, Information on treatment and care, Support and Patient Comfort. Convergent validity with the BSI-18 was verified. Both subscales of the FIN and each domain exceeded the minimum reliability standard of 0.70. Family members also reported important needs that were not adequately met by healthcare professionals. The Portuguese version of the FIN seems to be a reliable and valid tool for identifying cancer patients' important family needs and to what extent these are met. Copyright © 2017 Elsevier Ltd. All rights reserved.

Multi-mode of Four and Six Wave Parametric Amplified Process

NASA Astrophysics Data System (ADS)

Zhu, Dayu; Yang, Yiheng; Zhang, Da; Liu, Ruizhou; Ma, Danmeng; Li, Changbiao; Zhang, Yanpeng

2017-03-01

Multiple quantum modes in correlated fields are essential for future quantum information processing and quantum computing. Here we report the generation of multi-mode phenomenon through parametric amplified four- and six-wave mixing processes in a rubidium atomic ensemble. The multi-mode properties in both frequency and spatial domains are studied. On one hand, the multi-mode behavior is dominantly controlled by the intensity of external dressing effect, or nonlinear phase shift through internal dressing effect, in frequency domain; on the other hand, the multi-mode behavior is visually demonstrated from the images of the biphoton fields directly, in spatial domain. Besides, the correlation of the two output fields is also demonstrated in both domains. Our approach supports efficient applications for scalable quantum correlated imaging.

Multi-mode of Four and Six Wave Parametric Amplified Process.

PubMed

Zhu, Dayu; Yang, Yiheng; Zhang, Da; Liu, Ruizhou; Ma, Danmeng; Li, Changbiao; Zhang, Yanpeng

2017-03-03

Multiple quantum modes in correlated fields are essential for future quantum information processing and quantum computing. Here we report the generation of multi-mode phenomenon through parametric amplified four- and six-wave mixing processes in a rubidium atomic ensemble. The multi-mode properties in both frequency and spatial domains are studied. On one hand, the multi-mode behavior is dominantly controlled by the intensity of external dressing effect, or nonlinear phase shift through internal dressing effect, in frequency domain; on the other hand, the multi-mode behavior is visually demonstrated from the images of the biphoton fields directly, in spatial domain. Besides, the correlation of the two output fields is also demonstrated in both domains. Our approach supports efficient applications for scalable quantum correlated imaging.

Rational site-directed mutations of the LLP-1 and LLP-2 lentivirus lytic peptide domains in the intracytoplasmic tail of human immunodeficiency virus type 1 gp41 indicate common functions in cell-cell fusion but distinct roles in virion envelope incorporation.

PubMed

Kalia, Vandana; Sarkar, Surojit; Gupta, Phalguni; Montelaro, Ronald C

2003-03-01

Two highly conserved cationic amphipathic alpha-helical motifs, designated lentivirus lytic peptides 1 and 2 (LLP-1 and LLP-2), have been characterized in the carboxyl terminus of the transmembrane (TM) envelope glycoprotein (Env) of lentiviruses. Although various properties have been attributed to these domains, their structural and functional significance is not clearly understood. To determine the specific contributions of the Env LLP domains to Env expression, processing, and incorporation and to viral replication and syncytium induction, site-directed LLP mutants of a primary dualtropic infectious human immunodeficiency virus type 1 (HIV-1) isolate (ME46) were examined. Substitutions were made for highly conserved arginine residues in either the LLP-1 or LLP-2 domain (MX1 or MX2, respectively) or in both domains (MX4). The HIV-1 mutants with altered LLP domains demonstrated distinct phenotypes. The LLP-1 mutants (MX1 and MX4) were replication defective and showed an average of 85% decrease in infectivity, which was associated with an evident decrease in gp41 incorporation into virions without a significant decrease in Env expression or processing in transfected 293T cells. In contrast, MX2 virus was replication competent and incorporated a full complement of Env into its virions, indicating a differential role for the LLP-1 domain in Env incorporation. Interestingly, the replication-competent MX2 virus was impaired in its ability to induce syncytia in T-cell lines. This defect in cell-cell fusion did not correlate with apparent defects in the levels of cell surface Env expression, oligomerization, or conformation. The lack of syncytium formation, however, correlated with a decrease of about 90% in MX2 Env fusogenicity compared to that of wild-type Env in quantitative luciferase-based cell-cell fusion assays. The LLP-1 mutant MX1 and MX4 Envs also exhibited an average of 80% decrease in fusogenicity. Altogether, these results demonstrate for the first time that the highly conserved LLP domains perform critical but distinct functions in Env incorporation and fusogenicity.

Domain Hierarchy and closed Loops (DHcL): a server for exploring hierarchy of protein domain structure

PubMed Central

Koczyk, Grzegorz; Berezovsky, Igor N.

2008-01-01

Domain hierarchy and closed loops (DHcL) (http://sitron.bccs.uib.no/dhcl/) is a web server that delineates energy hierarchy of protein domain structure and detects domains at different levels of this hierarchy. The server also identifies closed loops and van der Waals locks, which constitute a structural basis for the protein domain hierarchy. The DHcL can be a useful tool for an express analysis of protein structures and their alternative domain decompositions. The user submits a PDB identifier(s) or uploads a 3D protein structure in a PDB format. The results of the analysis are the location of domains at different levels of hierarchy, closed loops, van der Waals locks and their interactive visualization. The server maintains a regularly updated database of domains, closed loop and van der Waals locks for all X-ray structures in PDB. DHcL server is available at: http://sitron.bccs.uib.no/dhcl. PMID:18502776

[Analysis of characteristics shown in self introduction letter and professor's recommendation letter].

PubMed

Kim, Sang Hyun

2013-09-01

The purpose of this study was to investigate applicants' behavioral characteristics based on the evaluation of cognitive, affective and social domain shown in self introduction letter and professor's recommendation letter. Self introduction letters and professor's recommendation letters of 109 applicants students who applied to medical school were collected. Frequency analysis and simple correlation were done in self introduction letter and professor's recommendation letter. Frequency analysis showed affective characteristics were most often mentioned in self introduction letter, and cognitive characteristics were most frequently described in professor's recommendation letter. There was a strong correlation between cognitive domains of self introduction letter and cognitive domain of professor's recommendation letter. There was a strong correlation between affective domain of self introduction letter and cognitive domain professor's recommendation letter. It is very important to make full use of self introduction letter and professor's recommendation letter for selecting medical students. Through the frequency analysis and simple correlation, more specific guidelines need to be suggested in order to secure fairness and objectivity in the evaluation of self-introduction letter and professor's recommendation letter.

An analysis of scatter decomposition

NASA Technical Reports Server (NTRS)

Nicol, David M.; Saltz, Joel H.

1990-01-01

A formal analysis of a powerful mapping technique known as scatter decomposition is presented. Scatter decomposition divides an irregular computational domain into a large number of equal sized pieces, and distributes them modularly among processors. A probabilistic model of workload in one dimension is used to formally explain why, and when scatter decomposition works. The first result is that if correlation in workload is a convex function of distance, then scattering a more finely decomposed domain yields a lower average processor workload variance. The second result shows that if the workload process is stationary Gaussian and the correlation function decreases linearly in distance until becoming zero and then remains zero, scattering a more finely decomposed domain yields a lower expected maximum processor workload. Finally it is shown that if the correlation function decreases linearly across the entire domain, then among all mappings that assign an equal number of domain pieces to each processor, scatter decomposition minimizes the average processor workload variance. The dependence of these results on the assumption of decreasing correlation is illustrated with situations where a coarser granularity actually achieves better load balance.

Crustal Seismic Structure of Central Alberta from Receiver Function Inversions

NASA Astrophysics Data System (ADS)

Chen, Y.; Dokht, R.; Gu, Y. J.; Sacchi, M. D.

2013-12-01

It is widely believed that the basement structure of central Alberta represents the tectonic assembly and evolution of several Archean lithospheric fragments. These fragments underwent episodes of rifting, collision, subduction and melting during the Proterozoic, giving rise to a complex network of tectonic domains with considerable differences in the crustal magnetic and seismic signatures. Observational support for these episodes, e.g., the coeval subduction around the Hearne province, has been limited due to the lack of exposed geology and insufficient teleseismic data prior to 2006. Since mid 2007, the establishment of the Canadian Rockies and Alberta Network (CRANE) has greatly improved the broadband seismic data coverage in central and southern Alberta. Based on 5+ years of CRANE data, we systematically analyze crust and shallow mantle shear velocities through simultaneous inversions of low and high frequency receiver functions. P-to-S converted waves from several stations in central Alberta suggest a significant mid crustal low velocity zone (LVZ), where shear velocity could vary by as much as 35 percent in a depth range of 15-35 km. This structure is not required by the receiver functions from stations along the foothills of the Rocky Mountains. While LVZ of notable magnitudes have been suggested previously in an overlapped part of the study region and attributed to the presence of serpentine or intrusive sill, the spatial dimensions of the anomaly reported in the current study is significantly larger: this anomaly spans hundreds of kilometers horizontally and is generally thicker than 10 km. The presence of mid/lower crustal LVZ in central Alberta is supported by recent group velocity maps based on noise correlation tomography, and the southeastward orientation of this LVZ is consistent with the proposed direction of the subducted oceanic microplate beneath the northwestern Hearne province during the Proterozoic. Still, the cause of the LVZ remains inconclusive, as the broad dimension of the anomaly would require major, potentially multiple, episodes of serpentinization and/or rework after the Paleoproterzoic. This process may span multiple domains and the correlation of present-day seismic structure with the domain boundaries (hence aeromagnetic signatures) remain questionable on the regional scale.

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.

Assessing Psycho-social Barriers to Rehabilitation in Injured Workers with Chronic Musculoskeletal Pain: Development and Item Properties of the Yellow Flag Questionnaire (YFQ).

PubMed

Salathé, Cornelia Rolli; Trippolini, Maurizio Alen; Terribilini, Livio Claudio; Oliveri, Michael; Elfering, Achim

2018-06-01

Purpose To develop a multidimensional scale to asses psychosocial beliefs-the Yellow Flag Questionnaire (YFQ)-aimed at guiding interventions for workers with chronic musculoskeletal (MSK) pain. Methods Phase 1 consisted of item selection based on literature search, item development and expert consensus rounds. In phase 2, items were reduced with calculating a quality-score per item, using structure equation modeling and confirmatory factor analysis on data from 666 workers. In phase 3, Cronbach's α, and Pearson correlations coefficients were computed to compare YFQ with disability, anxiety, depression and self-efficacy and the YFQ score based on data from 253 injured workers. Regressions of YFQ total score on disability, anxiety, depression and self-efficacy were calculated. Results After phase 1, the YFQ included 116 items and 15 domains. Further reductions of items in phase 2 by applying the item quality criteria reduced the total to 48 items. Phase factor analysis with structural equation modeling confirmed 32 items in seven domains: activity, work, emotions, harm & blame, diagnosis beliefs, co-morbidity and control. Cronbach α was 0.91 for the total score, between 0.49 and 0.81 for the 7 distinct scores of each domain, respectively. Correlations between YFQ total score ranged with disability, anxiety, depression and self-efficacy was .58, .66, .73, -.51, respectively. After controlling for age and gender the YFQ total score explained between R2 27% and R2 53% variance of disability, anxiety, depression and self-efficacy. Conclusions The YFQ, a multidimensional screening scale is recommended for use to assess psychosocial beliefs of workers with chronic MSK pain. Further evaluation of the measurement properties such as the test-retest reliability, responsiveness and prognostic validity is warranted.

Imaging-based biomarkers of cognitive performance in older adults constructed via high-dimensional pattern regression applied to MRI and PET.

PubMed

Wang, Ying; Goh, Joshua O; Resnick, Susan M; Davatzikos, Christos

2013-01-01

In this study, we used high-dimensional pattern regression methods based on structural (gray and white matter; GM and WM) and functional (positron emission tomography of regional cerebral blood flow; PET) brain data to identify cross-sectional imaging biomarkers of cognitive performance in cognitively normal older adults from the Baltimore Longitudinal Study of Aging (BLSA). We focused on specific components of executive and memory domains known to decline with aging, including manipulation, semantic retrieval, long-term memory (LTM), and short-term memory (STM). For each imaging modality, brain regions associated with each cognitive domain were generated by adaptive regional clustering. A relevance vector machine was adopted to model the nonlinear continuous relationship between brain regions and cognitive performance, with cross-validation to select the most informative brain regions (using recursive feature elimination) as imaging biomarkers and optimize model parameters. Predicted cognitive scores using our regression algorithm based on the resulting brain regions correlated well with actual performance. Also, regression models obtained using combined GM, WM, and PET imaging modalities outperformed models based on single modalities. Imaging biomarkers related to memory performance included the orbito-frontal and medial temporal cortical regions with LTM showing stronger correlation with the temporal lobe than STM. Brain regions predicting executive performance included orbito-frontal, and occipito-temporal areas. The PET modality had higher contribution to most cognitive domains except manipulation, which had higher WM contribution from the superior longitudinal fasciculus and the genu of the corpus callosum. These findings based on machine-learning methods demonstrate the importance of combining structural and functional imaging data in understanding complex cognitive mechanisms and also their potential usage as biomarkers that predict cognitive status.

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

Correlative infrared nanospectroscopic and nanomechanical imaging of block copolymer microdomains

PubMed Central

Pollard, Benjamin

2016-01-01

Summary Intermolecular interactions and nanoscale phase separation govern the properties of many molecular soft-matter systems. Here, we combine infrared vibrational scattering scanning near-field optical microscopy (IR s-SNOM) with force–distance spectroscopy for simultaneous characterization of both nanoscale optical and nanomechanical molecular properties through hybrid imaging. The resulting multichannel images and correlative analysis of chemical composition, spectral IR line shape, modulus, adhesion, deformation, and dissipation acquired for a thin film of a nanophase separated block copolymer (PS-b-PMMA) reveal complex structural variations, in particular at domain interfaces, not resolved in any individual signal channel alone. These variations suggest that regions of multicomponent chemical composition, such as the interfacial mixing regions between microdomains, are correlated with high spatial heterogeneity in nanoscale material properties. PMID:27335750

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

Architecture and High-Resolution Structure of Bacillus thuringiensis and Bacillus cereus Spore Coat Surfaces

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

Plomp, M; Leighton, T; Wheeler, K

2005-02-18

We have utilized atomic force microscopy (AFM) to visualize the native surface topology and ultrastructure of Bacillus thuringiensis and Bacillus cereus spores in water and in air. AFM was able to resolve the nanostructure of the exosporium and three distinctive classes of appendages. Removal of the exosporium exposed either a hexagonal honeycomb layer (B. thuringiensis) or a rodlet outer spore coat layer (B. cereus). Removal of the rodlet structure from B. cereus spores revealed an underlying honeycomb layer similar to that observed with B. thuringiensis spores. The periodicity of the rodlet structure on the outer spore coat of B. cereusmore » was {approx}8 nm, and the length of the rodlets was limited to the cross-patched domain structure of this layer to {approx}200 nm. The lattice constant of the honeycomb structures was {approx}9 nm for both B. cereus and B. thuringiensis spores. Both honeycomb structures were composed of multiple, disoriented domains with distinct boundaries. Our results demonstrate that variations in storage and preparation procedures result in architectural changes in individual spore surfaces, which establish AFM as a useful tool for evaluation of preparation and processing ''fingerprints'' of bacterial spores. These results establish that high-resolution AFM has the capacity to reveal species-specific assembly and nanometer scale structure of spore surfaces. These species-specific spore surface structural variations are correlated with sequence divergences in a spore core structural protein SspE.« less

Correlation between CD16a binding and immuno effector functionality of an antigen specific immunoglobulin Fc fragment (Fcab).

PubMed

Kainer, Manuela; Antes, Bernhard; Wiederkum, Susanne; Wozniak-Knopp, Gordana; Bauer, Anton; Rüker, Florian; Woisetschläger, Max

2012-10-15

Antigen binding immunoglobulin Fc fragments (Fcab) are generated by engineering loop regions in the CH3 domain of human IgG1 Fc. Variants of an Fcab specific for Her-2 were designed to display either enhanced (S239D:A330L:I332E) or diminished (L234A:L235A) binding affinities to the Fc receptor CD16a based on mutations described previously. The two mutant Fcab proteins demonstrated the expected modulation of CD16a binding. Interaction with recombinant or cell surface expressed Her-2 was unaffected in both mutants compared to the parental Fcab. Binding affinities for CD16a correlated with the ADCC-potencies of the Fcab variants. Additional studies indicated that the L234A:L235A variant Fcab had equivalent structural features as the unmodified Fcab since their DSC profiles were similar and antigen binding after re-folding upon partial heat denaturation had not changed. Introduction of the S239D:A330L:I332E mutations resulted in a significant reduction of the CH2 domain melting temperature, a moderate decrease of the thermal transition of the CH3 domain and lower antigen binding after thermal stress compared to the parental Fcab. We conclude that the known correlation between CD16a binding affinity and ADCC potency is also valid in Fcab proteins and that antigen specific Fcab molecules can be further engineered for fine tuning of immuno effector functions. Copyright © 2012 Elsevier Inc. All rights reserved.

Validation of World Health Organization Assessment Schedule 2.0 in specialized somatic rehabilitation services in Norway.

PubMed

Moen, Vegard Pihl; Drageset, Jorunn; Eide, Geir Egil; Klokkerud, Mari; Gjesdal, Sturla

2017-02-01

The World Health Organization Disability Assessment Schedule (WHODAS) 2.0 is a generic instrument to assess disability covering six domains. The purpose of this study was to investigate the potential of the instrument for monitoring disability in specialized somatic rehabilitation by testing reliability, construct validity and responsiveness of WHODAS 2.0, Norwegian version, among patients with various health conditions. For taxonomy, terminology and definitions, the Consensus-based Standards for the Selection of Health Measurement Instruments were followed. Reproducibility was investigated by the intra-class correlation coefficient (ICC) in a randomly selected sample. Internal consistency was assessed by Cronbach's alpha. Construct validity was evaluated by correlations between WHODAS 2.0 and the Medical Outcomes Study 36-item Short Form, and fit of the hypothesized structure using confirmatory factor analysis (CFA). Responsiveness was evaluated in another randomly selected sample by testing a priori formulated hypotheses. Nine hundred seventy patients were included in the study. Reproducibility and responsiveness were evaluated in 53 and 104 patients, respectively. The ICC for the WHODAS 2.0 domains ranged from 0.63 to 0.84 and was 0.87 for total score. Cronbach's alpha for domains ranged from 0.75 to 0.94 and was 0.93 for total score. For construct validity, 6 of 12 expected correlations were confirmed and CFA did not achieve satisfactory fit indices. For responsiveness, 3 of 8 hypotheses were confirmed. The Norwegian version of WHODAS 2.0 showed moderate to satisfactory reliability and moderate validity in rehabilitation patients. However, the present study indicated possible limitations in terms of responsiveness.

Complex bifurcation patterns in a discrete predator-prey model with periodic environmental modulation

NASA Astrophysics Data System (ADS)

Harikrishnan, K. P.

2018-02-01

We consider the simplest model in the family of discrete predator-prey system and introduce for the first time an environmental factor in the evolution of the system by periodically modulating the natural death rate of the predator. We show that with the introduction of environmental modulation, the bifurcation structure becomes much more complex with bubble structure and inverse period doubling bifurcation. The model also displays the peculiar phenomenon of coexistence of multiple limit cycles in the domain of attraction for a given parameter value that combine and finally gets transformed into a single strange attractor as the control parameter is increased. To identify the chaotic regime in the parameter plane of the model, we apply the recently proposed scheme based on the correlation dimension analysis. We show that the environmental modulation is more favourable for the stable coexistence of the predator and the prey as the regions of fixed point and limit cycle in the parameter plane increase at the expense of chaotic domain.

Insights using the molecular model of Lipoxygenase from Finger millet (Eleusine coracana (L.)).

PubMed

Tiwari, Apoorv; Avashthi, Himanshu; Jha, Richa; Srivastava, Ambuj; Kumar Garg, Vijay; Wasudev Ramteke, Pramod; Kumar, Anil

2016-01-01

Lipoxygenase-1 (LOX-1) protein provides defense against pests and pathogens and its presence have been positively correlated with plant resistance against pathogens. Linoleate is a known substrate of lipoxygenase and it induces necrosis leading to the accumulation of isoflavonoid phytoalexins in plant leaves. Therefore, it is of interest to study the structural features of LOX-1 from Finger millet. However, the structure ofLOX-1 from Finger millet is not yet known. A homology model of LOX-1 from Finger millet is described. Domain architecture study suggested the presence of two domains namely PLAT (Phospho Lipid Acyl Transferase) and lipoxygenase. Molecular docking models of linoleate with lipoxygenase from finger millet, rice and sorghum are reported. The features of docked models showed that finger millet have higher pathogen resistance in comparison to other cereal crops. This data is useful for the molecular cloning of fulllength LOX-1 gene for validating its role in improving plant defense against pathogen infection and for various other biological processes.

Surfactant protein B: lipid interactions of synthetic peptides representing the amino-terminal amphipathic domain.

PubMed Central

Bruni, R; Taeusch, H W; Waring, A J

1991-01-01

The mechanisms by which pulmonary surfactant protein B (SP-B) affects the surface activity of surfactant lipids are unclear. We have studied the peptide/lipid interactions of the amino-terminal amphipathic domain of SP-B by comparing the secondary conformations and surface activities of a family of synthetic peptides based on the native human SP-B sequence, modified by site-specific amino acid substitutions. Circular dichroism measurements show an alpha-helical structure correlating with the ability of the peptides to interact with lipids and with the surface activity of peptide/lipid dispersions. Amino acid substitutions altering either the charge or the hydrophobicity of the residues lowered the helical content and reduced the association of the aminoterminal segment with lipid dispersions. Surface activity of peptide/lipid mixtures was maximally altered by reversal of charge in synthetic peptides. These observations indicate that electrostatic interactions and hydrophobicity are important factors in determining optimal structure and function of surfactant peptides in lipid dispersions. Images PMID:1871144

Structure-function relationships in Gan42B, an intracellular GH42 β-galactosidase from Geobacillus stearothermophilus.

PubMed

Solomon, Hodaya V; Tabachnikov, Orly; Lansky, Shifra; Salama, Rachel; Feinberg, Hadar; Shoham, Yuval; Shoham, Gil

2015-12-01

Geobacillus stearothermophilus T-6 is a Gram-positive thermophilic soil bacterium that contains a battery of degrading enzymes for the utilization of plant cell-wall polysaccharides, including xylan, arabinan and galactan. A 9.4 kb gene cluster has recently been characterized in G. stearothermophilus that encodes a number of galactan-utilization elements. A key enzyme of this degradation system is Gan42B, an intracellular GH42 β-galactosidase capable of hydrolyzing short β-1,4-galactosaccharides into galactose units, making it of high potential for various biotechnological applications. The Gan42B monomer is made up of 686 amino acids, and based on sequence homology it was suggested that Glu323 is the catalytic nucleophile and Glu159 is the catalytic acid/base. In the current study, the detailed three-dimensional structure of wild-type Gan42B (at 2.45 Å resolution) and its catalytic mutant E323A (at 2.50 Å resolution), as determined by X-ray crystallography, are reported. These structures demonstrate that the three-dimensional structure of the Gan42B monomer generally correlates with the overall fold observed for GH42 proteins, consisting of three main domains: an N-terminal TIM-barrel domain, a smaller mixed α/β domain, and the smallest all-β domain at the C-terminus. The two catalytic residues are located in the TIM-barrel domain in a pocket-like active site such that their carboxylic functional groups are about 5.3 Å from each other, consistent with a retaining mechanism. The crystal structure demonstrates that Gan42B is a homotrimer, resembling a flowerpot in general shape, in which each monomer interacts with the other two to form a cone-shaped tunnel cavity in the centre. The cavity is ∼35 Å at the wide opening and ∼5 Å at the small opening and ∼40 Å in length. The active sites are situated at the interfaces between the monomers, so that every two neighbouring monomers participate in the formation of each of the three active sites of the trimer. They are located near the small opening of the cone tunnel, all facing the centre of the cavity. The biological relevance of this trimeric structure is supported by independent results obtained from gel-permeation chromatography. These data and their comparison to the structural data of related GH42 enzymes are used for a more general discussion concerning structure-activity aspects in this GH family.

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.

Brain Structural Concomitants of Resting State Heart Rate Variability in the Young and Old – Evidence from Two Independent Samples

PubMed Central

Yoo, Hyun Joo; Thayer, Julian F; Greening, Steven; Lee, Tae-Ho; Ponzio, Allison; Min, Jungwon; Sakaki, Michiko; Nga, Lin; Mather, Mara; Koenig, Julian

2018-01-01

Previous research has shown associations between brain structure and resting state high-frequency heart rate variability (HF-HRV). Age affects both brain structure and HF-HRV. Therefore we sought to examine the relationship between brain structure and HF-HRV as a function of age. Data from two independent studies were used for the present analysis. Study 1 included 19 older adults (10 males, age range 62–78 years) and 19 younger adults (12 males, age range 19–37). Study 2 included 23 older adults (12 males; age range 55–75) and 27 younger adults (17 males; age range 18–34). The root-mean-square of successive R-R-interval differences (RMSSD) from ECG recordings was used as time-domain measure of HF-HRV. MRI scans were performed on a 3.0-T Siemens Magnetom Trio scanner. Cortical reconstruction and volumetric segmentation were performed with the Freesurfer image analysis suite, including 12 regions as regions-of-interests (ROI). Zero-order and partial correlations were used to assess the correlation of RMSSD with cortical thickness in selected ROIs. Lateral orbitofrontal cortex (OFC) cortical thickness was significantly associated with RMSSD. Further, both studies, in line with previous research, showed correlations between RMSSD and anterior cingulate cortex (ACC) cortical thickness. Meta-analysis on adjusted correlation coefficients from individual studies confirmed an association of RMSSD with the left rostral ACC and the left lateral OFC. Future longitudinal studies are necessary to trace individual trajectories in the association of HRV and brain structure across aging. PMID:28921167

Dynamics of wave packets in two-dimensional random systems with anisotropic disorder.

PubMed

Samelsohn, Gregory; Gruzdev, Eugene

2008-09-01

A theoretical model is proposed to describe narrowband pulse dynamics in two-dimensional systems with arbitrary correlated disorder. In anisotropic systems with elongated cigarlike inhomogeneities, fast propagation is predicted in the direction across the structure where the wave is exponentially localized and tunneling of evanescent modes plays a dominant role in typical realizations. Along the structure, where the wave is channeled as in a waveguide, the motion of the wave energy is relatively slow. Numerical simulations performed for ultra-wide-band pulses show that even at the initial stage of wave evolution, the radiation diffuses predominantly in the direction along the major axis of the correlation ellipse. Spectral analysis of the results relates the long tail of the wave observed in the transverse direction to a number of frequency domain "lucky shots" associated with the long-living resonant modes localized inside the sample.

Dynamics of wave packets in two-dimensional random systems with anisotropic disorder

NASA Astrophysics Data System (ADS)

Samelsohn, Gregory; Gruzdev, Eugene

2008-09-01

A theoretical model is proposed to describe narrowband pulse dynamics in two-dimensional systems with arbitrary correlated disorder. In anisotropic systems with elongated cigarlike inhomogeneities, fast propagation is predicted in the direction across the structure where the wave is exponentially localized and tunneling of evanescent modes plays a dominant role in typical realizations. Along the structure, where the wave is channeled as in a waveguide, the motion of the wave energy is relatively slow. Numerical simulations performed for ultra-wide-band pulses show that even at the initial stage of wave evolution, the radiation diffuses predominantly in the direction along the major axis of the correlation ellipse. Spectral analysis of the results relates the long tail of the wave observed in the transverse direction to a number of frequency domain “lucky shots” associated with the long-living resonant modes localized inside the sample.

Evaluation of the reliability and validity for X16 balance testing scale for the elderly.

PubMed

Ju, Jingjuan; Jiang, Yu; Zhou, Peng; Li, Lin; Ye, Xiaolei; Wu, Hongmei; Shen, Bin; Zhang, Jialei; He, Xiaoding; Niu, Chunjin; Xia, Qinghua

2018-05-10

Balance performance is considered as an indicator of functional status in the elderly, a large scale population screening and evaluation in the community context followed by proper interventions would be of great significance at public health level. However, there has been no suitable balance testing scale available for large scale studies in the unique community context of urban China. A balance scale named X16 balance testing scale was developed, which was composed of 3 domains and 16 items. A total of 1985 functionally independent and active community-dwelling elderly adults' balance abilities were tested using the X16 scale. The internal consistency, split-half reliability, content validity, construct validity, discriminant validity of X16 balance testing scale were evaluated. Factor analysis was performed to identify alternative factor structure. The Eigenvalues of factors 1, 2, and 3 were 8.53, 1.79, and 1.21, respectively, and their cumulative contribution to the total variance reached 72.0%. These 3 factors mainly represented domains static balance, postural stability, and dynamic balance. The Cronbach alpha coefficient for the scale was 0.933. The Spearman correlation coefficients between items and its corresponding domains were ranged from 0.538 to 0.964. The correlation coefficients between each item and its corresponding domain were higher than the coefficients between this item and other domains. With the increase of age, the scores of balance performance, domains static balance, postural stability, and dynamic balance in the elderly declined gradually (P < 0.001). With the increase of age, the proportion of the elderly with intact balance performance decreased gradually (P < 0.001). The reliability and validity of the X16 balance testing scale is both adequate and acceptable. Due to its simple and quick use features, it is practical to be used repeatedly and routinely especially in community setting and on large scale screening.

Structural Interplay - Tuning Mechanics in Peptide-Polyurea Hybrids

NASA Astrophysics Data System (ADS)

Korley, Lashanda

Utilizing cues from natural materials, we have been inspired to explore the hierarchical arrangement critical to energy absorption and mechanical enhancement in synthetic systems. Of particular interest is the soft domain ordering proposed as a contributing element to the observed toughness in spider silk. Multiblock copolymers, are ideal and dynamic systems in which to explore this approach via variations in secondary structure of nature's building blocks - peptides. We have designed a new class of polyurea hybrids that incorporate peptidic copolymers as the soft segment. The impact of hierarchical ordering on the thermal, mechanical, and morphological behavior of these bio-inspired polyurethanes with a siloxane-based, peptide soft segment was investigated. These peptide-polyurethane/urea hybrids were microphase segregated, and the beta-sheet secondary structure of the soft segment was preserved during polymerization and film casting. Toughness enhancement at low strains was achieved, but the overall extensibility of the peptide-incorporated systems was reduced due to the unique hard domain organization. To decouple the secondary structure influence in the siloxane-peptide soft segment from mechanics dominated by the hard domain, we also developed non-chain extended peptide-polyurea hybrids in which the secondary structure (beta sheet vs. alpha helix) was tuned via choice of peptide and peptide length. It was shown that this structural approach allowed tailoring of extensibility, toughness, and modulus. The sheet-dominant hybrid materials were typically tougher and more elastic due to intermolecular H-bonding facilitating load distribution, while the helical-prevalent systems generally exhibited higher stiffness. Recently, we have explored the impact of a molecular design strategy that overlays a covalent and physically crosslinked architecture in these peptide-polyurea hybrids, demonstrating that physical constraints in the network hybrids influences peptide hydrogen bonding and morphology. These structural features correlated well with systematic changes in modulus, extensibility, and hysteresis. Complementary to this effort is the design of PEG-based peptide-polyurea hybrids with tunable and responsive as structural and injectable hydrogels. The authors acknowledge funding support from the National Science Foundation (CAREER DMR-0953236).

Reliability, Validity, and Responsiveness of InFLUenza Patient-Reported Outcome (FLU-PRO©) Scores in Influenza-Positive Patients.

PubMed

Powers, John H; Bacci, Elizabeth D; Guerrero, M Lourdes; Leidy, Nancy Kline; Stringer, Sonja; Kim, Katherine; Memoli, Matthew J; Han, Alison; Fairchok, Mary P; Chen, Wei-Ju; Arnold, John C; Danaher, Patrick J; Lalani, Tahaniyat; Ridoré, Michelande; Burgess, Timothy H; Millar, Eugene V; Hernández, Andrés; Rodríguez-Zulueta, Patricia; Smolskis, Mary C; Ortega-Gallegos, Hilda; Pett, Sarah; Fischer, William; Gillor, Daniel; Macias, Laura Moreno; DuVal, Anna; Rothman, Richard; Dugas, Andrea; Ruiz-Palacios, Guillermo M

2018-02-01

To assess the reliability, validity, and responsiveness of InFLUenza Patient-Reported Outcome (FLU-PRO©) scores for quantifying the presence and severity of influenza symptoms. An observational prospective cohort study of adults (≥18 years) with influenza-like illness in the United States, the United Kingdom, Mexico, and South America was conducted. Participants completed the 37-item draft FLU-PRO daily for up to 14 days. Item-level and factor analyses were used to remove items and determine factor structure. Reliability of the final tool was estimated using Cronbach α and intraclass correlation coefficients (2-day reliability). Convergent and known-groups validity and responsiveness were assessed using global assessments of influenza severity and return to usual health. Of the 536 patients enrolled, 221 influenza-positive subjects comprised the analytical sample. The mean age of the patients was 40.7 years, 60.2% were women, and 59.7% were white. The final 32-item measure has six factors/domains (nose, throat, eyes, chest/respiratory, gastrointestinal, and body/systemic), with a higher order factor representing symptom severity overall (comparative fit index = 0.92; root mean square error of approximation = 0.06). Cronbach α was high (total = 0.92; domain range = 0.71-0.87); test-retest reliability (intraclass correlation coefficient, day 1-day 2) was 0.83 for total scores and 0.57 to 0.79 for domains. Day 1 FLU-PRO domain and total scores were moderately to highly correlated (≥0.30) with Patient Global Rating of Flu Severity (except nose and throat). Consistent with known-groups validity, scores differentiated severity groups on the basis of global rating (total: F = 57.2, P < 0.001; domains: F = 8.9-67.5, P < 0.001). Subjects reporting return to usual health showed significantly greater (P < 0.05) FLU-PRO score improvement by day 7 than did those who did not, suggesting score responsiveness. Results suggest that FLU-PRO scores are reliable, valid, and responsive to change in influenza-positive adults. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Cultural adaptation and validation of a peninsular Spanish version of the MSTCQ© (Multiple Sclerosis Treatment Concerns Questionnaire).

PubMed

Muntéis Olivas, E; Navarro Mascarell, G; Meca Lallana, J; Maestre Martínez, A; Pérez Sempere, Á; Gracia Gil, J; Pato Pato, A

Although subcutaneous treatments for multiple sclerosis (MS) have been shown to be effective, adverse reactions and pain may adversely affect treatment satisfaction and adherence. This study presents an adapted and validated Spanish version of the Multiple Sclerosis Treatment Concerns Questionnaire © (MSTCQ), which evaluates satisfaction with the injection device (ID) across 4 domains: injection system (A), side effects (B) (flu-like symptoms, reactions, and satisfaction), experience with treatment (C) and benefits (D). Two study phases: 1) Cultural adaptation process with input from experts (n=6) and patients (n=30). 2) Validation obtained by means of an observational, cross-sectional, multi-centre study evaluating 143 adult MS patients using an ID. Tools employed: MSTCQ © , Patient-Reported Indices for Multiple Sclerosis (PRIMUS © ), and Treatment Satisfaction Questionnaire for Medication (TSQM © ). Psychometric properties: Feasibility (percentage of valid cases and floor/ceiling effects); Reliability (Cronbach α) and test-retest correlation (n=41, intraclass correlation coefficient, ICC); and construct validity (factor analysis of domains A and B) and convergent validity (Spearman rank-order correlation for MSTCQ © vs TSQM © ). Mean age (SD) was 41.94 (10.47) years, 63% of the group were women, and 88.11% presented relapsing-remitting MS. Mean (SD) EDSS score was 2.68 (1.82) points. MSTCQ © completion was high (0%-2.80% missing data). Internal consistency was high at α=0.89 for the total score (A+B) and α=0.76, 0.89, and 0.92 for domains A, B, and C, respectively. The version demonstrated excellent test-retest reliability for the total (ICC=0.98) and for domains A, B, and C: ICC=0.82, 0.97, and 0.89, respectively. Factor analysis corroborated the internal structure of the original questionnaire. The association between total and domain scores on both the MSTCQ © and the TSQM © was moderately strong (Rho=0.42-0.74) and significant (P<.05 and P<.01). The Spanish version of MSTCQ © demonstrates appropriate psychometric properties. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Relationship among visual field, blood flow, and neural structure measurements in glaucoma.

PubMed

Hwang, John C; Konduru, Ranjith; Zhang, Xinbo; Tan, Ou; Francis, Brian A; Varma, Rohit; Sehi, Mitra; Greenfield, David S; Sadda, Srinivas R; Huang, David

2012-05-17

To determine the relationship among visual field, neural structural, and blood flow measurements in glaucoma. Case-control study. Forty-seven eyes of 42 patients with perimetric glaucoma were age-matched with 27 normal eyes of 27 patients. All patients underwent Doppler Fourier-domain optical coherence tomography to measure retinal blood flow and standard glaucoma evaluation with visual field testing and quantitative structural imaging. Linear regression analysis was performed to analyze the relationship among visual field, blood flow, and structure, after all variables were converted to logarithmic decibel scale. Retinal blood flow was reduced in glaucoma eyes compared to normal eyes (P < 0.001). Visual field loss was correlated with both reduced retinal blood flow and structural loss of rim area and retinal nerve fiber layer (RNFL). There was no correlation or paradoxical correlation between blood flow and structure. Multivariate regression analysis revealed that reduced blood flow and structural loss are independent predictors of visual field loss. Each dB decrease in blood flow was associated with at least 1.62 dB loss in mean deviation (P ≤ 0.001), whereas each dB decrease in rim area and RNFL was associated with 1.15 dB and 2.56 dB loss in mean deviation, respectively (P ≤ 0.03). There is a close link between reduced retinal blood flow and visual field loss in glaucoma that is largely independent of structural loss. Further studies are needed to elucidate the causes of the vascular dysfunction and potential avenues for therapeutic intervention. Blood flow measurement may be useful as an independent assessment of glaucoma severity.

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.

Structural and functional dissection reveals distinct roles of Ca2+-binding sites in the giant adhesin SiiE of Salmonella enterica

PubMed Central

Klingl, Stefan; Sandmann, Achim; Taccardi, Nicola; Sticht, Heinrich; Muller, Yves A.; Hensel, Michael

2017-01-01

The giant non-fimbrial adhesin SiiE of Salmonella enterica mediates the first contact to the apical site of epithelial cells and enables subsequent invasion. SiiE is a 595 kDa protein composed of 53 repetitive bacterial immunoglobulin (BIg) domains and the only known substrate of the SPI4-encoded type 1 secretion system (T1SS). The crystal structure of BIg50-52 of SiiE revealed two distinct Ca2+-binding sites per BIg domain formed by conserved aspartate or glutamate residues. In a mutational analysis Ca2+-binding sites were disrupted by aspartate to serine exchange at various positions in the BIg domains of SiiE. Amounts of secreted SiiE diminish with a decreasing number of intact Ca2+-binding sites. BIg domains of SiiE contain distinct Ca2+-binding sites, with type I sites being similar to other T1SS-secreted proteins and type II sites newly identified in SiiE. We functionally and structurally dissected the roles of type I and type II Ca2+-binding sites in SiiE, as well as the importance of Ca2+-binding sites in various positions of SiiE. Type I Ca2+-binding sites were critical for efficient secretion of SiiE and a decreasing number of type I sites correlated with reduced secretion. Type II sites were less important for secretion, stability and surface expression of SiiE, however integrity of type II sites in the C-terminal portion was required for the function of SiiE in mediating adhesion and invasion. PMID:28558023

Structural basis for norovirus neutralization by an HBGA blocking human IgA antibody.

PubMed

Shanker, Sreejesh; Czakó, Rita; Sapparapu, Gopal; Alvarado, Gabriela; Viskovska, Maria; Sankaran, Banumathi; Atmar, Robert L; Crowe, James E; Estes, Mary K; Prasad, B V Venkataram

2016-10-04

Human noroviruses (HuNoVs) cause sporadic and epidemic gastroenteritis worldwide. They are classified into two major genogroups (GI and GII), with each genogroup further divided into multiple genotypes. Susceptibility to these viruses is influenced by genetically determined histo-blood group antigen (HBGA) expression. HBGAs function as cell attachment factors by binding to a surface-exposed region in the protruding (P) domain of the capsid protein. Sequence variations in this region that result in differential HBGA binding patterns and antigenicity are suggested to form a basis for strain diversification. Recent studies show that serum antibodies that block HBGA binding correlate with protection against illness. Although genogroup-dependent variation in HBGA binding specificity is structurally well characterized, an understanding of how antibodies block HBGA binding and how genotypic variations affect such blockade is lacking. Our crystallographic studies of the GI.1 P domain in complex with the Fab fragment of a human IgA monoclonal antibody (IgA 5I2) with HBGA blocking activity show that the antibody recognizes a conformational epitope formed by two surface-exposed loop clusters in the P domain. The antibody engulfs the HBGA binding site but does not affect its structural integrity. An unusual feature of the antigen recognition by IgA 5I2 is the predominant involvement of the CDR light chain 1 in contrast to the commonly observed CDR heavy chain 3, providing a unique perspective into antibody diversity in antigen recognition. Identification of the antigenic site in the P domain shows how genotypic variations might allow escape from antibody neutralization and exemplifies the interplay between antigenicity and HBGA specificity in HuNoV evolution.

Conserved Cysteine Residues Provide a Protein-Protein Interaction Surface in Dual Oxidase (DUOX) Proteins*

PubMed Central

Meitzler, Jennifer L.; Hinde, Sara; Bánfi, Botond; Nauseef, William M.; Ortiz de Montellano, Paul R.

2013-01-01

Intramolecular disulfide bond formation is promoted in oxidizing extracellular and endoplasmic reticulum compartments and often contributes to protein stability and function. DUOX1 and DUOX2 are distinguished from other members of the NOX protein family by the presence of a unique extracellular N-terminal region. These peroxidase-like domains lack the conserved cysteines that confer structural stability to mammalian peroxidases. Sequence-based structure predictions suggest that the thiol groups present are solvent-exposed on a single protein surface and are too distant to support intramolecular disulfide bond formation. To investigate the role of these thiol residues, we introduced four individual cysteine to glycine mutations in the peroxidase-like domains of both human DUOXs and purified the recombinant proteins. The mutations caused little change in the stabilities of the monomeric proteins, supporting the hypothesis that the thiol residues are solvent-exposed and not involved in disulfide bonds that are critical for structural integrity. However, the ability of the isolated hDUOX1 peroxidase-like domain to dimerize was altered, suggesting a role for these cysteines in protein-protein interactions that could facilitate homodimerization of the peroxidase-like domain or, in the full-length protein, heterodimeric interactions with a maturation protein. When full-length hDUOX1 was expressed in HEK293 cells, the mutations resulted in decreased H2O2 production that correlated with a decreased amount of the enzyme localized to the membrane surface rather than with a loss of activity or with a failure to synthesize the mutant proteins. These results support a role for the cysteine residues in intermolecular disulfide bond formation with the DUOX maturation factor DUOXA1. PMID:23362256

Homology-based Modeling of Rhodopsin-like Family Members in the Inactive State: Structural Analysis and Deduction of Tips for Modeling and Optimization.

PubMed

Pappalardo, Matteo; Rayan, Mahmoud; Abu-Lafi, Saleh; Leonardi, Martha E; Milardi, Danilo; Guccione, Salvatore; Rayan, Anwar

2017-08-01

Modeling G-Protein Coupled Receptors (GPCRs) is an emergent field of research, since utility of high-quality models in receptor structure-based strategies might facilitate the discovery of interesting drug candidates. The findings from a quantitative analysis of eighteen resolved structures of rhodopsin family "A" receptors crystallized with antagonists and 153 pairs of structures are described. A strategy termed endeca-amino acids fragmentation was used to analyze the structures models aiming to detect the relationship between sequence identity and Root Mean Square Deviation (RMSD) at each trans-membrane-domain. Moreover, we have applied the leave-one-out strategy to study the shiftiness likelihood of the helices. The type of correlation between sequence identity and RMSD was studied using the aforementioned set receptors as representatives of membrane proteins and 98 serine proteases with 4753 pairs of structures as representatives of globular proteins. Data analysis using fragmentation strategy revealed that there is some extent of correlation between sequence identity and global RMSD of 11AA width windows. However, spatial conservation is not always close to the endoplasmic side as was reported before. A comparative study with globular proteins shows that GPCRs have higher standard deviation and higher slope in the graph with correlation between sequence identity and RMSD. The extracted information disclosed in this paper could be incorporated in the modeling protocols while using technique for model optimization and refinement. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cone Structure in Retinal Degeneration Associated with Mutations in the peripherin/RDS Gene

PubMed Central

Talcott, Katherine E.; Ratnam, Kavitha; Sundquist, Sanna M.; Lucero, Anya S.; Day, Shelley; Zhang, Yuhua; Roorda, Austin

2011-01-01

Purpose. To study cone photoreceptor structure and function associated with mutations in the second intradiscal loop region of peripherin/RDS. Methods. High-resolution macular images were obtained with adaptive optics scanning laser ophthalmoscopy and spectral domain optical coherence tomography in four patients with peripherin/RDS mutations and 27 age-similar healthy subjects. Measures of retinal structure and fundus autofluorescence (AF) were correlated with visual function, including best-corrected visual acuity (BCVA), kinetic and static perimetry, fundus-guided microperimetry, full-field electroretinography (ERG), and multifocal ERG. The coding regions of the peripherin/RDS gene were sequenced in each patient. Results. Heterozygous mutations in peripherin/RDS were predicted to affect protein structure in the second intradiscal domain in each patient (Arg172Trp, Gly208Asp, Pro210Arg and Cys213Tyr). BCVA was at least 20/32 in the study eye of each patient. Diffuse cone-greater-than-rod dysfunction was present in patient 1, while rod-greater-than-cone dysfunction was present in patient 4; macular outer retinal dysfunction was present in all patients. Macular AF was heterogeneous, and the photoreceptor-retinal pigment epithelial (RPE) junction layer showed increased reflectivity at the fovea in all patients except patient 1, who showed cone-rod dystrophy. Cone packing was irregular, and cone spacing was significantly increased (z-scores >2) at most locations throughout the central 4° in each patient. Conclusions. peripherin/RDS mutations produced diffuse AF abnormalities, disruption of the photoreceptor/RPE junction, and increased cone spacing, consistent with cone loss in the macula. The abnormalities observed suggest that the integrity of the second intradiscal domain of peripherin/RDS is critical for normal macular cone structure. PMID:21071739

Allostery in the ferredoxin protein motif does not involve a conformational switch.

PubMed

Nechushtai, Rachel; Lammert, Heiko; Michaeli, Dorit; Eisenberg-Domovich, Yael; Zuris, John A; Luca, Maria A; Capraro, Dominique T; Fish, Alex; Shimshon, Odelia; Roy, Melinda; Schug, Alexander; Whitford, Paul C; Livnah, Oded; Onuchic, José N; Jennings, Patricia A

2011-02-08

Regulation of protein function via cracking, or local unfolding and refolding of substructures, is becoming a widely recognized mechanism of functional control. Oftentimes, cracking events are localized to secondary and tertiary structure interactions between domains that control the optimal position for catalysis and/or the formation of protein complexes. Small changes in free energy associated with ligand binding, phosphorylation, etc., can tip the balance and provide a regulatory functional switch. However, understanding the factors controlling function in single-domain proteins is still a significant challenge to structural biologists. We investigated the functional landscape of a single-domain plant-type ferredoxin protein and the effect of a distal loop on the electron-transfer center. We find the global stability and structure are minimally perturbed with mutation, whereas the functional properties are altered. Specifically, truncating the L1,2 loop does not lead to large-scale changes in the structure, determined via X-ray crystallography. Further, the overall thermal stability of the protein is only marginally perturbed by the mutation. However, even though the mutation is distal to the iron-sulfur cluster (∼20 Å), it leads to a significant change in the redox potential of the iron-sulfur cluster (57 mV). Structure-based all-atom simulations indicate correlated dynamical changes between the surface-exposed loop and the iron-sulfur cluster-binding region. Our results suggest intrinsic communication channels within the ferredoxin fold, composed of many short-range interactions, lead to the propagation of long-range signals. Accordingly, protein interface interactions that involve L1,2 could potentially signal functional changes in distal regions, similar to what is observed in other allosteric systems.

Predicting detection performance with model observers: Fourier domain or spatial domain?

PubMed

Chen, Baiyu; Yu, Lifeng; Leng, Shuai; Kofler, James; Favazza, Christopher; Vrieze, Thomas; McCollough, Cynthia

2016-02-27

The use of Fourier domain model observer is challenged by iterative reconstruction (IR), because IR algorithms are nonlinear and IR images have noise texture different from that of FBP. A modified Fourier domain model observer, which incorporates nonlinear noise and resolution properties, has been proposed for IR and needs to be validated with human detection performance. On the other hand, the spatial domain model observer is theoretically applicable to IR, but more computationally intensive than the Fourier domain method. The purpose of this study is to compare the modified Fourier domain model observer to the spatial domain model observer with both FBP and IR images, using human detection performance as the gold standard. A phantom with inserts of various low contrast levels and sizes was repeatedly scanned 100 times on a third-generation, dual-source CT scanner at 5 dose levels and reconstructed using FBP and IR algorithms. The human detection performance of the inserts was measured via a 2-alternative-forced-choice (2AFC) test. In addition, two model observer performances were calculated, including a Fourier domain non-prewhitening model observer and a spatial domain channelized Hotelling observer. The performance of these two mode observers was compared in terms of how well they correlated with human observer performance. Our results demonstrated that the spatial domain model observer correlated well with human observers across various dose levels, object contrast levels, and object sizes. The Fourier domain observer correlated well with human observers using FBP images, but overestimated the detection performance using IR images.

Predicting detection performance with model observers: Fourier domain or spatial domain?

PubMed Central

Chen, Baiyu; Yu, Lifeng; Leng, Shuai; Kofler, James; Favazza, Christopher; Vrieze, Thomas; McCollough, Cynthia

2016-01-01

The use of Fourier domain model observer is challenged by iterative reconstruction (IR), because IR algorithms are nonlinear and IR images have noise texture different from that of FBP. A modified Fourier domain model observer, which incorporates nonlinear noise and resolution properties, has been proposed for IR and needs to be validated with human detection performance. On the other hand, the spatial domain model observer is theoretically applicable to IR, but more computationally intensive than the Fourier domain method. The purpose of this study is to compare the modified Fourier domain model observer to the spatial domain model observer with both FBP and IR images, using human detection performance as the gold standard. A phantom with inserts of various low contrast levels and sizes was repeatedly scanned 100 times on a third-generation, dual-source CT scanner at 5 dose levels and reconstructed using FBP and IR algorithms. The human detection performance of the inserts was measured via a 2-alternative-forced-choice (2AFC) test. In addition, two model observer performances were calculated, including a Fourier domain non-prewhitening model observer and a spatial domain channelized Hotelling observer. The performance of these two mode observers was compared in terms of how well they correlated with human observer performance. Our results demonstrated that the spatial domain model observer correlated well with human observers across various dose levels, object contrast levels, and object sizes. The Fourier domain observer correlated well with human observers using FBP images, but overestimated the detection performance using IR images. PMID:27239086

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.

NMR Study Reveals the Receiver Domain of Arabidopsis ETHYLENE RESPONSE1 Ethylene Receptor as an Atypical Type Response Regulator.

PubMed

Hung, Yi-Lin; Jiang, Ingjye; Lee, Yi-Zong; Wen, Chi-Kuang; Sue, Shih-Che

2016-01-01

The gaseous plant hormone ethylene, recognized by plant ethylene receptors, plays a pivotal role in various aspects of plant growth and development. ETHYLENE RESPONSE1 (ETR1) is an ethylene receptor isolated from Arabidopsis and has a structure characteristic of prokaryotic two-component histidine kinase (HK) and receiver domain (RD), where the RD structurally resembles bacteria response regulators (RRs). The ETR1 HK domain has autophosphorylation activity, and little is known if the HK can transfer the phosphoryl group to the RD for receptor signaling. Unveiling the correlation of the receptor structure and phosphorylation status would advance the studies towards the underlying mechanisms of ETR1 receptor signaling. In this study, using the nuclear magnetic resonance technique, our data suggested that the ETR1-RD is monomeric in solution and the rigid structure of the RD prevents the conserved aspartate residue phosphorylation. Comparing the backbone dynamics with other RRs, we propose that backbone flexibility is critical to the RR phosphorylation. Besides the limited flexibility, ETR1-RD has a unique γ loop conformation of opposite orientation, which makes ETR1-RD unfavorable for phosphorylation. These two features explain why ETR1-RD cannot be phosphorylated and is classified as an atypical type RR. As a control, phosphorylation of the ETR1-RD was also impaired when the sequence was swapped to the fragment of the bacterial typical type RR, CheY. Here, we suggest a molecule insight that the ETR1-RD already exists as an active formation and executes its function through binding with the downstream factors without phosphorylation.

Scale-free crystallization of two-dimensional complex plasmas: Domain analysis using Minkowski tensors

NASA Astrophysics Data System (ADS)

Böbel, A.; Knapek, C. A.; Räth, C.

2018-05-01

Experiments of the recrystallization processes in two-dimensional complex plasmas are analyzed to rigorously test a recently developed scale-free phase transition theory. The "fractal-domain-structure" (FDS) theory is based on the kinetic theory of Frenkel. It assumes the formation of homogeneous domains, separated by defect lines, during crystallization and a fractal relationship between domain area and boundary length. For the defect number fraction and system energy a scale-free power-law relation is predicted. The long-range scaling behavior of the bond-order correlation function shows clearly that the complex plasma phase transitions are not of the Kosterlitz, Thouless, Halperin, Nelson, and Young type. Previous preliminary results obtained by counting the number of dislocations and applying a bond-order metric for structural analysis are reproduced. These findings are supplemented by extending the use of the bond-order metric to measure the defect number fraction and furthermore applying state-of-the-art analysis methods, allowing a systematic testing of the FDS theory with unprecedented scrutiny: A morphological analysis of lattice structure is performed via Minkowski tensor methods. Minkowski tensors form a complete family of additive, motion covariant and continuous morphological measures that are sensitive to nonlinear properties. The FDS theory is rigorously confirmed and predictions of the theory are reproduced extremely well. The predicted scale-free power-law relation between defect fraction number and system energy is verified for one more order of magnitude at high energies compared to the inherently discontinuous bond-order metric. It is found that the fractal relation between crystalline domain area and circumference is independent of the experiment, the particular Minkowski tensor method, and the particular choice of parameters. Thus, the fractal relationship seems to be inherent to two-dimensional phase transitions in complex plasmas. Minkowski tensor analysis turns out to be a powerful tool for investigations of crystallization processes. It is capable of revealing nonlinear local topological properties, however, still provides easily interpretable results founded on a solid mathematical framework.

Characterizing the local optoelectronic performance of organic solar cells with scanning-probe microscopy

NASA Astrophysics Data System (ADS)

Coffey, David C.

2007-12-01

Conjugated polymers, small molecules, and colloidal semiconductor nanocrystals are promising materials for use in low-cost, thin-film solar cells. The photovoltaic performance of these materials, however, is highly dependent on film structure, and directly correlating local film structures with device performance remains challenging. This dissertation describes several techniques we have developed to probe and control the local optoelectronic properties of organic semiconducting films. First, with an aim of rapidly fabricating photovoltaic films with varying morphology, we demonstrate that Dip-Pen Nanolithography (DPN) can be used to control nanoscale phase separation with sub-150 nm lateral resolution in polymer films that are 20--80 nm thick. This control is based on writing monolayer chemical templates that nucleate phase separation, and we use this technique to study heterogeneous nucleation in thin films. Second, we use time-resolved electrostatic force microscopy (trEFM) to measure photoexcited charge in polymer films with a resolution of 100 nm and 100 mus. We show that such data can predict the external quantum efficiencies of polymer photodiodes, and can thus link device performance with local optoelectronic properties. When applied to the study of blended polyfluorene films, we show that domain centers can buildup charge faster then domain interfaces, which indicates that polymer/polymer blend devices should be modeled as having impure donor/acceptor domains. Third, we use photoconductive atomic force microscopy (pcAFM) to map local photocurrents with 20 nm-resolution in polymer/fullerene solar cells- achieving an order of magnitude better resolution than previous techniques. We present photocurrent maps under short-circuit conditions (zero applied bias), as well as under various applied voltages. We find significant variations in the short-circuit current between regions that appear identical in AFM topography. These variations occur from one domain to another, as well as on larger length scales incorporating multiple domains. Our results suggest that organic solar cells can be significantly improved with better donor/acceptor structuring.

DbPTM 3.0: an informative resource for investigating substrate site specificity and functional association of protein post-translational modifications.

PubMed

Lu, Cheng-Tsung; Huang, Kai-Yao; Su, Min-Gang; Lee, Tzong-Yi; Bretaña, Neil Arvin; Chang, Wen-Chi; Chen, Yi-Ju; Chen, Yu-Ju; Huang, Hsien-Da

2013-01-01

Protein modification is an extremely important post-translational regulation that adjusts the physical and chemical properties, conformation, stability and activity of a protein; thus altering protein function. Due to the high throughput of mass spectrometry (MS)-based methods in identifying site-specific post-translational modifications (PTMs), dbPTM (http://dbPTM.mbc.nctu.edu.tw/) is updated to integrate experimental PTMs obtained from public resources as well as manually curated MS/MS peptides associated with PTMs from research articles. Version 3.0 of dbPTM aims to be an informative resource for investigating the substrate specificity of PTM sites and functional association of PTMs between substrates and their interacting proteins. In order to investigate the substrate specificity for modification sites, a newly developed statistical method has been applied to identify the significant substrate motifs for each type of PTMs containing sufficient experimental data. According to the data statistics in dbPTM, >60% of PTM sites are located in the functional domains of proteins. It is known that most PTMs can create binding sites for specific protein-interaction domains that work together for cellular function. Thus, this update integrates protein-protein interaction and domain-domain interaction to determine the functional association of PTM sites located in protein-interacting domains. Additionally, the information of structural topologies on transmembrane (TM) proteins is integrated in dbPTM in order to delineate the structural correlation between the reported PTM sites and TM topologies. To facilitate the investigation of PTMs on TM proteins, the PTM substrate sites and the structural topology are graphically represented. Also, literature information related to PTMs, orthologous conservations and substrate motifs of PTMs are also provided in the resource. Finally, this version features an improved web interface to facilitate convenient access to the resource.

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

Structural analysis of determinants of histo-blood group antigen binding specificity in genogroup I noroviruses.

PubMed

Shanker, Sreejesh; Czako, Rita; Sankaran, Banumathi; Atmar, Robert L; Estes, Mary K; Prasad, B V Venkataram

2014-06-01

Human noroviruses (NoVs) cause acute epidemic gastroenteritis. Susceptibility to the majority of NoV infections is determined by genetically controlled secretor-dependent expression of histo-blood group antigens (HBGAs), which are also critical for NoV attachment to host cells. Human NoVs are classified into two major genogroups (genogroup I [GI] and GII), with each genogroup further divided into several genotypes. GII NoVs are more prevalent and exhibit periodic emergence of new variants, suggested to be driven by altered HBGA binding specificities and antigenic drift. Recent epidemiological studies show increased activity among GI NoVs, with some members showing the ability to bind nonsecretor HBGAs. NoVs bind HBGAs through the protruding (P) domain of the major capsid protein VP1. GI NoVs, similar to GII, exhibit significant sequence variations in the P domain; it is unclear how these variations affect HBGA binding specificities. To understand the determinants of possible strain-specific HBGA binding among GI NoVs, we determined the structure of the P domain of a GI.7 clinical isolate and compared it to the previously determined P domain structures of GI.1 and GI.2 strains. Our crystallographic studies revealed significant structural differences, particularly in the loop regions of the GI.7 P domain, altering its surface topography and electrostatic landscape and potentially indicating antigenic variation. The GI.7 strain bound to H- and A-type, Lewis secretor, and Lewis nonsecretor families of HBGAs, allowing us to further elucidate the structural determinants of nonsecretor HBGA binding among GI NoVs and to infer several contrasting and generalizable features of HBGA binding in the GI NoVs. Human noroviruses (NoVs) cause acute epidemic gastroenteritis. Recent epidemiological studies have shown increased prevalence of genogroup I (GI) NoVs. Although secretor-positive status is strongly correlated with NoV infection, cases of NoV infection associated with secretor-negative individuals are reported. Biochemical studies have shown that GI NoVs exhibit genotype-dependent binding to nonsecretor histo-blood group antigens (HBGAs). From our crystallographic studies of a GI.7 NoV, in comparison with previous studies on GI.1 and GI.2 NoVs, we show that genotypic differences translate to extensive structural changes in the loop regions that significantly alter the surface topography and electrostatic landscape of the P domain; these features may be indicative of antigenic variations contributing to serotypic differentiation in GI NoVs and also differential modulation of the HBGA binding characteristics. A significant finding is that the threshold length and the structure of one of the loops are critical determinants in the binding of GI NoVs to nonsecretor HBGAs.

Generalizing the correlated chromophore domain model of reversible photodegradation to include the effects of an applied electric field

NASA Astrophysics Data System (ADS)

Anderson, Benjamin; Kuzyk, Mark G.

2014-03-01

All observations of photodegradation and self-healing follow the predictions of the correlated chromophore domain model [Ramini et al., Polym. Chem. 4, 4948 (2013), 10.1039/c3py00263b]. In the present work, we generalize the domain model to describe the effects of an electric field by including induced dipole interactions between molecules in a domain by means of a self-consistent field approach. This electric field correction is added to the statistical mechanical model to calculate the distribution of domains that are central to healing. Also included in the model are the dynamics due to the formation of an irreversibly damaged species, which we propose involves damage to the polymer mediated through energy transfer from a dopant molecule after absorbing a photon. As in previous studies, the model with one-dimensional domains best explains all experimental data of the population as a function of time, temperature, intensity, concentration, and now applied electric field. Though the precise nature of a domain is yet to be determined, the fact that only one-dimensional domain models are consistent with observations suggests that they might be made of correlated dye molecules along polymer chains. Furthermore, the voltage-dependent measurements suggest that the largest polarizability axis of the molecules are oriented perpendicular to the chain.

Creativity and working memory capacity in sports: working memory capacity is not a limiting factor in creative decision making amongst skilled performers.

PubMed

Furley, Philip; Memmert, Daniel

2015-01-01

The goal of the study was to investigate the relationship between domain-general working memory capacity and domain-specific creativity amongst experienced soccer players. We administered the automated operation span task in combination with a domain-specific soccer creativity task to a group of 61 experienced soccer players to address the question whether an athlete's domain-specific creativity is restricted by their domain-general cognitive abilities (i.e., working memory capacity). Given that previous studies have either found a positive correlation, a negative correlation, or no correlation between working memory capacity and creativity, we analyzed the data in an exploratory manner by following recent recommendations to report effect-size estimations and their precision in form of 95% confidence intervals. The pattern of results provided evidence that domain-general working memory capacity is not associated with creativity in a soccer-specific creativity task. This pattern of results suggests that future research and theorizing on the role of working memory in everyday creative performance needs to distinguish between different types of creative performance while also taking the role of domain-specific experience into account.

Creativity and working memory capacity in sports: working memory capacity is not a limiting factor in creative decision making amongst skilled performers

PubMed Central

Furley, Philip; Memmert, Daniel

2015-01-01

The goal of the study was to investigate the relationship between domain-general working memory capacity and domain-specific creativity amongst experienced soccer players. We administered the automated operation span task in combination with a domain-specific soccer creativity task to a group of 61 experienced soccer players to address the question whether an athlete’s domain-specific creativity is restricted by their domain-general cognitive abilities (i.e., working memory capacity). Given that previous studies have either found a positive correlation, a negative correlation, or no correlation between working memory capacity and creativity, we analyzed the data in an exploratory manner by following recent recommendations to report effect-size estimations and their precision in form of 95% confidence intervals. The pattern of results provided evidence that domain-general working memory capacity is not associated with creativity in a soccer-specific creativity task. This pattern of results suggests that future research and theorizing on the role of working memory in everyday creative performance needs to distinguish between different types of creative performance while also taking the role of domain-specific experience into account. PMID:25713552

Polymorphic phase transitions and molecular motion in pyridinium chlorochromate

NASA Astrophysics Data System (ADS)

Pajaķ, Z.; Szafrańska, B.; Czarnecki, P.; Mayer, J.; Kozak, A.

1997-08-01

DTA, DSC, NMR and dielectric studies have been performed for pyridinium chlorochromate over a wide temperature range. A sequence of four solid-solid phase transitions was discovered. The in-plane complex reorientation of the cation is described by a three-well potential model with two correlation times. At higher temperatures one observes simultaneous cation tumbling and diffusion. Thus existence of a new ionic plastic phase is revealed. The domain structure observed suggests ferroelastic properties of the compound.

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.

Translation and validation of chronic liver disease questionnaire (CLDQ) in Tamil language.

PubMed

Goel, Amit; Arivazhagan, Karunanithi; Sasi, Avani; Shanmugam, Vanathy; Koshi, Seleena; Pottakkat, Biju; Lakshmi, C P; Awasthi, Ashish

2017-05-01

Chronic liver disease questionnaire (CLDQ), a self-administered quality-of-life (QOL) instrument for chronic liver disease (CLD) patients, was originally developed in English language. We aimed to translate and validate CLDQ in Tamil language (CLDQ-T). CLDQ-T, prepared by two forward and two backward independent translations by four bilingual (Tamil and English) persons, and repeated iterative modifications, was validated in adult, native-Tamil patients with CLD. CLDQ-T was re-tested in some patients 2 weeks later. Convergent validity was assessed using Spearman's correlation, and discriminant validity by comparison with World Health Organization's brief QOL tool (WHOQOL-BREF). Reliability was assessed through internal consistency (Cronbach's alpha) and test-retest reliability (intra-class correlation). Cutoff used for statistical significance was p<0.05. The study included 126 patients (age: mean [SD] 46 years [12.5]; male 104; cause: alcohol 42%, HBV 25%, HCV 4%, cryptogenic 29%; CTP class A 47%, B 37%, and C 16%). In convergent validity, all domains except the "abdominal domain" showed significant correlation between CLDQ-T and WHOQOL-BREF. Patients with severe disease had lower scores for all domains of CLDQ-T except the "abdominal" domain, but not for any of the domains for WHOQOL-BREF. Overall Cronbach's alpha was 0.942, and more than 0.7 for all the individual domains except the "activity" domain. On retesting in 44 (35%) patients, intraclass correlation coefficient was 0.879 for the overall CLDQ-T score and >0.700 for individual domains. CLDQ-T was easily understood and showed good performance characteristics in assessing QOL in Tamil-speaking patients with CLD.

Structure-Function Modeling of Optical Coherence Tomography and Standard Automated Perimetry in the Retina of Patients with Autosomal Dominant Retinitis Pigmentosa

PubMed Central

Smith, Travis B.; Parker, Maria; Steinkamp, Peter N.; Weleber, Richard G.; Smith, Ning; Wilson, David J.

2016-01-01

Purpose To assess relationships between structural and functional biomarkers, including new topographic measures of visual field sensitivity, in patients with autosomal dominant retinitis pigmentosa. Methods Spectral domain optical coherence tomography line scans and hill of vision (HOV) sensitivity surfaces from full-field standard automated perimetry were semi-automatically aligned for 60 eyes of 35 patients. Structural biomarkers were extracted from outer retina b-scans along horizontal and vertical midlines. Functional biomarkers were extracted from local sensitivity profiles along the b-scans and from the full visual field. These included topographic measures of functional transition such as the contour of most rapid sensitivity decline around the HOV, herein called HOV slope for convenience. Biomarker relationships were assessed pairwise by coefficients of determination (R2) from mixed-effects analysis with automatic model selection. Results Structure-function relationships were accurately modeled (conditional R2>0.8 in most cases). The best-fit relationship models and correlation patterns for horizontally oriented biomarkers were different than vertically oriented ones. The structural biomarker with the largest number of significant functional correlates was the ellipsoid zone (EZ) width, followed by the total photoreceptor layer thickness. The strongest correlation observed was between EZ width and HOV slope distance (marginal R2 = 0.85, p<10−10). The mean sensitivity defect at the EZ edge was 7.6 dB. Among all functional biomarkers, the HOV slope mean value, HOV slope mean distance, and maximum sensitivity along the b-scan had the largest number of significant structural correlates. Conclusions Topographic slope metrics show promise as functional biomarkers relevant to the transition zone. EZ width is strongly associated with the location of most rapid HOV decline. PMID:26845445

Structure-Function Modeling of Optical Coherence Tomography and Standard Automated Perimetry in the Retina of Patients with Autosomal Dominant Retinitis Pigmentosa.

PubMed

Smith, Travis B; Parker, Maria; Steinkamp, Peter N; Weleber, Richard G; Smith, Ning; Wilson, David J

2016-01-01

To assess relationships between structural and functional biomarkers, including new topographic measures of visual field sensitivity, in patients with autosomal dominant retinitis pigmentosa. Spectral domain optical coherence tomography line scans and hill of vision (HOV) sensitivity surfaces from full-field standard automated perimetry were semi-automatically aligned for 60 eyes of 35 patients. Structural biomarkers were extracted from outer retina b-scans along horizontal and vertical midlines. Functional biomarkers were extracted from local sensitivity profiles along the b-scans and from the full visual field. These included topographic measures of functional transition such as the contour of most rapid sensitivity decline around the HOV, herein called HOV slope for convenience. Biomarker relationships were assessed pairwise by coefficients of determination (R2) from mixed-effects analysis with automatic model selection. Structure-function relationships were accurately modeled (conditional R(2)>0.8 in most cases). The best-fit relationship models and correlation patterns for horizontally oriented biomarkers were different than vertically oriented ones. The structural biomarker with the largest number of significant functional correlates was the ellipsoid zone (EZ) width, followed by the total photoreceptor layer thickness. The strongest correlation observed was between EZ width and HOV slope distance (marginal R(2) = 0.85, p<10(-10)). The mean sensitivity defect at the EZ edge was 7.6 dB. Among all functional biomarkers, the HOV slope mean value, HOV slope mean distance, and maximum sensitivity along the b-scan had the largest number of significant structural correlates. Topographic slope metrics show promise as functional biomarkers relevant to the transition zone. EZ width is strongly associated with the location of most rapid HOV decline.

Carbonate substitution in the mineral component of bone: Discriminating the structural changes, simultaneously imposed by carbonate in A and B sites of apatite

NASA Astrophysics Data System (ADS)

Madupalli, Honey; Pavan, Barbara; Tecklenburg, Mary M. J.

2017-11-01

The mineral component of bone and other biological calcifications is primarily a carbonate substituted calcium apatite. Integration of carbonate into two sites, substitution for phosphate (B-type carbonate) and substitution for hydroxide (A-type carbonate), influences the crystal properties which relate to the functional properties of bone. In the present work, a series of AB-type carbonated apatites (AB-CAp) having varying A-type and B-type carbonate weight fractions were prepared and analyzed by Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (XRD), and carbonate analysis. A detailed characterization of A-site and B-site carbonate assignment in the FTIR ν3 region is proposed. The mass fractions of carbonate in A-site and B-site of AB-CAp correlate differently with crystal axis length and crystallite domain size. In this series of samples reduction in crystal domain size correlates only with A-type carbonate which indicates that carbonate in the A-site is more disruptive to the apatite structure than carbonate in the B-site. High temperature methods were required to produce significant A-type carbonation of apatite, indicating a higher energy barrier for the formation of A-type carbonate than for B-type carbonate. This is consistent with the dominance of B-type carbonate substitution in low temperature synthetic and biological apatites.

Computational Analysis of Residue Interaction Networks and Coevolutionary Relationships in the Hsp70 Chaperones: A Community-Hopping Model of Allosteric Regulation and Communication

PubMed Central

Stetz, Gabrielle; Verkhivker, Gennady M.

2017-01-01

Allosteric interactions in the Hsp70 proteins are linked with their regulatory mechanisms and cellular functions. Despite significant progress in structural and functional characterization of the Hsp70 proteins fundamental questions concerning modularity of the allosteric interaction networks and hierarchy of signaling pathways in the Hsp70 chaperones remained largely unexplored and poorly understood. In this work, we proposed an integrated computational strategy that combined atomistic and coarse-grained simulations with coevolutionary analysis and network modeling of the residue interactions. A novel aspect of this work is the incorporation of dynamic residue correlations and coevolutionary residue dependencies in the construction of allosteric interaction networks and signaling pathways. We found that functional sites involved in allosteric regulation of Hsp70 may be characterized by structural stability, proximity to global hinge centers and local structural environment that is enriched by highly coevolving flexible residues. These specific characteristics may be necessary for regulation of allosteric structural transitions and could distinguish regulatory sites from nonfunctional conserved residues. The observed confluence of dynamics correlations and coevolutionary residue couplings with global networking features may determine modular organization of allosteric interactions and dictate localization of key mediating sites. Community analysis of the residue interaction networks revealed that concerted rearrangements of local interacting modules at the inter-domain interface may be responsible for global structural changes and a population shift in the DnaK chaperone. The inter-domain communities in the Hsp70 structures harbor the majority of regulatory residues involved in allosteric signaling, suggesting that these sites could be integral to the network organization and coordination of structural changes. Using a network-based formalism of allostery, we introduced a community-hopping model of allosteric communication. Atomistic reconstruction of signaling pathways in the DnaK structures captured a direction-specific mechanism and molecular details of signal transmission that are fully consistent with the mutagenesis experiments. The results of our study reconciled structural and functional experiments from a network-centric perspective by showing that global properties of the residue interaction networks and coevolutionary signatures may be linked with specificity and diversity of allosteric regulation mechanisms. PMID:28095400

Computational Analysis of Residue Interaction Networks and Coevolutionary Relationships in the Hsp70 Chaperones: A Community-Hopping Model of Allosteric Regulation and Communication.

PubMed

Stetz, Gabrielle; Verkhivker, Gennady M

2017-01-01

Allosteric interactions in the Hsp70 proteins are linked with their regulatory mechanisms and cellular functions. Despite significant progress in structural and functional characterization of the Hsp70 proteins fundamental questions concerning modularity of the allosteric interaction networks and hierarchy of signaling pathways in the Hsp70 chaperones remained largely unexplored and poorly understood. In this work, we proposed an integrated computational strategy that combined atomistic and coarse-grained simulations with coevolutionary analysis and network modeling of the residue interactions. A novel aspect of this work is the incorporation of dynamic residue correlations and coevolutionary residue dependencies in the construction of allosteric interaction networks and signaling pathways. We found that functional sites involved in allosteric regulation of Hsp70 may be characterized by structural stability, proximity to global hinge centers and local structural environment that is enriched by highly coevolving flexible residues. These specific characteristics may be necessary for regulation of allosteric structural transitions and could distinguish regulatory sites from nonfunctional conserved residues. The observed confluence of dynamics correlations and coevolutionary residue couplings with global networking features may determine modular organization of allosteric interactions and dictate localization of key mediating sites. Community analysis of the residue interaction networks revealed that concerted rearrangements of local interacting modules at the inter-domain interface may be responsible for global structural changes and a population shift in the DnaK chaperone. The inter-domain communities in the Hsp70 structures harbor the majority of regulatory residues involved in allosteric signaling, suggesting that these sites could be integral to the network organization and coordination of structural changes. Using a network-based formalism of allostery, we introduced a community-hopping model of allosteric communication. Atomistic reconstruction of signaling pathways in the DnaK structures captured a direction-specific mechanism and molecular details of signal transmission that are fully consistent with the mutagenesis experiments. The results of our study reconciled structural and functional experiments from a network-centric perspective by showing that global properties of the residue interaction networks and coevolutionary signatures may be linked with specificity and diversity of allosteric regulation mechanisms.

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.

Discrete capacity limits and neuroanatomical correlates of visual short-term memory for objects and spatial locations.

PubMed

Konstantinou, Nikos; Constantinidou, Fofi; Kanai, Ryota

2017-02-01

Working memory is responsible for keeping information in mind when it is no longer in view, linking perception with higher cognitive functions. Despite such crucial role, short-term maintenance of visual information is severely limited. Research suggests that capacity limits in visual short-term memory (VSTM) are correlated with sustained activity in distinct brain areas. Here, we investigated whether variability in the structure of the brain is reflected in individual differences of behavioral capacity estimates for spatial and object VSTM. Behavioral capacity estimates were calculated separately for spatial and object information using a novel adaptive staircase procedure and were found to be unrelated, supporting domain-specific VSTM capacity limits. Voxel-based morphometry (VBM) analyses revealed dissociable neuroanatomical correlates of spatial versus object VSTM. Interindividual variability in spatial VSTM was reflected in the gray matter density of the inferior parietal lobule. In contrast, object VSTM was reflected in the gray matter density of the left insula. These dissociable findings highlight the importance of considering domain-specific estimates of VSTM capacity and point to the crucial brain regions that limit VSTM capacity for different types of visual information. Hum Brain Mapp 38:767-778, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Cognition and connectomes in nondementia idiopathic Parkinson’s disease

PubMed Central

Tanner, Jared J.; Couret, Michelle; Goicochea, Shelby; Mareci, Thomas H.; Price, Catherine C.

2018-01-01

In this study, we investigate the organization of the structural connectome in cognitively well participants with Parkinson’s disease (PD-Well; n = 31) and a subgroup of participants with Parkinson’s disease who have amnestic disturbances (PD-MI; n = 9). We explore correlations between connectome topology and vulnerable cognitive domains in Parkinson’s disease relative to non-Parkinson’s disease peers (control, n = 40). Diffusion-weighted MRI data and deterministic tractography were used to generate connectomes. Connectome topological indices under study included weighted indices of node strength, path length, clustering coefficient, and small-worldness. Relative to controls, node strength was reduced 4.99% for PD-Well (p = 0.041) and 13.2% for PD-MI (p = 0.004). We found bilateral differences in the node strength between PD-MI and controls for inferior parietal, caudal middle frontal, posterior cingulate, precentral, and rostral middle frontal. Correlations between connectome and cognitive domains of interest showed that topological indices of global connectivity negatively associated with working memory and displayed more and larger negative correlations with neuropsychological indices of memory in PD-MI than in PD-Well and controls. These findings suggest that indices of network connectivity are reduced in PD-MI relative to PD-Well and control participants. PMID:29911667

Structural requirements for fibromodulin binding to collagen and the control of type I collagen fibrillogenesis--critical roles for disulphide bonding and the C-terminal region.

PubMed

Font, B; Eichenberger, D; Goldschmidt, D; Boutillon, M M; Hulmes, D J

1998-06-15

Fibromodulin belongs to the family of small, leucine-rich proteoglycans which have been reported to interact with collagens and to inhibit type I collagen fibrillogenesis. Decorin and fibromodulin exhibit a noticeable degree of sequence similarity. However, as previously reported [Font, B., Eichenberger, D., Rosenberg, L. M. & van der Rest, M. (1996) Matrix Biol. 15, 341-348] the domains of these molecules implicated in the interactions with type XII and type XIV collagens are different, these being the dermatan sulphate/chondroitin sulphate chain for decorin and the core protein for fibromodulin. At the present time the fibromodulin domains implicated in the interactions with fibrillar collagens remain unknown. In experiments reported here, we have sought to identify the structural requirements for fibromodulin interaction with collagen and for the control of type I collagen fibrillogenesis. Circular dichroism spectra and fibrillogenesis inhibition studies show that fibromodulin structure and its collagen fibrillogenesis control function are strictly dependent on the presence of intact disulphide bridge(s). In addition, we show that the binding of fibromodulin (or fibromodulin-derived fragments) to type I collagen is not necessarily correlated with fibrillogenesis inhibition. To isolate fibromodulin domains, the native proteoglycan was submitted to mild proteolysis. We have isolated an alpha-chymotrypsin-resistant fragment which contains the bulk of the N-terminal and central region of the molecule including the leucine-rich repeats 4 and 6 reported for decorin to be involved in type I collagen binding. This fragment does not bind to type I collagen. Using enzymes with different specificities, a number of large fragments of fibromodulin were obtained, suggesting a compact structure for this molecule which is relatively resistant to proteolysis. None of these N-glycosylated fragments were able to bind to type I collagen in co-sedimentation experiments. Taken together these results suggest that fibromodulin-type I collagen interactions leading to fibrillogenesis inhibition require more than one binding domain. One of these domains could be the C-terminal end of the molecule containing the disulphide loop which is absent in the chymotrypsin-resistant fragment.

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

Associated impairment of the categories of conspecifics and biological entities: cognitive and neuroanatomical aspects of a new case.

PubMed

Capitani, Erminio; Chieppa, Francesca; Laiacona, Marcella

2010-05-01

Case A.C.A. presented an associated impairment of visual recognition and semantic knowledge for celebrities and biological objects. This case was relevant for (a) the neuroanatomical correlations, and (b) the relationship between visual recognition and semantics within the biological domain and the conspecifics domain. A.C.A. was not affected by anterior temporal damage. Her bilateral vascular lesions were localized on the medial and inferior temporal gyrus on the right and on the intermediate fusiform gyrus on the left, without concomitant lesions of the parahippocampal gyrus or posterior fusiform. Data analysis was based on a novel methodology developed to estimate the rate of stored items in the visual structural description system (SDS) or in the face recognition unit. For each biological object, no particular correlation was found between the visual information accessed through the semantic system and that tapped by the picture reality judgement. Findings are discussed with reference to whether a putative resource commonality is likely between biological objects and conspecifics, and whether or not either category may depend on an exclusive neural substrate.

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.

Characterization of Near-Surface Geology and Possible Voids Using Resistivity and Electromagnetic Methods at the Gran Quivira Unit of Salinas Pueblo Missions National Monument, Central New Mexico, June 2005

USGS Publications Warehouse

Ball, Lyndsay B.; Lucius, Jeffrey E.; Land, Lewis A.; Teeple, Andrew

2006-01-01

At the Gran Quivira Unit of Salinas Pueblo Missions National Monument in central New Mexico, a partially excavated pueblo known as Mound 7 has recently become architecturally unstable. Historical National Park Service records indicate both natural caves and artificial tunnels may be present in the area. Knowledge of the local near-surface geology and possible locations of voids would aid in preservation of the ruins. Time-domain and frequency-domain electromagnetic as well as direct-current resistivity methods were used to characterize the electrical structure of the near-surface geology and to identify discrete electrical features that may be associated with voids. Time-domain electromagnetic soundings indicate three major electrical layers; however, correlation of these layers to geologic units was difficult because of the variability of lithologic data from existing test holes. Although resistivity forward modeling was unable to conclusively determine the presence or absence of voids in most cases, the high-resistivity values (greater than 5,000 ohm-meters) in the direct-current resistivity data indicate that voids may exist in the upper 50 meters. Underneath Mound 7, there is a possibility of large voids below a depth of 20 meters, but there is no indication of substantial voids in the upper 20 meters. Gridded lines and profiled inversions of frequency-domain electromagnetic data showed excellent correlation to resistivity features in the upper 5 meters of the direct-current resistivity data. This technique showed potential as a reconnaissance tool for detecting voids in the very near surface.

Reliability, convergent validity and factor structure of the DASS-21 in a sample of Vietnamese adolescents

PubMed Central

Tran, Thach Duc; Holton, Sara; Nguyen, Huong Thanh; Wolfe, Rory; Fisher, Jane

2017-01-01

Objectives To assess the internal consistency, latent structure and convergent validity of the Depression, Anxiety and Stress Scale-21 (DASS-21) among adolescents in Vietnam. Method An anonymous, self-completed questionnaire was conducted among 1,745 high school students in Hanoi, Vietnam between October, 2013 and January, 2014. Confirmatory factor analyses were performed to assess the latent structure of the DASS-21. Factorial invariance between girls and boys was examined. Cronbach alphas and correlation coefficients between DASS-21 factor scores and the domain scores of the Duke Health Profile Adolescent Vietnamese validated version (ADHP-V) were calculated to assess DASS-21 internal consistency and convergent validity. Results A total of 1,606/ 1,745 (92.6%) students returned the questionnaire. Of those, 1,387 students provided complete DASS-21 data. The scale demonstrated adequate internal consistency (Cronbach α: 0.761 to 0.906). A four-factor model showed the best fit to the data. Items loaded significantly on a common general distress factor, the depression, and the anxiety factors, but few on the stress factor (p<0.05). DASS-21 convergent validity was confirmed with moderate correlation coefficients (-0.47 to -0.66) between its factor scores and the ADHP-V mental health related domains. Conclusions The DASS-21 is reliable and suitable for use to assess symptoms of common mental health problems, especially depression and anxiety among Vietnamese adolescents. However, its ability in detecting stress among these adolescents may be limited. Further research is warrant to explore these results. PMID:28723909

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

The C-terminal region of Escherichia coli UvrC contributes to the flexibility of the UvrABC nucleotide excision repair system

PubMed Central

Verhoeven, Esther E. A.; van Kesteren, Marian; Turner, John J.; van der Marel, Gijs A.; van Boom, Jacques H.; Moolenaar, Geri F.; Goosen, Nora

2002-01-01

Nucleotide excision repair in Escherichia coli involves formation of the UvrB–DNA complex and subsequent DNA incisions on either site of the damage by UvrC. In this paper, we studied the incision of substrates with different damages in varying sequence contexts. We show that there is not always a correlation between the incision efficiency and the stability of the UvrB–DNA complex. Both stable and unstable UvrB–DNA complexes can be efficiently incised. However some lesions that give rise to stable UvrB–DNA complexes do result in a very low incision. We present evidence that this poor incision is due to sterical hindrance of the damage itself. In its C-terminal region UvrC contains two helix–hairpin–helix (HhH) motifs. Mutational analysis shows that these motifs constitute one functional unit, probably folded as one structural unit; the (HhH)2 domain. This (HhH)2 domain was previously shown to be important for the 5′ incision on a substrate containing a (cis-Pt)·GG adduct, but not for 3′ incision. Here we show that, mainly depending on the sequence context of the lesion, the (HhH)2 domain can be important for 3′ and/or 5′ incision. We propose that the (HhH)2 domain stabilises specific DNA structures required for the two incisions, thereby contributing to the flexibility of the UvrABC repair system. PMID:12034838

Revealing the magnetic proximity effect in EuS/Al bilayers through superconducting tunneling spectroscopy

NASA Astrophysics Data System (ADS)

Strambini, E.; Golovach, V. N.; De Simoni, G.; Moodera, J. S.; Bergeret, F. S.; Giazotto, F.

2017-10-01

A ferromagnetic insulator in contact with a superconductor is known to induce an exchange splitting of the singularity in the Bardeen-Cooper-Schrieffer (BCS) density of states (DoS). The magnitude of the splitting is proportional to the exchange field that penetrates into the superconductor to a depth comparable with the superconducting coherence length and which ranges in magnitude from a few to a few tens of tesla. We study this magnetic proximity effect in EuS/Al bilayers and show that the domain structure of the EuS affects the positions and the line shapes of the exchange-split BCS peaks. Remarkably, a clear exchange splitting is observed even in the unmagnetized state of the EuS layer, suggesting that the domain size of the EuS is comparable with the superconducting coherence length. Upon magnetizing the EuS layer, the splitting increases while the peaks change shape. Conductance measurements as a function of bias voltage at the lowest temperatures allowed us to relate the line shape of the split BCS DoS to the characteristic domain structure in the ultrathin EuS layer. These results pave the way to engineering triplet superconducting correlations at domain walls in EuS/Al bilayers. Furthermore, the hard gap and large splitting observed in our tunneling spectroscopy measurements make EuS/Al an excellent candidate for substituting strong magnetic fields in experiments studying Majorana bound states.

Mechanistic insights into the urea-induced denaturation of kinase domain of human integrin linked kinase.

PubMed

Syed, Sunayana Begum; Khan, Faez Iqbal; Khan, Sabab Hasan; Srivastava, Saurabha; Hasan, Gulam Mustafa; Lobb, Kevin A; Islam, Asimul; Ahmad, Faizan; Hassan, Md Imtaiyaz

2018-05-01

Integrin-linked kinase (ILK), a ubiquitously expressed intracellular Ser/Thr protein kinase, plays a major role in the oncogenesis and tumour progression. The conformational stability and unfolding of kinase domain of ILK (ILK 193-446 ) was examined in the presence of increasing concentrations of urea. The stability parameters of the urea-induced denaturation were measured by monitoring changes in [θ] 222 (mean residue ellipticity at 222nm), difference absorption coefficient at 292nm (Δε 292 ) and intrinsic fluorescence emission intensity at pH7.5 and 25±0.1°C. The urea-induced denaturation was found to be reversible. The protein unfolding transition occurred in the urea concentration range 3.0-7.0M. A coincidence of normalized denaturation curves of optical properties ([θ] 222 , Δε 292 and λ max , the wavelength of maximum emission intensity) suggested that urea-induced denaturation of kinase domain of ILK is a two-state process. We further performed molecular dynamics simulation for 100ns to see the effect of urea on structural stability of kinase domain of ILK at atomic level. Structural changes with increasing concentrations of urea were analysed, and we observed a significant increase in the root mean square deviation, root mean square fluctuations, solvent accessible surface area and radius of gyration. A correlation was observed between in vitro and in silico studies. Copyright © 2018 Elsevier B.V. All rights reserved.

Scanning fluorescence correlation spectroscopy comes full circle.

PubMed

Gunther, German; Jameson, David M; Aguilar, Joao; Sánchez, Susana A

2018-02-07

In this article, we review the application of fluorescence correlation spectroscopy (FCS) methods to studies on live cells. We begin with a brief overview of the theory underlying FCS, highlighting the type of information obtainable. We then focus on circular scanning FCS. Specifically, we discuss instrumentation and data analysis and offer some considerations regarding sample preparation. Two examples from the literature are discussed in detail. First, we show how this method, coupled with the photon counting histogram analysis, can provide information on yeast ribosomal structures in live cells. The combination of scanning FCS with dual channel detection in the study of lipid domains in live cells is also illustrated. Copyright © 2018 Elsevier Inc. All rights reserved.

X-ray fluctuation timescale and Black Hole mass relation in AGN

NASA Astrophysics Data System (ADS)

Wandel, Amri; Malkan, Mathew

We analyze the fluctuations in the X-ray flux of 20 AGN (mainly Seyfert 1 galaxies) monitored by RXTE and XMM-Newton with a sampling frequency ranging from hours to years, using structure function (SF) analysis. We derive SFs over four orders of magnitude in the time domain (0.03-300 days). Most objects show a characteristic time scale, where the SF flattens or changes slope. For 10 objects with published power-spectral density (PSD) the break time scales in the SF and PSD are similar and show a good correlation. We also find a significant correlation between the SF timescale and the mass of the central black hole, determined for most objects by reverberation mapping.

Attenuation - The Ugly Stepsister of Velocity in the Noise Correlation Family

NASA Astrophysics Data System (ADS)

Lawrence, J. F.; Prieto, G.; Denolle, M.; Seats, K. J.

2012-12-01

Noise correlation functions and noise transfer functions have shown in practice to preserve the relative amplitude information, despite the challenge to reliably resolve it compared to phase information. Yet amplitude contains important information about wavefield interactions with the subsurface structure, including focusing/defocusing and seismic attenuation. To focus on the anelastic effects, or attenuation, we measure amplitude decay with increased station separation (distance). We present numerical results showing that the noise correlation functions (NCFs) preserve the relative amplitude information and properly retrieve seismic attenuation for sufficient noise source distribution and appropriate processing. Attenuation is only preserved through the relative decay of distinct waves from multiple simultaneous source locations. With appropriate whitening (and no time domain normalization), the coherency preserves correlation amplitudes proportional to the relative decay expected with all the inter-station spacing. We present new attenuation results for the United States, and particularly the Yellowstone region that illustrate lateral variations that strongly correlate with known geological features such as sedimentary basins, crustal blocks and active volcanism.

Cognitive correlates of pragmatic language comprehension in adult traumatic brain injury: A systematic review and meta-analyses.

PubMed

Rowley, Dane A; Rogish, Miles; Alexander, Timothy; Riggs, Kevin J

2017-01-01

Effective pragmatic comprehension of language is critical for successful communication and interaction, but this ability is routinely impaired following Traumatic Brain Injury (TBI) (1,2). Individual studies have investigated the cognitive domains associated with impaired pragmatic comprehension, but there remains little understanding of the relative importance of these domains in contributing to pragmatic comprehension impairment following TBI. This paper presents a systematic meta-analytic review of the observed correlations between pragmatic comprehension and cognitive processes following TBI. Five meta-analyses were computed, which quantified the relationship between pragmatic comprehension and five key cognitive constructs (declarative memory; working memory; attention; executive functions; social cognition). Significant moderate-to-strong correlations were found between all cognitive measures and pragmatic comprehension, where declarative memory was the strongest correlate. Thus, our findings indicate that pragmatic comprehension in TBI is associated with an array of domain general cognitive processes, and as such deficits in these cognitive domains may underlie pragmatic comprehension difficulties following TBI. The clinical implications of these findings are discussed.

Development and Psychometric Evaluation of the Hypoglycemia Perspectives Questionnaire in Patients with Type 2 Diabetes Mellitus.

PubMed

Kawata, Ariane K; Wilson, Hilary; Ong, Siew Hwa; Kulich, Karoly; Coyne, Karin

2016-10-01

The aim of this study was to evaluate the factor structure and psychometric characteristics of the Hypoglycemia Perspectives Questionnaire (HPQ) assessing experience and perceptions of hypoglycemia in patients with type 2 diabetes mellitus (T2DM). HPQ was administered to adults with T2DM in a clinical sample from Cyprus (HYPO-Cyprus, n = 500) and a community sample in the United States (US, n = 1257) from the 2011 US National Health and Wellness Survey. Demographic and clinical data were collected. Analysis of HPQ data from two convenience samples examined item performance, factor structure, and HPQ measurement properties (reliability, convergent validity, known-groups validity). Analyses supported three HPQ domains: symptom concern (six items), compensatory behavior (five items), and worry (five items). Internal consistency was high for all three domains (all ≥0.75), supporting reliability. Convergent validity was supported by moderate Spearman correlations between HPQ domain scores and the Audit of Diabetes-Dependent Quality of Life (ADDQoL-19) total score. Patients with recent hypoglycemia events had significantly higher HPQ scores, supporting known-group validity. HPQ may be a valid and reliable measure capturing the experience and impact of hypoglycemia and useful in clinical trials and community-based settings.

A sequential assignment procedure for proteins that have intermediate line widths in MAS NMR spectra: amyloid fibrils of human CA150.WW2.

PubMed

Becker, Johanna; Ferguson, Neil; Flinders, Jeremy; van Rossum, Barth-Jan; Fersht, Alan R; Oschkinat, Hartmut

2008-08-11

The second WW domain (WW2) of CA150, a human transcriptional activator, forms amyloid fibrils in vitro under physiological conditions. Based on experimental constraints from MAS NMR spectroscopy experiments, alanine scanning and electron microscopy, a structural model of CA150.WW2 amyloid fibrils was calculated earlier. Here, the assignment strategy is presented and suggested as a general approach for proteins that show intermediate line width. The (13)C,(13)C correlation experiments were recorded on fully or partially (13)C-labelled fibrils. The earlier (13)C assignment (26 residues) was extended to 34 of the 40 residues by direct (13)C-excitation experiments by using a deuterated sample that showed strongly improved line width. A 3D HNC-TEDOR (transferred-echo double-resonance) experiment with deuterated CA150.WW2 fibrils yielded 14 amide nitrogen and proton resonance assignments. The obtained chemical shifts were compared with the chemical shifts determined with the natively folded WW domain. TALOS (Torsion angle likelihood obtained from shift and sequence similarity) predictions confirmed that, under physiological conditions, the fibrillar form of CA150.WW2 adopts a significantly different beta structure than the native WW-domain fold.

Structural basis of the 3′-end recognition of a leading strand in stalled replication forks by PriA

PubMed Central

Sasaki, Kaori; Ose, Toyoyuki; Okamoto, Naoaki; Maenaka, Katsumi; Tanaka, Taku; Masai, Hisao; Saito, Mihoko; Shirai, Tsuyoshi; Kohda, Daisuke

2007-01-01

In eubacteria, PriA helicase detects the stalled DNA replication forks. This critical role of PriA is ascribed to its ability to bind to the 3′ end of a nascent leading DNA strand in the stalled replication forks. The crystal structures in complexes with oligonucleotides and the combination of fluorescence correlation spectroscopy and mutagenesis reveal that the N-terminal domain of PriA possesses a binding pocket for the 3′-terminal nucleotide residue of DNA. The interaction with the deoxyribose 3′-OH is essential for the 3′-terminal recognition. In contrast, the direct interaction with 3′-end nucleobase is unexpected, considering the same affinity for oligonucleotides carrying the four bases at the 3′ end. Thus, the N-terminal domain of PriA recognizes the 3′-end base in a base-non-selective manner, in addition to the deoxyribose and 5′-side phosphodiester group, of the 3′-terminal nucleotide to acquire both sufficient affinity and non-selectivity to find all of the stalled replication forks generated during DNA duplication. This unique feature is prerequisite for the proper positioning of the helicase domain of PriA on the unreplicated double-stranded DNA. PMID:17464287