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

International Nuclear Information System (INIS)

Svintradze, David V.; Peterson, Darrell L.; Collazo-Santiago, Evys A.; Lewis, Janina P.; Wright, H. Tonie

2013-01-01

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, 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

Postinduction represssion of the β-interferon gene is mediated through two positive regulatory domains

International Nuclear Information System (INIS)

Whittemore, L.A.; Maniatis, T.

1990-01-01

Virus induction of the human β-interferon (β-IFN) gene results in an increase in the rate of β-IFN mRNA synthesis, followed by a rapid postinduction decrease. In this paper, the authors show that two β-IFN promoter elements, positive regulatory domains I and II (PRDI and PRDII), which are required for virus induction of the β-IFN gene are also required for the postinduction turnoff. Although protein synthesis is not necessary for activation, it is necessary for repression of these promoter elements. Examination of nuclear extracts from cells infected with virus reveals the presence of virus-inducible, cycloheximide-sensitive, DNA-binding activities that interact specifically with PRDI or PRDII. They propose that the postinduction repression of β-IFN gene transcription involves virus inducible repressors that either bind directly to the positive regulatory elements of the β-IFN promoter or inactivate the positive regulatory factors bound to PRDI and PRDII

Chromatin Heterogeneity and Distribution of Regulatory Elements in the Late-Replicating Intercalary Heterochromatin Domains of Drosophila melanogaster Chromosomes.

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Varvara A Khoroshko

Full Text Available Late-replicating domains (intercalary heterochromatin in the Drosophila genome display a number of features suggesting their organization is quite unique. Typically, they are quite large and encompass clusters of functionally unrelated tissue-specific genes. They correspond to the topologically associating domains and conserved microsynteny blocks. Our study aims at exploring further details of molecular organization of intercalary heterochromatin and has uncovered surprising heterogeneity of chromatin composition in these regions. Using the 4HMM model developed in our group earlier, intercalary heterochromatin regions were found to host chromatin fragments with a particular epigenetic profile. Aquamarine chromatin fragments (spanning 0.67% of late-replicating regions are characterized as a class of sequences that appear heterogeneous in terms of their decompactization. These fragments are enriched with enhancer sequences and binding sites for insulator proteins. They likely mark the chromatin state that is related to the binding of cis-regulatory proteins. Malachite chromatin fragments (11% of late-replicating regions appear to function as universal transitional regions between two contrasting chromatin states. Namely, they invariably delimit intercalary heterochromatin regions from the adjacent active chromatin of interbands. Malachite fragments also flank aquamarine fragments embedded in the repressed chromatin of late-replicating regions. Significant enrichment of insulator proteins CP190, SU(HW, and MOD2.2 was observed in malachite chromatin. Neither aquamarine nor malachite chromatin types appear to correlate with the positions of highly conserved non-coding elements (HCNE that are typically replete in intercalary heterochromatin. Malachite chromatin found on the flanks of intercalary heterochromatin regions tends to replicate earlier than the malachite chromatin embedded in intercalary heterochromatin. In other words, there exists a

Computational Studies of the Active and Inactive Regulatory Domains of Response Regulator PhoP Using Molecular Dynamics Simulations.

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Qing, Xiao-Yu; Steenackers, Hans; Venken, Tom; De Maeyer, Marc; Voet, Arnout

2017-11-01

The response regulator PhoP is part of the PhoP/PhoQ two-component system, which is responsible for regulating the expression of multiple genes involved in controlling virulence, biofilm formation, and resistance to antimicrobial peptides. Therefore, modulating the transcriptional function of the PhoP protein is a promising strategy for developing new antimicrobial agents. There is evidence suggesting that phosphorylation-mediated dimerization in the regulatory domain of PhoP is essential for its transcriptional function. Disruption or stabilization of protein-protein interactions at the dimerization interface may inhibit or enhance the expression of PhoP-dependent genes. In this study, we performed molecular dynamics simulations on the active and inactive dimers and monomers of the PhoP regulatory domains, followed by pocket-detecting screenings and a quantitative hot-spot analysis in order to assess the druggability of the protein. Consistent with prior hypothesis, the calculation of the binding free energy shows that phosphorylation enhances dimerization of PhoP. Furthermore, we have identified two different putative binding sites at the dimerization active site (the α4-β5-α5 face) with energetic "hot-spot" areas, which could be used to search for modulators of protein-protein interactions. This study delivers insight into the dynamics and druggability of the dimerization interface of the PhoP regulatory domain, and may serve as a basis for the rational identification of new antimicrobial drugs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Activation of PI3K/Akt signaling by n-terminal SH2 domain mutants of the p85α regulatory subunit of PI3K is enhanced by deletion of its c-terminal SH2 domain.

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Hofmann, Bianca T; Jücker, Manfred

2012-10-01

The phosphoinositide 3-kinase (PI3K) is frequently activated in human cancer cells due to gain of function mutations in the catalytic (p110) and the regulatory (p85) subunits. The regulatory subunit consists of an SH3 domain and two SH2 domains. An oncogenic form of p85α named p65 lacking the c-terminal SH2 domain (cSH2) has been cloned from an irradiation-induced murine thymic lymphoma and transgenic mice expressing p65 in T lymphocytes develop a lymphoproliferative disorder. We have recently detected a c-terminal truncated form of p85α named p76α in a human lymphoma cell line lacking most of the cSH2 domain due to a frame shift mutation. Here, we report that the deletion of the cSH2 domain enhances the activating effects of the n-terminal SH2 domain (nSH2) mutants K379E and R340E on the PI3K/Akt pathway and micro tumor formation in a focus assay. Further analysis revealed that this transforming effect is mediated by activation of the catalytic PI3K isoform p110α and downstream signaling through mTOR. Our data further support a mechanistic model in which mutations of the cSH2 domain of p85α can abrogate its negative regulatory function on PI3K activity via the nSH2 domain of p85α. Copyright © 2012 Elsevier Inc. All rights reserved.

The crystal structure of the regulatory domain of the human sodium-driven chloride/bicarbonate exchanger.

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Alvadia, Carolina M; Sommer, Theis; Bjerregaard-Andersen, Kaare; Damkier, Helle Hasager; Montrasio, Michele; Aalkjaer, Christian; Morth, J Preben

2017-09-21

The sodium-driven chloride/bicarbonate exchanger (NDCBE) is essential for maintaining homeostatic pH in neurons. The crystal structure at 2.8 Å resolution of the regulatory N-terminal domain of human NDCBE represents the first crystal structure of an electroneutral sodium-bicarbonate cotransporter. The crystal structure forms an equivalent dimeric interface as observed for the cytoplasmic domain of Band 3, and thus establishes that the consensus motif VTVLP is the key minimal dimerization motif. The VTVLP motif is highly conserved and likely to be the physiologically relevant interface for all other members of the SLC4 family. A novel conserved Zn 2+ -binding motif present in the N-terminal domain of NDCBE is identified and characterized in vitro. Cellular studies confirm the Zn 2+ dependent transport of two electroneutral bicarbonate transporters, NCBE and NBCn1. The Zn 2+ site is mapped to a cluster of histidines close to the conserved ETARWLKFEE motif and likely plays a role in the regulation of this important motif. The combined structural and bioinformatics analysis provides a model that predicts with additional confidence the physiologically relevant interface between the cytoplasmic domain and the transmembrane domain.

Verbal and Visual-Spatial Working Memory: What Develops over a Life Span?

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Swanson, H. Lee

2017-01-01

This study investigates whether age-related changes in the structure of 5 complex working memory (WM) tasks (a) reflect a general or domain specific system, (b) follows a similar trajectory across different age spans, and (c) contribute domain general or domain specific resources to achievement measures. The study parsed the sample (N = 2,471)…

Signal Enhancement with Variable Span Linear Filters

DEFF Research Database (Denmark)

Benesty, Jacob; Christensen, Mads Græsbøll; Jensen, Jesper Rindom

. Variable span filters combine the ideas of optimal linear filters with those of subspace methods, as they involve the joint diagonalization of the correlation matrices of the desired signal and the noise. The book shows how some well-known filter designs, e.g. the minimum distortion, maximum signal...... the time and STFT domains, and, lastly, in time-domain binaural enhancement. In these contexts, the properties of these filters are analyzed in terms of their noise reduction capabilities and desired signal distortion, and the analyses are validated and further explored in simulations....

Like cognitive function, decision making across the life span shows profound age-related changes.

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Tymula, Agnieszka; Rosenberg Belmaker, Lior A; Ruderman, Lital; Glimcher, Paul W; Levy, Ifat

2013-10-15

It has long been known that human cognitive function improves through young adulthood and then declines across the later life span. Here we examined how decision-making function changes across the life span by measuring risk and ambiguity attitudes in the gain and loss domains, as well as choice consistency, in an urban cohort ranging in age from 12 to 90 y. We identified several important age-related patterns in decision making under uncertainty: First, we found that healthy elders between the ages of 65 and 90 were strikingly inconsistent in their choices compared with younger subjects. Just as elders show profound declines in cognitive function, they also show profound declines in choice rationality compared with their younger peers. Second, we found that the widely documented phenomenon of ambiguity aversion is specific to the gain domain and does not occur in the loss domain, except for a slight effect in older adults. Finally, extending an earlier report by our group, we found that risk attitudes across the life span show an inverted U-shaped function; both elders and adolescents are more risk-averse than their midlife counterparts. Taken together, these characterizations of decision-making function across the life span in this urban cohort strengthen the conclusions of previous reports suggesting a profound impact of aging on cognitive function in this domain.

Structure and catalytic regulatory function of ubiquitin specific protease 11 N-terminal and ubiquitin-like domains.

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Harper, Stephen; Gratton, Hayley E; Cornaciu, Irina; Oberer, Monika; Scott, David J; Emsley, Jonas; Dreveny, Ingrid

2014-05-13

The ubiquitin specific protease 11 (USP11) is implicated in DNA repair, viral RNA replication, and TGFβ signaling. We report the first characterization of the USP11 domain architecture and its role in regulating the enzymatic activity. USP11 consists of an N-terminal "domain present in USPs" (DUSP) and "ubiquitin-like" (UBL) domain, together referred to as DU domains, and the catalytic domain harboring a second UBL domain. Crystal structures of the DU domains show a tandem arrangement with a shortened β-hairpin at the two-domain interface and altered surface characteristics compared to the homologues USP4 and USP15. A conserved VEVY motif is a signature feature at the two-domain interface that shapes a potential protein interaction site. Small angle X-ray scattering and gel filtration experiments are consistent with the USP11DU domains and full-length USP11 being monomeric. Unexpectedly, we reveal, through kinetic assays of a series of deletion mutants, that the catalytic activity of USP11 is not regulated through intramolecular autoinhibition or activation by the N-terminal DU or UBL domains. Moreover, ubiquitin chain cleavage assays with all eight linkages reveal a preference for Lys(63)-, Lys(6)-, Lys(33)-, and Lys(11)-linked chains over Lys(27)-, Lys(29)-, and Lys(48)-linked and linear chains consistent with USP11's function in DNA repair pathways that is mediated by the protease domain. Our data support a model whereby USP11 domains outside the catalytic core domain serve as protein interaction or trafficking modules rather than a direct regulatory function of the proteolytic activity. This highlights the diversity of USPs in substrate recognition and regulation of ubiquitin deconjugation.

SH2-catalytic domain linker heterogeneity influences allosteric coupling across the SFK family.

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Register, A C; Leonard, Stephen E; Maly, Dustin J

2014-11-11

Src-family kinases (SFKs) make up a family of nine homologous multidomain tyrosine kinases whose misregulation is responsible for human disease (cancer, diabetes, inflammation, etc.). Despite overall sequence homology and identical domain architecture, differences in SH3 and SH2 regulatory domain accessibility and ability to allosterically autoinhibit the ATP-binding site have been observed for the prototypical SFKs Src and Hck. Biochemical and structural studies indicate that the SH2-catalytic domain (SH2-CD) linker, the intramolecular binding epitope for SFK SH3 domains, is responsible for allosterically coupling SH3 domain engagement to autoinhibition of the ATP-binding site through the conformation of the αC helix. As a relatively unconserved region between SFK family members, SH2-CD linker sequence variability across the SFK family is likely a source of nonredundant cellular functions between individual SFKs via its effect on the availability of SH3 and SH2 domains for intermolecular interactions and post-translational modification. Using a combination of SFKs engineered with enhanced or weakened regulatory domain intramolecular interactions and conformation-selective inhibitors that report αC helix conformation, this study explores how SH2-CD sequence heterogeneity affects allosteric coupling across the SFK family by examining Lyn, Fyn1, and Fyn2. Analyses of Fyn1 and Fyn2, isoforms that are identical but for a 50-residue sequence spanning the SH2-CD linker, demonstrate that SH2-CD linker sequence differences can have profound effects on allosteric coupling between otherwise identical kinases. Most notably, a dampened allosteric connection between the SH3 domain and αC helix leads to greater autoinhibitory phosphorylation by Csk, illustrating the complex effects of SH2-CD linker sequence on cellular function.

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

International Nuclear Information System (INIS)

Shang Liang; Hunter, Eric

2010-01-01

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

Self-Regulatory Capacities Are Depleted in a Domain-Specific Manner.

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Zhang, Rui; Stock, Ann-Kathrin; Rzepus, Anneka; Beste, Christian

2017-01-01

Performing an act of self-regulation such as making decisions has been suggested to deplete a common limited resource, which impairs all subsequent self-regulatory actions (ego depletion theory). It has however remained unclear whether self-referred decisions truly impair behavioral control even in seemingly unrelated cognitive domains, and which neurophysiological mechanisms are affected by these potential depletion effects. In the current study, we therefore used an inter-individual design to compare two kinds of depletion, namely a self-referred choice-based depletion and a categorization-based switching depletion, to a non-depleted control group. We used a backward inhibition (BI) paradigm to assess the effects of depletion on task switching and associated inhibition processes. It was combined with EEG and source localization techniques to assess both behavioral and neurophysiological depletion effects. The results challenge the ego depletion theory in its current form: Opposing the theory's prediction of a general limited resource, which should have yielded comparable effects in both depletion groups, or maybe even a larger depletion in the self-referred choice group, there were stronger performance impairments following a task domain-specific depletion (i.e., the switching-based depletion) than following a depletion based on self-referred choices. This suggests at least partly separate and independent resources for various cognitive control processes rather than just one joint resource for all self-regulation activities. The implications are crucial to consider for people making frequent far-reaching decisions e.g., in law or economy.

Phonological similarity effect in complex span task.

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Camos, Valérie; Mora, Gérôme; Barrouillet, Pierre

2013-01-01

The aim of our study was to test the hypothesis that two systems are involved in verbal working memory; one is specifically dedicated to the maintenance of phonological representations through verbal rehearsal while the other would maintain multimodal representations through attentional refreshing. This theoretical framework predicts that phonologically related phenomena such as the phonological similarity effect (PSE) should occur when the domain-specific system is involved in maintenance, but should disappear when concurrent articulation hinders its use. Impeding maintenance in the domain-general system by a concurrent attentional demand should impair recall performance without affecting PSE. In three experiments, we manipulated the concurrent articulation and the attentional demand induced by the processing component of complex span tasks in which participants had to maintain lists of either similar or dissimilar words. Confirming our predictions, PSE affected recall performance in complex span tasks. Although both the attentional demand and the articulatory requirement of the concurrent task impaired recall, only the induction of an articulatory suppression during maintenance made the PSE disappear. These results suggest a duality in the systems devoted to verbal maintenance in the short term, constraining models of working memory.

DNA-binding site of major regulatory protein alpha 4 specifically associated with promoter-regulatory domains of alpha genes of herpes simplex virus type 1.

OpenAIRE

Kristie, T M; Roizman, B

1986-01-01

Herpes simplex virus type 1 genes form at least five groups (alpha, beta 1, beta 2, gamma 1, and gamma 2) whose expression is coordinately regulated and sequentially ordered in a cascade fashion. Previous studies have shown that functional alpha 4 gene product is essential for the transition from alpha to beta protein synthesis and have suggested that alpha 4 gene expression is autoregulatory. We have previously reported that labeled DNA fragments containing promoter-regulatory domains of thr...

The composite complex span: French validation of a short working memory task.

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Gonthier, Corentin; Thomassin, Noémylle; Roulin, Jean-Luc

2016-03-01

Most studies in individual differences in the field of working memory research use complex span tasks to measure working memory capacity. Various complex span tasks based on different materials have been developed, and these tasks have proven both reliable and valid; several complex span tasks are often combined to provide a domain-general estimate of working memory capacity with even better psychometric properties. The present work sought to address two issues. Firstly, having participants perform several full-length complex span tasks in succession makes for a long and tedious procedure. Secondly, few complex span tasks have been translated and validated in French. We constructed a French working memory task labeled the Composite Complex Span (CCS). The CCS includes shortened versions of three classic complex span tasks: the reading span, symmetry span, and operation span. We assessed the psychometric properties of the CCS, including test-retest reliability and convergent validity, with Raven's Advanced Progressive Matrices and with an alpha span task; the CCS demonstrated satisfying qualities in a sample of 1,093 participants. This work provides evidence that shorter versions of classic complex span tasks can yield valid working memory estimates. The materials and normative data for the CCS are also included.

The complexities of complex span: explaining individual differences in working memory in children and adults.

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Bayliss, Donna M; Jarrold, Christopher; Gunn, Deborah M; Baddeley, Alan D

2003-03-01

Two studies are presented that investigated the constraints underlying working memory performance in children and adults. In each case, independent measures of processing efficiency and storage capacity are assessed to determine their relative importance in predicting performance on complex span tasks,which measure working memory capacity. Results show that complex span performance was independently constrained by individual differences in domain-general processing efficiency and domain-specific storage capacity. Residual variance, which may reflect the ability to coordinate storage and processing, also predicted academic achievement. These results challenge the view that complex span taps a limited-capacity resource pool shared between processing and storage operations. Rather, they are consistent with a multiple-component model in which separate resource pools support the processing and storage functions of working memory.

The complex between SOS3 and SOS2 regulatory domain from Arabidopsis thaliana: cloning, expression, purification, crystallization and preliminary X-ray analysis

Energy Technology Data Exchange (ETDEWEB)

Sánchez-Barrena, María José; Moreno-Pérez, Sandra; Angulo, Iván; Martínez-Ripoll, Martín; Albert, Armando, E-mail: xalbert@iqfr.csic.es [Grupo de Cristalografía Macromolecular y Biología Estructural, Instituto de Química Física ‘Rocasolano’, Consejo Superior de Investigaciones Científicas, Serrano 119, E-28006 Madrid (Spain)

2007-07-01

Recombinant SOS3 and SOS2 regulatory domain from A. thaliana have been coexpressed in E. coli, purified and crystallized by the hanging-drop vapour-diffusion method. An X-ray data set has been collected at 2.0 Å resolution. The salt-tolerance genes SOS3 (salt overly sensitive 3) and SOS2 (salt overly sensitive 2) regulatory domain of Arabidopsis thaliana were cloned into a polycistronic plasmid and the protein complex was expressed in Escherichia coli, allowing purification to homogeneity in three chromatographic steps. Crystals were grown using vapour-diffusion techniques. The crystals belonged to space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 44.14, b = 57.39, c = 141.90 Å.

Span Restoration in Optical Networks with Limited Wavelength Conversion

DEFF Research Database (Denmark)

Ruepp, Sarah Renée; Buron, Jakob Due; Andriolli, N

2007-01-01

Next generation optical networks provide functionalities to dynamically provision and recover connections, while emerging technologies allow for the conversion between wavelengths. These devices are however expensive and hence it is likely that only few are deployed throughout the network...... converter-saving wavelength assignment in GMPLS networks. The converter saving property of the Suggested Vector is particularly desirable in span restoration, where the pre-failure path stubs have to be merged to the restoration path at the failure-adjacent nodes. In order to avoid wavelength conversion....... Furthermore, we describe different scenarios to extend the suggested vector wavelength assignment scheme to multi-domain networks with focus on span restoration....

Age Stereotypes and Self-Views Revisited: Patterns of Internalization and Projection Processes Across the Life Span.

Science.gov (United States)

Kornadt, Anna E; Voss, Peggy; Rothermund, Klaus

2017-07-01

We investigated processes of age stereotype internalization into the self and projection of self-views onto age stereotypes from a life-span perspective, taking age-related differences in the relevance of life domains into account. Age stereotypes and self-views in eight life domains were assessed in a sample of N = 593 persons aged 30-80 years (T1) at two time points that were separated by a 4-year time interval. We estimated cross-lagged projection and internalization effects in multigroup structural equation models. Internalization and projection effects were contingent on age group and life domain: Internalization effects were strongest in the young and middle-aged groups and emerged in the domains family, personality, work, and leisure. Projection effects in different domains were most pronounced for older participants. Our findings suggest that the internalization of age stereotypes is triggered by domain-specific expectations of impending age-related changes and transitions during certain phases of the life span. Projection processes, however, seem to occur in response to changes that have already been experienced by the individual. Our study demonstrates the dynamic interrelation of age stereotypes and self-views across the life course and highlights the importance of a differentiated, life-span perspective for the understanding of these mechanisms. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Akt1 binds focal adhesion kinase via the Akt1 kinase domain independently of the pleckstrin homology domain.

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Basson, M D; Zeng, B; Wang, S

2015-10-01

Akt1 and focal adhesion kinase (FAK) are protein kinases that play key roles in normal cell signaling. Individually, aberrant expression of these kinases has been linked to a variety of cancers. Together, Akt1/FAK interactions facilitate cancer metastasis by increasing cell adhesion under conditions of increased extracellular pressure. Pathological and iatrogenic sources of pressure arise from tumor growth against constraining stroma or direct perioperative manipulation. We previously reported that 15 mmHg increased extracellular pressure causes Akt1 to both directly interact with FAK and to phosphorylate and activate it. We investigated the nature of the Akt1/FAK binding by creating truncations of recombinant FAK, conjugated to glutathione S-transferase (GST), to pull down full-length Akt1. Western blots probing for Akt1 showed that FAK/Akt1 binding persisted in FAK truncations consisting of only amino acids 1-126, FAK(NT1), which contains the F1 subdomain of its band 4.1, ezrin, radixin, and moesin (FERM) domain. Using FAK(NT1) as bait, we then pulled down truncated versions of recombinant Akt1 conjugated to HA (human influenza hemagglutinin). Probes for GST-FAK(NT1) showed Akt1-FAK binding to occur in the absence of the both the Akt1 (N)-terminal pleckstrin homology (PH) domain and its adjacent hinge region. The Akt1 (C)-terminal regulatory domain was equally unnecessary for Akt1/FAK co-immunoprecipitation. Truncations involving the Akt1 catalytic domain showed that the domain by itself was enough to pull down FAK. Additionally, a fragment spanning from the PH domain to half way through the catalytic domain demonstrated increased FAK binding compared to full length Akt1. These results begin to delineate the Akt1/FAK interaction and can be used to manipulate their force-activated signal interactions. Furthermore, the finding that the N-terminal half of the Akt1 catalytic domain binds so strongly to FAK when cleaved from the rest of the protein may suggest a means

The carboxy-terminal domain of Dictyostelium C-module-binding factor is an independent gene regulatory entity.

Directory of Open Access Journals (Sweden)

Jörg Lucas

Full Text Available The C-module-binding factor (CbfA is a multidomain protein that belongs to the family of jumonji-type (JmjC transcription regulators. In the social amoeba Dictyostelium discoideum, CbfA regulates gene expression during the unicellular growth phase and multicellular development. CbfA and a related D. discoideum CbfA-like protein, CbfB, share a paralogous domain arrangement that includes the JmjC domain, presumably a chromatin-remodeling activity, and two zinc finger-like (ZF motifs. On the other hand, the CbfA and CbfB proteins have completely different carboxy-terminal domains, suggesting that the plasticity of such domains may have contributed to the adaptation of the CbfA-like transcription factors to the rapid genome evolution in the dictyostelid clade. To support this hypothesis we performed DNA microarray and real-time RT-PCR measurements and found that CbfA regulates at least 160 genes during the vegetative growth of D. discoideum cells. Functional annotation of these genes revealed that CbfA predominantly controls the expression of gene products involved in housekeeping functions, such as carbohydrate, purine nucleoside/nucleotide, and amino acid metabolism. The CbfA protein displays two different mechanisms of gene regulation. The expression of one set of CbfA-dependent genes requires at least the JmjC/ZF domain of the CbfA protein and thus may depend on chromatin modulation. Regulation of the larger group of genes, however, does not depend on the entire CbfA protein and requires only the carboxy-terminal domain of CbfA (CbfA-CTD. An AT-hook motif located in CbfA-CTD, which is known to mediate DNA binding to A+T-rich sequences in vitro, contributed to CbfA-CTD-dependent gene regulatory functions in vivo.

The Regulatory and Kinase Domains but Not the Interdomain Linker Determine Human Double-stranded RNA-activated Kinase (PKR) Sensitivity to Inhibition by Viral Non-coding RNAs.

Science.gov (United States)

Sunita, S; Schwartz, Samantha L; Conn, Graeme L

2015-11-20

Double-stranded RNA (dsRNA)-activated protein kinase (PKR) is an important component of the innate immune system that presents a crucial first line of defense against viral infection. PKR has a modular architecture comprising a regulatory N-terminal dsRNA binding domain and a C-terminal kinase domain interposed by an unstructured ∼80-residue interdomain linker (IDL). Guided by sequence alignment, we created IDL deletions in human PKR (hPKR) and regulatory/kinase domain swap human-rat chimeric PKRs to assess the contributions of each domain and the IDL to regulation of the kinase activity by RNA. Using circular dichroism spectroscopy, limited proteolysis, kinase assays, and isothermal titration calorimetry, we show that each PKR protein is properly folded with similar domain boundaries and that each exhibits comparable polyinosinic-cytidylic (poly(rI:rC)) dsRNA activation profiles and binding affinities for adenoviral virus-associated RNA I (VA RNAI) and HIV-1 trans-activation response (TAR) RNA. From these results we conclude that the IDL of PKR is not required for RNA binding or mediating changes in protein conformation or domain interactions necessary for PKR regulation by RNA. In contrast, inhibition of rat PKR by VA RNAI and TAR RNA was found to be weaker than for hPKR by 7- and >300-fold, respectively, and each human-rat chimeric domain-swapped protein showed intermediate levels of inhibition. These findings indicate that PKR sequence or structural elements in the kinase domain, present in hPKR but absent in rat PKR, are exploited by viral non-coding RNAs to accomplish efficient inhibition of PKR. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

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

Science.gov (United States)

Keyamura, Kenji; Katayama, Tsutomu

2011-08-19

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

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

Science.gov (United States)

Keyamura, Kenji; Katayama, Tsutomu

2011-01-01

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

Solution structure and dynamics of C-terminal regulatory domain of Vibrio vulnificus extracellular metalloprotease

Energy Technology Data Exchange (ETDEWEB)

Yun, Ji-Hye; Kim, Heeyoun [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Park, Jung Eun [Department of Biotechnology, College of Natural Sciences, Chosun University, Gwangju 501-759 (Korea, Republic of); Lee, Jung Sup, E-mail: jsplee@mail.chosun.ac.kr [Department of Biotechnology, College of Natural Sciences, Chosun University, Gwangju 501-759 (Korea, Republic of); Lee, Weontae, E-mail: wlee@spin.yonsei.ac.kr [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)

2013-01-11

Highlights: Black-Right-Pointing-Pointer We have determined solution structures of vEP C-terminal regulatory domain. Black-Right-Pointing-Pointer vEP C-ter100 has a compact {beta}-barrel structure with eight anti-parallel {beta}-strands. Black-Right-Pointing-Pointer Solution structure of vEP C-ter100 shares its molecular topology with that of the collagen-binding domain of collagenase. Black-Right-Pointing-Pointer Residues in the {beta}3 region of vEP C-ter100 might be important in putative ligand/receptor binding. Black-Right-Pointing-Pointer vEP C-ter100 interacts strongly with iron ion. -- Abstract: An extracellular metalloprotease (vEP) secreted by Vibrio vulnificus ATCC29307 is a 45-kDa proteolytic enzyme that has prothrombin activation and fibrinolytic activities during bacterial infection. The action of vEP could result in clotting that could serve to protect the bacteria from the host defense machinery. Very recently, we showed that the C-terminal propeptide (C-ter100), which is unique to vEP, is involved in regulation of vEP activity. To understand the structural basis of this function of vEP C-ter100, we have determined the solution structure and backbone dynamics using multidimensional nuclear magnetic resonance spectroscopy. The solution structure shows that vEP C-ter100 is composed of eight anti-parallel {beta}-strands with a unique fold that has a compact {beta}-barrel formation which stabilized by hydrophobic and hydrogen bonding networks. Protein dynamics shows that the overall structure, including loops, is very rigid and stabilized. By structural database analysis, we found that vEP C-ter100 shares its topology with that of the collagen-binding domain of collagenase, despite low sequence homology between the two domains. Fluorescence assay reveals that vEP C-ter100 interacts strongly with iron (Fe{sup 3+}). These findings suggest that vEP protease might recruit substrate molecules, such as collagen, by binding at C-ter100 and that vEP participates

Defining Tobacco Regulatory Science Competencies.

Science.gov (United States)

Wipfli, Heather L; Berman, Micah; Hanson, Kacey; Kelder, Steven; Solis, Amy; Villanti, Andrea C; Ribeiro, Carla M P; Meissner, Helen I; Anderson, Roger

2017-02-01

In 2013, the National Institutes of Health and the Food and Drug Administration funded a network of 14 Tobacco Centers of Regulatory Science (TCORS) with a mission that included research and training. A cross-TCORS Panel was established to define tobacco regulatory science (TRS) competencies to help harmonize and guide their emerging educational programs. The purpose of this paper is to describe the Panel's work to develop core TRS domains and competencies. The Panel developed the list of domains and competencies using a semistructured Delphi method divided into four phases occurring between November 2013 and August 2015. The final proposed list included a total of 51 competencies across six core domains and 28 competencies across five specialized domains. There is a need for continued discussion to establish the utility of the proposed set of competencies for emerging TRS curricula and to identify the best strategies for incorporating these competencies into TRS training programs. Given the field's broad multidisciplinary nature, further experience is needed to refine the core domains that should be covered in TRS training programs versus knowledge obtained in more specialized programs. Regulatory science to inform the regulation of tobacco products is an emerging field. The paper provides an initial list of core and specialized domains and competencies to be used in developing curricula for new and emerging training programs aimed at preparing a new cohort of scientists to conduct critical TRS research. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Negative regulation of retrovirus expression in embryonal carcinoma cells mediated by an intragenic domain.

Science.gov (United States)

Loh, T P; Sievert, L L; Scott, R W

1988-11-01

An intragenic region spanning the tRNA primer binding site of a Moloney murine leukemia virus recombinant retrovirus was found to restrict expression specifically in embryonal carcinoma (EC) cells. When the inhibitory domain was present, the levels of steady-state RNA synthesized from integrated recombinant templates in stable cotransformation assays were reduced 20-fold in EC cells but not in C2 myoblast cells. Transient-cotransfection assays showed that repression of a template containing the EC-specific inhibitory component was relieved by an excess of specific competitor DNA. In addition, repression mediated by the inhibitory component was orientation independent. This evidence demonstrates the presence of a saturable, trans-acting negative regulatory factor(s) in EC cells and suggests that the interaction of the factor(s) with the intragenic inhibitory component occurs at the DNA level.

Structure-borne low-frequency noise from multi-span bridges: A prediction method and spatial distribution

Science.gov (United States)

Song, X. D.; Wu, D. J.; Li, Q.; Botteldooren, D.

2016-04-01

Structure-borne noise from railway bridges at far-field points is an important indicator in environmental noise assessment. However, studies that predict structure-borne noise tend to model only single-span bridges, thus ignoring the sound pressure radiating from adjacent spans. To simulate the noise radiating from multi-span bridges induced by moving vehicles, the vibrations of a multi-span bridge are first obtained from a three-dimensional (3D) vehicle-track-bridge dynamic interaction simulation using the mode superposition method. A procedure based on the 2.5-dimensional (2.5D) boundary element method (BEM) is then presented to promote the efficiency of acoustical computation compared with the 3D BEM. The simulated results obtained from both the single-span and multi-span bridge models are compared with the measured results. The sound predictions calculated from the single-span model are accurate only for a minority of near-field points. In contrast, the sound pressures calculated from the multi-span bridge model match the measured results in both the time and frequency domains for all of the near-field and far-field points. The number of bridge spans required in the noise simulation is then recommended related to the distance between the track center and the field points of interest. The spatial distribution of multi-span structure-borne noise is also studied. The variation in sound pressure levels is insignificant along the length of the bridge, which validates the finding that the sound test section can be selected at an arbitrary plane perpendicular to the multi-span bridge.

Span of control matters.

Science.gov (United States)

Cathcart, Deb; Jeska, Susan; Karnas, Joan; Miller, Sue E; Pechacek, Judy; Rheault, Lolita

2004-09-01

Prompted by manager concerns about span of control, a large, integrated health system set out to determine if span of control really mattered. Was there something to it, or was it just an excuse for poor performance? A team of middle managers studied the problem and ultimately demonstrated a strong relationship between span of control and employee engagement. Consequently, it was decided to add 4 management positions to note the effect. One year later, positive changes were observed in employee engagement scores in all 4 areas. This study suggests careful review of manager spans of control to address the untoward effects of large spans of control on employee engagement.

Are Some Technologies Beyond Regulatory Regimes?

Energy Technology Data Exchange (ETDEWEB)

Jones, Wendell B. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Kusnezov, Dimitri [National Nuclear Security Administration (NNSA), Washington, DC (United States)

2017-08-01

Regulatory frameworks are a common tool in governance to incent and coerce behaviors supporting national or strategic stability. This includes domestic regulations and international agreements. Though regulation is always a challenge, the domain of fast evolving threats, like cyber, are proving much more difficult to control. Many discussions are underway searching for approaches that can provide national security in these domains. We use game theoretic learning models to explore the question of strategic stability with respect to the democratization of certain technologies (such as cyber). We suggest that such many-player games could inherently be chaotic with no corresponding (Nash) equilibria. In the absence of such equilibria, traditional approaches, as measures to achieve levels of overall security, may not be suitable approaches to support strategic stability in these domains. Altogether new paradigms may be needed for these issues. At the very least, regulatory regimes that fail to address the basic nature of the technology domains should not be pursued as a default solution, regardless of success in other domains. In addition, the very chaotic nature of these domains may hold the promise of novel approaches to regulation.

Regulatory domain selectivity in the cell-type specific PKN-dependence of cell migration.

Directory of Open Access Journals (Sweden)

Sylvie Lachmann

Full Text Available The mammalian protein kinase N (PKN family of Serine/Threonine kinases comprises three isoforms, which are targets for Rho family GTPases. Small GTPases are major regulators of the cellular cytoskeleton, generating interest in the role(s of specific PKN isoforms in processes such as cell migration and invasion. It has been reported that PKN3 is required for prostate tumour cell invasion but not PKN1 or 2. Here we employ a cell model, the 5637 bladder tumour cell line where PKN2 is relatively highly expressed, to assess the potential redundancy of these isoforms in migratory responses. It is established that PKN2 has a critical role in the migration and invasion of these cells. Furthermore, using a PKN wild-type and chimera rescue strategy, it is shown that PKN isoforms are not simply redundant in supporting migration, but appear to be linked through isoform specific regulatory domain properties to selective upstream signals. It is concluded that intervention in PKNs may need to be directed at multiple isoforms to be effective in different cell types.

Regulatory domain selectivity in the cell-type specific PKN-dependence of cell migration.

Science.gov (United States)

Lachmann, Sylvie; Jevons, Amy; De Rycker, Manu; Casamassima, Adele; Radtke, Simone; Collazos, Alejandra; Parker, Peter J

2011-01-01

The mammalian protein kinase N (PKN) family of Serine/Threonine kinases comprises three isoforms, which are targets for Rho family GTPases. Small GTPases are major regulators of the cellular cytoskeleton, generating interest in the role(s) of specific PKN isoforms in processes such as cell migration and invasion. It has been reported that PKN3 is required for prostate tumour cell invasion but not PKN1 or 2. Here we employ a cell model, the 5637 bladder tumour cell line where PKN2 is relatively highly expressed, to assess the potential redundancy of these isoforms in migratory responses. It is established that PKN2 has a critical role in the migration and invasion of these cells. Furthermore, using a PKN wild-type and chimera rescue strategy, it is shown that PKN isoforms are not simply redundant in supporting migration, but appear to be linked through isoform specific regulatory domain properties to selective upstream signals. It is concluded that intervention in PKNs may need to be directed at multiple isoforms to be effective in different cell types.

Executive function and attention span in euthymic patients with bipolar 1 disorder.

Science.gov (United States)

Normala, I; Abdul, Hamid A R; Azlin, B; Nik Ruzyanei, N J; Hazli, Z; Shah, S A

2010-09-01

This is a cross sectional comparison study to assess executive function and attention span in euthymic patients with bipolar 1 disorder. It compares the performance of these two cognitive domains in 40 patients with bipolar 1 disorder to that of 40 healthy normal subjects using Trail Making (TMT), Digit Span (Forward and Backward) and Verbal Fluency (VF) tests. The association between demographic, clinical characteristics and performance in all tests were examined. Patients with bipolar illness showed significant impairment with moderate to large effect sizes (VF = 0.67, TMT A = 0.52, TMT B = 0.81, Digit Forward = 0.97, Digit backward = 1.10) in all tasks of executive and attention functioning. These impairments are observed in the absence of active mood symptoms while duration and severity of illness are not found to have an effect on both cognitive domains. Medications received by patients with bipolar disorder have significant association with performance on executive tasks. The results of this study add on to the existing global evidence of cognitive impairment in bipolar illness despite its cross cultural differences. Its presence in the absence of mania, depression or mixed episode indicates that cognitive impairment is stable even after symptoms recovery.

Damping-controlled fluidelastic instability forces in multi-span tubes with loose supports

International Nuclear Information System (INIS)

Hassan, Marwan A.; Rogers, Robert J.; Gerber, Andrew G.

2011-01-01

This paper presents simulations of a loosely supported multi-span tube subjected to turbulence and fluidelastic instability forces in order to compare several time-domain fluid force models simulating the damping-controlled fluidelastic instability mechanism in tube arrays. These models include the negative damping model based on the Connors equation, fluid force coefficient-based models (Chen; Tanaka and Takahara), and two semi-analytical models (Price and Paidoussis; and Lever and Weaver). Time domain modelling challenges for each of these theories are discussed. The implemented models are validated against available experimental data. The linear simulations (without tube/support clearance) show that the Connors-equation based model exhibits the most conservative prediction of the critical flow velocity when the recommended design values for the Connors equation are used. The models are then utilized to simulate the nonlinear response of a three-span cantilever tube in a lattice bar support subjected to air crossflow. The tube is subjected to a single-phase flow passing over the spans where the flow velocity and the support clearance are varied. Special attention is paid to the tube/support interaction parameters that affect wear, such as impact forces, contact ratio, and normal work rate. As was seen for the linear cases, the reduced flow velocity at the instability threshold differs for the fluid force models considered. The investigated models do, however, exhibit similar response characteristics for the impact force, tip lift response, and work rate, except for the Connors-based model that overestimates the response and the tube/support interaction parameters for the loose support case, especially at large clearances.

Working memory span in mild cognitive impairment. Influence of processing speed and cognitive reserve.

Science.gov (United States)

Facal, David; Juncos-Rabadán, Onésimo; Pereiro, Arturo X; Lojo-Seoane, Cristina

2014-04-01

Mild cognitive impairment (MCI) often includes episodic memory impairment, but can also involve other types of cognitive decline. Although previous studies have shown poorer performance of MCI patients in working memory (WM) span tasks, different MCI subgroups were not studied. In the present exploratory study, 145 participants underwent extensive cognitive evaluation, which included three different WM span tasks, and were classified into the following groups: multiple-domain amnestic MCI (mda-MCI), single-domain amnestic MCI (sda-MCI), and controls. General linear model was conducted by considering the WM span tasks as the within-subject factor; the group (mda-MCI, sda-MCI, and controls) as the inter-subject factor; and processing speed, vocabulary and age as covariates. Multiple linear regression models were also used to test the influence of processing speed, vocabulary, and other cognitive reserve (CR) proxies. Results indicate different levels of impairment of WM, with more severe impairment in mda-MCI patients. The differences were still present when processing resources and CR were controlled. Between-group differences can be understood as a manifestation of the greater severity and widespread memory impairment in mda-MCI patients and may contribute to a better understanding of continuum from normal controls to mda-MCI patients. Processing speed and CR have a limited influence on WM scores, reducing but not removing differences between groups.

Boundary Spanning

DEFF Research Database (Denmark)

Zølner, Mette

The paper explores how locals span boundaries between corporate and local levels. The aim is to better comprehend potentialities and challenges when MNCs draws on locals’ culture specific knowledge. The study is based on an in-depth, interpretive case study of boundary spanning by local actors in...... approach with pattern matching is a way to shed light on the tacit local knowledge that organizational actors cannot articulate and that an exclusively inductive research is not likely to unveil....

The effect of span length and girder type on bridge costs

Directory of Open Access Journals (Sweden)

Batikha Mustafa

2017-01-01

Full Text Available Bridges have an important role in impacting the civilization, growth and economy of cities from ancient time until these days due to their function in reducing transportation cost and time. Therefore, development of bridges has been a knowledge domain in civil engineering studies in terms of their types and construction materials to confirm a reliable, safe, economic design and construction. Girder-bridge of concrete deck and I-beam girder has been used widely for short and medium span bridges because of ease and low-cost of fabrication. However, many theoretical and practical investigations are still undertaken regarding the type of beam girder; i.e steel composite or prestressed concrete. This paper evaluates the effect of bridge span and the type of girder on the capital cost and life cycle costs of bridges. Three types of girders were investigated in this research: steel composite, pre-tensioned pre-stressed concrete and post-tensioned pre-stressed concrete. The structural design was analyzed for 5 span lengths: 20, 25, 30, 35 and 40m. Then, the capital construction cost was accounted for 15 bridges according to each span and construction materials. Moreover, the maintenance required for 50 years of bridge life was evaluated and built up as whole life costs for each bridge. As a result of this study, the influence of both span length and type of girder on initial construction cost and maintenance whole life costs were assessed to support the decision makers and designers in the selection process for the optimum solution of girder bridges.

Long Span Bridges in Scandinavia

DEFF Research Database (Denmark)

Gimsing, Niels Jørgen

1998-01-01

The first Scandinavian bridge with a span of more than 500 m was the Lillebælt Suspension Bridge opened to traffic in 1970.Art the end of the 20th century the longest span of any European bridge is found in the Storebælt East Bridge with a main span of 1624 m. Also the third longest span in Europe...... is found in Scandinavia - the 1210 m span of the Höga Kusten Bridge in Sweden.The Kvarnsund Bridge in Norway was at the completion in 1991 the longest cable-stayed bridge in the world, and the span of 530 m is still thge longest for cable-stayed bridges in concrete. The Øresund Bridge with its sapn of 490...

A saturation screen for cis-acting regulatory DNA in the Hox genes of Ciona intestinalis

Energy Technology Data Exchange (ETDEWEB)

Keys, David N.; Lee, Byung-in; Di Gregorio, Anna; Harafuji, Naoe; Detter, Chris; Wang, Mei; Kahsai, Orsalem; Ahn, Sylvia; Arellano, Andre; Zhang, Quin; Trong, Stephan; Doyle, Sharon A.; Satoh, Noriyuki; Satou, Yutaka; Saiga, Hidetoshi; Christian, Allen; Rokhsar, Dan; Hawkins, Trevor L.; Levine, Mike; Richardson, Paul

2005-01-05

A screen for the systematic identification of cis-regulatory elements within large (>100 kb) genomic domains containing Hox genes was performed by using the basal chordate Ciona intestinalis. Randomly generated DNA fragments from bacterial artificial chromosomes containing two clusters of Hox genes were inserted into a vector upstream of a minimal promoter and lacZ reporter gene. A total of 222 resultant fusion genes were separately electroporated into fertilized eggs, and their regulatory activities were monitored in larvae. In sum, 21 separable cis-regulatory elements were found. These include eight Hox linked domains that drive expression in nested anterior-posterior domains of ectodermally derived tissues. In addition to vertebrate-like CNS regulation, the discovery of cis-regulatory domains that drive epidermal transcription suggests that C. intestinalis has arthropod-like Hox patterning in the epidermis.

SH3 domain tyrosine phosphorylation--sites, role and evolution.

Directory of Open Access Journals (Sweden)

Zuzana Tatárová

Full Text Available BACKGROUND: SH3 domains are eukaryotic protein domains that participate in a plethora of cellular processes including signal transduction, proliferation, and cellular movement. Several studies indicate that tyrosine phosphorylation could play a significant role in the regulation of SH3 domains. RESULTS: To explore the incidence of the tyrosine phosphorylation within SH3 domains we queried the PhosphoSite Plus database of phosphorylation sites. Over 100 tyrosine phosphorylations occurring on 20 different SH3 domain positions were identified. The tyrosine corresponding to c-Src Tyr-90 was by far the most frequently identified SH3 domain phosphorylation site. A comparison of sequences around this tyrosine led to delineation of a preferred sequence motif ALYD(Y/F. This motif is present in about 15% of human SH3 domains and is structurally well conserved. We further observed that tyrosine phosphorylation is more abundant than serine or threonine phosphorylation within SH3 domains and other adaptor domains, such as SH2 or WW domains. Tyrosine phosphorylation could represent an important regulatory mechanism of adaptor domains. CONCLUSIONS: While tyrosine phosphorylation typically promotes signaling protein interactions via SH2 or PTB domains, its role in SH3 domains is the opposite - it blocks or prevents interactions. The regulatory function of tyrosine phosphorylation is most likely achieved by the phosphate moiety and its charge interfering with binding of polyproline helices of SH3 domain interacting partners.

Advance features in the SPAN and SPAN/XRF gamma ray and X ray spectrum analysis software

International Nuclear Information System (INIS)

Wang Liyu

1998-01-01

This paper describes the advanced techniques, integral peak background, experimental peak shape and complex peak shape, which have been used successfully in the software packages SPAN and SPAN/XRF to process gamma ray and X ray spectra from HPGe and Si(Li) detector. Main features of SPAN and SPAN/XRF are also described. The software runs on PC and has convenient graphical capabilities and a powerful user interface. (author)

Chemical Shift Assignments of the C-terminal Eps15 Homology Domain-3 EH Domain*

Science.gov (United States)

Caplan, Steve; Sorgen, Paul L.

2013-01-01

The C-terminal Eps15 homology (EH) domain 3 (EHD3) belongs to a eukaryotic family of endocytic regulatory proteins and is involved in the recycling of various receptors from the early endosome to the endocytic recycling compartment or in retrograde transport from the endosomes to the Golgi. EH domains are highly conserved in the EHD family and function as protein-protein interaction units that bind to Asn-Pro-Phe (NPF) motif-containing proteins. The EH domain of EHD1 was the first C-terminal EH domain from the EHD family to be solved by NMR. The differences observed between this domain and proteins with N-terminal EH domains helped describe a mechanism for the differential binding of NPF-containing proteins. Here, structural studies were expanded to include the EHD3 EH domain. While the EHD1 and EHD3 EH domains are highly homologous, they have different protein partners. A comparison of these structures will help determine the selectivity in protein binding between the EHD family members and lead to a better understanding of their unique roles in endocytic regulation. PMID:23754701

Molecular dissection of the C-terminal regulatory domain of the plant plasma membrane H+-ATPase AHA2: Mapping of residues that when altered give rise to an activated enzyme

DEFF Research Database (Denmark)

Axelsen, K.B.; Venema, K.; Jah, T.

1999-01-01

in an extension of the C-terminus unique to plant H+-ATPases, Alteration of residues in both regions led to increased binding of yeast 14-3-3 protein to the plasma membrane of transformed cells. Taken together, our data suggest that modification of residues in two regions of the C-terminal regulatory domain......The plasma membrane H+-ATPase is a proton pump belonging to the P-type ATPase superfamily and is important for nutrient acquisition in plants, The H+-ATPase is controlled by an autoinhibitory C-terminal regulatory domain and is activated by 14-3-3 proteins which bind to this part of the enzyme......+-ATPase. The enzymes were characterized by their ability to promote growth in acidic conditions and to promote H+ extrusion from intact cells, both of which are measures of plasma membrane H+-ATPase activity, and were also characterized with respect to kinetic properties such as affinity for H+ and ATP. Residues...

Dynamically Coupled Residues within the SH2 Domain of FYN Are Key to Unlocking Its Activity

NARCIS (Netherlands)

Huculeci, Radu; Cilia, Elisa; Lyczek, Agatha; Buts, Lieven; Houben, Klaartje; Seeliger, Markus A; van Nuland, Nico; Lenaerts, Tom

2016-01-01

Src kinase activity is controlled by various mechanisms involving a coordinated movement of kinase and regulatory domains. Notwithstanding the extensive knowledge related to the backbone dynamics, little is known about the more subtle side-chain dynamics within the regulatory domains and their role

KEJAHATAN NAMA DOMAIN BERKAITAN DENGAN MEREK

Directory of Open Access Journals (Sweden)

Muhammad Nizar

2018-02-01

Full Text Available Indonesia already has an ITE Law governing domain names in general terms and on certain provisions in chapter VI, but the regulation of domain name crimes is not regulated in the ITE Law as mandated in the academic draft of the ITE Bill. The absence of regulation of domain name norm in the ITE Law creates problems with registrant of domain name (registrant which deliberately register the domain name is bad faith. The characteristic of a crime in a domain name relating to the mark is that the registered domain name has an equation in essence with another party’s well-known brand, the act of doing so by exploiting a reputation for well-known or previously commercially valuable names as domain names for addresses for sites (websites it manages. The Prosecutor may include articles of the KUHP in filing his indictment before the Court during the absence of special regulatory provisions concerning domain name crime.

Determinantal spanning forests on planar graphs

OpenAIRE

Kenyon, Richard

2017-01-01

We generalize the uniform spanning tree to construct a family of determinantal measures on essential spanning forests on periodic planar graphs in which every component tree is bi-infinite. Like the uniform spanning tree, these measures arise naturally from the laplacian on the graph. More generally these results hold for the "massive" laplacian determinant which counts rooted spanning forests with weight $M$ per finite component. These measures typically have a form of conformal invariance, ...

Same but not alike: Structure, flexibility and energetics of domains in multi-domain proteins are influenced by the presence of other domains.

Science.gov (United States)

Vishwanath, Sneha; de Brevern, Alexandre G; Srinivasan, Narayanaswamy

2018-02-01

The majority of the proteins encoded in the genomes of eukaryotes contain more than one domain. Reasons for high prevalence of multi-domain proteins in various organisms have been attributed to higher stability and functional and folding advantages over single-domain proteins. Despite these advantages, many proteins are composed of only one domain while their homologous domains are part of multi-domain proteins. In the study presented here, differences in the properties of protein domains in single-domain and multi-domain systems and their influence on functions are discussed. We studied 20 pairs of identical protein domains, which were crystallized in two forms (a) tethered to other proteins domains and (b) tethered to fewer protein domains than (a) or not tethered to any protein domain. Results suggest that tethering of domains in multi-domain proteins influences the structural, dynamic and energetic properties of the constituent protein domains. 50% of the protein domain pairs show significant structural deviations while 90% of the protein domain pairs show differences in dynamics and 12% of the residues show differences in the energetics. To gain further insights on the influence of tethering on the function of the domains, 4 pairs of homologous protein domains, where one of them is a full-length single-domain protein and the other protein domain is a part of a multi-domain protein, were studied. Analyses showed that identical and structurally equivalent functional residues show differential dynamics in homologous protein domains; though comparable dynamics between in-silico generated chimera protein and multi-domain proteins were observed. From these observations, the differences observed in the functions of homologous proteins could be attributed to the presence of tethered domain. Overall, we conclude that tethered domains in multi-domain proteins not only provide stability or folding advantages but also influence pathways resulting in differences in

Thermodynamics and life span estimation

International Nuclear Information System (INIS)

Kuddusi, Lütfullah

2015-01-01

In this study, the life span of people living in seven regions of Turkey is estimated by applying the first and second laws of thermodynamics to the human body. The people living in different regions of Turkey have different food habits. The first and second laws of thermodynamics are used to calculate the entropy generation rate per unit mass of a human due to the food habits. The lifetime entropy generation per unit mass of a human was previously found statistically. The two entropy generations, lifetime entropy generation and entropy generation rate, enable one to determine the life span of people living in seven regions of Turkey with different food habits. In order to estimate the life span, some statistics of Turkish Statistical Institute regarding the food habits of the people living in seven regions of Turkey are used. The life spans of people that live in Central Anatolia and Eastern Anatolia regions are the longest and shortest, respectively. Generally, the following inequality regarding the life span of people living in seven regions of Turkey is found: Eastern Anatolia < Southeast Anatolia < Black Sea < Mediterranean < Marmara < Aegean < Central Anatolia. - Highlights: • The first and second laws of thermodynamics are applied to the human body. • The entropy generation of a human due to his food habits is determined. • The life span of Turks is estimated by using the entropy generation method. • Food habits of a human have effect on his life span

Reading Ability and Memory Span: Long-Term Memory Contributions to Span for Good and Poor Readers.

Science.gov (United States)

McDougall, Sine J. P.; Donohoe, Rachael

2002-01-01

Investigates the extent to which differences in memory span for good and poor readers can be explained by differences in a long-term memory component to span as well as by differences in short-term memory processes. Discusses the nature of the interrelationships between memory span, reading and measures of phonological awareness. (SG)

Crystallization and preliminary crystallographic characterization of the PAS domains of EAG and ELK potassium channels

International Nuclear Information System (INIS)

Adaixo, Ricardo; Morais-Cabral, João Henrique

2010-01-01

The N-terminal PAS domains from the eukaryotic EAG potassium channels are thought to have a regulatory function. Here the expression, purification, crystallization and preliminary crystallographic characterization of two of these domains are described. Per–Arnt–Sim (PAS) domains are ubiquitous in nature; they are ∼130-amino-acid protein domains that adopt a fairly conserved three-dimensional structure despite their low degree of sequence homology. These domains constitute the N-terminus or, less frequently, the C-terminus of a number of proteins, where they exert regulatory functions. PAS-containing proteins generally display two or more copies of this motif. In this work, the crystallization and preliminary analysis of the PAS domains of two eukaryotic potassium channels from the ether-à-go-go (EAG) family are reported

Sensitivity analysis for missing data in regulatory submissions.

Science.gov (United States)

Permutt, Thomas

2016-07-30

The National Research Council Panel on Handling Missing Data in Clinical Trials recommended that sensitivity analyses have to be part of the primary reporting of findings from clinical trials. Their specific recommendations, however, seem not to have been taken up rapidly by sponsors of regulatory submissions. The NRC report's detailed suggestions are along rather different lines than what has been called sensitivity analysis in the regulatory setting up to now. Furthermore, the role of sensitivity analysis in regulatory decision-making, although discussed briefly in the NRC report, remains unclear. This paper will examine previous ideas of sensitivity analysis with a view to explaining how the NRC panel's recommendations are different and possibly better suited to coping with present problems of missing data in the regulatory setting. It will also discuss, in more detail than the NRC report, the relevance of sensitivity analysis to decision-making, both for applicants and for regulators. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Domain architecture conservation in orthologs

Science.gov (United States)

2011-01-01

Background As orthologous proteins are expected to retain function more often than other homologs, they are often used for functional annotation transfer between species. However, ortholog identification methods do not take into account changes in domain architecture, which are likely to modify a protein's function. By domain architecture we refer to the sequential arrangement of domains along a protein sequence. To assess the level of domain architecture conservation among orthologs, we carried out a large-scale study of such events between human and 40 other species spanning the entire evolutionary range. We designed a score to measure domain architecture similarity and used it to analyze differences in domain architecture conservation between orthologs and paralogs relative to the conservation of primary sequence. We also statistically characterized the extents of different types of domain swapping events across pairs of orthologs and paralogs. Results The analysis shows that orthologs exhibit greater domain architecture conservation than paralogous homologs, even when differences in average sequence divergence are compensated for, for homologs that have diverged beyond a certain threshold. We interpret this as an indication of a stronger selective pressure on orthologs than paralogs to retain the domain architecture required for the proteins to perform a specific function. In general, orthologs as well as the closest paralogous homologs have very similar domain architectures, even at large evolutionary separation. The most common domain architecture changes observed in both ortholog and paralog pairs involved insertion/deletion of new domains, while domain shuffling and segment duplication/deletion were very infrequent. Conclusions On the whole, our results support the hypothesis that function conservation between orthologs demands higher domain architecture conservation than other types of homologs, relative to primary sequence conservation. This supports the

Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control.

Science.gov (United States)

Carroni, Marta; Franke, Kamila B; Maurer, Michael; Jäger, Jasmin; Hantke, Ingo; Gloge, Felix; Linder, Daniela; Gremer, Sebastian; Turgay, Kürşad; Bukau, Bernd; Mogk, Axel

2017-11-22

Ring-forming AAA+ chaperones exert ATP-fueled substrate unfolding by threading through a central pore. This activity is potentially harmful requiring mechanisms for tight repression and substrate-specific activation. The AAA+ chaperone ClpC with the peptidase ClpP forms a bacterial protease essential to virulence and stress resistance. The adaptor MecA activates ClpC by targeting substrates and stimulating ClpC ATPase activity. We show how ClpC is repressed in its ground state by determining ClpC cryo-EM structures with and without MecA. ClpC forms large two-helical assemblies that associate via head-to-head contacts between coiled-coil middle domains (MDs). MecA converts this resting state to an active planar ring structure by binding to MD interaction sites. Loss of ClpC repression in MD mutants causes constitutive activation and severe cellular toxicity. These findings unravel an unexpected regulatory concept executed by coiled-coil MDs to tightly control AAA+ chaperone activity.

Working memory and inhibitory control across the life span: Intrusion errors in the Reading Span Test.

Science.gov (United States)

Robert, Christelle; Borella, Erika; Fagot, Delphine; Lecerf, Thierry; de Ribaupierre, Anik

2009-04-01

The aim of this study was to examine to what extent inhibitory control and working memory capacity are related across the life span. Intrusion errors committed by children and younger and older adults were investigated in two versions of the Reading Span Test. In Experiment 1, a mixed Reading Span Test with items of various list lengths was administered. Older adults and children recalled fewer correct words and produced more intrusions than did young adults. Also, age-related differences were found in the type of intrusions committed. In Experiment 2, an adaptive Reading Span Test was administered, in which the list length of items was adapted to each individual's working memory capacity. Age groups differed neither on correct recall nor on the rate of intrusions, but they differed on the type of intrusions. Altogether, these findings indicate that the availability of attentional resources influences the efficiency of inhibition across the life span.

Life Span Developmental Approach

OpenAIRE

Ali Eryilmaz

2011-01-01

The Life Span Developmental Approach examines development of individuals which occurs from birth to death. Life span developmental approach is a multi-disciplinary approach related with disciplines like psychology, psychiatry, sociology, anthropology and geriatrics that indicates the fact that development is not completed in adulthood, it continues during the life course. Development is a complex process that consists of dying and death. This approach carefully investigates the development of...

Feast/famine regulatory proteins (FFRPs): Escherichia coli Lrp, AsnC and related archaeal transcription factors.

Science.gov (United States)

Yokoyama, Katsushi; Ishijima, Sanae A; Clowney, Lester; Koike, Hideaki; Aramaki, Hironori; Tanaka, Chikako; Makino, Kozo; Suzuki, Masashi

2006-01-01

Feast/famine regulatory proteins comprise a diverse family of transcription factors, which have been referred to in various individual identifications, including Escherichia coli leucine-responsive regulatory protein and asparagine synthase C gene product. A full length feast/famine regulatory protein consists of the N-terminal DNA-binding domain and the C-domain, which is involved in dimerization and further assembly, thereby producing, for example, a disc or a chromatin-like cylinder. Various ligands of the size of amino acids bind at the interface between feast/famine regulatory protein dimers, thereby altering their assembly forms. Also, the combination of feast/famine regulatory protein subunits forming the same assembly is altered. In this way, a small number of feast/famine regulatory proteins are able to regulate a large number of genes in response to various environmental changes. Because feast/famine regulatory proteins are shared by archaea and eubacteria, the genome-wide regulation by feast/famine regulatory proteins is traceable back to their common ancestor, being the prototype of highly differentiated transcription regulatory mechanisms found in organisms nowadays.

Transition from many domain to single domain martensite morphology in small-scale shape memory alloys

International Nuclear Information System (INIS)

Ueland, Stian M.; Schuh, Christopher A.

2013-01-01

The morphology of the martensitic transformation during a superelastic cycle is studied by in situ scanning electron microscopy deformation experiments in microwires of Cu–Zn–Al. The diameters of the wires studied (21–136 μm) span the range in which significant size effects upon transformation hysteresis have been observed. In larger wires the transformation is accommodated by the continual nucleation of many new martensite plates that grow and eventually coalesce with their neighbors. In small wires a single martensite plate nucleates at the start of transformation and then proceeds to grow in a monolithic fashion; the wire transforms by smooth axial propagation of a single interface. The transition from many domain to single domain transformation is gradual with wire diameter, and is based upon scaling of the domain density with sample size. We attribute it to a crossover from bulk to surface obstacle control of transformation front propagation. This observation also sheds light on reported size effects in energy dissipation in shape memory alloys

SPAN: A Network Providing Integrated, End-to-End, Sensor-to-Database Solutions for Environmental Sciences

Science.gov (United States)

Benzel, T.; Cho, Y. H.; Deschon, A.; Gullapalli, S.; Silva, F.

2009-12-01

In recent years, advances in sensor network technology have shown great promise to revolutionize environmental data collection. Still, wide spread adoption of these systems by domain experts has been lacking, and these have remained the purview of the engineers who design them. While there are many data logging options for basic data collection in the field currently, scientists are often required to visit the deployment sites to retrieve their data and manually import it into spreadsheets. Some advanced commercial software systems do allow scientists to collect data remotely, but most of these systems only allow point-to-point access, and require proprietary hardware. Furthermore, these commercial solutions preclude the use of sensors from other manufacturers or integration with internet based database repositories and compute engines. Therefore, scientists often must download and manually reformat their data before uploading it to the repositories if they wish to share their data. We present an open-source, low-cost, extensible, turnkey solution called Sensor Processing and Acquisition Network (SPAN) which provides a robust and flexible sensor network service. At the deployment site, SPAN leverages low-power generic embedded processors to integrate variety of commercially available sensor hardware to the network of environmental observation systems. By bringing intelligence close to the sensed phenomena, we can remotely control configuration and re-use, establish rules to trigger sensor activity, manage power requirements, and control the two-way flow of sensed data as well as control information to the sensors. Key features of our design include (1) adoption of a hardware agnostic architecture: our solutions are compatible with several programmable platforms, sensor systems, communication devices and protocols. (2) information standardization: our system supports several popular communication protocols and data formats, and (3) extensible data support: our

Age Differences in Memory Span

Science.gov (United States)

Chi, Michelene T. H.

1977-01-01

Three experiments were conducted to determine processes underlying age differences in the level of recall in a memory-span task. Five-year-olds recalled fewer items than adults in memory-span tasks involving both familiar and unfamiliar faces, even though the use of rehearsal and recoding strategies was minimized for adults. (MS)

The regulatory control of radioactive sources in Argentina

International Nuclear Information System (INIS)

Rojkind, Roberto Hector

1997-01-01

Argentina has been conducting nuclear activities for more than forty years, and as early as in 1956 established a Regulatory Authority. Procedures for compliance monitoring and enforcement have been in use in the regulatory control of radioactive sources, and regulatory standards and regulations had been set in Argentina, before the accident in Goiania. The conclusions drawn from that accident encouraged in Argentina the improvement of some regulatory procedures and helped to enhance the quality of the regulatory process. Therefore, the effectiveness of the control of spent radioactive sources has gradually increased, and enforcement actions to prevent radioactive sources ending up in the public domain improved. Some lessons learned in Argentina from the accident in Goiania and the main characteristics of an effective enforcement program helpful to prevent radiological accidents in industrial, medical, research and teaching uses of radioactive sources are presented. (author)

On the size of monotone span programs

NARCIS (Netherlands)

Nikov, V.S.; Nikova, S.I.; Preneel, B.; Blundo, C.; Cimato, S.

2005-01-01

Span programs provide a linear algebraic model of computation. Monotone span programs (MSP) correspond to linear secret sharing schemes. This paper studies the properties of monotone span programs related to their size. Using the results of van Dijk (connecting codes and MSPs) and a construction for

London SPAN version 4 parameter file format

International Nuclear Information System (INIS)

2004-06-01

Powernext SA is a Multilateral Trading Facility in charge of managing the French power exchange through an optional and anonymous organised trading system. Powernext SA collaborates with the clearing organization LCH.Clearnet SA to secure and facilitate the transactions. The French Standard Portfolio Analysis of Risk (SPAN) is a system used by LCH.Clearnet to calculate the initial margins from and for its clearing members. SPAN is a computerized system which calculates the impact of several possible variations of rates and volatility on by-product portfolios. The initial margin call is equal to the maximum probable loss calculated by the system. This document contains details of the format of the London SPAN version 4 parameter file. This file contains all the parameters and risk arrays required to calculate SPAN margins. London SPAN Version 4 is an upgrade from Version 3, which is also known as LME SPAN. This document contains the full revised file specification, highlighting the changes from Version 3 to Version 4

cDNA for the human β2-adrenergic receptor: a protein with multiple membrane-spanning domains and encoded by a gene whose chromosomal location is shared with that of the receptor for platelet-derived growth factor

International Nuclear Information System (INIS)

Kobilka, B.K.; Dixon, R.A.F.; Frielle, T.

1987-01-01

The authors have isolated and sequenced a cDNA encoding the human β 2 -adrenergic receptor. The deduced amino acid sequence (413 residues) is that of a protein containing seven clusters of hydrophobic amino acids suggestive of membrane-spanning domains. While the protein is 87% identical overall with the previously cloned hamster β 2 -adrenergic receptor, the most highly conserved regions are the putative transmembrane helices (95% identical) and cytoplasmic loops (93% identical), suggesting that these regions of the molecule harbor important functional domains. Several of the transmembrane helices also share lesser degrees of identity with comparable regions of select members of the opsin family of visual pigments. They have localized the gene for the β 2 -adrenergic receptor to q31-q32 on chromosome 5. This is the same position recently determined for the gene encoding the receptor for platelet-derived growth factor and is adjacent to that for the FMS protooncogene, which encodes the receptor for the macrophage colony-stimulating factor

Regulation of plant plasma membrane H+- and Ca2+-ATPases by terminal domains

DEFF Research Database (Denmark)

Bækgaard, Lone; Fuglsang, Anja Thoe; Palmgren, Michael Gjedde

2005-01-01

In the last few years, major progress has been made to elucidate the structure, function, and regulation of P-type plasma membrane H(+)-and Ca(2+)-ATPases. Even though a number of regulatory proteins have been identified, many pieces are still lacking in order to understand the complete regulatory...... mechanisms of these pumps. In plant plasma membrane H(+)- and Ca(2+)-ATPases, autoinhibitory domains are situated in the C- and N-terminal domains, respectively. A model for a common mechanism of autoinhibition is discussed....

Legal Challenges Related to the Regulation of a Domain Name System

Directory of Open Access Journals (Sweden)

Marius Kalinauskas

2012-12-01

Full Text Available Purpose—to review and analyse the problematic aspects related to domain name allocation and further usage processes, highlighting legal regulation of a domain name system.Design/methodology/approach—based on the comparison analysis of scientific literature, authors discuss problematic issues related to the legal regulation of domain name allocation and usage processes, analyse practical approaches and collision cases in the context of a domain name system. The authors examine the positive and negative aspects of a domain naming system and conflicting regulatory specifics. This paper describes the development of institutional bodies responsible for DNS management, supervision approaches and inner functionality policies.Findings—the authors examine domain naming system models and dispute resolution mechanisms, their evolution in the context of Internet development and the structural changes of the Internet governance institutions. The authors analyse tendencies related to DNS regulation and the possible effect of new regulation models in practice, while reflecting interests of stakeholders in the subject field.Research limitations/implications—agreements on the registration of domain names are based on self-regulation principles. A number of different interests may collide when speaking about domain name registration or usage and this issue becomes a major challenge to scientists and lawyers who are seeking an optimal domain-naming regulatory mechanism. The article does not address trademark conflicts within domain names in this respect. This should be considered as an object for separate study, which requires deeper analysis.Practical implications—the authors review key aspects of the domain name system and describe tendencies for the regulatory models.Value—the article emphasizes potential domain naming conflicts and disputes concerning the usage of common terms and phrases in order to manipulate information for illicit purposes. The

Legal Challenges Related to the Regulation of a Domain Name System

Directory of Open Access Journals (Sweden)

Marius Kalinauskas

2013-02-01

Full Text Available Purpose—to review and analyse the problematic aspects related to domain name allocation and further usage processes, highlighting legal regulation of a domain name system. Design/methodology/approach—based on the comparison analysis of scientific literature, authors discuss problematic issues related to the legal regulation of domain name allocation and usage processes, analyse practical approaches and collision cases in the context of a domain name system. The authors examine the positive and negative aspects of a domain naming system and conflicting regulatory specifics. This paper describes the development of institutional bodies responsible for DNS management, supervision approaches and inner functionality policies. Findings—the authors examine domain naming system models and dispute resolution mechanisms, their evolution in the context of Internet development and the structural changes of the Internet governance institutions. The authors analyse tendencies related to DNS regulation and the possible effect of new regulation models in practice, while reflecting interests of stakeholders in the subject field. Research limitations/implications—agreements on the registration of domain names are based on self-regulation principles. A number of different interests may collide when speaking about domain name registration or usage and this issue becomes a major challenge to scientists and lawyers who are seeking an optimal domain-naming regulatory mechanism. The article does not address trademark conflicts within domain names in this respect. This should be considered as an object for separate study, which requires deeper analysis. Practical implications—the authors review key aspects of the domain name system and describe tendencies for the regulatory models. Value—the article emphasizes potential domain naming conflicts and disputes concerning the usage of common terms and phrases in order to manipulate information for illicit purposes

A Comparative Assessment of Aerodynamic Models for Buffeting and Flutter of Long-Span Bridges

Directory of Open Access Journals (Sweden)

Igor Kavrakov

2017-12-01

Full Text Available Wind-induced vibrations commonly represent the leading criterion in the design of long-span bridges. The aerodynamic forces in bridge aerodynamics are mainly based on the quasi-steady and linear unsteady theory. This paper aims to investigate different formulations of self-excited and buffeting forces in the time domain by comparing the dynamic response of a multi-span cable-stayed bridge during the critical erection condition. The bridge is selected to represent a typical reference object with a bluff concrete box girder for large river crossings. The models are viewed from a perspective of model complexity, comparing the influence of the aerodynamic properties implied in the aerodynamic models, such as aerodynamic damping and stiffness, fluid memory in the buffeting and self-excited forces, aerodynamic nonlinearity, and aerodynamic coupling on the bridge response. The selected models are studied for a wind-speed range that is typical for the construction stage for two levels of turbulence intensity. Furthermore, a simplified method for the computation of buffeting forces including the aerodynamic admittance is presented, in which rational approximation is avoided. The critical flutter velocities are also compared for the selected models under laminar flow. Keywords: Buffeting, Flutter, Long-span bridges, Bridge aerodynamics, Bridge aeroelasticity, Erection stage

AKAP18:PKA-RIIα structure reveals crucial anchor points for recognition of regulatory subunits of PKA.

Science.gov (United States)

Götz, Frank; Roske, Yvette; Schulz, Maike Svenja; Autenrieth, Karolin; Bertinetti, Daniela; Faelber, Katja; Zühlke, Kerstin; Kreuchwig, Annika; Kennedy, Eileen J; Krause, Gerd; Daumke, Oliver; Herberg, Friedrich W; Heinemann, Udo; Klussmann, Enno

2016-07-01

A-kinase anchoring proteins (AKAPs) interact with the dimerization/docking (D/D) domains of regulatory subunits of the ubiquitous protein kinase A (PKA). AKAPs tether PKA to defined cellular compartments establishing distinct pools to increase the specificity of PKA signalling. Here, we elucidated the structure of an extended PKA-binding domain of AKAP18β bound to the D/D domain of the regulatory RIIα subunits of PKA. We identified three hydrophilic anchor points in AKAP18β outside the core PKA-binding domain, which mediate contacts with the D/D domain. Such anchor points are conserved within AKAPs that bind regulatory RII subunits of PKA. We derived a different set of anchor points in AKAPs binding regulatory RI subunits of PKA. In vitro and cell-based experiments confirm the relevance of these sites for the interaction of RII subunits with AKAP18 and of RI subunits with the RI-specific smAKAP. Thus we report a novel mechanism governing interactions of AKAPs with PKA. The sequence specificity of each AKAP around the anchor points and the requirement of these points for the tight binding of PKA allow the development of selective inhibitors to unequivocally ascribe cellular functions to the AKAP18-PKA and other AKAP-PKA interactions. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Regulatory control of physical protection systems

International Nuclear Information System (INIS)

Rajdeep; Mayya, Y.S.

2017-01-01

The safety of facilities in BARC is under the regulatory oversight of BSC. The security architecture for these facilities incorporates multiple layers of Physical Protection Systems. The demands of safety may sometimes conflict with the needs of security. Realizing the need to identify these interfaces and extend the regulatory coverage to Physical Protection Systems, a Standing Committee named Physical Protection System Review Committee (PPSRC) has been constituted as a 2"n"d tier entity of BSC. PPSRC includes experts from various domains concerned with nuclear security, viz. physical protection systems, cyber security, radiation safety, security operations, technical services and security administration

Comparison on the heat requirements of a four-span greenhouse with a melting snow system and a single-span greenhouse

International Nuclear Information System (INIS)

Furuno, S.; Sase, S.; Ishii, M.

2004-01-01

The heat requirements were measured and compared between a four-span greenhouse with a melting snow system and a typical single-span greenhouse with no melting snow system. Generally, single-span greenhouses require no melting snow system because snow drops off naturally from the roofs by gravity. The results for the four-span greenhouse showed that the provided heat by a heater for melting snow increased with an increase in snowfall, and there was a high correlation between them. The heat requirement per unit floor area of the four-span greenhouse was slightly less than that of the single-span greenhouse. This suggests that the decrease in heat requirement for internal air because of the larger floor/surface area ratio of the four-span greenhouse was more than the increase in heat requirement for melting snow. The measured heat requirement of the four-span greenhouse with the melting snow system was equal to the estimated heat load based on a common calculation procedure. On the other hand, that of the single-span greenhouse was slightly smaller than the estimated heat load. These suggest that the estimated heat load based on the common calculation procedure was slightly overestimated and larger than the actual heat requirement excluding the heat for the melting snow in snowy area. This is likely due to the fact that the parameters in the common calculation procedure were determined under the condition of larger net radiation than that in snowy area

High-performance analysis of single interphase cells with custom DNA probes spanning translocation break points

Science.gov (United States)

Weier, Heinz-Ulli G.; Munne, S.; Lersch, Robert A.; Marquez, C.; Wu, J.; Pedersen, Roger A.; Fung, Jingly

1999-06-01

The chromatin organization of interphase cell nuclei, albeit an object of intense investigation, is only poorly understood. In the past, this has hampered the cytogenetic analysis of tissues derived from specimens where only few cells were actively proliferating or a significant number of metaphase cells could be obtained by induction of growth. Typical examples of such hard to analyze cell systems are solid tumors, germ cells and, to a certain extent, fetal cells such as amniocytes, blastomeres or cytotrophoblasts. Balanced reciprocal translocations that do not disrupt essential genes and thus do not led to disease symptoms exit in less than one percent of the general population. Since the presence of translocations interferes with homologue pairing in meiosis, many of these individuals experience problems in their reproduction, such as reduced fertility, infertility or a history of spontaneous abortions. The majority of translocation carriers enrolled in our in vitro fertilization (IVF) programs carry simple translocations involving only two autosomes. While most translocations are relatively easy to spot in metaphase cells, the majority of cells biopsied from embryos produced by IVF are in interphase and thus unsuitable for analysis by chromosome banding or FISH-painting. We therefore set out to analyze single interphase cells for presence or absence of specific translocations. Our assay, based on fluorescence in situ hybridization (FISH) of breakpoint-spanning DNA probes, detects translocations in interphase by visual microscopic inspection of hybridization domains. Probes are prepared so that they span a breakpoint and cover several hundred kb of DNA adjacent to the breakpoint. On normal chromosomes, such probes label a contiguous stretch of DNA and produce a single hybridization domain per chromosome in interphase cells. The translocation disrupts the hybridization domain and the resulting two fragments appear as physically separated hybridization domains in

Linking crowding, visual span, and reading.

Science.gov (United States)

He, Yingchen; Legge, Gordon E

2017-09-01

The visual span is hypothesized to be a sensory bottleneck on reading speed with crowding thought to be the major sensory factor limiting the size of the visual span. This proposed linkage between crowding, visual span, and reading speed is challenged by the finding that training to read crowded letters reduced crowding but did not improve reading speed (Chung, 2007). Here, we examined two properties of letter-recognition training that may influence the transfer to improved reading: the spatial arrangement of training stimuli and the presence of flankers. Three groups of nine young adults were trained with different configurations of letter stimuli at 10° in the lower visual field: a flanked-local group (flanked letters localized at one position), a flanked-distributed group (flanked letters distributed across different horizontal locations), and an isolated-distributed group (isolated and distributed letters). We found that distributed training, but not the presence of flankers, appears to be necessary for the training benefit to transfer to increased reading speed. Localized training may have biased attention to one specific, small area in the visual field, thereby failing to improve reading. We conclude that the visual span represents a sensory bottleneck on reading, but there may also be an attentional bottleneck. Reducing the impact of crowding can enlarge the visual span and can potentially facilitate reading, but not when adverse attentional bias is present. Our results clarify the association between crowding, visual span, and reading.

The regulatory control of radioactive sources in Argentina

International Nuclear Information System (INIS)

Rojkind, R.H.

1998-01-01

Argentina has been conducting nuclear activities for more than forty years, and had established a Regulatory Authority as early as in 1956. Procedures for compliance monitoring and enforcement have been in use in the regulatory control of radioactive sources, and regulatory standards and regulations were in force in Argentina before the accident in Goiania. The conclusions drawn from the Goiania accident encouraged the Argentine authorities to improve some regulatory procedures and helped to enhance the quality of the regulatory process. As a result, the effectiveness of the control of spent radioactive sources has gradually increased, and enforcement actions to prevent radioactive sources ending up in the public domain have improved. Lessons learned in Argentina from the accident in Goiania are presented as well as the main characteristics of an effective enforcement programme to prevent radiological accidents when radioactive sources are used for industrial, medical, research and teaching purposes. (author)

p21-ras effector domain mutants constructed by "cassette" mutagenesis

DEFF Research Database (Denmark)

Stone, J C; Vass, W C; Willumsen, B M

1988-01-01

A series of mutations encoding single-amino-acid substitutions within the v-rasH effector domain were constructed, and the ability of the mutants to induce focal transformation of NIH 3T3 cells was studied. The mutations, which spanned codons 32 to 40, were made by a "cassette" mutagenesis...

Regulatory compliance analysis for the closure of single-shell tanks

International Nuclear Information System (INIS)

Smith, E.H.; Boomer, K.D.; Letourneau, M.; Oakes, L.; Lorang, R.

1991-08-01

This document provides a regulatory compliance analysis of the baseline environmental protection requirements for the closure of single-shell tanks. In preparing this document, the Westinghouse Hanford Company has analyzed the regulatory pathways and decisions points that have been identified to data through systems engineering and related studies as they relate to environmental protection. This regulatory compliance analysis has resulted in several conclusions that will aid the US Department of Energy in managing the single-shell tank waste and in developing strategies for the closure of these tanks. These conclusions include likely outcomes of current strategies, regulatory rulings that are required for future actions, variances and exemptions to be pursued, where appropriate, and potential rulings that may affect systems engineering and other portions of the single-shell tank closure effort. The conclusions and recommendations presented here are based on analysis of current regulations, regulatory exemptions and variances, and federal facility agreements. Because the remediation of the single-shell tanks will span 30 years, regulations that have yet to be promulgated and future interpretations of existing laws and regulations may impact the recommendations and conclusions presented here. 50 refs., 22 figs

Longitudinal navigation log data on a large web domain

NARCIS (Netherlands)

Verberne, S.; Arends, B.; Kraaij, W.; Vries, A. de

2016-01-01

We have collected the access logs for our university's web domain over a time span of 4.5 years. We now release the pre-processed data of a 3-month period for research into user navigation behavior. We preprocessed the data so that only successful GET requests of web pages by non-bot users are kept.

Dual Nature of Translational Control by Regulatory BC RNAs ▿

Science.gov (United States)

Eom, Taesun; Berardi, Valerio; Zhong, Jun; Risuleo, Gianfranco; Tiedge, Henri

2011-01-01

In higher eukaryotes, increasing evidence suggests, gene expression is to a large degree controlled by RNA. Regulatory RNAs have been implicated in the management of neuronal function and plasticity in mammalian brains. However, much of the molecular-mechanistic framework that enables neuronal regulatory RNAs to control gene expression remains poorly understood. Here, we establish molecular mechanisms that underlie the regulatory capacity of neuronal BC RNAs in the translational control of gene expression. We report that regulatory BC RNAs employ a two-pronged approach in translational control. One of two distinct repression mechanisms is mediated by C-loop motifs in BC RNA 3′ stem-loop domains. These C-loops bind to eIF4B and prevent the factor's interaction with 18S rRNA of the small ribosomal subunit. In the second mechanism, the central A-rich domains of BC RNAs target eIF4A, specifically inhibiting its RNA helicase activity. Thus, BC RNAs repress translation initiation in a bimodal mechanistic approach. As BC RNA functionality has evolved independently in rodent and primate lineages, our data suggest that BC RNA translational control was necessitated and implemented during mammalian phylogenetic development of complex neural systems. PMID:21930783

Specificity and autoregulation of Notch binding by tandem WW domains in suppressor of Deltex.

Science.gov (United States)

Jennings, Martin D; Blankley, Richard T; Baron, Martin; Golovanov, Alexander P; Avis, Johanna M

2007-09-28

WW domains target proline-tyrosine (PY) motifs and frequently function as tandem pairs. When studied in isolation, single WW domains are notably promiscuous and regulatory mechanisms are undoubtedly required to ensure selective interactions. Here, we show that the fourth WW domain (WW4) of Suppressor of Deltex, a modular Nedd4-like protein that down-regulates the Notch receptor, is the primary mediator of a direct interaction with a Notch-PY motif. A natural Trp to Phe substitution in WW4 reduces its affinity for general PY sequences and enhances selective interaction with the Notch-PY motif via compensatory specificity-determining interactions with PY-flanking residues. When WW4 is paired with WW3, domain-domain association, impeding proper folding, competes with Notch-PY binding to WW4. This novel mode of autoinhibition is relieved by binding of another ligand to WW3. Such cooperativity may facilitate the transient regulatory interactions observed in vivo between Su(dx) and Notch in the endocytic pathway. The highly conserved tandem arrangement of WW domains in Nedd4 proteins, and similar arrangements in more diverse proteins, suggests domain-domain communication may be integral to regulation of their associated cellular activities.

Detailed free span assessment for Mexilhao flow lines

Energy Technology Data Exchange (ETDEWEB)

Pereira, Antonio; Franco, Luciano; Eigbe, Uwa; BomfimSilva, Carlos [INTECSEA, Houston, TX (United States); Escudero, Carlos [PETROBRAS S.A., Rio de Janeiro, RJ (Brazil)

2009-07-01

The subsea gas production system of Mexilhao Field SPS-35, Santos Basin, offshore Brazil, is composed basically of two rigid 12.75 inches production flow lines approximately 21 km long installed in a fairly rough seabed. During the basic design, the free span assessment was performed considering the maximum allowable free span length determined by the response model proposed by DNV-RP-F105. This approach resulted in a large number of predicted free span requiring corrections, leading to a higher capital cost for the project. In this sense, a detailed free span VIV fatigue assessment was proposed, considering multi-spans and multi-mode effects and also the post lay survey data. The assessment followed the DNV-RP-F105 recommendations for multi-spans and multi-mode effects, using Finite Element Analysis to determine the natural frequencies, mode shapes and corresponding stresses associated with the mode shapes. The assessment was performed in three stages, the first during the detailed design as part of the bottom roughness analysis using the expected residual pipelay tension. The second stage was performed after pipelay, considering the post-lay survey data, where the actual requirements for span correction were determined. Actual pipelay tension was used and seabed soil stiffness adjusted in the model to match the as-laid pipeline profile obtained from the survey data. The first and second stage assessments are seamlessly automated to speed up the evaluation process and allow for quick response in the field, which was important to keep the construction vessel time minimized. The third stage was performed once the corrections of the spans were made and the purpose was to confirm that the new pipeline configuration along the supported spans had sufficient fatigue life for the temporary and operational phases. For the assessment of all three stages, the probability of occurrence and directionality of the near bottom current was considered to improve prediction of the

Improved Digit Span in Children after a 6-Week Intervention of Playing a Musical Instrument: An Exploratory Randomized Controlled Trial.

Science.gov (United States)

Guo, Xia; Ohsawa, Chie; Suzuki, Akiko; Sekiyama, Kaoru

2017-01-01

Previous studies have reported that music training not only improves children's musical skills, but also enhances their cognitive functions. However, there is a disagreement about what domain(s) might be affected. Moreover, effects of short-term (musical scores to emphasize creating association between sound (auditory modality) and finger movement (somato-motor system). Cognitive measurements included verbal ability, processing speed, working memory, and inhibitory control, which were administered before and after the curriculum in both groups. After the 6-week training, only the experimental group showed a significant improvement in the Digit Span test (especially in the Digit Span Backward) that measures working memory. However, no significant influences were found on the other cognitive tests. The result suggests that several weeks of instrumental music training may be beneficial to improving children's working memory. In addition, we used an inexpensive and portable keyboard harmonica; therefore, our instructional method is easy to apply in classrooms or other circumstances. If the method is applied to music lessons in schools or in the community, it may help improve children's working memory.

REGULATORY T-CELLS IN CHRONIC LYMPHOCYTIC LEUKEMIA

Directory of Open Access Journals (Sweden)

Giovanni D'arena

2012-01-01

Full Text Available <span style="font-family: Times New Roman; font-size: small;">

<span lang="EN-US" style="line-height: 200%; font-family: "Times New Roman","serif"; font-size: 12pt; mso-ansi-language: EN-US; mso-bidi-font-size: 11.0pt;">Regulatory T-cells (Tregs constitute a small subset of cells that are actively involved in maintaining self-tolerance, in immune homeostasis and in antitumor immunity. They are thought to play a significant role in the progression of cancer and are generally increased in patient with chronic lymphocytic leukemia (CLL. Their number correlates with more aggressive disease status and is predictive of the time to treatment, as well. Moreover, it is now clear that dysregulation in Tregs cell frequency and/or function may result in a plethora of autoimmune diseases, including multiple sclerosis, type 1 diabetes mellitus, myasthenia gravis, systemic lupus erythematosis, autoimmune lymphoproliferative disorders, rheumatoid arthritis, and psoriasis. Efforts are made aiming to develop approaches to deplete Tregs or inhibit their function in either cancer and autoimmune disorders.

The regulatory control of radioactive sources in Argentina

Energy Technology Data Exchange (ETDEWEB)

Rojkind, Roberto Hector [Autoridade Regulatoria Nuclear, Buenos Aires (Argentina)

1997-12-31

Argentina has been conducting nuclear activities for more than forty years, and as early as in 1956 established a Regulatory Authority. Procedures for compliance monitoring and enforcement have been in use in the regulatory control of radioactive sources, and regulatory standards and regulations had been set in Argentina, before the accident in Goiania. The conclusions drawn from that accident encouraged in Argentina the improvement of some regulatory procedures and helped to enhance the quality of the regulatory process. Therefore, the effectiveness of the control of spent radioactive sources has gradually increased, and enforcement actions to prevent radioactive sources ending up in the public domain improved. Some lessons learned in Argentina from the accident in Goiania and the main characteristics of an effective enforcement program helpful to prevent radiological accidents in industrial, medical, research and teaching uses of radioactive sources are presented. (author) 9 refs; e-mail: rrojkind at sede.arn.gov.br

Constitutive NADPH-dependent electron transferase activity of the Nox4 dehydrogenase domain.

Science.gov (United States)

Nisimoto, Yukio; Jackson, Heather M; Ogawa, Hisamitsu; Kawahara, Tsukasa; Lambeth, J David

2010-03-23

NADPH oxidase 4 (Nox4) is constitutively active, while Nox2 requires the cytosolic regulatory subunits p47(phox) and p67(phox) and activated Rac with activation by phorbol 12-myristate 13-acetate (PMA). This study was undertaken to identify the domain on Nox4 that confers constitutive activity. Lysates from Nox4-expressing cells exhibited constitutive NADPH- but not NADH-dependent hydrogen peroxide production with a K(m) for NADPH of 55 +/- 10 microM. The concentration of Nox4 in cell lysates was estimated using Western blotting and allowed calculation of a turnover of approximately 200 mol of H(2)O(2) min(-1) (mol of Nox4)(-1). A chimeric protein (Nox2/4) consisting of the Nox2 transmembrane (TM) domain and the Nox4 dehydrogenase (DH) domain showed H(2)O(2) production in the absence of cytosolic regulatory subunits. In contrast, chimera Nox4/2, consisting of the Nox4 TM and Nox2 DH domains, exhibited PMA-dependent activation that required coexpression of regulatory subunits. Nox DH domains from several Nox isoforms were purified and evaluated for their electron transferase activities. Nox1 DH, Nox2 DH, and Nox5 DH domains exhibited barely detectable activities toward artificial electron acceptors, while the Nox4 DH domain exhibited significant rates of reduction of cytochrome c (160 min(-1), largely superoxide dismutase-independent), ferricyanide (470 min(-1)), and other electron acceptors (artificial dyes and cytochrome b(5)). Rates were similar to those observed for H(2)O(2) production by the Nox4 holoenzyme in cell lysates. The activity required added FAD and was seen with NADPH but not NADH. These results indicate that the Nox4 DH domain exists in an intrinsically activated state and that electron transfer from NADPH to FAD is likely to be rate-limiting in the NADPH-dependent reduction of oxygen by holo-Nox4.

Comparative Bioinformatics Analysis of Transcription Factor Genes Indicates Conservation of Key Regulatory Domains among Babesia bovis, Babesia microti, and Theileria equi.

Science.gov (United States)

Alzan, Heba F; Knowles, Donald P; Suarez, Carlos E

2016-11-01

Apicomplexa tick-borne hemoparasites, including Babesia bovis, Babesia microti, and Theileria equi are responsible for bovine and human babesiosis and equine theileriosis, respectively. These parasites of vast medical, epidemiological, and economic impact have complex life cycles in their vertebrate and tick hosts. Large gaps in knowledge concerning the mechanisms used by these parasites for gene regulation remain. Regulatory genes coding for DNA binding proteins such as members of the Api-AP2, HMG, and Myb families are known to play crucial roles as transcription factors. Although the repertoire of Api-AP2 has been defined and a HMG gene was previously identified in the B. bovis genome, these regulatory genes have not been described in detail in B. microti and T. equi. In this study, comparative bioinformatics was used to: (i) identify and map genes encoding for these transcription factors among three parasites' genomes; (ii) identify a previously unreported HMG gene in B. microti; (iii) define a repertoire of eight conserved Myb genes; and (iv) identify AP2 correlates among B. bovis and the better-studied Plasmodium parasites. Searching the available transcriptome of B. bovis defined patterns of transcription of these three gene families in B. bovis erythrocyte stage parasites. Sequence comparisons show conservation of functional domains and general architecture in the AP2, Myb, and HMG proteins, which may be significant for the regulation of common critical parasite life cycle transitions in B. bovis, B. microti, and T. equi. A detailed understanding of the role of gene families encoding DNA binding proteins will provide new tools for unraveling regulatory mechanisms involved in B. bovis, B. microti, and T. equi life cycles and environmental adaptive responses and potentially contributes to the development of novel convergent strategies for improved control of babesiosis and equine piroplasmosis.

Comparative Bioinformatics Analysis of Transcription Factor Genes Indicates Conservation of Key Regulatory Domains among Babesia bovis, Babesia microti, and Theileria equi.

Directory of Open Access Journals (Sweden)

Heba F Alzan

2016-11-01

Full Text Available Apicomplexa tick-borne hemoparasites, including Babesia bovis, Babesia microti, and Theileria equi are responsible for bovine and human babesiosis and equine theileriosis, respectively. These parasites of vast medical, epidemiological, and economic impact have complex life cycles in their vertebrate and tick hosts. Large gaps in knowledge concerning the mechanisms used by these parasites for gene regulation remain. Regulatory genes coding for DNA binding proteins such as members of the Api-AP2, HMG, and Myb families are known to play crucial roles as transcription factors. Although the repertoire of Api-AP2 has been defined and a HMG gene was previously identified in the B. bovis genome, these regulatory genes have not been described in detail in B. microti and T. equi. In this study, comparative bioinformatics was used to: (i identify and map genes encoding for these transcription factors among three parasites' genomes; (ii identify a previously unreported HMG gene in B. microti; (iii define a repertoire of eight conserved Myb genes; and (iv identify AP2 correlates among B. bovis and the better-studied Plasmodium parasites. Searching the available transcriptome of B. bovis defined patterns of transcription of these three gene families in B. bovis erythrocyte stage parasites. Sequence comparisons show conservation of functional domains and general architecture in the AP2, Myb, and HMG proteins, which may be significant for the regulation of common critical parasite life cycle transitions in B. bovis, B. microti, and T. equi. A detailed understanding of the role of gene families encoding DNA binding proteins will provide new tools for unraveling regulatory mechanisms involved in B. bovis, B. microti, and T. equi life cycles and environmental adaptive responses and potentially contributes to the development of novel convergent strategies for improved control of babesiosis and equine piroplasmosis.

L-fuzzy/span> fixed points theorems for L-fuzzy/span> mappings via βℱL-admissible pair.

Science.gov (United States)

Rashid, Maliha; Azam, Akbar; Mehmood, Nayyar

2014-01-01

We define the concept of βℱL-admissible for a pair of L-fuzzy/span> mappings and establish the existence of common L-fuzzy/span> fixed point theorem. Our result generalizes some useful results in the literature. We provide an example to support our result.

Sexual conflict, life span, and aging.

Science.gov (United States)

Adler, Margo I; Bonduriansky, Russell

2014-06-17

The potential for sexual conflict to influence the evolution of life span and aging has been recognized for more than a decade, and recent work also suggests that variation in life span and aging can influence sexually antagonistic coevolution. However, empirical exploration of these ideas is only beginning. Here, we provide an overview of the ideas and evidence linking inter- and intralocus sexual conflicts with life span and aging. We aim to clarify the conceptual basis of this research program, examine the current state of knowledge, and suggest key questions for further investigation. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

Insulator function and topological domain border strength scale with architectural protein occupancy

Science.gov (United States)

2014-01-01

Background Chromosome conformation capture studies suggest that eukaryotic genomes are organized into structures called topologically associating domains. The borders of these domains are highly enriched for architectural proteins with characterized roles in insulator function. However, a majority of architectural protein binding sites localize within topological domains, suggesting sites associated with domain borders represent a functionally different subclass of these regulatory elements. How topologically associating domains are established and what differentiates border-associated from non-border architectural protein binding sites remain unanswered questions. Results By mapping the genome-wide target sites for several Drosophila architectural proteins, including previously uncharacterized profiles for TFIIIC and SMC-containing condensin complexes, we uncover an extensive pattern of colocalization in which architectural proteins establish dense clusters at the borders of topological domains. Reporter-based enhancer-blocking insulator activity as well as endogenous domain border strength scale with the occupancy level of architectural protein binding sites, suggesting co-binding by architectural proteins underlies the functional potential of these loci. Analyses in mouse and human stem cells suggest that clustering of architectural proteins is a general feature of genome organization, and conserved architectural protein binding sites may underlie the tissue-invariant nature of topologically associating domains observed in mammals. Conclusions We identify a spectrum of architectural protein occupancy that scales with the topological structure of chromosomes and the regulatory potential of these elements. Whereas high occupancy architectural protein binding sites associate with robust partitioning of topologically associating domains and robust insulator function, low occupancy sites appear reserved for gene-specific regulation within topological domains. PMID

SH3 Domains Differentially Stimulate Distinct Dynamin I Assembly Modes and G Domain Activity.

Directory of Open Access Journals (Sweden)

Sai Krishnan

Full Text Available Dynamin I is a highly regulated GTPase enzyme enriched in nerve terminals which mediates vesicle fission during synaptic vesicle endocytosis. One regulatory mechanism involves its interactions with proteins containing Src homology 3 (SH3 domains. At least 30 SH3 domain-containing proteins bind dynamin at its proline-rich domain (PRD. Those that stimulate dynamin activity act by promoting its oligomerisation. We undertook a systematic parallel screening of 13 glutathione-S-transferase (GST-tagged endocytosis-related SH3 domains on dynamin binding, GTPase activity and oligomerisation. No correlation was found between dynamin binding and their potency to stimulate GTPase activity. There was limited correlation between the extent of their ability to stimulate dynamin activity and the level of oligomerisation, indicating an as yet uncharacterised allosteric coupling of the PRD and G domain. We examined the two variants, dynamin Iab and Ibb, which differ in the alternately splice middle domain α2 helix. They responded differently to the panel of SH3s, with the extent of stimulation between the splice variants varying greatly between the SH3s. This study reveals that SH3 binding can act as a heterotropic allosteric regulator of the G domain via the middle domain α2 helix, suggesting an involvement of this helix in communicating the PRD-mediated allostery. This indicates that SH3 binding both stabilises multiple conformations of the tetrameric building block of dynamin, and promotes assembly of dynamin-SH3 complexes with distinct rates of GTP hydrolysis.

Linguistic Evidence for the Failure Mindset as a Predictor of Life Span Longevity.

Science.gov (United States)

Penzel, Ian B; Persich, Michelle R; Boyd, Ryan L; Robinson, Michael D

2017-06-01

When people think that their efforts will fail to achieve positive outcomes, they sometimes give up their efforts after control, which can have negative health consequences. Problematic orientations of this type, such as pessimism, helplessness, or fatalism, seem likely to be associated with a cognitive mindset marked by higher levels of accessibility for failure words or concepts. Thus, the purpose of the present research was to determine whether there are individual differences in the frequency with which people think about failure, which in turn are likely to impact health across large spans of time. Following self-regulatory theories of health and the learned helplessness tradition, two archival studies (total n = 197) scored texts (books or speeches) for their use of failure words, a category within the Harvard IV dictionary of the General Inquirer. People who used failure words more frequently exhibited shorter subsequent life spans, and this relationship remained significant when controlling for birth year. Furthermore, study 2 implicated behavioral factors. For example, the failure/longevity relationship was numerically stronger among people whose causes of death appeared to be preventable rather than non-preventable. These results significantly extend our knowledge of the personality/longevity relationship while highlighting the value of individual differences in word usage as predictors of health and mortality.

Examining the Relative Contribution of Memory Updating, Attention Focus Switching, and Sustained Attention to Children’s Verbal Working Memory Span

Directory of Open Access Journals (Sweden)

Beula M. Magimairaj

2013-01-01

Full Text Available Whereas considerable developmental memory research has examined the contributions of short-term memory, processing efficiency, retention duration, and scope of attention to complex memory span, little is known about the influence of controlled attention. The present study investigated the relative influence of three understudied attention mechanisms on the verbal working memory span of school-age children: memory updating; attention focus switching; and sustained attention. Results of general linear modeling revealed that, after controlling for age, only updating accuracy emerged as a significant predictor of verbal working memory span. Memory updating speed (that subsumed attention focus switching speed also contributed but was mediated by age. The results extend the developmental memory literature by implicating the mechanism of memory updating and developmental improvement in speed of attention focus switching and updating as critical contributors to children’s verbal working memory. Theoretically, the results provide substantively new information about the role of domain-general executive attention in children’s verbal working memory.

Spanning forests and the vector bundle Laplacian

OpenAIRE

Kenyon, Richard

2011-01-01

The classical matrix-tree theorem relates the determinant of the combinatorial Laplacian on a graph to the number of spanning trees. We generalize this result to Laplacians on one- and two-dimensional vector bundles, giving a combinatorial interpretation of their determinants in terms of so-called cycle rooted spanning forests (CRSFs). We construct natural measures on CRSFs for which the edges form a determinantal process. ¶ This theory gives a natural generalization of the spanning tre...

Kinetic and equilibrium properties of regulatory Ca(2+)-binding domains in sodium-calcium exchangers 2 and 3.

Science.gov (United States)

Tal, Inbal; Kozlovsky, Tom; Brisker, Dafna; Giladi, Moshe; Khananshvili, Daniel

2016-04-01

In mammals, three sodium-calcium exchanger (NCX) protein isoforms (NCX1, NCX2, and NCX3) mediate Ca(2+) fluxes across the membrane to maintain cellular Ca(2+) homeostasis. NCX isoforms and their splice variants are expressed in a tissue-specific manner to meet physiological demands. NCX1 is ubiquitously expressed, NCX2 is expressed in the brain and spinal cord, and NCX3 is expressed in the brain and skeletal muscle. Eukaryotic NCXs contain two cytosolic regulatory Ca(2+)-binding domains, CBD1 and CBD2, which form a two-domain tandem (CBD12) through a short linker. Ca(2+) binding to the CBDs underlies allosteric regulation of NCX. Previous structural and functional studies in NCX1 have shown that the CBDs synergistically interact, where their interactions are modulated in a splice variant-specific manner by splicing segment at CBD2. Here, we analyze the equilibrium and kinetic properties of Ca(2+) binding to purified preparations of CBD1, CBD2, and CBD12 from NCX2 and from NCX3 splice variants. We show that CBD1 interacts with CBD2 in the context of the CBD12 tandem in all NCX isoforms, where these interactions specifically modulate Ca(2+) sensing at the primary sensor of CBD1 to meet the physiological requirements. For example, the rate-limiting slow dissociation of "occluded" Ca(2+) from the primary allosteric sensor of variants expressed in skeletal muscle is ∼10-fold slower than that of variants expressed in the brain. Notably, these kinetic differences between NCX variants occur while maintaining a similar Ca(2+) affinity of the primary sensor, since the resting [Ca(2+)]i levels are similar among different cell types. Copyright © 2016 Elsevier Ltd. All rights reserved.

Span efficiency in hawkmoths.

Science.gov (United States)

Henningsson, Per; Bomphrey, Richard J

2013-07-06

Flight in animals is the result of aerodynamic forces generated as flight muscles drive the wings through air. Aerial performance is therefore limited by the efficiency with which momentum is imparted to the air, a property that can be measured using modern techniques. We measured the induced flow fields around six hawkmoth species flying tethered in a wind tunnel to assess span efficiency, ei, and from these measurements, determined the morphological and kinematic characters that predict efficient flight. The species were selected to represent a range in wingspan from 40 to 110 mm (2.75 times) and in mass from 0.2 to 1.5 g (7.5 times) but they were similar in their overall shape and their ecology. From high spatio-temporal resolution quantitative wake images, we extracted time-resolved downwash distributions behind the hawkmoths, calculating instantaneous values of ei throughout the wingbeat cycle as well as multi-wingbeat averages. Span efficiency correlated positively with normalized lift and negatively with advance ratio. Average span efficiencies for the moths ranged from 0.31 to 0.60 showing that the standard generic value of 0.83 used in previous studies of animal flight is not a suitable approximation of aerodynamic performance in insects.

Ectopic hTERT expression extends the life span of human CD4(+) helper and regulatory T-cell clones and confers resistance to oxidative stress-induced apoptosis

NARCIS (Netherlands)

Luiten, Rosalie M.; Péne, Jérome; Yssel, Hans; Spits, Hergen

2003-01-01

Human somatic cells have a limited life span in vitro. Upon aging and with each cell division, shortening of telomeres occurs, which eventually will lead to cell cycle arrest. Ectopic hTERT expression has been shown to extend the life span of human T cells by preventing this telomere erosion. In the

Malingering in Toxic Exposure. Classification Accuracy of Reliable Digit Span and WAIS-III Digit Span Scaled Scores

Science.gov (United States)

Greve, Kevin W.; Springer, Steven; Bianchini, Kevin J.; Black, F. William; Heinly, Matthew T.; Love, Jeffrey M.; Swift, Douglas A.; Ciota, Megan A.

2007-01-01

This study examined the sensitivity and false-positive error rate of reliable digit span (RDS) and the WAIS-III Digit Span (DS) scaled score in persons alleging toxic exposure and determined whether error rates differed from published rates in traumatic brain injury (TBI) and chronic pain (CP). Data were obtained from the files of 123 persons…

Should the scope of human mixture risk assessment span legislative/regulatory silos for chemicals?

Science.gov (United States)

Evans, Richard M; Martin, Olwenn V; Faust, Michael; Kortenkamp, Andreas

2016-02-01

Current chemicals regulation operates almost exclusively on a chemical-by-chemical basis, however there is concern that this approach may not be sufficiently protective if two or more chemicals have the same toxic effect. Humans are indisputably exposed to more than one chemical at a time, for example to the multiple chemicals found in food, air and drinking water, and in household and consumer products, and in cosmetics. Assessment of cumulative risk to human health and/or the environment from multiple chemicals and routes can be done in a mixture risk assessment (MRA). Whilst there is a broad consensus on the basic science of mixture toxicology, the path to regulatory implementation of MRA within chemical risk assessment is less clear. In this discussion piece we pose an open question: should the scope of human MRA cross legislative remits or 'silos'? We define silos as, for instance, legislation that defines risk assessment practice for a subset of chemicals, usually on the basis of substance/product, media or process orientation. Currently any form of legal mandate for human MRA in the EU is limited to only a few pieces of legislation. We describe two lines of evidence, illustrated with selected examples, that are particularly pertinent to this question: 1) evidence that mixture effects have been shown for chemicals regulated in different silos and 2) evidence that humans are co-exposed to chemicals from different silos. We substantiate the position that, because there is no reason why chemicals allocated to specific regulatory silos would have non-overlapping risk profiles, then there is also no reason to expect that MRA limited only to chemicals within one silo can fully capture the risk that may be present to human consumers. Finally, we discuss possible options for implementation of MRA and we hope to prompt wider discussion of this issue. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Signal Enhancement with Variable Span Linear Filters

DEFF Research Database (Denmark)

Benesty, Jacob; Christensen, Mads Græsbøll; Jensen, Jesper Rindom

This book introduces readers to the novel concept of variable span speech enhancement filters, and demonstrates how it can be used for effective noise reduction in various ways. Further, the book provides the accompanying Matlab code, allowing readers to easily implement the main ideas discussed....... Variable span filters combine the ideas of optimal linear filters with those of subspace methods, as they involve the joint diagonalization of the correlation matrices of the desired signal and the noise. The book shows how some well-known filter designs, e.g. the minimum distortion, maximum signal......-to-noise ratio, Wiener, and tradeoff filters (including their new generalizations) can be obtained using the variable span filter framework. It then illustrates how the variable span filters can be applied in various contexts, namely in single-channel STFT-based enhancement, in multichannel enhancement in both...

Strengthening Regulatory Competence in Pakistan

International Nuclear Information System (INIS)

Sadiq, M.

2016-01-01

Capacity building of Pakistan Nuclear Regulatory Authority is considered an essential element in pursuit of its vision to become a world class regulatory body. Since its inception in 2001, PNRA has continuously endeavoured to invest in its people, develop training infrastructure and impart sound knowledge and professional skills with the aim to improve its regulatory effectiveness. The use of nuclear and radioactive material in Pakistan has increased manifold in recent years, thus induction of more manpower was needed for regulatory oversight. PNRA adopted two pronged approach for meeting the manpower demand (a) employment of university graduates through fast track recruitment drive and (b) induction of graduates by offering fellowships for Master degree programs. Although, the newly employed staff was selected on the basis of their excellent academic qualifications in basic and applied sciences, but they required rigorous knowledge and skills in regulatory perspectives. In order to implement a structured training program, PNRA conducted Training Needs Assessment (TNA) and identified competency gaps of the regulatory staff in legal, technical, regulatory practice and behavioural domains. PNRA took several initiatives for capacity building which included establishment of a training centre for sustainability of trainings, initiation of a fellowship scheme for Master program, attachment of staff at local institutes for on-the-job training and placement at foreign regulatory bodies and organizations for technical development with the assistance of IAEA. The above strategies have been very beneficial in competence building of the PNRA staff to perform all regulatory activities indigenously for nuclear power plants, research reactors and radiation facilities. Provision of vibrant technical support to IAEA and Member States in various programs by PNRA is a landmark of these competence development efforts. This paper summarizes PNRA initiatives and the International Atomic

Electrode spanning with partial tripolar stimulation mode in cochlear implants.

Science.gov (United States)

Wu, Ching-Chih; Luo, Xin

2014-12-01

The perceptual effects of electrode spanning (i.e., the use of nonadjacent return electrodes) in partial tripolar (pTP) mode were tested on a main electrode EL8 in five cochlear implant (CI) users. Current focusing was controlled by σ (the ratio of current returned within the cochlea), and current steering was controlled by α (the ratio of current returned to the basal electrode). Experiment 1 tested whether asymmetric spanning with α = 0.5 can create additional channels around standard pTP stimuli. It was found that in general, apical spanning (i.e., returning current to EL6 rather than EL7) elicited a pitch between those of standard pTP stimuli on main electrodes EL8 and EL9, while basal spanning (i.e., returning current to EL10 rather than EL9) elicited a pitch between those of standard pTP stimuli on main electrodes EL7 and EL8. The pitch increase caused by apical spanning was more salient than the pitch decrease caused by basal spanning. To replace the standard pTP channel on the main electrode EL8 when EL7 or EL9 is defective, experiment 2 tested asymmetrically spanned pTP stimuli with various α, and experiment 3 tested symmetrically spanned pTP stimuli with various σ. The results showed that pitch increased with decreasing α in asymmetric spanning, or with increasing σ in symmetric spanning. Apical spanning with α around 0.69 and basal spanning with α around 0.38 may both elicit a similar pitch as the standard pTP stimulus. With the same σ, the symmetrically spanned pTP stimulus was higher in pitch than the standard pTP stimulus. A smaller σ was thus required for symmetric spanning to match the pitch of the standard pTP stimulus. In summary, electrode spanning is an effective field-shaping technique that is useful for adding spectral channels and handling defective electrodes with CIs.

Functional Dissection of the Blocking and Bypass Activities of the Fab-8 Boundary in the Drosophila Bithorax Complex.

Science.gov (United States)

Kyrchanova, Olga; Mogila, Vladic; Wolle, Daniel; Deshpande, Girish; Parshikov, Alexander; Cléard, Fabienne; Karch, Francois; Schedl, Paul; Georgiev, Pavel

2016-07-01

Functionally autonomous regulatory domains direct the parasegment-specific expression of the Drosophila Bithorax complex (BX-C) homeotic genes. Autonomy is conferred by boundary/insulator elements that separate each regulatory domain from its neighbors. For six of the nine parasegment (PS) regulatory domains in the complex, at least one boundary is located between the domain and its target homeotic gene. Consequently, BX-C boundaries must not only block adventitious interactions between neighboring regulatory domains, but also be permissive (bypass) for regulatory interactions between the domains and their gene targets. To elucidate how the BX-C boundaries combine these two contradictory activities, we have used a boundary replacement strategy. We show that a 337 bp fragment spanning the Fab-8 boundary nuclease hypersensitive site and lacking all but 83 bp of the 625 bp Fab-8 PTS (promoter targeting sequence) fully rescues a Fab-7 deletion. It blocks crosstalk between the iab-6 and iab-7 regulatory domains, and has bypass activity that enables the two downstream domains, iab-5 and iab-6, to regulate Abdominal-B (Abd-B) transcription in spite of two intervening boundary elements. Fab-8 has two dCTCF sites and we show that they are necessary both for blocking and bypass activity. However, CTCF sites on their own are not sufficient for bypass. While multimerized dCTCF (or Su(Hw)) sites have blocking activity, they fail to support bypass. Moreover, this bypass defect is not rescued by the full length PTS. Finally, we show that orientation is critical for the proper functioning the Fab-8 replacement. Though the inverted Fab-8 boundary still blocks crosstalk, it disrupts the topology of the Abd-B regulatory domains and does not support bypass. Importantly, altering the orientation of the Fab-8 dCTCF sites is not sufficient to disrupt bypass, indicating that orientation dependence is conferred by other factors.

Birth and upgrowth of the Hox topological domains during evolution

NARCIS (Netherlands)

Deschamps, Jacqueline

The recently discovered chromatin compartments called topologically associating domains (TADs) are essential for the three-dimensional organization of regulatory interactions driving gene expression. A new study documents the emergence of a TAD flanking the amphioxus Hox cluster, prefiguring the

Birth and upgrowth of the Hox topological domains during evolution

NARCIS (Netherlands)

Deschamps, J.

2016-01-01

The recently discovered chromatin compartments called topologically associating domains (TADs) are essential for the three-dimensional organization of regulatory interactions driving gene expression. A new study documents the emergence of a TAD flanking the amphioxus Hox cluster, prefiguring the

Promoting Prosocial Behavior and Self-Regulatory Skills in Preschool Children through a Mindfulness-Based Kindness Curriculum

Science.gov (United States)

Flook, Lisa; Goldberg, Simon B.; Pinger, Laura; Davidson, Richard J.

2015-01-01

Self-regulatory abilities are robust predictors of important outcomes across the life span, yet they are rarely taught explicitly in school. Using a randomized controlled design, the present study investigated the effects of a 12-week mindfulness-based Kindness Curriculum (KC) delivered in a public school setting on executive function,…

Structural organization and chromosomal assignment of the mouse embryonic TEA domain-containing factor (ETF) gene.

Science.gov (United States)

Suzuki, K; Yasunami, M; Matsuda, Y; Maeda, T; Kobayashi, H; Terasaki, H; Ohkubo, H

1996-09-01

Embryonic TEA domain-containing factor (ETF) belongs to the family of proteins structurally related to transcriptional enhancer factor-1 (TEF-1) and is implicated in neural development. Isolation and characterization of the cosmid clones encoding the mouse ETF gene (Etdf) revealed that Etdf spans approximately 17.9 kb and consists of 12 exons. The exon-intron structure of Etdf closely resembles that of the Drosophila scalloped gene, indicating that these genes may have evolved from a common ancestor. The multiple transcription initiation sites revealed by S1 protection and primer extension analyses are consistent with the absence of the canonical TATA and CAAT boxes in the 5'-flanking region, which contains many potential regulatory sequences, such as the E-box, N-box, Sp1 element, GATA-1 element, TAATGARAT element, and B2 short interspersed element (SINE) as well as several direct and inverted repeat sequences. The Etdf locus was assigned to the proximal region of mouse chromosome 7 using fluorescence in situ hybridization and linkage mapping analyses. These results provide the molecular basis for studying the regulation, in vivo function, and evolution of Etdf.

Structure of a 14-3-3 coordinated hexamer of the plant plasma membrane H+-ATPase by combining X-ray crystallography and electron cryomicroscopy

NARCIS (Netherlands)

Ottmann, C.; Marco, S.; Jaspert, N.; Marcon, C.; Schauer, N.; Weyand, M.; Vandermeeren, C.; Duby, G.; Boutry, M.; Wittinghofer, A.; Rigaud, J.-L.; Oecking, C.

2007-01-01

Regulatory 14-3-3 proteins activate the plant plasma membrane H+-ATPase by binding to its C-terminal autoinhibitory domain. This interaction requires phosphorylation of a C-terminal, mode III, recognition motif as well as an adjacent span of approximately 50 amino acids. Here we report the X-ray

Small-angle scattering studies show distinct conformations of calmodulin in its complexes with two peptides based on the regulatory domain of the catalytic subunit of phosphorylase kinase

International Nuclear Information System (INIS)

Trewhella, J.; Blumenthal, D.K.; Rokop, S.E.; Seeger, P.A.

1990-01-01

Small-angle X-ray and neutron scattering have been used to study the solution structures of calmodulin complexed with synthetic peptides corresponding to residues 342-366 and 301-326, designated PhK5 and PhK13, respectively, in the regulatory domain of the catalytic subunit of skeletal muscle phosphorylase kinase. The scattering data show that binding of PhK5 to calmodulin induces a dramatic contraction of calmodulin, similar to that previously observed when calmodulin is complexed with the calmodulin-binding domain peptide from rabbit skeletal muscle myosin light chain kinase. In contrast, calmodulin remains extended upon binding PhK13. In the presence of both peptides, calmodulin also remains extended. Apparently, the presence of PhK13 inhibits calmodulin from undergoing the PhK5-induced contraction. These data indicate that there is a fundamentally different type of calmodulin-target enzyme interaction in the case of the catalytic subunit of phosphorylase kinase compared with that for myosin light chain kinase

Childhood self-regulatory skills predict adolescent smoking behavior.

Science.gov (United States)

deBlois, Madeleine E; Kubzansky, Laura D

2016-01-01

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

The SPAN cookbook: A practical guide to accessing SPAN

Science.gov (United States)

Mason, Stephanie; Tencati, Ronald D.; Stern, David M.; Capps, Kimberly D.; Dorman, Gary; Peters, David J.

1990-01-01

This is a manual for remote users who wish to send electronic mail messages from the Space Physics Analysis Network (SPAN) to scientific colleagues on other computer networks and vice versa. In several instances more than one gateway has been included for the same network. Users are provided with an introduction to each network listed with helpful details about accessing the system and mail syntax examples. Also included is information on file transfers, remote logins, and help telephone numbers.

Radiation effects on life span in Caenorhabditis elegans

International Nuclear Information System (INIS)

Johnson, T.E.; Hartman, P.S.

1988-01-01

Wild-type and radiation-sensitive (Rad) mutants of Caenorhabditis elegans were irradiated using a 137 Cs source (2.7 krads/min.) at several developmental stages and subsequently monitored for life span. Acute doses of radiation ranged from 1 krad to 300 krads. All stages required doses above 100 krads to reduce mean life span. Dauers and third stage larvae were more sensitive, and 8-day-old adults were the most resistant. Occasional statistically significant but nonrepeatable increases in survival were observed after intermediate levels of irradiation (10-30 krads). Unirradiated rad-4 and rad-7 had life spans similar to wild-type; all others had a significant reduction in survival. The mutants were about as sensitive as wild-type to the effects of ionizing radiation including occasional moderate life span extensions at intermediate doses. We conclude that the moderate life span extensions sometimes observed after irradiation are likely to be mediated by a means other than the induction of DNA repair enzymes

SH2 domains: modulators of nonreceptor tyrosine kinase activity.

Science.gov (United States)

Filippakopoulos, Panagis; Müller, Susanne; Knapp, Stefan

2009-12-01

The Src homology 2 (SH2) domain is a sequence-specific phosphotyrosine-binding module present in many signaling molecules. In cytoplasmic tyrosine kinases, the SH2 domain is located N-terminally to the catalytic kinase domain (SH1) where it mediates cellular localization, substrate recruitment, and regulation of kinase activity. Initially, structural studies established a role of the SH2 domain stabilizing the inactive state of Src family members. However, biochemical characterization showed that the presence of the SH2 domain is frequently required for catalytic activity, suggesting a crucial function stabilizing the active state of many nonreceptor tyrosine kinases. Recently, the structure of the SH2-kinase domain of Fes revealed that the SH2 domain stabilizes the active kinase conformation by direct interactions with the regulatory helix alphaC. Stabilizing interactions between the SH2 and the kinase domains have also been observed in the structures of active Csk and Abl. Interestingly, mutations in the SH2 domain found in human disease can be explained by SH2 domain destabilization or incorrect positioning of the SH2. Here we summarize our understanding of mechanisms that lead to tyrosine kinase activation by direct interactions mediated by the SH2 domain and discuss how mutations in the SH2 domain trigger kinase inactivation.

Crystal structure of the regulatory subunit of archaeal initiation factor 2B (aIF2B) from hyperthermophilic archaeon Pyrococcus horikoshii OT3: a proposed structure of the regulatory subcomplex of eukaryotic IF2B

International Nuclear Information System (INIS)

Kakuta, Yoshimitsu; Tahara, Maino; Maetani, Shigehiro; Yao, Min; Tanaka, Isao; Kimura, Makoto

2004-01-01

Eukaryotic translation initiation factor 2B (eIF2B) is the guanine-nucleotide exchange factor for eukaryotic initiation factor 2 (eIF2). eIF2B is a heteropentameric protein composed of α-ε subunits. The α, β, and δ subunits form a regulatory subcomplex, while the γ and ε form a catalytic subcomplex. Archaea possess homologues of α, β, and δ subunits of eIF2B. Here, we report the three-dimensional structure of an archaeal regulatory subunit (aIF2Bα) from the hyperthermophilic archaeon Pyrococcus horikoshii OT3 determined by X-ray crystallography at 2.2 A resolution. aIF2Bα consists of two subdomains, an N-domain (residues 1-95) and a C-domain (residues 96-276), connected by a long α-helix (α5: 78-106). The N-domain contains a five helix bundle structure, while the C-domain folds into the α/β structure, thus showing similarity to D-ribose-5-phosphate isomerase structure. The presence of two molecules in the crystallographic asymmetric unit and the gel filtration analysis suggest a dimeric structure of aIF2Bα in solution, interacting with each other by C-domains. Furthermore, the crystallographic 3-fold symmetry generates a homohexameric structure of aIF2Bα; the interaction is primarily mediated by the long α-helix at the N-domains. This structure suggests an architecture of the three subunits, α, β, and δ, in the regulatory subcomplex within eIF2B

23 CFR 650.809 - Movable span bridges.

Science.gov (United States)

2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false Movable span bridges. 650.809 Section 650.809 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC OPERATIONS BRIDGES, STRUCTURES, AND HYDRAULICS Navigational Clearances for Bridges § 650.809 Movable span bridges. A fixed bridge...

Basement domain map of the conterminous United States and Alaska

Science.gov (United States)

Lund, Karen; Box, Stephen E.; Holm-Denoma, Christopher S.; San Juan, Carma A.; Blakely, Richard J.; Saltus, Richard W.; Anderson, Eric D.; DeWitt, Ed

2015-01-01

The basement-domain map is a compilation of basement domains in the conterminous United States and Alaska designed to be used at 1:5,000,000-scale, particularly as a base layer for national-scale mineral resource assessments. Seventy-seven basement domains are represented as eighty-three polygons on the map. The domains are based on interpretations of basement composition, origin, and architecture and developed from a variety of sources. Analysis of previously published basement, lithotectonic, and terrane maps as well as models of planetary development were used to formulate the concept of basement and the methodology of defining domains that spanned the ages of Archean to present but formed through different processes. The preliminary compilations for the study areas utilized these maps, national-scale gravity and aeromagnetic data, published and limited new age and isotopic data, limited new field investigations, and conventional geologic maps. Citation of the relevant source data for compilations and the source and types of original interpretation, as derived from different types of data, are provided in supporting descriptive text and tables.

Resolving the Origin of Pseudo-Single Domain Magnetic Behavior

Science.gov (United States)

Roberts, Andrew P.; Almeida, Trevor P.; Church, Nathan S.; Harrison, Richard J.; Heslop, David; Li, Yiliang; Li, Jinhua; Muxworthy, Adrian R.; Williams, Wyn; Zhao, Xiang

2017-12-01

The term "pseudo-single domain" (PSD) has been used to describe the transitional state in rock magnetism that spans the particle size range between the single domain (SD) and multidomain (MD) states. The particle size range for the stable SD state in the most commonly occurring terrestrial magnetic mineral, magnetite, is so narrow ( 20-75 nm) that it is widely considered that much of the paleomagnetic record of interest is carried by PSD rather than stable SD particles. The PSD concept has, thus, become the dominant explanation for the magnetization associated with a major fraction of particles that record paleomagnetic signals throughout geological time. In this paper, we argue that in contrast to the SD and MD states, the term PSD does not describe the relevant physical processes, which have been documented extensively using three-dimensional micromagnetic modeling and by parallel research in material science and solid-state physics. We also argue that features attributed to PSD behavior can be explained by nucleation of a single magnetic vortex immediately above the maximum stable SD transition size. With increasing particle size, multiple vortices, antivortices, and domain walls can nucleate, which produce variable cancellation of magnetic moments and a gradual transition into the MD state. Thus, while the term PSD describes a well-known transitional state, it fails to describe adequately the physics of the relevant processes. We recommend that use of this term should be discontinued in favor of "vortex state," which spans a range of behaviors associated with magnetic vortices.

Comparative structural analysis of lipid binding START domains.

Directory of Open Access Journals (Sweden)

Ann-Gerd Thorsell

Full Text Available Steroidogenic acute regulatory (StAR protein related lipid transfer (START domains are small globular modules that form a cavity where lipids and lipid hormones bind. These domains can transport ligands to facilitate lipid exchange between biological membranes, and they have been postulated to modulate the activity of other domains of the protein in response to ligand binding. More than a dozen human genes encode START domains, and several of them are implicated in a disease.We report crystal structures of the human STARD1, STARD5, STARD13 and STARD14 lipid transfer domains. These represent four of the six functional classes of START domains.Sequence alignments based on these and previously reported crystal structures define the structural determinants of human START domains, both those related to structural framework and those involved in ligand specificity.This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.

The development of a short domain-general measure of working memory capacity.

Science.gov (United States)

Oswald, Frederick L; McAbee, Samuel T; Redick, Thomas S; Hambrick, David Z

2015-12-01

Working memory capacity is one of the most frequently measured individual difference constructs in cognitive psychology and related fields. However, implementation of complex span and other working memory measures is generally time-consuming for administrators and examinees alike. Because researchers often must manage the tension between limited testing time and measuring numerous constructs reliably, a short and effective measure of working memory capacity would often be a major practical benefit in future research efforts. The current study developed a shortened computerized domain-general measure of working memory capacity by representatively sampling items from three existing complex working memory span tasks: operation span, reading span, and symmetry span. Using a large archival data set (Study 1, N = 4,845), we developed and applied a principled strategy for developing the reduced measure, based on testing a series of confirmatory factor analysis models. Adequate fit indices from these models lent support to this strategy. The resulting shortened measure was then administered to a second independent sample (Study 2, N = 172), demonstrating that the new measure saves roughly 15 min (30%) of testing time on average, and even up to 25 min depending on the test-taker. On the basis of these initial promising findings, several directions for future research are discussed.

Crystal Structure of the FERM Domain of Focal Adhesion Kinase

International Nuclear Information System (INIS)

Ceccarelli, D.; Song, H.; Poy, F.; Schaller, M.; Eck, M.

2006-01-01

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that localizes to focal adhesions in adherent cells. Through phosphorylation of proteins assembled at the cytoplasmic tails of integrins, FAK promotes signaling events that modulate cellular growth, survival, and migration. The amino-terminal region of FAK contains a region of sequence homology with band 4.1 and ezrin/radixin/moesin (ERM) proteins termed a FERM domain. FERM domains are found in a variety of signaling and cytoskeletal proteins and are thought to mediate intermolecular interactions with partner proteins and phospholipids at the plasma membrane and intramolecular regulatory interactions. Here we report two crystal structures of an NH2-terminal fragment of avian FAK containing the FERM domain and a portion of the regulatory linker that connects the FERM and kinase domains. The tertiary folds of the three subdomains (F1, F2, and F3) are similar to those of known FERM structures despite low sequence conservation. Differences in the sequence and relative orientation of the F3 subdomain alters the nature of the interdomain interface, and the phosphoinositide binding site found in ERM family FERM domains is not present in FAK. A putative protein interaction site on the F3 lobe is masked by the proximal region of the linker. Additionally, in one structure the adjacent Src SH3 and SH2 binding sites in the linker associate with the surfaces of the F3 and F1 lobes, respectively. These structural features suggest the possibility that protein interactions of the FAK FERM domain can be regulated by binding of Src kinases to the linker segment

A Motivational Theory of Life-Span Development

Science.gov (United States)

Heckhausen, Jutta; Wrosch, Carsten; Schulz, Richard

2010-01-01

This article had four goals. First, the authors identified a set of general challenges and questions that a life-span theory of development should address. Second, they presented a comprehensive account of their Motivational Theory of Life-Span Development. They integrated the model of optimization in primary and secondary control and the…

The use of passwords to introduce theconcepts of spanning set and span

Directory of Open Access Journals (Sweden)

Andrea Cárcamo

2017-01-01

Full Text Available The aim of this paper is to present a proposal for teaching linear algebra based on heuristic of emergent models and mathematical modelling. This proposal begins with a problematic situation  related  to  the  creation  and  use  of  secure  passwords,  which  leads  first-year  students  of  engineering  toward  the  construction  of  the  concepts  of  spanning  set  and  span. The  proposal  is  designed  from  the  results  of  the  two  cycles  of  experimentation  teaching, design-based  research,  which  give  evidence  that  allows  students  to  progress  from  a  situation in a real context to the concepts of linear algebra. This proposal, previously adapted, could have similar results when applied to another group of students.

Structure of a WW domain-containing fragment of dystrophin complexed with {beta}-dystroglycan.

Energy Technology Data Exchange (ETDEWEB)

Huang, X.; Poy, F.; Zhang, R.; Joachimiak, A.; Sudol, M.; Eck, M. J.; Biosciences Division; Dana Farber Cancer Inst.; Harvard Medical School; Mount Sinai School of Medicine

2000-08-01

Dystrophin and {beta}-dystroglycan are components of the dystrophin--glycoprotein complex (DGC), a multimolecular assembly that spans the cell membrane and links the actin cytoskeleton to the extracellular basal lamina. Defects in the dystrophin gene are the cause of Duchenne and Becker muscular dystrophies. The C-terminal region of dystrophin binds the cytoplasmic tail of {beta}-dystroglycan, in part through the interaction of its WW domain with a proline-rich motif in the tail of {beta}-dystroglycan. Here we report the crystal structure of this portion of dystrophin in complex with the proline-rich binding site in {beta}-dystroglycan. The structure shows that the dystrophin WW domain is embedded in an adjacent helical region that contains two EF-hand-like domains. The {beta}-dystroglycan peptide binds a composite surface formed by the WW domain and one of these EF-hands. Additionally, the structure reveals striking similarities in the mechanisms of proline recognition employed by WW domains and SH3 domains.

Self-esteem development across the life span: a longitudinal study with a large sample from Germany.

Science.gov (United States)

Orth, Ulrich; Maes, Jürgen; Schmitt, Manfred

2015-02-01

The authors examined the development of self-esteem across the life span. Data came from a German longitudinal study with 3 assessments across 4 years of a sample of 2,509 individuals ages 14 to 89 years. The self-esteem measure used showed strong measurement invariance across assessments and birth cohorts. Latent growth curve analyses indicated that self-esteem follows a quadratic trajectory across the life span, increasing during adolescence, young adulthood, and middle adulthood, reaching a peak at age 60 years, and then declining in old age. No cohort effects on average levels of self-esteem or on the shape of the trajectory were found. Moreover, the trajectory did not differ across gender, level of education, or for individuals who had lived continuously in West versus East Germany (i.e., the 2 parts of Germany that had been separate states from 1949 to 1990). However, the results suggested that employment status, household income, and satisfaction in the domains of work, relationships, and health contribute to a more positive life span trajectory of self-esteem. The findings have significant implications, because they call attention to developmental stages in which individuals may be vulnerable because of low self-esteem (such as adolescence and old age) and to factors that predict successful versus problematic developmental trajectories. PsycINFO Database Record (c) 2015 APA, all rights reserved.

Structural studies of bacterial transcriptional regulatory proteins by multidimensional heteronuclear NMR

Energy Technology Data Exchange (ETDEWEB)

Volkman, Brian Finley [Univ. of California, Berkeley, CA (United States)

1995-02-01

Nuclear magnetic resonance spectroscopy was used to elucidate detailed structural information for peptide and protein molecules. A small peptide was designed and synthesized, and its three-dimensional structure was calculated using distance information derived from two-dimensional NMR measurements. The peptide was used to induce antibodies in mice, and the cross-reactivity of the antibodies with a related protein was analyzed with enzyme-linked immunosorbent assays. Two proteins which are involved in regulation of transcription in bacteria were also studied. The ferric uptake regulation (Fur) protein is a metal-dependent repressor which controls iron uptake in bacteria. Two- and three-dimensional NMR techniques, coupled with uniform and selective isotope labeling allowed the nearly complete assignment of the resonances of the metal-binding domain of the Fur protein. NTRC is a transcriptional enhancer binding protein whose N-terminal domain is a "receiver domain" in the family of "two-component" regulatory systems. Phosphorylation of the N-terminal domain of NTRC activates the initiation of transcription of aeries encoding proteins involved in nitrogen regulation. Three- and four-dimensional NMR spectroscopy methods have been used to complete the resonance assignments and determine the solution structure of the N-terminal receiver domain of the NTRC protein. Comparison of the solution structure of the NTRC receiver domain with the crystal structures of the homologous protein CheY reveals a very similar fold, with the only significant difference being the position of helix 4 relative to the rest of the protein. The determination of the structure of the NTRC receiver domain is the first step toward understanding a mechanism of signal transduction which is common to many bacterial regulatory systems.

EU Regulation of E-Commercspan>e A Commentary

NARCIS (Netherlands)

Lodder, A.R.; Murray, A.D.

2017-01-01

For the last twenty years the European Union has been extremely active in the field of e-commercspan>e. This important new book addresses the key pieces of EU legislation in the field of e-commercspan>e, including the E-Commercspan>e Directive, the Services Directive, the Consumer Directive, the General Data

A role for chromatin topology in imprinted domain regulation.

Science.gov (United States)

MacDonald, William A; Sachani, Saqib S; White, Carlee R; Mann, Mellissa R W

2016-02-01

Recently, many advancements in genome-wide chromatin topology and nuclear architecture have unveiled the complex and hidden world of the nucleus, where chromatin is organized into discrete neighbourhoods with coordinated gene expression. This includes the active and inactive X chromosomes. Using X chromosome inactivation as a working model, we utilized publicly available datasets together with a literature review to gain insight into topologically associated domains, lamin-associated domains, nucleolar-associating domains, scaffold/matrix attachment regions, and nucleoporin-associated chromatin and their role in regulating monoallelic expression. Furthermore, we comprehensively review for the first time the role of chromatin topology and nuclear architecture in the regulation of genomic imprinting. We propose that chromatin topology and nuclear architecture are important regulatory mechanisms for directing gene expression within imprinted domains. Furthermore, we predict that dynamic changes in chromatin topology and nuclear architecture play roles in tissue-specific imprint domain regulation during early development and differentiation.

Promoting prosocial behavior and self-regulatory skills in preschool children through a mindfulness-based Kindness Curriculum.

Science.gov (United States)

Flook, Lisa; Goldberg, Simon B; Pinger, Laura; Davidson, Richard J

2015-01-01

Self-regulatory abilities are robust predictors of important outcomes across the life span, yet they are rarely taught explicitly in school. Using a randomized controlled design, the present study investigated the effects of a 12-week mindfulness-based Kindness Curriculum (KC) delivered in a public school setting on executive function, self-regulation, and prosocial behavior in a sample of 68 preschool children. The KC intervention group showed greater improvements in social competence and earned higher report card grades in domains of learning, health, and social-emotional development, whereas the control group exhibited more selfish behavior over time. Interpretation of effect sizes overall indicate small to medium effects favoring the KC group on measures of cognitive flexibility and delay of gratification. Baseline functioning was found to moderate treatment effects with KC children initially lower in social competence and executive functioning demonstrating larger gains in social competence relative to the control group. These findings, observed over a relatively short intervention period, support the promise of this program for promoting self-regulation and prosocial behavior in young children. They also support the need for future investigation of program implementation across diverse settings.

Expression, purification, crystallization and preliminary X-ray analysis of calmodulin in complex with the regulatory domain of the plasma-membrane Ca2+-ATPase ACA8

International Nuclear Information System (INIS)

Tidow, Henning; Hein, Kim L.; Baekgaard, Lone; Palmgren, Michael G.; Nissen, Poul

2010-01-01

Plant plasma-membrane Ca 2+ -ATPase is regulated via binding of calmodulin to its autoinhibitory N-terminal domain. In this study, the expression, purification, crystallization and preliminary X-ray diffraction analysis of this protein complex from A. thaliana are reported. Plasma-membrane Ca 2+ -ATPases (PMCAs) are calcium pumps that expel Ca 2+ from eukaryotic cells to maintain overall Ca 2+ homoeostasis and to provide local control of intracellular Ca 2+ signalling. They are of major physiological importance, with different isoforms being essential, for example, for presynaptic and postsynaptic Ca 2+ regulation in neurons, feedback signalling in the heart and sperm motility. In the resting state, PMCAs are autoinhibited by binding of their C-terminal (in mammals) or N-terminal (in plants) tail to two major intracellular loops. Activation requires the binding of calcium-bound calmodulin (Ca 2+ -CaM) to this tail and a conformational change that displaces the autoinhibitory tail from the catalytic domain. The complex between calmodulin and the regulatory domain of the plasma-membrane Ca 2+ -ATPase ACA8 from Arabidopsis thaliana has been crystallized. The crystals belonged to space group C2, with unit-cell parameters a = 176.8, b = 70.0, c = 69.8 Å, β = 113.2°. A complete data set was collected to 3.0 Å resolution and structure determination is in progress in order to elucidate the mechanism of PMCA activation by calmodulin

Diferença entre span verbal e visual nos gêneros: estudo piloto Difference between verbal and visual span in genders: pilot study

Directory of Open Access Journals (Sweden)

Mariana Cristina Pedrassa Sagrilo

2012-01-01

Full Text Available OBJETIVO: avaliar a memória de trabalho analisando a capacidade de retenção de estímulos auditivos (span verbal e visuais (span visual e estabelecer a relação com o gênero (masculino e feminino. MÉTODO: participaram deste estudo 20 crianças entre seis anos e cinco meses e sete anos, sendo 10 sujeitos do sexo masculino e 10 sujeitos do sexo feminino. Todos os sujeitos foram submetidos às provas de avaliação do span verbal e visual em ordem direta e inversa. RESULTADOS: apenas na prova de palavras dissílabas com fonologia semelhante e semântica diferente do span verbal, houve variância significante entre os gêneros. As crianças do sexo feminino apresentaram melhor desempenho em relação ao outro gênero, bem como maior capacidade de retenção de palavras dissílabas com fonologia e semântica diferentes. No span visual (ordem direta e inversa as crianças do sexo masculino obtiveram melhor desempenho, apesar de não ter diferenças significantes. Em relação à idade não houve diferença de retenção de estímulos. CONCLUSÃO: as crianças do sexo feminino, neste estudo, apresentaram tendência à melhor desempenho do span verbal e as crianças do sexo masculino tendência a melhor desempenho no span visual. No entanto, o estudo é limitado devido ao reduzido número de participantes na amostra.PURPOSE: to evaluate the working memory analyzing the retention ability of auditory stimuli (verbal span and visual stimuli (visual span, and to establish its relation to gender (male and female. METHOD: 20 subjects - 10 female children and 10 male children - from six and five months to seven years old took part in this study. All subjects were submitted to evaluation tests for both verbal and visual spans in direct and inverse orders. RESULTS: there was a significant variance between genders only in the test involving disyllabic words with phonology similar to and semantics different from verbal span. Female children showed a better

Spanning trees and the Eurozone crisis

Science.gov (United States)

Dias, João

2013-12-01

The sovereign debt crisis in the euro area has not yet been solved and recent developments in Spain and Italy have further deteriorated the situation. In this paper we develop a new approach to analyze the ongoing Eurozone crisis. Firstly, we use Maximum Spanning Trees to analyze the topological properties of government bond rates’ dynamics. Secondly, we combine the information given by both Maximum and Minimum Spanning Trees to obtain a measure of market dissimilarity or disintegration. Thirdly, we extend this measure to include a convenient distance not limited to the interval [0, 2]. Our empirical results show that Maximum Spanning Tree gives an adequate description of the separation of the euro area into two distinct groups: those countries strongly affected by the crisis and those that have remained resilient during this period. The measures of market dissimilarity also reveal a persistent separation of these two groups and, according to our second measure, this separation strongly increased during the period July 2009-March 2012.

The European legal framework regarding e-commercspan>e

NARCIS (Netherlands)

Schaub, M.Y.

2004-01-01

The year 2000 is a memorable year in the history of e-commercspan>e. This is the year of the so-called 'dot.com shake-out'. The year 2000 is also the year the European Union issued its e-commercspan>e directive. The directive means to regulate but also facilitate e-commercspan>e in the internal market, by laying

Inter-domain cross-talk controls the NifA protein activity of Herbaspirillum seropedicae.

Science.gov (United States)

Monteiro, R A; de Souza, E M; Wassem, R; Yates, M G; Pedrosa, F O; Chubatsu, L S

2001-11-09

Herbaspirillum seropedicae is an endophytic diazotroph, which colonizes sugar cane, wheat, rice and maize. The activity of NifA, a transcriptional activator of nif genes in H. seropedicae, is controlled by ammonium ions through a mechanism involving its N-terminal domain. Here we show that this domain interacts specifically in vitro with the N-truncated NifA protein, as revealed by protection against proteolysis, and this interaction caused an inhibitory effect on both the ATPase and DNA-binding activities of the N-truncated NifA protein. We suggest that the N-terminal domain inhibits NifA-dependent transcriptional activation by an inter-domain cross-talk between the catalytic domain of the NifA protein and its regulatory N-terminal domain in response to fixed nitrogen.

The N domain of somatic angiotensin-converting enzyme negatively regulates ectodomain shedding and catalytic activity

OpenAIRE

Woodman, Zenda L.; Schwager, Sylva L. U.; Redelinghuys, Pierre; Carmona, Adriana K.; Ehlers, Mario R. W.; Sturrock, Edward D.

2005-01-01

sACE (somatic angiotensin-converting enzyme) consists of two homologous, N and C domains, whereas the testis isoenzyme [tACE (testis ACE)] consists of a single C domain. Both isoenzymes are shed from the cell surface by a sheddase activity, although sACE is shed much less efficiently than tACE. We hypothesize that the N domain of sACE plays a regulatory role, by occluding a recognition motif on the C domain required for ectodomain shedding and by influencing the catalytic efficiency. To test ...

Evaluating the efficiency of shortcut span protection

DEFF Research Database (Denmark)

Ruepp, Sarah Renée; Dittmann, Lars; Berger, Michael Stübert

2010-01-01

This paper presents a comparison of various recovery methods in terms of capacity efficiency with the underlying aim of reducing control plane load. In particular, a method where recovery requests are bundled towards the destination (Shortcut Span Protection) is evaluated can compared against tra...... traditional recovery methods. The optimization model is presented and our simulation results show that Shortcut Span Protection uses more capacity than the unbundled related methods, but this is compensated by easier control and management of the recovery actions.......This paper presents a comparison of various recovery methods in terms of capacity efficiency with the underlying aim of reducing control plane load. In particular, a method where recovery requests are bundled towards the destination (Shortcut Span Protection) is evaluated can compared against...

On the cardinality of smallest spanning sets of rings | Boudi ...

African Journals Online (AJOL)

Let R = (R, +, ·) be a ring. Then Z ⊆ R is called spanning if the R-module generated by Z is equal to the ring R. A spanning set Z ⊆ R is called smallest if there is no spanning set of smaller cardinality than Z. It will be shown that the cardinality of a smallest spanning set of a ring R is not always decidable. In particular, a ring R ...

Mitigating the Impact of Nurse Manager Large Spans of Control.

Science.gov (United States)

Simpson, Brenda Baird; Dearmon, Valorie; Graves, Rebecca

Nurse managers are instrumental in achievement of organizational and unit performance goals. Greater spans of control for managers are associated with decreased satisfaction and performance. An interprofessional team measured one organization's nurse manager span of control, providing administrative assistant support and transformational leadership development to nurse managers with the largest spans of control. Nurse manager satisfaction and transformational leadership competency significantly improved following the implementation of large span of control mitigation strategies.

Visual working memory span in adults with cochlear implants: Some preliminary findings

Directory of Open Access Journals (Sweden)

Aaron C. Moberly

2017-12-01

Full Text Available Objective: Neurocognitive functions, specifically verbal working memory (WM, contribute to speech recognition in postlingual adults with cochlear implants (CIs and normal-hearing (NH listener shearing degraded speech. Three hypotheses were tested: (1 WM accuracy as assessed using three visual span measures — digits, objects, and symbols — would correlate with recognition scores for spectrally degraded speech (through a CI or when noise-vocoded; (2 WM accuracy would be best for digit span, intermediate for object span, and lowest for symbol span, due to the increasing cognitive demands across these tasks. Likewise, response times, relating to processing demands, would be shortest for digit span, intermediate for object span, and longest for symbol span; (3 CI users would demonstrate poorer and slower performance than NH peers on WM tasks, as a result of less efficient verbally mediated encoding strategies associated with a period of prolonged auditory deprivation. Methods: Cross-sectional study of 30 postlingually deaf adults with CIs and 34 NH controls. Participants were tested for sentence recognition in quiet (CI users or after noise-vocoding (NH peers, along with WM using visual measures of digit span, object span, and symbol span. Results: Of the three measures of WM, digit span scores alone correlated with sentence recognition for CI users; no correlations were found using these three measures for NH peers. As predicted, WM accuracy (and response times were best (and fastest for digit span, intermediate for object span, and worst (and slowest for symbol span. CI users and NH peers demonstrated equivalent WM accuracy and response time for digit span and object span, and similar response times for symbol span, but contrary to our original predictions, CI users demonstrated better accuracy on symbol span than NH peers. Conclusions: Verbal WM assessed using visual tasks relates weakly to sentence recognition for degraded speech. CI users

Size and mobility of lipid domains tuned by geometrical constraints.

Science.gov (United States)

Schütte, Ole M; Mey, Ingo; Enderlein, Jörg; Savić, Filip; Geil, Burkhard; Janshoff, Andreas; Steinem, Claudia

2017-07-25

In the plasma membrane of eukaryotic cells, proteins and lipids are organized in clusters, the latter ones often called lipid domains or "lipid rafts." Recent findings highlight the dynamic nature of such domains and the key role of membrane geometry and spatial boundaries. In this study, we used porous substrates with different pore radii to address precisely the extent of the geometric constraint, permitting us to modulate and investigate the size and mobility of lipid domains in phase-separated continuous pore-spanning membranes (PSMs). Fluorescence video microscopy revealed two types of liquid-ordered ( l o ) domains in the freestanding parts of the PSMs: ( i ) immobile domains that were attached to the pore rims and ( ii ) mobile, round-shaped l o domains within the center of the PSMs. Analysis of the diffusion of the mobile l o domains by video microscopy and particle tracking showed that the domains' mobility is slowed down by orders of magnitude compared with the unrestricted case. We attribute the reduced mobility to the geometric confinement of the PSM, because the drag force is increased substantially due to hydrodynamic effects generated by the presence of these boundaries. Our system can serve as an experimental test bed for diffusion of 2D objects in confined geometry. The impact of hydrodynamics on the mobility of enclosed lipid domains can have great implications for the formation and lateral transport of signaling platforms.

APS, an adaptor molecule containing PH and SH2 domains, has a negative regulatory role in B cell proliferation

International Nuclear Information System (INIS)

Iseki, Masanori; Kubo-Akashi, Chiyomi; Kwon, Sang-Mo; Yamaguchi, Akiko; Takatsu, Kiyoshi; Takaki, Satoshi

2005-01-01

Adaptor molecule containing PH and SH2 domains (APS) is an intracellular adaptor protein that forms part of an adaptor family along with Lnk and SH2-B. APS transcripts are expressed in various tissues including brain, kidney, and muscle, as well as in splenic B cells but not in T cells. We investigated the functions of APS in B cell development and activation by generating APS-transgenic (APS-Tg) mice that overexpressed APS in lymphocytes. The number of B-1 cells in the peritoneal cavity was reduced in APS-Tg mice, as were B-2 cells in the spleen. B cell development in the bone marrow was partially impaired at the transition stage from proliferating large pre-B to small pre-B cells. B cell proliferation induced by B cell receptor (BCR) crosslinking but not by other B cell mitogens was also impaired in APS-Tg mice. APS co-localized with BCR complexes and filamentous actin in activated APS-Tg B cells. Thus, APS appears to play novel negative regulatory roles in BCR signaling, actin reorganization pathways, and control of compartment sizes of B-lineage cells

Regulatory agencies and regulatory risk

OpenAIRE

Knieps, Günter; Weiß, Hans-Jörg

2008-01-01

The aim of this paper is to show that regulatory risk is due to the discretionary behaviour of regulatory agencies, caused by a too extensive regulatory mandate provided by the legislator. The normative point of reference and a behavioural model of regulatory agencies based on the positive theory of regulation are presented. Regulatory risk with regard to the future behaviour of regulatory agencies is modelled as the consequence of the ex ante uncertainty about the relative influence of inter...

Visual-Attentional Span and Lexical ­Decision in Skilled Adult Readers

Science.gov (United States)

Holmes, Virginia M.; Dawson, Georgia

2014-01-01

The goal of the study was to examine the association between visual-attentional span and lexical decision in skilled adult readers. In the span tasks, an array of letters was presented briefly and recognition or production of a single cued letter (partial span) or production of all letters (whole span) was required. Independently of letter…

Examining the locus of age effects on complex span tasks.

Science.gov (United States)

McCabe, Jennifer; Hartman, Marilyn

2003-09-01

To investigate the locus of age effects on complex span tasks, the authors evaluated the contributions of working memory functions and processing speed. Age differences were found in measures of storage capacity, language processing speed, and lower level speed. Statistically controlling for each of these in hierarchical regressions substantially reduced, but did not eliminate, the complex span age effect. Accounting for lower level speed and storage, however, removed essentially the entire age effect, suggesting that both functions play important and independent roles. Additional evidence for the role of storage capacity was the absence of complex span age differences with span size calibrated to individual word span performance. Explanations for age differences based on inhibition and concurrent task performamce were not supported.

WildSpan: mining structured motifs from protein sequences

Directory of Open Access Journals (Sweden)

Chen Chien-Yu

2011-03-01

Full Text Available Abstract Background Automatic extraction of motifs from biological sequences is an important research problem in study of molecular biology. For proteins, it is desired to discover sequence motifs containing a large number of wildcard symbols, as the residues associated with functional sites are usually largely separated in sequences. Discovering such patterns is time-consuming because abundant combinations exist when long gaps (a gap consists of one or more successive wildcards are considered. Mining algorithms often employ constraints to narrow down the search space in order to increase efficiency. However, improper constraint models might degrade the sensitivity and specificity of the motifs discovered by computational methods. We previously proposed a new constraint model to handle large wildcard regions for discovering functional motifs of proteins. The patterns that satisfy the proposed constraint model are called W-patterns. A W-pattern is a structured motif that groups motif symbols into pattern blocks interleaved with large irregular gaps. Considering large gaps reflects the fact that functional residues are not always from a single region of protein sequences, and restricting motif symbols into clusters corresponds to the observation that short motifs are frequently present within protein families. To efficiently discover W-patterns for large-scale sequence annotation and function prediction, this paper first formally introduces the problem to solve and proposes an algorithm named WildSpan (sequential pattern mining across large wildcard regions that incorporates several pruning strategies to largely reduce the mining cost. Results WildSpan is shown to efficiently find W-patterns containing conserved residues that are far separated in sequences. We conducted experiments with two mining strategies, protein-based and family-based mining, to evaluate the usefulness of W-patterns and performance of WildSpan. The protein-based mining mode

Effects of Working Memory Capacity and Domain Knowledge on Recall for Grocery Prices.

Science.gov (United States)

Bermingham, Douglas; Gardner, Michael K; Woltz, Dan J

2016-01-01

Hambrick and Engle (2002) proposed 3 models of how domain knowledge and working memory capacity may work together to influence episodic memory: a "rich-get-richer" model, a "building blocks" model, and a "compensatory" model. Their results supported the rich-get-richer model, although later work by Hambrick and Oswald (2005) found support for a building blocks model. We investigated the effects of domain knowledge and working memory on recall of studied grocery prices. Working memory was measured with 3 simple span tasks. A contrast of realistic versus fictitious foods in the episodic memory task served as our manipulation of domain knowledge, because participants could not have domain knowledge of fictitious food prices. There was a strong effect for domain knowledge (realistic food-price pairs were easier to remember) and a moderate effect for working memory capacity (higher working memory capacity produced better recall). Furthermore, the interaction between domain knowledge and working memory produced a small but significant interaction in 1 measure of price recall. This supported the compensatory model and stands in contrast to previous research.

Broadening microwave absorption via a multi-domain structure

Directory of Open Access Journals (Sweden)

Zhengwang Liu

2017-04-01

Full Text Available Materials with a high saturation magnetization have gained increasing attention in the field of microwave absorption; therefore, the magnetization value depends on the magnetic configuration inside them. However, the broad-band absorption in the range of microwave frequency (2-18 GHz is a great challenge. Herein, the three-dimensional (3D Fe/C hollow microspheres are constructed by iron nanocrystals permeating inside carbon matrix with a saturation magnetization of 340 emu/g, which is 1.55 times as that of bulk Fe, unexpectedly. Electron tomography, electron holography, and Lorentz transmission electron microscopy imaging provide the powerful testimony about Fe/C interpenetration and multi-domain state constructed by vortex and stripe domains. Benefiting from the unique chemical and magnetic microstructures, the microwave minimum absorption is as strong as −55 dB and the bandwidth (<−10 dB spans 12.5 GHz ranging from 5.5 to 18 GHz. Morphology and distribution of magnetic nano-domains can be facilely regulated by a controllable reduction sintering under H2/Ar gas and an optimized temperature over 450–850 °C. The findings might shed new light on the synthesis strategies of the materials with the broad-band frequency and understanding the association between multi-domain coupling and microwave absorption performance.

Mapping the developmental constraints on working memory span performance.

Science.gov (United States)

Bayliss, Donna M; Jarrold, Christopher; Baddeley, Alan D; Gunn, Deborah M; Leigh, Eleanor

2005-07-01

This study investigated the constraints underlying developmental improvements in complex working memory span performance among 120 children of between 6 and 10 years of age. Independent measures of processing efficiency, storage capacity, rehearsal speed, and basic speed of processing were assessed to determine their contribution to age-related variance in complex span. Results showed that developmental improvements in complex span were driven by 2 age-related but separable factors: 1 associated with general speed of processing and 1 associated with storage ability. In addition, there was an age-related contribution shared between working memory, processing speed, and storage ability that was important for higher level cognition. These results pose a challenge for models of complex span performance that emphasize the importance of processing speed alone.

Performance, Career Dynamics, and Span of Control

DEFF Research Database (Denmark)

Smeets, Valerie Anne Rolande; Waldman, Michael; Warzynski, Frederic Michel Patrick

that higher ability managers should supervise more subordinates, or equivalently, have a larger span of control. And although some of this theory’s predictions have been empirically investigated, there has been little systematic investigation of the theory’s predictions concerning span of control....... In this paper we first extend the theoretical literature on the scale-of-operations effect to allow firms’ beliefs concerning a manager’s ability to evolve over the manager’s career, where much of our focus is the determinants of span of control. We then empirically investigate testable predictions from......There is an extensive theoretical literature based on what is called the scale-of-operations effect, i.e., the idea that the return to managerial ability is higher the more resources the manager influences with his or her decisions. This idea leads to various testable predictions including...

Dynamics of investor spanning trees around dot-com bubble.

Directory of Open Access Journals (Sweden)

Sindhuja Ranganathan

Full Text Available We identify temporal investor networks for Nokia stock by constructing networks from correlations between investor-specific net-volumes and analyze changes in the networks around dot-com bubble. The analysis is conducted separately for households, financial, and non-financial institutions. Our results indicate that spanning tree measures for households reflected the boom and crisis: the maximum spanning tree measures had a clear upward tendency in the bull markets when the bubble was building up, and, even more importantly, the minimum spanning tree measures pre-reacted the burst of the bubble. At the same time, we find less clear reactions in the minimal and maximal spanning trees of non-financial and financial institutions around the bubble, which suggests that household investors can have a greater herding tendency around bubbles.

Dynamics of investor spanning trees around dot-com bubble.

Science.gov (United States)

Ranganathan, Sindhuja; Kivelä, Mikko; Kanniainen, Juho

2018-01-01

We identify temporal investor networks for Nokia stock by constructing networks from correlations between investor-specific net-volumes and analyze changes in the networks around dot-com bubble. The analysis is conducted separately for households, financial, and non-financial institutions. Our results indicate that spanning tree measures for households reflected the boom and crisis: the maximum spanning tree measures had a clear upward tendency in the bull markets when the bubble was building up, and, even more importantly, the minimum spanning tree measures pre-reacted the burst of the bubble. At the same time, we find less clear reactions in the minimal and maximal spanning trees of non-financial and financial institutions around the bubble, which suggests that household investors can have a greater herding tendency around bubbles.

Developmental Dyslexia: The Visual Attention Span Deficit Hypothesis

Science.gov (United States)

Bosse, Marie-Line; Tainturier, Marie Josephe; Valdois, Sylviane

2007-01-01

The visual attention (VA) span is defined as the amount of distinct visual elements which can be processed in parallel in a multi-element array. Both recent empirical data and theoretical accounts suggest that a VA span deficit might contribute to developmental dyslexia, independently of a phonological disorder. In this study, this hypothesis was…

Noise Reduction with Optimal Variable Span Linear Filters

DEFF Research Database (Denmark)

Jensen, Jesper Rindom; Benesty, Jacob; Christensen, Mads Græsbøll

2016-01-01

In this paper, the problem of noise reduction is addressed as a linear filtering problem in a novel way by using concepts from subspace-based enhancement methods, resulting in variable span linear filters. This is done by forming the filter coefficients as linear combinations of a number...... included in forming the filter. Using these concepts, a number of different filter designs are considered, like minimum distortion, Wiener, maximum SNR, and tradeoff filters. Interestingly, all these can be expressed as special cases of variable span filters. We also derive expressions for the speech...... demonstrate the advantages and properties of the variable span filter designs, and their potential performance gain compared to widely used speech enhancement methods....

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

International Nuclear Information System (INIS)

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

2010-01-01

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

Enhancer-binding proteins with a forkhead-associated domain and the sigma(54) regulon in Myxococcus xanthus fruiting body development

DEFF Research Database (Denmark)

Jelsbak, Lars; Givskov, Michael Christian; Kaiser, D.

2005-01-01

-binding proteins. Here we report the finding of an unusual group of 12 genes encoding sigma(54)-dependent enhancer-binding proteins containing a forkhead-associated (FHA) domain as their N-terminal sensory domain. FHA domains in other proteins recognize phosphothreonine residues. An insertion mutation in one...... donor cell. Because FHA domains respond to phosphothreonine-containing proteins, these results suggest a regulatory link to the abundant Ser/Thr protein kinases in M. xanthus....

Dual boundary spanning

DEFF Research Database (Denmark)

Li-Ying, Jason

2016-01-01

The extant literature runs short in understanding openness of innovation regarding and the different pathways along which internal and external knowledge resources can be combined. This study proposes a unique typology for outside-in innovations based on two distinct ways of boundary spanning......: whether an innovation idea is created internally or externally and whether an innovation process relies on external knowledge resources. This yields four possible types of innovation, which represent the nuanced variation of outside-in innovations. Using historical data from Canada for 1945...

Senescence-associated barley NAC (NAM, ATAF1,2, CUC) transcription factor interacts with radical-induced cell death 1 through a disordered regulatory domain

DEFF Research Database (Denmark)

Kjaersgaard, Trine; Jensen, Michael K; Christiansen, Michael W

2011-01-01

as a transcriptional activator suggesting that an involvement of HvNAC013 and HvNAC005 in senescence will be different. HvNAC013 interacted with barley radical-induced cell death 1 (RCD1) via the very C-terminal part of its TRD, outside of the region containing the LP motif. No significant secondary structure...... (NAM, ATAF1,2, CUC) TF family are up-regulated during senescence in barley (Hordeum vulgare). Both HvNAC005 and HvNAC013 bound the conserved NAC DNA target sequence. Computational and biophysical analyses showed that both proteins are intrinsically disordered in their large C-terminal domains, which...... was induced in the HvNAC013 TRD upon interaction with RCD1. RCD1 also interacted with regions dominated by intrinsic disorder in TFs of the MYB and basic helix-loop-helix families. We propose that RCD1 is a regulatory protein capable of interacting with many different TFs by exploiting their intrinsic...

Exploring self-regulatory strategies for eating behaviour in Danish adolescents

DEFF Research Database (Denmark)

Nureeva, Liliya; Brunsø, Karen; Lähteenmäki, Liisa

2016-01-01

– Focusing on improving adolescents’ self-regulatory skills in the domain of eating behaviour is a promising approach in developing future interventions. Originality/value – The present article explores self-regulatory strategies for eating behaviour in adolescence and discusses their relevance.......Purpose – Healthy eating behaviour in adolescence may be negatively affected by lack of self-regulation. The purpose of this paper is to discuss strategies for regulating eating behaviour as formulated by adolescents themselves. Design/methodology/approach – Self-regulatory strategies were elicited...... with concept mapping, which is a group-based method. Three meetings were conducted with each of four school classes in Denmark. Participants in the 12-15-year age group were recruited for the study. At the first meeting, participants had to complete the phrase “Things I can do to ensure my healthy eating are...

Exploring boundary-spanning practices among creativity managers

DEFF Research Database (Denmark)

Andersen, Poul Houman; Kragh, Hanne

2015-01-01

Purpose – External inputs are critical for organisational creativity. In order to bridge different thought worlds and cross-organisational barriers, managers must initiate and motivate boundary spanning processes. The purpose of this paper is to explore how boundary spanners manage creativity...... and observation. Findings – Three meta-practices used by managers to manage boundary-spanning creative projects are presented: defining the creative space, making space for creativity and acting in the creative space. These practices are detailed in seven case studies of creative projects. Research limitations...

A Distributed Spanning Tree Algorithm

DEFF Research Database (Denmark)

Johansen, Karl Erik; Jørgensen, Ulla Lundin; Nielsen, Sven Hauge

We present a distributed algorithm for constructing a spanning tree for connected undirected graphs. Nodes correspond to processors and edges correspond to two-way channels. Each processor has initially a distinct identity and all processors perform the same algorithm. Computation as well...

Higher dimensional curved domain walls on Kähler surfaces

Energy Technology Data Exchange (ETDEWEB)

Akbar, Fiki T., E-mail: ftakbar@fi.itb.ac.id [Theoretical Physics Laboratory, Theoretical High Energy Physics and Instrumentation Research Group, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha no. 10 Bandung, 40132 (Indonesia); Gunara, Bobby E., E-mail: bobby@fi.itb.ac.id [Theoretical Physics Laboratory, Theoretical High Energy Physics and Instrumentation Research Group, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha no. 10 Bandung, 40132 (Indonesia); Radjabaycolle, Flinn C. [Theoretical Physics Laboratory, Theoretical High Energy Physics and Instrumentation Research Group, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha no. 10 Bandung, 40132 (Indonesia); Departement of Physics, Faculty of Mathematics and Natural Sciences, Cendrawasih University, Jl. Kampwolker Kampus Uncen Baru Waena-Jayapura 99351 (Indonesia); Wijaya, Rio N. [Theoretical Physics Laboratory, Theoretical High Energy Physics and Instrumentation Research Group, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha no. 10 Bandung, 40132 (Indonesia)

2017-03-15

In this paper we study some aspects of curved BPS-like domain walls in higher dimensional gravity theory coupled to scalars where the scalars span a complex Kähler surface with scalar potential turned on. Assuming that a fake superpotential has a special form which depends on Kähler potential and a holomorphic function, we prove that BPS-like equations have a local unique solution. Then, we analyze the vacuum structure of the theory including their stability using dynamical system and their existence in ultraviolet-infrared regions using renormalization group flow.

Higher dimensional curved domain walls on Kähler surfaces

International Nuclear Information System (INIS)

Akbar, Fiki T.; Gunara, Bobby E.; Radjabaycolle, Flinn C.; Wijaya, Rio N.

2017-01-01

In this paper we study some aspects of curved BPS-like domain walls in higher dimensional gravity theory coupled to scalars where the scalars span a complex Kähler surface with scalar potential turned on. Assuming that a fake superpotential has a special form which depends on Kähler potential and a holomorphic function, we prove that BPS-like equations have a local unique solution. Then, we analyze the vacuum structure of the theory including their stability using dynamical system and their existence in ultraviolet-infrared regions using renormalization group flow.

Controlling the spotlight of attention: visual span size and flexibility in schizophrenia.

Science.gov (United States)

Elahipanah, Ava; Christensen, Bruce K; Reingold, Eyal M

2011-10-01

The current study investigated the size and flexible control of visual span among patients with schizophrenia during visual search performance. Visual span is the region of the visual field from which one extracts information during a single eye fixation, and a larger visual span size is linked to more efficient search performance. Therefore, a reduced visual span may explain patients' impaired performance on search tasks. The gaze-contingent moving window paradigm was used to estimate the visual span size of patients and healthy participants while they performed two different search tasks. In addition, changes in visual span size were measured as a function of two manipulations of task difficulty: target-distractor similarity and stimulus familiarity. Patients with schizophrenia searched more slowly across both tasks and conditions. Patients also demonstrated smaller visual span sizes on the easier search condition in each task. Moreover, healthy controls' visual span size increased as target discriminability or distractor familiarity increased. This modulation of visual span size, however, was reduced or not observed among patients. The implications of the present findings, with regard to previously reported visual search deficits, and other functional and structural abnormalities associated with schizophrenia, are discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

Life Span Exercise Among Elite Intercollegiate Student Athletes

OpenAIRE

Sorenson, Shawn C.; Romano, Russell; Azen, Stanley P.; Schroeder, E. Todd; Salem, George J.

2015-01-01

Background: Despite prominent public attention, data on life span health and exercise outcomes among elite, competitive athletes are sparse and do not reflect the diversity of modern athletes. Hypothesis: Life span exercise behavior differs between National Collegiate Athletic Association (NCAA) student athletes and a nonathlete control group. Sustained exercise is associated with improved cardiopulmonary health outcomes. Study Design: Cross-sectional, descriptive epidemiology study. Level of...

Chapter 4: Regional magnetic domains of the Circum-Arctic: A framework for geodynamic interpretation

Science.gov (United States)

Saltus, R.W.; Miller, E.L.; Gaina, C.; Brown, P.J.

2011-01-01

We identify and discuss 57 magnetic anomaly pattern domains spanning the Circum-Arctic. The domains are based on analysis of a new Circum-Arctic data compilation. The magnetic anomaly patterns can be broadly related to general geodynamic classification of the crust into stable, deformed (magnetic and nonmagnetic), deep magnetic high, oceanic and large igneous province domains. We compare the magnetic domains with topography/bathymetry, regional geology, regional free air gravity anomalies and estimates of the relative magnetic 'thickness' of the crust. Most of the domains and their geodynamic classification assignments are consistent with their topographic/bathymetric and geological expression. A few of the domains are potentially controversial. For example, the extent of the Iceland Faroe large igneous province as identified by magnetic anomalies may disagree with other definitions for this feature. Also the lack of definitive magnetic expression of oceanic crust in Baffin Bay, the Norwegian-Greenland Sea and the Amerasian Basin is at odds with some previous interpretations. The magnetic domains and their boundaries provide clues for tectonic models and boundaries within this poorly understood portion of the globe. ?? 2011 The Geological Society of London.

A distributed spanning tree algorithm

DEFF Research Database (Denmark)

Johansen, Karl Erik; Jørgensen, Ulla Lundin; Nielsen, Svend Hauge

1988-01-01

We present a distributed algorithm for constructing a spanning tree for connected undirected graphs. Nodes correspond to processors and edges correspond to two way channels. Each processor has initially a distinct identity and all processors perform the same algorithm. Computation as well as comm...

Elucidating MicroRNA Regulatory Networks Using Transcriptional, Post-transcriptional, and Histone Modification Measurements

Directory of Open Access Journals (Sweden)

Sara J.C. Gosline

2016-01-01

Full Text Available MicroRNAs (miRNAs regulate diverse biological processes by repressing mRNAs, but their modest effects on direct targets, together with their participation in larger regulatory networks, make it challenging to delineate miRNA-mediated effects. Here, we describe an approach to characterizing miRNA-regulatory networks by systematically profiling transcriptional, post-transcriptional and epigenetic activity in a pair of isogenic murine fibroblast cell lines with and without Dicer expression. By RNA sequencing (RNA-seq and CLIP (crosslinking followed by immunoprecipitation sequencing (CLIP-seq, we found that most of the changes induced by global miRNA loss occur at the level of transcription. We then introduced a network modeling approach that integrated these data with epigenetic data to identify specific miRNA-regulated transcription factors that explain the impact of miRNA perturbation on gene expression. In total, we demonstrate that combining multiple genome-wide datasets spanning diverse regulatory modes enables accurate delineation of the downstream miRNA-regulated transcriptional network and establishes a model for studying similar networks in other systems.

Biomarkers of a five-domain translational substrate for schizophrenia and schizoaffective psychosis.

Science.gov (United States)

Fryar-Williams, Stephanie; Strobel, Jörg E

2015-01-01

The Mental Health Biomarker Project (2010-2014) selected commercial biochemistry markers related to monoamine synthesis and metabolism and measures of visual and auditory processing performance. Within a case-control discovery design with exclusion criteria designed to produce a highly characterised sample, results from 67 independently DSM IV-R-diagnosed cases of schizophrenia and schizoaffective disorder were compared with those from 67 control participants selected from a local hospital, clinic and community catchment area. Participants underwent protocol-based diagnostic-checking, functional-rating, biological sample-collection for thirty candidate markers and sensory-processing assessment. Fifteen biomarkers were identified on ROC analysis. Using these biomarkers, odds ratios, adjusted for a case-control design, indicated that schizophrenia and schizoaffective disorder were highly associated with dichotic listening disorder, delayed visual processing, low visual span, delayed auditory speed of processing, low reverse digit span as a measure of auditory working memory and elevated levels of catecholamines. Other nutritional and biochemical biomarkers were identified as elevated hydroxyl pyrroline-2-one as a marker of oxidative stress, vitamin D, B6 and folate deficits with elevation of serum B12 and free serum copper to zinc ratio. When individual biomarkers were ranked by odds ratio and correlated with clinical severity, five functional domains of visual processing, auditory processing, oxidative stress, catecholamines and nutritional-biochemical variables were formed. When the strengths of their inter-domain relationships were predicted by Lowess (non-parametric) regression, predominant bidirectional relationships were found between visual processing and catecholamine domains. At a cellular level, the nutritional-biochemical domain exerted a pervasive influence on the auditory domain as well as on all other domains. The findings of this biomarker research

The HTLV-1 Tax protein binding domain of cyclin-dependent kinase 4 (CDK4 includes the regulatory PSTAIRE helix

Directory of Open Access Journals (Sweden)

Grassmann Ralph

2005-09-01

Full Text Available Abstract Background The Tax oncoprotein of human T-cell leukemia virus type 1 (HTLV-1 is leukemogenic in transgenic mice and induces permanent T-cell growth in vitro. It is found in active CDK holoenzyme complexes from adult T-cell leukemia-derived cultures and stimulates the G1- to-S phase transition by activating the cyclin-dependent kinase (CDK CDK4. The Tax protein directly and specifically interacts with CDK4 and cyclin D2 and binding is required for enhanced CDK4 kinase activity. The protein-protein contact between Tax and the components of the cyclin D/CDK complexes increases the association of CDK4 and its positive regulatory subunit cyclin D and renders the complex resistant to p21CIP inhibition. Tax mutants affecting the N-terminus cannot bind cyclin D and CDK4. Results To analyze, whether the N-terminus of Tax is capable of CDK4-binding, in vitro binding -, pull down -, and mammalian two-hybrid analyses were performed. These experiments revealed that a segment of 40 amino acids is sufficient to interact with CDK4 and cyclin D2. To define a Tax-binding domain and analyze how Tax influences the kinase activity, a series of CDK4 deletion mutants was tested. Different assays revealed two regions which upon deletion consistently result in reduced binding activity. These were isolated and subjected to mammalian two-hybrid analysis to test their potential to interact with the Tax N-terminus. These experiments concurrently revealed binding at the N- and C-terminus of CDK4. The N-terminal segment contains the PSTAIRE helix, which is known to control the access of substrate to the active cleft of CDK4 and thus the kinase activity. Conclusion Since the N- and C-terminus of CDK4 are neighboring in the predicted three-dimensional protein structure, it is conceivable that they comprise a single binding domain, which interacts with the Tax N-terminus.

Needs of research for regulatory purposes

International Nuclear Information System (INIS)

Wanner, H.

2010-01-01

Hans Wanner, Swiss Federal Nuclear Safety Inspectorate (ENSI), presented a general overview of regulatory research at the international level based on a preliminary input from international colleagues and observed that the question of active involvement of nuclear regulatory and supervisory bodies in R and D projects has become a topic of increasing interest in recent years even if the way in which research is included in regulatory activities varies from country to country. The range spans from countries with no regulatory R and D activities to countries with extensive activities that are often carried out by independent research organisations acting on behalf of the regulatory body. In a few countries, the regulator and implementer have their research carried out by the same research institutes. As an example H. Wanner explained the organisation of R and D work in Switzerland. He presented the potential merits of R and D work carried out by the regulator and introduced a number of questions that would gain from being addressed at an international level. He stressed that the R and D work performed by the implementer must be comprehensive and there should be, in principle, no need for complementary work by the regulatory body. Nevertheless, R and D work of the regulator has still several merits. It improves the regulator's necessary competence to review the safety case allowing it to rely on the scientific community. It provides the regulator's independence, allowing a different view on the safety case from the implementer's view. By bringing to the fore the scientific and technical ability of the regulator, R and D work by the regulator provides additional confidence to the stakeholders in the credibility of the regulator. There may exist further motivations for the regulator to carry out its own R and D projects, among which is the verification of key safety issues or the investigation of topics not addressed by the implementer, i.e., to fill scientific gaps. The

Ancestral telomere shortening: a countdown that will increase mean life span?

Science.gov (United States)

Hertzog, Radu G

2006-01-01

Like cells, all mammals have a limited life span. Among cells there are a few exceptions (e.g., immortal cells), among mammals not, even if some of them live longer. Many in vitro and in vivo studies support the consensus that telomere length is strongly correlated with life span. At the somatic cellular level, long telomeres have been associated with longer life span. A different situation can be seen in immortal cells, such as cancer, germ and stem cells, where telomeres are maintained by telomerase, a specialized reverse transcriptase that is involved in synthesis of telomeres. Irrespective of telomere length, if telomerase is active, telomeres can be maintained at a sufficient length to ensure cell survival. To the contrary, telomeres shorten progressively with each cell division and when a critical telomere length (Hayflick limit) is reached, the cells undergo senescence and subsequently apoptosis. In mammals, those with the longest telomeres (e.g., mice) have the shortest life span. Furthermore, the shorter the mean telomere length, the longer the mean life span, as observed in humans (10-14 kpb) and bowhead-whales (undetermined telomere length), which have the longest mean life span among mammals. Over the past centuries, human average life span has increased. The hypothesis presented here suggests that this continual increase in the mean life span could be due to a decrease of mean telomere length over the last hundreds years. Actually, the life span is not directly influenced by length of telomeres, but rather by telomere length - dependent gene expression pattern. According to Greider, "rather than average telomere length, it is the shortest telomere length that makes the biggest difference to a cell". In the context of fast-growing global elderly population due to increase in life expectancy, it also seem to be an age related increase in cancer incidence. Nevertheless, extending healthy life span could depend on how good cells achieve, during the

Self-Regulatory Training for Helping Students with Special Needs to Learn Mathematics

Science.gov (United States)

Kang, Yanrong

2010-01-01

Previous research suggests that self-regulation interventions are effective in improving students' self-regulatory skill and school performance in a wide variety of educational domains. Inspired by social cognitive theory (Schunk & Zimmerman, 1997) and goal setting theory (Locke & Latham, 1990), I designed, implemented, and examined the beneficial…

Life-span development of self-esteem and its effects on important life outcomes.

Science.gov (United States)

Orth, Ulrich; Robins, Richard W; Widaman, Keith F

2012-06-01

We examined the life-span development of self-esteem and tested whether self-esteem influences the development of important life outcomes, including relationship satisfaction, job satisfaction, occupational status, salary, positive and negative affect, depression, and physical health. Data came from the Longitudinal Study of Generations. Analyses were based on 5 assessments across a 12-year period of a sample of 1,824 individuals ages 16 to 97 years. First, growth curve analyses indicated that self-esteem increases from adolescence to middle adulthood, reaches a peak at about age 50 years, and then decreases in old age. Second, cross-lagged regression analyses indicated that self-esteem is best modeled as a cause rather than a consequence of life outcomes. Third, growth curve analyses, with self-esteem as a time-varying covariate, suggested that self-esteem has medium-sized effects on life-span trajectories of affect and depression, small to medium-sized effects on trajectories of relationship and job satisfaction, a very small effect on the trajectory of health, and no effect on the trajectory of occupational status. These findings replicated across 4 generations of participants--children, parents, grandparents, and their great-grandparents. Together, the results suggest that self-esteem has a significant prospective impact on real-world life experiences and that high and low self-esteem are not mere epiphenomena of success and failure in important life domains. 2012 APA, all rights reserved

Vision in Flies: Measuring the Attention Span.

Directory of Open Access Journals (Sweden)

Sebastian Koenig

Full Text Available A visual stimulus at a particular location of the visual field may elicit a behavior while at the same time equally salient stimuli in other parts do not. This property of visual systems is known as selective visual attention (SVA. The animal is said to have a focus of attention (FoA which it has shifted to a particular location. Visual attention normally involves an attention span at the location to which the FoA has been shifted. Here the attention span is measured in Drosophila. The fly is tethered and hence has its eyes fixed in space. It can shift its FoA internally. This shift is revealed using two simultaneous test stimuli with characteristic responses at their particular locations. In tethered flight a wild type fly keeps its FoA at a certain location for up to 4s. Flies with a mutation in the radish gene, that has been suggested to be involved in attention-like mechanisms, display a reduced attention span of only 1s.

Vision in Flies: Measuring the Attention Span.

Science.gov (United States)

Koenig, Sebastian; Wolf, Reinhard; Heisenberg, Martin

2016-01-01

A visual stimulus at a particular location of the visual field may elicit a behavior while at the same time equally salient stimuli in other parts do not. This property of visual systems is known as selective visual attention (SVA). The animal is said to have a focus of attention (FoA) which it has shifted to a particular location. Visual attention normally involves an attention span at the location to which the FoA has been shifted. Here the attention span is measured in Drosophila. The fly is tethered and hence has its eyes fixed in space. It can shift its FoA internally. This shift is revealed using two simultaneous test stimuli with characteristic responses at their particular locations. In tethered flight a wild type fly keeps its FoA at a certain location for up to 4s. Flies with a mutation in the radish gene, that has been suggested to be involved in attention-like mechanisms, display a reduced attention span of only 1s.

Structural and dynamic characterization of eukaryotic gene regulatory protein domains in solution

Energy Technology Data Exchange (ETDEWEB)

Lee, Andrew Loyd [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry

1996-05-01

Solution NMR was primarily used to characterize structure and dynamics in two different eukaryotic protein systems: the δ-Al-ε activation domain from c-jun and the Drosophila RNA-binding protein Sex-lethal. The second system is the Drosophila Sex-lethal (Sxl) protein, an RNA-binding protein which is the ``master switch`` in sex determination. Sxl contains two adjacent RNA-binding domains (RBDs) of the RNP consensus-type. The NMR spectrum of the second RBD (Sxl-RBD2) was assigned using multidimensional heteronuclear NMR, and an intermediate-resolution family of structures was calculated from primarily NOE distance restraints. The overall fold was determined to be similar to other RBDs: a βαβ-βαβ pattern of secondary structure, with the two helices packed against a 4-stranded anti-parallel β-sheet. In addition ¹⁵N T₁, T₂, and ¹⁵N/¹H NOE relaxation measurements were carried out to characterize the backbone dynamics of Sxl-RBD2 in solution. RNA corresponding to the polypyrimidine tract of transformer pre-mRNA was generated and titrated into 3 different Sxl-RBD protein constructs. Combining Sxl-RBD1+2 (bht RBDs) with this RNA formed a specific, high affinity protein/RNA complex that is amenable to further NMR characterization. The backbone ¹H, ¹³C, and ¹⁵N resonances of Sxl-RBD1+2 were assigned using a triple-resonance approach, and ¹⁵N relaxation experiments were carried out to characterize the backbone dynamics of this complex. The changes in chemical shift in Sxl-RBD1+2 upon binding RNA are observed using Sxl-RBD2 as a substitute for unbound Sxl-RBD1+2. This allowed the binding interface to be qualitatively mapped for the second domain.

Thyrotropin-luteinizing hormone/chorionic gonadotropin receptor extracellular domain chimeras as probes for thyrotropin receptor function

International Nuclear Information System (INIS)

Nagayama, Yuji; Wadsworth, H.L.; Chazenbalk, G.D.; Russo, D.; Seto, Pui; Rapoport, B.

1991-01-01

To define the sites in the extracellular domain of the human thyrotropin (TSH) receptor that are involved in TSH binding and signal transduction the authors constructed chimeric thyrotropin-luteinizing hormone/chorionic gonadotropin (TSH-LH/CG) receptors. The extracellular domain of the human TSH receptor was divided into five regions that were replaced, either singly or in various combinations, with homologous regions of the rat LH/CG receptor. The chimeric receptors were stably expressed in Chinese hamster ovary cells. The data obtained suggest that the carboxyl region of the extracellular domain (amino acid residues 261-418) and particularly the middle region (residues 171-260) play a role in signal transduction. The possibility is also raised of an interaction between the amino and carboxyl regions of the extracellular domain in the process of signal transduction. In summary, these studies suggest that the middle region and carboxyl half of the extracellular domain of the TSH receptor are involved in signal transduction and that the TSH-binding region is likely to span the entire extracellular domain, with multiple discontinuous contact sites

Increasing Endurance by Building Fluency: Precision Teaching Attention Span.

Science.gov (United States)

Binder, Carl; And Others

1990-01-01

Precision teaching techniques can be used to chart students' attention span or endurance. Individual differences in attention span can then be better understood and dealt with effectively. The effects of performance duration on performance level, on error rates, and on learning rates are discussed. Implications for classroom practice are noted.…

Applications of pharmacogenomics in regulatory science: a product life cycle review.

Science.gov (United States)

Tan-Koi, W C; Leow, P C; Teo, Y Y

2018-05-22

With rapid developments of pharmacogenomics (PGx) and regulatory science, it is important to understand the current PGx integration in product life cycle, impact on clinical practice thus far and opportunities ahead. We conducted a cross-sectional review on PGx-related regulatory documents and implementation guidelines in the United States and Europe. Our review found that although PGx-related guidance in both markets span across the entire product life cycle, the scope of implementation guidelines varies across two continents. Approximately one-third of Food and Drug Administration (FDA)-approved drugs with PGx information in drug labels and half of the European labels posted on PharmGKB website contain recommendations on genetic testing. The drugs affected 19 and 15 World Health Organization Anatomical Therapeutic Chemical drug classes (fourth level) in the United States and Europe, respectively, with protein kinase inhibitors (13 drugs in the United States and 16 drugs in Europe) being most prevalent. Topics of emerging interest were novel technologies, adaptive design in clinical trial and sample collection.

Life span extension and neuronal cell protection by Drosophila nicotinamidase.

Science.gov (United States)

Balan, Vitaly; Miller, Gregory S; Kaplun, Ludmila; Balan, Karina; Chong, Zhao-Zhong; Li, Faqi; Kaplun, Alexander; VanBerkum, Mark F A; Arking, Robert; Freeman, D Carl; Maiese, Kenneth; Tzivion, Guri

2008-10-10

The life span of model organisms can be modulated by environmental conditions that influence cellular metabolism, oxidation, or DNA integrity. The yeast nicotinamidase gene pnc1 was identified as a key transcriptional target and mediator of calorie restriction and stress-induced life span extension. PNC1 is thought to exert its effect on yeast life span by modulating cellular nicotinamide and NAD levels, resulting in increased activity of Sir2 family class III histone deacetylases. In Caenorhabditis elegans, knockdown of a pnc1 homolog was shown recently to shorten the worm life span, whereas its overexpression increased survival under conditions of oxidative stress. The function and regulation of nicotinamidases in higher organisms has not been determined. Here, we report the identification and biochemical characterization of the Drosophila nicotinamidase, D-NAAM, and demonstrate that its overexpression significantly increases median and maximal fly life span. The life span extension was reversed in Sir2 mutant flies, suggesting Sir2 dependence. Testing for physiological effectors of D-NAAM in Drosophila S2 cells, we identified oxidative stress as a primary regulator, both at the transcription level and protein activity. In contrast to the yeast model, stress factors such as high osmolarity and heat shock, calorie restriction, or inhibitors of TOR and phosphatidylinositol 3-kinase pathways do not appear to regulate D-NAAM in S2 cells. Interestingly, the expression of D-NAAM in human neuronal cells conferred protection from oxidative stress-induced cell death in a sirtuin-dependent manner. Together, our findings establish a life span extending the ability of nicotinamidase in flies and offer a role for nicotinamide-modulating genes in oxidative stress regulated pathways influencing longevity and neuronal cell survival.

Verbal fluency in male and female schizophrenia patients: Different patterns of association with processing speed, working memory span, and clinical symptoms.

Science.gov (United States)

Brébion, Gildas; Stephan-Otto, Christian; Ochoa, Susana; Nieto, Lourdes; Contel, Montserrat; Usall, Judith

2018-01-01

Decreased processing speed in schizophrenia patients has been identified as a major impairment factor in various neuropsychological domains. Working memory span has been found to be involved in several deep or effortful cognitive processes. We investigated the impact that these 2 cognitive functions may have on phonological and semantic fluency in schizophrenia patients and healthy participants. Fifty-five patients with schizophrenia and 60 healthy participants were administered a neuropsychological battery including phonological and semantic fluency, working memory, and cognitive and motor speed. Regression analyses revealed that motor speed was related to phonological fluency in female patients, whereas cognitive speed was related to semantic fluency in male patients. In addition, working memory span was related to verbal fluency in women from both the patient and the healthy control groups. Decreased processing speed, but not decreased working memory span, accounted for the verbal fluency deficit in patients. Verbal fluency was inversely related to attention deficit in female patients and to negative symptoms in male patients. Decreased processing speed may be the main factor in verbal fluency impairment of patients. Further, the cognitive and clinical predictors of verbal fluency efficiency are different in men and women. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

A Minimum Spanning Tree Representation of Anime Similarities

OpenAIRE

Wibowo, Canggih Puspo

2016-01-01

In this work, a new way to represent Japanese animation (anime) is presented. We applied a minimum spanning tree to show the relation between anime. The distance between anime is calculated through three similarity measurements, namely crew, score histogram, and topic similarities. Finally, the centralities are also computed to reveal the most significance anime. The result shows that the minimum spanning tree can be used to determine the similarity anime. Furthermore, by using centralities c...

BPM-CUL3 E3 ligase modulates thermotolerance by facilitating negative regulatory domain-mediated degradation of DREB2A in Arabidopsis.

Science.gov (United States)

Morimoto, Kyoko; Ohama, Naohiko; Kidokoro, Satoshi; Mizoi, Junya; Takahashi, Fuminori; Todaka, Daisuke; Mogami, Junro; Sato, Hikaru; Qin, Feng; Kim, June-Sik; Fukao, Yoichiro; Fujiwara, Masayuki; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

2017-10-03

DEHYDRATION-RESPONSIVE ELEMENT BINDING PROTEIN 2A (DREB2A) acts as a key transcription factor in both drought and heat stress tolerance in Arabidopsis and induces the expression of many drought- and heat stress-inducible genes. Although DREB2A expression itself is induced by stress, the posttranslational regulation of DREB2A, including protein stabilization, is required for its transcriptional activity. The deletion of a 30-aa central region of DREB2A known as the negative regulatory domain (NRD) transforms DREB2A into a stable and constitutively active form referred to as DREB2A CA. However, the molecular basis of this stabilization and activation has remained unknown for a decade. Here we identified BTB/POZ AND MATH DOMAIN proteins (BPMs), substrate adaptors of the Cullin3 (CUL3)-based E3 ligase, as DREB2A-interacting proteins. We observed that DREB2A and BPMs interact in the nuclei, and that the NRD of DREB2A is sufficient for its interaction with BPMs. BPM -knockdown plants exhibited increased DREB2A accumulation and induction of DREB2A target genes under heat and drought stress conditions. Genetic analysis indicated that the depletion of BPM expression conferred enhanced thermotolerance via DREB2A stabilization. Thus, the BPM-CUL3 E3 ligase is likely the long-sought factor responsible for NRD-dependent DREB2A degradation. Through the negative regulation of DREB2A stability, BPMs modulate the heat stress response and prevent an adverse effect of excess DREB2A on plant growth. Furthermore, we found the BPM recognition motif in various transcription factors, implying a general contribution of BPM-mediated proteolysis to divergent cellular responses via an accelerated turnover of transcription factors.

Insights into Hox protein function from a large scale combinatorial analysis of protein domains.

Directory of Open Access Journals (Sweden)

Samir Merabet

2011-10-01

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

Power, Governance and Boundary Spanning Leadership in Public Sector Organisations

DEFF Research Database (Denmark)

Elmholdt, Claus Westergård; Fogsgaard, Morten

2015-01-01

the fact that analysis of boundary spanning leadership and power relations is an essential, significant, and critical tool in questioning different forms of management in public sector organizations. The aim of the workshop is to investigate, elucidate and discuss management across organizational units...... on the practice that evolves on the boundaries that span occupational groups, departments and organizations. The workshop takes it’s starting point in an interdisciplinary Scandinavian research project which deals with the question of how power processes can promote, or hinder, boundary spanning leadership...

Superbinder SH2 domains act as antagonists of cell signaling.

Science.gov (United States)

Kaneko, Tomonori; Huang, Haiming; Cao, Xuan; Li, Xing; Li, Chengjun; Voss, Courtney; Sidhu, Sachdev S; Li, Shawn S C

2012-09-25

Protein-ligand interactions mediated by modular domains, which often play important roles in regulating cellular functions, are generally of moderate affinities. We examined the Src homology 2 (SH2) domain, a modular domain that recognizes phosphorylated tyrosine (pTyr) residues, to investigate how the binding affinity of a modular domain for its ligand influences the structure and cellular function of the protein. We used the phage display method to perform directed evolution of the pTyr-binding residues in the SH2 domain of the tyrosine kinase Fyn and identified three amino acid substitutions that critically affected binding. We generated three SH2 domain triple-point mutants that were "superbinders" with much higher affinities for pTyr-containing peptides than the natural domain. Crystallographic analysis of one of these superbinders revealed that the superbinder SH2 domain recognized the pTyr moiety in a bipartite binding mode: A hydrophobic surface encompassed the phenyl ring, and a positively charged site engaged the phosphate. When expressed in mammalian cells, the superbinder SH2 domains blocked epidermal growth factor receptor signaling and inhibited anchorage-independent cell proliferation, suggesting that pTyr superbinders might be explored for therapeutic applications and useful as biological research tools. Although the SH2 domain fold can support much higher affinity for its ligand than is observed in nature, our results suggest that natural SH2 domains are not optimized for ligand binding but for specificity and flexibility, which are likely properties important for their function in signaling and regulatory processes.

Decision-making heuristics and biases across the life span

Science.gov (United States)

Strough, JoNell; Karns, Tara E.; Schlosnagle, Leo

2013-01-01

We outline a contextual and motivational model of judgment and decision-making (JDM) biases across the life span. Our model focuses on abilities and skills that correspond to deliberative, experiential, and affective decision-making processes. We review research that addresses links between JDM biases and these processes as represented by individual differences in specific abilities and skills (e.g., fluid and crystallized intelligence, executive functioning, emotion regulation, personality traits). We focus on two JDM biases—the sunk-cost fallacy (SCF) and the framing effect. We trace the developmental trajectory of each bias from preschool through middle childhood, adolescence, early adulthood, and later adulthood. We conclude that life-span developmental trajectories differ depending on the bias investigated. Existing research suggests relative stability in the framing effect across the life span and decreases in the SCF with age, including in later life. We highlight directions for future research on JDM biases across the life span, emphasizing the need for process-oriented research and research that increases our understanding of JDM biases in people’s everyday lives. PMID:22023568

Decision-making heuristics and biases across the life span.

Science.gov (United States)

Strough, Jonell; Karns, Tara E; Schlosnagle, Leo

2011-10-01

We outline a contextual and motivational model of judgment and decision-making (JDM) biases across the life span. Our model focuses on abilities and skills that correspond to deliberative, experiential, and affective decision-making processes. We review research that addresses links between JDM biases and these processes as represented by individual differences in specific abilities and skills (e.g., fluid and crystallized intelligence, executive functioning, emotion regulation, personality traits). We focus on two JDM biases-the sunk-cost fallacy (SCF) and the framing effect. We trace the developmental trajectory of each bias from preschool through middle childhood, adolescence, early adulthood, and later adulthood. We conclude that life-span developmental trajectories differ depending on the bias investigated. Existing research suggests relative stability in the framing effect across the life span and decreases in the SCF with age, including in later life. We highlight directions for future research on JDM biases across the life span, emphasizing the need for process-oriented research and research that increases our understanding of JDM biases in people's everyday lives. © 2011 New York Academy of Sciences.

The Life Span Dwelling

OpenAIRE

Hans-Peter Hebensperger-Hüther; Gabriele Franger-Huhle

2014-01-01

The paper presents the findings from a survey of 10 different experimental housing projects in Bavaria. In 2005 students of architecture and students of social work at the University of Applied Science in Coburg approached the topic of “Life Span Dwelling” using interdisciplinary research methods. The scope of the research ranges from urban planning concepts to common spaces in the different neighborhoods, documenting user satisfaction with the individual unit and feasibility of rooms offered...

High-speed polarization-sensitive OCT at 1060 nm using a Fourier domain mode-locked swept source

DEFF Research Database (Denmark)

Marschall, Sebastian; Torzicky, Teresa; Klein, Thomas

2012-01-01

sufficiently large datasets. Here, we demonstrate PS-OCT imaging at 350 kHz A-scan rate using a two-channel PS-OCT system in conjunction with a Fourier domain mode-locked laser. The light source spectrum spans up to 100nm around the water absorption minimum at 1060 nm. By modulating the laser pump current, we...

Life span of animals under acute and chronic irradiation

International Nuclear Information System (INIS)

Zapol'skaya, N.A.; Fedorova, A.V.; Borisova, V.V.

1978-01-01

The study has been designed to see to what extent a single and long-term external and internal irradiations shorten the life span of animals. LDsub(50/30) for certain radionuclides whose absorbed doses show different spatiotemporal distributions are considered. It has been found that as far as the average life span is concerned, 137 Cs and 90 Sr have approximately the same effect whether they enter the body on a single occasion or repeatedly. With chronic total-body external gamma-irradiation, the decrease in life span is 5 times smaller than than with single-occasion irradiation. The main reason for the observed differences are found to be differences in the rates with which the absorbed doses are formed

From elongated spanning trees to vicious random walks

OpenAIRE

Gorsky, A.; Nechaev, S.; Poghosyan, V. S.; Priezzhev, V. B.

2012-01-01

Given a spanning forest on a large square lattice, we consider by combinatorial methods a correlation function of $k$ paths ($k$ is odd) along branches of trees or, equivalently, $k$ loop--erased random walks. Starting and ending points of the paths are grouped in a fashion a $k$--leg watermelon. For large distance $r$ between groups of starting and ending points, the ratio of the number of watermelon configurations to the total number of spanning trees behaves as $r^{-\

Type IX secretion system PorM and gliding machinery GldM form arches spanning the periplasmic space.

Science.gov (United States)

Leone, Philippe; Roche, Jennifer; Vincent, Maxence S; Tran, Quang Hieu; Desmyter, Aline; Cascales, Eric; Kellenberger, Christine; Cambillau, Christian; Roussel, Alain

2018-01-30

Type IX secretion system (T9SS), exclusively present in the Bacteroidetes phylum, has been studied mainly in Flavobacterium johnsoniae and Porphyromonas gingivalis. Among the 18 genes, essential for T9SS function, a group of four, porK-N (P. gingivalis) or gldK-N (F. johnsoniae) belongs to a co-transcribed operon that expresses the T9SS core membrane complex. The central component of this complex, PorM (or GldM), is anchored in the inner membrane by a trans-membrane helix and interacts through the outer membrane PorK-N complex. There is a complete lack of available atomic structures for any component of T9SS, including the PorKLMN complex. Here we report the crystal structure of the GldM and PorM periplasmic domains. Dimeric GldM and PorM, each contain four domains of ~180-Å length that span most of the periplasmic space. These and previously reported results allow us to propose a model of the T9SS core membrane complex as well as its functional behavior.

Functional interaction of the DNA-binding transcription factor Sp1 through its DNA-binding domain with the histone chaperone TAF-I.

Science.gov (United States)

Suzuki, Toru; Muto, Shinsuke; Miyamoto, Saku; Aizawa, Kenichi; Horikoshi, Masami; Nagai, Ryozo

2003-08-01

Transcription involves molecular interactions between general and regulatory transcription factors with further regulation by protein-protein interactions (e.g. transcriptional cofactors). Here we describe functional interaction between DNA-binding transcription factor and histone chaperone. Affinity purification of factors interacting with the DNA-binding domain of the transcription factor Sp1 showed Sp1 to interact with the histone chaperone TAF-I, both alpha and beta isoforms. This interaction was specific as Sp1 did not interact with another histone chaperone CIA nor did other tested DNA-binding regulatory factors (MyoD, NFkappaB, p53) interact with TAF-I. Interaction of Sp1 and TAF-I occurs both in vitro and in vivo. Interaction with TAF-I results in inhibition of DNA-binding, and also likely as a result of such, inhibition of promoter activation by Sp1. Collectively, we describe interaction between DNA-binding transcription factor and histone chaperone which results in negative regulation of the former. This novel regulatory interaction advances our understanding of the mechanisms of eukaryotic transcription through DNA-binding regulatory transcription factors by protein-protein interactions, and also shows the DNA-binding domain to mediate important regulatory interactions.

Regulation of Na+ channel inactivation by the DIII and DIV voltage-sensing domains.

Science.gov (United States)

Hsu, Eric J; Zhu, Wandi; Schubert, Angela R; Voelker, Taylor; Varga, Zoltan; Silva, Jonathan R

2017-03-06

Functional eukaryotic voltage-gated Na + (Na V ) channels comprise four domains (DI-DIV), each containing six membrane-spanning segments (S1-S6). Voltage sensing is accomplished by the first four membrane-spanning segments (S1-S4), which together form a voltage-sensing domain (VSD). A critical Na V channel gating process, inactivation, has previously been linked to activation of the VSDs in DIII and DIV. Here, we probe this interaction by using voltage-clamp fluorometry to observe VSD kinetics in the presence of mutations at locations that have been shown to impair Na V channel inactivation. These locations include the DIII-DIV linker, the DIII S4-S5 linker, and the DIV S4-S5 linker. Our results show that, within the 10-ms timeframe of fast inactivation, the DIV-VSD is the primary regulator of inactivation. However, after longer 100-ms pulses, the DIII-DIV linker slows DIII-VSD deactivation, and the rate of DIII deactivation correlates strongly with the rate of recovery from inactivation. Our results imply that, over the course of an action potential, DIV-VSDs regulate the onset of fast inactivation while DIII-VSDs determine its recovery. © 2017 Hsu et al.

Structure of Thermotoga maritima TM0439: implications for the mechanism of bacterial GntR transcription regulators with Zn2+-binding FCD domains

International Nuclear Information System (INIS)

Zheng, Meiying; Cooper, David R.; Grossoehme, Nickolas E.; Yu, Minmin; Hung, Li-Wei; Cieslik, Marcin; Derewenda, Urszula; Lesley, Scott A.; Wilson, Ian A.; Giedroc, David P.; Derewenda, Zygmunt S.

2009-01-01

Here, the crystal structure of TM0439, a GntR regulator with an FCD domain found in the Thermotoga maritima genome, is described. The GntR superfamily of dimeric transcription factors, with more than 6200 members encoded in bacterial genomes, are characterized by N-terminal winged-helix DNA-binding domains and diverse C-terminal regulatory domains which provide a basis for the classification of the constituent families. The largest of these families, FadR, contains nearly 3000 proteins with all-α-helical regulatory domains classified into two related Pfam families: FadR-C and FCD. Only two crystal structures of FadR-family members, those of Escherichia coli FadR protein and LldR from Corynebacterium glutamicum, have been described to date in the literature. Here, the crystal structure of TM0439, a GntR regulator with an FCD domain found in the Thermotoga maritima genome, is described. The FCD domain is similar to that of the LldR regulator and contains a buried metal-binding site. Using atomic absorption spectroscopy and Trp fluorescence, it is shown that the recombinant protein contains bound Ni 2+ ions but that it is able to bind Zn 2+ with K d < 70 nM. It is concluded that Zn 2+ is the likely physiological metal and that it may perform either structural or regulatory roles or both. Finally, the TM0439 structure is compared with two other FadR-family structures recently deposited by structural genomics consortia. The results call for a revision in the classification of the FadR family of transcription factors

Life Span and Resiliency Theory: A Critical Review

Directory of Open Access Journals (Sweden)

Alexa Smith-Osborne

2007-05-01

Full Text Available Theories of life span development describe human growth and change over the life cycle (Robbins, Chatterjee, & Canda, 2006. Major types of developmental theories include biological, psychodynamic, behavioral, and social learning, cognitive, moral, and spiritual, and those influenced by systems, empowerment, and conflict theory. Life span development theories commonly focus on ontogenesis and sequential mastery of skills, tasks, and abilities. Social work scholars have pointed out that a limitation of life span and other developmental theory is lack of attention to resilience (Greene, 2007; Robbins et al., 1998. The concept of resilience was developed to “describe relative resistance to psychosocial risk experiences” (Rutter, 1999b, p. 119. Longitudinal studies focused on typical and atypical child development informed theory formulation in developmental psychopathology (Garmezy & Rutter, 1983; Luthar, Cichetti,& Becker, 2000 and in an evolving resilience model (Richardson, 2002; Werner & Smith, 1992. Research on resilience has found a positive relationship between a number of individual traits and contextual variables and resistance to a variety of risk factors among children and adolescents. More recently, resilience research has examined the operation of these same factors in the young adult, middle-age, and elder life stages. This article examines the historical and conceptual progression of the two developmental theories—life span and resiliency—and discusses their application to social work practice and education in human behavior in the social environment.

Dynamic working memory performance in individuals with single-domain amnestic mild cognitive impairment.

Science.gov (United States)

Guild, Emma B; Vasquez, Brandon P; Maione, Andrea M; Mah, Linda; Ween, Jon; Anderson, Nicole D

2014-01-01

Previous studies have observed poorer working memory performance in individuals with amnestic mild cognitive impairment than in healthy older adults. It is unclear, however, whether these difficulties are true only of the multiple-domain clinical subtype in whom poorer executive functioning is common. The current study examined working memory, as measured by the self-ordered pointing task (SOPT) and an n-back task, in healthy older adults and adults with single-domain amnestic mild cognitive impairment (aMCI). Individuals with single-domain aMCI committed more errors and required longer to develop an organizational strategy on the SOPT. The single-domain aMCI group did not differ from healthy older adults on the 1-back or 2-back, but had poorer discrimination on the 3-back task. This is, to our knowledge, the first characterization of dynamic working memory performance in a single-domain aMCI group. These results lend support for the idea that clinical amnestic MCI subtypes may reflect different stages on a continuum of progression to dementia and question whether standardized measures of working memory (span tasks) are sensitive enough to capture subtle changes in performance.

A protein-binding domain, EH, identified in the receptor tyrosine kinase substrate Eps15 and conserved in evolution

DEFF Research Database (Denmark)

Wong, W T; Schumacher, C; Salcini, A E

1995-01-01

In this report we structurally and functionally define a binding domain that is involved in protein association and that we have designated EH (for Eps15 homology domain). This domain was identified in the tyrosine kinase substrate Eps15 on the basis of regional conservation with several heteroge......In this report we structurally and functionally define a binding domain that is involved in protein association and that we have designated EH (for Eps15 homology domain). This domain was identified in the tyrosine kinase substrate Eps15 on the basis of regional conservation with several...... heterogeneous proteins of yeast and nematode. The EH domain spans about 70 amino acids and shows approximately 60% overall amino acid conservation. We demonstrated the ability of the EH domain to specifically bind cytosolic proteins in normal and malignant cells of mesenchymal, epithelial, and hematopoietic...... (for Eps15-related). Structural comparison of Eps15 and Eps15r defines a family of signal transducers possessing extensive networking abilities including EH-mediated binding and association with Src homology 3-containing proteins....

The optimum spanning catenary cable

Science.gov (United States)

Wang, C. Y.

2015-03-01

A heavy cable spans two points in space. There exists an optimum cable length such that the maximum tension is minimized. If the two end points are at the same level, the optimum length is 1.258 times the distance between the ends. The optimum lengths for end points of different heights are also found.

Van Kampen Colimits as Bicolimits in Span

Science.gov (United States)

Heindel, Tobias; Sobociński, Paweł

The exactness properties of coproducts in extensive categories and pushouts along monos in adhesive categories have found various applications in theoretical computer science, e.g. in program semantics, data type theory and rewriting. We show that these properties can be understood as a single universal property in the associated bicategory of spans. To this end, we first provide a general notion of Van Kampen cocone that specialises to the above colimits. The main result states that Van Kampen cocones can be characterised as exactly those diagrams in ℂ that induce bicolimit diagrams in the bicategory of spans mathcal{S}pan_{mathbb{C}}, provided that ℂ has pullbacks and enough colimits.

Spanning organizational boundaries to manage creative processes:

DEFF Research Database (Denmark)

Andersen, Poul Houman; Kragh, Hanne; Lettl, Christopher

2013-01-01

In order to continue to be innovative in the current fast-paced and competitive environment, organizations are increasingly dependent on creative inputs developed outside their boundaries. The paper addresses the boundary spanning activities that managers undertake to a) select and mobilize...... creative talent, b) create shared identity, and c) combine and integrate knowledge in innovation projects involving external actors. We study boundary spanning activities in two creative projects in the LEGO group. One involves identifying and integrating deep, specialized knowledge, the other focuses...... actors, and how knowledge is integrated across organizational boundaries. We discuss implications of our findings for managers and researchers in a business-to-business context...

Differential sensitivity of Src-family kinases to activation by SH3 domain displacement.

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Jamie A Moroco

Full Text Available Src-family kinases (SFKs are non-receptor protein-tyrosine kinases involved in a variety of signaling pathways in virtually every cell type. The SFKs share a common negative regulatory mechanism that involves intramolecular interactions of the SH3 domain with the PPII helix formed by the SH2-kinase linker as well as the SH2 domain with a conserved phosphotyrosine residue in the C-terminal tail. Growing evidence suggests that individual SFKs may exhibit distinct activation mechanisms dictated by the relative strengths of these intramolecular interactions. To elucidate the role of the SH3:linker interaction in the regulation of individual SFKs, we used a synthetic SH3 domain-binding peptide (VSL12 to probe the sensitivity of downregulated c-Src, Hck, Lyn and Fyn to SH3-based activation in a kinetic kinase assay. All four SFKs responded to VSL12 binding with enhanced kinase activity, demonstrating a conserved role for SH3:linker interaction in the control of catalytic function. However, the sensitivity and extent of SH3-based activation varied over a wide range. In addition, autophosphorylation of the activation loops of c-Src and Hck did not override regulatory control by SH3:linker displacement, demonstrating that these modes of activation are independent. Our results show that despite the similarity of their downregulated conformations, individual Src-family members show diverse responses to activation by domain displacement which may reflect their adaptation to specific signaling environments in vivo.

Dynamically Coupled Residues within the SH2 Domain of FYN Are Key to Unlocking Its Activity.

Science.gov (United States)

Huculeci, Radu; Cilia, Elisa; Lyczek, Agatha; Buts, Lieven; Houben, Klaartje; Seeliger, Markus A; van Nuland, Nico; Lenaerts, Tom

2016-11-01

Src kinase activity is controlled by various mechanisms involving a coordinated movement of kinase and regulatory domains. Notwithstanding the extensive knowledge related to the backbone dynamics, little is known about the more subtle side-chain dynamics within the regulatory domains and their role in the activation process. Here, we show through experimental methyl dynamic results and predicted changes in side-chain conformational couplings that the SH2 structure of Fyn contains a dynamic network capable of propagating binding information. We reveal that binding the phosphorylated tail of Fyn perturbs a residue cluster near the linker connecting the SH2 and SH3 domains of Fyn, which is known to be relevant in the regulation of the activity of Fyn. Biochemical perturbation experiments validate that those residues are essential for inhibition of Fyn, leading to a gain of function upon mutation. These findings reveal how side-chain dynamics may facilitate the allosteric regulation of the different members of the Src kinase family. Copyright © 2016 Elsevier Ltd. All rights reserved.

From elongated spanning trees to vicious random walks

Science.gov (United States)

Gorsky, A.; Nechaev, S.; Poghosyan, V. S.; Priezzhev, V. B.

2013-05-01

Given a spanning forest on a large square lattice, we consider by combinatorial methods a correlation function of k paths (k is odd) along branches of trees or, equivalently, k loop-erased random walks. Starting and ending points of the paths are grouped such that they form a k-leg watermelon. For large distance r between groups of starting and ending points, the ratio of the number of watermelon configurations to the total number of spanning trees behaves as r-ν log r with ν = (k2 - 1) / 2. Considering the spanning forest stretched along the meridian of this watermelon, we show that the two-dimensional k-leg loop-erased watermelon exponent ν is converting into the scaling exponent for the reunion probability (at a given point) of k (1 + 1)-dimensional vicious walkers, ν˜ =k2 / 2. At the end, we express the conjectures about the possible relation to integrable systems.

From elongated spanning trees to vicious random walks

Energy Technology Data Exchange (ETDEWEB)

Gorsky, A. [ITEP, B. Cheryomushkinskaya 25, 117218 Moscow (Russian Federation); Nechaev, S., E-mail: nechaev@lptms.u-psud.fr [LPTMS, Université Paris Sud, 91405 Orsay Cedex (France); P.N. Lebedev Physical Institute of the Russian Academy of Sciences, 119991 Moscow (Russian Federation); Poghosyan, V.S. [Institute for Informatics and Automation Problems NAS of Armenia, 375044 Yerevan (Armenia); Priezzhev, V.B. [Bogolubov Laboratory of Theoretical Physics, Joint Institute for Nuclear Research, 141980 Dubna (Russian Federation)

2013-05-01

Given a spanning forest on a large square lattice, we consider by combinatorial methods a correlation function of k paths (k is odd) along branches of trees or, equivalently, k loop-erased random walks. Starting and ending points of the paths are grouped such that they form a k-leg watermelon. For large distance r between groups of starting and ending points, the ratio of the number of watermelon configurations to the total number of spanning trees behaves as r{sup −ν}logr with ν=(k{sup 2}−1)/2. Considering the spanning forest stretched along the meridian of this watermelon, we show that the two-dimensional k-leg loop-erased watermelon exponent ν is converting into the scaling exponent for the reunion probability (at a given point) of k(1+1)-dimensional vicious walkers, ν{sup -tilde=}k{sup 2}/2. At the end, we express the conjectures about the possible relation to integrable systems.

From elongated spanning trees to vicious random walks

International Nuclear Information System (INIS)

Gorsky, A.; Nechaev, S.; Poghosyan, V.S.; Priezzhev, V.B.

2013-01-01

Given a spanning forest on a large square lattice, we consider by combinatorial methods a correlation function of k paths (k is odd) along branches of trees or, equivalently, k loop-erased random walks. Starting and ending points of the paths are grouped such that they form a k-leg watermelon. For large distance r between groups of starting and ending points, the ratio of the number of watermelon configurations to the total number of spanning trees behaves as r −ν logr with ν=(k 2 −1)/2. Considering the spanning forest stretched along the meridian of this watermelon, we show that the two-dimensional k-leg loop-erased watermelon exponent ν is converting into the scaling exponent for the reunion probability (at a given point) of k(1+1)-dimensional vicious walkers, ν -tilde= k 2 /2. At the end, we express the conjectures about the possible relation to integrable systems

USING GENETIC ALGORTIHM TO SOLVE STEINER MINIMUM SPANNING TREE PROBLEM

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Öznur İŞÇİ

2006-03-01

Full Text Available Genetic algorithms (GA are a stochastic research methods, and they produce solutions that are close to optimum or near optimum. In addition to GA's successful application to traveling salesman problem, square designation, allocation, workshop table, preparation of lesson/examination schedules, planning of communication networks, assembling line balanced, minimum spanning tree type many combinatorial optimization problems it would be applicable to make the best comparison in optimization. In this study a Java program is developed to solve Steiner minimum spanning tree problem by genetic algorithm and its performance is examined. According to the tests carried out on the problems that were given before in the literature, results that are close to optimum are obtained in by GA approach that is recommended in this study. For the predetermined points in the study, length and gain are calculated for Steiner minimum spanning tree problem and minimum spanning tree problem.

Distal loop flexibility of a regulatory domain modulates dynamics and activity of C-terminal SRC kinase (csk.

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Sulyman Barkho

Full Text Available The Src family of tyrosine kinases (SFKs regulate numerous aspects of cell growth and differentiation and are under the principal control of the C-terminal Src Kinase (Csk. Csk and SFKs share a modular design with the kinase domain downstream of the N-terminal SH2 and SH3 domains that regulate catalytic function and membrane localization. While the function of interfacial segments in these multidomain kinases are well-investigated, little is known about how surface sites and long-range, allosteric coupling control protein dynamics and catalytic function. The SH2 domain of Csk is an essential component for the down-regulation of all SFKs. A unique feature of the SH2 domain of Csk is the tight turn in place of the canonical CD loop in a surface site far removed from kinase domain interactions. In this study, we used a combination of experimental and computational methods to probe the importance of this difference by constructing a Csk variant with a longer SH2 CD loop to mimic the flexibility found in homologous kinase SH2 domains. Our results indicate that while the fold and function of the isolated domain and the full-length kinase are not affected by loop elongation, native protein dynamics that are essential for efficient catalysis are perturbed. We also identify key motifs and routes through which the distal SH2 site might influence catalysis at the active site. This study underscores the sensitivity of intramolecular signaling and catalysis to native protein dynamics that arise from modest changes in allosteric regions while providing a potential strategy to alter intrinsic activity and signaling modulation.

The DNA binding and activation domains of Gal4p are sufficient for conveying its regulatory signals.

OpenAIRE

Ding, W V; Johnston, S A

1997-01-01

The transcriptional activation function of the Saccharomyces cerevisiae activator Gal4p is known to rely on a DNA binding activity at its amino terminus and an activation domain at its carboxy terminus. Although both domains are required for activation, truncated forms of Gal4p containing only these domains activate poorly in vivo. Also, mutations in an internal conserved region of Gal4p inactivate the protein, suggesting that this internal region has some function critical to the activity of...

Is the superior verbal memory span of Mandarin speakers due to faster rehearsal?

Science.gov (United States)

Mattys, Sven L; Baddeley, Alan; Trenkic, Danijela

2018-04-01

It is well established that digit span in native Chinese speakers is atypically high. This is commonly attributed to a capacity for more rapid subvocal rehearsal for that group. We explored this hypothesis by testing a group of English-speaking native Mandarin speakers on digit span and word span in both Mandarin and English, together with a measure of speed of articulation for each. When compared to the performance of native English speakers, the Mandarin group proved to be superior on both digit and word spans while predictably having lower spans in English. This suggests that the Mandarin advantage is not limited to digits. Speed of rehearsal correlated with span performance across materials. However, this correlation was more pronounced for English speakers than for any of the Chinese measures. Further analysis suggested that speed of rehearsal did not provide an adequate account of differences between Mandarin and English spans or for the advantage of digits over words. Possible alternative explanations are discussed.

Exploratory and problem-solving consumer behavior across the life span.

Science.gov (United States)

Lesser, J A; Kunkel, S R

1991-09-01

Different cognitive functioning, social, and personality changes appear to occur systematically during the adult life span. This article synthesizes research on life span changes in order to develop age-specific models of shopping behavior. The models are tested within a naturalistic field study of shoppers.

Life Span Extension and Neuronal Cell Protection by Drosophila Nicotinamidase*S⃞

OpenAIRE

Balan, Vitaly; Miller, Gregory S.; Kaplun, Ludmila; Balan, Karina; Chong, Zhao-Zhong; Li, Faqi; Kaplun, Alexander; VanBerkum, Mark F. A.; Arking, Robert; Freeman, D. Carl; Maiese, Kenneth; Tzivion, Guri

2008-01-01

The life span of model organisms can be modulated by environmental conditions that influence cellular metabolism, oxidation, or DNA integrity. The yeast nicotinamidase gene pnc1 was identified as a key transcriptional target and mediator of calorie restriction and stress-induced life span extension. PNC1 is thought to exert its effect on yeast life span by modulating cellular nicotinamide and NAD levels, resulting in increased activity of Sir2 family class III histone ...

Individual differences in personality change across the adult life span.

Science.gov (United States)

Schwaba, Ted; Bleidorn, Wiebke

2018-06-01

A precise and comprehensive description of personality continuity and change across the life span is the bedrock upon which theories of personality development are built. Little research has quantified the degree to which individuals deviate from mean-level developmental trends. In this study, we addressed this gap by examining individual differences in personality trait change across the life span. Data came from a nationally representative sample of 9,636 Dutch participants who provided Big Five self-reports at five assessment waves across 7 years. We divided our sample into 14 age groups (ages 16-84 at initial measurement) and estimated latent growth curve models to describe individual differences in personality change across the study period for each trait and age group. Across the adult life span, individual differences in personality change were small but significant until old age. For Openness, Conscientiousness, Extraversion, and Agreeableness, individual differences in change were most pronounced in emerging adulthood and decreased throughout midlife and old age. For Emotional Stability, individual differences in change were relatively consistent across the life span. These results inform theories of life span development and provide future directions for research on the causes and conditions of personality change. © 2017 Wiley Periodicals, Inc.

As to achieve regulatory action, regulatory approaches

International Nuclear Information System (INIS)

Cid, R.; Encinas, D.

2014-01-01

The achievement of the effectiveness in the performance of a nuclear regulatory body has been a permanent challenge in the recent history of nuclear regulation. In the post-Fukushima era this challenge is even more important. This article addresses the subject from two complementary points of view: the characteristics of an effective regulatory body and the regulatory approaches. This work is based on the most recent studies carried out by the Committee on Nuclear Regulatory Activities, CNRA (OECD/NEA), as well as on the experience of the Consejo de Seguridad Nuclear, CSN, the Spanish regulatory body. Rafael Cid is the representative of CSN in these project: Diego Encinas has participated in the study on regulatory approaches. (Author)

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

Science.gov (United States)

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.

Facilitating conditions for boundary-spanning behavior in governance networks

OpenAIRE

Meerkerk, Ingmar; Edelenbos, Jurian

2017-01-01

textabstractThis article examines the impact of two facilitating conditions for boundary-spanning behaviour in urban governance networks. While research on boundary spanning is growing, there is little attention for antecedents. Combining governance network literature on project management and organizational literature on facilitative and servant leadership, we examine two potential conditions: a facilitative project management style and executive support. We conducted survey research among p...

Abl N-terminal cap stabilization of SH3 domain dynamics.

Science.gov (United States)

Chen, Shugui; Dumitrescu, Teodora Pene; Smithgall, Thomas E; Engen, John R

2008-05-27

Crystal structures and other biochemical data indicate that the N-terminal cap (NCap) region of the Abelson tyrosine kinase (c-Abl) is important for maintaining the downregulated conformation of the kinase domain. The exact contributions that the NCap makes in stabilizing the various intramolecular interactions within c-Abl are less clear. While the NCap appears to be important for locking the SH3 and SH2 domains to the back of the kinase domain, there may be other more subtle elements of regulation. Hydrogen exchange (HX) and mass spectrometry (MS) were used to determine if the NCap contributes to intramolecular interactions involving the Abl SH3 domain. Under physiological conditions, the Abl SH3 domain underwent partial unfolding and its unfolding half-life was slowed during binding to the SH2 kinase linker, providing a unique assay for testing NCap-induced stabilization of the SH3 domain in various constructs. The results showed that the NCap stabilizes the dynamics of the SH3 domain in certain constructs but does not increase the relative affinity of the SH3 domain for the native SH2 kinase linker. The stabilization effect was absent in constructs of just the NCap and SH3 but was obvious when the SH2 domain and the SH2 kinase linker were present. These results suggest that interactions between the NCap and the SH3 domain can contribute to c-Abl stabilization in constructs that contain at least the SH2 domain, an effect that may partially compensate for the absence of the negative regulatory C-terminal tail found in the related Src family of kinases.

Minimal spanning trees, filaments and galaxy clustering

International Nuclear Information System (INIS)

Barrow, J.D.; Sonoda, D.H.

1985-01-01

A graph theoretical technique for assessing intrinsic patterns in point data sets is described. A unique construction, the minimal spanning tree, can be associated with any point data set given all the inter-point separations. This construction enables the skeletal pattern of galaxy clustering to be singled out in quantitative fashion and differs from other statistics applied to these data sets. This technique is described and applied to two- and three-dimensional distributions of galaxies and also to comparable random samples and numerical simulations. The observed CfA and Zwicky data exhibit characteristic distributions of edge-lengths in their minimal spanning trees which are distinct from those found in random samples. (author)

Understanding retirement: the promise of life-span developmental frameworks.

Science.gov (United States)

Löckenhoff, Corinna E

2012-09-01

The impending retirement of large population cohorts creates a pressing need for practical interventions to optimize outcomes at the individual and societal level. This necessitates comprehensive theoretical models that acknowledge the multi-layered nature of the retirement process and shed light on the dynamic mechanisms that drive longitudinal patterns of adjustment. The present commentary highlights ways in which contemporary life-span developmental frameworks can inform retirement research, drawing on the specific examples of Bronfenbrenner's Ecological Model, Baltes and Baltes Selective Optimization with Compensation Framework, Schulz and Heckhausen's Motivational Theory of Life-Span Development, and Carstensen's Socioemotional Selectivity Theory. Ultimately, a life-span developmental perspective on retirement offers not only new interpretations of known phenomena but may also help to identify novel directions for future research as well as promising pathways for interventions.

Developmental Regulation across the Life Span: Toward a New Synthesis

Science.gov (United States)

Haase, Claudia M.; Heckhausen, Jutta; Wrosch, Carsten

2013-01-01

How can individuals regulate their own development to live happy, healthy, and productive lives? Major theories of developmental regulation across the life span have been proposed (e.g., dual-process model of assimilation and accommodation; motivational theory of life-span development; model of selection, optimization, and compensation), but they…

Causality analysis detects the regulatory role of maternal effect genes in the early Drosophila embryo

Directory of Open Access Journals (Sweden)

Zara Ghodsi

2017-03-01

Full Text Available In developmental studies, inferring regulatory interactions of segmentation genetic network play a vital role in unveiling the mechanism of pattern formation. As such, there exists an opportune demand for theoretical developments and new mathematical models which can result in a more accurate illustration of this genetic network. Accordingly, this paper seeks to extract the meaningful regulatory role of the maternal effect genes using a variety of causality detection techniques and to explore whether these methods can suggest a new analytical view to the gene regulatory networks. We evaluate the use of three different powerful and widely-used models representing time and frequency domain Granger causality and convergent cross mapping technique with the results being thoroughly evaluated for statistical significance. Our findings show that the regulatory role of maternal effect genes is detectable in different time classes and thereby the method is applicable to infer the possible regulatory interactions present among the other genes of this network.

RESEARCH OF USING OPEN DOUBLE T BEAMS FOR SPANS IN FLOATING BRIDGES

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YU. M. Gorbatiuk

2014-03-01

Full Text Available Purpose. The publication presents the results of calculations of spans for floating bridges with open double T beams. The purpose of research is to analyze the suitability of spans from open double T beams for floating bridges with minimum weight under loads, which is provided by standards for modern floating bridges designing. Methodology. Comparative method, analytical calculation methods (influence lines methodology, strength calculations, endurance, maximum shear stress are used in this paper. Findings. Current loads for bridges calculations are 75% more than those, for which the spans of floating bridge from NZhM-56 property are designed. The use of open double T beams that is formed with double T beam no. 70 (the height of the open one is 104 cm reduces the cross sectional area in a weakened spot, but virtually it does not influence the strength and durability of the material. The use of open double T beams for spans of floating bridges saves up to 22 % of metal that means one in five spans will made of saved metal. Savings on each spans, such as CRP, will be 33.6 - 263 thous. grn. (considering the price of 1 ton of final product 29 thous. grn.. Originality. Research allows making next step in material saving and use of open double T beams for spans in the whole. Practical value. The obtained results give us possibility to make a number of conclusions that allow us to become more familiar and more practical with the use of open double T beams for spans of floating bridges.

Guanine nucleotide binding to the Bateman domain mediates the allosteric inhibition of eukaryotic IMP dehydrogenases

Science.gov (United States)

Buey, Rubén M.; Ledesma-Amaro, Rodrigo; Velázquez-Campoy, Adrián; Balsera, Mónica; Chagoyen, Mónica; de Pereda, José M.; Revuelta, José L.

2015-11-01

Inosine-5'-monophosphate dehydrogenase (IMPDH) plays key roles in purine nucleotide metabolism and cell proliferation. Although IMPDH is a widely studied therapeutic target, there is limited information about its physiological regulation. Using Ashbya gossypii as a model, we describe the molecular mechanism and the structural basis for the allosteric regulation of IMPDH by guanine nucleotides. We report that GTP and GDP bind to the regulatory Bateman domain, inducing octamers with compromised catalytic activity. Our data suggest that eukaryotic and prokaryotic IMPDHs might have developed different regulatory mechanisms, with GTP/GDP inhibiting only eukaryotic IMPDHs. Interestingly, mutations associated with human retinopathies map into the guanine nucleotide-binding sites including a previously undescribed non-canonical site and disrupt allosteric inhibition. Together, our results shed light on the mechanisms of the allosteric regulation of enzymes mediated by Bateman domains and provide a molecular basis for certain retinopathies, opening the door to new therapeutic approaches.

Increased Life Span due to Calorie Restriction in Respiratory-Deficient Yeast.

Directory of Open Access Journals (Sweden)

2005-11-01

Full Text Available A model for replicative life span extension by calorie restriction (CR in yeast has been proposed whereby reduced glucose in the growth medium leads to activation of the NAD-dependent histone deacetylase Sir2. One mechanism proposed for this putative activation of Sir2 is that CR enhances the rate of respiration, in turn leading to altered levels of NAD or NADH, and ultimately resulting in enhanced Sir2 activity. An alternative mechanism has been proposed in which CR decreases levels of the Sir2 inhibitor nicotinamide through increased expression of the gene coding for nicotinamidase, PNC1. We have previously reported that life span extension by CR is not dependent on Sir2 in the long-lived BY4742 strain background. Here we have determined the requirement for respiration and the effect of nicotinamide levels on life span extension by CR. We find that CR confers robust life span extension in respiratory-deficient cells independent of strain background, and moreover, suppresses the premature mortality associated with loss of mitochondrial DNA in the short-lived PSY316 strain. Addition of nicotinamide to the medium dramatically shortens the life span of wild type cells, due to inhibition of Sir2. However, even in cells lacking both Sir2 and the replication fork block protein Fob1, nicotinamide partially prevents life span extension by CR. These findings (1 demonstrate that respiration is not required for the longevity benefits of CR in yeast, (2 show that nicotinamide inhibits life span extension by CR through a Sir2-independent mechanism, and (3 suggest that CR acts through a conserved, Sir2-independent mechanism in both PSY316 and BY4742.

Increased life span due to calorie restriction in respiratory-deficient yeast.

Directory of Open Access Journals (Sweden)

Matt Kaeberlein

2005-11-01

Full Text Available A model for replicative life span extension by calorie restriction (CR in yeast has been proposed whereby reduced glucose in the growth medium leads to activation of the NAD+-dependent histone deacetylase Sir2. One mechanism proposed for this putative activation of Sir2 is that CR enhances the rate of respiration, in turn leading to altered levels of NAD+ or NADH, and ultimately resulting in enhanced Sir2 activity. An alternative mechanism has been proposed in which CR decreases levels of the Sir2 inhibitor nicotinamide through increased expression of the gene coding for nicotinamidase, PNC1. We have previously reported that life span extension by CR is not dependent on Sir2 in the long-lived BY4742 strain background. Here we have determined the requirement for respiration and the effect of nicotinamide levels on life span extension by CR. We find that CR confers robust life span extension in respiratory-deficient cells independent of strain background, and moreover, suppresses the premature mortality associated with loss of mitochondrial DNA in the short-lived PSY316 strain. Addition of nicotinamide to the medium dramatically shortens the life span of wild type cells, due to inhibition of Sir2. However, even in cells lacking both Sir2 and the replication fork block protein Fob1, nicotinamide partially prevents life span extension by CR. These findings (1 demonstrate that respiration is not required for the longevity benefits of CR in yeast, (2 show that nicotinamide inhibits life span extension by CR through a Sir2-independent mechanism, and (3 suggest that CR acts through a conserved, Sir2-independent mechanism in both PSY316 and BY4742.

Crystal structure of Thermotoga maritima TM0439: implications for the mechanism of bacterial GntR transcription regulators with Zn2+-binding FCD domains

Energy Technology Data Exchange (ETDEWEB)

Zheng, Meiying; Cooper, David; Grossoehmerb, Nickolas; Yu, Minmin; Hung, Li-Wei; Cieslik, Murcin; Derewendaro, Urszula; Lesley, Scott; Wilson, Ian; Giedrocb, David; Derewenda, Zygmunt

2009-06-06

The GntR superfamily of dimeric transcription factors, with more than 6200 members encoded in bacterial genomes, are characterized by N-terminal winged helix (WH) DNA-binding domains and diverse C-terminal, regulatory domains, which provide a basis for the classification of the constituent families. The largest of these families, FadR, contains nearly 3000 proteins with all a-helical regulatory domains classified into two related Pfam families: FadR{_}C and FCD. Only two crystal structures of the FadR family members, i.e. the E. coli FadR protein and the LldR from C. glutamicum, have been described to date in literature. Here we describe the crystal structure of TM0439, a GntR regulator with an FCD domain, found in the Thermotoga maritima genome. The FCD domain is similar to that of the LldR regulator, and contains a buried metal binding site. Using atomic absorption spectroscopy and Trp fluorescence, we show that the recombinant protein contains bound Ni{sup 2+} ions, but it is able to bind Zn{sup 2+} with K{sub D} < 70 nM . We conclude that Zn{sup 2+} is the likely physiological metal, where it may perform either or both structural and regulatory roles. Finally, we compare the TM0439 structure to two other FadR family structures recently deposited by Structural Genomics consortia. The results call for a revision in the classification of the FadR family of transcription factors.

Boundary Spanning in Higher Education: How Universities Can Enable Success

Science.gov (United States)

Skolaski, Jennifer Pauline

2012-01-01

Purpose: The purpose of this research is to better understand the identity and work of academic and extension staff who have boundary spanning responsibilities. The results will help universities, especially public land-grant universities with an outreach mission, to create stronger policies and systems to support boundary spanning staff members…

Atomic resolution structure of the E. coli YajR transporter YAM domain

Energy Technology Data Exchange (ETDEWEB)

Jiang, Daohua [National Laboratory of Macromolecules, National Center of Protein Science-Beijing, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101 (China); School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074 (China); Zhao, Yan [National Laboratory of Macromolecules, National Center of Protein Science-Beijing, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101 (China); School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027 (China); Fan, Junping; Liu, Xuehui; Wu, Yan; Feng, Wei [National Laboratory of Macromolecules, National Center of Protein Science-Beijing, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101 (China); Zhang, Xuejun C., E-mail: zhangc@ibp.ac.cn [National Laboratory of Macromolecules, National Center of Protein Science-Beijing, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101 (China)

2014-07-25

Highlights: • We report the crystal structure of the YAM domain of YajR transporter at 1.07 Å. • The YAM dimerization is related to the halogen-dependent high thermal stability. • A belt of poly-pentagonal water molecules was observed in the dimer interface. - Abstract: YajR is an Escherichia coli transporter that belongs to the major facilitator superfamily. Unlike most MFS transporters, YajR contains a carboxyl terminal, cytosolic domain of 67 amino acid residues termed YAM domain. Although it is speculated that the function of this small soluble domain is to regulate the conformational change of the 12-helix transmembrane domain, its precise regulatory role remains unclear. Here, we report the crystal structure of the YAM domain at 1.07-Å resolution, along with its structure determined using nuclear magnetic resonance. Detailed analysis of the high resolution structure revealed a symmetrical dimer in which a belt of well-ordered poly-pentagonal water molecules is embedded. A mutagenesis experiment and a thermal stability assay were used to analyze the putative role of this dimerization in response to changes in halogen concentration.

From data repositories to submission portals: rethinking the role of domain-specific databases in CollecTF.

Science.gov (United States)

Kılıç, Sefa; Sagitova, Dinara M; Wolfish, Shoshannah; Bely, Benoit; Courtot, Mélanie; Ciufo, Stacy; Tatusova, Tatiana; O'Donovan, Claire; Chibucos, Marcus C; Martin, Maria J; Erill, Ivan

2016-01-01

Domain-specific databases are essential resources for the biomedical community, leveraging expert knowledge to curate published literature and provide access to referenced data and knowledge. The limited scope of these databases, however, poses important challenges on their infrastructure, visibility, funding and usefulness to the broader scientific community. CollecTF is a community-oriented database documenting experimentally validated transcription factor (TF)-binding sites in the Bacteria domain. In its quest to become a community resource for the annotation of transcriptional regulatory elements in bacterial genomes, CollecTF aims to move away from the conventional data-repository paradigm of domain-specific databases. Through the adoption of well-established ontologies, identifiers and collaborations, CollecTF has progressively become also a portal for the annotation and submission of information on transcriptional regulatory elements to major biological sequence resources (RefSeq, UniProtKB and the Gene Ontology Consortium). This fundamental change in database conception capitalizes on the domain-specific knowledge of contributing communities to provide high-quality annotations, while leveraging the availability of stable information hubs to promote long-term access and provide high-visibility to the data. As a submission portal, CollecTF generates TF-binding site information through direct annotation of RefSeq genome records, definition of TF-based regulatory networks in UniProtKB entries and submission of functional annotations to the Gene Ontology. As a database, CollecTF provides enhanced search and browsing, targeted data exports, binding motif analysis tools and integration with motif discovery and search platforms. This innovative approach will allow CollecTF to focus its limited resources on the generation of high-quality information and the provision of specialized access to the data.Database URL: http://www.collectf.org/. © The Author(s) 2016

A pluggable service platform architecture for e-commercspan>e

NARCIS (Netherlands)

Aulkemeier, Fabian; Paramartha, Mohammad Anggasta; Iacob, Maria Eugenia; van Hillegersberg, Jos

2016-01-01

In the beginning of the e-commercspan>e era, retailers mostly adopted vertically integrated solutions to control the entire e-commercspan>e value chain. However, they began to realize that to achieve agility, a better approach would be to focus on certain core capabilities and then create a partner ecosystem

Implications of e-commercspan>e for banking and finance

NARCIS (Netherlands)

Heng, Michael S.H.

2001-01-01

The aim of the paper is to show that e-commercspan>e holds the potential totransform banking and financial systems. There are three aspects in which e-commercecan affect banking and finance. First, banks and financial firms can use thetechnology and business practice of e-commercspan>e to market their

The control processes and subjective well-being of Chinese teachers: Evidence of convergence with and divergence from the key propositions of the motivational theory of life-span development

Directory of Open Access Journals (Sweden)

Wan-Chi eWong

2014-05-01

Full Text Available An analytical review of the motivational theory of life-span development reveals that this theory has undergone a series of elegant theoretical integrations. Its claim to universality nonetheless brings forth unresolved controversies. With the purpose of scrutinizing the key propositions of this theory, an empirical study was designed to examine the control processes and subjective well-being of Chinese teachers (N = 637. The OPS-Scales (Optimization in Primary and Secondary Control Scales for the Domain of Teaching were constructed to assess patterns of control processes. Three facets of subjective well-being were investigated with the Positive and Negative Affect Schedule, the Life Satisfaction Scale, and the Subjective Vitality Scale. The results revealed certain aspects of alignment with and certain divergences from the key propositions of the motivational theory of life-span development. Neither primacy of primary control nor primacy of secondary control was clearly supported. Notably, using different criteria for subjective well-being yielded different subtypes of primary and secondary control as predictors. The hypothesized life-span trajectories of primary and secondary control received limited support. To advance the theory in this area, we recommend incorporating Lakatos’ ideas about sophisticated falsification by specifying the hard core of the motivational theory of life-span development and articulating new auxiliary hypotheses.

"A general benevolence dimension that links neural, psychological, economic, and life-span data on altruistic tendencies": Correction to Hubbard et al. (2016).

Science.gov (United States)

2016-10-01

Reports an error in "A general benevolence dimension that links neural, psychological, economic, and life-span data on altruistic tendencies" by Jason Hubbard, William T. Harbaugh, Sanjay Srivastava, David Degras and Ulrich Mayr ( Journal of Experimental Psychology: General , Advanced Online Publication, Aug 11, 2016, np). In the article, there was an error in the Task, Stimuli, and Procedures section. In the 1st sentence in the 6th paragraph, “Following the scanning phase, participants completed self-report questionnaires meant to reflected the Prosocial Disposition construct: the agreeableness scale from the Big F, which includes empathic concern and perspective-taking, and a scale of personality descriptive adjectives related to altruistic behavior (Wood, Nye, & Saucier, 2010).” should have read: “Following the scanning phase, participants completed self-report questionnaires that contained scales to reflect the Prosocial Disposition construct: the Big Five Inventory (BFI; John et al., 1991), from which we used the agreeableness scale to measure prosocial disposition; the Interpersonal Reactivity Index (IRI; Davis, 1980), from which we used the empathic concern and perspective-taking scales; and a scale of personality descriptive adjectives related to altruistic behavior (Wood, Nye, & Saucier, 2010).” (The following abstract of the original article appeared in record 2016-39037-001.) Individual and life span differences in charitable giving are an important economic force, yet the underlying motives are not well understood. In an adult, life span sample, we assessed manifestations of prosocial tendencies across 3 different measurement domains: (a) psychological self-report measures, (b) actual giving choices, and (c) fMRI-derived, neural indicators of “pure altruism.” The latter expressed individuals’ activity in neural valuation areas when charities received money compared to when oneself received money and thus reflected an altruistic concern for

The Role of Covert Retrieval in Working Memory Span Tasks: Evidence from Delayed Recall Tests

Science.gov (United States)

McCabe, David P.

2008-01-01

The current study examined delayed recall of items that had been processed during simple and complex span tasks. Three experiments were reported showing that despite more items being recalled initially from a simple span task (i.e., word span) than a complex span task (i.e., operation span), on a delayed recall test more items were recalled that…

Paternal smoking habits affect the reproductive life span of daughters

DEFF Research Database (Denmark)

Fukuda, Misao; Fukuda, Kiyomi; Shimizu, Takashi

2011-01-01

The present study assessed whether the smoking habits of fathers around the time of conception affected the period in which daughters experienced menstrual cycles (i.e., the reproductive life span). The study revealed that the smoking habits of the farther shortened the daughters' reproductive life...... span compared with daughters whose fathers did not smoke....

On the number of spanning trees in random regular graphs

DEFF Research Database (Denmark)

Greenhill, Catherine; Kwan, Matthew; Wind, David Kofoed

2014-01-01

Let d >= 3 be a fixed integer. We give an asympotic formula for the expected number of spanning trees in a uniformly random d-regular graph with n vertices. (The asymptotics are as n -> infinity, restricted to even n if d is odd.) We also obtain the asymptotic distribution of the number of spanning...

Time-varying span efficiency through the wingbeat of desert locusts.

Science.gov (United States)

Henningsson, Per; Bomphrey, Richard J

2012-06-07

The flight performance of animals depends greatly on the efficacy with which they generate aerodynamic forces. Accordingly, maximum range, load-lifting capacity and peak accelerations during manoeuvres are all constrained by the efficiency of momentum transfer to the wake. Here, we use high-speed particle image velocimetry (1 kHz) to record flow velocities in the near wake of desert locusts (Schistocerca gregaria, Forskål). We use the measured flow fields to calculate time-varying span efficiency throughout the wing stroke cycle. The locusts are found to operate at a maximum span efficiency of 79 per cent, typically at a plateau of about 60 per cent for the majority of the downstroke, but at lower values during the upstroke. Moreover, the calculated span efficiencies are highest when the largest lift forces are being generated (90% of the total lift is generated during the plateau of span efficiency) suggesting that the combination of wing kinematics and morphology in locust flight perform most efficiently when doing the most work.

Life Span Extension and Neuronal Cell Protection by Drosophila Nicotinamidase*S⃞

Science.gov (United States)

Balan, Vitaly; Miller, Gregory S.; Kaplun, Ludmila; Balan, Karina; Chong, Zhao-Zhong; Li, Faqi; Kaplun, Alexander; VanBerkum, Mark F. A.; Arking, Robert; Freeman, D. Carl; Maiese, Kenneth; Tzivion, Guri

2008-01-01

The life span of model organisms can be modulated by environmental conditions that influence cellular metabolism, oxidation, or DNA integrity. The yeast nicotinamidase gene pnc1 was identified as a key transcriptional target and mediator of calorie restriction and stress-induced life span extension. PNC1 is thought to exert its effect on yeast life span by modulating cellular nicotinamide and NAD levels, resulting in increased activity of Sir2 family class III histone deacetylases. In Caenorhabditis elegans, knockdown of a pnc1 homolog was shown recently to shorten the worm life span, whereas its overexpression increased survival under conditions of oxidative stress. The function and regulation of nicotinamidases in higher organisms has not been determined. Here, we report the identification and biochemical characterization of the Drosophila nicotinamidase, D-NAAM, and demonstrate that its overexpression significantly increases median and maximal fly life span. The life span extension was reversed in Sir2 mutant flies, suggesting Sir2 dependence. Testing for physiological effectors of D-NAAM in Drosophila S2 cells, we identified oxidative stress as a primary regulator, both at the transcription level and protein activity. In contrast to the yeast model, stress factors such as high osmolarity and heat shock, calorie restriction, or inhibitors of TOR and phosphatidylinositol 3-kinase pathways do not appear to regulate D-NAAM in S2 cells. Interestingly, the expression of D-NAAM in human neuronal cells conferred protection from oxidative stress-induced cell death in a sirtuin-dependent manner. Together, our findings establish a life span extending the ability of nicotinamidase in flies and offer a role for nicotinamide-modulating genes in oxidative stress regulated pathways influencing longevity and neuronal cell survival. PMID:18678867

Evidence for deficits in the temporal attention span of poor readers.

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Troy A W Visser

Full Text Available While poor reading is often associated with phonological deficits, many studies suggest that visual processing might also be impaired. In particular, recent research has indicated that poor readers show impaired spatial visual attention spans in partial and whole report tasks. Given the similarities between competition-based accounts for reduced visual attention span and similar explanations for impairments in sequential object processing, the present work examined whether poor readers show deficits in their "temporal attention span"--that is, their ability to rapidly and accurately process sequences of consecutive target items.Poor and normal readers monitored a sequential stream of visual items for two (TT condition or three (TTT condition consecutive target digits. Target identification was examined using both unconditional and conditional measures of accuracy in order to gauge the overall likelihood of identifying a target and the likelihood of identifying a target given successful identification of previous items. Compared to normal readers, poor readers showed small but consistent deficits in identification across targets whether unconditional or conditional accuracy was used. Additionally, in the TTT condition, final-target conditional accuracy was poorer than unconditional accuracy, particularly for poor readers, suggesting a substantial cost arising from processing the previous two targets that was not present in normal readers.Mirroring the differences found between poor and normal readers in spatial visual attention span, the present findings suggest two principal differences between the temporal attention spans of poor and normal readers. First, the consistent pattern of reduced performance across targets suggests increased competition amongst items within the same span for poor readers. Second, the steeper decline in final target performance amongst poor readers in the TTT condition suggests a reduction in the extent of their

Evidence for deficits in the temporal attention span of poor readers.

Science.gov (United States)

Visser, Troy A W

2014-01-01

While poor reading is often associated with phonological deficits, many studies suggest that visual processing might also be impaired. In particular, recent research has indicated that poor readers show impaired spatial visual attention spans in partial and whole report tasks. Given the similarities between competition-based accounts for reduced visual attention span and similar explanations for impairments in sequential object processing, the present work examined whether poor readers show deficits in their "temporal attention span"--that is, their ability to rapidly and accurately process sequences of consecutive target items. Poor and normal readers monitored a sequential stream of visual items for two (TT condition) or three (TTT condition) consecutive target digits. Target identification was examined using both unconditional and conditional measures of accuracy in order to gauge the overall likelihood of identifying a target and the likelihood of identifying a target given successful identification of previous items. Compared to normal readers, poor readers showed small but consistent deficits in identification across targets whether unconditional or conditional accuracy was used. Additionally, in the TTT condition, final-target conditional accuracy was poorer than unconditional accuracy, particularly for poor readers, suggesting a substantial cost arising from processing the previous two targets that was not present in normal readers. Mirroring the differences found between poor and normal readers in spatial visual attention span, the present findings suggest two principal differences between the temporal attention spans of poor and normal readers. First, the consistent pattern of reduced performance across targets suggests increased competition amongst items within the same span for poor readers. Second, the steeper decline in final target performance amongst poor readers in the TTT condition suggests a reduction in the extent of their temporal attention

Spanning the Home/Work Creative Space

DEFF Research Database (Denmark)

Davis, Lee N.; Davis, Jerome; Hoisl, Karin

the employee brings to work. Based on Woodman et al.’s (1993) “interactionist perspective” on organizational creativity, supplemented by literature on search and knowledge re/combination, we explore whether and how leisure time activities can span the creative space between the employee’s home and workplace...

Unique ATPase site architecture triggers cis-mediated synchronized ATP binding in heptameric AAA+-ATPase domain of flagellar regulatory protein FlrC.

Science.gov (United States)

Dey, Sanjay; Biswas, Maitree; Sen, Udayaditya; Dasgupta, Jhimli

2015-04-03

Bacterial enhancer-binding proteins (bEBPs) oligomerize through AAA(+) domains and use ATP hydrolysis-driven energy to isomerize the RNA polymerase-σ(54) complex during transcriptional initiation. Here, we describe the first structure of the central AAA(+) domain of the flagellar regulatory protein FlrC (FlrC(C)), a bEBP that controls flagellar synthesis in Vibrio cholerae. Our results showed that FlrC(C) forms heptamer both in nucleotide (Nt)-free and -bound states without ATP-dependent subunit remodeling. Unlike the bEBPs such as NtrC1 or PspF, a novel cis-mediated "all or none" ATP binding occurs in the heptameric FlrC(C), because constriction at the ATPase site, caused by loop L3 and helix α7, restricts the proximity of the trans-protomer required for Nt binding. A unique "closed to open" movement of Walker A, assisted by trans-acting "Glu switch" Glu-286, facilitates ATP binding and hydrolysis. Fluorescence quenching and ATPase assays on FlrC(C) and mutants revealed that although Arg-349 of sensor II, positioned by trans-acting Glu-286 and Tyr-290, acts as a key residue to bind and hydrolyze ATP, Arg-319 of α7 anchors ribose and controls the rate of ATP hydrolysis by retarding the expulsion of ADP. Heptameric state of FlrC(C) is restored in solution even with the transition state mimicking ADP·AlF3. Structural results and pulldown assays indicated that L3 renders an in-built geometry to L1 and L2 causing σ(54)-FlrC(C) interaction independent of Nt binding. Collectively, our results underscore a novel mechanism of ATP binding and σ(54) interaction that strives to understand the transcriptional mechanism of the bEBPs, which probably interact directly with the RNA polymerase-σ(54) complex without DNA looping. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

[Survey on menopausal age and menstruation span in women in Pudong district of Shanghai].

Science.gov (United States)

Chen, Hua; Feng, You-ji; Shu, Hui-min; Lu, Tian-mei; Zhu, Hong-mei; Yang, Bin-lie; Xiong, Miao

2010-06-01

To investigate natural spontaneous menopausal age, menstruation span and their relationship with menarche age and parity in Pudong district of Shanghai. From Jan 2007 to Jul 2008, 15 083 spontaneous menopause women undergoing cervical cancer screening were enrolled in this study. The questionnaire included menarche age, parity, spontaneous menopausal age and menstruation span. Those women were divided into four groups based on age, which were group of 56 - 60, 61 - 65, 66 - 70 and more than 70.Analysis of variance (ANOVA) was used for comparing difference between menopausal age and menstruation span. Multiple factor regressions was used to analyze the relationship between menarche age, parity and menopausal age and menstruation span. (1) Spontaneous menopausal age: the minimum was 29 years old, the maximum was 61 years old, and the mean age was (50.6 ± 3.7) years old. The mean spontaneous menopause age were (50.9 ± 3.4), (50.7 ± 3.7), (50.0 ± 4.1), (49.6 ± 4.0) years in groups of 56 - 60, 61 - 65, 66 - 70 and more than 70 years. With the increasing age range in four groups, the increasing trends of menopausal age were observed, which the difference of 1.36 year was shown between groups of 56 - 60 and more than 70 years. (2) Menstruation span: the mean of menstruation span was (34.3 ± 4.1) years, which the minimal age of 12 years and maximal age of 48 years were recorded. (34.6 ± 3.8), (34.3 ± 4.1), (33.9 ± 4.6), (33.2 ± 4.5) were observed in groups of 56 - 60, 61 - 65, 66 - 70 and more than 70 years. With the increasing age range in four groups, the increasing trends of menstruation span were observed, which the difference of 1.41 year was shown between groups of 56 - 60 and more than 70 years. (3) The impact of menarche age on menopausal age and menstruation span: there was no correlation between menarche age and menopausal age (r = 0.02); however, menstruation span was found to be negatively correlated with the menarche age (r = -0.43). (4) The impact

Emotional Egocentricity Bias across the life-span

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Federica eRiva

2016-04-01

Full Text Available In our daily lives, we often have to quickly estimate the emotions of our conspecifics in order to have successful social interactions. While this estimation process seems quite easy when we are ourselves in a neutral or equivalent emotional state, it has recently been shown that in case of incongruent emotional states between ourselves and the others, our judgments can be biased. This phenomenon, introduced to the literature with the term Emotional Egocentricity Bias (EEB, has been found to occur in young adults and, to a greater extent, in children. However, how EEB changes across the life-span from adolescence to old age has been largely unexplored. In this study, we recruited 114 female participants subdivided in four cohorts (adolescents, young adults, middle-aged adults, older adults to examine EEB age-related changes. Participants were administered with a paradigm which, by making use of visuo-tactile stimulation that elicits conflicting feelings in paired participants, allows the valid and reliable exploration of EEB. Results highlighted a U-shaped relation between age and EEB, revealing higher emotional egocentricity in adolescents and older adults compared to young and middle-aged adults. These results are in line with the neuroscientific literature which has recently shown that overcoming EEB is associated with a greater activation of a portion of the parietal lobe, namely the right Supramarginal Gyrus (rSMG. This is an area that reaches full maturation only by the end of adolescence, and displays an early decay in older age. Thus, the age-related changes of the EEB could be possibly due to the life-span development of the rSMG. This study is the first one to show the quadratic relation between age and the EEB and set a milestone for further research exploring the neural correlates of the life-span development of the EEB. Future studies are needed in order to generalize these results to the male population and to explore gender

Improved Digit Span in Children after a 6-Week Intervention of Playing a Musical Instrument: An Exploratory Randomized Controlled Trial

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Xia Guo

2018-01-01

Full Text Available Previous studies have reported that music training not only improves children's musical skills, but also enhances their cognitive functions. However, there is a disagreement about what domain(s might be affected. Moreover, effects of short-term (Span test (especially in the Digit Span Backward that measures working memory. However, no significant influences were found on the other cognitive tests. The result suggests that several weeks of instrumental music training may be beneficial to improving children's working memory. In addition, we used an inexpensive and portable keyboard harmonica; therefore, our instructional method is easy to apply in classrooms or other circumstances. If the method is applied to music lessons in schools or in the community, it may help improve children's working memory.

Interorganizational Boundary Spanning in Global Software Development

DEFF Research Database (Denmark)

Søderberg, Anne-Marie; Romani, Laurence

, and which skills and competencies they draw on in their efforts to deal with emerging cross-cultural issues in a way that paves ground for developing a shared understanding and common platform for the client and vendor representatives. A framework of boundary spanning leadership practices is adapted...... to virtuality and cultural diversity. This paper, which draws on a case study of collaborative work in a global software development project, focuses on key boundary spanners in an Indian vendor company, who are responsible for developing trustful and sustainable client relations and coordinating complex...... projects across multiple cultures, languages, organisational boundaries, time zones and geographical distances. It looks into how these vendor managers get prepared for their complex boundary spanning work, which cross-cultural challenges they experience in their collaboration with Western clients...

Estimation of Height from Arm Span in 6-11 Years Children in Odisha, India

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Snigdha Prava Mishra

2017-10-01

Full Text Available Introduction: Standing height is an important anthropometric parameter to track longitudinal growth, to estimate body fatness and to calculate energy requirement. Measurement of height may be difficult in children who cannot stand. Aim: To establish regression equation for estimation of height from arm span in children. To check comparative relevancy of this equation with fixed height-to-arm span ratio (HAR for estimation of height. Materials and Methods: A cross-sectional study was conducted with 6-11 years school children (n=1465, Boys=774, Girls=691 in state of Odisha, India. Height was measured by portable stadiometer and arm span was measured by fiberglass measuring tape to nearest 0.1 cm. Pearson correlation and regression analysis was carried out between height and arm span data. p<0.05 (two tail was considered statistically significant. Results: Mean height and arm span in boys (124.16±8.74 cm and 125.57±10.43 cm respectively was significantly more (p<0.001 than height and arm span in girls (121.18±10.37 cm and 121.50±11.68 cm respectively. Mean HAR was 0.9942±0.0279. Correlation between height and arm span in boys was r = 0.94 (p<0.001 and in girls was r = 0.96 (p<0.001. Overall correlation coefficient was r = 0.95 (p<0.001. Regression equation for estimation of height from arm span was established: Height (cm = 0.8192 * arm span (cm + 21.46. Conclusion: Height in children of 6-11 years showed strong positive correlation with arm span. Regression equation established from this study can be used to estimate height from arm span. This estimation is more reliable than estimation of height from HAR.

The Influence of Dietary Fat Source on Life Span in Calorie Restricted Mice.

Science.gov (United States)

López-Domínguez, José A; Ramsey, Jon J; Tran, Dianna; Imai, Denise M; Koehne, Amanda; Laing, Steven T; Griffey, Stephen M; Kim, Kyoungmi; Taylor, Sandra L; Hagopian, Kevork; Villalba, José M; López-Lluch, Guillermo; Navas, Plácido; McDonald, Roger B

2015-10-01

Calorie restriction (CR) without malnutrition extends life span in several animal models. It has been proposed that a decrease in the amount of polyunsaturated fatty acids (PUFAs), and especially n-3 fatty acids, in membrane phospholipids may contribute to life span extension with CR. Phospholipid PUFAs are sensitive to dietary fatty acid composition, and thus, the purpose of this study was to determine the influence of dietary lipids on life span in CR mice. C57BL/6J mice were assigned to four groups (a 5% CR control group and three 40% CR groups) and fed diets with soybean oil (high in n-6 PUFAs), fish oil (high in n-3 PUFAs), or lard (high in saturated and monounsaturated fatty acids) as the primary lipid source. Life span was increased (p Life span was also increased (p life span in mice on CR, and suggest that a diet containing a low proportion of PUFAs and high proportion of monounsaturated and saturated fats may maximize life span in animals maintained on CR. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Mutations in actin used for structural studies partially disrupt β-thymosin/WH2 domains interaction.

Science.gov (United States)

Deville, Célia; Girard-Blanc, Christine; Assrir, Nadine; Nhiri, Naïma; Jacquet, Eric; Bontems, François; Renault, Louis; Petres, Stéphane; van Heijenoort, Carine

2016-10-01

Understanding the structural basis of actin cytoskeleton remodeling requires stabilization of actin monomers, oligomers, and filaments in complex with partner proteins, using various biochemical strategies. Here, we report a dramatic destabilization of the dynamic interaction with a model β-thymosin/WH2 domain induced by mutations in actin. This result underlines that mutant actins should be used with prudence to characterize interactions with intrinsically disordered partners as destabilization of dynamic interactions, although identifiable by NMR, may be invisible to other structural techniques. It also highlights how both β-thymosin/WH2 domains and actin tune local structure and dynamics in regulatory processes involving intrinsically disordered domains. © 2016 Federation of European Biochemical Societies.

A New Metal Binding Domain Involved in Cadmium, Cobalt and Zinc Transport

Energy Technology Data Exchange (ETDEWEB)

Smith, Aaron T. [Northwestern Univ., Evanston, IL (United States); Barupala, Dulmini [Wayne State Univ., Detroit, MI (United States); Stemmler, Timothy L. [Wayne State Univ., Detroit, MI (United States); Rosenzweig, Amy C. [Northwestern Univ., Evanston, IL (United States)

2015-07-20

In the P1B-ATPases, which couple cation transport across membranes to ATP hydrolysis, are central to metal homeostasis in all organisms. An important feature of P1B-ATPases is the presence of soluble metal binding domains (MBDs) that regulate transport activity. Only one type of MBD has been characterized extensively, but bioinformatics analyses indicate that a diversity of MBDs may exist in nature. Here we report the biochemical, structural and functional characterization of a new MBD from the Cupriavidus metallidurans P_1B-4-ATPase CzcP (CzcP MBD). The CzcP MBD binds two Cd²⁺, Co²⁺ or Zn²⁺ ions in distinct and unique sites and adopts an unexpected fold consisting of two fused ferredoxin-like domains. Both in vitro and in vivo activity assays using full-length CzcP, truncated CzcP and several variants indicate a regulatory role for the MBD and distinct functions for the two metal binding sites. Moreover, these findings elucidate a previously unknown MBD and suggest new regulatory mechanisms for metal transport by P_1B-ATPases.

The relationship between short-term memory and working memory: complex span made simple?

Science.gov (United States)

Bayliss, Donna M; Jarrold, Christopher; Baddeley, Alan D; Gunn, Deborah M

2005-01-01

This experiment addresses the question of what makes a working memory measure a good predictor of higher-level abilities. Verbal and visuospatial processing episodes were interleaved with distinct verbal and visuospatial storage episodes to form four complex span tasks. Although these measures were reliable predictors of reading and mathematics ability in children, they were no more predictive of these abilities than corresponding simple span tasks involving storage alone. However, when individual differences in storage ability and processing capacity were controlled for, residual variance in complex span performance was related to academic ability in some cases. These findings indicate that complex span tasks are multiply determined, and that differences in task structure can dramatically influence the relative importance of these multiple constraints and the predictive power of a complex span measure.

Glutamic acid decarboxylase-derived epitopes with specific domains expand CD4(+CD25(+ regulatory T cells.

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Guojiang Chen

Full Text Available BACKGROUND: CD4(+CD25(+ regulatory T cell (Treg-based immunotherapy is considered a promising regimen for controlling the progression of autoimmune diabetes. In this study, we tested the hypothesis that the therapeutic effects of Tregs in response to the antigenic epitope stimulation depend on the structural properties of the epitopes used. METHODOLOGY/PRINCIPAL FINDINGS: Splenic lymphocytes from nonobese diabetic (NOD mice were stimulated with different glutamic acid decarboxylase (GAD-derived epitopes for 7-10 days and the frequency and function of Tregs was analyzed. We found that, although all expanded Tregs showed suppressive functions in vitro, only p524 (GAD524-538-expanded CD4(+CD25(+ T cells inhibited diabetes development in the co-transfer models, while p509 (GAD509-528- or p530 (GAD530-543-expanded CD4(+CD25(+ T cells had no such effects. Using computer-guided molecular modeling and docking methods, the differences in structural characteristics of these epitopes and the interaction mode (including binding energy and identified domains in the epitopes between the above-mentioned epitopes and MHC class II I-A(g7 were analyzed. The theoretical results showed that the epitope p524, which induced protective Tregs, possessed negative surface-electrostatic potential and bound two chains of MHC class II I-A(g7, while the epitopes p509 and p530 which had no such ability exhibited positive surface-electrostatic potential and bound one chain of I-A(g7. Furthermore, p524 bound to I-A(g7 more stably than p509 and p530. Of importance, we hypothesized and subsequently confirmed experimentally that the epitope (GAD570-585, p570, which displayed similar characteristics to p524, was a protective epitope by showing that p570-expanded CD4(+CD25(+ T cells suppressed the onset of diabetes in NOD mice. CONCLUSIONS/SIGNIFICANCE: These data suggest that molecular modeling-based structural analysis of epitopes may be an instrumental tool for prediction of

1-Skeletons of the Spanning Tree Problems with Additional Constraints

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V. A. Bondarenko

2015-01-01

Full Text Available In this paper, we study polyhedral properties of two spanning tree problems with additional constraints. In the first problem, it is required to find a tree with a minimum sum of edge weights among all spanning trees with the number of leaves less than or equal to a given value. In the second problem, an additional constraint is the assumption that the degree of all nodes of the spanning tree does not exceed a given value. The recognition versions of both problems are NP-complete. We consider polytopes of these problems and their 1-skeletons. We prove that in both cases it is a NP-complete problem to determine whether the vertices of 1-skeleton are adjacent. Although it is possible to obtain a superpolynomial lower bounds on the clique numbers of these graphs. These values characterize the time complexity in a broad class of algorithms based on linear comparisons. The results indicate a fundamental difference between combinatorial and geometric properties of the considered problems from the classical minimum spanning tree problem.

The visual attention span deficit in dyslexia is visual and not verbal.

Science.gov (United States)

Lobier, Muriel; Zoubrinetzky, Rachel; Valdois, Sylviane

2012-06-01

The visual attention (VA) span deficit hypothesis of dyslexia posits that letter string deficits are a consequence of impaired visual processing. Alternatively, some have interpreted this deficit as resulting from a visual-to-phonology code mapping impairment. This study aims to disambiguate between the two interpretations by investigating performance in a non-verbal character string visual categorization task with verbal and non-verbal stimuli. Results show that VA span ability predicts performance for the non-verbal visual processing task in normal reading children. Furthermore, VA span impaired dyslexic children are also impaired for the categorization task independently of stimuli type. This supports the hypothesis that the underlying impairment responsible for the VA span deficit is visual, not verbal. Copyright © 2011 Elsevier Srl. All rights reserved.

The effects of age on processing and storage in working memory span tasks and reading comprehension.

Science.gov (United States)

Schroeder, Paul J

2014-01-01

BACKGROUND/STUDY CONTEXT: Declines in verbal working memory span task performance have been associated with deficits in the language processing abilities of healthy older adults, but it is unclear how storage and processing contribute to this relationship. Moreover, recent studies of the psychometric properties of span measures in the general cognitive literature highlight the need for a critical reassessment of age-related differences in working memory task performance. Forty-two young (Mage = 19.45 years) and 42 older participants (Mage = 73.00 years) completed a series of neuropsychological screening measures, four memory span tasks (one-syllable word span, three-syllable word span, reading span, and sentence span), and a measure of reading comprehension. Each span measure was completed under self-paced and timed encoding conditions. A 2 (age) × 2 (task type) × 2 (encoding conditions) mixed-model design was used. (1) Age effects were reliable for both simple and complex span task performance; (2) limiting the available encoding time yielded lower recall scores across tasks and exacerbated age differences in simple span performance; and (3) both encoding condition and age affected the relationship between each of the span measures and the relationship between span and reading comprehension. Declines in both storage and processing abilities contributed to age differences in span task performance and the relationship between span and reading comprehension. Although older people appear to benefit from task administration protocols that promote successful memory encoding, researchers should be aware of the potential risks to validity posed by such accommodations.

Relations between Preschool Attention Span-Persistence and Age 25 Educational Outcomes

Science.gov (United States)

McClelland, Megan M.; Acock, Alan C.; Piccinin, Andrea; Rhea, Sally Ann; Stallings, Michael C.

2013-01-01

This study examined relations between children's attention span-persistence in preschool and later school achievement and college completion. Children were drawn from the Colorado Adoption Project using adopted and non-adopted children (N = 430). Results of structural equation modeling indicated that children's age 4 attention span-persistence…

Assessment of regulatory effectiveness. Peer discussions on regulatory practices

International Nuclear Information System (INIS)

1999-09-01

This report arises from the seventh series of peer discussions on regulatory practices entitled 'Assessment of Regulatory Effectiveness'. The term 'regulatory effectiveness' covers the quality of the work and level of performance of a regulatory body. In this sense, regulatory effectiveness applies to regulatory body activities aimed at preventing safety degradation and ensuring that an acceptable level of safety is being maintained by the regulated operating organizations. In addition, regulatory effectiveness encompasses the promotion of safety improvements, the timely and cost effective performance of regulatory functions in a manner which ensures the confidence of the operating organizations, the general public and the government, and striving for continuous improvements to performance. Senior regulators from 22 Member States participated in two peer group discussions during March and May 1999. The discussions were focused on the elements of an effective regulatory body, possible indicators of regulatory effectiveness and its assessment. This report presents the outcome of these meetings and recommendations of good practices identified by senior regulators, which do not necessarily reflect those of the governments of the nominating Member States, the organizations they belong to, or the International Atomic Energy Agency. In order to protect people and the environment from hazards associated with nuclear facilities, the main objective of a nuclear regulatory body is to ensure that a high level of safety in the nuclear activities under its jurisdiction is achieved, maintained and within the control of operating organizations. Even if it is possible to directly judge objective safety levels at nuclear facilities, such safety levels would not provide an exclusive indicator of regulatory effectiveness. The way the regulatory body ensures the safety of workers and the public and the way it discharges its responsibilities also determine its effectiveness. Hence the

Motivated Cognition: Effects of Reward, Emotion, and Other Motivational Factors Across a Variety of Cognitive Domains

OpenAIRE

Christopher R. Madan

2017-01-01

A growing body of literature has demonstrated that motivation influences cognitive processing. The breadth of these effects is extensive and span influences of reward, emotion, and other motivational processes across all cognitive domains. As examples, this scope includes studies of emotional memory, value-based attentional capture, emotion effects on semantic processing, reward-related biases in decision making, and the role of approach/avoidance motivation on cognitive scope. Additionally, ...

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

Science.gov (United States)

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.

Towards development of a high quality public domain global roads database

Directory of Open Access Journals (Sweden)

Andrew Nelson

2006-12-01

Full Text Available There is clear demand for a global spatial public domain roads data set with improved geographic and temporal coverage, consistent coding of road types, and clear documentation of sources. The currently best available global public domain product covers only one-quarter to one-third of the existing road networks, and this varies considerably by region. Applications for such a data set span multiple sectors and would be particularly valuable for the international economic development, disaster relief, and biodiversity conservation communities, not to mention national and regional agencies and organizations around the world. The building blocks for such a global product are available for many countries and regions, yet thus far there has been neither strategy nor leadership for developing it. This paper evaluates the best available public domain and commercial data sets, assesses the gaps in global coverage, and proposes a number of strategies for filling them. It also identifies stakeholder organizations with an interest in such a data set that might either provide leadership or funding for its development. It closes with a proposed set of actions to begin the process.

Spanning k-ended trees of 3-regular connected graphs

Directory of Open Access Journals (Sweden)

Hamed Ghasemian Zoeram

2017-10-01

Full Text Available A vertex of degree one is called an end-vertex and the set of end-vertices of G is denoted by End(G. For a positive integer k, a tree T be called k-ended tree if $|End(T| \\leq k$. In this paper, we obtain sufficient conditions for spanning k-trees of 3-regular connected graphs. We give a construction sequence of graphs satisfying the condition. At the end, we present a conjecture about spanning k-ended trees of 3-regular connected graphs.

Faster Fully-Dynamic minimum spanning forest

DEFF Research Database (Denmark)

Holm, Jacob; Rotenberg, Eva; Wulff-Nilsen, Christian

2015-01-01

We give a new data structure for the fully-dynamic minimum spanning forest problem in simple graphs. Edge updates are supported in O(log4 n/log logn) expected amortized time per operation, improving the O(log4 n) amortized bound of Holm et al. (STOC’98, JACM’01).We also provide a deterministic data...

Long-term memory consolidation: The role of RNA-binding proteins with prion-like domains.

Science.gov (United States)

Sudhakaran, Indulekha P; Ramaswami, Mani

2017-05-04

Long-term and short-term memories differ primarily in the duration of their retention. At a molecular level, long-term memory (LTM) is distinguished from short-term memory (STM) by its requirement for new gene expression. In addition to transcription (nuclear gene expression) the translation of stored mRNAs is necessary for LTM formation. The mechanisms and functions for temporal and spatial regulation of mRNAs required for LTM is a major contemporary problem, of interest from molecular, cell biological, neurobiological and clinical perspectives. This review discusses primary evidence in support for translational regulatory events involved in LTM and a model in which different phases of translation underlie distinct phases of consolidation of memories. However, it focuses largely on mechanisms of memory persistence and the role of prion-like domains in this defining aspect of long-term memory. We consider primary evidence for the concept that Cytoplasmic Polyadenylation Element Binding (CPEB) protein enables the persistence of formed memories by transforming in prion-like manner from a soluble monomeric state to a self-perpetuating and persistent polymeric translationally active state required for maintaining persistent synaptic plasticity. We further discuss prion-like domains prevalent on several other RNA-binding proteins involved in neuronal translational control underlying LTM. Growing evidence indicates that such RNA regulatory proteins are components of mRNP (RiboNucleoProtein) granules. In these proteins, prion-like domains, being intrinsically disordered, could mediate weak transient interactions that allow the assembly of RNP granules, a source of silenced mRNAs whose translation is necessary for LTM. We consider the structural bases for RNA granules formation as well as functions of disordered domains and discuss how these complicate the interpretation of existing experimental data relevant to general mechanisms by which prion-domain containing RBPs

The nectin-1α transmembrane domain, but not the cytoplasmic tail, influences cell fusion induced by HSV-1 glycoproteins

International Nuclear Information System (INIS)

Subramanian, Ravi P.; Dunn, Jennifer E.; Geraghty, Robert J.

2005-01-01

Nectin-1 is a receptor for herpes simplex virus (HSV), a member of the immunoglobulin superfamily, and a cellular adhesion molecule. To study domains of nectin-1α involved in cell fusion, we measured the ability of nectin-1α/nectin-2α chimeras, nectin-1α/CD4 chimeras, and transmembrane domain and cytoplasmic tail mutants of nectin-1α to promote cell fusion induced by HSV-1 glycoproteins. Our results demonstrate that only chimeras and mutants containing the entire V-like domain and a link to the plasma membrane conferred cell-fusion activity. The transmembrane domain and cytoplasmic tail of nectin-1 were not required for any viral receptor or cell adhesion function tested. Cellular cytoplasmic factors that bind to the nectin-1α cytoplasmic tail, therefore, did not influence virus entry or cell fusion. Interestingly, the efficiency of cell fusion was reduced when membrane-spanning domains of nectin-1α and gD were replaced by glycosylphosphatidylinositol tethers, indicating that transmembrane domains may play a modulatory role in the gD/nectin-1α interaction in fusion

The effects of repeat testing, malingering, and traumatic brain injury on visuospatial memory span

Directory of Open Access Journals (Sweden)

David L Woods

2016-01-01

Full Text Available Spatial span tests such as the Corsi Block Test (CBT and the spatial span test of the Wechsler Memory Scale are widely used to assess deficits in spatial working memory. We conducted three experiments to evaluate the test-retest reliability and clinical sensitivity of a new computerized spatial span test (C-SST that incorporates psychophysical methods to improve the precision of spatial span measurement. In Experiment 1, we analyzed C-SST test-retest reliability in 49 participants who underwent three test sessions at weekly intervals. Intraclass correlation coefficients (ICC were higher for a psychophysically derived mean span (MnS metric (0.83 than for the maximal span and total correct metrics used in traditional spatial-span tests. Response times (ReTs also showed high ICCs (0.93 that correlated negatively with MnS scores and correlated positively with response-time latencies from other tests of processing speed. Learning effects were insignificant. Experiment 2 examined the performance of Experiment 1 participants when instructed to feign symptoms of traumatic brain injury: 57% showed abnormal MnS z-scores. A MnS z-score cutoff of 3.0 correctly classified 36% of simulated malingerers and 91% of the subgroup of 11 control participants with abnormal spans. Malingerers also made more substitution errors than control participants with abnormal spans (sensitivity = 43%, specificity = 91%. In addition, malingerers showed no evidence of ReT slowing, in contrast to significant abnormalities seen on other malingered tests of processing speed. As a result, differences between ReT z-scores and z-scores on other processing speed tests showed very high sensitivity and specificity in distinguishing malingering and control participants with either normal or abnormal spans. Experiment 3 examined C-SST performance in a group of patients with predominantly mild traumatic brain injury (TBI: neither MnS nor ReT z-scores showed significant group

Transcriptome sequencing from diverse human populations reveals differentiated regulatory architecture.

Directory of Open Access Journals (Sweden)

Alicia R Martin

2014-08-01

Full Text Available Large-scale sequencing efforts have documented extensive genetic variation within the human genome. However, our understanding of the origins, global distribution, and functional consequences of this variation is far from complete. While regulatory variation influencing gene expression has been studied within a handful of populations, the breadth of transcriptome differences across diverse human populations has not been systematically analyzed. To better understand the spectrum of gene expression variation, alternative splicing, and the population genetics of regulatory variation in humans, we have sequenced the genomes, exomes, and transcriptomes of EBV transformed lymphoblastoid cell lines derived from 45 individuals in the Human Genome Diversity Panel (HGDP. The populations sampled span the geographic breadth of human migration history and include Namibian San, Mbuti Pygmies of the Democratic Republic of Congo, Algerian Mozabites, Pathan of Pakistan, Cambodians of East Asia, Yakut of Siberia, and Mayans of Mexico. We discover that approximately 25.0% of the variation in gene expression found amongst individuals can be attributed to population differences. However, we find few genes that are systematically differentially expressed among populations. Of this population-specific variation, 75.5% is due to expression rather than splicing variability, and we find few genes with strong evidence for differential splicing across populations. Allelic expression analyses indicate that previously mapped common regulatory variants identified in eight populations from the International Haplotype Map Phase 3 project have similar effects in our seven sampled HGDP populations, suggesting that the cellular effects of common variants are shared across diverse populations. Together, these results provide a resource for studies analyzing functional differences across populations by estimating the degree of shared gene expression, alternative splicing, and

Spanning Tree Based Attribute Clustering

DEFF Research Database (Denmark)

Zeng, Yifeng; Jorge, Cordero Hernandez

2009-01-01

Attribute clustering has been previously employed to detect statistical dependence between subsets of variables. We propose a novel attribute clustering algorithm motivated by research of complex networks, called the Star Discovery algorithm. The algorithm partitions and indirectly discards...... inconsistent edges from a maximum spanning tree by starting appropriate initial modes, therefore generating stable clusters. It discovers sound clusters through simple graph operations and achieves significant computational savings. We compare the Star Discovery algorithm against earlier attribute clustering...

Paternal smoking habits affect the reproductive life span of daughters.

Science.gov (United States)

Fukuda, Misao; Fukuda, Kiyomi; Shimizu, Takashi; Nobunaga, Miho; Andersen, Elisabeth Wreford; Byskov, Anne Grete; Andersen, Claus Yding

2011-06-30

The present study assessed whether the smoking habits of fathers around the time of conception affected the period in which daughters experienced menstrual cycles (i.e., the reproductive life span). The study revealed that the smoking habits of the farther shortened the daughters' reproductive life span compared with daughters whose fathers did not smoke. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Free span burial inspection pig. Phase B

Energy Technology Data Exchange (ETDEWEB)

NONE

2002-04-01

This report deals with design and construction of a pipeline pig for on-line internal inspection of offshore trenched gas pipelines for pipeline burial, free spans, exposures and loss of concrete weight coating. The measuring principle uses detection of the natural gamma radiation emitted by sea bed formations and the concrete coating of the pipe to map pipeline condition. The gamma ray flux penetrating to the internal side of the pipeline is an effect of the outside conditions. The measuring principle was confirmed in a occasionally present in the gas, blurred seriously sensor signals of the previous instrumentation. The continued project activities have been divided in two phases. Phase A comprised design and construction of a detector system, which could identify and quantify radioactive components from decay of radon-222. During Phase A a new gamma detector was tested in full scale exposed to radon-222. New data analysis procedures for the correction for the influence of radon-222 inside the pipeline, where developed and its utility successfully demonstrated. During Phase B the new detector was mounted in a pipeline pig constructed for inspection of 30-inch gas pipelines. Working conditions were demonstrated in three runs through the southern route of the DONG owned 30-inch gas pipelines crossing the Danish strait named the Great Belt. The FSB-technology found 88% of the free spans identified with the latest acoustic survey. The FSB-technology found in addition 22 free spans that were termed ''invisible'', because they were not identified by the most recent acoustic survey. It is believed that ''invisible free spans'' are either real free spans or locations, where the pipeline has no or very little support from deposits in the pipeline trench. The FSB-survey confirmed all exposed sections longer than 20 metres found by the acoustic survey in the first 21 kilometre of the pipeline. However, the FSB-survey underestimated

The Transitory Phase to the Attainment of Self-Regulatory Skill in Mathematical Problem Solving

Science.gov (United States)

Lazakidou, G.; Paraskeva, F.; Retalis, S.

2007-01-01

Three phases of development of self-regulatory skill in the domain of mathematical problem solving were designed to examine students' behaviour and the effects on their problem solving ability. Forty-eight Grade 4 students (10 year olds) participated in this pilot study. The students were randomly assigned to one of three groups, each representing…

Enhancing reading performance through action video games: the role of visual attention span.

Science.gov (United States)

Antzaka, A; Lallier, M; Meyer, S; Diard, J; Carreiras, M; Valdois, S

2017-11-06

Recent studies reported that Action Video Game-AVG training improves not only certain attentional components, but also reading fluency in children with dyslexia. We aimed to investigate the shared attentional components of AVG playing and reading, by studying whether the Visual Attention (VA) span, a component of visual attention that has previously been linked to both reading development and dyslexia, is improved in frequent players of AVGs. Thirty-six French fluent adult readers, matched on chronological age and text reading proficiency, composed two groups: frequent AVG players and non-players. Participants performed behavioural tasks measuring the VA span, and a challenging reading task (reading of briefly presented pseudo-words). AVG players performed better on both tasks and performance on these tasks was correlated. These results further support the transfer of the attentional benefits of playing AVGs to reading, and indicate that the VA span could be a core component mediating this transfer. The correlation between VA span and pseudo-word reading also supports the involvement of VA span even in adult reading. Future studies could combine VA span training with defining features of AVGs, in order to build a new generation of remediation software.

Digit Span as a measure of everyday attention: a study of ecological validity.

Science.gov (United States)

Groth-Marnat, Gary; Baker, Sonya

2003-12-01

This study investigated the effectiveness of the WAIS-III Digit Span subtest to predict the everyday attention of 75 participants with heterogeneous neurological conditions who were administered the Digit Span subtest as well as the ecologically valid Test of Everyday Attention. In addition, the more visually oriented Picture Completion subtest along with the verbally loaded National Adult Reading Test were administered. Analysis indicated that, although Digit Span was a weak but statistically significant predictor of attentional ability (accounting for 12.7% of the unique variance). Picture Completion was a somewhat stronger predictor (accounting for 19% of the unique variance). The weak association of Digit Span and the Test of Everyday Attention, along with the finding that Picture Completion was a better predictor of performance on the Test of Everyday Attention, question the clinical utility of using Digit Span as a measure of everyday attention.

Crystal complexes of a predicted S-adenosylmethionine-dependent methyltransferase reveal a typical AdoMet binding domain and a substrate recognition domain

Energy Technology Data Exchange (ETDEWEB)

Miller, D.J.; Ouellette, N.; Evodokimova, E.; Savchenko, A.; Edwards, A.; Anderson, W.F. (Toronto); (NWU)

2010-03-08

S-adenosyl-L-methionine-dependent methyltransferases (MTs) are abundant, and highly conserved across phylogeny. These enzymes use the cofactor AdoMet to methylate a wide variety of molecular targets, thereby modulating important cellular and metabolic activities. Thermotoga maritima protein 0872 (TM0872) belongs to a large sequence family of predicted MTs, ranging phylogenetically from relatively simple bacteria to humans. The genes for many of the bacterial homologs are located within operons involved in cell wall synthesis and cell division. Despite preliminary biochemical studies in E. coli and B. subtilis, the substrate specificity of this group of more than 150 proteins is unknown. As part of the Midwest Center for Structural Genomics initiative (www.mcsg.anl.gov), we have determined the structure of TM0872 in complexes with AdoMet and with S-adenosyl-L-homocysteine (AdoHcy). As predicted, TM0872 has a typical MT domain, and binds endogenous AdoMet, or co-crystallized AdoHcy, in a manner consistent with other known MT structures. In addition, TM0872 has a second domain that is novel among MTs in both its location in the sequence and its structure. The second domain likely acts in substrate recognition and binding, and there is a potential substrate-binding cleft spanning the two domains. This long and narrow cleft is lined with positively charged residues which are located opposite the S{sup +}-CH{sub 3} bond, suggesting that a negatively charged molecule might be targeted for catalysis. However, AdoMet and AdoHcy are both buried, and access to the methyl group would presumably require structural rearrangement. These TM0872 crystal structures offer the first structural glimpses at this phylogenetically conserved sequence family.

Identification of functional domains of the IR2 protein of equine herpesvirus 1 required for inhibition of viral gene expression and replication

International Nuclear Information System (INIS)

Kim, Seong K.; Kim, Seongman; Dai Gan; Zhang Yunfei; Ahn, Byung C.; O'Callaghan, Dennis J.

2011-01-01

The equine herpesvirus 1 (EHV-1) negative regulatory IR2 protein (IR2P), an early 1,165-amino acid (aa) truncated form of the 1487-aa immediate-early protein (IEP), lacks the trans-activation domain essential for IEP activation functions but retains domains for binding DNA, TFIIB, and TBP and the nuclear localization signal. IR2P mutants of the N-terminal region which lack either DNA-binding activity or TFIIB-binding activity were unable to down-regulate EHV-1 promoters. In EHV-1-infected cells expressing full-length IR2P, transcription and protein expression of viral regulatory IE, early EICP0, IR4, and UL5, and late ETIF genes were dramatically inhibited. Viral DNA levels were reduced to 2.1% of control infected cells, but were vey weakly affected in cells that express the N-terminal 706 residues of IR2P. These results suggest that IR2P function requires the two N-terminal domains for binding DNA and TFIIB as well as the C-terminal residues 707 to 1116 containing the TBP-binding domain. - Highlights: → We examine the functional domains of IR2P that mediates negative regulation. → IR2P inhibits at the transcriptional level. → DNA-binding mutant or TFIIB-binding mutant fails to inhibit. → C-terminal aa 707 to 1116 are required for full inhibition. → Inhibition requires the DNA-binding domain, TFIIB-binding domain, and C-terminus.

Fatigue life assessment of free spanning pipelines containing corrosion defects

Energy Technology Data Exchange (ETDEWEB)

Lopes, Rita de Kassia D.; Campello, Georga C.; Matt, Cyntia G. da Costa; Benjamin, Adilson C.; Franciss, Ricardo [PETROBRAS S.A., Rio de Janeiro, RJ (Brazil). Centro de Pesquisas (CENPES)

2009-12-19

The free spanning pipelines assessment is a highlighted issue to be considered during the project and maintenance of the submarine pipelines. It is required to evaluate the fatigue life and the maximum stress due to VIV (Vortex Induced Vibration) as well as wave forces when applicable in case of shallow water. The code DNV-RP-F105 (2006) presents a methodology to calculate the fatigue life for free spanning pipelines. Such methodology however considers the pipe with no kind of defects. Nevertheless, sometimes corrosion defects are detected in periodic inspections and therefore their effects need to be taken into account in the fatigue life evaluation. The purpose of this paper thus is to present a procedure to assess the influence of the corrosion defects in the fatigue life of free spanning pipelines. Some FE analyses were performed to determine the stress concentrate factor (SCF) of the corrosion defects, which were used as input in the methodology presented in the code DNV-RP-F105 (2006). Curves of damage and so lifetime have been generated as function of the span length and water depth. As a practical application, this methodology was applied to a sub sea pipeline with several corrosion defects, localized in shallow water offshore Brazil. (author)

Skilled deaf readers have an enhanced perceptual span in reading.

Science.gov (United States)

Bélanger, Nathalie N; Slattery, Timothy J; Mayberry, Rachel I; Rayner, Keith

2012-07-01

Recent evidence suggests that, compared with hearing people, deaf people have enhanced visual attention to simple stimuli viewed in the parafovea and periphery. Although a large part of reading involves processing the fixated words in foveal vision, readers also utilize information in parafoveal vision to preprocess upcoming words and decide where to look next. In the study reported here, we investigated whether auditory deprivation affects low-level visual processing during reading by comparing the perceptual span of deaf signers who were skilled and less-skilled readers with the perceptual span of skilled hearing readers. Compared with hearing readers, the two groups of deaf readers had a larger perceptual span than would be expected given their reading ability. These results provide the first evidence that deaf readers' enhanced attentional allocation to the parafovea is used during complex cognitive tasks, such as reading.

Minimum spanning trees and random resistor networks in d dimensions.

Science.gov (United States)

Read, N

2005-09-01

We consider minimum-cost spanning trees, both in lattice and Euclidean models, in d dimensions. For the cost of the optimum tree in a box of size L , we show that there is a correction of order L(theta) , where theta or =1 . The arguments all rely on the close relation of Kruskal's greedy algorithm for the minimum spanning tree, percolation, and (for some arguments) random resistor networks. The scaling of the entropy and free energy at small nonzero T , and hence of the number of near-optimal solutions, is also discussed. We suggest that the Steiner tree problem is in the same universality class as the minimum spanning tree in all dimensions, as is the traveling salesman problem in two dimensions. Hence all will have the same value of theta=-3/4 in two dimensions.

PspF-binding domain PspA1-144 and the PspA·F complex: New insights into the coiled-coil-dependent regulation of AAA+ proteins.

Science.gov (United States)

Osadnik, Hendrik; Schöpfel, Michael; Heidrich, Eyleen; Mehner, Denise; Lilie, Hauke; Parthier, Christoph; Risselada, H Jelger; Grubmüller, Helmut; Stubbs, Milton T; Brüser, Thomas

2015-11-01

Phage shock protein A (PspA) belongs to the highy conserved PspA/IM30 family and is a key component of the stress inducible Psp system in Escherichia coli. One of its central roles is the regulatory interaction with the transcriptional activator of this system, the σ(54) enhancer-binding protein PspF, a member of the AAA+ protein family. The PspA/F regulatory system has been intensively studied and serves as a paradigm for AAA+ enzyme regulation by trans-acting factors. However, the molecular mechanism of how exactly PspA controls the activity of PspF and hence σ(54) -dependent expression of the psp genes is still unclear. To approach this question, we identified the minimal PspF-interacting domain of PspA, solved its structure, determined its affinity to PspF and the dissociation kinetics, identified residues that are potentially important for PspF regulation and analyzed effects of their mutation on PspF in vivo and in vitro. Our data indicate that several characteristics of AAA+ regulation in the PspA·F complex resemble those of the AAA+ unfoldase ClpB, with both proteins being regulated by a structurally highly conserved coiled-coil domain. The convergent evolution of both regulatory domains points to a general mechanism to control AAA+ activity for divergent physiologic tasks via coiled-coil domains. © 2015 John Wiley & Sons Ltd.

Sex differences in life span: Females homozygous for the X chromosome do not suffer the shorter life span predicted by the unguarded X hypothesis.

Science.gov (United States)

Brengdahl, Martin; Kimber, Christopher M; Maguire-Baxter, Jack; Friberg, Urban

2018-03-01

Life span differs between the sexes in many species. Three hypotheses to explain this interesting pattern have been proposed, involving different drivers: sexual selection, asymmetrical inheritance of cytoplasmic genomes, and hemizygosity of the X(Z) chromosome (the unguarded X hypothesis). Of these, the unguarded X has received the least experimental attention. This hypothesis suggests that the heterogametic sex suffers a shortened life span because recessive deleterious alleles on its single X(Z) chromosome are expressed unconditionally. In Drosophila melanogaster, the X chromosome is unusually large (∼20% of the genome), providing a powerful model for evaluating theories involving the X. Here, we test the unguarded X hypothesis by forcing D. melanogaster females from a laboratory population to express recessive X-linked alleles to the same degree as males, using females exclusively made homozygous for the X chromosome. We find no evidence for reduced life span or egg-to-adult viability due to X homozygozity. In contrast, males and females homozygous for an autosome both suffer similar, significant reductions in those traits. The logic of the unguarded X hypothesis is indisputable, but our results suggest that the degree to which recessive deleterious X-linked alleles depress performance in the heterogametic sex appears too small to explain general sex differences in life span. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

Suture spanning augmentation of single-row rotator cuff repair: a biomechanical analysis.

Science.gov (United States)

Early, Nicholas A; Elias, John J; Lippitt, Steven B; Filipkowski, Danielle E; Pedowitz, Robert A; Ciccone, William J

2017-02-01

This in vitro study evaluated the biomechanical benefit of adding spanning sutures to single-row rotator cuff repair. Mechanical testing was performed to evaluate 9 pairs of cadaveric shoulders with complete rotator cuff repairs, with a single-row technique used on one side and the suture spanning technique on the other. The spanning technique included sutures from 2 lateral anchors securing tendon near the musculotendinous junction, spanning the same anchor placement from single-row repair. The supraspinatus muscle was loaded to 100 N at 0.25 Hz for 100 cycles, followed by a ramp to failure. Markers and a video tracking system measured anterior and posterior gap formation across the repair at 25-cycle intervals. The force at which the stiffness decreased by 50% and 75% was determined. Data were compared using paired t-tests. One single-row repair failed at row repairs than for the suture spanning technique. The difference was statistically significant at all cycles for the posterior gap formation (P ≤ .02). The trends were not significant for the anterior gap (P ≥ .13). The loads at which the stiffness decreased by 50% and 75% did not differ significantly between the 2 types of repair (P ≥ .10). The suture spanning technique primarily improved posterior gap formation. Decreased posterior gap formation could reduce failure rates for rotator cuff repair. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Dual RNA regulatory control of a Staphylococcus aureus virulence factor.

Science.gov (United States)

Chabelskaya, Svetlana; Bordeau, Valérie; Felden, Brice

2014-04-01

In pathogens, the accurate programming of virulence gene expression is essential for infection. It is achieved by sophisticated arrays of regulatory proteins and ribonucleic acids (sRNAs), but in many cases their contributions and connections are not yet known. Based on genetic, biochemical and structural evidence, we report that the expression pattern of a Staphylococcus aureus host immune evasion protein is enabled by the collaborative actions of RNAIII and small pathogenicity island RNA D (SprD). Their combined expression profiles during bacterial growth permit early and transient synthesis of Sbi to avoid host immune responses. Together, these two sRNAs use antisense mechanisms to monitor Sbi expression at the translational level. Deletion analysis combined with structural analysis of RNAIII in complex with its novel messenger RNA (mRNA) target indicate that three distant RNAIII domains interact with distinct sites of the sbi mRNA and that two locations are deep in the sbi coding region. Through distinct domains, RNAIII lowers production of two proteins required for avoiding innate host immunity, staphylococcal protein A and Sbi. Toeprints and in vivo mutational analysis reveal a novel regulatory module within RNAIII essential for attenuation of Sbi translation. The sophisticated translational control of mRNA by two differentially expressed sRNAs ensures supervision of host immune escape by a major pathogen.

Flutter suppression and stability analysis for a variable-span wing via morphing technology

Science.gov (United States)

Li, Wencheng; Jin, Dongping

2018-01-01

A morphing wing can enhance aerodynamic characteristics and control authority as an alternative to using ailerons. To use morphing technology for flutter suppression, the dynamical behavior and stability of a variable-span wing subjected to the supersonic aerodynamic loads are investigated numerically in this paper. An axially moving cantilever plate is employed to model the variable-span wing, in which the governing equations of motion are established via the Kane method and piston theory. A morphing strategy based on axially moving rates is proposed to suppress the flutter that occurs beyond the critical span length, and the flutter stability is verified by Floquet theory. Furthermore, the transient stability during the morphing motion is analyzed and the upper bound of the morphing rate is obtained. The simulation results indicate that the proposed morphing law, which is varying periodically with a proper amplitude, could accomplish the flutter suppression. Further, the upper bound of the morphing speed decreases rapidly once the span length is close to its critical span length.

Modelling ecosystem service flows under uncertainty with stochiastic SPAN

Science.gov (United States)

Johnson, Gary W.; Snapp, Robert R.; Villa, Ferdinando; Bagstad, Kenneth J.

2012-01-01

Ecosystem service models are increasingly in demand for decision making. However, the data required to run these models are often patchy, missing, outdated, or untrustworthy. Further, communication of data and model uncertainty to decision makers is often either absent or unintuitive. In this work, we introduce a systematic approach to addressing both the data gap and the difficulty in communicating uncertainty through a stochastic adaptation of the Service Path Attribution Networks (SPAN) framework. The SPAN formalism assesses ecosystem services through a set of up to 16 maps, which characterize the services in a study area in terms of flow pathways between ecosystems and human beneficiaries. Although the SPAN algorithms were originally defined deterministically, we present them here in a stochastic framework which combines probabilistic input data with a stochastic transport model in order to generate probabilistic spatial outputs. This enables a novel feature among ecosystem service models: the ability to spatially visualize uncertainty in the model results. The stochastic SPAN model can analyze areas where data limitations are prohibitive for deterministic models. Greater uncertainty in the model inputs (including missing data) should lead to greater uncertainty expressed in the model’s output distributions. By using Bayesian belief networks to fill data gaps and expert-provided trust assignments to augment untrustworthy or outdated information, we can account for uncertainty in input data, producing a model that is still able to run and provide information where strictly deterministic models could not. Taken together, these attributes enable more robust and intuitive modelling of ecosystem services under uncertainty.

Singular Perturbation Analysis and Gene Regulatory Networks with Delay

Science.gov (United States)

Shlykova, Irina; Ponosov, Arcady

2009-09-01

There are different ways of how to model gene regulatory networks. Differential equations allow for a detailed description of the network's dynamics and provide an explicit model of the gene concentration changes over time. Production and relative degradation rate functions used in such models depend on the vector of steeply sloped threshold functions which characterize the activity of genes. The most popular example of the threshold functions comes from the Boolean network approach, where the threshold functions are given by step functions. The system of differential equations becomes then piecewise linear. The dynamics of this system can be described very easily between the thresholds, but not in the switching domains. For instance this approach fails to analyze stationary points of the system and to define continuous solutions in the switching domains. These problems were studied in [2], [3], but the proposed model did not take into account a time delay in cellular systems. However, analysis of real gene expression data shows a considerable number of time-delayed interactions suggesting that time delay is essential in gene regulation. Therefore, delays may have a great effect on the dynamics of the system presenting one of the critical factors that should be considered in reconstruction of gene regulatory networks. The goal of this work is to apply the singular perturbation analysis to certain systems with delay and to obtain an analog of Tikhonov's theorem, which provides sufficient conditions for constracting the limit system in the delay case.

Octave-Spanning Mid-IR Supercontinuum Generation with Ultrafast Cascaded Nonlinearities

DEFF Research Database (Denmark)

Zhou, Binbin; Guo, Hairun; Liu, Xing

2014-01-01

An octave-spanning mid-IR supercontinuum is observed experimentally using ultrafast cascaded nonlinearities in an LiInS2 quadratic nonlinear crystal pumped with 70 fs energetic mid-IR pulses and cut for strongly phase-mismatched second-harmonic generation.......An octave-spanning mid-IR supercontinuum is observed experimentally using ultrafast cascaded nonlinearities in an LiInS2 quadratic nonlinear crystal pumped with 70 fs energetic mid-IR pulses and cut for strongly phase-mismatched second-harmonic generation....

Comparative analysis of glutaredoxin domains from bacterial opportunistic pathogens

International Nuclear Information System (INIS)

Leeper, Thomas; Zhang, Suxin; Van Voorhis, Wesley C.; Myler, Peter J.; Varani, Gabriele

2011-01-01

NMR structures of the glutaredoxin (GLXR) domains from Br. melitensis and Ba. henselae have been determined as part of the SSGCID initiative. Comparison of the domains with known structures reveals overall structural similarity between these proteins and previously determined E. coli GLXR structures, with minor changes associated with the position of helix 1 and with regions that diverge from similar structures found in the closest related human homolog. Glutaredoxin proteins (GLXRs) are essential components of the glutathione system that reductively detoxify substances such as arsenic and peroxides and are important in the synthesis of DNA via ribonucleotide reductases. NMR solution structures of glutaredoxin domains from two Gram-negative opportunistic pathogens, Brucella melitensis and Bartonella henselae, are presented. These domains lack the N-terminal helix that is frequently present in eukaryotic GLXRs. The conserved active-site cysteines adopt canonical proline/tyrosine-stabilized geometries. A difference in the angle of α-helix 2 relative to the β-sheet surface and the presence of an extended loop in the human sequence suggests potential regulatory regions and/or protein–protein interaction motifs. This observation is consistent with mutations in this region that suppress defects in GLXR–ribonucleotide reductase interactions. These differences between the human and bacterial forms are adjacent to the dithiol active site and may permit species-selective drug design

Probing SH2-domains using Inhibitor Affinity Purification (IAP).

Science.gov (United States)

Höfener, Michael; Heinzlmeir, Stephanie; Kuster, Bernhard; Sewald, Norbert

2014-01-01

Many human diseases are correlated with the dysregulation of signal transduction processes. One of the most important protein interaction domains in the context of signal transduction is the Src homology 2 (SH2) domain that binds phosphotyrosine residues. Hence, appropriate methods for the investigation of SH2 proteins are indispensable in diagnostics and medicinal chemistry. Therefore, an affinity resin for the enrichment of all SH2 proteins in one experiment would be desirable. However, current methods are unable to address all SH2 proteins simultaneously with a single compound or a small array of compounds. In order to overcome these limitations for the investigation of this particular protein family in future experiments, a dipeptide-derived probe has been designed, synthesized and evaluated. This probe successfully enriched 22 SH2 proteins from mixed cell lysates which contained 50 SH2 proteins. Further characterization of the SH2 binding properties of the probe using depletion and competition experiments indicated its ability to enrich complexes consisting of SH2 domain bearing regulatory PI3K subunits and catalytic phosphoinositide 3-kinase (PI3K) subunits that have no SH2 domain. The results make this probe a promising starting point for the development of a mixed affinity resin with complete SH2 protein coverage. Moreover, the additional findings render it a valuable tool for the evaluation of PI3K complex interrupting inhibitors.

Slicing-independent RISC activation requires the argonaute PAZ domain.

Science.gov (United States)

Gu, Shuo; Jin, Lan; Huang, Yong; Zhang, Feijie; Kay, Mark A

2012-08-21

Small RNAs regulate genetic networks through a ribonucleoprotein complex called the RNA-induced silencing complex (RISC), which, in mammals, contains at its center one of four Argonaute proteins (Ago1-Ago4). A key regulatory event in the RNA interference (RNAi) and microRNA (miRNA) pathways is Ago loading, wherein double-stranded small-RNA duplexes are incorporated into RISC (pre-RISC) and then become single-stranded (mature RISC), a process that is not well understood. The Agos contain an evolutionarily conserved PAZ (Piwi/Argonaute/Zwille) domain whose primary function is to bind the 3' end of small RNAs. We created multiple PAZ-domain-disrupted mutant Ago proteins and studied their biochemical properties and biological functionality in cells. We found that the PAZ domain is dispensable for Ago loading of slicing-competent RISC. In contrast, in the absence of slicer activity or slicer-substrate duplex RNAs, PAZ-disrupted Agos bound duplex small interfering RNAs, but were unable to unwind or eject the passenger strand and form functional RISC complexes. We have discovered that the highly conserved PAZ domain plays an important role in RISC activation, providing new mechanistic insights into how miRNAs regulate genes, as well as new insights for future design of miRNA- and RNAi-based therapeutics. Copyright © 2012 Elsevier Ltd. All rights reserved.

Regulatory activities

International Nuclear Information System (INIS)

2001-01-01

This publication, compiled in 8 chapters, presents the regulatory system developed by the Nuclear Regulatory Authority (NRA) of the Argentine Republic. The following activities and developed topics in this document describe: the evolution of the nuclear regulatory activity in Argentina; the Argentine regulatory system; the nuclear regulatory laws and standards; the inspection and safeguards of nuclear facilities; the emergency systems; the environmental systems; the environmental monitoring; the analysis laboratories on physical and biological dosimetry, prenatal irradiation, internal irradiation, radiation measurements, detection techniques on nuclear testing, medical program on radiation protection; the institutional relations with national and international organization; the training courses and meeting; the technical information

The regulatory function in radioactive waste management

International Nuclear Information System (INIS)

Duncan, A.; Pescatore, C.

2008-01-01

Allan Duncan, expert to NEA and former Chief Inspector for Pollution (United Kingdom), elaborated on the regulatory function in the domain of radioactive waste management. The preparation of a document and a brochure on the subject has been one of the main tasks of the Regulators' Forum since its creation in 2001. He stressed that management of NORM waste was generally subject to different standards than similar radioactive waste from a nuclear source, for no obvious reason than that of public perception. He also pointed out the large number of 'regulatory bodies' involved in the regulation of radioactive waste management facilities and particularly geological disposal facilities, and their links to the Government. He gave the example of the United Kingdom. He stressed the fact that, since there will not be continuous control, licensing of geological disposal is an act of trust in the regulatory system. A. Duncan gave the position of two Commissions in England on deep geological disposal. The UK Sustainable Development Commission says, 'it is impossible to guarantee safety over long-term disposal of (nuclear) waste' which implies that nuclear fission power should be shut down; CoRWM, the Committee on Radioactive Waste Management, recommends instead geological disposal for existing wastes as a broadly acceptable solution. As a concluding remark A. Duncan focused the attention on the general question of what current society needs to do in order to meet its obligations to future generations with respect to disposal of long-lived wastes. (authors)

Accelerators: radiation safety and regulatory compliance

International Nuclear Information System (INIS)

Bandyopadhyay, Tapas

2013-01-01

Growth of accelerators, both positive ions and electron, is very high in India. This may be because of the wide acceptance of these machines in the industrial purposes, medical uses, material science studies, upcoming ADSS facility and many other reasons. Most of cases for societal uses, accelerators have to be installed in the dense public domain. Accelerators for basic research and development purposes to be installed may in public domain or in isolated site. These accelerators are to be classified into different categories in terms of regulatory compliance. Radiation shield design, HVAC system required to be in place with design so that the dose and effluent discharge in the public domain is within a limit considering different pathways. INDUS I and II at Indore, K-130 and K500 machine at VECC, Pelletron at TIFR, IUAC, BARC, EBC at Mumbai are in operation. Apart from this accelerators, a series of medical accelerators in operation and yet to be operational which are generally producing PET isotopes for the diagnosis purposes. VECC is aiming to operate 30 MeV proton machine with about 500 μA beam current for the production of PET, SPECT isotopes for diagnosis purposes and also therapeutic use in near future. Detail requirement in terms of choice of sites, source term estimation for achieving optimum shield thickness, ventilation system, site layout and planning , radioactive effluent handling both gaseous and liquid, decommission aspects will be discussed. (author)

Natural ventilation of large multi-span greenhouses

NARCIS (Netherlands)

Jong, de T.

1990-01-01

In this thesis the ventilation of large multi-span greenhouses caused by wind and temperature effects is studied. Quantification of the ventilation is important to improve the control of the greenhouse climate.

Knowledge of the flow characteristics of the one-side-mounted windows of

Leaf life span plasticity in tropical seedlings grown under contrasting light regimes.

Science.gov (United States)

Vincent, Gregoire

2006-02-01

The phenotypic plasticity of leaf life span in response to low resource conditions has a potentially large impact on the plant carbon budget, notably in evergreen species not subject to seasonal leaf shedding, but has rarely been well documented. This study evaluates the plasticity of leaf longevity, in terms of its quantitative importance to the plant carbon balance under limiting light. Seedlings of four tropical tree species with contrasting light requirements (Alstonia scholaris, Hevea brasiliensis, Durio zibethinus and Lansium domesticum) were grown under three light regimes (full sunlight, 45 % sunlight and 12 % sunlight). Their leaf dynamics were monitored over 18 months. All species showed a considerable level of plasticity with regard to leaf life span: over the range of light levels explored, the ratio of the range to the mean value of life span varied from 29 %, for the least plastic species, to 84 %, for the most. The common trend was for leaf life span to increase with decreasing light intensity. The plasticity apparent in leaf life span was similar in magnitude to the plasticity observed in specific leaf area and photosynthetic rate, implying that it has a significant impact on carbon gain efficiency when plants acclimate to different light regimes. In all species, median survival time was negatively correlated with leaf photosynthetic capacity (or its proxy, the nitrogen content per unit area) and leaf emergence rate. Longer leaf life spans under low light are likely to be a consequence of slower ageing as a result of a slower photosynthetic metabolism.

Time and resource limits on working memory: cross-age consistency in counting span performance.

Science.gov (United States)

Ransdell, Sarah; Hecht, Steven

2003-12-01

This longitudinal study separated resource demand effects from those of retention interval in a counting span task among 100 children tested in grade 2 and again in grades 3 and 4. A last card large counting span condition had an equivalent memory load to a last card small, but the last card large required holding the count over a longer retention interval. In all three waves of assessment, the last card large condition was found to be less accurate than the last card small. A model predicting reading comprehension showed that age was a significant predictor when entered first accounting for 26% of the variance, but counting span accounted for a further 22% of the variance. Span at Wave 1 accounted for significant unique variance at Wave 2 and at Wave 3. Results were similar for math calculation with age accounting for 31% of the variance and counting span accounting for a further 34% of the variance. Span at Wave 1 explained unique variance in math at Wave 2 and at Wave 3.

Relationships between Categorical Perception of Phonemes, Phoneme Awareness, and Visual Attention Span in Developmental Dyslexia.

Directory of Open Access Journals (Sweden)

Rachel Zoubrinetzky

Full Text Available We tested the hypothesis that the categorical perception deficit of speech sounds in developmental dyslexia is related to phoneme awareness skills, whereas a visual attention (VA span deficit constitutes an independent deficit. Phoneme awareness tasks, VA span tasks and categorical perception tasks of phoneme identification and discrimination using a d/t voicing continuum were administered to 63 dyslexic children and 63 control children matched on chronological age. Results showed significant differences in categorical perception between the dyslexic and control children. Significant correlations were found between categorical perception skills, phoneme awareness and reading. Although VA span correlated with reading, no significant correlations were found between either categorical perception or phoneme awareness and VA span. Mediation analyses performed on the whole dyslexic sample suggested that the effect of categorical perception on reading might be mediated by phoneme awareness. This relationship was independent of the participants' VA span abilities. Two groups of dyslexic children with a single phoneme awareness or a single VA span deficit were then identified. The phonologically impaired group showed lower categorical perception skills than the control group but categorical perception was similar in the VA span impaired dyslexic and control children. The overall findings suggest that the link between categorical perception, phoneme awareness and reading is independent from VA span skills. These findings provide new insights on the heterogeneity of developmental dyslexia. They suggest that phonological processes and VA span independently affect reading acquisition.

Relationships between Categorical Perception of Phonemes, Phoneme Awareness, and Visual Attention Span in Developmental Dyslexia.

Science.gov (United States)

Zoubrinetzky, Rachel; Collet, Gregory; Serniclaes, Willy; Nguyen-Morel, Marie-Ange; Valdois, Sylviane

2016-01-01

We tested the hypothesis that the categorical perception deficit of speech sounds in developmental dyslexia is related to phoneme awareness skills, whereas a visual attention (VA) span deficit constitutes an independent deficit. Phoneme awareness tasks, VA span tasks and categorical perception tasks of phoneme identification and discrimination using a d/t voicing continuum were administered to 63 dyslexic children and 63 control children matched on chronological age. Results showed significant differences in categorical perception between the dyslexic and control children. Significant correlations were found between categorical perception skills, phoneme awareness and reading. Although VA span correlated with reading, no significant correlations were found between either categorical perception or phoneme awareness and VA span. Mediation analyses performed on the whole dyslexic sample suggested that the effect of categorical perception on reading might be mediated by phoneme awareness. This relationship was independent of the participants' VA span abilities. Two groups of dyslexic children with a single phoneme awareness or a single VA span deficit were then identified. The phonologically impaired group showed lower categorical perception skills than the control group but categorical perception was similar in the VA span impaired dyslexic and control children. The overall findings suggest that the link between categorical perception, phoneme awareness and reading is independent from VA span skills. These findings provide new insights on the heterogeneity of developmental dyslexia. They suggest that phonological processes and VA span independently affect reading acquisition.

Relationships between Categorical Perception of Phonemes, Phoneme Awareness, and Visual Attention Span in Developmental Dyslexia

Science.gov (United States)

Zoubrinetzky, Rachel; Collet, Gregory; Serniclaes, Willy; Nguyen-Morel, Marie-Ange; Valdois, Sylviane

2016-01-01

We tested the hypothesis that the categorical perception deficit of speech sounds in developmental dyslexia is related to phoneme awareness skills, whereas a visual attention (VA) span deficit constitutes an independent deficit. Phoneme awareness tasks, VA span tasks and categorical perception tasks of phoneme identification and discrimination using a d/t voicing continuum were administered to 63 dyslexic children and 63 control children matched on chronological age. Results showed significant differences in categorical perception between the dyslexic and control children. Significant correlations were found between categorical perception skills, phoneme awareness and reading. Although VA span correlated with reading, no significant correlations were found between either categorical perception or phoneme awareness and VA span. Mediation analyses performed on the whole dyslexic sample suggested that the effect of categorical perception on reading might be mediated by phoneme awareness. This relationship was independent of the participants’ VA span abilities. Two groups of dyslexic children with a single phoneme awareness or a single VA span deficit were then identified. The phonologically impaired group showed lower categorical perception skills than the control group but categorical perception was similar in the VA span impaired dyslexic and control children. The overall findings suggest that the link between categorical perception, phoneme awareness and reading is independent from VA span skills. These findings provide new insights on the heterogeneity of developmental dyslexia. They suggest that phonological processes and VA span independently affect reading acquisition. PMID:26950210

Regulatory domain or CpG site variation in SLC12A5, encoding the chloride transporter KCC2, in human autism and schizophrenia

Directory of Open Access Journals (Sweden)

Nancy D Merner

2015-10-01

Full Text Available Many encoded gene products responsible for neurodevelopmental disorders (NDs like autism spectrum disorders (ASD, schizophrenia (SCZ, intellectual disability (ID, and idiopathic generalized epilepsy (IGE converge on networks controlling synaptic function. An increase in KCC2 (SLC12A5 Cl- transporter activity drives the developmental GABA excitatory-inhibitory sequence, but the role of KCC2 in human NDs is essentially unknown. Here, we report two rare, non-synonymous (NS, functionally-impairing variants in the KCC2 C-terminal regulatory domain (CTRD in human ASD (R952H and R1049C and SCZ (R952H previously linked with IGE and familial febrile seizures, and another novel NS KCC2 variant in ASD (R1048W with highly-predicted pathogenicity. Exome data from 2517 simplex families in the ASD Simon Simplex Collection revealed significantly more KCC2 CTRD variants in ASD cases than controls, and interestingly, these were more often synonymous and predicted to disrupt or introduce a CpG site. Furthermore, full gene analysis showed ASD cases are more likely to contain rare KCC2 variants affecting CpG sites than controls. These data suggest genetically-encoded dysregulation of KCC2-dependent GABA signaling may contribute to multiple human NDs.

Determinants to dose reduction in EMCCR - in regulatory perspective

International Nuclear Information System (INIS)

Mohan, V.; Venkataraman, S.; Venkataraman, R.; Sajeev, B.S.

2006-01-01

Indian PHWRs had experienced three en masse coolant channel replacement campaigns, (EMCCR) first in RAPS-2, next in MAPS-2 and the last in MAPS-1. The campaign is already in full swing at NAPS-1. At MAPS, two EMCCR campaigns were done in a span of four years. The collective dose consumption in the MAPS-1 campaign was only about 25 % that of MAPS-2, a commendable achievement. Based on the experience of RAPS-2 and MAPS-2 campaigns, AERB - through several regulatory means- had given directives for reduction in collective dose in MAPS-1 campaign which was successfully implemented. This paper analyses and quantifies the key factors that contributed to collective dose reduction in MAPS-1 EMCCR. These factors could be put to use in the on going NAPS and forthcoming KAPS campaigns. (author)

Comparison between BIDE, PrefixSpan, and TRuleGrowth for Mining of Indonesian Text

Science.gov (United States)

Sa'adillah Maylawati, Dian; Irfan, Mohamad; Budiawan Zulfikar, Wildan

2017-01-01

Mining proscess for Indonesian language still be an interesting research. Multiple of words representation was claimed can keep the meaning of text better than bag of words. In this paper, we compare several sequential pattern algortihm, among others BIDE (BIDirectional Extention), PrefixSpan, and TRuleGrowth. All of those algorithm produce frequent word sequence to keep the meaning of text. However, the experiment result, with 14.006 of Indonesian tweet from Twitter, shows that BIDE can produce more efficient frequent word sequence than PrefixSpan and TRuleGrowth without missing the meaning of text. Then, the average of time process of PrefixSpan is faster than BIDE and TRuleGrowth. In the other hand, PrefixSpan and TRuleGrowth is more efficient in using memory than BIDE.

Parents' and Teachers' Perceptions of Abnormal Attention Span of Elementary School-Age Children.

Science.gov (United States)

Segal-Triwitz, Yael; Kirchen, Louisa M; Shani Sherman, Tal; Levav, Miriam; Schonherz-Pine, Yael; Kushnir, Jonathan; Ariel, Raya; Gothelf, Doron

2016-01-01

To determine teacher and parental perception of minimal expected sustained attention span during various daily tasks among elementary school children. 54 parents and 47 teachers completed the attention span questionnaire (AtSQ) that was developed for this study. The AtSQ consists of 15 academic and leisure tasks that require a child's sustained attention. The study focused on third and fourth graders in Israel. There was a high degree of variability among teachers and parents in their responses to the AtSQ. The expected attention span of children as judged by parents was higher and more varied compared to teachers, and higher for girls than for boys. Our results indicate poor agreement in cutoff values for sustained attention span between teachers and parents and within each group.

DNA residence time is a regulatory factor of transcription repression

Science.gov (United States)

Clauß, Karen; Popp, Achim P.; Schulze, Lena; Hettich, Johannes; Reisser, Matthias; Escoter Torres, Laura; Uhlenhaut, N. Henriette

2017-01-01

Abstract Transcription comprises a highly regulated sequence of intrinsically stochastic processes, resulting in bursts of transcription intermitted by quiescence. In transcription activation or repression, a transcription factor binds dynamically to DNA, with a residence time unique to each factor. Whether the DNA residence time is important in the transcription process is unclear. Here, we designed a series of transcription repressors differing in their DNA residence time by utilizing the modular DNA binding domain of transcription activator-like effectors (TALEs) and varying the number of nucleotide-recognizing repeat domains. We characterized the DNA residence times of our repressors in living cells using single molecule tracking. The residence times depended non-linearly on the number of repeat domains and differed by more than a factor of six. The factors provoked a residence time-dependent decrease in transcript level of the glucocorticoid receptor-activated gene SGK1. Down regulation of transcription was due to a lower burst frequency in the presence of long binding repressors and is in accordance with a model of competitive inhibition of endogenous activator binding. Our single molecule experiments reveal transcription factor DNA residence time as a regulatory factor controlling transcription repression and establish TALE-DNA binding domains as tools for the temporal dissection of transcription regulation. PMID:28977492

Reconstruction of the gene regulatory network involved in the sonic hedgehog pathway with a potential role in early development of the mouse brain.

Directory of Open Access Journals (Sweden)

Jinhua Liu

2014-10-01

Full Text Available The Sonic hedgehog (Shh signaling pathway is crucial for pattern formation in early central nervous system development. By systematically analyzing high-throughput in situ hybridization data of E11.5 mouse brain, we found that Shh and its receptor Ptch1 define two adjacent mutually exclusive gene expression domains: Shh+Ptch1- and Shh-Ptch1+. These two domains are associated respectively with Foxa2 and Gata3, two transcription factors that play key roles in specifying them. Gata3 ChIP-seq experiments and RNA-seq assays on Gata3-knockdown cells revealed that Gata3 up-regulates the genes that are enriched in the Shh-Ptch1+ domain. Important Gata3 targets include Slit2 and Slit3, which are involved in the process of axon guidance, as well as Slc18a1, Th and Qdpr, which are associated with neurotransmitter synthesis and release. By contrast, Foxa2 both up-regulates the genes expressed in the Shh+Ptch1- domain and down-regulates the genes characteristic of the Shh-Ptch1+ domain. From these and other data, we were able to reconstruct a gene regulatory network governing both domains. Our work provides the first genome-wide characterization of the gene regulatory network involved in the Shh pathway that underlies pattern formation in the early mouse brain.

Three distinct domains contribute to nuclear transport of murine Foxp3.

Directory of Open Access Journals (Sweden)

Wayne W Hancock

2009-11-01

Full Text Available Foxp3, a 47-kDa transcription factor, is necessary for the function of CD4+CD25+ regulatory T cells (Tregs, with an essential role in the control of self-reactive T cells and in preventing autoimmunity. Activation of Tregs by TCR engagement results in upregulation of Foxp3 expression, followed by its rapid nuclear transport and binding to chromatin. Here, we identify three distinct Foxp3 domains that contribute to nuclear transport. The first domain (Domain 1 comprises the C-terminal 12 amino acids. The second domain (Domain 2 is located immediately N-terminal to the forkhead domain (FHD, recently reported to be a binding site for the runt-related transcription factor 1/acute myeloid leukemia 1 (Runx1/AML1. The third domain (Domain 3 is located within the N-terminal first 51 amino acids. Unlike the known nuclear localization signals (NLSs, none of these three regions are rich in basic residues and do not bear any similarity to known monopartite or bipartite NLSs that have one or more clusters of basic amino acids. The basic arginine-lysine-lysine-arginine (RKKR sequence, located 12-aa from the C-terminal end of Foxp3 was previously reported to be a nuclear localization signal (NLS for several proteins, including for a GFP-Foxp3 hybrid. Evidence is provided here that in the full-length native Foxp3 RKKR does not function as an NLS. The data reported in this study indicates that Foxp3 achieves nuclear transport by binding to other nuclear factors and co-transporting with them to the nucleus.

Aeroelastic stability of full-span tiltrotor aircraft model in forward flight

Directory of Open Access Journals (Sweden)

Zhiquan LI

2017-12-01

Full Text Available The existing full-span models of the tiltrotor aircraft adopted the rigid blade model without considering the coupling relationship among the elastic blade, wing and fuselage. To overcome the limitations of the existing full-span models and improve the precision of aeroelastic analysis of tiltrotor aircraft in forward flight, the aeroelastic stability analysis model of full-span tiltrotor aircraft in forward flight has been presented in this paper by considering the coupling among elastic blade, wing, fuselage and various components. The analytical model is validated by comparing with the calculation results and experimental data in the existing references. The influence of some structural parameters, such as the fuselage degrees of freedom, relative displacement between the hub center and the gravity center, and nacelle length, on the system stability is also investigated. The results show that the fuselage degrees of freedom decrease the critical stability velocity of tiltrotor aircraft, and the variation of the structural parameters has great influence on the system stability, and the instability form of system can change between the anti-symmetric and symmetric wing motions of vertical and chordwise bending. Keywords: Aeroelastic stability, Forward flight, Full-span model, Modal analysis, Tiltrotor aircraft

Young Skilled Deaf Readers Have an Enhanced Perceptual Span in Reading.

Science.gov (United States)

Bélanger, Nathalie N; Lee, Michelle; Schotter, Elizabeth R

2017-04-27

Recently, Bélanger, Slattery, Mayberry and Rayner (2012) showed, using the moving window paradigm, that profoundly deaf adults have a wider perceptual span during reading relative to hearing adults matched on reading level. This difference might be related to the fact that deaf adults allocate more visual attention to simple stimuli in the parafovea (Bavelier, Dye & Hauser, 2006). Importantly, this reorganization of visual attention in deaf individuals is already manifesting in deaf children (Dye, Hauser & Bavelier, 2009). This leads to questions about the time course of the emergence of an enhanced perceptual span (which is under attentional control; Rayner, 2014; Miellet, O'Donnell, & Sereno, 2009) in young deaf readers. The present research addressed this question by comparing the perceptual spans of young deaf readers (age 7-15) and young hearing children (age 7-15). Young deaf readers, like deaf adults, were found to have a wider perceptual span relative to their hearing peers matched on reading level, suggesting that strong and early reorganization of visual attention in deaf individuals goes beyond the processing of simple visual stimuli and emerges into more cognitively complex tasks, such as reading.

A novel calmodulin-regulated Ca2+-ATPase (ACA2) from Arabidopsis with an N-terminal autoinhibitory domain

Science.gov (United States)

Harper, J. F.; Hong, B.; Hwang, I.; Guo, H. Q.; Stoddard, R.; Huang, J. F.; Palmgren, M. G.; Sze, H.; Evans, M. L. (Principal Investigator)

1998-01-01

To study transporters involved in regulating intracellular Ca2+, we isolated a full-length cDNA encoding a Ca2+-ATPase from a model plant, Arabidopsis, and named it ACA2 (Arabidopsis Ca2+-ATPase, isoform 2). ACA2p is most similar to a "plasma membrane-type" Ca2+-ATPase, but is smaller (110 kDa), contains a unique N-terminal domain, and is missing a long C-terminal calmodulin-binding regulatory domain. In addition, ACA2p is localized to an endomembrane system and not the plasma membrane, as shown by aqueous-two phase fractionation of microsomal membranes. ACA2p was expressed in yeast as both a full-length protein (ACA2-1p) and an N-terminal truncation mutant (ACA2-2p; Delta residues 2-80). Only the truncation mutant restored the growth on Ca2+-depleted medium of a yeast mutant defective in both endogenous Ca2+ pumps, PMR1 and PMC1. Although basal Ca2+-ATPase activity of the full-length protein was low, it was stimulated 5-fold by calmodulin (50% activation around 30 nM). In contrast, the truncated pump was fully active and insensitive to calmodulin. A calmodulin-binding sequence was identified within the first 36 residues of the N-terminal domain, as shown by calmodulin gel overlays on fusion proteins. Thus, ACA2 encodes a novel calmodulin-regulated Ca2+-ATPase distinguished by a unique N-terminal regulatory domain and a non-plasma membrane localization.

[The evolution of plant life span: facts and hypotheses].

Science.gov (United States)

2006-01-01

There are two different views on the evolution of life forms in Cormophyta: from woody plants to herbaceous ones or in opposite direction - from herbs to trees. In accordance with these views it is supposed that life span in plants changed in the course of evolution from many years (perennials) to few years (annuals, biennials), or went in reverse - from few years to many years. The author discusses the problems of senescence and longevity in Cormophyta in the context of various hypotheses of ageing (programmed death theory, mutation accumulation, antagonistic pleiotropy, disposable soma, genes of ageing, genes of longevity). Special attention is given to bio-morphological aspects of longevity and cases of non-ageing plants ("negative senescence", "potential immortality"). It is proposed to distinguish seven models of simple ontogenesis in Cormophyta that can exemplify the diversity of mechanisms of ageing and longevity. The evolution of life span in plants is considered as an indirect result of natural selection of other characteristics of organisms or as a consequence of fixation of modifications (episelectional evolution). It seems that short life span could emerge several times during evolution of one group of plants, thus favoring its adaptive radiation.

Low doze γ-irradiation influence on drosophila life span in different genetics background

International Nuclear Information System (INIS)

Moskalev, A.

2007-01-01

Complete text of publication follows. The main goal of this work was to study in Drosophila melanogaster the contribution of DNA damage sensing and repair, apoptosis and heat shock defence into life span and physical activity alteration after gamma-irradiation at low doze rate. In our experiments, the strains were exposed to chronic gamma-irradiation from a 226Ra source (50 R/h) at doze rate 0.17 cGy/h at pre-imago development stages only. The absorbed radiation dose per generation (from embryo to imago, 12 days) was 60 cGy. Life span estimation was prepared in adult males and females separately. We compared the life span of apoptotic (p53, DIAP-1, dApaf-1, Dcp-1, reaper, grim and hid), heat shock defence (HSP70, HSP23, HSF), DNA damage sensing (ATR) and repair (XPF, XPC, PCNA, DSB repair helicase homologs) mutants after chronic irradiation with the control. On the basis of our investigation we have concluded: 1) Low doze irradiation alter the life span depending on genetic background (mutant alleles, heterozygosity level and sex); 2) Age dynamics of physical activity positively correlates with the life span; 3) Longevity potential forms at early development stages; 4) DNA damage sensing, DNA repair, heat shock defence and apoptosis as aging preventing mechanisms play crucial role in radiation-induced life span hormesis.

Megabase replication domains along the human genome: relation to chromatin structure and genome organisation.

Science.gov (United States)

Audit, Benjamin; Zaghloul, Lamia; Baker, Antoine; Arneodo, Alain; Chen, Chun-Long; d'Aubenton-Carafa, Yves; Thermes, Claude

2013-01-01

In higher eukaryotes, the absence of specific sequence motifs, marking the origins of replication has been a serious hindrance to the understanding of (i) the mechanisms that regulate the spatio-temporal replication program, and (ii) the links between origins activation, chromatin structure and transcription. In this chapter, we review the partitioning of the human genome into megabased-size replication domains delineated as N-shaped motifs in the strand compositional asymmetry profiles. They collectively span 28.3% of the genome and are bordered by more than 1,000 putative replication origins. We recapitulate the comparison of this partition of the human genome with high-resolution experimental data that confirms that replication domain borders are likely to be preferential replication initiation zones in the germline. In addition, we highlight the specific distribution of experimental and numerical chromatin marks along replication domains. Domain borders correspond to particular open chromatin regions, possibly encoded in the DNA sequence, and around which replication and transcription are highly coordinated. These regions also present a high evolutionary breakpoint density, suggesting that susceptibility to breakage might be linked to local open chromatin fiber state. Altogether, this chapter presents a compartmentalization of the human genome into replication domains that are landmarks of the human genome organization and are likely to play a key role in genome dynamics during evolution and in pathological situations.

Diferença entre span verbal e visual nos gêneros: estudo piloto

Directory of Open Access Journals (Sweden)

Mariana Cristina Pedrassa Sagrilo

2013-06-01

Full Text Available OBJETIVO: avaliar a memória de trabalho analisando a capacidade de retenção de estímulos auditivos (span verbal e visuais (span visual e estabelecer a relação com o gênero (masculino e feminino. MÉTODO: participaram deste estudo 20 crianças entre seis anos e cinco meses e sete anos, sendo 10 sujeitos do sexo masculino e 10 sujeitos do sexo feminino. Todos os sujeitos foram submetidos às provas de avaliação do span verbal e visual em ordem direta e inversa. RESULTADOS: apenas na prova de palavras dissílabas com fonologia semelhante e semântica diferente do span verbal, houve variância significante entre os gêneros. As crianças do sexo feminino apresentaram melhor desempenho em relação ao outro gênero, bem como maior capacidade de retenção de palavras dissílabas com fonologia e semântica diferentes. No span visual (ordem direta e inversa as crianças do sexo masculino obtiveram melhor desempenho, apesar de não ter diferenças significantes. Em relação à idade não houve diferença de retenção de estímulos. CONCLUSÃO: as crianças do sexo feminino, neste estudo, apresentaram tendência à melhor desempenho do span verbal e as crianças do sexo masculino tendência a melhor desempenho no span visual. No entanto, o estudo é limitado devido ao reduzido número de participantes na amostra.

Qualitative Exploration of Acculturation and Life-Span Issues of Elderly Asian Americans

Science.gov (United States)

Lee, Jee Hyang; Heo, Nanseol; Lu, Junfei; Portman, Tarrell Awe Agahe

2013-01-01

Awareness of aging issues across diverse populations begins the journey toward counselors becoming culturally competent across client life spans. Understanding the life-span experiences of cultural groups is important for helping professionals. The purpose of this research was to gain insight into the qualitative experiences of Asian American…

Theoretical Insights Reveal Novel Motions in Csk's SH3 Domain That Control Kinase Activation.

Directory of Open Access Journals (Sweden)

Sulyman Barkho

Full Text Available The Src family of tyrosine kinases (SFKs regulate numerous aspects of cell growth and differentiation and are under the principal control of the C-terminal Src Kinase (Csk. Although Csk and SFKs share conserved kinase, SH2 and SH3 domains, they differ considerably in three-dimensional structure, regulatory mechanism, and the intrinsic kinase activities. Although the SH2 and SH3 domains are known to up- or down-regulate tyrosine kinase function, little is known about the global motions in the full-length kinase that govern these catalytic variations. We use a combination of accelerated Molecular Dynamics (aMD simulations and experimental methods to provide a new view of functional motions in the Csk scaffold. These computational studies suggest that high frequency vibrations in the SH2 domain are coupled through the N-terminal lobe of the kinase domain to motions in the SH3 domain. The effects of these reflexive movements on the kinase domain can be viewed using both Deuterium Exchange Mass Spectrometry (DXMS and steady-state kinetic methods. Removal of several contacts, including a crystallographically unobserved N-terminal segment, between the SH3 and kinase domains short-circuit these coupled motions leading to reduced catalytic efficiency and stability of N-lobe motifs within the kinase domain. The data expands the model of Csk's activation whereby separate domains productively interact with two diametrically opposed surfaces of the kinase domain. Such reversible transitions may organize the active structure of the tyrosine kinase domain of Csk.

Experimental investigation of span length for flexural test of fiber reinforced polymer composite laminates

Directory of Open Access Journals (Sweden)

Akhil Mehndiratta

2018-01-01

Full Text Available Testing and evaluation of mechanical properties for FRP (Fiber Reinforced Polymer composite parts play a significant role to qualify it for the end use. Among the mechanical properties, the flexural strength is significant and vital as it may vary with specimen depth, temperature and the test span length. The flexural strength varies for different materials with varying the test span length hence the current work aims to find an optimum span length to test flexural strength for the specimens made of Glass (7781, EC9756 and Carbon (HTA7, G801 prepreg materials. Experiments are conducted as per the ASTM Standard D 790 for flexural test by varying the span lengths to understand the behavior of the flexural strength and flexural modulus. The experimental data were compared with those obtained from the finite element program software Altair Hyper works 14.0. The results indicate that flexural modulus increases with the span length to a point and then it decreases. Thereby, an optimum span length can be obtained for testing flexural strength, which will be useful to the designers and the composite manufacturers to accomplish better standard testing procedures.

A Wide Span Tractor concept developed for efficient and environmental friendly farming

DEFF Research Database (Denmark)

Pedersen, Hans Henrik; Grøn Sørensen, Claus; Oudshoorn, Frank W

2013-01-01

agricultural machines a new Wide Span (WS) tractor concept has been designed and a prototype tractor with a span of 9.6 m (wheel centre to wheel centre) has been built. It is designed to optimise the Controlled Traffic Farming (CTF) system that is already in place on the vegetable farm where it is being tested....... The tractor is designed to carry out all operations during vegetable production including harvest. Using the tractor means that less than 10% of the field area is affected by compaction due to field traffic. The economical and environmental effects of such a wide span CTF growing system will be assessed....

Structural studies of the activation of the two component receiver domain NTRC by multidimensional heteronuclear NMR

Energy Technology Data Exchange (ETDEWEB)

Nohaile, Michael James [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry

1996-05-01

Multidimensional heteronuclear NMR spectroscopy was used to investigate the N-terminal domain of the transcriptional enhancer NTRC (NiTrogen Regulatory protein C). This domain belongs to the family of receiver domains of two-component regulatory systems involved in signal transduction. Phosphorylation of NTRC at D54 leads to an activated form of the molecule which stimulates transcription of genes involved in nitrogen regulation. Three and four dimensional NMR techniques were used to determine an intermediate resolution structure of the unphosphorylated, inactive form of the N-terminal domain of NTRC. The structure is comprised of five α-helices and a five-stranded β-sheet in a (β/α)₅ topology. Analysis of the backbone dynamics of NTRC indicate that helix 4 and strand 5 are significantly more flexible than the rest of the secondary structure of the protein and that the loops making up the active site are flexible. The short lifetime of phospho-NTRC hampers the study of this form. However, conditions for determining the resonance assignments and, possibly, the three dimensional structure of phosphorylated NTRC have been obtained. Tentative assignments of the phosphorylated form indicate that the majority of the changes that NTRC experiences upon phosphorylation occur in helix 3, strand 4, helix 4, strand 5, and the loop between strand 5 and helix 5 (the 3445 face of NTRC) as well as near the site of phosphorylation. In order to examine a stable, activated form of the protein, constitutively active mutants of NTRC were investigated.

Politically Induced Regulatory Risk and Independent Regulatory Agencies

OpenAIRE

Strausz, Roland

2015-01-01

Uncertainty in election outcomes generates politically induced regulatory risk. Political parties' risk attitudes towards such risk depend on a fluctuation effect that hurts both parties and an output--expansion effect that benefits at least one party. Notwithstanding the parties' risk attitudes, political parties have incentives to negotiate away all regulatory risk by pre-electoral bargaining. Efficient pre-electoral bargaining outcomes fully eliminate politically induced regulatory risk. P...

Extended HSR/CARD domain mediates AIRE binding to DNA

Energy Technology Data Exchange (ETDEWEB)

Maslovskaja, Julia, E-mail: julia.maslovskaja@ut.ee; Saare, Mario; Liiv, Ingrid; Rebane, Ana; Peterson, Pärt

2015-12-25

Autoimmune regulator (AIRE) activates the transcription of many genes in an unusual promiscuous and stochastic manner. The mechanism by which AIRE binds to the chromatin and DNA is not fully understood, and the regulatory elements that AIRE target genes possess are not delineated. In the current study, we demonstrate that AIRE activates the expression of transiently transfected luciferase reporters that lack defined promoter regions, as well as intron and poly(A) signal sequences. Our protein-DNA interaction experiments with mutated AIRE reveal that the intact homogeneously staining region/caspase recruitment domain (HSR/CARD) and amino acids R113 and K114 are key elements involved in AIRE binding to DNA. - Highlights: • Promoter and mRNA processing elements are not important for AIRE to activate gene expression from reporter plasmids. • AIRE protein fragment aa 1–138 mediates direct binding to DNA. • Integrity of the HSR/CARD domain is needed for AIRE binding to DNA.

Extended HSR/CARD domain mediates AIRE binding to DNA

International Nuclear Information System (INIS)

Maslovskaja, Julia; Saare, Mario; Liiv, Ingrid; Rebane, Ana; Peterson, Pärt

2015-01-01

Autoimmune regulator (AIRE) activates the transcription of many genes in an unusual promiscuous and stochastic manner. The mechanism by which AIRE binds to the chromatin and DNA is not fully understood, and the regulatory elements that AIRE target genes possess are not delineated. In the current study, we demonstrate that AIRE activates the expression of transiently transfected luciferase reporters that lack defined promoter regions, as well as intron and poly(A) signal sequences. Our protein-DNA interaction experiments with mutated AIRE reveal that the intact homogeneously staining region/caspase recruitment domain (HSR/CARD) and amino acids R113 and K114 are key elements involved in AIRE binding to DNA. - Highlights: • Promoter and mRNA processing elements are not important for AIRE to activate gene expression from reporter plasmids. • AIRE protein fragment aa 1–138 mediates direct binding to DNA. • Integrity of the HSR/CARD domain is needed for AIRE binding to DNA.

The dynamic interplay of plasma membrane domains and cortical microtubules in secondary cell wall patterning

Directory of Open Access Journals (Sweden)

Yoshihisa eOda

2013-12-01

Full Text Available Patterning of the cellulosic cell wall underlies the shape and function of plant cells. The cortical microtubule array plays a central role in the regulation of cell wall patterns. However, the regulatory mechanisms by which secondary cell wall patterns are established through cortical microtubules remain to be fully determined. Our recent study in xylem vessel cells revealed that a mutual inhibitory interaction between cortical microtubules and distinct plasma membrane domains leads to distinctive patterning in secondary cell walls. Our research revealed that the recycling of active and inactive ROP proteins by a specific GAP and GEF pair establishes distinct de novo plasma membrane domains. Active ROP recruits a plant-specific microtubule-associated protein, MIDD1, which mediates the mutual interaction between cortical microtubules and plasma membrane domains. In this mini review, we summarize recent research regarding secondary wall patterning, with a focus on the emerging interplay between plasma membrane domains and cortical microtubules through MIDD1 and ROP.

Wavelength-Converter Saving Span Restoration in GMPLS Controlled WDM Optical Networks

DEFF Research Database (Denmark)

Ruepp, Sarah Renée; Buron, Jakob Due; Andriolli, N.

2006-01-01

We present two label preference schemes to reduce wavelength-conversion during restoration path setup in GMPLS controlled optical networks exploiting span restoration. The amount of required wavelength-conversions can be reduced up to 34 percent.......We present two label preference schemes to reduce wavelength-conversion during restoration path setup in GMPLS controlled optical networks exploiting span restoration. The amount of required wavelength-conversions can be reduced up to 34 percent....

Novel activation domain derived from Che-1 cofactor coupled with the artificial protein Jazz drives utrophin upregulation.

Science.gov (United States)

Desantis, Agata; Onori, Annalisa; Di Certo, Maria Grazia; Mattei, Elisabetta; Fanciulli, Maurizio; Passananti, Claudio; Corbi, Nicoletta

2009-02-01

Our aim is to upregulate the expression level of the dystrophin related gene utrophin in Duchenne muscular dystrophy, thus complementing the lack of dystrophin functions. To this end, we have engineered synthetic zinc finger based transcription factors. We have previously shown that the artificial three-zinc finger protein named Jazz fused with the Vp16 activation domain, is able to bind utrophin promoter A and to increase the endogenous level of utrophin in transgenic mice. Here, we report on an innovative artificial protein, named CJ7, that consists of Jazz DNA binding domain fused to a novel activation domain derived from the regulatory multivalent adaptor protein Che-1/AATF. This transcriptional activation domain is 100 amino acids in size and it is very powerful as compared to the Vp16 activation domain. We show that CJ7 protein efficiently promotes transcription and accumulation of the acetylated form of histone H3 on the genomic utrophin promoter locus.

Testing for Spanning with Futrures Contracts and Nontraded Assets : A General Approach

NARCIS (Netherlands)

Nijman, T.E.; de Roon, F.A.; Werker, B.J.M.

1996-01-01

This paper generalizes the notion of mean-variance spanning as de- ned in the seminal paper of Huberman & Kandel (1987) in three di- mensions.It is shown how regression techniques can be used to test for spanning for more general classes of utility functions, in case some as- sets are nontraded, and

Herbal supplement extends life span under some environmental conditions and boosts stress resistance.

Directory of Open Access Journals (Sweden)

Bryant Villeponteau

Full Text Available Genetic studies indicate that aging is modulated by a great number of genetic pathways. We have used Drosophila longevity and stress assays to test a multipath intervention strategy. To carry out this strategy, we supplemented the flies with herbal extracts (SC100 that are predicted to modulate the expression of many genes involved in aging and stress resistance, such as mTOR, NOS, NF-KappaB, and VEGF. When flies were housed in large cages with SC100 added, daily mortality rates of both male and female flies were greatly diminished in mid to late life. Surprisingly, SC100 also stabilized midlife mortality rate increases so as to extend the maximum life span substantially beyond the limits previously reported for D. melanogaster. Under these conditions, SC100 also promoted robust resistance to partial starvation stress and to heat stress. Fertility was the same initially in both treated and control flies, but it became significantly higher in treated flies at older ages as the fertility of control flies declined. Mean and maximum life spans of flies in vials at the same test site were also extended by SC100, but the life spans were short in absolute terms. In contrast, at an independent test site where stress was minimized, the flies exhibited much longer mean life spans, but the survival curves became highly rectangular and the effects of SC100 on both mean and maximum life spans declined greatly or were abolished. The data indicate that SC100 is a novel herbal mix with striking effects on enhancing Drosophila stress resistance and life span in some environments, while minimizing mid to late life mortality rates. They also show that the environment and other factors can have transformative effects on both the length and distribution of survivorship, and on the ability of SC100 to extend the life span.

Recognition memory span in autopsy-confirmed Dementia with Lewy Bodies and Alzheimer's Disease.

Science.gov (United States)

Salmon, David P; Heindel, William C; Hamilton, Joanne M; Vincent Filoteo, J; Cidambi, Varun; Hansen, Lawrence A; Masliah, Eliezer; Galasko, Douglas

2015-08-01

Evidence from patients with amnesia suggests that recognition memory span tasks engage both long-term memory (i.e., secondary memory) processes mediated by the diencephalic-medial temporal lobe memory system and working memory processes mediated by fronto-striatal systems. Thus, the recognition memory span task may be particularly effective for detecting memory deficits in disorders that disrupt both memory systems. The presence of unique pathology in fronto-striatal circuits in Dementia with Lewy Bodies (DLB) compared to AD suggests that performance on the recognition memory span task might be differentially affected in the two disorders even though they have quantitatively similar deficits in secondary memory. In the present study, patients with autopsy-confirmed DLB or AD, and Normal Control (NC) participants, were tested on separate recognition memory span tasks that required them to retain increasing amounts of verbal, spatial, or visual object (i.e., faces) information across trials. Results showed that recognition memory spans for verbal and spatial stimuli, but not face stimuli, were lower in patients with DLB than in those with AD, and more impaired relative to NC performance. This was despite similar deficits in the two patient groups on independent measures of secondary memory such as the total number of words recalled from long-term storage on the Buschke Selective Reminding Test. The disproportionate vulnerability of recognition memory span task performance in DLB compared to AD may be due to greater fronto-striatal involvement in DLB and a corresponding decrement in cooperative interaction between working memory and secondary memory processes. Assessment of recognition memory span may contribute to the ability to distinguish between DLB and AD relatively early in the course of disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Regulatory Body Safety Culture in Non-nuclear HROs: Lessons for Nuclear Regulators

International Nuclear Information System (INIS)

Fleming, M.; Bowers, K.

2016-01-01

Regulator safety culture is a relatively new area of investigation, even though deficiencies in regulatory oversight have been identified in a number of public inquiries (e.g., Piper Alpha, Deep Water Horizon). More recently the IAEA report into the Fukushima disaster specifically identified the need for regulatory bodies to have a positive safety culture. While there are clear parallels between duty holder safety culture and regulator safety culture there are also likely to be differences. To date they have been no published studies investigating regulator safety culture. In order to develop a framework to understand regulator safety culture we conducted a literature review and interviewed safety culture subject matter experts from a range of HRO domains (e.g., offshore oil and gas). There was general consensus among participants that regulatory safety culture was an important topic that was worthy of further investigation. That there was general agreement that regulatory safety culture was multi-dimensional and that some of the elements of existing safety culture models applied to regulator culture (e.g., learning and leadership). The participants also identified unique dimensions of regulator safety culture including commitment to high standards and ethics, transparency and perceived role of the regulator. In this paper we will present the results of the interviews and present a model of regulator safety culture. This model will be contrasted with models being used in the nuclear industry. Implications for assessing regulatory safety culture will be discussed. (author)

Beyond cross-domain learning: Multiple-domain nonnegative matrix factorization

KAUST Repository

Wang, Jim Jing-Yan; Gao, Xin

2014-01-01

Traditional cross-domain learning methods transfer learning from a source domain to a target domain. In this paper, we propose the multiple-domain learning problem for several equally treated domains. The multiple-domain learning problem assumes that samples from different domains have different distributions, but share the same feature and class label spaces. Each domain could be a target domain, while also be a source domain for other domains. A novel multiple-domain representation method is proposed for the multiple-domain learning problem. This method is based on nonnegative matrix factorization (NMF), and tries to learn a basis matrix and coding vectors for samples, so that the domain distribution mismatch among different domains will be reduced under an extended variation of the maximum mean discrepancy (MMD) criterion. The novel algorithm - multiple-domain NMF (MDNMF) - was evaluated on two challenging multiple-domain learning problems - multiple user spam email detection and multiple-domain glioma diagnosis. The effectiveness of the proposed algorithm is experimentally verified. © 2013 Elsevier Ltd. All rights reserved.

Beyond cross-domain learning: Multiple-domain nonnegative matrix factorization

KAUST Repository

Wang, Jim Jing-Yan

2014-02-01

Traditional cross-domain learning methods transfer learning from a source domain to a target domain. In this paper, we propose the multiple-domain learning problem for several equally treated domains. The multiple-domain learning problem assumes that samples from different domains have different distributions, but share the same feature and class label spaces. Each domain could be a target domain, while also be a source domain for other domains. A novel multiple-domain representation method is proposed for the multiple-domain learning problem. This method is based on nonnegative matrix factorization (NMF), and tries to learn a basis matrix and coding vectors for samples, so that the domain distribution mismatch among different domains will be reduced under an extended variation of the maximum mean discrepancy (MMD) criterion. The novel algorithm - multiple-domain NMF (MDNMF) - was evaluated on two challenging multiple-domain learning problems - multiple user spam email detection and multiple-domain glioma diagnosis. The effectiveness of the proposed algorithm is experimentally verified. © 2013 Elsevier Ltd. All rights reserved.

Mechanistically Distinct Pathways of Divergent Regulatory DNA Creation Contribute to Evolution of Human-Specific Genomic Regulatory Networks Driving Phenotypic Divergence of Homo sapiens.

Science.gov (United States)

Glinsky, Gennadi V

2016-09-19

Thousands of candidate human-specific regulatory sequences (HSRS) have been identified, supporting the hypothesis that unique to human phenotypes result from human-specific alterations of genomic regulatory networks. Collectively, a compendium of multiple diverse families of HSRS that are functionally and structurally divergent from Great Apes could be defined as the backbone of human-specific genomic regulatory networks. Here, the conservation patterns analysis of 18,364 candidate HSRS was carried out requiring that 100% of bases must remap during the alignments of human, chimpanzee, and bonobo sequences. A total of 5,535 candidate HSRS were identified that are: (i) highly conserved in Great Apes; (ii) evolved by the exaptation of highly conserved ancestral DNA; (iii) defined by either the acceleration of mutation rates on the human lineage or the functional divergence from non-human primates. The exaptation of highly conserved ancestral DNA pathway seems mechanistically distinct from the evolution of regulatory DNA segments driven by the species-specific expansion of transposable elements. Genome-wide proximity placement analysis of HSRS revealed that a small fraction of topologically associating domains (TADs) contain more than half of HSRS from four distinct families. TADs that are enriched for HSRS and termed rapidly evolving in humans TADs (revTADs) comprise 0.8-10.3% of 3,127 TADs in the hESC genome. RevTADs manifest distinct correlation patterns between placements of human accelerated regions, human-specific transcription factor-binding sites, and recombination rates. There is a significant enrichment within revTAD boundaries of hESC-enhancers, primate-specific CTCF-binding sites, human-specific RNAPII-binding sites, hCONDELs, and H3K4me3 peaks with human-specific enrichment at TSS in prefrontal cortex neurons (P sapiens is driven by the evolution of human-specific genomic regulatory networks via at least two mechanistically distinct pathways of creation of

High-Reynolds Number Active Blowing Semi-Span Force Measurement System Development

Science.gov (United States)

Lynn, Keith C.; Rhew, Ray D.; Acheson, Michael J.; Jones, Gregory S.; Milholen, William E.; Goodliff, Scott L.

2012-01-01

Recent wind-tunnel tests at the NASA Langley Research Center National Transonic Facility utilized high-pressure bellows to route air to the model for evaluating aircraft circulation control. The introduction of these bellows within the Sidewall Model Support System significantly impacted the performance of the external sidewall mounted semi-span balance. As a result of this impact on the semi-span balance measurement performance, it became apparent that a new capability needed to be built into the National Transonic Facility s infrastructure to allow for performing pressure tare calibrations on the balance in order to properly characterize its performance under the influence of static bellows pressure tare loads and bellows thermal effects. The objective of this study was to design both mechanical calibration hardware and an experimental calibration design that can be employed at the facility in order to efficiently and precisely perform the necessary loadings in order to characterize the semi-span balance under the influence of multiple calibration factors (balance forces/moments and bellows pressure/temperature). Using statistical design of experiments, an experimental design was developed allowing for strategically characterizing the behavior of the semi-span balance for use in circulation control and propulsion-type flow control testing at the National Transonic Facility.

Restoring speech perception with cochlear implants by spanning defective electrode contacts.

Science.gov (United States)

Frijns, Johan H M; Snel-Bongers, Jorien; Vellinga, Dirk; Schrage, Erik; Vanpoucke, Filiep J; Briaire, Jeroen J

2013-04-01

Even with six defective contacts, spanning can largely restore speech perception with the HiRes 120 speech processing strategy to the level supported by an intact electrode array. Moreover, the sound quality is not degraded. Previous studies have demonstrated reduced speech perception scores (SPS) with defective contacts in HiRes 120. This study investigated whether replacing defective contacts by spanning, i.e. current steering on non-adjacent contacts, is able to restore speech recognition to the level supported by an intact electrode array. Ten adult cochlear implant recipients (HiRes90K, HiFocus1J) with experience with HiRes 120 participated in this study. Three different defective electrode arrays were simulated (six separate defective contacts, three pairs or two triplets). The participants received three take-home strategies and were asked to evaluate the sound quality in five predefined listening conditions. After 3 weeks, SPS were evaluated with monosyllabic words in quiet and in speech-shaped background noise. The participants rated the sound quality equal for all take-home strategies. SPS with background noise were equal for all conditions tested. However, SPS in quiet (85% phonemes correct on average with the full array) decreased significantly with increasing spanning distance, with a 3% decrease for each spanned contact.

Developments and Prospects of Long-Span High-Speed Railway Bridge Technologies in China

OpenAIRE

Shunquan Qin; Zongyu Gao

2017-01-01

With the rapid developments of the high-speed railway in China, a great number of long-span bridges have been constructed in order to cross rivers and gorges. At present, the longest main span of a constructed high-speed railway bridge is only 630 m. The main span of Hutong Yangtze River Bridge and of Wufengshan Yangtze River Bridge, which are under construction, will be much longer, at 1092 m each. In order to overcome the technical issues that originate from the extremely large dead loading...

Terahertz time-domain spectroscopy of edible oils

Science.gov (United States)

Dinovitser, Alex; Valchev, Dimitar G.; Abbott, Derek

2017-06-01

Chemical degradation of edible oils has been studied using conventional spectroscopic methods spanning the spectrum from ultraviolet to mid-IR. However, the possibility of morphological changes of oil molecules that can be detected at terahertz frequencies is beginning to receive some attention. Furthermore, the rapidly decreasing cost of this technology and its capability for convenient, in situ measurement of material properties, raises the possibility of monitoring oil during cooking and processing at production facilities, and more generally within the food industry. In this paper, we test the hypothesis that oil undergoes chemical and physical changes when heated above the smoke point, which can be detected in the 0.05-2 THz spectral range, measured using the conventional terahertz time-domain spectroscopy technique. The measurements demonstrate a null result in that there is no significant change in the spectra of terahertz optical parameters after heating above the smoke point for 5 min.

Orion: a glimpse of hope in life span extension?

Science.gov (United States)

Muradian, K; Bondar, V; Bezrukov, V; Zhukovsky, O; Polyakov, V; Utko, N

2010-01-01

Orion is a multicomponent drug based on derivatives of taurocholic acid and several other compounds. Application of Orion into the feeding medium of Drosophila melanogaster resulted in increased life span and survival at stressful conditions. Two paradoxical features of the drug should be stressed: The "age-threshold" (life span extension was observed only when the drug was applied starting from the second half of life) and induction of "centenarian" flies (older 100 days). Orion enhanced survival at heat shock (38 degrees C) and acidic (pH = 1.6) or alkaline (pH = 11.8) feeding mediums, but not at oxidative stresses modeled by 100% oxygen or application of hydrogen peroxide (H(2)O(2)).

Post-Tensioned Concrete Long-Span Slabs in Projects of Modern Building Construction

Science.gov (United States)

Szydlowski, Rafal; Labuzek, Barbara

2017-10-01

Nowadays, design of modern an architectural building structures requires the use of slender and free from numerous supports slabs. The most suitable solution for above requirements are the post-tensioned slabs with unbounded tendons. Slabs prestressed by unbounded tendons are successfully used worldwide for several decades. During that time many recommendations dealing with the forming of geometry and prestressing, dimensioning and erection technology were issued. During the recent years prestressed slabs characterized by span and slenderness substantially exceeding recommended limitations were designed and erected with success in Poland. During the slabs erection and in two years of their using, the deflection of three oversized slabs were monitoring. In spite of designed the slabs significantly larger and slenderer than the recommended maximum value of span and span to depth ratio, the deflection of the slabs is definitely far from the limit value. The paper shows the geometry, characteristic and deflection of erected slabs and conclusion. Description of a very large span slab (21.3m), that was designed regarded to the information obtained from the previous realisation, is presented in this paper.

Front-line managers as boundary spanners: effects of span and time on nurse supervision satisfaction.

Science.gov (United States)

Meyer, Raquel M; O'Brien-Pallas, Linda; Doran, Diane; Streiner, David; Ferguson-Paré, Mary; Duffield, Christine

2011-07-01

To examine the influence of nurse manager span (number of direct report staff), time in staff contact, transformational leadership practices and operational hours on nurse supervision satisfaction. Increasing role complexity has intensified the boundary spanning functions of managers. Because work demands and scope vary by management position, time in staff contact rather than span may better explain managers' capacity to support staff. A descriptive, correlational design was used to collect cross-sectional survey and prospective work log and administrative data from a convenience sample of 558 nurses in 51 clinical areas and 31 front-line nurse managers from four acute care hospitals in 2007-2008. Data were analysed using hierarchical linear modelling. Span, but not time in staff contact, interacted with leadership and operational hours to explain supervision satisfaction. With compressed operational hours, supervision satisfaction was lower with highly transformational leadership in combination with wider spans. With extended operational hours, supervision satisfaction was higher with highly transformational leadership, and this effect was more pronounced under wider spans. Operational hours, which influence the manager's daily span (average number of direct report staff working per weekday), should be factored into the design of front-line management positions. © 2011 The Authors. Journal compilation © 2011 Blackwell Publishing Ltd.

Increments and duplication events of enzymes and transcription factors influence metabolic and regulatory diversity in prokaryotes.

Directory of Open Access Journals (Sweden)

Mario Alberto Martínez-Núñez

Full Text Available In this work, the content of enzymes and DNA-binding transcription factors (TFs in 794 non-redundant prokaryotic genomes was evaluated. The identification of enzymes was based on annotations deposited in the KEGG database as well as in databases of functional domains (COG and PFAM and structural domains (Superfamily. For identifications of the TFs, hidden Markov profiles were constructed based on well-known transcriptional regulatory families. From these analyses, we obtained diverse and interesting results, such as the negative rate of incremental changes in the number of detected enzymes with respect to the genome size. On the contrary, for TFs the rate incremented as the complexity of genome increased. This inverse related performance shapes the diversity of metabolic and regulatory networks and impacts the availability of enzymes and TFs. Furthermore, the intersection of the derivatives between enzymes and TFs was identified at 9,659 genes, after this point, the regulatory complexity grows faster than metabolic complexity. In addition, TFs have a low number of duplications, in contrast to the apparent high number of duplications associated with enzymes. Despite the greater number of duplicated enzymes versus TFs, the increment by which duplicates appear is higher in TFs. A lower proportion of enzymes among archaeal genomes (22% than in the bacterial ones (27% was also found. This low proportion might be compensated by the interconnection between the metabolic pathways in Archaea. A similar proportion was also found for the archaeal TFs, for which the formation of regulatory complexes has been proposed. Finally, an enrichment of multifunctional enzymes in Bacteria, as a mechanism of ecological adaptation, was detected.

Looking for an Explanation for the Low Sign Span. Is Order Involved?

Science.gov (United States)

Gozzi, Marta; Geraci, Carlo; Cecchetto, Carlo; Perugini, Marco; Papagno, Costanza

2011-01-01

Although signed and speech-based languages have a similar internal organization of verbal short-term memory, sign span is lower than word span. We investigated whether this is due to the fact that signs are not suited for serial recall, as proposed by Bavelier, Newport, Hall, Supalla, and Boutla (2008. Ordered short-term memory differs in signers…

Online versus conventional shopping: consumers' risk perception and regulatory focus.

Science.gov (United States)

van Noort, Guda; Kerkhof, Peter; Fennis, Bob M

2007-10-01

In two experiments, the impact of shopping context on consumers' risk perceptions and regulatory focus was examined. We predicted that individuals perceive an online (vs. conventional) shopping environment as more risky and that an online shopping environment, by its risky nature, primes a prevention focus. The findings in Study 1 demonstrate these effects by using self-report measures for risk perception and prevention focus. In Study 2, we replicated these findings and demonstrated that the effect of an online shopping environment carries over to behavior in a domain unrelated to shopping.

Linking and Cutting Spanning Trees

Directory of Open Access Journals (Sweden)

Luís M. S. Russo

2018-04-01

Full Text Available We consider the problem of uniformly generating a spanning tree for an undirected connected graph. This process is useful for computing statistics, namely for phylogenetic trees. We describe a Markov chain for producing these trees. For cycle graphs, we prove that this approach significantly outperforms existing algorithms. For general graphs, experimental results show that the chain converges quickly. This yields an efficient algorithm due to the use of proper fast data structures. To obtain the mixing time of the chain we describe a coupling, which we analyze for cycle graphs and simulate for other graphs.

Analytical investigation of bidirectional ductile diaphragms in multi-span bridges

Science.gov (United States)

Wei, Xiaone; Bruneau, Michel

2018-04-01

In the AASHTO Guide Specifications for Seismic Bridge Design Provisions, ductile diaphragms are identified as Permissible Earthquake-Resisting Elements (EREs), designed to help resist seismic loads applied in the transverse direction of bridges. When adding longitudinal ductile diaphragms, a bidirectional ductile diaphragm system is created that can address seismic excitations acting along both the bridge's longitudinal and transverse axes. This paper investigates bidirectional ductile diaphragms with Buckling Restrained Braces (BRBs) in straight multi-span bridge with simply supported floating spans. The flexibility of the substructures in the transverse and longitudinal direction of the bridge is considered. Design procedures for the bidirectional ductile diaphragms are first proposed. An analytical model of the example bridge with bidirectional ductile diaphragms, designed based on the proposed methodology, is then built in SAP2000. Pushover and nonlinear time history analyses are performed on the bridge model, and corresponding results are presented. The effect of changing the longitudinal stiffness of the bidirectional ductile diaphragms in the end spans connecting to the abutment is also investigated, in order to better understand the impact on the bridge's dynamic performance.

Characterisation of minimal-span plane Couette turbulence with pressure gradients

Science.gov (United States)

Sekimoto, Atsushi; Atkinson, Callum; Soria, Julio

2018-04-01

The turbulence statistics and dynamics in the spanwise-minimal plane Couette flow with pressure gradients, so-called, Couette-Poiseuille (C-P) flow, are investigated using direct numerical simulation. The large-scale motion is limited in the spanwise box dimension as in the minimal-span channel turbulence of Flores & Jiménez (Phys. Fluids, vol. 22, 2010, 071704). The effect of the top wall, where normal pressure-driven Poiseuille flow is realised, is distinguished from the events on the bottom wall, where the pressure gradient results in mild or almost-zero wall-shear stress. A proper scaling of turbulence statistics in minimal-span C-P flows is presented. Also the ‘shear-less’ wall-bounded turbulence, where the Corrsin shear parameter is very weak compared to normal wall-bounded turbulence, represents local separation, which is also observed as spanwise streaks of reversed flow in full-size plane C-P turbulence. The local separation is a multi-scale event, which grows up to the order of the channel height even in the minimal-span geometry.

Short-term memory predictions across the lifespan: monitoring span before and after conducting a task.

Science.gov (United States)

Bertrand, Julie Marilyne; Moulin, Chris John Anthony; Souchay, Céline

2017-05-01

Our objective was to explore metamemory in short-term memory across the lifespan. Five age groups participated in this study: 3 groups of children (4-13 years old), and younger and older adults. We used a three-phase task: prediction-span-postdiction. For prediction and postdiction phases, participants reported with a Yes/No response if they could recall in order a series of images. For the span task, they had to actually recall such series. From 4 years old, children have some ability to monitor their short-term memory and are able to adjust their prediction after experiencing the task. However, accuracy still improves significantly until adolescence. Although the older adults had a lower span, they were as accurate as young adults in their evaluation, suggesting that metamemory is unimpaired for short-term memory tasks in older adults. •We investigate metamemory for short-term memory tasks across the lifespan. •We find younger children cannot accurately predict their span length. •Older adults are accurate in predicting their span length. •People's metamemory accuracy was related to their short-term memory span.

alpha-helical structural elements within the voltage-sensing domains of a K(+) channel.

Science.gov (United States)

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

2000-01-01

Voltage-gated K(+) channels are tetramers with each subunit containing six (S1-S6) putative membrane spanning segments. The fifth through sixth transmembrane segments (S5-S6) from each of four subunits assemble to form a central pore domain. A growing body of evidence suggests that the first four segments (S1-S4) comprise a domain-like voltage-sensing structure. While the topology of this region is reasonably well defined, the secondary and tertiary structures of these transmembrane segments are not. To explore the secondary structure of the voltage-sensing domains, we used alanine-scanning mutagenesis through the region encompassing the first four transmembrane segments in the drk1 voltage-gated K(+) channel. We examined the mutation-induced perturbation in gating free energy for periodicity characteristic of alpha-helices. Our results are consistent with at least portions of S1, S2, S3, and S4 adopting alpha-helical secondary structure. In addition, both the S1-S2 and S3-S4 linkers exhibited substantial helical character. The distribution of gating perturbations for S1 and S2 suggest that these two helices interact primarily with two environments. In contrast, the distribution of perturbations for S3 and S4 were more complex, suggesting that the latter two helices make more extensive protein contacts, possibly interfacing directly with the shell of the pore domain.

Impact of the [delta]F508 Mutation in First Nucleotide-binding Domain of Human Cystic Fibrosis Transmembrane Conductance Regulator on Domain Folding and Structure

Energy Technology Data Exchange (ETDEWEB)

Lewis, Hal A.; Zhao, Xun; Wang, Chi; Sauder, J. Michael; Rooney, Isabelle; Noland, Brian W.; Lorimer, Don; Kearins, Margaret C.; Conners, Kris; Condon, Brad; Maloney, Peter C.; Guggino, William B.; Hunt, John F.; Emtage, Spencer (SG); (Columbia); (JHU)

2010-07-19

Cystic fibrosis is caused by defects in the cystic fibrosis transmembrane conductance regulator (CFTR), commonly the deletion of residue Phe-508 (DeltaF508) in the first nucleotide-binding domain (NBD1), which results in a severe reduction in the population of functional channels at the epithelial cell surface. Previous studies employing incomplete NBD1 domains have attributed this to aberrant folding of DeltaF508 NBD1. We report structural and biophysical studies on complete human NBD1 domains, which fail to demonstrate significant changes of in vitro stability or folding kinetics in the presence or absence of the DeltaF508 mutation. Crystal structures show minimal changes in protein conformation but substantial changes in local surface topography at the site of the mutation, which is located in the region of NBD1 believed to interact with the first membrane spanning domain of CFTR. These results raise the possibility that the primary effect of DeltaF508 is a disruption of proper interdomain interactions at this site in CFTR rather than interference with the folding of NBD1. Interestingly, increases in the stability of NBD1 constructs are observed upon introduction of second-site mutations that suppress the trafficking defect caused by the DeltaF508 mutation, suggesting that these suppressors might function indirectly by improving the folding efficiency of NBD1 in the context of the full-length protein. The human NBD1 structures also solidify the understanding of CFTR regulation by showing that its two protein segments that can be phosphorylated both adopt multiple conformations that modulate access to the ATPase active site and functional interdomain interfaces.

The visual attention span deficit in Chinese children with reading fluency difficulty.

Science.gov (United States)

Zhao, Jing; Liu, Menglian; Liu, Hanlong; Huang, Chen

2018-02-01

With reading development, some children fail to learn to read fluently. However, reading fluency difficulty (RFD) has not been fully investigated. The present study explored the underlying mechanism of RFD from the aspect of visual attention span. Fourteen Chinese children with RFD and fourteen age-matched normal readers participated. The visual 1-back task was adopted to examine visual attention span. Reaction time and accuracy were recorded, and relevant d-prime (d') scores were computed. Results showed that children with RFD exhibited lower accuracy and lower d' values than the controls did in the visual 1-back task, revealing a visual attention span deficit. Further analyses on d' values revealed that the attention distribution seemed to exhibit an inverted U-shaped pattern without lateralization for normal readers, but a W-shaped pattern with a rightward bias for children with RFD, which was discussed based on between-group variation in reading strategies. Results of the correlation analyses showed that visual attention span was associated with reading fluency at the sentence level for normal readers, but was related to reading fluency at the single-character level for children with RFD. The different patterns in correlations between groups revealed that visual attention span might be affected by the variation in reading strategies. The current findings extend previous data from alphabetic languages to Chinese, a logographic language with a particularly deep orthography, and have implications for reading-dysfluency remediation. Copyright © 2017 Elsevier Ltd. All rights reserved.

A National Regulatory Authority set up in a developing country: case of Mali

International Nuclear Information System (INIS)

Kone, Nagantie

2008-01-01

Full text: The Republic of Mali is member of the International Atomic Energy Agency since 1961. Of since the creation of the IAEA, some African countries are members. The technical cooperation with the Agency started in the years 1975. Through that cooperation, many pacific uses of nuclear techniques have been introduced, then developed at different levels in many socio- economic domains as medicine, agriculture, research, and so on. That development of nuclear techniques use has occurred without legislation at all or in some limited cases with part of the legislation of the colonizing country), in a precise field (like radiography in medicine). Later the need of regulatory infrastructure implementation started. That implementation has followed several ways in the different African countries. Also, it started earlier in countries which had advanced activities in nuclear techniques and very later in others. Most if not all of these infrastructure (say regulatory board) were created by the greatest users of the nuclear techniques, the Ministry of Health in most cases or Energy Commission for Countries having a research reactor. After the years 90, the Agency has developed new vision in the implementation of Regulatory Authorities. The new innovation was: 1-) Development of Regulatory Authority with independent statute (decisions and finance); 2-) Assuming post graduate training in developing countries to come other the lack of human resources. That new strategy of the IAEA has facilitated the apparition and development of several new regulatory authorities. We are going to develop here the progress done by one of these new regulatory authorities, through five years being. (author)

Some areas of concern in Indian PHWRs from regulatory perspective

Energy Technology Data Exchange (ETDEWEB)

Gupta, V K [Operating Plants Safety Division, Atomic Energy Regulatory Board, Bhabha Atomic Research Centre (BARC), Bombay (India)

1991-04-01

The basic concern from regulatory perspective in the operation of Indian PHWRs is for radiation exposure to the occupational workers and to the members of public during normal operation as well as abnormal conditions. The radiation exposure to the occupational workers is the result of radiation conditions in the plant and the practices followed for operation and maintenance. Both technical and administrative actions are responsible in controlling the radiation exposures. As far as exposure to the members of public is concerned, integrity of heat transport and moderator systems, performance of the ventilation system and integrity of fuel cladding are important elements during normal operation and some of the anticipated operational occurrences. Containment systems play an important role in controlling the impact in public domain during accident conditions. Elaborate emergency preparedness plans ready in advance perfected and optimised through drills and exercises give an assurance that should a mishap occur requiring emergency action in the public domain, adequate and necessary actions to reduce the radiological consequences will be taken. In this context, four areas of interest are: Radiation Exposure of Occupational Workers, Fuel Performance, Containment Systems and Emergency Preparedness in Public Domain. (author)

Some areas of concern in Indian PHWRs from regulatory perspective

International Nuclear Information System (INIS)

Gupta, V.K.

1991-01-01

The basic concern from regulatory perspective in the operation of Indian PHWRs is for radiation exposure to the occupational workers and to the members of public during normal operation as well as abnormal conditions. The radiation exposure to the occupational workers is the result of radiation conditions in the plant and the practices followed for operation and maintenance. Both technical and administrative actions are responsible in controlling the radiation exposures. As far as exposure to the members of public is concerned, integrity of heat transport and moderator systems, performance of the ventilation system and integrity of fuel cladding are important elements during normal operation and some of the anticipated operational occurrences. Containment systems play an important role in controlling the impact in public domain during accident conditions. Elaborate emergency preparedness plans ready in advance perfected and optimised through drills and exercises give an assurance that should a mishap occur requiring emergency action in the public domain, adequate and necessary actions to reduce the radiological consequences will be taken. In this context, four areas of interest are: Radiation Exposure of Occupational Workers, Fuel Performance, Containment Systems and Emergency Preparedness in Public Domain. (author)

Analysis of protection spanning-tree protocol

Directory of Open Access Journals (Sweden)

Б.Я. Корнієнко

2007-01-01

Full Text Available  Extraordinary sweeping  of  IT – development  causes vulnerabilities and, thereafter, attacks that use these vulnerabilities. That is why one must post factum or even in advance speed up invention of new information  security systems as well as develop the old ones. The matter of article concerns Spanning-Tree Protocol  – the vivid example of the case, when the cure of the vulnerability creates dozen of new "weak spots".

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

Science.gov (United States)

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

2018-04-01

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

Evaluating the life cycle environmental impact of short span bridges

DEFF Research Database (Denmark)

Du, Guangli; Pettersson, Lars; Karoumi, Raid

2016-01-01

impact of the construction sector. Life cycle assessment (LCA) is a systematic method for assessing the environmental impact of products and systems, but its application in bridges is scarce. In Swede, most of the bridges are short spans and the type of concrete slab-frame bridge (CFB) accounts...... for a large share. Soil steel composite bridge (SSCB) is a functional equivalent solution for CFB. In order to mitigate the environmental burdens of short span bridges, this paper performed a comparative LCA study between these two types of bridge. The results indicate that the initial material consumption...

A conserved inter-domain communication mechanism regulates the ATPase activity of the AAA-protein Drg1.

Science.gov (United States)

Prattes, Michael; Loibl, Mathias; Zisser, Gertrude; Luschnig, Daniel; Kappel, Lisa; Rössler, Ingrid; Grassegger, Manuela; Hromic, Altijana; Krieger, Elmar; Gruber, Karl; Pertschy, Brigitte; Bergler, Helmut

2017-03-17

AAA-ATPases fulfil essential roles in different cellular pathways and often act in form of hexameric complexes. Interaction with pathway-specific substrate and adaptor proteins recruits them to their targets and modulates their catalytic activity. This substrate dependent regulation of ATP hydrolysis in the AAA-domains is mediated by a non-catalytic N-terminal domain. The exact mechanisms that transmit the signal from the N-domain and coordinate the individual AAA-domains in the hexameric complex are still the topic of intensive research. Here, we present the characterization of a novel mutant variant of the eukaryotic AAA-ATPase Drg1 that shows dysregulation of ATPase activity and altered interaction with Rlp24, its substrate in ribosome biogenesis. This defective regulation is the consequence of amino acid exchanges at the interface between the regulatory N-domain and the adjacent D1 AAA-domain. The effects caused by these mutations strongly resemble those of pathological mutations of the AAA-ATPase p97 which cause the hereditary proteinopathy IBMPFD (inclusion body myopathy associated with Paget's disease of the bone and frontotemporal dementia). Our results therefore suggest well conserved mechanisms of regulation between structurally, but not functionally related members of the AAA-family.

Self-perceived successful weight regulators are less affected by self-regulatory depletion in the domain of eating behavior.

Science.gov (United States)

Friese, Malte; Engeler, Michèle; Florack, Arnd

2015-01-01

Weight loss and maintenance goals are highly prevalent in many affluent societies, but many weight regulators are not successful in the long term. Research started to reveal psychological mechanisms that help successful weight regulators in being successful. In the present study, we tested the assumption that these mechanisms facilitate successful self-regulation particularly under conditions of self-regulatory depletion. Participants exerted or did not exert self-control in a first task before engaging in a taste test of a tempting but unhealthy food. Participants who had initially exerted self-control ate more than participants in the control condition. This effect was reduced in self-perceived successful weight regulators as compared to perceived unsuccessful self-regulators. A reduced susceptibility to self-regulatory depletion may be an important contributor to long-term weight regulation success in successful weight regulators. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cross-language modulation of visual attention span: An Arabic-French-Spanish comparison in adult skilled readers.

Directory of Open Access Journals (Sweden)

Faris Haroon Rasheed Awadh

2016-03-01

Full Text Available In delineating the amount of orthographic information that can be processed in parallel during a single fixation, the visual attention (VA span acts as a key component of the reading system. Previous studies focused on the contribution of VA span to normal and pathological reading in monolingual and bilingual children from different European languages, without direct cross-language comparison. In the current paper, we explored modulations of VA span abilities in three languages --French, Spanish and Arabic-- that differ in transparency, reading direction and writing systems. The participants were adult skilled readers who were native speakers of French, Spanish or Arabic. They were administered tasks of global and partial letter report, single letter identification and text reading. Their VA span abilities were assessed using tasks that require the processing of briefly presented 5 consonant strings (e.g., R S H F T. All five consonants had to be reported in global report but a single cued letter in partial report. Results showed that the VA span was reduced in Arabic readers as compared to French or Spanish readers who otherwise show a similar high performance in the two report tasks. The analysis of VA span response patterns in global report showed a left-right asymmetry in all three languages. A leftward letter advantage was found in French and Spanish but a rightward advantage in Arabic. The response patterns were symmetric in partial report, regardless of the language. Last, a significant relationship was found between visual attention span abilities and reading speed but only for French. The overall findings suggest that the size of VA span, the shape of VA span response patterns and the VA Span-reading relationship are modulated by language-specific features.

Cross-Language Modulation of Visual Attention Span: An Arabic-French-Spanish Comparison in Skilled Adult Readers.

Science.gov (United States)

Awadh, Faris H R; Phénix, Thierry; Antzaka, Alexia; Lallier, Marie; Carreiras, Manuel; Valdois, Sylviane

2016-01-01

In delineating the amount of orthographic information that can be processed in parallel during a single fixation, the visual attention (VA) span acts as a key component of the reading system. Previous studies focused on the contribution of VA span to normal and pathological reading in monolingual and bilingual children from different European languages, without direct cross-language comparison. In the current paper, we explored modulations of VA span abilities in three languages -French, Spanish, and Arabic- that differ in transparency, reading direction and writing systems. The participants were skilled adult readers who were native speakers of French, Spanish or Arabic. They were administered tasks of global and partial letter report, single letter identification and text reading. Their VA span abilities were assessed using tasks that require the processing of briefly presented five consonant strings (e.g., R S H F T). All five consonants had to be reported in global report but a single cued letter in partial report. Results showed that VA span was reduced in Arabic readers as compared to French or Spanish readers who otherwise show a similar high performance in the two report tasks. The analysis of VA span response patterns in global report showed a left-right asymmetry in all three languages. A leftward letter advantage was found in French and Spanish but a rightward advantage in Arabic. The response patterns were symmetric in partial report, regardless of the language. Last, a significant relationship was found between VA span abilities and reading speed but only for French. The overall findings suggest that the size of VA span, the shape of VA span response patterns and the VA Span-reading relationship are modulated by language-specific features.

Calcium-Dependent Energetics of Calmodulin Domain Interactions with Regulatory Regions of the Ryanodine Receptor Type 1 (RyR1)

Science.gov (United States)

Newman, Rhonda A.; Sorensen, Brenda R.; Kilpatrick, Adina M.; Shea, Madeline A.

2014-01-01

Calmodulin (CaM) plays a vital role in calcium homeostasis by allosterically modulating intracellular calcium channels including the homo-tetrameric human Ryanodine Receptor Type 1 (hRyR1). Apo (calcium-free) CaM activates hRyR1 while calcium-saturated CaM inhibits it. Two CaM-binding regions (residues 1975–1999 and 3614–3643) identified in each RyR1 monomer were proposed to allow CaM to bridge adjacent RyR1 subunits. We explored the distinct roles of CaM domains by using fluorescence anisotropy to determine the affinity of CaM1–148 (full-length), CaM1–80 (N-domain) and CaM76–148 (C-domain) for peptides encompassing hRyR1 residues 1975–1999 or 3614–3643. Both CaM1–148 and CaM76–148 associated in a calcium-independent manner with similar affinities for hRyR1(3614–3643)p while CaM1–80 required calcium and bound ~250-fold more weakly. Association of CaM1–148, CaM1–80 and CaM76–148 with hRyR1(1975–1999)p was much less favorable than with hRyR1(3614–3643)p; differences between the two CaM domains were smaller. Equilibrium calcium titrations monitored by steady-state fluorescence demonstrated that both hRyR1 peptides increased the calcium-binding affinity of both CaM domains. These thermodynamic properties support a prior model in which the CaM C-domain associates with RyR1(3614–3643) at low levels of calcium, positioning CaM to rapidly respond to calcium efflux. However, the affinity of the N-domain of CaM for hRyR1(1975–1999)p is insufficient to explain a model in which CaM bridges adjacent RyR1 subunits within the tetramer. This indicates that other protein factors or properties of the tertiary or quaternary structure of hRyR1 contribute to the energetics of CaM-mediated regulation. PMID:25145833

Interaction mode between catalytic and regulatory subunits in glucosidase II involved in ER glycoprotein quality control.

Science.gov (United States)

Satoh, Tadashi; Toshimori, Takayasu; Noda, Masanori; Uchiyama, Susumu; Kato, Koichi

2016-11-01

The glycoside hydrolase family 31 (GH31) α-glucosidases play vital roles in catabolic and regulated degradation, including the α-subunit of glucosidase II (GIIα), which catalyzes trimming of the terminal glucose residues of N-glycan in glycoprotein processing coupled with quality control in the endoplasmic reticulum (ER). Among the known GH31 enzymes, only GIIα functions with its binding partner, regulatory β-subunit (GIIβ), which harbors a lectin domain for substrate recognition. Although the structural data have been reported for GIIα and the GIIβ lectin domain, the interaction mode between GIIα and GIIβ remains unknown. Here, we determined the structure of a complex formed between GIIα and the GIIα-binding domain of GIIβ, thereby providing a structural basis underlying the functional extension of this unique GH31 enzyme. © 2016 The Protein Society.

Functional Elements on SIRPα IgV domain Mediate Cell Surface Binding to CD47

OpenAIRE

Liu, Yuan; Tong, Qiao; Zhou, Yubin; Lee, Hsiau-Wei; Yang, Jenny J.; Bühring, Hans-Jörg; Chen, Yi-Tien; Ha, Binh; Chen, Celia X-J.; Zen, Ke

2006-01-01

SIRPα and SIRPβ1, the two major isoforms of the signal regulatory protein (SIRP) family, are co-expressed in human leukocytes but mediate distinct extracellular binding interactions and divergent cell signaling responses. Previous studies have demonstrated that binding of SIRPα with CD47, another important cell surface molecule, through the extracellular IgV domain regulates important leukocyte functions including macrophage recognition, leukocyte adhesion and transmigration. Although SIRPβ1 ...

Strengthening Regulatory Competence in a Changing Nuclear Regulatory Environment

International Nuclear Information System (INIS)

Illizastigui, P.F.

2016-01-01

The paper addresses the approach followed by the Cuban National Center for Nuclear Safety for the management of current and new competences of its regulatory staff with the aim of allowing those staff to effectively fulfill their core regulatory functions. The approach is realized through an Integrated System for Competence Building, which is based on the IAEA recommendations, shown to be effective in ensuring the necessary competence in the relevant areas. In the author’s opinion, competence of the regulatory staff in the area of human and organizational factors is of paramount importance and needs to be further strengthened in order to be able to assess safety performance at the facilities and detect early signs of deteriorating safety performance. The former is defined by the author as the core regulatory function “Analysis” which covers the entire spectrum of assessment tasks carried out by the regulatory staff to: a) detect declining safety performance, b) diagnose latent weaknesses (root causes) and c) make effective safety culture interventions. The author suggests that competence associated with the fulfillment of the analysis function is distinctly identified and dealt with separately in the current system of managing regulatory competence. (author)

Electrical performance of conducting polymer (SPAN) grown on GaAs with different substrate orientations

Science.gov (United States)

Jameel, D. A.; Aziz, M.; Felix, J. F.; Al Saqri, N.; Taylor, D.; Albalawi, H.; Alghamdi, H.; Al Mashary, F.; Henini, M.

2016-11-01

This article reports the effect of n-type GaAs substrate orientation, namely (100), (311)A and (311)B, on the electrical properties of sulfonated polyaniline (SPAN)/GaAs heterojunction devices. In addition, the inhomogeneity of the interface between various GaAs substrates and SPAN is investigated in terms of barrier height and ideality factor by performing I-V measurements at different temperatures (20-420 K). The I-V results indicate that the value of the rectification ratio (IF/IR) at 0.5 V is higher for SPAN/(311)B GaAs samples than for SPAN/(100) GaAs and SPAN/(311)A GaAs samples. Moreover, the barrier height decreases and the ideality factor increases with decreasing temperature for all three heterostructure devices. The high value of mean barrier Φbarb of SPAN/(311)B (calculated from the plots of Φb 0 as a function of 1/2kT) confirms that the GaAs substrate orientation results in an increase of barrier homogeneities. Furthermore, the C-V characteristics were obtained at room temperature. The C-V measurements showed that the carrier distributions at the interface and away from the interface in high index (311) GaAs orientations are more uniform and have better barrier homogeneity than those grown on the conventional (100) GaAs substrates.

DIRECT SELECTION ON LIFE-SPAN IN DROSOPHILA-MELANOGASTER

NARCIS (Netherlands)

ZWAAN, B; BIJLSMA, R; HOEKSTRA, RE

An important issue in the study of the evolution of aging in Drosophila melanogaster is whether decreased early fecundity is inextricably coupled with increased life span in selection experiments on age at reproduction. Here, this problem has been tackled using an experimental design in which

Life span effects of Hypericum perforatum extracts on Caenorhabditis elegans under heat stress.

Science.gov (United States)

Kılıçgün, Hasan; Göksen, Gülden

2012-10-01

The beneficial effects of antioxidants in plants are mainly extrapolated from in vitro studies or short-term dietary supplementation studies. Due to cost and duration, relatively little is known about whether dietary antioxidants are beneficial in whole animals' life span or not. To address this question, under heat stress (35°C), Hypericum perforatum was extracted with petroleum ether and the nematodes Caenorhabditis elegans exposed to three different extract concentrations (1mg/mL, 0.1mg/mL, 0.01mg/mL) of H. perforatum. We report that Hypericum perforatum extracts did not increase life span and slow aging related increase in C. elegans. Moreover, one fraction (1mg/mL) increased declines of C. elegans life span and thermotolerance. Given this mounting evidence for life span role of H. perforatum in the presence of heat stress in vivo, the question whether H. perforatum acts as a prooxidant or an antioxidant in vivo under heat stress arises.

Domains and domain loss

DEFF Research Database (Denmark)

Haberland, Hartmut

2005-01-01

politicians and in the media, especially in the discussion whether some languages undergo ‘domain loss’ vis-à-vis powerful international languages like English. An objection that has been raised here is that domains, as originally conceived, are parameters of language choice and not properties of languages...

Improving the performance of DomainDiscovery of protein domain boundary assignment using inter-domain linker index

Directory of Open Access Journals (Sweden)

Zomaya Albert Y

2006-12-01

Full Text Available Abstract Background Knowledge of protein domain boundaries is critical for the characterisation and understanding of protein function. The ability to identify domains without the knowledge of the structure – by using sequence information only – is an essential step in many types of protein analyses. In this present study, we demonstrate that the performance of DomainDiscovery is improved significantly by including the inter-domain linker index value for domain identification from sequence-based information. Improved DomainDiscovery uses a Support Vector Machine (SVM approach and a unique training dataset built on the principle of consensus among experts in defining domains in protein structure. The SVM was trained using a PSSM (Position Specific Scoring Matrix, secondary structure, solvent accessibility information and inter-domain linker index to detect possible domain boundaries for a target sequence. Results Improved DomainDiscovery is compared with other methods by benchmarking against a structurally non-redundant dataset and also CASP5 targets. Improved DomainDiscovery achieves 70% accuracy for domain boundary identification in multi-domains proteins. Conclusion Improved DomainDiscovery compares favourably to the performance of other methods and excels in the identification of domain boundaries for multi-domain proteins as a result of introducing support vector machine with benchmark_2 dataset.

Structural covariance networks across the life span, from 6 to 94 years of age

Directory of Open Access Journals (Sweden)

Elizabeth DuPre

2017-10-01

Full Text Available Structural covariance examines covariation of gray matter morphology between brain regions and across individuals. Despite significant interest in the influence of age on structural covariance patterns, no study to date has provided a complete life span perspective—bridging childhood with early, middle, and late adulthood—on the development of structural covariance networks. Here, we investigate the life span trajectories of structural covariance in six canonical neurocognitive networks: default, dorsal attention, frontoparietal control, somatomotor, ventral attention, and visual. By combining data from five open-access data sources, we examine the structural covariance trajectories of these networks from 6 to 94 years of age in a sample of 1,580 participants. Using partial least squares, we show that structural covariance patterns across the life span exhibit two significant, age-dependent trends. The first trend is a stable pattern whose integrity declines over the life span. The second trend is an inverted-U that differentiates young adulthood from other age groups. Hub regions, including posterior cingulate cortex and anterior insula, appear particularly influential in the expression of this second age-dependent trend. Overall, our results suggest that structural covariance provides a reliable definition of neurocognitive networks across the life span and reveal both shared and network-specific trajectories. The importance of life span perspectives is increasingly apparent in understanding normative interactions of large-scale neurocognitive networks. Although recent work has made significant strides in understanding the functional and structural connectivity of these networks, there has been comparatively little attention to life span trajectories of structural covariance networks. In this study we examine patterns of structural covariance across the life span for six neurocognitive networks. Our results suggest that networks exhibit

Within-Trait Heterogeneity in Age Group Differences in Personality Domains and Facets: Implications for the Development and Coherence of Personality Traits

Science.gov (United States)

Mõttus, René; Realo, Anu; Allik, Jüri; Esko, Tõnu; Metspalu, Andres; Johnson, Wendy

2015-01-01

The study investigated differences in the Five-Factor Model (FFM) domains and facets across adulthood. The main questions were whether personality scales reflected coherent units of trait development and thereby coherent personality traits more generally. These questions were addressed by testing if the components of the trait scales (items for facet scales and facets for domain scales) showed consistent age group differences. For this, measurement invariance (MI) framework was used. In a sample of 2,711 Estonians who had completed the NEO Personality Inventory 3 (NEO PI-3), more than half of the facet scales and one domain scale did not meet the criterion for weak MI (factor loading equality) across 12 age groups spanning ages from 18 to 91 years. Furthermore, none of the facet and domain scales met the criterion for strong MI (intercept equality), suggesting that items of the same facets and facets of the same domains varied in age group differences. When items were residualized for their respective facets, 46% of them had significant (p traits should show similar age group differences. Given this, the FFM domains and facets as embodied in the NEO PI-3 do not reflect aetiologically coherent traits. PMID:25751273

Processing Efficiency in Preschoolers' Memory Span: Individual Differences Related to Age and Anxiety

Science.gov (United States)

Visu-Petra, Laura; Miclea, Mircea; Cheie, Lavinia; Benga, Oana

2009-01-01

In self-paced auditory memory span tasks, the microanalysis of response timing measures represents a developmentally sensitive measure, providing insights into the development of distinct processing rates during recall performance. The current study first examined the effects of age and trait anxiety on span accuracy (effectiveness) and response…

'Localised creativity: a life span perspective'

OpenAIRE

Worth, Piers J.

2000-01-01

This thesis is based around a biographic study of the lives of 40 individuals (24 men and 16 women) with a reputation for creative work in a localised context (such as an organisation). The study examines life span development patterns from birth to middle age (45 - 60 years of age) with data gained by biographic interview and thematic analysis. Participants selected for this study are creative in that they have a reputation for producing new, novel and useful or appropriate contributions in ...

Characterization, cell-surface expression and ligand-binding properties of different truncated N-terminal extracellular domains of the ionotropic glutamate receptor subunit GluR1.

Science.gov (United States)

McIlhinney, R A; Molnár, E

1996-04-01

To identify the location of the first transmembrane segment of the GluR1 glutamate receptor subunit artificial stop codons have been introduced into the N-terminal domain at amino acid positions 442, 510, and 563, namely just before and spanning the proposed first two transmembrane regions. The resultant truncated N-terminal fragments of GluR1, termed NT1, NT2, and NT3 respectively were expressed in Cos-7 cells and their cellular distribution and cell-surface expression analysed using an N-terminal antibody to GluR1. All of the fragments were fully glycosylated and were found to be associated with cell membranes but none was secreted. Differential extraction of the cell membranes indicated that both NT1 and NT2 behave as peripheral membrane proteins. In contrast NT3, like the full subunit, has integral membrane protein properties. Furthermore only NT3 is expressed at the cell surface as determined by immunofluorescence and cell-surface biotinylation. Protease protection assays indicated that only NT3 had a cytoplasmic tail. Binding studies using the selective ligand [(3)H]alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate ([(3)H]AMPA) demonstrated that NT3 does not bind ligand. Together these results indicate that the first transmembrane domain of the GluR1 subunit lies between residues 509 and 562, that the N-terminal domain alone cannot form a functional ligand-binding site and that this domain can be targeted to the cell surface provided that it has a transmembrane-spanning region.

The N domain of somatic angiotensin-converting enzyme negatively regulates ectodomain shedding and catalytic activity.

Science.gov (United States)

Woodman, Zenda L; Schwager, Sylva L U; Redelinghuys, Pierre; Carmona, Adriana K; Ehlers, Mario R W; Sturrock, Edward D

2005-08-01

sACE (somatic angiotensin-converting enzyme) consists of two homologous, N and C domains, whereas the testis isoenzyme [tACE (testis ACE)] consists of a single C domain. Both isoenzymes are shed from the cell surface by a sheddase activity, although sACE is shed much less efficiently than tACE. We hypothesize that the N domain of sACE plays a regulatory role, by occluding a recognition motif on the C domain required for ectodomain shedding and by influencing the catalytic efficiency. To test this, we constructed two mutants: CNdom-ACE and CCdom-ACE. CNdom-ACE was shed less efficiently than sACE, whereas CCdom-ACE was shed as efficiently as tACE. Notably, cleavage occurred both within the stalk and the interdomain bridge in both mutants, suggesting that a sheddase recognition motif resides within the C domain and is capable of directly cleaving at both positions. Analysis of the catalytic properties of the mutants and comparison with sACE and tACE revealed that the k(cat) for sACE and CNdom-ACE was less than or equal to the sum of the kcat values for tACE and the N-domain, suggesting negative co-operativity, whereas the kcat value for the CCdom-ACE suggested positive co-operativity between the two domains. Taken together, the results provide support for (i) the existence of a sheddase recognition motif in the C domain and (ii) molecular flexibility of the N and C domains in sACE, resulting in occlusion of the C-domain recognition motif by the N domain as well as close contact of the two domains during hydrolysis of peptide substrates.

An in vivo cis-regulatory screen at the type 2 diabetes associated TCF7L2 locus identifies multiple tissue-specific enhancers.

Directory of Open Access Journals (Sweden)

Daniel Savic

Full Text Available Genome-wide association studies (GWAS have repeatedly shown an association between non-coding variants in the TCF7L2 locus and risk for type 2 diabetes (T2D, implicating a role for cis-regulatory variation within this locus in disease etiology. Supporting this hypothesis, we previously localized complex regulatory activity to the TCF7L2 T2D-associated interval using an in vivo bacterial artificial chromosome (BAC enhancer-trapping reporter strategy. To follow-up on this broad initial survey of the TCF7L2 regulatory landscape, we performed a fine-mapping enhancer scan using in vivo mouse transgenic reporter assays. We functionally interrogated approximately 50% of the sequences within the T2D-associated interval, utilizing sequence conservation within this 92-kb interval to determine the regulatory potential of all evolutionary conserved sequences that exhibited conservation to the non-eutherian mammal opossum. Included in this study was a detailed functional interrogation of sequences spanning both protective and risk alleles of single nucleotide polymorphism (SNP rs7903146, which has exhibited allele-specific enhancer function in pancreatic beta cells. Using these assays, we identified nine segments regulating various aspects of the TCF7L2 expression profile and that constitute nearly 70% of the sequences tested. These results highlight the regulatory complexity of this interval and support the notion that a TCF7L2 cis-regulatory disruption leads to T2D predisposition.

Blended Design Approach of Long Span Structure and Malay Traditional Architecture

Science.gov (United States)

Sundari, Titin

2017-12-01

The growing population in the world is so fast, which is followed by the increasing need of some new and large activities. Architects face the problem on how to facilitate buildings with various activities such as for large meeting, conference, indoors gymnasium and sports, and many others. The long span structure of building is one of the solutions to solve that problem. Generally, large buildings which implemented this structure will look as a technological, modern and futuristic ones or even neo futuristic performance. But on the other hand, many people still want to enjoy the specific and unique senses of local traditional architecture. So is the Malay people who want an easy pleasant large facilities which can be fulfilled by implementing modern long span building structure technology. In the same time, their unique sense of Malay traditional architecture can still be maintained. To overcome this double problems of design, it needs a blended design approach of long span structure and Malay Traditional Architecture.

Seismic Performance of Multi-Span RC Railway Bridges

DEFF Research Database (Denmark)

Georgakis, Christos; Barrau, Xavier

2008-01-01

Presently, there is no clear method for determining the optimal railway bridge design for a particular ground type and expected seismic intensity. Four main types of RC bridge dominate the current multi-span railway bridge design trends – the Simply Supported Beam, Continuous Box-Girder (CBG), CBG...

Spanning the Creative Space between Home and Work

DEFF Research Database (Denmark)

Davis, Lee N.; Hoisl, Karin; Davis, Jerome

the employee brings to work. Based on Woodman et al.’s (1993) “interactionist perspective” on organizational creativity, supplemented by literature on search and knowledge/combination, we explore whether leisure time activities can span the creative space between the employee’s home and workplace – given...

The Enzyme-Like Domain of Arabidopsis Nuclear β-Amylases Is Critical for DNA Sequence Recognition and Transcriptional Activation.

Science.gov (United States)

Soyk, Sebastian; Simková, Klára; Zürcher, Evelyne; Luginbühl, Leonie; Brand, Luise H; Vaughan, Cara K; Wanke, Dierk; Zeeman, Samuel C

2014-04-01

Plant BZR1-BAM transcription factors contain a β-amylase (BAM)-like domain, characteristic of proteins involved in starch breakdown. The enzyme-derived domains appear to be noncatalytic, but they determine the function of the two Arabidopsis thaliana BZR1-BAM isoforms (BAM7 and BAM8) during transcriptional initiation. Removal or swapping of the BAM domains demonstrates that the BAM7 BAM domain restricts DNA binding and transcriptional activation, while the BAM8 BAM domain allows both activities. Furthermore, we demonstrate that BAM7 and BAM8 interact on the protein level and cooperate during transcriptional regulation. Site-directed mutagenesis of residues in the BAM domain of BAM8 shows that its function as a transcriptional activator is independent of catalysis but requires an intact substrate binding site, suggesting it may bind a ligand. Microarray experiments with plants overexpressing truncated versions lacking the BAM domain indicate that the pseudo-enzymatic domain increases selectivity for the preferred cis-regulatory element BBRE (BZR1-BAM Responsive Element). Side specificity toward the G-box may allow crosstalk to other signaling networks. This work highlights the importance of the enzyme-derived domain of BZR1-BAMs, supporting their potential role as metabolic sensors. © 2014 American Society of Plant Biologists. All rights reserved.

Individual differences in memory span: the contribution of rehearsal, access to lexical memory, and output speed.

Science.gov (United States)

Tehan, G; Lalor, D M

2000-11-01

Rehearsal speed has traditionally been seen to be the prime determinant of individual differences in memory span. Recent studies, in the main using young children as the subject population, have suggested other contributors to span performance, notably contributions from long-term memory and forgetting and retrieval processes occurring during recall. In the current research we explore individual differences in span with respect to measures of rehearsal, output time, and access to lexical memory. We replicate standard short-term phenomena; we show that the variables that influence children's span performance influence adult performance in the same way; and we show that lexical memory access appears to be a more potent source of individual differences in span than either rehearsal speed or output factors.

The Problem of Predecessors on Spanning Trees

Directory of Open Access Journals (Sweden)

V. S. Poghosyan

2011-01-01

Full Text Available We consider the equiprobable distribution of spanning trees on the square lattice. All bonds of each tree can be oriented uniquely with respect to an arbitrary chosen site called the root. The problem of predecessors is to find the probability that a path along the oriented bonds passes sequentially fixed sites i and j. The conformal field theory for the Potts model predicts the fractal dimension of the path to be 5/4. Using this result, we show that the probability in the predecessors problem for two sites separated by large distance r decreases as P(r ∼ r −3/4. If sites i and j are nearest neighbors on the square lattice, the probability P(1 = 5/16 can be found from the analytical theory developed for the sandpile model. The known equivalence between the loop erased random walk (LERW and the directed path on the spanning tree states that P(1 is the probability for the LERW started at i to reach the neighboring site j. By analogy with the self-avoiding walk, P(1 can be called the return probability. Extensive Monte-Carlo simulations confirm the theoretical predictions.

Detection of suboptimal effort with symbol span: development of a new embedded index.

Science.gov (United States)

Young, J Christopher; Caron, Joshua E; Baughman, Brandon C; Sawyer, R John

2012-03-01

Developing embedded indicators of suboptimal effort on objective neurocognitive testing is essential for detecting increasingly sophisticated forms of symptom feigning. The current study explored whether Symbol Span, a novel Wechsler Memory Scale-fourth edition measure of supraspan visual attention, could be used to discriminate adequate effort from suboptimal effort. Archival data were collected from 136 veterans classified into Poor Effort (n = 42) and Good Effort (n = 94) groups based on symptom validity test (SVT) performance. The Poor Effort group had significantly lower raw scores (p Span test. A raw score cutoff of Span can effectively differentiate veterans with multiple failures on established free-standing and embedded SVTs.

Regulatory networks, legal federalism, and multi-level regulatory systems

OpenAIRE

Kerber, Wolfgang; Wendel, Julia

2016-01-01

Transnational regulatory networks play important roles in multi-level regulatory regimes, as e.g, the European Union. In this paper we analyze the role of regulatory networks from the perspective of the economic theory of legal federalism. Often sophisticated intermediate institutional solutions between pure centralisation and pure decentralisation can help to solve complex tradeoff problems between the benefits and problems of centralised and decentralised solutions. Drawing upon the insight...

Recognition of methylated DNA through methyl-CpG binding domain proteins

DEFF Research Database (Denmark)

Zou, Xueqing; Ma, Wen; Solov'yov, Ilia

2012-01-01

DNA methylation is a key regulatory control route in epigenetics, involving gene silencing and chromosome inactivation. It has been recognized that methyl-CpG binding domain (MBD) proteins play an important role in interpreting the genetic information encoded by methylated DNA (mDNA). Although...... the function of MBD proteins has attracted considerable attention and is well characterized, the mechanism underlying mDNA recognition by MBD proteins is still poorly understood. In this article, we demonstrate that the methyl-CpG dinucleotides are recognized at the MBD-mDNA interface by two MBD arginines...

Friendship in childhood and adulthood: lessons across the life span.

Science.gov (United States)

Sherman, A M; de Vries, B; Lansford, J E

2000-01-01

Friendship occupies an important place in the growing body of literature in child development and gerontological research. As such, it may be useful for researchers from both fields to consider what can be learned from work carried out in each tradition. Therefore, we present a selected review of topics in friendship research across the life span. Through discussion of the value of friendship, the development of friendship, challenges to friendship, the gendered nature of friendship, and the connection between friends and family, points of commonality and contrast are identified. We conclude by presenting possible avenues for future investigation for researchers interested in friendship at any point in the life span.

Proactive and coactive interference in age-related performance in a recognition-based operation span task.

Science.gov (United States)

Zeintl, Melanie; Kliegel, Matthias

2010-01-01

Generally, older adults perform worse than younger adults in complex working memory span tasks. So far, it is unclear which processes mainly contribute to age-related differences in working memory span. The aim of the present study was to investigate age effects and the roles of proactive and coactive interference in a recognition-based version of the operation span task. Younger and older adults performed standard versions and distracter versions of the operation span task. At retrieval, participants had to recognize target words in word lists containing targets as well as proactive and/or coactive interference-related lures. Results show that, overall, younger adults outperformed older adults in the recognition of target words. Furthermore, analyses of error types indicate that, while younger adults were only affected by simultaneously presented distracter words, older adults had difficulties with both proactive and coactive interference. Results suggest that age effects in complex span tasks may not be mainly due to retrieval deficits in old age. Copyright 2009 S. Karger AG, Basel.

How long will my mouse live? Machine learning approaches for prediction of mouse life span.

Science.gov (United States)

Swindell, William R; Harper, James M; Miller, Richard A

2008-09-01

Prediction of individual life span based on characteristics evaluated at middle-age represents a challenging objective for aging research. In this study, we used machine learning algorithms to construct models that predict life span in a stock of genetically heterogeneous mice. Life-span prediction accuracy of 22 algorithms was evaluated using a cross-validation approach, in which models were trained and tested with distinct subsets of data. Using a combination of body weight and T-cell subset measures evaluated before 2 years of age, we show that the life-span quartile to which an individual mouse belongs can be predicted with an accuracy of 35.3% (+/-0.10%). This result provides a new benchmark for the development of life-span-predictive models, but improvement can be expected through identification of new predictor variables and development of computational approaches. Future work in this direction can provide tools for aging research and will shed light on associations between phenotypic traits and longevity.

The Life Span of the BD-PND Bubble Detector

International Nuclear Information System (INIS)

Vanhavere, F.; Loos, M.; Thierens, H.

1999-01-01

BD-PND bubble detectors from Bubble Technology Industries (BTI) were used to conduct a study of the life span of these detectors. The manufacturer guarantees an optimum detector performance for three months after receipt. Nevertheless, it is important to know the evolution of their characteristics with time, also after those three months. On a standard set-up with a 252 Cf source the bubble detectors were irradiated until they reached the end of their life span. During this period, the evolution in sensitivity was monitored. The temperature compensating system seems to be the limiting factor with time for the use of the BTI bubble detectors. The change in temperature dependence with age was determined. The same parameters were also checked with several batches of detectors that were used in practice. (author)

Robustness Analysis of Big Span Glulam Truss Structure

DEFF Research Database (Denmark)

Rajčié, V.; čizmar, D.; Kirkegaard, Poul Henning

2010-01-01

(Eurocode 0 &1, Probabilistic model code etc.) Based on a project of big span glulam truss structure, build in Croatia few years ago, a probabilistic model is made with four failure elements. Reliability analysis of components is conducted and based on this a robustness analysis is preformed. It can...

Hard-Rock Stability Analysis for Span Design in Entry-Type Excavations with Learning Classifiers

Directory of Open Access Journals (Sweden)

Esperanza García-Gonzalo

2016-06-01

Full Text Available The mining industry relies heavily on empirical analysis for design and prediction. An empirical design method, called the critical span graph, was developed specifically for rock stability analysis in entry-type excavations, based on an extensive case-history database of cut and fill mining in Canada. This empirical span design chart plots the critical span against rock mass rating for the observed case histories and has been accepted by many mining operations for the initial span design of cut and fill stopes. Different types of analysis have been used to classify the observed cases into stable, potentially unstable and unstable groups. The main purpose of this paper is to present a new method for defining rock stability areas of the critical span graph, which applies machine learning classifiers (support vector machine and extreme learning machine. The results show a reasonable correlation with previous guidelines. These machine learning methods are good tools for developing empirical methods, since they make no assumptions about the regression function. With this software, it is easy to add new field observations to a previous database, improving prediction output with the addition of data that consider the local conditions for each mine.

Hard-Rock Stability Analysis for Span Design in Entry-Type Excavations with Learning Classifiers.

Science.gov (United States)

García-Gonzalo, Esperanza; Fernández-Muñiz, Zulima; García Nieto, Paulino José; Bernardo Sánchez, Antonio; Menéndez Fernández, Marta

2016-06-29

The mining industry relies heavily on empirical analysis for design and prediction. An empirical design method, called the critical span graph, was developed specifically for rock stability analysis in entry-type excavations, based on an extensive case-history database of cut and fill mining in Canada. This empirical span design chart plots the critical span against rock mass rating for the observed case histories and has been accepted by many mining operations for the initial span design of cut and fill stopes. Different types of analysis have been used to classify the observed cases into stable, potentially unstable and unstable groups. The main purpose of this paper is to present a new method for defining rock stability areas of the critical span graph, which applies machine learning classifiers (support vector machine and extreme learning machine). The results show a reasonable correlation with previous guidelines. These machine learning methods are good tools for developing empirical methods, since they make no assumptions about the regression function. With this software, it is easy to add new field observations to a previous database, improving prediction output with the addition of data that consider the local conditions for each mine.

E-commercspan>e in China and Germany: a Sino-German comparative analysis

NARCIS (Netherlands)

Purnhagen, K.

2012-01-01

The ways to approach the regulation of e-commercspan>e markets are in the focus of discussion both in China and Germany. While a general need for regulation is undisputed in both countries, the scope, means and aims regulation differ. The Chinese e-commercspan>e regulation is based on strong governmental

Safety culture as a matter of regulatory control and regulatory effectiveness

International Nuclear Information System (INIS)

Camargo, C.T.M.; Furieri, E.B.; Arrieta, L.A.I.; Almeida, C.U.C.

2002-01-01

More than 15 years have passed since the term 'safety culture' was introduced by the International Nuclear Safety Advisory Group (INSAG), and although the concept now is widely accepted, practical applications and characteristics have been disseminated mainly for nuclear power plant operating organizations. There is still a lack of international guidance on the use of safety culture as a regulatory matter and on the application of the concept within regulatory organizations. This work explores the meaning of safety culture in two different fields: as an element of safety management systems it shall be a matter of regulatory control; as a complementary tool for quality management it should be used to enhance regulatory effectiveness. Brazilian recent experience on regulating nuclear power reactors provide some examples on how the concept of safety culture may influence regulatory strategies and regulatory management. (author)

The eye-voice span during reading aloud

Directory of Open Access Journals (Sweden)

Jochen eLaubrock

2015-09-01

Full Text Available Although eye movements during reading are modulated by cognitive processing demands, they also reflect visual sampling of the input, and possibly preparation of output for speech or the inner voice. By simultaneously recording eye movements and the voice during reading aloud, we obtained an output measure that constrains the length of time spent on cognitive processing. Here we investigate the dynamics of the eye-voice span (EVS, the distance between eye and voice. We show that the EVS is regulated immediately during fixation of a word by either increasing fixation duration or programming a regressive eye movement against the reading direction. EVS size at the beginning of a fixation was positively correlated with the likelihood of regressions and refixations. Regression probability was further increased if the EVS was still large at the end of a fixation: if adjustment of fixation duration did not sufficiently reduce the EVS during a fixation, then a regression rather than a refixation followed with high probability. We further show that the EVS can help understand cognitive influences on fixation duration during reading: in mixed model analyses, the EVS was a stronger predictor of fixation durations than either word frequency or word length. The EVS modulated the influence of several other predictors on single fixation durations. For example, word-N frequency effects were larger with a large EVS, especially when word N-1 frequency was low. Finally, a comparison of single fixation durations during oral and silent reading showed that reading is governed by similar principles in both reading modes, although EVS maintenance and articulatory processing also cause some differences. In summary, the eye-voice span is regulated by adjusting fixation duration and/or by programming a regressive eye movement when the eye-voice span gets too large. Overall, the EVS appears to be directly related to updating of the working memory buffer during reading.

Blocking Reduction of Span Restoration Requests in GMPLS Controlled WDM Optical Networks

DEFF Research Database (Denmark)

Buron, Jakob Due; Ruepp, Sarah Renée; Andriolli, N.

2006-01-01

The proposed label preference scheme reduces blocking of span restoration requests in GMPLS optical networks with limited wavelength conversion. By minimizing resource contention and conversion usage, it increases recovery percentage and reduces control plane load.......The proposed label preference scheme reduces blocking of span restoration requests in GMPLS optical networks with limited wavelength conversion. By minimizing resource contention and conversion usage, it increases recovery percentage and reduces control plane load....

Boundary Spanning in Global Software Development

DEFF Research Database (Denmark)

Søderberg, Anne-Marie; Romani, Laurence

imbalances of power, exacerbated in the case of an Indian vendor and a European client, need to be taken into account. The paper thus contributes with a more context sensitive understanding of inter-organizational boundary work. Taking the vendor perspective also leads to problematization of common...... of Indian IT vendor managers who are responsible for developing client relations and coordinating complex global development projects. The authors revise a framework of boundary spanning leadership practices to adapt it to an offshore outsourcing context. The empirical investigation highlights how...

Mimicry of the regulatory role of urokinase in lamellipodia formation by introduction of a non-native interdomain disulfide bond in its receptor

DEFF Research Database (Denmark)

Gårdsvoll, Henrik; Kjærgaard, Magnus; Jacobsen, Benedikte

2011-01-01

The high-affinity interaction between the urokinase-type plasminogen activator (uPA) and its glycolipid-anchored receptor (uPAR) plays a regulatory role for both extravascular fibrinolysis and uPAR-mediated adhesion and migration on vitronectin-coated surfaces. We have recently proposed that the ......The high-affinity interaction between the urokinase-type plasminogen activator (uPA) and its glycolipid-anchored receptor (uPAR) plays a regulatory role for both extravascular fibrinolysis and uPAR-mediated adhesion and migration on vitronectin-coated surfaces. We have recently proposed...... that the adhesive function of uPAR is allosterically regulated via a "tightening" of its three-domain structure elicited by uPA binding. To challenge this proposition, we redesigned the uPAR structure to limit its inherent conformational flexibility by covalently tethering domains DI and DIII via a non...... adhering to vitronectin. In this respect, the engineered constraint in uPAR(H47C-N259C) thus bypasses the regulatory role of uPA binding, resulting in a constitutively active uPAR. In conclusion, our data argue for a biological relevance of the interdomain dynamics of the glycolipid-anchored u...

Sequence and structural analysis of the chitinase insertion domain reveals two conserved motifs involved in chitin-binding.

Directory of Open Access Journals (Sweden)

Hai Li

2010-01-01

Full Text Available Chitinases are prevalent in life and are found in species including archaea, bacteria, fungi, plants, and animals. They break down chitin, which is the second most abundant carbohydrate in nature after cellulose. Hence, they are important for maintaining a balance between carbon and nitrogen trapped as insoluble chitin in biomass. Chitinases are classified into two families, 18 and 19 glycoside hydrolases. In addition to a catalytic domain, which is a triosephosphate isomerase barrel, many family 18 chitinases contain another module, i.e., chitinase insertion domain. While numerous studies focus on the biological role of the catalytic domain in chitinase activity, the function of the chitinase insertion domain is not completely understood. Bioinformatics offers an important avenue in which to facilitate understanding the role of residues within the chitinase insertion domain in chitinase function.Twenty-seven chitinase insertion domain sequences, which include four experimentally determined structures and span five kingdoms, were aligned and analyzed using a modified sequence entropy parameter. Thirty-two positions with conserved residues were identified. The role of these conserved residues was explored by conducting a structural analysis of a number of holo-enzymes. Hydrogen bonding and van der Waals calculations revealed a distinct subset of four conserved residues constituting two sequence motifs that interact with oligosaccharides. The other conserved residues may be key to the structure, folding, and stability of this domain.Sequence and structural studies of the chitinase insertion domains conducted within the framework of evolution identified four conserved residues which clearly interact with the substrates. Furthermore, evolutionary studies propose a link between the appearance of the chitinase insertion domain and the function of family 18 chitinases in the subfamily A.

Chemical Ligation of Folded Recombinant Proteins: Segmental Isotopic Labeling of Domains for NMR Studies

Science.gov (United States)

Xu, Rong; Ayers, Brenda; Cowburn, David; Muir, Tom W.

1999-01-01

A convenient in vitro chemical ligation strategy has been developed that allows folded recombinant proteins to be joined together. This strategy permits segmental, selective isotopic labeling of the product. The src homology type 3 and 2 domains (SH3 and SH2) of Abelson protein tyrosine kinase, which constitute the regulatory apparatus of the protein, were individually prepared in reactive forms that can be ligated together under normal protein-folding conditions to form a normal peptide bond at the ligation junction. This strategy was used to prepare NMR sample quantities of the Abelson protein tyrosine kinase-SH(32) domain pair, in which only one of the domains was labeled with 15N Mass spectrometry and NMR analyses were used to confirm the structure of the ligated protein, which was also shown to have appropriate ligand-binding properties. The ability to prepare recombinant proteins with selectively labeled segments having a single-site mutation, by using a combination of expression of fusion proteins and chemical ligation in vitro, will increase the size limits for protein structural determination in solution with NMR methods. In vitro chemical ligation of expressed protein domains will also provide a combinatorial approach to the synthesis of linked protein domains.

Trans-acting translational regulatory RNA binding proteins.

Science.gov (United States)

Harvey, Robert F; Smith, Tom S; Mulroney, Thomas; Queiroz, Rayner M L; Pizzinga, Mariavittoria; Dezi, Veronica; Villenueva, Eneko; Ramakrishna, Manasa; Lilley, Kathryn S; Willis, Anne E

2018-05-01

The canonical molecular machinery required for global mRNA translation and its control has been well defined, with distinct sets of proteins involved in the processes of translation initiation, elongation and termination. Additionally, noncanonical, trans-acting regulatory RNA-binding proteins (RBPs) are necessary to provide mRNA-specific translation, and these interact with 5' and 3' untranslated regions and coding regions of mRNA to regulate ribosome recruitment and transit. Recently it has also been demonstrated that trans-acting ribosomal proteins direct the translation of specific mRNAs. Importantly, it has been shown that subsets of RBPs often work in concert, forming distinct regulatory complexes upon different cellular perturbation, creating an RBP combinatorial code, which through the translation of specific subsets of mRNAs, dictate cell fate. With the development of new methodologies, a plethora of novel RNA binding proteins have recently been identified, although the function of many of these proteins within mRNA translation is unknown. In this review we will discuss these methodologies and their shortcomings when applied to the study of translation, which need to be addressed to enable a better understanding of trans-acting translational regulatory proteins. Moreover, we discuss the protein domains that are responsible for RNA binding as well as the RNA motifs to which they bind, and the role of trans-acting ribosomal proteins in directing the translation of specific mRNAs. This article is categorized under: RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes Translation > Translation Regulation Translation > Translation Mechanisms. © 2018 Medical Research Council and University of Cambridge. WIREs RNA published by Wiley Periodicals, Inc.

Effect of practice and span length on the dual-task coordination executive test

Directory of Open Access Journals (Sweden)

Sylwan R.P.

1999-01-01

Full Text Available The measure "mu", proposed as an index of the ability to coordinate concurrent box-crossing (BC and digit-span (DS tasks in the dual task (DT, should reflect the capacity of the executive component of the working memory system. We investigated the effect of practice in BC and of a change in the digit span on mu by adding previous practice trials in BC and diminishing, maintaining or increasing the digit sequence length. The mu behavior was evaluated throughout three trials of the test. Reported strategies in digit tasks were also analyzed. Subjects with diminished span showed the best performance in DT due to a stable performance in DS and BC in the single- and dual-task conditions. These subjects also showed a more stable performance throughout trials. Subjects with diminished span tended to employ effortless strategies, whereas subjects with increased span employed effort-requiring strategies and showed the lowest means of mu. Subjects with initial practice trials showed the best performance in BC and the most differentiated performance between the single- and dual-task conditions in BC. The correlation coefficient between the mu values obtained in the first and second trials was 0.814 for subjects with diminished span and practice trials in BC. It seems that the within-session practice in BC and the performance variability in DS affect the reliability of the index mu. To control these factors we propose the introduction of previous practice trials in BC and a modification of the current method to determine the digit sequence length. This proposal should contribute to the development of a more reliable method to evaluate the executive capacity of coordination in the dual-task paradigm.

Spanning trees with many leaves: new extremal results and an improved FPT algorithm

NARCIS (Netherlands)

Bonsma, P.S.

We present two lower bounds for the maximum number of leaves in a spanning tree of a graph. For connected graphs without triangles, with minimum degree at least three, we show that a spanning tree with at least (n+4)/3 leaves exists, where n is the number of vertices of the graph. For connected

E-commercspan>e in the banking sector

NARCIS (Netherlands)

Stroeken, J.H.M.; Munck, S.G.E. de; Hawkins, R.

2001-01-01

Het doel van de studie is het verschaffen van inzicht in de effecten van e-commercspan>e in de Nederlandse banksector. Elektronische transactie omgevingen als zodanig zijn niet nieuw voor banken, en financiële dienstverlening heeft altijd al te maken gehad met intermediëring door elektronische netwerken.

Damage detection in multi-span beams based on the analysis of frequency changes

International Nuclear Information System (INIS)

Gillich, G R; Ntakpe, J L; Praisach, Z I; Mimis, M C; Abdel Wahab, M

2017-01-01

Crack identification in multi-span beams is performed to determine whether the structure is healthy or not. Among all crack identification methods, these based on measured natural frequency changes present the advantage of simplicity and easy to use in practical engineering. To accurately identify the cracks characteristics for multi-span beam structure, a mathematical model is established, which can predict frequency changes for any boundary conditions, the intermediate supports being hinges. This relation is based on the modal strain energy concept. Since frequency changes are relative small, to obtain natural frequencies with high resolution, a signal processing algorithm based on superposing of numerous spectra is also proposed, which overcomes the disadvantage of Fast Fourier Transform in the aspect of frequency resolution. Based on above-mentioned mathematical model and signal processing algorithm, the method of identifying cracks on multi-span beams is presented. To verify the accuracy of this identification method, experimental examples are conducted on a two-span structure. The results demonstrate that the method proposed in this paper can accurately identify the crack position and depth. (paper)

Post-tensioning and splicing of precast/prestressed bridge beams to extend spans

Science.gov (United States)

Collett, Brandon S.; Saliba, Joseph E.

2002-06-01

This paper explores the status and techniques of post-tensioning and splicing precast concrete I-beams in bridge applications. It will look at the current practices that have been used in the United States and comment on the advantages of these techniques. Representative projects are presented to demonstrate the application and success of specific methods used. To demonstrate the benefits of using post-tensioning and splicing to extend spans, multiple analysis of simple span post-tensioned I-beams were performed varying such characteristics as beam spacing, beam sections, beam depth and concrete strength. Tables were then developed to compare the maximum span length of a prestressed I-beam versus a one segment or a spliced three segment post-tensioned I-beam. The lateral stability of the beam during fabrication, transportation and erection is also examined and discussed. These tables are intended to aid designers and owners in preliminary project studies to determine if post-tensioning can be beneficial to their situation. AASHTO Standard Specifications(2) will be used as basic guidelines and specifications. In many cases, post-tensioning was found to extend the maximum span length of a typical 72-inch precast I-beam more than 40 feet over conventional prestress.

Constitutive NADPH-Dependent Electron Transferase Activity of the Nox4 Dehydrogenase Domain?

OpenAIRE

Nisimoto, Yukio; Jackson, Heather M.; Ogawa, Hisamitsu; Kawahara, Tsukasa; Lambeth, J. David

2010-01-01

NADPH oxidase 4 (Nox4) is constitutively active, while Nox2 requires the cytosolic regulatory subunits p47 phox and p67 phox and activated Rac with activation by phorbol 12-myristate 13-acetate (PMA). This study was undertaken to identify the domain on Nox4 that confers constitutive activity. Lysates from Nox4-expressing cells exhibited constitutive NADPH- but not NADH-dependent hydrogen peroxide production with a K m for NADPH of 55 ? 10 ?M. The concentration of Nox4 in cell lysates was esti...

STUDY THE CHARACTERISTICS OF SMALL AND VERY SMALL SPAN WINGS, USED ON SHIPS

Directory of Open Access Journals (Sweden)

Beazit ALI

2011-07-01

Full Text Available This scientific work presents the way in which the small, and very small span wings can be obtainedstarting from the great span wings and using the two scales of the similarity theory. Basing on two scales modelit can transcribe from model at nature the coefficients x c , y c and lengthening λ of Gottingen - 612 profile.

76 FR 21932 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

Science.gov (United States)

2011-04-19

... statement therein, as follows: I. Introduction On February 4, 2011, the Financial Industry Regulatory...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting Approval of a... Financial Industry Regulatory Authority, Inc. (``FINRA'') to amend Rule 13806 of the Code of Arbitration...

α-Helical Structural Elements within the Voltage-Sensing Domains of a K+ Channel

Science.gov (United States)

Li-Smerin, Yingying; Hackos, David H.; Swartz, Kenton J.

2000-01-01

Voltage-gated K+ channels are tetramers with each subunit containing six (S1–S6) putative membrane spanning segments. The fifth through sixth transmembrane segments (S5–S6) from each of four subunits assemble to form a central pore domain. A growing body of evidence suggests that the first four segments (S1–S4) comprise a domain-like voltage-sensing structure. While the topology of this region is reasonably well defined, the secondary and tertiary structures of these transmembrane segments are not. To explore the secondary structure of the voltage-sensing domains, we used alanine-scanning mutagenesis through the region encompassing the first four transmembrane segments in the drk1 voltage-gated K+ channel. We examined the mutation-induced perturbation in gating free energy for periodicity characteristic of α-helices. Our results are consistent with at least portions of S1, S2, S3, and S4 adopting α-helical secondary structure. In addition, both the S1–S2 and S3–S4 linkers exhibited substantial helical character. The distribution of gating perturbations for S1 and S2 suggest that these two helices interact primarily with two environments. In contrast, the distribution of perturbations for S3 and S4 were more complex, suggesting that the latter two helices make more extensive protein contacts, possibly interfacing directly with the shell of the pore domain. PMID:10613917

Lune/eye gone, a Pax-like protein, uses a partial paired domain and a homeodomain for DNA recognition.

Science.gov (United States)

Jun, S; Wallen, R V; Goriely, A; Kalionis, B; Desplan, C

1998-11-10

Pax proteins, characterized by the presence of a paired domain, play key regulatory roles during development. The paired domain is a bipartite DNA-binding domain that contains two helix-turn-helix domains joined by a linker region. Each of the subdomains, the PAI and RED domains, has been shown to be a distinct DNA-binding domain. The PAI domain is the most critical, but in specific circumstances, the RED domain is involved in DNA recognition. We describe a Pax protein, originally called Lune, that is the product of the Drosophila eye gone gene (eyg). It is unique among Pax proteins, because it contains only the RED domain. eyg seems to play a role both in the organogenesis of the salivary gland during embryogenesis and in the development of the eye. A high-affinity binding site for the Eyg RED domain was identified by using systematic evolution of ligands by exponential enrichment techniques. This binding site is related to a binding site previously identified for the RED domain of the Pax-6 5a isoform. Eyg also contains another DNA-binding domain, a Prd-class homeodomain (HD), whose palindromic binding site is similar to other Prd-class HDs. The ability of Pax proteins to use the PAI, RED, and HD, or combinations thereof, may be one mechanism that allows them to be used at different stages of development to regulate various developmental processes through the activation of specific target genes.

Bioconjugates of luminescent CdSe-ZnS quantum dots with an engineered two-domain protein G for use in fluoroimmunoassays

Science.gov (United States)

Tran, Phan T.; Goldman, Ellen R.; Mattoussi, Hedi M.; Anderson, George P.; Mauro, J. Matthew

2001-06-01

Colloidal semiconductor quantum dots (QDs) seem suitable for labeling certain biomolecules for use in fluorescent tagging applications, such as fluoro-immunoassays. Compared to organic dye labels, Qds are resistant to photo-degradation, and these luminescent nanoparticles have size-dependent emission spectra spanning a wide range of wavelengths in the visible and near IR. We previously described an electrostatic self-assembly approach for conjugating highly luminescent colloidal CdSe-ZnS core-shell Qds with engineered two-domain recombinant proteins. Here we describe the application of this approach to prepare QD conjugates with the (Beta) 2 immunoglobin G (IgG) binding domain of streptococcal protein G (PG) appended with a basic lucine zipper attachment domain (PG-zb). We also demonstrate that the QD/PG conjugates retain their ability to bind IgG antibodies, and that a specific antibody coupled to QD via the PG functional domain efficiently binds its antigen. These preliminary results indicate that electrostatically self-assembled QD/PG-zb/IgG bioconjugates can be used in fluoro-immunoassays.

Regulatory inspection of nuclear facilities and enforcement by the regulatory body. Safety guide

International Nuclear Information System (INIS)

2002-01-01

The purpose of this Safety Guide is to provide recommendations for regulatory bodies on the inspection of nuclear facilities, regulatory enforcement and related matters. The objective is to provide the regulatory body with a high level of confidence that operators have the processes in place to ensure compliance and that they do comply with legal requirements, including meeting the safety objectives and requirements of the regulatory body. However, in the event of non-compliance, the regulatory body should take appropriate enforcement action. This Safety Guide covers regulatory inspection and enforcement in relation to nuclear facilities such as: enrichment and fuel manufacturing plants; nuclear power plants; other reactors such as research reactors and critical assemblies; spent fuel reprocessing plants; and facilities for radioactive waste management, such as treatment, storage and disposal facilities. This Safety Guide also covers issues relating to the decommissioning of nuclear facilities, the closure of waste disposal facilities and site rehabilitation. Section 2 sets out the objectives of regulatory inspection and enforcement. Section 3 covers the management of regulatory inspections. Section 4 covers the performance of regulatory inspections, including internal guidance, planning and preparation, methods of inspection and reports of inspections. Section 5 deals with regulatory enforcement actions. Section 6 covers the assessment of regulatory inspections and enforcement activities. The Appendix provides further details on inspection areas for nuclear facilities

Fluorescent fusion proteins of soluble guanylyl cyclase indicate proximity of the heme nitric oxide domain and catalytic domain.

Directory of Open Access Journals (Sweden)

Tobias Haase

Full Text Available BACKGROUND: To examine the structural organisation of heterodimeric soluble guanylyl cyclase (sGC Förster resonance energy transfer (FRET was measured between fluorescent proteins fused to the amino- and carboxy-terminal ends of the sGC beta1 and alpha subunits. METHODOLOGY/PRINCIPAL FINDINGS: Cyan fluorescent protein (CFP was used as FRET donor and yellow fluorescent protein (YFP as FRET acceptor. After generation of recombinant baculovirus, fluorescent-tagged sGC subunits were co-expressed in Sf9 cells. Fluorescent variants of sGC were analyzed in vitro in cytosolic fractions by sensitized emission FRET. Co-expression of the amino-terminally tagged alpha subunits with the carboxy-terminally tagged beta1 subunit resulted in an enzyme complex that showed a FRET efficiency of 10% similar to fluorescent proteins separated by a helix of only 48 amino acids. Because these findings indicated that the amino-terminus of the alpha subunits is close to the carboxy-terminus of the beta1 subunit we constructed fusion proteins where both subunits are connected by a fluorescent protein. The resulting constructs were not only fluorescent, they also showed preserved enzyme activity and regulation by NO. CONCLUSIONS/SIGNIFICANCE: Based on the ability of an amino-terminal fragment of the beta1 subunit to inhibit activity of an heterodimer consisting only of the catalytic domains (alphacatbetacat, Winger and Marletta (Biochemistry 2005, 44:4083-90 have proposed a direct interaction of the amino-terminal region of beta1 with the catalytic domains. In support of such a concept of "trans" regulation of sGC activity by the H-NOX domains our results indicate that the domains within sGC are organized in a way that allows for direct interaction of the amino-terminal regulatory domains with the carboxy-terminal catalytic region. In addition, we constructed "fluorescent-conjoined" sGC's by fusion of the alpha amino-terminus to the beta1 carboxy-terminus leading to a

Symmetric Electrode Spanning Narrows the Excitation Patterns of Partial Tripolar Stimuli in Cochlear Implants.

Science.gov (United States)

Luo, Xin; Wu, Ching-Chih

2016-12-01

In cochlear implants (CIs), standard partial tripolar (pTP) mode reduces current spread by returning a fraction of the current to two adjacent flanking electrodes within the cochlea. Symmetric electrode spanning (i.e., separating both the apical and basal return electrodes from the main electrode by one electrode) has been shown to increase the pitch of pTP stimuli, when the ratio of intracochlear return current was fixed. To explain the pitch increase caused by symmetric spanning in pTP mode, this study measured the electrical potentials of both standard and symmetrically spanned pTP stimuli on a main electrode EL8 in five CI ears using electrical field imaging (EFI). In addition, the spatial profiles of evoked compound action potentials (ECAP) and the psychophysical forward masking (PFM) patterns were also measured for both stimuli. The EFI, ECAP, and PFM patterns of a given stimulus differed in shape details, reflecting the different levels of auditory processing and different ratios of intracochlear return current across the measurement methods. Compared to the standard pTP stimuli, the symmetrically spanned pTP stimuli significantly reduced the areas under the curves of the normalized EFI and PFM patterns, without shifting the pattern peaks and centroids (both around EL8). The more focused excitation patterns with symmetric spanning may have caused the previously reported pitch increase, due to an interaction between pitch and timbre perception. Being able to reduce the spread of excitation, pTP mode symmetric spanning is a promising stimulation strategy that may further increase spectral resolution and frequency selectivity with CIs.

DYNAMIC BEHAVIOR OF TWO-SPAN CONTINUOUS CONCRETE BRIDGES UNDER MOVING OF HIGH-SPEED TRAINS

Directory of Open Access Journals (Sweden)

O. H. Marinichenko

2017-10-01

Full Text Available Purpose. The scientific work provides a comparison of the results of the movement of a high-speed passenger train across the bridge, obtained as a result of finite element modeling in the SAP2000 software package, and real tests of a double-span concrete railway bridge. Analysis of the rigid characteristics of flying structures. Methodology.The numerical method presented in this study shows valid results concerning the dynamic analysis of the behavior of bridges in conditions of high-speed train traffic. The factors influencing the dynamic behavior of bridges under moving loads, the influence of design parameters and rolling stock, as well as the interaction of the train and spans are determined. The system was used in the form of moving concentrated forces simulating the axes of the train. Findings. Maximum movements and accelerations were obtained as a result of the dynamic calculation for different speeds of the train and compared with practical tests. The correctness of the model of a span structure with regard to continuous ferroconcrete spans was verified. Originality. Within the framework of the work, the latest test results were used, including those with speeds calculated on the prospect of rail passenger traffic. For these tests, a model of a span structure was developed. Practical value. The results of the research can be used to plan the introduction of high-speed train traffic on existing and planned flying structures of reinforced concrete bridges. An approach to the design of span structures that will be effective when passing high-speed passenger trains is implemented.

Short length transmembrane domains having voluminous exoplasmic halves determine retention of Type II membrane proteins in the Golgi complex

OpenAIRE

Quiroga, Rodrigo; Trenchi, Alejandra; Gonzalez Montoro, Ayelén; Valdez, Javier Esteban; Maccioni, Hugo Jose Fernando

2017-01-01

It is still unclear why some proteins that travel along the secretory pathway are retained in the Golgi complex whereas others make their way to the plasma membrane. Recent bioinformatic analyses on a large number of single-spanning membrane proteins support the hypothesis that specific features of the transmembrane domain (TMD) are relevant to the sorting of these proteins to particular organelles. Here we experimentally test this hypothesis for Golgi and plasma membrane proteins. Using the ...

USE OF MEMBRANE EMULSION SPAN 80 AND TOPO IN URANIUM EXTRACTION AND STRIPPING

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Kris Tri Basuki

2017-01-01

Full Text Available ABSTRACT USE OF MEMBRANE EMULSION SPAN 80 AND TOPO IN URANIUM EXTRACTION AND STRIPPING. Membrane emulsion span 80 and TOPO used in uranium extraction and stripping has been done. The extraction was carried outby emulsion membrane H3PO4 in TOPO-Kerosene. The feed or external aqueous phase was uranium in  HNO3. The emulgator span-80 was used to obtain a stable emulsion membrane system. The influence factors were percentage of TOPO-Kerosene, time extraction,  molarity of external aqueous phase and  molarity of internal aqueous. After the emulsion membrane was formed, the extractionand stripping process was performed. The ratio volume feed : volume membrane phase equal to 1 : 1 and volume of 5 % TOPO-Kerosene : Volume 3 M H3PO4 equal 1 : 1 were used. The relative good yield were obtained at concentration of TOPO in Kerosene and 3 M H3PO4 was 5 %, molarity of internal aqueous phase equal to 1 M, molarity of external aqueous phase 3 M H3PO4 and time extraction equalto 10 minutes with the speed of emulsification was 8000 rpm. At this condition the extraction efficiency of uranium obtained was 97.8 %, the stripping efficiency 52.56 %, and the total efficiency was 53.80 %. Keywords: membrane emulsion, extraction, stripping, span 80, kerosene, uranium. ABSTRAK PENGGUNAAN MEMBRAN EMULSI SPAN 80 DAN TOPO UNTUK EKSTRASI DAN STRIPPING URANIUM. Telah dilakukan penelitian membran emulsi span 80 dan TOPO yang digunakan untuk ekstraksi uranium. Extraksi dengan membran emulsi H3PO4 dalam TOPO-Kerosen. Larutan umpan untuk fasa air eksternal adalah uranium dalam asam nitrat. Untuk memperoleh sistem emulsi yang stabil dipakai emulgator Span 80. Parameter yang berpengaruh adalah persen TOPO-Kerosene, molaritas fasa air internal H3PO4, molaritas fasa air eksternal HNO3 dan waktu ekstraksi. Setelah diperoleh membran emulsi, kemudian dilakukan proses ekstraksi dan stripping, dengan rasio volume umpan : volume membran sebesar 1 : 1; volume 5% TOPO-Kerose : volume 3M

Demonstrations of analog-to-digital conversion using a frequency domain stretched processor.

Science.gov (United States)

Reibel, Randy Ray; Harrington, Calvin; Dahl, Jason; Ostrander, Charles; Roos, Peter Aaron; Berg, Trenton; Mohan, R Krishna; Neifeld, Mark A; Babbitt, Wm R

2009-07-06

The first proof-of-concept demonstrations are presented for a broadband photonic-assisted analog-to-digital converter (ADC) based on spatial spectral holography (SSH). The SSH-ADC acts as a frequency-domain stretch processor converting high bandwidth input signals to low bandwidth output signals, allowing the system to take advantage of high performance, low bandwidth electronic ADCs. Demonstrations with 50 MHz effective bandwidth are shown to highlight basic performance with approximately 5 effective bits of vertical resolution. Signal capture with 1600 MHz effective bandwidth is also shown. Because some SSH materials span over 100 GHz and have large time apertures (approximately 10 micros), this technique holds promise as a candidate for the next generation of ADCs.

Individual Differences in Digit Span, Susceptibility to Proactive Interference, and Aptitude/Achievement Test Scores.

Science.gov (United States)

Dempster, Frank N.; Cooney, John B.

1982-01-01

Individual differences in digit span, susceptibility to proactive interference, and various aptitude/achievement test scores were investigated in two experiments with college students. Results indicated that digit span was strongly correlated with aptitude/achievement scores, but did not indicate that susceptibility to proactive interference…

Several Families of Sequences with Low Correlation and Large Linear Span

Science.gov (United States)

Zeng, Fanxin; Zhang, Zhenyu

In DS-CDMA systems and DS-UWB radios, low correlation of spreading sequences can greatly help to minimize multiple access interference (MAI) and large linear span of spreading sequences can reduce their predictability. In this letter, new sequence sets with low correlation and large linear span are proposed. Based on the construction Trm1[Trnm(αbt+γiαdt)]r for generating p-ary sequences of period pn-1, where n=2m, d=upm±v, b=u±v, γi∈GF(pn), and p is an arbitrary prime number, several methods to choose the parameter d are provided. The obtained sequences with family size pn are of four-valued, five-valued, six-valued or seven-valued correlation and the maximum nontrivial correlation value is (u+v-1)pm-1. The simulation by a computer shows that the linear span of the new sequences is larger than that of the sequences with Niho-type and Welch-type decimations, and similar to that of [10].

Analysis of the effectiveness of various cross-sections in large-span post-tensioned ceilings

Science.gov (United States)

Bednarz, K.

2018-03-01

The correct construction of large span, slim post-tensioned concrete slabs is conditioned by an appropriate cross-section selection. It is generally accepted that the thinnest slab can be constructed using the full cross-section as the largest compression stress storage. However, completely different cross-sections may help to overcome large spans. The paper presents the results of the computational analysis of several types of cross-sections (full, with internal relieving inserts and ribbed) in the application to a post-tensioned slab with a span of 15.0m. Based on the results presented, appropriate conclusions were drawn.

Exploration of malingering indices in the Wechsler Adult Intelligence Scale-Fourth Edition Digit Span subtest.

Science.gov (United States)

Reese, Caitlin S; Suhr, Julie A; Riddle, Tara L

2012-03-01

Prior research shows that Digit Span is a useful embedded measure of malingering. However, the Wechsler Adult Intelligence Scale-IV (Wechsler, 2008) altered Digit Span in meaningful ways, necessitating another look at Digit Span as an embedded measure of malingering. Using a simulated malingerer design, we examined the predictive accuracy of existing Digit Span validity indices and explored whether patterns of performance utilizing the new version would provide additional evidence for malingering. Undergraduates with a history of mild head injury performed with best effort or simulated impaired cognition and were also compared with a large sample of non-head-injured controls. Previously established cutoffs for the age-corrected scaled score and Reliable Digit Span (RDS) performed similarly in the present samples. Patterns of RDS length using all three subscales of the new scale were different in malingerers when compared with both head-injured and non-head-injured controls. Two potential alternative RDS scores were introduced, which showed better sensitivity than the traditional RDS, while retaining specificity to malingering.

Structural covariance networks across the life span, from 6 to 94 years of age.

Science.gov (United States)

DuPre, Elizabeth; Spreng, R Nathan

2017-10-01

Structural covariance examines covariation of gray matter morphology between brain regions and across individuals. Despite significant interest in the influence of age on structural covariance patterns, no study to date has provided a complete life span perspective-bridging childhood with early, middle, and late adulthood-on the development of structural covariance networks. Here, we investigate the life span trajectories of structural covariance in six canonical neurocognitive networks: default, dorsal attention, frontoparietal control, somatomotor, ventral attention, and visual. By combining data from five open-access data sources, we examine the structural covariance trajectories of these networks from 6 to 94 years of age in a sample of 1,580 participants. Using partial least squares, we show that structural covariance patterns across the life span exhibit two significant, age-dependent trends. The first trend is a stable pattern whose integrity declines over the life span. The second trend is an inverted-U that differentiates young adulthood from other age groups. Hub regions, including posterior cingulate cortex and anterior insula, appear particularly influential in the expression of this second age-dependent trend. Overall, our results suggest that structural covariance provides a reliable definition of neurocognitive networks across the life span and reveal both shared and network-specific trajectories.

Efficient Reverse-Engineering of a Developmental Gene Regulatory Network

Science.gov (United States)

Cicin-Sain, Damjan; Ashyraliyev, Maksat; Jaeger, Johannes

2012-01-01

Understanding the complex regulatory networks underlying development and evolution of multi-cellular organisms is a major problem in biology. Computational models can be used as tools to extract the regulatory structure and dynamics of such networks from gene expression data. This approach is called reverse engineering. It has been successfully applied to many gene networks in various biological systems. However, to reconstitute the structure and non-linear dynamics of a developmental gene network in its spatial context remains a considerable challenge. Here, we address this challenge using a case study: the gap gene network involved in segment determination during early development of Drosophila melanogaster. A major problem for reverse-engineering pattern-forming networks is the significant amount of time and effort required to acquire and quantify spatial gene expression data. We have developed a simplified data processing pipeline that considerably increases the throughput of the method, but results in data of reduced accuracy compared to those previously used for gap gene network inference. We demonstrate that we can infer the correct network structure using our reduced data set, and investigate minimal data requirements for successful reverse engineering. Our results show that timing and position of expression domain boundaries are the crucial features for determining regulatory network structure from data, while it is less important to precisely measure expression levels. Based on this, we define minimal data requirements for gap gene network inference. Our results demonstrate the feasibility of reverse-engineering with much reduced experimental effort. This enables more widespread use of the method in different developmental contexts and organisms. Such systematic application of data-driven models to real-world networks has enormous potential. Only the quantitative investigation of a large number of developmental gene regulatory networks will allow us to

The importance of adult life-span perspective in explaining variations in political ideology.

Science.gov (United States)

Sedek, Grzegorz; Kossowska, Malgorzata; Rydzewska, Klara

2014-06-01

As a comment on Hibbing et al.'s paper, we discuss the evolution of political and social views from more liberal to more conservative over the span of adulthood. We show that Hibbing et al.'s theoretical model creates a false prediction from this developmental perspective, as increased conservatism in the adult life-span trajectory is accompanied by the avoidance of negative bias.

ETS-4 is a transcriptional regulator of life span in Caenorhabditis elegans.

Directory of Open Access Journals (Sweden)

Bargavi Thyagarajan

2010-09-01

Full Text Available Aging is a complex phenotype responsive to a plethora of environmental inputs; yet only a limited number of transcriptional regulators are known to influence life span. How the downstream expression programs mediated by these factors (or others are coordinated into common or distinct set of aging effectors is an addressable question in model organisms, such as C. elegans. Here, we establish the transcription factor ETS-4, an ortholog of vertebrate SPDEF, as a longevity determinant. Adult worms with ets-4 mutations had a significant extension of mean life span. Restoring ETS-4 activity in the intestine, but not neurons, of ets-4 mutant worms rescued life span to wild-type levels. Using RNAi, we demonstrated that ets-4 is required post-developmentally to regulate adult life span; thus uncoupling the role of ETS-4 in aging from potential functions in worm intestinal development. Seventy ETS-4-regulated genes, identified by gene expression profiling of two distinct ets-4 alleles and analyzed by bioinformatics, were enriched for known longevity effectors that function in lipid transport, lipid metabolism, and innate immunity. Putative target genes were enriched for ones that change expression during normal aging, the majority of which are controlled by the GATA factors. Also, some ETS-4-regulated genes function downstream of the FOXO factor, DAF-16 and the insulin/IGF-1 signaling pathway. However, epistasis and phenotypic analyses indicate that ets-4 functioned in parallel to the insulin/IGF-1 receptor, daf-2 and akt-1/2 kinases. Furthermore, ets-4 required daf-16 to modulate aging, suggesting overlap in function at the level of common targets that affect life span. In conclusion, ETS-4 is a new transcriptional regulator of aging, which shares transcriptional targets with GATA and FOXO factors, suggesting that overlapping pathways direct common sets of lifespan-related genes.

Truth-telling and Nash equilibria in minimum cost spanning tree models

DEFF Research Database (Denmark)

Hougaard, Jens Leth; Tvede, Mich

2012-01-01

In this paper we consider the minimum cost spanning tree model. We assume that a central planner aims at implementing a minimum cost spanning tree not knowing the true link costs. The central planner sets up a game where agents announce link costs, a tree is chosen and costs are allocated according...... to the rules of the game. We characterize ways of allocating costs such that true announcements constitute Nash equilibria both in case of full and incomplete information. In particular, we find that the Shapley rule based on the irreducible cost matrix is consistent with truthful announcements while a series...

The effects of age, glucose ingestion and gluco-regulatory control on episodic memory.

Science.gov (United States)

Riby, Leigh Martin; Meikle, Andrew; Glover, Cheryl

2004-09-01

Previous research has been inconclusive regarding the impact of glucose ingestion and gluco-regulatory control on cognitive performance in healthy older adults. The aim of this research was to determine whether glucose specifically enhanced episodic memory in an older population. In addition, the link between individual differences in glucose regulation and the magnitude of the enhancement effect was examined. A within subjects, counterbalanced, crossover design was used with 20 participants (60-80 year olds), each serving as his/her control. Episodic memory was tested by presenting unrelated paired associates followed by immediate and delayed cued recall, and delayed recognition, under single and dual task conditions. In addition, a battery of cognitive tests was administered, including tests of semantic memory, working memory and speed of processing. Glucose ingestion was found to largely facilitate performance of episodic memory. Furthermore, subsidiary analyses found that gluco-regulatory efficiency predicted episodic memory performance in both control and glucose conditions. A boost in performance after glucose ingestion was particularly seen in the episodic memory domain. Notably, strong evidence was provided for the utility of gluco-regulatory control measures as indicators of cognitive decline in the elderly.

A closed solution for the collapse load of pressurized pipelines in free spans

Energy Technology Data Exchange (ETDEWEB)

Bezerra, Luciano M. [Brasilia Univ., DF (Brazil). Dept. de Engenharia Civil; Murray, David W.; Xuejun Song [University of Alberta (Canada). Civil Engineering Dept.

2005-07-01

Submarine pipelines for oil exploitation, generally, are under internal pressure and compressive thermal loading. Due to rough see-bottom terrains, these pipelines may be supported only intermittently and span freely. The collapse of such pipelines may produce oil leakage to the environment. A common engineering practice for the determination of the collapse load of such pipelines is the use of finite element modeling. This paper presents an analytical method for the determination of the collapse load of pressurized pipelines extended over free spans. The formulation also takes into account the internal pressure and initial imperfection, generally present in these pipelines. Collapse load is determined from a deduced transcendental equation. Results of the presented formulation are compared with sophisticated finite element analyses. While sophisticated finite element analysis requires hours of computer processing, the present formulation takes practically no time to assess a good approximation for the collapse load of pressurized free span pipelines under compression. The present paper is not intended to substitute the more precise finite element analyses but to provide an easier, faster, and practical way to determine a first approximation of the collapse load of pressurized free span pipelines. (author)

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

DEFF Research Database (Denmark)

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

1995-01-01

of the mouse entactin gene closely corresponds to the organization of the polypeptide into distinct structural and functional domains. The two amino-terminal globular domains are encoded by three exons each. Single exons encode the two protease-sensitive, O-glycosylated linking regions. The six EGF......Entactin is a widespread basement membrane protein of 150 kDa that binds to type IV collagen and laminin. The complete exon-intron structure of the mouse entactin gene has been determined from lambda genomic DNA clones. The gene spans at least 65 kb and contains 20 exons. The exon organization...

Clinical Research Informatics: Challenges, Opportunities and Definition for an Emerging Domain

Science.gov (United States)

Embi, Peter J.; Payne, Philip R.O.

2009-01-01

Objectives Clinical Research Informatics, an emerging sub-domain of Biomedical Informatics, is currently not well defined. A formal description of CRI including major challenges and opportunities is needed to direct progress in the field. Design Given the early stage of CRI knowledge and activity, we engaged in a series of qualitative studies with key stakeholders and opinion leaders to determine the range of challenges and opportunities facing CRI. These phases employed complimentary methods to triangulate upon our findings. Measurements Study phases included: 1) a group interview with key stakeholders, 2) an email follow-up survey with a larger group of self-identified CRI professionals, and 3) validation of our results via electronic peer-debriefing and member-checking with a group of CRI-related opinion leaders. Data were collected, transcribed, and organized for formal, independent content analyses by experienced qualitative investigators, followed by an iterative process to identify emergent categorizations and thematic descriptions of the data. Results We identified a range of challenges and opportunities facing the CRI domain. These included 13 distinct themes spanning academic, practical, and organizational aspects of CRI. These findings also informed the development of a formal definition of CRI and supported further representations that illustrate areas of emphasis critical to advancing the domain. Conclusions CRI has emerged as a distinct discipline that faces multiple challenges and opportunities. The findings presented summarize those challenges and opportunities and provide a framework that should help inform next steps to advance this important new discipline. PMID:19261934

Regulatory guidance document

International Nuclear Information System (INIS)

1994-05-01

The Office of Civilian Radioactive Waste Management (OCRWM) Program Management System Manual requires preparation of the OCRWM Regulatory Guidance Document (RGD) that addresses licensing, environmental compliance, and safety and health compliance. The document provides: regulatory compliance policy; guidance to OCRWM organizational elements to ensure a consistent approach when complying with regulatory requirements; strategies to achieve policy objectives; organizational responsibilities for regulatory compliance; guidance with regard to Program compliance oversight; and guidance on the contents of a project-level Regulatory Compliance Plan. The scope of the RGD includes site suitability evaluation, licensing, environmental compliance, and safety and health compliance, in accordance with the direction provided by Section 4.6.3 of the PMS Manual. Site suitability evaluation and regulatory compliance during site characterization are significant activities, particularly with regard to the YW MSA. OCRWM's evaluation of whether the Yucca Mountain site is suitable for repository development must precede its submittal of a license application to the Nuclear Regulatory Commission (NRC). Accordingly, site suitability evaluation is discussed in Chapter 4, and the general statements of policy regarding site suitability evaluation are discussed in Section 2.1. Although much of the data and analyses may initially be similar, the licensing process is discussed separately in Chapter 5. Environmental compliance is discussed in Chapter 6. Safety and Health compliance is discussed in Chapter 7

C. elegans VANG-1 modulates life span via insulin/IGF-1-like signaling.

Directory of Open Access Journals (Sweden)

Sebastian J Honnen

Full Text Available The planar cell polarity (PCP pathway is highly conserved from Drosophila to humans and a PCP-like pathway has recently been described in the nematode Caenorhabditis elegans. The developmental function of this pathway is to coordinate the orientation of cells or structures within the plane of an epithelium or to organize cell-cell intercalation required for correct morphogenesis. Here, we describe a novel role of VANG-1, the only C. elegans ortholog of the conserved PCP component Strabismus/Van Gogh. We show that two alleles of vang-1 and depletion of the protein by RNAi cause an increase of mean life span up to 40%. Consistent with the longevity phenotype vang-1 animals also show enhanced resistance to thermal- and oxidative stress and decreased lipofuscin accumulation. In addition, vang-1 mutants show defects like reduced brood size, decreased ovulation rate and prolonged reproductive span, which are also related to gerontogenes. The germline, but not the intestine or neurons, seems to be the primary site of vang-1 function. Life span extension in vang-1 mutants depends on the insulin/IGF-1-like receptor DAF-2 and DAF-16/FoxO transcription factor. RNAi against the phase II detoxification transcription factor SKN-1/Nrf2 also reduced vang-1 life span that might be explained by gradual inhibition of insulin/IGF-1-like signaling in vang-1. This is the first time that a key player of the PCP pathway is shown to be involved in the insulin/IGF-1-like signaling dependent modulation of life span in C. elegans.

Crystal optimization and preliminary diffraction data analysis of the SCAN domain of Zfp206

International Nuclear Information System (INIS)

Liang, Yu; Choo, Siew Hua; Rossbach, Michael; Baburajendran, Nithya; Palasingam, Paaventhan; Kolatkar, Prasanna R

2012-01-01

Crystals of the SCAN domain of Zfp206 are tetragonal, belonging to space group I422 with unit-cell parameters a = 67.57, c = 87.54 Å and one molecule in the asymmetric unit, and diffract to 1.85 Å resolution. Zfp206 (also named Zscan10) is a transcription factor that plays an important role in maintaining the pluripotent state of embryonic stem cells. Zfp206 is a member of the SCAN-domain family of C 2 H 2 zinc-finger transcription factors. The SCAN domain is a highly conserved motif of 84 residues which mediates the self-association of and heterodimerization between SCAN-domain family transcription factors. The SCAN domain may therefore be the key to the selective oligomerization of and may combinatorially enhance the regulatory versatility of C 2 H 2 zinc fingers. This paper describes crystallization attempts with the SCAN domain of Zfp206 (Zfp206SCAN) and optimization strategies to obtain diffraction-quality crystals. The best diffracting crystal was grown in a solution consisting of 0.3 M ammonium sulfate, 0.1 M Tris–HCl pH 8.6, 25% PEG 3350, 0.1 M ethylenediaminetetraacetic acid disodium salt dehydrate (EDTA) using the hanging-drop vapour-diffusion technique. Optimized crystals diffracted to 1.85 Å resolution and belonged to space group I422, with unit-cell parameters a = 67.57, c = 87.54 Å. A Matthews analysis indicated the presence of one Zfp206SCAN molecule per asymmetric unit

Impact Coefficient Analysis of Long-Span Railway Cable-Stayed Bridge Based on Coupled Vehicle-Bridge Vibration

Directory of Open Access Journals (Sweden)

Yongle Li

2015-01-01

Full Text Available Compared with medium and small span bridges, very limited attention has been paid on the research of the impact coefficient of long-span railway bridges. To estimate the impact effects of long-span railway bridges subjected to moving vehicles, a real long-span railway cable-stayed bridge is regarded as the research object in this study, and a coupled model of vehicle-bridge system is established. The track irregularities are taken as the system excitation and the dynamic responses of the vehicle-bridge system are calculated. The impact effects on main girder, stayed cable, bearings, and bridge tower are discussed at various vehicle speeds. The results show that different components of the long-span railway cable-stayed bridge have different impact coefficients. Even for each part, the impact coefficient is also different at different local positions. It reveals that the impact coefficients in the actual situation may have significant differences with the related code clauses in the present design codes.

Working Memory Capacity and Fluid Abilities: Examining the Correlation between Operation Span and Raven

Science.gov (United States)

Unsworth, N.; Engle, R.W.

2005-01-01

The correlation between a measure of working memory capacity (WMC) (Operation Span) and a measure of fluid abilities (Raven Advanced Progressive Matrices) was examined. Specifically, performance on Raven problems was decomposed by difficulty, memory load, and rule type. The results suggest that the relation between Operation Span and Raven is…

Working Memory Deficits in Children with Reading Difficulties: Memory Span and Dual Task Coordination

Science.gov (United States)

Wang, Shinmin; Gathercole, Susan E.

2013-01-01

The current study investigated the cause of the reported problems in working memory in children with reading difficulties. Verbal and visuospatial simple and complex span tasks, and digit span and reaction times tasks performed singly and in combination, were administered to 46 children with single word reading difficulties and 45 typically…

Age differences in personality traits from 10 to 65: Big Five domains and facets in a large cross-sectional sample.

Science.gov (United States)

Soto, Christopher J; John, Oliver P; Gosling, Samuel D; Potter, Jeff

2011-02-01

Hypotheses about mean-level age differences in the Big Five personality domains, as well as 10 more specific facet traits within those domains, were tested in a very large cross-sectional sample (N = 1,267,218) of children, adolescents, and adults (ages 10-65) assessed over the World Wide Web. The results supported several conclusions. First, late childhood and adolescence were key periods. Across these years, age trends for some traits (a) were especially pronounced, (b) were in a direction different from the corresponding adult trends, or (c) first indicated the presence of gender differences. Second, there were some negative trends in psychosocial maturity from late childhood into adolescence, whereas adult trends were overwhelmingly in the direction of greater maturity and adjustment. Third, the related but distinguishable facet traits within each broad Big Five domain often showed distinct age trends, highlighting the importance of facet-level research for understanding life span age differences in personality. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

Heritability of life span in the Old Order Amish.

Science.gov (United States)

Mitchell, B D; Hsueh, W C; King, T M; Pollin, T I; Sorkin, J; Agarwala, R; Schäffer, A A; Shuldiner, A R

2001-09-01

Although a familial contribution to human longevity is recognized, the nature of this contribution is largely unknown. We have examined the familial contribution to life span in the Old Order Amish (OOA) population of Lancaster County, Pennsylvania. Analyses were conducted on 1,655 individuals, representing all those born prior to 1890 and appearing in the most widely available genealogy, surviving until at least age 30 years, and with known date of death. Mean age at death (+/-SD) in this population was 70.7 +/- 15.6 years, and this did not change appreciably over time. Parental and offspring ages at death were significantly correlated, as were ages of death among siblings. Offspring longevity was correlated with longevity of both parents, and in more or less additive fashion. For example, mean offspring age at death was 69.4 +/- 15.3 years in individuals for whom both parents died before the age of 75 years (n = 280) and increased to 73.5 +/- 16.0 years in individuals for whom neither parent died before the age of 75 years (n = 311). These differences were highly significant (P = 0.006). We estimated heritability of life span to be 25% +/- 5%, suggesting that the additive effects of genes account for one quarter of the total variability in life span in the OOA. We conclude that longevity is moderately heritable in the OOA, that the genetic effects are additive, and that genetic influences on longevity are likely to be expressed across a broad range of ages. Published 2001 Wiley-Liss, Inc.

Asymmetry in auditory and spatial attention span in normal elderly genetically at risk for Alzheimer's disease.

Science.gov (United States)

Jacobson, Mark W; Delis, Dean C; Bondi, Mark W; Salmon, David P

2005-02-01

Some studies of elderly individuals with the ApoE-e4 genotype noted subtle deficits on tests of attention such as the WAIS-R Digit Span subtest, but these findings have not been consistently reported. One possible explanation for the inconsistent results could be the presence of subgroups of e4+ individuals with asymmetric cognitive profiles (i.e., significant discrepancies between verbal and visuospatial skills). Comparing genotype groups with individual, modality-specific tests might obscure subtle differences between verbal and visuospatial attention in these asymmetric subgroups. In this study, we administered the WAIS-R Digit Span and WMS-R Visual Memory Span subtests to 21 nondemented elderly e4+ individuals and 21 elderly e4- individuals matched on age, education, and overall cognitive ability. We hypothesized that a) the e4+ group would show a higher incidence of asymmetric cognitive profiles when comparing Digit Span/Visual Memory Span performance relative to the e4- group; and (b) an analysis of individual test performance would fail to reveal differences between the two subject groups. Although the groups' performances were comparable on the individual attention span tests, the e4+ group showed a significantly larger discrepancy between digit span and spatial span scores compared to the e4- group. These findings suggest that contrast measures of modality-specific attentional skills may be more sensitive to subtle group differences in at-risk groups, even when the groups do not differ on individual comparisons of standardized test means. The increased discrepancy between verbal and visuospatial attention may reflect the presence of "subgroups" within the ApoE-e4 group that are qualitatively similar to asymmetric subgroups commonly associated with the earliest stages of AD.

Cloning of the pig aminopeptidase N gene. Identification of possible regulatory elements and the exon distribution in relation to the membrane-spanning region

DEFF Research Database (Denmark)

Sjöström, H; Norén, O; Olsen, Jørgen

1989-01-01

. By sequence comparisons we have found three domains showing similarity to promoter regions of the genes encoding human alpha 1-antitrypsin and human intestinal alkaline phosphatase. The gene sequence includes the first three exons and two introns. It shows that a single exon encodes the cytoplasmic tail...

A Heparin Binding Motif Rich in Arginine and Lysine is the Functional Domain of YKL-40

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Nipaporn Ngernyuang

2018-02-01

Full Text Available The heparin-binding glycoprotein YKL-40 (CHI3L1 is intimately associated with microvascularization in multiple human diseases including cancer and inflammation. However, the heparin-binding domain(s pertinent to the angiogenic activity have yet been identified. YKL-40 harbors a consensus heparin-binding motif that consists of positively charged arginine (R and lysine (K (RRDK; residues 144–147; but they don't bind to heparin. Intriguingly, we identified a separate KR-rich domain (residues 334–345 that does display strong heparin binding affinity. A short synthetic peptide spanning this KR-rich domain successfully competed with YKL-40 and blocked its ability to bind heparin. Three individual point mutations, where alanine (A substituted for K or R (K337A, K342A, R344A, led to remarkable decreases in heparin-binding ability and angiogenic activity. In addition, a neutralizing anti-YKL-40 antibody that targets these residues and prevents heparin binding impeded angiogenesis in vitro. MDA-MB-231 breast cancer cells engineered to express ectopic K337A, K342A or R344A mutants displayed reduced tumor development and compromised tumor vessel formation in mice relative to control cells expressing wild-type YKL-40. These data reveal that the KR-rich heparin-binding motif is the functional heparin-binding domain of YKL-40. Our findings shed light on novel molecular mechanisms underlying endothelial cell angiogenesis promoted by YKL-40 in a variety of diseases.

The element level time domain (ELTD) method for the analysis of nano-optical systems: I. Nondispersive media

Science.gov (United States)

Fallahi, Arya; Oswald, Benedikt; Leidenberger, Patrick

2012-04-01

We study a 3-dimensional, dual-field, fully explicit method for the solution of Maxwell's equations in the time domain on unstructured, tetrahedral grids. The algorithm uses the element level time domain (ELTD) discretization of the electric and magnetic vector wave equations. In particular, the suitability of the method for the numerical analysis of nanometer structured systems in the optical region of the electromagnetic spectrum is investigated. The details of the theory and its implementation as a computer code are introduced and its convergence behavior as well as conditions for stable time domain integration is examined. Here, we restrict ourselves to non-dispersive dielectric material properties since dielectric dispersion will be treated in a subsequent paper. Analytically solvable problems are analyzed in order to benchmark the method. Eventually, a dielectric microlens is considered to demonstrate the potential of the method. A flexible method of 2nd order accuracy is obtained that is applicable to a wide range of nano-optical configurations and can be a serious competitor to more conventional finite difference time domain schemes which operate only on hexahedral grids. The ELTD scheme can resolve geometries with a wide span of characteristic length scales and with the appropriate level of detail, using small tetrahedra where delicate, physically relevant details must be modeled.

Partitioning Heritability of Regulatory and Cell-Type-Specific Variants across 11 Common Diseases

DEFF Research Database (Denmark)

Gusev, Alexander; Lee, S Hong; Trynka, Gosia

2014-01-01

Regulatory and coding variants are known to be enriched with associations identified by genome-wide association studies (GWASs) of complex disease, but their contributions to trait heritability are currently unknown. We applied variance-component methods to imputed genotype data for 11 common...... diseases to partition the heritability explained by genotyped SNPs (hg(2)) across functional categories (while accounting for shared variance due to linkage disequilibrium). Extensive simulations showed that in contrast to current estimates from GWAS summary statistics, the variance-component approach...... partitions heritability accurately under a wide range of complex-disease architectures. Across the 11 diseases DNaseI hypersensitivity sites (DHSs) from 217 cell types spanned 16% of imputed SNPs (and 24% of genotyped SNPs) but explained an average of 79% (SE = 8%) of hg(2) from imputed SNPs (5.1× enrichment...

75 FR 11166 - Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission...

Science.gov (United States)

2010-03-10

... the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission; Notice of Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission March 2, 2010. The Federal Energy Regulatory Commission (FERC) and the Nuclear Regulatory Commission (NRC) will hold...