Sample records for related jmjc domain

  1. Cold-dependent alternative splicing of a Jumonji C domain-containing gene MtJMJC5 in Medicago truncatula.

    PubMed

    Shen, Yingfang; Wu, Xiaopei; Liu, Demei; Song, Shengjing; Liu, Dengcai; Wang, Haiqing

    2016-05-27

    Histone methylation is an epigenetic modification mechanism that regulates gene expression in eukaryotic cells. Jumonji C domain-containing demethylases are involved in removal of methyl groups at lysine or arginine residues. The JmjC domain-only member, JMJ30/JMJD5 of Arabidopsis, is a component of the plant circadian clock. Although some plant circadian clock genes undergo alternative splicing in response to external cues, there is no evidence that JMJ30/JMJD5 is regulated by alternative splicing. In this study, the expression of an Arabidopsis JMJ30/JMJD5 ortholog in Medicago truncatula, MtJMJC5, in response to circadian clock and abiotic stresses were characterized. The results showed that MtJMJC5 oscillates with a circadian rhythm, and undergoes cold specifically induced alternative splicing. The cold-induced alternative splicing could be reversed after ambient temperature returning to the normal. Sequencing results revealed four alternative splicing RNA isoforms including a full-length authentic protein encoding variant, and three premature termination condon-containing variants due to alternative 3' splice sites at the first and second intron. Under cold treatment, the variants that share a common 3' alternative splicing site at the second intron were intensively up-regulated while the authentic protein encoding variant and the premature termination condon-containing variant only undergoing a 3' alternative splicing at the first intron were down regulated. Although all the premature termination condon-harboring alternative splicing variants were sensitive to nonsense-mediated decay, the premature termination codon-harboring alternative splicing variants sharing the 3' alternative splicing site at the second intron showed less sensitivity than the one only containing the 3' alternative slicing site at the first intron under cold treatment. These results suggest that the cold-dependent alternative splicing of MtJMJC5 is likely a species or genus

  2. IBM1, a JmjC domain-containing histone demethylase, is involved in the regulation of RNA-directed DNA methylation through the epigenetic control of RDR2 and DCL3 expression in Arabidopsis

    PubMed Central

    Fan, Di; Dai, Yan; Wang, Xuncheng; Wang, Zhenjie; He, Hang; Yang, Hongchun; Cao, Ying; Deng, Xing Wang; Ma, Ligeng

    2012-01-01

    Small RNA-directed DNA methylation (RdDM) is an important epigenetic pathway in Arabidopsis that controls the expression of multiple genes and several developmental processes. RNA-DEPENDENT RNA POLYMERASE 2 (RDR2) and DICER-LIKE 3 (DCL3) are necessary factors in 24-nt small interfering RNA (siRNA) biogenesis, which is part of the RdDM pathway. Here, we found that Increase in BONSAI Methylation 1 (IBM1), a conserved JmjC family histone demethylase, is directly associated with RDR2 and DCL3 chromatin. The mutation of IBM1 induced the hypermethylation of H3K9 and DNA non-CG sites within RDR2 and DCL3, which repressed their expression. A genome-wide analysis suggested that the reduction in RDR2 and DCL3 expression affected siRNA biogenesis in a locus-specific manner and disrupted RdDM-directed gene repression. Together, our results suggest that IBM1 regulates gene expression through two distinct pathways: direct association to protect genes from silencing by preventing the coupling of histone and DNA methylation, and indirect silencing of gene expression through RdDM-directed repression. PMID:22772985

  3. JMJ27, an Arabidopsis H3K9 histone demethylase, modulates defense against Pseudomonas syringae and flowering time.

    PubMed

    Dutta, Aditya; Choudhary, Pratibha; Caruana, Julie; Raina, Ramesh

    2017-09-01

    Histone methylation is known to dynamically regulate diverse developmental and physiological processes. Histone methyl marks are written by methyltransferases and erased by demethylases, and result in modification of chromatin structure to repress or activate transcription. However, little is known about how histone methylation may regulate defense mechanisms and flowering time in plants. Here we report characterization of JmjC DOMAIN-CONTAINING PROTEIN 27 (JMJ27), an Arabidopsis JHDM2 (JmjC domain-containing histone demethylase 2) family protein, which modulates defense against pathogens and flowering time. JMJ27 is a nuclear protein containing a zinc-finger motif and a catalytic JmjC domain with conserved Fe(II) and α-ketoglutarate binding sites, and displays H3K9me1/2 demethylase activity both in vitro and in vivo. JMJ27 is induced in response to virulent Pseudomonas syringae pathogens and is required for resistance against these pathogens. JMJ27 is a negative modulator of WRKY25 (a repressor of defense) and a positive modulator of several pathogenesis-related (PR) proteins. Additionally, loss of JMJ27 function leads to early flowering. JMJ27 negatively modulates the major flowering regulator CONSTANS (CO) and positively modulates FLOWERING LOCUS C (FLC). Taken together, our results indicate that JMJ27 functions as a histone demethylase to modulate both physiological (defense) and developmental (flowering time) processes in Arabidopsis. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  4. Redistribution of demethylated RNA helicase A during foot-and-mouth disease virus infection: Role of Jumonji C-domain containing protein 6 in RHA demethylation

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

    Lawrence, Paul; Conderino, Joseph S.; Rieder, Elizabeth, E-mail: elizabeth.rieder@ars.usda.gov

    Previously, RNA helicase A (RHA) re-localization from the nucleus to the cytoplasm in foot-and-mouth disease virus (FMDV) infected cells was shown to coincide with loss of RHA methylated arginine residues at its C-terminus. The potential interaction between RHA and Jumonji C-domain (JmjC) protein 6 (JMJD6) arginine demethylase in infected cells was investigated. Treatment with N-oxalylglycine (NOG) inhibitor of JmjC demethylases prevented FMDV-induced RHA demethylation and re-localization, and also decreased viral protein synthesis and virus titers. Physical interaction between JMJD6 and RHA was demonstrated via reciprocal co-immunoprecipitation, where RHA preferentially bound JMJD6 monomers. Nuclear efflux of demethylated RHA (DM-RHA) coincided withmore » nuclear influx of JMJD6, which was not observed using another picornavirus. A modified biochemical assay demonstrated JMJD6 induced dose-dependent demethylation of RHA and two RHA-derived isoforms, which could be inhibited by NOG. We propose a role for JMJD6 in RHA demethylation stimulated by FMDV, that appears to facilitate virus replication. - Highlights: • We examined the role of JMJD6 in FMDV-induced RHA demethylation process. • Using an arginine demethylation assay showed that JMJD6 is involved in RHA demethylation. • A demethylases inhibitor reduced cytoplasmic accumulation of RHA and FMDV titers.« less

  5. Between-domain relations of students' academic emotions and their judgments of school domain similarity

    PubMed Central

    Goetz, Thomas; Haag, Ludwig; Lipnevich, Anastasiya A.; Keller, Melanie M.; Frenzel, Anne C.; Collier, Antonie P. M.

    2014-01-01

    With the aim to deepen our understanding of the between-domain relations of academic emotions, a series of three studies was conducted. We theorized that between-domain relations of trait (i.e., habitual) emotions reflected students' judgments of domain similarities, whereas between-domain relations of state (i.e., momentary) emotions did not. This supposition was based on the accessibility model of emotional self-report, according to which individuals' beliefs tend to strongly impact trait, but not state emotions. The aim of Study 1 (interviews; N = 40; 8th and 11th graders) was to gather salient characteristics of academic domains from students' perspective. In Study 2 (N = 1709; 8th and 11th graders) the 13 characteristics identified in Study 1 were assessed along with academic emotions in four different domains (mathematics, physics, German, and English) using a questionnaire-based trait assessment. With respect to the same domains, state emotions were assessed in Study 3 (N = 121; 8th and 11th graders) by employing an experience sampling approach. In line with our initial assumptions, between-domain relations of trait but not state academic emotions reflected between-domain relations of domain characteristics. Implications for research and practice are discussed. PMID:25374547

  6. Domain fusion analysis by applying relational algebra to protein sequence and domain databases.

    PubMed

    Truong, Kevin; Ikura, Mitsuhiko

    2003-05-06

    Domain fusion analysis is a useful method to predict functionally linked proteins that may be involved in direct protein-protein interactions or in the same metabolic or signaling pathway. As separate domain databases like BLOCKS, PROSITE, Pfam, SMART, PRINTS-S, ProDom, TIGRFAMs, and amalgamated domain databases like InterPro continue to grow in size and quality, a computational method to perform domain fusion analysis that leverages on these efforts will become increasingly powerful. This paper proposes a computational method employing relational algebra to find domain fusions in protein sequence databases. The feasibility of this method was illustrated on the SWISS-PROT+TrEMBL sequence database using domain predictions from the Pfam HMM (hidden Markov model) database. We identified 235 and 189 putative functionally linked protein partners in H. sapiens and S. cerevisiae, respectively. From scientific literature, we were able to confirm many of these functional linkages, while the remainder offer testable experimental hypothesis. Results can be viewed at http://calcium.uhnres.utoronto.ca/pi. As the analysis can be computed quickly on any relational database that supports standard SQL (structured query language), it can be dynamically updated along with the sequence and domain databases, thereby improving the quality of predictions over time.

  7. Domain fusion analysis by applying relational algebra to protein sequence and domain databases

    PubMed Central

    Truong, Kevin; Ikura, Mitsuhiko

    2003-01-01

    Background Domain fusion analysis is a useful method to predict functionally linked proteins that may be involved in direct protein-protein interactions or in the same metabolic or signaling pathway. As separate domain databases like BLOCKS, PROSITE, Pfam, SMART, PRINTS-S, ProDom, TIGRFAMs, and amalgamated domain databases like InterPro continue to grow in size and quality, a computational method to perform domain fusion analysis that leverages on these efforts will become increasingly powerful. Results This paper proposes a computational method employing relational algebra to find domain fusions in protein sequence databases. The feasibility of this method was illustrated on the SWISS-PROT+TrEMBL sequence database using domain predictions from the Pfam HMM (hidden Markov model) database. We identified 235 and 189 putative functionally linked protein partners in H. sapiens and S. cerevisiae, respectively. From scientific literature, we were able to confirm many of these functional linkages, while the remainder offer testable experimental hypothesis. Results can be viewed at . Conclusion As the analysis can be computed quickly on any relational database that supports standard SQL (structured query language), it can be dynamically updated along with the sequence and domain databases, thereby improving the quality of predictions over time. PMID:12734020

  8. Text Processing of Domain-Related Information for Individuals with High and Low Domain Knowledge.

    ERIC Educational Resources Information Center

    Spilich, George J.; And Others

    1979-01-01

    The way in which previously acquired knowledge affects the processing on new domain-related information was investigated. Text processing was studied in two groups differing in knowledge of the domain of baseball. A knowledge structure for the domain was constructed, and text propositions were classified. (SW)

  9. Characterization of a Linked Jumonji Domain of the KDM5/JARID1 Family of Histone H3 Lysine 4 Demethylases.

    PubMed

    Horton, John R; Engstrom, Amanda; Zoeller, Elizabeth L; Liu, Xu; Shanks, John R; Zhang, Xing; Johns, Margaret A; Vertino, Paula M; Fu, Haian; Cheng, Xiaodong

    2016-02-05

    The KDM5/JARID1 family of Fe(II)- and α-ketoglutarate-dependent demethylases remove methyl groups from tri- and dimethylated lysine 4 of histone H3. Accumulating evidence from primary tumors and model systems supports a role for KDM5A (JARID1A/RBP2) and KDM5B (JARID1B/PLU1) as oncogenic drivers. The KDM5 family is unique among the Jumonji domain-containing histone demethylases in that there is an atypical insertion of a DNA-binding ARID domain and a histone-binding PHD domain into the Jumonji domain, which separates the catalytic domain into two fragments (JmjN and JmjC). Here we demonstrate that internal deletion of the ARID and PHD1 domains has a negligible effect on in vitro enzymatic kinetics of the KDM5 family of enzymes. We present a crystal structure of the linked JmjN-JmjC domain from KDM5A, which reveals that the linked domain fully reconstitutes the cofactor (metal ion and α-ketoglutarate) binding characteristics of other structurally characterized Jumonji domain demethylases. Docking studies with GSK-J1, a selective inhibitor of the KDM6/KDM5 subfamilies, identify critical residues for binding of the inhibitor to the reconstituted KDM5 Jumonji domain. Further, we found that GSK-J1 inhibited the demethylase activity of KDM5C with 8.5-fold increased potency compared with that of KDM5B at 1 mm α-ketoglutarate. In contrast, JIB-04 (a pan-inhibitor of the Jumonji demethylase superfamily) had the opposite effect and was ~8-fold more potent against KDM5B than against KDM5C. Interestingly, the relative selectivity of JIB-04 toward KDM5B over KDM5C in vitro translates to a ~10-50-fold greater growth-inhibitory activity against breast cancer cell lines. These data define the minimal requirements for enzymatic activity of the KDM5 family to be the linked JmjN-JmjC domain coupled with the immediate C-terminal helical zinc-binding domain and provide structural characterization of the linked JmjN-JmjC domain for the KDM5 family, which should prove useful in the

  10. Cross-Domain Analogies as Relating Derived Relations among Two Separate Relational Networks

    PubMed Central

    Ruiz, Francisco J; Luciano, Carmen

    2011-01-01

    Contemporary behavior analytic research is making headway in analyzing analogy as the establishment of a relation of coordination among common types of trained or derived relations. Previous studies have been focused on within-domain analogy. The current study expands previous research by analyzing cross-domain analogy as relating relations among separate relational networks and by correlating participants' performance with a standard measure of analogical reasoning. In two experiments, adult participants first completed general intelligence and analogical reasoning tests. Subsequently, they were exposed to a computerized conditional discrimination training procedure designed to create two relational networks, each consisting of two 3-member equivalence classes. The critical test was a two-part analogical test in which participants had to relate combinatorial relations of coordination and distinction between the two relational networks. In Experiment 1, combinatorial relations for each network were individually tested prior to analogical testing, but in Experiment 2 they were not. Across both experiments, 65% of participants passed the analogical test on the first attempt. Moreover, results from the training procedure were strongly correlated with the standard measure of analogical reasoning. PMID:21547072

  11. Phylogenetic and specificity studies of two-domain GNA-related lectins: generation of multispecificity through domain duplication and divergent evolution

    PubMed Central

    Van Damme, Els J. M.; Nakamura-Tsuruta, Sachiko; Smith, David F.; Ongenaert, Maté; Winter, Harry C.; Rougé, Pierre; Goldstein, Irwin J.; Mo, Hanqing; Kominami, Junko; Culerrier, Raphaël; Barre, Annick; Hirabayashi, Jun; Peumans, Willy J.

    2007-01-01

    A re-investigation of the occurrence and taxonomic distribution of proteins built up of protomers consisting of two tandem arrayed domains equivalent to the GNA [Galanthus nivalis (snowdrop) agglutinin] revealed that these are widespread among monotyledonous plants. Phylogenetic analysis of the available sequences indicated that these proteins do not represent a monophylogenetic group but most probably result from multiple independent domain duplication/in tandem insertion events. To corroborate the relationship between inter-domain sequence divergence and the widening of specificity range, a detailed comparative analysis was made of the sequences and specificity of a set of two-domain GNA-related lectins. Glycan microarray analyses, frontal affinity chromatography and surface plasmon resonance measurements demonstrated that the two-domain GNA-related lectins acquired a marked diversity in carbohydrate-binding specificity that strikingly contrasts the canonical exclusive specificity of their single domain counterparts towards mannose. Moreover, it appears that most two-domain GNA-related lectins interact with both high mannose and complex N-glycans and that this dual specificity relies on the simultaneous presence of at least two different independently acting binding sites. The combined phylogenetic, specificity and structural data strongly suggest that plants used domain duplication followed by divergent evolution as a mechanism to generate multispecific lectins from a single mannose-binding domain. Taking into account that the shift in specificity of some binding sites from high mannose to complex type N-glycans implies that the two-domain GNA-related lectins are primarily directed against typical animal glycans, it is tempting to speculate that plants developed two-domain GNA-related lectins for defence purposes. PMID:17288538

  12. A relational metric, its application to domain analysis, and an example analysis and model of a remote sensing domain

    NASA Technical Reports Server (NTRS)

    Mcgreevy, Michael W.

    1995-01-01

    An objective and quantitative method has been developed for deriving models of complex and specialized spheres of activity (domains) from domain-generated verbal data. The method was developed for analysis of interview transcripts, incident reports, and other text documents whose original source is people who are knowledgeable about, and participate in, the domain in question. To test the method, it is applied here to a report describing a remote sensing project within the scope of the Earth Observing System (EOS). The method has the potential to improve the designs of domain-related computer systems and software by quickly providing developers with explicit and objective models of the domain in a form which is useful for design. Results of the analysis include a network model of the domain, and an object-oriented relational analysis report which describes the nodes and relationships in the network model. Other products include a database of relationships in the domain, and an interactive concordance. The analysis method utilizes a newly developed relational metric, a proximity-weighted frequency of co-occurrence. The metric is applied to relations between the most frequently occurring terms (words or multiword entities) in the domain text, and the terms found within the contexts of these terms. Contextual scope is selectable. Because of the discriminating power of the metric, data reduction from the association matrix to the network is simple. In addition to their value for design. the models produced by the method are also useful for understanding the domains themselves. They can, for example, be interpreted as models of presence in the domain.

  13. The Definition, Dimensions, and Domain of Public Relations.

    ERIC Educational Resources Information Center

    Hutton, James G.

    1999-01-01

    Discusses how the field of public relations has left itself vulnerable to other fields that are making inroads into public relations' traditional domain, and to critics who are filling in their own definitions of public relations. Proposes a definition and a three-dimensional framework to compare competing philosophies of public relations and to…

  14. On thick domain walls in general relativity

    NASA Technical Reports Server (NTRS)

    Goetz, Guenter; Noetzold, Dirk

    1989-01-01

    Planar scalar field configurations in general relativity differ considerably from those in flat space. It is shown that static domain walls of finite thickness in curved space-time do not possess a reflection symmetry. At infinity, the space-time tends to the Taub vacuum on one side of the wall and to the Minkowski vacuum (Rindler space-time) on the other. Massive test particles are always accelerated towards the Minkowski side, i.e., domain walls are attractive on the Taub side, but repulsive on the Minkowski side (Taub-vacuum cleaner). It is also proved that the pressure in all directions is always negative. Finally, a brief comment is made concerning the possibility of infinite, i.e., bigger than horizon size, domain walls in our universe. All of the results are independent of the form of the potential V(phi) greater than or equal to 0 of the scalar field phi.

  15. Mechanisms for integration of information models across related domains

    NASA Astrophysics Data System (ADS)

    Atkinson, Rob

    2010-05-01

    It is well recognised that there are opportunities and challenges in cross-disciplinary data integration. A significant barrier, however, is creating a conceptual model of the combined domains and the area of integration. For example, a groundwater domain application may require information from several related domains: geology, hydrology, water policy, etc. Each domain may have its own data holdings and conceptual models, but these will share various common concepts (eg. The concept of an aquifer). These areas of semantic overlap present significant challenges, firstly to choose a single representation (model) of a concept that appears in multiple disparate models,, then to harmonise these other models with the single representation. In addition, models may exist at different levels of abstraction depending on how closely aligned they are with a particular implementation. This makes it hard for modellers in one domain to introduce elements from another domain without either introducing a specific style of implementation, or conversely dealing with a set of abstract patterns that are hard to integrate with existing implementations. Models are easier to integrate if they are broken down into small units, with common concepts implemented using common models from well-known, and predictably managed shared libraries. This vision however requires development of a set of mechanisms (tools and procedures) for implementing and exploiting libraries of model components. These mechanisms need to handle publication, discovery, subscription, versioning and implementation of models in different forms. In this presentation a coherent suite of such mechanisms is proposed, using a scenario based on re-use of geosciences models. This approach forms the basis of a comprehensive strategy to empower domain modellers to create more interoperable systems. The strategy address a range of concerns and practice, and includes methodologies, an accessible toolkit, improvements to available

  16. A meta-analysis of work-family conflict and various outcomes with a special emphasis on cross-domain versus matching-domain relations.

    PubMed

    Amstad, Fabienne T; Meier, Laurenz L; Fasel, Ursula; Elfering, Achim; Semmer, Norbert K

    2011-04-01

    A literature review of studies analyzing work-family conflict and its consequences was conducted, and 427 effect sizes were analyzed meta-analytically. Work-family conflict was analyzed bidirectionally in terms of work interference with family (WIF) and family interference with work (FIW). We assessed 3 categories of potential outcomes: work-related outcomes, family-related outcomes, and domain-unspecific outcomes. Results show that WIF and FIW are consistently related to all 3 types of outcomes. Both types of interrole conflict showed stronger relationships to same-domain outcomes than to cross-domain outcomes. Thus, WIF was more strongly associated with work-related than with family-related outcomes, and FIW was more strongly associated with family-related than with work-related outcomes. In moderator analyses, parenthood could not explain variability in effect sizes. However, time spent at work did moderate the relationships between WIF and family-related outcomes, as well as FIW and domain-unspecific outcomes.

  17. Protein domain analysis of genomic sequence data reveals regulation of LRR related domains in plant transpiration in Ficus.

    PubMed

    Lang, Tiange; Yin, Kangquan; Liu, Jinyu; Cao, Kunfang; Cannon, Charles H; Du, Fang K

    2014-01-01

    Predicting protein domains is essential for understanding a protein's function at the molecular level. However, up till now, there has been no direct and straightforward method for predicting protein domains in species without a reference genome sequence. In this study, we developed a functionality with a set of programs that can predict protein domains directly from genomic sequence data without a reference genome. Using whole genome sequence data, the programming functionality mainly comprised DNA assembly in combination with next-generation sequencing (NGS) assembly methods and traditional methods, peptide prediction and protein domain prediction. The proposed new functionality avoids problems associated with de novo assembly due to micro reads and small single repeats. Furthermore, we applied our functionality for the prediction of leucine rich repeat (LRR) domains in four species of Ficus with no reference genome, based on NGS genomic data. We found that the LRRNT_2 and LRR_8 domains are related to plant transpiration efficiency, as indicated by the stomata index, in the four species of Ficus. The programming functionality established in this study provides new insights for protein domain prediction, which is particularly timely in the current age of NGS data expansion.

  18. Structural genomics reveals EVE as a new ASCH/PUA-related domain

    PubMed Central

    Bertonati, Claudia; Punta, Marco; Fischer, Markus; Yachdav, Guy; Forouhar, Farhad; Zhou, Weihong; Kuzin, Alexander P.; Seetharaman, Jayaraman; Abashidze, Mariam; Ramelot, Theresa A.; Kennedy, Michael A.; Cort, John R.; Belachew, Adam; Hunt, John F.; Tong, Liang; Montelione, Gaetano T.; Rost, Burkhard

    2014-01-01

    Summary We report on several proteins recently solved by structural genomics consortia, in particular by the Northeast Structural Genomics consortium (NESG). The proteins considered in this study differ substantially in their sequences but they share a similar structural core, characterized by a pseudobarrel five-stranded beta sheet. This core corresponds to the PUA domain-like architecture in the SCOP database. By connecting sequence information with structural knowledge, we characterize a new subgroup of these proteins that we propose to be distinctly different from previously described PUA domain-like domains such as PUA proper or ASCH. We refer to these newly defined domains as EVE. Although EVE may have retained the ability of PUA domains to bind RNA, the available experimental and computational data suggests that both the details of its molecular function and its cellular function differ from those of other PUA domain-like domains. This study of EVE and its relatives illustrates how the combination of structure and genomics creates new insights by connecting a cornucopia of structures that map to the same evolutionary potential. Primary sequence information alone would have not been sufficient to reveal these evolutionary links. PMID:19191354

  19. Structural Genomics Reveals EVE as a New ASCH/PUA-Related Domain

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

    Bertonati, C.; Punta, M; Fischer, M

    2008-01-01

    We report on several proteins recently solved by structural genomics consortia, in particular by the Northeast Structural Genomics consortium (NESG). The proteins considered in this study differ substantially in their sequences but they share a similar structural core, characterized by a pseudobarrel five-stranded beta sheet. This core corresponds to the PUA domain-like architecture in the SCOP database. By connecting sequence information with structural knowledge, we characterize a new subgroup of these proteins that we propose to be distinctly different from previously described PUA domain-like domains such as PUA proper or ASCH. We refer to these newly defined domains as EVE.more » Although EVE may have retained the ability of PUA domains to bind RNA, the available experimental and computational data suggests that both the details of its molecular function and its cellular function differ from those of other PUA domain-like domains. This study of EVE and its relatives illustrates how the combination of structure and genomics creates new insights by connecting a cornucopia of structures that map to the same evolutionary potential. Primary sequence information alone would have not been sufficient to reveal these evolutionary links.« less

  20. Domain-Specific Creativity in Relation to the Level of Empathy and Systemizing

    ERIC Educational Resources Information Center

    Dostál, Daniel; Plháková, Alena; Záškodná, Tereza

    2017-01-01

    This study aimed to explore self-reported domain-specific creativity in relation to the level of empathy, systemizing, and the Big Five personality dimensions. The research sample consisted of 1112 college students to whom the Kaufman Domains of Creativity Scale (K-DOCS), the Creative Achievement Questionnaire (CAQ), Baron-Cohen's empathy and…

  1. Quantitative relation between intermolecular and intramolecular binding of pro-rich peptides to SH3 domains.

    PubMed

    Zhou, Huan-Xiang

    2006-11-01

    Flexible linkers are often found to tether binding sequence motifs or connect protein domains. Here we analyze three usages of flexible linkers: 1), intramolecular binding of proline-rich peptides (PRPs) to SH3 domains for kinase regulation; 2), intramolecular binding of PRP for increasing the folding stability of SH3 domains; and 3), covalent linking of PRPs and other ligands for high-affinity bivalent binding. The basis of these analyses is a quantitative relation between intermolecular and intramolecular binding constants. This relation has the form K(i) = K(e0)p for intramolecular binding and K(e) = K(e01)K(e02)p for bivalent binding. The effective concentration p depends on the length of the linker and the distance between the linker attachment points in the bound state. Several applications illustrate the usefulness of the quantitative relation. These include intramolecular binding to the Itk SH3 domain by an internal PRP and to a circular permutant of the alpha-spectrin SH3 domain by a designed PRP, and bivalent binding to the two SH3 domains of Grb2 by two linked PRPs. These and other examples suggest that flexible linkers and sequence motifs tethered to them, like folded protein domains, are also subject to tight control during evolution.

  2. A case for restricted-domain relational learning.

    PubMed

    Wright, Anthony A; Katz, Jeffrey S

    2009-10-01

    Monkeys and pigeons learned a same/different task with pairs that were selected from a training set of eight picture stimuli. They showed no novel-stimulus transfer and hence no abstract-concept learning. They were also tested with novel pairs of the eight training pictures (i.e., combinations that had not been used in training) and with inverted pictures of the training pairs. If the subjects had learned the task item-specifically (e.g., if-then or configural learning), they should have failed these tests, but they performed well with novel combinations of training pictures and inverted pictures, suggesting that they learned the task relationally (i.e., on the basis of the relationship between the two pictures that were presented in each trial). This somewhat paradoxical conclusion of relational learning in the absence of abstract-concept learning is contrary to most theories of abstract-concept learning. The implications of this conclusion are discussed in the context of restricted-domain relational learning.

  3. Kernel-Based Learning for Domain-Specific Relation Extraction

    NASA Astrophysics Data System (ADS)

    Basili, Roberto; Giannone, Cristina; Del Vescovo, Chiara; Moschitti, Alessandro; Naggar, Paolo

    In a specific process of business intelligence, i.e. investigation on organized crime, empirical language processing technologies can play a crucial role. The analysis of transcriptions on investigative activities, such as police interrogatories, for the recognition and storage of complex relations among people and locations is a very difficult and time consuming task, ultimately based on pools of experts. We discuss here an inductive relation extraction platform that opens the way to much cheaper and consistent workflows. The presented empirical investigation shows that accurate results, comparable to the expert teams, can be achieved, and parametrization allows to fine tune the system behavior for fitting domain-specific requirements.

  4. Domain-specific physical activity and health-related quality of life in university students.

    PubMed

    Pedišić, Zeljko; Rakovac, Marija; Titze, Sylvia; Jurakić, Danijel; Oja, Pekka

    2014-01-01

    Information on the relationship between domain-specific physical activity (PA) and health-related quality of life (HRQoL) in the general population and specific groups is still scarce. The aim of this study was to determine the relationship between PA in work, transport, domestic and leisure-time domains and HRQoL among university students. PA and HRQoL were assessed in a random stratified sample of 1750 university students using the International Physical Activity Questionnaire - long form and 12-item Short Form Health Survey, respectively. The Spearman's rank correlations, adjusted for age, community size, personal monthly budget, body mass index, smoking habits and alcohol intake ranged from -0.11 to 0.18 in female students and -0.29 to 0.19 in male students. Leisure-time, domestic, transport-related PA and total PA were positively related to HRQoL. Inverse correlations with HRQoL were only found for work-related PA in male students. Multiple linear regression analysis showed that only leisure-time PA was related to the Physical Summary Component score (β = 0.08 for females and β = 0.10 for males, P < 0.05). Domain-specific PA levels were not significantly related to the Mental Component Summary score. To get a more comprehensive insight in the relationship between PA and HRQoL, future studies should not only analyse total PA levels but also domain-specific PA levels. The evidence on the positive relationship of leisure-time, transport and domestic PA with HRQoL can potentially be used to support evidence-based promotion of PA in a university setting, and as a hypothesis for future longitudinal studies on such potential causal relationships.

  5. Ring-like oligomers of Synaptotagmins and related C2 domain proteins

    PubMed Central

    Zanetti, Maria N; Bello, Oscar D; Wang, Jing; Coleman, Jeff; Cai, Yiying; Sindelar, Charles V; Rothman, James E; Krishnakumar, Shyam S

    2016-01-01

    We recently reported that the C2AB portion of Synaptotagmin 1 (Syt1) could self-assemble into Ca2+-sensitive ring-like oligomers on membranes, which could potentially regulate neurotransmitter release. Here we report that analogous ring-like oligomers assemble from the C2AB domains of other Syt isoforms (Syt2, Syt7, Syt9) as well as related C2 domain containing protein, Doc2B and extended Synaptotagmins (E-Syts). Evidently, circular oligomerization is a general and conserved structural aspect of many C2 domain proteins, including Synaptotagmins. Further, using electron microscopy combined with targeted mutations, we show that under physiologically relevant conditions, both the Syt1 ring assembly and its rapid disruption by Ca2+ involve the well-established functional surfaces on the C2B domain that are important for synaptic transmission. Our data suggests that ring formation may be triggered at an early step in synaptic vesicle docking and positions Syt1 to synchronize neurotransmitter release to Ca2+ influx. DOI: http://dx.doi.org/10.7554/eLife.17262.001 PMID:27434670

  6. A cross-cultural comparison of the coexistence and domain superiority of individuating and relating autonomy.

    PubMed

    Yeh, Kuang-Hui; Bedford, Olwen; Yang, Yung-Jui

    2009-06-01

    The consensus definition of autonomy in the psychological literature emphasizes self-governance through free volition, not separation or independence from others. Since the concept of self may differ cross-culturally, several researchers have tried to incorporate types of self into the notion of autonomy; however, only the dual model of autonomy has been able to do this while retaining an emphasis on volition. The dual model describes two distinct forms of autonomy-individuating and relating-each with superior function in a specific domain of individual functioning. Individuating autonomy represents a volitional capacity to act against social constraints and offers a route to achieve an independent self-identity by expressing individualistic attributes and distinctions. Relating autonomy represents a volitional capacity to act by emphasizing the harmony of self-in-relation-to-others, the quality of interpersonal relationships, and self-transcendence. These two forms of autonomy have been shown to coexist at the individual level in a Taiwanese sample. This study takes the next step, with a cross-cultural test of the coexistence and domain superiority hypotheses of individuating and relating autonomy. Participants included 306 college students from Taiwan and 183 college students from the United States. Structural equation modelling by multigroup analyses confirmed the cross-cultural equivalence of the two-factor individuating autonomy and relating autonomy measurement model. Across both samples the two forms of autonomy were shown to be mutually inclusive and not exclusive or independent. The domain-superior function of each form of autonomy was also confirmed cross-culturally; each form of autonomy has a dominant, but not necessarily exclusive, domain of functioning. Specifically, individuating autonomy was more associated with intrapersonal than interpersonal domain dependent variables, while relating autonomy was more associated with interpersonal than

  7. Severity of personality disorders and domains of general personality dysfunction related to attachment.

    PubMed

    Hengartner, Michael P; von Wyl, Agnes; Tanis, Thachell; Halmi, Winter; Galynker, Igor; Cohen, Lisa J

    2015-08-01

    This is the first study to link attachment to both severity of total DSM-IV personality disorder (PD) traits and domains of general personality dysfunction, using a sample of 72 inpatients from New York City. We assessed a measure of global PD severity and the core domains of personality functioning using the severity indices of personality problems (SIPP-118). Attachment was measured with the experience in close relationships-revised (ECR-R) and the relationship style questionnaire (RSQ). Global PD severity correlated most strongly with attachment anxiety (r = 0.65). Regression of the SIPP-118 domains on attachment produced models that accounted for a substantial proportion of variance in those scales (R(2) ranging from 28.2 to 54.2%). SIPP-118 relational capacities were the strongest predictor of ECR-R avoidance (β = -0.88) and anxiety (β = -0.58), as well as RSQ secure (β = 0.53) and fearful (β = -0.65). In conclusion, insecure attachment strongly related to the severity of global PD traits and specifically to relational capacities, which are a higher-order domain of general personality dysfunction. These findings provide further evidence that interpersonal problems are at the core of PDs and that attachment could constitute an important mediator of the social dysfunction in persons with personality pathology. Copyright © 2015 John Wiley & Sons, Ltd.

  8. International note: between-domain relations of Chinese high school students' academic achievements.

    PubMed

    Yangyang, Liu

    2012-08-01

    The present study examined the between-domain relations of Chinese high school students' academic achievements. In a sample of 1870 Chinese 10th grade students, the results indicated that Chinese high school students' academic achievements were correlated across nine subjects. In line with the previous Western findings, the findings suggested that academic achievement was largely domain-general in nature. Copyright © 2012 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  9. Bidirectional Transfer between Metaphorical Related Domains in Implicit Learning of Form-Meaning Connections

    PubMed Central

    Yang, Zhiliang; Dienes, Zoltan

    2013-01-01

    People can implicitly learn a connection between linguistic forms and meanings, for example between specific determiners (e.g. this, that…) and the type of nouns to which they apply. Li et al (2013) recently found that transfer of form-meaning connections from a concrete domain (height) to an abstract domain (power) was achieved in a metaphor-consistent way without awareness, showing that unconscious knowledge can be abstract and flexibly deployed. The current study aims to determine whether people transfer knowledge of form-meaning connections not only from a concrete domain to an abstract one, but also vice versa, consistent with metaphor representation being bi-directional. With a similar paradigm as used by Li et al, participants learnt form- meaning connections of different domains (concrete vs. abstract) and then were tested on two kinds of generalizations (same and different domain generalization). As predicted, transfer of form-meaning connections occurred bidirectionally when structural knowledge was unconscious. Moreover, the present study also revealed that more transfer occurred between metaphorically related domains when judgment knowledge was conscious (intuition) rather than unconscious (guess). Conscious and unconscious judgment knowledge may have different functional properties. PMID:23844159

  10. Children's Comprehension of Object Relative Sentences: It's Extant Language Knowledge That Matters, Not Domain-General Working Memory.

    PubMed

    Rusli, Yazmin Ahmad; Montgomery, James W

    2017-10-17

    The aim of this study was to determine whether extant language (lexical) knowledge or domain-general working memory is the better predictor of comprehension of object relative sentences for children with typical development. We hypothesized that extant language knowledge, not domain-general working memory, is the better predictor. Fifty-three children (ages 9-11 years) completed a word-level verbal working-memory task, indexing extant language (lexical) knowledge; an analog nonverbal working-memory task, representing domain-general working memory; and a hybrid sentence comprehension task incorporating elements of both agent selection and cross-modal picture-priming paradigms. Images of the agent and patient were displayed at the syntactic gap in the object relative sentences, and the children were asked to select the agent of the sentence. Results of general linear modeling revealed that extant language knowledge accounted for a unique 21.3% of variance in the children's object relative sentence comprehension over and above age (8.3%). Domain-general working memory accounted for a nonsignificant 1.6% of variance. We interpret the results to suggest that extant language knowledge and not domain-general working memory is a critically important contributor to children's object relative sentence comprehension. Results support a connectionist view of the association between working memory and object relative sentence comprehension. https://doi.org/10.23641/asha.5404573.

  11. Age-related functional changes in domain-specific medial temporal lobe pathways.

    PubMed

    Berron, David; Neumann, Katja; Maass, Anne; Schütze, Hartmut; Fliessbach, Klaus; Kiven, Verena; Jessen, Frank; Sauvage, Magdalena; Kumaran, Dharshan; Düzel, Emrah

    2018-05-01

    There is now converging evidence from studies in animals and humans that the medial temporal lobes (MTLs) harbor anatomically distinct processing pathways for object and scene information. Recent functional magnetic resonance imaging studies in humans suggest that this domain-specific organization may be associated with a functional preference of the anterior-lateral part of the entorhinal cortex (alErC) for objects and the posterior-medial entorhinal cortex (pmErC) for scenes. As MTL subregions are differentially affected by aging and neurodegenerative diseases, the question was raised whether aging may affect the 2 pathways differentially. To address this possibility, we developed a paradigm that allows the investigation of object memory and scene memory in a mnemonic discrimination task. A group of young (n = 43) and healthy older subjects (n = 44) underwent functional magnetic resonance imaging recordings during this novel task, while they were asked to discriminate exact repetitions of object and scene stimuli from novel stimuli that were similar but modified versions of the original stimuli ("lures"). We used structural magnetic resonance images to manually segment anatomical components of the MTL including alErC and pmErC and used these segmented regions to analyze domain specificity of functional activity. Across the entire sample, object processing was associated with activation of the perirhinal cortex (PrC) and alErC, whereas for scene processing, activation was more predominant in the parahippocampal cortex and pmErC. Functional activity related to mnemonic discrimination of object and scene lures from exact repetitions was found to overlap between processing pathways and suggests that while the PrC-alErC pathway was more involved in object discrimination, both pathways were involved in the discrimination of similar scenes. Older adults were behaviorally less accurate than young adults in discriminating similar lures from exact repetitions, but this

  12. Lysine-specific demethylase 2A (KDM2A) normalizes human embryonic stem cell derived keratinocytes

    PubMed Central

    Iuchi, Shiro; Green, Howard

    2012-01-01

    Studies on human lysine-specific demethylase 2A (KDM2A) by others have recently begun. To date, the demethylase activity has been known to reduce expression of genes and eventually inhibit proliferation of cells. However, while attempting to improve proliferation of hES-cell–derived Nod keratinocytes, which grow poorly and have a short life span, we found that high expression of the KDM2A gene improves the poor proliferation of the cells. Of the four isomer cDNAs that we prepared from alternatively spliced KDM2A transcripts, only one stimulates the proliferation. This (KDM2A-N782) encodes the 782AA protein containing the JmjC, CXXC, and Ring domains, but not the F-box and AMN1 domains, unlike KDM2A, which has been studied by other groups. Our results not only show that differently spliced transcripts from a gene result in totally opposite outcomes, but also present critical evidence of the complicated activities of KDM2A, which contains all of the five domains. PMID:22635273

  13. Prioritisation of associations between protein domains and complex diseases using domain-domain interaction networks.

    PubMed

    Wang, W; Zhang, W; Jiang, R; Luan, Y

    2010-05-01

    It is of vital importance to find genetic variants that underlie human complex diseases and locate genes that are responsible for these diseases. Since proteins are typically composed of several structural domains, it is reasonable to assume that harmful genetic variants may alter structures of protein domains, affect functions of proteins and eventually cause disorders. With this understanding, the authors explore the possibility of recovering associations between protein domains and complex diseases. The authors define associations between protein domains and disease families on the basis of associations between non-synonymous single nucleotide polymorphisms (nsSNPs) and complex diseases, similarities between diseases, and relations between proteins and domains. Based on a domain-domain interaction network, the authors propose a 'guilt-by-proximity' principle to rank candidate domains according to their average distance to a set of seed domains in the domain-domain interaction network. The authors validate the method through large-scale cross-validation experiments on simulated linkage intervals, random controls and the whole genome. Results show that areas under receiver operating characteristic curves (AUC scores) can be as high as 77.90%, and the mean rank ratios can be as low as 21.82%. The authors further offer a freely accessible web interface for a genome-wide landscape of associations between domains and disease families.

  14. Willingness-to-pay stated preferences for 8 health-related quality-of-life domains in psoriatic arthritis: a pilot study.

    PubMed

    Hu, Stephanie W; Holt, Elizabeth W; Husni, M Elaine; Qureshi, Abrar A

    2010-04-01

    Psoriatic arthritis (PsA) is a seronegative inflammatory arthritis found in up to 5 to 42% of patients with psoriasis. As current instruments do not fully capture health-related quality of life (HR-QOL) in PsA from the patient's perspective, we piloted a novel application of "willingness-to-pay" (WTP) as a Patient Reported Outcome to measure the relative impact of PsA in 8 domains of HR-QOL. Fifty-nine PsA patients were interviewed on 8 WTP HR-QOL domains (physical, emotional, sleep, work, social, self-care, intimacy, and concentration). Participants were asked to rank the 8 domains of health in order of HR-QOL impact. In each domain, participants were asked whether PsA affected that domain, whether they were willing to pay for a cure in that domain, and the amount they were willing to pay. Median WTP amounts were compared with the proportion of participants affected by and willing to pay in each domain. Responses in US dollars were interpreted as strength of preference rather than absolute monetary values. The majority of participants were white (98%), > or =45 years of age (70%), insured (98%), and earned >$65,000/yr (66%). The physical domain was most affected by PsA; intimacy and concentration were ranked lowest. Participants reported a wide range of WTP amounts ($0 to $1,000,000), and median WTP amounts were highest in the physical, work, sleep, and self-care domains. Related domains elicited median WTP amounts that were highly correlated. No significant differences in median WTP amounts were found across ages, genders, and income levels for the different domains. WTP is a novel quantitative patient-perspective measure that is comprehensible and feasible to administer in PsA patients. It represents a unique tool for capturing the complex manifestations of PsA and its impact on the individual, allowing the quantification of specific HR-QOL parameters and providing the potential for comparison across various disease processes in a given individual. Copyright

  15. Connective Tissue Growth Factor Domain 4 Amplifies Fibrotic Kidney Disease through Activation of LDL Receptor-Related Protein 6.

    PubMed

    Johnson, Bryce G; Ren, Shuyu; Karaca, Gamze; Gomez, Ivan G; Fligny, Cécile; Smith, Benjamin; Ergun, Ayla; Locke, George; Gao, Benbo; Hayes, Sebastian; MacDonnell, Scott; Duffield, Jeremy S

    2017-06-01

    Connective tissue growth factor (CTGF), a matrix-associated protein with four distinct cytokine binding domains, has roles in vasculogenesis, wound healing responses, and fibrogenesis and is upregulated in fibroblasts and myofibroblasts in disease. Here, we investigated the role of CTGF in fibrogenic cells. In mice, tissue-specific inducible overexpression of CTGF by kidney pericytes and fibroblasts had no bearing on nephrogenesis or kidney homeostasis but exacerbated inflammation and fibrosis after ureteral obstruction. These effects required the WNT receptor LDL receptor-related protein 6 (LRP6). Additionally, pericytes isolated from these mice became hypermigratory and hyperproliferative on overexpression of CTGF. CTGF is cleaved in vivo into distinct domains. Treatment with recombinant domain 1, 1+2 (N terminus), or 4 (C terminus) independently activated myofibroblast differentiation and wound healing responses in cultured pericytes, but domain 4 showed the broadest profibrotic activity. Domain 4 exhibited low-affinity binding to LRP6 in in vitro binding assays, and inhibition of LRP6 or critical signaling cascades downstream of LRP6, including JNK and WNT/ β -catenin, inhibited the biologic activity of domain 4. Administration of blocking antibodies specifically against CTGF domain 4 or recombinant Dickkopf-related protein-1, an endogenous inhibitor of LRP6, effectively inhibited inflammation and fibrosis associated with ureteral obstruction in vivo Therefore, domain 4 of CTGF and the WNT signaling pathway are important new targets in fibrosis. Copyright © 2017 by the American Society of Nephrology.

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

    PubMed

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

    2004-02-20

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

  17. Constructing Domain-Specific Knowledge in Kindergarten: Relations among Knowledge, Intelligence, and Strategic Performance

    ERIC Educational Resources Information Center

    Alexander, Joyce M.; Johnson, Kathy E.; Leibham, Mary E.; DeBauge, Christiane

    2005-01-01

    Thirty kindergarten children from two classrooms participated in a 3-week curricular unit on dinosaurs designed to teach taxonomic relations and distinguishing features aligned with 15 dinosaur species. Both domain-specific learning and strategic performance on a Twenty Questions game were assessed twice throughout the curriculum, as well as…

  18. Comparative analysis of barophily-related amino acid content in protein domains of Pyrococcus abyssi and Pyrococcus furiosus.

    PubMed

    Yafremava, Liudmila S; Di Giulio, Massimo; Caetano-Anollés, Gustavo

    2013-01-01

    Amino acid substitution patterns between the nonbarophilic Pyrococcus furiosus and its barophilic relative P. abyssi confirm that hydrostatic pressure asymmetry indices reflect the extent to which amino acids are preferred by barophilic archaeal organisms. Substitution patterns in entire protein sequences, shared protein domains defined at fold superfamily level, domains in homologous sequence pairs, and domains of very ancient and very recent origin now provide further clues about the environment that led to the genetic code and diversified life. The pyrococcal proteomes are very similar and share a very early ancestor. Relative amino acid abundance analyses showed that biases in the use of amino acids are due to their shared fold superfamilies. Within these repertoires, only two of the five amino acids that are preferentially barophilic, aspartic acid and arginine, displayed this preference significantly and consistently across structure and in domains appearing in the ancestor. The more primordial asparagine, lysine and threonine displayed a consistent preference for nonbarophily across structure and in the ancestor. Since barophilic preferences are already evident in ancient domains that are at least ~3 billion year old, we conclude that barophily is a very ancient trait that unfolded concurrently with genetic idiosyncrasies in convergence towards a universal code.

  19. Domain atrophy creates rare cases of functional partial protein domains.

    PubMed

    Prakash, Ananth; Bateman, Alex

    2015-04-30

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

  20. Imaging genetics in attention-deficit/hyperactivity disorder and related neurodevelopmental domains: state of the art.

    PubMed

    Vilor-Tejedor, Natàlia; Cáceres, Alejandro; Pujol, Jesús; Sunyer, Jordi; González, Juan R

    2017-12-01

    Joint analysis of genetic and neuroimaging data, known as Imaging Genetics (IG), offers an opportunity to deepen our knowledge of the biological mechanisms of neurodevelopmental domains. There has been exponential growth in the literature on IG studies, which challenges the standardization of analysis methods in this field. In this review we give a complete up-to-date account of IG studies on attention deficit hyperactivity disorder (ADHD) and related neurodevelopmental domains, which serves as a reference catalog for researchers working on this neurological disorder. We searched MEDLINE/Pubmed and identified 37 articles on IG of ADHD that met our eligibility criteria. We carefully cataloged these articles according to imaging technique, genes and brain region, and summarized the main results and characteristics of each study. We found that IG studies on ADHD generally focus on dopaminergic genes and the structure of basal ganglia using structural Magnetic Resonance Imaging (MRI). We found little research involving multiple genetic factors and brain regions because of the scarce use of multivariate strategies in data analysis. IG of ADHD and related neurodevelopmental domains is still in its early stages, and a lack of replicated findings is one of the most pressing challenges in the field.

  1. The impact of socioenvironmental characteristics on domains of oral health-related quality of life in Brazilian schoolchildren.

    PubMed

    de Paula, Janice Simpson; Leite, Isabel Cristina Gonçalves; de Almeida, Anderson Barbosa; Ambrosano, Glaucia Maria Bovi; Mialhe, Fábio Luiz

    2013-01-28

    Recent researches have pointed out the need to consider the functional and psychosocial dimensions of oral health, such as Oral Health-related Quality of Life (OHRQoL). The aim of this study was to investigate the influence of oral health status, socioeconomic factors and home environment of children on the four health domains of Child Perceptions Questionnaire (CPQ11-14). A cross-sectional study was conducted in Brazil with a sample of 286 schoolchildren aged 12 years and their parents. The schoolchildren were clinically examined, and participants were asked to complete the CPQ11-14, as well as a questionnaire about home environment. In addition, a questionnaire was sent to each child's parents asking them about family socioeconomic status. The chi-square test and Poisson's regression analysis were performed. After adjusting for potential confounders, variables sex, monthly family income, mothers' education showed a statistically significant association with all health domains of the CPQ11-14. The family structure and presence of bleeding impacted on emotional (p = 0.0135), and social (p = 0.0010) well-being health domain scores. Orthodontic treatment need showed a strong negative effect on functional limitations domain score (p = 0.0021). Clinical and socio-environmental factors had different impacts on domains of oral health-related quality of life, demonstrating the need to consider these conditions in planning strategies for the oral health of schoolchildren.

  2. Crystal structures of the reverse transcriptase-associated ribonuclease H domain of xenotropic murine leukemia-virus related virus

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

    Zhou, Dongwen; Chung, Suhman; Miller, Maria

    2012-06-19

    The ribonuclease H (RNase H) domain of retroviral reverse transcriptase (RT) plays a critical role in the life cycle by degrading the RNA strands of DNA/RNA hybrids. In addition, RNase H activity is required to precisely remove the RNA primers from nascent (-) and (+) strand DNA. We report here three crystal structures of the RNase H domain of xenotropic murine leukemia virus-related virus (XMRV) RT, namely (i) the previously identified construct from which helix C was deleted, (ii) the intact domain, and (iii) the intact domain complexed with an active site {alpha}-hydroxytropolone inhibitor. Enzymatic assays showed that the intactmore » RNase H domain retained catalytic activity, whereas the variant lacking helix C was only marginally active, corroborating the importance of this helix for enzymatic activity. Modeling of the enzyme-substrate complex elucidated the essential role of helix C in binding a DNA/RNA hybrid and its likely mode of recognition. The crystal structure of the RNase H domain complexed with {beta}-thujaplicinol clearly showed that coordination by two divalent cations mediates recognition of the inhibitor.« less

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

    PubMed Central

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

    2015-01-01

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

  4. Habitual Cognitive Reappraisal Was Negatively Related to Perceived Immorality in the Harm and Fairness Domains

    PubMed Central

    Li, Zhongquan; Wu, Xiaoyuan; Zhang, Lisong; Zhang, Ziyuan

    2017-01-01

    Emotion plays an important role in moral judgment, and people always use emotion regulation strategies to modulate emotion, consciously or unconsciously. Previous studies had investigated only the relationship between emotion regulation strategies and moral judgment in the Harm domain, and revealed divergent results. Based on Moral Foundations Theory, the present study extended the investigation into moral judgment in all five moral domains and used a set of standardized moral vignettes. Two hundred and six college students filled in the Emotion Regulation Questionnaire and completed emotional ratings and moral judgment on moral vignettes from Moral Foundations Vignettes. Correlation analysis indicated that habitual cognitive reappraisal was negatively related to immorality rating in Harm, Fairness, and Loyalty domains. Regression analysis revealed that after controlling the effect of other variables, cognitive reappraisal negatively predicted immorality ratings in the Harm and Fairness domains. Further mediation analysis showed that emotional valence only partially explained the association between cognitive reappraisal and moral judgment in Harm area. Some other factors beyond emotional valence were suggested for future studies. PMID:29075229

  5. Habitual Cognitive Reappraisal Was Negatively Related to Perceived Immorality in the Harm and Fairness Domains.

    PubMed

    Li, Zhongquan; Wu, Xiaoyuan; Zhang, Lisong; Zhang, Ziyuan

    2017-01-01

    Emotion plays an important role in moral judgment, and people always use emotion regulation strategies to modulate emotion, consciously or unconsciously. Previous studies had investigated only the relationship between emotion regulation strategies and moral judgment in the Harm domain, and revealed divergent results. Based on Moral Foundations Theory, the present study extended the investigation into moral judgment in all five moral domains and used a set of standardized moral vignettes. Two hundred and six college students filled in the Emotion Regulation Questionnaire and completed emotional ratings and moral judgment on moral vignettes from Moral Foundations Vignettes. Correlation analysis indicated that habitual cognitive reappraisal was negatively related to immorality rating in Harm, Fairness, and Loyalty domains. Regression analysis revealed that after controlling the effect of other variables, cognitive reappraisal negatively predicted immorality ratings in the Harm and Fairness domains. Further mediation analysis showed that emotional valence only partially explained the association between cognitive reappraisal and moral judgment in Harm area. Some other factors beyond emotional valence were suggested for future studies.

  6. Myocardin-Related Transcription Factor A Activation by Competition with WH2 Domain Proteins for Actin Binding

    PubMed Central

    Weissbach, Julia; Schikora, Franziska; Weber, Anja; Kessels, Michael

    2016-01-01

    The myocardin-related transcription factors (MRTFs) are coactivators of serum response factor (SRF)-mediated gene expression. Activation of MRTF-A occurs in response to alterations in actin dynamics and critically requires the dissociation of repressive G-actin–MRTF-A complexes. However, the mechanism leading to the release of MRTF-A remains unclear. Here we show that WH2 domains compete directly with MRTF-A for actin binding. Actin nucleation-promoting factors, such as N-WASP and WAVE2, as well as isolated WH2 domains, including those of Spire2 and Cobl, activate MRTF-A independently of changes in actin dynamics. Simultaneous inhibition of Arp2-Arp3 or mutation of the CA region only partially reduces MRTF-A activation by N-WASP and WAVE2. Recombinant WH2 domains and the RPEL domain of MRTF-A bind mutually exclusively to cellular and purified G-actin in vitro. The competition by different WH2 domains correlates with MRTF-SRF activation. Following serum stimulation, nonpolymerizable actin dissociates from MRTF-A, and de novo formation of the G-actin–RPEL complex is impaired by a transferable factor. Our work demonstrates that WH2 domains activate MRTF-A and contribute to target gene regulation by a competitive mechanism, independently of their role in actin filament formation. PMID:26976641

  7. Domains of health-related quality of life in age-related macular degeneration: a qualitative study in the Chinese cultural context

    PubMed Central

    Bian, Wei; Wan, Junli; Smith, Graeme; Li, Shiying; Tan, Mingqiong; Zhou, Fengjiao

    2018-01-01

    Objective To explore which areas of health-related quality of life were affected in Chinese patients, and to identify whether the areas are well covered by validated questionnaires. Design A qualitative study based on semistructured interviews was conducted. A qualitative thematic analysis following the approach of Colaizzi was used to analyse the interview data for significant statements and phrases. The themes and subthemes organised from the analysis were then compared by using the following current instruments: National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), Macular Disease Quality of life Questionnaire (MacDQoL) and Low-Luminance Questionnaire (LLD). Participants and setting Twenty-one patients with age-related macular degeneration were recruited from the eye clinic of Southwest Eye Hospital in Chongqing, mainland China. Results The mean age of the participants was 69.8 years (range 57–82 years) and the duration of the disease ranged from 3 months to 6 years. The qualitative analysis revealed nine important domains including symptoms, difficulties with daily activities, depending on others, depression and uncertainty, optimism and hope, social isolation, role change, family support and financial burden. However, all the three questionnaires were insufficient to capture the full extent of quality of life issues of Chinese patients with AMD, and MacDQoL covered more domains when compared with NEI-VFQ-25 and LLD. Conclusion The domains of concepts important to people with AMD in the Chinese culture are not fully represented in the three widely used questionnaires. Nine important domains were identified for the assessment of quality of life and should be considered when assessing the impact of AMD on Chinese individuals. Further studies are needed to develop an AMD quality of life questionnaire, better tailored to the needs and culture of Chinese patients. PMID:29666126

  8. Myocardin-Related Transcription Factor A Activation by Competition with WH2 Domain Proteins for Actin Binding.

    PubMed

    Weissbach, Julia; Schikora, Franziska; Weber, Anja; Kessels, Michael; Posern, Guido

    2016-05-15

    The myocardin-related transcription factors (MRTFs) are coactivators of serum response factor (SRF)-mediated gene expression. Activation of MRTF-A occurs in response to alterations in actin dynamics and critically requires the dissociation of repressive G-actin-MRTF-A complexes. However, the mechanism leading to the release of MRTF-A remains unclear. Here we show that WH2 domains compete directly with MRTF-A for actin binding. Actin nucleation-promoting factors, such as N-WASP and WAVE2, as well as isolated WH2 domains, including those of Spire2 and Cobl, activate MRTF-A independently of changes in actin dynamics. Simultaneous inhibition of Arp2-Arp3 or mutation of the CA region only partially reduces MRTF-A activation by N-WASP and WAVE2. Recombinant WH2 domains and the RPEL domain of MRTF-A bind mutually exclusively to cellular and purified G-actin in vitro The competition by different WH2 domains correlates with MRTF-SRF activation. Following serum stimulation, nonpolymerizable actin dissociates from MRTF-A, and de novo formation of the G-actin-RPEL complex is impaired by a transferable factor. Our work demonstrates that WH2 domains activate MRTF-A and contribute to target gene regulation by a competitive mechanism, independently of their role in actin filament formation. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  9. Cysteine-rich domains related to Frizzled receptors and Hedgehog-interacting proteins

    PubMed Central

    Pei, Jimin; Grishin, Nick V

    2012-01-01

    Frizzled and Smoothened are homologous seven-transmembrane proteins functioning in the Wnt and Hedgehog signaling pathways, respectively. They harbor an extracellular cysteine-rich domain (FZ-CRD), a mobile evolutionary unit that has been found in a number of other metazoan proteins and Frizzled-like proteins in Dictyostelium. Domains distantly related to FZ-CRDs, in Hedgehog-interacting proteins (HHIPs), folate receptors and riboflavin-binding proteins (FRBPs), and Niemann-Pick Type C1 proteins (NPC1s), referred to as HFN-CRDs, exhibit similar structures and disulfide connectivity patterns compared with FZ-CRDs. We used computational analyses to expand the homologous set of FZ-CRDs and HFN-CRDs, providing a better understanding of their evolution and classification. First, FZ-CRD-containing proteins with various domain compositions were identified in several major eukaryotic lineages including plants and Chromalveolata, revealing a wider phylogenetic distribution of FZ-CRDs than previously recognized. Second, two new and distinct groups of highly divergent FZ-CRDs were found by sensitive similarity searches. One of them is present in the calcium channel component Mid1 in fungi and the uncharacterized FAM155 proteins in metazoans. Members of the other new FZ-CRD group occur in the metazoan-specific RECK (reversion-inducing-cysteine-rich protein with Kazal motifs) proteins that are putative tumor suppressors acting as inhibitors of matrix metalloproteases. Finally, sequence and three-dimensional structural comparisons helped us uncover a divergent HFN-CRD in glypicans, which are important morphogen-binding heparan sulfate proteoglycans. Such a finding reinforces the evolutionary ties between the Wnt and Hedgehog signaling pathways and underscores the importance of gene duplications in creating essential signaling components in metazoan evolution. PMID:22693159

  10. Skyrmion domain wall collision and domain wall-gated skyrmion logic

    NASA Astrophysics Data System (ADS)

    Xing, Xiangjun; Pong, Philip W. T.; Zhou, Yan

    2016-08-01

    Skyrmions and domain walls are significant spin textures of great technological relevance to magnetic memory and logic applications, where they can be used as carriers of information. The unique topology of skyrmions makes them display emergent dynamical properties as compared with domain walls. Some studies have demonstrated that the two topologically inequivalent magnetic objects could be interconverted by using cleverly designed geometric structures. Here, we numerically address the skyrmion domain wall collision in a magnetic racetrack by introducing relative motion between the two objects based on a specially designed junction. An electric current serves as the driving force that moves a skyrmion toward a trapped domain wall pair. We see different types of collision dynamics depending on the driving parameters. Most importantly, the modulation of skyrmion transport using domain walls is realized in this system, allowing a set of domain wall-gated logical NOT, NAND, and NOR gates to be constructed. This work provides a skyrmion-based spin-logic architecture that is fully compatible with racetrack memories.

  11. MIT domain of Vps4 is a Ca2+-dependent phosphoinositide-binding domain.

    PubMed

    Iwaya, Naoko; Takasu, Hirotoshi; Goda, Natsuko; Shirakawa, Masahiro; Tanaka, Toshiki; Hamada, Daizo; Hiroaki, Hidekazu

    2013-05-01

    The microtubule interacting and trafficking (MIT) domain is a small protein module that is conserved in proteins of diverged function, such as Vps4, spastin and sorting nexin 15 (SNX15). The molecular function of the MIT domain is protein-protein interaction, in which the domain recognizes peptides containing MIT-interacting motifs. Recently, we identified an evolutionarily related domain, 'variant' MIT domain at the N-terminal region of the microtubule severing enzyme katanin p60. We found that the domain was responsible for binding to microtubules and Ca(2+). Here, we have examined whether the authentic MIT domains also bind Ca(2+). We found that the loop between the first and second α-helices of the MIT domain binds a Ca(2+) ion. Furthermore, the MIT domains derived from Vps4b and SNX15a showed phosphoinositide-binding activities in a Ca(2+)-dependent manner. We propose that the MIT domain is a novel membrane-associating domain involved in endosomal trafficking.

  12. Domains of health-related quality of life in age-related macular degeneration: a qualitative study in the Chinese cultural context.

    PubMed

    Bian, Wei; Wan, Junli; Smith, Graeme; Li, Shiying; Tan, Mingqiong; Zhou, Fengjiao

    2018-04-17

    To explore which areas of health-related quality of life were affected in Chinese patients, and to identify whether the areas are well covered by validated questionnaires. A qualitative study based on semistructured interviews was conducted. A qualitative thematic analysis following the approach of Colaizzi was used to analyse the interview data for significant statements and phrases. The themes and subthemes organised from the analysis were then compared by using the following current instruments: National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), Macular Disease Quality of life Questionnaire (MacDQoL) and Low-Luminance Questionnaire (LLD). Twenty-one patients with age-related macular degeneration were recruited from the eye clinic of Southwest Eye Hospital in Chongqing, mainland China. The mean age of the participants was 69.8 years (range 57-82 years) and the duration of the disease ranged from 3 months to 6 years. The qualitative analysis revealed nine important domains including symptoms, difficulties with daily activities, depending on others, depression and uncertainty, optimism and hope, social isolation, role change, family support and financial burden. However, all the three questionnaires were insufficient to capture the full extent of quality of life issues of Chinese patients with AMD, and MacDQoL covered more domains when compared with NEI-VFQ-25 and LLD. The domains of concepts important to people with AMD in the Chinese culture are not fully represented in the three widely used questionnaires. Nine important domains were identified for the assessment of quality of life and should be considered when assessing the impact of AMD on Chinese individuals. Further studies are needed to develop an AMD quality of life questionnaire, better tailored to the needs and culture of Chinese patients. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is

  13. A topologically related singularity suggests a maximum preferred size for protein domains.

    PubMed

    Zbilut, Joseph P; Chua, Gek Huey; Krishnan, Arun; Bossa, Cecilia; Rother, Kristian; Webber, Charles L; Giuliani, Alessandro

    2007-02-15

    A variety of protein physicochemical as well as topological properties, demonstrate a scaling behavior relative to chain length. Many of the scalings can be modeled as a power law which is qualitatively similar across the examples. In this article, we suggest a rational explanation to these observations on the basis of both protein connectivity and hydrophobic constraints of residues compactness relative to surface volume. Unexpectedly, in an examination of these relationships, a singularity was shown to exist near 255-270 residues length, and may be associated with an upper limit for domain size. Evaluation of related G-factor data points to a wide range of conformational plasticity near this point. In addition to its theoretical importance, we show by an application of CASP experimental and predicted structures, that the scaling is a practical filter for protein structure prediction. 2006 Wiley-Liss, Inc.

  14. Rating knowledge sharing in cross-domain collaborative filtering.

    PubMed

    Li, Bin; Zhu, Xingquan; Li, Ruijiang; Zhang, Chengqi

    2015-05-01

    Cross-domain collaborative filtering (CF) aims to share common rating knowledge across multiple related CF domains to boost the CF performance. In this paper, we view CF domains as a 2-D site-time coordinate system, on which multiple related domains, such as similar recommender sites or successive time-slices, can share group-level rating patterns. We propose a unified framework for cross-domain CF over the site-time coordinate system by sharing group-level rating patterns and imposing user/item dependence across domains. A generative model, say ratings over site-time (ROST), which can generate and predict ratings for multiple related CF domains, is developed as the basic model for the framework. We further introduce cross-domain user/item dependence into ROST and extend it to two real-world cross-domain CF scenarios: 1) ROST (sites) for alleviating rating sparsity in the target domain, where multiple similar sites are viewed as related CF domains and some items in the target domain depend on their correspondences in the related ones; and 2) ROST (time) for modeling user-interest drift over time, where a series of time-slices are viewed as related CF domains and a user at current time-slice depends on herself in the previous time-slice. All these ROST models are instances of the proposed unified framework. The experimental results show that ROST (sites) can effectively alleviate the sparsity problem to improve rating prediction performance and ROST (time) can clearly track and visualize user-interest drift over time.

  15. A Relational Metric, Its Application to Domain Analysis, and an Example Analysis and Model of a Remote Sensing Domain

    DOT National Transportation Integrated Search

    1995-07-01

    An objective and quantitative method has been developed for deriving models of complex and specialized spheres of activity (domains) from domain-generated verbal data. The method was developed for analysis of interview transcripts, incident reports, ...

  16. Institutionalizing the Human Domain: Achieving Cross Domain Synergy for Every Day Missions

    DTIC Science & Technology

    2017-04-06

    AIR WAR COLLEGE AIR UNIVERSITY INSTITUTIONALIZING THE HUMAN DOMAIN: ACHIEVING CROSS DOMAIN SYNERGY FOR “EVERY DAY ” MISSIONS by...war. Next, this paper will focus on the importance of the Human Domain as it relates to success within every day missions of the U.S. Military and...socially complex environment. History demonstrates that the U.S. Military has and will continue to conduct these every day missions amongst the

  17. The effect of domain-general inhibition-related training on language switching: An ERP study.

    PubMed

    Liu, Huanhuan; Liang, Lijuan; Dunlap, Susan; Fan, Ning; Chen, Baoguo

    2016-01-01

    Previous studies have demonstrated that inhibitory control ability could be improved by training, and the Inhibitory Control (IC) Model implies that enhanced domain-general inhibition may elicit certain changes in language switch costs. In the present study, we aimed to examine the effects of domain-general inhibition training on performance in a language switching task, including which phase of domain-general inhibitory control benefits from training during an overt picture naming task in L1 and L2, using the event-related brain potentials (ERPs). Results showed that the language switch costs of bilinguals with high inhibitory control (high-IC) were symmetrical in both pretest and posttest, and those of bilinguals with low inhibitory control (low-IC) were asymmetrical in the pretest, but symmetrical in the posttest. Moreover, the high-IC group showed a larger LPC (late positive component) for L2 switch trials than for L1 trials in both pretest and posttest. In contrast, the low-IC group only exhibited a similar pattern of LPC in the posttest, but not in the pretest. These results indicate that inhibition training could increase the efficiency of language switching, and inhibitory control may play a key role during the lexical selection response phase. Overall, the present study is the first one to provide electrophysiological evidence for individual differences in the domain-general inhibition impact on language switching performance in low-proficient bilinguals. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    PubMed Central

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

    2012-01-01

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

  19. A novel firmicute protein family related to the actinobacterial resuscitation-promoting factors by non-orthologous domain displacement.

    PubMed

    Ravagnani, Adriana; Finan, Christopher L; Young, Michael

    2005-03-17

    In Micrococcus luteus growth and resuscitation from starvation-induced dormancy is controlled by the production of a secreted growth factor. This autocrine resuscitation-promoting factor (Rpf) is the founder member of a family of proteins found throughout and confined to the actinobacteria (high G + C Gram-positive bacteria). The aim of this work was to search for and characterise a cognate gene family in the firmicutes (low G + C Gram-positive bacteria) and obtain information about how they may control bacterial growth and resuscitation. In silico analysis of the accessory domains of the Rpf proteins permitted their classification into several subfamilies. The RpfB subfamily is related to a group of firmicute proteins of unknown function, represented by YabE of Bacillus subtilis. The actinobacterial RpfB and firmicute YabE proteins have very similar domain structures and genomic contexts, except that in YabE, the actinobacterial Rpf domain is replaced by another domain, which we have called Sps. Although totally unrelated in both sequence and secondary structure, the Rpf and Sps domains fulfil the same function. We propose that these proteins have undergone "non-orthologous domain displacement", a phenomenon akin to "non-orthologous gene displacement" that has been described previously. Proteins containing the Sps domain are widely distributed throughout the firmicutes and they too fall into a number of distinct subfamilies. Comparative analysis of the accessory domains in the Rpf and Sps proteins, together with their weak similarity to lytic transglycosylases, provide clear evidence that they are muralytic enzymes. The results indicate that the firmicute Sps proteins and the actinobacterial Rpf proteins are cognate and that they control bacterial culturability via enzymatic modification of the bacterial cell envelope.

  20. A new principle technic for the transformation from frequency domain to time domain

    NASA Astrophysics Data System (ADS)

    Gao, Ben-Qing

    2017-03-01

    A principle technic for the transformation from frequency domain to time domain is presented. Firstly, a special type of frequency domain transcendental equation is obtained for an expected frequency domain parameter which is a rational or irrational fraction expression. Secondly, the inverse Laplace transformation is performed. When the two time-domain factors corresponding to the two frequency domain factors at two sides of frequency domain transcendental equation are known quantities, a time domain transcendental equation is reached. At last, the expected time domain parameter corresponding to the expected frequency domain parameter can be solved by the inverse convolution process. Proceeding from rational or irrational fraction expression, all solving process is provided. In the meantime, the property of time domain sequence is analyzed and the strategy for choosing the parameter values is described. Numerical examples are presented to verify the proposed theory and technic. Except for rational or irrational fraction expressions, examples of complex relative permittivity of water and plasma are used as verification method. The principle method proposed in the paper can easily solve problems which are difficult to be solved by Laplace transformation.

  1. Domain architecture conservation in orthologs

    PubMed Central

    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

  2. Exploring the functional architecture of person recognition system with event-related potentials in a within- and cross-domain self-priming of faces.

    PubMed

    Jemel, Boutheina; Pisani, Michèle; Rousselle, Laurence; Crommelinck, Marc; Bruyer, Raymond

    2005-01-01

    In this paper, we explored the functional properties of person recognition system by investigating the onset, magnitude, and scalp distribution of within- and cross-domain self-priming effects on event-related potentials (ERPs). Recognition of degraded pictures of famous people was enhanced by a prior exposure to the same person's face (within-domain self-priming) or name (cross-domain self-priming) as compared to those preceded by neutral or unrelated primes. The ERP results showed first that the amplitude of the N170 component to famous face targets was modulated by within- and cross-domain self-priming, suggesting not only that the N170 component can be affected by top-down influences but also that this top-down effect crosses domains. Second, similar to our behavioral data, later ERPs to famous faces showed larger ERP self-priming effects in the within-domain than in the cross-domain condition. In addition, the present data dissociated between two topographically and temporally overlapping priming-sensitive ERP components: the first one, with a strongly posterior distribution arising at an early onset, was modulated more by within-domain priming irrespective whether the repeated face was familiar or not. The second component, with a relatively uniform scalp distribution, was modulated by within- and cross-domain priming of familiar faces. Moreover, there was no evidence for ERP-induced modulations for unfamiliar face targets in the cross-domain condition. Together, our findings suggest that multiple neurocognitive events that are possibly mediated by distinct brain loci contribute to face priming effects.

  3. Characterization of the SAM domain of the PKD-related protein ANKS6 and its interaction with ANKS3.

    PubMed

    Leettola, Catherine N; Knight, Mary Jane; Cascio, Duilio; Hoffman, Sigrid; Bowie, James U

    2014-07-07

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder leading to end-stage renal failure in humans. In the PKD/Mhm(cy/+) rat model of ADPKD, the point mutation R823W in the sterile alpha motif (SAM) domain of the protein ANKS6 is responsible for disease. SAM domains are known protein-protein interaction domains, capable of binding each other to form polymers and heterodimers. Despite its physiological importance, little is known about the function of ANKS6 and how the R823W point mutation leads to PKD. Recent work has revealed that ANKS6 interacts with a related protein called ANKS3. Both ANKS6 and ANKS3 have a similar domain structure, with ankyrin repeats at the N-terminus and a SAM domain at the C-terminus. The SAM domain of ANKS3 is identified as a direct binding partner of the ANKS6 SAM domain. We find that ANKS3-SAM polymerizes and ANKS6-SAM can bind to one end of the polymer. We present crystal structures of both the ANKS3-SAM polymer and the ANKS3-SAM/ANKS6-SAM complex, revealing the molecular details of their association. We also learn how the R823W mutation disrupts ANKS6 function by dramatically destabilizing the SAM domain such that the interaction with ANKS3-SAM is lost. ANKS3 is a direct interacting partner of ANKS6. By structurally and biochemically characterizing the interaction between the ANKS3 and ANKS6 SAM domains, our work provides a basis for future investigation of how the interaction between these proteins mediates kidney function.

  4. Characterization of the SAM domain of the PKD-related protein ANKS6 and its interaction with ANKS3

    PubMed Central

    2014-01-01

    Background Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder leading to end-stage renal failure in humans. In the PKD/Mhm(cy/+) rat model of ADPKD, the point mutation R823W in the sterile alpha motif (SAM) domain of the protein ANKS6 is responsible for disease. SAM domains are known protein-protein interaction domains, capable of binding each other to form polymers and heterodimers. Despite its physiological importance, little is known about the function of ANKS6 and how the R823W point mutation leads to PKD. Recent work has revealed that ANKS6 interacts with a related protein called ANKS3. Both ANKS6 and ANKS3 have a similar domain structure, with ankyrin repeats at the N-terminus and a SAM domain at the C-terminus. Results The SAM domain of ANKS3 is identified as a direct binding partner of the ANKS6 SAM domain. We find that ANKS3-SAM polymerizes and ANKS6-SAM can bind to one end of the polymer. We present crystal structures of both the ANKS3-SAM polymer and the ANKS3-SAM/ANKS6-SAM complex, revealing the molecular details of their association. We also learn how the R823W mutation disrupts ANKS6 function by dramatically destabilizing the SAM domain such that the interaction with ANKS3-SAM is lost. Conclusions ANKS3 is a direct interacting partner of ANKS6. By structurally and biochemically characterizing the interaction between the ANKS3 and ANKS6 SAM domains, our work provides a basis for future investigation of how the interaction between these proteins mediates kidney function. PMID:24998259

  5. Relationship between the domains of the Multidimensional Students' Life Satisfaction Scale, satisfaction with food-related life and happiness in university students.

    PubMed

    Schnettler, Berta; Orellana, Ligia; Lobos, Germán; Miranda, Horacio; Sepúlveda, José; Etchebarne, Soledad; Mora, Marcos; Adasme-Berríos, Cristian; Grunert, Klaus G

    2015-06-01

    To characterize types of university students based on satisfaction with life domains that affect eating habits, satisfaction with food-related life and subjective happiness. A questionnaire was applied to a nonrandom sample of 305 students of both genders in five universities in Chile. The questionnaire included the abbreviated Multidimensional Student's Life Satisfaction Scale (MSLSS), Satisfaction with Food-related Life Scale (SWFL) and the Subjective Happiness Scale (SHS). Eating habits, frequency of food consumption in and outside the place of residence, approximate height and weight and sociodemographic variables were measured. Using factor analysis, the five-domain structure of the MSLSS was confirmed with 26 of the 30 items of the abbreviated version: Family, Friends, Self, Environment and University. Using cluster analysis four types of students were distinguished that differ significantly in the MSLSS global and domain scores, SWFL and SHS scores, gender, ownership of a food allowance card funded by the Chilean government, importance attributed to food for well-being and socioeconomic status. Higher levels of life satisfaction and happiness are associated with greater satisfaction with food-related life. Other major life domains that affect students' subjective well-being are Family, Friends, University and Self. Greater satisfaction in some domains may counterbalance the lower satisfaction in others. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  6. Polyphase tectono-magmatic and fluid history related to mantle exhumation in an ultra-distal rift domain: example of the fossil Platta domain, SE Switzerland

    NASA Astrophysics Data System (ADS)

    Epin, Marie-Eva; Manatschal, Gianreto; Amann, Méderic; Lescanne, Marc

    2017-04-01

    Despite the fact that many studies have investigated mantle exhumation at magma-poor rifted margins, there are still numerous questions concerning the 3D architecture, magmatic, fluid and thermal evolution of these ultra-distal domains that remain unexplained. Indeed, it has been observed in seismic data from ultra-distal magma-poor rifted margins that top basement is heavily structured and complex, however, the processes controlling the morpho-tectonic and magmatic evolution of these domains remain unknown. The aim of this study is to describe the 3D top basement morphology of an exhumed mantle domain, exposed over 200 km2 in the fossil Platta domain in SE Switzerland, and to define the timing and processes controlling its evolution. The examined Platta nappe corresponds to a remnant of the former ultra-distal Adriatic margin of the Alpine Tethys. The rift-structures are relatively well preserved due to the weak Alpine tectonic and metamorphic overprint during the emplacement in the Alpine nappe stack. Detailed mapping of parts of the Platta nappe enabled us to document the top basement architecture of an exhumed mantle domain and to investigate its link to later, rift/oceanic structures, magmatic additions and fluids. Our observations show a polyphase and/or complex: 1) deformation history associated with mantle exhumation along low-angle exhumation faults overprinted by later high-angle normal faults, 2) top basement morphology capped by magmato-sedimentary rocks, 3) tectono-magmatic evolution that includes gabbros, emplaced at deeper levels and subsequently exhumed and overlain by younger extrusive magmatic additions, and 4) fluid history including serpentinization, calcification, hydrothermal vent, rodingitization and spilitization affecting exhumed mantle and associated magmatic rocks. The overall observations provide important information on the temporal and spatial evolution of the tectonic, magmatic and fluid systems controlling the formation of ultra

  7. Statistical significance of task related deep brain EEG dynamic changes in the time-frequency domain.

    PubMed

    Chládek, J; Brázdil, M; Halámek, J; Plešinger, F; Jurák, P

    2013-01-01

    We present an off-line analysis procedure for exploring brain activity recorded from intra-cerebral electroencephalographic data (SEEG). The objective is to determine the statistical differences between different types of stimulations in the time-frequency domain. The procedure is based on computing relative signal power change and subsequent statistical analysis. An example of characteristic statistically significant event-related de/synchronization (ERD/ERS) detected across different frequency bands following different oddball stimuli is presented. The method is used for off-line functional classification of different brain areas.

  8. Domain adaptation via transfer component analysis.

    PubMed

    Pan, Sinno Jialin; Tsang, Ivor W; Kwok, James T; Yang, Qiang

    2011-02-01

    Domain adaptation allows knowledge from a source domain to be transferred to a different but related target domain. Intuitively, discovering a good feature representation across domains is crucial. In this paper, we first propose to find such a representation through a new learning method, transfer component analysis (TCA), for domain adaptation. TCA tries to learn some transfer components across domains in a reproducing kernel Hilbert space using maximum mean miscrepancy. In the subspace spanned by these transfer components, data properties are preserved and data distributions in different domains are close to each other. As a result, with the new representations in this subspace, we can apply standard machine learning methods to train classifiers or regression models in the source domain for use in the target domain. Furthermore, in order to uncover the knowledge hidden in the relations between the data labels from the source and target domains, we extend TCA in a semisupervised learning setting, which encodes label information into transfer components learning. We call this extension semisupervised TCA. The main contribution of our work is that we propose a novel dimensionality reduction framework for reducing the distance between domains in a latent space for domain adaptation. We propose both unsupervised and semisupervised feature extraction approaches, which can dramatically reduce the distance between domain distributions by projecting data onto the learned transfer components. Finally, our approach can handle large datasets and naturally lead to out-of-sample generalization. The effectiveness and efficiency of our approach are verified by experiments on five toy datasets and two real-world applications: cross-domain indoor WiFi localization and cross-domain text classification.

  9. Children's Comprehension of Object Relative Sentences: It's Extant Language Knowledge That Matters, Not Domain-General Working Memory

    ERIC Educational Resources Information Center

    Rusli, Yazmin Ahmad; Montgomery, James W.

    2017-01-01

    Purpose: The aim of this study was to determine whether extant language (lexical) knowledge or domain-general working memory is the better predictor of comprehension of object relative sentences for children with typical development. We hypothesized that extant language knowledge, not domain-general working memory, is the better predictor. Method:…

  10. Relations between the Development of Future Time Perspective in Three Life Domains, Investment in Learning, and Academic Achievement

    ERIC Educational Resources Information Center

    Peetsma, Thea; van der Veen, Ineke

    2011-01-01

    Relations between the development of future time perspectives in three life domains (i.e., school and professional career, social relations, and leisure time) and changes in students' investment in learning and academic achievement were examined in this study. Participants were 584 students in the first and 584 in the second year of the lower…

  11. Multivariate trajectories across multiple domains of health-related quality of life in children with new-onset epilepsy.

    PubMed

    Sajobi, Tolulope T; Wang, Meng; Ferro, Mark A; Brobbey, Anita; Goodwin, Shane; Speechley, Kathy N; Wiebe, Samuel

    2017-10-01

    The diagnosis of epilepsy in children is known to impact the trajectory of their health-related quality of life (HRQOL) over time. However, there is limited knowledge about variations in longitudinal trajectories across multiple domains of HRQOL. This study aims to characterize the heterogeneity in HRQOL trajectories across multiple HRQOL domains and to evaluate predictors of differences among the identified trajectory groups in children with new-onset epilepsy. Data were obtained from the Health Related Quality of Life in Children with Epilepsy Study (HERQULES), a prospective multi-center study of 373 children newly diagnosed with new-onset epilepsy who were followed up over 2years. Child HRQOL and family factors were reported by parents, and clinical characteristics were reported by neurologists. Group-based multi-trajectory modeling was adopted to characterize longitudinal trajectories of HRQOL as measured by the individual domains of cognitive, emotional, physical, and social functioning in the 55-item Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55). Multinomial logistic regression was used to assess potential factors that explain differences among the identified latent trajectory groups. Three distinct HRQOL trajectory subgroups were identified in children with new-onset epilepsy based on HRQOL scores: "High" (44.7%), "Intermediate" (37.0%), and "Low" (18.3%). While most trajectory groups exhibited increasing scores over time on physical and social domains, both flat and declining trajectories were noted on emotional and cognitive domains. Less severe epilepsy, an absence of cognitive and behavioral problems, lower parental depression scores, better family functioning, and fewer family demands were associated with a "Higher" or "Intermediate" HRQOL trajectory. The course of HRQOL over time in children with new-onset epilepsy appears to follow one of three different trajectories. Addressing the clinical and psychosocial determinants identified

  12. AMISH EYE STUDY: Baseline Spectral Domain Optical Coherence Tomography Characteristics of Age-Related Macular Degeneration.

    PubMed

    Nittala, Muneeswar G; Song, Yeunjoo E; Sardell, Rebecca; Adams, Larry D; Pan, Samuel; Velaga, Swetha B; Horst, Violet; Dana, Debra; Caywood, Laura; Laux, Renee; Fuzzell, Denise; Fuzzell, Sarada; Scott, William K; Cooke Bailey, Jessica N; Igo, Robert P; Haines, Jonathan; Pericak-Vance, Margaret A; Sadda, SriniVas R; Stambolian, Dwight

    2018-05-09

    To describe spectral domain optical coherence tomography (SD-OCT) findings in an Amish cohort to assess SD-OCT markers for early age-related macular degeneration (AMD). The authors performed a family-based prospective cohort study of 1,146 elderly Amish subjects (age range 50-99 years) (2,292 eyes) who had a family history of at least 1 individual with AMD. All subjects underwent complete ophthalmic examinations, SD-OCT using both Cirrus and Spectralis (20 × 20° scan area) instruments, fundus autofluorescence, infrared imaging, and color fundus photography. Spectral domain optical coherence tomography characteristics were analyzed in subjects with AMD (with and without subretinal drusenoid deposits [SDDs]) and normal healthy cohorts. Participants' mean age was 65.2 years (SD ± 11). Color fundus photographic findings in 596 (53%) subjects (1,009 eyes) were consistent with AMD; the remaining 478 (43%) subjects showed no signs of AMD. The choroid was significantly thinner on OCT (242 ± 76 µm, P < 0.001) in those with AMD compared with those without (263 ± 63 µm). Subretinal drusenoid deposits were found in 143 eyes (7%); 11 of the 143 eyes (8%) had no other manifestations of AMD. Drusen volume (P < 0.001) and area of geographic atrophy (P < 0.001) were significantly greater, and choroid was significantly (P < 0.001) thinner in subjects with SDDs versus those without SDDs. The authors describe spectral domain optical coherence tomography characteristics in an elderly Amish population with and without AMD, including the frequency of SDD. Although relatively uncommon in this population, the authors confirmed that SDDs can be found in the absence of other features of AMD and that eyes with SDDs have thinner choroids.

  13. Structural and Biochemical Basis for Ubiquitin Ligase Recruitment by Arrestin-related Domain-containing Protein-3 (ARRDC3)*

    PubMed Central

    Qi, Shiqian; O'Hayre, Morgan; Gutkind, J. Silvio; Hurley, James H.

    2014-01-01

    After protracted stimulation, the β2-adrenergic receptor and many other G-protein-coupled receptors are ubiquitinated and down-regulated. Arrestin-related domain-containing protein-3 (ARRDC3) has been proposed to recruit the ubiquitin ligase Nedd4 to the β2-adrenergic receptor. ARRDC3 contains two PPXY motifs that could potentially interact with any of the four WW domains of Nedd4. Here we dissect the interaction determinants. ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 μm for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3. Structures of the uncomplexed and PPXY1-bound WW3 domain were determined at 1.1 and 1.7 Å resolution. The structures revealed conformational changes upon binding and the hydrogen bonding network in exquisite detail. Tight packing of ARRDC3 Val-352′, part of a 310 helix at the C terminus of PPXY1, is important for high affinity binding to WW3. Although no single WW domain is strictly essential for the binding of Nedd4 and ARRDC3 expressed in HEK293 cells, high affinity binding of full-length ARRDC3 and Nedd4 is driven by the avid interaction of both PPXY motifs with either the WW2-WW3 or WW3-WW4 combinations, with Kd values as low as 300 nm. PMID:24379409

  14. Structural and biochemical basis for ubiquitin ligase recruitment by arrestin-related domain-containing protein-3 (ARRDC3).

    PubMed

    Qi, Shiqian; O'Hayre, Morgan; Gutkind, J Silvio; Hurley, James H

    2014-02-21

    After protracted stimulation, the β2-adrenergic receptor and many other G-protein-coupled receptors are ubiquitinated and down-regulated. Arrestin-related domain-containing protein-3 (ARRDC3) has been proposed to recruit the ubiquitin ligase Nedd4 to the β2-adrenergic receptor. ARRDC3 contains two PPXY motifs that could potentially interact with any of the four WW domains of Nedd4. Here we dissect the interaction determinants. ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 μM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3. Structures of the uncomplexed and PPXY1-bound WW3 domain were determined at 1.1 and 1.7 Å resolution. The structures revealed conformational changes upon binding and the hydrogen bonding network in exquisite detail. Tight packing of ARRDC3 Val-352', part of a 310 helix at the C terminus of PPXY1, is important for high affinity binding to WW3. Although no single WW domain is strictly essential for the binding of Nedd4 and ARRDC3 expressed in HEK293 cells, high affinity binding of full-length ARRDC3 and Nedd4 is driven by the avid interaction of both PPXY motifs with either the WW2-WW3 or WW3-WW4 combinations, with Kd values as low as 300 nM.

  15. Multifunctionalities driven by ferroic domains

    NASA Astrophysics Data System (ADS)

    Yang, J. C.; Huang, Y. L.; He, Q.; Chu, Y. H.

    2014-08-01

    Considerable attention has been paid to ferroic systems in pursuit of advanced applications in past decades. Most recently, the emergence and development of multiferroics, which exhibit the coexistence of different ferroic natures, has offered a new route to create functionalities in the system. In this manuscript, we step from domain engineering to explore a roadmap for discovering intriguing phenomena and multifunctionalities driven by periodic domain patters. As-grown periodic domains, offering exotic order parameters, periodic local perturbations and the capability of tailoring local spin, charge, orbital and lattice degrees of freedom, are introduced as modeling templates for fundamental studies and novel applications. We discuss related significant findings on ferroic domain, nanoscopic domain walls, and conjunct heterostructures based on the well-organized domain patterns, and end with future prospects and challenges in the field.

  16. Structural and functional characterization of the CAP domain of pathogen-related yeast 1 (Pry1) protein

    NASA Astrophysics Data System (ADS)

    Darwiche, Rabih; Kelleher, Alan; Hudspeth, Elissa M.; Schneiter, Roger; Asojo, Oluwatoyin A.

    2016-06-01

    The production, crystal structure, and functional characterization of the C-terminal cysteine-rich secretory protein/antigen 5/pathogenesis related-1 (CAP) domain of pathogen-related yeast protein-1 (Pry1) from Saccharomyces cerevisiae is presented. The CAP domain of Pry1 (Pry1CAP) is functional in vivo as its expression restores cholesterol export to yeast mutants lacking endogenous Pry1 and Pry2. Recombinant Pry1CAP forms dimers in solution, is sufficient for in vitro cholesterol binding, and has comparable binding properties as full-length Pry1. Two crystal structures of Pry1CAP are reported, one with Mg2+ coordinated to the conserved CAP tetrad (His208, Glu215, Glu233 and His250) in spacegroup I41 and the other without divalent cations in spacegroup P6122. The latter structure contains four 1,4-dioxane molecules from the crystallization solution, one of which sits in the cholesterol binding site. Both structures reveal that the divalent cation and cholesterol binding sites are connected upon dimerization, providing a structural basis for the observed Mg2+-dependent sterol binding by Pry1.

  17. Protein domain organisation: adding order.

    PubMed

    Kummerfeld, Sarah K; Teichmann, Sarah A

    2009-01-29

    Domains are the building blocks of proteins. During evolution, they have been duplicated, fused and recombined, to produce proteins with novel structures and functions. Structural and genome-scale studies have shown that pairs or groups of domains observed together in a protein are almost always found in only one N to C terminal order and are the result of a single recombination event that has been propagated by duplication of the multi-domain unit. Previous studies of domain organisation have used graph theory to represent the co-occurrence of domains within proteins. We build on this approach by adding directionality to the graphs and connecting nodes based on their relative order in the protein. Most of the time, the linear order of domains is conserved. However, using the directed graph representation we have identified non-linear features of domain organization that are over-represented in genomes. Recognising these patterns and unravelling how they have arisen may allow us to understand the functional relationships between domains and understand how the protein repertoire has evolved. We identify groups of domains that are not linearly conserved, but instead have been shuffled during evolution so that they occur in multiple different orders. We consider 192 genomes across all three kingdoms of life and use domain and protein annotation to understand their functional significance. To identify these features and assess their statistical significance, we represent the linear order of domains in proteins as a directed graph and apply graph theoretical methods. We describe two higher-order patterns of domain organisation: clusters and bi-directionally associated domain pairs and explore their functional importance and phylogenetic conservation. Taking into account the order of domains, we have derived a novel picture of global protein organization. We found that all genomes have a higher than expected degree of clustering and more domain pairs in forward and

  18. Generic domain models in software engineering

    NASA Technical Reports Server (NTRS)

    Maiden, Neil

    1992-01-01

    This paper outlines three research directions related to domain-specific software development: (1) reuse of generic models for domain-specific software development; (2) empirical evidence to determine these generic models, namely elicitation of mental knowledge schema possessed by expert software developers; and (3) exploitation of generic domain models to assist modelling of specific applications. It focuses on knowledge acquisition for domain-specific software development, with emphasis on tool support for the most important phases of software development.

  19. Relations between Young Students' Strategic Behaviours, Domain-Specific Self-Concept, and Performance in a Problem-Solving Situation

    ERIC Educational Resources Information Center

    Dermitzaki, Irini; Leondari, Angeliki; Goudas, Marios

    2009-01-01

    This study aimed at investigating the relations between students' strategic behaviour during problem solving, task performance and domain-specific self-concept. A total of 167 first- and second-graders were individually examined in tasks involving cubes assembly and in academic self-concept in mathematics. Students' cognitive, metacognitive, and…

  20. How Working Memory Relates to Children's Reading Comprehension: The Importance of Domain-Specificity in Storage and Processing

    ERIC Educational Resources Information Center

    Nouwens, Suzan; Groen, Margriet A.; Verhoeven, Ludo

    2017-01-01

    Working memory is considered a well-established predictor of individual variation in reading comprehension in children and adults. However, how storage and processing capacities of working memory in both the phonological and semantic domain relate to reading comprehension is still unclear. In the current study, we investigated the contribution of…

  1. Semantic domain-specific functional integration for action-related vs. abstract concepts.

    PubMed

    Ghio, Marta; Tettamanti, Marco

    2010-03-01

    A central topic in cognitive neuroscience concerns the representation of concepts and the specific neural mechanisms that mediate conceptual knowledge. Recently proposed modal theories assert that concepts are grounded on the integration of multimodal, distributed representations. The aim of the present work is to complement the available neuropsychological and neuroimaging evidence suggesting partially segregated anatomo-functional correlates for concrete vs. abstract concepts, by directly testing the semantic domain-specific patterns of functional integration between language and modal semantic brain regions. We report evidence from a functional magnetic resonance imaging study, in which healthy participants listened to sentences with either an action-related (actions involving physical entities) or an abstract (no physical entities involved) content. We measured functional integration using dynamic causal modeling, and found that the left superior temporal gyrus was more strongly connected: (1) for action-related vs. abstract sentences, with the left-hemispheric action representation system, including sensorimotor areas; (2) for abstract vs. action-related sentences, with left infero-ventral frontal, temporal, and retrosplenial cingulate areas. A selective directionality effect was observed, with causal modulatory effects exerted by perisylvian language regions on peripheral modal areas, and not vice versa. The observed condition-specific modulatory effects are consistent with embodied and situated language processing theories, and indicate that linguistic areas promote a semantic content-specific reactivation of modal simulations by top-down mechanisms. Copyright 2008 Elsevier Inc. All rights reserved.

  2. Simplicity and Specificity in Language: Domain-General Biases Have Domain-Specific Effects

    PubMed Central

    Culbertson, Jennifer; Kirby, Simon

    2016-01-01

    The extent to which the linguistic system—its architecture, the representations it operates on, the constraints it is subject to—is specific to language has broad implications for cognitive science and its relation to evolutionary biology. Importantly, a given property of the linguistic system can be “specific” to the domain of language in several ways. For example, if the property evolved by natural selection under the pressure of the linguistic function it serves then the property is domain-specific in the sense that its design is tailored for language. Equally though, if that property evolved to serve a different function or if that property is domain-general, it may nevertheless interact with the linguistic system in a way that is unique. This gives a second sense in which a property can be thought of as specific to language. An evolutionary approach to the language faculty might at first blush appear to favor domain-specificity in the first sense, with individual properties of the language faculty being specifically linguistic adaptations. However, we argue that interactions between learning, culture, and biological evolution mean any domain-specific adaptations that evolve will take the form of weak biases rather than hard constraints. Turning to the latter sense of domain-specificity, we highlight a very general bias, simplicity, which operates widely in cognition and yet interacts with linguistic representations in domain-specific ways. PMID:26793132

  3. Supporting multiple domains in a single reuse repository

    NASA Technical Reports Server (NTRS)

    Eichmann, David A.

    1992-01-01

    Domain analysis typically results in the construction of a domain-specific repository. Such a repository imposes artificial boundaries on the sharing of similar assets between related domains. A lattice-based approach to repository modeling can preserve a reuser's domain specific view of the repository, while avoiding replication of commonly used assets and supporting a more general perspective on domain interrelationships.

  4. Persistent Complex Bereavement Disorder Symptom Domains Relate Differentially to PTSD and Depression: A Study of War-Exposed Bosnian Adolescents.

    PubMed

    Claycomb, Meredith A; Charak, Ruby; Kaplow, Julie; Layne, Christopher M; Pynoos, Robert; Elhai, Jon D

    2016-10-01

    Persistent Complex Bereavement Disorder (PCBD) is a newly proposed diagnosis placed in the Appendix of the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as an invitation for further research. To date, no studies have examined the dimensionality of PCBD or explored whether different PCBD criteria domains relate in similar, versus differential, ways to other psychological conditions common to war-exposed bereaved youth, including symptoms of Posttraumatic Stress Disorder (PTSD) and depression. We evaluated the dimensionality of proposed PCBD B and C symptom domains, and their respective relations with measures of PTSD and depression, in 1142 bereaved Bosnian adolescents exposed to the 1992-1995 Bosnian civil war. Instruments included the UCLA PTSD Reaction Index, the Depression Self-Rating Scale, and the UCLA Grief Screening Scale (a prototype measure of PCBD symptoms). We investigated potential differences in grief, PTSD, and depression scores as a function of cause of death. We then examined hypothesized differential relations between PCBD B and C symptom domain subscales and selected external correlates, specifically measures of depression and the four-factor emotional numbing model of PTSD. Results of both analyses provide preliminary evidence of a multidimensional structure for PCBD in this population, in that the PCBD Criterion C subscale score covaried more strongly with each of the four PTSD factors and with depression than did PCBD Criterion B. We conclude by discussing theoretical, methodological, clinical, and policy-related implications linked to the ongoing study of essential features of PCBD.

  5. Molecular recognition of the Tes LIM2-3 domains by the actin-related protein Arp7A.

    PubMed

    Boëda, Batiste; Knowles, Phillip P; Briggs, David C; Murray-Rust, Judith; Soriano, Erika; Garvalov, Boyan K; McDonald, Neil Q; Way, Michael

    2011-04-01

    Actin-related proteins (Arps) are a highly conserved family of proteins that have extensive sequence and structural similarity to actin. All characterized Arps are components of large multimeric complexes associated with chromatin or the cytoskeleton. In addition, the human genome encodes five conserved but largely uncharacterized "orphan" Arps, which appear to be mostly testis-specific. Here we show that Arp7A, which has 43% sequence identity with β-actin, forms a complex with the cytoskeletal proteins Tes and Mena in the subacrosomal layer of round spermatids. The N-terminal 65-residue extension to the actin-like fold of Arp7A interacts directly with Tes. The crystal structure of the 1-65(Arp7A)·LIM2-3(Tes)·EVH1(Mena) complex reveals that residues 28-49 of Arp7A contact the LIM2-3 domains of Tes. Two alanine residues from Arp7A that occupy equivalent apolar pockets in both LIM domains as well as an intervening GPAK linker that binds the LIM2-3 junction are critical for the Arp7A-Tes interaction. Equivalent occupied apolar pockets are also seen in the tandem LIM domain structures of LMO4 and Lhx3 bound to unrelated ligands. Our results indicate that apolar pocket interactions are a common feature of tandem LIM domain interactions, but ligand specificity is principally determined by the linker sequence.

  6. Optical coherence tomography-based decision making in exudative age-related macular degeneration: comparison of time- vs spectral-domain devices.

    PubMed

    Cukras, C; Wang, Y D; Meyerle, C B; Forooghian, F; Chew, E Y; Wong, W T

    2010-05-01

    To determine whether optical coherence tomography (OCT) device-type influences clinical grading of OCT imaging in the context of exudative age-related macular degeneration (AMD). Ninety-six paired OCT scans from 49 patients with active exudative AMD were obtained on both the time-domain Stratus OCT system and the spectral-domain Cirrus OCT system at the same visit. Three independent graders judged each scan for the presence of intraretinal fluid (IRF) or subretinal fluid (SRF). The degree of grader consensus was evaluated and the ability of the systems to detect the presence of disease activity was analysed. Cirrus OCT generated a higher degree of inter-grader consensus than Stratus OCT with higher intraclass correlation coefficients for all parameters analysed. A pair-wise comparison of Cirrus OCT with Stratus OCT systems revealed that Cirrus-based gradings more frequently reported the presence of SRF and IRF and detected overall neovascular activity at a higher rate (P<0.05) compared with Stratus-based gradings. The choice of time-domain (Stratus) vs spectra-domain (Cirrus) OCT systems has a measurable impact on clinical decision making in exudative AMD. Spectral-domain OCT systems may be able to generate more consensus in clinical interpretation and, in particular cases, detect disease activity not detected by time-domain systems. Clinical trials using OCT-based clinical evaluations of exudative AMD may need to account for these inter-system differences in planning and analysis.

  7. Optical Coherence Tomography-Based Decision Making in Exudative Age-related Macular Degeneration: Comparison of Time- versus Spectral-Domain Devices

    PubMed Central

    Cukras, Catherine; Wang, Yunqing D.; Meyerle, Catherine B.; Forooghian, Farzin; Chew, Emily Y.; Wong, Wai T.

    2010-01-01

    Purpose To determine if optical coherence tomography (OCT) device-type influences clinical grading of OCT imaging in the context of exudative age-related macular degeneration (AMD). Methods Ninety-six paired OCT scans from 49 patients with active exudative AMD were obtained on both the time-domain Stratus™ OCT system and the spectral-domain Cirrus™ OCT system at the same visit. Three independent graders judged each scan for the presence of intraretinal fluid (IRF) or subretinal fluid (SRF). The degree of grader consensus was evaluated and the ability of the systems to detect the presence of disease activity was analyzed. Results Cirrus™ OCT generated a higher degree of inter-grader consensus than Stratus OCT with higher intraclass correlation coefficients (ICC) for all parameters analyzed. A pair-wise comparison of Cirrus™ OCT to Stratus™ OCT systems revealed that Cirrus™-based gradings more frequently reported the presence of SRF and IRF and detected overall neovascular activity at a higher rate (p<0.05) compared to Stratus™-based gradings Conclusions The choice of time-domain (Stratus™) versus spectra-domain (Cirrus™) OCT systems has a measurable impact on clinical decision making in exudative AMD. Spectral-domain OCT systems may be able to generate more consensus in clinical interpretation and, in particular cases, detect disease activity not detected by time-domain systems. Clinical trials employing OCT-based clinical evaluations of exudative AMD may need to account for these inter-system differences in planning and analysis. PMID:19696804

  8. Enabling Interoperability in Heliophysical Domains

    NASA Astrophysics Data System (ADS)

    Bentley, Robert

    2013-04-01

    There are many aspects of science in the Solar System that are overlapping - phenomena observed in one domain can have effects in other domains. However, there are many problems related to exploiting the data in cross-disciplinary studies because of lack of interoperability of the data and services. The CASSIS project is a Coordination Action funded under FP7 that has the objective of improving the interoperability of data and services related Solar System science. CASSIS has been investigating how the data could be made more accessible with some relatively minor changes to the observational metadata. The project has been looking at the services that are used within the domain and determining whether they are interoperable with each other and if not what would be required make them so. It has also been examining all types of metadata that are used when identifying and using observations and trying to make them more compliant with techniques and standards developed by bodies such as the International Virtual Observatory Alliance (IVOA). Many of the lessons that are being learnt in the study are applicable to domains that go beyond those directly involved in heliophysics. Adopting some simple standards related to the design of the services interfaces and metadata that are used would make it much easier to investigate interdisciplinary science topics. We will report on our finding and describe a roadmap for the future. For more information about CASSIS, please visit the project Web site on cassis-vo.eu

  9. Formal Language Design in the Context of Domain Engineering

    DTIC Science & Technology

    2000-03-28

    73 Related Work 75 5.1 Feature oriented domain analysis ( FODA ) 75 5.2 Organizational domain modeling (ODM) 76 5.3 Domain-Specific Software...However there are only a few that are well defined and used repeatedly in practice. These include: Feature oriented domain analysis ( FODA ), Organizational...Feature oriented domain analysis ( FODA ) Feature oriented domain analysis ( FODA ) is a domain analysis method being researched and applied by the SEI

  10. Domain-specific and domain-general constraints on word and sequence learning.

    PubMed

    Archibald, Lisa M D; Joanisse, Marc F

    2013-02-01

    The relative influences of language-related and memory-related constraints on the learning of novel words and sequences were examined by comparing individual differences in performance of children with and without specific deficits in either language or working memory. Children recalled lists of words in a Hebbian learning protocol in which occasional lists repeated, yielding improved recall over the course of the task on the repeated lists. The task involved presentation of pictures of common nouns followed immediately by equivalent presentations of the spoken names. The same participants also completed a paired-associate learning task involving word-picture and nonword-picture pairs. Hebbian learning was observed for all groups. Domain-general working memory constrained immediate recall, whereas language abilities impacted recall in the auditory modality only. In addition, working memory constrained paired-associate learning generally, whereas language abilities disproportionately impacted novel word learning. Overall, all of the learning tasks were highly correlated with domain-general working memory. The learning of nonwords was additionally related to general intelligence, phonological short-term memory, language abilities, and implicit learning. The results suggest that distinct associations between language- and memory-related mechanisms support learning of familiar and unfamiliar phonological forms and sequences.

  11. [Analysis of time domain and frequency domain heart rate variability in fighter pilot before and after upright tilt].

    PubMed

    Wang, L; Wu, L; Ji, G; Zhang, X; Chen, T; Wang, L

    1998-12-01

    Effects of upright tilt on mechanism of autonomic nervous regulation of cardiovascular system and characteristics of heart rate variability (HRV) were observed in sixty healthy male pilots. Relation between time domain and frequency domain indexes of short-time HRV (5 min) were analysed before and after upright tilt. The results showed that there are significant difference in short time HRV parameters before and after upright tilt. Significant relationship was formed between time domain and frequency domain indexes of HRV. It suggests that time domain and frequency domain HRV analysis is capable of revealing certain informations embedded in a short series of R-R intervals and can help to evaluate the status of autonomic regulation of cardiovascular function in pilots.

  12. Time Domain and Frequency Domain Deterministic Channel Modeling for Tunnel/Mining Environments.

    PubMed

    Zhou, Chenming; Jacksha, Ronald; Yan, Lincan; Reyes, Miguel; Kovalchik, Peter

    2017-01-01

    Understanding wireless channels in complex mining environments is critical for designing optimized wireless systems operated in these environments. In this paper, we propose two physics-based, deterministic ultra-wideband (UWB) channel models for characterizing wireless channels in mining/tunnel environments - one in the time domain and the other in the frequency domain. For the time domain model, a general Channel Impulse Response (CIR) is derived and the result is expressed in the classic UWB tapped delay line model. The derived time domain channel model takes into account major propagation controlling factors including tunnel or entry dimensions, frequency, polarization, electrical properties of the four tunnel walls, and transmitter and receiver locations. For the frequency domain model, a complex channel transfer function is derived analytically. Based on the proposed physics-based deterministic channel models, channel parameters such as delay spread, multipath component number, and angular spread are analyzed. It is found that, despite the presence of heavy multipath, both channel delay spread and angular spread for tunnel environments are relatively smaller compared to that of typical indoor environments. The results and findings in this paper have application in the design and deployment of wireless systems in underground mining environments.

  13. A Novel Domain Assembly Routine for Creating Full-Length Models of Membrane Proteins from Known Domain Structures.

    PubMed

    Koehler Leman, Julia; Bonneau, Richard

    2018-04-03

    Membrane proteins composed of soluble and membrane domains are often studied one domain at a time. However, to understand the biological function of entire protein systems and their interactions with each other and drugs, knowledge of full-length structures or models is required. Although few computational methods exist that could potentially be used to model full-length constructs of membrane proteins, none of these methods are perfectly suited for the problem at hand. Existing methods require an interface or knowledge of the relative orientations of the domains or are not designed for domain assembly, and none of them are developed for membrane proteins. Here we describe the first domain assembly protocol specifically designed for membrane proteins that assembles intra- and extracellular soluble domains and the transmembrane domain into models of the full-length membrane protein. Our protocol does not require an interface between the domains and samples possible domain orientations based on backbone dihedrals in the flexible linker regions, created via fragment insertion, while keeping the transmembrane domain fixed in the membrane. For five examples tested, our method mp_domain_assembly, implemented in RosettaMP, samples domain orientations close to the known structure and is best used in conjunction with experimental data to reduce the conformational search space.

  14. The home literacy and numeracy environment in preschool: Cross-domain relations of parent-child practices and child outcomes.

    PubMed

    Napoli, Amy R; Purpura, David J

    2018-02-01

    There is a growing body of evidence indicating that home literacy and numeracy environments are predictive of children's literacy and numeracy skills within their respective domains. However, there is limited research on the relations between the home literacy environment and numeracy outcomes and between the home numeracy environment and literacy outcomes. Specifically, there is limited information on relations between the home numeracy environment and specific literacy outcomes (e.g., vocabulary). The purpose of the current study was to investigate the relations of the home literacy and numeracy environments to children's literacy and numeracy outcomes both within and across domains. Participants were 114 preschool children and their parents. Children ranged in age from 3.01 to 5.17 years (M = 4.09 years) and were 54% female and 72% Caucasian. Parents reported the frequency of parent-child literacy (code-related practices and storybook reading) and numeracy practices. Children were assessed in the fall and spring of their preschool year on their literacy (definitional vocabulary, phonological awareness, and print knowledge) and numeracy skills. Four mixed-effects regression analyses were conducted to predict each of the child outcomes. Results indicate that although code-related literacy practices and storybook reading were not broadly predictive of children's literacy and numeracy outcomes, the home numeracy environment was predictive of numeracy and definitional vocabulary outcomes. These findings demonstrate a relation between the home numeracy environment and children's language development and contribute to the growing body of research indicating the important relations between early numeracy and language development. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Issues Related to the Construction of a Purpose-Built Domain-Specific Word Corpus

    ERIC Educational Resources Information Center

    Thomas, Lisa; Pfister, H. Peter; Peterson, Peter

    2004-01-01

    There is growing interest in the use of semantic collections in order to identify and analyse domain knowledge. This paper describes some technical issues to consider when contemplating research which incorporates small-to-medium domain-specific word sets. The purpose of the corpus construction described was to provide an external word collection…

  16. Requirements analysis, domain knowledge, and design

    NASA Technical Reports Server (NTRS)

    Potts, Colin

    1988-01-01

    Two improvements to current requirements analysis practices are suggested: domain modeling, and the systematic application of analysis heuristics. Domain modeling is the representation of relevant application knowledge prior to requirements specification. Artificial intelligence techniques may eventually be applicable for domain modeling. In the short term, however, restricted domain modeling techniques, such as that in JSD, will still be of practical benefit. Analysis heuristics are standard patterns of reasoning about the requirements. They usually generate questions of clarification or issues relating to completeness. Analysis heuristics can be represented and therefore systematically applied in an issue-based framework. This is illustrated by an issue-based analysis of JSD's domain modeling and functional specification heuristics. They are discussed in the context of the preliminary design of simple embedded systems.

  17. Emergence of novel domains in proteins

    PubMed Central

    2013-01-01

    Background Proteins are composed of a combination of discrete, well-defined, sequence domains, associated with specific functions that have arisen at different times during evolutionary history. The emergence of novel domains is related to protein functional diversification and adaptation. But currently little is known about how novel domains arise and how they subsequently evolve. Results To gain insights into the impact of recently emerged domains in protein evolution we have identified all human young protein domains that have emerged in approximately the past 550 million years. We have classified them into vertebrate-specific and mammalian-specific groups, and compared them to older domains. We have found 426 different annotated young domains, totalling 995 domain occurrences, which represent about 12.3% of all human domains. We have observed that 61.3% of them arose in newly formed genes, while the remaining 38.7% are found combined with older domains, and have very likely emerged in the context of a previously existing protein. Young domains are preferentially located at the N-terminus of the protein, indicating that, at least in vertebrates, novel functional sequences often emerge there. Furthermore, young domains show significantly higher non-synonymous to synonymous substitution rates than older domains using human and mouse orthologous sequence comparisons. This is also true when we compare young and old domains located in the same protein, suggesting that recently arisen domains tend to evolve in a less constrained manner than older domains. Conclusions We conclude that proteins tend to gain domains over time, becoming progressively longer. We show that many proteins are made of domains of different age, and that the fastest evolving parts correspond to the domains that have been acquired more recently. PMID:23425224

  18. Understanding domains of health-related quality of life concerns of Singapore Chinese patients with advanced cancer: a qualitative analysis.

    PubMed

    Lee, G L; Pang, G S Y; Akhileswaran, R; Ow, M Y L; Fan, G K T; Wong, C C F; Wee, H L; Cheung, Y B

    2016-03-01

    Quality of life concerns in patients with advanced diseases might be different from other patients and are shaped by sociocultural context. The objective of this qualitative study was to identify domains and themes of health-related quality of life (HRQoL) that Chinese patients with advanced cancer in Singapore considered relevant and important. English- and Chinese-speaking patients with advanced solid cancer were recruited from a tertiary cancer center and a community-based hospice for in-depth interview or focused group discussion. Thematic analysis was used to identify subthemes, themes, and domains from the transcripts. Forty-six ethnic Chinese (aged 26-86, 48% male) participated in the study. Six domains of HRQoL concerns were identified: pain and suffering, physical health, social health, mental health, financial well-being, and spiritual health. Pain and suffering are not limited to the physical domain, reflecting the multidimensional nature of this concept. Pain and suffering must also be understood within the cultural context. Healthcare relations (i.e., social health), existential well-being and religious well-being (i.e., spiritual health), and suffering (i.e., pain and suffering) are not fully captured in the existing HRQoL instruments. In addition, financial issues and the practice of secrecy in interpersonal relationships emerged as unique features possibly arising from our sociocultural context and healthcare financing landscape. Socioculturally specific issues not measured by the existing HRQoL instruments for use in patients with advanced cancers or terminal diseases were found in our study. These are non-physical pain and suffering, meaning of illness, meaning of death, financial issues, and practice of secrecy in interpersonal relationships.

  19. Method of assessing the state of a rolling bearing based on the relative compensation distance of multiple-domain features and locally linear embedding

    NASA Astrophysics Data System (ADS)

    Kang, Shouqiang; Ma, Danyang; Wang, Yujing; Lan, Chaofeng; Chen, Qingguo; Mikulovich, V. I.

    2017-03-01

    To effectively assess different fault locations and different degrees of performance degradation of a rolling bearing with a unified assessment index, a novel state assessment method based on the relative compensation distance of multiple-domain features and locally linear embedding is proposed. First, for a single-sample signal, time-domain and frequency-domain indexes can be calculated for the original vibration signal and each sensitive intrinsic mode function obtained by improved ensemble empirical mode decomposition, and the singular values of the sensitive intrinsic mode function matrix can be extracted by singular value decomposition to construct a high-dimensional hybrid-domain feature vector. Second, a feature matrix can be constructed by arranging each feature vector of multiple samples, the dimensions of each row vector of the feature matrix can be reduced by the locally linear embedding algorithm, and the compensation distance of each fault state of the rolling bearing can be calculated using the support vector machine. Finally, the relative distance between different fault locations and different degrees of performance degradation and the normal-state optimal classification surface can be compensated, and on the basis of the proposed relative compensation distance, the assessment model can be constructed and an assessment curve drawn. Experimental results show that the proposed method can effectively assess different fault locations and different degrees of performance degradation of the rolling bearing under certain conditions.

  20. The SPOR Domain, a Widely Conserved Peptidoglycan Binding Domain That Targets Proteins to the Site of Cell Division.

    PubMed

    Yahashiri, Atsushi; Jorgenson, Matthew A; Weiss, David S

    2017-07-15

    Sporulation-related repeat (SPOR) domains are small peptidoglycan (PG) binding domains found in thousands of bacterial proteins. The name "SPOR domain" stems from the fact that several early examples came from proteins involved in sporulation, but SPOR domain proteins are quite diverse and contribute to a variety of processes that involve remodeling of the PG sacculus, especially with respect to cell division. SPOR domains target proteins to the division site by binding to regions of PG devoid of stem peptides ("denuded" glycans), which in turn are enriched in septal PG by the intense, localized activity of cell wall amidases involved in daughter cell separation. This targeting mechanism sets SPOR domain proteins apart from most other septal ring proteins, which localize via protein-protein interactions. In addition to SPOR domains, bacteria contain several other PG-binding domains that can exploit features of the cell wall to target proteins to specific subcellular sites. Copyright © 2017 American Society for Microbiology.

  1. Structure of the USP15 N-terminal domains: a β-hairpin mediates close association between the DUSP and UBL domains.

    PubMed

    Harper, Stephen; Besong, Tabot M D; Emsley, Jonas; Scott, David J; Dreveny, Ingrid

    2011-09-20

    Ubiquitin specific protease 15 (USP15) functions in COP9 signalosome mediated regulation of protein degradation and cellular signaling through catalyzing the ubiquitin deconjugation reaction of a discrete number of substrates. It influences the stability of adenomatous polyposis coli, IκBα, caspase-3, and the human papillomavirus type 16 E6. USP15 forms a subfamily with USP4 and USP11 related through a shared presence of N-terminal "domain present in ubiquitin specific proteases" (DUSP) and "ubiquitin-like" (UBL) domains (DU subfamily). Here we report the 1.5 Å resolution crystal structure of the human USP15 N-terminal domains revealing a 80 Å elongated arrangement with the DU domains aligned in tandem. This architecture is generated through formation of a defined interface that is dominated by an intervening β-hairpin structure (DU finger) that engages in an intricate hydrogen-bonding network between the domains. The UBL domain is closely related to ubiquitin among β-grasp folds but is characterized by the presence of longer loop regions and different surface characteristics, indicating that this domain is unlikely to act as ubiquitin mimic. Comparison with the related murine USP4 DUSP-UBL crystal structure reveals that the main DU interdomain contacts are conserved. Analytical ultracentrifugation, small-angle X-ray scattering, and gel filtration experiments revealed that USP15 DU is monomeric in solution. Our data provide a framework to advance study of the structure and function of the DU subfamily. © 2011 American Chemical Society

  2. Time Domain and Frequency Domain Deterministic Channel Modeling for Tunnel/Mining Environments

    PubMed Central

    Zhou, Chenming; Jacksha, Ronald; Yan, Lincan; Reyes, Miguel; Kovalchik, Peter

    2018-01-01

    Understanding wireless channels in complex mining environments is critical for designing optimized wireless systems operated in these environments. In this paper, we propose two physics-based, deterministic ultra-wideband (UWB) channel models for characterizing wireless channels in mining/tunnel environments — one in the time domain and the other in the frequency domain. For the time domain model, a general Channel Impulse Response (CIR) is derived and the result is expressed in the classic UWB tapped delay line model. The derived time domain channel model takes into account major propagation controlling factors including tunnel or entry dimensions, frequency, polarization, electrical properties of the four tunnel walls, and transmitter and receiver locations. For the frequency domain model, a complex channel transfer function is derived analytically. Based on the proposed physics-based deterministic channel models, channel parameters such as delay spread, multipath component number, and angular spread are analyzed. It is found that, despite the presence of heavy multipath, both channel delay spread and angular spread for tunnel environments are relatively smaller compared to that of typical indoor environments. The results and findings in this paper have application in the design and deployment of wireless systems in underground mining environments.† PMID:29457801

  3. Cohesin and related coiled-coil domain-containing complexes physically and functionally connect the dots across the genome

    PubMed Central

    Poon, Betty P.K

    2011-01-01

    Interactions between genetic regions located across the genome maintain its three-dimensional organization and function. Recent studies point to key roles for a set of coiled-coil domain-containing complexes (cohibin, cohesin, condensin and monopolin) and related factors in the regulation of DNA-DNA connections across the genome. These connections are critical to replication, recombination, gene expression as well as chromosome segregation. PMID:21822055

  4. Examining Complexity across Domains: Relating Subjective and Objective Measures of Affective Environmental Scenes, Paintings and Music

    PubMed Central

    Marin, Manuela M.; Leder, Helmut

    2013-01-01

    Subjective complexity has been found to be related to hedonic measures of preference, pleasantness and beauty, but there is no consensus about the nature of this relationship in the visual and musical domains. Moreover, the affective content of stimuli has been largely neglected so far in the study of complexity but is crucial in many everyday contexts and in aesthetic experiences. We thus propose a cross-domain approach that acknowledges the multidimensional nature of complexity and that uses a wide range of objective complexity measures combined with subjective ratings. In four experiments, we employed pictures of affective environmental scenes, representational paintings, and Romantic solo and chamber music excerpts. Stimuli were pre-selected to vary in emotional content (pleasantness and arousal) and complexity (low versus high number of elements). For each set of stimuli, in a between-subjects design, ratings of familiarity, complexity, pleasantness and arousal were obtained for a presentation time of 25 s from 152 participants. In line with Berlyne’s collative-motivation model, statistical analyses controlling for familiarity revealed a positive relationship between subjective complexity and arousal, and the highest correlations were observed for musical stimuli. Evidence for a mediating role of arousal in the complexity-pleasantness relationship was demonstrated in all experiments, but was only significant for females with regard to music. The direction and strength of the linear relationship between complexity and pleasantness depended on the stimulus type and gender. For environmental scenes, the root mean square contrast measures and measures of compressed file size correlated best with subjective complexity, whereas only edge detection based on phase congruency yielded equivalent results for representational paintings. Measures of compressed file size and event density also showed positive correlations with complexity and arousal in music, which is

  5. Examining complexity across domains: relating subjective and objective measures of affective environmental scenes, paintings and music.

    PubMed

    Marin, Manuela M; Leder, Helmut

    2013-01-01

    Subjective complexity has been found to be related to hedonic measures of preference, pleasantness and beauty, but there is no consensus about the nature of this relationship in the visual and musical domains. Moreover, the affective content of stimuli has been largely neglected so far in the study of complexity but is crucial in many everyday contexts and in aesthetic experiences. We thus propose a cross-domain approach that acknowledges the multidimensional nature of complexity and that uses a wide range of objective complexity measures combined with subjective ratings. In four experiments, we employed pictures of affective environmental scenes, representational paintings, and Romantic solo and chamber music excerpts. Stimuli were pre-selected to vary in emotional content (pleasantness and arousal) and complexity (low versus high number of elements). For each set of stimuli, in a between-subjects design, ratings of familiarity, complexity, pleasantness and arousal were obtained for a presentation time of 25 s from 152 participants. In line with Berlyne's collative-motivation model, statistical analyses controlling for familiarity revealed a positive relationship between subjective complexity and arousal, and the highest correlations were observed for musical stimuli. Evidence for a mediating role of arousal in the complexity-pleasantness relationship was demonstrated in all experiments, but was only significant for females with regard to music. The direction and strength of the linear relationship between complexity and pleasantness depended on the stimulus type and gender. For environmental scenes, the root mean square contrast measures and measures of compressed file size correlated best with subjective complexity, whereas only edge detection based on phase congruency yielded equivalent results for representational paintings. Measures of compressed file size and event density also showed positive correlations with complexity and arousal in music, which is

  6. The C-Terminal Domain of the Virulence Factor MgtC Is a Divergent ACT Domain

    PubMed Central

    Yang, Yinshan; Labesse, Gilles; Carrère-Kremer, Séverine; Esteves, Kevin; Kremer, Laurent

    2012-01-01

    MgtC is a virulence factor of unknown function important for survival inside macrophages in several intracellular bacterial pathogens, including Mycobacterium tuberculosis. It is also involved in adaptation to Mg2+ deprivation, but previous work suggested that MgtC is not a Mg2+ transporter. In this study, we demonstrated that the amount of the M. tuberculosis MgtC protein is not significantly increased by Mg2+ deprivation. Members of the MgtC protein family share a conserved membrane N-terminal domain and a more divergent cytoplasmic C-terminal domain. To get insights into MgtC functional and structural organization, we have determined the nuclear magnetic resonance (NMR) structure of the C-terminal domain of M. tuberculosis MgtC. This structure is not affected by the Mg2+ concentration, indicating that it does not bind Mg2+. The structure of the C-terminal domain forms a βαββαβ fold found in small molecule binding domains called ACT domains. However, the M. tuberculosis MgtC ACT domain differs from canonical ACT domains because it appears to lack the ability to dimerize and to bind small molecules. We have shown, using a bacterial two-hybrid system, that the M. tuberculosis MgtC protein can dimerize and that the C-terminal domain somehow facilitates this dimerization. Taken together, these results indicate that M. tuberculosis MgtC does not have an intrinsic function related to Mg2+ uptake or binding but could act as a regulatory factor based on protein-protein interaction that could be facilitated by its ACT domain. PMID:22984256

  7. Identification of Scoliosis Research Society-22r Health-Related Quality of Life questionnaire domains using factor analysis methodology.

    PubMed

    Lai, Sue-Min; Asher, Marc A; Burton, Douglas C; Carlson, Brandon B

    2010-05-20

    Cross-sectional mail questionnaire. Examination of the underlying construct validity of the Scoliosis Research Society-22r (SRS-22r) Health-Related Quality of Life (HRQoL) Questionnaire using factor analysis. The original SRS-24 HRQoL questionnaire has undergone a series of modifications in an effort to further improve its psychometric properties and validate its use in patients from 10 years of age until well into adulthood. The SRS-22r questionnaire is the result of this effort. To date, the underlying construct validity of the original English version has not been analyzed by factor analysis. A questionnaire including all questions on the SRS-24, -23, -22, and -22r questionnaires (49 total questions) was mailed to a consecutive series of 235 patients who had received primary posterior or anterior instrumentation and arthrodesis. Domain structure of the SRS-22r questions was analyzed using iterated principal factor analysis with orthogonal rotation. One hundred twenty-one (51%) of the patients, age 23.34 +/- 4.52 years (range, 14.16-34.57 years), returned the questionnaire at 8.63 +/- 4.00 years (range, 2.32-15.94 years) following surgery. Factor analysis using all 22 questions resulted in 3 factors with many shared items because of significant collinearity of the satisfaction/dissatisfaction with management questions with the others. After 18 iterations, factor analysis using the 20 nonmanagement questions revealed 4 factors that explained 98% of the variance. These factors parallel the assigned domains of the SRS-22r questionnaire. Three questions (2 self-image and 1 function) were identified that had high loading in 2 factors. However, internal consistency was best when 2 of the questions (1 self-image and 1 function) were retained in their assigned SRS-22r domains and the third decreased self-image internal consistency by only 0.01%. The internal consistencies (Cronbach alpha) of the assigned SRS-22r nonmanagement domains were excellent or very good: function

  8. Structure of a double-domain phosphagen kinase reveals an asymmetric arrangement of the tandem domains.

    PubMed

    Wang, Zhiming; Qiao, Zhu; Ye, Sheng; Zhang, Rongguang

    2015-04-01

    Tandem duplications and fusions of single genes have led to magnificent expansions in the divergence of protein structures and functions over evolutionary timescales. One of the possible results is polydomain enzymes with interdomain cooperativities, few examples of which have been structurally characterized at the full-length level to explore their innate synergistic mechanisms. This work reports the crystal structures of a double-domain phosphagen kinase in both apo and ligand-bound states, revealing a novel asymmetric L-shaped arrangement of the two domains. Unexpectedly, the interdomain connections are not based on a flexible hinge linker but on a rigid secondary-structure element: a long α-helix that tethers the tandem domains in relatively fixed positions. Besides the connective helix, the two domains also contact each other directly and form an interdomain interface in which hydrogen bonds and hydrophobic interactions further stabilize the L-shaped domain arrangement. Molecular-dynamics simulations show that the interface is generally stable, suggesting that the asymmetric domain arrangement crystallographically observed in the present study is not a conformational state simply restrained by crystal-packing forces. It is possible that the asymmetrically arranged tandem domains could provide a structural basis for further studies of the interdomain synergy.

  9. Stable spin domains in a nondegenerate ultracold gas

    NASA Astrophysics Data System (ADS)

    Graham, S. D.; Niroomand, D.; Ragan, R. J.; McGuirk, J. M.

    2018-05-01

    We study the stability of two-domain spin structures in an ultracold gas of magnetically trapped 87Rb atoms above quantum degeneracy. Adding a small effective magnetic field gradient stabilizes the domains via coherent collective spin rotation effects, despite negligibly perturbing the potential energy relative to the thermal energy. We demonstrate that domain stabilization is accomplished through decoupling the dynamics of longitudinal magnetization, which remains in time-independent domains, from transverse magnetization, which undergoes a purely transverse spin wave trapped within the domain wall. We explore the effect of temperature and density on the steady-state domains, and compare our results to a hydrodynamic solution to a quantum Boltzmann equation.

  10. XML Based Markup Languages for Specific Domains

    NASA Astrophysics Data System (ADS)

    Varde, Aparna; Rundensteiner, Elke; Fahrenholz, Sally

    A challenging area in web based support systems is the study of human activities in connection with the web, especially with reference to certain domains. This includes capturing human reasoning in information retrieval, facilitating the exchange of domain-specific knowledge through a common platform and developing tools for the analysis of data on the web from a domain expert's angle. Among the techniques and standards related to such work, we have XML, the eXtensible Markup Language. This serves as a medium of communication for storing and publishing textual, numeric and other forms of data seamlessly. XML tag sets are such that they preserve semantics and simplify the understanding of stored information by users. Often domain-specific markup languages are designed using XML, with a user-centric perspective. Standardization bodies and research communities may extend these to include additional semantics of areas within and related to the domain. This chapter outlines the issues to be considered in developing domain-specific markup languages: the motivation for development, the semantic considerations, the syntactic constraints and other relevant aspects, especially taking into account human factors. Illustrating examples are provided from domains such as Medicine, Finance and Materials Science. Particular emphasis in these examples is on the Materials Markup Language MatML and the semantics of one of its areas, namely, the Heat Treating of Materials. The focus of this chapter, however, is not the design of one particular language but rather the generic issues concerning the development of domain-specific markup languages.

  11. Implementation of Instrument Based on Eight Health Related Quality of Life Domains for Measuring of Willingness to Pay for Psoriasis Treatment.

    PubMed

    Dobrev, Hristo P; Atanasov, Nikolay G; Dimitrova, Donka D

    2017-09-01

    Psoriasis vulgaris (PsV) is a chronic skin condition that has a major impact on health-related quality of life (HRQOL). To determine the individual burden of PsV on HRQOL using willingness to pay (WTP) instrument. Fifty-one consecutive PsV patients were asked to evaluate their overall health and psoriasis affected health by visual analogue scale (VAS), and interviewed on 8 domains (physical, emotional, sleep, work, social, self-care, intimacy, and concentration) of HRQOL and WTP for a hypothetical cure in each domain. Two additional questions proposing 6 alternatives for therapy were also asked. The analysis is performed with descriptive and frequency statistics, Mann-Whitney and Kruskal-Wallis tests. The domains ranked highly were: physical comfort (90%), social comfort (77%), emotional health (75%) and work (53%). The following tendencies concerning WTP for top four impacted domains were found: the median WTP were the highest in the top impacted domains; the younger patients were willing to pay more than the older ones; the highest median WTP amounts appear in the lowest income group; the highest median WTP is associated with smaller psoriasis affected health VAS scores. The largest proportion and number of patients (37.3%, n=19) stated preferences for the systemic therapy. The second preferred choice was the thalassotherapy (29.4%, n=15). The utility and reliability of the instrument based on the assessment of WTP stated preferences for 8 domains of HRQOL for evaluation the individual burden of psoriasis were strongly supported.

  12. Frequency domain FIR and IIR adaptive filters

    NASA Technical Reports Server (NTRS)

    Lynn, D. W.

    1990-01-01

    A discussion of the LMS adaptive filter relating to its convergence characteristics and the problems associated with disparate eigenvalues is presented. This is used to introduce the concept of proportional convergence. An approach is used to analyze the convergence characteristics of block frequency-domain adaptive filters. This leads to a development showing how the frequency-domain FIR adaptive filter is easily modified to provide proportional convergence. These ideas are extended to a block frequency-domain IIR adaptive filter and the idea of proportional convergence is applied. Experimental results illustrating proportional convergence in both FIR and IIR frequency-domain block adaptive filters is presented.

  13. Domains of awareness in schizophrenia.

    PubMed

    Gilleen, J; Greenwood, K; David, A S

    2011-01-01

    Patients with schizophrenia are often characterized as lacking insight or awareness into their illness and symptoms, yet despite considerable research, we still lack a full understanding of the factors involved in causing poor awareness. Within schizophrenia, there has been shown to be a fractionation across dimensions of awareness into mental illness: of being ill, of symptoms, and of treatment compliance. Recently, attention has turned to evidence of a fractionation between awareness of illness and of cognitive impairments and functioning. The current study investigated the degree of fractionation across a broad range of domains of function in schizophrenia and how each domain may be associated with neuropsychological functioning, clinical, mood, and demographic variables. Thirty-one mostly chronic stable patients with schizophrenia completed a battery of neuropsychological tests and measures of psychopathology, including mood. Cognitive insight and awareness of illness, symptoms, memory, and behavioral functioning were also measured. Insight and awareness were assessed using a combination of semistructured interview, observer-rated, self-rated, and objective measures, and included measures of the discrepancy between carer and self-ratings of impairment. Results revealed that awareness of functioning in each domain was largely independent and that awareness in each domain was predicted by different factors. Insight into symptoms was relatively poor while insight into cognitive deficits was preserved. Relative to neuropsychological variables, cognitive insight, comprising self-certainty and self-reflexivity, was a greater predictor of awareness. In conclusion, awareness is multiply fractionated and multiply determined. Therapeutic interventions could, therefore, produce beneficial changes within specific domains of awareness.

  14. Domains of Awareness in Schizophrenia

    PubMed Central

    Gilleen, J.; Greenwood, K.; David, A. S.

    2011-01-01

    Patients with schizophrenia are often characterized as lacking insight or awareness into their illness and symptoms, yet despite considerable research, we still lack a full understanding of the factors involved in causing poor awareness. Within schizophrenia, there has been shown to be a fractionation across dimensions of awareness into mental illness: of being ill, of symptoms, and of treatment compliance. Recently, attention has turned to evidence of a fractionation between awareness of illness and of cognitive impairments and functioning. The current study investigated the degree of fractionation across a broad range of domains of function in schizophrenia and how each domain may be associated with neuropsychological functioning, clinical, mood, and demographic variables. Thirty-one mostly chronic stable patients with schizophrenia completed a battery of neuropsychological tests and measures of psychopathology, including mood. Cognitive insight and awareness of illness, symptoms, memory, and behavioral functioning were also measured. Insight and awareness were assessed using a combination of semistructured interview, observer-rated, self-rated, and objective measures, and included measures of the discrepancy between carer and self-ratings of impairment. Results revealed that awareness of functioning in each domain was largely independent and that awareness in each domain was predicted by different factors. Insight into symptoms was relatively poor while insight into cognitive deficits was preserved. Relative to neuropsychological variables, cognitive insight, comprising self-certainty and self-reflexivity, was a greater predictor of awareness. In conclusion, awareness is multiply fractionated and multiply determined. Therapeutic interventions could, therefore, produce beneficial changes within specific domains of awareness. PMID:20851850

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

    PubMed

    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.

  16. Structural diversity of domain superfamilies in the CATH database.

    PubMed

    Reeves, Gabrielle A; Dallman, Timothy J; Redfern, Oliver C; Akpor, Adrian; Orengo, Christine A

    2006-07-14

    The CATH database of domain structures has been used to explore the structural variation of homologous domains in 294 well populated domain structure superfamilies, each containing at least three sequence diverse relatives. Our analyses confirm some previously detected trends relating sequence divergence to structural variation but for a much larger dataset and in some superfamilies the new data reveal exceptional structural variation. Use of a new algorithm (2DSEC) to analyse variability in secondary structure compositions across a superfamily sheds new light on how structures evolve. 2DSEC detects inserted secondary structures that embellish the core of conserved secondary structures found throughout the superfamily. Analysis showed that for 56% of highly populated superfamilies (>9 sequence diverse relatives), there are twofold or more increases in the numbers of secondary structures in some relatives. In some families fivefold increases occur, sometimes modifying the fold of the domain. Manual inspection of secondary structure insertions or embellishments in 48 particularly variable superfamilies revealed that although these insertions were usually discontiguous in the sequence they were often co-located in 3D resulting in a larger structural motif that often modified the geometry of the active site or the surface conformation promoting diverse domain partnerships and protein interactions. These observations, supported by automatic analysis of all well populated CATH families, suggest that accretion of small secondary structure insertions may provide a simple mechanism for evolving new functions in diverse relatives. Some layered domain architectures (e.g. mainly-beta and alpha-beta sandwiches) that recur highly in the genomes more frequently exploit these types of embellishments to modify function. In these architectures, aggregation occurs most often at the edges, top or bottom of the beta-sheets. Information on structural variability across domain

  17. Cognitive regulation alters social and dietary choice by changing attribute representations in domain-general and domain-specific brain circuits

    PubMed Central

    Hutcherson, Cendri A

    2018-01-01

    Are some people generally more successful using cognitive regulation or does it depend on the choice domain? Why? We combined behavioral computational modeling and multivariate decoding of fMRI responses to identify neural loci of regulation-related shifts in value representations across goals and domains (dietary or altruistic choice). Surprisingly, regulatory goals did not alter integrative value representations in the ventromedial prefrontal cortex, which represented all choice-relevant attributes across goals and domains. Instead, the dorsolateral prefrontal cortex (DLPFC) flexibly encoded goal-consistent values and predicted regulatory success for the majority of choice-relevant attributes, using attribute-specific neural codes. We also identified domain-specific exceptions: goal-dependent encoding of prosocial attributes localized to precuneus and temporo-parietal junction (not DLPFC). Our results suggest that cognitive regulation operated by changing specific attribute representations (not integrated values). Evidence of domain-general and domain-specific neural loci reveals important divisions of labor, explaining when and why regulatory success generalizes (or doesn’t) across contexts and domains. PMID:29813018

  18. Developmental Change in the Influence of Domain-General Abilities and Domain-Specific Knowledge on Mathematics Achievement: An Eight-Year Longitudinal Study

    PubMed Central

    Geary, David C.; Nicholas, Alan; Li, Yaoran; Sun, Jianguo

    2016-01-01

    The contributions of domain-general abilities and domain-specific knowledge to subsequent mathematics achievement were longitudinally assessed (n = 167) through 8th grade. First grade intelligence and working memory and prior grade reading achievement indexed domain-general effects and domain-specific effects were indexed by prior grade mathematics achievement and mathematical cognition measures of prior grade number knowledge, addition skills, and fraction knowledge. Use of functional data analysis enabled grade-by-grade estimation of overall domain-general and domain-specific effects on subsequent mathematics achievement, the relative importance of individual domain-general and domain-specific variables on this achievement, and linear and non-linear across-grade estimates of these effects. The overall importance of domain-general abilities for subsequent achievement was stable across grades, with working memory emerging as the most important domain-general ability in later grades. The importance of prior mathematical competencies on subsequent mathematics achievement increased across grades, with number knowledge and arithmetic skills critical in all grades and fraction knowledge in later grades. Overall, domain-general abilities were more important than domain-specific knowledge for mathematics learning in early grades but general abilities and domain-specific knowledge were equally important in later grades. PMID:28781382

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

    PubMed

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

    2006-03-31

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

  20. The Vanderbilt Expertise Test Reveals Domain-General and Domain-Specific Sex Effects in Object Recognition

    PubMed Central

    McGugin, Rankin W.; Richler, Jennifer J.; Herzmann, Grit; Speegle, Magen; Gauthier, Isabel

    2012-01-01

    Individual differences in face recognition are often contrasted with differences in object recognition using a single object category. Likewise, individual differences in perceptual expertise for a given object domain have typically been measured relative to only a single category baseline. In Experiment 1, we present a new test of object recognition, the Vanderbilt Expertise Test (VET), which is comparable in methods to the Cambridge Face Memory Task (CFMT) but uses eight different object categories. Principal component analysis reveals that the underlying structure of the VET can be largely explained by two independent factors, which demonstrate good reliability and capture interesting sex differences inherent in the VET structure. In Experiment 2, we show how the VET can be used to separate domain-specific from domain-general contributions to a standard measure of perceptual expertise. While domain-specific contributions are found for car matching for both men and women and for plane matching in men, women in this sample appear to use more domain-general strategies to match planes. In Experiment 3, we use the VET to demonstrate that holistic processing of faces predicts face recognition independently of general object recognition ability, which has a sex-specific contribution to face recognition. Overall, the results suggest that the VET is a reliable and valid measure of object recognition abilities and can measure both domain-general skills and domain-specific expertise, which were both found to depend on the sex of observers. PMID:22877929

  1. What domains of clinical function should be assessed after sport-related concussion? A systematic review.

    PubMed

    Feddermann-Demont, Nina; Echemendia, Ruben J; Schneider, Kathryn J; Solomon, Gary S; Hayden, K Alix; Turner, Michael; Dvořák, Jiří; Straumann, Dominik; Tarnutzer, Alexander A

    2017-06-01

    Sport-related concussion (SRC) is a clinical diagnosis made after a sport-related head trauma. Inconsistency exists regarding appropriate methods for assessing SRC, which focus largely on symptom-scores, neurocognitive functioning and postural stability. Systematic literature review. MEDLINE, EMBASE, PsycINFO, Cochrane-DSR, Cochrane CRCT, CINAHL, SPORTDiscus (accessed July 9, 2016). Original (prospective) studies reporting on postinjury assessment in a clinical setting and evaluation of diagnostic tools within 2 weeks after an SRC. Forty-six studies covering 3284 athletes were included out of 2170 articles. Only the prospective studies were considered for final analysis (n=33; 2416 athletes). Concussion diagnosis was typically made on the sideline by an (certified) athletic trainer (55.0%), mainly on the basis of results from a symptom-based questionnaire. Clinical domains affected included cognitive, vestibular and headache/migraine. Headache, fatigue, difficulty concentrating and dizziness were the symptoms most frequently reported. Neurocognitive testing was used in 30/33 studies (90.9%), whereas balance was assessed in 9/33 studies (27.3%). The overall quality of the studies was considered low. The absence of an objective, gold standard criterion makes the accurate diagnosis of SRC challenging. Current approaches tend to emphasise cognition, symptom assessment and postural stability with less of a focus on other domains of functioning. We propose that the clinical assessment of SRC should be symptom based and interdisciplinary. Whenever possible, the SRC assessment should incorporate neurological, vestibular, ocular motor, visual, neurocognitive, psychological and cervical aspects. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. Knowing, Applying, and Reasoning about Arithmetic: Roles of Domain-General and Numerical Skills in Multiple Domains of Arithmetic Learning

    ERIC Educational Resources Information Center

    Zhang, Xiao; Räsänen, Pekka; Koponen, Tuire; Aunola, Kaisa; Lerkkanen, Marja-Kristiina; Nurmi, Jari-Erik

    2017-01-01

    The longitudinal relations of domain-general and numerical skills at ages 6-7 years to 3 cognitive domains of arithmetic learning, namely knowing (written computation), applying (arithmetic word problems), and reasoning (arithmetic reasoning) at age 11, were examined for a representative sample of 378 Finnish children. The results showed that…

  3. An information theory framework for dynamic functional domain connectivity.

    PubMed

    Vergara, Victor M; Miller, Robyn; Calhoun, Vince

    2017-06-01

    Dynamic functional network connectivity (dFNC) analyzes time evolution of coherent activity in the brain. In this technique dynamic changes are considered for the whole brain. This paper proposes an information theory framework to measure information flowing among subsets of functional networks call functional domains. Our method aims at estimating bits of information contained and shared among domains. The succession of dynamic functional states is estimated at the domain level. Information quantity is based on the probabilities of observing each dynamic state. Mutual information measurement is then obtained from probabilities across domains. Thus, we named this value the cross domain mutual information (CDMI). Strong CDMIs were observed in relation to the subcortical domain. Domains related to sensorial input, motor control and cerebellum form another CDMI cluster. Information flow among other domains was seldom found. Other methods of dynamic connectivity focus on whole brain dFNC matrices. In the current framework, information theory is applied to states estimated from pairs of multi-network functional domains. In this context, we apply information theory to measure information flow across functional domains. Identified CDMI clusters point to known information pathways in the basal ganglia and also among areas of sensorial input, patterns found in static functional connectivity. In contrast, CDMI across brain areas of higher level cognitive processing follow a different pattern that indicates scarce information sharing. These findings show that employing information theory to formally measured information flow through brain domains reveals additional features of functional connectivity. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Further insight into BRUTUS domain composition and functionality

    PubMed Central

    Matthiadis, Anna; Long, Terri A.

    2016-01-01

    ABSTRACT BRUTUS (BTS) is a hemerythrin (HHE) domain containing E3 ligase that facilitates the degradation of POPEYE-like (PYEL) proteins in a proteasomal-dependent manner. Deletion of BTS HHE domains enhances BTS stability in the presence of iron and also complements loss of BTS function, suggesting that the HHE domains are critical for protein stability but not for enzymatic function. The RING E3 domain plays an essential role in BTS' capacity to both interact with PYEL proteins and to act as an E3 ligase. Here we show that removal of the RING domain does not complement loss of BTS function. We conclude that enzymatic activity of BTS via the RING domain is essential for response to iron deficiency in plants. Further, we analyze possible BTS domain structure evolution and predict that the combination of domains found in BTS is specific to photosynthetic organisms, potentially indicative of a role for BTS and its orthologs in mitigating the iron-related challenges presented by photosynthesis. PMID:27359166

  5. Further insight into BRUTUS domain composition and functionality.

    PubMed

    Matthiadis, Anna; Long, Terri A

    2016-08-02

    BRUTUS (BTS) is a hemerythrin (HHE) domain containing E3 ligase that facilitates the degradation of POPEYE-like (PYEL) proteins in a proteasomal-dependent manner. Deletion of BTS HHE domains enhances BTS stability in the presence of iron and also complements loss of BTS function, suggesting that the HHE domains are critical for protein stability but not for enzymatic function. The RING E3 domain plays an essential role in BTS' capacity to both interact with PYEL proteins and to act as an E3 ligase. Here we show that removal of the RING domain does not complement loss of BTS function. We conclude that enzymatic activity of BTS via the RING domain is essential for response to iron deficiency in plants. Further, we analyze possible BTS domain structure evolution and predict that the combination of domains found in BTS is specific to photosynthetic organisms, potentially indicative of a role for BTS and its orthologs in mitigating the iron-related challenges presented by photosynthesis.

  6. Evidence-based practice implementation in community mental health settings: the relative importance of key domains of implementation activity.

    PubMed

    Torrey, William C; Bond, Gary R; McHugo, Gregory J; Swain, Karin

    2012-09-01

    Implementation research has examined practice prioritization, implementation leadership, workforce development, workflow re-engineering, and practice reinforcement, but not addressed their relative importance as implementation drivers. This study investigated domains of implementation activities and correlated them to implementation success during a large national evidence-based practice implementation project. Implementation success was correlated with active leadership strategically devoted to redesigning the flow of work and reinforcing implementation through measurement and feedback. Relative attention to workforce development was negatively correlated with implementation. Active leaders should focus on redesigning the flow of work to support the implementation and on reinforcing program improvements.

  7. Fusion activity of HIV gp41 fusion domain is related to its secondary structure and depth of membrane insertion in a cholesterol-dependent fashion.

    PubMed

    Lai, Alex L; Moorthy, Anna Eswara; Li, Yinling; Tamm, Lukas K

    2012-04-20

    The human immunodeficiency virus (HIV) gp41 fusion domain plays a critical role in membrane fusion during viral entry. A thorough understanding of the relationship between the structure and the activity of the fusion domain in different lipid environments helps to formulate mechanistic models on how it might function in mediating membrane fusion. The secondary structure of the fusion domain in small liposomes composed of different lipid mixtures was investigated by circular dichroism spectroscopy.  The fusion domain formed an α-helix in membranes containing less than 30 mol% cholesterol and  formed β-sheet secondary structure in membranes containing ≥30 mol% cholesterol. EPR spectra of spin-labeled fusion domains also indicated different conformations in membranes with and without cholesterol. Power saturation EPR data were further used to determine the orientation and depth of α-helical fusion domains in lipid bilayers. Fusion and membrane perturbation activities of the gp41 fusion domain were measured by lipid mixing and contents leakage. The fusion domain fused membranes in both its helical form and its β-sheet form. High cholesterol, which induced β-sheets, promoted fusion; however, acidic lipids, which promoted relatively deep membrane insertion as an α-helix, also induced fusion. The results indicate that the structure of the HIV gp41 fusion domain is plastic and depends critically on the lipid environment. Provided that their membrane insertion is deep, α-helical and β-sheet conformations contribute to membrane fusion. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Accelerating Imitation Learning in Relational Domains via Transfer by Initialization

    DTIC Science & Technology

    2013-08-28

    Warcraft , regulation of traffic lights, logistics, and a variety of planning domains. A supervised learning method for imitation learning was recently...some information about the world (traffic density at a signal, distance to the goal etc.). We assume a functional parametrization over the policy and...strategy (RTS) game engine written in C based off the Warcraft series of games. Like all RTS games, it allows multiple agents to be controlled

  9. Twin related domains in 3D microstructures of conventionally processed and grain boundary engineered materials

    DOE PAGES

    Lind, Jonathan; Li, Shiu Fai; Kumar, Mukul

    2016-05-20

    The concept of twin-limited microstructures has been explored in the literature as a crystallographically constrained grain boundary network connected via only coincident site lattice (CSL) boundaries. The advent of orientation imaging has made classification of twin-related domains (TRD) or any other orientation cluster experimentally accessible in 2D using EBSD. With the emergence of 3D orientation mapping, a comparison of TRDs in measured 3D microstructures is performed in this paper and compared against their 2D counterparts. The TRD analysis is performed on a conventionally processed (CP) and a grain boundary engineered (EM) high purity copper sample that have been subjected tomore » successive anneal procedures to promote grain growth. Finally, the EM sample shows extremely large TRDs which begin to approach that of a twin-limited microstructure, while the TRDs in the CP sample remain relatively small and remote.« less

  10. PREFACE: Domain wall dynamics in nanostructures Domain wall dynamics in nanostructures

    NASA Astrophysics Data System (ADS)

    Marrows, C. H.; Meier, G.

    2012-01-01

    forms of ordered phases such as antiferromagnetism and ferroelectricity. We would like to thank the scientists from all over the world who happily agreed to contribute their latest results to this special issue, and the Journal of Physics: Condensed Matter staff for their help, patience and professionalism. In such a fast-moving field it is not possible to give a definitive account, and this special issue can be no more than a snapshot of the current state of knowledge regarding this topic. Nevertheless, we hope that this collection of papers is a useful resource for experienced workers in the field, forms a useful introduction to researchers early in their careers and inspires others in related areas of nanotechnology to enter into the study of domain dynamics in nanostructures. Domain wall dynamics in nanostructures contents Temperature estimation in a ferromagnetic Fe-Ni nanowire involving a current-driven domain wall motionA Yamaguchi, A Hirohata, T Ono and H Miyajima Magnetization reversal in magnetic nanostripes via Bloch wall formation M Zeisberger and R Mattheis Magnetic soft x-ray microscopy of the domain wall depinning process in permalloy magnetic nanowiresMi-Young Im, Lars Bocklage, Guido Meier and Peter Fischer Domain wall propagation in meso- and nanoscale ferroelectrics R G P McQuaid, M McMillen, L-W Chang, A Gruverman and J M Gregg Transverse and vortex domain wall structure in magnetic nanowires with uniaxial in-plane anisotropyM T Bryan, S Bance, J Dean, T Schrefl and D A Allwood The stochastic nature of the domain wall motion along high perpendicular anisotropy strips with surface roughness Eduardo Martinez Temperature-dependent dynamics of stochastic domain-wall depinning in nanowiresClemens Wuth, Peter Lendecke and Guido Meier Controlled pinning and depinning of domain walls in nanowires with perpendicular magnetic anisotropyTheo Gerhardt, André Drews and Guido Meier The interaction of transverse domain wallsBenjamin Krüger The increase of the

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

    PubMed Central

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

    2018-01-01

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

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

    PubMed

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

    2018-01-01

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

  13. Inferring Domain-Domain Interactions from Protein-Protein Interactions with Formal Concept Analysis

    PubMed Central

    Khor, Susan

    2014-01-01

    Identifying reliable domain-domain interactions will increase our ability to predict novel protein-protein interactions, to unravel interactions in protein complexes, and thus gain more information about the function and behavior of genes. One of the challenges of identifying reliable domain-domain interactions is domain promiscuity. Promiscuous domains are domains that can occur in many domain architectures and are therefore found in many proteins. This becomes a problem for a method where the score of a domain-pair is the ratio between observed and expected frequencies because the protein-protein interaction network is sparse. As such, many protein-pairs will be non-interacting and domain-pairs with promiscuous domains will be penalized. This domain promiscuity challenge to the problem of inferring reliable domain-domain interactions from protein-protein interactions has been recognized, and a number of work-arounds have been proposed. This paper reports on an application of Formal Concept Analysis to this problem. It is found that the relationship between formal concepts provides a natural way for rare domains to elevate the rank of promiscuous domain-pairs and enrich highly ranked domain-pairs with reliable domain-domain interactions. This piggybacking of promiscuous domain-pairs onto less promiscuous domain-pairs is possible only with concept lattices whose attribute-labels are not reduced and is enhanced by the presence of proteins that comprise both promiscuous and rare domains. PMID:24586450

  14. Protein domain definition should allow for conditional disorder

    PubMed Central

    Yegambaram, Kavestri; Bulloch, Esther MM; Kingston, Richard L

    2013-01-01

    Abstract: Proteins are often classified in a binary fashion as either structured or disordered. However this approach has several deficits. Firstly, protein folding is always conditional on the physiochemical environment. A protein which is structured in some circumstances will be disordered in others. Secondly, it hides a fundamental asymmetry in behavior. While all structured proteins can be unfolded through a change in environment, not all disordered proteins have the capacity for folding. Failure to accommodate these complexities confuses the definition of both protein structural domains and intrinsically disordered regions. We illustrate these points with an experimental study of a family of small binding domains, drawn from the RNA polymerase of mumps virus and its closest relatives. Assessed at face value the domains fall on a structural continuum, with folded, partially folded, and near unstructured members. Yet the disorder present in the family is conditional, and these closely related polypeptides can access the same folded state under appropriate conditions. Any heuristic definition of the protein domain emphasizing conformational stability divides this domain family in two, in a way that makes no biological sense. Structural domains would be better defined by their ability to adopt a specific tertiary structure: a structure that may or may not be realized, dependent on the circumstances. This explicitly allows for the conditional nature of protein folding, and more clearly demarcates structural domains from intrinsically disordered regions that may function without folding. PMID:23963781

  15. Changing Your Domain Name in 25 Nail-Biting Steps

    ERIC Educational Resources Information Center

    Hassler, Carol

    2012-01-01

    When staff at the Wisconsin State Law Library began compiling a wish list for a new website, the topic of a new domain name came up almost immediately. Their old website was located at http://wsll.state.wi.us. Spelling that relatively complex domain over the phone day after day provided the impetus to explore other options. Whatever domain name…

  16. Krebs cycle intermediates regulate DNA and histone methylation: epigenetic impact on the aging process.

    PubMed

    Salminen, Antero; Kauppinen, Anu; Hiltunen, Mikko; Kaarniranta, Kai

    2014-07-01

    Many aging theories have proposed that mitochondria and energy metabolism have a major role in the aging process. There are recent studies indicating that Krebs cycle intermediates can shape the epigenetic landscape of chromatin by regulating DNA and histone methylation. A growing evidence indicates that epigenetics plays an important role in the regulation of healthspan but also is involved in the aging process. 2-Oxoglutarate (α-ketoglutarate) is a key metabolite in the Krebs cycle but it is also an obligatory substrate for 2-oxoglutarate-dependent dioxygenases (2-OGDO). The 2-OGDO enzyme family includes the major enzymes of DNA and histone demethylation, i.e. Ten-Eleven Translocation (TETs) and Jumonji C domain containing (JmjC) demethylases. In addition, 2-OGDO members can regulate collagen synthesis and hypoxic responses in a non-epigenetical manner. Interestingly, succinate and fumarate, also Krebs cycle intermediates, are potent inhibitors of 2-OGDO enzymes, i.e. the balance of Krebs cycle reactions can affect the level of DNA and histone methylation and thus control gene expression. We will review the epigenetic mechanisms through which Krebs cycle intermediates control the DNA and histone methylation. We propose that age-related disturbances in the Krebs cycle function induce stochastic epigenetic changes in chromatin structures which in turn promote the aging process. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Cooperative interactions between paired domain and homeodomain.

    PubMed

    Jun, S; Desplan, C

    1996-09-01

    The Pax proteins are a family of transcriptional regulators involved in many developmental processes in all higher eukaryotes. They are characterized by the presence of a paired domain (PD), a bipartite DNA binding domain composed of two helix-turn-helix (HTH) motifs,the PAI and RED domains. The PD is also often associated with a homeodomain (HD) which is itself able to form homo- and hetero-dimers on DNA. Many of these proteins therefore contain three HTH motifs each able to recognize DNA. However, all PDs recognize highly related DNA sequences, and most HDs also recognize almost identical sites. We show here that different Pax proteins use multiple combinations of their HTHs to recognize several types of target sites. For instance, the Drosophila Paired protein can bind, in vitro, exclusively through its PAI domain, or through a dimer of its HD, or through cooperative interaction between PAI domain and HD. However, prd function in vivo requires the synergistic action of both the PAI domain and the HD. Pax proteins with only a PD appear to require both PAI and RED domains, while a Pax-6 isoform and a new Pax protein, Lune, may rely on the RED domain and HD. We propose a model by which Pax proteins recognize different target genes in vivo through various combinations of their DNA binding domains, thus expanding their recognition repertoire.

  18. Domain Specificity in Relationship History, Social-Information Processing, and Violent Behavior in Early Adulthood

    PubMed Central

    Pettit, Gregory S.; Lansford, Jennifer E.; Malone, Patrick S.; Dodge, Kenneth A.; Bates, John E.

    2013-01-01

    Using prospective longitudinal data, we tested 5 hypotheses: (a) that the relation between earlier developmental experiences (peer social rejection and victimization in a romantic relationship) and adult violent behavior toward peers and romantic partners is specific to relationship domain; (b) that the relation between social-information processing (SIP) biases and subsequent violence is also specific to relational domain (romantic partner vs. peer); (c) that the relation between developmental experiences and SIP biases is domain specific; (d) that domain-specific SIP mediates the impact of earlier developmental experiences on later violent behavior; and (e) that harsh parenting early in life is a domain-general predictor of SIP and later violent behavior. Harsh parenting was assessed through interviews with parents when their children were age 5 years. Classroom sociometric assessments indexing peer rejection were completed in elementary school, and self-report of victimization by romantic partners was provided at age 18 years. SIP was assessed via interview at age 22 years, and violent behavior was measured via self-and partner report at ages 23 years and 24 years. Structural equation analyses revealed specificity in the relation between developmental experiences and violence and in the prediction to and from SIP in the peer domain, but not in the romantic-relationship domain. The impact of early harsh treatment on violence toward peers was mediated by SIP biases in the peer domain. These findings provide support for domain specificity in the peer domain but for cross-domain generality in the romantic relationship domain in the development of violent behavior in early adulthood. PMID:20085394

  19. Arabidopsis dynamin-related protein 1E in sphingolipid-enriched plasma membrane domains is associated with the development of freezing tolerance.

    PubMed

    Minami, Anzu; Tominaga, Yoko; Furuto, Akari; Kondo, Mariko; Kawamura, Yukio; Uemura, Matsuo

    2015-08-01

    The freezing tolerance of Arabidopsis thaliana is enhanced by cold acclimation, resulting in changes in the compositions and function of the plasma membrane. Here, we show that a dynamin-related protein 1E (DRP1E), which is thought to function in the vesicle trafficking pathway in cells, is related to an increase in freezing tolerance during cold acclimation. DRP1E accumulated in sphingolipid and sterol-enriched plasma membrane domains after cold acclimation. Analysis of drp1e mutants clearly showed that DRP1E is required for full development of freezing tolerance after cold acclimation. DRP1E fused with green fluorescent protein was visible as small foci that overlapped with fluorescent dye-labelled plasma membrane, providing evidence that DRP1E localizes non-uniformly in specific areas of the plasma membrane. These results suggest that DRP1E accumulates in sphingolipid and sterol-enriched plasma membrane domains and plays a role in freezing tolerance development during cold acclimation. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

  20. Predicting domain-domain interaction based on domain profiles with feature selection and support vector machines

    PubMed Central

    2010-01-01

    Background Protein-protein interaction (PPI) plays essential roles in cellular functions. The cost, time and other limitations associated with the current experimental methods have motivated the development of computational methods for predicting PPIs. As protein interactions generally occur via domains instead of the whole molecules, predicting domain-domain interaction (DDI) is an important step toward PPI prediction. Computational methods developed so far have utilized information from various sources at different levels, from primary sequences, to molecular structures, to evolutionary profiles. Results In this paper, we propose a computational method to predict DDI using support vector machines (SVMs), based on domains represented as interaction profile hidden Markov models (ipHMM) where interacting residues in domains are explicitly modeled according to the three dimensional structural information available at the Protein Data Bank (PDB). Features about the domains are extracted first as the Fisher scores derived from the ipHMM and then selected using singular value decomposition (SVD). Domain pairs are represented by concatenating their selected feature vectors, and classified by a support vector machine trained on these feature vectors. The method is tested by leave-one-out cross validation experiments with a set of interacting protein pairs adopted from the 3DID database. The prediction accuracy has shown significant improvement as compared to InterPreTS (Interaction Prediction through Tertiary Structure), an existing method for PPI prediction that also uses the sequences and complexes of known 3D structure. Conclusions We show that domain-domain interaction prediction can be significantly enhanced by exploiting information inherent in the domain profiles via feature selection based on Fisher scores, singular value decomposition and supervised learning based on support vector machines. Datasets and source code are freely available on the web at http

  1. Medical Resident Ability to Self-Assess in Relation to Their Competence within the Assessed Domain

    ERIC Educational Resources Information Center

    Whicker, Shari Ann

    2012-01-01

    The purpose of the study was to examine the relationship between resident communication skills competence and their ability to self-assess within that domain. Six research questions guided the study. The first research question sought to explore the varied levels with which residents demonstrated competence within the domain of communication…

  2. Critical role of domain crystallinity, domain purity and domain interface sharpness for reduced bimolecular recombination in polymer solar cells

    DOE PAGES

    Venkatesan, Swaminathan; Chen, Jihua; Ngo, Evan C.; ...

    2014-12-31

    In this study, inverted bulk heterojunction solar cells were fabricated using poly(3-hexylthiophene) (P3HT) blended with two different fullerene derivatives namely phenyl-C61-butyric acid methyl ester (PC 60BM) and indene-C 60 bis-adduct (IC 60BA). The effects of annealing temperatures on the morphology, optical and structural properties were studied and correlated to differences in photovoltaic device performance. It was observed that annealing temperature significantly improved the performance of P3HT:IC 60BA solar cells while P3HT:PC 60BM cells showed relatively less improvement. The performance improvement is attributed to the extent of fullerene mixing with polymer domains. Energy filtered transmission electron microscopy (EFTEM) and x-ray diffractionmore » (XRD) results showed that ICBA mixes with disordered P3HT much more readily than PC 60BM which leads to lower short circuit current density and fill factor for P3HT:IC 60BA cells annealed below 120°C. Annealing above 120°C improves the crystallinity of P3HT in case of P3HT:IC 60BA whereas in P3HT:PC 60BM films, annealing above 80°C leads to negligible change in crystallinity. Crystallization of P3HT also leads to higher domain purity as seen EFTEM. Further it is seen that cells processed with additive nitrobenzene (NB) showed enhanced short circuit current density and power conversion efficiency regardless of the fullerene derivative used. Addition of NB led to nanoscale phase separation between purer polymer and fullerene domains. Kelvin probe force microscopy (KPFM) images showed that enhanced domain purity in additive casted films led to a sharper interface between polymer and fullerene. Lastly, enhanced domain purity and interfacial sharpness led to lower bimolecular recombination and higher mobility and charge carrier lifetime in NB modified devices.« less

  3. Biology and Beyond: Domain Specificity in a Broader Developmental Context

    ERIC Educational Resources Information Center

    Keil, Frank C.

    2007-01-01

    The assumption of domain specificity has been invaluable to the study of the emergence of biological thought in young children. Yet, domains of thought must be understood within a broader context that explains how those domains relate to the surrounding cultures, to different kinds of cognitive constraints, to framing effects, to abilities to…

  4. Abl N-terminal Cap stabilization of SH3 domain dynamics†

    PubMed Central

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

    2008-01-01

    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 NCap makes in stabilizing the various intramolecular interactions within c-Abl are less clear. While the NCap appears important for locking the SH3/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 to test NCap-induced stabilization of the SH3 domain in various constructs. The results showed that 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 NCap + SH3 but was obvious when the SH2 domain and the SH2-kinase linker were present. These results suggest that interactions between 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. PMID:18452309

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

    PubMed Central

    Vishwanath, Sneha

    2018-01-01

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

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

    PubMed

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

    2018-02-01

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

  7. A Fast, Efficient Domain Adaptation Technique for Cross-Domain Electroencephalography(EEG)-Based Emotion Recognition.

    PubMed

    Chai, Xin; Wang, Qisong; Zhao, Yongping; Li, Yongqiang; Liu, Dan; Liu, Xin; Bai, Ou

    2017-05-03

    of 77.88% and 7.33% on average, respectively. For the online analysis, the average classification accuracy and standard deviation of ASFM in the subject-to-subject evaluation for all the 15 subjects in a dataset was 75.11% and 7.65%, respectively, gaining a significant performance improvement compared to the best baseline LR which achieves 56.38% and 7.48%, respectively. The experimental results confirm the effectiveness of the proposed method relative to state-of-the-art methods. Moreover, computational efficiency of the proposed ASFM method is much better than standard domain adaptation; if the numbers of training samples and test samples are controlled within certain range, it is suitable for real-time classification. It can be concluded that ASFM is a useful and effective tool for decreasing domain discrepancy and reducing performance degradation across subjects and sessions in the field of EEG-based emotion recognition.

  8. The PYRIN domain: A member of the death domain-fold superfamily

    PubMed Central

    Fairbrother, Wayne J.; Gordon, Nathaniel C.; Humke, Eric W.; O'Rourke, Karen M.; Starovasnik, Melissa A.; Yin, Jian-Ping; Dixit, Vishva M.

    2001-01-01

    PYRIN domains were identified recently as putative protein–protein interaction domains at the N-termini of several proteins thought to function in apoptotic and inflammatory signaling pathways. The ∼95 residue PYRIN domains have no statistically significant sequence homology to proteins with known three-dimensional structure. Using secondary structure prediction and potential-based fold recognition methods, however, the PYRIN domain is predicted to be a member of the six-helix bundle death domain-fold superfamily that includes death domains (DDs), death effector domains (DEDs), and caspase recruitment domains (CARDs). Members of the death domain-fold superfamily are well established mediators of protein–protein interactions found in many proteins involved in apoptosis and inflammation, indicating further that the PYRIN domains serve a similar function. An homology model of the PYRIN domain of CARD7/DEFCAP/NAC/NALP1, a member of the Apaf-1/Ced-4 family of proteins, was constructed using the three-dimensional structures of the FADD and p75 neurotrophin receptor DDs, and of the Apaf-1 and caspase-9 CARDs, as templates. Validation of the model using a variety of computational techniques indicates that the fold prediction is consistent with the sequence. Comparison of a circular dichroism spectrum of the PYRIN domain of CARD7/DEFCAP/NAC/NALP1 with spectra of several proteins known to adopt the death domain-fold provides experimental support for the structure prediction. PMID:11514682

  9. The DIMA web resource--exploring the protein domain network.

    PubMed

    Pagel, Philipp; Oesterheld, Matthias; Stümpflen, Volker; Frishman, Dmitrij

    2006-04-15

    Conserved domains represent essential building blocks of most known proteins. Owing to their role as modular components carrying out specific functions they form a network based both on functional relations and direct physical interactions. We have previously shown that domain interaction networks provide substantially novel information with respect to networks built on full-length protein chains. In this work we present a comprehensive web resource for exploring the Domain Interaction MAp (DIMA), interactively. The tool aims at integration of multiple data sources and prediction techniques, two of which have been implemented so far: domain phylogenetic profiling and experimentally demonstrated domain contacts from known three-dimensional structures. A powerful yet simple user interface enables the user to compute, visualize, navigate and download domain networks based on specific search criteria. http://mips.gsf.de/genre/proj/dima

  10. Assessing the co-occurrence of intimate partner violence domains across the life-course: relating typologies to mental health.

    PubMed

    Armour, Cherie; Sleath, Emma

    2014-01-01

    The inter-generational transmission of violence (ITV) hypothesis and polyvictimisation have been studied extensively. The extant evidence suggests that individuals from violent families are at increased risk of subsequent intimate partner violence (IPV) and that a proportion of individuals experience victimisation across multiple rather than single IPV domains. Both ITV and polyvictimisation are shown to increase the risk of psychiatric morbidity, alcohol use, and anger expression. The current study aimed to 1) ascertain if underlying typologies of victimisation across the life-course and over multiple victimisation domains were present and 2) ascertain if groupings differed on mean scores of posttraumatic stress disorder (PTSD), depression, alcohol use, and anger expression. University students (N=318) were queried in relation to victimisation experiences and psychological well-being. Responses across multiple domains of IPV spanning the life-course were used in a latent profile analysis. ANOVA was subsequently used to determine if profiles differed in their mean scores on PTSD, depression, alcohol use, and anger expression. Three distinct profiles were identified; one of which comprised individuals who experienced "life-course polyvictimisation," another showing individuals who experienced "witnessing parental victimisation," and one which experienced "psychological victimisation only." Life-course polyvictims scored the highest across most assessed measures. Witnessing severe physical aggression and injury in parental relationships as a child has an interesting impact on the ITV into adolescence and adulthood. Life-course polyvictims are shown to experience increased levels of psychiatric morbidity and issues with alcohol misuse and anger expression.

  11. Time-domain simulation of constitutive relations for nonlinear acoustics including relaxation for frequency power law attenuation media modeling

    NASA Astrophysics Data System (ADS)

    Jiménez, Noé; Camarena, Francisco; Redondo, Javier; Sánchez-Morcillo, Víctor; Konofagou, Elisa E.

    2015-10-01

    We report a numerical method for solving the constitutive relations of nonlinear acoustics, where multiple relaxation processes are included in a generalized formulation that allows the time-domain numerical solution by an explicit finite differences scheme. Thus, the proposed physical model overcomes the limitations of the one-way Khokhlov-Zabolotskaya-Kuznetsov (KZK) type models and, due to the Lagrangian density is implicitly included in the calculation, the proposed method also overcomes the limitations of Westervelt equation in complex configurations for medical ultrasound. In order to model frequency power law attenuation and dispersion, such as observed in biological media, the relaxation parameters are fitted to both exact frequency power law attenuation/dispersion media and also empirically measured attenuation of a variety of tissues that does not fit an exact power law. Finally, a computational technique based on artificial relaxation is included to correct the non-negligible numerical dispersion of the finite difference scheme, and, on the other hand, improve stability trough artificial attenuation when shock waves are present. This technique avoids the use of high-order finite-differences schemes leading to fast calculations. The present algorithm is especially suited for practical configuration where spatial discontinuities are present in the domain (e.g. axisymmetric domains or zero normal velocity boundary conditions in general). The accuracy of the method is discussed by comparing the proposed simulation solutions to one dimensional analytical and k-space numerical solutions.

  12. Mutation of domain III and domain VI in L gene conserved domain of Nipah virus

    NASA Astrophysics Data System (ADS)

    Jalani, Siti Aishah; Ibrahim, Nazlina

    2016-11-01

    Nipah virus (NiV) is the etiologic agent responsible for the respiratory illness and causes fatal encephalitis in human. NiV L protein subunit is thought to be responsible for the majority of enzymatic activities involved in viral transcription and replication. The L protein which is the viral RNA dependent RNA polymerase has high sequence homology among negative sense RNA viruses. In negative stranded RNA viruses, based on sequence alignment six conserved domain (domain I-IV) have been determined. Each domain is separated on variable regions that suggest the structure to consist concatenated functional domain. To directly address the roles of domains III and VI, site-directed mutations were constructed by the substitution of bases at sequences 2497, 2500, 5528 and 5532. Each mutated L gene can be used in future studies to test the ability for expression on in vitro translation.

  13. The effect of education on age-related changes in three cognitive domains: a cross-sectional study in primary care.

    PubMed

    Martins, Isabel Pavão; Maruta, Carolina; Silva, Cláudia; Rodrigues, Pedro; Chester, Catarina; Ginó, Sandra; Freitas, Vanda; Freitas, Sara; Oliveira, António Gouveia

    2012-01-01

    The present study aims to investigate the protective effect of formal education on age-related changes in different cognitive domains with the hypothesis that it may attenuate the rate of decline. Individuals aged 50 years or older attending primary care physicians without known brain disease (431 participants, mostly [60.3%] female with 66.3 [±9.1] years of age and 7.7 [±4.1] years of education, on average), were evaluated with a neuropsychological battery including 28 cognitive measures. Cognitive domains identified by factor analysis were subject to repeated multiple regression analyses to determine the variance explained by age and education controlling for gender, depressive symptoms, and vascular risk factors. The slope of the regression equation was compared between two educational groups with an average of 4 years and 11 years of education, respectively. Factors identified corresponded to processing ability (Factor 1), memory (Factor 2), and acquired knowledge (Factor 3). Although education improved performance in Factors 1 and 3, it did not change the slope of age-related decline in any factor. This study suggests that in culturally heterogeneous groups, small increments in education enhance cognition but do not modify the rate of decline of executive functioning with age. These results contradict some clinical findings and need to be confirmed in longitudinal studies.

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

    PubMed

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

    2010-02-18

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

  15. Abl N-terminal cap stabilization of SH3 domain dynamics.

    PubMed

    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.

  16. Examining the Domain-Specificity of Metacognition Using Academic Domains and Task-Specific Individual Differences

    ERIC Educational Resources Information Center

    Scott, Brianna M.; Berman, Ashleigh F.

    2013-01-01

    Metacognition refers to students' knowledge and regulation of cognition, as well as their accuracy in predicting their academic performance. This study addressed two major questions: 1) how do metacognitive knowledge, regulation and accuracy differ across domains?, and 2) how do students' individual differences relate to their reported…

  17. Domain wall nanoelectronics

    NASA Astrophysics Data System (ADS)

    Catalan, G.; Seidel, J.; Ramesh, R.; Scott, J. F.

    2012-01-01

    Domains in ferroelectrics were considered to be well understood by the middle of the last century: They were generally rectilinear, and their walls were Ising-like. Their simplicity stood in stark contrast to the more complex Bloch walls or Néel walls in magnets. Only within the past decade and with the introduction of atomic-resolution studies via transmission electron microscopy, electron holography, and atomic force microscopy with polarization sensitivity has their real complexity been revealed. Additional phenomena appear in recent studies, especially of magnetoelectric materials, where functional properties inside domain walls are being directly measured. In this paper these studies are reviewed, focusing attention on ferroelectrics and multiferroics but making comparisons where possible with magnetic domains and domain walls. An important part of this review will concern device applications, with the spotlight on a new paradigm of ferroic devices where the domain walls, rather than the domains, are the active element. Here magnetic wall microelectronics is already in full swing, owing largely to the work of Cowburn and of Parkin and their colleagues. These devices exploit the high domain wall mobilities in magnets and their resulting high velocities, which can be supersonic, as shown by Kreines’ and co-workers 30 years ago. By comparison, nanoelectronic devices employing ferroelectric domain walls often have slower domain wall speeds, but may exploit their smaller size as well as their different functional properties. These include domain wall conductivity (metallic or even superconducting in bulk insulating or semiconducting oxides) and the fact that domain walls can be ferromagnetic while the surrounding domains are not.

  18. Domain-specific physical activity and sedentary behaviour in relation to colon and rectal cancer risk: a systematic review and meta-analysis.

    PubMed

    Mahmood, Shahid; MacInnis, Robert J; English, Dallas R; Karahalios, Amalia; Lynch, Brigid M

    2017-12-01

    Physical activity is associated with reduced risk of colorectal cancer, but most epidemiological studies have focused on occupational and recreational physical activity. The evidence for other domains of activity, and for sedentary behaviour, is limited. Medline, Embase and Web of Science were searched from inception to December 2015 for studies examining domain-specific physical activity or sedentary behaviour and the risk of colon and/or rectal cancer. We extracted maximally adjusted relative risks (RRs) except when RRs not adjusted for body mass index, were also presented. We used random-effects meta-analysis to compute pooled RRs comparing the highest versus the lowest level of exposure. We used meta-regression to assess sources of heterogeneity in estimates. We identified 17 cohort and 21 case-control studies, of which 17 had occupational data, 23 had recreational data, three each had data on transport and household physical activity domains, and 6 studies had data on occupational sedentary behaviour. The pooled relative risks (RRs) for colon cancer were 0.74 (95% confidence interval (CI): 0.67, 0.82) for occupational activity, 0.80 (95% CI: 0.71, 0.89) for recreational activity, 0.66 (95% CI: 0.45, 0.98) for transport-related physical activity, 0.85 (95% CI: 0.71, 1.02) for household physical activity, and 1.44 (95% CI: 1.28, 1.62) for occupational sedentary behaviour. For rectal cancer, the pooled RRs were 0.88 (95% CI: 0.79, 0.98) for occupational activity, 0.87 (95% CI: 0.75, 1.01) for recreational activity, 0.88 (95% CI: 0.70, 1.12) for transport-related physical activity, 1.01 (95% CI: 0.80, 1.27) for household physical activity, and 1.02 (95% CI: 0.82, 1.28) for occupational sedentary behaviour. In addition to increasing occupational and recreational physical activity, promoting physical activity during transport and reducing sedentary behaviour in the workplace may also be useful colorectal cancer prevention strategies. © The Author 2017; all rights

  19. Formation of self-organized domain structures with charged domain walls in lithium niobate with surface layer modified by proton exchange

    NASA Astrophysics Data System (ADS)

    Shur, V. Ya.; Akhmatkhanov, A. R.; Chuvakova, M. A.; Dolbilov, M. A.; Zelenovskiy, P. S.; Lobov, A. I.

    2017-03-01

    We have studied the self-organized dendrite domain structures appeared as a result of polarization reversal in the uniform field in lithium niobate single crystals with the artificial surface layer created by proton exchange. We have revealed the self-organized sub-micron scale dendrite domain patterns consisting of domain stripes oriented along the X crystallographic directions separated by arrays of dashed residual domains at the surface by scanning probe microscopy. Raman confocal microscopy allowed visualizing the quasi-regular dendrite domain structures with similar geometry in the vicinity of both polar surfaces. The depth of the structure was about 20 μm for Z+ polar surface and 70 μm for Z- one. According to the proposed mechanism, the dendrite structure formation at the surface was related to the ineffective screening of the residual depolarization field. The computer simulation of the structure formation based on the cellular automata model with probabilistic switching rule proved the eligibility of the proposed scheme, the simulated dendrite domain patterns at various depths being similar to the experimental ones.

  20. Frequency Domain Full-Waveform Inversion in Imaging Thrust Related Features

    NASA Astrophysics Data System (ADS)

    Jaiswal, P.; Zelt, C. A.

    2010-12-01

    Seismic acquisition in rough terrain such as mountain belts suffers from problems related to near-surface conditions such as statics, inconsistent energy penetration, rapid decay of signal, and imperfect receiver coupling. Moreover in the presence of weakly compacted soil, strong ground roll may obscure the reflection arrivals at near offsets further diminishing the scope of estimating a reliable near surface image though conventional processing. Traveltime and waveform inversion not only overcome the simplistic assumptions inherent in conventional processing such as hyperbolic moveout and convolution model, but also use parts of the seismic coda, such as the direct arrival and refractions, that are discarded in the latter. Traveltime and waveform inversion are model-based methods that honour the physics of wave propagation. Given the right set of preconditioned data and starting model, waveform inversion in particular has been realized as a powerful tool for velocity model building. This paper examines two case studies on waveform inversion using real data from the Naga Thrust Belt in the Northeast India. Waveform inversion in this paper is performed in the frequency domain and is multiscale in nature i.e., the inversion progressively ascends from the lower to the higher end of the frequency spectra increasing the wavenumber content of the recovered model. Since the real data are band limited, the success of waveform inversion depends on how well the starting model can account for the missing low wavenumbers. In this paper it is observed that the required starting model can be prepared using the regularized inversion of direct and reflected arrival times.

  1. Mechanistic Insight into Human ether-à-go-go-related Gene (hERG) K+ Channel Deactivation Gating from the Solution Structure of the EAG Domain

    PubMed Central

    Muskett, Frederick W.; Thouta, Samrat; Thomson, Steven J.; Bowen, Alexander; Stansfeld, Phillip J.; Mitcheson, John S.

    2011-01-01

    Human ether-à-go-go-related gene (hERG) K+ channels have a critical role in cardiac repolarization. hERG channels close (deactivate) very slowly, and this is vital for regulating the time course and amplitude of repolarizing current during the cardiac action potential. Accelerated deactivation is one mechanism by which inherited mutations cause long QT syndrome and potentially lethal arrhythmias. hERG deactivation is highly dependent upon an intact EAG domain (the first 135 amino acids of the N terminus). Importantly, deletion of residues 2–26 accelerates deactivation to a similar extent as removing the entire EAG domain. These and other experiments suggest the first 26 residues (NT1–26) contain structural elements required to slow deactivation by stabilizing the open conformation of the pore. Residues 26–135 form a Per-Arnt-Sim domain, but a structure for NT1–26 has not been forthcoming, and little is known about its site of interaction on the channel. In this study, we present an NMR structure for the entire EAG domain, which reveals that NT1–26 is structurally independent from the Per-Arnt-Sim domain and contains a stable amphipathic helix with one face being positively charged. Mutagenesis and electrophysiological studies indicate that neutralizing basic residues and breaking the amphipathic helix dramatically accelerate deactivation. Furthermore, scanning mutagenesis and molecular modeling studies of the cyclic nucleotide binding domain suggest that negatively charged patches on its cytoplasmic surface form an interface with the NT1–26 domain. We propose a model in which NT1–26 obstructs gating motions of the cyclic nucleotide binding domain to allosterically stabilize the open conformation of the pore. PMID:21135103

  2. The pepper GNA-related lectin and PAN domain protein gene, CaGLP1, is required for plant cell death and defense signaling during bacterial infection.

    PubMed

    Kim, Nak Hyun; Lee, Dong Hyuk; Choi, Du Seok; Hwang, Byung Kook

    2015-12-01

    Carbohydrate-binding proteins, commonly referred to as lectins or agglutinins, function in defense responses to microbial pathogens. Pepper (Capsicum annuum) GNA-related lectin and PAN-domain protein gene CaGLP1 was isolated and functionally characterized from pepper leaves infected with Xanthomonas campestris pv. vesicatoria (Xcv). CaGLP1 contained an amine-terminus prokaryotic membrane lipoprotein lipid attachment site, a Galanthus nivalis agglutinin (GNA)-related lectin domain responsible for the recognition of high-mannose N-glycans, and a carboxyl-terminus PAN/apple domain. RNA gel blot and immunoblot analyses determined that CaGLP1 was strongly induced in pepper by compatible and incompatible Xcv infection. CaGLP1 protein localized primarily to the plasma membrane and exhibited mannose-binding specificity. CaGLP1-silenced pepper plants were more susceptible to compatible or incompatible Xcv infection compared with that of non-silenced control plants. CaGLP1 silencing in pepper leaves did not accumulate H2O2 and induce cell death during incompatible Xcv infection. Defense-related CaDEF1 (defensin) gene expression was significantly reduced in CaGLP1-silenced pepper plants. CaGLP1-overexpression in Arabidopsis thaliana enhanced resistance to Pseudomonas syringae pv. tomato. Defense-related AtPDF1.2 expression was elevated in CaGLP1-overexpression lines. Together, these results suggest that CaGLP1 is required for plant cell death and defense responses through the reactive oxygen species burst and downstream defense-related gene expression in response to bacterial pathogen challenge. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Unfolding of titin immunoglobulin domains by steered molecular dynamics simulation.

    PubMed

    Lu, H; Isralewitz, B; Krammer, A; Vogel, V; Schulten, K

    1998-08-01

    Titin, a 1-microm-long protein found in striated muscle myofibrils, possesses unique elastic and extensibility properties in its I-band region, which is largely composed of a PEVK region (70% proline, glutamic acid, valine, and lysine residue) and seven-strand beta-sandwich immunoglobulin-like (Ig) domains. The behavior of titin as a multistage entropic spring has been shown in atomic force microscope and optical tweezer experiments to partially depend on the reversible unfolding of individual Ig domains. We performed steered molecular dynamics simulations to stretch single titin Ig domains in solution with pulling speeds of 0.5 and 1.0 A/ps. Resulting force-extension profiles exhibit a single dominant peak for each Ig domain unfolding, consistent with the experimentally observed sequential, as opposed to concerted, unfolding of Ig domains under external stretching forces. This force peak can be attributed to an initial burst of backbone hydrogen bonds, which takes place between antiparallel beta-strands A and B and between parallel beta-strands A' and G. Additional features of the simulations, including the position of the force peak and relative unfolding resistance of different Ig domains, can be related to experimental observations.

  4. Domain Engineering

    NASA Astrophysics Data System (ADS)

    Bjørner, Dines

    Before software can be designed we must know its requirements. Before requirements can be expressed we must understand the domain. So it follows, from our dogma, that we must first establish precise descriptions of domains; then, from such descriptions, “derive” at least domain and interface requirements; and from those and machine requirements design the software, or, more generally, the computing systems.

  5. Visualizing domain wall and reverse domain superconductivity.

    PubMed

    Iavarone, M; Moore, S A; Fedor, J; Ciocys, S T; Karapetrov, G; Pearson, J; Novosad, V; Bader, S D

    2014-08-28

    In magnetically coupled, planar ferromagnet-superconductor (F/S) hybrid structures, magnetic domain walls can be used to spatially confine the superconductivity. In contrast to a superconductor in a uniform applied magnetic field, the nucleation of the superconducting order parameter in F/S structures is governed by the inhomogeneous magnetic field distribution. The interplay between the superconductivity localized at the domain walls and far from the walls leads to effects such as re-entrant superconductivity and reverse domain superconductivity with the critical temperature depending upon the location. Here we use scanning tunnelling spectroscopy to directly image the nucleation of superconductivity at the domain wall in F/S structures realized with Co-Pd multilayers and Pb thin films. Our results demonstrate that such F/S structures are attractive model systems that offer the possibility to control the strength and the location of the superconducting nucleus by applying an external magnetic field, potentially useful to guide vortices for computing application.

  6. Visualizing domain wall and reverse domain superconductivity

    PubMed Central

    Iavarone, M.; Moore, S. A.; Fedor, J.; Ciocys, S. T.; Karapetrov, G.; Pearson, J.; Novosad, V.; Bader, S. D.

    2014-01-01

    In magnetically coupled, planar ferromagnet-superconductor (F/S) hybrid structures, magnetic domain walls can be used to spatially confine the superconductivity. In contrast to a superconductor in a uniform applied magnetic field, the nucleation of the superconducting order parameter in F/S structures is governed by the inhomogeneous magnetic field distribution. The interplay between the superconductivity localized at the domain walls and far from the walls leads to effects such as re-entrant superconductivity and reverse domain superconductivity with the critical temperature depending upon the location. Here we use scanning tunnelling spectroscopy to directly image the nucleation of superconductivity at the domain wall in F/S structures realized with Co-Pd multilayers and Pb thin films. Our results demonstrate that such F/S structures are attractive model systems that offer the possibility to control the strength and the location of the superconducting nucleus by applying an external magnetic field, potentially useful to guide vortices for computing application. PMID:25164004

  7. UXDs-Driven Transferring Method from TRIZ Solution to Domain Solution

    NASA Astrophysics Data System (ADS)

    Ma, Lihui; Cao, Guozhong; Chang, Yunxia; Wei, Zihui; Ma, Kai

    The translation process from TRIZ solutions to domain solutions is an analogy-based process. TRIZ solutions, such as 40 inventive principles and the related cases, are medium-solutions for domain problems. Unexpected discoveries (UXDs) are the key factors to trigger designers to generate new ideas for domain solutions. The Algorithm of UXD resolving based on Means-Ends Analysis(MEA) is studied and an UXDs-driven transferring method from TRIZ solution to domain solution is formed. A case study shows the application of the process.

  8. A Fast, Efficient Domain Adaptation Technique for Cross-Domain Electroencephalography(EEG)-Based Emotion Recognition

    PubMed Central

    Chai, Xin; Wang, Qisong; Zhao, Yongping; Li, Yongqiang; Liu, Dan; Liu, Xin; Bai, Ou

    2017-01-01

    of 77.88% and 7.33% on average, respectively. For the online analysis, the average classification accuracy and standard deviation of ASFM in the subject-to-subject evaluation for all the 15 subjects in a dataset was 75.11% and 7.65%, respectively, gaining a significant performance improvement compared to the best baseline LR which achieves 56.38% and 7.48%, respectively. The experimental results confirm the effectiveness of the proposed method relative to state-of-the-art methods. Moreover, computational efficiency of the proposed ASFM method is much better than standard domain adaptation; if the numbers of training samples and test samples are controlled within certain range, it is suitable for real-time classification. It can be concluded that ASFM is a useful and effective tool for decreasing domain discrepancy and reducing performance degradation across subjects and sessions in the field of EEG-based emotion recognition. PMID:28467371

  9. Domain Specific vs Domain General: Implications for Dynamic Assessment

    ERIC Educational Resources Information Center

    Kaniel, Shlomo

    2010-01-01

    The article responds to the need for evidence-based dynamic assessment. The article is divided into two sections: In Part 1 we examine the scientific answer to the question of how far human mental activities and capabilities are domain general (DG) / domain specific (DS). A highly complex answer emerges from the literature review of domains such…

  10. Molecular representation of molar domain (volume), evolution equations, and linear constitutive relations for volume transport.

    PubMed

    Eu, Byung Chan

    2008-09-07

    In the traditional theories of irreversible thermodynamics and fluid mechanics, the specific volume and molar volume have been interchangeably used for pure fluids, but in this work we show that they should be distinguished from each other and given distinctive statistical mechanical representations. In this paper, we present a general formula for the statistical mechanical representation of molecular domain (volume or space) by using the Voronoi volume and its mean value that may be regarded as molar domain (volume) and also the statistical mechanical representation of volume flux. By using their statistical mechanical formulas, the evolution equations of volume transport are derived from the generalized Boltzmann equation of fluids. Approximate solutions of the evolution equations of volume transport provides kinetic theory formulas for the molecular domain, the constitutive equations for molar domain (volume) and volume flux, and the dissipation of energy associated with volume transport. Together with the constitutive equation for the mean velocity of the fluid obtained in a previous paper, the evolution equations for volume transport not only shed a fresh light on, and insight into, irreversible phenomena in fluids but also can be applied to study fluid flow problems in a manner hitherto unavailable in fluid dynamics and irreversible thermodynamics. Their roles in the generalized hydrodynamics will be considered in the sequel.

  11. Small domain-size multiblock copolymer electrolytes

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

    Pistorino, Jonathan; Eitouni, Hany Basam

    2016-09-20

    New block polymer electrolytes have been developed which have higher conductivities than previously reported for other block copolymer electrolytes. The new materials are constructed of multiple blocks (>5) of relatively low domain size. The small domain size provides greater protection against formation of dendrites during cycling against lithium in an electrochemical cell, while the large total molecular weight insures poor long range alignment, which leads to higher conductivity. In addition to higher conductivity, these materials can be more easily synthesized because of reduced requirements on the purity level of the reagents.

  12. OST-HTH: a novel predicted RNA-binding domain

    PubMed Central

    2010-01-01

    Background The mechanism by which the arthropod Oskar and vertebrate TDRD5/TDRD7 proteins nucleate or organize structurally related ribonucleoprotein (RNP) complexes, the polar granule and nuage, is poorly understood. Using sequence profile searches we identify a novel domain in these proteins that is widely conserved across eukaryotes and bacteria. Results Using contextual information from domain architectures, sequence-structure superpositions and available functional information we predict that this domain is likely to adopt the winged helix-turn-helix fold and bind RNA with a potential specificity for dsRNA. We show that in eukaryotes this domain is often combined in the same polypeptide with protein-protein- or lipid- interaction domains that might play a role in anchoring these proteins to specific cytoskeletal structures. Conclusions Thus, proteins with this domain might have a key role in the recognition and localization of dsRNA, including miRNAs, rasiRNAs and piRNAs hybridized to their targets. In other cases, this domain is fused to ubiquitin-binding, E3 ligase and ubiquitin-like domains indicating a previously under-appreciated role for ubiquitination in regulating the assembly and stability of nuage-like RNP complexes. Both bacteria and eukaryotes encode a conserved family of proteins that combines this predicted RNA-binding domain with a previously uncharacterized domain (DUF88). We present evidence that it is an RNAse belonging to the superfamily that includes the 5'->3' nucleases, PIN and NYN domains and might be recruited to degrade certain RNAs. Reviewers This article was reviewed by Sandor Pongor and Arcady Mushegian. PMID:20302647

  13. Dynamics of the Tec‐family tyrosine kinase SH3 domains

    PubMed Central

    Roberts, Justin M.; Tarafdar, Sreya; Joseph, Raji E.; Andreotti, Amy H.; Smithgall, Thomas E.; Engen, John R.

    2016-01-01

    Abstract The Src Homology 3 (SH3) domain is an important regulatory domain found in many signaling proteins. X‐ray crystallography and NMR structures of SH3 domains are generally conserved but other studies indicate that protein flexibility and dynamics are not. We previously reported that based on hydrogen exchange mass spectrometry (HX MS) studies, there is variable flexibility and dynamics among the SH3 domains of the Src‐family tyrosine kinases and related proteins. Here we have extended our studies to the SH3 domains of the Tec family tyrosine kinases (Itk, Btk, Tec, Txk, Bmx). The SH3 domains of members of this family augment the variety in dynamics observed in previous SH3 domains. Txk and Bmx SH3 were found to be highly dynamic in solution by HX MS and Bmx was unstructured by NMR. Itk and Btk SH3 underwent a clear EX1 cooperative unfolding event, which was localized using pepsin digestion and mass spectrometry after hydrogen exchange labeling. The unfolding was localized to peptide regions that had been previously identified in the Src‐family and related protein SH3 domains, yet the kinetics of unfolding were not. Sequence alignment does not provide an easy explanation for the observed dynamics behavior, yet the similarity of location of EX1 unfolding suggests that higher‐order structural properties may play a role. While the exact reason for such dynamics is not clear, such motions can be exploited in intra‐ and intermolecular binding assays of proteins containing the domains. PMID:26808198

  14. Domains of health-related quality of life important and relevant to multiethnic English-speaking Asian systemic lupus erythematosus patients: a focus group study.

    PubMed

    Ow, Yen Ling Mandy; Thumboo, Julian; Cella, David; Cheung, Yin Bun; Yong Fong, Kok; Wee, Hwee Lin

    2011-06-01

    To identify health-related quality of life (HRQOL) domains of importance to multiethnic Asian systemic lupus erythematosus (SLE) patients, to identify content gaps in existing SLE-specific HRQOL measures, and to determine whether the Patient-Reported Outcomes Measurement Information System (PROMIS) item banks could serve as a core set of questions for HRQOL assessment among SLE patients. English-speaking patients with physician-diagnosed SLE from a specialist clinic in a tertiary care hospital in Singapore and a patient support group were recruited. Thematic analysis was performed to distill themes from transcripts through open coding by 2 independent coders and axial coding for refinement of categories. Items from 3 existing SLE-specific measures and PROMIS Version 1.0 Item Banks were compared with identified subthemes. Twenty-seven female and 2 male participants (21 Chinese, 4 Malay, 3 Indian, 1 other) ages 23-62 years participated in 6 focus groups and 2 individual interviews, respectively. Twenty-one domains and 92 subthemes were identified. Domains of family, relationships, stigma and discrimination, and freedom were unaddressed by existing SLE-specific measures. Forty subthemes from 14 domains were addressed by the PROMIS Version 1.0 Item Banks (Physical Function, Pain, Fatigue, Sleep Disturbance, Sleep-Related Impairment, Anger, Anxiety, and Depression banks). Family and stigma and discrimination (identified as content gaps) may be accentuated in the Asian sociocultural context. PROMIS item banks have tremendous potential to serve as a core set of items for HRQOL assessment in SLE patients. Additional items may be written to fill the gaps in existing PROMIS item banks. Copyright © 2011 by the American College of Rheumatology.

  15. How does processing affect storage in working memory tasks? Evidence for both domain-general and domain-specific effects.

    PubMed

    Jarrold, Christopher; Tam, Helen; Baddeley, Alan D; Harvey, Caroline E

    2011-05-01

    Two studies that examine whether the forgetting caused by the processing demands of working memory tasks is domain-general or domain-specific are presented. In each, separate groups of adult participants were asked to carry out either verbal or nonverbal operations on exactly the same processing materials while maintaining verbal storage items. The imposition of verbal processing tended to produce greater forgetting even though verbal processing operations took no longer to complete than did nonverbal processing operations. However, nonverbal processing did cause forgetting relative to baseline control conditions, and evidence from the timing of individuals' processing responses suggests that individuals in both processing groups slowed their responses in order to "refresh" the memoranda. Taken together the data suggest that processing has a domain-general effect on working memory performance by impeding refreshment of memoranda but can also cause effects that appear domain-specific and that result from either blocking of rehearsal or interference.

  16. Health numeracy: the importance of domain in assessing numeracy.

    PubMed

    Levy, Helen; Ubel, Peter A; Dillard, Amanda J; Weir, David R; Fagerlin, Angela

    2014-01-01

    Existing research concludes that measures of general numeracy can be used to predict individuals' ability to assess health risks. We posit that the domain in which questions are posed affects the ability to perform mathematical tasks, raising the possibility of a separate construct of "health numeracy" that is distinct from general numeracy. The objective was to determine whether older adults' ability to perform simple math depends on domain. Community-based participants completed 4 math questions posed in 3 different domains: a health domain, a financial domain, and a pure math domain. Participants were 962 individuals aged 55 and older, representative of the community-dwelling US population over age 54. We found that respondents performed significantly worse when questions were posed in the health domain (54% correct) than in either the pure math domain (66% correct) or the financial domain (63% correct). Our experimental measure of numeracy consisted of only 4 questions, and it is possible that the apparent effect of domain is specific to the mathematical tasks that these questions require. These results suggest that health numeracy is strongly related to general numeracy but that the 2 constructs may not be the same. Further research is needed into how different aspects of general numeracy and health numeracy translate into actual medical decisions.

  17. Domain-Specific Self-Concept in Relation to Traditional and Cyber Peer Aggression

    ERIC Educational Resources Information Center

    Toledano, Shanee; Werch, Brittany L.; Wiens, Brenda A.

    2015-01-01

    Individuals who aggress against others have been described both as having overall low self-concept and as having high, inflated self-concept. The conceptualization of self-concept as domain specific provides an alternate means to resolving this controversy. In this study, 223 middle school students completed self-report measures assessing…

  18. Domain General Mediators of the Relation between Kindergarten Number Sense and First-Grade Mathematics Achievement

    PubMed Central

    Hassinger-Das, Brenna; Jordan, Nancy C.; Glutting, Joseph; Irwin, Casey; Dyson, Nancy

    2013-01-01

    Domain general skills that mediate the relation between kindergarten number sense and first-grade mathematics skills were investigated. Participants were 107 children who displayed low number sense in the fall of kindergarten. Controlling for background variables, multiple regression analyses showed that attention problems and executive functioning both were unique predictors of mathematics outcomes. Attention problems were more important for predicting first-grade calculation performance while executive functioning was more important for predicting first-grade performance on applied problems. Moreover, both executive functioning and attention problems were unique partial mediators of the relationship between kindergarten and first-grade mathematics skills. The results provide empirical support for developing interventions that target executive functioning and attention problems in addition to instruction in number skills for kindergartners with initial low number sense. PMID:24237789

  19. Certifying Domain-Specific Policies

    NASA Technical Reports Server (NTRS)

    Lowry, Michael; Pressburger, Thomas; Rosu, Grigore; Koga, Dennis (Technical Monitor)

    2001-01-01

    Proof-checking code for compliance to safety policies potentially enables a product-oriented approach to certain aspects of software certification. To date, previous research has focused on generic, low-level programming-language properties such as memory type safety. In this paper we consider proof-checking higher-level domain -specific properties for compliance to safety policies. The paper first describes a framework related to abstract interpretation in which compliance to a class of certification policies can be efficiently calculated Membership equational logic is shown to provide a rich logic for carrying out such calculations, including partiality, for certification. The architecture for a domain-specific certifier is described, followed by an implemented case study. The case study considers consistency of abstract variable attributes in code that performs geometric calculations in Aerospace systems.

  20. Assessing the co-occurrence of intimate partner violence domains across the life-course: relating typologies to mental health

    PubMed Central

    Armour, Cherie; Sleath, Emma

    2014-01-01

    Background The inter-generational transmission of violence (ITV) hypothesis and polyvictimisation have been studied extensively. The extant evidence suggests that individuals from violent families are at increased risk of subsequent intimate partner violence (IPV) and that a proportion of individuals experience victimisation across multiple rather than single IPV domains. Both ITV and polyvictimisation are shown to increase the risk of psychiatric morbidity, alcohol use, and anger expression. Objective The current study aimed to 1) ascertain if underlying typologies of victimisation across the life-course and over multiple victimisation domains were present and 2) ascertain if groupings differed on mean scores of posttraumatic stress disorder (PTSD), depression, alcohol use, and anger expression. Method University students (N=318) were queried in relation to victimisation experiences and psychological well-being. Responses across multiple domains of IPV spanning the life-course were used in a latent profile analysis. ANOVA was subsequently used to determine if profiles differed in their mean scores on PTSD, depression, alcohol use, and anger expression. Results Three distinct profiles were identified; one of which comprised individuals who experienced “life-course polyvictimisation,” another showing individuals who experienced “witnessing parental victimisation,” and one which experienced “psychological victimisation only.” Life-course polyvictims scored the highest across most assessed measures. Conclusion Witnessing severe physical aggression and injury in parental relationships as a child has an interesting impact on the ITV into adolescence and adulthood. Life-course polyvictims are shown to experience increased levels of psychiatric morbidity and issues with alcohol misuse and anger expression. PMID:25279106

  1. Light-induced conformational changes of LOV1 (light oxygen voltage-sensing domain 1) and LOV2 relative to the kinase domain and regulation of kinase activity in Chlamydomonas phototropin.

    PubMed

    Okajima, Koji; Aihara, Yusuke; Takayama, Yuki; Nakajima, Mihoko; Kashojiya, Sachiko; Hikima, Takaaki; Oroguchi, Tomotaka; Kobayashi, Amane; Sekiguchi, Yuki; Yamamoto, Masaki; Suzuki, Tomomi; Nagatani, Akira; Nakasako, Masayoshi; Tokutomi, Satoru

    2014-01-03

    Phototropin (phot), a blue light (BL) receptor in plants, has two photoreceptive domains named LOV1 and LOV2 as well as a Ser/Thr kinase domain (KD) and acts as a BL-regulated protein kinase. A LOV domain harbors a flavin mononucleotide that undergoes a cyclic photoreaction upon BL excitation via a signaling state in which the inhibition of the kinase activity by LOV2 is negated. To understand the molecular mechanism underlying the BL-dependent activation of the kinase, the photochemistry, kinase activity, and molecular structure were studied with the phot of Chlamydomonas reinhardtii. Full-length and LOV2-KD samples of C. reinhardtii phot showed cyclic photoreaction characteristics with the activation of LOV- and BL-dependent kinase. Truncation of LOV1 decreased the photosensitivity of the kinase activation, which was well explained by the fact that the signaling state lasted for a shorter period of time compared with that of the phot. Small angle x-ray scattering revealed monomeric forms of the proteins in solution and detected BL-dependent conformational changes, suggesting an extension of the global molecular shapes of both samples. Constructed molecular model of full-length phot based on the small angle x-ray scattering data proved the arrangement of LOV1, LOV2, and KD for the first time that showed a tandem arrangement both in the dark and under BL irradiation. The models suggest that LOV1 alters its position relative to LOV2-KD under BL irradiation. This finding demonstrates that LOV1 may interact with LOV2 and modify the photosensitivity of the kinase activation through alteration of the duration of the signaling state in LOV2.

  2. Domain switching in single-phase multiferroics

    NASA Astrophysics Data System (ADS)

    Jia, Tingting; Cheng, Zhenxiang; Zhao, Hongyang; Kimura, Hideo

    2018-06-01

    Multiferroics are a time-honoured research subject by reason for their tremendous application potential in the information industry, such as in multi-state information storage devices and new types of sensors. An outburst of studies on multiferroicity has been witnessed in the 21st century, although this field has a long research history since the 19th century. Multiferroicity has now become one of the hottest research topics in condensed matter physics and materials science. Numerous efforts have been made to investigate the cross-coupling phenomena among ferroic orders such as ferroelectricity, (anti-)ferromagnetism, and ferroelasticity, especially the coupling between electric and magnetic orderings that would account for the magnetoelectric (ME) effect in multiferroic materials. The magnetoelectric properties and coupling behavior of single phase multiferroics are dominated by their domain structures. It was also noted that, however, the multiferroic materials exhibit very complicated domain structures. Studies on domain structure characterization and domain switching are a crucial step in the exploration of approaches to the control and manipulation of magnetic (electric) properties using an electric (magnetic) field or other means. In this review, following a concise outline of our current basic knowledge on the magnetoelectric (ME) effect, we summarize some important research activities on domain switching in single-phase multiferroic materials in the form of single crystals and thin films, especially domain switching behavior involving strain and the related physics in the last decade. We also introduce recent developments in characterization techniques for domain structures of ferroelectric or multiferroic materials, which have significantly advanced our understanding of domain switching dynamics and interactions. The effects of a series of issues such as electric field, magnetic field, and stress effects on domain switching are been discussed as well. It

  3. Domain-Specific Impulsivity in School-Age Children

    PubMed Central

    Tsukayama, Eli; Duckworth, Angela Lee; Kim, Betty

    2013-01-01

    Impulsivity is a salient individual difference in children with well-established predictive validity for life outcomes. The current investigation proposes that impulsive behaviors vary systematically by domain. In a series of studies with ethnically and socioeconomically diverse samples of middle school students, we find that schoolwork-related and interpersonal-related impulsivity, as observed by teachers, parents, and the students themselves, are distinct, moderately correlated behavioral tendencies. Each demonstrates differentiated relationships with dimensions of childhood temperament, Big Five personality factors, and outcomes, such as sociometric popularity, report card grades, and classroom conduct. Implications for theoretical conceptions of impulsivity as well as for practical applications (e.g., domain-specific interventions) are discussed. PMID:24118714

  4. Geometrical Dependence of Domain-Wall Propagation and Nucleation Fields in Magnetic-Domain-Wall Sensors

    NASA Astrophysics Data System (ADS)

    Borie, B.; Kehlberger, A.; Wahrhusen, J.; Grimm, H.; Kläui, M.

    2017-08-01

    We study the key domain-wall properties in segmented nanowire loop-based structures used in domain-wall-based sensors. The two reasons for device failure, namely, distribution of the domain-wall propagation field (depinning) and the nucleation field are determined with magneto-optical Kerr effect and giant-magnetoresistance (GMR) measurements for thousands of elements to obtain significant statistics. Single layers of Ni81 Fe19 , a complete GMR stack with Co90 Fe10 /Ni81Fe19 as a free layer, and a single layer of Co90 Fe10 are deposited and industrially patterned to determine the influence of the shape anisotropy, the magnetocrystalline anisotropy, and the fabrication processes. We show that the propagation field is influenced only slightly by the geometry but significantly by material parameters. Simulations for a realistic wire shape yield a curling-mode type of magnetization configuration close to the nucleation field. Nonetheless, we find that the domain-wall nucleation fields can be described by a typical Stoner-Wohlfarth model related to the measured geometrical parameters of the wires and fitted by considering the process parameters. The GMR effect is subsequently measured in a substantial number of devices (3000) in order to accurately gauge the variation between devices. This measurement scheme reveals a corrected upper limit to the nucleation fields of the sensors that can be exploited for fast characterization of the working elements.

  5. Domain-to-domain coupling in voltage-sensing phosphatase.

    PubMed

    Sakata, Souhei; Matsuda, Makoto; Kawanabe, Akira; Okamura, Yasushi

    2017-01-01

    Voltage-sensing phosphatase (VSP) consists of a transmembrane voltage sensor and a cytoplasmic enzyme region. The enzyme region contains the phosphatase and C2 domains, is structurally similar to the tumor suppressor phosphatase PTEN, and catalyzes the dephosphorylation of phosphoinositides. The transmembrane voltage sensor is connected to the phosphatase through a short linker region, and phosphatase activity is induced upon membrane depolarization. Although the detailed molecular characteristics of the voltage sensor domain and the enzyme region have been revealed, little is known how these two regions are coupled. In addition, it is important to know whether mechanism for coupling between the voltage sensor domain and downstream effector function is shared among other voltage sensor domain-containing proteins. Recent studies in which specific amino acid sites were genetically labeled using a fluorescent unnatural amino acid have enabled detection of the local structural changes in the cytoplasmic region of Ciona intestinalis VSP that occur with a change in membrane potential. The results of those studies provide novel insight into how the enzyme activity of the cytoplasmic region of VSP is regulated by the voltage sensor domain.

  6. Domain-to-domain coupling in voltage-sensing phosphatase

    PubMed Central

    Sakata, Souhei; Matsuda, Makoto; Kawanabe, Akira; Okamura, Yasushi

    2017-01-01

    Voltage-sensing phosphatase (VSP) consists of a transmembrane voltage sensor and a cytoplasmic enzyme region. The enzyme region contains the phosphatase and C2 domains, is structurally similar to the tumor suppressor phosphatase PTEN, and catalyzes the dephosphorylation of phosphoinositides. The transmembrane voltage sensor is connected to the phosphatase through a short linker region, and phosphatase activity is induced upon membrane depolarization. Although the detailed molecular characteristics of the voltage sensor domain and the enzyme region have been revealed, little is known how these two regions are coupled. In addition, it is important to know whether mechanism for coupling between the voltage sensor domain and downstream effector function is shared among other voltage sensor domain-containing proteins. Recent studies in which specific amino acid sites were genetically labeled using a fluorescent unnatural amino acid have enabled detection of the local structural changes in the cytoplasmic region of Ciona intestinalis VSP that occur with a change in membrane potential. The results of those studies provide novel insight into how the enzyme activity of the cytoplasmic region of VSP is regulated by the voltage sensor domain. PMID:28744425

  7. Functional electronic inversion layers at ferroelectric domain walls

    NASA Astrophysics Data System (ADS)

    Mundy, J. A.; Schaab, J.; Kumagai, Y.; Cano, A.; Stengel, M.; Krug, I. P.; Gottlob, D. M.; Doğanay, H.; Holtz, M. E.; Held, R.; Yan, Z.; Bourret, E.; Schneider, C. M.; Schlom, D. G.; Muller, D. A.; Ramesh, R.; Spaldin, N. A.; Meier, D.

    2017-06-01

    Ferroelectric domain walls hold great promise as functional two-dimensional materials because of their unusual electronic properties. Particularly intriguing are the so-called charged walls where a polarity mismatch causes local, diverging electrostatic potentials requiring charge compensation and hence a change in the electronic structure. These walls can exhibit significantly enhanced conductivity and serve as a circuit path. The development of all-domain-wall devices, however, also requires walls with controllable output to emulate electronic nano-components such as diodes and transistors. Here we demonstrate electric-field control of the electronic transport at ferroelectric domain walls. We reversibly switch from resistive to conductive behaviour at charged walls in semiconducting ErMnO3. We relate the transition to the formation--and eventual activation--of an inversion layer that acts as the channel for the charge transport. The findings provide new insight into the domain-wall physics in ferroelectrics and foreshadow the possibility to design elementary digital devices for all-domain-wall circuitry.

  8. A structural analysis of the AAA+ domains in Saccharomyces cerevisiae cytoplasmic dynein

    PubMed Central

    Gleave, Emma S.; Schmidt, Helgo; Carter, Andrew P.

    2014-01-01

    Dyneins are large protein complexes that act as microtubule based molecular motors. The dynein heavy chain contains a motor domain which is a member of the AAA+ protein family (ATPases Associated with diverse cellular Activities). Proteins of the AAA+ family show a diverse range of functionalities, but share a related core AAA+ domain, which often assembles into hexameric rings. Dynein is unusual because it has all six AAA+ domains linked together, in one long polypeptide. The dynein motor domain generates movement by coupling ATP driven conformational changes in the AAA+ ring to the swing of a motile element called the linker. Dynein binds to its microtubule track via a long antiparallel coiled-coil stalk that emanates from the AAA+ ring. Recently the first high resolution structures of the dynein motor domain were published. Here we provide a detailed structural analysis of the six AAA+ domains using our Saccharomycescerevisiae crystal structure. We describe how structural similarities in the dynein AAA+ domains suggest they share a common evolutionary origin. We analyse how the different AAA+ domains have diverged from each other. We discuss how this is related to the function of dynein as a motor protein and how the AAA+ domains of dynein compare to those of other AAA+ proteins. PMID:24680784

  9. The evolution of filamin-a protein domain repeat perspective.

    PubMed

    Light, Sara; Sagit, Rauan; Ithychanda, Sujay S; Qin, Jun; Elofsson, Arne

    2012-09-01

    Particularly in higher eukaryotes, some protein domains are found in tandem repeats, performing broad functions often related to cellular organization. For instance, the eukaryotic protein filamin interacts with many proteins and is crucial for the cytoskeleton. The functional properties of long repeat domains are governed by the specific properties of each individual domain as well as by the repeat copy number. To provide better understanding of the evolutionary and functional history of repeating domains, we investigated the mode of evolution of the filamin domain in some detail. Among the domains that are common in long repeat proteins, sushi and spectrin domains evolve primarily through cassette tandem duplications while scavenger and immunoglobulin repeats appear to evolve through clustered tandem duplications. Additionally, immunoglobulin and filamin repeats exhibit a unique pattern where every other domain shows high sequence similarity. This pattern may be the result of tandem duplications, serve to avert aggregation between adjacent domains or it is the result of functional constraints. In filamin, our studies confirm the presence of interspersed integrin binding domains in vertebrates, while invertebrates exhibit more varied patterns, including more clustered integrin binding domains. The most notable case is leech filamin, which contains a 20 repeat expansion and exhibits unique dimerization topology. Clearly, invertebrate filamins are varied and contain examples of similar adjacent integrin-binding domains. Given that invertebrate integrin shows more similarity to the weaker filamin binder, integrin β3, it is possible that the distance between integrin-binding domains is not as crucial for invertebrate filamins as for vertebrates. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Quantifying the mechanisms of domain gain in animal proteins.

    PubMed

    Buljan, Marija; Frankish, Adam; Bateman, Alex

    2010-01-01

    Protein domains are protein regions that are shared among different proteins and are frequently functionally and structurally independent from the rest of the protein. Novel domain combinations have a major role in evolutionary innovation. However, the relative contributions of the different molecular mechanisms that underlie domain gains in animals are still unknown. By using animal gene phylogenies we were able to identify a set of high confidence domain gain events and by looking at their coding DNA investigate the causative mechanisms. Here we show that the major mechanism for gains of new domains in metazoan proteins is likely to be gene fusion through joining of exons from adjacent genes, possibly mediated by non-allelic homologous recombination. Retroposition and insertion of exons into ancestral introns through intronic recombination are, in contrast to previous expectations, only minor contributors to domain gains and have accounted for less than 1% and 10% of high confidence domain gain events, respectively. Additionally, exonization of previously non-coding regions appears to be an important mechanism for addition of disordered segments to proteins. We observe that gene duplication has preceded domain gain in at least 80% of the gain events. The interplay of gene duplication and domain gain demonstrates an important mechanism for fast neofunctionalization of genes.

  11. Fine-grained semantic categorization across the abstract and concrete domains.

    PubMed

    Ghio, Marta; Vaghi, Matilde Maria Serena; Tettamanti, Marco

    2013-01-01

    A consolidated approach to the study of the mental representation of word meanings has consisted in contrasting different domains of knowledge, broadly reflecting the abstract-concrete dichotomy. More fine-grained semantic distinctions have emerged in neuropsychological and cognitive neuroscience work, reflecting semantic category specificity, but almost exclusively within the concrete domain. Theoretical advances, particularly within the area of embodied cognition, have more recently put forward the idea that distributed neural representations tied to the kinds of experience maintained with the concepts' referents might distinguish conceptual meanings with a high degree of specificity, including those within the abstract domain. Here we report the results of two psycholinguistic rating studies incorporating such theoretical advances with two main objectives: first, to provide empirical evidence of fine-grained distinctions within both the abstract and the concrete semantic domains with respect to relevant psycholinguistic dimensions; second, to develop a carefully controlled linguistic stimulus set that may be used for auditory as well as visual neuroimaging studies focusing on the parametrization of the semantic space beyond the abstract-concrete dichotomy. Ninety-six participants rated a set of 210 sentences across pre-selected concrete (mouth, hand, or leg action-related) and abstract (mental state-, emotion-, mathematics-related) categories, with respect either to different semantic domain-related scales (rating study 1), or to concreteness, familiarity, and context availability (rating study 2). Inferential statistics and correspondence analyses highlighted distinguishing semantic and psycholinguistic traits for each of the pre-selected categories, indicating that a simple abstract-concrete dichotomy is not sufficient to account for the entire semantic variability within either domains.

  12. Fine-Grained Semantic Categorization across the Abstract and Concrete Domains

    PubMed Central

    Tettamanti, Marco

    2013-01-01

    A consolidated approach to the study of the mental representation of word meanings has consisted in contrasting different domains of knowledge, broadly reflecting the abstract-concrete dichotomy. More fine-grained semantic distinctions have emerged in neuropsychological and cognitive neuroscience work, reflecting semantic category specificity, but almost exclusively within the concrete domain. Theoretical advances, particularly within the area of embodied cognition, have more recently put forward the idea that distributed neural representations tied to the kinds of experience maintained with the concepts' referents might distinguish conceptual meanings with a high degree of specificity, including those within the abstract domain. Here we report the results of two psycholinguistic rating studies incorporating such theoretical advances with two main objectives: first, to provide empirical evidence of fine-grained distinctions within both the abstract and the concrete semantic domains with respect to relevant psycholinguistic dimensions; second, to develop a carefully controlled linguistic stimulus set that may be used for auditory as well as visual neuroimaging studies focusing on the parametrization of the semantic space beyond the abstract-concrete dichotomy. Ninety-six participants rated a set of 210 sentences across pre-selected concrete (mouth, hand, or leg action-related) and abstract (mental state-, emotion-, mathematics-related) categories, with respect either to different semantic domain-related scales (rating study 1), or to concreteness, familiarity, and context availability (rating study 2). Inferential statistics and correspondence analyses highlighted distinguishing semantic and psycholinguistic traits for each of the pre-selected categories, indicating that a simple abstract-concrete dichotomy is not sufficient to account for the entire semantic variability within either domains. PMID:23825625

  13. Interaction between the PH and START domains of ceramide transfer protein competes with phosphatidylinositol 4-phosphate binding by the PH domain

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

    Prashek, Jennifer; Bouyain, Samuel; Fu, Mingui

    De novo synthesis of the sphingolipid sphingomyelin requires non-vesicular transport of ceramide from the endoplasmic reticulum to the Golgi by the multidomain protein ceramide transfer protein (CERT). CERT's N-terminal pleckstrin homology (PH) domain targets it to the Golgi by binding to phosphatidylinositol 4-phosphate (PtdIns(4)P) in the Golgi membrane, whereas its C-terminal StAR-related lipid transfer domain (START) carries out ceramide transfer. Hyperphosphorylation of a serine-rich motif immediately after the PH domain decreases both PtdIns(4)P binding and ceramide transfer by CERT. This down-regulation requires both the PH and START domains, suggesting a possible inhibitory interaction between the two domains. In this studymore » we show that isolated PH and START domains interact with each other. The crystal structure of a PH–START complex revealed that the START domain binds to the PH domain at the same site for PtdIns(4)P-binding, suggesting that the START domain competes with PtdIns(4)P for association with the PH domain. We further report that mutations disrupting the PH–START interaction increase both PtdIns(4)P-binding affinity and ceramide transfer activity of a CERT-serine–rich phosphorylation mimic. We also found that these mutations increase the Golgi localization of CERT inside the cell, consistent with enhanced PtdIns(4)P binding of the mutant. Collectively, our structural, biochemical, and cellular investigations provide important structural insight into the regulation of CERT function and localization.« less

  14. Health Numeracy: The Importance of Domain in Assessing Numeracy

    PubMed Central

    Levy, Helen; Ubel, Peter A.; Dillard, Amanda J.; Weir, David R.; Fagerlin, Angela

    2014-01-01

    Background Existing research concludes that measures of general numeracy can be used to predict individuals’ ability to assess health risks. We posit that the domain in which questions are posed affects the ability to perform mathematical tasks, raising the possibility of a separate construct of “health numeracy” that is distinct from general numeracy. Objective To determine whether older adults’ ability to perform simple math depends on domain. Design Community-based participants completed four math questions posed in three different domains: a health domain, a financial domain, and a pure math domain. Participants 962 individuals aged 55 and older, representative of the community-dwelling U.S. population over age 54. Results We found that respondents performed significantly worse when questions were posed in the health domain (54 percent correct) than in either the pure math domain (66 percent correct) or the financial domain (63 percent correct). Limitations Our experimental measure of numeracy consisted of only four questions, and it is possible that the apparent effect of domain is specific to the mathematical tasks that these questions require. Conclusions These results suggest that health numeracy is strongly related to general numeracy but that the two constructs may not be the same. Further research is needed into how different aspects of general numeracy and health numeracy translate into actual medical decisions. PMID:23824401

  15. Predicting detection performance with model observers: Fourier domain or spatial domain?

    PubMed

    Chen, Baiyu; Yu, Lifeng; Leng, Shuai; Kofler, James; Favazza, Christopher; Vrieze, Thomas; McCollough, Cynthia

    2016-02-27

    The use of Fourier domain model observer is challenged by iterative reconstruction (IR), because IR algorithms are nonlinear and IR images have noise texture different from that of FBP. A modified Fourier domain model observer, which incorporates nonlinear noise and resolution properties, has been proposed for IR and needs to be validated with human detection performance. On the other hand, the spatial domain model observer is theoretically applicable to IR, but more computationally intensive than the Fourier domain method. The purpose of this study is to compare the modified Fourier domain model observer to the spatial domain model observer with both FBP and IR images, using human detection performance as the gold standard. A phantom with inserts of various low contrast levels and sizes was repeatedly scanned 100 times on a third-generation, dual-source CT scanner at 5 dose levels and reconstructed using FBP and IR algorithms. The human detection performance of the inserts was measured via a 2-alternative-forced-choice (2AFC) test. In addition, two model observer performances were calculated, including a Fourier domain non-prewhitening model observer and a spatial domain channelized Hotelling observer. The performance of these two mode observers was compared in terms of how well they correlated with human observer performance. Our results demonstrated that the spatial domain model observer correlated well with human observers across various dose levels, object contrast levels, and object sizes. The Fourier domain observer correlated well with human observers using FBP images, but overestimated the detection performance using IR images.

  16. Predicting detection performance with model observers: Fourier domain or spatial domain?

    PubMed Central

    Chen, Baiyu; Yu, Lifeng; Leng, Shuai; Kofler, James; Favazza, Christopher; Vrieze, Thomas; McCollough, Cynthia

    2016-01-01

    The use of Fourier domain model observer is challenged by iterative reconstruction (IR), because IR algorithms are nonlinear and IR images have noise texture different from that of FBP. A modified Fourier domain model observer, which incorporates nonlinear noise and resolution properties, has been proposed for IR and needs to be validated with human detection performance. On the other hand, the spatial domain model observer is theoretically applicable to IR, but more computationally intensive than the Fourier domain method. The purpose of this study is to compare the modified Fourier domain model observer to the spatial domain model observer with both FBP and IR images, using human detection performance as the gold standard. A phantom with inserts of various low contrast levels and sizes was repeatedly scanned 100 times on a third-generation, dual-source CT scanner at 5 dose levels and reconstructed using FBP and IR algorithms. The human detection performance of the inserts was measured via a 2-alternative-forced-choice (2AFC) test. In addition, two model observer performances were calculated, including a Fourier domain non-prewhitening model observer and a spatial domain channelized Hotelling observer. The performance of these two mode observers was compared in terms of how well they correlated with human observer performance. Our results demonstrated that the spatial domain model observer correlated well with human observers across various dose levels, object contrast levels, and object sizes. The Fourier domain observer correlated well with human observers using FBP images, but overestimated the detection performance using IR images. PMID:27239086

  17. Domain-General and Domain-Specific Strategies for the Assessment of Distress Intolerance

    PubMed Central

    McHugh, R. Kathryn; Otto, Michael W.

    2011-01-01

    Recent research has provided evidence that distress intolerance—the perceived inability to tolerate distressing states—varies based on the domain of distress (e.g., pain, anxiety). Although domain-specific assessment strategies may provide information targeted to specific disorders or maladaptive behaviors, domain-general measures have the potential to facilitate comparisons across studies, disorders, and populations. The current study evaluated the utilization of self-report measures of distress intolerance as domain-general measures by examining their association with indices of behavioral avoidance and substance craving. Two groups of participants (N = 55) were recruited including a substance-dependent group and a comparison group equated based on the presence of an affective disorder. Results provided support for the validity of domain-general measures for assessing distress intolerance across varied domains. The importance of both domain-general and domain-specific measurement of distress intolerance is discussed. PMID:21823763

  18. Preparation for Old Age in Different Life Domains: Dimensions and Age Differences

    ERIC Educational Resources Information Center

    Kornadt, Anna E.; Rothermund, Klaus

    2014-01-01

    We investigated preparation for age-related changes from a multidimensional, life span perspective and administered a newly developed questionnaire to a large sample aged 30-80 years. Preparing for age-related changes was organized by life domains, with domain-specific types of preparation addressing obstacles and opportunities in the respective…

  19. The Influence of Domain Knowledge on the Functional Capacity of Working Memory

    ERIC Educational Resources Information Center

    Ricks, Travis Rex; Wiley, Jennifer

    2009-01-01

    Theories of expertise have proposed that superior cognitive performance is in part due to increases in the functional capacity of working memory during domain-related tasks. Consistent with this approach Fincher-Kiefer et al. (1988), found that domain knowledge increased scores on baseball-related reading span tasks. The present studies extended…

  20. Domain-general mediators of the relation between kindergarten number sense and first-grade mathematics achievement.

    PubMed

    Hassinger-Das, Brenna; Jordan, Nancy C; Glutting, Joseph; Irwin, Casey; Dyson, Nancy

    2014-02-01

    Domain-general skills that mediate the relation between kindergarten number sense and first-grade mathematics skills were investigated. Participants were 107 children who displayed low number sense in the fall of kindergarten. Controlling for background variables, multiple regression analyses showed that both attention problems and executive functioning were unique predictors of mathematics outcomes. Attention problems were more important for predicting first-grade calculation performance, whereas executive functioning was more important for predicting first-grade performance on applied problems. Moreover, both executive functioning and attention problems were unique partial mediators of the relationship between kindergarten and first-grade mathematics skills. The results provide empirical support for developing interventions that target executive functioning and attention problems in addition to instruction in number skills for kindergartners with initial low number sense. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Displacement Current in Domain Walls of Bismuth Ferrite

    NASA Astrophysics Data System (ADS)

    Prosandeev, Sergey; Yang, Yurong; Paillard, Charles; Bellaiche, L.

    2018-03-01

    In 1861, Maxwell conceived the idea of the displacement current, which then made laws of electrodynamics more complete and also resulted in the realization of devices exploiting such displacement current. Interestingly, it is presently unknown if such displacement current can result in large intrinsic ac current in ferroic systems possessing domains, despite the flurry of recent activities that have been devoted to domains and their corresponding conductivity in these compounds. Here, we report first-principles-based atomistic simulations that predict that the transverse (polarization-related) displacement currents of 71° and 109° domains in the prototypical BiFeO3 multiferroic material are significant at the walls of such domains and in the GHz regime, and, in fact, result in currents that are at least of the same order of magnitude than previously reported dc currents (that are likely extrinsic in nature and due to electrons). Such large, localized and intrinsic ac currents are found to originate from low-frequency vibrations at the domain walls, and may open the door to the design of novel devices functioning in the GHz or THz range and in which currents would be confined within the domain wall.

  2. Method for identification of rigid domains and hinge residues in proteins based on exhaustive enumeration.

    PubMed

    Sim, Jaehyun; Sim, Jun; Park, Eunsung; Lee, Julian

    2015-06-01

    Many proteins undergo large-scale motions where relatively rigid domains move against each other. The identification of rigid domains, as well as the hinge residues important for their relative movements, is important for various applications including flexible docking simulations. In this work, we develop a method for protein rigid domain identification based on an exhaustive enumeration of maximal rigid domains, the rigid domains not fully contained within other domains. The computation is performed by mapping the problem to that of finding maximal cliques in a graph. A minimal set of rigid domains are then selected, which cover most of the protein with minimal overlap. In contrast to the results of existing methods that partition a protein into non-overlapping domains using approximate algorithms, the rigid domains obtained from exact enumeration naturally contain overlapping regions, which correspond to the hinges of the inter-domain bending motion. The performance of the algorithm is demonstrated on several proteins. © 2015 Wiley Periodicals, Inc.

  3. Generation of a consensus protein domain dictionary

    PubMed Central

    Schaeffer, R. Dustin; Jonsson, Amanda L.; Simms, Andrew M.; Daggett, Valerie

    2011-01-01

    Motivation: The discovery of new protein folds is a relatively rare occurrence even as the rate of protein structure determination increases. This rarity reinforces the concept of folds as reusable units of structure and function shared by diverse proteins. If the folding mechanism of proteins is largely determined by their topology, then the folding pathways of members of existing folds could encompass the full set used by globular protein domains. Results: We have used recent versions of three common protein domain dictionaries (SCOP, CATH and Dali) to generate a consensus domain dictionary (CDD). Surprisingly, 40% of the metafolds in the CDD are not composed of autonomous structural domains, i.e. they are not plausible independent folding units. This finding has serious ramifications for bioinformatics studies mining these domain dictionaries for globular protein properties. However, our main purpose in deriving this CDD was to generate an updated CDD to choose targets for MD simulation as part of our dynameomics effort, which aims to simulate the native and unfolding pathways of representatives of all globular protein consensus folds (metafolds). Consequently, we also compiled a list of representative protein targets of each metafold in the CDD. Availability and implementation: This domain dictionary is available at www.dynameomics.org. Contact: daggett@u.washington.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:21068000

  4. A structural analysis of the AAA+ domains in Saccharomyces cerevisiae cytoplasmic dynein.

    PubMed

    Gleave, Emma S; Schmidt, Helgo; Carter, Andrew P

    2014-06-01

    Dyneins are large protein complexes that act as microtubule based molecular motors. The dynein heavy chain contains a motor domain which is a member of the AAA+ protein family (ATPases Associated with diverse cellular Activities). Proteins of the AAA+ family show a diverse range of functionalities, but share a related core AAA+ domain, which often assembles into hexameric rings. Dynein is unusual because it has all six AAA+ domains linked together, in one long polypeptide. The dynein motor domain generates movement by coupling ATP driven conformational changes in the AAA+ ring to the swing of a motile element called the linker. Dynein binds to its microtubule track via a long antiparallel coiled-coil stalk that emanates from the AAA+ ring. Recently the first high resolution structures of the dynein motor domain were published. Here we provide a detailed structural analysis of the six AAA+ domains using our Saccharomycescerevisiae crystal structure. We describe how structural similarities in the dynein AAA+ domains suggest they share a common evolutionary origin. We analyse how the different AAA+ domains have diverged from each other. We discuss how this is related to the function of dynein as a motor protein and how the AAA+ domains of dynein compare to those of other AAA+ proteins. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Protein domain assignment from the recurrence of locally similar structures

    PubMed Central

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

    2010-01-01

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

  6. Models of the Joint Structure of Domain-Related and Global Distress: Implications for the Reconciliation of Quality of Life and Mental Health Perspectives

    ERIC Educational Resources Information Center

    Magee, William; St-Arnaud, Sebastien

    2012-01-01

    Research on subjective wellbeing includes studies of both domain-related and global distress. The mental health literature, though, focuses almost exclusively on global distress. This seems to be partly due to a common belief that psychological distress, and the moods that comprise distress, necessarily lack referential content. However, if that…

  7. A Logic for Inclusion of Administrative Domains and Administrators in Multi-domain Authorization

    NASA Astrophysics Data System (ADS)

    Iranmanesh, Zeinab; Amini, Morteza; Jalili, Rasool

    Authorization policies for an administrative domain or a composition of multiple domains in multi-domain environments are determined by either one administrator or multiple administrators' cooperation. Several logic-based models for multi-domain environments' authorization have been proposed; however, they have not considered administrators and administrative domains in policies' representation. In this paper, we propose the syntax, proof theory, and semantics of a logic for multi-domain authorization policies including administrators and administrative domains. Considering administrators in policies provides the possibility of presenting composite administration having applicability in many collaborative applications. Indeed, administrators and administrative domains stated in policies can be used in authorization. The presented logic is based on modal logic and utilizes two calculi named the calculus of administrative domains and the calculus of administrators. It is also proved that the logic is sound. A case study is presented signifying the logic application in practical projects.

  8. On the Analysis Methods for the Time Domain and Frequency Domain Response of a Buried Objects*

    NASA Astrophysics Data System (ADS)

    Poljak, Dragan; Šesnić, Silvestar; Cvetković, Mario

    2014-05-01

    There has been a continuous interest in the analysis of ground-penetrating radar systems and related applications in civil engineering [1]. Consequently, a deeper insight of scattering phenomena occurring in a lossy half-space, as well as the development of sophisticated numerical methods based on Finite Difference Time Domain (FDTD) method, Finite Element Method (FEM), Boundary Element Method (BEM), Method of Moments (MoM) and various hybrid methods, is required, e.g. [2], [3]. The present paper deals with certain techniques for time and frequency domain analysis, respectively, of buried conducting and dielectric objects. Time domain analysis is related to the assessment of a transient response of a horizontal straight thin wire buried in a lossy half-space using a rigorous antenna theory (AT) approach. The AT approach is based on the space-time integral equation of the Pocklington type (time domain electric field integral equation for thin wires). The influence of the earth-air interface is taken into account via the simplified reflection coefficient arising from the Modified Image Theory (MIT). The obtained results for the transient current induced along the electrode due to the transmitted plane wave excitation are compared to the numerical results calculated via an approximate transmission line (TL) approach and the AT approach based on the space-frequency variant of the Pocklington integro-differential approach, respectively. It is worth noting that the space-frequency Pocklington equation is numerically solved via the Galerkin-Bubnov variant of the Indirect Boundary Element Method (GB-IBEM) and the corresponding transient response is obtained by the aid of inverse fast Fourier transform (IFFT). The results calculated by means of different approaches agree satisfactorily. Frequency domain analysis is related to the assessment of frequency domain response of dielectric sphere using the full wave model based on the set of coupled electric field integral

  9. Arabidopsis F-box protein containing a Nictaba-related lectin domain interacts with N-acetyllactosamine structures.

    PubMed

    Stefanowicz, Karolina; Lannoo, Nausicaä; Proost, Paul; Van Damme, Els J M

    2012-01-01

    The Arabidopsis thaliana genome contains a small group of bipartite F-box proteins, consisting of an N-terminal F-box domain and a C-terminal domain sharing sequence similarity with Nictaba, the jasmonate-induced glycan-binding protein (lectin) from tobacco. Based on the high sequence similarity between the C-terminal domain of these proteins and Nictaba, the hypothesis was put forward that the so-called F-box-Nictaba proteins possess carbohydrate-binding activity and accordingly can be considered functional homologs of the mammalian sugar-binding F-box or Fbs proteins which are involved in proteasomal degradation of glycoproteins. To obtain experimental evidence for the carbohydrate-binding activity and specificity of the A. thaliana F-box-Nictaba proteins, both the complete F-box-Nictaba sequence of one selected Arabidopsis F-box protein (in casu At2g02360) as well as the Nictaba-like domain only were expressed in Pichia pastoris and analyzed by affinity chromatography, agglutination assays and glycan micro-array binding assays. These results demonstrated that the C-terminal Nictaba-like domain provides the F-box-protein with a carbohydrate-binding activity that is specifically directed against N- and O-glycans containing N-acetyllactosamine (Galβ1-3GlcNAc and Galβ1-4GlcNAc) and poly-N-acetyllactosamine ([Galβ1-4GlcNAc]n) as well as Lewis A (Galβ1-3(Fucα1-4)GlcNAc), Lewis X (Galβ1-4(Fucα1-3)GlcNAc, Lewis Y (Fucα1-2Galβ1-4(Fucα1-3)GlcNAc) and blood type B (Galα1-3(Fucα1-2)Galβ1-3GlcNAc) motifs. Based on these findings one can reasonably conclude that at least the A. thaliana F-box-Nictaba protein encoded by At2g02360 can act as a carbohydrate-binding protein. The results from the glycan array assays revealed differences in sugar-binding specificity between the F-box protein and Nictaba, indicating that the same carbohydrate-binding motif can accommodate unrelated oligosaccharides.

  10. Heat conductivity in graphene and related materials: A time-domain modal analysis

    NASA Astrophysics Data System (ADS)

    Gill-Comeau, Maxime; Lewis, Laurent J.

    2015-11-01

    We use molecular dynamics (MD) simulations to study heat conductivity in single-layer graphene and graphite. We analyze the MD trajectories through a time-domain modal analysis and show that this is essential for obtaining a reliable representation of the heat flow in graphene and graphite as it permits the proper treatment of collective vibrational excitations, in contrast to a frequency-domain formulation. Our temperature-dependent results are in very good agreement with experiment and, for temperatures in the range 300-1200 K, we find that the ZA branch allows more heat flow than all other branches combined while the contributions of the TA, LA, and ZO branches are comparable at all temperatures. Conductivity mappings reveal strong collective excitations associated with low-frequency ZA modes. We demonstrate that these collective effects are a consequence of the quadratic nature of the ZA branch as they also show up in graphite but are reduced in strained graphene, where the dispersion becomes linear, and are absent in diamond, where acoustic branches are linear. In general, neglecting collective excitations yields errors similar to those from the single-mode relaxation-time approximation.

  11. Using domain knowledge and domain-inspired discourse model for coreference resolution for clinical narratives

    PubMed Central

    Roth, Dan

    2013-01-01

    Objective This paper presents a coreference resolution system for clinical narratives. Coreference resolution aims at clustering all mentions in a single document to coherent entities. Materials and methods A knowledge-intensive approach for coreference resolution is employed. The domain knowledge used includes several domain-specific lists, a knowledge intensive mention parsing, and task informed discourse model. Mention parsing allows us to abstract over the surface form of the mention and represent each mention using a higher-level representation, which we call the mention's semantic representation (SR). SR reduces the mention to a standard form and hence provides better support for comparing and matching. Existing coreference resolution systems tend to ignore discourse aspects and rely heavily on lexical and structural cues in the text. The authors break from this tradition and present a discourse model for “person” type mentions in clinical narratives, which greatly simplifies the coreference resolution. Results This system was evaluated on four different datasets which were made available in the 2011 i2b2/VA coreference challenge. The unweighted average of F1 scores (over B-cubed, MUC and CEAF) varied from 84.2% to 88.1%. These experiments show that domain knowledge is effective for different mention types for all the datasets. Discussion Error analysis shows that most of the recall errors made by the system can be handled by further addition of domain knowledge. The precision errors, on the other hand, are more subtle and indicate the need to understand the relations in which mentions participate for building a robust coreference system. Conclusion This paper presents an approach that makes an extensive use of domain knowledge to significantly improve coreference resolution. The authors state that their system and the knowledge sources developed will be made publicly available. PMID:22781192

  12. Reconstituting protein interaction networks using parameter-dependent domain-domain interactions

    PubMed Central

    2013-01-01

    Background We can describe protein-protein interactions (PPIs) as sets of distinct domain-domain interactions (DDIs) that mediate the physical interactions between proteins. Experimental data confirm that DDIs are more consistent than their corresponding PPIs, lending support to the notion that analyses of DDIs may improve our understanding of PPIs and lead to further insights into cellular function, disease, and evolution. However, currently available experimental DDI data cover only a small fraction of all existing PPIs and, in the absence of structural data, determining which particular DDI mediates any given PPI is a challenge. Results We present two contributions to the field of domain interaction analysis. First, we introduce a novel computational strategy to merge domain annotation data from multiple databases. We show that when we merged yeast domain annotations from six annotation databases we increased the average number of domains per protein from 1.05 to 2.44, bringing it closer to the estimated average value of 3. Second, we introduce a novel computational method, parameter-dependent DDI selection (PADDS), which, given a set of PPIs, extracts a small set of domain pairs that can reconstruct the original set of protein interactions, while attempting to minimize false positives. Based on a set of PPIs from multiple organisms, our method extracted 27% more experimentally detected DDIs than existing computational approaches. Conclusions We have provided a method to merge domain annotation data from multiple sources, ensuring large and consistent domain annotation for any given organism. Moreover, we provided a method to extract a small set of DDIs from the underlying set of PPIs and we showed that, in contrast to existing approaches, our method was not biased towards DDIs with low or high occurrence counts. Finally, we used these two methods to highlight the influence of the underlying annotation density on the characteristics of extracted DDIs. Although

  13. Novel interactions of ankyrins-G at the costameres: The muscle-specific Obscurin/Titin-Binding-related Domain (OTBD) binds plectin and filamin C

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

    Maiweilidan, Yimingjiang; Klauza, Izabela; Kordeli, Ekaterini, E-mail: ekaterini.kordeli@inserm.fr

    2011-04-01

    Ankyrins, the adapters of the spectrin skeleton, are involved in local accumulation and stabilization of integral proteins to the appropriate membrane domains. In striated muscle, tissue-dependent alternative splicing generates unique Ank3 gene products (ankyrins-G); they share the Obscurin/Titin-Binding-related Domain (OTBD), a muscle-specific insert of the C-terminal domain which is highly conserved among ankyrin genes, and binds obscurin and titin to Ank1 gene products. We previously proposed that OTBD sequences constitute a novel domain of protein-protein interactions which confers ankyrins with specific cellular functions in muscle. Here we searched for muscle proteins binding to ankyrin-G OTBD by yeast two hybrid assay,more » and we found plectin and filamin C, two organizing elements of the cytoskeleton with essential roles in myogenesis, muscle cell cytoarchitecture, and muscle disease. The three proteins coimmunoprecipitate from skeletal muscle extracts and colocalize at costameres in adult muscle fibers. During in vitro myogenesis, muscle ankyrins-G are first expressed in postmitotic myocytes undergoing fusion to myotubes. In western blots of subcellular fractions from C2C12 cells, the majority of muscle ankyrins-G appear associated with membrane compartments. Occasional but not extensive co-localization at nascent costameres suggested that ankyrin-G interactions with plectin and filamin C are not involved in costamere assembly; they would rather reinforce stability and/or modulate molecular interactions in sarcolemma microdomains by establishing novel links between muscle-specific ankyrins-G and the two costameric dystrophin-associated glycoprotein and integrin-based protein complexes. These results report the first protein-protein interactions involving the ankyrin-G OTBD domain and support the hypothesis that OTBD sequences confer ankyrins with a gain of function in vertebrates, bringing further consolidation and resilience of the linkage between

  14. Universal features in the genome-level evolution of protein domains.

    PubMed

    Cosentino Lagomarsino, Marco; Sellerio, Alessandro L; Heijning, Philip D; Bassetti, Bruno

    2009-01-01

    Protein domains can be used to study proteome evolution at a coarse scale. In particular, they are found on genomes with notable statistical distributions. It is known that the distribution of domains with a given topology follows a power law. We focus on a further aspect: these distributions, and the number of distinct topologies, follow collective trends, or scaling laws, depending on the total number of domains only, and not on genome-specific features. We present a stochastic duplication/innovation model, in the class of the so-called 'Chinese restaurant processes', that explains this observation with two universal parameters, representing a minimal number of domains and the relative weight of innovation to duplication. Furthermore, we study a model variant where new topologies are related to occurrence in genomic data, accounting for fold specificity. Both models have general quantitative agreement with data from hundreds of genomes, which indicates that the domains of a genome are built with a combination of specificity and robust self-organizing phenomena. The latter are related to the basic evolutionary 'moves' of duplication and innovation, and give rise to the observed scaling laws, a priori of the specific evolutionary history of a genome. We interpret this as the concurrent effect of neutral and selective drives, which increase duplication and decrease innovation in larger and more complex genomes. The validity of our model would imply that the empirical observation of a small number of folds in nature may be a consequence of their evolution.

  15. Predicting Children's Reading and Mathematics Achievement from Early Quantitative Knowledge and Domain-General Cognitive Abilities

    PubMed Central

    Chu, Felicia W.; vanMarle, Kristy; Geary, David C.

    2016-01-01

    One hundred children (44 boys) participated in a 3-year longitudinal study of the development of basic quantitative competencies and the relation between these competencies and later mathematics and reading achievement. The children's preliteracy knowledge, intelligence, executive functions, and parental educational background were also assessed. The quantitative tasks assessed a broad range of symbolic and nonsymbolic knowledge and were administered four times across 2 years of preschool. Mathematics achievement was assessed at the end of each of 2 years of preschool, and mathematics and word reading achievement were assessed at the end of kindergarten. Our goals were to determine how domain-general abilities contribute to growth in children's quantitative knowledge and to determine how domain-general and domain-specific abilities contribute to children's preschool mathematics achievement and kindergarten mathematics and reading achievement. We first identified four core quantitative competencies (e.g., knowledge of the cardinal value of number words) that predict later mathematics achievement. The domain-general abilities were then used to predict growth in these competencies across 2 years of preschool, and the combination of domain-general abilities, preliteracy skills, and core quantitative competencies were used to predict mathematics achievement across preschool and mathematics and word reading achievement at the end of kindergarten. Both intelligence and executive functions predicted growth in the four quantitative competencies, especially across the first year of preschool. A combination of domain-general and domain-specific competencies predicted preschoolers' mathematics achievement, with a trend for domain-specific skills to be more strongly related to achievement at the beginning of preschool than at the end of preschool. Preschool preliteracy skills, sensitivity to the relative quantities of collections of objects, and cardinal knowledge predicted

  16. Predicting Children's Reading and Mathematics Achievement from Early Quantitative Knowledge and Domain-General Cognitive Abilities.

    PubMed

    Chu, Felicia W; vanMarle, Kristy; Geary, David C

    2016-01-01

    One hundred children (44 boys) participated in a 3-year longitudinal study of the development of basic quantitative competencies and the relation between these competencies and later mathematics and reading achievement. The children's preliteracy knowledge, intelligence, executive functions, and parental educational background were also assessed. The quantitative tasks assessed a broad range of symbolic and nonsymbolic knowledge and were administered four times across 2 years of preschool. Mathematics achievement was assessed at the end of each of 2 years of preschool, and mathematics and word reading achievement were assessed at the end of kindergarten. Our goals were to determine how domain-general abilities contribute to growth in children's quantitative knowledge and to determine how domain-general and domain-specific abilities contribute to children's preschool mathematics achievement and kindergarten mathematics and reading achievement. We first identified four core quantitative competencies (e.g., knowledge of the cardinal value of number words) that predict later mathematics achievement. The domain-general abilities were then used to predict growth in these competencies across 2 years of preschool, and the combination of domain-general abilities, preliteracy skills, and core quantitative competencies were used to predict mathematics achievement across preschool and mathematics and word reading achievement at the end of kindergarten. Both intelligence and executive functions predicted growth in the four quantitative competencies, especially across the first year of preschool. A combination of domain-general and domain-specific competencies predicted preschoolers' mathematics achievement, with a trend for domain-specific skills to be more strongly related to achievement at the beginning of preschool than at the end of preschool. Preschool preliteracy skills, sensitivity to the relative quantities of collections of objects, and cardinal knowledge predicted

  17. The Enigmatic Origin of Papillomavirus Protein Domains

    PubMed Central

    Kirsip, Heleri; Gaston, Kevin

    2017-01-01

    Almost a century has passed since the discovery of papillomaviruses. A few decades of research have given a wealth of information on the molecular biology of papillomaviruses. Several excellent studies have been performed looking at the long- and short-term evolution of these viruses. However, when and how papillomaviruses originate is still a mystery. In this study, we systematically searched the (sequenced) biosphere to find distant homologs of papillomaviral protein domains. Our data show that, even including structural information, which allows us to find deeper evolutionary relationships compared to sequence-only based methods, only half of the protein domains in papillomaviruses have relatives in the rest of the biosphere. We show that the major capsid protein L1 and the replication protein E1 have relatives in several viral families, sharing three protein domains with Polyomaviridae and Parvoviridae. However, only the E1 replication protein has connections with cellular organisms. Most likely, the papillomavirus ancestor is of marine origin, a biotope that is not very well sequenced at the present time. Nevertheless, there is no evidence as to how papillomaviruses originated and how they became vertebrate and epithelium specific. PMID:28832519

  18. The Enigmatic Origin of Papillomavirus Protein Domains.

    PubMed

    Puustusmaa, Mikk; Kirsip, Heleri; Gaston, Kevin; Abroi, Aare

    2017-08-23

    Almost a century has passed since the discovery of papillomaviruses. A few decades of research have given a wealth of information on the molecular biology of papillomaviruses. Several excellent studies have been performed looking at the long- and short-term evolution of these viruses. However, when and how papillomaviruses originate is still a mystery. In this study, we systematically searched the (sequenced) biosphere to find distant homologs of papillomaviral protein domains. Our data show that, even including structural information, which allows us to find deeper evolutionary relationships compared to sequence-only based methods, only half of the protein domains in papillomaviruses have relatives in the rest of the biosphere. We show that the major capsid protein L1 and the replication protein E1 have relatives in several viral families, sharing three protein domains with Polyomaviridae and Parvoviridae . However, only the E1 replication protein has connections with cellular organisms. Most likely, the papillomavirus ancestor is of marine origin, a biotope that is not very well sequenced at the present time. Nevertheless, there is no evidence as to how papillomaviruses originated and how they became vertebrate and epithelium specific.

  19. Domain organization of p130, PLC-related catalytically inactive protein, and structural basis for the lack of enzyme activity.

    PubMed

    Kanematsu, T; Yoshimura, K; Hidaka, K; Takeuchi, H; Katan, M; Hirata, M

    2000-05-01

    The 130-kDa protein (p130) was isolated as a novel inositol 1,4, 5-trisphosphate [Ins(1,4,5)P3]-binding protein similar to phospholipase C-delta1 (PLC-delta1), but lacking catalytic activity [Kanematsu, T., Takeya, H., Watanabe, Y., Ozaki, S., Yoshida, M., Koga, T., Iwanaga, S. & Hirata, M. (1992) J. Biol. Chem. 267, 6518-6525; Kanematsu, T., Misumi, Y., Watanabe, Y., Ozaki, S., Koga, T., Iwanaga, S., Ikehara, Y. & Hirata, M. (1996) Biochem. J. 313, 319-325]. To test experimentally the domain organization of p130 and structural basis for lack of PLC activity, we subjected p130 to limited proteolysis and also constructed a number of chimeras with PLC-delta1. Trypsin treatment of p130 produced four major polypeptides with molecular masses of 86 kDa, 55 kDa, 33 kDa and 25 kDa. Two polypeptides of 86 kDa and 55 kDa started at Lys93 and were calculated to end at Arg851 and Arg568, respectively. Using the same approach, it has been found that the polypeptides of 33 kDa and 25 kDa are likely to correspond to regions between Val569 and Arg851 and Lys869 and Leu1096, respectively. All the proteolytic sites were in interconnecting regions between the predicted domains, therefore supporting domain organization based on sequence similarity to PLC-delta1 and demonstrating that all domains of p130, including the unique region at the C-terminus, are stable, tightly folded structures. p130 truncated at either or both the N-terminus (94 amino acids) and C-terminus (851-1096 amino acids) expressed in COS-1 cells showed no catalytic activity, indicating that p130 has intrinsically no PLC activity. A number of chimeric molecules between p130 and PLC-delta1 were constructed and assayed for PLC activity. It was shown that structural differences in interdomain interactions exist between the two proteins, as only some domains of p130 could replace the corresponding structures in PLC-delta1 to form a functional enzyme. These results suggest that p130 and the related proteins could

  20. Assessing subjective quality of life domains after multiple sclerosis diagnosis disclosure.

    PubMed

    Mattarozzi, Katia; Casini, Federica; Baldin, Elisa; Baldini, Martina; Lugaresi, Alessandra; Milani, Paola; Pietrolongo, Erika; Gajofatto, Alberto; Leone, Maurizio; Riise, Trond; Vignatelli, Luca; D'Alessandro, Roberto

    2016-04-01

    An investigation of the domains Italian patients with multiple sclerosis (MS) named as constituting their quality of life over time. We assessed, in 68 patients, QoL domains using the Schedule for the Evaluation of Individual QoL: (a) before MS diagnosis disclosure, (b) thirty days after disclosure, and (c) after one and (d) four years' follow-up. The life domains most frequently named by patients were as follows: Family, Work and Finance, Hobbies, Health, Relationship with Friends and Job Effectiveness. Only Health and Job Effectiveness domains varied with time. The Health domain became a critical dimension when MS diagnosis was revealed. In addition, patients tended to be more satisfied with their health after disclosure compared to pre-diagnosis. Job Effectiveness seemed to be an important aspect until 1 year after diagnosis disclosure, but it tended to become less crucial over time. Family seems to be the most important domain over time, and psychological adaptation to MS seems to be characterized by a reconceptualization of aspects that revolve around oneself, such as professional success, rather than relational or affective factors. Evaluating the most relevant life domains for patients and their alteration over time may provide practitioners with an important tool in making health-related decisions, thus improving health outcomes and QoL. © 2015 John Wiley & Sons Ltd.

  1. The cysteine-rich domain regulates ADAM protease function in vivo.

    PubMed

    Smith, Katherine M; Gaultier, Alban; Cousin, Helene; Alfandari, Dominique; White, Judith M; DeSimone, Douglas W

    2002-12-09

    ADAMs are membrane-anchored proteases that regulate cell behavior by proteolytically modifying the cell surface and ECM. Like other membrane-anchored proteases, ADAMs contain candidate "adhesive" domains downstream of their metalloprotease domains. The mechanism by which membrane-anchored cell surface proteases utilize these putative adhesive domains to regulate protease function in vivo is not well understood. We address this important question by analyzing the relative contributions of downstream extracellular domains (disintegrin, cysteine rich, and EGF-like repeat) of the ADAM13 metalloprotease during Xenopus laevis development. When expressed in embryos, ADAM13 induces hyperplasia of the cement gland, whereas ADAM10 does not. Using chimeric constructs, we find that the metalloprotease domain of ADAM10 can substitute for that of ADAM13, but that specificity for cement gland expansion requires a downstream extracellular domain of ADAM13. Analysis of finer resolution chimeras indicates an essential role for the cysteine-rich domain and a supporting role for the disintegrin domain. These and other results reveal that the cysteine-rich domain of ADAM13 cooperates intramolecularly with the ADAM13 metalloprotease domain to regulate its function in vivo. Our findings thus provide the first evidence that a downstream extracellular adhesive domain plays an active role in regulating ADAM protease function in vivo. These findings are likely relevant to other membrane-anchored cell surface proteases.

  2. Transactions in domain-specific information systems

    NASA Astrophysics Data System (ADS)

    Zacek, Jaroslav

    2017-07-01

    Substantial number of the current information system (IS) implementations is based on transaction approach. In addition, most of the implementations are domain-specific (e.g. accounting IS, resource planning IS). Therefore, we have to have a generic transaction model to build and verify domain-specific IS. The paper proposes a new transaction model for domain-specific ontologies. This model is based on value oriented business process modelling technique. The transaction model is formalized by the Petri Net theory. First part of the paper presents common business processes and analyses related to business process modeling. Second part defines the transactional model delimited by REA enterprise ontology paradigm and introduces states of the generic transaction model. The generic model proposal is defined and visualized by the Petri Net modelling tool. Third part shows application of the generic transaction model. Last part of the paper concludes results and discusses a practical usability of the generic transaction model.

  3. An exact solution for a thick domain wall in general relativity

    NASA Technical Reports Server (NTRS)

    Goetz, Guenter; Noetzold, Dirk

    1989-01-01

    An exact solution of the Einstein equations for a static, planar domain wall with finite thickness is presented. At infinity, density and pressure vanish and the space-time tends to the Minkowski vacuum on one side of the wall and to the Taub vacuum on the other side. A surprising feature of this solution is that the density and pressure distribution are symmetric about the central plane of the wall whereas the space-time metric and therefore also the gravitational field experienced by a test particle is asymmetric.

  4. Specificity profiling of protein-binding domains using one-bead-one-compound Peptide libraries.

    PubMed

    Kunys, Andrew R; Lian, Wenlong; Pei, Dehua

    2012-12-01

    One-bead-one-compound (OBOC) libraries consist of structurally related compounds (e.g., peptides) covalently attached to a solid support, with each resin bead carrying a unique compound. OBOC libraries of high structural diversity can be rapidly synthesized and screened without the need for any special equipment, and therefore can be employed in any chemical or biochemical laboratory. OBOC peptide libraries have been widely used to map the ligand specificity of proteins, to determine the substrate specificity of enzymes, and to develop inhibitors against macromolecular targets. They have proven particularly useful in profiling the binding specificity of protein modular domains (e.g., SH2 domains, BIR domains, and PDZ domains); subsequently, the specificity information can be used to predict the protein targets of these domains. The protocols outlined in this article describe the methodologies for synthesizing and screening OBOC peptide libraries against SH2 and PDZ domains, and the related data analysis. Curr. Protoc. Chem. Biol. 4:331-355 © 2012 by John Wiley & Sons, Inc.

  5. Separated matter and antimatter domains with vanishing domain walls

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

    Dolgov, A.D.; Godunov, S.I.; Rudenko, A.S.

    2015-10-01

    We present a model of spontaneous (or dynamical) C and CP violation where it is possible to generate domains of matter and antimatter separated by cosmologically large distances. Such C(CP) violation existed only in the early universe and later it disappeared with the only trace of generated baryonic and/or antibaryonic domains. So the problem of domain walls in this model does not exist. These features are achieved through a postulated form of interaction between inflaton and a new scalar field, realizing short time C(CP) violation.

  6. Analysis of a two-domain binding site for the urokinase-type plasminogen activator-plasminogen activator inhibitor-1 complex in low-density-lipoprotein-receptor-related protein.

    PubMed

    Andersen, O M; Petersen, H H; Jacobsen, C; Moestrup, S K; Etzerodt, M; Andreasen, P A; Thøgersen, H C

    2001-07-01

    The low-density-lipoprotein-receptor (LDLR)-related protein (LRP) is composed of several classes of domains, including complement-type repeats (CR), which occur in clusters that contain binding sites for a multitude of different ligands. Each approximately 40-residue CR domain contains three conserved disulphide linkages and an octahedral Ca(2+) cage. LRP is a scavenging receptor for ligands from extracellular fluids, e.g. alpha(2)-macroglobulin (alpha(2)M)-proteinase complexes, lipoprotein-containing particles and serine proteinase-inhibitor complexes, like the complex between urokinase-type plasminogen activator (uPA) and the plasminogen activator inhibitor-1 (PAI-1). In the present study we analysed the interaction of the uPA-PAI-1 complex with an ensemble of fragments representing a complete overlapping set of two-domain fragments accounting for the ligand-binding cluster II (CR3-CR10) of LRP. By ligand blotting, solid-state competition analysis and surface-plasmon-resonance analysis, we demonstrate binding to multiple CR domains, but show a preferential interaction between the uPA-PAI-1 complex and a two-domain fragment comprising CR domains 5 and 6 of LRP. We demonstrate that surface-exposed aspartic acid and tryptophan residues at identical positions in the two homologous domains, CR5 and CR6 (Asp(958,CR5), Asp(999,CR6), Trp(953,CR5) and Trp(994,CR6)), are critical for the binding of the complex as well as for the binding of the receptor-associated protein (RAP) - the folding chaperone/escort protein required for transport of LRP to the cell surface. Accordingly, the present work provides (1) an identification of a preferred binding site within LRP CR cluster II; (2) evidence that the uPA-PAI-1 binding site involves residues from two adjacent protein domains; and (3) direct evidence identifying specific residues as important for the binding of uPA-PAI-1 as well as for the binding of RAP.

  7. Screening retinal transplants with Fourier-domain OCT

    NASA Astrophysics Data System (ADS)

    Rao, Bin

    2009-02-01

    Transplant technologies have been studied for the recovery of vision loss from retinitis pigmentosa (RP) and age-related macular degeneration (AMD). In several rodent retinal degeneration models and in patients, retinal progenitor cells transplanted as layers to the subretinal space have been shown to restore or preserve vision. The methods for evaluation of transplants are expensive considering the large amount of animals. Alternatively, time-domain Stratus OCT was previously shown to be able to image the morphological structure of transplants to some extent, but could not clearly identify laminated transplants. The efficacy of screening retinal transplants with Fourier-domain OCT was studied on 37 S334ter line 3 rats with retinal degeneration 6-67 days after transplant surgery. The transplants were morphologically categorized as no transplant, detachment, rosettes, small laminated area and larger laminated area with both Fourier-domain OCT and histology. The efficacy of Fourier-domain OCT in screening retinal transplants was evaluated by comparing the categorization results with OCT and histology. Additionally, 4 rats were randomly selected for multiple OCT examinations (1, 5, 9, 14 and 21days post surgery) in order to determine the earliest image time of OCT examination since the transplanted tissue may need some time to show its tendency of growing. Finally, we demonstrated the efficacy of Fourier-domain OCT in screening retinal transplants in early stages and determined the earliest imaging time for OCT. Fourier-domain OCT makes itself valuable in saving resource spent on animals with unsuccessful transplants.

  8. Work domain constraints for modelling surgical performance.

    PubMed

    Morineau, Thierry; Riffaud, Laurent; Morandi, Xavier; Villain, Jonathan; Jannin, Pierre

    2015-10-01

    Three main approaches can be identified for modelling surgical performance: a competency-based approach, a task-based approach, both largely explored in the literature, and a less known work domain-based approach. The work domain-based approach first describes the work domain properties that constrain the agent's actions and shape the performance. This paper presents a work domain-based approach for modelling performance during cervical spine surgery, based on the idea that anatomical structures delineate the surgical performance. This model was evaluated through an analysis of junior and senior surgeons' actions. Twenty-four cervical spine surgeries performed by two junior and two senior surgeons were recorded in real time by an expert surgeon. According to a work domain-based model describing an optimal progression through anatomical structures, the degree of adjustment of each surgical procedure to a statistical polynomial function was assessed. Each surgical procedure showed a significant suitability with the model and regression coefficient values around 0.9. However, the surgeries performed by senior surgeons fitted this model significantly better than those performed by junior surgeons. Analysis of the relative frequencies of actions on anatomical structures showed that some specific anatomical structures discriminate senior from junior performances. The work domain-based modelling approach can provide an overall statistical indicator of surgical performance, but in particular, it can highlight specific points of interest among anatomical structures that the surgeons dwelled on according to their level of expertise.

  9. Information Pre-Processing using Domain Meta-Ontology and Rule Learning System

    NASA Astrophysics Data System (ADS)

    Ranganathan, Girish R.; Biletskiy, Yevgen

    Around the globe, extraordinary amounts of documents are being created by Enterprises and by users outside these Enterprises. The documents created in the Enterprises constitute the main focus of the present chapter. These documents are used to perform numerous amounts of machine processing. While using thesedocuments for machine processing, lack of semantics of the information in these documents may cause misinterpretation of the information, thereby inhibiting the productiveness of computer assisted analytical work. Hence, it would be profitable to the Enterprises if they use well defined domain ontologies which will serve as rich source(s) of semantics for the information in the documents. These domain ontologies can be created manually, semi-automatically or fully automatically. The focus of this chapter is to propose an intermediate solution which will enable relatively easy creation of these domain ontologies. The process of extracting and capturing domain ontologies from these voluminous documents requires extensive involvement of domain experts and application of methods of ontology learning that are substantially labor intensive; therefore, some intermediate solutions which would assist in capturing domain ontologies must be developed. This chapter proposes a solution in this direction which involves building a meta-ontology that will serve as an intermediate information source for the main domain ontology. This chapter proposes a solution in this direction which involves building a meta-ontology as a rapid approach in conceptualizing a domain of interest from huge amount of source documents. This meta-ontology can be populated by ontological concepts, attributes and relations from documents, and then refined in order to form better domain ontology either through automatic ontology learning methods or some other relevant ontology building approach.

  10. Internationalized Domain Names.

    ERIC Educational Resources Information Center

    Wielansky, Marc D.

    2002-01-01

    Reports on an investigation of what may appear at first to be an arcane topic--the internationalization of domain names on the Internet. Concludes that expanding domain names internationally poses challenges to the inherent open structure of the Internet; to its ease of use for those accustomed to Latin-alphabet-only domain names; and to corporate…

  11. The evolution of filamin – A protein domain repeat perspective

    PubMed Central

    Light, Sara; Sagit, Rauan; Ithychanda, Sujay S.; Qin, Jun; Elofsson, Arne

    2013-01-01

    Particularly in higher eukaryotes, some protein domains are found in tandem repeats, performing broad functions often related to cellular organization. For instance, the eukaryotic protein filamin interacts with many proteins and is crucial for the cytoskeleton. The functional properties of long repeat domains are governed by the specific properties of each individual domain as well as by the repeat copy number. To provide better understanding of the evolutionary and functional history of repeating domains, we investigated the mode of evolution of the filamin domain in some detail. Among the domains that are common in long repeat proteins, sushi and spectrin domains evolve primarily through cassette tandem duplications while scavenger and immunoglobulin repeats appear to evolve through clustered tandem duplications. Additionally, immunoglobulin and filamin repeats exhibit a unique pattern where every other domain shows high sequence similarity. This pattern may be the result of tandem duplications, serve to avert aggregation between adjacent domains or it is the result of functional constraints. In filamin, our studies confirm the presence of interspersed integrin binding domains in vertebrates, while invertebrates exhibit more varied patterns, including more clustered integrin binding domains. The most notable case is leech filamin, which contains a 20 repeat expansion and exhibits unique dimerization topology. Clearly, invertebrate filamins are varied and contain examples of similar adjacent integrin-binding domains. Given that invertebrate integrin shows more similarity to the weaker filamin binder, integrin β3, it is possible that the distance between integrin-binding domains is not as crucial for invertebrate filamins as for vertebrates. PMID:22414427

  12. Comparison of frequency-domain and time-domain rotorcraft vibration control methods

    NASA Technical Reports Server (NTRS)

    Gupta, N. K.

    1984-01-01

    Active control of rotor-induced vibration in rotorcraft has received significant attention recently. Two classes of techniques have been proposed. The more developed approach works with harmonic analysis of measured time histories and is called the frequency-domain approach. The more recent approach computes the control input directly using the measured time history data and is called the time-domain approach. The report summarizes the results of a theoretical investigation to compare the two approaches. Five specific areas were addressed: (1) techniques to derive models needed for control design (system identification methods), (2) robustness with respect to errors, (3) transient response, (4) susceptibility to noise, and (5) implementation difficulties. The system identification methods are more difficult for the time-domain models. The time-domain approach is more robust (e.g., has higher gain and phase margins) than the frequency-domain approach. It might thus be possible to avoid doing real-time system identification in the time-domain approach by storing models at a number of flight conditions. The most significant error source is the variation in open-loop vibrations caused by pilot inputs, maneuvers or gusts. The implementation requirements are similar except that the time-domain approach can be much simpler to implement if real-time system identification were not necessary.

  13. Protein domains of unknown function are essential in bacteria.

    PubMed

    Goodacre, Norman F; Gerloff, Dietlind L; Uetz, Peter

    2013-12-31

    More than 20% of all protein domains are currently annotated as "domains of unknown function" (DUFs). About 2,700 DUFs are found in bacteria compared with just over 1,500 in eukaryotes. Over 800 DUFs are shared between bacteria and eukaryotes, and about 300 of these are also present in archaea. A total of 2,786 bacterial Pfam domains even occur in animals, including 320 DUFs. Evolutionary conservation suggests that many of these DUFs are important. Here we show that 355 essential proteins in 16 model bacterial species contain 238 DUFs, most of which represent single-domain proteins, clearly establishing the biological essentiality of DUFs. We suggest that experimental research should focus on conserved and essential DUFs (eDUFs) for functional analysis given their important function and wide taxonomic distribution, including bacterial pathogens. The functional units of proteins are domains. Typically, each domain has a distinct structure and function. Genomes encode thousands of domains, and many of the domains have no known function (domains of unknown function [DUFs]). They are often ignored as of little relevance, given that many of them are found in only a few genomes. Here we show that many DUFs are essential DUFs (eDUFs) based on their presence in essential proteins. We also show that eDUFs are often essential even if they are found in relatively few genomes. However, in general, more common DUFs are more often essential than rare DUFs.

  14. Characterizing protein domain associations by Small-molecule ligand binding

    PubMed Central

    Li, Qingliang; Cheng, Tiejun; Wang, Yanli; Bryant, Stephen H.

    2012-01-01

    Background Protein domains are evolutionarily conserved building blocks for protein structure and function, which are conventionally identified based on protein sequence or structure similarity. Small molecule binding domains are of great importance for the recognition of small molecules in biological systems and drug development. Many small molecules, including drugs, have been increasingly identified to bind to multiple targets, leading to promiscuous interactions with protein domains. Thus, a large scale characterization of the protein domains and their associations with respect to small-molecule binding is of particular interest to system biology research, drug target identification, as well as drug repurposing. Methods We compiled a collection of 13,822 physical interactions of small molecules and protein domains derived from the Protein Data Bank (PDB) structures. Based on the chemical similarity of these small molecules, we characterized pairwise associations of the protein domains and further investigated their global associations from a network point of view. Results We found that protein domains, despite lack of similarity in sequence and structure, were comprehensively associated through binding the same or similar small-molecule ligands. Moreover, we identified modules in the domain network that consisted of closely related protein domains by sharing similar biochemical mechanisms, being involved in relevant biological pathways, or being regulated by the same cognate cofactors. Conclusions A novel protein domain relationship was identified in the context of small-molecule binding, which is complementary to those identified by traditional sequence-based or structure-based approaches. The protein domain network constructed in the present study provides a novel perspective for chemogenomic study and network pharmacology, as well as target identification for drug repurposing. PMID:23745168

  15. [Preparation and characterization of monoclonal antibodies against Micrococcus luteus Rpf domain].

    PubMed

    Fan, Ai-lin; Shi, Chang-hong; Su, Ming-quan; Ma, Jing; Bai, Yin-lan; Cheng, Xiao-dong; Xu, Zhi-kai; Hao, Xiao-ke

    2008-05-01

    To express Micrococcus luteus Rpf domain in prokaryotic cells and prepare monoclonal antibodies against Rpf domain. The gene encoding Micrococcus luteus Rpf domain was amplified from genome of Micrococcus luteus by polymerase chain reaction(PCR), and inserted into cloning vector pUC-19. After sequenced, Micrococcus luteus Rpf domain gene was subcloned into the expression vector pPro-EXHT and transfected into E.coli DH5alpha. After induced by IPTG, the bacteria controlled by T7 promoter expressed the fused Micrococcus luteus Rpf domain protein with a hexahistidine tail at its N-terminal and the target protein was purified under denaturing conditions. Using this protein as antigen to immunize the BALB/c mice and prepare monoclonal antibodies against Micrococcus luteus Rpf domain. Then specifities and relative affinities of mAbs were identified by ELISA. The fusion protein was purified by metal chelate affinity chromatography under denaturing condition. Three cloned mAbs were prepared from the mice immunized by Rpf domain. All of them could recognize Rpf domain. specifically. The prepared mAbs against Rpf domain have strong specificity with high titers, which provides useful tools for further study of the function of Rpf domain in TB prevention.

  16. Classification of Domain Movements in Proteins Using Dynamic Contact Graphs

    PubMed Central

    Taylor, Daniel; Cawley, Gavin; Hayward, Steven

    2013-01-01

    A new method for the classification of domain movements in proteins is described and applied to 1822 pairs of structures from the Protein Data Bank that represent a domain movement in two-domain proteins. The method is based on changes in contacts between residues from the two domains in moving from one conformation to the other. We argue that there are five types of elemental contact changes and that these relate to five model domain movements called: “free”, “open-closed”, “anchored”, “sliding-twist”, and “see-saw.” A directed graph is introduced called the “Dynamic Contact Graph” which represents the contact changes in a domain movement. In many cases a graph, or part of a graph, provides a clear visual metaphor for the movement it represents and is a motif that can be easily recognised. The Dynamic Contact Graphs are often comprised of disconnected subgraphs indicating independent regions which may play different roles in the domain movement. The Dynamic Contact Graph for each domain movement is decomposed into elemental Dynamic Contact Graphs, those that represent elemental contact changes, allowing us to count the number of instances of each type of elemental contact change in the domain movement. This naturally leads to sixteen classes into which the 1822 domain movements are classified. PMID:24260562

  17. A Note on a Sampling Theorem for Functions over GF(q)n Domain

    NASA Astrophysics Data System (ADS)

    Ukita, Yoshifumi; Saito, Tomohiko; Matsushima, Toshiyasu; Hirasawa, Shigeichi

    In digital signal processing, the sampling theorem states that any real valued function ƒ can be reconstructed from a sequence of values of ƒ that are discretely sampled with a frequency at least twice as high as the maximum frequency of the spectrum of ƒ. This theorem can also be applied to functions over finite domain. Then, the range of frequencies of ƒ can be expressed in more detail by using a bounded set instead of the maximum frequency. A function whose range of frequencies is confined to a bounded set is referred to as bandlimited function. And a sampling theorem for bandlimited functions over Boolean domain has been obtained. Here, it is important to obtain a sampling theorem for bandlimited functions not only over Boolean domain (GF(q)n domain) but also over GF(q)n domain, where q is a prime power and GF(q) is Galois field of order q. For example, in experimental designs, although the model can be expressed as a linear combination of the Fourier basis functions and the levels of each factor can be represented by GF(q)n, the number of levels often take a value greater than two. However, the sampling theorem for bandlimited functions over GF(q)n domain has not been obtained. On the other hand, the sampling points are closely related to the codewords of a linear code. However, the relation between the parity check matrix of a linear code and any distinct error vectors has not been obtained, although it is necessary for understanding the meaning of the sampling theorem for bandlimited functions. In this paper, we generalize the sampling theorem for bandlimited functions over Boolean domain to a sampling theorem for bandlimited functions over GF(q)n domain. We also present a theorem for the relation between the parity check matrix of a linear code and any distinct error vectors. Lastly, we clarify the relation between the sampling theorem for functions over GF(q)n domain and linear codes.

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

    PubMed

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

    2015-06-01

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

  19. Parental behavioral control in academic and non-academic domains: a three-year longitudinal study in the Chinese culture.

    PubMed

    Shek, Daniel T L; Lee, Tak Yan

    2007-01-01

    For over three consecutive years, 2559 Chinese adolescents (mean age = 12.65 years at Wave 1) responded to instruments assessing their perceived parental behavioral control based on measures of parental knowledge, expectation, monitoring, and discipline. The results show that compared with parental control in the academic domain, parental control in the non-academic domain (peer relations domain) was relatively weaker, using parental knowledge, parental expectation, parental monitoring, and parental discipline as indicators, and a decline in parental behavioral control occurred over time. Although domain (academic domain versus non-academic domain) X time (Time 1, Time 2 versus Time 3) interaction effects were found, the findings mirrored the main effects of domain and time. Parental education and economic sufficiency were linearly related to differences in parental behavioral control in the academic domain and non-academic domain. The present findings suggest that traditional Chinese cultural emphasis on academic excellence still prevails in the contemporary Chinese culture.

  20. Creativity as action: findings from five creative domains

    PubMed Central

    Glaveanu, Vlad; Lubart, Todd; Bonnardel, Nathalie; Botella, Marion; de Biaisi, Pierre-Marc; Desainte-Catherine, Myriam; Georgsdottir, Asta; Guillou, Katell; Kurtag, Gyorgy; Mouchiroud, Christophe; Storme, Martin; Wojtczuk, Alicja; Zenasni, Franck

    2013-01-01

    The present paper outlines an action theory of creativity and substantiates this approach by investigating creative expression in five different domains. We propose an action framework for the analysis of creative acts built on the assumption that creativity is a relational, inter-subjective phenomenon. This framework, drawing extensively from the work of Dewey (1934) on art as experience, is used to derive a coding frame for the analysis of interview material. The article reports findings from the analysis of 60 interviews with recognized French creators in five creative domains: art, design, science, scriptwriting, and music. Results point to complex models of action and inter-action specific for each domain and also to interesting patterns of similarity and differences between domains. These findings highlight the fact that creative action takes place not “inside” individual creators but “in between” actors and their environment. Implications for the field of educational psychology are discussed. PMID:23596431

  1. Axial current generation by P-odd domains in QCD matter

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

    Iatrakis, Ioannis; Yin, Yi; Lin, Shu

    2015-06-23

    The dynamics of topological domains which break parity (P) and charge-parity (CP) symmetry of QCD are studied. We derive in a general setting that those local domains will generate an axial current and quantify the strength of the induced axial current. Thus, our findings are verified in a top-down holographic model. The relation between the real time dynamics of those local domains and the chiral magnetic field is also elucidated. We finally argue that such an induced axial current would be phenomenologically important in a heavy-ion collisions experiment.

  2. A test of safety, violence prevention, and civility climate domain-specific relationships with relevant workplace hazards.

    PubMed

    Gazica, Michele W; Spector, Paul E

    2016-01-01

    Safety climate, violence prevention climate, and civility climate were independently developed and linked to domain-specific workplace hazards, although all three were designed to promote the physical and psychological safety of workers. To test domain specificity between conceptually related workplace climates and relevant workplace hazards. Data were collected from 368 persons employed in various industries and descriptive statistics were calculated for all study variables. Correlational and relative weights analyses were used to test for domain specificity. The three climate domains were similarly predictive of most workplace hazards, regardless of domain specificity. This study suggests that the three climate domains share a common higher order construct that may predict relevant workplace hazards better than any of the scales alone.

  3. Domain-specific learning of grammatical structure in musical and phonological sequences.

    PubMed

    Bly, Benjamin Martin; Carrión, Ricardo E; Rasch, Björn

    2009-01-01

    Artificial grammar learning depends on acquisition of abstract structural representations rather than domain-specific representational constraints, or so many studies tell us. Using an artificial grammar task, we compared learning performance in two stimulus domains in which respondents have differing tacit prior knowledge. We found that despite grammatically identical sequence structures, learning was better for harmonically related chord sequences than for letter name sequences or harmonically unrelated chord sequences. We also found transfer effects within the musical and letter name tasks, but not across the domains. We conclude that knowledge acquired in implicit learning depends not only on abstract features of structured stimuli, but that the learning of regularities is in some respects domain-specific and strongly linked to particular features of the stimulus domain.

  4. Telomere Capping Proteins are Structurally Related to RPA with an additional Telomere-Specific Domain

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

    Gelinas, A.; Paschini, M; Reyes, F

    Telomeres must be capped to preserve chromosomal stability. The conserved Stn1 and Ten1 proteins are required for proper capping of the telomere, although the mechanistic details of how they contribute to telomere maintenance are unclear. Here, we report the crystal structures of the C-terminal domain of the Saccharomyces cerevisiae Stn1 and the Schizosaccharomyces pombe Ten1 proteins. These structures reveal striking similarities to corresponding subunits in the replication protein A complex, further supporting an evolutionary link between telomere maintenance proteins and DNA repair complexes. Our structural and in vivo data of Stn1 identify a new domain that has evolved to supportmore » a telomere-specific role in chromosome maintenance. These findings endorse a model of an evolutionarily conserved mechanism of DNA maintenance that has developed as a result of increased chromosomal structural complexity.« less

  5. Socioeconomic inequality in domains of health: results from the World Health Surveys

    PubMed Central

    2012-01-01

    Background In all countries people of lower socioeconomic status evaluate their health more poorly. Yet in reporting overall health, individuals consider multiple domains that comprise their perceived health state. Considered alone, overall measures of self-reported health mask differences in the domains of health. The aim of this study is to compare and assess socioeconomic inequalities in each of the individual health domains and in a separate measure of overall health. Methods Data on 247,037 adults aged 18 or older were analyzed from 57 countries, drawn from all national income groups, participating in the World Health Survey 2002-2004. The analysis was repeated for lower- and higher-income countries. Prevalence estimates of poor self-rated health (SRH) were calculated for each domain and for overall health according to wealth quintiles and education levels. Relative socioeconomic inequalities in SRH were measured for each of the eight health domains and for overall health, according to wealth quintiles and education levels, using the relative index of inequality (RII). A RII value greater than one indicated greater prevalence of self-reported poor health among populations of lower socioeconomic status, called pro-rich inequality. Results There was a descending gradient in the prevalence of poor health, moving from the poorest wealth quintile to the richest, and moving from the lowest to the highest educated groups. Inequalities which favor groups who are advantaged either with respect to wealth or education, were consistently statistically significant in each of the individual domains of health, and in health overall. However the size of these inequalities differed between health domains. The prevalence of reporting poor health was higher in the lower-income country group. Relative socioeconomic inequalities in the health domains and overall health were higher in the higher-income country group than the lower-income country group. Conclusions Using a common

  6. Characteristic microwave background distortions from collapsing domain wall bubbles

    NASA Technical Reports Server (NTRS)

    Goetz, Guenter; Noetzold, Dirk

    1990-01-01

    The magnitude and angular pattern of distortions of the microwave background are analyzed by collapsing spherical domain walls. A characteristic pattern of redshift distortions of red or blue spikes surrounded by blue discs was found. The width and height of a spike is related to the diameter and magnitude of the disc. A measurement of the relations between these quantities thus can serve as an unambiguous indicator for a collapsing spherical domain wall. From the redshift distortion in the blue discs an upper bound was found on the surface energy density of the walls sigma is less than or approximately 8 MeV cubed.

  7. Camelid Single-Domain Antibodies As an Alternative to Overcome Challenges Related to the Prevention, Detection, and Control of Neglected Tropical Diseases.

    PubMed

    Fernandes, Carla F C; Pereira, Soraya Dos S; Luiz, Marcos B; Zuliani, Juliana P; Furtado, Gilvan P; Stabeli, Rodrigo G

    2017-01-01

    Due mainly to properties such as high affinity and antigen specificity, antibodies have become important tools for biomedical research, diagnosis, and treatment of several human diseases. When the objective is to administer them for therapy, strategies are used to reduce the heterologous protein immunogenicity and to improve pharmacokinetic and pharmacodynamic characteristics. Size minimization contributes to ameliorate these characteristics, while preserving the antigen-antibody interaction site. Since the discovery that camelids produce functional antibodies devoid of light chains, studies have proposed the use of single domains for biosensors, monitoring and treatment of tumors, therapies for inflammatory and neurodegenerative diseases, drug delivery, or passive immunotherapy. Despite an expected increase in antibody and related products in the pharmaceutical market over the next years, few research initiatives are related to the development of alternatives for helping to manage neglected tropical diseases (NTDs). In this review, we summarize developments of camelid single-domain antibodies (VHH) in the field of NTDs. Particular attention is given to VHH-derived products, i.e., VHHs fused to nanoparticles, constructed for the development of rapid diagnostic kits; fused to oligomeric matrix proteins for viral neutralization; and conjugated with proteins for the treatment of human parasites. Moreover, paratransgenesis technology using VHHs is an interesting approach to control parasite development in vectors. With enormous biotechnological versatility, facility and low cost for heterologous production, and greater ability to recognize different epitopes, VHHs have appeared as an opportunity to overcome challenges related to the prevention, detection, and control of human diseases, especially NTDs.

  8. Camelid Single-Domain Antibodies As an Alternative to Overcome Challenges Related to the Prevention, Detection, and Control of Neglected Tropical Diseases

    PubMed Central

    Fernandes, Carla F. C.; Pereira, Soraya dos S.; Luiz, Marcos B.; Zuliani, Juliana P.; Furtado, Gilvan P.; Stabeli, Rodrigo G.

    2017-01-01

    Due mainly to properties such as high affinity and antigen specificity, antibodies have become important tools for biomedical research, diagnosis, and treatment of several human diseases. When the objective is to administer them for therapy, strategies are used to reduce the heterologous protein immunogenicity and to improve pharmacokinetic and pharmacodynamic characteristics. Size minimization contributes to ameliorate these characteristics, while preserving the antigen–antibody interaction site. Since the discovery that camelids produce functional antibodies devoid of light chains, studies have proposed the use of single domains for biosensors, monitoring and treatment of tumors, therapies for inflammatory and neurodegenerative diseases, drug delivery, or passive immunotherapy. Despite an expected increase in antibody and related products in the pharmaceutical market over the next years, few research initiatives are related to the development of alternatives for helping to manage neglected tropical diseases (NTDs). In this review, we summarize developments of camelid single-domain antibodies (VHH) in the field of NTDs. Particular attention is given to VHH-derived products, i.e., VHHs fused to nanoparticles, constructed for the development of rapid diagnostic kits; fused to oligomeric matrix proteins for viral neutralization; and conjugated with proteins for the treatment of human parasites. Moreover, paratransgenesis technology using VHHs is an interesting approach to control parasite development in vectors. With enormous biotechnological versatility, facility and low cost for heterologous production, and greater ability to recognize different epitopes, VHHs have appeared as an opportunity to overcome challenges related to the prevention, detection, and control of human diseases, especially NTDs. PMID:28649245

  9. Cholesterol Bilayer Domains in the Eye Lens Health: A Review.

    PubMed

    Widomska, Justyna; Subczynski, Witold K; Mainali, Laxman; Raguz, Marija

    2017-12-01

    The most unique biochemical characteristic of the eye lens fiber cell plasma membrane is its extremely high cholesterol content, the need for which is still unclear. It is evident, however, that the disturbance of Chol homeostasis may result in damages associated with cataracts. Electron paramagnetic resonance methods allow discrimination of two types of lipid domains in model membranes overloaded with Chol, namely, phospholipid-cholesterol domains and pure Chol bilayer domains. These domains are also detected in human lens lipid membranes prepared from the total lipids extracted from lens cortices and nuclei of donors from different age groups. Independent of the age-related changes in phospholipid composition, the physical properties of phospholipid-Chol domains remain the same for all age groups and are practically identical for cortical and nuclear membranes. The presence of Chol bilayer domains in these membranes provides a buffering capacity for cholesterol concentration in the surrounding phospholipid-Chol domains, keeping it at a constant saturating level and thus keeping the physical properties of the membrane consistent with and independent of changes in phospholipid composition. It seems that the presence of Chol bilayer domains plays an integral role in the regulation of cholesterol-dependent processes in fiber cell plasm membranes and in the maintenance of fiber cell membrane homeostasis.

  10. Domain shape instabilities and dendrite domain growth in uniaxial ferroelectrics

    NASA Astrophysics Data System (ADS)

    Shur, Vladimir Ya.; Akhmatkhanov, Andrey R.

    2018-01-01

    The effects of domain wall shape instabilities and the formation of nanodomains in front of moving walls obtained in various uniaxial ferroelectrics are discussed. Special attention is paid to the formation of self-assembled nanoscale and dendrite domain structures under highly non-equilibrium switching conditions. All obtained results are considered in the framework of the unified kinetic approach to domain structure evolution based on the analogy with first-order phase transformation. This article is part of the theme issue `From atomistic interfaces to dendritic patterns'.

  11. Expansion of divergent SEA domains in cell surface proteins and nucleoporin 54.

    PubMed

    Pei, Jimin; Grishin, Nick V

    2017-03-01

    SEA (sea urchin sperm protein, enterokinase, agrin) domains, many of which possess autoproteolysis activity, have been found in a number of cell surface and secreted proteins. Despite high sequence divergence, SEA domains were also proposed to be present in dystroglycan based on a conserved autoproteolysis motif and receptor-type protein phosphatase IA-2 based on structural similarity. The presence of a SEA domain adjacent to the transmembrane segment appears to be a recurring theme in quite a number of type I transmembrane proteins on the cell surface, such as MUC1, dystroglycan, IA-2, and Notch receptors. By comparative sequence and structural analyses, we identified dystroglycan-like proteins with SEA domains in Capsaspora owczarzaki of the Filasterea group, one of the closest single-cell relatives of metazoans. We also detected novel and divergent SEA domains in a variety of cell surface proteins such as EpCAM, α/ε-sarcoglycan, PTPRR, collectrin/Tmem27, amnionless, CD34, KIAA0319, fibrocystin-like protein, and a number of cadherins. While these proteins are mostly from metazoans or their single cell relatives such as choanoflagellates and Filasterea, fibrocystin-like proteins with SEA domains were found in several other eukaryotic lineages including green algae, Alveolata, Euglenozoa, and Haptophyta, suggesting an ancient evolutionary origin. In addition, the intracellular protein Nucleoporin 54 (Nup54) acquired a divergent SEA domain in choanoflagellates and metazoans. © 2016 The Protein Society.

  12. Relative increase in Alzheimer's disease of soluble forms of cerebral Abeta amyloid protein precursor containing the Kunitz protease inhibitory domain.

    PubMed

    Moir, R D; Lynch, T; Bush, A I; Whyte, S; Henry, A; Portbury, S; Multhaup, G; Small, D H; Tanzi, R E; Beyreuther, K; Masters, C L

    1998-02-27

    Although a number of studies have examined amyloid precursor protein (APP) mRNA levels in Alzheimer's disease (AD), no clear consensus has emerged as to whether the levels of transcripts for isoforms containing a Kunitz protease inhibitory (KPI)-encoded region are increased or decreased in AD. Here we compare AD and control brain for the relative amounts of APP protein containing KPI to APP protein lacking this domain. APP protein was purified from the soluble subcellular fraction and Triton X-100 membrane pellet extract of one hemisphere of AD (n = 10), normal (n = 7), and neurological control (n = 5) brains. The amount of KPI-containing APP in the purified protein samples was determined using two independent assay methods. The first assay exploited the inhibitory action of KPI-containing APP on trypsin. The second assay employed reflectance analysis of Western blots. The proportion of KPI-containing forms of APP in the soluble subcellular fraction of AD brains is significantly elevated (p < 0.01) compared with controls. Species containing a KPI domain comprise 32-41 and 76-77% of purified soluble APP from control and AD brains, respectively. For purified membrane-associated APP, 72-77 and 65-82% of control and AD samples, respectively, contain a KPI domain. Since KPI-containing species of APP may be more amyloidogenic (Ho, L., Fukuchi, K., and Yonkin, S. G. (1996) J. Biol. Chem. 271, 30929-30934), our findings support an imbalance of isoforms as one possible mechanism for amyloid deposition in sporadic AD.

  13. A test of safety, violence prevention, and civility climate domain-specific relationships with relevant workplace hazards

    PubMed Central

    Spector, Paul E.

    2016-01-01

    Background Safety climate, violence prevention climate, and civility climate were independently developed and linked to domain-specific workplace hazards, although all three were designed to promote the physical and psychological safety of workers. Purpose To test domain specificity between conceptually related workplace climates and relevant workplace hazards. Methods Data were collected from 368 persons employed in various industries and descriptive statistics were calculated for all study variables. Correlational and relative weights analyses were used to test for domain specificity. Results The three climate domains were similarly predictive of most workplace hazards, regardless of domain specificity. Discussion This study suggests that the three climate domains share a common higher order construct that may predict relevant workplace hazards better than any of the scales alone. PMID:27110930

  14. Network Search: A New Way of Seeing the Education Knowledge Domain

    ERIC Educational Resources Information Center

    McFarland, Daniel; Klopfer, Eric

    2010-01-01

    Background: The educational knowledge domain may be understood as a system composed of multiple, co-evolving networks that reflect the form and content of a cultural field. This paper describes the educational knowledge domain as having a community structure (form) based in relations of production (authoring) and consumption (referencing), and a…

  15. Public Domain Generic Tools: An Overview.

    ERIC Educational Resources Information Center

    Erjavec, Tomaz

    This paper presents an introduction to language engineering software, especially for computerized language and text corpora. The focus of the paper is on small and relatively independent pieces of software designed for specific, often low-level language analysis tasks, and on tools in the public domain. Discussion begins with the application of…

  16. Domain-Generality versus Domain-Specificity: The Life and Impending Death of a False Dichotomy.

    ERIC Educational Resources Information Center

    Sternberg, Robert J.

    1989-01-01

    Argues that the question of whether information representation and processing are domain-general or domain-specific is neither meaningful nor answerable. Researchers should be asking questions about ways in which representation and processing are domain-general and ways in which they are domain-specific. (RH)

  17. Inference of domain-disease associations from domain-protein, protein-disease and disease-disease relationships.

    PubMed

    Zhang, Wangshu; Coba, Marcelo P; Sun, Fengzhu

    2016-01-11

    Protein domains can be viewed as portable units of biological function that defines the functional properties of proteins. Therefore, if a protein is associated with a disease, protein domains might also be associated and define disease endophenotypes. However, knowledge about such domain-disease relationships is rarely available. Thus, identification of domains associated with human diseases would greatly improve our understanding of the mechanism of human complex diseases and further improve the prevention, diagnosis and treatment of these diseases. Based on phenotypic similarities among diseases, we first group diseases into overlapping modules. We then develop a framework to infer associations between domains and diseases through known relationships between diseases and modules, domains and proteins, as well as proteins and disease modules. Different methods including Association, Maximum likelihood estimation (MLE), Domain-disease pair exclusion analysis (DPEA), Bayesian, and Parsimonious explanation (PE) approaches are developed to predict domain-disease associations. We demonstrate the effectiveness of all the five approaches via a series of validation experiments, and show the robustness of the MLE, Bayesian and PE approaches to the involved parameters. We also study the effects of disease modularization in inferring novel domain-disease associations. Through validation, the AUC (Area Under the operating characteristic Curve) scores for Bayesian, MLE, DPEA, PE, and Association approaches are 0.86, 0.84, 0.83, 0.83 and 0.79, respectively, indicating the usefulness of these approaches for predicting domain-disease relationships. Finally, we choose the Bayesian approach to infer domains associated with two common diseases, Crohn's disease and type 2 diabetes. The Bayesian approach has the best performance for the inference of domain-disease relationships. The predicted landscape between domains and diseases provides a more detailed view about the disease

  18. Traditions in Spider Monkeys Are Biased towards the Social Domain

    PubMed Central

    Santorelli, Claire J.; Schaffner, Colleen M.; Campbell, Christina J.; Notman, Hugh; Pavelka, Mary S.; Weghorst, Jennifer A.; Aureli, Filippo

    2011-01-01

    Cross-site comparison studies of behavioral variation can provide evidence for traditions in wild species once ecological and genetic factors are excluded as causes for cross-site differences. These studies ensure behavior variants are considered within the context of a species' ecology and evolutionary adaptations. We examined wide-scale geographic variation in the behavior of spider monkeys (Ateles geoffroyi) across five long-term field sites in Central America using a well established ethnographic cross-site survey method. Spider monkeys possess a relatively rare social system with a high degree of fission-fusion dynamics, also typical of chimpanzees (Pan troglodytes) and humans (Homo sapiens). From the initial 62 behaviors surveyed 65% failed to meet the necessary criteria for traditions. The remaining 22 behaviors showed cross-site variation in occurrence ranging from absent through to customary, representing to our knowledge, the first documented cases of traditions in this taxon and only the second case of multiple traditions in a New World monkey species. Of the 22 behavioral variants recorded across all sites, on average 57% occurred in the social domain, 19% in food-related domains and 24% in other domains. This social bias contrasts with the food-related bias reported in great ape cross-site comparison studies and has implications for the evolution of human culture. No pattern of geographical radiation was found in relation to distance across sites. Our findings promote A. geoffroyi as a model species to investigate traditions with field and captive based experiments and emphasize the importance of the social domain for the study of animal traditions. PMID:21373196

  19. Characterizing Implicit Mental Health Associations across Clinical Domains

    PubMed Central

    Werntz, Alexandra J.; Steinman, Shari A.; Glenn, Jeffrey J.; Nock, Matthew K.; Teachman, Bethany A.

    2016-01-01

    Background and objectives Implicit associations are relatively uncontrollable associations between concepts in memory. The current investigation focuses on implicit associations in four mental health domains (alcohol use, anxiety, depression, and eating disorders) and how these implicit associations: a) relate to explicit associations and b) self-reported clinical symptoms within the same domains, and c) vary based on demographic characteristics (age, gender, race, ethnicity, and education). Methods Participants (volunteers over age 18 to a research website) completed implicit association (Implicit Association Tests), explicit association (self+psychopathology or attitudes toward food, using semantic differential items), and symptom measures at the Project Implicit Mental Health website tied to: alcohol use (N=12,387), anxiety (N=21,304), depression (N=24,126), or eating disorders (N=10,115). Results Within each domain, implicit associations showed small to moderate associations with explicit associations and symptoms, and predicted self-reported symptoms beyond explicit associations. In general, implicit association strength varied little by race and ethnicity, but showed small ties to age, gender, and education. Limitations This research was conducted on a public research and education website, where participants could take more than one of the studies. Conclusions Among a large and diverse sample, implicit associations in the four domains are congruent with explicit associations and self-reported symptoms, and also add to our prediction of self-reported symptoms over and above explicit associations, pointing to the potential future clinical utility and validity of using implicit association measures with diverse populations. PMID:26962979

  20. Health-Related Quality of Life of Adolescent and Young Adult Survivors of Central Nervous System Tumors: Identifying Domains From a Survivor Perspective.

    PubMed

    Kuhlthau, Karen; Luff, Donna; Delahaye, Jennifer; Wong, Alicia; Yock, Torunn; Huang, Mary; Park, Elyse R

    2015-01-01

    This article uses qualitative methods to describe the domains of health-related quality of life (HRQoL) that adolescent and young adult (AYA) survivors of central nervous system (CNS) tumors identify as important. Survivors clearly attributed aspects of their current HRQoL to their disease or its treatment. We identified 7 key domains of AYA CNS tumor survivorship: physical health, social well-being, mental health, cognitive functioning, health behaviors, sexual and reproductive health, and support systems. Although most aspects of HRQoL that survivors discussed represented new challenges, there were several areas where survivors pointed out positive outcomes. There is a need for a HRQoL tool designed for this population of survivors, given their unique treatment and survivorship experience. Aspects of HRQoL related to cognition, sexual and reproductive health, health behaviors, and support systems are not typically included in generic HRQoL tools but should be assessed for this population. Developing HRQoL measurement instruments that capture the most significant aspects of HRQoL will improve the ability to track HRQoL in AYA CNS tumor survivors and in the long-term management of common sequelae from CNS tumors and their treatments. © 2015 by Association of Pediatric Hematology/Oncology Nurses.

  1. Structural mapping of the coiled-coil domain of a bacterial condensin and comparative analyses across all domains of life suggest conserved features of SMC proteins.

    PubMed

    Waldman, Vincent M; Stanage, Tyler H; Mims, Alexandra; Norden, Ian S; Oakley, Martha G

    2015-06-01

    The structural maintenance of chromosomes (SMC) proteins form the cores of multisubunit complexes that are required for the segregation and global organization of chromosomes in all domains of life. These proteins share a common domain structure in which N- and C- terminal regions pack against one another to form a globular ATPase domain. This "head" domain is connected to a central, globular, "hinge" or dimerization domain by a long, antiparallel coiled coil. To date, most efforts for structural characterization of SMC proteins have focused on the globular domains. Recently, however, we developed a method to map interstrand interactions in the 50-nm coiled-coil domain of MukB, the divergent SMC protein found in γ-proteobacteria. Here, we apply that technique to map the structure of the Bacillus subtilis SMC (BsSMC) coiled-coil domain. We find that, in contrast to the relatively complicated coiled-coil domain of MukB, the BsSMC domain is nearly continuous, with only two detectable coiled-coil interruptions. Near the middle of the domain is a break in coiled-coil structure in which there are three more residues on the C-terminal strand than on the N-terminal strand. Close to the head domain, there is a second break with a significantly longer insertion on the same strand. These results provide an experience base that allows an informed interpretation of the output of coiled-coil prediction algorithms for this family of proteins. A comparison of such predictions suggests that these coiled-coil deviations are highly conserved across SMC types in a wide variety of organisms, including humans. © 2015 Wiley Periodicals, Inc.

  2. Investigation of Ferroelectric Domain Walls by Raman Spectroscopy

    NASA Astrophysics Data System (ADS)

    Stone, Gregory A.

    Ferroelectric materials are characterized by an intrinsic spontaneous electric dipole moment that can be manipulated by the application of an electric field. Regions inside the crystal, known as domains, can have the spontaneous dipole moments oriented in a different direction than the surrounding crystal. Due to favorable piezoelectric, pyroelectric, electro-optic, and nonlinear optical properties, ferroelectric materials are attractive for commercial applications. Many devices, such as nonlinear frequency converters, require precisely engineered domain patterns. The properties of domains and their boundaries, known as domain walls, are vital to the performance and limitations of these devices. As a result, ferroelectric domains and the domain walls have been the focus of many scientific studies. Despite all this work, questions remain regarding their properties. This work is aimed at developing a better understanding of the properties of the domain wall using confocal Raman spectroscopy. Raman spectra taken from domain walls in Lithium Niobate and Lithium Tantalate reveal two distinct changes in the Raman spectra: (1) Shifts in frequency of the bulk Raman modes, which persists over a range of 0.2-0.5 mu m from the domain wall. The absence of this effect in defect free stoichiometric Lithium Tantalate indicates that the shifts are related to defects inside the crystal. (2) The presence of Raman modes corresponding to phonons propagating orthogonal to the laser beam axis, which are not collected in the bulk crystal. The phonons also preferential propagate normal to the domain wall. These modes are detected up to 0.35 mum from the domain wall. The observation and separation of these effects was made possible by the optimized spatial resolution (0.23 mum) of a home-built scanning confocal microscope and the fact that degeneracy of the transverse and longitudinal phonon polarization is lifted by polar phonons in Lithium Niobate and Lithium Tantalate. Raman

  3. Improving the Effectiveness of Speaker Verification Domain Adaptation With Inadequate In-Domain Data

    DTIC Science & Technology

    2017-08-20

    Improving the Effectiveness of Speaker Verification Domain Adaptation With Inadequate In-Domain Data Bengt J. Borgström1, Elliot Singer1, Douglas...ll.mit.edu.edu, dar@ll.mit.edu, es@ll.mit.edu, omid.sadjadi@nist.gov Abstract This paper addresses speaker verification domain adaptation with...contain speakers with low channel diversity. Existing domain adaptation methods are reviewed, and their shortcomings are discussed. We derive an

  4. Evolution of domain promiscuity in eukaryotic genomes—a perspective from the inferred ancestral domain architectures†

    PubMed Central

    Cohen-Gihon, Inbar; Fong, Jessica H.; Sharan, Roded; Nussinov, Ruth

    2012-01-01

    Most eukaryotic proteins are composed of two or more domains. These assemble in a modular manner to create new proteins usually by the acquisition of one or more domains to an existing protein. Promiscuous domains which are found embedded in a variety of proteins and co-exist with many other domains are of particular interest and were shown to have roles in signaling pathways and mediating network communication. The evolution of domain promiscuity is still an open problem, mostly due to the lack of sequenced ancestral genomes. Here we use inferred domain architectures of ancestral genomes to trace the evolution of domain promiscuity in eukaryotic genomes. We find an increase in average promiscuity along many branches of the eukaryotic tree. Moreover, domain promiscuity can proceed at almost a steady rate over long evolutionary time or exhibit lineage-specific acceleration. We also observe that many signaling and regulatory domains gained domain promiscuity around the Bilateria divergence. In addition we show that those domains that played a role in the creation of two body axes and existed before the divergence of the bilaterians from fungi/metazoan achieve a boost in their promiscuities during the bilaterian evolution. PMID:21127809

  5. Domainal cleavage as an Anisotropic Reaction-diffusion Process

    NASA Astrophysics Data System (ADS)

    Mulchrone, Kieran; Meere, Patrick

    2017-04-01

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

  6. An Internet-Mediated Pedometer-Based Program Improves Health-Related Quality-of-Life Domains and Daily Step Counts in COPD

    PubMed Central

    Moy, Marilyn L.; Collins, Riley J.; Martinez, Carlos H.; Kadri, Reema; Roman, Pia; Holleman, Robert G.; Kim, Hyungjin Myra; Nguyen, Huong Q.; Cohen, Miriam D.; Goodrich, David E.; Giardino, Nicholas D.

    2015-01-01

    BACKGROUND: Low levels of physical activity (PA) are associated with poor outcomes in people with COPD. Interventions to increase PA could improve outcomes. METHODS: We tested the efficacy of a novel Internet-mediated, pedometer-based exercise intervention. Veterans with COPD (N = 239) were randomized in a 2:1 ratio to the (1) intervention group (Omron HJ-720 ITC pedometer and Internet-mediated program) or (2) wait-list control group (pedometer). The primary outcome was health-related quality of life (HRQL), assessed by the St. George’s Respiratory Questionnaire (SGRQ), at 4 months. We examined the SGRQ total score (SGRQ-TS) and three domain scores: Symptoms, Activities, and Impact. The secondary outcome was daily step counts. Linear regression models assessed the effect of intervention on outcomes. RESULTS: Participants had a mean age of 67 ± 9 years, and 94% were men. There was no significant between-group difference in mean 4-month SGRQ-TS (2.3 units, P = .14). Nevertheless, a significantly greater proportion of intervention participants than control subjects had at least a 4-unit improvement in SGRQ-TS, the minimum clinically important difference (53% vs 39%, respectively, P = .05). For domain scores, the intervention group had a lower (reflecting better HRQL) mean than the control group by 4.6 units for Symptoms (P = .046) and by 3.3 units for Impact (P = .049). There was no significant difference in Activities score between the two groups. Compared with the control subjects, intervention participants walked 779 more steps per day at 4 months (P = .005). CONCLUSIONS: An Internet-mediated, pedometer-based walking program can improve domains of HRQL and daily step counts at 4 months in people with COPD. TRIAL REGISTRY: Clinical Trials.gov; No.: NCT01102777; URL: www.clinicaltrials.gov PMID:25811395

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

    PubMed Central

    An, Donggun; Runco, Mark A.

    2016-01-01

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

  8. Prevalence of the F-type lectin domain.

    PubMed

    Bishnoi, Ritika; Khatri, Indu; Subramanian, Srikrishna; Ramya, T N C

    2015-08-01

    F-type lectins are fucolectins with characteristic fucose and calcium-binding sequence motifs and a unique lectin fold (the "F-type" fold). F-type lectins are phylogenetically widespread with selective distribution. Several eukaryotic F-type lectins have been biochemically and structurally characterized, and the F-type lectin domain (FLD) has also been studied in the bacterial proteins, Streptococcus mitis lectinolysin and Streptococcus pneumoniae SP2159. However, there is little knowledge about the extent of occurrence of FLDs and their domain organization, especially, in bacteria. We have now mined the extensive genomic sequence information available in the public databases with sensitive sequence search techniques in order to exhaustively survey prokaryotic and eukaryotic FLDs. We report 437 FLD sequence clusters (clustered at 80% sequence identity) from eukaryotic, eubacterial and viral proteins. Domain architectures are diverse but mostly conserved in closely related organisms, and domain organizations of bacterial FLD-containing proteins are very different from their eukaryotic counterparts, suggesting unique specialization of FLDs to suit different requirements. Several atypical phylogenetic associations hint at lateral transfer. Among eukaryotes, we observe an expansion of FLDs in terms of occurrence and domain organization diversity in the taxa Mollusca, Hemichordata and Branchiostomi, perhaps coinciding with greater emphasis on innate immune strategies in these organisms. The naturally occurring FLDs with diverse domain organizations that we have identified here will be useful for future studies aimed at creating designer molecular platforms for directing desired biological activities to fucosylated glycoconjugates in target niches. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Identification of the WW domain-interaction sites in the unstructured N-terminal domain of EBV LMP 2A.

    PubMed

    Seo, Min-Duk; Park, Sung Jean; Kim, Hyun-Jung; Lee, Bong Jin

    2007-01-09

    Epstein-Barr virus latency is maintained by the latent membrane protein (LMP) 2A, which mimics the B-cell receptor (BCR) and perturbs BCR signaling. The cytoplasmic N-terminal domain of LMP2A is composed of 119 amino acids. The N-terminal domain of LMP2A (LMP2A NTD) contains two PY motifs (PPPPY) that interact with the WW domains of Nedd4 family ubiquitin-protein ligases. Based on our analysis of NMR data, we found that the LMP2A NTD adopts an overall random-coil structure in its native state. However, the region between residues 60 and 90 was relatively ordered, and seemed to form the hydrophobic core of the LMP2A NTD. This region resides between two PY motifs and is important for WW domain binding. Mapping of the residues involved in the interaction between the LMP2A NTD and WW domains was achieved by chemical shift perturbation, by the addition of WW2 and WW3 peptides. Interestingly, the binding of the WW domains mainly occurred in the hydrophobic core of the LMP2A NTD. In addition, we detected a difference in the binding modes of the two PY motifs against the two WW peptides. The binding of the WW3 peptide caused the resonances of five residues (Tyr(60), Glu(61), Asp(62), Trp(65), and Gly(66)) just behind the N-terminal PY motif of the LMP2A NTD to disappear. A similar result was obtained with WW2 binding. However, near the C-terminal PY motif, the chemical shift perturbation caused by WW2 binding was different from that due to WW3 binding, indicating that the residues near the PY motifs are involved in selective binding of WW domains. The present work represents the first structural study of the LMP2A NTD and provides fundamental structural information about its interaction with ubiquitin-protein ligase.

  10. Birdsong dialect patterns explained using magnetic domains

    NASA Astrophysics Data System (ADS)

    Burridge, James; Kenney, Steven

    2016-06-01

    The songs and calls of many bird species, like human speech, form distinct regional dialects. We suggest that the process of dialect formation is analogous to the physical process of magnetic domain formation. We take the coastal breeding grounds of the Puget Sound white crowned sparrow as an example. Previous field studies suggest that birds of this species learn multiple songs early in life, and when establishing a territory for the first time, retain one of these dialects in order to match the majority of their neighbors. We introduce a simple lattice model of the process, showing that this matching behavior can produce single dialect domains provided the death rate of adult birds is sufficiently low. We relate death rate to thermodynamic temperature in magnetic materials, and calculate the critical death rate by analogy with the Ising model. Using parameters consistent with the known behavior of these birds we show that coastal dialect domain shapes may be explained by viewing them as low-temperature "stripe states."

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

    PubMed Central

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

    2014-01-01

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

  12. Functional and structural characterization of domain truncated violaxanthin de-epoxidase.

    PubMed

    Hallin, Erik Ingmar; Guo, Kuo; Åkerlund, Hans-Erik

    2016-08-01

    Photosynthetic organisms need protection against excessive light. By using non-photochemical quenching, where the excess light is converted into heat, the organism can survive at higher light intensities. This process is partly initiated by the formation of zeaxanthin, which is achieved by the de-epoxidation of violaxanthin and antheraxanthin to zeaxanthin. This reaction is catalyzed by violaxanthin de-epoxidase (VDE). VDE consists of three domains of which the central lipocalin-like domain has been the most characterized. By truncating the domains surrounding the lipocalin-like domain, we show that VDE activity is possible without the C-terminal domain but not without the N-terminal domain. The N-terminal domain shows no VDE activity by itself but when separately expressed domains are mixed, VDE activity is possible. This shows that these domains can be folded separately and could therefore be studied separately. An increase of the hydrodynamic radius of wild-type VDE was observed when pH was lowered toward the pH required for activity, consistent with a pH-dependent oligomerization. The C-terminally truncated VDE did not show such an oligomerization, was relatively more active at higher pH but did not alter the KM for ascorbate. Circular dichroism measurements revealed the presence of α-helical structure in both the N- and C-terminal domains. By measuring the initial formation of the product, VDE was found to convert a large number of violaxanthin molecules to antheraxanthin before producing any zeaxanthin, favoring a model where violaxanthin is bound non-symmetrically in VDE. © 2016 Scandinavian Plant Physiology Society.

  13. Shape of isolated domains in lithium tantalate single crystals at elevated temperatures

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

    Shur, V. Ya., E-mail: vladimir.shur@usu.ru; Akhmatkhanov, A. R.; Baturin, I. S.

    2013-12-09

    The shape of isolated domains has been investigated in congruent lithium tantalate (CLT) single crystals at elevated temperatures and analyzed in terms of kinetic approach. The obtained temperature dependence of the growing domain shape in CLT including circular shape at temperatures above 190 °C has been attributed to increase of relative input of isotropic ionic conductivity. The observed nonstop wall motion and independent domain growth after merging in CLT as opposed to stoichiometric lithium tantalate have been attributed to difference in wall orientation. The computer simulation has confirmed applicability of the kinetic approach to the domain shape explanation.

  14. Shape of isolated domains in lithium tantalate single crystals at elevated temperatures

    NASA Astrophysics Data System (ADS)

    Shur, V. Ya.; Akhmatkhanov, A. R.; Chezganov, D. S.; Lobov, A. I.; Baturin, I. S.; Smirnov, M. M.

    2013-12-01

    The shape of isolated domains has been investigated in congruent lithium tantalate (CLT) single crystals at elevated temperatures and analyzed in terms of kinetic approach. The obtained temperature dependence of the growing domain shape in CLT including circular shape at temperatures above 190 °C has been attributed to increase of relative input of isotropic ionic conductivity. The observed nonstop wall motion and independent domain growth after merging in CLT as opposed to stoichiometric lithium tantalate have been attributed to difference in wall orientation. The computer simulation has confirmed applicability of the kinetic approach to the domain shape explanation.

  15. A unique GCN5-related glucosamine N-acetyltransferase region exist in the fungal multi-domain glycoside hydrolase family 3 β-N-acetylglucosaminidase.

    PubMed

    Qin, Zhen; Xiao, Yibei; Yang, Xinbin; Mesters, Jeroen R; Yang, Shaoqing; Jiang, Zhengqiang

    2015-12-16

    Glycoside hydrolase (GH) family 3 β-N-acetylglucosaminidases widely exist in the filamentous fungi, which may play a key role in chitin metabolism of fungi. A multi-domain GH family 3 β-N-acetylglucosaminidase from Rhizomucor miehei (RmNag), exhibiting a potential N-acetyltransferase region, has been recently reported to show great potential in industrial applications. In this study, the crystal structure of RmNag was determined at 2.80 Å resolution. The three-dimensional structure of RmNag showed four distinctive domains, which belong to two distinguishable functional regions--a GH family 3 β-N-acetylglucosaminidase region (N-terminal) and a N-acetyltransferase region (C-terminal). From structural and functional analysis, the C-terminal region of RmNag was identified as a unique tandem array linking general control non-derepressible 5 (GCN5)-related N-acetyltransferase (GNAT), which displayed glucosamine N-acetyltransferase activity. Structural analysis of this glucosamine N-acetyltransferase region revealed that a unique glucosamine binding pocket is located in the pantetheine arm binding terminal region of the conserved CoA binding pocket, which is different from all known GNAT members. This is the first structural report of a glucosamine N-acetyltransferase, which provides novel structural information about substrate specificity of GNATs. The structural and functional features of this multi-domain β-N-acetylglucosaminidase could be useful in studying the catalytic mechanism of GH family 3 proteins.

  16. PDE and cognitive processing: beyond the memory domain.

    PubMed

    Heckman, P R A; Blokland, A; Ramaekers, J; Prickaerts, J

    2015-03-01

    Phosphodiesterase inhibitors (PDE-Is) enhance cAMP and/or cGMP signaling via reducing the degradation of these cyclic nucleotides. Both cAMP and cGMP signaling are essential for a variety of cellular functions and exert their effects both pre- and post-synaptically. Either of these second messengers relays and amplifies incoming signals at receptors on the cell surface making them important elements in signal transduction cascades and essential in cellular signaling in a variety of cell functions including neurotransmitter release and neuroprotection. Consequently, these processes can be influenced by PDE-Is as they increase cAMP and/or cGMP concentrations. PDE-Is have been considered as possible therapeutic agents to treat impaired memory function linked to several brain disorders, including depression, schizophrenia and Alzheimer's disease (AD). This review will, however, focus on the possible role of phosphodiesterases (PDEs) in cognitive decline beyond the memory domain. Here we will discuss the involvement of PDEs on three related domains: attention, information filtering (sensory- and sensorimotor gating) and response inhibition (drug-induced hyperlocomotion). Currently, these are emerging cognitive domains in the field of PDE research. Here we discuss experimental studies and the potential beneficial effects of PDE-I drugs on these cognitive domains, as effects of PDE-Is on these domains could potentially influence effects on memory performance. Overall, PDE4 seems to be the most promising target for all domains discussed in this review. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Tandem-repeat protein domains across the tree of life.

    PubMed

    Jernigan, Kristin K; Bordenstein, Seth R

    2015-01-01

    Tandem-repeat protein domains, composed of repeated units of conserved stretches of 20-40 amino acids, are required for a wide array of biological functions. Despite their diverse and fundamental functions, there has been no comprehensive assessment of their taxonomic distribution, incidence, and associations with organismal lifestyle and phylogeny. In this study, we assess for the first time the abundance of armadillo (ARM) and tetratricopeptide (TPR) repeat domains across all three domains in the tree of life and compare the results to our previous analysis on ankyrin (ANK) repeat domains in this journal. All eukaryotes and a majority of the bacterial and archaeal genomes analyzed have a minimum of one TPR and ARM repeat. In eukaryotes, the fraction of ARM-containing proteins is approximately double that of TPR and ANK-containing proteins, whereas bacteria and archaea are enriched in TPR-containing proteins relative to ARM- and ANK-containing proteins. We show in bacteria that phylogenetic history, rather than lifestyle or pathogenicity, is a predictor of TPR repeat domain abundance, while neither phylogenetic history nor lifestyle predicts ARM repeat domain abundance. Surprisingly, pathogenic bacteria were not enriched in TPR-containing proteins, which have been associated within virulence factors in certain species. Taken together, this comparative analysis provides a newly appreciated view of the prevalence and diversity of multiple types of tandem-repeat protein domains across the tree of life. A central finding of this analysis is that tandem repeat domain-containing proteins are prevalent not just in eukaryotes, but also in bacterial and archaeal species.

  18. Tandem-repeat protein domains across the tree of life

    PubMed Central

    Jernigan, Kristin K.

    2015-01-01

    Tandem-repeat protein domains, composed of repeated units of conserved stretches of 20–40 amino acids, are required for a wide array of biological functions. Despite their diverse and fundamental functions, there has been no comprehensive assessment of their taxonomic distribution, incidence, and associations with organismal lifestyle and phylogeny. In this study, we assess for the first time the abundance of armadillo (ARM) and tetratricopeptide (TPR) repeat domains across all three domains in the tree of life and compare the results to our previous analysis on ankyrin (ANK) repeat domains in this journal. All eukaryotes and a majority of the bacterial and archaeal genomes analyzed have a minimum of one TPR and ARM repeat. In eukaryotes, the fraction of ARM-containing proteins is approximately double that of TPR and ANK-containing proteins, whereas bacteria and archaea are enriched in TPR-containing proteins relative to ARM- and ANK-containing proteins. We show in bacteria that phylogenetic history, rather than lifestyle or pathogenicity, is a predictor of TPR repeat domain abundance, while neither phylogenetic history nor lifestyle predicts ARM repeat domain abundance. Surprisingly, pathogenic bacteria were not enriched in TPR-containing proteins, which have been associated within virulence factors in certain species. Taken together, this comparative analysis provides a newly appreciated view of the prevalence and diversity of multiple types of tandem-repeat protein domains across the tree of life. A central finding of this analysis is that tandem repeat domain-containing proteins are prevalent not just in eukaryotes, but also in bacterial and archaeal species. PMID:25653910

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

    PubMed Central

    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

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

    USGS Publications Warehouse

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

    2011-01-01

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

  1. Domain-Specific Relationships in Sexual Measures of Impulsive Behavior.

    PubMed

    Mahoney, Colin T; Lawyer, Steven R

    2018-04-25

    Impulsivity is an important construct for understanding sexual behaviors, but behavioral and self-report measures of impulsivity often are not correlated. One possible explanation for this is that there is little shared variance in the measures because behavioral measures index impulsivity by asking questions about monetary preferences, while self-report measures index impulsivity by asking about a broad range of real-world outcomes (including those of a sexual nature) largely unrelated to money-related preferences. Undergraduate students (total N = 105; female n = 77, male n = 28) completed laboratory measures-delay discounting (DD) and probability discounting (PD)-for two different outcomes-money and sexual activity. Participants also completed the Delaying Gratification Inventory (DGI), which measures difficulty with delaying gratification (i.e., impulsivity) across different domains, including money and physical pleasures. Findings indicated that DD and PD for money were not related to any of the DGI subscales. However, DD for sexual activity was significantly related to the DGI Physical Pleasures subscale, but not other subscales. These findings suggest that the relationship between behavioral and self-report measures of impulsive choice may be stronger when both are measuring domain-specific rather than domain-general behavioral patterns, but further research is warranted.

  2. ATP Binding to p97/VCP D1 Domain Regulates Selective Recruitment of Adaptors to Its Proximal N-Domain

    PubMed Central

    Chia, Wei Sheng; Chia, Diana Xueqi; Rao, Feng; Bar Nun, Shoshana; Geifman Shochat, Susana

    2012-01-01

    p97/Valosin-containing protein (VCP) is a member of the AAA-ATPase family involved in many cellular processes including cell division, intracellular trafficking and extraction of misfolded proteins in endoplasmic reticulum-associated degradation (ERAD). It is a homohexamer with each subunit containing two tandem D1 and D2 ATPase domains and N- and C-terminal regions that function as adaptor protein binding domains. p97/VCP is directed to its many different functional pathways by associating with various adaptor proteins. The regulation of the recruitment of the adaptor proteins remains unclear. Two adaptor proteins, Ufd1/Npl4 and p47, which bind exclusively to the p97/VCP N-domain and direct p97/VCP to either ERAD-related processes or homotypic fusion of Golgi fragments, were studied here. Surface plasmon resonance biosensor-based assays allowed the study of binding kinetics in real time. In competition experiments, it was observed that in the presence of ATP, Ufd1/Npl4 was able to compete more effectively with p47 for binding to p97/VCP. By using non-hydrolysable ATP analogues and the hexameric truncated p97/N-D1 fragment, it was shown that binding rather than hydrolysis of ATP to the proximal D1 domain strengthened the Ufd1/Npl4 association with the N-domain, thus regulating the recruitment of either Ufd1/Npl4 or p47. This novel role of ATP and an assigned function to the D1 AAA-ATPase domain link the multiple functions of p97/VCP to the metabolic status of the cell. PMID:23226521

  3. ATP binding to p97/VCP D1 domain regulates selective recruitment of adaptors to its proximal N-domain.

    PubMed

    Chia, Wei Sheng; Chia, Diana Xueqi; Rao, Feng; Bar Nun, Shoshana; Geifman Shochat, Susana

    2012-01-01

    p97/Valosin-containing protein (VCP) is a member of the AAA-ATPase family involved in many cellular processes including cell division, intracellular trafficking and extraction of misfolded proteins in endoplasmic reticulum-associated degradation (ERAD). It is a homohexamer with each subunit containing two tandem D1 and D2 ATPase domains and N- and C-terminal regions that function as adaptor protein binding domains. p97/VCP is directed to its many different functional pathways by associating with various adaptor proteins. The regulation of the recruitment of the adaptor proteins remains unclear. Two adaptor proteins, Ufd1/Npl4 and p47, which bind exclusively to the p97/VCP N-domain and direct p97/VCP to either ERAD-related processes or homotypic fusion of Golgi fragments, were studied here. Surface plasmon resonance biosensor-based assays allowed the study of binding kinetics in real time. In competition experiments, it was observed that in the presence of ATP, Ufd1/Npl4 was able to compete more effectively with p47 for binding to p97/VCP. By using non-hydrolysable ATP analogues and the hexameric truncated p97/N-D1 fragment, it was shown that binding rather than hydrolysis of ATP to the proximal D1 domain strengthened the Ufd1/Npl4 association with the N-domain, thus regulating the recruitment of either Ufd1/Npl4 or p47. This novel role of ATP and an assigned function to the D1 AAA-ATPase domain link the multiple functions of p97/VCP to the metabolic status of the cell.

  4. Crystallization and preliminary X-ray analysis of Na-ASP-1, a multi-domain pathogenesis-related-1 protein from the human hookworm parasite Necator americanus

    PubMed Central

    Asojo, Oluwatoyin A.; Loukas, Alex; Inan, Mehmet; Barent, Rick; Huang, Jicai; Plantz, Brad; Swanson, Amber; Gouthro, Mark; Meagher, Michael M.; Hotez, Peter J.

    2005-01-01

    Human hookworm infection is a major cause of anemia and malnutrition in the developing world. In an effort to control hookworm infection, the Human Hookworm Vaccine Initiative has identified candidate vaccine antigens from the infective larval stage (L3) of the parasite, including a family of pathogenesis-related-1 (PR-1) proteins known as the ancylostoma-secreted proteins (ASPs). The functions of the ASPs are unknown. In addition, it is unclear why some ASPs have one while others have multiple PR-1 domains. There are no known structures of a multi-domain ASP and in an effort to remedy this situation, recombinant Na-ASP-1 has been expressed, purified and crystallized. Na-ASP-1 is a 406-amino-acid multi-domain ASP from the prevalent human hookworm parasite Necator americanus. Useful X-ray data to 2.2 Å have been collected from a crystal that belongs to the monoclinic space group P21 with unit-cell parameters a = 67.7, b = 74.27, c = 84.60 Å, β = 112.12°. An initial molecular-replacement solution has been obtained with one monomer in the asymmetric unit. PMID:16511050

  5. Health Domains for Sale: The Need for Global Health Internet Governance

    PubMed Central

    Liang, Bryan A; Kohler, Jillian C; Attaran, Amir

    2014-01-01

    A debate on Internet governance for health, or “eHealth governance”, is emerging with the impending award of a new dot-health (.health) generic top-level domain name (gTLD) along with a host of other health-related domains. This development is critical as it will shape the future of the health Internet, allowing largely unrestricted use of .health second-level domain names by future registrants, raising concerns about the potential for privacy, use and marketing of health-related information, credibility of online health content, and potential for Internet fraud and abuse. Yet, prospective .health gTLD applicants do not provide adequate safeguards for use of .health or related domains and have few or no ties to the global health community. If approved, one of these for-profit corporate applicants would effectively control the future of the .health address on the Internet with arguably no active oversight from important international public health stakeholders. This would represent a lost opportunity for the public health, medical, and broader health community in establishing a trusted, transparent and reliable source for health on the Internet. Countries, medical associations, civil society, and consumer advocates have objected to these applications on grounds that they do not meet the public interest. We argue that there is an immediate need for action to postpone awarding of the .health gTLD and other health-related gTLDs to address these concerns and ensure the appropriate development of sound eHealth governance rules, principles, and use. This would support the crucial need of ensuring access to quality and evidence-based sources of health information online, as well as establishing a safe and reliable space on the Internet for health. We believe, if properly governed, .health and other domains could represent such a promise in the future. PMID:24598602

  6. Health domains for sale: the need for global health Internet governance.

    PubMed

    Mackey, Tim Ken; Liang, Bryan A; Kohler, Jillian C; Attaran, Amir

    2014-03-05

    A debate on Internet governance for health, or "eHealth governance", is emerging with the impending award of a new dot-health (.health) generic top-level domain name (gTLD) along with a host of other health-related domains. This development is critical as it will shape the future of the health Internet, allowing largely unrestricted use of .health second-level domain names by future registrants, raising concerns about the potential for privacy, use and marketing of health-related information, credibility of online health content, and potential for Internet fraud and abuse. Yet, prospective .health gTLD applicants do not provide adequate safeguards for use of .health or related domains and have few or no ties to the global health community. If approved, one of these for-profit corporate applicants would effectively control the future of the .health address on the Internet with arguably no active oversight from important international public health stakeholders. This would represent a lost opportunity for the public health, medical, and broader health community in establishing a trusted, transparent and reliable source for health on the Internet. Countries, medical associations, civil society, and consumer advocates have objected to these applications on grounds that they do not meet the public interest. We argue that there is an immediate need for action to postpone awarding of the .health gTLD and other health-related gTLDs to address these concerns and ensure the appropriate development of sound eHealth governance rules, principles, and use. This would support the crucial need of ensuring access to quality and evidence-based sources of health information online, as well as establishing a safe and reliable space on the Internet for health. We believe, if properly governed, .health and other domains could represent such a promise in the future.

  7. Identifying protein domains by global analysis of soluble fragment data.

    PubMed

    Bulloch, Esther M M; Kingston, Richard L

    2014-11-15

    The production and analysis of individual structural domains is a common strategy for studying large or complex proteins, which may be experimentally intractable in their full-length form. However, identifying domain boundaries is challenging if there is little structural information concerning the protein target. One experimental procedure for mapping domains is to screen a library of random protein fragments for solubility, since truncation of a domain will typically expose hydrophobic groups, leading to poor fragment solubility. We have coupled fragment solubility screening with global data analysis to develop an effective method for identifying structural domains within a protein. A gene fragment library is generated using mechanical shearing, or by uracil doping of the gene and a uracil-specific enzymatic digest. A split green fluorescent protein (GFP) assay is used to screen the corresponding protein fragments for solubility when expressed in Escherichia coli. The soluble fragment data are then analyzed using two complementary approaches. Fragmentation "hotspots" indicate possible interdomain regions. Clustering algorithms are used to group related fragments, and concomitantly predict domain location. The effectiveness of this Domain Seeking procedure is demonstrated by application to the well-characterized human protein p85α. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Structure of the SANT domain from the Xenopus chromatin remodeling factor ISWI

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

    Horton, John R.; Elgar, Stuart J.; Khan, Seema I.

    2008-09-17

    The SANT (Swi3, Ada2, N-Cor, and TFIIIB) module was first described as a putative DNA-binding domain with strong similarity to the helix-turn-helix DNA binding domain of Myb-related proteins. The X-ray structure of the C-terminal one third portion of the ATPase ISWI of Drosophila melangoaster, containing both SANT and SLIDE (SANT-Like ISWI Domain), confirmed the overall helix-turn-helix structural architecture of SANT as well as SLIDE. However, the DNA-contacting residues in Myb are not conserved in SANT and the structurally corresponding residues in the ISWI SANT domain are acidic, and therefore incompatible with DNA interaction. Recent studies suggested that SANT domains mightmore » be a histone-tail-binding module, including the DNA binding SANT domain of c-Myb. Here they present the X-ray structure of Xenopus laevis ISWI SANT domain, derived from limited proteolysis of a C-terminal fragment of ISWI protein.« less

  9. Detecting Coevolution in and among Protein Domains

    PubMed Central

    Yeang, Chen-Hsiang; Haussler, David

    2007-01-01

    Correlated changes of nucleic or amino acids have provided strong information about the structures and interactions of molecules. Despite the rich literature in coevolutionary sequence analysis, previous methods often have to trade off between generality, simplicity, phylogenetic information, and specific knowledge about interactions. Furthermore, despite the evidence of coevolution in selected protein families, a comprehensive screening of coevolution among all protein domains is still lacking. We propose an augmented continuous-time Markov process model for sequence coevolution. The model can handle different types of interactions, incorporate phylogenetic information and sequence substitution, has only one extra free parameter, and requires no knowledge about interaction rules. We employ this model to large-scale screenings on the entire protein domain database (Pfam). Strikingly, with 0.1 trillion tests executed, the majority of the inferred coevolving protein domains are functionally related, and the coevolving amino acid residues are spatially coupled. Moreover, many of the coevolving positions are located at functionally important sites of proteins/protein complexes, such as the subunit linkers of superoxide dismutase, the tRNA binding sites of ribosomes, the DNA binding region of RNA polymerase, and the active and ligand binding sites of various enzymes. The results suggest sequence coevolution manifests structural and functional constraints of proteins. The intricate relations between sequence coevolution and various selective constraints are worth pursuing at a deeper level. PMID:17983264

  10. Assimilative domain proficiency and performance in chemistry coursework

    NASA Astrophysics Data System (ADS)

    Byrnes, Scott William

    The assimilation and synthesis of knowledge is essential for students to be successful in chemistry, yet not all students synthesize knowledge as intended. The study used the Learning Preference Checklist to classify students into one of three learning modalities -- visual, auditory, or kinesthetic (VAK). It also used the Kolb Learning Style Inventory (KLSI), which utilizes four learning domains - Converging, Accommodating, Diverging, and Assimilating - to explain the students' maturation process by showing shift from any domain towards the Assimilating domain. A shift approaching this domain was considered as improvement in the assimilation and synthesis of knowledge. This pre-experimental one-group pretest-posttest study was used to test the hypothesis that modifying a high school chemistry curriculum to accentuate a student's learning preference would result in a shift towards the Assimilative domain on the KLSI and if there was a correlation between the improvement in student learning and a shift towards the KLSI Assimilating domain. Forty-two high school students were issued the VAK and provided with differentiated instruction via homologous cooperative learning groups. Pre- and post-KLSI and chemistry concepts tests were administered. T test analyses showed no significant shift towards the Assimilating domain. Further Pearson's r analyses showed no significant correlation between the KLSI and exam scores. This study contributes to social change by providing empirical evidence related to the effectiveness infusing learning styles into the science curriculum and the integration of the KLSI to monitor cognitive development as tools in raising standardized test scores and enhancing academic achievement. Results from the study can also inform future research into learning styles through their incorporation into the science curriculum.

  11. Testing for Granger Causality in the Frequency Domain: A Phase Resampling Method.

    PubMed

    Liu, Siwei; Molenaar, Peter

    2016-01-01

    This article introduces phase resampling, an existing but rarely used surrogate data method for making statistical inferences of Granger causality in frequency domain time series analysis. Granger causality testing is essential for establishing causal relations among variables in multivariate dynamic processes. However, testing for Granger causality in the frequency domain is challenging due to the nonlinear relation between frequency domain measures (e.g., partial directed coherence, generalized partial directed coherence) and time domain data. Through a simulation study, we demonstrate that phase resampling is a general and robust method for making statistical inferences even with short time series. With Gaussian data, phase resampling yields satisfactory type I and type II error rates in all but one condition we examine: when a small effect size is combined with an insufficient number of data points. Violations of normality lead to slightly higher error rates but are mostly within acceptable ranges. We illustrate the utility of phase resampling with two empirical examples involving multivariate electroencephalography (EEG) and skin conductance data.

  12. Reconstitution of the NF1 GAP-related domain in NF1-deficient human Schwann cells

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

    Thomas, Stacey L.; Neuroscience Program, Loyola University Medical Center, Maywood, IL; Department of Anatomy and Cell Biology, University of Illinois Chicago, Chicago, IL

    Schwann cells derived from peripheral nerve sheath tumors from individuals with Neurofibromatosis Type 1 (NF1) are deficient for the protein neurofibromin, which contains a GAP-related domain (NF1-GRD). Neurofibromin-deficient Schwann cells have increased Ras activation, increased proliferation in response to certain growth stimuli, increased angiogenic potential, and altered cell morphology. This study examined whether expression of functional NF1-GRD can reverse the transformed phenotype of neurofibromin-deficient Schwann cells from both benign and malignant peripheral nerve sheath tumors. We reconstituted the NF1-GRD using retroviral transduction and examined the effects on cell morphology, growth potential, and angiogenic potential. NF1-GRD reconstitution resulted in morphologic changes,more » a 16-33% reduction in Ras activation, and a 53% decrease in proliferation in neurofibromin-deficient Schwann cells. However, NF1-GRD reconstitution was not sufficient to decrease the in vitro angiogenic potential of the cells. This study demonstrates that reconstitution of the NF1-GRD can at least partially reverse the transformation of human NF1 tumor-derived Schwann cells.« less

  13. Domains of psychosocial disability and mental disorders.

    PubMed

    Ro, Eunyoe; Watson, David; Clark, Lee Anna

    2018-06-07

    This study examined relations between comprehensive domains of psychosocial disability and mental disorders to determine (1) whether differential patterns of associations exist between psychosocial disability dimensions and commonly diagnosed mental disorders and (2) whether these relations differ between self-reported and interviewer-rated psychosocial disability domains. Self-reported and interviewer-rated psychosocial functioning measures and an interviewer-rated diagnostic assessment tool were administered to 181 psychiatric outpatients. Internalizing disorders showed the strongest and most pervasive associations with psychosocial impairment across both self-reported and interviewer-rated measures, followed by thought disorder; externalizing showed the weakest associations. More specifically, logistic regression analyses indicated that lower well-being factor score significantly increased the odds of distress-disorder diagnoses, and poor basic functioning increased the odds of PTSD. Results clearly showed differences in the magnitude of associations between three dimensions of psychosocial-disability and commonly diagnosed disorders, and that these differences were similar regardless of rater type. © 2018 Wiley Periodicals, Inc.

  14. Mechanical Unfolding Studies on Single-Domain SUMO and Multi-Domain Periplasmic Binding Proteins

    NASA Astrophysics Data System (ADS)

    Kotamarthi, Hema Chandra; Ainavarapu, Sri Rama Koti

    Protein mechanics is a key component of many cellular and sub-cellular processes. The current review focuses on recent studies from our laboratory that probe the effect of sequence on the mechanical stability of structurally similar proteins and the unfolding mechanisms of multi-domain periplasmic binding proteins. Ubiquitin and small ubiquitin-related modifiers (SUMOs) are structurally similar and possess different mechanical stabilities, ubiquitin being stronger than SUMOs as revealed from their unfolding forces. These differences are plausibly due to the variation in number of inter-residue contacts. The unfolding potential widths determined from the pulling speed-dependent studies revealed that SUMOs are mechanically more flexible than ubiquitin. This flexibility of SUMOs plays a role in ligand binding and our single-molecule studies on SUMO interaction with SUMO binding motifs (SBMs) have shown that ligand binding decreases the SUMO flexibility and increases its mechanical stability. Studies on multi-domain periplasmic binding proteins have revealed that the unfolding energy landscape of these proteins is complex and they follow kinetic partitioning between two-state and multiple three-state pathways.

  15. Geomorphic domains and linear features on Landsat images, Circle Quadrangle, Alaska

    USGS Publications Warehouse

    Simpson, S.L.

    1984-01-01

    A remote sensing study using Landsat images was undertaken as part of the Alaska Mineral Resource Assessment Program (AMRAP). Geomorphic domains A and B, identified on enhanced Landsat images, divide Circle quadrangle south of Tintina fault zone into two regional areas having major differences in surface characteristics. Domain A is a roughly rectangular, northeast-trending area of relatively low relief and simple, widely spaced drainages, except where igneous rocks are exposed. In contrast, domain B, which bounds two sides of domain A, is more intricately dissected showing abrupt changes in slope and relatively high relief. The northwestern part of geomorphic domain A includes a previously mapped tectonostratigraphic terrane. The southeastern boundary of domain A occurs entirely within the adjoining tectonostratigraphic terrane. The sharp geomorphic contrast along the southeastern boundary of domain A and the existence of known faults along this boundary suggest that the southeastern part of domain A may be a subdivision of the adjoining terrane. Detailed field studies would be necessary to determine the characteristics of the subdivision. Domain B appears to be divisible into large areas of different geomorphic terrains by east-northeast-trending curvilinear lines drawn on Landsat images. Segments of two of these lines correlate with parts of boundaries of mapped tectonostratigraphic terranes. On Landsat images prominent north-trending lineaments together with the curvilinear lines form a large-scale regional pattern that is transected by mapped north-northeast-trending high-angle faults. The lineaments indicate possible lithlogic variations and/or structural boundaries. A statistical strike-frequency analysis of the linear features data for Circle quadrangle shows that northeast-trending linear features predominate throughout, and that most northwest-trending linear features are found south of Tintina fault zone. A major trend interval of N.64-72E. in the linear

  16. Formin homology 2 domains occur in multiple contexts in angiosperms

    PubMed Central

    Cvrčková, Fatima; Novotný, Marian; Pícková, Denisa; Žárský, Viktor

    2004-01-01

    Background Involvement of conservative molecular modules and cellular mechanisms in the widely diversified processes of eukaryotic cell morphogenesis leads to the intriguing question: how do similar proteins contribute to dissimilar morphogenetic outputs. Formins (FH2 proteins) play a central part in the control of actin organization and dynamics, providing a good example of evolutionarily versatile use of a conserved protein domain in the context of a variety of lineage-specific structural and signalling interactions. Results In order to identify possible plant-specific sequence features within the FH2 protein family, we performed a detailed analysis of angiosperm formin-related sequences available in public databases, with particular focus on the complete Arabidopsis genome and the nearly finished rice genome sequence. This has led to revision of the current annotation of half of the 22 Arabidopsis formin-related genes. Comparative analysis of the two plant genomes revealed a good conservation of the previously described two subfamilies of plant formins (Class I and Class II), as well as several subfamilies within them that appear to predate the separation of monocot and dicot plants. Moreover, a number of plant Class II formins share an additional conserved domain, related to the protein phosphatase/tensin/auxilin fold. However, considerable inter-species variability sets limits to generalization of any functional conclusions reached on a single species such as Arabidopsis. Conclusions The plant-specific domain context of the conserved FH2 domain, as well as plant-specific features of the domain itself, may reflect distinct functional requirements in plant cells. The variability of formin structures found in plants far exceeds that known from both fungi and metazoans, suggesting a possible contribution of FH2 proteins in the evolution of the plant type of multicellularity. PMID:15256004

  17. Application of Feature-Oriented Domain Analysis to the Army Movement Control Domain (Appendices A-I)

    DTIC Science & Technology

    1992-06-01

    Cohen, James A. Hess, William E. Novak, & A. Spen- cer Peterson. Feature-Oriented Domain Analysis ( FODA ) Feasibility Study (CMU/SEI-90- TR-21...Oriented Domain Analysis to the Army Movement Control Domain (Appendices A -1) Sholom G. Cohen Jay L. Stanley, Jr. A. Spencer Peterson Robert W...Appendices) June 1992 Application of Feature-Oriented Domain Analysis to the Army Movement Control Domain (Appendices A -1) Sholom G. Cohen Jay L

  18. 3D-Printed Ultratough Hydrogel Structures with Titin-like Domains.

    PubMed

    Zhu, Fengbo; Cheng, Libo; Wang, Zhi Jian; Hong, Wei; Wu, Zi Liang; Yin, Jun; Qian, Jin; Zheng, Qiang

    2017-04-05

    Titin is composed of repeated modular domains which unfold and dissipate energy upon loading. Here we employed such molecular-level paradigm to fabricate macroscopic ultratough hydrogel structures with titin-like domains, enabled by three-dimensional printing with multiple nozzles. Under stretch, the relatively thin and weak gel fibers in the printed structures break first and the hidden lengths postpone the failure of the main structures, mimicking the toughening principle in titin. These titin-like folded domains have been incorporated into a synthetic spider-web, which shows significantly enhanced extensibility and toughness. This work provides a new avenue of topological design for materials/structures with desired properties.

  19. Characterizing implicit mental health associations across clinical domains.

    PubMed

    Werntz, Alexandra J; Steinman, Shari A; Glenn, Jeffrey J; Nock, Matthew K; Teachman, Bethany A

    2016-09-01

    Implicit associations are relatively uncontrollable associations between concepts in memory. The current investigation focuses on implicit associations in four mental health domains (alcohol use, anxiety, depression, and eating disorders) and how these implicit associations: a) relate to explicit associations and b) self-reported clinical symptoms within the same domains, and c) vary based on demographic characteristics (age, gender, race, ethnicity, and education). Participants (volunteers over age 18 to a research website) completed implicit association (Implicit Association Tests), explicit association (self + psychopathology or attitudes toward food, using semantic differential items), and symptom measures at the Project Implicit Mental Health website tied to: alcohol use (N = 12,387), anxiety (N = 21,304), depression (N = 24,126), or eating disorders (N = 10,115). Within each domain, implicit associations showed small to moderate associations with explicit associations and symptoms, and predicted self-reported symptoms beyond explicit associations. In general, implicit association strength varied little by race and ethnicity, but showed small ties to age, gender, and education. This research was conducted on a public research and education website, where participants could take more than one of the studies. Among a large and diverse sample, implicit associations in the four domains are congruent with explicit associations and self-reported symptoms, and also add to our prediction of self-reported symptoms over and above explicit associations, pointing to the potential future clinical utility and validity of using implicit association measures with diverse populations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Memory and Comprehension for Health Information among Older Adults: Distinguishing the Effects of Domain-General and Domain-Specific Knowledge

    PubMed Central

    Chin, Jessie; Payne, Brennan; Gao, Xuefei; Conner-Garcia, Thembi; Graumlich, James F.; Murray, Michael D.; Morrow, Daniel G.; Stine-Morrow, Elizabeth A.L.

    2014-01-01

    While there is evidence that knowledge influences understanding of health information, less is known about the processing mechanisms underlying this effect and its impact on memory. We used the moving window paradigm to examine how older adults varying in domain-general crystallized ability (verbal ability) and health knowledge allocate attention to understand health and domain-general texts. Participants (n=107, aged 60 to 88 yrs) read and recalled single sentences about hypertension and about non-health topics. Mixed-effects modeling of word-by-word reading times suggested that domain-general crystallized ability increased conceptual integration regardless of text domain, while health knowledge selectively increased resource allocation to conceptual integration at clause boundaries in health texts. These patterns of attentional allocation were related to subsequent recall performance. Although older adults with lower levels of crystallized ability were less likely to engage in integrative processing, when they did, this strategy had a compensatory effect in improving recall. These findings suggest that semantic integration during reading is an important comprehension process that supports the construction of the memory representation and is engendered by knowledge. Implications of the findings for theories of text processing and memory as well as for designing patient education materials are discussed. PMID:24787361

  1. Memory and comprehension for health information among older adults: distinguishing the effects of domain-general and domain-specific knowledge.

    PubMed

    Chin, Jessie; Payne, Brennan; Gao, Xuefei; Conner-Garcia, Thembi; Graumlich, James F; Murray, Michael D; Morrow, Daniel G; Stine-Morrow, Elizabeth A L

    2015-01-01

    While there is evidence that knowledge influences understanding of health information, less is known about the processing mechanisms underlying this effect and its impact on memory. We used the moving window paradigm to examine how older adults varying in domain-general crystallised ability (verbal ability) and health knowledge allocate attention to understand health and domain-general texts. Participants (n = 107, age: 60-88 years) read and recalled single sentences about hypertension and about non-health topics. Mixed-effects modelling of word-by-word reading times suggested that domain-general crystallised ability increased conceptual integration regardless of text domain, while health knowledge selectively increased resource allocation to conceptual integration at clause boundaries in health texts. These patterns of attentional allocation were related to subsequent recall performance. Although older adults with lower levels of crystallised ability were less likely to engage in integrative processing, when they did, this strategy had a compensatory effect in improving recall. These findings suggest that semantic integration during reading is an important comprehension process that supports the construction of the memory representation and is engendered by knowledge. Implications of the findings for theories of text processing and memory as well as for designing patient education materials are discussed.

  2. Recovering Protein-Protein and Domain-Domain Interactions from Aggregation of IP-MS Proteomics of Coregulator Complexes

    PubMed Central

    Mazloom, Amin R.; Dannenfelser, Ruth; Clark, Neil R.; Grigoryan, Arsen V.; Linder, Kathryn M.; Cardozo, Timothy J.; Bond, Julia C.; Boran, Aislyn D. W.; Iyengar, Ravi; Malovannaya, Anna; Lanz, Rainer B.; Ma'ayan, Avi

    2011-01-01

    Coregulator proteins (CoRegs) are part of multi-protein complexes that transiently assemble with transcription factors and chromatin modifiers to regulate gene expression. In this study we analyzed data from 3,290 immuno-precipitations (IP) followed by mass spectrometry (MS) applied to human cell lines aimed at identifying CoRegs complexes. Using the semi-quantitative spectral counts, we scored binary protein-protein and domain-domain associations with several equations. Unlike previous applications, our methods scored prey-prey protein-protein interactions regardless of the baits used. We also predicted domain-domain interactions underlying predicted protein-protein interactions. The quality of predicted protein-protein and domain-domain interactions was evaluated using known binary interactions from the literature, whereas one protein-protein interaction, between STRN and CTTNBP2NL, was validated experimentally; and one domain-domain interaction, between the HEAT domain of PPP2R1A and the Pkinase domain of STK25, was validated using molecular docking simulations. The scoring schemes presented here recovered known, and predicted many new, complexes, protein-protein, and domain-domain interactions. The networks that resulted from the predictions are provided as a web-based interactive application at http://maayanlab.net/HT-IP-MS-2-PPI-DDI/. PMID:22219718

  3. A domain-centric solution to functional genomics via dcGO Predictor

    PubMed Central

    2013-01-01

    Background Computational/manual annotations of protein functions are one of the first routes to making sense of a newly sequenced genome. Protein domain predictions form an essential part of this annotation process. This is due to the natural modularity of proteins with domains as structural, evolutionary and functional units. Sometimes two, three, or more adjacent domains (called supra-domains) are the operational unit responsible for a function, e.g. via a binding site at the interface. These supra-domains have contributed to functional diversification in higher organisms. Traditionally functional ontologies have been applied to individual proteins, rather than families of related domains and supra-domains. We expect, however, to some extent functional signals can be carried by protein domains and supra-domains, and consequently used in function prediction and functional genomics. Results Here we present a domain-centric Gene Ontology (dcGO) perspective. We generalize a framework for automatically inferring ontological terms associated with domains and supra-domains from full-length sequence annotations. This general framework has been applied specifically to primary protein-level annotations from UniProtKB-GOA, generating GO term associations with SCOP domains and supra-domains. The resulting 'dcGO Predictor', can be used to provide functional annotation to protein sequences. The functional annotation of sequences in the Critical Assessment of Function Annotation (CAFA) has been used as a valuable opportunity to validate our method and to be assessed by the community. The functional annotation of all completely sequenced genomes has demonstrated the potential for domain-centric GO enrichment analysis to yield functional insights into newly sequenced or yet-to-be-annotated genomes. This generalized framework we have presented has also been applied to other domain classifications such as InterPro and Pfam, and other ontologies such as mammalian phenotype and

  4. Full waveform inversion in the frequency domain using classified time-domain residual wavefields

    NASA Astrophysics Data System (ADS)

    Son, Woohyun; Koo, Nam-Hyung; Kim, Byoung-Yeop; Lee, Ho-Young; Joo, Yonghwan

    2017-04-01

    We perform the acoustic full waveform inversion in the frequency domain using residual wavefields that have been separated in the time domain. We sort the residual wavefields in the time domain according to the order of absolute amplitudes. Then, the residual wavefields are separated into several groups in the time domain. To analyze the characteristics of the residual wavefields, we compare the residual wavefields of conventional method with those of our residual separation method. From the residual analysis, the amplitude spectrum obtained from the trace before separation appears to have little energy at the lower frequency bands. However, the amplitude spectrum obtained from our strategy is regularized by the separation process, which means that the low-frequency components are emphasized. Therefore, our method helps to emphasize low-frequency components of residual wavefields. Then, we generate the frequency-domain residual wavefields by taking the Fourier transform of the separated time-domain residual wavefields. With these wavefields, we perform the gradient-based full waveform inversion in the frequency domain using back-propagation technique. Through a comparison of gradient directions, we confirm that our separation method can better describe the sub-salt image than the conventional approach. The proposed method is tested on the SEG/EAGE salt-dome model. The inversion results show that our algorithm is better than the conventional gradient based waveform inversion in the frequency domain, especially for deeper parts of the velocity model.

  5. Inhibition deficit in the spatial tendency of the response in multiple-domain amnestic mild cognitive impairment. An event-related potential study

    PubMed Central

    Cespón, Jesús; Galdo-Álvarez, Santiago; Díaz, Fernando

    2015-01-01

    Longitudinal studies have shown that a high percentage of people with amnestic mild cognitive impairment (MCI) develop Alzheimer’s disease (AD). Prodromal AD is known to involve deficits in executive control processes. In the present study, we examined such deficits by recording EEG in 13 single-domain amnestic MCI (sdaMCI), 12 multiple-domain amnestic MCI (mdaMCI) and 18 healthy elderly (control group, CG) participants while they performed a Simon task. The Simon task demands deployment of executive processes because participants have to respond to non-spatial features of a lateralized stimulus and inhibit the more automatic spatial tendency of the response. We specifically focused on the negativity central contralateral (N2cc), an event-related potential (ERP) component related to brain activity that prevents the cross-talk between direction of spatial attention and manual response preparation. The reaction time (RT) was not significantly different among the three groups of participants. The percentage of errors (PE) was higher in mdaMCI than in CG and sdaMCI participants. In addition, N2cc latency was delayed in mdaMCI (i.e., delayed implementation of mechanisms for controlling the spatial tendency of the response). The N2cc latency clearly distinguished among mdaMCI and CG/sdaMCI participants (area under curve: 0.91). Longer N2cc was therefore associated with executive control deficits, which suggests that N2cc latency is a correlate of mdaMCI. PMID:25999853

  6. From Cognitive-Domain Theory to Assessment Practice

    ERIC Educational Resources Information Center

    Bennett, Randy E.; Deane, Paul; van Rijn, Peter W.

    2016-01-01

    This article exemplifies how assessment design might be grounded in theory, thereby helping to strengthen validity claims. Spanning work across multiple related projects, the article first briefly summarizes an assessment system model for the elementary and secondary levels. Next the article describes how cognitive-domain theory and principles are…

  7. Apoplastic domains and sub-domains in the shoots of etiolated corn seedlings

    NASA Technical Reports Server (NTRS)

    Epel, B. L.; Bandurski, R. S.

    1990-01-01

    Light Green, an apoplastic probe, was applied to the cut mesocotyl base or to the cut coleoptile apex of etiolated seedlings of Zea mays L. cv. Silver Queen. Probe transport was measured and its tissue distribution determined. In the mesocotyl, there is an apoplastic barrier between cortex and stele. This barrier creates two apoplastic domains which are non-communicating. A kinetic barrier exists between the apoplast of the mesocotyl stele and that of the coleoptile. This kinetic barrier is not absolute and there is limited communication between the apoplasts of the two regions. This kinetic barrier effectively creates two sub-domains. In the coleoptile, there is communication between the apoplast of the vascular strands and that of the surrounding cortical tissue. No apoplastic communication was observed between the coleoptile cortex and the mesocotyl cortex. Thus, the apoplastic space of the coleoptile cortex is a sub-domain of the integrated coleoptile domain and is separate from that of the apoplastic domain of the mesocotyl cortex.

  8. Domains in Ferroelectric Nanostructures

    NASA Astrophysics Data System (ADS)

    Gregg, Marty

    2010-03-01

    Ferroelectric materials have great potential in influencing the future of small scale electronics. At a basic level, this is because ferroelectric surfaces are charged, and so interact strongly with charge-carrying metals and semiconductors - the building blocks for all electronic systems. Since the electrical polarity of the ferroelectric can be reversed, surfaces can both attract and repel charges in nearby materials, and can thereby exert complete control over both charge distribution and movement. It should be no surprise, therefore, that microelectronics industries have already looked very seriously at harnessing ferroelectric materials in a variety of applications, from solid state memory chips (FeRAMs) to field effect transistors (FeFETs). In all such applications, switching the direction of the polarity of the ferroelectric is a key aspect of functional behavior. The mechanism for switching involves the field-induced nucleation and growth of domains. Domain coarsening, through domain wall propagation, eventually causes the entire ferroelectric to switch its polar direction. It is thus the existence and behavior of domains that determine the switching response, and ultimately the performance of the ferroelectric device. A major issue, associated with the integration of ferroelectrics into microelectronic devices, has been that the fundamental properties associated with ferroelectrics, when in bulk form, appear to change quite dramatically and unpredictably when at the nanoscale: new modes of behaviour, and different functional characteristics from those seen in bulk appear. For domains, in particular, the proximity of surfaces and boundaries have a dramatic effect: surface tension and depolarizing fields both serve to increase the equilibrium density of domains, such that minor changes in scale or morphology can have major ramifications for domain redistribution. Given the importance of domains in dictating the overall switching characteristics of a device

  9. Quantifying water flow and retention in an unsaturated fracture-facial domain

    USGS Publications Warehouse

    Nimmo, John R.; Malek-Mohammadi, Siamak

    2015-01-01

    Hydrologically significant flow and storage of water occur in macropores and fractures that are only partially filled. To accommodate such processes in flow models, we propose a three-domain framework. Two of the domains correspond to water flow and water storage in a fracture-facial region, in addition to the third domain of matrix water. The fracture-facial region, typically within a fraction of a millimeter of the fracture wall, includes a flowing phase whose fullness is determined by the availability and flux of preferentially flowing water, and a static storage portion whose fullness is determined by the local matric potential. The flow domain can be modeled with the source-responsive preferential flow model, and the roughness-storage domain can be modeled with capillary relations applied on the fracture-facial area. The matrix domain is treated using traditional unsaturated flow theory. We tested the model with application to the hydrology of the Chalk formation in southern England, coherently linking hydrologic information including recharge estimates, streamflow, water table fluctuation, imaging by electron microscopy, and surface roughness. The quantitative consistency of the three-domain matrix-microcavity-film model with this body of diverse data supports the hypothesized distinctions and active mechanisms of the three domains and establishes the usefulness of this framework.

  10. Modeling the evolution of protein domain architectures using maximum parsimony.

    PubMed

    Fong, Jessica H; Geer, Lewis Y; Panchenko, Anna R; Bryant, Stephen H

    2007-02-09

    Domains are basic evolutionary units of proteins and most proteins have more than one domain. Advances in domain modeling and collection are making it possible to annotate a large fraction of known protein sequences by a linear ordering of their domains, yielding their architecture. Protein domain architectures link evolutionarily related proteins and underscore their shared functions. Here, we attempt to better understand this association by identifying the evolutionary pathways by which extant architectures may have evolved. We propose a model of evolution in which architectures arise through rearrangements of inferred precursor architectures and acquisition of new domains. These pathways are ranked using a parsimony principle, whereby scenarios requiring the fewest number of independent recombination events, namely fission and fusion operations, are assumed to be more likely. Using a data set of domain architectures present in 159 proteomes that represent all three major branches of the tree of life allows us to estimate the history of over 85% of all architectures in the sequence database. We find that the distribution of rearrangement classes is robust with respect to alternative parsimony rules for inferring the presence of precursor architectures in ancestral species. Analyzing the most parsimonious pathways, we find 87% of architectures to gain complexity over time through simple changes, among which fusion events account for 5.6 times as many architectures as fission. Our results may be used to compute domain architecture similarities, for example, based on the number of historical recombination events separating them. Domain architecture "neighbors" identified in this way may lead to new insights about the evolution of protein function.

  11. The HARP domain dictates the annealing helicase activity of HARP/SMARCAL1.

    PubMed

    Ghosal, Gargi; Yuan, Jingsong; Chen, Junjie

    2011-06-01

    Mutations in HepA-related protein (HARP, or SMARCAL1) cause Schimke immunoosseous dysplasia (SIOD). HARP has ATP-dependent annealing helicase activity, which helps to stabilize stalled replication forks and facilitate DNA repair during replication. Here, we show that the conserved tandem HARP (2HP) domain dictates this annealing helicase activity. Furthermore, chimeric proteins generated by fusing the 2HP domain of HARP with the SNF2 domain of BRG1 or HELLS show annealing helicase activity in vitro and, when targeted to replication forks, mimic the functions of HARP in vivo. We propose that the HARP domain endows HARP with this ATP-driven annealing helicase activity.

  12. DIMA 3.0: Domain Interaction Map.

    PubMed

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

    2011-01-01

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

  13. Crystal structure of tandem type III fibronectin domains from Drosophila neuroglian at 2.0 A.

    PubMed

    Huber, A H; Wang, Y M; Bieber, A J; Bjorkman, P J

    1994-04-01

    We report the crystal structure of two adjacent fibronectin type III repeats from the Drosophila neural cell adhesion molecule neuroglian. Each domain consists of two antiparallel beta sheets and is folded topologically identically to single fibronectin type III domains from the extracellular matrix proteins tenascin and fibronectin. beta bulges and left-handed polyproline II helices disrupt the regular beta sheet structure of both neuroglian domains. The hydrophobic interdomain interface includes a metal-binding site, presumably involved in stabilizing the relative orientation between domains and predicted by sequence comparision to be present in the vertebrate homolog molecule L1. The neuroglian domains are related by a near perfect 2-fold screw axis along the longest molecular dimension. Using this relationship, a model for arrays of tandem fibronectin type III repeats in neuroglian and other molecules is proposed.

  14. Entropy gives rise to topologically associating domains

    PubMed Central

    Vasquez, Paula A.; Hult, Caitlin; Adalsteinsson, David; Lawrimore, Josh; Forest, Mark G.; Bloom, Kerry

    2016-01-01

    We investigate chromosome organization within the nucleus using polymer models whose formulation is closely guided by experiments in live yeast cells. We employ bead-spring chromosome models together with loop formation within the chains and the presence of nuclear bodies to quantify the extent to which these mechanisms shape the topological landscape in the interphase nucleus. By investigating the genome as a dynamical system, we show that domains of high chromosomal interactions can arise solely from the polymeric nature of the chromosome arms due to entropic interactions and nuclear confinement. In this view, the role of bio-chemical related processes is to modulate and extend the duration of the interacting domains. PMID:27257057

  15. Mapping knowledge domains: Characterizing PNAS

    PubMed Central

    Boyack, Kevin W.

    2004-01-01

    A review of data mining and analysis techniques that can be used for the mapping of knowledge domains is given. Literature mapping techniques can be based on authors, documents, journals, words, and/or indicators. Most mapping questions are related to research assessment or to the structure and dynamics of disciplines or networks. Several mapping techniques are demonstrated on a data set comprising 20 years of papers published in PNAS. Data from a variety of sources are merged to provide unique indicators of the domain bounded by PNAS. By using funding source information and citation counts, it is shown that, on an aggregate basis, papers funded jointly by the U.S. Public Health Service (which includes the National Institutes of Health) and non-U.S. government sources outperform papers funded by other sources, including by the U.S. Public Health Service alone. Grant data from the National Institute on Aging show that, on average, papers from large grants are cited more than those from small grants, with performance increasing with grant amount. A map of the highest performing papers over the 20-year period was generated by using citation analysis. Changes and trends in the subjects of highest impact within the PNAS domain are described. Interactions between topics over the most recent 5-year period are also detailed. PMID:14963238

  16. Roots of angiosperm formins: The evolutionary history of plant FH2 domain-containing proteins

    PubMed Central

    2008-01-01

    Background Shuffling of modular protein domains is an important source of evolutionary innovation. Formins are a family of actin-organizing proteins that share a conserved FH2 domain but their overall domain architecture differs dramatically between opisthokonts (metazoans and fungi) and plants. We performed a phylogenomic analysis of formins in most eukaryotic kingdoms, aiming to reconstruct an evolutionary scenario that may have produced the current diversity of domain combinations with focus on the origin of the angiosperm formin architectures. Results The Rho GTPase-binding domain (GBD/FH3) reported from opisthokont and Dictyostelium formins was found in all lineages except plants, suggesting its ancestral character. Instead, mosses and vascular plants possess the two formin classes known from angiosperms: membrane-anchored Class I formins and Class II formins carrying a PTEN-like domain. PTEN-related domains were found also in stramenopile formins, where they have been probably acquired independently rather than by horizontal transfer, following a burst of domain rearrangements in the chromalveolate lineage. A novel RhoGAP-related domain was identified in some algal, moss and lycophyte (but not angiosperm) formins that define a specific branch (Class III) of the formin family. Conclusion We propose a scenario where formins underwent multiple domain rearrangements in several eukaryotic lineages, especially plants and chromalveolates. In plants this replaced GBD/FH3 by a probably inactive RhoGAP-like domain, preserving a formin-mediated association between (membrane-anchored) Rho GTPases and the actin cytoskeleton. Subsequent amplification of formin genes, possibly coincident with the expansion of plants to dry land, was followed by acquisition of alternative membrane attachment mechanisms present in extant Class I and Class II formins, allowing later loss of the RhoGAP-like domain-containing formins in angiosperms. PMID:18430232

  17. Structural Analyses of the Ankyrin Repeat Domain of TRPV6 and Related TRPV Ion Channels

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

    Phelps, C.B.; Huang, R.J.; Lishko, P.V.

    2008-06-03

    Transient receptor potential (TRP) proteins are cation channels composed of a transmembrane domain flanked by large N- and C-terminal cytoplasmic domains. All members of the vanilloid family of TRP channels (TRPV) possess an N-terminal ankyrin repeat domain (ARD). The ARD of mammalian TRPV6, an important regulator of calcium uptake and homeostasis, is essential for channel assembly and regulation. The 1.7 A crystal structure of the TRPV6-ARD reveals conserved structural elements unique to the ARDs of TRPV proteins. First, a large twist between the fourth and fifth repeats is induced by residues conserved in all TRPV ARDs. Second, the third fingermore » loop is the most variable region in sequence, length and conformation. In TRPV6, a number of putative regulatory phosphorylation sites map to the base of this third finger. Size exclusion chromatography and crystal packing indicate that the TRPV6-ARD does not assemble as a tetramer and is monomeric in solution. Adenosine triphosphate-agarose and calmodulin-agarose pull-down assays show that the TRPV6-ARD does not interact with either ligand, indicating a different functional role for the TRPV6-ARD than in the paralogous thermosensitive TRPV1 channel. Similar biochemical findings are also presented for the highly homologous mammalian TRPV5-ARD. The implications of the structural and biochemical data on the role of the ankyrin repeats in different TRPV channels are discussed.« less

  18. ECOD: An Evolutionary Classification of Protein Domains

    PubMed Central

    Kinch, Lisa N.; Pei, Jimin; Shi, Shuoyong; Kim, Bong-Hyun; Grishin, Nick V.

    2014-01-01

    Understanding the evolution of a protein, including both close and distant relationships, often reveals insight into its structure and function. Fast and easy access to such up-to-date information facilitates research. We have developed a hierarchical evolutionary classification of all proteins with experimentally determined spatial structures, and presented it as an interactive and updatable online database. ECOD (Evolutionary Classification of protein Domains) is distinct from other structural classifications in that it groups domains primarily by evolutionary relationships (homology), rather than topology (or “fold”). This distinction highlights cases of homology between domains of differing topology to aid in understanding of protein structure evolution. ECOD uniquely emphasizes distantly related homologs that are difficult to detect, and thus catalogs the largest number of evolutionary links among structural domain classifications. Placing distant homologs together underscores the ancestral similarities of these proteins and draws attention to the most important regions of sequence and structure, as well as conserved functional sites. ECOD also recognizes closer sequence-based relationships between protein domains. Currently, approximately 100,000 protein structures are classified in ECOD into 9,000 sequence families clustered into close to 2,000 evolutionary groups. The classification is assisted by an automated pipeline that quickly and consistently classifies weekly releases of PDB structures and allows for continual updates. This synchronization with PDB uniquely distinguishes ECOD among all protein classifications. Finally, we present several case studies of homologous proteins not recorded in other classifications, illustrating the potential of how ECOD can be used to further biological and evolutionary studies. PMID:25474468

  19. ECOD: an evolutionary classification of protein domains.

    PubMed

    Cheng, Hua; Schaeffer, R Dustin; Liao, Yuxing; Kinch, Lisa N; Pei, Jimin; Shi, Shuoyong; Kim, Bong-Hyun; Grishin, Nick V

    2014-12-01

    Understanding the evolution of a protein, including both close and distant relationships, often reveals insight into its structure and function. Fast and easy access to such up-to-date information facilitates research. We have developed a hierarchical evolutionary classification of all proteins with experimentally determined spatial structures, and presented it as an interactive and updatable online database. ECOD (Evolutionary Classification of protein Domains) is distinct from other structural classifications in that it groups domains primarily by evolutionary relationships (homology), rather than topology (or "fold"). This distinction highlights cases of homology between domains of differing topology to aid in understanding of protein structure evolution. ECOD uniquely emphasizes distantly related homologs that are difficult to detect, and thus catalogs the largest number of evolutionary links among structural domain classifications. Placing distant homologs together underscores the ancestral similarities of these proteins and draws attention to the most important regions of sequence and structure, as well as conserved functional sites. ECOD also recognizes closer sequence-based relationships between protein domains. Currently, approximately 100,000 protein structures are classified in ECOD into 9,000 sequence families clustered into close to 2,000 evolutionary groups. The classification is assisted by an automated pipeline that quickly and consistently classifies weekly releases of PDB structures and allows for continual updates. This synchronization with PDB uniquely distinguishes ECOD among all protein classifications. Finally, we present several case studies of homologous proteins not recorded in other classifications, illustrating the potential of how ECOD can be used to further biological and evolutionary studies.

  20. Annihilation of Domain Walls in a Ferromagnetic Wire

    NASA Astrophysics Data System (ADS)

    Ghosh, Anirban; Huang, Kevin; Tchernyshyov, Oleg

    We study the annihilation of topological solitons in one of the simplest systems that support them: a one-dimensional ferromagnetic wire with an easy axis along its length. In the presence of energy dissipation due to viscous losses, two solitons (domain walls) on the wire, when released from afar, approach each other and eventually annihilate to create a uniformly magnetized state. Starting from a class of exact solutions for stationary two-domain-wall configurations in the absence of dissipation, we develop an effective theory that describes this annihilation in terms of four collective coordinates: a) the two zero modes corresponding to the location of the center and the average azimuthal angle of the full structure and b) their two conjugate momenta which describe the relative twist and the relative separation of the two domain walls respectively. Comparison with micromagnetic simulation on OOOMF confirms that this theory captures well the essential physics of the process. We believe this work will be a good starting point for studying the annihilation of more complicated topological solitons like vortices and skyrmions in ferromagnetic thin films. This work is supported by the U.S. Department of Energy, Office of Basic Energy Sciences, Division of Materials Sciences and Engineering under Award DE-FG02-08ER46544.

  1. Domain-General and Domain-Specific Patterns of Activity Supporting Metacognition in Human Prefrontal Cortex

    PubMed Central

    2018-01-01

    Metacognition is the capacity to evaluate the success of one's own cognitive processes in various domains; for example, memory and perception. It remains controversial whether metacognition relies on a domain-general resource that is applied to different tasks or if self-evaluative processes are domain specific. Here, we investigated this issue directly by examining the neural substrates engaged when metacognitive judgments were made by human participants of both sexes during perceptual and memory tasks matched for stimulus and performance characteristics. By comparing patterns of fMRI activity while subjects evaluated their performance, we revealed both domain-specific and domain-general metacognitive representations. Multivoxel activity patterns in anterior prefrontal cortex predicted levels of confidence in a domain-specific fashion, whereas domain-general signals predicting confidence and accuracy were found in a widespread network in the frontal and posterior midline. The demonstration of domain-specific metacognitive representations suggests the presence of a content-rich mechanism available to introspection and cognitive control. SIGNIFICANCE STATEMENT We used human neuroimaging to investigate processes supporting memory and perceptual metacognition. It remains controversial whether metacognition relies on a global resource that is applied to different tasks or if self-evaluative processes are specific to particular tasks. Using multivariate decoding methods, we provide evidence that perceptual- and memory-specific metacognitive representations coexist with generic confidence signals. Our findings reconcile previously conflicting results on the domain specificity/generality of metacognition and lay the groundwork for a mechanistic understanding of metacognitive judgments. PMID:29519851

  2. Objectively-determined intensity- and domain-specific physical activity and sedentary behavior in relation to percent body fat.

    PubMed

    Scheers, Tineke; Philippaerts, Renaat; Lefevre, Johan

    2013-12-01

    This study examined the independent and joint associations of overall, intensity-specific and domain-specific physical activity and sedentary behavior with bioelectrical impedance-determined percent body fat. Physical activity was measured in 442 Flemish adults (41.4 ± 9.8 years) using the SenseWear Armband and an electronic diary. Two-way analyses of covariance investigated the interaction of physical activity and sedentary behavior with percent body fat. Multiple linear regression analyses, adjusted for potential confounders, examined the associations of intensity-specific and domain-specific physical activity and sedentary behavior with percent body fat. Results showed a significant main effect for physical activity in both genders and for sedentary behavior in women, but no interaction effects. Light activity was positively (β = 0.41 for men and 0.43 for women) and moderate (β = -0.64 and -0.41), vigorous (β = -0.21 and -0.24) and moderate-to-vigorous physical activity (MVPA) inversely associated with percent body fat, independent of sedentary time. Regarding domain-specific physical activity, significant associations were present for occupation, leisure time and household chores, irrespective of sedentary time. The positive associations between body fat and total and domain-specific sedentary behavior diminished after MVPA was controlled for. MVPA during leisure time, occupation and household chores may be essential to prevent fat gain. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  3. Topological domain walls in helimagnets

    NASA Astrophysics Data System (ADS)

    Schoenherr, P.; Müller, J.; Köhler, L.; Rosch, A.; Kanazawa, N.; Tokura, Y.; Garst, M.; Meier, D.

    2018-05-01

    Domain walls naturally arise whenever a symmetry is spontaneously broken. They interconnect regions with different realizations of the broken symmetry, promoting structure formation from cosmological length scales to the atomic level1,2. In ferroelectric and ferromagnetic materials, domain walls with unique functionalities emerge, holding great promise for nanoelectronics and spintronics applications3-5. These walls are usually of Ising, Bloch or Néel type and separate homogeneously ordered domains. Here we demonstrate that a wide variety of new domain walls occurs in the presence of spatially modulated domain states. Using magnetic force microscopy and micromagnetic simulations, we show three fundamental classes of domain walls to arise in the near-room-temperature helimagnet iron germanium. In contrast to conventional ferroics, the domain walls exhibit a well-defined inner structure, which—analogous to cholesteric liquid crystals—consists of topological disclination and dislocation defects. Similar to the magnetic skyrmions that form in the same material6,7, the domain walls can carry a finite topological charge, permitting an efficient coupling to spin currents and contributions to a topological Hall effect. Our study establishes a new family of magnetic nano-objects with non-trivial topology, opening the door to innovative device concepts based on helimagnetic domain walls.

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

    PubMed Central

    Weininger, Arthur; Weininger, Susan

    2015-01-01

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

  5. Anger, preoccupied attachment, and domain disorganization in borderline personality disorder

    PubMed Central

    Morse, Jennifer Q.; Hill, Jonathan; Pilkonis, Paul A.; Yaggi, Kirsten; Broyden, Nichaela; Stepp, Stephanie; Reed, Lawrence Ian; Feske, Ulrike

    2010-01-01

    Emotional dysregulation and attachment insecurity have been reported in borderline personality disorder (BPD). Domain disorganization, evidenced in poor regulation of emotions and behaviors in relation to the demands of different social domains, may be a distinguishing feature of BPD. Understanding the interplay between these factors may be critical for identifying interacting processes in BPD and potential subtypes of BPD. Therefore, we examined the joint and interactive effects of anger, preoccupied attachment, and domain disorganization on BPD traits in clinical sample of 128 psychiatric patients. The results suggest that these factors contribute to BPD both independently and in interaction, even when controlling for other personality disorder traits and Axis I symptoms. In regression analyses, the interaction between anger and domain disorganization predicted BPD traits. In recursive partitioning analyses, two possible paths to BPD were identified: high anger combined with high domain disorganization and low anger combined with preoccupied attachment. These results may suggest possible subtypes of BPD or possible mechanisms by which BPD traits are established and maintained. PMID:19538080

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

    PubMed

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

    2000-02-01

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

  7. A unique GCN5-related glucosamine N-acetyltransferase region exist in the fungal multi-domain glycoside hydrolase family 3 β-N-acetylglucosaminidase

    PubMed Central

    Qin, Zhen; Xiao, Yibei; Yang, Xinbin; Mesters, Jeroen R.; Yang, Shaoqing; Jiang, Zhengqiang

    2015-01-01

    Glycoside hydrolase (GH) family 3 β-N-acetylglucosaminidases widely exist in the filamentous fungi, which may play a key role in chitin metabolism of fungi. A multi-domain GH family 3 β-N-acetylglucosaminidase from Rhizomucor miehei (RmNag), exhibiting a potential N-acetyltransferase region, has been recently reported to show great potential in industrial applications. In this study, the crystal structure of RmNag was determined at 2.80 Å resolution. The three-dimensional structure of RmNag showed four distinctive domains, which belong to two distinguishable functional regions — a GH family 3 β-N-acetylglucosaminidase region (N-terminal) and a N-acetyltransferase region (C-terminal). From structural and functional analysis, the C-terminal region of RmNag was identified as a unique tandem array linking general control non-derepressible 5 (GCN5)-related N-acetyltransferase (GNAT), which displayed glucosamine N-acetyltransferase activity. Structural analysis of this glucosamine N-acetyltransferase region revealed that a unique glucosamine binding pocket is located in the pantetheine arm binding terminal region of the conserved CoA binding pocket, which is different from all known GNAT members. This is the first structural report of a glucosamine N-acetyltransferase, which provides novel structural information about substrate specificity of GNATs. The structural and functional features of this multi-domain β-N-acetylglucosaminidase could be useful in studying the catalytic mechanism of GH family 3 proteins. PMID:26669854

  8. Critical domain interactions for type A RNase P RNA catalysis with and without the specificity domain

    PubMed Central

    Mao, Guanzhong; Srivastava, Abhishek S.; Wu, Shiying; Kosek, David; Lindell, Magnus

    2018-01-01

    The natural trans-acting ribozyme RNase P RNA (RPR) is composed of two domains in which the catalytic (C-) domain mediates cleavage of various substrates. The C-domain alone, after removal of the second specificity (S-) domain, catalyzes this reaction as well, albeit with reduced efficiency. Here we provide experimental evidence indicating that efficient cleavage mediated by the Escherichia coli C-domain (Eco CP RPR) with and without the C5 protein likely depends on an interaction referred to as the "P6-mimic". Moreover, the P18 helix connects the C- and S-domains between its loop and the P8 helix in the S-domain (the P8/ P18-interaction). In contrast to the "P6-mimic", the presence of P18 does not contribute to the catalytic performance by the C-domain lacking the S-domain in cleavage of an all ribo model hairpin loop substrate while deletion or disruption of the P8/ P18-interaction in full-size RPR lowers the catalytic efficiency in cleavage of the same model hairpin loop substrate in keeping with previously reported data using precursor tRNAs. Consistent with that P18 is not required for cleavage mediated by the C-domain we show that the archaeal Pyrococcus furiosus RPR C-domain, which lacks the P18 helix, is catalytically active in trans without the S-domain and any protein. Our data also suggest that the S-domain has a larger impact on catalysis for E. coli RPR compared to P. furiosus RPR. Finally, we provide data indicating that the absence of the S-domain and P18, or the P8/ P18-interaction in full-length RPR influences the charge distribution near the cleavage site in the RPR-substrate complex to a small but reproducible extent. PMID:29509761

  9. Electrophysiological Evidence for Domain-General Processes in Task-Switching

    PubMed Central

    Capizzi, Mariagrazia; Ambrosini, Ettore; Arbula, Sandra; Mazzonetto, Ilaria; Vallesi, Antonino

    2016-01-01

    The ability to flexibly switch between tasks is a hallmark of cognitive control. Despite previous studies that have investigated whether different task-switching types would be mediated by distinct or overlapping neural mechanisms, no definitive consensus has been reached on this question yet. Here, we aimed at directly addressing this issue by recording the event-related potentials (ERPs) elicited by two types of task-switching occurring in the context of spatial and verbal cognitive domains. Source analysis was also applied to the ERP data in order to track the spatial dynamics of brain activity underlying task-switching abilities. In separate blocks of trials, participants had to perform either spatial or verbal switching tasks both of which employed the same type of stimuli. The ERP analysis, which was carried out through a channel- and time-uninformed mass univariate approach, showed no significant differences between the spatial and verbal domains in the modulation of switch and repeat trials. Specifically, relative to repeat trials, switch trials in both domains were associated with a first larger positivity developing over left parieto-occipital electrodes and with a subsequent larger negativity distributed over mid-left fronto-central sites. The source analysis reconstruction for the two ERP components complemented these findings by highlighting the involvement of left-lateralized prefrontal areas in task-switching. Overall, our results join and extend recent research confirming the existence of left-lateralized domain-general task-switching processes. PMID:27047366

  10. Mapping small molecule binding data to structural domains

    PubMed Central

    2012-01-01

    Background Large-scale bioactivity/SAR Open Data has recently become available, and this has allowed new analyses and approaches to be developed to help address the productivity and translational gaps of current drug discovery. One of the current limitations of these data is the relative sparsity of reported interactions per protein target, and complexities in establishing clear relationships between bioactivity and targets using bioinformatics tools. We detail in this paper the indexing of targets by the structural domains that bind (or are likely to bind) the ligand within a full-length protein. Specifically, we present a simple heuristic to map small molecule binding to Pfam domains. This profiling can be applied to all proteins within a genome to give some indications of the potential pharmacological modulation and regulation of all proteins. Results In this implementation of our heuristic, ligand binding to protein targets from the ChEMBL database was mapped to structural domains as defined by profiles contained within the Pfam-A database. Our mapping suggests that the majority of assay targets within the current version of the ChEMBL database bind ligands through a small number of highly prevalent domains, and conversely the majority of Pfam domains sampled by our data play no currently established role in ligand binding. Validation studies, carried out firstly against Uniprot entries with expert binding-site annotation and secondly against entries in the wwPDB repository of crystallographic protein structures, demonstrate that our simple heuristic maps ligand binding to the correct domain in about 90 percent of all assessed cases. Using the mappings obtained with our heuristic, we have assembled ligand sets associated with each Pfam domain. Conclusions Small molecule binding has been mapped to Pfam-A domains of protein targets in the ChEMBL bioactivity database. The result of this mapping is an enriched annotation of small molecule bioactivity data and a

  11. Coupling between Current and Dynamic Magnetization : from Domain Walls to Spin Waves

    NASA Astrophysics Data System (ADS)

    Lucassen, M. E.

    2012-05-01

    So far, we have derived some general expressions for domain-wall motion and the spin motive force. We have seen that the β parameter plays a large role in both subjects. In all chapters of this thesis, there is an emphasis on the determination of this parameter. We also know how to incorporate thermal fluctuations for rigid domain walls, as shown above. In Chapter 2, we study a different kind of fluctuations: shot noise. This noise is caused by the fact that an electric current consists of electrons, and therefore has fluctuations. In the process, we also compute transmission and reflection coefficients for a rigid domain wall, and from them the linear momentum transfer. More work on fluctuations is done in Chapter 3. Here, we consider a (extrinsically pinned) rigid domain wall under the influence of thermal fluctuations that induces a current via spin motive force. We compute how the resulting noise in the current is related to the β parameter. In Chapter 4 we look into in more detail into the spin motive forces from field driven domain walls. Using micro magnetic simulations, we compute the spin motive force due to vortex domain walls explicitly. As mentioned before, this gives qualitatively different results than for a rigid domain wall. The final subject in Chapter 5 is the application of the general expression for spin motive forces to magnons. Although this might seem to be unrelated to domain-wall motion, this calculation allows us to relate the β parameter to macroscopic transport coefficients. This work was supported by Stichting voor Fundamenteel Onderzoek der Materie (FOM), the Netherlands Organization for Scientific Research (NWO), and by the European Research Council (ERC) under the Seventh Framework Program (FP7).

  12. (In)Consistent estimates of changes in relative precipitation in an European domain over the last 350 years

    NASA Astrophysics Data System (ADS)

    Bothe, Oliver; Wagner, Sebastian; Zorita, Eduardo

    2015-04-01

    estimates are generally not consistent among the different data sets. Only few common signals are evident. Even the relatively strong exogenous forcing history of the late 18th and early 19th century appears to have only small effects on the precipitation distributions. The reconstructions differ systematically from the long instrumental data in displaying much stronger variability compared to the observations over their common period. Distributional properties for both data sets show to some extent opposite evolutions. The reconstructions do not reliably represent the distributions in specific periods but rather reflect low-frequency changes in the mean plus a certain amount of noise. Moreover, also multi-model simulations do not agree on the changes over this period. The lack of consistent simulated relations under purely naturally forced and internal variability on multi-decadal time-scales therefore questions our ability to conclude on dynamical inferences about regional climate variability in the PMIP3 ensemble and, in turn, in climate simulations in general. The potentially opposite evolution of reconstructions and instrumental data for the chosen domain further hampers reconciling available information about past regional precipitation variability in England and Wales. However, we find some possibly surprising but encouraging agreement between the observed data and the regional simulation.

  13. Modeling the Evolution of Protein Domain Architectures Using Maximum Parsimony

    PubMed Central

    Fong, Jessica H.; Geer, Lewis Y.; Panchenko, Anna R.; Bryant, Stephen H.

    2007-01-01

    Domains are basic evolutionary units of proteins and most proteins have more than one domain. Advances in domain modeling and collection are making it possible to annotate a large fraction of known protein sequences by a linear ordering of their domains, yielding their architecture. Protein domain architectures link evolutionarily related proteins and underscore their shared functions. Here, we attempt to better understand this association by identifying the evolutionary pathways by which extant architectures may have evolved. We propose a model of evolution in which architectures arise through rearrangements of inferred precursor architectures and acquisition of new domains. These pathways are ranked using a parsimony principle, whereby scenarios requiring the fewest number of independent recombination events, namely fission and fusion operations, are assumed to be more likely. Using a data set of domain architectures present in 159 proteomes that represent all three major branches of the tree of life allows us to estimate the history of over 85% of all architectures in the sequence database. We find that the distribution of rearrangement classes is robust with respect to alternative parsimony rules for inferring the presence of precursor architectures in ancestral species. Analyzing the most parsimonious pathways, we find 87% of architectures to gain complexity over time through simple changes, among which fusion events account for 5.6 times as many architectures as fission. Our results may be used to compute domain architecture similarities, for example, based on the number of historical recombination events separating them. Domain architecture “neighbors” identified in this way may lead to new insights about the evolution of protein function. PMID:17166515

  14. Temporal Annotation in the Clinical Domain

    PubMed Central

    Styler, William F.; Bethard, Steven; Finan, Sean; Palmer, Martha; Pradhan, Sameer; de Groen, Piet C; Erickson, Brad; Miller, Timothy; Lin, Chen; Savova, Guergana; Pustejovsky, James

    2014-01-01

    This article discusses the requirements of a formal specification for the annotation of temporal information in clinical narratives. We discuss the implementation and extension of ISO-TimeML for annotating a corpus of clinical notes, known as the THYME corpus. To reflect the information task and the heavily inference-based reasoning demands in the domain, a new annotation guideline has been developed, “the THYME Guidelines to ISO-TimeML (THYME-TimeML)”. To clarify what relations merit annotation, we distinguish between linguistically-derived and inferentially-derived temporal orderings in the text. We also apply a top performing TempEval 2013 system against this new resource to measure the difficulty of adapting systems to the clinical domain. The corpus is available to the community and has been proposed for use in a SemEval 2015 task. PMID:29082229

  15. Ferroelectricity of domain walls in rare earth iron garnet films.

    PubMed

    Popov, A I; Zvezdin, K A; Gareeva, Z V; Mazhitova, F A; Vakhitov, R M; Yumaguzin, A R; Zvezdin, A K

    2016-11-16

    In this paper, we report on electric polarization arising in a vicinity of Bloch-like domain walls in rare-earth iron garnet films. The domain walls generate an intrinsic magnetic field that breaks an antiferroelectric structure formed in the garnets due to an exchange interaction between rare earth and iron sublattices. We explore 180° domain walls whose formation is energetically preferable in the films with perpendicular magnetic anisotropy. Magnetic and electric structures of the 180° quasi-Bloch domain walls have been simulated at various relations between system parameters. Singlet, doublet ground states of rare earth ions and strongly anisotropic rare earth Ising ions have been considered. Our results show that electric polarization appears in rare earth garnet films at Bloch domain walls, and the maximum of magnetic inhomogeneity is not always linked to the maximum of electric polarization. A number of factors including the temperature, the state of the rare earth ion and the type of a wall influence magnetically induced electric polarization. We show that the value of polarization can be enhanced by the shrinking of the Bloch domain wall width, decreasing the temperature, and increasing the deviations of magnetization from the Bloch rotation that are regulated by impacts given by magnetic anisotropies of the films.

  16. Structural domains and main-chain flexibility in prion proteins.

    PubMed

    Blinov, N; Berjanskii, M; Wishart, D S; Stepanova, M

    2009-02-24

    In this study we describe a novel approach to define structural domains and to characterize the local flexibility in both human and chicken prion proteins. The approach we use is based on a comprehensive theory of collective dynamics in proteins that was recently developed. This method determines the essential collective coordinates, which can be found from molecular dynamics trajectories via principal component analysis. Under this particular framework, we are able to identify the domains where atoms move coherently while at the same time to determine the local main-chain flexibility for each residue. We have verified this approach by comparing our results for the predicted dynamic domain systems with the computed main-chain flexibility profiles and the NMR-derived random coil indexes for human and chicken prion proteins. The three sets of data show excellent agreement. Additionally, we demonstrate that the dynamic domains calculated in this fashion provide a highly sensitive measure of protein collective structure and dynamics. Furthermore, such an analysis is capable of revealing structural and dynamic properties of proteins that are inaccessible to the conventional assessment of secondary structure. Using the collective dynamic simulation approach described here along with a high-temperature simulations of unfolding of human prion protein, we have explored whether locations of relatively low stability could be identified where the unfolding process could potentially be facilitated. According to our analysis, the locations of relatively low stability may be associated with the beta-sheet formed by strands S1 and S2 and the adjacent loops, whereas helix HC appears to be a relatively stable part of the protein. We suggest that this kind of structural analysis may provide a useful background for a more quantitative assessment of potential routes of spontaneous misfolding in prion proteins.

  17. Respiratory sinus arrhythmia: time domain characterization using autoregressive moving average analysis

    NASA Technical Reports Server (NTRS)

    Triedman, J. K.; Perrott, M. H.; Cohen, R. J.; Saul, J. P.

    1995-01-01

    Fourier-based techniques are mathematically noncausal and are therefore limited in their application to feedback-containing systems, such as the cardiovascular system. In this study, a mathematically causal time domain technique, autoregressive moving average (ARMA) analysis, was used to parameterize the relations of respiration and arterial blood pressure to heart rate in eight humans before and during total cardiac autonomic blockade. Impulse-response curves thus generated showed the relation of respiration to heart rate to be characterized by an immediate increase in heart rate of 9.1 +/- 1.8 beats.min-1.l-1, followed by a transient mild decrease in heart rate to -1.2 +/- 0.5 beats.min-1.l-1 below baseline. The relation of blood pressure to heart rate was characterized by a slower decrease in heart rate of -0.5 +/- 0.1 beats.min-1.mmHg-1, followed by a gradual return to baseline. Both of these relations nearly disappeared after autonomic blockade, indicating autonomic mediation. Maximum values obtained from the respiration to heart rate impulse responses were also well correlated with frequency domain measures of high-frequency "vagal" heart rate control (r = 0.88). ARMA analysis may be useful as a time domain representation of autonomic heart rate control for cardiovascular modeling.

  18. Boundary shape identification problems in two-dimensional domains related to thermal testing of materials

    NASA Technical Reports Server (NTRS)

    Banks, H. T.; Kojima, Fumio

    1988-01-01

    The identification of the geometrical structure of the system boundary for a two-dimensional diffusion system is reported. The domain identification problem treated here is converted into an optimization problem based on a fit-to-data criterion and theoretical convergence results for approximate identification techniques are discussed. Results of numerical experiments to demonstrate the efficacy of the theoretical ideas are reported.

  19. Classification of intrinsic variables. IX - The Cepheid domain

    NASA Astrophysics Data System (ADS)

    Eggen, O. J.

    1983-03-01

    Intermediate band, Hβ and RI observations have been obtained throughout the cycle of variation for 135 high mass, long-period and short-period cepheids (LPC and SPC). This material, together with the observations previously discussed for some 100 ultrashort periods cepheids (USPC), is used to delineate the cepheid domain in the (β,[C1]) and (MBol,log Te) planes. The independently derived luminosity calibrations for bright giants and supergiants previously published are found to closely reproduce the luminosities derived from the Sandage-Tammann PL relation for most variables. The theoretical "fundamental blue edge," computed by Iben and Tuggle with Y = 0.38, closely represents the blue edge of the cepheid domain.

  20. Changes in Quaternary Structure in the Signaling Mechanisms of PAS Domains

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

    Ayers, Rebecca A.; Moffat, Keith

    2008-12-15

    FixL from Bradyrhizobium japonicum is a PAS sensor protein in which two PAS domains covalently linked to a histidine kinase domain are responsible for regulating nitrogen fixation in an oxygen-dependent manner. The more C-terminal PAS domain, denoted bjFixLH, contains a heme cofactor that binds diatomic molecules such as carbon monoxide and oxygen and regulates the activity of the FixL histidine kinase as part of a two-component signaling system. We present the structures of ferric, deoxy, and carbon monoxide-bound bjFixLH in a new space group (P1) and at resolutions (1.5--1.8 {angstrom}) higher than the resolutions of those previously obtained. Interestingly, bjFixLHmore » can form two different dimers (in P1 and R32 crystal forms) in the same crystallization solution, where the monomers in one dimer are rotated {approx}175 deg. relative to the second. This suggests that PAS monomers are plastic and that two quite distinct quaternary structures are closely similar in free energy. We use screw rotation analysis to carry out a quantitative pairwise comparison of PAS quaternary structures, which identifies five different relative orientations adopted by isolated PAS monomers. We conclude that PAS monomer arrangement is context-dependent and could differ depending on whether the PAS domains are isolated or are part of a full-length protein. Structurally homologous residues comprise a conserved dimer interface. Using network analysis, we find that the architecture of the PAS dimer interface is continuous rather than modular; the network of residues comprising the interface is strongly connected. A continuous dimer interface is consistent with the low dimer-monomer dissociation equilibrium constant. Finally, we quantitate quaternary structural changes induced by carbon monoxide binding to a bjFixLH dimer, in which monomers rotate by up to 2 deg. relative to each other. We relate these changes to those in other dimeric PAS domains and discuss the role of quaternary

  1. Structure and Regulatory Interactions of the Cytoplasmic Terminal Domains of Serotonin Transporter

    PubMed Central

    2014-01-01

    Uptake of neurotransmitters by sodium-coupled monoamine transporters of the NSS family is required for termination of synaptic transmission. Transport is tightly regulated by protein–protein interactions involving the small cytoplasmic segments at the amino- and carboxy-terminal ends of the transporter. Although structures of homologues provide information about the transmembrane regions of these transporters, the structural arrangement of the terminal domains remains largely unknown. Here, we combined molecular modeling, biochemical, and biophysical approaches in an iterative manner to investigate the structure of the 82-residue N-terminal and 30-residue C-terminal domains of human serotonin transporter (SERT). Several secondary structures were predicted in these domains, and structural models were built using the Rosetta fragment-based methodology. One-dimensional 1H nuclear magnetic resonance and circular dichroism spectroscopy supported the presence of helical elements in the isolated SERT N-terminal domain. Moreover, introducing helix-breaking residues within those elements altered the fluorescence resonance energy transfer signal between terminal cyan fluorescent protein and yellow fluorescent protein tags attached to full-length SERT, consistent with the notion that the fold of the terminal domains is relatively well-defined. Full-length models of SERT that are consistent with these and published experimental data were generated. The resultant models predict confined loci for the terminal domains and predict that they move apart during the transport-related conformational cycle, as predicted by structures of homologues and by the “rocking bundle” hypothesis, which is consistent with spectroscopic measurements. The models also suggest the nature of binding to regulatory interaction partners. This study provides a structural context for functional and regulatory mechanisms involving SERT terminal domains. PMID:25093911

  2. Discussion summary: Fictitious domain methods

    NASA Technical Reports Server (NTRS)

    Glowinski, Rowland; Rodrigue, Garry

    1991-01-01

    Fictitious Domain methods are constructed in the following manner: Suppose a partial differential equation is to be solved on an open bounded set, Omega, in 2-D or 3-D. Let R be a rectangle domain containing the closure of Omega. The partial differential equation is first solved on R. Using the solution on R, the solution of the equation on Omega is then recovered by some procedure. The advantage of the fictitious domain method is that in many cases the solution of a partial differential equation on a rectangular region is easier to compute than on a nonrectangular region. Fictitious domain methods for solving elliptic PDEs on general regions are also very efficient when used on a parallel computer. The reason is that one can use the many domain decomposition methods that are available for solving the PDE on the fictitious rectangular region. The discussion on fictitious domain methods began with a talk by R. Glowinski in which he gave some examples of a variational approach to ficititious domain methods for solving the Helmholtz and Navier-Stokes equations.

  3. Genetic and Environmental Influences on Symptom Domains in Twins and Siblings with Autism

    ERIC Educational Resources Information Center

    Mazefsky, Carla A.; Goin-Kochel, Robin P.; Riley, Brien P.; Maes, Hermine H.

    2008-01-01

    Clarifying the sources of variation among autism symptom domains is important to the identification of homogenous subgroups for molecular genetic studies. This study explored the genetic and environmental bases of nonverbal communication and social interaction, two symptom domains that have also been related to treatment response, in 1294 child…

  4. Influence of social relationship domains and their combinations on incident dementia: a prospective cohort study

    PubMed Central

    Saito, Tami; Murata, Chiyoe; Saito, Masashige; Takeda, Tokunori; Kondo, Katsunori

    2018-01-01

    Background Social relationships consist of mutually related but distinct dimensions. It remains unclear how these domains independently contribute to incident dementia. This large-scale, prospective cohort study examines associations between the social relationship domains as well as their combinations and incident dementia among community-dwelling older adults. Methods We analysed data from 13 984 community-dwelling adults aged 65+ without long-term care needs living in Aichi prefecture in Japan. Incident dementia was assessed based on the Long-term Care Insurance records, followed for 3436 days from the baseline survey conducted in 2003. Three social relationships domains (social support, social networks and social activities) were further divided into a total of eight subdomains. A social relationship diversity score was calculated using the social relationship domains which were significantly related to incident dementia. Results A Cox proportional hazards model showed that being married, exchanging support with family members, having contact with friends, participating in community groups and engaging in paid work were related to a lower likelihood of developing incident dementia, controlling for covariates and other social relationship domains. The diversity scores, ranging from 0 to 5, were linearly associated with incident dementia (p<0.001), and those who scored highest were 46% less likely to develop incident dementia compared with those in the lowest category. Conclusions Our findings revealed five social relationship subdomains which were negatively related to incident dementia, suggesting that dementia may potentially be prevented by enhancing these social relationships. Future studies should examine independent pathways between each social relationship domain and incident dementia. PMID:29089367

  5. It's Greek to me: Domain specific relationships between intellectual helplessness and academic performance.

    PubMed

    Krejtz, Izabela; Nezlek, John B

    2016-01-01

    In a study of the domain specificity of intellectual learned helplessness, we collected data from 376 students in 14 classrooms. We measured feelings of intellectual helplessness for mathematics and language skills, anxiety about performance in each of these domains, and general working memory. Multilevel modeling analyses found that feelings of helplessness in language skills were negatively related to grades in language but were unrelated to grades in mathematics. Similarly, feelings of helplessness in mathematics were negatively related to grades in mathematics but were unrelated to grades in language. Controlling for anxiety or working memory did not change these relationships, nor did they vary across the age of students. The results support conceptualizations in which learned helplessness has a domain specific component.

  6. Structure of the Nucleoprotein Binding Domain of Mokola Virus Phosphoprotein▿

    PubMed Central

    Assenberg, René; Delmas, Olivier; Ren, Jingshan; Vidalain, Pierre-Olivier; Verma, Anil; Larrous, Florence; Graham, Stephen C.; Tangy, Frédéric; Grimes, Jonathan M.; Bourhy, Hervé

    2010-01-01

    Mokola virus (MOKV) is a nonsegmented, negative-sense RNA virus that belongs to the Lyssavirus genus and Rhabdoviridae family. MOKV phosphoprotein P is an essential component of the replication and transcription complex and acts as a cofactor for the viral RNA-dependent RNA polymerase. P recruits the viral polymerase to the nucleoprotein-bound viral RNA (N-RNA) via an interaction between its C-terminal domain and the N-RNA complex. Here we present a structure for this domain of MOKV P, obtained by expression of full-length P in Escherichia coli, which was subsequently truncated during crystallization. The structure has a high degree of homology with P of rabies virus, another member of Lyssavirus genus, and to a lesser degree with P of vesicular stomatitis virus (VSV), a member of the related Vesiculovirus genus. In addition, analysis of the crystal packing of this domain reveals a potential binding site for the nucleoprotein N. Using both site-directed mutagenesis and yeast two-hybrid experiments to measure P-N interaction, we have determined the relative roles of key amino acids involved in this interaction to map the region of P that binds N. This analysis also reveals a structural relationship between the N-RNA binding domain of the P proteins of the Rhabdoviridae and the Paramyxoviridae. PMID:19906936

  7. Reductive evolution and the loss of PDC/PAS domains from the genus Staphylococcus

    PubMed Central

    2013-01-01

    Background The Per-Arnt-Sim (PAS) domain represents a ubiquitous structural fold that is involved in bacterial sensing and adaptation systems, including several virulence related functions. Although PAS domains and the subclass of PhoQ-DcuS-CitA (PDC) domains have a common structure, there is limited amino acid sequence similarity. To gain greater insight into the evolution of PDC/PAS domains present in the bacterial kingdom and staphylococci in specific, the PDC/PAS domains from the genomic sequences of 48 bacteria, representing 5 phyla, were identified using the sensitive search method based on HMM-to-HMM comparisons (HHblits). Results A total of 1,007 PAS domains and 686 PDC domains distributed over 1,174 proteins were identified. For 28 Gram-positive bacteria, the distribution, organization, and molecular evolution of PDC/PAS domains were analyzed in greater detail, with a special emphasis on the genus Staphylococcus. Compared to other bacteria the staphylococci have relatively fewer proteins (6–9) containing PDC/PAS domains. As a general rule, the staphylococcal genomes examined in this study contain a core group of seven PDC/PAS domain-containing proteins consisting of WalK, SrrB, PhoR, ArlS, HssS, NreB, and GdpP. The exceptions to this rule are: 1) S. saprophyticus lacks the core NreB protein; 2) S. carnosus has two additional PAS domain containing proteins; 3) S. epidermidis, S. aureus, and S. pseudintermedius have an additional protein with two PDC domains that is predicted to code for a sensor histidine kinase; 4) S. lugdunensis has an additional PDC containing protein predicted to be a sensor histidine kinase. Conclusions This comprehensive analysis demonstrates that variation in PDC/PAS domains among bacteria has limited correlations to the genome size or pathogenicity; however, our analysis established that bacteria having a motile phase in their life cycle have significantly more PDC/PAS-containing proteins. In addition, our analysis revealed a

  8. Reductive evolution and the loss of PDC/PAS domains from the genus Staphylococcus.

    PubMed

    Shah, Neethu; Gaupp, Rosmarie; Moriyama, Hideaki; Eskridge, Kent M; Moriyama, Etsuko N; Somerville, Greg A

    2013-07-31

    The Per-Arnt-Sim (PAS) domain represents a ubiquitous structural fold that is involved in bacterial sensing and adaptation systems, including several virulence related functions. Although PAS domains and the subclass of PhoQ-DcuS-CitA (PDC) domains have a common structure, there is limited amino acid sequence similarity. To gain greater insight into the evolution of PDC/PAS domains present in the bacterial kingdom and staphylococci in specific, the PDC/PAS domains from the genomic sequences of 48 bacteria, representing 5 phyla, were identified using the sensitive search method based on HMM-to-HMM comparisons (HHblits). A total of 1,007 PAS domains and 686 PDC domains distributed over 1,174 proteins were identified. For 28 Gram-positive bacteria, the distribution, organization, and molecular evolution of PDC/PAS domains were analyzed in greater detail, with a special emphasis on the genus Staphylococcus. Compared to other bacteria the staphylococci have relatively fewer proteins (6-9) containing PDC/PAS domains. As a general rule, the staphylococcal genomes examined in this study contain a core group of seven PDC/PAS domain-containing proteins consisting of WalK, SrrB, PhoR, ArlS, HssS, NreB, and GdpP. The exceptions to this rule are: 1) S. saprophyticus lacks the core NreB protein; 2) S. carnosus has two additional PAS domain containing proteins; 3) S. epidermidis, S. aureus, and S. pseudintermedius have an additional protein with two PDC domains that is predicted to code for a sensor histidine kinase; 4) S. lugdunensis has an additional PDC containing protein predicted to be a sensor histidine kinase. This comprehensive analysis demonstrates that variation in PDC/PAS domains among bacteria has limited correlations to the genome size or pathogenicity; however, our analysis established that bacteria having a motile phase in their life cycle have significantly more PDC/PAS-containing proteins. In addition, our analysis revealed a tremendous amount of variation in the

  9. Grammatical Language Impairment and the Specificity of Cognitive Domains: Relations between Auditory and Language Abilities

    ERIC Educational Resources Information Center

    van der Lely, Heather K. J.; Rosen, Stuart; Adlard, Alan

    2004-01-01

    Grammatical-specific language impairment (G-SLI) in children, arguably, provides evidence for the existence of a specialised grammatical sub-system in the brain, necessary for normal language development. Some researchers challenge this, claiming that domain-general, low-level auditory deficits, particular to rapid processing, cause phonological…

  10. De novo design of RNA-binding proteins with a prion-like domain related to ALS/FTD proteinopathies.

    PubMed

    Mitsuhashi, Kana; Ito, Daisuke; Mashima, Kyoko; Oyama, Munenori; Takahashi, Shinichi; Suzuki, Norihiro

    2017-12-04

    Aberrant RNA-binding proteins form the core of the neurodegeneration cascade in spectrums of disease, such as amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). Six ALS-related molecules, TDP-43, FUS, TAF15, EWSR1, heterogeneous nuclear (hn)RNPA1 and hnRNPA2 are RNA-binding proteins containing candidate mutations identified in ALS patients and those share several common features, including harboring an aggregation-prone prion-like domain (PrLD) containing a glycine/serine-tyrosine-glycine/serine (G/S-Y-G/S)-motif-enriched low-complexity sequence and rich in glutamine and/or asparagine. Additinally, these six molecules are components of RNA granules involved in RNA quality control and become mislocated from the nucleus to form cytoplasmic inclusion bodies (IBs) in the ALS/FTD-affected brain. To reveal the essential mechanisms involved in ALS/FTD-related cytotoxicity associated with RNA-binding proteins containing PrLDs, we designed artificial RNA-binding proteins harboring G/S-Y-G/S-motif repeats with and without enriched glutamine residues and nuclear-import/export-signal sequences and examined their cytotoxicity in vitro. These proteins recapitulated features of ALS-linked molecules, including insoluble aggregation, formation of cytoplasmic IBs and components of RNA granules, and cytotoxicity instigation. These findings indicated that these artificial RNA-binding proteins mimicked features of ALS-linked molecules and allowed the study of mechanisms associated with gain of toxic functions related to ALS/FTD pathogenesis.

  11. Recombinant Domain V of Human Perlecan Is a Bioactive Vascular Proteoglycan.

    PubMed

    Rnjak-Kovacina, Jelena; Tang, Fengying; Lin, Xiaoting; Whitelock, John M; Lord, Megan S

    2017-12-01

    The C-terminal domain V of the extracellular matrix proteoglycan perlecan plays unique and often divergent roles in a number of biological processes, including angiogenesis, vascular cell interactions, wound healing, and autophagy. Recombinant forms of domain V have been proposed as therapeutic agents for the treatment of cancer, stroke, and the development of cardiovascular devices and bioartificial tissues. However, the effect of domain V appears to be related to the differences in domain V structure and function observed in different expression systems and environments and exactly how this occurs is not well understood. In this study, the sequence from amino acid 3626 to 4391 of the perlecan protein core, which includes domain V, is expressed in HEK-293 cells and purified as a secreted product from conditioned media. This recombinant domain V (rDV) is expressed as a proteoglycan decorated with heparan sulfate and chondroitin sulfate chains and supports endothelial cell interactions to the same extent as full-length perlecan. This expression system serves as an important model of recombinant proteoglycan expression, as well as a source of biologically active rDV for therapeutic applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Low performance on mathematical tasks in preschoolers: the importance of domain-general and domain-specific abilities.

    PubMed

    Costa, H M; Nicholson, B; Donlan, C; Van Herwegen, J

    2018-04-01

    Different domain-specific and domain-general cognitive precursors play a key role in the development of mathematical abilities. The contribution of these domains to mathematical ability changes during development. Primary school-aged children who show mathematical difficulties form a heterogeneous group, but it is not clear whether this also holds for preschool low achievers (LAs) and how domain-specific and domain-general abilities contribute to mathematical difficulties at a young age. The aim of this study was to explore the cognitive characteristics of a sample of preschool LAs and identify sub-types of LAs. 81 children were identified as LAs from 283 preschoolers aged 3 to 5 years old and were assessed on a number of domain-general and domain-specific tasks. Cluster analysis revealed four subgroups of LAs in mathematics: (1) a weak processing sub-type; (2) a general mathematical LAs sub-type; (3) a mixed abilities sub-type; and (4) a visuo-spatial deficit sub-type. Whilst two of the groups showed specific domain-general difficulties, none showed only domain-specific difficulties. Current findings suggest that preschool LAs constitute a heterogeneous group and stress the importance of domain-general factors for the development of mathematical abilities during the preschool years. © 2018 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

  13. Polar Domain Discovery with Sparkler

    NASA Astrophysics Data System (ADS)

    Duerr, R.; Khalsa, S. J. S.; Mattmann, C. A.; Ottilingam, N. K.; Singh, K.; Lopez, L. A.

    2017-12-01

    The scientific web is vast and ever growing. It encompasses millions of textual, scientific and multimedia documents describing research in a multitude of scientific streams. Most of these documents are hidden behind forms which require user action to retrieve and thus can't be directly accessed by content crawlers. These documents are hosted on web servers across the world, most often on outdated hardware and network infrastructure. Hence it is difficult and time-consuming to aggregate documents from the scientific web, especially those relevant to a specific domain. Thus generating meaningful domain-specific insights is currently difficult. We present an automated discovery system (Figure 1) using Sparkler, an open-source, extensible, horizontally scalable crawler which facilitates high throughput and focused crawling of documents pertinent to a particular domain such as information about polar regions. With this set of highly domain relevant documents, we show that it is possible to answer analytical questions about that domain. Our domain discovery algorithm leverages prior domain knowledge to reach out to commercial/scientific search engines to generate seed URLs. Subject matter experts then annotate these seed URLs manually on a scale from highly relevant to irrelevant. We leverage this annotated dataset to train a machine learning model which predicts the `domain relevance' of a given document. We extend Sparkler with this model to focus crawling on documents relevant to that domain. Sparkler avoids disruption of service by 1) partitioning URLs by hostname such that every node gets a different host to crawl and by 2) inserting delays between subsequent requests. With an NSF-funded supercomputer Wrangler, we scaled our domain discovery pipeline to crawl about 200k polar specific documents from the scientific web, within a day.

  14. Four Critical Domains of Accountability for School Counselors

    ERIC Educational Resources Information Center

    Bemak, Fred; Willians, Joseph M.; Chung, Rita Chi-Ying

    2015-01-01

    Despite recognition of accountability for school counselors, no clear set of interrelated performance measures exists to guide school counselors in collecting and evaluating data that relates to student academic success. This article outlines four critical domains of accountability for school counselors (i.e., grades, attendance, disciplinary…

  15. The prokaryotic antecedents of the ubiquitin-signaling system and the early evolution of ubiquitin-like β-grasp domains

    PubMed Central

    Iyer, Lakshminarayan M; Burroughs, A Maxwell; Aravind, L

    2006-01-01

    Background Ubiquitin (Ub)-mediated signaling is one of the hallmarks of all eukaryotes. Prokaryotic homologs of Ub (ThiS and MoaD) and E1 ligases have been studied in relation to sulfur incorporation reactions in thiamine and molybdenum/tungsten cofactor biosynthesis. However, there is no evidence for entire protein modification systems with Ub-like proteins and deconjugation by deubiquitinating enzymes in prokaryotes. Hence, the evolutionary assembly of the eukaryotic Ub-signaling apparatus remains unclear. Results We systematically analyzed prokaryotic Ub-related β-grasp fold proteins using sensitive sequence profile searches and structural analysis. Consequently, we identified novel Ub-related proteins beyond the characterized ThiS, MoaD, TGS, and YukD domains. To understand their functional associations, we sought and recovered several conserved gene neighborhoods and domain architectures. These included novel associations involving diverse sulfur metabolism proteins, siderophore biosynthesis and the gene encoding the transfer mRNA binding protein SmpB, as well as domain fusions between Ub-like domains and PIN-domain related RNAses. Most strikingly, we found conserved gene neighborhoods in phylogenetically diverse bacteria combining genes for JAB domains (the primary de-ubiquitinating isopeptidases of the proteasomal complex), along with E1-like adenylating enzymes and different Ub-related proteins. Further sequence analysis of other conserved genes in these neighborhoods revealed several Ub-conjugating enzyme/E2-ligase related proteins. Genes for an Ub-like protein and a JAB domain peptidase were also found in the tail assembly gene cluster of certain caudate bacteriophages. Conclusion These observations imply that members of the Ub family had already formed strong functional associations with E1-like proteins, UBC/E2-related proteins, and JAB peptidases in the bacteria. Several of these Ub-like proteins and the associated protein families are likely to

  16. Bile acids modulate signaling by functional perturbation of plasma membrane domains.

    PubMed

    Zhou, Yong; Maxwell, Kelsey N; Sezgin, Erdinc; Lu, Maryia; Liang, Hong; Hancock, John F; Dial, Elizabeth J; Lichtenberger, Lenard M; Levental, Ilya

    2013-12-13

    Eukaryotic cell membranes are organized into functional lipid and protein domains, the most widely studied being membrane rafts. Although rafts have been associated with numerous plasma membrane functions, the mechanisms by which these domains themselves are regulated remain undefined. Bile acids (BAs), whose primary function is the solubilization of dietary lipids for digestion and absorption, can affect cells by interacting directly with membranes. To investigate whether these interactions affected domain organization in biological membranes, we assayed the effects of BAs on biomimetic synthetic liposomes, isolated plasma membranes, and live cells. At cytotoxic concentrations, BAs dissolved synthetic and cell-derived membranes and disrupted live cell plasma membranes, implicating plasma membrane damage as the mechanism for BA cellular toxicity. At subtoxic concentrations, BAs dramatically stabilized domain separation in Giant Plasma Membrane Vesicles without affecting protein partitioning between coexisting domains. Domain stabilization was the result of BA binding to and disordering the nonraft domain, thus promoting separation by enhancing domain immiscibility. Consistent with the physical changes observed in synthetic and isolated biological membranes, BAs reorganized intact cell membranes, as evaluated by the spatial distribution of membrane-anchored Ras isoforms. Nanoclustering of K-Ras, related to nonraft membrane domains, was enhanced in intact plasma membranes, whereas the organization of H-Ras was unaffected. BA-induced changes in Ras lateral segregation potentiated EGF-induced signaling through MAPK, confirming the ability of BAs to influence cell signal transduction by altering the physical properties of the plasma membrane. These observations suggest general, membrane-mediated mechanisms by which biological amphiphiles can produce their cellular effects.

  17. Multiple standards of aging: gender-specific age stereotypes in different life domains.

    PubMed

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

    2013-12-01

    Whereas it is often stated that aging might have more negative consequences for the evaluation of women compared to men, evidence for this assumption is mixed. We took a differentiated look at age stereotypes of men and women, assuming that the life domain in which older persons are rated moderates gender differences in age stereotypes. A sample of 298 participants aged 20-92 rated 65 - year-old men and women on evaluative statements in eight different life domains. Furthermore, perceptions of gender- and domain-specific age-related changes were assessed by comparing the older targets to 45 - year-old men and women, respectively. The results speak in favor of the domain specificity of evaluative asymmetries in age stereotypes for men and women, and imply that an understanding of gendered perceptions of aging requires taking into account the complexities of domain-specific views on aging.

  18. Magnetoresistance of non-180° domain wall in the presence of electron-photon interaction

    NASA Astrophysics Data System (ADS)

    Majidi, Roya

    2013-04-01

    In the present paper, influence of photon on resistance of non-180° domain wall in metallic magnetic nanowires has been studied using the semiclassical approach. The analysis has been based on the Boltzmann transport equation, within the relaxation time approximation. The one-dimensional Néel-type domain wall between two ferromagnetic domains with relative magnetization angle less than 180° is considered. By increasing this angle, the contribution of the domain wall in the resistivity of the nanowire becomes considerable. It is also found that the fundamental contribution of the domain wall in resistivity can be controlled by propagating photon. These results are valuable in designing spintronic devices based on magnetic nanowires.

  19. Novel alternative splicings of BPAG1 (bullous pemphigoid antigen 1) including the domain structure closely related to MACF (microtubule actin cross-linking factor).

    PubMed

    Okumura, Masayo; Yamakawa, Hisashi; Ohara, Osamu; Owaribe, Katsushi

    2002-02-22

    BPAG1 (bullous pemphigoid antigen 1) was originally identified as a 230-kDa hemidesmosomal protein and belongs to the plakin family, because it consists of a plakin domain, a coiled-coil rod domain and a COOH-terminal intermediate filament binding domain. To date, alternatively spliced products of BPAG1, BPAG1e, and BPAG1n are known. BPAG1e is expressed in epithelial tissues and localized to hemidesmosomes, on the other hand, BPAG1n is expressed in neural tissues and muscles and has an actin binding domain at the NH(2)-terminal of BPAG1e. BPAG1 is also known as a gene responsible for Dystonia musculorum (dt) neurodegeneration syndrome of the mouse. Another plakin family protein MACF (microtubule actin cross-linking factor) has also an actin binding domain and the plakin domain at the NH(2)-terminal. However, in contrast to its high homology with BPAG1 at the NH(2)-terminal, the COOH-terminal structure of MACF, including a microtubule binding domain, resembles dystrophin rather than plakins. Here, we investigated RNAs and proteins expressed from the BPAG1 locus and suggest novel alternative splicing variants, which include one consisting of the COOH-terminal domain structure homologous to MACF. The results indicate that BPAG1 has three kinds of cytoskeletal binding domains and seems to play an important role in linking the different types of cytoskeletons.

  20. Modeling software systems by domains

    NASA Technical Reports Server (NTRS)

    Dippolito, Richard; Lee, Kenneth

    1992-01-01

    The Software Architectures Engineering (SAE) Project at the Software Engineering Institute (SEI) has developed engineering modeling techniques that both reduce the complexity of software for domain-specific computer systems and result in systems that are easier to build and maintain. These techniques allow maximum freedom for system developers to apply their domain expertise to software. We have applied these techniques to several types of applications, including training simulators operating in real time, engineering simulators operating in non-real time, and real-time embedded computer systems. Our modeling techniques result in software that mirrors both the complexity of the application and the domain knowledge requirements. We submit that the proper measure of software complexity reflects neither the number of software component units nor the code count, but the locus of and amount of domain knowledge. As a result of using these techniques, domain knowledge is isolated by fields of engineering expertise and removed from the concern of the software engineer. In this paper, we will describe kinds of domain expertise, describe engineering by domains, and provide relevant examples of software developed for simulator applications using the techniques.

  1. Ferroelectric negative capacitance domain dynamics

    NASA Astrophysics Data System (ADS)

    Hoffmann, Michael; Khan, Asif Islam; Serrao, Claudy; Lu, Zhongyuan; Salahuddin, Sayeef; Pešić, Milan; Slesazeck, Stefan; Schroeder, Uwe; Mikolajick, Thomas

    2018-05-01

    Transient negative capacitance effects in epitaxial ferroelectric Pb(Zr0.2Ti0.8)O3 capacitors are investigated with a focus on the dynamical switching behavior governed by domain nucleation and growth. Voltage pulses are applied to a series connection of the ferroelectric capacitor and a resistor to directly measure the ferroelectric negative capacitance during switching. A time-dependent Ginzburg-Landau approach is used to investigate the underlying domain dynamics. The transient negative capacitance is shown to originate from reverse domain nucleation and unrestricted domain growth. However, with the onset of domain coalescence, the capacitance becomes positive again. The persistence of the negative capacitance state is therefore limited by the speed of domain wall motion. By changing the applied electric field, capacitor area or external resistance, this domain wall velocity can be varied predictably over several orders of magnitude. Additionally, detailed insights into the intrinsic material properties of the ferroelectric are obtainable through these measurements. A new method for reliable extraction of the average negative capacitance of the ferroelectric is presented. Furthermore, a simple analytical model is developed, which accurately describes the negative capacitance transient time as a function of the material properties and the experimental boundary conditions.

  2. Functional domains of plant chimeric calcium/calmodulin-dependent protein kinase: regulation by autoinhibitory and visinin-like domains

    NASA Technical Reports Server (NTRS)

    Ramachandiran, S.; Takezawa, D.; Wang, W.; Poovaiah, B. W.

    1997-01-01

    A novel calcium-binding calcium/calmodulin-dependent protein kinase (CCaMK) with a catalytic domain, calmodulin-binding domain, and a neural visinin-like domain was cloned and characterized from plants [Patil et al., (1995) Proc. Natl. Acad. Sci. USA 92, 4797-4801; Takezawa et al. (1996) J. Biol. Chem. 271, 8126-8132]. The mechanisms of CCaMK activation by calcium and calcium/calmodulin were investigated using various deletion mutants. The use of deletion mutants of CCaMK lacking either one, two, or all three calcium-binding EF hands indicated that all three calcium-binding sites in the visinin-like domain were crucial for the full calcium/calmodulin-dependent kinase activity. As each calcium-binding EF hand was deleted, there was a gradual reduction in calcium/calmodulin-dependent kinase activity from 100 to 4%. Another mutant (amino acids 1-322) which lacks both the visinin-like domain containing three EF hands and the calmodulin-binding domain was constitutively active, indicating the presence of an autoinhibitory domain around the calmodulin-binding domain. By using various synthetic peptides and the constitutively active mutant, we have shown that CCaMK contains an autoinhibitory domain within the residues 322-340 which overlaps its calmodulin-binding domain. Kinetic studies with both ATP and the GS peptide substrate suggest that the autoinhibitory domain of CCaMK interacts only with the peptide substrate binding motif of the catalytic domain, but not with the ATP-binding motif.

  3. Saturation recovery EPR spin-labeling method for quantification of lipids in biological membrane domains.

    PubMed

    Mainali, Laxman; Camenisch, Theodore G; Hyde, James S; Subczynski, Witold K

    2017-12-01

    The presence of integral membrane proteins induces the formation of distinct domains in the lipid bilayer portion of biological membranes. Qualitative application of both continuous wave (CW) and saturation recovery (SR) electron paramagnetic resonance (EPR) spin-labeling methods allowed discrimination of the bulk, boundary, and trapped lipid domains. A recently developed method, which is based on the CW EPR spectra of phospholipid (PL) and cholesterol (Chol) analog spin labels, allows evaluation of the relative amount of PLs (% of total PLs) in the boundary plus trapped lipid domain and the relative amount of Chol (% of total Chol) in the trapped lipid domain [ M. Raguz, L. Mainali, W. J. O'Brien, and W. K. Subczynski (2015), Exp. Eye Res., 140:179-186 ]. Here, a new method is presented that, based on SR EPR spin-labeling, allows quantitative evaluation of the relative amounts of PLs and Chol in the trapped lipid domain of intact membranes. This new method complements the existing one, allowing acquisition of more detailed information about the distribution of lipids between domains in intact membranes. The methodological transition of the SR EPR spin-labeling approach from qualitative to quantitative is demonstrated. The abilities of this method are illustrated for intact cortical and nuclear fiber cell plasma membranes from porcine eye lenses. Statistical analysis (Student's t -test) of the data allowed determination of the separations of mean values above which differences can be treated as statistically significant ( P ≤ 0.05) and can be attributed to sources other than preparation/technique.

  4. The GP(Y/F) domain of TF1 integrase multimerizes when present in a fragment, and substitutions in this domain reduce enzymatic activity of the full-length protein.

    PubMed

    Ebina, Hirotaka; Chatterjee, Atreyi Ghatak; Judson, Robert L; Levin, Henry L

    2008-06-06

    Integrases (INs) of retroviruses and long terminal repeat retrotransposons possess a C-terminal domain with DNA binding activity. Other than this binding activity, little is known about how the C-terminal domain contributes to integration. A stretch of conserved amino acids called the GP(Y/F) domain has been identified within the C-terminal IN domains of two distantly related families, the gamma-retroviruses and the metavirus retrotransposons. To enhance understanding of the C-terminal domain, we examined the function of the GP(Y/F) domain in the IN of Tf1, a long terminal repeat retrotransposon of Schizosaccharomyces pombe. The activities of recombinant IN were measured with an assay that modeled the reverse of integration called disintegration. Although deletion of the entire C-terminal domain disrupted disintegration activity, an alanine substitution (P365A) in a conserved amino acid of the GP(Y/F) domain did not significantly reduce disintegration. When assayed for the ability to join two molecules of DNA in a reaction that modeled forward integration, the P365A substitution disrupted activity. UV cross-linking experiments detected DNA binding activity in the C-terminal domain and found that this activity was not reduced by substitutions in two conserved amino acids of the GP(Y/F) domain, G364A and P365A. Gel filtration and cross-linking of a 71-amino acid fragment containing the GP(Y/F) domain revealed a surprising ability to form dimers, trimers, and tetramers that was disrupted by the G364A and P365A substitutions. These results suggest that the GP(Y/F) residues may play roles in promoting multimerization and intermolecular strand joining.

  5. Translocation of the Catalytic Domain of Diphtheria Toxin across Planar Phospholipid Bilayers by Its Own T Domain

    NASA Astrophysics Data System (ADS)

    Oh, Kyoung Joon; Senzel, Lisa; Collier, R. John; Finkelstein, Alan

    1999-07-01

    The T domain of diphtheria toxin is known to participate in the pH-dependent translocation of the catalytic C domain of the toxin across the endosomal membrane, but how it does so, and whether cellular proteins are also required for this process, remain unknown. Here, we report results showing that the T domain alone is capable of translocating the entire C domain across model, planar phospholipid bilayers in the absence of other proteins. The T domain therefore contains the entire molecular machinery for mediating transfer of the catalytic domain of diphtheria toxin across membranes.

  6. Accuracy of time-domain and frequency-domain methods used to characterize catchment transit time distributions

    NASA Astrophysics Data System (ADS)

    Godsey, S. E.; Kirchner, J. W.

    2008-12-01

    The mean residence time - the average time that it takes rainfall to reach the stream - is a basic parameter used to characterize catchment processes. Heterogeneities in these processes lead to a distribution of travel times around the mean residence time. By examining this travel time distribution, we can better predict catchment response to contamination events. A catchment system with shorter residence times or narrower distributions will respond quickly to contamination events, whereas systems with longer residence times or longer-tailed distributions will respond more slowly to those same contamination events. The travel time distribution of a catchment is typically inferred from time series of passive tracers (e.g., water isotopes or chloride) in precipitation and streamflow. Variations in the tracer concentration in streamflow are usually damped compared to those in precipitation, because precipitation inputs from different storms (with different tracer signatures) are mixed within the catchment. Mathematically, this mixing process is represented by the convolution of the travel time distribution and the precipitation tracer inputs to generate the stream tracer outputs. Because convolution in the time domain is equivalent to multiplication in the frequency domain, it is relatively straightforward to estimate the parameters of the travel time distribution in either domain. In the time domain, the parameters describing the travel time distribution are typically estimated by maximizing the goodness of fit between the modeled and measured tracer outputs. In the frequency domain, the travel time distribution parameters can be estimated by fitting a power-law curve to the ratio of precipitation spectral power to stream spectral power. Differences between the methods of parameter estimation in the time and frequency domain mean that these two methods may respond differently to variations in data quality, record length and sampling frequency. Here we evaluate how

  7. Scientific Reasoning across Different Domains.

    ERIC Educational Resources Information Center

    Glaser, Robert; And Others

    This study seeks to establish which scientific reasoning skills are primarily domain-general and which appear to be domain-specific. The subjects, 12 university undergraduates, each participated in self-directed experimentation with three different content domains. The experimentation contexts were computer-based laboratories in d.c. circuits…

  8. Detecting atypical examples of known domain types by sequence similarity searching: the SBASE domain library approach.

    PubMed

    Dhir, Somdutta; Pacurar, Mircea; Franklin, Dino; Gáspári, Zoltán; Kertész-Farkas, Attila; Kocsor, András; Eisenhaber, Frank; Pongor, Sándor

    2010-11-01

    SBASE is a project initiated to detect known domain types and predicting domain architectures using sequence similarity searching (Simon et al., Protein Seq Data Anal, 5: 39-42, 1992, Pongor et al, Nucl. Acids. Res. 21:3111-3115, 1992). The current approach uses a curated collection of domain sequences - the SBASE domain library - and standard similarity search algorithms, followed by postprocessing which is based on a simple statistics of the domain similarity network (http://hydra.icgeb.trieste.it/sbase/). It is especially useful in detecting rare, atypical examples of known domain types which are sometimes missed even by more sophisticated methodologies. This approach does not require multiple alignment or machine learning techniques, and can be a useful complement to other domain detection methodologies. This article gives an overview of the project history as well as of the concepts and principles developed within this the project.

  9. Fourier Phase Domain Steganography: Phase Bin Encoding Via Interpolation

    NASA Astrophysics Data System (ADS)

    Rivas, Edward

    2007-04-01

    In recent years there has been an increased interest in audio steganography and watermarking. This is due primarily to two reasons. First, an acute need to improve our national security capabilities in light of terrorist and criminal activity has driven new ideas and experimentation. Secondly, the explosive proliferation of digital media has forced the music industry to rethink how they will protect their intellectual property. Various techniques have been implemented but the phase domain remains a fertile ground for improvement due to the relative robustness to many types of distortion and immunity to the Human Auditory System. A new method for embedding data in the phase domain of the Discrete Fourier Transform of an audio signal is proposed. Focus is given to robustness and low perceptibility, while maintaining a relatively high capacity rate of up to 172 bits/s.

  10. Influence of image compression on the interpretation of spectral-domain optical coherence tomography in exudative age-related macular degeneration

    PubMed Central

    Kim, J H; Kang, S W; Kim, J-r; Chang, Y S

    2014-01-01

    Purpose To evaluate the effect of image compression of spectral-domain optical coherence tomography (OCT) images in the examination of eyes with exudative age-related macular degeneration (AMD). Methods Thirty eyes from 30 patients who were diagnosed with exudative AMD were included in this retrospective observational case series. The horizontal OCT scans centered at the center of the fovea were conducted using spectral-domain OCT. The images were exported to Tag Image File Format (TIFF) and 100, 75, 50, 25 and 10% quality of Joint Photographic Experts Group (JPEG) format. OCT images were taken before and after intravitreal ranibizumab injections, and after relapse. The prevalence of subretinal and intraretinal fluids was determined. Differences in choroidal thickness between the TIFF and JPEG images were compared with the intra-observer variability. Results The prevalence of subretinal and intraretinal fluids was comparable regardless of the degree of compression. However, the chorio–scleral interface was not clearly identified in many images with a high degree of compression. In images with 25 and 10% quality of JPEG, the difference in choroidal thickness between the TIFF images and the respective JPEG images was significantly greater than the intra-observer variability of the TIFF images (P=0.029 and P=0.024, respectively). Conclusions In OCT images of eyes with AMD, 50% of the quality of the JPEG format would be an optimal degree of compression for efficient data storage and transfer without sacrificing image quality. PMID:24788012

  11. Rsp5 WW domains interact directly with the carboxyl-terminal domain of RNA polymerase II.

    PubMed

    Chang, A; Cheang, S; Espanel, X; Sudol, M

    2000-07-07

    RSP5 is an essential gene in Saccharomyces cerevisiae and was recently shown to form a physical and functional complex with RNA polymerase II (RNA pol II). The amino-terminal half of Rsp5 consists of four domains: a C2 domain, which binds membrane phospholipids; and three WW domains, which are protein interaction modules that bind proline-rich ligands. The carboxyl-terminal half of Rsp5 contains a HECT (homologous to E6-AP carboxyl terminus) domain that catalytically ligates ubiquitin to proteins and functionally classifies Rsp5 as an E3 ubiquitin-protein ligase. The C2 and WW domains are presumed to act as membrane localization and substrate recognition modules, respectively. We report that the second (and possibly third) Rsp5 WW domain mediates binding to the carboxyl-terminal domain (CTD) of the RNA pol II large subunit. The CTD comprises a heptamer (YSPTSPS) repeated 26 times and a PXY core that is critical for interaction with a specific group of WW domains. An analysis of synthetic peptides revealed a minimal CTD sequence that is sufficient to bind to the second Rsp5 WW domain (Rsp5 WW2) in vitro and in yeast two-hybrid assays. Furthermore, we found that specific "imperfect" CTD repeats can form a complex with Rsp5 WW2. In addition, we have shown that phosphorylation of this minimal CTD sequence on serine, threonine and tyrosine residues acts as a negative regulator of the Rsp5 WW2-CTD interaction. In view of the recent data pertaining to phosphorylation-driven interactions between the RNA pol II CTD and the WW domain of Ess1/Pin1, we suggest that CTD dephosphorylation may be a prerequisite for targeted RNA pol II degradation.

  12. Metrology for terahertz time-domain spectrometers

    NASA Astrophysics Data System (ADS)

    Molloy, John F.; Naftaly, Mira

    2015-12-01

    In recent years the terahertz time-domain spectrometer (THz TDS) [1] has emerged as a key measurement device for spectroscopic investigations in the frequency range of 0.1-5 THz. To date, almost every type of material has been studied using THz TDS, including semiconductors, ceramics, polymers, metal films, liquid crystals, glasses, pharmaceuticals, DNA molecules, proteins, gases, composites, foams, oils, and many others. Measurements with a TDS are made in the time domain; conversion from the time domain data to a frequency spectrum is achieved by applying the Fourier Transform, calculated numerically using the Fast Fourier Transform (FFT) algorithm. As in many other types of spectrometer, THz TDS requires that the sample data be referenced to similarly acquired data with no sample present. Unlike frequency-domain spectrometers which detect light intensity and measure absorption spectra, a TDS records both amplitude and phase information, and therefore yields both the absorption coefficient and the refractive index of the sample material. The analysis of the data from THz TDS relies on the assumptions that: a) the frequency scale is accurate; b) the measurement of THz field amplitude is linear; and c) that the presence of the sample does not affect the performance characteristics of the instrument. The frequency scale of a THz TDS is derived from the displacement of the delay line; via FFT, positioning errors may give rise to frequency errors that are difficult to quantify. The measurement of the field amplitude in a THz TDS is required to be linear with a dynamic range of the order of 10 000. And attention must be given to the sample positioning and handling in order to avoid sample-related errors.

  13. The relative influence of metal ion binding sites in the I-like domain and the interface with the hybrid domain on rolling and firm adhesion by integrin alpha4beta7.

    PubMed

    Chen, JianFeng; Takagi, Junichi; Xie, Can; Xiao, Tsan; Luo, Bing-Hao; Springer, Timothy A

    2004-12-31

    We examined the effect of conformational change at the beta(7) I-like/hybrid domain interface on regulating the transition between rolling and firm adhesion by integrin alpha(4)beta(7). An N-glycosylation site was introduced into the I-like/hybrid domain interface to act as a wedge and to stabilize the open conformation of this interface and hence the open conformation of the alpha(4) beta(7) headpiece. Wild-type alpha(4)beta(7) mediates rolling adhesion in Ca(2+) and Ca(2+)/Mg(2+) but firm adhesion in Mg(2+) and Mn(2+). Stabilizing the open headpiece resulted in firm adhesion in all divalent cations. The interaction between metal binding sites in the I-like domain and the interface with the hybrid domain was examined in double mutants. Changes at these two sites can either counterbalance one another or be additive, emphasizing mutuality and the importance of multiple interfaces in integrin regulation. A double mutant with counterbalancing deactivating ligand-induced metal ion binding site (LIMBS) and activating wedge mutations could still be activated by Mn(2+), confirming the importance of the adjacent to metal ion-dependent adhesion site (ADMIDAS) in integrin activation by Mn(2+). Overall, the results demonstrate the importance of headpiece allostery in the conversion of rolling to firm adhesion.

  14. Primordial domains in the depleted upper mantle identified by noble gases in MORBs

    NASA Astrophysics Data System (ADS)

    Tucker, J.; Mukhopadhyay, S.; Langmuir, C. H.; Hamelin, C.; Fuentes, J.

    2017-12-01

    The distribution of noble gas isotopic compositions in the mantle provides important constraints on the large-scale mantle evolution, as noble gases can trace the interaction between degassed, or processed, mantle domains and undegassed, or primitive, mantle domains. Data from the radiogenic He, Ne, Ar and Xe isotopic systems have shown that plume-related lavas sample relatively undegassed mantle domains, and the recent identification of isotopic anomalies in the short-lived I-Xe and Hf-W isotopic systems in plume-related lavas further suggests that these domains may be ancient, dating back to Earth's accretion. However, little is known about the potential variability of the heavy noble gas systems and the distribution of undegassed domains in the ambient upper mantle not influenced by plumes. Here, we present new high-precision He, Ne, Ar, and Xe isotopic data for a series of MORBs from a depleted section of the subtropical north Mid-Atlantic Ridge, distant from any known plume influence. Some samples have extremely low (unradiogenic) 4He/3He, 21Ne/22Ne, 40Ar/36Ar, and 129Xe/130Xe ratios, including some of the lowest values ever determined for MORBs. Such unradiogenic compositions are reminiscent of OIBs and plume-influenced E-MORBs, suggesting the presence of a relatively undegassed or primitive reservoir in the source of these depleted MORBs. The He, Ne, and Ar isotopic systems are sensitive to the long-term degassing history, suggesting that this domain in the MORB source is ancient. The 129Xe/130Xe ratio is sensitive to degassing only during the first 100 Ma of Earth history, suggesting that some of the isotopic character of these samples has been preserved since Earth's accretion. Together, these observations suggest that primordial or undegassed material is not only sampled in plumes-related lavas, but also normal, depleted MORBs. Along with data from E-MORBs in the southern EPR (Kurz et al., 2005), southern MAR (Sarda et al., 2000), and equatorial MAR

  15. Domain wall fermion and CP symmetry breaking

    NASA Astrophysics Data System (ADS)

    Fujikawa, Kazuo; Suzuki, Hiroshi

    2003-02-01

    We examine the CP properties of chiral gauge theory defined by a formulation of the domain wall fermion, where the light field variables q and q¯ together with Pauli-Villars fields Q and Q¯ are utilized. It is shown that this domain wall representation in the infinite flavor limit N=∞ is valid only in the topologically trivial sector, and that the conflict among lattice chiral symmetry, strict locality and CP symmetry still persists for finite lattice spacing a. The CP transformation generally sends one representation of lattice chiral gauge theory into another representation of lattice chiral gauge theory, resulting in the inevitable change of propagators. A modified form of lattice CP transformation motivated by the domain wall fermion, which keeps the chiral action in terms of the Ginsparg-Wilson fermion invariant, is analyzed in detail; this provides an alternative way to understand the breaking of CP symmetry at least in the topologically trivial sector. We note that the conflict with CP symmetry could be regarded as a topological obstruction. We also discuss the issues related to the definition of Majorana fermions in connection with the supersymmetric Wess-Zumino model on the lattice.

  16. Fresnel Lorentz Microscopy Imaging of Domains in Fe3O4 Nanoparticle Arrays

    NASA Astrophysics Data System (ADS)

    Majetich, S. A.; Evarts, E. R.; Hogg, C.; Yamamoto, K.; Hirayama, T.

    2009-03-01

    Fresnel Lorentz microscopy was used to study the magnetic domain structures of self-assembled nanoparticle arrays as a function of temperature, from 24 to 605 C. 11 nm diameter Fe3O4 nanoparticles with an edge-to-edge spacing of 2.5 nm form magnetic domains through magnetostatic interactions alone. At room temperature stripe domains were evident in monolayer arrays. The average domain size in monolayer regions is larger than that in bilayers. Mean field theories predict a reduced stabilization energy for bilayers, relative to that for monolayers. The domain wall positions were fairly stable up to 500 C, though the contrast in the walls diminished, indicating reduced magnetic order. Above 500 C there were large temperature-dependent changes. The walls surrounding the smaller domains disappeared at lower temperatures than those of the larger domains. Some magnetic contrast was visible up to 575 C, close to the Curie temperature of Fe3O4 (585 C). Transmission electron microscopy after cooling showed that the particle shape and position in the ordered arrays had been preserved during the high temperature imaging experiments.

  17. Individual negative symptoms and domains - Relevance for assessment, pathomechanisms and treatment.

    PubMed

    Kaiser, Stefan; Lyne, John; Agartz, Ingrid; Clarke, Mary; Mørch-Johnsen, Lynn; Faerden, Ann

    2017-08-01

    The negative symptoms of schizophrenia can be divided into two domains. Avolition/apathy includes the individual symptoms of avolition, asociality and anhedonia. Diminished expression includes blunted affect and alogia. Until now, causes and treatment of negative symptoms have remained a major challenge, which is partially related to the focus on negative symptoms as a broad entity. Here, we propose that negative symptoms may become more tractable when the different domains and individual symptoms are taken into account. There is now increasing evidence that the relationship with clinical variables - in particular outcome - differs between the domains of avolition/apathy and diminished expression. Regarding models of negative symptom formation, those relevant to avolition/apathy are now converging on processes underlying goal-directed behavior and dysfunctions of the reward system. In contrast, models of the diminished expression domains are only beginning to emerge. The aim of this article is to review the specific clinical, behavioral and neural correlates of individual symptoms and domains as a better understanding of these areas may facilitate specific treatment approaches. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Differential Evolution and Neofunctionalization of Snake Venom Metalloprotease Domains*

    PubMed Central

    Brust, Andreas; Sunagar, Kartik; Undheim, Eivind A.B.; Vetter, Irina; Yang, Daryl C.; Casewell, Nicholas R.; Jackson, Timothy N. W.; Koludarov, Ivan; Alewood, Paul F.; Hodgson, Wayne C.; Lewis, Richard J.; King, Glenn F.; Antunes, Agostinho; Hendrikx, Iwan; Fry, Bryan G.

    2013-01-01

    Snake venom metalloproteases (SVMP) are composed of five domains: signal peptide, propeptide, metalloprotease, disintegrin, and cysteine-rich. Secreted toxins are typically combinatorial variations of the latter three domains. The SVMP-encoding genes of Psammophis mossambicus venom are unique in containing only the signal and propeptide domains. We show that the Psammophis SVMP propeptide evolves rapidly and is subject to a high degree of positive selection. Unlike Psammophis, some species of Echis express both the typical multidomain and the unusual monodomain (propeptide only) SVMP, with the result that a lower level of variation is exerted upon the latter. We showed that most mutations in the multidomain Echis SVMP occurred in the protease domain responsible for proteolytic and hemorrhagic activities. The cysteine-rich and disintegrin-like domains, which are putatively responsible for making the P-III SVMPs more potent than the P-I and P-II forms, accumulate the remaining variation. Thus, the binding sites on the molecule's surface are evolving rapidly whereas the core remains relatively conserved. Bioassays conducted on two post-translationally cleaved novel proline-rich peptides from the P. mossambicus propeptide domain showed them to have been neofunctionalized for specific inhibition of mammalian a7 neuronal nicotinic acetylcholine receptors. We show that the proline rich postsynaptic specific neurotoxic peptides from Azemiops feae are the result of convergent evolution within the precursor region of the C-type natriuretic peptide instead of the SVMP. The results of this study reinforce the value of studying obscure venoms for biodiscovery of novel investigational ligands. PMID:23242553

  19. Differential evolution and neofunctionalization of snake venom metalloprotease domains.

    PubMed

    Brust, Andreas; Sunagar, Kartik; Undheim, Eivind A B; Vetter, Irina; Yang, Daryl C; Yang, Dary C; Casewell, Nicholas R; Jackson, Timothy N W; Koludarov, Ivan; Alewood, Paul F; Hodgson, Wayne C; Lewis, Richard J; King, Glenn F; Antunes, Agostinho; Hendrikx, Iwan; Fry, Bryan G

    2013-03-01

    Snake venom metalloproteases (SVMP) are composed of five domains: signal peptide, propeptide, metalloprotease, disintegrin, and cysteine-rich. Secreted toxins are typically combinatorial variations of the latter three domains. The SVMP-encoding genes of Psammophis mossambicus venom are unique in containing only the signal and propeptide domains. We show that the Psammophis SVMP propeptide evolves rapidly and is subject to a high degree of positive selection. Unlike Psammophis, some species of Echis express both the typical multidomain and the unusual monodomain (propeptide only) SVMP, with the result that a lower level of variation is exerted upon the latter. We showed that most mutations in the multidomain Echis SVMP occurred in the protease domain responsible for proteolytic and hemorrhagic activities. The cysteine-rich and disintegrin-like domains, which are putatively responsible for making the P-III SVMPs more potent than the P-I and P-II forms, accumulate the remaining variation. Thus, the binding sites on the molecule's surface are evolving rapidly whereas the core remains relatively conserved. Bioassays conducted on two post-translationally cleaved novel proline-rich peptides from the P. mossambicus propeptide domain showed them to have been neofunctionalized for specific inhibition of mammalian a7 neuronal nicotinic acetylcholine receptors. We show that the proline rich postsynaptic specific neurotoxic peptides from Azemiops feae are the result of convergent evolution within the precursor region of the C-type natriuretic peptide instead of the SVMP. The results of this study reinforce the value of studying obscure venoms for biodiscovery of novel investigational ligands.

  20. Time-domain imaging

    NASA Technical Reports Server (NTRS)

    Tolliver, C. L.

    1989-01-01

    The quest for the highest resolution microwave imaging and principle of time-domain imaging has been the primary motivation for recent developments in time-domain techniques. With the present technology, fast time varying signals can now be measured and recorded both in magnitude and in-phase. It has also enhanced our ability to extract relevant details concerning the scattering object. In the past, the interface of object geometry or shape for scattered signals has received substantial attention in radar technology. Various scattering theories were proposed to develop analytical solutions to this problem. Furthermore, the random inversion, frequency swept holography, and the synthetic radar imaging, have two things in common: (1) the physical optic far-field approximation, and (2) the utilization of channels as an extra physical dimension, were also advanced. Despite the inherent vectorial nature of electromagnetic waves, these scalar treatments have brought forth some promising results in practice with notable examples in subsurface and structure sounding. The development of time-domain techniques are studied through the theoretical aspects as well as experimental verification. The use of time-domain imaging for space robotic vision applications has been suggested.

  1. Structural insights into the functional versatility of WW domain-containing oxidoreductase tumor suppressor

    PubMed Central

    2015-01-01

    Recent work on WW domain-containing oxidoreductase (WWOX) tumor suppressor is beginning to shed new light on both the molecular mechanism of action of its WW domains as well as the contiguous catalytic domain. Herein, the structural basis underlying the ability of WW1 domain to bind to various physiological ligands and how the orphan WW2 tandem partner synergizes its ligand binding in the context of WW1–WW2 tandem module of WWOX is discussed. Notably, the WW domains within the WW1–WW2 tandem module physically associate so as to adopt a fixed spatial orientation relative to each other. In this manner, the association of WW2 domain with WW1 hinders ligand binding to the latter. Consequently, ligand binding to WW1 domain not only results in the displacement of WW2 lid but also disrupts the fixed orientation of WW domains in the liganded conformation. Equally importantly, structure-guided functional approach suggests that the catalytic domain of WWOX likely serves as a retinal oxidoreductase that catalyzes the reversible oxidation and reduction of all-trans-retinal. Collectively, this review provides structural insights into the functional versatility of a key signaling protein with important implications on its biology. PMID:25662954

  2. Structural insights into the functional versatility of WW domain-containing oxidoreductase tumor suppressor.

    PubMed

    Farooq, Amjad

    2015-03-01

    Recent work on WW domain-containing oxidoreductase (WWOX) tumor suppressor is beginning to shed new light on both the molecular mechanism of action of its WW domains as well as the contiguous catalytic domain. Herein, the structural basis underlying the ability of WW1 domain to bind to various physiological ligands and how the orphan WW2 tandem partner synergizes its ligand binding in the context of WW1-WW2 tandem module of WWOX is discussed. Notably, the WW domains within the WW1-WW2 tandem module physically associate so as to adopt a fixed spatial orientation relative to each other. In this manner, the association of WW2 domain with WW1 hinders ligand binding to the latter. Consequently, ligand binding to WW1 domain not only results in the displacement of WW2 lid but also disrupts the fixed orientation of WW domains in the liganded conformation. Equally importantly, structure-guided functional approach suggests that the catalytic domain of WWOX likely serves as a retinal oxidoreductase that catalyzes the reversible oxidation and reduction of all-trans-retinal. Collectively, this review provides structural insights into the functional versatility of a key signaling protein with important implications on its biology. © 2015 by the Society for Experimental Biology and Medicine.

  3. Domain Hierarchy and closed Loops (DHcL): a server for exploring hierarchy of protein domain structure

    PubMed Central

    Koczyk, Grzegorz; Berezovsky, Igor N.

    2008-01-01

    Domain hierarchy and closed loops (DHcL) (http://sitron.bccs.uib.no/dhcl/) is a web server that delineates energy hierarchy of protein domain structure and detects domains at different levels of this hierarchy. The server also identifies closed loops and van der Waals locks, which constitute a structural basis for the protein domain hierarchy. The DHcL can be a useful tool for an express analysis of protein structures and their alternative domain decompositions. The user submits a PDB identifier(s) or uploads a 3D protein structure in a PDB format. The results of the analysis are the location of domains at different levels of hierarchy, closed loops, van der Waals locks and their interactive visualization. The server maintains a regularly updated database of domains, closed loop and van der Waals locks for all X-ray structures in PDB. DHcL server is available at: http://sitron.bccs.uib.no/dhcl. PMID:18502776

  4. Unsupervised Spatial Event Detection in Targeted Domains with Applications to Civil Unrest Modeling

    PubMed Central

    Zhao, Liang; Chen, Feng; Dai, Jing; Hua, Ting; Lu, Chang-Tien; Ramakrishnan, Naren

    2014-01-01

    Twitter has become a popular data source as a surrogate for monitoring and detecting events. Targeted domains such as crime, election, and social unrest require the creation of algorithms capable of detecting events pertinent to these domains. Due to the unstructured language, short-length messages, dynamics, and heterogeneity typical of Twitter data streams, it is technically difficult and labor-intensive to develop and maintain supervised learning systems. We present a novel unsupervised approach for detecting spatial events in targeted domains and illustrate this approach using one specific domain, viz. civil unrest modeling. Given a targeted domain, we propose a dynamic query expansion algorithm to iteratively expand domain-related terms, and generate a tweet homogeneous graph. An anomaly identification method is utilized to detect spatial events over this graph by jointly maximizing local modularity and spatial scan statistics. Extensive experiments conducted in 10 Latin American countries demonstrate the effectiveness of the proposed approach. PMID:25350136

  5. Close encounters of the third kind: disordered domains and the interactions of proteins.

    PubMed

    Tompa, Peter; Fuxreiter, Monika; Oldfield, Christopher J; Simon, Istvan; Dunker, A Keith; Uversky, Vladimir N

    2009-03-01

    Protein-protein interactions are thought to be mediated by domains, which are autonomous folding units of proteins. Recently, a second type of interaction has been suggested, mediated by short segments termed linear motifs, which are related to recognition elements of intrinsically disordered regions. Here, we propose a third kind of protein-protein recognition mechanism, mediated by disordered regions longer than 20-30 residues. Bioinformatics predictions and well-characterized examples, such as the kinase-inhibitory domain of Cdk inhibitors and the Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 of actin-binding proteins, show that these disordered regions conform to the definition of domains rather than motifs, i.e., they represent functional, evolutionary, and structural units. Their functions are distinct from those of short motifs and ordered domains, and establish a third kind of interaction principle. With these points, we argue that these long disordered regions should be recognized as a distinct class of biologically functional protein domains.

  6. The Relation between Preschool Children's False-Belief Understanding and Domain-General Experimentation Skills

    ERIC Educational Resources Information Center

    Piekny, Jeanette; Grube, Dietmar; Maehler, Claudia

    2013-01-01

    The focus of the present study is on the developmental antecedents of domain-general experimentation skills. We hypothesized that false-belief understanding would predict the ability to distinguish a conclusive from an inconclusive experiment. We conducted a longitudinal study with two assessment points (t1 and t2) to investigate this hypothesis.…

  7. Two conformations of the integrin A-domain (I-domain): a pathway for activation?

    PubMed

    Lee, J O; Bankston, L A; Arnaout, M A; Liddington, R C

    1995-12-15

    Integrins are plasma membrane proteins that mediate adhesion to other cells and to components of the extracellular matrix. Most integrins are constitutively inactive in resting cells, but are rapidly and reversibly activated in response to agonists, leading to highly regulated cell adhesion. This activation is associated with conformational changes in their extracellular portions, but the nature of the structural changes that lead to a change in adhesiveness is not understood. The interactions of several integrins with their extracellular ligands are mediated by an A-type domain (generally called the I-domain in integrins). Binding of the I-domain to protein ligands is dependent on divalent cations. We have described previously the structure of the I-domain from complement receptor 3 with bound Mg2+, in which the glutamate side chain from a second I-domain completes the octahedral coordination sphere of the metal, acting as a ligand mimetic. We now describe a new crystal form of the I-domain with bound Mn2+, in which water completes the metal coordination sphere and there is no equivalent of the glutamate ligand. Comparison of the two crystal forms reveals a change in metal coordination which is linked to a large (10 A) shift of the C-terminal helix and the burial of two phenylalanine residues into the hydrophobic core of the Mn2+ form. These structural changes, analogous to those seen in the signal-transducing G-proteins, alter the electrophilicity of the metal, reducing its ability to bind ligand-associated acidic residues, and dramatically alter the surface of the protein implicated in binding ligand. Our observations provide the first atomic resolution view of conformational changes in an integrin domain, and suggest how these changes are linked to a change in integrin adhesiveness. We propose that the Mg2+ form represents the conformation of the domain in the active state and the Mn2+ form the conformation in the inactive state of the integrin.

  8. Comprehensive analysis of orthologous protein domains using the HOPS database.

    PubMed

    Storm, Christian E V; Sonnhammer, Erik L L

    2003-10-01

    One of the most reliable methods for protein function annotation is to transfer experimentally known functions from orthologous proteins in other organisms. Most methods for identifying orthologs operate on a subset of organisms with a completely sequenced genome, and treat proteins as single-domain units. However, it is well known that proteins are often made up of several independent domains, and there is a wealth of protein sequences from genomes that are not completely sequenced. A comprehensive set of protein domain families is found in the Pfam database. We wanted to apply orthology detection to Pfam families, but first some issues needed to be addressed. First, orthology detection becomes impractical and unreliable when too many species are included. Second, shorter domains contain less information. It is therefore important to assess the quality of the orthology assignment and avoid very short domains altogether. We present a database of orthologous protein domains in Pfam called HOPS: Hierarchical grouping of Orthologous and Paralogous Sequences. Orthology is inferred in a hierarchic system of phylogenetic subgroups using ortholog bootstrapping. To avoid the frequent errors stemming from horizontally transferred genes in bacteria, the analysis is presently limited to eukaryotic genes. The results are accessible in the graphical browser NIFAS, a Java tool originally developed for analyzing phylogenetic relations within Pfam families. The method was tested on a set of curated orthologs with experimentally verified function. In comparison to tree reconciliation with a complete species tree, our approach finds significantly more orthologs in the test set. Examples for investigating gene fusions and domain recombination using HOPS are given.

  9. Working memory delay period activity marks a domain-unspecific attention mechanism.

    PubMed

    Katus, Tobias; Müller, Matthias M

    2016-03-01

    Working memory (WM) recruits neural circuits that also perform perception- and action-related functions. Among the functions that are shared between the domains of WM and perception is selective attention, which supports the maintenance of task-relevant information during the retention delay of WM tasks. The tactile contralateral delay activity (tCDA) component of the event-related potential (ERP) marks the attention-based rehearsal of tactile information in somatosensory brain regions. We tested whether the tCDA reflects the competition for shared attention resources between a WM task and a perceptual task under dual-task conditions. The two tasks were always performed on opposite hands. In different blocks, the WM task had higher or lower priority than the perceptual task. The tCDA's polarity consistently reflected the hand where the currently prioritized task was performed. This suggests that the process indexed by the tCDA is not specific to the domain of WM, but mediated by a domain-unspecific attention mechanism. The analysis of transient ERP components evoked by stimuli in the two tasks further supports the interpretation that the tCDA marks a goal-directed bias in the allocation of selective attention. Larger spatially selective modulations were obtained for stimulus material related to the high-, as compared to low-priority, task. While our results generally indicate functional overlap between the domains of WM and perception, we also found evidence suggesting that selection in internal (mnemonic) and external (perceptual) stimulus representations involves processes that are not active during shifts of preparatory attention. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Twinning, Epitaxy and Domain Switching in Ferroelastic Inclusion Compounds

    NASA Technical Reports Server (NTRS)

    Hollingsworth, Mark D.; Peterson, Matthew L.

    2003-01-01

    Our research is in the area of solid-state organic chemistry, which lies at the interface between physical organic chemistry and materials science. We use crystalline solids as models to probe fundamental issues about physical processes, molecular interactions and chemical reactions that are important for fabrication, stabilization and application of technological materials. Much of our most recent work has focused on the phenomena of ferroelastic and ferroelectric domain switching, in which application of an external force or electric field to a crystal causes the molecules inside the crystal to reorient, in tandem, to a new orientational state. To better understand and control the domain switching process, we have designed and synthesized over twenty closely related, ferroelastic organic crystals. Our approach has been to use crystalline inclusion compounds, in which one molecule (the guest) is trapped within the crystalline framework of a second molecule (the host). By keeping the host constant and varying the proportions and kinds of guests, it has been possible to tailor these materials so that domain switching is rapid and reversible (which is desirable for high technology applications). Inclusion compounds therefore serve as powerful systems for understanding the specific molecular mechanisms that control domain switching.

  11. Cetacean distribution and abundance in relation to oceanographic domains on the eastern Bering Sea shelf: 1999-2004

    NASA Astrophysics Data System (ADS)

    Friday, Nancy A.; Waite, Janice M.; Zerbini, Alexandre N.; Moore, Sue E.

    2012-06-01

    Visual line transect surveys for cetaceans were conducted on the eastern Bering Sea shelf in association with pollock stock assessment surveys aboard the NOAA ship Miller Freeman in June and July of 1999, 2000, 2002, and 2004. Transect survey effort ranged from 1188 km in 1999 to 3761 km in 2002. Fin whales (Balaenoptera physalus) were the most common large whale in all years except 2004 when humpback whales (Megaptera novaeangliae) were more abundant. Dall's porpoise (Phocoenoides dalli) were the most common small cetacean in all years. Abundance estimates were calculated by year for each oceanographic domain: coastal, middle, and outer/slope. The middle and outer/slope domains were divided into two strata ("north" and "south") because of variable survey effort. The distribution and abundance of baleen whales changed between the earlier (colder) and later (warmer) survey years. Fin whales consistently occupied the outer shelf and secondarily the middle shelf, and their abundance was an order of magnitude greater in cold compared to warm years. Humpback whales "lived on the margin" of the northern Alaska Peninsula, eastern Aleutian Islands and Bristol Bay; their preferred habitat is possibly associated with areas of high prey availability due to nutrient upwelling and aggregation mechanisms. Minke whales (Balaenoptera acutorostrata) occur shoreward of fin whales in the outer and middle shelf and in coastal habitats along the Alaska Peninsula. The highest abundance for this species was observed in a cold (1999) year. No clear relationship emerged for odontocetes with regard to warm and cold years. Dall's porpoise occupied both outer and middle domains and harbor porpoise (Phocoena phocoena) were more common in middle and coastal domains. This study provided a unique, broad-scale assessment of cetacean distribution and abundance on the eastern Bering Sea shelf and a baseline for future comparisons.

  12. Domain Adaptation with Conditional Transferable Components

    PubMed Central

    Gong, Mingming; Zhang, Kun; Liu, Tongliang; Tao, Dacheng; Glymour, Clark; Schölkopf, Bernhard

    2017-01-01

    Domain adaptation arises in supervised learning when the training (source domain) and test (target domain) data have different distributions. Let X and Y denote the features and target, respectively, previous work on domain adaptation mainly considers the covariate shift situation where the distribution of the features P(X) changes across domains while the conditional distribution P(Y∣X) stays the same. To reduce domain discrepancy, recent methods try to find invariant components T(X) that have similar P(T(X)) on different domains by explicitly minimizing a distribution discrepancy measure. However, it is not clear if P(Y∣T(X)) in different domains is also similar when P(Y∣X) changes. Furthermore, transferable components do not necessarily have to be invariant. If the change in some components is identifiable, we can make use of such components for prediction in the target domain. In this paper, we focus on the case where P(X∣Y) and P(Y) both change in a causal system in which Y is the cause for X. Under appropriate assumptions, we aim to extract conditional transferable components whose conditional distribution P(T(X)∣Y) is invariant after proper location-scale (LS) transformations, and identify how P(Y) changes between domains simultaneously. We provide theoretical analysis and empirical evaluation on both synthetic and real-world data to show the effectiveness of our method. PMID:28239433

  13. Magnetic and magneto-optical properties and domain structure of Co/Pd multilayers

    NASA Technical Reports Server (NTRS)

    Gadetsky, S.; Wu, Teho; Suzuki, T.; Mansuripur, M.

    1993-01-01

    The domain structure of Co/Pd(1.6/6.3 A)xN multilayers and its relation to the bulk magnetic properties of the samples were studied. The Co/Pd multilayers were deposited by rf and dc magnetron sputtering onto different substrates. It was found that magnetic and magnetooptical properties and domain structure of the multilayers were affected by total film thickness and substrate condition. Magnetization, coercivity, and anisotropy of the films decreased significantly as the film thickness dropped below 100 A. However, Kerr rotation angle had a maximum at the same thickness. The width of the domain structure increased with the decrease of the film thickness attaining the single domain state at N = 10. The initial curves in Co/Pd multilayers were found to depend on demagnetization process. The samples demagnetized by inplane field showed the largest difference between initial curves and the corresponding parts of the loops. Different domain structures were observed in the samples demagnetized by perpendicular and in-plane magnetic fields.

  14. The Importance of Domain-Specific Expertise in Creativity

    ERIC Educational Resources Information Center

    Baer, John

    2015-01-01

    Although creativity and expertise are related, they are nonetheless very different things. Expertise does not usually require creativity, but creativity generally does require a certain level of expertise. There are similarities in the relationships of both expertise and creativity to domains, however. Research has shown that just as expertise in…

  15. Electronic structure and switching behavior of the metastable silicene domain boundary

    NASA Astrophysics Data System (ADS)

    Oh, Youngtek; Cho, Yeonchoo; Kwon, Hyeokshin; Lee, Junsu; Jeon, Insu; Ko, Wonhee; Kim, Hyo Won; Ku, JiYeon; Kim, Gunn; Suh, Hwansoo; Hwang, Sung Woo

    2017-06-01

    Silicene, a silicon allotrope with a buckled honeycomb lattice, has been extensively studied in the search for materials with graphene-like properties. Here, we study the domain boundaries of a silicene 4 × 4 superstructure on an Ag(111) surface at the atomic resolution using scanning tunneling microscopy (STM) and spectroscopy (STS) along with density functional theory calculations. The silicene domain boundaries (β-phases) are formed at the interface between misaligned domains (α-phases) and show a bias dependence, forming protrusions or depressions as the sample bias changes. In particular, the STM topographs of the silicene-substrate system at a bias of ˜2.0 V show brightly protruding domain boundaries, which can be explained by an energy state originating from the Si 3s and 3pz orbitals. In addition, the topographs depicting the vicinity of the domain boundaries show that the structure does not follow the buckled geometry of the atomic ball-and-stick model. Inside the domain, STS data showed a step-up at ˜0.4 V, which originated from the Si 3p orbitals. We found this step-up to have shifted, which may be attributed to the strain effect at the interface regions between silver and silicene and between the domain and its boundary upon performing spatially resolved STS measurements. The metastable characteristic of the domain boundary (β-phase) causes changes, such as creation or annihilation, in the buckling structures (switching behavior). The observed low activation energy for the buckling change between distinct states may find applications in the electronic control of properties related to domain boundary structures in silicene.

  16. Monte Carlo simulation of ferroelectric domain growth

    NASA Astrophysics Data System (ADS)

    Li, B. L.; Liu, X. P.; Fang, F.; Zhu, J. L.; Liu, J.-M.

    2006-01-01

    The kinetics of two-dimensional isothermal domain growth in a quenched ferroelectric system is investigated using Monte Carlo simulation based on a realistic Ginzburg-Landau ferroelectric model with cubic-tetragonal (square-rectangle) phase transitions. The evolution of the domain pattern and domain size with annealing time is simulated, and the stability of trijunctions and tetrajunctions of domain walls is analyzed. It is found that in this much realistic model with strong dipole alignment anisotropy and long-range Coulomb interaction, the powerlaw for normal domain growth still stands applicable. Towards the late stage of domain growth, both the average domain area and reciprocal density of domain wall junctions increase linearly with time, and the one-parameter dynamic scaling of the domain growth is demonstrated.

  17. Domain wall magnetoresistance in BiFeO3 thin films measured by scanning probe microscopy

    NASA Astrophysics Data System (ADS)

    Domingo, N.; Farokhipoor, S.; Santiso, J.; Noheda, B.; Catalan, G.

    2017-08-01

    We measure the magnetotransport properties of individual 71° domain walls in multiferroic BiFeO3 by means of conductive—atomic force microscopy (C-AFM) in the presence of magnetic fields up to one Tesla. The results suggest anisotropic magnetoresistance at room temperature, with the sign of the magnetoresistance depending on the relative orientation between the magnetic field and the domain wall plane. A consequence of this finding is that macroscopically averaged magnetoresistance measurements for domain wall bunches are likely to underestimate the magnetoresistance of each individual domain wall.

  18. Domain-Specific Control of Selective Attention

    PubMed Central

    Lin, Szu-Hung; Yeh, Yei-Yu

    2014-01-01

    Previous research has shown that loading information on working memory affects selective attention. However, whether the load effect on selective attention is domain-general or domain-specific remains unresolved. The domain-general effect refers to the findings that load in one content (e.g. phonological) domain in working memory influences processing in another content (e.g., visuospatial) domain. Attentional control supervises selection regardless of information domain. The domain-specific effect refers to the constraint of influence only when maintenance and processing operate in the same domain. Selective attention operates in a specific content domain. This study is designed to resolve this controversy. Across three experiments, we manipulated the type of representation maintained in working memory and the type of representation upon which the participants must exert control to resolve conflict and select a target into the focus of attention. In Experiments 1a and 1b, participants maintained digits and nonverbalized objects, respectively, in working memory while selecting a target in a letter array. In Experiment 2, we presented auditory digits with a letter flanker task to exclude the involvement of resource competition within the same input modality. In Experiments 3a and 3b, we replaced the letter flanker task with an object flanker task while manipulating the memory load on object and digit representation, respectively. The results consistently showed that memory load modulated distractibility only when the stimuli of the two tasks were represented in the same domain. The magnitude of distractor interference was larger under high load than under low load, reflecting a lower efficacy of information prioritization. When the stimuli of the two tasks were represented in different domains, memory load did not modulate distractibility. Control of processing priority in selective attention demands domain-specific resources. PMID:24866977

  19. The Relationship between Defense Patterns and DSM-5 Maladaptive Personality Domains.

    PubMed

    Granieri, Antonella; La Marca, Luana; Mannino, Giuseppe; Giunta, Serena; Guglielmucci, Fanny; Schimmenti, Adriano

    2017-01-01

    Aim: Research has extensively examined the relationship between defense mechanisms (DM) and personality traits. However, no study to date has explored if specific defenses (alone or in combination) are able to predict dysfunctional variants of personality domains, as conceived in the alternative DSM-5 model for personality disorders. This study aimed to investigate the relationship between DMs and DSM-5 maladaptive personality domains among adults. Materials and Methods: Three hundred and twenty-eight adults aged between 18 and 64 years old completed measures on DMs and maladapive personality domains. Regression analyses were performed to determine which DMs predicted the maladaptive personality domains of negative affectivity, detachment, antagonism, disinhibition, and psychoticism. Results: According to psychoanalytic literature, results showed that immature defenses positively predicted maladaptive personality domain scores, whereas mature defenses were generally related with better personality functioning. Moreover, different defense patterns emerged as significant predictors of the maladaptive personality domains comprised in the alternative DSM-5 model for personality disorder. Discussion: Our findings support the view that defense patterns represent core components of personality and its disorders, and suggest that an increased use of immature defenses and a reduced use of mature defenses have a negative impact on the development of personality.

  20. The Relationship between Defense Patterns and DSM-5 Maladaptive Personality Domains

    PubMed Central

    Granieri, Antonella; La Marca, Luana; Mannino, Giuseppe; Giunta, Serena; Guglielmucci, Fanny; Schimmenti, Adriano

    2017-01-01

    Aim: Research has extensively examined the relationship between defense mechanisms (DM) and personality traits. However, no study to date has explored if specific defenses (alone or in combination) are able to predict dysfunctional variants of personality domains, as conceived in the alternative DSM-5 model for personality disorders. This study aimed to investigate the relationship between DMs and DSM-5 maladaptive personality domains among adults. Materials and Methods: Three hundred and twenty-eight adults aged between 18 and 64 years old completed measures on DMs and maladapive personality domains. Regression analyses were performed to determine which DMs predicted the maladaptive personality domains of negative affectivity, detachment, antagonism, disinhibition, and psychoticism. Results: According to psychoanalytic literature, results showed that immature defenses positively predicted maladaptive personality domain scores, whereas mature defenses were generally related with better personality functioning. Moreover, different defense patterns emerged as significant predictors of the maladaptive personality domains comprised in the alternative DSM-5 model for personality disorder. Discussion: Our findings support the view that defense patterns represent core components of personality and its disorders, and suggest that an increased use of immature defenses and a reduced use of mature defenses have a negative impact on the development of personality. PMID:29163301

  1. Drug resistance-associated changes in sphingolipids and ABC transporters occur in different regions of membrane domains.

    PubMed

    Hinrichs, John W J; Klappe, Karin; van Riezen, Manon; Kok, Jan W

    2005-11-01

    We have recently shown that two ATP binding cassette (ABC) transporters are enriched in Lubrol-resistant noncaveolar membrane domains in multidrug-resistant human cancer cells [Hinrichs, J. W. J., K. Klappe, I. Hummel, and J. W. Kok. 2004. ATP-binding cassette transporters are enriched in non-caveolar detergent-insoluble glycosphingolipid-enriched membrane domains (DIGs) in human multidrug-resistant cancer cells. J. Biol. Chem. 279: 5734-5738]. Here, we show that aminophospholipids are relatively enriched in Lubrol-resistant membrane domains compared with Triton X-100-resistant membrane domains, whereas sphingolipids are relatively enriched in the latter. Moreover, Lubrol-resistant membrane domains contain more protein and lipid mass. Based on these results, we postulate a model for detergent-insoluble glycosphingolipid-enriched membrane domains consisting of a Lubrol-insoluble/Triton X-100-insoluble region and a Lubrol-insoluble/Triton X-100-soluble region. The latter region contains most of the ABC transporters as well as lipids known to be necessary for their efflux activity. Compared with drug-sensitive cells, the detergent-insoluble glycosphingolipid-enriched membrane domains (DIGs) in drug-resistant cells differ specifically in sphingolipid content and not in protein, phospholipid, or cholesterol content. In drug-resistant cells, sphingolipids with specific fatty acids (especially C24:1) are enriched in these membrane domains. Together, these data show that multidrug resistance-associated changes in both sphingolipids and ABC transporters occur in DIGs, but in different regions of these domains.

  2. Adherence to hydroxyurea, health-related quality of life domains, and patients' perceptions of sickle cell disease and hydroxyurea: a cross-sectional study in adolescents and young adults.

    PubMed

    Badawy, Sherif M; Thompson, Alexis A; Lai, Jin-Shei; Penedo, Frank J; Rychlik, Karen; Liem, Robert I

    2017-07-05

    Sickle cell disease (SCD) patients have impaired domains of health-related quality of life (HRQOL). Hydroxyurea is safe and efficacious in SCD; however, adherence is suboptimal, and patients' perceptions are poorly understood amongst adolescents and young adults (AYA). Study objectives were to: (1) examine patients' perceptions of SCD and hydroxyurea; and (2) explore the relationship of their perceptions to clinical characteristics, HRQOL domains and hydroxyurea adherence. Thirty-four SCD patients on hydroxyurea (≥6 months) participated in a single-institution study. Study measures included Brief-Illness Perceptions Questionnaire, ©Modified Morisky Adherence Scale 8-items, and Patient Reported Outcomes Measurement Information System (PROMIS®). We assessed the relationship of patients' perceptions to hydroxyurea adherence using Wilcoxon rank-sum test, the number of hospitalizations using Kruskal-Wallis test, and the number of ED visits, adherence level, HRQOL domain scores using Spearman's rho correlations. We conducted a sub-analysis in HbSS patients to evaluate the relationship of patients' perceptions to laboratory markers of hydroxyurea adherence. Participants were 59% male and 91% Black, and had a median age of 13.5 (range 12-18) years. Participants with ≥4 hospitalizations over 1-year prior (using electronic medical chart review) reported more negative perceptions of SCD-related symptoms and emotional response, and perceived hydroxyurea as less beneficial; all p-values ≤0.01. Most participants (74%) reported low hydroxyurea adherence. Participants with higher hydroxyurea adherence perceived more hydroxyurea benefits (r s  = 0.44, p < 0.01) and had better emotional response to SCD (r s  = -0.44, p = 0.01). In a sub-analysis of HbSS patients, perceived benefits of hydroxyurea positively correlated with HbF (r s  = 0.37, p = 0.05) and MCV values (r s  = 0.35, p = 0.05). Participants with more negative perceptions of SCD-related

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

    PubMed

    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.

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

    DOE PAGES

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

    2017-04-11

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

  5. The GP(Y/F) Domain of TF1 Integrase Multimerizes when Present in a Fragment, and Substitutions in This Domain Reduce Enzymatic Activity of the Full-length Protein*S⃞

    PubMed Central

    Ebina, Hirotaka; Chatterjee, Atreyi Ghatak; Judson, Robert L.; Levin, Henry L.

    2008-01-01

    Integrases (INs) of retroviruses and long terminal repeat retrotransposons possess a C-terminal domain with DNA binding activity. Other than this binding activity, little is known about how the C-terminal domain contributes to integration. A stretch of conserved amino acids called the GP(Y/F) domain has been identified within the C-terminal IN domains of two distantly related families, the γ-retroviruses and the metavirus retrotransposons. To enhance understanding of the C-terminal domain, we examined the function of the GP(Y/F) domain in the IN of Tf1, a long terminal repeat retrotransposon of Schizosaccharomyces pombe. The activities of recombinant IN were measured with an assay that modeled the reverse of integration called disintegration. Although deletion of the entire C-terminal domain disrupted disintegration activity, an alanine substitution (P365A) in a conserved amino acid of the GP(Y/F) domain did not significantly reduce disintegration. When assayed for the ability to join two molecules of DNA in a reaction that modeled forward integration, the P365A substitution disrupted activity. UV cross-linking experiments detected DNA binding activity in the C-terminal domain and found that this activity was not reduced by substitutions in two conserved amino acids of the GP(Y/F) domain, G364A and P365A. Gel filtration and cross-linking of a 71-amino acid fragment containing the GP(Y/F) domain revealed a surprising ability to form dimers, trimers, and tetramers that was disrupted by the G364A and P365A substitutions. These results suggest that the GP(Y/F) residues may play roles in promoting multimerization and intermolecular strand joining. PMID:18397885

  6. Blue Light-excited Light-Oxygen-Voltage-sensing Domain 2 (LOV2) Triggers a Rearrangement of the Kinase Domain to Induce Phosphorylation Activity in Arabidopsis Phototropin1.

    PubMed

    Oide, Mao; Okajima, Koji; Kashojiya, Sachiko; Takayama, Yuki; Oroguchi, Tomotaka; Hikima, Takaaki; Yamamoto, Masaki; Nakasako, Masayoshi

    2016-09-16

    Phototropin1 is a blue light (BL) receptor in plants and shows BL-dependent kinase activation. The BL-excited light-oxygen-voltage-sensing domain 2 (LOV2) is primarily responsible for the activation of the kinase domain; however, the molecular mechanism by which conformational changes in LOV2 are transmitted to the kinase domain remains unclear. Here, we investigated BL-induced structural changes of a minimum functional fragment of Arabidopsis phototropin1 composed of LOV2, the kinase domain, and a linker connecting the two domains using small-angle x-ray scattering (SAXS). The fragment existed as a dimer and displayed photoreversible SAXS changes reflected in the radii of gyration of 42.9 Å in the dark and 48.8 Å under BL irradiation. In the dark, the molecular shape reconstructed from the SAXS profiles appeared as two bean-shaped lobes in a twisted arrangement that was 170 Å long, 80 Å wide, and 50 Å thick. The molecular shape under BL became slightly elongated from that in the dark. By fitting the crystal structure of the LOV2 dimer and a homology model of the kinase domain to their inferred shapes, the BL-dependent change could be interpreted as the positional shift in the kinase domain relative to that of the LOV2 dimer. In addition, we found that lysine 475, a functionally important residue, in the N-terminal region of LOV2 plays a critical role in transmitting the structural changes in LOV2 to the kinase domain. The interface between the domains is critical for signaling, suitably changing the structure to activate the kinase in response to conformational changes in the adjoining LOV2. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. The Relative Influence of Metal Ion Binding Sites in the I-like Domain and the Interface with the Hybrid Domain on Rolling and Firm Adhesion by Integrin α4β7*

    PubMed Central

    Chen, JianFeng; Takagi, Junichi; Xie, Can; Xiao, Tsan; Luo, Bing-Hao; Springer, Timothy A.

    2015-01-01

    We examined the effect of conformational change at the β7 I-like/hybrid domain interface on regulating the transition between rolling and firm adhesion by integrin α4β7. An N-glycosylation site was introduced into the I-like/hybrid domain interface to act as a wedge and to stabilize the open conformation of this interface and hence the open conformation of the α4β7 headpiece. Wild-type α4β7 mediates rolling adhesion in Ca2+ and Ca2+/Mg2+ but firm adhesion in Mg2+ and Mn2+. Stabilizing the open headpiece resulted in firm adhesion in all divalent cations. The interaction between metal binding sites in the I-like domain and the interface with the hybrid domain was examined in double mutants. Changes at these two sites can either counterbalance one another or be additive, emphasizing mutuality and the importance of multiple interfaces in integrin regulation. A double mutant with counterbalancing deactivating ligand-induced metal ion binding site (LIMBS) and activating wedge mutations could still be activated by Mn2+, confirming the importance of the adjacent to metal ion-dependent adhesion site (ADMIDAS) in integrin activation by Mn2+. Overall, the results demonstrate the importance of headpiece allostery in the conversion of rolling to firm adhesion. PMID:15448154

  8. The SAM domain inhibits EphA2 interactions in the plasma membrane.

    PubMed

    Singh, Deo R; Ahmed, Fozia; Paul, Michael D; Gedam, Manasee; Pasquale, Elena B; Hristova, Kalina

    2017-01-01

    All members of the Eph receptor family of tyrosine kinases contain a SAM domain near the C terminus, which has been proposed to play a role in receptor homotypic interactions and/or interactions with binding partners. The SAM domain of EphA2 is known to be important for receptor function, but its contribution to EphA2 lateral interactions in the plasma membrane has not been determined. Here we use a FRET-based approach to directly measure the effect of the SAM domain on the stability of EphA2 dimers on the cell surface in the absence of ligand binding. We also investigate the functional consequences of EphA2 SAM domain deletion. Surprisingly, we find that the EphA2 SAM domain inhibits receptor dimerization and decreases EphA2 tyrosine phosphorylation. This role is dramatically different from the role of the SAM domain of the related EphA3 receptor, which we previously found to stabilize EphA3 dimers and increase EphA3 tyrosine phosphorylation in cells in the absence of ligand. Thus, the EphA2 SAM domain likely contributes to a unique mode of EphA2 interaction that leads to distinct signaling outputs. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Phylogeny of the TRAF/MATH domain.

    PubMed

    Zapata, Juan M; Martínez-García, Vanesa; Lefebvre, Sophie

    2007-01-01

    The TNF-receptor associated factor (TRAF) domain (TD), also known as the meprin and TRAF-C homology (MATH) domain is a fold of seven anti-parallel p-helices that participates in protein-protein interactions. This fold is broadly represented among eukaryotes, where it is found associated with a discrete set of protein-domains. Virtually all protein families encompassing a TRAF/MATH domain seem to be involved in the regulation of protein processing and ubiquitination, strongly suggesting a parallel evolution of the TRAF/MATH domain and certain proteolysis pathways in eukaryotes. The restricted number of living organisms for which we have information of their genetic and protein make-up limits the scope and analysis of the MATH domain in evolution. However, the available information allows us to get a glimpse on the origins, distribution and evolution of the TRAF/MATH domain, which will be overviewed in this chapter.

  10. Diverse oligomeric states of CEACAM IgV domains

    DOE PAGES

    Bonsor, Daniel A.; Günther, Sebastian; Beadenkopf, Robert; ...

    2015-10-19

    Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) comprise a large family of cell surface adhesion molecules that bind to themselves and other family members to carry out numerous cellular functions, including proliferation, signaling, differentiation, tumor suppression, and survival. They also play diverse and significant roles in immunity and infection. The formation of CEACAM oligomers is caused predominantly by interactions between their N-terminal IgV domains. Although X-ray crystal structures of CEACAM IgV domain homodimers have been described, how CEACAMs form heterodimers or remain monomers is poorly understood. To address this key aspect of CEACAM function, we determined in this paper the crystalmore » structures of IgV domains that form a homodimeric CEACAM6 complex, monomeric CEACAM8, and a heterodimeric CEACAM6–CEACAM8 complex. To confirm and quantify these interactions in solution, we used analytical ultracentrifugation to measure the dimerization constants of CEACAM homodimers and isothermal titration calorimetry to determine the thermodynamic parameters and binding affinities of CEACAM heterodimers. We found the CEACAM6–CEACAM8 heterodimeric state to be substantially favored energetically relative to the CEACAM6 homodimer. Finally, our data provide a molecular basis for the adoption of the diverse oligomeric states known to exist for CEACAMs and suggest ways in which CEACAM6 and CEACAM8 regulate the biological functions of one another, as well as of additional CEACAMs with which they interact, both in cis and in trans.« less

  11. Diverse oligomeric states of CEACAM IgV domains

    PubMed Central

    Bonsor, Daniel A.; Günther, Sebastian; Beadenkopf, Robert; Beckett, Dorothy; Sundberg, Eric J.

    2015-01-01

    Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) comprise a large family of cell surface adhesion molecules that bind to themselves and other family members to carry out numerous cellular functions, including proliferation, signaling, differentiation, tumor suppression, and survival. They also play diverse and significant roles in immunity and infection. The formation of CEACAM oligomers is caused predominantly by interactions between their N-terminal IgV domains. Although X-ray crystal structures of CEACAM IgV domain homodimers have been described, how CEACAMs form heterodimers or remain monomers is poorly understood. To address this key aspect of CEACAM function, we determined the crystal structures of IgV domains that form a homodimeric CEACAM6 complex, monomeric CEACAM8, and a heterodimeric CEACAM6–CEACAM8 complex. To confirm and quantify these interactions in solution, we used analytical ultracentrifugation to measure the dimerization constants of CEACAM homodimers and isothermal titration calorimetry to determine the thermodynamic parameters and binding affinities of CEACAM heterodimers. We found the CEACAM6–CEACAM8 heterodimeric state to be substantially favored energetically relative to the CEACAM6 homodimer. Our data provide a molecular basis for the adoption of the diverse oligomeric states known to exist for CEACAMs and suggest ways in which CEACAM6 and CEACAM8 regulate the biological functions of one another, as well as of additional CEACAMs with which they interact, both in cis and in trans. PMID:26483485

  12. Diverse oligomeric states of CEACAM IgV domains.

    PubMed

    Bonsor, Daniel A; Günther, Sebastian; Beadenkopf, Robert; Beckett, Dorothy; Sundberg, Eric J

    2015-11-03

    Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) comprise a large family of cell surface adhesion molecules that bind to themselves and other family members to carry out numerous cellular functions, including proliferation, signaling, differentiation, tumor suppression, and survival. They also play diverse and significant roles in immunity and infection. The formation of CEACAM oligomers is caused predominantly by interactions between their N-terminal IgV domains. Although X-ray crystal structures of CEACAM IgV domain homodimers have been described, how CEACAMs form heterodimers or remain monomers is poorly understood. To address this key aspect of CEACAM function, we determined the crystal structures of IgV domains that form a homodimeric CEACAM6 complex, monomeric CEACAM8, and a heterodimeric CEACAM6-CEACAM8 complex. To confirm and quantify these interactions in solution, we used analytical ultracentrifugation to measure the dimerization constants of CEACAM homodimers and isothermal titration calorimetry to determine the thermodynamic parameters and binding affinities of CEACAM heterodimers. We found the CEACAM6-CEACAM8 heterodimeric state to be substantially favored energetically relative to the CEACAM6 homodimer. Our data provide a molecular basis for the adoption of the diverse oligomeric states known to exist for CEACAMs and suggest ways in which CEACAM6 and CEACAM8 regulate the biological functions of one another, as well as of additional CEACAMs with which they interact, both in cis and in trans.

  13. Function-selective domain architecture plasticity potentials in eukaryotic genome evolution

    PubMed Central

    Linkeviciute, Viktorija; Rackham, Owen J.L.; Gough, Julian; Oates, Matt E.; Fang, Hai

    2015-01-01

    To help evaluate how protein function impacts on genome evolution, we introduce a new concept of ‘architecture plasticity potential’ – the capacity to form distinct domain architectures – both for an individual domain, or more generally for a set of domains grouped by shared function. We devise a scoring metric to measure the plasticity potential for these domain sets, and evaluate how function has changed over time for different species. Applying this metric to a phylogenetic tree of eukaryotic genomes, we find that the involvement of each function is not random but highly selective. For certain lineages there is strong bias for evolution to involve domains related to certain functions. In general eukaryotic genomes, particularly animals, expand complex functional activities such as signalling and regulation, but at the cost of reducing metabolic processes. We also observe differential evolution of transcriptional regulation and a unique evolutionary role of channel regulators; crucially this is only observable in terms of the architecture plasticity potential. Our findings provide a new layer of information to understand the significance of function in eukaryotic genome evolution. A web search tool, available at http://supfam.org/Pevo, offers a wide spectrum of options for exploring functional importance in eukaryotic genome evolution. PMID:25980317

  14. Disentangling the Role of Domain-Specific Knowledge in Student Modeling

    NASA Astrophysics Data System (ADS)

    Ruppert, John; Duncan, Ravit Golan; Chinn, Clark A.

    2017-08-01

    This study explores the role of domain-specific knowledge in students' modeling practice and how this knowledge interacts with two domain-general modeling strategies: use of evidence and developing a causal mechanism. We analyzed models made by middle school students who had a year of intensive model-based instruction. These models were made to explain a familiar but unstudied biological phenomenon: late onset muscle pain. Students were provided with three pieces of evidence related to this phenomenon and asked to construct a model to account for this evidence. Findings indicate that domain-specific resources play a significant role in the extent to which the models accounted for provided evidence. On the other hand, familiarity with the situation appeared to contribute to the mechanistic character of models. Our results indicate that modeling strategies alone are insufficient for the development of a mechanistic model that accounts for provided evidence and that, while learners can develop a tentative model with a basic familiarity of the situation, scaffolding certain domain-specific knowledge is necessary to assist students with incorporating evidence in modeling tasks.

  15. The influenza virus neuraminidase protein transmembrane and head domains have coevolved.

    PubMed

    da Silva, Diogo V; Nordholm, Johan; Dou, Dan; Wang, Hao; Rossman, Jeremy S; Daniels, Robert

    2015-01-15

    Transmembrane domains (TMDs) from single-spanning membrane proteins are commonly viewed as membrane anchors for functional domains. Influenza virus neuraminidase (NA) exemplifies this concept, as it retains enzymatic function upon proteolytic release from the membrane. However, the subtype 1 NA TMDs have become increasingly more polar in human strains since 1918, which suggests that selection pressure exists on this domain. Here, we investigated the N1 TMD-head domain relationship by exchanging a prototypical "old" TMD (1933) with a "recent" (2009), more polar TMD and an engineered hydrophobic TMD. Each exchange altered the TMD association, decreased the NA folding efficiency, and significantly reduced viral budding and replication at 37°C compared to at 33°C, at which NA folds more efficiently. Passaging the chimera viruses at 37°C restored the NA folding efficiency, viral budding, and infectivity by selecting for NA TMD mutations that correspond with their polar or hydrophobic assembly properties. These results demonstrate that single-spanning membrane protein TMDs can influence distal domain folding, as well as membrane-related processes, and suggest the NA TMD in H1N1 viruses has become more polar to maintain compatibility with the evolving enzymatic head domain. The neuraminidase (NA) protein from influenza A viruses (IAVs) functions to promote viral release and is one of the major surface antigens. The receptor-destroying activity in NA resides in the distal head domain that is linked to the viral membrane by an N-terminal hydrophobic transmembrane domain (TMD). Over the last century, the subtype 1 NA TMDs (N1) in human H1N1 viruses have become increasingly more polar, and the head domains have changed to alter their antigenicity. Here, we provide the first evidence that an "old" N1 head domain from 1933 is incompatible with a "recent" (2009), more polar N1 TMD sequence and that, during viral replication, the head domain drives the selection of TMD

  16. Domains of quality of life: results of a three-stage Delphi consensus procedure among patients, family of patients, clinicians, scientists and the general public.

    PubMed

    Pietersma, Suzanne; de Vries, Marieke; van den Akker-van Marle, M Elske

    2014-06-01

    Our key objective is to identify the core domains of health-related quality of life (QoL). Health-related QoL utility scales are commonly used in economic evaluations to assess the effectiveness of health-care interventions. However, health-care interventions are likely to affect QoL in a broader sense than is quantifiable with traditional scales. Therefore, measures need to go beyond these scales. Unfortunately, there is no consensus in the scientific literature on the essential domains of QoL. We conducted a three-stage online Delphi consensus procedure to identify the key domains of health-related QoL. Five stakeholder groups (i.e., patients, family of patients, clinicians, scientists and general public) were asked, on three consecutive occasions, what they perceive as the most important domains of health-related QoL. An analysis of existing (health-related) QoL and well-being measurements formed the basis of the Delphi-procedure. In total, 42 domains of QoL were judged, covering physical, mental and social aspects. All participants rated 'self-acceptance', 'self-esteem' and 'good social contacts' as essential. Strikingly, mental and social domains are perceived as more essential than physical domains across stakeholders groups. In traditionally used health-related QoL utility measures, physical domains like 'mobility' are prominently present. The Delphi-procedure shows that health-related QoL (utility) scales need to put sufficient emphasis on mental and social domains to capture aspects of QoL that are essential to people.

  17. Engineered Human Antibody Constant Domains with Increased Stability*S⃞

    PubMed Central

    Gong, Rui; Vu, Bang K.; Feng, Yang; Prieto, DaRue A.; Dyba, Marzena A.; Walsh, Joseph D.; Prabakaran, Ponraj; Veenstra, Timothy D.; Tarasov, Sergey G.; Ishima, Rieko; Dimitrov, Dimiter S.

    2009-01-01

    The immunoglobulin (Ig) constant CH2 domain is critical for antibody effector functions. Isolated CH2 domains are promising as scaffolds for construction of libraries containing diverse binders that could also confer some effector functions. However, previous work has shown that an isolated murine CH2 domain is relatively unstable to thermally induced unfolding. To explore unfolding mechanisms of isolated human CH2 and increase its stability γ1 CH2 was cloned and a panel of cysteine mutants was constructed. Human γ1 CH2 unfolded at a higher temperature (Tm = 54.1 °C, as measured by circular dichroism) than that previously reported for a mouse CH2 (41 °C). One mutant (m01) was remarkably stable (Tm = 73.8 °C). Similar results were obtained by differential scanning calorimetry. This mutant was also significantly more stable than the wild-type CH2 against urea induced unfolding (50% unfolding at urea concentration of 6.8 m versus 4.2 m). The m01 was highly soluble and monomeric. The existence of the second disulfide bond in m01 and its correct position were demonstrated by mass spectrometry and nuclear magnetic resonance spectroscopy, respectively. The loops were on average more flexible than the framework in both CH2 and m01, and the overall secondary structure was not affected by the additional disulfide bond. These data suggest that a human CH2 domain is relatively stable to unfolding at physiological temperature, and that both CH2 and the highly stable mutant m01 are promising new scaffolds for the development of therapeutics against human diseases. PMID:19307178

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

    PubMed

    Fong, Jessica H; Marchler-Bauer, Aron

    2009-08-01

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

  19. Metabolomics method to comprehensively analyze amino acids in different domains.

    PubMed

    Gu, Haiwei; Du, Jianhai; Carnevale Neto, Fausto; Carroll, Patrick A; Turner, Sally J; Chiorean, E Gabriela; Eisenman, Robert N; Raftery, Daniel

    2015-04-21

    Amino acids play essential roles in both metabolism and the proteome. Many studies have profiled free amino acids (FAAs) or proteins; however, few have connected the measurement of FAA with individual amino acids in the proteome. In this study, we developed a metabolomics method to comprehensively analyze amino acids in different domains, using two examples of different sample types and disease models. We first examined the responses of FAAs and insoluble-proteome amino acids (IPAAs) to the Myc oncogene in Tet21N human neuroblastoma cells. The metabolic and proteomic amino acid profiles were quite different, even under the same Myc condition, and their combination provided a better understanding of the biological status. In addition, amino acids were measured in 3 domains (FAAs, free and soluble-proteome amino acids (FSPAAs), and IPAAs) to study changes in serum amino acid profiles related to colon cancer. A penalized logistic regression model based on the amino acids from the three domains had better sensitivity and specificity than that from each individual domain. To the best of our knowledge, this is the first study to perform a combined analysis of amino acids in different domains, and indicates the useful biological information available from a metabolomics analysis of the protein pellet. This study lays the foundation for further quantitative tracking of the distribution of amino acids in different domains, with opportunities for better diagnosis and mechanistic studies of various diseases.

  20. Influence of social relationship domains and their combinations on incident dementia: a prospective cohort study.

    PubMed

    Saito, Tami; Murata, Chiyoe; Saito, Masashige; Takeda, Tokunori; Kondo, Katsunori

    2018-01-01

    Social relationships consist of mutually related but distinct dimensions. It remains unclear how these domains independently contribute to incident dementia. This large-scale, prospective cohort study examines associations between the social relationship domains as well as their combinations and incident dementia among community-dwelling older adults. We analysed data from 13 984 community-dwelling adults aged 65+ without long-term care needs living in Aichi prefecture in Japan. Incident dementia was assessed based on the Long-term Care Insurance records, followed for 3436 days from the baseline survey conducted in 2003. Three social relationships domains (social support, social networks and social activities) were further divided into a total of eight subdomains. A social relationship diversity score was calculated using the social relationship domains which were significantly related to incident dementia. A Cox proportional hazards model showed that being married, exchanging support with family members, having contact with friends, participating in community groups and engaging in paid work were related to a lower likelihood of developing incident dementia, controlling for covariates and other social relationship domains. The diversity scores, ranging from 0 to 5, were linearly associated with incident dementia (p<0.001), and those who scored highest were 46% less likely to develop incident dementia compared with those in the lowest category. Our findings revealed five social relationship subdomains which were negatively related to incident dementia, suggesting that dementia may potentially be prevented by enhancing these social relationships. Future studies should examine independent pathways between each social relationship domain and incident dementia. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

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

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

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

  2. Domain and Specification Models for Software Engineering

    NASA Technical Reports Server (NTRS)

    Iscoe, Neil; Liu, Zheng-Yang; Feng, Guohui

    1992-01-01

    This paper discusses our approach to representing application domain knowledge for specific software engineering tasks. Application domain knowledge is embodied in a domain model. Domain models are used to assist in the creation of specification models. Although many different specification models can be created from any particular domain model, each specification model is consistent and correct with respect to the domain model. One aspect of the system-hierarchical organization is described in detail.

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

    PubMed

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

    2017-10-01

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

  4. Wavelet-domain de-noising technique for THz pulsed spectroscopy

    NASA Astrophysics Data System (ADS)

    Chernomyrdin, Nikita V.; Zaytsev, Kirill I.; Gavdush, Arsenii A.; Fokina, Irina N.; Karasik, Valeriy E.; Reshetov, Igor V.; Kudrin, Konstantin G.; Nosov, Pavel A.; Yurchenko, Stanislav O.

    2014-09-01

    De-noising of terahertz (THz) pulsed spectroscopy (TPS) data is an essential problem, since a noise in the TPS system data prevents correct reconstruction of the sample spectral dielectric properties and to perform the sample internal structure studying. There are certain regions in TPS signal Fourier spectrum, where Fourier-domain signal-to-noise ratio is relatively small. Effective de-noising might potentially expand the range of spectrometer spectral sensitivity and reduce the time of waveform registration, which is an essential problem for biomedical applications of TPS. In this work, it is shown how the recent progress in signal processing in wavelet-domain could be used for TPS waveforms de-noising. It demonstrates the ability to perform effective de-noising of TPS data using the algorithm of the Fast Wavelet Transform (FWT). The results of the optimal wavelet basis selection and wavelet-domain thresholding technique selection are reported. Developed technique is implemented for reconstruction of in vivo healthy and deseased skin samplesspectral characteristics at THz frequency range.

  5. One-Dimensional Singlet Exciton Diffusion in Poly(3-hexylthiophene) Crystalline Domains.

    PubMed

    Tamai, Yasunari; Matsuura, Yuu; Ohkita, Hideo; Benten, Hiroaki; Ito, Shinzaburo

    2014-01-16

    Singlet exciton dynamics in crystalline domains of regioregular poly(3-hexylthiophene) (P3HT) films was studied by transient absorption spectroscopy. Upon the selective excitation of crystalline P3HT at the absorption edge, no red shift of the singlet exciton band was observed with an elapse of time, suggesting singlet exciton dynamics in relatively homogeneous P3HT crystalline domains without downhill relaxation in the energetic disorder. Even under such selective excitation conditions, the annihilation rate coefficient γ(t) was still dependent on time, γ(t) ∝ t(-1/2), which is attributed to anisotropic exciton diffusion in P3HT crystalline domains. From the annihilation rate coefficient, the singlet exciton diffusion coefficient D and exciton diffusion length LD in the crystalline domains were evaluated to be 7.9 × 10(-3) cm(2) s(-1) and 20 nm, respectively. The origin of the time-dependent exciton dynamics is discussed in terms of dimensionality.

  6. The central domain of bovine submaxillary mucin consists of over 50 tandem repeats of 329 amino acids. Chromosomal localization of the BSM1 gene and relations to ovine and porcine counterparts.

    PubMed

    Jiang, W; Gupta, D; Gallagher, D; Davis, S; Bhavanandan, V P

    2000-04-01

    We previously elucidated five distinct protein domains (I-V) for bovine submaxillary mucin, which is encoded by two genes, BSM1 and BSM2. Using Southern blot analysis, genomic cloning and sequencing of the BSM1 gene, we now show that the central domain (V) consists of approximately 55 tandem repeats of 329 amino acids and that domains III-V are encoded by a 58.4-kb exon, the largest exon known for all genes to date. The BSM1 gene was mapped by fluorescence in situ hybridization to the proximal half of chromosome 5 at bands q2. 2-q2.3. The amino-acid sequence of six tandem repeats (two full and four partial) were found to have only 92-94% identities. We propose that the variability in the amino-acid sequences of the mucin tandem repeat is important for generating the combinatorial library of saccharides that are necessary for the protective function of mucins. The deduced peptide sequences of the central domain match those determined from the purified bovine submaxillary mucin and also show 68-94% identity to published peptide sequences of ovine submaxillary mucin. This indicates that the core protein of ovine submaxillary mucin is closely related to that of bovine submaxillary mucin and contains similar tandem repeats in the central domain. In contrast, the central domain of porcine submaxillary mucin is reported to consist of 81-amino-acid tandem repeats. However, both bovine submaxillary mucin and porcine submaxillary mucin contain similar N-terminal and C-terminal domains and the corresponding genes are in the conserved linkage regions of the respective genomes.

  7. A non-chromatographic protein purification strategy using Src 3 homology domains as generalized capture domains.

    PubMed

    Kim, Heejae; Chen, Wilfred

    2016-09-20

    Protein purification using inverse phase transition of elastin-like polypeptide (ELP) domains is a useful alternative to chromatography. Genetic fusions of ELP domains to various proteins have the ability to reversibly transition between soluble monomers and micron-sized aggregates and this has been used to selectively purify many ELP fusions. Affinity domains can enhance this technology by using specific protein binding domains to enable ELP mediated affinity capture (EMAC) of proteins of interest (POI) that have been fused to corresponding affinity ligands. In this paper, we highlight the use of Src homology 3 (SH3) domains and corresponding peptide ligands in EMAC that have differential binding affinities towards SH3 for efficient capture and elution of proteins. Furthermore, differences between capture and elution of a monomeric and a multimeric protein were also studied. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Multiple graph regularized protein domain ranking.

    PubMed

    Wang, Jim Jing-Yan; Bensmail, Halima; Gao, Xin

    2012-11-19

    Protein domain ranking is a fundamental task in structural biology. Most protein domain ranking methods rely on the pairwise comparison of protein domains while neglecting the global manifold structure of the protein domain database. Recently, graph regularized ranking that exploits the global structure of the graph defined by the pairwise similarities has been proposed. However, the existing graph regularized ranking methods are very sensitive to the choice of the graph model and parameters, and this remains a difficult problem for most of the protein domain ranking methods. To tackle this problem, we have developed the Multiple Graph regularized Ranking algorithm, MultiG-Rank. Instead of using a single graph to regularize the ranking scores, MultiG-Rank approximates the intrinsic manifold of protein domain distribution by combining multiple initial graphs for the regularization. Graph weights are learned with ranking scores jointly and automatically, by alternately minimizing an objective function in an iterative algorithm. Experimental results on a subset of the ASTRAL SCOP protein domain database demonstrate that MultiG-Rank achieves a better ranking performance than single graph regularized ranking methods and pairwise similarity based ranking methods. The problem of graph model and parameter selection in graph regularized protein domain ranking can be solved effectively by combining multiple graphs. This aspect of generalization introduces a new frontier in applying multiple graphs to solving protein domain ranking applications.

  9. Annealing effect on current-driven domain wall motion in Pt/[Co/Ni] wire

    NASA Astrophysics Data System (ADS)

    Furuta, Masaki; Liu, Yang; Sepehri-Amin, Hossein; Hono, Kazuhiro; Zhu, Jian-Gang Jimmy

    2017-09-01

    The annealing effect on the efficiency of current-driven domain wall motion governed by the spin Hall effect in perpendicularly magnetized Pt/[Co/Ni] wires is investigated experimentally. Important physical parameters, such as the Dzyaloshinskii-Moriya Interaction (DMI), spin Hall angle, and perpendicular anisotropy field strength, for the domain wall motion are all characterized at each annealing temperature. It is found that annealing of wires at temperatures over 120 °C causes significant reduction of the domain wall velocity. Energy dispersive X-ray spectroscopy analysis shows pronounced Co diffusion across the Pt/Co interface resulted from annealing at relatively high temperatures. The combined modeling study shows that the reduction of DMI caused by annealing is mostly responsible for the domain wall velocity reduction due to annealing.

  10. Structural Studies of the Tandem Tudor Domains of Fragile X Mental Retardation Related Proteins FXR1 and FXR2

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

    Adams-Cioaba, Melanie A.; Guo, Yahong; Bian, ChuanBing

    Expansion of the CGG trinucleotide repeat in the 5'-untranslated region of the FMR1, fragile X mental retardation 1, gene results in suppression of protein expression for this gene and is the underlying cause of Fragile X syndrome. In unaffected individuals, the FMRP protein, together with two additional paralogues (Fragile X Mental Retardation Syndrome-related Protein 1 and 2), associates with mRNA to form a ribonucleoprotein complex in the nucleus that is transported to dendrites and spines of neuronal cells. It is thought that the fragile X family of proteins contributes to the regulation of protein synthesis at sites where mRNAs aremore » locally translated in response to stimuli. Here, we report the X-ray crystal structures of the non-canonical nuclear localization signals of the FXR1 and FXR2 autosomal paralogues of FMRP, which were determined at 2.50 and 1.92 {angstrom}, respectively. The nuclear localization signals of the FXR1 and FXR2 comprise tandem Tudor domain architectures, closely resembling that of UHRF1, which is proposed to bind methylated histone H3K9. The FMRP, FXR1 and FXR2 proteins comprise a small family of highly conserved proteins that appear to be important in translational regulation, particularly in neuronal cells. The crystal structures of the N-terminal tandem Tudor domains of FXR1 and FXR2 revealed a conserved architecture with that of FMRP. Biochemical analysis of the tandem Tudor doamins reveals their ability to preferentially recognize trimethylated peptides in a sequence-specific manner.« less

  11. Dynamics and Predictability of The Eta Regional Model: The Role of Domain Size

    NASA Astrophysics Data System (ADS)

    Vannitsem, S.; Chomé, F.; Nicolis, C.

    This paper investigates the dynamical properties of the Eta model, a state-of-the- art nested limited-area model, following the approach previously developed by the present authors. It is first shown that the intrinsic dynamics of the model depends crucially on the size of the domain, with a non-chaotic behavior for small domains, supporting earlier findings on the absence of sensitivity to the initial conditions in these models. The quality of the predictions of several Eta model versions differing by their domain size is next evaluated and compared with the Avn analyses on a targeted region, centered on France. Contrary to what is usually taken for granted, a non-trivial relation between predictability and domain size is found, the best model versions be- ing the ones integrated on the smallest and the largest domain sizes. An explanation in connection with the intrinsic dynamics of the model is advanced.

  12. Correlation between the ripple phase and stripe domains in membranes.

    PubMed

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

    2011-12-01

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

  13. Time-Domain Stability Margin Assessment

    NASA Technical Reports Server (NTRS)

    Clements, Keith

    2016-01-01

    The baseline stability margins for NASA's Space Launch System (SLS) launch vehicle were generated via the classical approach of linearizing the system equations of motion and determining the gain and phase margins from the resulting frequency domain model. To improve the fidelity of the classical methods, the linear frequency domain approach can be extended by replacing static, memoryless nonlinearities with describing functions. This technique, however, does not address the time varying nature of the dynamics of a launch vehicle in flight. An alternative technique for the evaluation of the stability of the nonlinear launch vehicle dynamics along its trajectory is to incrementally adjust the gain and/or time delay in the time domain simulation until the system exhibits unstable behavior. This technique has the added benefit of providing a direct comparison between the time domain and frequency domain tools in support of simulation validation.

  14. Self-reported domain-specific and accelerometer-based physical activity and sedentary behaviour in relation to psychological distress among an urban Asian population.

    PubMed

    Chu, A H Y; van Dam, R M; Biddle, S J H; Tan, C S; Koh, D; Müller-Riemenschneider, F

    2018-04-05

    with less psychological distress using K6 (OR = 0.65 [0.43-0.97]; p-trend = 0.02) and GHQ-12 (OR = 0.72 [0.55-0.93]; p-trend = 0.01). Self-reported sedentary behaviour was not associated with K6 (p-trend = 0.90) and GHQ-12 (p-trend = 0.33). The highest tertile of accelerometry-assessed sedentary behaviour was associated with significantly higher odds for K6 (OR = 1.93 [1.00-3.75]; p-trend = 0.04), but not GHQ-12 (OR = 1.34 [0.86-2.08]; p-trend = 0.18). Higher levels of leisure-time physical activity and lower levels of accelerometer-based sedentary behaviour were associated with lower psychological distress. This study underscores the importance of assessing accelerometer-based and domain-specific activity in relation to mental health, instead of solely focusing on total volume of activity.

  15. Conformational instability of the MARK3 UBA domain compromises ubiquitin recognition and promotes interaction with the adjacent kinase domain

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

    Murphy, James M.; Korzhnev, Dmitry M.; Ceccarelli, Derek F.

    2012-10-23

    The Par-1/MARK protein kinases play a pivotal role in establishing cellular polarity. This family of kinases contains a unique domain architecture, in which a ubiquitin-associated (UBA) domain is located C-terminal to the kinase domain. We have used a combination of x-ray crystallography and NMR dynamics experiments to understand the interaction of the human (h) MARK3 UBA domain with the adjacent kinase domain as compared with ubiquitin. The x-ray crystal structure of the linked hMARK3 kinase and UBA domains establishes that the UBA domain forms a stable intramolecular interaction with the N-terminal lobe of the kinase domain. However, solution-state NMR studiesmore » of the isolated UBA domain indicate that it is highly dynamic, undergoing conformational transitions that can be explained by a folding-unfolding equilibrium. NMR titration experiments indicated that the hMARK3 UBA domain has a detectable but extremely weak affinity for mono ubiquitin, which suggests that conformational instability of the isolated hMARK3 UBA domain attenuates binding to ubiquitin despite the presence of residues typically involved in ubiquitin recognition. Our data identify a molecular mechanism through which the hMARK3 UBA domain has evolved to bind the kinase domain, in a fashion that stabilizes an open conformation of the N- and C-terminal lobes, at the expense of its capacity to engage ubiquitin. These results may be relevant more generally to the 30% of UBA domains that lack significant ubiquitin-binding activity, and they suggest a unique mechanism by which interaction domains may evolve new binding properties.« less

  16. Optimising predictor domains for spatially coherent precipitation downscaling

    NASA Astrophysics Data System (ADS)

    Radanovics, S.; Vidal, J.-P.; Sauquet, E.; Ben Daoud, A.; Bontron, G.

    2012-04-01

    Relationships between local precipitation (predictands) and large-scale circulation (predictors) are used for statistical downscaling purposes in various contexts, from medium-term forecasting to climate change impact studies. For hydrological purposes like flood forecasting, the downscaled precipitation spatial fields have furthermore to be coherent over possibly large basins. This thus first requires to know what predictor domain can be associated to the precipitation over each part of the studied basin. This study addresses this issue by identifying the optimum predictor domains over the whole of France, for a specific downscaling method based on a analogue approach and developed by Ben Daoud et al. (2011). The downscaling method used here is based on analogies on different variables: temperature, relative humidity, vertical velocity and geopotentials. The optimum predictor domain has been found to consist of the nearest grid cell for all variables except geopotentials (Ben Daoud et al., 2011). Moreover, geopotential domains have been found to be sensitive to the target location by Obled et al. (2002), and the present study thus focuses on optimizing the domains of this specific predictor over France. The predictor domains for geopotential at 500 hPa and 1000 hPa are optimised for 608 climatologically homogeneous zones in France using the ERA-40 reanalysis data for the large-scale predictors and local precipitation from the Safran near-surface atmospheric reanalysis (Vidal et al., 2010). The similarity of geopotential fields is measured by the Teweles and Wobus shape criterion. The predictive skill of different predictor domains for the different regions is tested with the Continuous Ranked Probability Score (CRPS) for the 25 best analogue days found with the statistical downscaling method. Rectangular predictor domains of different sizes, shapes and locations are tested, and the one that leads to the smallest CRPS for the zone in question is retained. The

  17. A de novo redesign of the WW domain.

    PubMed

    Kraemer-Pecore, Christina M; Lecomte, Juliette T J; Desjarlais, John R

    2003-10-01

    We have used a sequence prediction algorithm and a novel sampling method to design protein sequences for the WW domain, a small beta-sheet motif. The procedure, referred to as SPANS, designs sequences to be compatible with an ensemble of closely related polypeptide backbones, mimicking the inherent flexibility of proteins. Two designed sequences (termed SPANS-WW1 and SPANS-WW2), using only naturally occurring L-amino acids, were selected for study and the corresponding polypeptides were prepared in Escherichia coli. Circular dichroism data suggested that both purified polypeptides adopted secondary structure features related to those of the target without the aid of disulfide bridges or bound cofactors. The structure exhibited by SPANS-WW2 melted cooperatively by raising the temperature of the solution. Further analysis of this polypeptide by proton nuclear magnetic resonance spectroscopy demonstrated that at 5 degrees C, it folds into a structure closely resembling a natural WW domain. This achievement constitutes one of a small number of successful de novo protein designs through fully automated computational methods and highlights the feasibility of including backbone flexibility in the design strategy.

  18. Development of Veteran-Centric Competency Domains for Psychiatric-Mental Health Nurse Practitioner Residents.

    PubMed

    York, Janet; Sternke, Lisa Marie; Myrick, Donald Hugh; Lauerer, Joy; Hair, Carole

    2016-11-01

    The mental health needs of military service members, Veterans, and their families are a designated national priority; however, there has been little emphasis on the inclusion of Veteran-centric domains in competency-based nursing education for psychiatric-mental health nurse practitioners (PMHNPs). The current article describes the identification and application of Veteran-centric domains in an innovative pilot residency program for PMHNPs, funded by the Veterans Health Administration Office of Academic Affiliations. Fourteen Veteran-centric competency domains were developed from literature review, including knowledge, attitudes, and skill behaviors. Adoption and application of these domains in curricular components included the resident competency evaluation, baseline assessment of military experience, and evidence-based practice seminars and training. Methods of competency domain evaluation are presented, along with gaps related to the evaluation of competency skills. The delivery of mental health services reflecting these domains is consistent with the VA core values and goal of developing a positive service culture. [Journal of Psychosocial Nursing and Mental Health Services, 54(11), 31-36.]. Copyright 2016, SLACK Incorporated.

  19. Prefrontal contributions to domain-general executive control processes during temporal context retrieval.

    PubMed

    Rajah, M Natasha; Ames, Blaine; D'Esposito, Mark

    2008-03-07

    Neuroimaging studies have reported increased prefrontal cortex (PFC) activity during temporal context retrieval versus recognition memory. However, it remains unclear if these activations reflect PFC contributions to domain-general executive control processes or domain-specific retrieval processes. To gain a better understanding of the functional roles of these various PFC regions during temporal context retrieval we propose it is necessary to examine PFC activity across tasks from different domains, in which parallel manipulations are included targeting specific cognitive processes. In the current fMRI study, we examined domain-general and domain-specific PFC contributions to temporal context retrieval by increasing stimulus (but maintaining response number) and increasing response number (but maintaining stimulus number) across temporal context memory and ordering control tasks, for faces. The control task required subjects to order faces from youngest to oldest. Our behavioral results indicate that the combination of increased stimulus and response numbers significantly increased task difficulty for temporal context retrieval and ordering tasks. Across domains, increasing stimulus number, while maintaining response numbers, caused greater right lateral premotor cortex (BA 6/8) activity; whereas increasing response number, while maintaining stimulus number, caused greater domain-general left DLPFC (BA 9) and VLPFC (BA 44/45) activity. In addition, we found domain-specific right DLPFC (BA 9) activity only during retrieval events. These results highlight the functional heterogeneity of frontal cortex, and suggest its involvement in temporal context retrieval is related to its role in various cognitive control processes.

  20. Effect of dipolar moments in domain sizes of lipid bilayers and monolayers

    NASA Astrophysics Data System (ADS)

    Travesset, A.

    2006-08-01

    Lipid domains are found in systems such as multicomponent bilayer membranes and single component monolayers at the air-water interface. It was shown by Keller et al. [J. Phys. Chem. 91, 6417 (1987)] that in monolayers, the size of the domains results from balancing the line tension, which favors the formation of a large single circular domain, against the electrostatic cost of assembling the dipolar moments of the lipids. In this paper, we present an exact analytical expression for the electric potential, ion distribution, and electrostatic free energy for different problems consisting of three different slabs with different dielectric constants and Debye lengths, with a circular homogeneous dipolar density in the middle slab. From these solutions, we extend the calculation of domain sizes for monolayers to include the effects of finite ionic strength, dielectric discontinuities (or image charges), and the polarizability of the dipoles and further generalize the calculations to account for domains in lipid bilayers. In monolayers, the size of the domains is dependent on the different dielectric constants but independent of ionic strength. In asymmetric bilayers, where the inner and outer leaflets have different dipolar densities, domains show a strong size dependence with ionic strength, with molecular-sized domains that grow to macroscopic phase separation with increasing ionic strength. We discuss the implications of the results for experiments and briefly consider their relation to other two dimensional systems such as Wigner crystals or heteroepitaxial growth.

  1. Dual-domain point diffraction interferometer

    DOEpatents

    Naulleau, Patrick P.; Goldberg, Kenneth Alan

    2000-01-01

    A hybrid spatial/temporal-domain point diffraction interferometer (referred to as the dual-domain PS/PDI) that is capable of suppressing the scattered-reference-light noise that hinders the conventional PS/PDI is provided. The dual-domain PS/PDI combines the separate noise-suppression capabilities of the widely-used phase-shifting and Fourier-transform fringe pattern analysis methods. The dual-domain PS/PDI relies on both a more restrictive implementation of the image plane PS/PDI mask and a new analysis method to be applied to the interferograms generated and recorded by the modified PS/PDI. The more restrictive PS/PDI mask guarantees the elimination of spatial-frequency crosstalk between the signal and the scattered-light noise arising from scattered-reference-light interfering with the test beam. The new dual-domain analysis method is then used to eliminate scattered-light noise arising from both the scattered-reference-light interfering with the test beam and the scattered-reference-light interfering with the "true" pinhole-diffracted reference light. The dual-domain analysis method has also been demonstrated to provide performance enhancement when using the non-optimized standard PS/PDI design. The dual-domain PS/PDI is essentially a three-tiered filtering system composed of lowpass spatial-filtering the test-beam electric field using the more restrictive PS/PDI mask, bandpass spatial-filtering the individual interferogram irradiance frames making up the phase-shifting series, and bandpass temporal-filtering the phase-shifting series as a whole.

  2. Domain decomposition and matching for time-domain analysis of motions of ships advancing in head sea

    NASA Astrophysics Data System (ADS)

    Tang, Kai; Zhu, Ren-chuan; Miao, Guo-ping; Fan, Ju

    2014-08-01

    A domain decomposition and matching method in the time-domain is outlined for simulating the motions of ships advancing in waves. The flow field is decomposed into inner and outer domains by an imaginary control surface, and the Rankine source method is applied to the inner domain while the transient Green function method is used in the outer domain. Two initial boundary value problems are matched on the control surface. The corresponding numerical codes are developed, and the added masses, wave exciting forces and ship motions advancing in head sea for Series 60 ship and S175 containership, are presented and verified. A good agreement has been obtained when the numerical results are compared with the experimental data and other references. It shows that the present method is more efficient because of the panel discretization only in the inner domain during the numerical calculation, and good numerical stability is proved to avoid divergence problem regarding ships with flare.

  3. Time Domain Diffraction by Composite Structures

    NASA Astrophysics Data System (ADS)

    Riccio, Giovanni; Frongillo, Marcello

    2017-04-01

    Time domain (TD) diffraction problems are receiving great attention because of the widespread use of ultra wide band (UWB) communication and radar systems. It is commonly accepted that, due to the large bandwidth of the UWB signals, the analysis of the wave propagation mechanisms in the TD framework is preferable to the frequency domain (FD) data processing. Furthermore, the analysis of transient scattering phenomena is also of importance for predicting the effects of electromagnetic pulses on civil structures. Diffraction in the TD framework represents a challenging problem and numerical discretization techniques can be used to support research and industry activities. Unfortunately, these methods become rapidly intractable when considering excitation pulses with high frequency content. This contribution deals with the TD diffraction phenomenon related to composite structures containing a dielectric wedge with arbitrary apex angle when illuminated by a plane wave. The approach is the same used in [1]-[3]. The transient diffracted field originated by an arbitrary function plane wave is evaluated via a convolution integral involving the TD diffraction coefficients, which are determined in closed form starting from the knowledge of the corresponding FD counterparts. In particular, the inverse Laplace transform is applied to the FD Uniform Asymptotic Physical Optics (FD-UAPO) diffraction coefficients available for the internal region of the structure and the surrounding space. For each observation domain, the FD-UAPO expressions are obtained by considering electric and magnetic equivalent PO surface currents located on the interfaces. The surface radiation integrals using these sources is assumed as starting point and manipulated for obtaining integrals able to be solved by means of the Steepest Descent Method and the Multiplicative Method. [1] G. Gennarelli and G. Riccio, "Time domain diffraction by a right-angled penetrable wedge," IEEE Trans. Antennas Propag., Vol

  4. Neuronal differentiation of human mesenchymal stem cells in response to the domain size of graphene substrates.

    PubMed

    Lee, Yoo-Jung; Seo, Tae Hoon; Lee, Seula; Jang, Wonhee; Kim, Myung Jong; Sung, Jung-Suk

    2018-01-01

    Graphene is a noncytotoxic monolayer platform with unique physical, chemical, and biological properties. It has been demonstrated that graphene substrate may provide a promising biocompatible scaffold for stem cell therapy. Because chemical vapor deposited graphene has a two dimensional polycrystalline structure, it is important to control the individual domain size to obtain desirable properties for nano-material. However, the biological effects mediated by differences in domain size of graphene have not yet been reported. On the basis of the control of graphene domain achieved by one-step growth (1step-G, small domain) and two-step growth (2step-G, large domain) process, we found that the neuronal differentiation of bone marrow-derived human mesenchymal stem cells (hMSCs) highly depended on the graphene domain size. The defects at the domain boundaries in 1step-G graphene was higher (×8.5) and had a relatively low (13% lower) contact angle of water droplet than 2step-G graphene, leading to enhanced cell-substrate adhesion and upregulated neuronal differentiation of hMSCs. We confirmed that the strong interactions between cells and defects at the domain boundaries in 1step-G graphene can be obtained due to their relatively high surface energy, which is stronger than interactions between cells and graphene surfaces. Our results may provide valuable information on the development of graphene-based scaffold by understanding which properties of graphene domain influence cell adhesion efficacy and stem cell differentiation. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 43-51, 2018. © 2017 Wiley Periodicals, Inc.

  5. Ubiquitin-like domains can target to the proteasome but proteolysis requires a disordered region.

    PubMed

    Yu, Houqing; Kago, Grace; Yellman, Christopher M; Matouschek, Andreas

    2016-07-15

    Ubiquitin and some of its homologues target proteins to the proteasome for degradation. Other ubiquitin-like domains are involved in cellular processes unrelated to the proteasome, and proteins containing these domains remain stable in the cell. We find that the 10 yeast ubiquitin-like domains tested bind to the proteasome, and that all 11 identified domains can target proteins for degradation. Their apparent proteasome affinities are not directly related to their stabilities or functions. That is, ubiquitin-like domains in proteins not part of the ubiquitin proteasome system may bind the proteasome more tightly than domains in proteins that are bona fide components. We propose that proteins with ubiquitin-like domains have properties other than proteasome binding that confer stability. We show that one of these properties is the absence of accessible disordered regions that allow the proteasome to initiate degradation. In support of this model, we find that Mdy2 is degraded in yeast when a disordered region in the protein becomes exposed and that the attachment of a disordered region to Ubp6 leads to its degradation. © 2016 The Authors.

  6. Distinct Ubiquitin Binding Modes Exhibited by SH3 Domains: Molecular Determinants and Functional Implications

    PubMed Central

    Ortega Roldan, Jose L.; Casares, Salvador; Ringkjøbing Jensen, Malene; Cárdenes, Nayra; Bravo, Jerónimo; Blackledge, Martin; Azuaga, Ana I.; van Nuland, Nico A. J.

    2013-01-01

    SH3 domains constitute a new type of ubiquitin-binding domains. We previously showed that the third SH3 domain (SH3-C) of CD2AP binds ubiquitin in an alternative orientation. We have determined the structure of the complex between first CD2AP SH3 domain and ubiquitin and performed a structural and mutational analysis to decipher the determinants of the SH3-C binding mode to ubiquitin. We found that the Phe-to-Tyr mutation in CD2AP and in the homologous CIN85 SH3-C domain does not abrogate ubiquitin binding, in contrast to previous hypothesis and our findings for the first two CD2AP SH3 domains. The similar alternative binding mode of the SH3-C domains of these related adaptor proteins is characterised by a higher affinity to C-terminal extended ubiquitin molecules. We conclude that CD2AP/CIN85 SH3-C domain interaction with ubiquitin constitutes a new ubiquitin-binding mode involved in a different cellular function and thus changes the previously established mechanism of EGF-dependent CD2AP/CIN85 mono-ubiquitination. PMID:24039852

  7. Interpreting multiscale domains of tree cover disturbance patterns in North America

    Treesearch

    Kurt Riitters; Jennifer K. Costanza; Brian Buma

    2017-01-01

    Spatial patterns at multiple observation scales provide a framework to improve understanding of pattern-related phenomena. However, the metrics that are most sensitive to local patterns are least likely to exhibit consistent scaling relations with increasing extent (observation scale). A conceptual framework based on multiscale domains (i.e., geographic locations...

  8. Low Performance on Mathematical Tasks in Preschoolers: The Importance of Domain-General and Domain-Specific Abilities

    ERIC Educational Resources Information Center

    Costa, H. M.; Nicholson, B.; Donlan, C.; Van Herwegen, J.

    2018-01-01

    Background: Different domain-specific and domain-general cognitive precursors play a key role in the development of mathematical abilities. The contribution of these domains to mathematical ability changes during development. Primary school-aged children who show mathematical difficulties form a heterogeneous group, but it is not clear whether…

  9. Spectral identification of topological domains

    PubMed Central

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

    2016-01-01

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

  10. Rheological Models in the Time-Domain Modeling of Seismic Motion

    NASA Astrophysics Data System (ADS)

    Moczo, P.; Kristek, J.

    2004-12-01

    The time-domain stress-strain relation in a viscoelastic medium has a form of the convolutory integral which is numerically intractable. This was the reason for the oversimplified models of attenuation in the time-domain seismic wave propagation and earthquake motion modeling. In their pioneering work, Day and Minster (1984) showed the way how to convert the integral into numerically tractable differential form in the case of a general viscoelastic modulus. In response to the work by Day and Minster, Emmerich and Korn (1987) suggested using the rheology of their generalized Maxwell body (GMB) while Carcione et al. (1988) suggested using the generalized Zener body (GZB). The viscoelastic moduli of both rheological models have a form of the rational function and thus the differential form of the stress-strain relation is rather easy to obtain. After the papers by Emmerich and Korn and Carcione et al. numerical modelers decided either for the GMB or GZB rheology and developed 'non-communicating' algorithms. In the many following papers the authors using the GMB never commented the GZB rheology and the corresponding algorithms, and the authors using the GZB never related their methods to the GMB rheology and algorithms. We analyze and compare both rheologies and the corresponding incorporations of the realistic attenuation into the time-domain computations. We then focus on the most recent staggered-grid finite-difference modeling, mainly on accounting for the material heterogeneity in the viscoelastic media, and the computational efficiency of the finite-difference algorithms.

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

    PubMed

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

    2018-03-06

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

  12. Multiple graph regularized protein domain ranking

    PubMed Central

    2012-01-01

    Background Protein domain ranking is a fundamental task in structural biology. Most protein domain ranking methods rely on the pairwise comparison of protein domains while neglecting the global manifold structure of the protein domain database. Recently, graph regularized ranking that exploits the global structure of the graph defined by the pairwise similarities has been proposed. However, the existing graph regularized ranking methods are very sensitive to the choice of the graph model and parameters, and this remains a difficult problem for most of the protein domain ranking methods. Results To tackle this problem, we have developed the Multiple Graph regularized Ranking algorithm, MultiG-Rank. Instead of using a single graph to regularize the ranking scores, MultiG-Rank approximates the intrinsic manifold of protein domain distribution by combining multiple initial graphs for the regularization. Graph weights are learned with ranking scores jointly and automatically, by alternately minimizing an objective function in an iterative algorithm. Experimental results on a subset of the ASTRAL SCOP protein domain database demonstrate that MultiG-Rank achieves a better ranking performance than single graph regularized ranking methods and pairwise similarity based ranking methods. Conclusion The problem of graph model and parameter selection in graph regularized protein domain ranking can be solved effectively by combining multiple graphs. This aspect of generalization introduces a new frontier in applying multiple graphs to solving protein domain ranking applications. PMID:23157331

  13. Evaluation of Selected Binding Domains for the Analysis of Ubiquitinated Proteomes

    NASA Astrophysics Data System (ADS)

    Nakayasu, Ernesto S.; Ansong, Charles; Brown, Joseph N.; Yang, Feng; Lopez-Ferrer, Daniel; Qian, Wei-Jun; Smith, Richard D.; Adkins, Joshua N.

    2013-08-01

    Ubiquitination is an abundant post-translational modification that consists of covalent attachment of ubiquitin to lysine residues or the N-terminus of proteins. Mono- and polyubiquitination have been shown to be involved in many critical eukaryotic cellular functions and are often disrupted by intracellular bacterial pathogens. Affinity enrichment of ubiquitinated proteins enables global analysis of this key modification. In this context, the use of ubiquitin-binding domains is a promising but relatively unexplored alternative to more broadly used immunoaffinity or tagged affinity enrichment methods. In this study, we evaluated the application of eight ubiquitin-binding domains that have differing affinities for ubiquitination states. Small-scale proteomics analysis identified ~200 ubiquitinated protein candidates per ubiquitin-binding domain pull-down experiment. Results from subsequent Western blot analyses that employed anti-ubiquitin or monoclonal antibodies against polyubiquitination at lysine 48 and 63 suggest that ubiquitin-binding domains from Dsk2 and ubiquilin-1 have the broadest specificity in that they captured most types of ubiquitination, whereas the binding domain from NBR1 was more selective to polyubiquitination. These data demonstrate that with optimized purification conditions, ubiquitin-binding domains can be an alternative tool for proteomic applications. This approach is especially promising for the analysis of tissues or cells resistant to transfection, of which the overexpression of tagged ubiquitin is a major hurdle.

  14. Flexible DNA binding of the BTB/POZ-domain protein FBI-1.

    PubMed

    Pessler, Frank; Hernandez, Nouria

    2003-08-01

    POZ-domain transcription factors are characterized by the presence of a protein-protein interaction domain called the POZ or BTB domain at their N terminus and zinc fingers at their C terminus. Despite the large number of POZ-domain transcription factors that have been identified to date and the significant insights that have been gained into their cellular functions, relatively little is known about their DNA binding properties. FBI-1 is a BTB/POZ-domain protein that has been shown to modulate HIV-1 Tat trans-activation and to repress transcription of some cellular genes. We have used various viral and cellular FBI-1 binding sites to characterize the interaction of a POZ-domain protein with DNA in detail. We find that FBI-1 binds to inverted sequence repeats downstream of the HIV-1 transcription start site. Remarkably, it binds efficiently to probes carrying these repeats in various orientations and spacings with no particular rotational alignment, indicating that its interaction with DNA is highly flexible. Indeed, FBI-1 binding sites in the adenovirus 2 major late promoter, the c-fos gene, and the c-myc P1 and P2 promoters reveal variously spaced direct, inverted, and everted sequence repeats with the consensus sequence G(A/G)GGG(T/C)(C/T)(T/C)(C/T) for each repeat.

  15. Evaluation of selected binding domains for the analysis of ubiquitinated proteomes

    PubMed Central

    Nakayasu, Ernesto S.; Ansong, Charles; Brown, Joseph N.; Yang, Feng; Lopez-Ferrer, Daniel; Qian, Wei-Jun; Smith, Richard D.; Adkins, Joshua N.

    2013-01-01

    Ubiquitination is an abundant post-translational modification that consists of covalent attachment of ubiquitin to lysine residues or the N-terminus of proteins. Mono and polyubiquitination have been shown to be involved in many critical eukaryotic cellular functions and are often disrupted by intracellular bacterial pathogens. Affinity enrichment of ubiquitinated proteins enables global analysis of this key modification. In this context, the use of ubiquitin-binding domains is a promising, but relatively unexplored alternative to more broadly used immunoaffinity or tagged affinity enrichment methods. In this study, we evaluated the application of eight ubiquitin-binding domains that have differing affinities for ubiquitination states. Small-scale proteomics analysis identified ∼200 ubiquitinated protein candidates per ubiquitin-binding domain pull-down experiment. Results from subsequent Western blot analyses that employed anti-ubiquitin or monoclonal antibodies against polyubiquitination at lysine 48 and 63 suggest that ubiquitin-binding domains from Dsk2 and ubiquilin-1 have the broadest specificity in that they captured most types of ubiquitination, whereas the binding domain from NBR1 was more selective to polyubiquitination. These data demonstrate that with optimized purification conditions, ubiquitin-binding domains can be an alternative tool for proteomic applications. This approach is especially promising for the analysis of tissues or cells resistant to transfection, of which the overexpression of tagged ubiquitin is a major hurdle. PMID:23649778

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

    PubMed

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

    2018-04-01

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

  17. [Sex and gender: Two different scientific domains to be clarified].

    PubMed

    Fernández, Juan

    2010-05-01

    Nowadays, the word sex and its related terms (sexual differences, sexual roles and stereotypes), so common not long ago, seems to have been replaced by gender and its related terms (gender differences, gender roles and stereotypes). We can sometimes find both sex and gender sharing the same space in scientific articles, although referring to different domains. In this paper, I try to explain the need for a model that can integrate both of these complex domains of sex and gender, leading to two independent, although complementary, disciplines: Sexology and Genderology. In both cases, I start from a functional standpoint, which will give meaning to both disciplines' specificities, as it is meant to link contributions from different fields of knowledge. This approach can have consequences for research, education, the experience of women, men, and ambiguous individuals, and therapy.

  18. Structure-function relations in the NTPase domain of the antiviral tRNA ribotoxin Escherichia coli PrrC

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

    Meineke, Birthe; Shuman, Stewart, E-mail: s-shuman@ski.mskcc.org

    2012-06-05

    Breakage of tRNA by Escherichia coli anticodon nuclease PrrC (EcoPrrC) underlies a host antiviral response to phage T4 infection. Expression of EcoPrrC is cytocidal in yeast, signifying that PrrC ribotoxicity crosses phylogenetic domain boundaries. EcoPrrC consists of an N-terminal NTPase module that resembles ABC transporters and a C-terminal nuclease module that is sui generis. PrrC homologs are prevalent in many other bacteria. Here we report that Haemophilus influenzae PrrC is toxic in E. coli and yeast. To illuminate structure-activity relations, we conducted a new round of mutational analysis of EcoPrrC guided by primary structure conservation among toxic PrrC homologs. Wemore » indentify 17 candidate active site residues in the NTPase module that are essential for toxicity in yeast when EcoPrrC is expressed at high gene dosage. Their functions could be educed by integrating mutational data with the atomic structure of the transition-state complex of a homologous ABC protein.« less

  19. Interference between face and non-face domains of perceptual expertise: a replication and extension

    PubMed Central

    Curby, Kim M.; Gauthier, Isabel

    2014-01-01

    As car expertise increases, so does interference between the visual processing of faces and that of cars; this suggests performance trade-offs across domains of real-world expertise. Such interference between expert domains has been previously revealed in a relatively complex design, interleaving 2-back part-judgment task with faces and cars (Gauthier et al., 2003). However, the basis of this interference is unclear. Experiment 1A replicated the finding of interference between faces and cars, as a function of car expertise. Experiments 1B and 2 investigated the mechanisms underlying this effect by (1) providing baseline measures of performance and (2) assessing the specificity of this interference effect. Our findings support the presence of expertise-dependent interference between face and non-face domains of expertise. However, surprisingly, it is in the condition where faces are processed among cars with a disrupted configuration where expertise has a greater influence on faces. This finding highlights how expertise-related processing changes also occur for transformed objects of expertise and that such changes can also drive interference across domains of expertise. PMID:25346702

  20. Human-computer interface incorporating personal and application domains

    DOEpatents

    Anderson, Thomas G [Albuquerque, NM

    2011-03-29

    The present invention provides a human-computer interface. The interface includes provision of an application domain, for example corresponding to a three-dimensional application. The user is allowed to navigate and interact with the application domain. The interface also includes a personal domain, offering the user controls and interaction distinct from the application domain. The separation into two domains allows the most suitable interface methods in each: for example, three-dimensional navigation in the application domain, and two- or three-dimensional controls in the personal domain. Transitions between the application domain and the personal domain are under control of the user, and the transition method is substantially independent of the navigation in the application domain. For example, the user can fly through a three-dimensional application domain, and always move to the personal domain by moving a cursor near one extreme of the display.

  1. Human-computer interface incorporating personal and application domains

    DOEpatents

    Anderson, Thomas G.

    2004-04-20

    The present invention provides a human-computer interface. The interface includes provision of an application domain, for example corresponding to a three-dimensional application. The user is allowed to navigate and interact with the application domain. The interface also includes a personal domain, offering the user controls and interaction distinct from the application domain. The separation into two domains allows the most suitable interface methods in each: for example, three-dimensional navigation in the application domain, and two- or three-dimensional controls in the personal domain. Transitions between the application domain and the personal domain are under control of the user, and the transition method is substantially independent of the navigation in the application domain. For example, the user can fly through a three-dimensional application domain, and always move to the personal domain by moving a cursor near one extreme of the display.

  2. Creating and Manipulating a Domain-Specific Formal Object Base to Support a Domain-Oriented Application Composition System

    DTIC Science & Technology

    1992-12-01

    and add new attributes as needed (11:129). 2.2.3.2 Feature Oriented Domain Analysis In their Feature-Oriented Domain Analysis ( FODA ) study, the...dissertation, The University of Texas at Austin, Austin Texas, 1990. 12. Kang, Kyo C. and others. Feature-Oriented Domain Analysis ( FODA ) Feasibil- ity Study...2-1 2.2.2 Requirements Languages ..................... 2-2 2.2.3 Domain Analysis ............................ 2-3 2.2.4

  3. In Situ Visualization of Lipid Raft Domains by Fluorescent Glycol Chitosan Derivatives.

    PubMed

    Jiang, Yao-Wen; Guo, Hao-Yue; Chen, Zhan; Yu, Zhi-Wu; Wang, Zhifei; Wu, Fu-Gen

    2016-07-05

    Lipid rafts are highly ordered small microdomains mainly composed of glycosphingolipids, cholesterol, and protein receptors. Optically distinguishing lipid raft domains in cell membranes would greatly facilitate the investigations on the structure and dynamics of raft-related cellular behaviors, such as signal transduction, membrane transport (endocytosis), adhesion, and motility. However, current strategies about the visualization of lipid raft domains usually suffer from the low biocompatibility of the probes, invasive detection, or ex situ observation. At the same time, naturally derived biomacromolecules have been extensively used in biomedical field and their interaction with cells remains a long-standing topic since it is closely related to various fundamental studies and potential applications. Herein, noninvasive visualization of lipid raft domains in model lipid bilayers (supported lipid bilayers and giant unilamellar vesicles) and live cells was successfully realized in situ using fluorescent biomacromolecules: the fluorescein isothiocyanate (FITC)-labeled glycol chitosan molecules. We found that the lipid raft domains in model or real membranes could be specifically stained by the FITC-labeled glycol chitosan molecules, which could be attributed to the electrostatic attractive interaction and/or hydrophobic interaction between the probes and the lipid raft domains. Since the FITC-labeled glycol chitosan molecules do not need to completely insert into the lipid bilayer and will not disturb the organization of lipids, they can more accurately visualize the raft domains as compared with other fluorescent dyes that need to be premixed with the various lipid molecules prior to the fabrication of model membranes. Furthermore, the FITC-labeled glycol chitosan molecules were found to be able to resist cellular internalization and could successfully visualize rafts in live cells. The present work provides a new way to achieve the imaging of lipid rafts and also

  4. The Separate, Relative, and Joint Effects of Employee Job Performance Domains on Supervisors' Willingness to Mentor

    ERIC Educational Resources Information Center

    Lapierre, Laurent M.; Bonaccio, Silvia; Allen, Tammy D.

    2009-01-01

    The purpose of our study was to further elucidate how employees should behave at work to increase their chances of being mentored by their immediate supervisor. To that end, we experimentally tested how three domains of employee performance [task performance (TP), organizational citizenship behavior (OCB) targeting the supervisor, and…

  5. Domain-Specificity of Self-Concept and Parent Expectation Influences on Short-Term and Long-Term Learning of Physics

    ERIC Educational Resources Information Center

    Yeung, Alexander Seeshing; Kuppan, Loganantham; Foong, See Kit; Wong, Darren Jon Sien; Kadir, Munirah Shaik; Lee, Paul Choon Keat; Yau, Che Ming

    2010-01-01

    Background: Students' academic self-concepts are known to be domain specific. Researchers have also identified two related components of self-concept:cognitive (how competent students feel about a subject domain) and affective (their interest in the subject). This paper examines whether both components are domain specific. Research has also shown…

  6. Domain size and structure in exchange coupled [Co/Pt]/NiO/[Co/Pt] multilayers.

    PubMed

    Baruth, A; Adenwalla, S

    2011-09-21

    We investigate the competing effects of interlayer exchange coupling and magnetostatic coupling in the magnetic heterostructure ([Co/Pt]/NiO/[Co/Pt]) with perpendicular magnetic anisotropy (PMA). This particular heterostructure is unique among coupled materials with PMA in directly exhibiting both ferromagnetic and antiferromagnetic coupling, oscillating between the two as a function of spacer layer thickness. By systematically tuning the coupling interactions via a wedge-shaped NiO spacer layer, we explore the energetics that dictate magnetic domain formation using high resolution magnetic force microscopy coupled with the magneto-optical Kerr effect. This technique probes the microscopic and macroscopic magnetic behavior as a continuous function of thickness and the interlayer exchange coupling, including the regions where interlayer coupling goes through zero. We see significant changes in domain structure based on the sign of coupling, and also show that magnetic domain size is directly related to the magnitude of the interlayer exchange coupling energy, which generally dominates over the magnetostatic interactions. When magnetostatic interactions become comparable to the interlayer exchange coupling, a delicate interplay between the differing energy contributions is apparent and energy scales are extracted. The results are of intense interest to the magnetic recording industry and also illustrate a relatively new avenue of undiscovered physics, primarily dealing with the delicate balance of energies in the formation of magnetic domains for coupled systems with PMA, defining limits on domain size as well as the interplay between roughness, domains and magnetic coupling.

  7. Age-Related Differences in Longitudinal Structural Change by Spectral-Domain Optical Coherence Tomography in Early Experimental Glaucoma

    PubMed Central

    Yang, Hongli; He, Lin; Gardiner, Stuart K.; Reynaud, Juan; Williams, Galen; Hardin, Christy; Strouthidis, Nicholas G.; Downs, J. Crawford; Fortune, Brad; Burgoyne, Claude F.

    2014-01-01

    Purpose. To characterize age-related differences in the magnitude of spectral-domain optical coherence tomography (SD-OCT) structural change in early experimental glaucoma (EG). Methods. Both eyes from four young (1.4–2.6 years) and four old (18.6–21.9 years) rhesus monkeys were imaged at least three times at baseline, and then every 2 weeks after laser-induced, chronic, unilateral IOP elevation until the onset of EG (confocal scanning laser tomographic surface change confirmed twice). Two to 20 weeks after EG onset, animals were euthanized and optic nerve axon counts for all eyes were performed. Masked operators delineated retinal and ONH landmarks in 40 radial B-scans from each eye and imaging session to quantify change from baseline in five SD-OCT neural and connective tissue parameters. The effects of EG, age, and EG × age interactions on the magnitude, rate (magnitude per postlaser time), and IOP responsiveness (magnitude per cumulative IOP insult) of postlaser parameter change were individually assessed using general estimating equation models. Results. Presac SD-OCT RNFLT and minimum rim width change and postmortem axon loss was not significantly different in old compared with young EG eyes. The rate of change and IOP responsiveness of the parameters anterior lamina cribrosa surface depth relative to Bruch's membrane opening (BMO) and BMO depth relative to peripheral Bruch's membrane were significantly lower (P < 0.05) in the old compared with the young EG eyes. Conclusions. At similar postlaser times, levels of cumulative IOP insult and axonal damage, SD-OCT–detected ONH connective tissue structural change is greater in young compared with old monkey EG eyes. PMID:25190652

  8. Structure of a two-CAP-domain protein from the human hookworm parasite Necator americanus

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

    Asojo, Oluwatoyin A., E-mail: oasojo@unmc.edu

    2011-05-01

    The first structure of a two-CAP-domain protein, Na-ASP-1, from the major human hookworm parasite N. americanus refined to a resolution limit of 2.2 Å is presented. Major proteins secreted by the infective larval stage hookworms upon host entry include Ancylostoma secreted proteins (ASPs), which are characterized by one or two CAP (cysteine-rich secretory protein/antigen 5/pathogenesis related-1) domains. The CAP domain has been reported in diverse phylogenetically unrelated proteins, but has no confirmed function. The first structure of a two-CAP-domain protein, Na-ASP-1, from the major human hookworm parasite Necator americanus was refined to a resolution limit of 2.2 Å. The structuremore » was solved by molecular replacement (MR) using Na-ASP-2, a one-CAP-domain ASP, as the search model. The correct MR solution could only be obtained by truncating the polyalanine model of Na-ASP-2 and removing several loops. The structure reveals two CAP domains linked by an extended loop. Overall, the carboxyl-terminal CAP domain is more similar to Na-ASP-2 than to the amino-terminal CAP domain. A large central cavity extends from the amino-terminal CAP domain to the carboxyl-terminal CAP domain, encompassing the putative CAP-binding cavity. The putative CAP-binding cavity is a characteristic cavity in the carboxyl-terminal CAP domain that contains a His and Glu pair. These residues are conserved in all single-CAP-domain proteins, but are absent in the amino-terminal CAP domain. The conserved His residues are oriented such that they appear to be capable of directly coordinating a zinc ion as observed for CAP proteins from reptile venoms. This first structure of a two-CAP-domain ASP can serve as a template for homology modeling of other two-CAP-domain proteins.« less

  9. Modeling Protein Domain Function

    ERIC Educational Resources Information Center

    Baker, William P.; Jones, Carleton "Buck"; Hull, Elizabeth

    2007-01-01

    This simple but effective laboratory exercise helps students understand the concept of protein domain function. They use foam beads, Styrofoam craft balls, and pipe cleaners to explore how domains within protein active sites interact to form a functional protein. The activity allows students to gain content mastery and an understanding of the…

  10. Mechanism of Mediator recruitment by tandem Gcn4 activation domains and three Gal11 activator-binding domains.

    PubMed

    Herbig, Eric; Warfield, Linda; Fish, Lisa; Fishburn, James; Knutson, Bruce A; Moorefield, Beth; Pacheco, Derek; Hahn, Steven

    2010-05-01

    Targets of the tandem Gcn4 acidic activation domains in transcription preinitiation complexes were identified by site-specific cross-linking. The individual Gcn4 activation domains cross-link to three common targets, Gal11/Med15, Taf12, and Tra1, which are subunits of four conserved coactivator complexes, Mediator, SAGA, TFIID, and NuA4. The Gcn4 N-terminal activation domain also cross-links to the Mediator subunit Sin4/Med16. The contribution of the two Gcn4 activation domains to transcription was gene specific and varied from synergistic to less than additive. Gcn4-dependent genes had a requirement for Gal11 ranging from 10-fold dependence to complete Gal11 independence, while the Gcn4-Taf12 interaction did not significantly contribute to the expression of any gene studied. Complementary methods identified three conserved Gal11 activator-binding domains that bind each Gcn4 activation domain with micromolar affinity. These Gal11 activator-binding domains contribute additively to transcription activation and Mediator recruitment at Gcn4- and Gal11-dependent genes. Although we found that the conserved Gal11 KIX domain contributes to Gal11 function, we found no evidence of specific Gcn4-KIX interaction and conclude that the Gal11 KIX domain does not function by specific interaction with Gcn4. Our combined results show gene-specific coactivator requirements, a surprising redundancy in activator-target interactions, and an activator-coactivator interaction mediated by multiple low-affinity protein-protein interactions.

  11. A probabilistic model for detecting rigid domains in protein structures.

    PubMed

    Nguyen, Thach; Habeck, Michael

    2016-09-01

    Large-scale conformational changes in proteins are implicated in many important biological functions. These structural transitions can often be rationalized in terms of relative movements of rigid domains. There is a need for objective and automated methods that identify rigid domains in sets of protein structures showing alternative conformational states. We present a probabilistic model for detecting rigid-body movements in protein structures. Our model aims to approximate alternative conformational states by a few structural parts that are rigidly transformed under the action of a rotation and a translation. By using Bayesian inference and Markov chain Monte Carlo sampling, we estimate all parameters of the model, including a segmentation of the protein into rigid domains, the structures of the domains themselves, and the rigid transformations that generate the observed structures. We find that our Gibbs sampling algorithm can also estimate the optimal number of rigid domains with high efficiency and accuracy. We assess the power of our method on several thousand entries of the DynDom database and discuss applications to various complex biomolecular systems. The Python source code for protein ensemble analysis is available at: https://github.com/thachnguyen/motion_detection : mhabeck@gwdg.de. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Repetitive Domain-Referenced Testing Using Computers: the TITA System.

    ERIC Educational Resources Information Center

    Olympia, P. L., Jr.

    The TITA (Totally Interactive Testing and Analysis) System algorithm for the repetitive construction of domain-referenced tests utilizes a compact data bank, is highly portable, is useful in any discipline, requires modest computer hardware, and does not present a security problem. Clusters of related keyphrases, statement phrases, and distractors…

  13. Interaction Between the Biotin Carboxyl Carrier Domain and the Biotin Carboxylase Domain in Pyruvate Carboxylase from Rhizobium etli†

    PubMed Central

    Lietzan, Adam D.; Menefee, Ann L.; Zeczycki, Tonya N.; Kumar, Sudhanshu; Attwood, Paul V.; Wallace, John C.; Cleland, W. Wallace; Maurice, Martin St.

    2011-01-01

    Pyruvate carboxylase (PC) catalyzes the ATP-dependent carboxylation of pyruvate to oxaloacetate, an important anaplerotic reaction in mammalian tissues. To effect catalysis, the tethered biotin of PC must gain access to active sites in both the biotin carboxylase domain and the carboxyl transferase domain. Previous studies have demonstrated that a mutation of threonine 882 to alanine in PC from Rhizobium etli renders the carboxyl transferase domain inactive and favors the positioning of biotin in the biotin carboxylase domain. We report the 2.4 Å resolution X-ray crystal structure of the Rhizobium etli PC T882A mutant which reveals the first high-resolution description of the domain interaction between the biotin carboxyl carrier protein domain and the biotin carboxylase domain. The overall quaternary arrangement of Rhizobium etli PC remains highly asymmetrical and is independent of the presence of allosteric activator. While biotin is observed in the biotin carboxylase domain, its access to the active site is precluded by the interaction between Arg353 and Glu248, revealing a mechanism for regulating carboxybiotin access to the BC domain active site. The binding location for the biotin carboxyl carrier protein domain demonstrates that tethered biotin cannot bind in the biotin carboxylase domain active site in the same orientation as free biotin, helping to explain the difference in catalysis observed between tethered biotin and free biotin substrates in biotin carboxylase enzymes. Electron density located in the biotin carboxylase domain active site is assigned to phosphonoacetate, offering a probable location for the putative carboxyphosphate intermediate formed during biotin carboxylation. The insights gained from the T882A Rhizobium etli PC crystal structure provide a new series of catalytic snapshots in PC and offer a revised perspective on catalysis in the biotin-dependent enzyme family. PMID:21958016

  14. Embedding Open-domain Common-sense Knowledge from Text

    PubMed Central

    Goodwin, Travis; Harabagiu, Sanda

    2017-01-01

    Our ability to understand language often relies on common-sense knowledge – background information the speaker can assume is known by the reader. Similarly, our comprehension of the language used in complex domains relies on access to domain-specific knowledge. Capturing common-sense and domain-specific knowledge can be achieved by taking advantage of recent advances in open information extraction (IE) techniques and, more importantly, of knowledge embeddings, which are multi-dimensional representations of concepts and relations. Building a knowledge graph for representing common-sense knowledge in which concepts discerned from noun phrases are cast as vertices and lexicalized relations are cast as edges leads to learning the embeddings of common-sense knowledge accounting for semantic compositionality as well as implied knowledge. Common-sense knowledge is acquired from a vast collection of blogs and books as well as from WordNet. Similarly, medical knowledge is learned from two large sets of electronic health records. The evaluation results of these two forms of knowledge are promising: the same knowledge acquisition methodology based on learning knowledge embeddings works well both for common-sense knowledge and for medical knowledge Interestingly, the common-sense knowledge that we have acquired was evaluated as being less neutral than than the medical knowledge, as it often reflected the opinion of the knowledge utterer. In addition, the acquired medical knowledge was evaluated as more plausible than the common-sense knowledge, reflecting the complexity of acquiring common-sense knowledge due to the pragmatics and economicity of language. PMID:28649676

  15. Design of a Low-Cost Adaptive Question Answering System for Closed Domain Factoid Queries

    ERIC Educational Resources Information Center

    Toh, Huey Ling

    2010-01-01

    Closed domain question answering (QA) systems achieve precision and recall at the cost of complex language processing techniques to parse the answer corpus. We propose a "query-based" model for indexing answers in a closed domain factoid QA system. Further, we use a phrase term inference method for improving the ranking order of related questions.…

  16. The Personality Domains and Styles of the Five-Factor Model are Related to Incident Depression in Medicare Recipients Aged 65 to 100

    PubMed Central

    Weiss, Alexander; Sutin, Angelina R.; Duberstein, Paul R.; Friedman, Bruce; Bagby, R. Michael; Costa, Paul T.

    2009-01-01

    Objectives Few prospective studies have examined personality and depression in older adults. We investigated whether the Five Factor Model (FFM) of personality traits --- Neuroticism, Extraversion, Openness to Experience, Agreeableness, and Conscientiousness --- and trait combinations (styles) are related to incident major or minor depression. Participants/Setting Prospective data were gathered on a community sample of 512 older adults with disability and a history of significant health care utilization who were enrolled in a Medicare Demonstration Project. Measurements Depression and personality traits and styles were assessed at baseline; depression was assessed again at approximately 12 and 22 months. Design Participants who developed incident major depression were compared to those free of depression at all three assessments. Similar analyses were done for minor depression. Results High Neuroticism and low Conscientiousness were risk factors for both major and minor depression. Combinations of high Neuroticism with low or high Extraversion or high Openness conferred risk for major depression. Other novel findings for major depression revealed new trait combinations of low Conscientiousness with low or high Extraversion, high Openness, or low Agreeableness. Three trait combinations, all involving low Conscientiousness, predicted risk for minor depression: high Neuroticism, high Agreeableness, and low Openness. Conclusion The present findings highlight the importance of examining combinations of personality traits or personality styles when identifying those who are most at-risk for geriatric depression. Since other personality domains may modify the risk related to high Neuroticism and low Conscientiousness, the prevention, diagnosis, and treatment of depression could be greatly improved by assessing older patients not only on all five domains of personality but in terms of their combinations. PMID:19554673

  17. A thermodynamic definition of protein domains.

    PubMed

    Porter, Lauren L; Rose, George D

    2012-06-12

    Protein domains are conspicuous structural units in globular proteins, and their identification has been a topic of intense biochemical interest dating back to the earliest crystal structures. Numerous disparate domain identification algorithms have been proposed, all involving some combination of visual intuition and/or structure-based decomposition. Instead, we present a rigorous, thermodynamically-based approach that redefines domains as cooperative chain segments. In greater detail, most small proteins fold with high cooperativity, meaning that the equilibrium population is dominated by completely folded and completely unfolded molecules, with a negligible subpopulation of partially folded intermediates. Here, we redefine structural domains in thermodynamic terms as cooperative folding units, based on m-values, which measure the cooperativity of a protein or its substructures. In our analysis, a domain is equated to a contiguous segment of the folded protein whose m-value is largely unaffected when that segment is excised from its parent structure. Defined in this way, a domain is a self-contained cooperative unit; i.e., its cooperativity depends primarily upon intrasegment interactions, not intersegment interactions. Implementing this concept computationally, the domains in a large representative set of proteins were identified; all exhibit consistency with experimental findings. Specifically, our domain divisions correspond to the experimentally determined equilibrium folding intermediates in a set of nine proteins. The approach was also proofed against a representative set of 71 additional proteins, again with confirmatory results. Our reframed interpretation of a protein domain transforms an indeterminate structural phenomenon into a quantifiable molecular property grounded in solution thermodynamics.

  18. A multi-domain spectral method for time-fractional differential equations

    NASA Astrophysics Data System (ADS)

    Chen, Feng; Xu, Qinwu; Hesthaven, Jan S.

    2015-07-01

    This paper proposes an approach for high-order time integration within a multi-domain setting for time-fractional differential equations. Since the kernel is singular or nearly singular, two main difficulties arise after the domain decomposition: how to properly account for the history/memory part and how to perform the integration accurately. To address these issues, we propose a novel hybrid approach for the numerical integration based on the combination of three-term-recurrence relations of Jacobi polynomials and high-order Gauss quadrature. The different approximations used in the hybrid approach are justified theoretically and through numerical examples. Based on this, we propose a new multi-domain spectral method for high-order accurate time integrations and study its stability properties by identifying the method as a generalized linear method. Numerical experiments confirm hp-convergence for both time-fractional differential equations and time-fractional partial differential equations.

  19. Protein domain evolution is associated with reproductive diversification and adaptive radiation in the genus Eucalyptus.

    PubMed

    Kersting, Anna R; Mizrachi, Eshchar; Bornberg-Bauer, Erich; Myburg, Alexander A

    2015-06-01

    Eucalyptus is a pivotal genus within the rosid order Myrtales with distinct geographic history and adaptations. Comparative analysis of protein domain evolution in the newly sequenced Eucalyptus grandis genome and other rosid lineages sheds light on the adaptive mechanisms integral to the success of this genus of woody perennials. We reconstructed the ancestral domain content to elucidate the gain, loss and expansion of protein domains and domain arrangements in Eucalyptus in the context of rosid phylogeny. We used functional gene ontology (GO) annotation of genes to investigate the possible biological and evolutionary consequences of protein domain expansion. We found that protein modulation within the angiosperms occurred primarily on the level of expansion of certain domains and arrangements. Using RNA-Seq data from E. grandis, we showed that domain expansions have contributed to tissue-specific expression of tandemly duplicated genes. Our results indicate that tandem duplication of genes, a key feature of the Eucalyptus genome, has played an important role in the expansion of domains, particularly in proteins related to the specialization of reproduction and biotic and abiotic interactions affecting root and floral biology, and that tissue-specific expression of proteins with expanded domains has facilitated subfunctionalization in domain families. © 2014 University of Pretoria New Phytologist © 2014 New Phytologist Trust.

  20. Independent Structural Domains in Paramyxovirus Polymerase Protein*

    PubMed Central

    Dochow, Melanie; Krumm, Stefanie A.; Crowe, James E.; Moore, Martin L.; Plemper, Richard K.

    2012-01-01

    All enzymatic activities required for genomic replication and transcription of nonsegmented negative strand RNA viruses (or Mononegavirales) are believed to be concentrated in the viral polymerase (L) protein. However, our insight into the organization of these different enzymatic activities into a bioactive tertiary structure remains rudimentary. Fragments of Mononegavirales polymerases analyzed to date cannot restore bioactivity through trans-complementation, unlike the related L proteins of segmented NSVs. We investigated the domain organization of phylogenetically diverse Paramyxovirus L proteins derived from measles virus (MeV), Nipah virus (NiV), and respiratory syncytial virus (RSV). Through a comprehensive in silico and experimental analysis of domain intersections, we defined MeV L position 615 as an interdomain candidate in addition to the previously reported residue 1708. Only position 1708 of MeV and the homologous positions in NiV and RSV L also tolerated the insertion of epitope tags. Splitting of MeV L at residue 1708 created fragments that were unable to physically interact and trans-complement, but strikingly, these activities were reconstituted by the addition of dimerization tags to the fragments. Equivalently split fragments of NiV, RSV, and MeV L oligomerized with comparable efficiency in all homo- and heterotypic combinations, but only the homotypic pairs were able to trans-complement. These results demonstrate that synthesis as a single polypeptide is not required for the Mononegavirales polymerases to adopt a proper tertiary conformation. Paramyxovirus polymerases are composed of at least two truly independent folding domains that lack a traditional interface but require molecular compatibility for bioactivity. The functional probing of the L domain architecture through trans-complementation is anticipated to be applicable to all Mononegavirales polymerases. PMID:22215662

  1. The ability of GAP1IP4BP to function as a Rap1 GTPase-activating protein (GAP) requires its Ras GAP-related domain and an arginine finger rather than an asparagine thumb.

    PubMed

    Kupzig, Sabine; Bouyoucef-Cherchalli, Dalila; Yarwood, Sam; Sessions, Richard; Cullen, Peter J

    2009-07-01

    GAP1(IP4BP) is a member of the GAP1 family of Ras GTPase-activating proteins (GAPs) that includes GAP1(m), CAPRI, and RASAL. Composed of a central Ras GAP-related domain (RasGRD), surrounded by amino-terminal C2 domains and a carboxy-terminal PH/Btk domain, these proteins, with the notable exception of GAP1(m), possess an unexpected arginine finger-dependent GAP activity on the Ras-related protein Rap1 (S. Kupzig, D. Deaconescu, D. Bouyoucef, S. A. Walker, Q. Liu, C. L. Polte, O. Daumke, T. Ishizaki, P. J. Lockyer, A. Wittinghofer, and P. J. Cullen, J. Biol. Chem. 281:9891-9900, 2006). Here, we have examined the mechanism through which GAP1(IP4BP) can function as a Rap1 GAP. We show that deletion of domains on either side of the RasGRD, while not affecting Ras GAP activity, do dramatically perturb Rap1 GAP activity. By utilizing GAP1(IP4BP)/GAP1(m) chimeras, we establish that although the C2 and PH/Btk domains are required to stabilize the RasGRD, it is this domain which contains the catalytic machinery required for Rap1 GAP activity. Finally, a key residue in Rap1-specific GAPs is a catalytic asparagine, the so-called asparagine thumb. By generating a molecular model describing the predicted Rap1-binding site in the RasGRD of GAP1(IP4BP), we show that mutagenesis of individual asparagine or glutamine residues that lie in close proximity to the predicted binding site has no detectable effect on the in vivo Rap1 GAP activity of GAP1(IP4BP). In contrast, we present evidence consistent with a model in which the RasGRD of GAP1(IP4BP) functions to stabilize the switch II region of Rap1, allowing stabilization of the transition state during GTP hydrolysis initiated by the arginine finger.

  2. Quantifying behavioural determinants relating to health professional reporting of medication errors: a cross-sectional survey using the Theoretical Domains Framework.

    PubMed

    Alqubaisi, Mai; Tonna, Antonella; Strath, Alison; Stewart, Derek

    2016-11-01

    The aims of this study were to quantify the behavioural determinants of health professional reporting of medication errors in the United Arab Emirates (UAE) and to explore any differences between respondents. A cross-sectional survey of patient-facing doctors, nurses and pharmacists within three major hospitals of Abu Dhabi, the UAE. An online questionnaire was developed based on the Theoretical Domains Framework (TDF, a framework of behaviour change theories). Principal component analysis (PCA) was used to identify components and internal reliability determined. Ethical approval was obtained from a UK university and all hospital ethics committees. Two hundred and ninety-four responses were received. Questionnaire items clustered into six components of knowledge and skills, feedback and support, action and impact, motivation, effort and emotions. Respondents generally gave positive responses for knowledge and skills, feedback and support and action and impact components. Responses were more neutral for the motivation and effort components. In terms of emotions, the component with the most negative scores, there were significant differences in terms of years registered as health professional (those registered longest most positive, p = 0.002) and age (older most positive, p < 0.001) with no differences for gender and health profession. Emotional-related issues are the dominant barrier to reporting and are common to all professions. There is a need to develop, test and implement an intervention to impact health professionals' emotions. Such an intervention should focus on evidence-based behaviour change techniques of reducing negative emotions, focusing on emotional consequences and providing social support. • This research used the Theoretical Domains Framework to quantify the behavioural determinants of health professional reporting of medication errors. • Questionnaire items relating to emotions surrounding reporting generated the most negative responses

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

    PubMed

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

    2018-02-01

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

  4. Differential structural properties of GLP-1 and exendin-4 determine their relative affinity for the GLP-1 receptor N-terminal extracellular domain.

    PubMed

    Runge, Steffen; Schimmer, Susann; Oschmann, Jan; Schiødt, Christine Bruun; Knudsen, Sanne Möller; Jeppesen, Claus Bekker; Madsen, Kjeld; Lau, Jesper; Thøgersen, Henning; Rudolph, Rainer

    2007-05-15

    Glucagon-like peptide-1 (GLP-1) and exendin-4 (Ex4) are homologous peptides with established potential for treatment of type 2 diabetes. They bind and activate the pancreatic GLP-1 receptor (GLP-1R) with similar affinity and potency and thereby promote insulin secretion in a glucose-dependent manner. GLP-1R belongs to family B of the seven transmembrane G-protein coupled receptors. The N-terminal extracellular domain (nGLP-1R) is a ligand binding domain with differential affinity for Ex4 and GLP-1: low affinity for GLP-1 and high affinity for exendin-4. The superior affinity of nGLP-1R for Ex4 was previously explained by an additional interaction between nGLP-1R and the C-terminal Trp-cage of Ex4. In this study we have combined biophysical and pharmacological approaches thus relating structural properties of the ligands in solution to their relative binding affinity for nGLP-1R. We used both a tracer competition assay and ligand-induced thermal stabilization of nGLP-1R to measure the relative affinity of full length, truncated, and chimeric ligands for soluble refolded nGLP-1R. The ligands in solution and the conformational consequences of ligand binding to nGLP-1R were characterized by circular dichroism and fluorescence spectroscopy. We found a correlation between the helical content of the free ligands and their relative binding affinity for nGLP-1R, supporting the hypothesis that the ligands are helical at least in the segment that binds to nGLP-1R. The Trp-cage of Ex4 was not necessary to maintain a superior helicity of Ex4 compared to GLP-1. The results suggest that the differential affinity of nGLP-1R is explained almost entirely by divergent residues in the central part of the ligands: Leu10-Gly30 of Ex4 and Val16-Arg36 of GLP-1. In view of our results it appears that the Trp-cage plays only a minor role for the interaction between Ex4 and nGLP-1R and for the differential affinity of nGLP-1R for GLP-1 and Ex4.

  5. Magnonic band structure in a Co/Pd stripe domain system investigated by Brillouin light scattering and micromagnetic simulations

    NASA Astrophysics Data System (ADS)

    Banerjee, Chandrima; Gruszecki, Pawel; Klos, Jaroslaw W.; Hellwig, Olav; Krawczyk, Maciej; Barman, Anjan

    2017-07-01

    By combining Brillouin light scattering and micromagnetic simulations, we studied the spin-wave (SW) dynamics of a Co/Pd thin film multilayer, which features a stripe domain structure at remanence. The periodic up and down domains are separated by corkscrew type domain walls. The existence of these domains causes a scattering of the otherwise bulk and surface SW modes, which form mode families, similar to a one-dimensional magnonic crystal. The dispersion relation and mode profiles of SWs are measured for the transferred wave vector parallel and perpendicular to the domain axis.

  6. Structural and functional properties of the N transcriptional activation domain of thyroid transcription factor-1: similarities with the acidic activation domains.

    PubMed Central

    Tell, G; Perrone, L; Fabbro, D; Pellizzari, L; Pucillo, C; De Felice, M; Acquaviva, R; Formisano, S; Damante, G

    1998-01-01

    The thyroid transcription factor 1 (TTF-1) is a tissue-specific transcription factor involved in the development of thyroid and lung. TTF-1 contains two transcriptional activation domains (N and C domain). The primary amino acid sequence of the N domain does not show any typical characteristic of known transcriptional activation domains. In aqueous solution the N domain exists in a random-coil conformation. The increase of the milieu hydrophobicity, by the addition of trifluoroethanol, induces a considerable gain of alpha-helical structure. Acidic transcriptional activation domains are largely unstructured in solution, but, under hydrophobic conditions, folding into alpha-helices or beta-strands can be induced. Therefore our data indicate that the inducibility of alpha-helix by hydrophobic conditions is a property not restricted to acidic domains. Co-transfections experiments indicate that the acidic domain of herpes simplex virus protein VP16 (VP16) and the TTF-1 N domain are interchangeable and that a chimaeric protein, which combines VP16 linked to the DNA-binding domain of TTF-1, undergoes the same regulatory constraints that operate for the wild-type TTF-1. In addition, we demonstrate that the TTF-1 N domain possesses two typical properties of acidic activation domains: TBP (TATA-binding protein) binding and ability to activate transcription in yeast. Accordingly, the TTF-1 N domain is able to squelch the activity of the p65 acidic domain. Altogether, these structural and functional data suggest that a non-acidic transcriptional activation domain (TTF-1 N domain) activates transcription by using molecular mechanisms similar to those used by acidic domains. TTF-1 N domain and acidic domains define a family of proteins whose common property is to activate transcription through the use of mechanisms largely conserved during evolutionary development. PMID:9425125

  7. Mechanical switching of ferroelectric domains beyond flexoelectricity

    NASA Astrophysics Data System (ADS)

    Chen, Weijin; Liu, Jianyi; Ma, Lele; Liu, Linjie; Jiang, G. L.; Zheng, Yue

    2018-02-01

    The resurgence of interest in flexoelectricity has prompted discussions on the feasibility of switching ferroelectric domains 'non-electrically'. In this work, we perform three-dimensional thermodynamic simulations in combination with ab initio calculations and effective Hamiltonian simulations to demonstrate the great effects of surface screening and surface bonding on ferroelectric domain switching triggered by local tip loading. A three-dimensional simulation scheme has been developed to capture the tip-induced domain switching behavior in ferroelectric thin films by adequately taking into account the surface screening effect and surface bonding effect of the ferroelectric film, as well as the finite elastic stiffness of the substrate and the electrode layers. The major findings are as follows. (i) Compared with flexoelectricity, surface effects can be overwhelming and lead to much more efficient mechanical switching caused by tip loading. (ii) The surface-assisted mechanical switching can be bi-directional without the necessity of reversing strain gradients. (iii) A mode transition from local to propagating domain switching occurs when the screening below a critical value. A ripple effect of domain switching appears with the formation of concentric loop domains. (iv) The ripple effect can lead to 'domain interference' and a deterministic writing of confined loop domain patterns by local excitations. Our study reveals the hidden switching mechanisms of ferroelectric domains and the possible roles of surface in mechanical switching. The ripple effect of domain switching, which is believed to be general in dipole systems, broadens our current knowledge of domain engineering.

  8. Functional Dynamics of PDZ Binding Domains: A Normal-Mode Analysis

    PubMed Central

    De Los Rios, Paolo; Cecconi, Fabio; Pretre, Anna; Dietler, Giovanni; Michielin, Olivier; Piazza, Francesco; Juanico, Brice

    2005-01-01

    Postsynaptic density-95/disks large/zonula occludens-1 (PDZ) domains are relatively small (80–120 residues) protein binding modules central in the organization of receptor clusters and in the association of cellular proteins. Their main function is to bind C-terminals of selected proteins that are recognized through specific amino acids in their carboxyl end. Binding is associated with a deformation of the PDZ native structure and is responsible for dynamical changes in regions not in direct contact with the target. We investigate how this deformation is related to the harmonic dynamics of the PDZ structure and show that one low-frequency collective normal mode, characterized by the concerted movements of different secondary structures, is involved in the binding process. Our results suggest that even minimal structural changes are responsible for communication between distant regions of the protein, in agreement with recent NMR experiments. Thus, PDZ domains are a very clear example of how collective normal modes are able to characterize the relation between function and dynamics of proteins, and to provide indications on the precursors of binding/unbinding events. PMID:15821164

  9. Numerical time-domain electromagnetics based on finite-difference and convolution

    NASA Astrophysics Data System (ADS)

    Lin, Yuanqu

    Time-domain methods posses a number of advantages over their frequency-domain counterparts for the solution of wideband, nonlinear, and time varying electromagnetic scattering and radiation phenomenon. Time domain integral equation (TDIE)-based methods, which incorporate the beneficial properties of integral equation method, are thus well suited for solving broadband scattering problems for homogeneous scatterers. Widespread adoption of TDIE solvers has been retarded relative to other techniques by their inefficiency, inaccuracy and instability. Moreover, two-dimensional (2D) problems are especially problematic, because 2D Green's functions have infinite temporal support, exacerbating these difficulties. This thesis proposes a finite difference delay modeling (FDDM) scheme for the solution of the integral equations of 2D transient electromagnetic scattering problems. The method discretizes the integral equations temporally using first- and second-order finite differences to map Laplace-domain equations into the Z domain before transforming to the discrete time domain. The resulting procedure is unconditionally stable because of the nature of the Laplace- to Z-domain mapping. The first FDDM method developed in this thesis uses second-order Lagrange basis functions with Galerkin's method for spatial discretization. The second application of the FDDM method discretizes the space using a locally-corrected Nystrom method, which accelerates the precomputation phase and achieves high order accuracy. The Fast Fourier Transform (FFT) is applied to accelerate the marching-on-time process in both methods. While FDDM methods demonstrate impressive accuracy and stability in solving wideband scattering problems for homogeneous scatterers, they still have limitations in analyzing interactions between several inhomogenous scatterers. Therefore, this thesis devises a multi-region finite-difference time-domain (MR-FDTD) scheme based on domain-optimal Green's functions for solving

  10. Dissociations among linguistic, cognitive, and auditory-motor neuroanatomical domains in children who stutter.

    PubMed

    Choo, Ai Leen; Burnham, Evamarie; Hicks, Kristin; Chang, Soo-Eun

    2016-01-01

    The onset of developmental stuttering typically occurs between 2 to 4 years of age, coinciding with a period of rapid development in speech, language, motor and cognitive domains. Previous studies have reported generally poorer performance and uneven, or "dissociated" development across speech and language domains in children who stutter (CWS) relative to children who do not stutter (CWNS) (Anderson, Pellowski, & Conture, 2005). The aim of this study was to replicate and expand previous findings by examining whether CWS exhibit dissociated development across speech-language, cognitive, and motor domains that are also reflected in measures of neuroanatomical development. Participants were 66CWS (23 females) and 53CWNS (26 females) ranging from 3 to 10 years. Standardized speech, language, cognitive, and motor skills measures, and fractional anisotropy (FA) values derived from diffusion tensor imaging from speech relevant "dorsal auditory" left perisylvian areas (Hickok & Poeppel, 2007) were analyzed using a correlation-based statistical procedure (Coulter, Anderson, & Conture, 2009) that quantified dissociations across domains. Overall, CWS scored consistently lower on speech, language, cognitive and motor measures, and exhibited dissociated development involving these same measures and white matter neuroanatomical indices relative to CWNS. Boys who stutter exhibited a greater number of dissociations compared to girls who stutter. Results suggest a subgroup of CWS may have incongruent development across multiple domains, and the resolution of this imbalance may be a factor in recovery from stuttering. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. When a domain isn’t a domain, and why it’s important to properly filter proteins in databases

    PubMed Central

    Towse, Clare-Louise; Daggett, Valerie

    2013-01-01

    Summary Membership in a protein domain database does not a domain make; a feature we realized when generating a consensus view of protein fold space with our Consensus Domain Dictionary (CDD). This dictionary was used to select representative structures for characterization of the protein dynameome: the Dynameomics initiative. Through this endeavor we rejected a surprising 40% of the 1695 folds in the CDD as being non-autonomous folding units. Although some of this was due to the challenges of grouping similar fold topologies, the dissonance between the cataloguing and structural qualification of protein domains remains surprising. Another potential factor is previously overlooked intrinsic disorder; predicted estimates suggest 40% of proteins to have either local or global disorder. One thing is clear, filtering a structural database and ensuring a consistent definition for protein domains is crucial, and caution is prescribed when generalizations of globular domains are drawn from unfiltered protein domain datasets. PMID:23108912

  12. Modeling epigenome folding: formation and dynamics of topologically associated chromatin domains

    PubMed Central

    Jost, Daniel; Carrivain, Pascal; Cavalli, Giacomo; Vaillant, Cédric

    2014-01-01

    Genomes of eukaryotes are partitioned into domains of functionally distinct chromatin states. These domains are stably inherited across many cell generations and can be remodeled in response to developmental and external cues, hence contributing to the robustness and plasticity of expression patterns and cell phenotypes. Remarkably, recent studies indicate that these 1D epigenomic domains tend to fold into 3D topologically associated domains forming specialized nuclear chromatin compartments. However, the general mechanisms behind such compartmentalization including the contribution of epigenetic regulation remain unclear. Here, we address the question of the coupling between chromatin folding and epigenome. Using polymer physics, we analyze the properties of a block copolymer model that accounts for local epigenomic information. Considering copolymers build from the epigenomic landscape of Drosophila, we observe a very good agreement with the folding patterns observed in chromosome conformation capture experiments. Moreover, this model provides a physical basis for the existence of multistability in epigenome folding at sub-chromosomal scale. We show how experiments are fully consistent with multistable conformations where topologically associated domains of the same epigenomic state interact dynamically with each other. Our approach provides a general framework to improve our understanding of chromatin folding during cell cycle and differentiation and its relation to epigenetics. PMID:25092923

  13. Multiple reputation domains and cooperative behaviour in two Latin American communities

    PubMed Central

    Macfarlan, Shane J.; Lyle, Henry F.

    2015-01-01

    Reputations are a ubiquitous feature of human social life, and a large literature has been dedicated to explaining the relationship between prosocial reputations and cooperation in social dilemmas. However, humans form reputations in domains other than prosociality, such as economic competency that could affect cooperation. To date, no research has evaluated the relative effects of multiple reputation domains on cooperation. To bridge this gap, we analyse how prosocial and competency reputations affect cooperation in two Latin American communities (Bwa Mawego, Dominica, and Pucucanchita, Peru) across a number of social contexts (Dominica: labour contracting, labour exchange and conjugal partnership formation; Peru: agricultural and health advice network size). First, we examine the behavioural correlates of prosocial and competency reputations. Following, we analyse whether prosocial, competency, or both reputation domains explain the flow of cooperative benefits within the two communities. Our analyses suggest that (i) although some behaviours affect both reputation domains simultaneously, each reputation domain has a unique behavioural signature; and (ii) competency reputations affect cooperation across a greater number of social contexts compared to prosocial reputations. Results are contextualized with reference to the social markets in which behaviour is embedded and a call for greater theory development is stressed. PMID:26503682

  14. Context Influences on the Subjective Experience of Aging: The Impact of Culture and Domains of Functioning.

    PubMed

    O'Brien, Erica L; Hess, Thomas M; Kornadt, Anna E; Rothermund, Klaus; Fung, Helene; Voss, Peggy

    2017-08-01

    Attitudes about aging influence how people feel about their aging and affect psychological and health outcomes in later life. Given cross-cultural variability in such attitudes, the subjective experience of aging (e.g., subjective age [SA]) may also vary, potentially accounting for culture-specific patterns of aging-related outcomes. Our study explored cultural variation in SA and its determinants. American (N = 569), Chinese (N = 492), and German (N = 827) adults aged 30-95 years completed a questionnaire that included instruments measuring basic demographic information, SA, beliefs about thresholds of old age, control over life changes, and age dependency of changes in eight different life domains (i.e., family, work). Analyses revealed consistency across cultures in the domain-specificity of SA, but differences in the amount of shared variance across domains (e.g., Chinese adults exhibited greater homogeneity across domains than did Americans and Germans). Cultural differences were also observed in levels of SA in some domains, which were attenuated by domain-specific beliefs (e.g., control). Interestingly, beliefs about aging accounted for more cultural variation in SA than did sociodemographic factors (e.g., education). Our results demonstrate that subjective perceptions of aging and everyday functioning may be best understood from a perspective focused on context (i.e., culture, life domain). Given its important relation to functioning, examination of cross-cultural differences in the subjective experience of aging may highlight factors that determine variations in aging-related outcomes that then could serve as targets of culture-specific interventions promoting well-being in later life. © The Author 2017. 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.

  15. Ageing influences myonuclear domain size differently in fast and slow skeletal muscle of rats.

    PubMed

    Brooks, Naomi E; Schuenke, M D; Hikida, R S

    2009-09-01

    In multinucleated skeletal muscle, a myonuclear domain is the region of cytoplasm governed by one nucleus, and myofibres are mosaics of overlapping myonuclear domains. Association of ageing and myonuclear domain is important in the understanding of sarcopenia and with prevention or combating age-related muscle declines. This study examined the effects of age, fibre type and muscle on nucleo-cytoplasmic (N/C) relationships as reflecting myonuclear domain size. The N/C was compared in fibre types of soleus and plantaris muscles from young (n = 6) and ageing (n = 8) male Fisher 344 rats. There were no significant differences in fibre type composition or cross-sectional area of the soleus across ages. The old soleus had significantly more myonuclei, resulting in a significantly smaller myonuclear domain size. The plantaris muscle showed a higher percentage of slow fibres in old compared with young fibres. There were no differences in the number of myonuclei or in myonuclear domain size between young and older animals. We found muscle-specific differences in the effects of ageing on myonuclear domain, possibly as a result of reduced efficiency of the myonuclei in the slow muscles.

  16. High-Throughput Quantification of SH2 Domain-Phosphopeptide Interactions with Cellulose-Peptide Conjugate Microarrays.

    PubMed

    Engelmann, Brett W

    2017-01-01

    The Src Homology 2 (SH2) domain family primarily recognizes phosphorylated tyrosine (pY) containing peptide motifs. The relative affinity preferences among competing SH2 domains for phosphopeptide ligands define "specificity space," and underpins many functional pY mediated interactions within signaling networks. The degree of promiscuity exhibited and the dynamic range of affinities supported by individual domains or phosphopeptides is best resolved by a carefully executed and controlled quantitative high-throughput experiment. Here, I describe the fabrication and application of a cellulose-peptide conjugate microarray (CPCMA) platform to the quantitative analysis of SH2 domain specificity space. Included herein are instructions for optimal experimental design with special attention paid to common sources of systematic error, phosphopeptide SPOT synthesis, microarray fabrication, analyte titrations, data capture, and analysis.

  17. Quantitative analysis of domain texture in polycrystalline barium titanate by polarized Raman microprobe spectroscopy

    NASA Astrophysics Data System (ADS)

    Sakashita, Tatsuo; Chazono, Hirokazu; Pezzotti, Giuseppe

    2007-12-01

    A quantitative determination of domain distribution in polycrystalline barium titanate (BaTiO3, henceforth BT) ceramics has been pursued with the aid of a microprobe polarized Raman spectrometer. The crystallographic texture and domain orientation distribution of BT ceramics, which switched upon applying stress according to ferroelasticity principles, were determined from the relative intensity of selected phonon modes, taking into consideration a theoretical analysis of the angular dependence of phonon mode intensity for the tetragonal BT phase. Furthermore, the angular dependence of Raman intensity measured in polycrystalline BT depended on the statistical distribution of domain angles in the laser microprobe, which was explicitly taken into account in this work for obtaining a quantitative analysis of domain orientation for in-plane textured BT polycrystalline materials.

  18. A solid-state NMR method to determine domain sizes in multi-component polymer formulations

    NASA Astrophysics Data System (ADS)

    Schlagnitweit, Judith; Tang, Mingxue; Baias, Maria; Richardson, Sara; Schantz, Staffan; Emsley, Lyndon

    2015-12-01

    Polymer domain sizes are related to many of the physical properties of polymers. Here we present a solid-state NMR experiment that is capable of measuring domain sizes in multi-component mixtures. The method combines selective excitation of carbon magnetization to isolate a specific component with proton spin diffusion to report on domain size. We demonstrate the method in the context of controlled release formulations, which represents one of today's challenges in pharmaceutical science. We show that we can measure domain sizes of interest in the different components of industrial pharmaceutical formulations at natural isotopic abundance containing various (modified) cellulose derivatives, such as microcrystalline cellulose matrixes that are film-coated with a mixture of ethyl cellulose (EC) and hydroxypropyl cellulose (HPC).

  19. Ubiquitin Regulates Caspase Recruitment Domain-mediated Signaling by Nucleotide-binding Oligomerization Domain-containing Proteins NOD1 and NOD2*

    PubMed Central

    Ver Heul, Aaron M.; Fowler, C. Andrew; Ramaswamy, S.; Piper, Robert C.

    2013-01-01

    NOD1 and NOD2 (nucleotide-binding oligomerization domain-containing proteins) are intracellular pattern recognition receptors that activate inflammation and autophagy. These pathways rely on the caspase recruitment domains (CARDs) within the receptors, which serve as protein interaction platforms that coordinately regulate immune signaling. We show that NOD1 CARD binds ubiquitin (Ub), in addition to directly binding its downstream targets receptor-interacting protein kinase 2 (RIP2) and autophagy-related protein 16-1 (ATG16L1). NMR spectroscopy and structure-guided mutagenesis identified a small hydrophobic surface of NOD1 CARD that binds Ub. In vitro, Ub competes with RIP2 for association with NOD1 CARD. In vivo, we found that the ligand-stimulated activity of NOD1 with a mutant CARD lacking Ub binding but retaining ATG16L1 and RIP2 binding is increased relative to wild-type NOD1. Likewise, point mutations in the tandem NOD2 CARDs at positions analogous to the surface residues defining the Ub interface on NOD1 resulted in loss of Ub binding and increased ligand-stimulated NOD2 signaling. These data suggest that Ub binding provides a negative feedback loop upon NOD-dependent activation of RIP2. PMID:23300079

  20. Cache domains that are homologous to, but different from PAS domains comprise the largest superfamily of extracellular sensors in prokaryotes

    DOE PAGES

    Upadhyay, Amit A.; Fleetwood, Aaron D.; Adebali, Ogun; ...

    2016-04-06

    Cellular receptors usually contain a designated sensory domain that recognizes the signal. Per/Arnt/Sim (PAS) domains are ubiquitous sensors in thousands of species ranging from bacteria to humans. Although PAS domains were described as intracellular sensors, recent structural studies revealed PAS-like domains in extracytoplasmic regions in several transmembrane receptors. However, these structurally defined extracellular PAS-like domains do not match sequence-derived PAS domain models, and thus their distribution across the genomic landscape remains largely unknown. Here we show that structurally defined extracellular PAS-like domains belong to the Cache superfamily, which is homologous to, but distinct from the PAS superfamily. Our newly builtmore » computational models enabled identification of Cache domains in tens of thousands of signal transduction proteins including those from important pathogens and model organisms.Moreover, we show that Cache domains comprise the dominant mode of extracellular sensing in prokaryotes.« less