Science.gov

Sample records for related jmjc domain

  1. Emerging Roles of JmjC Domain-Containing Proteins.

    PubMed

    Accari, Sandra L; Fisher, Paul R

    2015-01-01

    Jumonji C (JmjC) domain-containing proteins are a diverse superfamily of proteins containing a characteristic, evolutionarily conserved β-barrel structure that normally contains binding sites for Fe(II) and α-ketoglutarate. In the best studied JmjC-domain proteins, the JmjC barrel has a histone demethylase catalytic activity. Histones are evolutionarily conserved proteins intimately involved in the packaging of DNA within the nucleus of eukaryotic organisms. The N-termini ("tails") of the histone proteins are subject to a diverse array of posttranslational modifications including methylation. Unlike many of the other histone modifications which are transient, methylation was thought to be permanent, until the relatively recent identification of the first demethylases. Jumonji C domain-containing proteins were first identified with a role in the modulation of histone methylation marks. This family of proteins is broken up into seven distinct subgroups based on domain architecture and their ability to antagonize specific histone methylation marks. Their biological functions derive from their ability to regulate gene expression and include roles in cell differentiation, growth, proliferation, and stress responses. However, one subgroup remains, the largest, in which the JmjC domain has no known biochemical function. These proteins belong to the JmjC-domain-only subgroup and as their name suggests, the only bioinformatically recognizable domain they contain is the highly conserved JmjC domain. PMID:26404469

  2. Studies on the catalytic domains of multiple JmjC oxygenases using peptide substrates

    PubMed Central

    Williams, Sophie T; Walport, Louise J; Hopkinson, Richard J; Madden, Sarah K; Chowdhury, Rasheduzzaman; Schofield, Christopher J; Kawamura, Akane

    2014-01-01

    The JmjC-domain-containing 2-oxoglutarate-dependent oxygenases catalyze protein hydroxylation and Nε-methyllysine demethylation via hydroxylation. A subgroup of this family, the JmjC lysine demethylases (JmjC KDMs) are involved in histone modifications at multiple sites. There are conflicting reports as to the substrate selectivity of some JmjC oxygenases with respect to KDM activities. In this study, a panel of modified histone H3 peptides was tested for demethylation against 15 human JmjC-domain-containing proteins. The results largely confirmed known Nε-methyllysine substrates. However, the purified KDM4 catalytic domains showed greater substrate promiscuity than previously reported (i.e., KDM4A was observed to catalyze demethylation at H3K27 as well as H3K9/K36). Crystallographic analyses revealed that the Nε-methyllysine of an H3K27me3 peptide binds similarly to Nε-methyllysines of H3K9me3/H3K36me3 with KDM4A. A subgroup of JmjC proteins known to catalyze hydroxylation did not display demethylation activity. Overall, the results reveal that the catalytic domains of the KDM4 enzymes may be less selective than previously identified. They also draw a distinction between the Nε-methyllysine demethylation and hydroxylation activities within the JmjC subfamily. These results will be of use to those working on functional studies of the JmjC enzymes. PMID:25625844

  3. Structure of the JmjC domain-containing protein NO66 complexed with ribosomal protein Rpl8

    SciTech Connect

    Wang, Chengliang; Zhang, Qiongdi; Hang, Tianrong; Tao, Yue; Ma, Xukai; Wu, Minhao; Zhang, Xuan Zang, Jianye

    2015-08-28

    The structure of the complex of NO66 and Rpl8 was solved in the native state and NO66 recognizes the consensus motif NHXH . Tetramerization is required for efficient substrate binding and catalysis by NO66. The JmjC domain-containing proteins belong to a large family of oxygenases possessing distinct substrate specificities which are involved in the regulation of different biological processes, such as gene transcription, RNA processing and translation. Nucleolar protein 66 (NO66) is a JmjC domain-containing protein which has been reported to be a histone demethylase and a ribosome protein 8 (Rpl8) hydroxylase. The present biochemical study confirmed the hydroxylase activity of NO66 and showed that oligomerization is required for NO66 to efficiently catalyze the hydroxylation of Rpl8. The structures of NO66{sup 176–C} complexed with Rpl8{sup 204–224} in a tetrameric form and of the mutant protein M2 in a dimeric form were solved. Based on the results of structural and biochemical analyses, the consensus sequence motif NHXH recognized by NO66 was confirmed. Several potential substrates of NO66 were found by a BLAST search according to the consensus sequence motif. When binding to substrate, the relative positions of each subunit in the NO66 tetramer shift. Oligomerization may facilitate the motion of each subunit in the NO66 tetramer and affect the catalytic activity.

  4. 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

  5. Knockdown of a JmjC domain-containing gene JMJ524 confers altered gibberellin responses by transcriptional regulation of GRAS protein lacking the DELLA domain genes in tomato

    PubMed Central

    Li, Jinhua; Yu, Chuying; Wu, Hua; Luo, Zhidan; Ouyang, Bo; Cui, Long; Zhang, Junhong; Ye, Zhibiao

    2015-01-01

    Plants integrate responses to independent hormonal and environmental signals to survive adversity. In particular, the phytohormone gibberellin (GA) regulates a variety of developmental processes and stress responses. In this study, the Jumonji-C (JmjC) domain-containing gene JMJ524 was characterized in tomato. JMJ524 responded to circadian rhythms and was upregulated by GA treatment. Knockdown of JMJ524 by RNAi caused a GA-insensitive dwarf phenotype with shrunken leaves and shortened internodes. However, in these transgenic plants, higher levels of endogenous GAs were detected. A genome-wide gene expression analysis by RNA-seq indicated that the expression levels of two DELLA-like genes, SlGLD1 (‘GRAS protein Lacking the DELLA domain’) and SlGLD2, were increased in JMJ524-RNAi transgenic plants. Nevertheless, only the overexpression of SlGLD1 in tomato resulted in a GA-insensitive dwarf phenotype, suggesting that SlGLD1 acts as a repressor of GA signalling. This study proposes that JMJ524 is required for stem elongation by altering GA responses, at least partially by regulating SlGLD1. PMID:25680796

  6. A Cell-Permeable Ester Derivative of the JmjC Histone Demethylase Inhibitor IOX1

    PubMed Central

    Schiller, Rachel; Scozzafava, Giuseppe; Tumber, Anthony; Wickens, James R; Bush, Jacob T; Rai, Ganesha; Lejeune, Clarisse; Choi, Hwanho; Yeh, Tzu-Lan; Chan, Mun Chiang; Mott, Bryan T; McCullagh, James S O; Maloney, David J; Schofield, Christopher J; Kawamura, Akane

    2014-01-01

    The 2-oxoglutarate (2OG)-dependent Jumonji C domain (JmjC) family is the largest family of histone lysine demethylases. There is interest in developing small-molecule probes that modulate JmjC activity to investigate their biological roles. 5-Carboxy-8-hydroxyquinoline (IOX1) is the most potent broad-spectrum inhibitor of 2OG oxygenases, including the JmjC demethylases, reported to date; however, it suffers from low cell permeability. Here, we describe structure–activity relationship studies leading to the discovery of an n-octyl ester form of IOX1 with improved cellular potency (EC50 value of 100 to 4 μm). These findings are supported by in vitro inhibition and selectivity studies, docking studies, activity versus toxicity analysis in cell cultures, and intracellular uptake measurements. The n-octyl ester was found to have improved cell permeability; it was found to inhibit some JmjC demethylases in its intact ester form and to be more selective than IOX1. The n-octyl ester of IOX1 should find utility as a starting point for the development of JmjC inhibitors and as a use as a cell-permeable tool compound for studies investigating the roles of 2OG oxygenases in epigenetic regulation. PMID:24504543

  7. Purification, Biochemical Analysis, and Structure Determination of JmjC Lysine Demethylases.

    PubMed

    Krishnan, S; Trievel, R C

    2016-01-01

    Jumonji C (JmjC) lysine demethylases (KDMs) catalyze the site- and state-specific demethylation of lysine residues in histone and nonhistone protein substrates. These enzymes have been implicated in diverse genomic processes, including epigenetic gene regulation, DNA damage response, DNA replication, and regulation of heterochromatin structure. In addition, a number of JmjC KDMs contribute to the incidence of numerous cancers, rendering them targets for the development of novel chemotherapeutic drugs. Using the JMJD2 KDM subfamily as representative examples, this chapter outlines strategies for purifying highly active, recombinant JmjC KDMs lacking inhibitory transition metal ions, characterizing kinetic parameters of these enzymes using a coupled fluorescent assay, and determining crystal structures of the enzymes in complex with methylated histone peptides. Together, these approaches provide a foundation for structural and biochemical characterization of the JmjC KDMs and facilitate efforts to identify small molecule inhibitors through high-throughput screening and structure-guided design. PMID:27372758

  8. Chromatin and oxygen sensing in the context of JmjC histone demethylases

    PubMed Central

    Shmakova, Alena; Batie, Michael; Druker, Jimena; Rocha, Sonia

    2014-01-01

    Responding appropriately to changes in oxygen availability is essential for multicellular organism survival. Molecularly, cells have evolved intricate gene expression programmes to handle this stressful condition. Although it is appreciated that gene expression is co-ordinated by changes in transcription and translation in hypoxia, much less is known about how chromatin changes allow for transcription to take place. The missing link between co-ordinating chromatin structure and the hypoxia-induced transcriptional programme could be in the form of a class of dioxygenases called JmjC (Jumonji C) enzymes, the majority of which are histone demethylases. In the present review, we will focus on the function of JmjC histone demethylases, and how these could act as oxygen sensors for chromatin in hypoxia. The current knowledge concerning the role of JmjC histone demethylases in the process of organism development and human disease will also be reviewed. PMID:25145438

  9. Arginine demethylation is catalysed by a subset of JmjC histone lysine demethylases.

    PubMed

    Walport, Louise J; Hopkinson, Richard J; Chowdhury, Rasheduzzaman; Schiller, Rachel; Ge, Wei; Kawamura, Akane; Schofield, Christopher J

    2016-01-01

    While the oxygen-dependent reversal of lysine N(ɛ)-methylation is well established, the existence of bona fide N(ω)-methylarginine demethylases (RDMs) is controversial. Lysine demethylation, as catalysed by two families of lysine demethylases (the flavin-dependent KDM1 enzymes and the 2-oxoglutarate- and oxygen-dependent JmjC KDMs, respectively), proceeds via oxidation of the N-methyl group, resulting in the release of formaldehyde. Here we report detailed biochemical studies clearly demonstrating that, in purified form, a subset of JmjC KDMs can also act as RDMs, both on histone and non-histone fragments, resulting in formaldehyde release. RDM catalysis is studied using peptides of wild-type sequences known to be arginine-methylated and sequences in which the KDM's methylated target lysine is substituted for a methylated arginine. Notably, the preferred sequence requirements for KDM and RDM activity vary even with the same JmjC enzymes. The demonstration of RDM activity by isolated JmjC enzymes will stimulate efforts to detect biologically relevant RDM activity. PMID:27337104

  10. Arginine demethylation is catalysed by a subset of JmjC histone lysine demethylases

    PubMed Central

    Walport, Louise J.; Hopkinson, Richard J.; Chowdhury, Rasheduzzaman; Schiller, Rachel; Ge, Wei; Kawamura, Akane; Schofield, Christopher J.

    2016-01-01

    While the oxygen-dependent reversal of lysine Nɛ-methylation is well established, the existence of bona fide Nω-methylarginine demethylases (RDMs) is controversial. Lysine demethylation, as catalysed by two families of lysine demethylases (the flavin-dependent KDM1 enzymes and the 2-oxoglutarate- and oxygen-dependent JmjC KDMs, respectively), proceeds via oxidation of the N-methyl group, resulting in the release of formaldehyde. Here we report detailed biochemical studies clearly demonstrating that, in purified form, a subset of JmjC KDMs can also act as RDMs, both on histone and non-histone fragments, resulting in formaldehyde release. RDM catalysis is studied using peptides of wild-type sequences known to be arginine-methylated and sequences in which the KDM's methylated target lysine is substituted for a methylated arginine. Notably, the preferred sequence requirements for KDM and RDM activity vary even with the same JmjC enzymes. The demonstration of RDM activity by isolated JmjC enzymes will stimulate efforts to detect biologically relevant RDM activity. PMID:27337104

  11. 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.

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

    ERIC Educational Resources Information Center

    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…

  13. Between- and Within-Domain Relations of Students' Academic Emotions

    ERIC Educational Resources Information Center

    Goetz, Thomas; Frenzel, Anne C.; Pekrun, Reinhard; Hall, Nathan C.; Ludtke, Oliver

    2007-01-01

    The authors investigated between- and within-domain relations of academic emotions, including students' enjoyment, pride, anxiety, anger, and boredom experienced in mathematics, physics, German, and English classes (N = 542; Grades 8 and 11). Corroborating assumptions of domain specificity, the between-domains relations of these emotions were weak…

  14. 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

  15. 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…

  16. Multiorder boundaries among discrete domains: relative fractal dimension and others.

    PubMed

    Xuan, Qi; Du, Fang; Wu, Tie-Jun

    2010-03-01

    In nature and society, most of competitions take place on the boundaries among a group of domains where different individuals or colonies share common resources; therefore, it is widely believed that domain boundaries play important roles in the evolution of many complex systems. Here, we first give a definition for multiorder boundaries among discrete domains and then propose a general method to calculate their relative fractal dimension, i.e., the ratio of the fractal dimension of the boundaries versus that of the domains themselves. Through analyzing three types of real-world discrete domains, several interesting results are revealed. For example, the limitation on the number of domains that an individual can join in may produce longer boundaries indicating more cruel competitions among the domains. Besides, the individuals with more social links are always considered more important in social networks, and it is found that these individuals as valuable resources of social domains are always centralized on the boundaries of higher order. PMID:20370288

  17. Cross-domain analogies as relating derived relations among two separate relational networks.

    PubMed

    Ruiz, Francisco J; Luciano, Carmen

    2011-05-01

    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

  18. 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

  19. Approximation method to compute domain related integrals in structural studies

    NASA Astrophysics Data System (ADS)

    Oanta, E.; Panait, C.; Raicu, A.; Barhalescu, M.; Axinte, T.

    2015-11-01

    Various engineering calculi use integral calculus in theoretical models, i.e. analytical and numerical models. For usual problems, integrals have mathematical exact solutions. If the domain of integration is complicated, there may be used several methods to calculate the integral. The first idea is to divide the domain in smaller sub-domains for which there are direct calculus relations, i.e. in strength of materials the bending moment may be computed in some discrete points using the graphical integration of the shear force diagram, which usually has a simple shape. Another example is in mathematics, where the surface of a subgraph may be approximated by a set of rectangles or trapezoids used to calculate the definite integral. The goal of the work is to introduce our studies about the calculus of the integrals in the transverse section domains, computer aided solutions and a generalizing method. The aim of our research is to create general computer based methods to execute the calculi in structural studies. Thus, we define a Boolean algebra which operates with ‘simple’ shape domains. This algebraic standpoint uses addition and subtraction, conditioned by the sign of every ‘simple’ shape (-1 for the shapes to be subtracted). By ‘simple’ shape or ‘basic’ shape we define either shapes for which there are direct calculus relations, or domains for which their frontiers are approximated by known functions and the according calculus is carried out using an algorithm. The ‘basic’ shapes are linked to the calculus of the most significant stresses in the section, refined aspect which needs special attention. Starting from this idea, in the libraries of ‘basic’ shapes, there were included rectangles, ellipses and domains whose frontiers are approximated by spline functions. The domain triangularization methods suggested that another ‘basic’ shape to be considered is the triangle. The subsequent phase was to deduce the exact relations for the

  20. Some proposed relations among the domains of behavior analysis

    PubMed Central

    Moore, J.; Cooper, John O.

    2003-01-01

    The present article examines the nature of and relations among the domains of behavior analysis. It first proposes a set of annotated, descriptive criteria to aid in distinguishing the experimental analysis of behavior, applied behavior analysis, and service delivery. It then argues that the experimental analysis of behavior lies at one end of a continuum of behavior-analytic activity, with applied behavior analysis in the middle, service delivery at the other end, and the theoretical-philosophical-conceptual position known as “radical behaviorism” informing the three domains on the continuum. Finally, it argues that clarifying the distinctions among the domains of behavior analysis will help the behavior-analytic community to focus its efforts in training programs and overall support of behavior analysis. PMID:22478395

  1. 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.

  2. A Time Domain Waveform for Testing General Relativity

    NASA Astrophysics Data System (ADS)

    Huwyler, Cédric; Porter, Edward K.; Jetzer, Philippe

    2015-05-01

    Gravitational-wave parameter estimation is only as good as the theory the waveform generation models are based upon. It is therefore crucial to test General Relativity (GR) once data becomes available. Many previous works, such as studies connected with the ppE framework by Yunes and Pretorius, rely on the stationary phase approximation (SPA) to model deviations from GR in the frequency domain. As Fast Fourier Transform algorithms have become considerably faster and in order to circumvent possible problems with the SPA, we test GR with corrected time domain waveforms instead of SPA waveforms. Since a considerable amount of work has been done already in the field using SPA waveforms, we establish a connection between leading-order-corrected waveforms in time and frequency domain, concentrating on phase-only corrected terms. In a Markov Chain Monte Carlo study, whose results are preliminary and will only be available later, we will assess the ability of the eLISA detector to measure deviations from GR for signals coming from supermassive black hole inspirals using these corrected waveforms.

  3. 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.

  4. Examining the Relation between Domain-Related Communication and Collaborative Inquiry Learning

    ERIC Educational Resources Information Center

    Anjewierden, Anjo; Gijlers, Hannie; Kolloffel, Bas; Saab, Nadira; de Hoog, Robert

    2011-01-01

    Research suggests that providing others with elaborated explanations is more beneficial for learning than receiving explanations (e.g., Webb, 1989). Applied to chat communication in a collaborative inquiry learning environment, we would expect that in a dyad learners with more domain-related contributions than their partners would learn more. In…

  5. The Aretaic Domain and Its Relation to the Deontic Domain in Moral Reasoning.

    ERIC Educational Resources Information Center

    Lourenco, Orlando

    2000-01-01

    Investigates the ways in which young adults make judgments about two contrasting kinds of rights: moral worthiness (the aretaic) and moral obligation (the deontic), reflecting on how thinking in these areas may be coordinated with responsibility judgments and behavior. Discusses what might be gained if the aretaic domain were taken into account in…

  6. A Structure for the Affective Domain in Relation to Science Education.

    ERIC Educational Resources Information Center

    Klopfer, Leopold E.

    A classification scheme for the affective domain in relation to science education is presented in this article to clarify student's affective behaviors and their representative phenomena. Discussion is made in connection with the content-objectives grid in the cognitive domain. An analogous grid for the affective domain is delineated by a…

  7. Extending Black Domain Name List by Using Co-occurrence Relation between DNS Queries

    NASA Astrophysics Data System (ADS)

    Sato, Kazumichi; Ishibashi, Keisuke; Toyono, Tsuyoshi; Hasegawa, Haruhisa; Yoshino, Hideaki

    Botnet threats, such as server attacks or sending of spam e-mail, have been increasing. Therefore, infected hosts must be found and their malicious activities mitigated. An effective method for finding infected hosts is to use a blacklist of domain names. When a bot receives attack commands from a Command and Control (C&C) server, it attempts to resolve domain names of C&C servers. We can thus detect infected hosts by finding these that send queries on black domain names. However, we cannot find all infected hosts because of the inaccuracy of blacklists. There are many black domain names, and the lifetimes of these domain names are short; therefore a blacklist cannot cover all black domain names. We thus present a method for finding unknown black domain names by using DNS query data and an existing blacklist of known black domain names. To achieve this, we focus on DNS queries sent by infected hosts. One bot sends several queries on black domain names due to C&C server redundancy. We use the co-occurrence relation of two different domain names to find unknown black domain names and extend the blacklist. If a domain name frequently co-occurs with a known black name, we assume that the domain name is also black. A cross-validation evaluation of the proposed method showed that 91.2% of domain names that are on the validation list scored in the top 1%.

  8. Overexpression and purification of folded domain of prostate cancer related proteins MSMB and PSA.

    PubMed

    Tiwary, Mohini; Agarwal, Nipanshu; Dinda, Amit; Yadav, Subhash C

    2016-05-01

    Overexpression of domains of a human protein using recombinant DNA technology has been challenging because individual domains intend to accumulate as non-soluble aggregate when expressed separately. Studies on identifying right sequences for a domain to be able to fold independently may help understand the folding pattern and underlying protein-engineering events to isolate the functional domains of a protein. In this report, individual domains of prostate cancer related biomarkers; MSMB and PSA were overexpressed in bacterial system and purified in their folded forms using affinity chromatography. The western blotting experiment using domain specific antibodies further confirmed these proteins. The designed nucleotide sequences domains were truncated using fold index software and folding were predicted by phyre2 and I-TASSER software. Other parameters were optimized for their overexpression and purification using Co-NTA affinity chromatography. Purified domains of each protein showed secondary structures such as α + β type for PSA, α/β and β type for the each domains of PSA and MSMB respectively. This is the first report on producing PSA and MSMB individual domains in functional folded forms. This study may help produce the folded domain of many such proteins to be used for better diagnostic purpose. PMID:27038170

  9. Relative age effect revisited: findings from the dance domain.

    PubMed

    van Rossum, Jacques H A

    2006-04-01

    The relative age effect is a worldwide phenomenon. While there is solid empirical evidence for the existence in sports like soccer and ice hockey, there are also some findings indicating the absence of the phenomenon. In an earlier study, no support was found with Dutch top-level athletes in table tennis and in volleyball. The explanation was that in athletic tasks which depend heavily on the technical ability (or motor skill) of the participant, a relative age effect will not be observed. In the present study this supposition was tested again with three samples of Dutch preprofessional dance students (overall number of subjects: 546). Again no support was obtained for the relative age effect. Therefore, a case is being built that the relative age effect is not an omnipresent phenomenon. PMID:16826648

  10. Ribosome origins: The relative age of 23S rRNA Domains

    NASA Astrophysics Data System (ADS)

    Hury, James; Nagaswamy, Uma; Larios-Sanz, Maia; Fox, George E.

    2006-08-01

    The modern ribosome and its component RNAs are quite large and it is likely that at an earlier time they were much smaller. Hence, not all regions of the modern ribosomal RNAs (rRNA) are likely to be equally old. In the work described here, it is hypothesized that the oldest regions of the RNAs will usually be highly integrated into the machinery. When this is the case, an examination of the interconnectivity between local RNA regions can provide insight to the relative age of the various regions. Herein, we describe an analysis of all known long-range RNA/RNA interactions within the 23S rRNA and between the 23S rRNA and the 16S rRNA in order to assess the interconnectivity between the usual Domains as defined by secondary structure. Domain V, which contains the peptidyl transferase center is centrally located, extensively connected, and therefore likely to be the oldest region. Domain IV and Domain II are extensively interconnected with both themselves and Domain V. A portion of Domain IV is also extensively connected with the 30S subunit and hence Domain IV may be older than Domain II. These results are consistent with other evidence relating to the relative age of RNA regions. Although the relative time of addition of the GTPase center can not be reliably deduced it is pointed out that the development of this may have dramatically affected the progenotes that preceded the last common ancestor.

  11. Histone Demethylase Jumonji AT-rich Interactive Domain 1B (JARID1B) Controls Mammary Gland Development by Regulating Key Developmental and Lineage Specification Genes*

    PubMed Central

    Zou, Mike Ran; Cao, Jian; Liu, Zongzhi; Huh, Sung Jin; Polyak, Kornelia; Yan, Qin

    2014-01-01

    The JmjC domain-containing H3K4 histone demethylase jumonji AT-rich interactive domain 1B (JARID1B) (also known as KDM5B and PLU1) is overexpressed in breast cancer and is a potential target for breast cancer treatment. To investigate the in vivo function of JARID1B, we developed Jarid1b−/− mice and characterized their phenotypes in detail. Unlike previously reported Jarid1b−/− strains, the majority of these Jarid1b−/− mice were viable beyond embryonic and neonatal stages. This allowed us to further examine phenotypes associated with the loss of JARID1B in pubertal development and pregnancy. These Jarid1b−/− mice exhibited decreased body weight, premature mortality, decreased female fertility, and delayed mammary gland development. Related to these phenotypes, JARID1B loss decreased serum estrogen level and reduced mammary epithelial cell proliferation in early puberty. In mammary epithelial cells, JARID1B loss diminished the expression of key regulators for mammary morphogenesis and luminal lineage specification, including FOXA1 and estrogen receptor α. Mechanistically, JARID1B was required for GATA3 recruitment to the Foxa1 promoter to activate Foxa1 expression. These results indicate that JARID1B positively regulates mammary ductal development through both extrinsic and cell-autonomous mechanisms. PMID:24802759

  12. 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

  13. The neurofibromin recruitment factor Spred1 binds to the GAP related domain without affecting Ras inactivation.

    PubMed

    Dunzendorfer-Matt, Theresia; Mercado, Ellen L; Maly, Karl; McCormick, Frank; Scheffzek, Klaus

    2016-07-01

    Neurofibromatosis type 1 (NF1) and Legius syndrome are related diseases with partially overlapping symptoms caused by alterations of the tumor suppressor genes NF1 (encoding the protein neurofibromin) and SPRED1 (encoding sprouty-related, EVH1 domain-containing protein 1, Spred1), respectively. Both proteins are negative regulators of Ras/MAPK signaling with neurofibromin functioning as a Ras-specific GTPase activating protein (GAP) and Spred1 acting on hitherto undefined components of the pathway. Importantly, neurofibromin has been identified as a key protein in the development of cancer, as it is genetically altered in a large number of sporadic human malignancies unrelated to NF1. Spred1 has previously been demonstrated to interact with neurofibromin via its N-terminal Ena/VASP Homology 1 (EVH1) domain and to mediate membrane translocation of its target dependent on its C-terminal Sprouty domain. However, the region of neurofibromin required for the interaction with Spred1 has remained unclear. Here we show that the EVH1 domain of Spred1 binds to the noncatalytic (GAPex) portion of the GAP-related domain (GRD) of neurofibromin. Binding is compatible with simultaneous binding of Ras and does not interfere with GAP activity. Our study points to a potential targeting function of the GAPex subdomain of neurofibromin that is present in all known canonical RasGAPs. PMID:27313208

  14. The neurofibromin recruitment factor Spred1 binds to the GAP related domain without affecting Ras inactivation

    PubMed Central

    Dunzendorfer-Matt, Theresia; Mercado, Ellen L.; Maly, Karl; McCormick, Frank; Scheffzek, Klaus

    2016-01-01

    Neurofibromatosis type 1 (NF1) and Legius syndrome are related diseases with partially overlapping symptoms caused by alterations of the tumor suppressor genes NF1 (encoding the protein neurofibromin) and SPRED1 (encoding sprouty-related, EVH1 domain-containing protein 1, Spred1), respectively. Both proteins are negative regulators of Ras/MAPK signaling with neurofibromin functioning as a Ras-specific GTPase activating protein (GAP) and Spred1 acting on hitherto undefined components of the pathway. Importantly, neurofibromin has been identified as a key protein in the development of cancer, as it is genetically altered in a large number of sporadic human malignancies unrelated to NF1. Spred1 has previously been demonstrated to interact with neurofibromin via its N-terminal Ena/VASP Homology 1 (EVH1) domain and to mediate membrane translocation of its target dependent on its C-terminal Sprouty domain. However, the region of neurofibromin required for the interaction with Spred1 has remained unclear. Here we show that the EVH1 domain of Spred1 binds to the noncatalytic (GAPex) portion of the GAP-related domain (GRD) of neurofibromin. Binding is compatible with simultaneous binding of Ras and does not interfere with GAP activity. Our study points to a potential targeting function of the GAPex subdomain of neurofibromin that is present in all known canonical RasGAPs. PMID:27313208

  15. 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

    2016-02-01

    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

  16. 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

  17. Lung cancer-associated JmjC domain protein mdig suppresses formation of tri-methyl lysine 9 of histone H3.

    PubMed

    Lu, Yongju; Chang, Qingshan; Zhang, Yadong; Beezhold, Kevin; Rojanasakul, Yon; Zhao, Hongwen; Castranova, Vince; Shi, Xianglin; Chen, Fei

    2009-07-01

    Lung cancer is the most common cancer worldwide, accounting for 1.3 million cancer deaths annually. Despite extensive studies over the past decade, the detailed mechanism about the initiation and development of the lung cancer is still elusive. In the present report, we showed that overexpression of mdig is a common feature of the non-small cell lung cancer. Gene silencing or overexpression of mdig revealed that mdig is involved in demethylation of tri-methyl lysine 9 on histone H3, leading to an increase in ribosomal RNA expression. The transcriptional regulation of ribosomal RNA gene by mdig is achieved through abrogating tri-methyl lysine 9 on histone H3 and enhancing RNA polymerase I occupancy in the promoter region of the ribosomal RNA gene as demonstrated by chromatin immunoprecipitation. The pronounced expression of mdig in lung cancer tissues but not normal lung tissues, thus, suggests that mdig possesses oncogenic property through antagonizing tri-methyl lysine 9 on histone H3 and promoting ribosomal RNA synthesis. PMID:19502796

  18. A Novel Approach to Predict Core Residues on Cancer-Related DNA-Binding Domains

    PubMed Central

    Wong, Ka-Chun

    2016-01-01

    Protein–DNA interactions are involved in different cancer pathways. In particular, the DNA-binding domains of proteins can determine where and how gene regulatory regions are bound in different cell lines at different stages. Therefore, it is essential to develop a method to predict and locate the core residues on cancer-related DNA-binding domains. In this study, we propose a computational method to predict and locate core residues on DNA-binding domains. In particular, we have selected the cancer-related DNA-binding domains for in-depth studies, namely, winged Helix Turn Helix family, homeodomain family, and basic Helix-Loop-Helix family. The results demonstrate that the proposed method can predict the core residues involved in protein–DNA interactions, as verified by the existing structural data. Given its good performance, various aspects of the method are discussed and explored: for instance, different uses of prediction algorithm, different protein domains, and hotspot threshold setting. PMID:27279732

  19. A Novel Approach to Predict Core Residues on Cancer-Related DNA-Binding Domains.

    PubMed

    Wong, Ka-Chun

    2016-01-01

    Protein-DNA interactions are involved in different cancer pathways. In particular, the DNA-binding domains of proteins can determine where and how gene regulatory regions are bound in different cell lines at different stages. Therefore, it is essential to develop a method to predict and locate the core residues on cancer-related DNA-binding domains. In this study, we propose a computational method to predict and locate core residues on DNA-binding domains. In particular, we have selected the cancer-related DNA-binding domains for in-depth studies, namely, winged Helix Turn Helix family, homeodomain family, and basic Helix-Loop-Helix family. The results demonstrate that the proposed method can predict the core residues involved in protein-DNA interactions, as verified by the existing structural data. Given its good performance, various aspects of the method are discussed and explored: for instance, different uses of prediction algorithm, different protein domains, and hotspot threshold setting. PMID:27279732

  20. International Note: Between-Domain Relations of Chinese High School Students' Academic Achievements

    ERIC Educational Resources Information Center

    Yangyang, Liu

    2012-01-01

    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…

  1. 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…

  2. Osteogenesis induced by frizzled-related protein (FRZB) is linked to the netrin-like domain.

    PubMed

    Thysen, Sarah; Cailotto, Frederic; Lories, Rik

    2016-05-01

    Abnormal Wnt signaling is associated with bone mass disorders. Frizzled-related protein (FRZB, also known as secreted frizzled-related protein-3 (SFRP3)) is a Wnt modulator that contains an amino-terminal cysteine-rich domain (CRD) and a carboxy-terminal Netrin-like (NTN) motif. Frzb(-/-) mice show increased cortical thickness. However, the direct effect of FRZB on osteogenic differentiation and the involvement of the structural domains herein are not fully understood. In this study, we observed that stable overexpression of Frzb in MC3T3-E1 cells increased calcium deposition and osteoblast markers compared with control. Western blot analysis showed that the increased osteogenesis was associated with reduced canonical, but increased non-canonical Wnt signaling. On the contrary, loss of Frzb induced the opposite effects on osteogenesis and Wnt signaling. To translationally validate the positive effects of FRZB on primary human cells, we treated human periosteal and human bone marrow stromal cells with conditioned medium from MC3T3-E1 cells overexpressing Frzb and observed an increase in Alizarin red staining. We further studied the effect of the domains. FrzbNTN overexpression induced similar effects on osteogenesis as full-length Frzb, whereas FrzbCRD overexpressing cells mimicked loss of Frzb experiments. The CRD is considered as the Wnt binding domain, but the NTN domain also has important effects on bone biology. FRZB and other SFRPs or their specific domains may hold surprising potential as therapeutics for bone and joint disorders considering that excess of SFRPs has effects that are not expected under physiological, endogenous expression conditions. PMID:26927515

  3. 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. PMID:26491833

  4. 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

  5. Relative Movements of Domains in Large Molecules of the Immune System

    PubMed Central

    Schreiner, Wolfgang; Karch, Rudolf; Ribarics, Reiner; Cibena, Michael; Ilieva, Nevena

    2015-01-01

    Molecular dynamics was used to simulate large molecules of the immune system (major histocompatibility complex class I, presented epitope, T-cell receptor, and a CD8 coreceptor.) To characterize the relative orientation and movements of domains local coordinate systems (based on principal component analysis) were generated and directional cosines and Euler angles were computed. As a most interesting result, we found that the presence of the coreceptor seems to influence the dynamics within the protein complex, in particular the relative movements of the two α-helices, Gα1 and Gα2. PMID:26798660

  6. 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. PMID:24109865

  7. Source-domain spectral EEG analysis of sports-related concussion via Measure Projection Analysis.

    PubMed

    Balkan, Ozgur; Virji-Babul, Naznin; Miyakoshi, Makoto; Makeig, Scott; Garudadri, Harinath

    2015-01-01

    Here, we investigated EEG-based source-level spectral differences between adolescents with sports-related concussions and healthy age matched controls. We transformed resting state EEG collected in both groups to the source domain using Independent Component Analysis (ICA) and computed the component process power spectra. For group-level analysis in the source domain, we used a probabilistic framework, Measure Projection Analysis (MPA), that has advantages over parametric k-means clustering of brain sources. MPA revealed that some frontal brain sources in the concussed group had significantly more power in the beta band (p<;0.005) and significantly less delta (p<;0.01) and theta band power (p<;0.05) than the healthy control group. These results suggest that a shift in spectral profile toward higher frequencies in some frontal brain regions might distinguish individuals with concussion from healthy controls. PMID:26737184

  8. Parametric forcing of waves with a nonmonotonic dispersion relation: Domain structures in ferrofluids

    SciTech Connect

    Raitt, D.; Riecke, H.

    1997-05-01

    Surface waves on ferrofluids exposed to a dc magnetic field exhibit a nonmonotonic dispersion relation. The effect of a parametric driving on such waves is studied within suitable coupled Ginzburg-Landau equations. Due to the nonmonotonicity the neutral curve for the excitation of standing waves can have up to three minima. The stability of the waves with respect to long-wave perturbations is determined via a phase-diffusion equation. It shows that the band of stable wave numbers can split up into two or three subbands. The resulting competition between the wave numbers corresponding to the respective subbands leads quite naturally to patterns consisting of multiple domains of standing waves which differ in their wave number. The coarsening dynamics of such domain structures is addressed. {copyright} {ital 1997} {ital The American Physical Society}

  9. Hillslopes to Hollows to Channels: Identifying Process Transitions and Domains using Characteristic Scaling Relations

    NASA Astrophysics Data System (ADS)

    Williams, K.; Locke, W. W.

    2011-12-01

    Headwater catchments are partitioned into hillslopes, unchanneled valleys (hollows), and channels. Low order (less than or equal to two) channels comprise most of the stream length in the drainage network so defining where hillslopes end and hollows begin, and where hollows end and channels begin, is important for calibration and verification of hydrologic runoff and sediment production modeling. We test the use of landscape scaling relations to detect flow regimes characteristic of diffusive, concentrated, and incisive runoff, and use these flow regimes as proxies for hillslope, hollow, and channeled landforms. We use LiDAR-derived digital elevation models (DEMs) of two pairs of headwater catchments in southwest and north-central Montana to develop scaling relations of flowpath length, total stream power, and contributing area. The catchment pairs contrast low versus high drainage density and north versus south aspect. Inflections in scaling relations of contributing area and flowpath length in a single basin (modified Hack's law) and contributing area and total stream power were used to identify hillslope and fluvial process domain transitions. In the modified Hack's law, inflections in the slope of the log-log power law are hypothesized to correspond to changes in flow regime used as proxies for hillslope, hollow, and channeled landforms. Similarly, rate of change of total stream power with contributing area is hypothesized to become constant and then decrease at the hillslope to fluvial domain transition. Power law scaling of frequency-magnitude plots of curvature and an aspect-related parameter were also tested as an indicator of the transition from scale-dependent hillslope length to the scale invariant fluvial domain. Curvature and aspect were calculated at each cell in spectrally filtered DEMs. Spectral filtering by fast Fourier and wavelet transforms enhances detection of fine-scale fluvial features by removing long wavelength topography. Using the

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

    PubMed

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

    2012-12-01

    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

  11. On the relation between traditional iterative methods and modern multilevel/domain decomposition methods

    SciTech Connect

    Griebel, M.

    1994-12-31

    In recent years, it has turned out that many modern iterative algorithms (multigrid schemes, multilevel preconditioners, domain decomposition methods etc.) for solving problems resulting from the discretization of PDEs can be interpreted as additive (Jacobi-like) or multiplicative (Gauss-Seidel-like) subspace correction methods. The key to their analysis is the study of certain metric properties of the underlying splitting of the discretization space V into a sum of subspaces V{sub j}, j = 1{hor_ellipsis}, J resp. of the variational problem on V into auxiliary problems on these subspaces. Here, the author proposes a modified approach to the abstract convergence theory of these additive and multiplicative Schwarz iterative methods, that makes the relation to traditional iteration methods more explicit. To this end he introduces the enlarged Hilbert space V = V{sub 0} x {hor_ellipsis} x V{sub j} which is nothing else but the usual construction of the Cartesian product of the Hilbert spaces V{sub j} and use it now in the discretization process. This results in an enlarged, semidefinite linear system to be solved instead of the usual definite system. Then, modern multilevel methods as well as domain decomposition methods simplify to just traditional (block-) iteration methods. Now, the convergence analysis can be carried out directly for these traditional iterations on the enlarged system, making convergence proofs of multilevel and domain decomposition methods more clear, or, at least, more classical. The terms that enter the convergence proofs are exactly the ones of the classical iterative methods. It remains to estimate them properly. The convergence proof itself follow basically line by line the old proofs of the respective traditional iterative methods. Additionally, new multilevel/domain decomposition methods are constructed straightforwardly by now applying just other old and well known traditional iterative methods to the enlarged system.

  12. 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

  13. 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

  14. Determine the Dispersion Relation of an A6 Magnetron Using Conformal Finite Difference Time Domain Method

    NASA Astrophysics Data System (ADS)

    Lin, M. C.; Nieter, C.; Stoltz, P. H.; Smithe, D. N.

    2009-05-01

    This work introduces a conformal finite difference time domain (CFDTD) method to accurately determine the dispersion relation of an A6 relativistic magnetron. The accuracy is measured by comparing with accurate SUPERFISH calculations based on finite element method. The results show that an accuracy of 99.4% can be achieved by using only 10,000 mesh points with Dey-Mittra algorithm. By comparison, a mesh number of 360,000 is needed to preserve 99% accuracy using conventional FDTD method. This suggests one can efficiently and accurately study the hot tests of microwave tubes using CFDTD particle-in-cell method instead of conventional FDTD one.

  15. Development of quantitative diagnostic observables for age-related macular degeneration using Spectral Domain OCT

    NASA Astrophysics Data System (ADS)

    Bower, Bradley A.; Chiu, Stephanie J.; Davies, Emily; Davis, Anjul M.; Zawadzki, Robert J.; Fuller, Alfred R.; Wiley, David F.; Izatt, Joseph A.; Toth, Cynthia A.

    2007-02-01

    We report on the development of quantitative, reproducible diagnostic observables for age-related macular degeneration (AMD) based on high speed spectral domain optical coherence tomography (SDOCT). 3D SDOCT volumetric data sets (512 x 1000 x 100 voxels) were collected (5.7 seconds acquisition time) in over 50 patients with age-related macular degeneration and geographic atrophy using a state-of-the-art SDOCT scanner. Commercial and custom software utilities were used for manual and semi-automated segmentation of photoreceptor layer thickness, total drusen volume, and geographic atrophy cross-sectional area. In a preliminary test of reproducibility in segmentation of total drusen volume and geographic atrophy surface area, inter-observer error was less than 5%. Extracted volume and surface area of AMD-related drusen and geographic atrophy, respectively, may serve as useful observables for tracking disease state that were not accessible without the rapid 3D volumetric imaging capability unique to retinal SDOCT.

  16. The ubiquitin-associated domain of AMPK-related kinases regulates conformation and LKB1-mediated phosphorylation and activation

    PubMed Central

    Jaleel, Mahaboobi; Villa, Fabrizio; Deak, Maria; Toth, Rachel; Prescott, Alan R.; van Aalten, Daan M. F.; Alessi, Dario R.

    2006-01-01

    Recent work indicates that the LKB1 tumour suppressor protein kinase, which is mutated in Peutz–Jeghers cancer syndrome, phosphorylates and activates a group of protein kinases that are related to AMPK (AMP-activated protein kinase). Ten of the 14 AMPK-related protein kinases activated by LKB1, including SIK (salt-induced kinase), MARK (microtubule-affinity-regulating kinase) and BRSK (brain-specific kinase) isoforms, possess a ubiquitin-associated (UBA) domain immediately C-terminal to the kinase catalytic domain. These are the only protein kinases in the human genome known to possess a UBA domain, but their roles in regulating AMPK-related kinases are unknown. We have investigated the roles that the UBA domain may play in regulating these enzymes. Limited proteolysis of MARK2 revealed that the kinase and UBA domains were contained within a fragment that was resistant to trypsin proteolysis. SAXS (small-angle X-ray scattering) analysis of inactive and active LKB1-phosphorylated MARK2 revealed that activation of MARK2 is accompanied by a significant conformational change that alters the orientation of the UBA domain with respect to the catalytic domain. Our results indicate that none of the UBA domains found in AMPK-related kinases interact with polyubiquitin or other ubiquitin-like molecules. Instead, the UBA domains appear to play an essential conformational role and are required for the LKB1-mediated phosphorylation and activation of AMPK-related kinases. This is based on the findings that mutation or removal of the UBA domains of several AMPK-related kinases, including isoforms of MARK, SIK and BRSK, markedly impaired the catalytic activity and LKB1-mediated phosphorylation of these enzymes. We also provide evidence that the UBA domains do not function as LKB1–STRAD (STE20-related adaptor)–MO25 (mouse protein 25) docking/interacting sites and that mutations in the UBA domain of SIK suppressed the ability of SIK to localize within punctate regions of the

  17. 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

  18. Polarized Defense Against Fungal Pathogens Is Mediated by the Jacalin-Related Lectin Domain of Modular Poaceae-Specific Proteins.

    PubMed

    Weidenbach, Denise; Esch, Lara; Möller, Claudia; Hensel, Goetz; Kumlehn, Jochen; Höfle, Caroline; Hückelhoven, Ralph; Schaffrath, Ulrich

    2016-04-01

    Modular proteins are an evolutionary answer to optimize performance of proteins that physically interact with each other for functionality. Using a combination of genetic and biochemical experiments, we characterized the rice protein OsJAC1, which consists of a jacalin-related lectin (JRL) domain predicted to bind mannose-containing oligosaccharides, and a dirigent domain which might function in stereoselective coupling of monolignols. Transgenic overexpression of OsJAC1 in rice resulted in quantitative broad-spectrum resistance against different pathogens including bacteria, oomycetes, and fungi. Overexpression of this gene or its wheat ortholog TAJA1 in barley enhanced resistance against the powdery mildew fungus. Both protein domains of OsJAC1 are required to establish resistance as indicated by single or combined transient expression of individual domains. Expression of artificially separated and fluorescence-tagged protein domains showed that the JRL domain is sufficient for targeting the powdery mildew penetration site. Nevertheless, co-localization of the lectin and the dirigent domain occurred. Phylogenetic analyses revealed orthologs of OsJAC1 exclusively within the Poaceae plant family. Dicots, by contrast, only contain proteins with either JRL or dirigent domain(s). Altogether, our results identify OsJAC1 as a representative of a novel type of resistance protein derived from a plant lineage-specific gene fusion event for better function in local pathogen defense. PMID:26708413

  19. Application of wearable computing in the manufacture and other related domain

    NASA Astrophysics Data System (ADS)

    XiaHou, Shi-Ji; Chen, Dong-Yi

    2005-12-01

    A survey of application of Wearable Computing in the Manufacture and other correlative domain is presented. At first, a short introduction to the Wearable Computing, such as the characters and its applications in some large manufacturing enterprises, is given, and then, an elaborate analysis of its typical applications scenario in the manufacture and other correlative domains is provided. Thirdly, a few typical wearable application research works on equipment installment, maintenance, operation watch, and fault diagnose, repair and corresponding operation training, is summed up. Fourthly, these scenarios character in special working environment and complex task process is analyzed. Fifthly, the related research works and depict the typical work flow of the wearable computer operators in these application scenarios is summarized, and the demand of the wearable computer's support soft system is depicted. Some key technologies for implementing this support soft system is presented according to these demands include Adaptive Human-Computer Interface, Augment Reality, Workflow Design and Sensor Network, etc. At last, an infrastructure for the system design, include software and hardware architecture, is introduced.

  20. Complex domain interactions regulate stability and activity of closely related proneural transcription factors

    PubMed Central

    McDowell, Gary S.; Hardwick, Laura J.A.; Philpott, Anna

    2014-01-01

    Characterising post-translational regulation of key transcriptional activators is crucial for understanding how cell division and differentiation are coordinated in developing organisms and cycling cells. One important mode of protein post-translational control is by regulation of half-life via ubiquitin-mediated proteolysis. Two key basic Helix-Loop-Helix transcription factors, Neurogenin 2 (Ngn2) and NeuroD, play central roles in development of the central nervous system but despite their homology, Ngn2 is a highly unstable protein whilst NeuroD is, by comparison, very stable. The basis for and the consequences of the difference in stability of these two structurally and functionally related proteins has not been explored. Here we see that ubiquitylation alone does not determine Ngn2 or NeuroD stability. By making chimeric proteins, we see that the N-terminus of NeuroD in particular has a stabilising effect, whilst despite their high levels of homology, the most conserved bHLH domains of these proneural proteins alone can confer significant changes in protein stability. Despite widely differing stabilities of Ngn2, NeuroD and the chimeric proteins composed of domains of both, there is little correlation between protein half-life and ability to drive neuronal differentiation. Therefore, we conclude that despite significant homology between Ngn2 and NeuroD, the regulation of their stability differs markedly and moreover, stability/instability of the proteins is not a direct correlate of their activity. PMID:24998442

  1. Expanding the Landscape of Chromatin Modification (CM)-Related Functional Domains and Genes in Human

    PubMed Central

    Pu, Shuye; Turinsky, Andrei L.; Vlasblom, James; On, Tuan; Xiong, Xuejian; Emili, Andrew; Zhang, Zhaolei; Greenblatt, Jack; Parkinson, John; Wodak, Shoshana J.

    2010-01-01

    Chromatin modification (CM) plays a key role in regulating transcription, DNA replication, repair and recombination. However, our knowledge of these processes in humans remains very limited. Here we use computational approaches to study proteins and functional domains involved in CM in humans. We analyze the abundance and the pair-wise domain-domain co-occurrences of 25 well-documented CM domains in 5 model organisms: yeast, worm, fly, mouse and human. Results show that domains involved in histone methylation, DNA methylation, and histone variants are remarkably expanded in metazoan, reflecting the increased demand for cell type-specific gene regulation. We find that CM domains tend to co-occur with a limited number of partner domains and are hence not promiscuous. This property is exploited to identify 47 potentially novel CM domains, including 24 DNA-binding domains, whose role in CM has received little attention so far. Lastly, we use a consensus Machine Learning approach to predict 379 novel CM genes (coding for 329 proteins) in humans based on domain compositions. Several of these predictions are supported by very recent experimental studies and others are slated for experimental verification. Identification of novel CM genes and domains in humans will aid our understanding of fundamental epigenetic processes that are important for stem cell differentiation and cancer biology. Information on all the candidate CM domains and genes reported here is publicly available. PMID:21124763

  2. Dual-band Fourier domain optical coherence tomography with depth-related compensations

    PubMed Central

    Zhang, Miao; Ma, Lixin; Yu, Ping

    2013-01-01

    Dual-band Fourier domain optical coherence tomography (FD-OCT) provides depth-resolved spectroscopic imaging that enhances tissue contrast and reduces image speckle. However, previous dual-band FD-OCT systems could not correctly give the tissue spectroscopic contrast due to depth-related discrepancy in the imaging method and attenuation in biological tissue samples. We designed a new dual-band full-range FD-OCT imaging system and developed an algorithm to compensate depth-related fall-off and light attenuation. In our imaging system, the images from two wavelength bands were intrinsically overlapped and their intensities were balanced. The processing time of dual-band OCT image reconstruction and depth-related compensations were minimized by using multiple threads that execute in parallel. Using the newly developed system, we studied tissue phantoms and human cancer xenografts and muscle tissues dissected from severely compromised immune deficient mice. Improved spectroscopic contrast and sensitivity were achieved, benefiting from the depth-related compensations. PMID:24466485

  3. 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

  4. Topography of Somatostatin Gene Expression Relative to Molecular Progenitor Domains during Ontogeny of the Mouse Hypothalamus

    PubMed Central

    Morales-Delgado, Nicanor; Merchan, Paloma; Bardet, Sylvia M.; Ferrán, José L.; Puelles, Luis; Díaz, Carmen

    2010-01-01

    The hypothalamus comprises alar, basal, and floor plate developmental compartments. Recent molecular data support a rostrocaudal subdivision into rostral (terminal) and caudal (peduncular) halves. In this context, the distribution of neuronal populations expressing somatostatin (Sst) mRNA was analyzed in the developing mouse hypothalamus, comparing with the expression pattern of the genes Orthopedia (Otp), Distal-less 5 (Dlx5), Sonic Hedgehog (Shh), and Nk2 homeobox 1 (Nkx2.1). At embryonic day 10.5 (E10.5), Sst mRNA was first detectable in the anterobasal nucleus, a Nkx2.1-, Shh-, and Otp-positive basal domain. By E13.5, nascent Sst expression was also related to two additional Otp-positive domains within the alar plate and one in the basal plate. In the alar plate, Sst-positive cells were observed in rostral and caudal ventral subdomains of the Otp-positive paraventricular complex. An additional basal Sst-expressing cell group was found within a longitudinal Otp-positive periretromamillary band that separates the retromamillary area from tuberal areas. Apart of subsequent growth of these initial populations, at E13.5 and E15.5 some Sst-positive derivatives migrate tangentially into neighboring regions. A subset of cells produced at the anterobasal nucleus disperses ventralward into the shell of the ventromedial hypothalamic nucleus and the arcuate nucleus. Cells from the rostroventral paraventricular subdomain reach the suboptic nucleus, whereas a caudal contingent migrates radially into lateral paraventricular, perifornical, and entopeduncular nuclei. Our data provide a topologic map of molecularly defined progenitor areas originating a specific neuron type during early hypothalamic development. Identification of four main separate sources helps to understand causally its complex adult organization. PMID:21441981

  5. Identifying key domains of health-related quality of life for patients with Chronic Obstructive Pulmonary Disease: the patient perspective

    PubMed Central

    2014-01-01

    Background Numerous instruments are available to measure health-related quality of life (HRQoL) in patients with Chronic Obstructive Pulmonary Disease (COPD), covering a wide array of domains ranging from symptoms such as dyspnea, cough and wheezing, to social and emotional functioning. Currently no information or guide is available yet to aid the selection of domains for a particular study or disease population. The aim of this paper is to identify which domains of HRQoL are most important with respect to COPD, from the patient perspective. Methods Twenty-one Dutch patients with COPD were asked to describe important domains impacted by COPD freely; second, they were presented with cues (domains from the Patient-Reported Outcomes Measurement Information System (PROMIS) framework) and were asked to select the domains that were most relevant to them. During the interview, the patients were asked to indicate in which way the selected domains impact their lives. Both the answers to the open question, and the patient statements motivating nomination of PROMIS domains were coded into themes. Results The most relevant (sub)domains of HRQoL for patients with COPD were: physical health (fatigue, physical functioning), social health (instrumental support, ability to participate in social roles and activities, companionship, and emotional support), and coping with COPD. Conclusion We identified which domains of HRQoL are most important to patients with COPD. One of these (coping with COPD) is not explicitly covered by PROMIS, or by traditional questionnaires that are used to measure HRQoL in COPD. PMID:25005552

  6. Influence of voxelization on finite difference time domain simulations of head-related transfer functions.

    PubMed

    Prepeliță, Sebastian; Geronazzo, Michele; Avanzini, Federico; Savioja, Lauri

    2016-05-01

    The scattering around the human pinna that is captured by the Head-Related Transfer Functions (HRTFs) is a complex problem that creates uncertainties in both acoustical measurements and simulations. Within the simulation framework of Finite Difference Time Domain (FDTD) with axis-aligned staircase boundaries resulting from a voxelization process, the voxelization-based uncertainty propagating in the HRTF-captured sound field is quantified for one solid and two surface voxelization algorithms. Simulated results utilizing a laser-scanned mesh of Knowles Electronics Manikin for Acoustic Research (KEMAR) show that in the context of complex geometries with local topology comparable to grid spacing such as the human pinna, the voxelization-related uncertainties in simulations emerge at lower frequencies than the generally used accuracy bandwidths. Numerical simulations show that the voxelization process induces both random error and algorithm-dependent bias in the simulated HRTF spectral features. Frequencies fr below which the random error is bounded by various dB thresholds are estimated and predicted. Particular shortcomings of the used voxelization algorithms are identified and the influence of the surface impedance on the induced errors is studied. Simulations are also validated against measurements. PMID:27250145

  7. A method for finding candidate conformations for molecular replacement using relative rotation between domains of a known structure.

    PubMed

    Jeong, Jay I; Lattman, Eaton E; Chirikjian, Gregory S

    2006-04-01

    This paper presents a methodology to obtain candidate conformations of multidomain proteins for use in molecular replacement. For each separate domain, the orientational relationship between the template and the target structure is obtained using standard molecular replacement. The orientational relationships of the domains are then used to calculate the relative rotation between the domains in the target conformation by using pose-estimation techniques from the field of robotics and computer vision. With the angle of relative rotation between the domains as a cost function, iterative normal-mode analysis is used to drive the template structure to a candidate conformation that matches the X-ray crystallographic data obtained for the target conformation. The selection of the correct intra-protein domain orientations from among the many spurious maxima in the rotation function (including orientations obtained from domains in symmetry mates rather than within the same copy of the protein) presents a challenge. This problem is resolved by checking R factors of each domain, measuring the absolute value of relative rotation between domains, and evaluating the cost value after each candidate conformation is driven to convergence with iterative NMA. As a validation, the proposed method is applied to three test proteins: ribose-binding protein, lactoferrin and calcium ATPase. In each test case, the orientation and translation of the final candidate conformation in the unit cell are generated correctly from the suggested procedure. The results show that the proposed method can yield viable candidate conformations for use in molecular replacement and can reveal the structural details and pose of the target conformation in the crystallographic unit cell. PMID:16552141

  8. 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…

  9. Response Biases and Their Relation to Sex Differences in Multiple Domains of Self-Concept.

    ERIC Educational Resources Information Center

    Vispoel, Walter P.; Forte Fast, Ellen E.

    2000-01-01

    Examined the influence of two forms of socially desirable responding on scores within 17 domains of self-concept from 3 measures completed by 390 college students. Found significant sex differences in 12 domains. Discusses the role of impression management in creating some apparent sex differences. (SLD)

  10. 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…

  11. 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…

  12. 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

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

    SciTech Connect

    Thomas, Stacey L.; Deadwyler, Gail D.; Tang, Jun; Stubbs, Evan B.; Muir, David; Hiatt, Kelly K. . E-mail: George.Devries@med.va.gov

    2006-09-29

    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, 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.

  14. A Computer Program to Relate Factors Across Separately Factor Analyzed Variable Domains

    ERIC Educational Resources Information Center

    Morris, John D.; Guertin, Wilson H.

    1976-01-01

    A Fortran IV program is presented which will cross-correlate least squares estimated factor scores across separately factor analyzed variable domains without the tedious necessity of actually calculating the factor scores. (RC)

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

    SciTech Connect

    Zhou, Dongwen; Chung, Suhman; Miller, Maria; Le Grice, Stuart F.J.; Wlodawer, Alexander

    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 intact 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.

  16. Relative Orientation of POTRA Domains from Cyanobacterial Omp85 Studied by Pulsed EPR Spectroscopy.

    PubMed

    Dastvan, Reza; Brouwer, Eva-Maria; Schuetz, Denise; Mirus, Oliver; Schleiff, Enrico; Prisner, Thomas F

    2016-05-24

    Many proteins of the outer membrane of Gram-negative bacteria and of the outer envelope of the endosymbiotically derived organelles mitochondria and plastids have a β-barrel fold. Their insertion is assisted by membrane proteins of the Omp85-TpsB superfamily. These proteins are composed of a C-terminal β-barrel and a different number of N-terminal POTRA domains, three in the case of cyanobacterial Omp85. Based on structural studies of Omp85 proteins, including the five POTRA-domain-containing BamA protein of Escherichia coli, it is predicted that anaP2 and anaP3 bear a fixed orientation, whereas anaP1 and anaP2 are connected via a flexible hinge. We challenged this proposal by investigating the conformational space of the N-terminal POTRA domains of Omp85 from the cyanobacterium Anabaena sp. PCC 7120 using pulsed electron-electron double resonance (PELDOR, or DEER) spectroscopy. The pronounced dipolar oscillations observed for most of the double spin-labeled positions indicate a rather rigid orientation of the POTRA domains in frozen liquid solution. Based on the PELDOR distance data, structure refinement of the POTRA domains was performed taking two different approaches: 1) treating the individual POTRA domains as rigid bodies; and 2) using an all-atom refinement of the structure. Both refinement approaches yielded ensembles of model structures that are more restricted compared to the conformational ensemble obtained by molecular dynamics simulations, with only a slightly different orientation of N-terminal POTRA domains anaP1 and anaP2 compared with the x-ray structure. The results are discussed in the context of the native environment of the POTRA domains in the periplasm. PMID:27224485

  17. Mutational analysis of the NF1 GAP-related domain in neuroectodermal tumors

    SciTech Connect

    Vinanzi, C.; Basso, G.; Perilongo, G.

    1994-09-01

    To try to contribute to the more precise characterization of the function of the NF1 gene in tumorigenesis we have analyzed the most conserved region of its coding sequence, the GAP-related domain (NF1 GRD), which is attributed with tumor suppressor function. The rationale for the study was based on the likelihood of finding structural alterations resulting in loss of function of this region, in situations such as tumors of neuroepithelial tissues. In these situations, the activity of the NF1 gene product, neurofibromis, a GTPase activating protein, seems to be crucial in regulating the mechanisms of signal transduction mediated by p21 ras. We have studied the NF1 GRD region by PCR amplification of each exon (exons 21-27a) followed by subsequent PAGE and SSCP analysis of the amplification products in 60 primary sporadic neuroectodermal tumors. Our sample included: 14 neuroblastoma, 11 glioblastoma, 8 medulloblastoma, 7 ependimoma, 6 peripheral PNET, 1 ganglioneuroma, 1 glioma, 1 Ewing sarcoma, 1 meningioma and 1 schwannoma. We have not identified structural alterations of the NF1 GRD region in the tumors analysed, with one possible exception now in the process of being characterized. We can conclude that the loss of the NF1 gene tumor suppressor function that might lead or contribute to the development of malignancies in tissues of neuroectodermal origin is not due to structural abnormalities of the region of the gene interacting with p21 ras, either as a negative regulator or as a downstream effector of it. These data, together with the observation that the oncogene ras 21 is not typically mutated in neuroectodermal tumors, and that GTP-ras has been found normally regulated in neurofibromis-deficient melanoma and neuroblastoma cell lines, seem to support the hypothesis that the antioncogene activity of the NF1 gene could be totally independent from its interaction with ras.

  18. Comparative Analysis of Barophily-Related Amino Acid Content in Protein Domains of Pyrococcus abyssi and Pyrococcus furiosus

    PubMed Central

    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. PMID:24187517

  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. Relative roles of the different Pax6 domains for pancreatic alpha cell development

    PubMed Central

    2010-01-01

    Background The transcription factor Pax6 functions in the specification and maintenance of the differentiated cell lineages in the endocrine pancreas. It has two DNA binding domains, the paired domain and the homeodomain, in addition to a C-terminal transactivation domain. The phenotype of Pax6-/- knockout mice suggests non-redundant functions of the transcription factor in the development of glucagon-expressing α-cells as this cell type is absent in the mutants. We ask the question of how the differentiation of pancreatic endocrine cells, in particular that of α-cells, is affected by selective inactivation of either one of the three major domains of Pax6. Results The Pax6Aey18 mutant mouse line, in which the paired domain is inactivated, showed a phenotype similar to that of Pax6-/- knockout mice with a near complete absence of glucagon-positive α-cells (0-4 cells/section; ≤1% of wt), reduced β-cell area (74% of wt) and disorganized islets. The proportion of ghrelin-positive ε-cells was expanded. In Pax6Sey-Neu mutants, which lack the transactivation domain, α-and β-cells where reduced to 25 and 40% of wt, respectively. We also studied two mouse lines with mutations in the homeodomain, Pax64Neu and Pax6132-14Neu. Neighboring amino acids are affected in the two lines and both point mutations abolish DNA binding of the classical P3 homeodomain target sequence. The pancreatic phenotype of the two mutants however was divergent. While Pax64Neu homozygotes showed a reduction of α- and β-cells to 59 and 61%, respectively, pancreatic endocrine development was unaltered in the Pax6132-14Neu mutant strain. Conclusions We show that inactivation of the Pax6 paired domain leads to a more severe phenotype with regards to the differentiation of pancreatic α-cells than the loss of the transactivation domain. The analysis of two different homeodomain mutants suggests that the binding of Pax6 to P3 homeodomain consensus sequences is not required for α-cell development

  1. 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. PMID:24379409

  2. 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

  3. Axionic domain wall number related to U(1)anom global symmetry

    NASA Astrophysics Data System (ADS)

    Kim, Jihn E.

    2016-08-01

    The QCD axion with fa at an intermediate scale, 109 GeV ∼1012 GeV, seems in conflict with the gravity spoil of global symmetries and may face the axionic domain wall problem. We point out that the string compactifications with an anomalous U(1) gauge symmetry, allowing desirable chiral matter spectra, circumvent these two problems simultaneously.

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

    PubMed

    Eu, Byung Chan

    2008-09-01

    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. PMID:19044872

  5. Moral/Non-Moral Domain Shift in Young Adolescents in Relation to Delinquent Behaviour

    ERIC Educational Resources Information Center

    Leenders, Ineke; Brugman, Daniel

    2005-01-01

    Because moral transgressions are considered more serious than non-moral (i.e. conventional or personal) transgressions, it is less threatening to self-esteem to interpret one's own delinquent act as a non-moral transgression rather than a moral transgression. This 'domain shift' could be a way of reducing cognitive dissonance. It was expected that…

  6. 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…

  7. The Relative Influence of Different Domains of Social Connectedness on Self-Directed Violence in Adolescence

    ERIC Educational Resources Information Center

    Kaminski, Jennifer W.; Puddy, Richard W.; Hall, Diane M.; Cashman, Sandra Y.; Crosby, Alexander E.; Ortega, LaVonne A. G.

    2010-01-01

    Previous research has linked greater social connectedness with a lowered risk of self-directed violence among adolescents. However, few studies have analyzed the comparative strength of different domains of connectedness (e.g., family, peers and school) to determine where limited resources might best be focused. Data to address that gap were taken…

  8. 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.

  9. 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…

  10. Structural priming across cognitive domains: from simple arithmetic to relative-clause attachment.

    PubMed

    Scheepers, Christoph; Sturt, Patrick; Martin, Catherine J; Myachykov, Andriy; Teevan, Kay; Viskupova, Izabela

    2011-10-01

    In the two experiments reported here, we uncovered evidence for shared structural representations between arithmetic and language. Specifically, we primed subjects using mathematical equations either with or without parenthetical groupings, such as 80 - (9 + 1) × 5 or 80 - 9 + 1 × 5, and then presented a target sentence fragment, such as "The tourist guide mentioned the bells of the church that . . .," which subjects had to complete. When the mathematical equations were solved correctly, their structure influenced the noun phrase--for example, either "the bells of the church" or "the church," respectively--that subjects chose to attach their sentence completion to. These experiments provide the first demonstration of cross-domain structural priming from mathematics to language. They highlight the importance of global structural representations at a very high level of abstraction and have potentially far-reaching implications regarding the domain generality of structural representations. PMID:21873569

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

    SciTech Connect

    Gelinas, A.; Paschini, M; Reyes, F; Heroux, A; Batey, R; Lundblad, V; Wuttke, D

    2009-01-01

    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 support 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.

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

    SciTech Connect

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

    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 finger 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.

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

    SciTech Connect

    Lawrence, Paul; Conderino, Joseph S.; Rieder, Elizabeth

    2014-03-15

    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 with 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.

  14. 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.

  15. The New Health-Related Top-Level Domains Are Coming: Will Cureforcancer.health Go to the Highest Bidder?

    PubMed Central

    2014-01-01

    In 2012, the Internet Corporation for Assigned Names and Numbers (ICANN) opened a new round of applications for generic top-level domain (gTLD) names, receiving 1930 applications, of which at least 18 were related to health (eg, “.doctor”, “.health”, “.med”). The entry of new, commercial players applying to create health-related names reopens the debate on the role of international organizations, governments, non-governmental organizations, and other stakeholders regarding the safeguards and policies needed to protect consumers. PMID:24598704

  16. Overexpression of the JmjC histone demethylase KDM5B in human carcinogenesis: involvement in the proliferation of cancer cells through the E2F/RB pathway

    PubMed Central

    2010-01-01

    Background Although an increasing number of histone demethylases have been identified and biochemically characterized, their biological functions largely remain uncharacterized, particularly in the context of human diseases such as cancer. We investigated the role of KDM5B, a JmjC histone demethylase, in human carcinogenesis. Quantitative RT-PCR and microarray analyses were used to examine the expression profiles of histone demethylases in clinical tissue samples. We also examined the functional effects of KDM5B on the growth of cancer cell lines treated with small interfering RNAs (siRNAs). Downstream genes and signal cascades induced by KDM5B expression were identified from Affymetrix Gene Chip experiments, and validated by real-time PCR and reporter assays. Cell cycle-dependent characteristics of KDM5B were identified by immunofluorescence and FACS. Results Quantitative RT-PCR analysis confirmed that expression levels of KDM5B are significantly higher in human bladder cancer tissues than in their corresponding non-neoplastic bladder tissues (P < 0.0001). The expression profile analysis of clinical tissues also revealed up-regulation of KDM5B in various kinds of malignancies. Transfection of KDM5B-specific siRNA into various bladder and lung cancer cell lines significantly suppressed the proliferation of cancer cells and increased the number of cells in sub-G1 phase. Microarray expression analysis indicated that E2F1 and E2F2 are downstream genes in the KDM5B pathway. Conclusions Inhibition of KDM5B may affect apoptosis and reduce growth of cancer cells. Further studies will explore the pan-cancer therapeutic potential of KDM5B inhibition. PMID:20226085

  17. Extraction of gene-disease relations from Medline using domain dictionaries and machine learning.

    PubMed

    Chun, Hong-Woo; Tsuruoka, Yoshimasa; Kim, Jin-Dong; Shiba, Rie; Nagata, Naoki; Hishiki, Teruyoshi; Tsujii, Jun'ichi

    2006-01-01

    We describe a system that extracts disease-gene relations from Medline. We constructed a dictionary for disease and gene names from six public databases and extracted relation candidates by dictionary matching. Since dictionary matching produces a large number of false positives, we developed a method of machine learning-based named entity recognition (NER) to filter out false recognitions of disease/gene names. We found that the performance of relation extraction is heavily dependent upon the performance of NER filtering and that the filtering improves the precision of relation extraction by 26.7% at the cost of a small reduction in recall. PMID:17094223

  18. 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.

  19. Expression and purification of human MHC class I-related chain molecule B-α1 domain.

    PubMed

    Wang, Shufen; Xiang, Zemin; Wang, Ya; Xu, Huanhuan; Zhang, Dengyang; Wang, Xuanjun; Sheng, Jun

    2016-07-01

    Major histocompatibility complex (MHC) class I-related chain A/B (MICA/B) is a type of stress-induced molecule that plays an important role in tumor surveillance. MICA/B shares a similar structure with MHC class I molecules, but MICA/B contains a closed cleft, not an open one, in its N-terminal alpha1 domain. The alpha 1 domain was believed to have no roles in antigen presentation, because the closed cleft provides limited space for binding with known molecules, and the cleft of MICA/B have been reported no known functions. To study the possible function of the cleft located in human MICA/B's alpha 1 domain, we attempted to express the human MICB-α1 (hMICB-α1) domain allele protein, which is approximately 20.5 kDa, by utilizing an Escherichia coli (E. coli) secretory pathway. Protein expression was accomplished through the phosphate-limited inducible promoter. After purification using ammonium sulfate precipitation, phenyl hydrophobic Sepharose, SP Sepharose and HisTrap affinity Sepharose, recombinant human MICB-α1 (rhMICB-α1) was obtained with 94.3% purity. The binding capacity of rhMICB-α1 with natural killer group 2, member D (NKG2D) was evaluated in vitro. The results demonstrated that rhMICB-α1 can be prepared through the E. coli secretory pathway. Purified rhMICB-α1 protein was able to functionally bind with NKG2D. This method can be further used to obtain functionally active rhMICB-α1 protein, which can served as the basis for further studies of the possible function of the MICB cleft. PMID:27036081

  20. Demand-Driven Clustering in Relational Domains for Predicting Adverse Drug Events

    PubMed Central

    Davis, Jesse; Costa, Vítor Santos; Peissig, Peggy; Caldwell, Michael; Berg, Elizabeth; Page, David

    2013-01-01

    Learning from electronic medical records (EMR) is challenging due to their relational nature and the uncertain dependence between a patient's past and future health status. Statistical relational learning is a natural fit for analyzing EMRs but is less adept at handling their inherent latent structure, such as connections between related medications or diseases. One way to capture the latent structure is via a relational clustering of objects. We propose a novel approach that, instead of pre-clustering the objects, performs a demand-driven clustering during learning. We evaluate our algorithm on three real-world tasks where the goal is to use EMRs to predict whether a patient will have an adverse reaction to a medication. We find that our approach is more accurate than performing no clustering, pre-clustering, and using expert-constructed medical heterarchies. PMID:25285329

  1. Domain-Specific Expertise of Chemistry Teachers on Context-Based Education about Macro-Micro Thinking in Structure-Property Relations

    ERIC Educational Resources Information Center

    Dolfing, Ria; Bulte, Astrid M. W.; Pilot, Albert; Vermunt, Jan D.

    2012-01-01

    This study aims to determine and describe the new domain-specific expertise of experienced chemistry teachers in teaching an innovative context-based unit about macro-micro thinking in structure-property relations. The construct of "teachers' domain-specific expertise" was used to analyse the new repertoire chemistry teachers need to acquire to…

  2. Fusion Activity of HIV gp41 Fusion Domain is Related to its Secondary Structure and Depth of Membrane Insertion in a Cholesterol-Dependent Fashion

    PubMed Central

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

    2013-01-01

    The HIV gp41 fusion domain plays a critical role in membrane fusion during viral entry. A thorough understanding of the relationship between the structure and 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. In membranes containing less than 30 mol% cholesterol the fusion domain formed an α-helix and in membranes containing equal to or more than 30 mol% cholesterol the fusion domain formed β-sheet secondary structure. 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 and β-sheet forms. High cholesterol, which induced β-sheet, promoted fusion, but 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 their membrane insertion is deep, α-helical and β-sheet conformations contribute to membrane fusion. PMID:22343048

  3. Module swaps between related translocator proteins pIV(f1), pIV(IKe) and PulD: identification of a specificity domain.

    PubMed

    Daefler, S; Russel, M; Model, P

    1997-03-14

    In Gram-negative bacteria, type II and type III secretion and filamentous phage assembly systems use related outer membrane proteins for substrate-specific transport across the outer membrane. We show here that the specificity domain of the phage f1 outer membrane protein pIV is contained within the 149 N-terminal amino acid residues. When the pIV(f1) specificity domain is fused to the translocator domain of the related pIV of phage IKe, the chimeric construct supports f1 but not IKe assembly. Functional coupling between the two domains in this chimeric construct is poor and is improved by a single amino acid change in the translocator domain of the pIV(IKe). In native pIV(IKe), two amino acid changes within its specificity domain are both necessary and sufficient to change the specificity from IKe to f1 assembly. Analysis of 39 chimeric constructs between pIV(f1) and the outer membrane protein PulD of the pullulanase secretion system failed to identify a comparable exchangeable specificity domain. These results indicate that the two domains may not function autonomously, and suggest that tertiary and quarternary changes of the entire translocator component rather than of an autonomous functional domain are required for specific translocation across the outer membrane. PMID:9086275

  4. Academic Self-Concept and Emotion Relations: Domain Specificity and Age Effects

    ERIC Educational Resources Information Center

    Goetz, Thomas; Cronjaeger, Hanna; Frenzel, Anne C.; Ludtke, Oliver; Hall, Nathan C.

    2010-01-01

    The present study investigated the relations between academic self-concepts and the emotions of enjoyment, pride, anxiety, anger, and boredom as experienced in mathematics, physics, German, and English classes (N=1710; grades 8 and 11). In line with our hypotheses derived from appraisal-based emotion theories and self-efficacy research,…

  5. Quality of Parental Homework Involvement: Predictors and Reciprocal Relations with Academic Functioning in the Reading Domain

    ERIC Educational Resources Information Center

    Dumont, Hanna; Trautwein, Ulrich; Nagy, Gabriel; Nagengast, Benjamin

    2014-01-01

    This study examined predictors of the quality of parental homework involvement and reciprocal relations between the quality of parental homework involvement and students' reading achievement and academic functioning in a reading-intensive subject (German). Data from 2,830 students in nonacademic tracks and their parents who were surveyed in both…

  6. Nonlinear Time Domain Relation between Respiratory Phase and Timing of the First Heart Sound.

    PubMed

    Tang, Hong; Park, Yongwan; Ruan, Chengjie

    2015-01-01

    The previous studies on respiratory physiology have indicated that inspiration and expiration have opposite effects on heart hemodynamics. The basic reason why these opposite hemodynamic changes cause regular timing variations in heart sounds is the heart sound generation mechanism that the acoustic vibration is triggered by heart hemodynamics. It is observed that the timing of the first heart sound has nonlinear relation with respiratory phase; that is, the timing delay with respect to the R-wave increases with inspiration and oppositely decreases with expiration. This paper models the nonlinear relation by a Hammerstein-Wiener model where the respiratory phase is the input and the timing is the output. The parameter estimation for the model is presented. The model is tested by the data collected from 12 healthy subjects in terms of mean square error and model fitness. The results show that the model can approximate the nonlinear relation very well. The average square error and the average fitness for all the subjects are about 0.01 and 0.94, respectively. The timing of the first heart sound related to respiratory phase can be accurately predicted by the model. The model has potential applications in fast and easy monitoring of respiration and heart hemodynamics induced by respiration. PMID:26550022

  7. What Is Learned when Concept Learning Fails?--A Theory of Restricted-Domain Relational Learning

    ERIC Educational Resources Information Center

    Wright, Anthony A.; Lickteig, Mark T.

    2010-01-01

    Two matching-to-sample (MTS) and four same/different (S/D) experiments employed tests to distinguish between item-specific learning and relational learning. One MTS experiment showed item-specific learning when concept learning failed (i.e., no novel-stimulus transfer). Another MTS experiment showed item-specific learning when pigeons'…

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

    PubMed

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

    2016-01-01

    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 Mg(2+) 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 Mg(2+)-dependent sterol binding by Pry1. PMID:27344972

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

    PubMed Central

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

    2016-01-01

    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. PMID:27344972

  10. 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.

  11. Student Agency: an Analysis of Students' Networked Relations Across the Informal and Formal Learning Domains

    NASA Astrophysics Data System (ADS)

    Rappa, Natasha Anne; Tang, Kok-Sing

    2016-05-01

    Agency is a construct facilitating our examination of when and how young people extend their own learning across contexts. However, little is known about the role played by adolescent learners' sense of agency. This paper reports two cases of students' agentively employing and developing science literacy practices—one in Singapore and the other in the USA. The paper illustrates how these two adolescent learners in different ways creatively accessed, navigated and integrated in-school and out-of-school discourses to support and nurture their learning of physics. Data were gleaned from students' work and interviews with students participating in a physics curricular programme in which they made linkages between their chosen out-of-school texts and several physics concepts learnt in school. The students' agentive moves were identified by means of situational mapping, which involved a relational analysis of the students' chosen artefacts and discourses across time and space. This relational analysis enabled us to address questions of student agency—how it can be effected, realised, construed and examined. It highlights possible ways to intervene in these networked relations to facilitate adolescents' agentive moves in their learning endeavours.

  12. 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

  13. GNBP domain of Anopheles darlingi: are polymorphic inversions and gene variation related to adaptive evolution?

    PubMed

    Bridi, L C; Rafael, M S

    2016-02-01

    Anopheles darlingi is the main malaria vector in humans in South America. In the Amazon basin, it lives along the banks of rivers and lakes, which responds to the annual hydrological cycle (dry season and rainy season). In these breeding sites, the larvae of this mosquito feed on decomposing organic and microorganisms, which can be pathogenic and trigger the activation of innate immune system pathways, such as proteins Gram-negative binding protein (GNBP). Such environmental changes affect the occurrence of polymorphic inversions especially at the heterozygote frequency, which confer adaptative advantage compared to homozygous inversions. We mapped the GNBP probe to the An. darlingi 2Rd inversion by fluorescent in situ hybridization (FISH), which was a good indicator of the GNBP immune response related to the chromosomal polymorphic inversions and adaptative evolution. To better understand the evolutionary relations and time of divergence of the GNBP of An. darlingi, we compared it with nine other mosquito GNBPs. The results of the phylogenetic analysis of the GNBP sequence between the species of mosquitoes demonstrated three clades. Clade I and II included the GNBPB5 sequence, and clade III the sequence of GNBPB1. Most of these sequences of GNBP analyzed were homologous with that of subfamily B, including that of An. gambiae (87 %), therefore suggesting that GNBP of An. darling belongs to subfamily B. This work helps us understand the role of inversion polymorphism in evolution of An. darlingi. PMID:26767379

  14. Ductile shear zones related to crustal shortening and domain boundary evolution in the central Fennoscandian Shield

    NASA Astrophysics Data System (ADS)

    HöGdahl, Karin; SjöStröM, HâKan; Bergman, Stefan

    2009-02-01

    The Paleoproterozoic part of the Fennoscandian Shield is composed of crustal components formed in different tectonic settings and generally separated by well-defined shear zone systems. An anomalous transitional boundary has been investigated by integrating structural analysis and geochronology with published geophysical data. The nature of this boundary is interpreted to be a consequence of an apparent stacking in the lower and middle crust initiating 1.87-1.86 Ga dextral shear along the Gävle-Rättvik Zone (GRZ) and adjacent shear zones, resulting in an arcuate northern boundary of the Bergslagen province. This boundary coincides with geophysical anomalies and temporal and metamorphic breaks. Owing to continuous convergence the pure-shear overprint component increased on the GRZ and caused a shift of dextral shear to the Hagsta Gneiss Zone with recorded shear at 1809 ± 2 Ma. Most likely, both these structures are related to coeval shear zones farther to the east as a part of an ˜1500 km long crustal, or possibly terrane, boundary.

  15. A detailed consideration of a principal domain of vertebrate fibrinogen and its relatives.

    PubMed Central

    Doolittle, R. F.

    1992-01-01

    Vertebrate fibrinogen is a complex multidomained protein, the structure of which has been inferred mainly from electron microscopy and amino acid sequence studies. Among its most prominent features are two terminal globules, moieties that are mostly composed of the carboxyl-terminal two-thirds of the beta and gamma chains. Sequences homologous to the latter segments are found in several other animal proteins, always as the carboxyl-terminal contributions. An alignment of 15 amino acid sequences from various fibrinogens and related proteins has been used to make judgments about secondary structure. The nature of amino acids at each position in the alignment was used to distinguish alpha helices and beta structure on the one hand from loops and turns on the other, and the resulting assignments compared with predictions of secondary structure by other methods. Additionally, constraints imposed by the locations of cystines, carbohydrate attachment residues, and proteinase-sensitive points provided further insights into the general organization of the postulated secondary structures. Other ancillary data, including the effects of bound calcium and the locations of labeled or variant residues, were also considered. An intriguing similarity to a portion of the recently reported structure of a calcium-dependent lectin is noted. PMID:1304888

  16. 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. PMID:24237789

  17. A highly conserved family of domains related to the DNA-glycosylase fold helps predict multiple novel pathways for RNA modifications

    PubMed Central

    Burroughs, A Maxwell; Aravind, L

    2014-01-01

    A protein family including mammalian NEMF, Drosophila caliban, yeast Tae2, and bacterial FpbA-like proteins was first defined over a decade ago and found to be universally distributed across the three domains/superkingdoms of life. Since its initial characterization, this family of proteins has been tantalizingly linked to a wide range of biochemical functions. Tapping the enormous wealth of genome information that has accumulated since the initial characterization of these proteins, we perform a detailed computational analysis of the family, identifying multiple conserved domains. Domains identified include an enzymatic domain related to the formamidopyrimidine (Fpg), MutM, and Nei/EndoVIII family of DNA glycosylases, a novel, predicted RNA-binding domain, and a domain potentially mediating protein–protein interactions. Through this characterization, we predict that the DNA glycosylase-like domain catalytically operates on double-stranded RNA, as part of a hitherto unknown base modification mechanism that probably targets rRNAs. At least in archaea, and possibly eukaryotes, this pathway might additionally include the AMMECR1 family of proteins. The predicted RNA-binding domain associated with this family is also observed in distinct architectural contexts in other proteins across phylogenetically diverse prokaryotes. Here it is predicted to play a key role in a new pathway for tRNA 4-thiouridylation along with TusA-like sulfur transfer proteins. PMID:24646681

  18. The DYX2 locus and neurochemical signaling genes contribute to speech sound disorder and related neurocognitive domains.

    PubMed

    Eicher, J D; Stein, C M; Deng, F; Ciesla, A A; Powers, N R; Boada, R; Smith, S D; Pennington, B F; Iyengar, S K; Lewis, B A; Gruen, J R

    2015-04-01

    A major milestone of child development is the acquisition and use of speech and language. Communication disorders, including speech sound disorder (SSD), can impair a child's academic, social and behavioral development. Speech sound disorder is a complex, polygenic trait with a substantial genetic component. However, specific genes that contribute to SSD remain largely unknown. To identify associated genes, we assessed the association of the DYX2 dyslexia risk locus and markers in neurochemical signaling genes (e.g., nicotinic and dopaminergic) with SSD and related endophenotypes. We first performed separate primary associations in two independent samples - Cleveland SSD (210 affected and 257 unaffected individuals in 127 families) and Denver SSD (113 affected individuals and 106 unaffected individuals in 85 families) - and then combined results by meta-analysis. DYX2 markers, specifically those in the 3' untranslated region of DCDC2 (P = 1.43 × 10(-4) ), showed the strongest associations with phonological awareness. We also observed suggestive associations of dopaminergic-related genes ANKK1 (P = 1.02 × 10(-2) ) and DRD2 (P = 9.22 × 10(-3) ) and nicotinic-related genes CHRNA3 (P = 2.51 × 10(-3) ) and BDNF (P = 8.14 × 10(-3) ) with case-control status and articulation. Our results further implicate variation in putative regulatory regions in the DYX2 locus, particularly in DCDC2, influencing language and cognitive traits. The results also support previous studies implicating variation in dopaminergic and nicotinic neural signaling influencing human communication and cognitive development. Our findings expand the literature showing genetic factors (e.g., DYX2) contributing to multiple related, yet distinct neurocognitive domains (e.g., dyslexia, language impairment, and SSD). How these factors interactively yield different neurocognitive and language-related outcomes remains to be elucidated. PMID:25778907

  19. The DYX2 locus and neurochemical signaling genes contribute to speech sound disorder and related neurocognitive domains

    PubMed Central

    Eicher, J. D.; Stein, C. M.; Deng, F.; Ciesla, A. A.; Powers, N. R.; Boada, R.; Smith, S. D.; Pennington, B. F.; Iyengar, S. K.; Lewis, B. A.; Gruen, J. R.

    2015-01-01

    A major milestone of child development is the acquisition and use of speech and language. Communication disorders, including speech sound disorder (SSD), can impair a child's academic, social and behavioral development. Speech sound disorder is a complex, polygenic trait with a substantial genetic component. However, specific genes that contribute to SSD remain largely unknown. To identify associated genes, we assessed the association of the DYX2 dyslexia risk locus and markers in neurochemical signaling genes (e.g., nicotinic and dopaminergic) with SSD and related endophenotypes. We first performed separate primary associations in two independent samples – Cleveland SSD (210 affected and 257 unaffected individuals in 127 families) and Denver SSD (113 affected individuals and 106 unaffected individuals in 85 families) – and then combined results by meta-analysis. DYX2 markers, specifically those in the 3′ untranslated region of DCDC2 (P = 1.43 × 10–4), showed the strongest associations with phonological awareness. We also observed suggestive associations of dopaminergic-related genes ANKK1 (P = 1.02 × 10–2) and DRD2 (P = 9.22 × 10–3) and nicotinic-related genes CHRNA3 (P = 2.51 × 10–3) and BDNF (P = 8.14 × 10–3) with case–control status and articulation. Our results further implicate variation in putative regulatory regions in the DYX2 locus, particularly in DCDC2, influencing language and cognitive traits. The results also support previous studies implicating variation in dopaminergic and nicotinic neural signaling influencing human communication and cognitive development. Our findings expand the literature showing genetic factors (e.g., DYX2) contributing to multiple related, yet distinct neurocognitive domains (e.g., dyslexia, language impairment, and SSD). How these factors interactively yield different neurocognitive and language-related outcomes remains to be elucidated. PMID:25778907

  20. Clinically detectable drusen domains in fibulin-5-associated age-related macular degeneration (AMD) : Drusen subdomains in fibulin-5 AMD.

    PubMed

    Kucukevcilioglu, Murat; Patel, Chetankumar B; Stone, Edwin M; Russell, Stephen R

    2016-08-01

    To evaluate whether drusen of subjects with fibulin-5 mutation-associated age-related macular degeneration (AMD) have clinically demonstrable drusen domains as evidenced by differences between color and fluorescein angiographic profiles. Of seven patients we identified with AMD due to mutations in the fibulin-5 gene (Fib-5 AMD), five had color fundus photography and fluorescein angiography (FA). One had bilateral choroidal neovascularization and no drusen. For each eye, the green channel (GC) of the digital RGB (Red-Green-Blue) color image and hyperfluorescent domain (HD) intensity of the FA image were registered and drusen were manually segmented and measured. Totally 75 small (≤62 μm), 110 intermediate (63-125 μm), and 30 large (>125 μm) drusen were measured in four patients within the 6 × 6 mm central macular areas. All four subjects demonstrated central or paracentral HDs within each drusen perimeter. HDs were found in association with each druse, with a HD/GC ratio of 0.82, 0.76, and 0.72 respectively for small, intermediate, and large drusen (Student T Test: P < 0.01, P < 0.01, P < 0.01). A statistical difference was found for the HD/GC ratios between small- and intermediate-sized drusen and small- and large-sized drusen but not between intermediate-sized and large-sized drusen (P = 0.001, P < 0.001, P > 0.05, respectively). AMD patients with mutations in fibulin-5 share drusen phenotypic structure and have HD/GC ratios that are similar to individuals with cuticular or basal laminar drusen. Drusen substructure may reflect similarities in drusen stage and/or genesis and appear to vary among AMD genotypes. PMID:26694911

  1. Structural Studies of the Tandem Tudor Domains of Fragile X Mental Retardation Related Proteins FXR1 and FXR2

    SciTech Connect

    Adams-Cioaba, Melanie A.; Guo, Yahong; Bian, ChuanBing; Amaya, Maria F.; Lam, Robert; Wasney, Gregory A.; Vedadi, Masoud; Xu, Chao; Min, Jinrong

    2011-11-23

    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 are 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.

  2. C-terminal domains of a histone demethylase interact with a pair of transcription factors and mediate specific chromatin association

    PubMed Central

    Zhang, Shuaibin; Zhou, Bing; Kang, Yanyuan; Cui, Xia; Liu, Ao; Deleris, Angelique; Greenberg, Maxim V. C.; Cui, Xiekui; Qiu, Qi; Lu, Falong; Wohlschlegel, James A.; Jacobsen, Steven E.; Cao, Xiaofeng

    2015-01-01

    JmjC domain containing protein 14 (JMJ14) is an H3K4-specific histone demethylase that plays important roles in RNA-mediated gene silencing and flowering time regulation in Arabidopsis. However, how JMJ14 is recruited to its target genes remains unclear. Here, we show that the C-terminal FYRN and FYRC domains of JMJ14 are required for RNA silencing and flowering time regulation. Chromatin binding of JMJ14 is lost upon deletion of its FYRN and FYRC domains, and H3K4me3 is increased. FYRN and FYRC domains interact with a pair of NAC domain containing transcription factors, NAC050 and NAC052. Genome-wide ChIP analysis revealed that JMJ14 and NAC050/052 share a set of common target genes with CTTGNNNNNCAAG consensus sequences. Mutations in either NAC052 or NAC050 impair RNA-mediated gene silencing. Together, our findings demonstrate an important role of FYRN and FYRC domains in targeting JMJ14 through direct interaction with NAC050/052 proteins, which reveals a novel mechanism of histone demethylase recruitment. PMID:26617990

  3. (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.

  4. Maize beta-glucosidase-aggregating factor is a polyspecific jacalin-related chimeric lectin, and its lectin domain is responsible for beta-glucosidase aggregation.

    PubMed

    Kittur, Farooqahmed S; Lalgondar, Mallikarjun; Yu, Hyun Young; Bevan, David R; Esen, Asim

    2007-03-01

    In certain maize genotypes, called "null," beta-glucosidase does not enter gels and therefore cannot be detected on zymograms after electrophoresis. Such genotypes were originally thought to be homozygous for a null allele at the glu1 gene and thus devoid of enzyme. We have shown that a beta-glucosidase-aggregating factor (BGAF) is responsible for the "null" phenotype. BGAF is a chimeric protein consisting of two distinct domains: the disease response or "dirigent" domain and the jacalin-related lectin (JRL) domain. First, it was not known whether the lectin domain in BGAF is functional. Second, it was not known which of the two BGAF domains is involved in beta-glucosidase binding and aggregation. To this end, we purified BGAF to homogeneity from a maize null inbred line called H95. The purified protein gave a single band on SDS-PAGE, and the native protein was a homodimer of 32-kDa monomers. Native and recombinant BGAF (produced in Escherichia coli) agglutinated rabbit erythrocytes, and various carbohydrates and glycoproteins inhibited their hemagglutination activity. Sugars did not have any effect on the binding of BGAF to the beta-glucosidase isozyme 1 (Glu1), and the BGAF-Glu1 complex could still bind lactosyl-agarose, indicating that the sugar-binding site of BGAF is distinct from the beta-glucosidase-binding site. Neither the dirigent nor the JRL domains alone (produced separately in E. coli) produced aggregates of Glu1 based on results from pull-down assays. However, gel shift and competitive binding assays indicated that the JRL domain binds beta-glucosidase without causing it to aggregate. These results with those from deletion mutagenesis and replacement of the JRL domain of a BGAF homolog from sorghum, which does not bind Glu1, with that from maize allowed us to conclude that the JRL domain of BGAF is responsible for its lectin and beta-glucosidase binding and aggregating activities. PMID:17210577

  5. Expression of Nucleotide-oligomerization Domain (NOD) and Related Genes in Mouse Tissues Infected with Mycobacterium leprae

    PubMed Central

    Kim, Tae Hoon; Chae, Gue-Tae

    2015-01-01

    The nucleotide-oligomerization domain (NOD) is an important molecule involved in host defense against bacterial infection. To study the role of NODs in the host response to Mycobacterium leprae, we measured the mRNA levels of NODs and related genes in infected mouse tissues. The mRNA expression of NOD1, NOD2, caspase-1 and ASC was increased in mouse footpads. Whereas NOD2 expression in macrophages was increased at 2 and 24 h post-infection with M. leprae, there was no expression of NOD1 at these time points. An increase in caspase-1 expression was observed at 2 h and continued at 24 h. However, the expression of ASC was increased only at the early time point. The expression of caspase-1 is regulated by NOD2-dependent pathway in established HEK 293. Our results suggest NOD2, rather than NOD1, may be associated with the host response to M. leprae and that caspase-1 activation is essential for the host response. PMID:26770186

  6. Expression of Nucleotide-oligomerization Domain (NOD) and Related Genes in Mouse Tissues Infected with Mycobacterium leprae.

    PubMed

    Kim, Tae Hoon; Chae, Gue-Tae; Kang, Tae Jin

    2015-12-01

    The nucleotide-oligomerization domain (NOD) is an important molecule involved in host defense against bacterial infection. To study the role of NODs in the host response to Mycobacterium leprae, we measured the mRNA levels of NODs and related genes in infected mouse tissues. The mRNA expression of NOD1, NOD2, caspase-1 and ASC was increased in mouse footpads. Whereas NOD2 expression in macrophages was increased at 2 and 24 h post-infection with M. leprae, there was no expression of NOD1 at these time points. An increase in caspase-1 expression was observed at 2 h and continued at 24 h. However, the expression of ASC was increased only at the early time point. The expression of caspase-1 is regulated by NOD2-dependent pathway in established HEK 293. Our results suggest NOD2, rather than NOD1, may be associated with the host response to M. leprae and that caspase-1 activation is essential for the host response. PMID:26770186

  7. Synergy between loss of NF1 and overexpression of MYCN in neuroblastoma is mediated by the GAP-related domain.

    PubMed

    He, Shuning; Mansour, Marc R; Zimmerman, Mark W; Ki, Dong Hyuk; Layden, Hillary M; Akahane, Koshi; Gjini, Evisa; de Groh, Eric D; Perez-Atayde, Antonio R; Zhu, Shizhen; Epstein, Jonathan A; Look, A Thomas

    2016-01-01

    Earlier reports showed that hyperplasia of sympathoadrenal cell precursors during embryogenesis in Nf1-deficient mice is independent of Nf1's role in down-modulating RAS-MAPK signaling. We demonstrate in zebrafish that nf1 loss leads to aberrant activation of RAS signaling in MYCN-induced neuroblastomas that arise in these precursors, and that the GTPase-activating protein (GAP)-related domain (GRD) is sufficient to suppress the acceleration of neuroblastoma in nf1-deficient fish, but not the hypertrophy of sympathoadrenal cells in nf1 mutant embryos. Thus, even though neuroblastoma is a classical "developmental tumor", NF1 relies on a very different mechanism to suppress malignant transformation than it does to modulate normal neural crest cell growth. We also show marked synergy in tumor cell killing between MEK inhibitors (trametinib) and retinoids (isotretinoin) in primary nf1a-/- zebrafish neuroblastomas. Thus, our model system has considerable translational potential for investigating new strategies to improve the treatment of very high-risk neuroblastomas with aberrant RAS-MAPK activation. PMID:27130733

  8. Verticillium infection triggers VASCULAR-RELATED NAC DOMAIN7-dependent de novo xylem formation and enhances drought tolerance in Arabidopsis.

    PubMed

    Reusche, Michael; Thole, Karin; Janz, Dennis; Truskina, Jekaterina; Rindfleisch, Sören; Drübert, Christine; Polle, Andrea; Lipka, Volker; Teichmann, Thomas

    2012-09-01

    The soilborne fungal plant pathogen Verticillium longisporum invades the roots of its Brassicaceae hosts and proliferates in the plant vascular system. Typical aboveground symptoms of Verticillium infection on Brassica napus and Arabidopsis thaliana are stunted growth, vein clearing, and leaf chloroses. Here, we provide evidence that vein clearing is caused by pathogen-induced transdifferentiation of chloroplast-containing bundle sheath cells to functional xylem elements. In addition, our findings suggest that reinitiation of cambial activity and transdifferentiation of xylem parenchyma cells results in xylem hyperplasia within the vasculature of Arabidopsis leaves, hypocotyls, and roots. The observed de novo xylem formation correlates with Verticillium-induced expression of the VASCULAR-RELATED NAC DOMAIN (VND) transcription factor gene VND7. Transgenic Arabidopsis plants expressing the chimeric repressor VND7-SRDX under control of a Verticillium infection-responsive promoter exhibit reduced de novo xylem formation. Interestingly, infected Arabidopsis wild-type plants show higher drought stress tolerance compared with noninfected plants, whereas this effect is attenuated by suppression of VND7 activity. Together, our results suggest that V. longisporum triggers a tissue-specific developmental plant program that compensates for compromised water transport and enhances the water storage capacity of infected Brassicaceae host plants. In conclusion, we provide evidence that this natural plant-fungus pathosystem has conditionally mutualistic features. PMID:23023171

  9. Structure-function relations in the NTPase domain of the antiviral tRNA ribotoxin Escherichia coli PrrC

    SciTech Connect

    Meineke, Birthe; Shuman, Stewart

    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. We 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.

  10. Grading of Age-Related Macular Degeneration: Comparison between Color Fundus Photography, Fluorescein Angiography, and Spectral Domain Optical Coherence Tomography

    PubMed Central

    Mokwa, Nils F.; Keane, Pearse A.; Kirchhof, Bernd; Sadda, Srinivas R.

    2013-01-01

    Purpose. To compare color fundus photography (FP), fluorescein angiography (FA), and spectral domain optical coherence tomography (SDOCT) for the detection of age-related macular degeneration (AMD), choroidal neovascularisation (CNV), and CNV activity. Methods. FPs, FAs, and SDOCT volume scans from 120 eyes of 66 AMD and control patients were randomly collected. Control eyes were required to show no AMD, but other retinal pathology was allowed. The presence of drusen, pigmentary changes, CNV, and signs for CNV activity was independently analyzed for all imaging modalities. Results. AMD was diagnosed based on FP in 75 eyes. SDOCT and FA showed sensitivity (specificity) of 89% (76%) and 92% (82%), respectively. CNV was present on FA in 68 eyes. Sensitivity (specificity) was 78% (100%) for FP and 94% (98%) for SDOCT. CNV activity was detected by SDOCT or FA in 60 eyes with an agreement in 46 eyes. Sensitivity was 88% for SDOCT and 88% for FA. FP showed sensitivity of 38% and specificity of 98%. Conclusions. CNV lesions and activity may be missed by FP alone, but FP may help identifying drusen and pigmentary changes. SDOCT is highly sensitive for the detection of AMD, CNV, and CNV activity; however, it cannot fully replace FA. PMID:23762528

  11. Synergy between loss of NF1 and overexpression of MYCN in neuroblastoma is mediated by the GAP-related domain

    PubMed Central

    He, Shuning; Mansour, Marc R; Zimmerman, Mark W; Ki, Dong Hyuk; Layden, Hillary M; Akahane, Koshi; Gjini, Evisa; de Groh, Eric D; Perez-Atayde, Antonio R; Zhu, Shizhen; Epstein, Jonathan A; Look, A Thomas

    2016-01-01

    Earlier reports showed that hyperplasia of sympathoadrenal cell precursors during embryogenesis in Nf1-deficient mice is independent of Nf1’s role in down-modulating RAS-MAPK signaling. We demonstrate in zebrafish that nf1 loss leads to aberrant activation of RAS signaling in MYCN-induced neuroblastomas that arise in these precursors, and that the GTPase-activating protein (GAP)-related domain (GRD) is sufficient to suppress the acceleration of neuroblastoma in nf1-deficient fish, but not the hypertrophy of sympathoadrenal cells in nf1 mutant embryos. Thus, even though neuroblastoma is a classical “developmental tumor”, NF1 relies on a very different mechanism to suppress malignant transformation than it does to modulate normal neural crest cell growth. We also show marked synergy in tumor cell killing between MEK inhibitors (trametinib) and retinoids (isotretinoin) in primary nf1a-/- zebrafish neuroblastomas. Thus, our model system has considerable translational potential for investigating new strategies to improve the treatment of very high-risk neuroblastomas with aberrant RAS-MAPK activation. DOI: http://dx.doi.org/10.7554/eLife.14713.001 PMID:27130733

  12. Interaction between a Domain of the Negative Regulator of the Ras-ERK Pathway, SPRED1 Protein, and the GTPase-activating Protein-related Domain of Neurofibromin Is Implicated in Legius Syndrome and Neurofibromatosis Type 1.

    PubMed

    Hirata, Yasuko; Brems, Hilde; Suzuki, Mayu; Kanamori, Mitsuhiro; Okada, Masahiro; Morita, Rimpei; Llano-Rivas, Isabel; Ose, Toyoyuki; Messiaen, Ludwine; Legius, Eric; Yoshimura, Akihiko

    2016-02-12

    Constitutional heterozygous loss-of-function mutations in the SPRED1 gene cause a phenotype known as Legius syndrome, which consists of symptoms of multiple café-au-lait macules, axillary freckling, learning disabilities, and macrocephaly. Legius syndrome resembles a mild neurofibromatosis type 1 (NF1) phenotype. It has been demonstrated that SPRED1 functions as a negative regulator of the Ras-ERK pathway and interacts with neurofibromin, the NF1 gene product. However, the molecular details of this interaction and the effects of the mutations identified in Legius syndrome and NF1 on this interaction have not yet been investigated. In this study, using a yeast two-hybrid system and an immunoprecipitation assay in HEK293 cells, we found that the SPRED1 EVH1 domain interacts with the N-terminal 16 amino acids and the C-terminal 20 amino acids of the GTPase-activating protein (GAP)-related domain (GRD) of neurofibromin, which form two crossing α-helix coils outside the GAP domain. These regions have been shown to be dispensable for GAP activity and are not present in p120(GAP). Several mutations in these N- and C-terminal regions of the GRD in NF1 patients and pathogenic missense mutations in the EVH1 domain of SPRED1 in Legius syndrome reduced the binding affinity between the EVH1 domain and the GRD. EVH1 domain mutations with reduced binding to the GRD also disrupted the ERK suppression activity of SPRED1. These data clearly demonstrate that SPRED1 inhibits the Ras-ERK pathway by recruiting neurofibromin to Ras through the EVH1-GRD interaction, and this study also provides molecular basis for the pathogenic mutations of NF1 and Legius syndrome. PMID:26635368

  13. An Investigation of Broad and Narrow Personality Traits in Relation to General and Domain-Specific Life Satisfaction of College Students

    ERIC Educational Resources Information Center

    Lounsbury, John W.; Saudargas, Richard A.; Gibson, Lucy W.; Leong, Frederick T.

    2005-01-01

    Based on a sample of 532 undergraduates at a Southeastern U.S. university, Big Five and narrow personality traits were examined in relation to a measure of satisfaction with specific domains of college experience (College Satisfaction) and a measure of General Life Satisfaction. Four of the Big Five traits--Agreeableness, Conscientiousness,…

  14. 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…

  15. Inactivation of pRB-related proteins p130 and p107 mediated by the J domain of simian virus 40 large T antigen.

    PubMed Central

    Stubdal, H; Zalvide, J; Campbell, K S; Schweitzer, C; Roberts, T M; DeCaprio, J A

    1997-01-01

    Inactivation of the retinoblastoma tumor suppressor protein (pRB) contributes to tumorigenesis in a wide variety of cancers. In contrast, the role of the two pRB-related proteins, p130 and p107, in oncogenic transformation is unclear. The LXCXE domain of simian virus 40 large T antigen (TAg) specifically binds to pRB, p107, and p130. We have previously shown that the N terminus and the LXCXE domain of TAg cooperate to alter the phosphorylation state of p130 and p107. Here, we demonstrate that TAg promotes the degradation of p130 and that the N terminus of TAg is required for this activity. The N terminus of TAg has homology to the J domain of the DnaJ family of molecular chaperone proteins. Mutants with mutations in the J-domain homology region of TAg are defective for altering p130 and p107 phosphorylation and for p130 degradation. A heterologous J-domain from a human DnaJ protein can functionally substitute for the N terminus of TAg in the effect on p107 and p130 phosphorylation and p130 stability. We further demonstrate that the J-domain homology region of TAg confers a growth advantage to wild-type mouse embryo fibroblasts (MEFs) but is dispensable in the case of MEFs lacking both p130 and p107. This indicates that p107 and p130 have overlapping growth-suppressing activities whose inactivation is mediated by the J domain of TAg. PMID:9271376

  16. 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.…

  17. The Relative Contribution of Health Status and Quality of Life Domains in Subjective Health in Old Age

    ERIC Educational Resources Information Center

    Prieto-Flores, Maria-Eugenia; Moreno-Jimenez, Antonio; Fernandez-Mayoralas, Gloria; Rojo-Perez, Fermina; Forjaz, Maria Joao

    2012-01-01

    To analyze the influence of different health status dimensions and quality of life (QoL) domains on older adults' subjective health, and to assess the role that residential satisfaction plays in these relationships. A QoL survey was conducted on a representative sample of the community-dwelling older adult population in Madrid province (Spain).…

  18. How Students' Epistemological Beliefs in the Domain of Physics and Their Conceptual Change Are Related?

    ERIC Educational Resources Information Center

    Kaymak, Ercan; Ogan-Bekiroglu, Feral

    2013-01-01

    The purposes of this study were to determine high school students' epistemological beliefs in the domain of physics and to explore and explain the possible relationship between their beliefs and their conceptual change in physics by taking the students' learning strategies into account. A multi-case study design was used for the research…

  19. Sensing the Coherence of Biology in Contrast to Psychology: Young Children's Use of Causal Relations to Distinguish Two Foundational Domains

    ERIC Educational Resources Information Center

    Erickson, Jane E.; Keil, Frank C.; Lockhart, Kristi L.

    2010-01-01

    To what extent do children understand that biological processes fall into 1 coherent domain unified by distinct causal principles? In Experiments 1 and 2 (N = 125) kindergartners are given triads of biological and psychological processes and asked to identify which 2 members of the triad belong together. Results show that 5-year-olds correctly…

  20. 3D acoustic wave modelling with time-space domain dispersion-relation-based finite-difference schemes and hybrid absorbing boundary conditions

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Sen, Mrinal K.

    2011-09-01

    Most conventional finite-difference methods adopt second-order temporal and (2M)th-order spatial finite-difference stencils to solve the 3D acoustic wave equation. When spatial finite-difference stencils devised from the time-space domain dispersion relation are used to replace these conventional spatial finite-difference stencils devised from the space domain dispersion relation, the accuracy of modelling can be increased from second-order along any directions to (2M)th-order along 48 directions. In addition, the conventional high-order spatial finite-difference modelling accuracy can be improved by using a truncated finite-difference scheme. In this paper, we combine the time-space domain dispersion-relation-based finite difference scheme and the truncated finite-difference scheme to obtain optimised spatial finite-difference coefficients and thus to significantly improve the modelling accuracy without increasing computational cost, compared with the conventional space domain dispersion-relation-based finite difference scheme. We developed absorbing boundary conditions for the 3D acoustic wave equation, based on predicting wavefield values in a transition area by weighing wavefield values from wave equations and one-way wave equations. Dispersion analyses demonstrate that high-order spatial finite-difference stencils have greater accuracy than low-order spatial finite-difference stencils for high frequency components of wavefields, and spatial finite-difference stencils devised in the time-space domain have greater precision than those devised in the space domain under the same discretisation. The modelling accuracy can be improved further by using the truncated spatial finite-difference stencils. Stability analyses show that spatial finite-difference stencils devised in the time-space domain have better stability condition. Numerical modelling experiments for homogeneous, horizontally layered and Society of Exploration Geophysicists/European Association of

  1. Domain-Specific Expertise of Chemistry Teachers on Context-Based Education About Macro-Micro Thinking in Structure-Property Relations

    NASA Astrophysics Data System (ADS)

    Dolfing, Ria; Bulte, Astrid M. W.; Pilot, Albert; Vermunt, Jan D.

    2012-06-01

    This study aims to determine and describe the new domain-specific expertise of experienced chemistry teachers in teaching an innovative context-based unit about macro-micro thinking in structure-property relations. The construct of `teachers' domain-specific expertise' was used to analyse the new repertoire chemistry teachers need to acquire to teach a context-based unit and achieve the intended effects of the curriculum innovation. A phenomenological approach of exploration and verification of teachers' new repertoire resulted in the description of seven themes. These themes were related to the new aspects of the unit: the context-setting, the teacher's role and the new content. In addition, the results show that the theoretical framework of teachers' domain-specific expertise is feasible for the analysis and description of their new repertoire in the domain of teaching a context-based unit. Further research is necessary to explore the use of the framework from the perspective of teachers' professional development, where affective components in teachers' learning processes play an important role.

  2. Architecture of a single membrane spanning cytochrome P450 suggests constraints that orient the catalytic domain relative to a bilayer

    PubMed Central

    Monk, Brian C.; Tomasiak, Thomas M.; Keniya, Mikhail V.; Huschmann, Franziska U.; Tyndall, Joel D. A.; O’Connell, Joseph D.; Cannon, Richard D.; McDonald, Jeffrey G.; Rodriguez, Andrew; Finer-Moore, Janet S.; Stroud, Robert M.

    2014-01-01

    Bitopic integral membrane proteins with a single transmembrane helix play diverse roles in catalysis, cell signaling, and morphogenesis. Complete monospanning protein structures are needed to show how interaction between the transmembrane helix and catalytic domain might influence association with the membrane and function. We report crystal structures of full-length Saccharomyces cerevisiae lanosterol 14α-demethylase, a membrane monospanning cytochrome P450 of the CYP51 family that catalyzes the first postcyclization step in ergosterol biosynthesis and is inhibited by triazole drugs. The structures reveal a well-ordered N-terminal amphipathic helix preceding a putative transmembrane helix that would constrain the catalytic domain orientation to lie partly in the lipid bilayer. The structures locate the substrate lanosterol, identify putative substrate and product channels, and reveal constrained interactions with triazole antifungal drugs that are important for drug design and understanding drug resistance. PMID:24613931

  3. Architecture of a single membrane spanning cytochrome P450 suggests constraints that orient the catalytic domain relative to a bilayer.

    PubMed

    Monk, Brian C; Tomasiak, Thomas M; Keniya, Mikhail V; Huschmann, Franziska U; Tyndall, Joel D A; O'Connell, Joseph D; Cannon, Richard D; McDonald, Jeffrey G; Rodriguez, Andrew; Finer-Moore, Janet S; Stroud, Robert M

    2014-03-11

    Bitopic integral membrane proteins with a single transmembrane helix play diverse roles in catalysis, cell signaling, and morphogenesis. Complete monospanning protein structures are needed to show how interaction between the transmembrane helix and catalytic domain might influence association with the membrane and function. We report crystal structures of full-length Saccharomyces cerevisiae lanosterol 14α-demethylase, a membrane monospanning cytochrome P450 of the CYP51 family that catalyzes the first postcyclization step in ergosterol biosynthesis and is inhibited by triazole drugs. The structures reveal a well-ordered N-terminal amphipathic helix preceding a putative transmembrane helix that would constrain the catalytic domain orientation to lie partly in the lipid bilayer. The structures locate the substrate lanosterol, identify putative substrate and product channels, and reveal constrained interactions with triazole antifungal drugs that are important for drug design and understanding drug resistance. PMID:24613931

  4. Effects of gender-related domain violations and sexual orientation on perceptions of male and female targets: an analogue study.

    PubMed

    Blashill, Aaron J; Powlishta, Kimberly K

    2012-10-01

    The current study examined factors that influenced heterosexual male and female raters' evaluations of male and female targets who were gay or heterosexual, and who displayed varying gender roles (i.e., typical vs. atypical) in multiple domains (i.e., activities, traits, and appearance). Participants were 305 undergraduate students from a private, midwestern Jesuit institution who read vignettes describing one of 24 target types and then rated the target on possession of positive and negative characteristics, psychological adjustment, and on measures reflecting the participants' anticipated behavior toward or comfort with the target. Results showed that gender atypical appearance and activity attributes (but not traits) were viewed more negatively than their gender typical counterparts. It was also found that male participants in particular viewed gay male targets as less desirable than lesbian and heterosexual male targets. These findings suggest a nuanced approach for understanding sexual prejudice, which incorporates a complex relationship among sex, gender, sexual orientation, and domain of gendered attributes. PMID:22722956

  5. 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.

  6. Glial cell interactions with tenascin-C: adhesion and repulsion to different tenascin-C domains is cell type related.

    PubMed

    Scholze, A; Götz, B; Faissner, A

    1996-06-01

    The multimodular glycoprotein tenascin-C is transiently expressed, predominantly by glial cells, during the development of the central and peripheral nervous systems. This extracellular matrix glycoprotein is involved in the control of cell adhesion, neuron migration and neurite outgrowth. Distinct functional properties for neuronal cell types have been attributed to separate tenascin-C domains using antibody perturbation studies and in vitro experiments on tenascin-C fragments. In order to study potential roles of tenascin-C for glial cell biology, a library of recombinant tenascin-C domains was used in a bioassay in vitro. Embryonic day 14 astrocytes, various astroglial-derived cell lines (C6, A7 and Neu7) and oligodendroglial-derived cell types (Oli-neu and G26-20) were examined in an adhesion assay and compared to the neuroblastoma cell line N2A. A binding site for most cell types, except for A7 and N2A, could be assigned to the first three fibronectin type III domains. Repulsive properties could be mapped to three different sites the epidermal growth factor-like repeats, fibronectin type III repeats 4 and 5 and to the alternatively spliced region of the molecule. The responses to these repulsive sites varied according to the cell type. These data are consistent with the interpretation that different cell types express distinct sets of tenascin-C receptors which might regulate cellular responses via distinct second messenger pathways. PMID:8842807

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

    SciTech Connect

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

    2005-04-01

    In order to clarify the structural basis of the pathogenesis-related-1 domain, Na-ASP-1, the first multi-domain ASP from the human hookworm parasite N. americanus, has been crystallized. 2.2 Å resolution data have been collected from a crystal belonging to the monoclinic space group P2{sub 1}. 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 P2{sub 1} 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.

  8. GT-2: a transcription factor with twin autonomous DNA-binding domains of closely related but different target sequence specificity.

    PubMed Central

    Dehesh, K; Hung, H; Tepperman, J M; Quail, P H

    1992-01-01

    A triplet of adjacent, highly similar GT motifs in the phyA promoter of rice functions to support maximal expression of this gene. We have obtained a recombinant clone that encodes a full-length nuclear protein, designated GT-2, which binds specifically to these target sequences. This novel protein contains acidic, basic and proline- + glutamine-rich regions, as well as two autonomous DNA-binding domains, one NH2-terminal and the other COOH-terminal, that discriminate with high resolution between the three GT motifs. A duplicated sequence of 75 amino acids, present once in each DNA-binding domain, appears likely to mediate DNA target element recognition. Each copy of this duplicated protein sequence is predicted to form three amphipathic alpha-helices separated from each other by two short loops. The absence of sequence similarity to other known proteins suggests that this predicted structural unit, which we term the trihelix motif, might be representative of a new class of DNA-binding proteins. Images PMID:1396594

  9. Proteins Related to the Type I Secretion System Are Associated with Secondary SecA_DEAD Domain Proteins in Some Species of Planctomycetes, Verrucomicrobia, Proteobacteria, Nitrospirae and Chlorobi

    PubMed Central

    Kamneva, Olga K.; Poudel, Saroj; Ward, Naomi L.

    2015-01-01

    A number of bacteria belonging to the PVC (Planctomycetes-Verrucomicrobia-Chlamydiae) super-phylum contain unusual ribosome-bearing intracellular membranes. The evolutionary origins and functions of these membranes are unknown. Some proteins putatively associated with the presence of intracellular membranes in PVC bacteria contain signal peptides. Signal peptides mark proteins for translocation across the cytoplasmic membrane in prokaryotes, and the membrane of the endoplasmic reticulum in eukaryotes, by highly conserved Sec machinery. This suggests that proteins might be targeted to intracellular membranes in PVC bacteria via the Sec pathway. Here, we show that canonical signal peptides are significantly over-represented in proteins preferentially present in PVC bacteria possessing intracellular membranes, indicating involvement of Sec translocase in their cellular targeting. We also characterized Sec proteins using comparative genomics approaches, focusing on the PVC super-phylum. While we were unable to detect unique changes in Sec proteins conserved among membrane-bearing PVC species, we identified (1) SecA ATPase domain re-arrangements in some Planctomycetes, and (2) secondary SecA_DEAD domain proteins in the genomes of some Planctomycetes, Verrucomicrobia, Proteobacteria, Nitrospirae and Chlorobi. This is the first report of potentially duplicated SecA in Gram-negative bacteria. The phylogenetic distribution of secondary SecA_DEAD domain proteins suggests that the presence of these proteins is not related to the occurrence of PVC endomembranes. Further genomic analysis showed that secondary SecA_DEAD domain proteins are located within genomic neighborhoods that also encode three proteins possessing domains specific for the Type I secretion system. PMID:26030905

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

    SciTech Connect

    Maiweilidan, Yimingjiang; Klauza, Izabela; Kordeli, Ekaterini

    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, 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 sarcomeres

  11. Proteins Related to the Type I Secretion System Are Associated with Secondary SecA_DEAD Domain Proteins in Some Species of Planctomycetes, Verrucomicrobia, Proteobacteria, Nitrospirae and Chlorobi.

    PubMed

    Kamneva, Olga K; Poudel, Saroj; Ward, Naomi L

    2015-01-01

    A number of bacteria belonging to the PVC (Planctomycetes-Verrucomicrobia-Chlamydiae) super-phylum contain unusual ribosome-bearing intracellular membranes. The evolutionary origins and functions of these membranes are unknown. Some proteins putatively associated with the presence of intracellular membranes in PVC bacteria contain signal peptides. Signal peptides mark proteins for translocation across the cytoplasmic membrane in prokaryotes, and the membrane of the endoplasmic reticulum in eukaryotes, by highly conserved Sec machinery. This suggests that proteins might be targeted to intracellular membranes in PVC bacteria via the Sec pathway. Here, we show that canonical signal peptides are significantly over-represented in proteins preferentially present in PVC bacteria possessing intracellular membranes, indicating involvement of Sec translocase in their cellular targeting. We also characterized Sec proteins using comparative genomics approaches, focusing on the PVC super-phylum. While we were unable to detect unique changes in Sec proteins conserved among membrane-bearing PVC species, we identified (1) SecA ATPase domain re-arrangements in some Planctomycetes, and (2) secondary SecA_DEAD domain proteins in the genomes of some Planctomycetes, Verrucomicrobia, Proteobacteria, Nitrospirae and Chlorobi. This is the first report of potentially duplicated SecA in Gram-negative bacteria. The phylogenetic distribution of secondary SecA_DEAD domain proteins suggests that the presence of these proteins is not related to the occurrence of PVC endomembranes. Further genomic analysis showed that secondary SecA_DEAD domain proteins are located within genomic neighborhoods that also encode three proteins possessing domains specific for the Type I secretion system. PMID:26030905

  12. 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

  13. 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

    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

  14. 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. PMID:26706081

  15. Different expression domains for two closely related amphibian TAARs generate a bimodal distribution similar to neuronal responses to amine odors.

    PubMed

    Syed, Adnan S; Sansone, Alfredo; Röner, Sebastian; Bozorg Nia, Shahrzad; Manzini, Ivan; Korsching, Sigrun I

    2015-01-01

    Olfactory perception is mediated by a multitude of olfactory receptors, whose expression in the sensory surface, the olfactory epithelium, is spatially regulated. A common theme is the segregation of different olfactory receptors in different expression domains, which in turn leads to corresponding segregation in the neuronal responses to different odor groups. The amphibian olfactory receptor gene family of trace amine associated receptors, in short TAARs, is exceedingly small and allows a comprehensive analysis of spatial expression patterns, as well as a comparison with neuronal responses to the expected ligands for this receptor family, amines. Here we report that TAAR4b exhibits a spatial expression pattern characteristically different in two dimensions from that of TAAR4a, its close homolog. Together, these two genes result in a bimodal distribution resembling that of amine responses as visualized by calcium imaging. A stringent quantitative analysis suggests the involvement of additional olfactory receptors in amphibian responses to amine odors. PMID:26358883

  16. Different expression domains for two closely related amphibian TAARs generate a bimodal distribution similar to neuronal responses to amine odors

    PubMed Central

    Syed, Adnan S.; Sansone, Alfredo; Röner, Sebastian; Bozorg Nia, Shahrzad; Manzini, Ivan; Korsching, Sigrun I.

    2015-01-01

    Olfactory perception is mediated by a multitude of olfactory receptors, whose expression in the sensory surface, the olfactory epithelium, is spatially regulated. A common theme is the segregation of different olfactory receptors in different expression domains, which in turn leads to corresponding segregation in the neuronal responses to different odor groups. The amphibian olfactory receptor gene family of trace amine associated receptors, in short TAARs, is exceedingly small and allows a comprehensive analysis of spatial expression patterns, as well as a comparison with neuronal responses to the expected ligands for this receptor family, amines. Here we report that TAAR4b exhibits a spatial expression pattern characteristically different in two dimensions from that of TAAR4a, its close homolog. Together, these two genes result in a bimodal distribution resembling that of amine responses as visualized by calcium imaging. A stringent quantitative analysis suggests the involvement of additional olfactory receptors in amphibian responses to amine odors. PMID:26358883

  17. Emotional Modulation of Conflict Processing in the Affective Domain: Evidence from Event-related Potentials and Event-related Spectral Perturbation Analysis.

    PubMed

    Ma, Jianling; Liu, Chang; Chen, Xu

    2016-01-01

    Previous studies have revealed the impact of emotion on conflict processing. The present study was conducted to investigate whether cognitive control in the affective domain is also affected by emotion. Emotional face-word and body-word Stroop tasks were explored and contrasted, and both behavioural and electrophysiological measures were recorded. Behavioural results showed that both tasks replicated previous robust interference effects. At the physiological level, the two tasks showed dissociable neural activity in the early attention and perception stages. It was also found that the face-word task evoked more pronounced N1 and P2 amplitudes than the body-word task. However, the two tasks evoked comparable N450 amplitudes. At later processing stages, positive slow potentials were modulated by target emotion and congruency. In addition, time-frequency analyses also revealed that the face-word task induced enhanced theta activity compared to the body-word task at both early and later stages of processing. The present findings provide support for the dual competition framework and suggest the dynamic modulation of emotion on cognitive control in the affective domain. PMID:27511609

  18. Emotional Modulation of Conflict Processing in the Affective Domain: Evidence from Event-related Potentials and Event-related Spectral Perturbation Analysis

    PubMed Central

    Ma, Jianling; Liu, Chang; Chen, Xu

    2016-01-01

    Previous studies have revealed the impact of emotion on conflict processing. The present study was conducted to investigate whether cognitive control in the affective domain is also affected by emotion. Emotional face-word and body-word Stroop tasks were explored and contrasted, and both behavioural and electrophysiological measures were recorded. Behavioural results showed that both tasks replicated previous robust interference effects. At the physiological level, the two tasks showed dissociable neural activity in the early attention and perception stages. It was also found that the face-word task evoked more pronounced N1 and P2 amplitudes than the body-word task. However, the two tasks evoked comparable N450 amplitudes. At later processing stages, positive slow potentials were modulated by target emotion and congruency. In addition, time-frequency analyses also revealed that the face-word task induced enhanced theta activity compared to the body-word task at both early and later stages of processing. The present findings provide support for the dual competition framework and suggest the dynamic modulation of emotion on cognitive control in the affective domain. PMID:27511609

  19. 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.

  20. PASS2 database for the structure-based sequence alignment of distantly related SCOP domain superfamilies: update to version 5 and added features.

    PubMed

    Gandhimathi, Arumugam; Ghosh, Pritha; Hariharaputran, Sridhar; Mathew, Oommen K; Sowdhamini, R

    2016-01-01

    Structure-based sequence alignment is an essential step in assessing and analysing the relationship of distantly related proteins. PASS2 is a database that records such alignments for protein domain superfamilies and has been constantly updated periodically. This update of the PASS2 version, named as PASS2.5, directly corresponds to the SCOPe 2.04 release. All SCOPe structural domains that share less than 40% sequence identity, as defined by the ASTRAL compendium of protein structures, are included. The current version includes 1977 superfamilies and has been assembled utilizing the structure-based sequence alignment protocol. Such an alignment is obtained initially through MATT, followed by a refinement through the COMPARER program. The JOY program has been used for structural annotations of such alignments. In this update, we have automated the protocol and focused on inclusion of new features such as mapping of GO terms, absolutely conserved residues among the domains in a superfamily and inclusion of PDBs, that are absent in SCOPe 2.04, using the HMM profiles from the alignments of the superfamily members and are provided as a separate list. We have also implemented a more user-friendly manner of data presentation and options for downloading more features. PASS2.5 version is available at http://caps.ncbs.res.in/pass2/. PMID:26553811

  1. 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

  2. Structure-function analysis of the human TFIIB-related factor II protein reveals an essential role for the C-terminal domain in RNA polymerase III transcription.

    PubMed

    Saxena, Ashish; Ma, Beicong; Schramm, Laura; Hernandez, Nouria

    2005-11-01

    The transcription factors TFIIB, Brf1, and Brf2 share related N-terminal zinc ribbon and core domains. TFIIB bridges RNA polymerase II (Pol II) with the promoter-bound preinitiation complex, whereas Brf1 and Brf2 are involved, as part of activities also containing TBP and Bdp1 and referred to here as Brf1-TFIIIB and Brf2-TFIIIB, in the recruitment of Pol III. Brf1-TFIIIB recruits Pol III to type 1 and 2 promoters and Brf2-TFIIIB to type 3 promoters such as the human U6 promoter. Brf1 and Brf2 both have a C-terminal extension absent in TFIIB, but their C-terminal extensions are unrelated. In yeast Brf1, the C-terminal extension interacts with the TBP/TATA box complex and contributes to the recruitment of Bdp1. Here we have tested truncated Brf2, as well as Brf2/TFIIB chimeric proteins for U6 transcription and for assembly of U6 preinitiation complexes. Our results characterize functions of various human Brf2 domains and reveal that the C-terminal domain is required for efficient association of the protein with U6 promoter-bound TBP and SNAP(c), a type 3 promoter-specific transcription factor, and for efficient recruitment of Bdp1. This in turn suggests that the C-terminal extensions in Brf1 and Brf2 are crucial to specific recruitment of Pol III over Pol II. PMID:16227591

  3. Structure-Function Analysis of the Human TFIIB-Related Factor II Protein Reveals an Essential Role for the C-Terminal Domain in RNA Polymerase III Transcription

    PubMed Central

    Saxena, Ashish; Ma, Beicong; Schramm, Laura; Hernandez, Nouria

    2005-01-01

    The transcription factors TFIIB, Brf1, and Brf2 share related N-terminal zinc ribbon and core domains. TFIIB bridges RNA polymerase II (Pol II) with the promoter-bound preinitiation complex, whereas Brf1 and Brf2 are involved, as part of activities also containing TBP and Bdp1 and referred to here as Brf1-TFIIIB and Brf2-TFIIIB, in the recruitment of Pol III. Brf1-TFIIIB recruits Pol III to type 1 and 2 promoters and Brf2-TFIIIB to type 3 promoters such as the human U6 promoter. Brf1 and Brf2 both have a C-terminal extension absent in TFIIB, but their C-terminal extensions are unrelated. In yeast Brf1, the C-terminal extension interacts with the TBP/TATA box complex and contributes to the recruitment of Bdp1. Here we have tested truncated Brf2, as well as Brf2/TFIIB chimeric proteins for U6 transcription and for assembly of U6 preinitiation complexes. Our results characterize functions of various human Brf2 domains and reveal that the C-terminal domain is required for efficient association of the protein with U6 promoter-bound TBP and SNAPc, a type 3 promoter-specific transcription factor, and for efficient recruitment of Bdp1. This in turn suggests that the C-terminal extensions in Brf1 and Brf2 are crucial to specific recruitment of Pol III over Pol II. PMID:16227591

  4. PASS2 database for the structure-based sequence alignment of distantly related SCOP domain superfamilies: update to version 5 and added features

    PubMed Central

    Gandhimathi, Arumugam; Ghosh, Pritha; Hariharaputran, Sridhar; Mathew, Oommen K.; Sowdhamini, R.

    2016-01-01

    Structure-based sequence alignment is an essential step in assessing and analysing the relationship of distantly related proteins. PASS2 is a database that records such alignments for protein domain superfamilies and has been constantly updated periodically. This update of the PASS2 version, named as PASS2.5, directly corresponds to the SCOPe 2.04 release. All SCOPe structural domains that share less than 40% sequence identity, as defined by the ASTRAL compendium of protein structures, are included. The current version includes 1977 superfamilies and has been assembled utilizing the structure-based sequence alignment protocol. Such an alignment is obtained initially through MATT, followed by a refinement through the COMPARER program. The JOY program has been used for structural annotations of such alignments. In this update, we have automated the protocol and focused on inclusion of new features such as mapping of GO terms, absolutely conserved residues among the domains in a superfamily and inclusion of PDBs, that are absent in SCOPe 2.04, using the HMM profiles from the alignments of the superfamily members and are provided as a separate list. We have also implemented a more user-friendly manner of data presentation and options for downloading more features. PASS2.5 version is available at http://caps.ncbs.res.in/pass2/. PMID:26553811

  5. Relationship of work-family conflict with burnout and marital satisfaction: cross-domain or source attribution relations?

    PubMed Central

    Bagherzadeh, Razieh; Taghizadeh, Ziba; Mohammadi, Eesa; Kazemnejad, Anoshirvan; Pourreza, Abolghasem; Ebadi, Abbas

    2016-01-01

    Background: The present study was conducted to examine the relationship between two dimensions of work-family conflict (WFC) with marital satisfaction and burnout in a society in which few studies have been done about the consequences of WFC. Methods: A cross-sectional study was conducted in 2015. Surveys were distributed to 420 employed married women with various jobs living in Bushehr province, Iran. Data were collected using a questionnaire for demographic characteristic, the Netmeyer’s WFC questionnaire, Maslach Burnout Inventory: General Survey (MBI-GS), and Enrich maritalsatisfaction questionnaire. The data were analyzed using descriptive and inferential statistics. Results: There was a negatively significant association between work interference with family(WIF) and overall burnout as well as emotional exhaustion (P < .01). Family interference with work (FIW) was significantly associated with depersonalization (P < .01). The overall marital satisfaction and its subscales were significantly associated with WIF (P < .01) and FIW (P < .01 for overall marital satisfaction and P < .05 for its subscales). Conclusion: In terms of practical implication, to avoid creating disadvantages of WIF and FIW,facilitation in two domains of improving work and family conditions can be a useful means to prevent WFC and its consequences. PMID:27123434

  6. Gender and age related expression of Oct-6--a POU III domain transcription factor, in the adult mouse brain.

    PubMed

    Ilia, Maria; Sugiyama, Yuka; Price, Jack

    2003-06-26

    Oct-6 is a POU III domain transcription factor whose primary role is thought to be developmental. It is expressed in embryonic stem cells, Schwann cells, and in neuronal subpopulations during telencephalic development. Its best characterised role is in Schwann cells where it is thought to regulate myelin specific gene expression. Expression of Oct-6 was recently discovered in neurons in post-mortem human schizophrenic specimens while being undetectable in matched controls. This study of human tissue contrasted in a number of regards with earlier studies of rodent brain, and questioned what we can consider to be normal adult expression of this gene. In this study, we have investigated Oct-6 expression via in situ hybridisation and Western blot analysis in normal adult female mice of different ages. We show that both RNA and protein levels of Oct-6 expression are highly sustained in the adult and aging cerebellum, whereas they are attenuated in the telencephalon by PW30 (postnatal week 30). These observations suggest that Oct-6 expression takes place in a sex and age dependent way. PMID:12782346

  7. Catalytic domain of plasmid pAD1 relaxase TraX defines a group of relaxases related to restriction endonucleases

    PubMed Central

    Francia, María Victoria; Clewell, Don B.; de la Cruz, Fernando; Moncalián, Gabriel

    2013-01-01

    Plasmid pAD1 is a 60-kb conjugative element commonly found in clinical isolates of Enterococcus faecalis. The relaxase TraX and the primary origin of transfer oriT2 are located close to each other and have been shown to be essential for conjugation. The oriT2 site contains a large inverted repeat (where the nic site is located) adjacent to a series of short direct repeats. TraX does not show any of the typical relaxase sequence motifs but is the prototype of a unique family of relaxases (MOBC). The present study focuses on the genetic, biochemical, and structural analysis of TraX, whose 3D structure could be predicted by protein threading. The structure consists of two domains: (i) an N-terminal domain sharing the topology of the DNA binding domain of the MarR family of transcriptional regulators and (ii) a C-terminal catalytic domain related to the PD-(D/E)XK family of restriction endonucleases. Alignment of MOBC relaxase amino acid sequences pointed to several conserved polar amino acid residues (E28, D152, E170, E172, K176, R180, Y181, and Y203) that were mutated to alanine. Functional analysis of these mutants (in vivo DNA transfer and cleavage assays) revealed the importance of these residues for relaxase activity and suggests Y181 as a potential catalytic residue similarly to His-hydrophobe-His relaxases. We also show that TraX binds specifically to dsDNA containing the oriT2 direct repeat sequences, confirming their role in transfer specificity. The results provide insights into the catalytic mechanism of MOBC relaxases, which differs radically from that of His-hydrophobe-His relaxases. PMID:23904483

  8. Xerostomia After Treatment for Oral and Oropharyngeal Cancer Using the University of Washington Saliva Domain and a Xerostomia-Related Quality-of-Life Scale

    SciTech Connect

    Rogers, Simon N.; Johnson, Ian A.; Lowe, Derek

    2010-05-01

    Purpose: The first aim of this study was to identify which clinical factors are associated with xerostomia in patients after treatment for oral and oropharyngeal squamous cell carcinoma, using the Xerostomia-Related Quality-of-Life Scale (XeQoLS) and the University of Washington Quality-of-Life Questionnaire Version 4 dry mouth item (UW-QOL v4). The second aim was to compare these two questionnaires and postulate a cutoff in the UW-QOL below which patients are doing sufficient badly to warrant further evaluation and support. Methods and Materials: In all, 371 patients alive and disease free treated between 1992 and 2005 were sent the survey, of whom 250 (67%) responded. Various clinical factors correlated with xerostomia, particularly adjuvant radiotherapy and Pstage. Results: In logistic regression analyses to predict three or more problems on the XeQoLS, only adjuvant radiotherapy (p < 0.001) was significant at the 5% level. There were significant (p < 0.001) correlations between the XeQoLS scores (total average and domain) with all the UW-QOL domain scores, the strongest with swallowing (-0.69), taste (-0.64), chewing (-0.64), mood (-0.60), and saliva (-0.59) domains. Patients scoring <70 (i.e., 0 or 30) on the UW-QOL could be used as a screening cutoff because it formed 1 in 5 of all patients (49/242) but accounted for half (299/566) of the significant problems generated by the XeQoLS. This also identified 13/21 patients with 10 or more problems. Conclusion: The UW-QOL saliva domain seems to be a suitable means of screening for dry mouth in head-and-neck clinics and could be used to trigger interventions.

  9. Identification of monoclonal antibody-binding domains within antigen P1 of Streptococcus mutans and cross-reactivity with related surface antigens of oral streptococci.

    PubMed Central

    Brady, L J; Piacentini, D A; Crowley, P J; Bleiweis, A S

    1991-01-01

    Eleven monoclonal antibodies (MAbs) specific for P1, the major protein surface antigen of Streptococcus mutans serotype c, were characterized by Western blot (immunoblot) analysis and by radioimmunoassay using whole bacterial cells. The approximate binding domains of the MAbs were determined by using full-length and truncated P1 polypeptides. The accessibility of these binding sites on the surfaces of intact bacteria was determined by radioimmunoassay. The ability of each MAb to cross-react with related proteins from strains of S. mutans serotypes e and f, S. sanguis, and S. sobrinus serotype g is also reported. Images PMID:1937801

  10. Measuring postural-related changes of spontaneous baroreflex sensitivity after repeated long-duration diving: frequency domain approaches.

    PubMed

    Faes, Luca; Masè, Michela; Nollo, Giandomenico; Chon, Ki H; Florian, John P

    2013-11-01

    Sustained water immersion is thought to modulate orthostatic tolerance to an extent dependent on the duration and repetition over consecutive days of the diving sessions. We tested this hypothesis investigating in ten healthy subjects the potential changes in the cardiovascular response to head-up tilt induced by single and multiple resting air dives. Parametric cross-spectral analysis of spontaneous RR interval and systolic arterial pressure variability was performed in three experimental sessions: before diving (BD), after single 6-hour dive (ASD), and after multiple 6-hour dives (AMD, 5 consecutive days with 18-hour surface interval). From this analysis, baroreflex sensitivity (BRS) was computed as spectral power ratio (αBRS), non-causal transfer function gain (tfBRS) and causal transfer function gain (γBRS) evaluated at low frequency (0.04-0.14Hz) in the supine position (su) as well as in the standing upright position in the early tilt (et) and late tilt (lt) epochs. We found that, while αBRS decreased significantly in et and lt compared to su during all sessions, tfBRS and γBRS decreased during ASD and AMD but not during BD; moreover γBRS evidenced a progressive decrease from BD to ASD and to AMD in both et and lt epochs. These results indicate the necessity of following a causal approach for the estimation of BRS in the frequency domain, and suggest a progressive impairment of the baroreflex response to postural stress after single and multiple dives, which may reflect symptoms of increasing orthostatic intolerance. PMID:23587978

  11. Learning and Domain Adaptation

    NASA Astrophysics Data System (ADS)

    Mansour, Yishay

    Domain adaptation is a fundamental learning problem where one wishes to use labeled data from one or several source domains to learn a hypothesis performing well on a different, yet related, domain for which no labeled data is available. This generalization across domains is a very significant challenge for many machine learning applications and arises in a variety of natural settings, including NLP tasks (document classification, sentiment analysis, etc.), speech recognition (speakers and noise or environment adaptation) and face recognition (different lighting conditions, different population composition).

  12. Evolution of paired domains: Isolation and sequencing of jellyfish and hydra Pax genes related to Pax-5 and Pax-6

    PubMed Central

    Sun, Hongmin; Rodin, Andrei; Zhou, Yihong; Dickinson, Douglas P.; Harper, Donald E.; Hewett-Emmett, David; Li, Wen-Hsiung

    1997-01-01

    Pax proteins are a family of transcription factors with a highly conserved paired domain; many members also contain a paired-type homeodomain and/or an octapeptide. Nine mammalian Pax genes are known and classified into four subgroups: Pax-1/9, Pax-2/5/8, Pax-3/7, and Pax-4/6. Most of these genes are involved in nervous system development. In particular, Pax-6 is a key regulator that controls eye development in vertebrates and Drosophila. Although the Pax-4/6 subgroup seems to be more closely related to Pax-2/5/8 than to Pax-3/7 or Pax-1/9, its evolutionary origin is unknown. We therefore searched for a Pax-6 homolog and related genes in Cnidaria, which is the lowest phylum of animals that possess a nervous system and eyes. A sea nettle (a jellyfish) genomic library was constructed and two pax genes (Pax-A and -B) were isolated and partially sequenced. Surprisingly, unlike most known Pax genes, the paired box in these two genes contains no intron. In addition, the complete cDNA sequences of hydra Pax-A and -B were obtained. Hydra Pax-B contains both the homeodomain and the octapeptide, whereas hydra Pax-A contains neither. DNA binding assays showed that sea nettle Pax-A and -B and hydra Pax-A paired domains bound to a Pax-5/6 site and a Pax-5 site, although hydra Pax-B paired domain bound neither. An alignment of all available paired domain sequences revealed two highly conserved regions, which cover the DNA binding contact positions. Phylogenetic analysis showed that Pax-A and especially Pax-B were more closely related to Pax-2/5/8 and Pax-4/6 than to Pax-1/9 or Pax-3/7 and that the Pax genes can be classified into two supergroups: Pax-A/Pax-B/Pax-2/5/8/4/6 and Pax-1/9/3/7. From this analysis and the gene structure, we propose that modern Pax-4/6 and Pax-2/5/8 genes evolved from an ancestral gene similar to cnidarian Pax-B, having both the homeodomain and the octapeptide. PMID:9144207

  13. Chinese Students' Implicit Theories of Intelligence and Other Personal Attributes: Cross-Domain Generality and Age-Related Differences.

    ERIC Educational Resources Information Center

    Cheng, Zi-Juan; Hau, Kit-Tai; Wen, Jian-Bing; Kong, Chit-Kwong

    Using structural equation modeling (SEM), researchers examined whether there was a general dominating factor that governed students' implicit theories of intelligence, morality, personality, creativity, and social intelligence. The possible age-related changes of students' implicit theories were also studied. In all, 1,650 elementary and junior…

  14. Cloning, expression and purification of binding domains of lethal factor and protective antigen of Bacillus anthracis in Escherichia coli and evaluation of their related murine antibody.

    PubMed

    Rezaee, Mehdi; Honari, Hossein; Kooshk, Mohammad Reza Ashrafi

    2014-01-01

    Anthrax is common disease between human and animals caused by Bacillus anthracis. The cell binding domain of protective antigen (PAD4) and the binding domain of lethal factor (LFD1) have high immunogenicity potential and always were considered as a vaccine candidate against anthrax. The aims of this study are cloning and expressing of PAD4 and LFD1 in Escherichia coli, purification of the recombinant proteins and determination of their immunogenicity through evaluating of the relative produced polyclonal antibodies in mice. PAD4 and LFD1 genes were cloned in pET28a(+) vector and expressed in E. coli Bl21(DE3)PlysS. Expression and purification of the two recombinant proteins were confirmed by SDS-PAGE and Western blotting techniques. The PAD4 and LFD1 were purified using Ni(+)-NTA affinity chromatography (95-98 %), yielding 37.5 and 45 mg/l of culture, respectively. The antigens were injected three times into mice and production of relative antibodies was evaluated by ELISA test. The results showed that both PAD4 and LFD1 are immunogenic, but LFD1 has higher potential to stimulate Murine immune system. With regard to the high level of LFD1 and PAD4 expression and also significant increment in produced polyclonal antibodies, these recombinant proteins can be considered as a recombinant vaccine candidate against anthrax. PMID:24430302

  15. 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

  16. The amino-acid sequence of the glucose/mannose-specific lectin isolated from Parkia platycephala seeds reveals three tandemly arranged jacalin-related domains.

    PubMed

    Mann, K; Farias, C M; Del Sol, F G; Santos, C F; Grangeiro, T B; Nagano, C S; Cavada, B S; Calvete, J J

    2001-08-01

    A mannose/glucose-specific lectin was isolated from seeds of Parkia platycephala, the most primitive subfamily of Leguminosae plants. The molecular mass of the purified lectin determined by mass spectrometry was 47 946 +/- 6 Da (by electrospray ionization) and 47 951 +/- 9 Da (by matrix-assisted laser-desoption ionization). The apparent molecular mass of the lectin in solutions of pH in the range 4.5-8.5 determined by analytical ultracentrifugation equilibrium sedimentation was 94 +/- 3 kDa, showing that the protein behaved as a non-pH-dependent dimer. The amino-acid sequence of the Parkia lectin was determined by Edman degradation of overlapping peptides. This is the first report of the primary structure of a Mimosoideae lectin. The protein contained a blocked N-terminus and a single, nonglycosylated polypeptide chain composed of three tandemly arranged homologous domains. Each of these domains shares sequence similarity with jacalin-related lectin monomers from Asteraceae, Convolvulaceae, Moraceae, Musaceae, Gramineae, and Fagaceae plant families. Based on this homology, we predict that each Parkia lectin repeat may display a beta prism fold similar to that observed in the crystal structure of the lectin from Helianthus tuberosus. The P. platycephala lectin also shows sequence similarity with stress- and pathogen-upregulated defence genes of a number of different plants, suggesting a common ancestry for jacalin-related lectins and inducible defence proteins. PMID:11502201

  17. A Preliminary Prospective Study of an Escalation in 'Maximum Daily Drinks', Fronto-Parietal Circuitry and Impulsivity-Related Domains in Young Adult Drinkers.

    PubMed

    Worhunsky, Patrick D; Dager, Alecia D; Meda, Shashwath A; Khadka, Sabin; Stevens, Michael C; Austad, Carol S; Raskin, Sarah A; Tennen, Howard; Wood, Rebecca M; Fallahi, Carolyn R; Potenza, Marc N; Pearlson, Godfrey D

    2016-05-01

    Excessive alcohol use in young adults is associated with greater impulsivity and neurobiological alterations in executive control systems. The maximum number of drinks consumed during drinking occasions ('MaxDrinks') represents a phenotype linked to vulnerability of alcohol use disorders, and an increase, or 'escalation', in MaxDrinks may be indicative of greater risk for problematic drinking. Thirty-six young adult drinkers performed a Go/No-Go task during fMRI, completed impulsivity-related assessments, and provided monthly reports of alcohol use during a 12-month follow-up period. Participants were characterized by MaxDrinks at baseline and after follow-up, identifying 18 escalating drinkers and 18 constant drinkers. Independent component analysis was used to investigate functional brain networks associated with response inhibition, and relationships with principal component analysis derived impulsivity-related domains were examined. Greater baseline MaxDrinks was associated with an average reduction in the engagement of a right-lateralized fronto-parietal functional network, while an escalation in MaxDrinks was associated with a greater difference in fronto-parietal engagement between successful inhibitions and error trials. Escalating drinkers displayed greater impulsivity/compulsivity-related domain scores that were positively associated with fronto-parietal network engagement and change in MaxDrinks during follow-up. In young adults, an escalating MaxDrinks trajectory was prospectively associated with altered fronto-parietal control mechanisms and greater impulsivity/compulsivity scores. Continued longitudinal studies of MaxDrinks trajectories, functional network activity, and impulsivity/compulsivity-related features may lend further insight into an intermediate phenotype vulnerable for alcohol use and addictive disorders. PMID:26514582

  18. 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

  19. Combination of genetic screening and molecular dynamics as a useful tool for identification of disease-related mutations: ZASP PDZ domain G54S mutation case.

    PubMed

    Fratev, Filip; Mihaylova, Elina; Pajeva, Ilza

    2014-05-27

    Cypher/ZASP (LDB3 gene) is known to interact with a network of proteins. It binds to α-actinin and the calcium voltage channels (LTCC) via its PDZ domain. Here we report the identification of a highly conserved ZASP G54S mutation classified as a variant of unknown significance in a sample of an adult with hypertrophic cardiomyopathy (HCM). The initial bioinformatics calculations strongly evaluated G54S as damaging. Furthermore, we employed accelerated and classical molecular dynamics and free energy calculations to study the structural impact of this mutation on the ZASP apo form and to address the question of whether it can be linked to HCM. Seventeen independent MD runs and simulations of 2.5 μs total were performed and showed that G54S perturbs the α2 helix position via destabilization of the adjacent loop linked to the β5 sheet. This also leads to the formation of a strong H-bond between peptide target residues Leu17 and Gln66, thus restricting both the α-actinin2 and LTCC C-terminal peptides to access their natural binding site and reducing in this way their binding capacity. On the basis of these observations and the adult's clinical data, we propose that ZASP(G54S) and presumably other ZASP PDZ domain mutations can cause HCM. To the best of our knowledge, this is the first reported ZASP PDZ domain mutation that might be linked to HCM. The integrated workflow used in this study can be applied for the identification and description of other mutations that might be related to particular diseases. PMID:24730657

  20. 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

  1. 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

    2015-01-01

    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

  2. The La-related protein 1-specific domain repurposes HEAT-like repeats to directly bind a 5'TOP sequence

    SciTech Connect

    Lahr, Roni M.; Mack, Seshat M.; Heroux, Annie; Blagden, Sarah P.; Bousquet-Antonelli, Cecile; Deragon, Jean -Marc; Berman, Andrea J.

    2015-07-22

    La-related protein 1 (LARP1) regulates the stability of many mRNAs. These include 5'TOPs, mTOR-kinase responsive mRNAs with pyrimidine-rich 5' UTRs, which encode ribosomal proteins and translation factors. We determined that the highly conserved LARP1-specific C-terminal DM15 region of human LARP1 directly binds a 5'TOP sequence. The crystal structure of this DM15 region refined to 1.86 Å resolution has three structurally related and evolutionarily conserved helix-turn-helix modules within each monomer. These motifs resemble HEAT repeats, ubiquitous helical protein-binding structures, but their sequences are inconsistent with consensus sequences of known HEAT modules, suggesting this structure has been repurposed for RNA interactions. A putative mTORC1-recognition sequence sits within a flexible loop C-terminal to these repeats. We also present modelling of pyrimidine-rich single-stranded RNA onto the highly conserved surface of the DM15 region. Ultimately, these studies lay the foundation necessary for proceeding toward a structural mechanism by which LARP1 links mTOR signalling to ribosome biogenesis.

  3. The La-related protein 1-specific domain repurposes HEAT-like repeats to directly bind a 5'TOP sequence

    DOE PAGESBeta

    Lahr, Roni M.; Mack, Seshat M.; Heroux, Annie; Blagden, Sarah P.; Bousquet-Antonelli, Cecile; Deragon, Jean -Marc; Berman, Andrea J.

    2015-07-22

    La-related protein 1 (LARP1) regulates the stability of many mRNAs. These include 5'TOPs, mTOR-kinase responsive mRNAs with pyrimidine-rich 5' UTRs, which encode ribosomal proteins and translation factors. We determined that the highly conserved LARP1-specific C-terminal DM15 region of human LARP1 directly binds a 5'TOP sequence. The crystal structure of this DM15 region refined to 1.86 Å resolution has three structurally related and evolutionarily conserved helix-turn-helix modules within each monomer. These motifs resemble HEAT repeats, ubiquitous helical protein-binding structures, but their sequences are inconsistent with consensus sequences of known HEAT modules, suggesting this structure has been repurposed for RNA interactions. Amore » putative mTORC1-recognition sequence sits within a flexible loop C-terminal to these repeats. We also present modelling of pyrimidine-rich single-stranded RNA onto the highly conserved surface of the DM15 region. Ultimately, these studies lay the foundation necessary for proceeding toward a structural mechanism by which LARP1 links mTOR signalling to ribosome biogenesis.« less

  4. Convergent Signaling Pathways Controlled by LRP1 (Receptor-related Protein 1) Cytoplasmic and Extracellular Domains Limit Cellular Cholesterol Accumulation.

    PubMed

    El Asmar, Zeina; Terrand, Jérome; Jenty, Marion; Host, Lionel; Mlih, Mohamed; Zerr, Aurélie; Justiniano, Hélène; Matz, Rachel L; Boudier, Christian; Scholler, Estelle; Garnier, Jean-Marie; Bertaccini, Diego; Thiersé, Danièle; Schaeffer, Christine; Van Dorsselaer, Alain; Herz, Joachim; Bruban, Véronique; Boucher, Philippe

    2016-03-01

    The low density lipoprotein receptor-related protein 1 (LRP1) is a ubiquitously expressed cell surface receptor that protects from intracellular cholesterol accumulation. However, the underlying mechanisms are unknown. Here we show that the extracellular (α) chain of LRP1 mediates TGFβ-induced enhancement of Wnt5a, which limits intracellular cholesterol accumulation by inhibiting cholesterol biosynthesis and by promoting cholesterol export. Moreover, we demonstrate that the cytoplasmic (β) chain of LRP1 suffices to limit cholesterol accumulation in LRP1(-/-) cells. Through binding of Erk2 to the second of its carboxyl-terminal NPXY motifs, LRP1 β-chain positively regulates the expression of ATP binding cassette transporter A1 (ABCA1) and of neutral cholesterol ester hydrolase (NCEH1). These results highlight the unexpected functions of LRP1 and the canonical Wnt5a pathway and new therapeutic potential in cholesterol-associated disorders including cardiovascular diseases. PMID:26792864

  5. A truncated fragment of Ov-ASP-1 consisting of the core pathogenesis-related-1 (PR-1) domain maintains adjuvanticity as the full-length protein.

    PubMed

    Guo, Jingjing; Yang, Yi; Xiao, Wenjun; Sun, Weilai; Yu, Hong; Du, Lanying; Lustigman, Sara; Jiang, Shibo; Kou, Zhihua; Zhou, Yusen

    2015-04-15

    The Onchocerca volvulus activation-associated secreted protein-1 (Ov-ASP-1) has good adjuvanticity for a variety of antigens and vaccines, probably due to its ability activate antigen-processing cells (APCs). However, the functional domain of Ov-ASP-1 as an adjuvant is not clearly defined. Based on the structural prediction of this protein family, we constructed a 16-kDa recombinant protein of Ov-ASP-1 that contains only the core pathogenesis-related-1 (PR-1) domain (residues 10-153), designated ASPPR. We found that ASPPR exhibits adjuvanticity similar to that of the full-length Ov-ASP-1 (residues 10-220) for various antigens, including ovalbumin (OVA), HBsAg protein antigen, and the HIV peptide 5 (Pep5) antigen, but it is more suitable for vaccine design in ASPPR-antigen fusion proteins, and more stable in PBS than Ov-ASP-1 stored at -70 °C. These results suggest that ASPPR might be the functional region of Ov-ASP-1 as an adjuvant, and therefore could be developed as an adjuvant for human use. PMID:25736195

  6. Stress induced and nuclear localized HIPP26 from Arabidopsis thaliana interacts via its heavy metal associated domain with the drought stress related zinc finger transcription factor ATHB29.

    PubMed

    Barth, Olaf; Vogt, Sebastian; Uhlemann, Ria; Zschiesche, Wiebke; Humbeck, Klaus

    2009-01-01

    HIPP26 from Arabidopsis thaliana belongs to a novel class of plant proteins, characterized by a heavy metal associated domain and an additional isoprenylation motif. It is induced during cold, salt and drought stress. The nuclear localization of HIPP26, predicted by a NLS motif, could be confirmed in onion epidermal cells overexpressing GFP-HIPP26. Experiments with modified HIPP26 indicate that the isoprenylation plays a role in the spatial distribution in the nucleus. Using promoter-GUS constructs, a tissue specific expression pattern of HIPP26 could be shown, with high expression in the vascular tissue. By a yeast-two-hybrid approach a strong interaction of HIPP26 with the zinc finger homeodomain transcription factor ATHB29, which is known to play a role in dehydration stress response could be detected. This was confirmed by GST pull-down assays. When using a modified HIPP26 lacking the two central cysteines of the heavy metal associated domain, ATHB29 was not bound in the GST pull-down assay, indicating that this structure is necessary for the interaction. Further yeast-two-hybrid analyses testing interaction of different members of the HIPP family with related zinc finger transcription factors revealed a specific interaction of ATHB29 with several HIPP proteins. A functional relationship between HIPP26 and ATHB29 is also indicated by experiments with mutants of HIPP26 showing altered expression levels of such genes known to be regulated by ATHB29. PMID:18974936

  7. Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials

    PubMed Central

    Saketkoo, Lesley Ann; Mittoo, Shikha; Huscher, Dörte; Khanna, Dinesh; Dellaripa, Paul F; Distler, Oliver; Flaherty, Kevin R; Frankel, Sid; Oddis, Chester V; Denton, Christopher P; Fischer, Aryeh; Kowal-Bielecka, Otylia M; LeSage, Daphne; Merkel, Peter A; Phillips, Kristine; Pittrow, David; Swigris, Jeffrey; Antoniou, Katerina; Baughman, Robert P; Castelino, Flavia V; Christmann, Romy B; Christopher-Stine, Lisa; Collard, Harold R; Cottin, Vincent; Danoff, Sonye; Highland, Kristin B; Hummers, Laura; Shah, Ami A; Kim, Dong Soon; Lynch, David A; Miller, Frederick W; Proudman, Susanna M; Richeldi, Luca; Ryu, Jay H; Sandorfi, Nora; Sarver, Catherine; Wells, Athol U; Strand, Vibeke; Matteson, Eric L; Brown, Kevin K; Seibold, James R

    2014-01-01

    Rationale Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. Methods The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology—a non-profit international organisation dedicated to consensus methodology in identification of outcome measures—conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). Results A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Conclusion Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field. PMID:24368713

  8. PL3 Amidase, a Tailor-made Lysin Constructed by Domain Shuffling with Potent Killing Activity against Pneumococci and Related Species.

    PubMed

    Blázquez, Blas; Fresco-Taboada, Alba; Iglesias-Bexiga, Manuel; Menéndez, Margarita; García, Pedro

    2016-01-01

    The emergence and spread of antibiotic-resistant bacteria is pushing the need of alternative treatments. In this context, phage therapy is already a reality to successfully fight certain multiresistant bacteria. Among different phage gene products, murein hydrolases responsible of phage progeny liberation (also called lysins or endolysins) are weapons that target specific peptidoglycan bonds, leading to lysis and death of susceptible bacteria when added from the outside. In the pneumococcal system, all but one phage murein hydrolases reported to date share a choline-binding domain that recognizes cell walls containing choline residues in the (lipo)teichoic acids. Some purified pneumococcal or phage murein hydrolases, as well as several chimeric proteins combining natural catalytic and cell wall-binding domains (CBDs) have been used as effective antimicrobials. In this work we have constructed a novel chimeric N-acetylmuramoyl-L-alanine amidase (PL3) by fusing the catalytic domain of the Pal amidase (a phage-coded endolysin) to the CBD of the LytA amidase, the major pneumococcal autolysin. The physicochemical properties of PL3 and the bacteriolytic effect against several pneumococci (including 48 multiresistant representative strain) and related species, like Streptococcus pseudopneumoniae, Streptococcus mitis, and Streptococcus oralis, have been studied. Results have shown that low doses of PL3, in the range of 0.5-5 μg/ml, are enough to practically sterilize all choline-containing strains tested. Moreover, a single 20-μg dose of PL3 fully protected zebrafish embryos from infection by S. pneumoniae D39 strain. Importantly, PL3 keeps 95% enzymatic activity after 4 weeks at 37°C and can be lyophilized without losing activity, demonstrating a remarkable robustness. Such stability, together with a prominent efficacy against a narrow spectrum of human pathogens, confers to PL3 the characteristic to be an effective therapeutic. In addition, our results demonstrate

  9. PL3 Amidase, a Tailor-made Lysin Constructed by Domain Shuffling with Potent Killing Activity against Pneumococci and Related Species

    PubMed Central

    Blázquez, Blas; Fresco-Taboada, Alba; Iglesias-Bexiga, Manuel; Menéndez, Margarita; García, Pedro

    2016-01-01

    The emergence and spread of antibiotic-resistant bacteria is pushing the need of alternative treatments. In this context, phage therapy is already a reality to successfully fight certain multiresistant bacteria. Among different phage gene products, murein hydrolases responsible of phage progeny liberation (also called lysins or endolysins) are weapons that target specific peptidoglycan bonds, leading to lysis and death of susceptible bacteria when added from the outside. In the pneumococcal system, all but one phage murein hydrolases reported to date share a choline-binding domain that recognizes cell walls containing choline residues in the (lipo)teichoic acids. Some purified pneumococcal or phage murein hydrolases, as well as several chimeric proteins combining natural catalytic and cell wall-binding domains (CBDs) have been used as effective antimicrobials. In this work we have constructed a novel chimeric N-acetylmuramoyl-L-alanine amidase (PL3) by fusing the catalytic domain of the Pal amidase (a phage-coded endolysin) to the CBD of the LytA amidase, the major pneumococcal autolysin. The physicochemical properties of PL3 and the bacteriolytic effect against several pneumococci (including 48 multiresistant representative strain) and related species, like Streptococcus pseudopneumoniae, Streptococcus mitis, and Streptococcus oralis, have been studied. Results have shown that low doses of PL3, in the range of 0.5–5 μg/ml, are enough to practically sterilize all choline-containing strains tested. Moreover, a single 20-μg dose of PL3 fully protected zebrafish embryos from infection by S. pneumoniae D39 strain. Importantly, PL3 keeps 95% enzymatic activity after 4 weeks at 37°C and can be lyophilized without losing activity, demonstrating a remarkable robustness. Such stability, together with a prominent efficacy against a narrow spectrum of human pathogens, confers to PL3 the characteristic to be an effective therapeutic. In addition, our results demonstrate

  10. Laboratory permittivity measurements of icy planetary analogs in the millimeter and submillimeter domains, in relation with JUICE mission.

    NASA Astrophysics Data System (ADS)

    Brouet, Y.; Jacob, K.; Murk, A.; Poch, O.; Pommerol, A.; Thomas, N.; Levasseur-Regourd, A. C.

    2015-12-01

    The European Space Agency's JUpiter ICy moons Explorer (JUICE) spacecraft is planned for launch in 2022 and arrival at Jupiter in 2030. It will observe the planet Jupiter and three of its largest moons, Ganymede, Callisto and Europa. One instrument on the JUICE spacecraft is the Sub-millimeter Wave Instrument (SWI), which will measure brightness temperatures from Jupiter's stratosphere and troposphere, and from subsurfaces of Jupiter's icy moons. In the baseline configuration SWI consists of two tunable sub-millimeter wave receivers operating from 530 to 625 GHz. As an alternative one of the receivers could cover the range of 1080 and 1275 GHz. Inversion models are strongly dependent on the knowledge of the complex relative permittivity (hereafter permittivity) of the target material to retrieve the physical properties of the subsurface (e.g. [1][2]). We set up a laboratory experiment allowing us to perform reproducible measurements of the complex scattering parameters S11 and S21 in the ranges of 70 to 110 GHz, of 100 to 160 GHz, of 140 to 220 GHz, of 140 to 220 GHz and of 510 to 715 GHz. These scattering parameters can be used to retrieve the permittivity of icy analogs of the surfaces and subsurfaces of Jupiter's icy moons in order to prepare the data interpretation of SWI [3]. The measurements are performed under laboratory conditions with a quasi-optical bench (Institute of Applied Physics, University of Bern). The icy analogs that we prepare in the Laboratory for Outflow Studies of Sublimating Materials (LOSSy, Physics Institute, University of Bern), include two different porous water ice samples composed of fine-grained ice particles with a size range of 4 to 6 microns and ice particles with a size range of 50 to 100 microns [4][5]; and possibly CO2 ice. We will present the general experimental set-up and the first results in the context to prepare the data interpretation of SWI. [1] Ulaby, F. T., Long, D. G., 2014. Microwave radar and radiometric remote

  11. Perspectives on the Two-Pore Domain Potassium Channel TREK-1 (TWIK-Related K(+) Channel 1). A Novel Therapeutic Target?

    PubMed

    Vivier, Delphine; Bennis, Khalil; Lesage, Florian; Ducki, Sylvie

    2016-06-01

    Potassium (K(+)) channels are membrane proteins expressed in most living cells that selectively control the flow of K(+) ions. More than 80 genes encode the K(+) channel subunits in the human genome. The TWIK-related K(+) channel (TREK-1) belongs to the two-pore domain K(+) channels (K2P) and displays various properties including sensitivity to physical (membrane stretch, acidosis, temperature) and chemical stimuli (signaling lipids, volatile anesthetics). The distribution of TREK-1 in the central nervous system, coupled with the physiological consequences of its opening and closing, leads to the emergence of this channel as an attractive therapeutic target. We review the TREK-1 channel, its structural and functional properties, and the pharmacological agents (agonists and antagonists) able to modulate its gating. PMID:26588045

  12. Fibrinogen-Related Proteins in Tissue Repair: How a Unique Domain with a Common Structure Controls Diverse Aspects of Wound Healing

    PubMed Central

    Zuliani-Alvarez, Lorena; Midwood, Kim S.

    2015-01-01

    Significance: Fibrinogen-related proteins (FRePs) comprise an intriguing collection of extracellular molecules, each containing a conserved fibrinogen-like globe (FBG). This group includes the eponymous fibrinogen as well as the tenascin, angiopoietin, and ficolin families. Many of these proteins are upregulated during tissue repair and exhibit diverse roles during wound healing. Recent Advances: An increasing body of evidence highlights the specific expression of a number of FRePs following tissue injury and infection. Upon induction, each FReP uses its FBG domain to mediate quite distinct effects that contribute to different stages of tissue repair, such as driving coagulation, pathogen detection, inflammation, angiogenesis, and tissue remodeling. Critical Issues: Despite a high degree of homology among FRePs, each contains unique sequences that enable their diversification of function. Comparative analysis of the structure and function of FRePs and precise mapping of regions that interact with a variety of ligands has started to reveal the underlying molecular mechanisms by which these proteins play very different roles using their common domain. Future Directions: Fibrinogen has long been used in the clinic as a synthetic matrix serving as a scaffold or a delivery system to aid tissue repair. Novel therapeutic strategies are now emerging that harness the use of other FRePs to improve wound healing outcomes. As we learn more about the underlying mechanisms by which each FReP contributes to the repair response, specific blockade, or indeed potentiation, of their function offers real potential to enable regulation of distinct processes during pathological wound healing. PMID:26005593

  13. Self-Esteem is Relatively Stable Late in Life: The Role of Resources in the Health, Self-Regulation, and Social Domains

    PubMed Central

    Wagner, Jenny; Hoppmann, Christiane; Ram, Nilam; Gerstorf, Denis

    2015-01-01

    A large body of research has documented changes in self-esteem across adulthood and individual-difference correlates thereof. However, little is known about whether people maintain their self-esteem until the end of life and what role key risk factors in the health, cognitive, self-regulatory, and social domains play. To examine these questions, we apply growth modeling to 13-year longitudinal data obtained from by now deceased participants of the Berlin Aging Study (BASE, N = 462; age 70 – 103, M = 86.3 yrs., SD = 8.3; 51% male). Results revealed that self-esteem, on average, does decline in very old age and close to death, but the amount of typical decline is minor. Health-related constraints and disabilities as well as lower control beliefs and higher loneliness were each associated with lower self-esteem late in life. We obtained initial evidence that some of these associations were stronger among the oldest-old participants. Our results corroborate and extend initial reports that self-esteem is, on average, fairly stable into the last years of life. We discuss possible pathways by which common and often severe late-life challenges may undermine an otherwise relatively robust self-esteem system. PMID:25546600

  14. Searching for single domain magnetite in the “pseudo-single-domain” sedimentary haystack: Implications of biogenic magnetite preservation for sediment magnetism and relative paleointensity determinations

    NASA Astrophysics Data System (ADS)

    Roberts, Andrew P.; Chang, Liao; Heslop, David; Florindo, Fabio; Larrasoaña, Juan C.

    2012-08-01

    Magnetic hysteresis measurements of sediments have resulted in widespread reporting of “pseudo-single-domain”-like magnetic properties. In contrast, the ideal single domain (SD) properties that would be expected to be responsible for high quality paleomagnetic records are rare. Determining whether SD particles are rare or common in sediments requires application of techniques that enable discrimination among different magnetic components in a sediment. We apply a range of such techniques and find that SD particles are much more common than has been reported in the literature and that magnetite magnetofossils (the inorganic remains of magnetotactic bacteria) are widely preserved at depth in a range of sediment types, including biogenic pelagic carbonates, lacustrine and marine clays, and possibly even in glaci-marine sediments. Thus, instead of being rarely preserved in the geological record, we find that magnetofossils are widespread. This observation has important implications for our understanding of how sediments become magnetized and highlights the need to develop a more robust basis for understanding how biogenic magnetite contributes to the magnetization of sediments. Magnetofossils also have grain sizes that are substantially smaller than the 1-15 μm size range for which there is reasonable empirical support for relative paleointensity studies. The different magnetic response of coexisting fine biogenic and coarser lithogenic particles is likely to complicate relative paleointensity studies. This issue needs much closer attention. Despite the fact that sediments have been subjected to paleomagnetic investigation for over 60 years, much remains to be understood about how they become magnetized.

  15. Antecedent–Consequent Relations of Perceived Control to Health and Social Support: Longitudinal Evidence for Between-Domain Associations Across Adulthood

    PubMed Central

    Röcke, Christina; Lachman, Margie E.

    2011-01-01

    Objectives. To examine antecedent–consequent relations of perceived control to health and social support across adulthood and old age. Methods. We applied (multigroup) change score models to two waves of data collected 9 years apart from 6,210 participants of the Midlife in the United States survey (MIDUS, 24–75 years at baseline). We used composite measures of perceived control (personal mastery and constraints), health (chronic conditions, acute conditions, and functional limitations), and social support (support and strain associated with spouse/partner, family, and friends). Results. Analyses revealed evidence for direct and independent multidirectional accounts. Greater initial control predicted weaker declines in health and stronger increases in support. In turn, increases in control were predicted by better initial health and more support. Changes in control were also accompanied by concurrent changes in the other two domains, and relations involving control were larger in size than those between health and support. We found only small sociodemographic differences across age, gender, and education group. Discussion. We conclude that perceiving control may serve as both a precursor and an outcome of health and social support across the adult age range and suggest routes for further inquiry. PMID:21041231

  16. Loss of Function of Saccharomyces Cerevisiae Kinesin-Related Cin8 and Kip1 Is Suppressed by Kar3 Motor Domain Mutations

    PubMed Central

    Hoyt, M. A.; He, L.; Totis, L.; Saunders, W. S.

    1993-01-01

    The kinesin-related products of the CIN8 and KIP1 genes of Saccharomyces cerevisiae redundantly perform an essential function in mitosis. The action of either gene-product is required for an outwardly directed force that acts upon the spindle poles. We have selected mutations that suppress the temperature-sensitivity of a cin8-temperature-sensitive kip1-δ strain. The extragenic suppressors analyzed were all found to be alleles of the KAR3 gene. KAR3 encodes a distinct kinesin-related protein whose action antagonizes Cin8p/Kip1p function. All seven alleles analyzed were altered within the region of KAR3 that encodes the putative force-generating (or ``motor'') domain. These mutations also suppressed the inviability associated with the cin8-δ kip1-δ genotype, a property not shared by a deletion of KAR3. Other properties of the suppressing alleles revealed that they were not null for function. Six of the seven were unaffected for the essential karyogamy and meiosis properties of KAR3 and the seventh was dominant for the suppressing trait. Our findings suggest that despite an antagonistic relationship between Cin8p/Kip1p and Kar3p, aspects of their mitotic roles may be similar. PMID:8224825

  17. Technical Problem Solving among 10-Year-Old Students as Related to Science Achievement, Out-of-School Experience, Domain-Specific Control Beliefs, and Attribution Patterns.

    ERIC Educational Resources Information Center

    Baumert, Jurgen; Evans, Robert H.; Geiser, Helmut

    1998-01-01

    Ten-year-old students (n=531) from the U.S. and Germany were studied to determine the relationships between everyday experience, domain-specific control beliefs, acquisition of science knowledge, and solving of everyday technical problems. A causal model, developed and tested through structural equation modeling, showed that domain-specific…

  18. Verticillium Infection Triggers VASCULAR-RELATED NAC DOMAIN7–Dependent de Novo Xylem Formation and Enhances Drought Tolerance in Arabidopsis[W

    PubMed Central

    Reusche, Michael; Thole, Karin; Janz, Dennis; Truskina, Jekaterina; Rindfleisch, Sören; Drübert, Christine; Polle, Andrea; Lipka, Volker; Teichmann, Thomas

    2012-01-01

    The soilborne fungal plant pathogen Verticillium longisporum invades the roots of its Brassicaceae hosts and proliferates in the plant vascular system. Typical aboveground symptoms of Verticillium infection on Brassica napus and Arabidopsis thaliana are stunted growth, vein clearing, and leaf chloroses. Here, we provide evidence that vein clearing is caused by pathogen-induced transdifferentiation of chloroplast-containing bundle sheath cells to functional xylem elements. In addition, our findings suggest that reinitiation of cambial activity and transdifferentiation of xylem parenchyma cells results in xylem hyperplasia within the vasculature of Arabidopsis leaves, hypocotyls, and roots. The observed de novo xylem formation correlates with Verticillium-induced expression of the VASCULAR-RELATED NAC DOMAIN (VND) transcription factor gene VND7. Transgenic Arabidopsis plants expressing the chimeric repressor VND7-SRDX under control of a Verticillium infection-responsive promoter exhibit reduced de novo xylem formation. Interestingly, infected Arabidopsis wild-type plants show higher drought stress tolerance compared with noninfected plants, whereas this effect is attenuated by suppression of VND7 activity. Together, our results suggest that V. longisporum triggers a tissue-specific developmental plant program that compensates for compromised water transport and enhances the water storage capacity of infected Brassicaceae host plants. In conclusion, we provide evidence that this natural plant–fungus pathosystem has conditionally mutualistic features. PMID:23023171

  19. C1q-TNF-related protein-9, a novel cardioprotetcive cardiokine, requires proteolytic cleavage to generate a biologically active globular domain isoform.

    PubMed

    Yuan, Yuexing; Lau, Wayne Bond; Su, Hui; Sun, Yang; Yi, Wei; Du, Yunhui; Christopher, Theodore; Lopez, Bernard; Wang, Yajing; Ma, Xin-Liang

    2015-05-15

    Prevalence and severity of postmyocardial infarction heart failure continually escalate in type 2 diabetes via incompletely understood mechanisms. The discovery of the cardiac secretomes, collectively known as "cardiokines", has significantly enhanced appreciation of the local microenvironment's influence on disease development. Recent studies demonstrated that C1q-TNF-related protein-9 (CTRP9), a newly discovered adiponectin (APN) paralog, is highly expressed in the heart. However, its relationship with APN (concerning diabetic cardiovascular injury in particular) remains unknown. Plasma CTRP9 levels are elevated in APN knockout and reduced in diabetic mice. In contrast to APN, which circulates as full-length multimers, CTRP9 circulates in the plasma primarily in the globular domain isoform (gCTRP9). Recombinant full-length CTRP9 (fCTRP9) was cleaved when incubated with cardiac tissue extracts, generating gCTRP9, a process inhibited by protease inhibitor cocktail. gCTRP9 rapidly activates cardiac survival kinases, including AMPK, Akt, and endothelial NOS. However, fCTRP9-mediated kinase activation is much less potent and significantly delayed. Kinase activation by fCTRP9, but not gCTRP9, is inhibited by protease inhibitor cocktail. These results demonstrate for the first time that the novel cardiokine CTRP9 undergoes proteolytic cleavage to generate gCTRP9, the dominant circulatory and actively cardioprotective isoform. Enhancing cardiac CTRP9 production and/or its proteolytic posttranslational modification are of therapeutic potential, attenuating diabetic cardiac injury. PMID:25783894

  20. Development of a high capacity bubble domain memory element and related epitaxial garnet materials for application in spacecraft data recorders. Item 2: The optimization of material-device parameters for application in bubble domain memory elements for spacecraft data recorders

    NASA Technical Reports Server (NTRS)

    Besser, P. J.

    1976-01-01

    Bubble domain materials and devices are discussed. One of the materials development goals was a materials system suitable for operation of 16 micrometer period bubble domain devices at 150 kHz over the temperature range -10 C to +60 C. Several material compositions and hard bubble suppression techniques were characterized and the most promising candidates were evaluated in device structures. The technique of pulsed laser stroboscopic microscopy was used to characterize bubble dynamic properties and device performance at 150 kHz. Techniques for large area LPE film growth were developed as a separate task. Device studies included detector optimization, passive replicator design and test and on-chip bridge evaluation. As a technology demonstration an 8 chip memory cell was designed, tested and delivered. The memory elements used in the cell were 10 kilobit serial registers.

  1. Cloning, expression analysis, and RNA interference study of a HORMA domain containing autophagy-related gene 13 (ATG13) from the coleopteran beetle, Tenebrio molitor

    PubMed Central

    Lee, Jung Hee; Jo, Yong Hun; Patnaik, Bharat Bhusan; Park, Ki Beom; Tindwa, Hamisi; Seo, Gi Won; Chandrasekar, Raman; Lee, Yong Seok; Han, Yeon Soo

    2015-01-01

    Autophagy is a process that is necessary during starvation, as it replenishes metabolic precursors by eliminating damaged organelles. Autophagy is mediated by more than 35 autophagy-related (Atg) proteins that participate in the nucleation, elongation, and curving of the autophagosome membrane. In a pursuit to address the role of autophagy during development and immune resistance of the mealworm beetle, Tenebrio molitor, we screened ATG gene sequences from the whole-larva transcriptome database. We identified a homolog of ATG13 gene in T. molitor (designated as TmATG13) that comprises a cDNA of 1176 bp open reading frame (ORF) encoding a protein of 391 amino acids. Analyses of the structure-specific features of TmAtg13 showed an intrinsically disordered middle and C-terminal region that was rich in regulatory phosphorylation sites. The N-terminal Atg13 domain had a HORMA (Hop1, Rev7, and Mad2) fold containing amino acid residues conserved across the Atg13 insect orthologs. A quantitative reverse-transcription-polymerase chain reaction analysis revealed that TmATG13 was expressed ubiquitously during all developmental stages of the insect. TmATG13 mRNA expression was high in the fat body and gut of the larval and adult stages of the insect. The TmATG13 transcripts were expressed at a high level until 6 days of ovarian development, followed by a significant decline. Silencing of ATG13 transcripts in T. molitor larvae showed a reduced survivability of 39 and 38% in response to Escherichia coli and Staphylococcus aureus infection. Furthermore, the role of TmAtg13 in initiating autophagy as a part of the host cell autophagic complex of the host cells against the intracellular pathogen Listeria monocytogenes is currently under study and will be critical to unfold the structure-function relationships. PMID:26136688

  2. Cetacean distribution and abundance in relation to oceanographic domains on the eastern Bering Sea shelf, June and July of 2002, 2008, and 2010

    NASA Astrophysics Data System (ADS)

    Friday, Nancy A.; Zerbini, Alexandre N.; Waite, Janice M.; Moore, Sue E.; Clapham, Phillip J.

    2013-10-01

    As part of the Bering Sea Project, cetacean surveys were conducted to describe distribution and estimate abundance on the eastern Bering Sea shelf. Three marine mammal observers conducted visual surveys along transect lines sampled during the Alaska Fisheries Science Center walleye pollock assessment survey in June and July of 2008 and 2010. Distribution and abundance in 2008 and 2010 (cold years) are compared with results from a similar survey conducted in 2002 (a warm year), as the only three years that the entire survey area was sampled; patterns largely match those previously observed. Abundance estimates for comparable areas in 2002, 2008 and 2010 were as follows: humpback whales (Megaptera novaeangliae): 231 (CV=0.63), 436 (CV=0.45), and 675 (CV=0.80); fin whales (Balaenoptera physalus): 419 (CV=0.33), 1368 (CV=0.34), and 1061 (CV=0.38); minke whales (Balaenoptera acutorostrata): 389 (CV=0.52), 517 (CV=0.69), and 2020 (CV=0.73); Dall's porpoise (Phocoenoides dalli): 35,303 (CV=0.53), 14,543 (CV=0.32), and 11,143 (CV=0.32); and harbor porpoise (Phocoena phocoena): 1971 (CV=0.46), 4056 (CV=0.40), and 833 (CV=0.66). It should be noted that these abundance estimates are not corrected for biases due to perception, availability, or responsive movement. Estimates for humpback, fin and minke whales increased from 2002 to 2010, while those for harbor and Dall's porpoise decreased; trends were significant for fin whales. It is likely that changes in estimated abundance are due at least in part to shifts in distribution and not just changes in overall population size. Annual abundance estimates were examined by oceanographic domain. Humpback whales were consistently concentrated in coastal waters north of Unimak Pass. Fin whales were broadly distributed in the outer domain and slope in 2008 and 2010, but sightings were sparse in 2002. Minke whales were distributed throughout the study area in 2002 and 2008, but in 2010 they were concentrated in the outer domain and

  3. NON-CONFORMING FINITE ELEMENTS; MESH GENERATION, ADAPTIVITY AND RELATED ALGEBRAIC MULTIGRID AND DOMAIN DECOMPOSITION METHODS IN MASSIVELY PARALLEL COMPUTING ENVIRONMENT

    SciTech Connect

    Lazarov, R; Pasciak, J; Jones, J

    2002-02-01

    Construction, analysis and numerical testing of efficient solution techniques for solving elliptic PDEs that allow for parallel implementation have been the focus of the research. A number of discretization and solution methods for solving second order elliptic problems that include mortar and penalty approximations and domain decomposition methods for finite elements and finite volumes have been investigated and analyzed. Techniques for parallel domain decomposition algorithms in the framework of PETC and HYPRE have been studied and tested. Hierarchical parallel grid refinement and adaptive solution methods have been implemented and tested on various model problems. A parallel code implementing the mortar method with algebraically constructed multiplier spaces was developed.

  4. Self-Esteem Is Relatively Stable Late in Life: The Role of Resources in the Health, Self-Regulation, and Social Domains

    ERIC Educational Resources Information Center

    Wagner, Jenny; Hoppmann, Christiane; Ram, Nilam; Gerstorf, Denis

    2015-01-01

    A large body of research has documented changes in self-esteem across adulthood and individual-difference correlates thereof. However, little is known about whether people maintain their self-esteem until the end of life and what role key risk factors in the health, cognitive, self-regulatory, and social domains play. To examine these questions,…

  5. Convergence in the Domains of Static Spatial Relations and Events of Putting and Taking: Evidence from Bilingual Speakers of Romansh and German

    ERIC Educational Resources Information Center

    Berthele, Raphael

    2015-01-01

    In this article the way bilinguals handle differing semantic categories in their two languages will be investigated. Drawing on bilingual data from multilingual speakers of Romansh as well as from speakers of (Swiss) German, the tensions that emerge from "conflicting habits" in the two languages are analyzed in the semantic domain of…

  6. Do Nice Guys Really Finish Last? Exploring the Relations between Ethical Conduct, Motivation and Satisfaction among Undergraduates in the Domains of Academics and Athletics

    ERIC Educational Resources Information Center

    Yukhymenko, Mariya A.

    2012-01-01

    This study explored patterns of the ethical conduct of collegiate students in academic and athletic domains employing social cognitive theory (Bandura, 1986, 1997) using non-experimental, comparative and correlational designs. The study explored response patterns on anonymous surveys between varsity (N = 1151) and non-varsity (N = 227)…

  7. Relative stabilities of IgG1 and IgG4 Fab domains: Influence of the light–heavy interchain disulfide bond architecture

    PubMed Central

    Heads, James T; Adams, Ralph; D'Hooghe, Lena E; Page, Matt J T; Humphreys, David P; Popplewell, Andrew G; Lawson, Alastair D; Henry, Alistair J

    2012-01-01

    The stability of therapeutic antibodies is a prime pharmaceutical concern. In this work we examined thermal stability differences between human IgG1 and IgG4 Fab domains containing the same variable regions using the thermofluor assay. It was found that the IgG1 Fab domain is up to 11°C more stable than the IgG4 Fab domain containing the same variable region. We investigated the cause of this difference with the aim of developing a molecule with the enhanced stability of the IgG1 Fab and the biological properties of an IgG4 Fc. We found that replacing the seven residues, which differ between IgG1 CH1 and IgG4 CH1 domains, while retaining the native IgG1 light-heavy interchain disulfide (L–H) bond, did not affect thermal stability. Introducing the IgG1 type L–H interchain disulfide bond (DSB) into the IgG4 Fab resulted in an increase in thermal stability to levels observed in the IgG1 Fab with the same variable region. Conversely, replacement of the IgG1 L–H interchain DSB with the IgG4 type L–H interchain DSB reduced the thermal stability. We utilized the increased stability of the IgG1 Fab and designed a hybrid antibody with an IgG1 CH1 linked to an IgG4 Fc via an IgG1 hinge. This construct has the expected biophysical properties of both the IgG4 Fc and IgG1 Fab domains and may therefore be a pharmaceutically relevant format. PMID:22761163

  8. Analysis of multi-domain protein dynamics

    PubMed Central

    Roy, Amitava; Hua, Duy P; Post, Carol Beth

    2016-01-01

    Proteins with a modular architecture of multiple domains connected by linkers often exhibit diversity in the relative positions of domains while the domain tertiary structure remains unchanged. The biological function of these modular proteins, or the regulation of their activity depends on the variation in domain orientation and separation. Accordingly, careful characterization of inter-domain motion and correlated fluctuations of multi-domain systems is relevant for understanding the functional behavior of modular proteins. Molecular dynamics (MD) simulations provides a powerful approach to study these motions in atomic detail. Nevertheless, the common procedure for analyzing fluctuations from MD simulations after overall rigid-body alignment fails for multi-domain proteins; it greatly overestimates correlated positional fluctuations in the presence of relative domain motion. We show here that expressing the atomic motions of a multi-domain protein as a combination of displacement within the domain reference frame and motion of the relative domains correctly separates the internal motions to allow a useful description of correlated fluctuations. We illustrate the methodology of separating the domain fluctuations and local fluctuations by application to the tandem SH2 domains of human Syk protein kinase and by characterizing an effect of phosphorylation on the dynamics. Correlated motions are assessed from a distance covariance rather than the more common vector-coordinate covariance. The approach makes it possible to calculate the proper correlations in fluctuations internal to a domain as well as between domains. PMID:26675644

  9. Multifunctionalities driven by ferroic domains

    SciTech Connect

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

    2014-08-14

    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.

  10. Transcriptome analyses reveal protein and domain families that delineate stage-related development in the economically important parasitic nematodes, Ostertagia ostertagi and Cooperia oncophora

    PubMed Central

    2013-01-01

    Background Cooperia oncophora and Ostertagia ostertagi are among the most important gastrointestinal nematodes of cattle worldwide. The economic losses caused by these parasites are on the order of hundreds of millions of dollars per year. Conventional treatment of these parasites is through anthelmintic drugs; however, as resistance to anthelmintics increases, overall effectiveness has begun decreasing. New methods of control and alternative drug targets are necessary. In-depth analysis of transcriptomic data can help provide these targets. Results The assembly of 8.7 million and 11 million sequences from C. oncophora and O. ostertagi, respectively, resulted in 29,900 and 34,792 transcripts. Among these, 69% and 73% of the predicted peptides encoded by C. oncophora and O. ostertagi had homologues in other nematodes. Approximately 21% and 24% were constitutively expressed in both species, respectively; however, the numbers of transcripts that were stage specific were much smaller (~1% of the transcripts expressed in a stage). Approximately 21% of the transcripts in C. oncophora and 22% in O. ostertagi were up-regulated in a particular stage. Functional molecular signatures were detected for 46% and 35% of the transcripts in C. oncophora and O. ostertagi, respectively. More in-depth examinations of the most prevalent domains led to knowledge of gene expression changes between the free-living (egg, L1, L2 and L3 sheathed) and parasitic (L3 exsheathed, L4, and adult) stages. Domains previously implicated in growth and development such as chromo domains and the MADF domain tended to dominate in the free-living stages. In contrast, domains potentially involved in feeding such as the zinc finger and CAP domains dominated in the parasitic stages. Pathway analyses showed significant associations between life-cycle stages and peptides involved in energy metabolism in O. ostertagi whereas metabolism of cofactors and vitamins were specifically up-regulated in the parasitic

  11. The Ras suppressor Rsu-1 binds to the LIM 5 domain of the adaptor protein PINCH1 and participates in adhesion-related functions

    SciTech Connect

    Dougherty, Gerard W.; Chopp, Treasa; Qi Shengmei; Cutler, Mary Lou . E-mail: mcutler@usuhs.mil

    2005-05-15

    Rsu-1 is a highly conserved leucine rich repeat (LRR) protein that is expressed ubiquitously in mammalian cells. Rsu-1 was identified based on its ability to inhibit transformation by Ras, and previous studies demonstrated that ectopic expression of Rsu-1 inhibited anchorage-independent growth of Ras-transformed cells and human tumor cell lines. Using GAL4-based yeast two-hybrid screening, the LIM domain protein, PINCH1, was identified as the binding partner of Rsu-1. PINCH1 is an adaptor protein that localizes to focal adhesions and it has been implicated in the regulation of adhesion functions. Subdomain mapping in yeast revealed that Rsu-1 binds to the LIM 5 domain of PINCH1, a region not previously identified as a specific binding domain for any other protein. Additional testing demonstrated that PINCH2, which is highly homologous to PINCH1, except in the LIM 5 domain, does not interact with Rsu-1. Glutathione transferase fusion protein binding studies determined that the LRR region of Rsu-1 interacts with PINCH1. Transient expression studies using epitope-tagged Rsu-1 and PINCH1 revealed that Rsu-1 co-immunoprecipitated with PINCH1 and colocalized with vinculin at sites of focal adhesions in mammalian cells. In addition, endogenous P33 Rsu-1 from 293T cells co-immunoprecipitated with transiently expressed myc-tagged PINCH1. Furthermore, RNAi-induced reduction in Rsu-1 RNA and protein inhibited cell attachment, and while previous studies demonstrated that ectopic expression of Rsu-1 inhibited Jun kinase activation, the depletion of Rsu-1 resulted in activation of Jun and p38 stress kinases. These studies demonstrate that Rsu-1 interacts with PINCH1 in mammalian cells and functions, in part, by altering cell adhesion.

  12. Identification of a novel cell death-inducing domain reveals that fungal amyloid-controlled programmed cell death is related to necroptosis.

    PubMed

    Daskalov, Asen; Habenstein, Birgit; Sabaté, Raimon; Berbon, Mélanie; Martinez, Denis; Chaignepain, Stéphane; Coulary-Salin, Bénédicte; Hofmann, Kay; Loquet, Antoine; Saupe, Sven J

    2016-03-01

    Recent findings have revealed the role of prion-like mechanisms in the control of host defense and programmed cell death cascades. In fungi, HET-S, a cell death-inducing protein containing a HeLo pore-forming domain, is activated through amyloid templating by a Nod-like receptor (NLR). Here we characterize the HELLP protein behaving analogously to HET-S and bearing a new type of N-terminal cell death-inducing domain termed HeLo-like (HELL) and a C-terminal regulatory amyloid motif known as PP. The gene encoding HELLP is part of a three-gene cluster also encoding a lipase (SBP) and a Nod-like receptor, both of which display the PP motif. The PP motif is similar to the RHIM amyloid motif directing formation of the RIP1/RIP3 necrosome in humans. The C-terminal region of HELLP, HELLP(215-278), encompassing the motif, allows prion propagation and assembles into amyloid fibrils, as demonstrated by X-ray diffraction and FTIR analyses. Solid-state NMR studies reveal a well-ordered local structure of the amyloid core residues and a primary sequence that is almost entirely arranged in a rigid conformation, and confirm a β-sheet structure in an assigned stretch of three amino acids. HELLP is activated by amyloid templating and displays membrane-targeting and cell death-inducing activity. HELLP targets the SBP lipase to the membrane, suggesting a synergy between HELLP and SBP in membrane dismantling. Remarkably, the HeLo-like domain of HELLP is homologous to the pore-forming domain of MLKL, the cell death-execution protein in necroptosis, revealing a transkingdom evolutionary relationship between amyloid-controlled fungal programmed cell death and mammalian necroptosis. PMID:26903619

  13. Magnetic bubble domain memories

    NASA Technical Reports Server (NTRS)

    Ypma, J. E.

    1974-01-01

    Some attractive features of Bubble Domain Memory and its relation to existing technologies are discussed. Two promising applications are block access mass memory and tape recorder replacement. The required chip capabilities for these uses are listed, and the specifications for a block access mass memory designed to fit between core and HPT disk are presented. A feasibility model for a tape recorder replacement is introduced.

  14. The Putative “Switch 2” Domain of the Ras-related GTPase, Rab1B, Plays an Essential Role in the Interaction with Rab Escort Protein

    PubMed Central

    Overmeyer, Jean H.; Wilson, Amy L.; Erdman, Robert A.; Maltese, William A.

    1998-01-01

    Posttranslational modification of Rab proteins by geranylgeranyltransferase type II requires that they first bind to Rab escort protein (REP). Following prenylation, REP is postulated to accompany the modified GTPase to its specific target membrane. REP binds preferentially to Rab proteins that are in the GDP state, but the specific structural domains involved in this interaction have not been defined. In p21 Ras, the α2 helix of the Switch 2 domain undergoes a major conformational change upon GTP hydrolysis. Therefore, we hypothesized that the corresponding region in Rab1B might play a key role in the interaction with REP. Introduction of amino acid substitutions (I73N, Y78D, and A81D) into the putative α2 helix of Myc-tagged Rab1B prevented prenylation of the recombinant protein in cell-free assays, whereas mutations in the α3 and α4 helices did not. Additionally, upon transient expression in transfected HEK-293 cells, the Myc-Rab1B α2 helix mutants were not efficiently prenylated as determined by incorporation of [3H]mevalonate. Metabolic labeling studies using [32P]orthophosphate indicated that the poor prenylation of the Rab1B α2 helix mutants was not directly correlated with major disruptions in guanine nucleotide binding or intrinsic GTPase activity. Finally, gel filtration analysis of cytosolic fractions from 293 cells that were coexpressing T7 epitope-tagged REP with various Myc-Rab1B constructs revealed that mutations in the α2 helix of Rab1B prevented the association of nascent (i.e., nonprenylated) Rab1B with REP. These data indicate that the Switch 2 domain of Rab1B is a key structural determinant for REP interaction and that nucleotide-dependent conformational changes in this region are largely responsible for the selective interaction of REP with the GDP-bound form of the Rab substrate. PMID:9437002

  15. Supporting multiple domains in a single reuse repository

    NASA Technical Reports Server (NTRS)

    Eichmann, David

    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.

  16. 22 CFR 120.11 - Public domain.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Public domain. 120.11 Section 120.11 Foreign... Public domain. (a) Public domain means information which is published and which is generally accessible or available to the public: (1) Through sales at newsstands and bookstores; (2) Through...

  17. Mid-infrared pump-related electric-field domains in GaAs/(Al,Ga)As quantum-cascade structures for terahertz lasing without population inversion

    SciTech Connect

    Giehler, M.; Wienold, M.; Schrottke, L.; Hey, R.; Grahn, H. T.; Pavlov, S. G.; Huebers, H.-W.; Winnerl, S.; Schneider, H.

    2011-11-15

    We investigate the effect of mid-infrared (MIR) pumping on the transport properties of GaAs/(Al,Ga)As terahertz (THz) quantum lasers (TQLs), which rely on quantum coherence effects of intersubband transitions. Aiming at THz lasing at elevated temperatures, we extend the concept of THz gain with and without population inversion of a single, MIR-pumped, electrically driven THz stage proposed by Waldmueller et al.[Phys. Rev. Lett. 99, 117401 (2007)] to an entire TQL. However, experiments using a CO{sub 2} as well as a free-electron laser and numerical simulations show that this resonant MIR pumping causes a negative differential conductivity (NDC) in addition to the NDC caused by sequential tunneling. Lasing of these TQLs is prevented by the formation of electric-field domains below the resonance field strength for gain of each single THz stage.

  18. Identification of hormone-interacting amino acid residues within the steroid-binding domain of the glucocorticoid receptor in relation to other steroid hormone receptors

    SciTech Connect

    Carlstedt-Duke, J.; Stroemstedt, P.E.; Persson, B.; Cederlund, E.; Gustafsson, J.A.; Joernvall, H.

    1988-05-15

    Purified rat liver glucocorticoid receptor was covalently charged with (/sup 3/H)glucocorticoid by photoaffinity labeling (UV irradiation of (/sup 3/H)triamcinolone acetonide-glucocorticoid receptor) or affinity labeling (incubation with (/sup 3/H)dexamethasone mesylate). After labeling, separate samples of the denatured receptor were cleaved with trypsin (directly or after prior succinylation), chymotrypsin, and cyanogen bromide. Labeled residues in the peptides obtained were identified by radiosequence analysis. The peaks of radioactivity corresponded to Met-622 and Cys-754 after photoaffinity labeling with (/sup 3/H)triamcinolone acetonide and Cys-656 after affinity labeling with (/sup 3/H)dexamethasone mesylate. The labeled residues are all positioned within hydrophobic segments of the steroid-binding domain. The patterns of hydropathy and secondary structure for the glucocorticoid receptor are highly similar to those for the progestin receptor and similar but less so to those for the estrogen receptor and to those for c-erb A.

  19. Sensing the Coherence of Biology in Contrast to Psychology: Young Children’s Use of Causal Relations to Distinguish Two Foundational Domains

    PubMed Central

    Erickson, Jane E.; Keil, Frank C.; Lockhart, Kristi L.

    2011-01-01

    To what extent do children understand that biological processes fall into 1 coherent domain unified by distinct causal principles? In Experiments 1 and 2 (N = 125) kindergartners are given triads of biological and psychological processes and asked to identify which 2 members of the triad belong together. Results show that 5-year-olds correctly cluster biological processes and separate them from psychological ones. Experiments 3 and 4 (N = 64) examine whether or not children make this distinction because they understand that biological and psychological processes operate according to fundamentally different causal mechanisms. The results suggest that 5-year-olds do possess this understanding, and furthermore, they have intuitions about the nature of these different mechanisms. PMID:20331675

  20. Blocking Metabotropic Glutamate Receptor Subtype 7 (mGlu7) via the Venus Flytrap Domain (VFTD) Inhibits Amygdala Plasticity, Stress, and Anxiety-related Behavior♦

    PubMed Central

    Gee, Christine E.; Peterlik, Daniel; Neuhäuser, Christoph; Bouhelal, Rochdi; Kaupmann, Klemens; Laue, Grit; Uschold-Schmidt, Nicole; Feuerbach, Dominik; Zimmermann, Kaspar; Ofner, Silvio; Cryan, John F.; van der Putten, Herman; Fendt, Markus; Vranesic, Ivo; Glatthar, Ralf; Flor, Peter J.

    2014-01-01

    The metabotropic glutamate receptor subtype 7 (mGlu7) is an important presynaptic regulator of neurotransmission in the mammalian CNS. mGlu7 function has been linked to autism, drug abuse, anxiety, and depression. Despite this, it has been difficult to develop specific blockers of native mGlu7 signaling in relevant brain areas such as amygdala and limbic cortex. Here, we present the mGlu7-selective antagonist 7-hydroxy-3-(4-iodophenoxy)-4H-chromen-4-one (XAP044), which inhibits lateral amygdala long term potentiation (LTP) in brain slices from wild type mice with a half-maximal blockade at 88 nm. There was no effect of XAP044 on LTP of mGlu7-deficient mice, indicating that this pharmacological effect is mGlu7-dependent. Unexpectedly and in contrast to all previous mGlu7-selective drugs, XAP044 does not act via the seven-transmembrane region but rather via a binding pocket localized in mGlu7's extracellular Venus flytrap domain, a region generally known for orthosteric agonist binding. This was shown by chimeric receptor studies in recombinant cell line assays. XAP044 demonstrates good brain exposure and wide spectrum anti-stress and antidepressant- and anxiolytic-like efficacy in rodent behavioral paradigms. XAP044 reduces freezing during acquisition of Pavlovian fear and reduces innate anxiety, which is consistent with the phenotypes of mGlu7-deficient mice, the results of mGlu7 siRNA knockdown studies, and the inhibition of amygdala LTP by XAP044. Thus, we present an mGlu7 antagonist with a novel molecular mode of pharmacological action, providing significant application potential in psychiatry. Modeling the selective interaction between XAP044 and mGlu7's Venus flytrap domain, whose three-dimensional structure is already known, will facilitate future drug development supported by computer-assisted drug design. PMID:24596089

  1. Distinct phenotypes of new transmembrane-domain neuregulin 1 mutant mice and the rescue effects of valproate on the observed schizophrenia-related cognitive deficits

    PubMed Central

    Pei, Ju-Chun; Liu, Chih-Min; Lai, Wen-Sung

    2014-01-01

    Accumulating evidence suggests that neuregulin 1 (NRG1) might be involved in the neurodevelopment, neural plasticity, GABAergic neurotransmission, and pathogenesis of schizophrenia. NRG1 is abundantly expressed in the hippocampus, and emerging studies have begun to reveal the link between NRG1 signaling and cognitive deficits in schizophrenic patients. Because the transmembrane domain of NRG1 is vital for both forward and reverse signaling cascades, new Nrg1-deficient mice that carry a truncation of the transmembrane domain of the Nrg1 gene were characterized and used in this study to test a NRG1 loss-of-function hypothesis for schizophrenia. Both male and female Nrg1 heterozygous mutant mice and their wild-type littermates were used in a series of 4 experiments to characterize the impact of Nrg1 on behavioral phenotypes and to determine the importance of Nrg1 in the regulation of hippocampal neuromorphology and local GABAergic interneurons. First, a comprehensive battery of behavioral tasks indicated that male Nrg1-deficient mice exhibited significant impairments in cognitive functions. Second, pharmacological challenges were conducted and revealed that Nrg1 haploinsufficiency altered GABAergic activity in males. Third, although no genotype-specific neuromorphological alterations were found in the hippocampal CA1 pyramidal neurons, significant reductions in the hippocampal expressions of GAD67 and parvalbumin were revealed in the Nrg1-deficient males. Fourth, chronic treatment with valproate rescued the observed behavioral deficits and hippocampal GAD67 reduction in Nrg1-deficient males. Collectively, these results indicate the potential therapeutic effect of valproate and the importance of Nrg1 in the regulation of cognitive functions and hippocampal GABAergic interneurons, especially in males. PMID:24782733

  2. Health-Related Quality of Life Domains and Household Preparedness for Public Health Emergencies: Behavioral Risk Factor Surveillance System, 2006-2010

    PubMed Central

    Strine, Tara W.; Neff, Linda J.; Crawford, Sara

    2015-01-01

    Background This study examined the association between self-reported levels of household disaster preparedness and a range of physical and mental health quality of life outcomes. Methods Data collected from 14 states participating in a large state-based telephone survey were analyzed (n 5 104 654). Household disaster-preparedness items included having a 3-day supply of food, water, and prescription medications; a working battery-powered radio and flashlight; an evacuation plan; and a willingness to evacuate when instructed to do so. Quality-of-life items were categorized into 2 domains: physical health (general health, unhealthy physical days, and activity-limited days) and mental health (unhealthy mental days, social and emotional support, and life satisfaction). Results Persons with self-reported impaired mental health were generally less likely to report being prepared for a disaster than those who did not report impairment in each domain. Persons with low life satisfaction were among the least likely to be prepared, followed by those with inadequate social and emotional support, and then by those with frequent mental distress. Persons reporting physical impairments also reported deficits in many of the preparedness items. However, after adjusting for sociodemographic characteristics, some of the associations were attenuated and no longer significant Conclusion Persons reporting impaired quality of life are vulnerable to increased mental and physical distress during a disaster, and their vulnerability is compounded if they are ill-prepared. Therefore, persons reporting impaired quality of life should be included in the list of vulnerable populations that need disaster preparedness and response outreach. PMID:24618171

  3. 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.

  4. Indirect DNA Readout by an H-NS Related Protein: Structure of the DNA Complex of the C-Terminal Domain of Ler

    PubMed Central

    Cordeiro, Tiago N.; Schmidt, Holger; Madrid, Cristina; Juárez, Antonio; Bernadó, Pau; Griesinger, Christian; García, Jesús; Pons, Miquel

    2011-01-01

    Ler, a member of the H-NS protein family, is the master regulator of the LEE pathogenicity island in virulent Escherichia coli strains. Here, we determined the structure of a complex between the DNA-binding domain of Ler (CT-Ler) and a 15-mer DNA duplex. CT-Ler recognizes a preexisting structural pattern in the DNA minor groove formed by two consecutive regions which are narrower and wider, respectively, compared with standard B-DNA. The compressed region, associated with an AT-tract, is sensed by the side chain of Arg90, whose mutation abolishes the capacity of Ler to bind DNA. The expanded groove allows the approach of the loop in which Arg90 is located. This is the first report of an experimental structure of a DNA complex that includes a protein belonging to the H-NS family. The indirect readout mechanism not only explains the capacity of H-NS and other H-NS family members to modulate the expression of a large number of genes but also the origin of the specificity displayed by Ler. Our results point to a general mechanism by which horizontally acquired genes may be specifically recognized by members of the H-NS family. PMID:22114557

  5. The proliferation potential protein-related (P2P-R) gene with domains encoding heterogeneous nuclear ribonucleoprotein association and Rb1 binding shows repressed expression during terminal differentiation.

    PubMed

    Witte, M M; Scott, R E

    1997-02-18

    Terminal differentiation is associated with repression in the expression of the proliferation potential proteins (P2P) subset of heterogeneous nuclear ribonucleoprotein (hnRNP) proteins. We report here the cloning and characterization of a 5173-bp P2P-related (P2P-R) cDNA that contains a 4214-bp open reading frame. Probes to this cDNA detect a single 8-kb mRNA in multiple murine tissues and in proliferating 3T3T cells, but not in terminally differentiated 3T3T adipocytes. Evidence that this cDNA can encode peptides with domains for hnRNP association was established by showing that such peptides are recognized by two monoclonal antibodies known to detect core hnRNP proteins, and by showing that the C130 monoclonal antibody, produced against a cDNA-derived fusion protein, also selectively detects native P2P hnRNP proteins. In addition, P2P-R cDNA-derived fusion proteins bind single-stranded nucleic acids, and a P2P-R cDNA-derived antisense oligonucleotide selectively represses P2P expression. Because terminal differentiation is associated with modulation in Rb1 function, we assayed if products of this cDNA might interact with Rb1. Evidence that the P2P-R cDNA encodes a protein domain that binds Rb1 was established using a glutathione S-transferase fusion protein to selectively precipitate Rb1 from cellular extracts. Data also show that this binding is reduced by competition with the adenovirus E1a protein, indicating that binding occurs through the "pocket" domain of Rb1. These results establish that the P2P-R cDNA encodes protein domains involved in both hnRNP association and Rb1 binding and complement recent reports that localize Rb1 to sites of RNA processing in the nucleus. PMID:9037032

  6. High Affinity Binding of the Receptor-associated Protein D1D2 Domains with the Low Density Lipoprotein Receptor-related Protein (LRP1) Involves Bivalent Complex Formation: CRITICAL ROLES OF LYSINES 60 AND 191.

    PubMed

    Prasad, Joni M; Young, Patricia A; Strickland, Dudley K

    2016-08-26

    The LDL receptor-related protein 1 (LRP1) is a large endocytic receptor that binds and mediates the endocytosis of numerous structurally diverse ligands. Currently, the basis for ligand recognition by LRP1 is not well understood. LRP1 requires a molecular chaperone, termed the receptor-associated protein (RAP), to escort the newly synthesized receptor from the endoplasmic reticulum to the Golgi. RAP is a three-domain protein that contains the following two high affinity binding sites for LRP1: one is located within domains 1 and 2, and one is located in its third domain. Studies on the interaction of the RAP third domain with LRP1 reveal critical contributions by lysine 256 and lysine 270 for this interaction. From these studies, a model for ligand recognition by this class of receptors has been proposed. Here, we employed surface plasmon resonance to investigate the binding of RAP D1D2 to LRP1. Our results reveal that the high affinity of D1D2 for LRP1 results from avidity effects mediated by the simultaneous interactions of lysine 60 in D1 and lysine 191 in D2 with sites on LRP1 to form a bivalent D1D2-LRP1 complex. When lysine 60 and 191 are both mutated to alanine, the binding of D1D2 to LRP1 is ablated. Our data also reveal that D1D2 is able to bind to a second distinct site on LRP1 to form a monovalent complex. The studies confirm the canonical model for ligand recognition by this class of receptors, which is initiated by pairs of lysine residues that dock into acidic pockets on the receptor. PMID:27402839

  7. On Probability Domains III

    NASA Astrophysics Data System (ADS)

    Frič, Roman; Papčo, Martin

    2015-12-01

    Domains of generalized probability have been introduced in order to provide a general construction of random events, observables and states. It is based on the notion of a cogenerator and the properties of product. We continue our previous study and show how some other quantum structures fit our categorical approach. We discuss how various epireflections implicitly used in the classical probability theory are related to the transition to fuzzy probability theory and describe the latter probability theory as a genuine categorical extension of the former. We show that the IF-probability can be studied via the fuzzy probability theory. We outline a "tensor modification" of the fuzzy probability theory.

  8. Characterization of lipid domains in erythrocyte membranes.

    PubMed Central

    Rodgers, W; Glaser, M

    1991-01-01

    Fluorescence digital imaging microscopy was used to study the lateral distribution of the lipid components in erythrocyte membranes. Intact erythrocytes labeled with phospholipids containing a fluorophore attached to one fatty acid chain showed an uneven distribution of the phospholipids in the membrane thereby demonstrating the presence of membrane domains. The enrichment of the lipotropic compound chlor-promazine in domains in intact erythrocytes also suggested that the domains are lipid-enriched regions. Similar membrane domains were present in erythrocyte ghosts. The phospholipid enrichment was increased in the domains by inducing membrane protein aggregation. Double-labeling experiments were done to determine the relative distributions of different phospholipids in the membrane. Vesicles made from extracted lipids did not show the presence of domains consistent with the conclusion that membrane proteins were responsible for creating the domains. Overall, it was found that large domains exist in the red blood cell membrane with unequal enrichment of the different phospholipid species. Images PMID:1996337

  9. The leucine twenty homeobox (LEUTX) gene, which lacks a histone acetyltransferase domain, is fused to KAT6A in therapy-related acute myeloid leukemia with t(8;19)(p11;q13).

    PubMed

    Chinen, Yoshiaki; Taki, Tomohiko; Tsutsumi, Yasuhiko; Kobayashi, Satoru; Matsumoto, Yosuke; Sakamoto, Natsumi; Kuroda, Junya; Horiike, Shigeo; Nishida, Kazuhiro; Ohno, Hirofumi; Uike, Naokuni; Taniwaki, Masafumi

    2014-04-01

    The monocytic leukemia zinc finger protein KAT6A (formerly MOZ) gene is recurrently rearranged by chromosomal translocations in acute myeloid leukemia (AML). KAT6A is known to be fused to several genes, all of which have histone acetyltransferase (HAT) activity and interact with a number of transcription factors as a transcriptional coactivator. The present study shows that the leucine twenty homeobox (LEUTX) gene on 19q13 is fused to the KAT6A gene on 8p11 in a therapy-related AML with t(8;19)(p11;q13) using the cDNA bubble PCR method. The fusion transcripts contained 83 nucleotides upstream of the first ATG of LEUTX and are presumed to create in-frame fusion proteins. LEUTX is known to have a homeobox domain. Expression of the LEUTX gene was only detected in placenta RNA by RT-PCR, but not in any tissues by Northern blot analysis. The putative LEUTX protein does not contain any HAT domain, and this is the first study to report that KAT6A can fuse to the homeobox gene. The current study, with identification of a new partner gene to KAT6A in a therapy-related AML, does not elucidate the mechanisms of leukemogenesis in KAT6A-related AML but describes a new gene with a different putative function. PMID:24446090

  10. Inhibition of Ca(2+) signalling by p130, a phospholipase-C-related catalytically inactive protein: critical role of the p130 pleckstrin homology domain.

    PubMed Central

    Takeuchi, H; Oike, M; Paterson, H F; Allen, V; Kanematsu, T; Ito, Y; Erneux, C; Katan, M; Hirata, M

    2000-01-01

    p130 was originally identified as an Ins(1,4,5)P(3)-binding protein similar to phospholipase C-delta but lacking any phospholipase activity. In the present study we have further analysed the interactions of p130 with inositol compounds in vitro. To determine which of the potential ligands interacts with p130 in cells, we performed an analysis of the cellular localization of this protein, the isolation of a protein-ligand complex from cell lysates and studied the effects of p130 on Ins(1,4,5)P(3)-mediated Ca(2+) signalling by using permeabilized and transiently or stably transfected COS-1 cells (COS-1(p130)). In vitro, p130 bound Ins(1,4,5)P(3) with a higher affinity than that for phosphoinositides. When the protein was isolated from COS-1(p130) cells by immunoprecipitation, it was found to be associated with Ins(1,4,5)P(3). Localization studies demonstrated the presence of the full-length p130 in the cytoplasm of living cells, not at the plasma membrane. In cell-based assays, p130 had an inhibitory effect on Ca(2+) signalling. When fura-2-loaded COS-1(p130) cells were stimulated with bradykinin, epidermal growth factor or ATP, it was found that the agonist-induced increase in free Ca(2+) concentration, observed in control cells, was inhibited in COS-1(p130). This inhibition was not accompanied by the decreased production of Ins(1,4,5)P(3); the intact p130 pleckstrin homology domain, known to be the ligand-binding site in vitro, was required for this effect in cells. These results suggest that Ins(1,4,5)P(3) could be the main p130 ligand in cells and that this binding has the potential to inhibit Ins(1,4,5)P(3)-mediated Ca(2+) signalling. PMID:10861248

  11. Analyses of disease-related GNPTAB mutations define a novel GlcNAc-1-phosphotransferase interaction domain and an alternative site-1 protease cleavage site

    PubMed Central

    Velho, Renata Voltolini; De Pace, Raffaella; Klünder, Sarah; Sperb-Ludwig, Fernanda; Lourenço, Charles Marques; Schwartz, Ida V. D.; Braulke, Thomas; Pohl, Sandra

    2015-01-01

    Mucolipidosis II (MLII) and III alpha/beta are autosomal-recessive diseases of childhood caused by mutations in GNPTAB encoding the α/β-subunit precursor protein of the GlcNAc-1-phosphotransferase complex. This enzyme modifies lysosomal hydrolases with mannose 6-phosphate targeting signals. Upon arrival in the Golgi apparatus, the newly synthesized α/β-subunit precursor is catalytically activated by site-1 protease (S1P). Here we performed comprehensive expression studies of GNPTAB mutations, including two novel mutations T644M and T1223del, identified in Brazilian MLII/MLIII alpha/beta patients. We show that the frameshift E757KfsX1 and the non-sense R587X mutations result in the retention of enzymatically inactive truncated precursor proteins in the endoplasmic reticulum (ER) due to loss of cytosolic ER exit motifs consistent with a severe clinical phenotype in homozygosity. The luminal missense mutations, C505Y, G575R and T644M, partially impaired ER exit and proteolytic activation in accordance with less severe MLIII alpha/beta disease symptoms. Analogous to the previously characterized S399F mutant, we found that the missense mutation I403T led to retention in the ER and loss of catalytic activity. Substitution of further conserved residues in stealth domain 2 (I346 and W357) revealed similar biochemical properties and allowed us to define a putative binding site for accessory proteins required for ER exit of α/β-subunit precursors. Interestingly, the analysis of the Y937_M972del mutant revealed partial Golgi localization and formation of abnormal inactive β-subunits generated by S1P which correlate with a clinical MLII phenotype. Expression analyses of mutations identified in patients underline genotype–phenotype correlations in MLII/MLIII alpha/beta and provide novel insights into structural requirements of proper GlcNAc-1-phosphotransferase activity. PMID:25788519

  12. The Temporal Context Model in Spatial Navigation and Relational Learning: Toward a Common Explanation of Medial Temporal Lobe Function Across Domains

    ERIC Educational Resources Information Center

    Howard, Marc W.; Fotedar, Mrigankka S.; Datey, Aditya V.; Hasselmo, Michael E.

    2005-01-01

    The medial temporal lobe (MTL) has been studied extensively at all levels of analysis, yet its function remains unclear. Theory regarding the cognitive function of the MTL has centered along 3 themes. Different authors have emphasized the role of the MTL in episodic recall, spatial navigation, or relational memory. Starting with the temporal…

  13. Structural and Semiotic Diversity in the Didactic Transition from the Natural-Number Domain to the Integers: A Study of Understanding in the Field of Additive Relativity

    ERIC Educational Resources Information Center

    Gonzalez-Mari, Jose Luis; Rico, Luis; Gallardo, Jesus

    2009-01-01

    Introduction: In the present-day didactic process of transition from natural numbers to integers, a certain kind of measure is involved which is neither easy nor appropriate to integrate into the familiar numerical systems. We refer to measures and comparisons for which we need a third numerical system--what we will call "relative natural"…

  14. Domain walls riding the wave.

    SciTech Connect

    Karapetrov, G.; Novosad, V.; Materials Science Division

    2010-11-01

    the preferred method, as it combines manipulation and readout of the domain-wall state. The electrons that take part in the process of readout and manipulation of the domain-wall structure in the nanowire do so through the so-called spin transfer torque: When spin-polarized electrons in the ferromagnet nanowire pass through the domain wall they experience a nonuniform magnetization, and they try to align their spins with the local magnetic moments. The force that the electrons experience has a reaction force counterpart that 'pushes' the local magnetic moments, resulting in movement of the domain wall in the direction of the electron flow through the spin-transfer torque. The forces between the electrons and the local magnetic moments in the ferromagnet also create additional electrical resistance for the electrons passing through the domain wall. By measuring resistance across a segment of the nanowire, one determines if a domain wall is present; i.e., one can read the stored information. The interaction of the spin-polarized electrons with the domain wall in the ferromagnetic nanowire is not very efficient. Even for materials achieving high polarization of the free electrons, it is very difficult to move the magnetic domain wall. Several factors contribute to this problem, with imperfections of the ferromagnetic nanowire that cause domain-wall pinning being the dominant one. Permalloy nanowires, one of the best candidates for domain-wall-based memory and logic devices, require current densities of the order of 10{sup 8} A/cm{sup 2} in order to move a domain wall from a pinning well. Considering that this current has to pass through a relatively long wire, it is not very difficult to imagine that most of the energy will go to Joule heating. The efficiency of the process - the ratio of the energy converted to domain-wall motion to the total energy consumed - is comparable to that of an incandescent light bulb converting electricity to light. A step towards more

  15. The Temporal Context Model in spatial navigation and relational learning: Toward a common explanation of medial temporal lobe function across domains

    PubMed Central

    Howard, Marc W.; Fotedar, Mrigankka S.; Datey, Aditya V.; Hasselmo, Michael E.

    2005-01-01

    The medial temporal lobe (MTL) has been studied extensively at all levels of analysis, yet its function remains unclear. Theory regarding the cognitive function of the MTL has centered along 3 themes. Different authors have emphasized the role of the MTL in episodic recall, spatial navigation, or relational memory. Starting with the temporal context model (M. W. Howard and M. J. Kahana, 2002), a distributed memory model that has been applied to benchmark data from episodic recall tasks, the authors propose that the entorhinal cortex supports a gradually changing representation of temporal context and the hippocampus proper enables retrieval of these contextual states. Simulation studies show this hypothesis explains the firing of place cells in the entorhinal cortex and the behavioral effects of hippocampal lesion in relational memory tasks. These results constitute a first step towards a unified computational theory of MTL function that integrates neurophysiological, neuropsychological and cognitive findings. PMID:15631589

  16. Patterns of depressive symptoms and social relating behaviors differ over time from other behavioral domains for young people with Down syndrome.

    PubMed

    Foley, Kitty-Rose; Bourke, Jenny; Einfeld, Stewart L; Tonge, Bruce J; Jacoby, Peter; Leonard, Helen

    2015-05-01

    People with intellectual disabilities are at a higher risk for experiencing behavioral, emotional, and psychiatric problems in comparison with the general population. People with Down syndrome have been reported as experiencing fewer behavioral problems than others with intellectual disability, although still at a greater level than the non-intellectually disabled population, except for depression and Alzheimer disease. The aim of this study was to describe the trajectories of subscales of behavior, including depressive symptoms, communication disturbance, anxiety, disruptiveness, and social relating abilities, for young adults with Down syndrome.Families of young adults with Down syndrome living in Perth, Western Australia, participated in a questionnaire study over 8 years, 2004 (n = 255), 2009 (n = 191), and 2011 (n = 188). Questionnaires collected information about young person characteristics and family functioning. The parent-completed Developmental Behavior Checklist-Adult (DBC-A) and Developmental Behavior Checklist-Primary Carer Version (DBC-P) were used to measure emotional and behavioral problems. These measures include the following subscales: disruptive, communication and anxiety disturbances, self-absorbed, antisocial, depressive, and social relating.DBC score declined from 2004 to 2011 reflecting an improvement in behavior in the self-absorbed (coeff -0.011, 95% confidence interval (CI) -0.031, -0.008), anxiety (coef -0.009 95%CI -0.129, -0.006), communication disturbances (coeff -0.008, 95% CI -0.012, -0.005) and disruptive/antisocial behavior (coeff -0.013, 95% CI -0.016, -0.009) subscales. Subscales for depressive symptoms and social relating problems decreased less (coeff -0.003, 95% CI -0.007, -0.0001) (coeff -0.003 95% CI -0.007, 0.001). Young people who were lower functioning were reported as exhibiting significantly more behavioral problems across every subscale when compared with those who were higher functioning.Behavior of

  17. Crystallization of the receptor-binding domain of parathyroid hormone-related protein in complex with a neutralizing monoclonal antibody Fab fragment

    SciTech Connect

    McKinstry, William J.; Polekhina, Galina; Diefenbach-Jagger, Hannelore; Sato, Koh; Onuma, Etsuro; Gillespie, Matthew T.; Martin, Thomas J.; Parker, Michael W.

    2009-04-01

    Parathyroid hormone-related protein (PTHrP) plays an important role in regulating embryonic skeletal development and is abnormally regulated in the pathogenesis of skeletal complications observed with many cancers and osteoporosis. It exerts its action through binding to a G-protein-coupled seven-transmembrane cell-surface receptor (GPCR). Structurally, GPCRs are very difficult to study by X-ray crystallography. In this study, a monoclonal antibody Fab fragment which recognizes the same region of PTHrP as its receptor, PTH1R, was used to aid in the crystallization of PTHrP. The resultant protein complex was crystallized using the hanging-drop vapour-diffusion method with polyethylene glycol as a precipitant. The crystals belonged to the orthorhombic space group P2{sub 1}2{sub 1}2, with unit-cell parameters a = 72.6, b = 96.3, c = 88.5 {angstrom}, and diffracted to 2.0 {angstrom} resolution using synchrotron radiation. The crystal structure will shed light on the nature of the key residues of PTHrP that interact with the antibody and will provide insights into how the antibody is able to discriminate between PTHrP and the related molecule parathyroid homone.

  18. The La-related protein 1-specific domain repurposes HEAT-like repeats to directly bind a 5′TOP sequence

    PubMed Central

    Lahr, Roni M.; Mack, Seshat M.; Héroux, Annie; Blagden, Sarah P.; Bousquet-Antonelli, Cécile; Deragon, Jean-Marc; Berman, Andrea J.

    2015-01-01

    La-related protein 1 (LARP1) regulates the stability of many mRNAs. These include 5′TOPs, mTOR-kinase responsive mRNAs with pyrimidine-rich 5′ UTRs, which encode ribosomal proteins and translation factors. We determined that the highly conserved LARP1-specific C-terminal DM15 region of human LARP1 directly binds a 5′TOP sequence. The crystal structure of this DM15 region refined to 1.86 Å resolution has three structurally related and evolutionarily conserved helix-turn-helix modules within each monomer. These motifs resemble HEAT repeats, ubiquitous helical protein-binding structures, but their sequences are inconsistent with consensus sequences of known HEAT modules, suggesting this structure has been repurposed for RNA interactions. A putative mTORC1-recognition sequence sits within a flexible loop C-terminal to these repeats. We also present modelling of pyrimidine-rich single-stranded RNA onto the highly conserved surface of the DM15 region. These studies lay the foundation necessary for proceeding toward a structural mechanism by which LARP1 links mTOR signalling to ribosome biogenesis. PMID:26206669

  19. Large-scale brain networks in board game experts: insights from a domain-related task and task-free resting state.

    PubMed

    Duan, Xujun; Liao, Wei; Liang, Dongmei; Qiu, Lihua; Gao, Qing; Liu, Chengyi; Gong, Qiyong; Chen, Huafu

    2012-01-01

    Cognitive performance relies on the coordination of large-scale networks of brain regions that are not only temporally correlated during different tasks, but also networks that show highly correlated spontaneous activity during a task-free state. Both task-related and task-free network activity has been associated with individual differences in cognitive performance. Therefore, we aimed to examine the influence of cognitive expertise on four networks associated with cognitive task performance: the default mode network (DMN) and three other cognitive networks (central-executive network, dorsal attention network, and salience network). During fMRI scanning, fifteen grandmaster and master level Chinese chess players (GM/M) and fifteen novice players carried out a Chinese chess task and a task-free resting state. Modulations of network activity during task were assessed, as well as resting-state functional connectivity of those networks. Relative to novices, GM/Ms showed a broader task-induced deactivation of DMN in the chess problem-solving task, and intrinsic functional connectivity of DMN was increased with a connectivity pattern associated with the caudate nucleus in GM/Ms. The three other cognitive networks did not exhibit any difference in task-evoked activation or intrinsic functional connectivity between the two groups. These findings demonstrate the effect of long-term learning and practice in cognitive expertise on large-scale brain networks, suggesting the important role of DMN deactivation in expert performance and enhanced functional integration of spontaneous activity within widely distributed DMN-caudate circuitry, which might better support high-level cognitive control of behavior. PMID:22427852

  20. Relativity

    NASA Astrophysics Data System (ADS)

    Stephani, Hans

    2004-02-01

    Preface; Notation; Part I. Special Relativity: 1. Introduction: inertial systems and Galilei invariance of classical mechanics; 2. Light propagation in moving coordinate systems and Lorentz transformations; 3. Our world as a Minkowski space; 4. Mechanics of special relativity; 5. Optics of plane waves; 6. Four-dimensional vectors and tensors; 7. Electrodynamics in vacuo; 8. Transformation properties of electromagnetic fields: examples; 9. Null vectors and the algebraic properties of electromagnetic field tensors; 10. Charged point particles and their field; 11. Pole-dipole particles and their field; 12. Electrodynamics in media; 13. Perfect fluids and other physical theories; Part II. Riemannian Geometry: 14. Introduction: the force-free motion of particles in Newtonian mechanics; 15. Why Riemannian geometry?; 16. Riemannian space; 17. Tensor algebra; 18. The covariant derivative and parallel transport; 19. The curvature tensor; 20. Differential operators, integrals and integral laws; 21. Fundamental laws of physics in Riemannian spaces; Part III. Foundations of Einstein's Theory of Gravitation: 22. The fundamental equations of Einstein's theory of gravitation; 23. The Schwarzschild solution; 24. Experiments to verify the Schwarzschild metric; 25. Gravitational lenses; 26. The interior Schwarzschild solution; Part IV. Linearized Theory of Gravitation, Far Fields and Gravitational Waves: 27. The linearized Einstein theory of gravity; 28. Far fields due to arbitrary matter distributions and balance equations for momentum and angular momentum; 29. Gravitational waves; 30. The Cauchy problem for the Einstein field equations; Part V. Invariant Characterization of Exact Solutions: 31. Preferred vector fields and their properties; 32. The Petrov classification; 33. Killing vectors and groups of motion; 34. A survey of some selected classes of exact solutions; Part VI. Gravitational Collapse and Black Holes: 35. The Schwarzschild singularity; 36. Gravitational collapse

  1. 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

  2. Reporting Valid and Reliable Overall Scores and Domain Scores

    ERIC Educational Resources Information Center

    Yao, Lihua

    2010-01-01

    In educational assessment, overall scores obtained by simply averaging a number of domain scores are sometimes reported. However, simply averaging the domain scores ignores the fact that different domains have different score points, that scores from those domains are related, and that at different score points the relationship between overall…

  3. C2-Domain Abscisic Acid-Related Proteins Mediate the Interaction of PYR/PYL/RCAR Abscisic Acid Receptors with the Plasma Membrane and Regulate Abscisic Acid Sensitivity in Arabidopsis[C][W

    PubMed Central

    Rodriguez, Lesia; Diaz, Maira; Rodrigues, Americo; Izquierdo-Garcia, Ana C.; Peirats-Llobet, Marta; Fernandez, Maria A.; Antoni, Regina; Fernandez, Daniel; Marquez, Jose A.; Mulet, Jose M.; Albert, Armando; Rodriguez, Pedro L.

    2014-01-01

    Membrane-delimited abscisic acid (ABA) signal transduction plays a critical role in early ABA signaling, but the molecular mechanisms linking core signaling components to the plasma membrane are unclear. We show that transient calcium-dependent interactions of PYR/PYL ABA receptors with membranes are mediated through a 10-member family of C2-domain ABA-related (CAR) proteins in Arabidopsis thaliana. Specifically, we found that PYL4 interacted in an ABA-independent manner with CAR1 in both the plasma membrane and nucleus of plant cells. CAR1 belongs to a plant-specific gene family encoding CAR1 to CAR10 proteins, and bimolecular fluorescence complementation and coimmunoprecipitation assays showed that PYL4-CAR1 as well as other PYR/PYL-CAR pairs interacted in plant cells. The crystal structure of CAR4 was solved, which revealed that, in addition to a classical calcium-dependent lipid binding C2 domain, a specific CAR signature is likely responsible for the interaction with PYR/PYL receptors and their recruitment to phospholipid vesicles. This interaction is relevant for PYR/PYL function and ABA signaling, since different car triple mutants affected in CAR1, CAR4, CAR5, and CAR9 genes showed reduced sensitivity to ABA in seedling establishment and root growth assays. In summary, we identified PYR/PYL-interacting partners that mediate a transient Ca2+-dependent interaction with phospholipid vesicles, which affects PYR/PYL subcellular localization and positively regulates ABA signaling. PMID:25465408

  4. C2-domain abscisic acid-related proteins mediate the interaction of PYR/PYL/RCAR abscisic acid receptors with the plasma membrane and regulate abscisic acid sensitivity in Arabidopsis.

    PubMed

    Rodriguez, Lesia; Gonzalez-Guzman, Miguel; Diaz, Maira; Rodrigues, Americo; Izquierdo-Garcia, Ana C; Peirats-Llobet, Marta; Fernandez, Maria A; Antoni, Regina; Fernandez, Daniel; Marquez, Jose A; Mulet, Jose M; Albert, Armando; Rodriguez, Pedro L

    2014-12-01

    Membrane-delimited abscisic acid (ABA) signal transduction plays a critical role in early ABA signaling, but the molecular mechanisms linking core signaling components to the plasma membrane are unclear. We show that transient calcium-dependent interactions of PYR/PYL ABA receptors with membranes are mediated through a 10-member family of C2-domain ABA-related (CAR) proteins in Arabidopsis thaliana. Specifically, we found that PYL4 interacted in an ABA-independent manner with CAR1 in both the plasma membrane and nucleus of plant cells. CAR1 belongs to a plant-specific gene family encoding CAR1 to CAR10 proteins, and bimolecular fluorescence complementation and coimmunoprecipitation assays showed that PYL4-CAR1 as well as other PYR/PYL-CAR pairs interacted in plant cells. The crystal structure of CAR4 was solved, which revealed that, in addition to a classical calcium-dependent lipid binding C2 domain, a specific CAR signature is likely responsible for the interaction with PYR/PYL receptors and their recruitment to phospholipid vesicles. This interaction is relevant for PYR/PYL function and ABA signaling, since different car triple mutants affected in CAR1, CAR4, CAR5, and CAR9 genes showed reduced sensitivity to ABA in seedling establishment and root growth assays. In summary, we identified PYR/PYL-interacting partners that mediate a transient Ca(2+)-dependent interaction with phospholipid vesicles, which affects PYR/PYL subcellular localization and positively regulates ABA signaling. PMID:25465408

  5. Oral health related quality of life in pregnant and post partum women in two social network domains; predominantly home-based and work-based networks

    PubMed Central

    2012-01-01

    Background Individuals connected to supportive social networks have better general and oral health quality of life. The objective of this study was to assess whether there were differences in oral health related quality of life (OHRQoL) between women connected to either predominantly home-based and work-based social networks. Methods A follow-up prevalence study was conducted on 1403 pregnant and post-partum women (mean age of 25.2 ± 6.3 years) living in two cities in the State of Rio de Janeiro, Brazil. Women were participants in an established cohort followed from pregnancy (baseline) to post-partum period (follow-up). All participants were allocated to two groups; 1. work-based social network group - employed women with paid work, and, 2. home-based social network group - women with no paid work, housewives or unemployed women. Measures of social support and social network were used as well as questions on sociodemographic characteristics and OHRQoL and health related behaviors. Multinomial logistic regression was performed to obtain OR of relationships between occupational contexts, affectionate support and positive social interaction on the one hand, and oral health quality of life, using the Oral Health Impacts Profile (OHIP) measure, adjusted for age, ethnicity, family income, schooling, marital status and social class. Results There was a modifying effect of positive social interaction on the odds of occupational context on OHRQoL. The odds of having a poorer OHIP score, ≥4, was significantly higher for women with home-based social networks and moderate levels of positive social interactions [OR 1.64 (95% CI: 1.08-2.48)], and for women with home-based social networks and low levels of positive social interactions [OR 2.15 (95% CI: 1.40-3.30)] compared with women with work-based social networks and high levels of positive social interactions. Black ethnicity was associated with OHIP scores ≥4 [OR 1.73 (95% CI: 1.23-2.42)]. Conclusions Pregnant and post

  6. 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

  7. Enhanced protein domain discovery using taxonomy

    PubMed Central

    Coin, Lachlan; Bateman, Alex; Durbin, Richard

    2004-01-01

    Background It is well known that different species have different protein domain repertoires, and indeed that some protein domains are kingdom specific. This information has not yet been incorporated into statistical methods for finding domains in sequences of amino acids. Results We show that by incorporating our understanding of the taxonomic distribution of specific protein domains, we can enhance domain recognition in protein sequences. We identify 4447 new instances of Pfam domains in the SP-TREMBL database using this technique, equivalent to the coverage increase given by the last 8.3% of Pfam families and to a 0.7% increase in the number of domain predictions. We use PSI-BLAST to cross-validate our new predictions. We also benchmark our approach using a SCOP test set of proteins of known structure, and demonstrate improvements relative to standard Hidden Markov model techniques. Conclusions Explicitly including knowledge about the taxonomic distribution of protein domains can enhance protein domain recognition. Our method can also incorporate other context-specific domain distributions – such as domain co-occurrence and protein localisation. PMID:15137915

  8. Functional domain walls in multiferroics

    NASA Astrophysics Data System (ADS)

    Meier, Dennis

    2015-11-01

    During the last decade a wide variety of novel and fascinating correlation phenomena has been discovered at domain walls in multiferroic bulk systems, ranging from unusual electronic conductance to inseparably entangled spin and charge degrees of freedom. The domain walls represent quasi-2D functional objects that can be induced, positioned, and erased on demand, bearing considerable technological potential for future nanoelectronics. Most of the challenges that remain to be solved before turning related device paradigms into reality, however, still fall in the field of fundamental condensed matter physics and materials science. In this topical review seminal experimental findings gained on electric and magnetic domain walls in multiferroic bulk materials are addressed. A special focus is put on the physical properties that emerge at so-called charged domain walls and the added functionality that arises from coexisting magnetic order. The research presented in this review highlights that we are just entering a whole new world of intriguing nanoscale physics that is yet to be explored in all its details. The goal is to draw attention to the persistent challenges and identify future key directions for the research on functional domain walls in multiferroics.

  9. Functional domain walls in multiferroics.

    PubMed

    Meier, Dennis

    2015-11-25

    During the last decade a wide variety of novel and fascinating correlation phenomena has been discovered at domain walls in multiferroic bulk systems, ranging from unusual electronic conductance to inseparably entangled spin and charge degrees of freedom. The domain walls represent quasi-2D functional objects that can be induced, positioned, and erased on demand, bearing considerable technological potential for future nanoelectronics. Most of the challenges that remain to be solved before turning related device paradigms into reality, however, still fall in the field of fundamental condensed matter physics and materials science. In this topical review seminal experimental findings gained on electric and magnetic domain walls in multiferroic bulk materials are addressed. A special focus is put on the physical properties that emerge at so-called charged domain walls and the added functionality that arises from coexisting magnetic order. The research presented in this review highlights that we are just entering a whole new world of intriguing nanoscale physics that is yet to be explored in all its details. The goal is to draw attention to the persistent challenges and identify future key directions for the research on functional domain walls in multiferroics. PMID:26523728

  10. 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.

  11. K Domain CR9 of Low Density Lipoprotein (LDL) Receptor-related Protein 1 (LRP1) Is Critical for Aggregated LDL-induced Foam Cell Formation from Human Vascular Smooth Muscle Cells*

    PubMed Central

    Costales, Paula; Fuentes-Prior, Pablo; Castellano, Jose; Revuelta-Lopez, Elena; Corral-Rodríguez, Maria Ángeles; Nasarre, Laura; Badimon, Lina; Llorente-Cortes, Vicenta

    2015-01-01

    Low density lipoprotein receptor-related protein (LRP1) mediates the internalization of aggregated LDL (AgLDL), which in turn increases the expression of LRP1 in human vascular smooth muscle cells (hVSMCs). This positive feedback mechanism is thus highly efficient to promote the formation of hVSMC foam cells, a crucial vascular component determining the susceptibility of atherosclerotic plaque to rupture. Here we have determined the LRP1 domains involved in AgLDL recognition with the aim of specifically blocking AgLDL internalization in hVSMCs. The capacity of fluorescently labeled AgLDL to bind to functional LRP1 clusters was tested in a receptor-ligand fluorometric assay made by immobilizing soluble LRP1 “minireceptors” (sLRP1-II, sLRP1-III, and sLRP1-IV) recombinantly expressed in CHO cells. This assay showed that AgLDL binds to cluster II. We predicted three well exposed and potentially immunogenic peptides in the CR7–CR9 domains of this cluster (termed P1 (Cys1051–Glu1066), P2 (Asp1090–Cys1104), and P3 (Gly1127–Cys1140)). AgLDL, but not native LDL, bound specifically and tightly to P3-coated wells. Rabbit polyclonal antibodies raised against P3 prevented AgLDL uptake by hVSMCs and were almost twice as effective as anti-P1 and anti-P2 Abs in reducing intracellular cholesteryl ester accumulation. Moreover, anti-P3 Abs efficiently prevented AgLDL-induced LRP1 up-regulation and counteracted the down-regulatory effect of AgLDL on hVSMC migration. In conclusion, domain CR9 appears to be critical for LRP1-mediated AgLDL binding and internalization in hVSMCs. Our results open new avenues for an innovative anti-VSMC foam cell-based strategy for the treatment of vascular lipid deposition in atherosclerosis. PMID:25918169

  12. Is the myonuclear domain size fixed?

    PubMed

    Van der Meer, S F T; Jaspers, R T; Degens, H

    2011-12-01

    It has been suggested that the number of myonuclei in a muscle fibre changes in proportion to the change in fibre size, resulting in a constant myonuclear domain size, defined as the cytoplasmic volume per myonucleus. The myonuclear domain size varies, however, between fibre types and is inversely related with the oxidative capacity of a fibre. Overall, the observations of an increase in myonuclear domain size during both maturational growth and overload-induced hypertrophy, and the decrease in myonuclear domain size during disuse- and ageing-associated muscle atrophy suggest that the concept of a constant myonuclear domain size needs to be treated cautiously. It also suggests that only when the myonuclear domain size exceeds a certain threshold during growth or overload-induced hypertrophy acquisition of new myonuclei is required for further fibre hypertrophy. PMID:22130137

  13. Domains and Naive Theories

    PubMed Central

    Gelman, Susan A.; Noles, Nicholaus S.

    2013-01-01

    Human cognition entails domain-specific cognitive processes that influence memory, attention, categorization, problem-solving, reasoning, and knowledge organization. This review examines domain-specific causal theories, which are of particular interest for permitting an examination of how knowledge structures change over time. We first describe the properties of commonsense theories, and how commonsense theories differ from scientific theories, illustrating with children’s classification of biological and non-biological kinds. We next consider the implications of domain-specificity for broader issues regarding cognitive development and conceptual change. We then examine the extent to which domain-specific theories interact, and how people reconcile competing causal frameworks. Future directions for research include examining how different content domains interact, the nature of theory change, the role of context (including culture, language, and social interaction) in inducing different frameworks, and the neural bases for domain-specific reasoning. PMID:24187603

  14. Causal Learning Across Domains

    ERIC Educational Resources Information Center

    Schulz, Laura E.; Gopnik, Alison

    2004-01-01

    Five studies investigated (a) children's ability to use the dependent and independent probabilities of events to make causal inferences and (b) the interaction between such inferences and domain-specific knowledge. In Experiment 1, preschoolers used patterns of dependence and independence to make accurate causal inferences in the domains of…

  15. 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…

  16. Domain wall filters

    SciTech Connect

    Baer, Oliver; Narayanan, Rajamani; Neuberger, Herbert; Witzel, Oliver

    2007-03-15

    We propose using the extra dimension separating the domain walls carrying lattice quarks of opposite handedness to gradually filter out the ultraviolet fluctuations of the gauge fields that are felt by the fermionic excitations living in the bulk. This generalization of the homogeneous domain wall construction has some theoretical features that seem nontrivial.

  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. PMID:8787739

  18. Domain Transfer Learning for MCI Conversion Prediction

    PubMed Central

    Cheng, Bo; Liu, Mingxia; Zhang, Daoqiang; Munsell, Brent C.; Shen, Dinggang

    2015-01-01

    Machine learning methods have been increasingly used to predict the conversion of mild cognitive impairment (MCI) to Alzheimer's disease (AD), by classifying MCI converters (MCI-C) from MCI non-converters (MCI-NC). However, most of existing methods construct classifiers using only data from one particular target domain (e.g., MCI), and ignore data in the other related domains (e.g., AD and normal control (NC)) that could provide valuable information to promote the performance of MCI conversion prediction. To this end, we develop a novel domain transfer learning method for MCI conversion prediction, which can use data from both the target domain (i.e., MCI) and the auxiliary domains (i.e., AD and NC). Specifically, the proposed method consists of three key components: 1) a domain transfer feature selection (DTFS) component that selects the most informative feature-subset from both target domain and auxiliary domains with different imaging modalities, 2) a domain transfer sample selection (DTSS) component that selects the most informative sample-subset from the same target and auxiliary domains with different data modalities, and 3) a domain transfer support vector machine (DTSVM) classification component that fuses the selected features and samples to separate MCI-C and MCI-NC patients. We evaluate our method on 202 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) with MRI, FDG-PET and CSF data. The experimental results show that the proposed method can classify MCI-C patients from MCI-NC patients with an accuracy of 79.4%, with the aid of additional domain knowledge learned from AD and NC. PMID:25751861

  19. Domain Transfer Learning for MCI Conversion Prediction.

    PubMed

    Cheng, Bo; Liu, Mingxia; Zhang, Daoqiang; Munsell, Brent C; Shen, Dinggang

    2015-07-01

    Machine learning methods have successfully been used to predict the conversion of mild cognitive impairment (MCI) to Alzheimer's disease (AD), by classifying MCI converters (MCI-C) from MCI nonconverters (MCI-NC). However, most existing methods construct classifiers using data from one particular target domain (e.g., MCI), and ignore data in other related domains (e.g., AD and normal control (NC)) that may provide valuable information to improve MCI conversion prediction performance. To address is limitation, we develop a novel domain transfer learning method for MCI conversion prediction, which can use data from both the target domain (i.e., MCI) and auxiliary domains (i.e., AD and NC). Specifically, the proposed method consists of three key components: 1) a domain transfer feature selection component that selects the most informative feature-subset from both target domain and auxiliary domains from different imaging modalities; 2) a domain transfer sample selection component that selects the most informative sample-subset from the same target and auxiliary domains from different data modalities; and 3) a domain transfer support vector machine classification component that fuses the selected features and samples to separate MCI-C and MCI-NC patients. We evaluate our method on 202 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) that have MRI, FDG-PET, and CSF data. The experimental results show the proposed method can classify MCI-C patients from MCI-NC patients with an accuracy of 79.4%, with the aid of additional domain knowledge learned from AD and NC. PMID:25751861

  20. cpc-3, the Neurospora crassa homologue of yeast GCN2, encodes a polypeptide with juxtaposed eIF2alpha kinase and histidyl-tRNA synthetase-related domains required for general amino acid control.

    PubMed

    Sattlegger, E; Hinnebusch, A G; Barthelmess, I B

    1998-08-01

    Based on characteristic amino acid sequences of kinases that phosphorylate the alpha subunit of eukaryotic translation initiation factor 2 (eIF2alpha kinases), degenerate oligonucleotide primers were constructed and used to polymerase chain reaction-amplify from genomic DNA of Neurospora crassa a sequence encoding part of a putative protein kinase. With this sequence an open reading frame was identified encoding a predicted polypeptide with juxtaposed eIF2alpha kinase and histidyl-tRNA synthetase-related domains. The 1646 amino acid sequence of this gene, called cpc-3, showed 35% positional identity over almost the entire sequence with GCN2 of yeast, which stimulates translation of the transcriptional activator of amino acid biosynthetic genes encoded by GCN4. Strains disrupted for cpc-3 were unable to induce increased transcription and derepression of amino acid biosynthetic enzymes in amino acid-deprived cells. The cpc-3 mutation did not affect the ability to up-regulate mRNA levels of cpc-1, encoding the GCN4 homologue and transcriptional activator of amino acid biosynthetic genes in N. crassa, but the mutation abolished the dramatic increase of CPC1 protein level in response to amino acid deprivation. These findings suggest that cpc-3 is the functional homologue of GCN2, being required for increased translation of cpc-1 mRNA in amino acid-starved cells. PMID:9685394

  1. SOT1, a pentatricopeptide repeat protein with a small MutS-related domain, is required for correct processing of plastid 23S-4.5S rRNA precursors in Arabidopsis thaliana.

    PubMed

    Wu, Wenjuan; Liu, Sheng; Ruwe, Hannes; Zhang, Delin; Melonek, Joanna; Zhu, Yajuan; Hu, Xupeng; Gusewski, Sandra; Yin, Ping; Small, Ian D; Howell, Katharine A; Huang, Jirong

    2016-03-01

    Ribosomal RNA processing is essential for plastid ribosome biogenesis, but is still poorly understood in higher plants. Here, we show that SUPPRESSOR OF THYLAKOID FORMATION1 (SOT1), a plastid-localized pentatricopeptide repeat (PPR) protein with a small MutS-related domain, is required for maturation of the 23S-4.5S rRNA dicistron. Loss of SOT1 function leads to slower chloroplast development, suppression of leaf variegation, and abnormal 23S and 4.5S processing. Predictions based on the PPR motif sequences identified the 5' end of the 23S-4.5S rRNA dicistronic precursor as a putative SOT1 binding site. This was confirmed by electrophoretic mobility shift assay, and by loss of the abundant small RNA 'footprint' associated with this site in sot1 mutants. We found that more than half of the 23S-4.5S rRNA dicistrons in sot1 mutants contain eroded and/or unprocessed 5' and 3' ends, and that the endonucleolytic cleavage product normally released from the 5' end of the precursor is absent in a sot1 null mutant. We postulate that SOT1 binding protects the 5' extremity of the 23S-4.5S rRNA dicistron from exonucleolytic attack, and favours formation of the RNA structure that allows endonucleolytic processing of its 5' and 3' ends. PMID:26800847

  2. Optical Frequency Domain Imaging

    NASA Astrophysics Data System (ADS)

    Bouma, Brett E.; Tearney, Guillermo J.; Vakoc, Benjamin; Yun, Seok Hyun

    In this chapter, we discuss a frequency-domain approach, optical frequency-domain imaging (OFDI), which is based on optical frequency-domain reflectometry and uses a wavelength-swept laser and standard single-element photodetectors. The chapter begins with an overview of the fundamental aspects of the technology, including the detected signal, sensitivity, depth range, and resolution, and then goes on to discuss specific component technologies including the light source, interferometer and acquisition electronics, and image processing. The final section of the chapter provides a brief glimpse at some of the biomedical applications that most directly take advantage of the improved speed and sensitivity of OFDI.

  3. Optimal Control of Flows in Moving Domains

    NASA Astrophysics Data System (ADS)

    Protas, Bartosz; Liao, Wenyuan; Glander, Donn

    2006-11-01

    This investigation concerns adjoint--based optimization of viscous incompressible flows (the Navier-Stokes problem) coupled with heat conduction involving change of phase (the Stefan problem) and occurring in domains with moving boundaries such as the free and solidification surfaces. This problem is motivated by optimization of advanced welding techniques used in automotive manufacturing. We characterize the sensitivity of a suitable cost functional defined for the system with respect to control (the heat input) using adjoint equations. Given that the shape of the domain is also a dependent variable, characterizing sensitivities necessitates the introduction of ``non-cylindrical'' calculus required to differentiate a cost functional defined on a variable domain. As a result, unlike the forward problem, the adjoint system is defined on a domain with a predetermined evolution in time and also involves ordinary differential equations defined on the domain boundary (``the adjoint transverse system''). We will discuss certain computational issues related to numerical solution of such adjoint problems.

  4. 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.

  5. Visualizing Knowledge Domains.

    ERIC Educational Resources Information Center

    Borner, Katy; Chen, Chaomei; Boyack, Kevin W.

    2003-01-01

    Reviews visualization techniques for scientific disciplines and information retrieval and classification. Highlights include historical background of scientometrics, bibliometrics, and citation analysis; map generation; process flow of visualizing knowledge domains; measures and similarity calculations; vector space model; factor analysis;…

  6. Oscillons and domain walls

    SciTech Connect

    Hindmarsh, Mark; Salmi, Petja

    2008-05-15

    Oscillons, extremely long-lived localized oscillations of a scalar field, are shown to be produced by evolving domain wall networks in {phi}{sup 4} theory in two spatial dimensions. We study the oscillons in frequency space using the classical spectral function at zero momentum, and obtain that the velocity distribution is suppressed as {gamma}{sup -2} at large Lorentz factor {gamma}, with oscillons produced up to at least {gamma}{approx}10. This leads us to speculate that oscillons are produced at cusps, regions of the domain wall travelling near the speed of light. In order to gain some insight onto the dilute oscillon 'gas' produced by the domain walls, we prepare a denser gas by filling the simulation volume with oscillons boosted in random directions. We finish the study by revisiting collisions between oscillons and between an oscillon and a domain wall, showing that in the latter case they can pass straight through with minimal distortion.

  7. 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…

  8. 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…

  9. Inhalational anesthetics disrupt postsynaptic density protein-95, Drosophila disc large tumor suppressor, and zonula occludens-1 domain protein interactions critical to action of several excitatory receptor channels related to anesthesia

    PubMed Central

    Tao, Feng; Chen, Qiang; Sato, Yuko; Skinner, John; Tang, Pei; Johns, Roger A.

    2015-01-01

    Background We have shown previously that inhaled anesthetics disrupt the interaction between the second postsynaptic density protein-95, Drosophila disc large tumor suppressor, and zonula occludens-1 (PDZ) domain of postsynaptic density protein-95 (PSD-95) and the C-terminus of N-methyl-D-aspartate receptor subunits NR2A and NR2B. Our data indicate that PDZ domains may serve as a molecular target for inhaled anesthetics. However, the underlying molecular mechanisms remain to be illustrated. Methods Glutathione S-transferase pull-down assay, co-immunoprecipitation and yeast two-hybrid analysis were used to assess PDZ domain-mediated protein-protein interactions in different conditions. Nuclear magnetic resonance spectroscopy was used to investigate isoflurane-induced chemical shift changes in the PDZ1–3 domains of PSD-95. A surface plasmon resonance-based BIAcore assay was used to examine the ability of isoflurane to inhibit the PDZ domain-mediated protein-protein interactions in real time. Results Halothane and isoflurane dose dependently inhibited PDZ domain-mediated interactions between PSD-95 and Shaker-type potassium channel Kv1.4 and between α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor subunit GluA2 and its interacting proteins— glutamate receptor interacting protein or protein interacting with c kinase 1. However, halothane and isoflurane had no effect on PDZ domain-mediated interactions between γ-aminobutyric acid, type B receptor and its interacting proteins. The inhaled anesthetic isoflurane mostly affected the residues close to or in the peptide binding groove of PSD-95 PDZ1 and PDZ2 (especially PDZ2), while barely affecting the peptide binding groove of PSD-95 PDZ3. Conclusion These results suggest that inhaled anesthetics interfere with PDZ domain-mediated protein-protein interactions at several receptors important to neuronal excitation, anesthesia and pain processing. PMID:25654436

  10. 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.

  11. Tandem BRCT Domains

    PubMed Central

    Mesquita, Rafael D.; Woods, Nicholas T.; Seabra-Junior, Eloy S.; Monteiro, Alvaro N.A.

    2010-01-01

    The cell’s ability to sense and respond to specific stimuli is a complex system derived from precisely regulated protein-protein interactions. Some of these protein-protein interactions are mediated by the recognition of linear peptide motifs by protein modular domains. BRCT (BRCA1 C-terminal) domains and their linear motif counterparts, which contain phosphoserines, are one such pair-wise interaction system that seems to have evolved to serve as a surveillance system to monitor threats to the cell’s genetic integrity. Evidence indicates that BRCT domains found in tandem can cooperate to provide sequence-specific binding of phosphorylated peptides as is the case for the breast and ovarian cancer susceptibility gene BRCA1 and the PAX transcription factor–interacting protein PAXIP1. Particular interest has been paid to tandem BRCT domains as “readers” of signaling events in the form of phosphorylated serine moieties induced by the activation of DNA damage response kinases ATM, ATR, and DNA-PK. However, given the diversity of tandem BRCT-containing proteins, questions remain as to the origin and evolution of this domain. Here, we discuss emerging views of the origin and evolving roles of tandem BRCT domain repeats in the DNA damage response. PMID:21533002

  12. The dynamics of the asymmetric motion of domain walls of sandwich domain structure in a Fe-based amorphous ribbon

    NASA Astrophysics Data System (ADS)

    Zhmetko, D. N.; Zhmetko, S. D.; Troschenkov, Y. N.; Matsura, A. V.

    2013-08-01

    The frequency dependence of asymmetry of the domain walls velocity relative to the middle plane of amorphous ribbon is investigated. An additional pressure of the same direction acting on each domain wall caused by dependence of eddy current damping on the coordinate of the domain wall is revealed. The microscopic mechanisms of this additional pressure are considered.

  13. The ASH1-RELATED3 SET-Domain Protein Controls Cell Division Competence of the Meristem and the Quiescent Center of the Arabidopsis Primary Root1[W][OPEN

    PubMed Central

    Kumpf, Robert; Thorstensen, Tage; Rahman, Mohummad Aminur; Heyman, Jefri; Nenseth, H. Zeynep; Lammens, Tim; Herrmann, Ullrich; Swarup, Ranjan; Veiseth, Silje Veie; Emberland, Gitika; Bennett, Malcolm J.; De Veylder, Lieven; Aalen, Reidunn B.

    2014-01-01

    The stem cell niche of the Arabidopsis (Arabidopsis thaliana) primary root apical meristem is composed of the quiescent (or organizing) center surrounded by stem (initial) cells for the different tissues. Initial cells generate a population of transit-amplifying cells that undergo a limited number of cell divisions before elongating and differentiating. It is unclear whether these divisions occur stochastically or in an orderly manner. Using the thymidine analog 5-ethynyl-2′-deoxyuridine to monitor DNA replication of cells of Arabidopsis root meristems, we identified a pattern of two, four, and eight neighboring cells with synchronized replication along the cortical, epidermal, and endodermal cell files, suggested to be daughters, granddaughters, and great-granddaughters of the direct progeny of each stem cell. Markers of mitosis and cytokinesis were not present in the region closest to the transition zone where the cells start to elongate, suggesting that great-granddaughter cells switch synchronously from the mitotic cell cycle to endoreduplication. Mutations in the stem cell niche-expressed ASH1-RELATED3 (ASHR3) gene, encoding a SET-domain protein conferring histone H3 lysine-36 methylation, disrupted this pattern of coordinated DNA replication and cell division and increased the cell division rate in the quiescent center. E2Fa/E2Fb transcription factors controlling the G1-to-S-phase transition regulate ASHR3 expression and bind to the ASHR3 promoter, substantiating a role for ASHR3 in cell division control. The reduced length of the root apical meristem and primary root of the mutant ashr3-1 indicate that synchronization of replication and cell divisions is required for normal root growth and development. PMID:25034019

  14. Enhanced amino acid selection in fully evolved tryptophanyl-tRNA synthetase, relative to its urzyme, requires domain motion sensed by the D1 switch, a remote dynamic packing motif.

    PubMed

    Weinreb, Violetta; Li, Li; Chandrasekaran, Srinivas Niranj; Koehl, Patrice; Delarue, Marc; Carter, Charles W

    2014-02-14

    We previously showed (Li, L., and Carter, C. W., Jr. (2013) J. Biol. Chem. 288, 34736-34745) that increased specificity for tryptophan versus tyrosine by contemporary Bacillus stearothermophilus tryptophanyl-tRNA synthetase (TrpRS) over that of TrpRS Urzyme results entirely from coupling between the anticodon-binding domain and an insertion into the Rossmann-fold known as Connecting Peptide 1. We show that this effect is closely related to a long range catalytic effect, in which side chain repacking in a region called the D1 Switch, accounts fully for the entire catalytic contribution of the catalytic Mg(2+) ion. We report intrinsic and higher order interaction effects on the specificity ratio, (kcat/Km)Trp/(kcat/Km)Tyr, of 15 combinatorial mutants from a previous study (Weinreb, V., Li, L., and Carter, C. W., Jr. (2012) Structure 20, 128-138) of the catalytic role of the D1 Switch. Unexpectedly, the same four-way interaction both activates catalytic assist by Mg(2+) ion and contributes -4.4 kcal/mol to the free energy of the specificity ratio. A minimum action path computed for the induced-fit and catalytic conformation changes shows that repacking of the four residues precedes a decrease in the volume of the tryptophan-binding pocket. We suggest that previous efforts to alter amino acid specificities of TrpRS and glutaminyl-tRNA synthetase (GlnRS) by mutagenesis without extensive, modular substitution failed because mutations were incompatible with interdomain motions required for catalysis. PMID:24394410

  15. The bldC Developmental Locus of Streptomyces coelicolor Encodes a Member of a Family of Small DNA-Binding Proteins Related to the DNA-Binding Domains of the MerR Family

    PubMed Central

    Hunt, Alison C.; Servín-González, Luis; Kelemen, Gabriella H.; Buttner, Mark J.

    2005-01-01

    The bldC locus, required for formation of aerial hyphae in Streptomyces coelicolor, was localized by map-based cloning to the overlap between cosmids D17 and D25 of a minimal ordered library. Subcloning and sequencing showed that bldC encodes a member of a previously unrecognized family of small (58- to 78-residue) DNA-binding proteins, related to the DNA-binding domains of the MerR family of transcriptional activators. BldC family members are found in a wide range of gram-positive and gram-negative bacteria. Constructed ΔbldC mutants were defective in differentiation and antibiotic production. They failed to form an aerial mycelium on minimal medium and showed severe delays in aerial mycelium formation on rich medium. In addition, they failed to produce the polyketide antibiotic actinorhodin, and bldC was shown to be required for normal and sustained transcription of the pathway-specific activator gene actII-orf4. Although ΔbldC mutants produced the tripyrrole antibiotic undecylprodigiosin, transcripts of the pathway-specific activator gene (redD) were reduced to almost undetectable levels after 48 h in the bldC mutant, in contrast to the bldC+ parent strain in which redD transcription continued during aerial mycelium formation and sporulation. This suggests that bldC may be required for maintenance of redD transcription during differentiation. bldC is expressed from a single promoter. S1 nuclease protection assays and immunoblotting showed that bldC is constitutively expressed and that transcription of bldC does not depend on any of the other known bld genes. The bldC18 mutation that originally defined the locus causes a Y49C substitution that results in instability of the protein. PMID:15629942

  16. Quantitative Fluorescence Resonance Energy Transfer Microscopy Analysis of the Human Immunodeficiency Virus Type 1 Gag-Gag Interaction: Relative Contributions of the CA and NC Domains and Membrane Binding▿ †

    PubMed Central

    Hogue, Ian B.; Hoppe, Adam; Ono, Akira

    2009-01-01

    The human immunodeficiency virus type 1 structural polyprotein Pr55Gag is necessary and sufficient for the assembly of virus-like particles on cellular membranes. Previous studies demonstrated the importance of the capsid C-terminal domain (CA-CTD), nucleocapsid (NC), and membrane association in Gag-Gag interactions, but the relationships between these factors remain unclear. In this study, we systematically altered the CA-CTD, NC, and the ability to bind membrane to determine the relative contributions of, and interplay between, these factors. To directly measure Gag-Gag interactions, we utilized chimeric Gag-fluorescent protein fusion constructs and a fluorescence resonance energy transfer (FRET) stoichiometry method. We found that the CA-CTD is essential for Gag-Gag interactions at the plasma membrane, as the disruption of the CA-CTD has severe impacts on FRET. Data from experiments in which wild-type (WT) and CA-CTD mutant Gag molecules are coexpressed support the idea that the CA-CTD dimerization interface consists of two reciprocal interactions. Mutations in NC have less-severe impacts on FRET between normally myristoylated Gag proteins than do CA-CTD mutations. Notably, when nonmyristoylated Gag interacts with WT Gag, NC is essential for FRET despite the presence of the CA-CTD. In contrast, constitutively enhanced membrane binding eliminates the need for NC to produce a WT level of FRET. These results from cell-based experiments suggest a model in which both membrane binding and NC-RNA interactions serve similar scaffolding functions so that one can functionally compensate for a defect in the other. PMID:19403686

  17. 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

  18. Construction of Galerkin's matrix for elementary potentials and an ellipsoidal solution domain based on series developments and general relations between Legendre's functions of the first and the second kind: Application in Earth's gravity field studies

    NASA Astrophysics Data System (ADS)

    Holota, Petr; Nesvadba, Otakar

    2016-04-01

    The role of boundary value problems in physical geodesy and in Earth's gravity field studies in particular is well-known. The paper focuses on Neumann's problem formulated for the exterior of an oblate ellipsoid of revolution as this is considered a basis for an iteration solution of the linear gravimetric boundary value problem in the determination of the disturbing potential. The approach follows the concept of variational methods and the notion of the weak solution. Hence Galerkin's approximations are applied, which means that the solution of the problem is approximated by linear combinations of basis functions with scalar coefficients. Our aim is to discuss the construction of Galerkin's matrix for basis functions generated by elementary potentials. Possibly, the computation of the entries of Galerkin's matrix is expected to be very simple for the elementary functions like these. Nevertheless, the opposite is true. Ellipsoidal harmonics are applied as a natural tool and elementary potentials are expressed by means of series of ellipsoidal harmonics. The problem, however, is the summation of the series that represent the entries of Galerkin's matrix. It is difficult to reduce the number of summation indices since in the ellipsoidal case there is no analogue to the addition theorem known for spherical harmonics. This makes the computation of Galerkin's matrix rather demanding. Therefore, the straightforward application of series of ellipsoidal harmonics is complemented by deeper relations contained in the theory of ordinary differential equations of second order and Legendre's functions. Subsequently, hypergeometric functions and series are used. Moreover, within some approximations the entries are split into parts. Some of the resulting series may be summed relatively easily, apart from technical tricks. For the remaining series the summation needs more complex tools. It was converted to elliptic integrals. The approach made it possible to deduce a closed

  19. 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

  20. Axion domain wall baryogenesis

    SciTech Connect

    Daido, Ryuji; Kitajima, Naoya; Takahashi, Fuminobu

    2015-07-28

    We propose a new scenario of baryogenesis, in which annihilation of axion domain walls generates a sizable baryon asymmetry. Successful baryogenesis is possible for a wide range of the axion mass and decay constant, m≃10{sup 8}–10{sup 13} GeV and f≃10{sup 13}–10{sup 16} GeV. Baryonic isocurvature perturbations are significantly suppressed in our model, in contrast to various spontaneous baryogenesis scenarios in the slow-roll regime. In particular, the axion domain wall baryogenesis is consistent with high-scale inflation which generates a large tensor-to-scalar ratio within the reach of future CMB B-mode experiments. We also discuss the gravitational waves produced by the domain wall annihilation and its implications for the future gravitational wave experiments.

  1. Predicting domain-domain interactions using a parsimony approach

    PubMed Central

    Guimarães, Katia S; Jothi, Raja; Zotenko, Elena; Przytycka, Teresa M

    2006-01-01

    We propose a novel approach to predict domain-domain interactions from a protein-protein interaction network. In our method we apply a parsimony-driven explanation of the network, where the domain interactions are inferred using linear programming optimization, and false positives in the protein network are handled by a probabilistic construction. This method outperforms previous approaches by a considerable margin. The results indicate that the parsimony principle provides a correct approach for detecting domain-domain contacts. PMID:17094802

  2. Domain reduction method for atomistic simulations

    SciTech Connect

    Medyanik, Sergey N. . E-mail: medyanik@northwestern.edu; Karpov, Eduard G. . E-mail: edkarpov@gmail.com; Liu, Wing Kam . E-mail: w-liu@northwestern.edu

    2006-11-01

    In this paper, a quasi-static formulation of the method of multi-scale boundary conditions (MSBCs) is derived and applied to atomistic simulations of carbon nano-structures, namely single graphene sheets and multi-layered graphite. This domain reduction method allows for the simulation of deformable boundaries in periodic atomic lattice structures, reduces the effective size of the computational domain, and consequently decreases the cost of computations. The size of the reduced domain is determined by the value of the domain reduction parameter. This parameter is related to the distance between the boundary of the reduced domain, where MSBCs are applied, and the boundary of the full domain, where the standard displacement boundary conditions are prescribed. Two types of multi-scale boundary conditions are derived: one for simulating in-layer multi-scale boundaries in a single graphene sheet and the other for simulating inter-layer multi-scale boundaries in multi-layered graphite. The method is tested on benchmark nano-indentation problems and the results are consistent with the full domain solutions.

  3. 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.

  4. Cellulose binding domain proteins

    DOEpatents

    Shoseyov, O.; Shpiegl, I.; Goldstein, M.; Doi, R.

    1998-11-17

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 16 figs.

  5. Cellulose binding domain proteins

    DOEpatents

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc; Doi, Roy

    1998-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  6. Domain wall manipulation with a magnetic tip.

    PubMed

    Stapelfeldt, T; Wieser, R; Vedmedenko, E Y; Wiesendanger, R

    2011-07-01

    A theoretical concept of local manipulation of magnetic domain walls is introduced. In the proposed procedure, a domain wall is driven by a spin-polarized current induced by a magnetic tip, as used in a scanning tunneling microscope, placed above a magnetic nanostripe and then moved along its long axis with a current flowing through the vacuum barrier. The angular momentum from the spin-polarized current exerts a torque on the magnetic moments underneath the tip and leads to a displacement of the domain wall. Particularly, the manipulation of a ferromagnetic 180° transverse domain wall has been studied by means of Landau-Lifshitz-Gilbert dynamics and Monte Carlo simulations. Different relative orientations of the tip and the sample magnetization have been considered. PMID:21797636

  7. Scanning secondary-electron microscopy on ferroelectric domains and domain walls in YMnO{sub 3}

    SciTech Connect

    Li, J.; Yang, H. X.; Tian, H. F.; Ma, C.; Li, J. Q.; Zhang, S.; Zhao, Y. G.

    2012-04-09

    Ferroelectric domain structures in YMnO{sub 3} single crystals on the hexagonal polar surface have been investigated by scanning electron microscopy in secondary electron emission mode. The experimental results demonstrate that the domain, as well as domain walls, can be clearly revealed under the operation voltages ranging from 0.6 to 3 kV. Evolution of domain contrasts arising from electron-beam irradiation can be mainly explained by the pyroelectric effect and related charging process. A rich variety of microstructure features of ferroelectric domains can be clearly revealed in YMnO{sub 3} by this high-resolution technique.

  8. Conducting Ferroelectric Walls, Domain Topology, and Domain Switching Kinetics in a Hybrid Improper Ferroelectric

    NASA Astrophysics Data System (ADS)

    Cheong, Sang-Wook; Rutgers Center For Emergent Materials Team

    Charged polar interfaces such as charged ferroelectric domain walls or heterostructured interfaces of ZnO/(Zn,Mg)O and LaAlO 3 /SrTiO 3 , across which the normal component of electric polarization changes suddenly, can host large two-dimensional conduction. Charged ferroelectric domain walls can be highly conducting but energetically unfavored; however, they were found to be mysteriously abundant in hybrid improper ferroelectric (Ca,Sr) 3 Ti 2 O 7 single crystals. From the exploration of antiphase domain boundaries, which are hidden in piezoresponse force microscopy, using dark-field electron microscopy, we have explored the macroscopic topology of polarization domains and antiphase domains. We found that the macroscopic domain topology is directly responsible for the presence of charged domain walls, and is closely related with the polarization domain switching mechanism in (Ca,Sr) 3 Ti 2 O 7 . Rutgers Center for Emergent Materials and Department of Physics and Astronomy, Rutgers University, Piscataway, New Jersey 08854, USA.

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

    PubMed Central

    Krishnan, Sai; Collett, Michael; Robinson, Phillip J.

    2015-01-01

    Dynamin I is a highly regulated GTPase enzyme enriched in nerve terminals which mediates vesicle fission during synaptic vesicle endocytosis. One regulatory mechanism involves its interactions with proteins containing Src homology 3 (SH3) domains. At least 30 SH3 domain-containing proteins bind dynamin at its proline-rich domain (PRD). Those that stimulate dynamin activity act by promoting its oligomerisation. We undertook a systematic parallel screening of 13 glutathione-S-transferase (GST)-tagged endocytosis-related SH3 domains on dynamin binding, GTPase activity and oligomerisation. No correlation was found between dynamin binding and their potency to stimulate GTPase activity. There was limited correlation between the extent of their ability to stimulate dynamin activity and the level of oligomerisation, indicating an as yet uncharacterised allosteric coupling of the PRD and G domain. We examined the two variants, dynamin Iab and Ibb, which differ in the alternately splice middle domain α2 helix. They responded differently to the panel of SH3s, with the extent of stimulation between the splice variants varying greatly between the SH3s. This study reveals that SH3 binding can act as a heterotropic allosteric regulator of the G domain via the middle domain α2 helix, suggesting an involvement of this helix in communicating the PRD-mediated allostery. This indicates that SH3 binding both stabilises multiple conformations of the tetrameric building block of dynamin, and promotes assembly of dynamin-SH3 complexes with distinct rates of GTP hydrolysis. PMID:26659814

  10. Simplified Parallel Domain Traversal

    SciTech Connect

    Erickson III, David J

    2011-01-01

    Many data-intensive scientific analysis techniques require global domain traversal, which over the years has been a bottleneck for efficient parallelization across distributed-memory architectures. Inspired by MapReduce and other simplified parallel programming approaches, we have designed DStep, a flexible system that greatly simplifies efficient parallelization of domain traversal techniques at scale. In order to deliver both simplicity to users as well as scalability on HPC platforms, we introduce a novel two-tiered communication architecture for managing and exploiting asynchronous communication loads. We also integrate our design with advanced parallel I/O techniques that operate directly on native simulation output. We demonstrate DStep by performing teleconnection analysis across ensemble runs of terascale atmospheric CO{sub 2} and climate data, and we show scalability results on up to 65,536 IBM BlueGene/P cores.

  11. Crystal structure of domain-swapped STE20 OSR1 kinase domain

    SciTech Connect

    Lee, Seung-Jae; Cobb, Melanie H.; Goldsmith, Elizabeth J.

    2009-09-15

    OSR1 (oxidative stress-responsive-1) and SPAK (Ste20/Sps1-related proline/alanine-rich kinase) belong to the GCK-VI subfamily of Ste20 group kinases. OSR1 and SPAK are key regulators of NKCCs (Na{sup +}/K{sup +}/2Cl{sup -} cotransporters) and activated by WNK family members (with-no-lysine kinase), mutations of which are known to cause Gordon syndrome, an autosomal dominant form of inherited hypertension. The crystal structure of OSR1 kinase domain has been solved at 2.25 {angstrom}. OSR1 forms a domain-swapped dimer in an inactive conformation, in which P+1 loop and {alpha}EF helix are swapped between dimer-related monomers. Structural alignment with nonswapped Ste20 TAO2 kinase indicates that the integrity of chemical interactions in the kinase domain is well preserved in the domain-swapped interfaces. The OSR1 kinase domain has now been added to a growing list of domain-swapped protein kinases recently reported, suggesting that the domain-swapping event provides an additional layer of complexity in regulating protein kinase activity.

  12. Multi-domain training enhances attentional control.

    PubMed

    Binder, Julia C; Martin, Mike; Zöllig, Jacqueline; Röcke, Christina; Mérillat, Susan; Eschen, Anne; Jäncke, Lutz; Shing, Yee Lee

    2016-06-01

    Multi-domain training potentially increases the likelihood of overlap in processing components with transfer tasks and everyday life, and hence is a promising training approach for older adults. To empirically test this, 84 healthy older adults aged 64 to 75 years were randomly assigned to one of three single-domain training conditions (inhibition, visuomotor function, spatial navigation) or to the simultaneous training of all three cognitive functions (multi-domain training condition). All participants trained on an iPad at home for 50 training sessions. Before and after the training, and at a 6-month follow-up measurement, cognitive functioning and training transfer were assessed with a neuropsychological test battery including tests targeting the trained functions (near transfer) and transfer to executive functions (far transfer: attentional control, working memory, speed). Participants in all four training groups showed a linear increase in training performance over the 50 training sessions. Using a latent difference score model, the multi-domain training group, compared with the single-domain training groups, showed more improvement on the far transfer attentional control composite. Individuals with initially lower baseline performance showed higher training-related improvements, indicating that training compensated for lower initial cognitive performance. At the 6-month follow-up, performance on the cognitive test battery remained stable. This is one of the first studies to investigate systematically multi-domain training including comparable single-domain training conditions. Our findings suggest that multi-domain training enhances attentional control involved in handling several different tasks at the same time, an aspect in everyday life that is particularly challenging for older people. (PsycINFO Database Record PMID:27294719

  13. 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…

  14. Frequency domain nonlinear optics

    NASA Astrophysics Data System (ADS)

    Legare, Francois

    2016-05-01

    The universal dilemma of gain narrowing occurring in fs amplifiers prevents ultra-high power lasers from delivering few-cycle pulses. This problem is overcome by a new amplification concept: Frequency domain Optical Parametric Amplification - FOPA. It enables simultaneous up-scaling of peak power and amplified spectral bandwidth and can be performed at any wavelength range of conventional amplification schemes, however, with the capability to amplify single cycles of light. The key idea for amplification of octave-spanning spectra without loss of spectral bandwidth is to amplify the broad spectrum ``slice by slice'' in the frequency domain, i.e. in the Fourier plane of a 4f-setup. The striking advantages of this scheme, are its capability to amplify (more than) one octave of bandwidth without shorting the corresponding pulse duration. This is because ultrabroadband phase matching is not defined by the properties of the nonlinear crystal employed but the number of crystals employed. In the same manner, to increase the output energy one simply has to increase the spectral extension in the Fourier plane and to add one more crystal. Thus, increasing pulse energy and shortening its duration accompany each other. A proof of principle experiment was carried out at ALLS on the sub-two cycle IR beam line and yielded record breaking performance in the field of few-cycle IR lasers. 100 μJ two-cycle pulses from a hollow core fibre compression setup were amplified to 1.43mJ without distorting spatial or temporal properties. Pulse duration at the input of FOPA and after FOPA remains the same. Recently, we have started upgrading this system to be pumped by 250 mJ to reach 40 mJ two-cycle IR few-cycle pulses and latest results will be presented at the conference. Furthermore, the extension of the concept of FOPA to other nonlinear optical processes will be discussed. Frequency domain nonlinear optics.

  15. Transfer of high domain knowledge to a similar domain.

    PubMed

    Jessup, Ryan K

    2009-01-01

    Researchers have widely examined domain knowledge yet rarely investigate the transfer of knowledge from one domain to another. This study sought to fill in the literature gap concerning the impact of domain knowledge on memory in a similar situation. Specifically, this study examined whether high knowledge of baseball could enhance memory for the similar yet unknown domain of cricket, using a 2 (knowledge) x 2 (prime) design. An interaction occurred, indicating that when primed, baseball knowledge improves memory for cricket events in participants with high baseball knowledge but reduces memory in their low-knowledge counterparts. These results suggest that extensive knowledge in one domain allows it to serve as an organizational framework for incoming information in a similar domain; conversely, priming poorly understood domain knowledge results in negative transfer. PMID:19353932

  16. Surface forcing of the infrared cooling profile over the Tibetan Plateau. I - Influence of relative longwave radiative heating at high altitude. II - Cooling-rate variation over large-scale plateau domain during summer monsoon transition

    NASA Technical Reports Server (NTRS)

    Smith, Eric A.; Shi, Lei

    1992-01-01

    The role of the Tibetan Plateau on the behavior of the surface longwave radiation budget is investigated, and the behavior of the vertical profile of longwave cooling over the plateau, including its diurnal variation, is quantified. A medium spectral-resolution IR radiative transfer model utilizing a simple modification for applications in idealized complex (valley) terrain is developed for the investigation. An understanding of how surface and elevation biophysical factors, which are highly variable over the large-scale plateau domain, regulate the spatial distribution of clear-sky IR cooling during the transition phase of the summer monsoon, is described.

  17. 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

  18. Crystallographic studies on protein misfolding: Domain swapping and amyloid formation in the SH3 domain.

    PubMed

    Cámara-Artigas, Ana

    2016-07-15

    Oligomerization by 3D domain swapping is found in a variety of proteins of diverse size, fold and function. In the early 1960s this phenomenon was postulated for the oligomers of ribonuclease A, but it was not until the 1990s that X-ray diffraction provided the first experimental evidence of this special manner of oligomerization. Nowadays, structural information has allowed the identification of these swapped oligomers in over one hundred proteins. Although the functional relevance of this phenomenon is not clear, this alternative folding of protomers into intertwined oligomers has been related to amyloid formation. Studies on proteins that develop 3D domain swapping might provide some clues on the early stages of amyloid formation. The SH3 domain is a small modular domain that has been used as a model to study the basis of protein folding. Among SH3 domains, the c-Src-SH3 domain emerges as a helpful model to study 3D domain swapping and amyloid formation. PMID:26924596

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

    PubMed

    Culbertson, Jennifer; Kirby, Simon

    2015-01-01

    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

  20. NMR studies of the R2 repeat and related peptide fragments of the DNA binding domain of c-Myb. New light on the structure and folding of R2.

    NASA Astrophysics Data System (ADS)

    Ségalas, I.; Desjardins, S.; Oulyadi, H.; Prigent, Y.; Tribouillard, S.; Bernardi, E.; Schoofs, A. R.; Davoust1, D.; Toma, F.

    1999-10-01

    The solution structure of the R2 repeat of the DNA binding domain of the protooncogene c-Myb contains a N-terminal structural motif comprising two antiparallel helices. The motif is stabilized by interactions involving conserved residues. The recognition region in C-terminal position is flexible. This structure differs from that of R2 of another c-Myb protein. La structure en solution de la répétition R2 du domaine de liaison à l'ADN du protooncogène c-Myb possède un motif à deux hélices antiparallèles dans la moitié N-terminale, stabilisé par des interactions entre résidus conservés. La région de reconnaissance à l'ADN en position C-terminale est flexible. Cette structure diffère de celle montrée pour la répétition R2 d'une autre protéine c-Myb.

  1. Nano and micro reoriented domains and their relation with the crystal structure in the New Fe1.5Zn1.5B7O13Cl boracite.

    PubMed

    Ulloa-Godínez, S; Barrera, A; Rosales, I; Bucio, L; Castillon, F F; Farias, M H; Siqueiros, J M; Campa-Molina, J

    2011-06-01

    New iron-zinc chlorine single crystals of Fe1.5Zn1.5B7O13Cl boracite were grown by chemical transport reactions in closed quartz ampoules, at a temperature of 1173 K. The crystal structure was characterized by X-ray powder diffraction (XRD) using the Rietveld refinement method and belongs to the trigonal/rombohedral system with space group R3c (No. 161). The cell parameters were a = 8.5726(1) angstroms, c = 21.0116(4) angstroms, V = 1337.26(3) angstroms3 and Z = 6. The refinement successfully proceeded and ended with sound merit figure values chi2 = 2.25, R(B) = 6.12%. Chemical analysis was performed with X-ray energy dispersive spectroscopy (EDS) and X-ray fluorescence (XRF). Ferroelectric nano and micro reoriented domains were found in this material using polarizing optical microscopy (PLM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The examination by TEM showed that in the trigonal/rombohedral system of Fe1.5Zn1.5B7O13Cl nanodomain structures exist. Thin (50-100 nm) mostly planar domains parallel to (100) were frequently observed in Fe1.5Zn1.5B7O13Cl boracite. PMID:21770219

  2. POU domain factors in neural development.

    PubMed

    Schonemann, M D; Ryan, A K; Erkman, L; McEvilly, R J; Bermingham, J; Rosenfeld, M G

    1998-01-01

    contacts are also conserved. A homodimer of the Pit-1 POU domain was crystallized bound to a Pit-1 dimer DNA element that is closely related to a site in the proximal promoter of the prolactin gene. The structure of the Pit-1 POU domain on DNA is very similar to that of Oct-1, and the Pit-1 POU-homeodomain/DNA structure is strikingly similar to that of other homeodomains, including the Oct-1 POU-homeodomain. The DNA contacts made by the Pit-1 POU-specific domain are also similar to those of Oct-1 and conserved with many made by the prokaryotic repressors. In the Oct-1 crystal, the POU-specific domain recognizes a GCAT half-site, while the corresponding sequence recognized by the Pit-1 POU-specific domain, GTAT, is on the opposing strand. As a result, the orientation of the Pit-1 POU-specific domain relative to the POU-homeodomain is flipped, as compared to the Oct-1 crystal structure, indicating the remarkable flexibility of the POU-specific domain in adapting to variations in sequence within the site. Also in contrast to the Oct-1 monomer structure is the observation that the POU-specific and POU-homeodomain of each Pit-1 molecule make major groove contacts on the same face of the DNA, consistent with the constraints imposed by its 15 amino acid linker. As a result, the Pit-1 POU domain homodimer essentially surrounds its DNA binding site. In the Pit-1 POU domain homodimer the dimerization interface is formed between the C-terminal end of helix 3 of the POU-homeodomain of one Pit-1 molecule and the N-terminus of helix 1 and the loop between helices 3 and 4 of the POU-specific domain of the other Pit-1 molecule. In contrast to other homeodomain crystal structures, the C-terminus of helix 3 in the Pit-1 POU-homeo-domain has an extended structure. (ABSTRACT TRUNCATED) PMID:10026784

  3. Photo-induced poly-domain to mono-domain switching in ultrathin PbTiO3 films

    NASA Astrophysics Data System (ADS)

    Vailionis, A.; Meyer, R.; McIntyre, P. C.

    2010-03-01

    Ferroelectric (FE) domain structures play a crucial role in polarization switching dynamics, ferroelectric random access memory (FRAM) data retention and polarization fatigue and it is therefore of practical importance to gain a more fundamental understanding of the origin of the transition between poly-domain and mono-domain states. Methods that promote the mono-domain state in the FE films are also of interest for model studies of ferroelectricity and its dimensional scaling. We investigate a novel poly-domain to mono-domain (P-M) switching mechanism in thin ferroelectric PbTiO3 (PTO) films induced by ultraviolet (UV) light illumination. The switching occurs within minutes if a sample is irradiated with light of wavelength < 390 nm which corresponds to a photon energy that is roughly equivalent to the band gap of PbTiO3 (3.2 eV). Based on a developed electrostatic model, we show that the observed phenomenon is related to photo generation of free carriers at the PbTiO3/SrTiO3 interface which effectively screens the PTO polarization charge at the interface and therefore promotes the transition of the ferroelectric film from a poly-domain to a mono-domain state. The model successfully describes not only the observed illumination effects on PTO stripe domain patterns but also a longer-term poly-domain to mono-domain (P-M) transition that occurs without intentional illumination.

  4. STAS Domain Structure and Function

    PubMed Central

    Sharma, Alok K.; Rigby, Alan C.; Alper, Seth L.

    2011-01-01

    Pendrin shares with nearly all SLC26/SulP anion transporters a carboxy-terminal cytoplasmic segment organized around a Sulfate Transporter and Anti-Sigma factor antagonist (STAS) domain. STAS domains of divergent amino acid sequence exhibit a conserved fold of 4 β strands interspersed among 5 α helices. The first STAS domain proteins studied were single-domain anti-sigma factor antagonists (anti-anti-σ). These anti-anti-σ indirectly stimulate bacterial RNA polymerase by inactivating inhibitory anti-σ kinases, liberating σ factors to direct specific transcription of target genes or operons. Some STAS domains are nucleotide-binding phosphoproteins or nucleotidases. Others are interaction/transduction modules within multidomain sensors of light, oxygen and other gasotransmitters, cyclic nucleotides, inositol phosphates, and G proteins. Additional multidomain STAS protein sequences suggest functions in sensing, metabolism, or transport of nutrients such as sugars, amino acids, lipids, anions, vitamins, or hydrocarbons. Still other multidomain STAS polypeptides include histidine and serine/threonine kinase domains and ligand-activated transcription factor domains. SulP/SLC26 STAS domains and adjacent sequences interact with other transporters, cytoskeletal scaffolds, and with enzymes metabolizing transported anion substrates, forming putative metabolons. STAS domains are central to membrane targeting of many SulP/SLC26 anion transporters, and STAS domain mutations are associated with at least three human recessive diseases. This review summarizes STAS domain structure and function. PMID:22116355

  5. 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. PMID:25820699

  6. Domain walls as probes of gravity

    SciTech Connect

    Dvali, Gia; Gabadadze, Gregory; Pujolas, Oriol; Rahman, Rakibur

    2007-06-15

    We show that domain walls are probes that enable one to distinguish large-distance modified gravity from general relativity (GR) at short distances. For example, low-tension domain walls are stealth in modified gravity, while they do produce global gravitational effects in GR. We demonstrate this by finding exact solutions for various domain walls in the DGP model. A wall with tension lower than the fundamental Planck scale does not inflate and has no gravitational effects on a 4D observer, since its 4D tension is completely screened by gravity itself. We argue that this feature remains valid in a generic class of models of infrared modified gravity. As a byproduct, we obtain exact solutions for supermassive codimension-2 branes.

  7. Domain walls and the creation of strings

    NASA Astrophysics Data System (ADS)

    Bergshoeff, Eric; Gran, Ulf; Linares, Román; Nielsen, Mikkel; Roest, Diederik

    2003-08-01

    The phenomenon of creation of strings, occurring when particles pass through a domain wall and related to the Hanany Witten effect via dualities, is discussed in ten and nine dimensions. We consider both the particle actions in massive backgrounds and the 1/4-supersymmetric particle string domain-wall supergravity solutions and discuss their physical interpretation. In 10D we discuss the D0 F1 D8 system in massive IIA theory while in 9D the SL(2, Bbb R)-generalization is constructed. It consists of (p, q)-particles, (r, s)-strings and the double domain-wall solution of the three different 9D gauged supergravities where a subgroup of SL(2, Bbb R) is gauged.

  8. Targeting SH2 domains in breast cancer

    PubMed Central

    Morlacchi, Pietro; Robertson, Fredika M; Klostergaard, Jim; McMurray, John S

    2014-01-01

    Breast cancer is among the most commonly diagnosed cancer types in women worldwide and is the second leading cause of cancer-related disease in the USA. SH2 domains recruit signaling proteins to phosphotyrosine residues on aberrantly activated growth factor and cytokine receptors and contribute to cancer cell cycling, metastasis, angiogenesis and so on. Herein we review phosphopeptide mimetic and small-molecule approaches targeting the SH2 domains of Grb2, Grb7 and STAT3 that inhibit their targets and reduce proliferation in in vitro breast cancer models. Only STAT3 inhibitors have been evaluated in in vivo models and have led to tumor reduction. Taken together, these studies suggest that targeting SH2 domains is an important approach to the treatment of breast cancer. PMID:25495984

  9. Beyond the Number Domain

    PubMed Central

    Cantlon, Jessica F.; Platt, Michael L.; Brannon, Elizabeth M.

    2009-01-01

    In a world without numbers, we would be unable to build a skyscraper, hold a national election, plan a wedding, or pay for a chicken at the market. The numerical symbols used in all these behaviors build on the approximate number system (ANS) which represents the number of discrete objects or events as a continuous mental magnitude. In this review, we first discuss evidence that the ANS bears a set of behavioral and brain signatures that are universally displayed across animal species, human cultures, and development. We then turn to the question of whether the ANS constitutes a specialized cognitive and neural domain--a question central to understanding how this system works, the nature of its evolutionary and developmental trajectory, and its physical instantiation in the brain. PMID:19131268

  10. Crystallization of PTP Domains.

    PubMed

    Levy, Colin; Adams, James; Tabernero, Lydia

    2016-01-01

    Protein crystallography is the most powerful method to obtain atomic resolution information on the three-dimensional structure of proteins. An essential step towards determining the crystallographic structure of a protein is to produce good quality crystals from a concentrated sample of purified protein. These crystals are then used to obtain X-ray diffraction data necessary to determine the 3D structure by direct phasing or molecular replacement if the model of a homologous protein is available. Here, we describe the main approaches and techniques to obtain suitable crystals for X-ray diffraction. We include tools and guidance on how to evaluate and design the protein construct, how to prepare Se-methionine derivatized protein, how to assess the stability and quality of the sample, and how to crystallize and prepare crystals for diffraction experiments. While general strategies for protein crystallization are summarized, specific examples of the application of these strategies to the crystallization of PTP domains are discussed. PMID:27514806

  11. Fifth Graders Metacognitive Knowledge: General or Domain-Specific?

    ERIC Educational Resources Information Center

    Neuenhaus, Nora; Artelt, Cordula; Lingel, Klaus; Schneider, Wolfgang

    2011-01-01

    The purpose of the present study was to investigate the structure of metacognitive knowledge in fifth grade pupils and its relation to school achievement. Since the structure of metacognitive knowledge is controversially discussed with little empirical evidence for either its domain specificity or its domain transferability, the debate remains…

  12. The Influence of Domain Specificity on Motivation in Physical Education

    ERIC Educational Resources Information Center

    Shen, Bo; McCaughtry, Nate; Martin, Jeffrey

    2008-01-01

    With the assumption that domain specificity would significantly influence students' motivation, our study was designed to investigate between- and within-domain relations of task value, perceived autonomy and competence, and achievement goal orientations across physical education and mathematics. Urban adolescents (N = 273, ages 12-14 years)…

  13. 43 CFR 3110.5-2 - Public domain.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Public domain. 3110.5-2 Section 3110.5-2 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT... Public domain. (a) If the lands have been surveyed under the public land rectangular survey system,...

  14. 43 CFR 3110.5-2 - Public domain.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Public domain. 3110.5-2 Section 3110.5-2 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT... Public domain. (a) If the lands have been surveyed under the public land rectangular survey system,...

  15. 43 CFR 3110.5-2 - Public domain.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Public domain. 3110.5-2 Section 3110.5-2 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT... Public domain. (a) If the lands have been surveyed under the public land rectangular survey system,...

  16. Protein Complex Interactor Analysis and Differential Activity of KDM3 Subfamily Members Towards H3K9 Methylation

    PubMed Central

    Brauchle, Michael; Yao, Zhiping; Arora, Rishi; Thigale, Sachin; Clay, Ieuan; Inverardi, Bruno; Fletcher, Joy; Taslimi, Paul; Acker, Michael G.; Gerrits, Bertran; Voshol, Johannes; Bauer, Andreas; Schübeler, Dirk; Bouwmeester, Tewis; Ruffner, Heinz

    2013-01-01

    Histone modifications play an important role in chromatin organization and gene regulation, and their interpretation is referred to as epigenetic control. The methylation levels of several lysine residues in histone tails are tightly controlled, and JmjC domain-containing proteins are one class of broadly expressed enzymes catalyzing methyl group removal. However, several JmjC proteins remain uncharacterized, gaps persist in understanding substrate recognition, and the integration of JmjC proteins into signaling pathways is just emerging. The KDM3 subfamily is an evolutionarily conserved group of histone demethylase proteins, thought to share lysine substrate specificity. Here we use a systematic approach to compare KDM3 subfamily members. We show that full-length KDM3A and KDM3B are H3K9me1/2 histone demethylases whereas we fail to observe histone demethylase activity for JMJD1C using immunocytochemical and biochemical approaches. Structure-function analyses revealed the importance of a single amino acid in KDM3A implicated in the catalytic activity towards H3K9me1/2 that is not conserved in JMJD1C. Moreover, we use quantitative proteomic analyses to identify subsets of the interactomes of the 3 proteins. Specific interactor candidates were identified for each of the three KDM3 subfamily members. Importantly, we find that SCAI, a known transcriptional repressor, interacts specifically with KDM3B. Taken together, we identify substantial differences in the biology of KDM3 histone demethylases, namely enzymatic activity and protein-protein interactions. Such comparative approaches pave the way to a better understanding of histone demethylase specificity and protein function at a systems level and are instrumental in identifying the more subtle differences between closely related proteins. PMID:23593242

  17. Dynamical domain wall and localization

    NASA Astrophysics Data System (ADS)

    Toyozato, Yuta; Higuchi, Masafumi; Nojiri, Shin'ichi

    2016-03-01

    Based on the previous works (Toyozato et al., 2013 [24]; Higuchi and Nojiri, 2014 [25]), we investigate the localization of the fields on the dynamical domain wall, where the four-dimensional FRW universe is realized on the domain wall in the five-dimensional space-time. Especially we show that the chiral spinor can localize on the domain wall, which has not been succeeded in the past works as the seminal work in George et al. (2009) [23].

  18. Impaired binding of standard initiation factors eIF3b, eIF4G and eIF4B to domain V of the live-attenuated coxsackievirus B3 Sabin3-like IRES - alternatives for 5′UTR-related cardiovirulence mechanisms

    PubMed Central

    2013-01-01

    Abstract Internal ribosome entry site (IRES) elements fold into highly organized conserved secondary and probably tertiary structures that guide the ribosome to an internal site of the RNA at the IRES 3′end. The composition of the cellular proteome is under the control of multiple processes, one of the most important being translation initiation. In each poliovirus Sabin vaccine strain, a single point mutation in the IRES secondary-structure domain V is a major determinant of neurovirulence and translation attenuation. Here we are extrapolating poliovirus findings to a genomic related virus named coxsackievirus B3 CVB3); a causative agent of viral myocarditis. We have previously reported that Sabin3-like mutation (U473 → C) introduced in the domain V sequence of the CVB3 IRES led to a defective mutant with a serious reduction in translation efficiency and ribosomal initiation complex assembly, besides an impaired RNA-protein binding pattern. With the aim to identify proteins interacting with both CVB3 wild-type and Sabin3-like domain V RNAs and to assess the effect of the Sabin3-like mutation on these potential interactions, we have used a proteomic approach. This procedure allowed the identification of three RNA-binding proteins interacting with the domain V: eIF4G (p220), eIF3b (p116) and eIF4B (p80). Moreover, we report that this single-nucleotide exchange impairs the interaction pattern and the binding affinity of these standard translation initiation factors within the IRES domain V of the mutant strain. Taken together, these data indicate how this decisive Sabin3-like mutation mediates viral translation attenuation; playing a key role in the understanding of the cardiovirulence attenuation within this construct. Hence, these data provide further evidence for the crucial role of RNA structure for the IRES activity, and reinforce the idea of a distribution of function between the different IRES structural domains. Virtual slide The virtual slide(s) for

  19. Domain transfer multiple kernel learning.

    PubMed

    Duan, Lixin; Tsang, Ivor W; Xu, Dong

    2012-03-01

    Cross-domain learning methods have shown promising results by leveraging labeled patterns from the auxiliary domain to learn a robust classifier for the target domain which has only a limited number of labeled samples. To cope with the considerable change between feature distributions of different domains, we propose a new cross-domain kernel learning framework into which many existing kernel methods can be readily incorporated. Our framework, referred to as Domain Transfer Multiple Kernel Learning (DTMKL), simultaneously learns a kernel function and a robust classifier by minimizing both the structural risk functional and the distribution mismatch between the labeled and unlabeled samples from the auxiliary and target domains. Under the DTMKL framework, we also propose two novel methods by using SVM and prelearned classifiers, respectively. Comprehensive experiments on three domain adaptation data sets (i.e., TRECVID, 20 Newsgroups, and email spam data sets) demonstrate that DTMKL-based methods outperform existing cross-domain learning and multiple kernel learning methods. PMID:21646679

  20. Hydrophilic Domains Enhance Nanobubble Stability.

    PubMed

    Nishiyama, Takashi; Takahashi, Koji; Ikuta, Tatsuya; Yamada, Yutaka; Takata, Yasuyuki

    2016-05-18

    Highly stable nanoscale gas states at solid/liquid interfaces, referred to as nanobubbles, have been widely studied for over a decade. In this study, nanobubbles generated on a hydrophobic Teflon amorphous fluoroplastic thin film in the presence and absence of hydrophilic carbon domains are investigated by peak force quantitative nanomechanics. On the hydrophobic surface without hydrophilic domains, a small number of nanobubbles are generated and then rapidly decrease in size. On the hydrophobic surface with hydrophilic domains, the hydrophilic domains have a significant effect on the generation and stability of nanobubbles, with bubbles remaining on the surface for up to three days. PMID:26864857

  1. 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.

  2. Mapping the Moral Domain

    PubMed Central

    Graham, Jesse; Nosek, Brian A.; Haidt, Jonathan; Iyer, Ravi; Koleva, Spassena; Ditto, Peter H.

    2010-01-01

    The moral domain is broader than the empathy and justice concerns assessed by existing measures of moral competence, and it is not just a subset of the values assessed by value inventories. To fill the need for reliable and theoretically-grounded measurement of the full range of moral concerns, we developed the Moral Foundations Questionnaire (MFQ) based on a theoretical model of five universally available (but variably developed) sets of moral intuitions: Harm/care, Fairness/reciprocity, Ingroup/loyalty, Authority/respect, and Purity/sanctity. We present evidence for the internal and external validity of the scale and the model, and in doing so present new findings about morality: 1. Comparative model fitting of confirmatory factor analyses provides empirical justification for a five-factor structure of moral concerns. 2. Convergent/discriminant validity evidence suggests that moral concerns predict personality features and social group attitudes not previously considered morally relevant. 3. We establish pragmatic validity of the measure in providing new knowledge and research opportunities concerning demographic and cultural differences in moral intuitions. These analyses provide evidence for the usefulness of Moral Foundations Theory in simultaneously increasing the scope and sharpening the resolution of psychological views of morality. PMID:21244182

  3. Ontology development for Sufism domain

    NASA Astrophysics Data System (ADS)

    Iqbal, Rizwan

    2012-01-01

    Domain ontology is a descriptive representation of any particular domain which in detail describes the concepts in a domain, the relationships among those concepts and organizes them in a hierarchal manner. It is also defined as a structure of knowledge, used as a means of knowledge sharing to the community. An Important aspect of using ontologies is to make information retrieval more accurate and efficient. Thousands of domain ontologies from all around the world are available online on ontology repositories. Ontology repositories like SWOOGLE currently have over 1000 ontologies covering a wide range of domains. It was found that up to date there was no ontology available covering the domain of "Sufism". This unavailability of "Sufism" domain ontology became a motivation factor for this research. This research came up with a working "Sufism" domain ontology as well a framework, design of the proposed framework focuses on the resolution to problems which were experienced while creating the "Sufism" ontology. The development and working of the "Sufism" domain ontology are covered in detail in this research. The word "Sufism" is a term which refers to Islamic mysticism. One of the reasons to choose "Sufism" for ontology creation is its global curiosity. This research has also managed to create some individuals which inherit the concepts from the "Sufism" ontology. The creation of individuals helps to demonstrate the efficient and precise retrieval of data from the "Sufism" domain ontology. The experiment of creating the "Sufism" domain ontology was carried out on a tool called Protégé. Protégé is a tool which is used for ontology creation, editing and it is open source.

  4. Ontology development for Sufism domain

    NASA Astrophysics Data System (ADS)

    Iqbal, Rizwan

    2011-12-01

    Domain ontology is a descriptive representation of any particular domain which in detail describes the concepts in a domain, the relationships among those concepts and organizes them in a hierarchal manner. It is also defined as a structure of knowledge, used as a means of knowledge sharing to the community. An Important aspect of using ontologies is to make information retrieval more accurate and efficient. Thousands of domain ontologies from all around the world are available online on ontology repositories. Ontology repositories like SWOOGLE currently have over 1000 ontologies covering a wide range of domains. It was found that up to date there was no ontology available covering the domain of "Sufism". This unavailability of "Sufism" domain ontology became a motivation factor for this research. This research came up with a working "Sufism" domain ontology as well a framework, design of the proposed framework focuses on the resolution to problems which were experienced while creating the "Sufism" ontology. The development and working of the "Sufism" domain ontology are covered in detail in this research. The word "Sufism" is a term which refers to Islamic mysticism. One of the reasons to choose "Sufism" for ontology creation is its global curiosity. This research has also managed to create some individuals which inherit the concepts from the "Sufism" ontology. The creation of individuals helps to demonstrate the efficient and precise retrieval of data from the "Sufism" domain ontology. The experiment of creating the "Sufism" domain ontology was carried out on a tool called Protégé. Protégé is a tool which is used for ontology creation, editing and it is open source.

  5. Fractional diffusion on bounded domains

    DOE PAGESBeta

    Defterli, Ozlem; D'Elia, Marta; Du, Qiang; Gunzburger, Max Donald; Lehoucq, Richard B.; Meerschaert, Mark M.

    2015-03-13

    We found that the mathematically correct specification of a fractional differential equation on a bounded domain requires specification of appropriate boundary conditions, or their fractional analogue. In this paper we discuss the application of nonlocal diffusion theory to specify well-posed fractional diffusion equations on bounded domains.

  6. VOLUME CALCULATION OF RATS' ORGANS AND ITS APPLICATION IN THE VALIDATION OF THE VOLUME RELATION BETWEEN THE ABDOMINAL CAVITY AND THE HERNIAL SAC IN INCISIONAL HERNIAS WITH "LOSS OF ABDOMINAL DOMAIN"

    PubMed Central

    de ARAÚJO, Luz Marina Gonçalves; SERIGIOLLE, Leonardo Carvalho; GOMES, Helbert Minuncio Pereira; RODRIGUES, Daren Athiê Boy; LOPES, Carolina Marques; LEME, Pedro Luiz Squilacci

    2014-01-01

    Background The calculation of the volume ratio between the hernia sac and the abdominal cavity of incisional hernias is based on tomographic sections as well as the mathematical formula of the volume of the ellipsoid, which allows determining whether this is a giant hernia or there is a "loss of domain". As the images used are not exact geometric figures, the study of the volume of two solid organs of Wistar rats was performed to validate these calculations. Aim To correlate two methods for determining the volume of the kidney and spleen of rats, comparing a direct method of observation of the volume with the mathematical calculation of this value. Methods The volume of left kidney, geometrically more regular, and spleen, with its peculiar shape, of ten animals was established in cubic centimeters after complete immersion in water with the aid of a beaker graduated in millimeters. These values ​​were compared with those obtained by calculating the same volume with a specific mathematical formula: V = 4/3 × π × (r1 x r2 x r3). Data were compared and statistically analyzed by Student's t test. RESULTS: Although the average volume obtained was higher through the direct method (1.13 cm3 for the left kidney and 0.71 cm3 for the spleen) than the values ​​calculated with the mathematical formula (0.81 cm3 and 0.54 cm3), there were no statistically significant differences between the values ​​found for the two organs (p>0.05). Conclusion There was adequate correlation between the direct calculation of the volume of the kidney and spleen with the result of mathematical calculation of these values ​​in the animals' studies. PMID:25184766

  7. Polarized domains of myelinated axons.

    PubMed

    Salzer, James L

    2003-10-01

    The entire length of myelinated axons is organized into a series of polarized domains that center around nodes of Ranvier. These domains, which are crucial for normal saltatory conduction, consist of distinct multiprotein complexes of cell adhesion molecules, ion channels, and scaffolding molecules; they also differ in their diameter, organelle content, and rates of axonal transport. Juxtacrine signals from myelinating glia direct their sequential assembly. The composition, mechanisms of assembly, and function of these molecular domains will be reviewed. I also discuss similarities of this domain organization to that of polarized epithelia and present emerging evidence that disorders of domain organization and function contribute to the axonopathies of myelin and other neurologic disorders. PMID:14556710

  8. Evidence for PDZ domains in bacteria, yeast, and plants.

    PubMed Central

    Ponting, C. P.

    1997-01-01

    Several dozen signaling proteins are now known to contain 80-100 residue repeats, called PDZ (or DHR or GLGF) domains, several of which interact with the C-terminal tetrapeptide motifs X-Ser/Thr-X-Val-COO- of ion channels and/or receptors. PDZ domains have previously been noted only in mammals, flies, and worms, suggesting that the primordial PDZ domain arose relatively late in eukaryotic evolution. Here, techniques of sequence analysis-including local alignment, profile, and motif database searches-indicate that PDZ domain homologues are present in yeast, plants, and bacteria. It is suggested that two PDZ domains occur in bacterial high-temperature requirement A (htrA) and one in tail-specific protease (tsp) homologues, and that a yeast htrA homologue contains four PDZ domains. Sequence comparisons suggest that the spread of PDZ domains in these diverse organisms may have occurred via horizontal gene transfer. The known affinity of Escherichia coli tsp for C-terminal polypeptides is proposed to be mediated by its PDZ-like domain, in a similar manner to the binding of C-terminal polypeptides by animal PDZ domains. PMID:9041651

  9. The monocyte binding domain(s) on human immunoglobulin G.

    PubMed

    Woof, J M; Nik Jaafar, M I; Jefferis, R; Burton, D R

    1984-06-01

    Monocyte binding has previously been assigned to the C gamma 3 domain of human immunoglobulin G (IgG) largely on the ability of the pFc' fragment to inhibit the monocyte-IgG interaction. This ability is markedly reduced compared to the intact parent IgG. We find this result with a conventional pFc' preparation but this preparation is found to contain trace contamination of parent IgG as demonstrated by reactivity with monoclonal antibodies directed against C gamma 2 domain and light-chain epitopes of human IgG. Extensive immunoaffinity purification of the pFc' preparation removes its inhibitory ability indicating that this originates in the trace contamination of parent IgG (or Fc). Neither of the human IgG1 paraproteins TIM, lacking the C gamma 2 domain, or SIZ, lacking the C gamma 3 domain, are found to inhibit the monocyte-IgG interaction. The hinge-deleted IgG1 Dob protein shows little or no inhibitory ability. Indirect evidence for the involvement of the C gamma 2 domain in monocyte binding is considered. We suggest finally that the site of interaction is found either on the C gamma 2 domain alone or between the C gamma 2 and C gamma 3 domains. PMID:6235444

  10. 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…

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

    DOE PAGESBeta

    Venkatesan, Swaminathan; Chen, Jihua; Ngo, Evan C.; Dubey, Ashish; Khatiwada, Devendra; Zhang, Cheng; Qiao, Qiquan

    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 (PC60BM) and indene-C60 bis-adduct (IC60BA). 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:IC60BA solar cells while P3HT:PC60BM 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 diffraction (XRD) results showed that ICBAmore » mixes with disordered P3HT much more readily than PC60BM which leads to lower short circuit current density and fill factor for P3HT:IC60BA cells annealed below 120°C. Annealing above 120°C improves the crystallinity of P3HT in case of P3HT:IC60BA whereas in P3HT:PC60BM 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

  12. 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.

  13. SARS Coronavirus-unique Domain (SUD): Three-domain Molecular Architecture in Solution and RNA Binding

    PubMed Central

    Johnson, Margaret A.; Chatterjee, Amarnath; Neuman, Benjamin W.; Wüthrich, Kurt

    2010-01-01

    The nonstructural protein 3 (nsp3) of the severe acute respiratory syndrome coronavirus (SARS-CoV) includes a “SARS-unique region” (SUD) consisting of three globular domains separated by short linker peptide segments. This paper reports NMR structure determinations of the C-terminal domain (SUD-C) and of a two-domain construct (SUD-MC) containing the middle domain (SUD-M) and the C-terminal domain, and NMR data on the conformational states of the N-terminal domain (SUD-N) and the SUD-NM two-domain construct. Both SUD-N and SUD-NM are monomeric and globular in solution, and in SUD-NM there is high mobility in the two-residue interdomain linking sequence, with no preferred relative orientation of the two domains. SUD-C adopts a frataxin-like fold and has structural similarity to DNA-binding domains of DNA-modifying enzymes. The structures of both SUD-M (previously determined) and SUD-C (from the present study) are maintained in SUD-MC, where the two domains are flexibly linked. Gel shift experiments showed that both SUD-C and SUD-MC bind to single-stranded RNA and recognize purine bases more strongly than pyrimidine bases, whereby SUD-MC binds to a more restricted set of purine-containing RNA sequences than SUD-M. NMR chemical shift perturbation experiments with observation of the 15N-labeled proteins further resulted in the delineation of the RNA binding sites, i.e., in SUD-M a positively charged surface area with a pronounced cavity, and in SUD-C several residues of an antiparallel β-sheet. Overall, the present data provide evidence for molecular mechanisms involving concerted actions of SUD-M and SUD-C, which result in specific RNA-binding that might be unique to the SUD, and thus to the SARS-CoV. PMID:20493876

  14. Information Fusion: Moving from domain independent to domain literate approaches

    NASA Astrophysics Data System (ADS)

    McGuinness, D.

    2008-12-01

    Information Fusion has been a focus of research within the field of computer science for a number of years. Numerous environments aimed at general schema evaluation, diagnosis, and evolution have evolved within those communities including for example the Chimaera Ontology Evolution Environment and the Prompt environment for mapping schema alignment. General (domain independent) efforts have produced useful research results and numerous tools, however these results have predominantly been generated and used by computer scientists and have been focused largely on information schema integration and diagnosis. More recently semantically-enabled web-centric approaches have emerged that utilize domain knowledge to provide tools and services aimed at natural scientists needs for data fusion. In this talk, we will introduce some foundations for information fusion and provide deployed examples of how these foundations and evolving tools have been and are being used today in natural science domains by domain scientists. Some examples will be provided from deployed virtual observatory settings.

  15. Matching Recommendation Technologies and Domains

    NASA Astrophysics Data System (ADS)

    Burke, Robin; Ramezani, Maryam

    Recommender systems form an extremely diverse body of technologies and approaches. The chapter aims to assist researchers and developers to identify the recommendation technologies that are most likely to be applicable to different domains of recommendation. Unlike other taxonomies of recommender systems, our approach is centered on the question of knowledge: what knowledge does a recommender system need in order to function, and where does that knowledge come from? Different recommendation domains (books vs condominiums, for example) provide different opportunities for the gathering and application of knowledge. These considerations give rise to a mapping between domain characteristics and recommendation technologies.

  16. 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

  17. POU proteins bend DNA via the POU-specific domain.

    PubMed Central

    Verrijzer, C P; van Oosterhout, J A; van Weperen, W W; van der Vliet, P C

    1991-01-01

    POU proteins constitute a family of ubiquitous as well as cell type-specific transcription factors that share the conserved POU DNA binding domain. This domain consists of two distinct subdomains, a POU-specific domain and a POU homeodomain, that are both required for high affinity sequence-specific DNA binding. In a circular permutation assay, several POU proteins, including Oct-1, Oct-2A, Oct-6 and Pit-1, demonstrated a position dependent mobility of the protein-DNA complexes, suggesting induction of DNA bending. This was confirmed by detection of relative bend direction, using pre-bent DNA, and by enhanced ligase mediated cyclization. Bending was caused by interaction with the POU domain. By contrast, binding of the POU homeodomain did not distort the DNA structure, indicating that the POU-specific domain confers DNA bending. Images PMID:1915275

  18. Control of lateral domain spreading in congruent lithium niobate by selective proton exchange

    NASA Astrophysics Data System (ADS)

    Grilli, S.; Canalias, C.; Laurell, F.; Ferraro, P.; De Natale, P.

    2006-07-01

    Proton exchange was observed to increase the poling voltage for congruent lithium niobate. Patterned proton exchange was then used to control domain nucleation and inhibit broadening of reversed domains. Periodically proton exchanged samples were used to form domain gratings by electric field poling just using planar electrodes and without need for poling current control. The reversed domain gratings had a duty cycle faithfully reproducing that of the proton exchanged pattern with straight domain walls parallel to the x face, thus demonstrating that high-fidelity reversed domain patterning is possible to obtain by a relatively simple process.

  19. Engineered CH2 domains (nanoantibodies).

    PubMed

    Dimitrov, Dimiter S

    2009-01-01

    Currently, almost all FDA approved therapeutic antibodies (except ReoPro, Lucentis and Cimzia which are Fabs), and the vast majority of those in clinical trials are full-size antibodies mostly in IgG1 format of about 150 kDa size. A fundamental problem for such large molecules is their poor penetration into tissues (e.g., solid tumors) and poor or absent binding to regions on the surface of some molecules (e.g., on the HIV envelope glycoprotein) which are fully accessible only by molecules of smaller size. Therefore, much work especially during the last decade has been aimed at developing novel scaffolds of much smaller size and high stability. Here I briefly describe a proposition to use the immunoglobulin (Ig) constant CH2 domain (CH3 for IgE and IgM) as a scaffold. CH2 is critical for the Ig effector functions. Isolated CH2 is stable monomer in contrast to all other constant domains and most of the variable domains. CH2 and engineered CH2 domains with improved stability can be used as scaffolds for construction of libraries containing diverse binders to various antigens. Such binders based on a CH2 scaffold could also confer some effector functions. Because the CH2 domains are the smallest independently folded antibody domains that can be engineered to contain simultaneously antigen-binding sites and binding sites mediating effector and stability functions, and to distinguish them from domain antibodies which are used to denote engineered VH or VL domains or nanobodies which are used to denote camelid VHH, I termed them nanoantibodies (nAbs). PMID:20046570

  20. Domain Walls with Strings Attached

    SciTech Connect

    Shmakova, Marina

    2001-08-20

    We have constructed a bulk and brane action of IIA theory which describes a pair of BPS domain walls on S{sub 1}/Z{sub 2}, with strings attached. The walls are given by two orientifold O8-planes with coincident D8-branes and F1-D0-strings are stretched between the walls. This static configuration satisfies all matching conditions for the string and domain wall sources and has 1/4 of unbroken supersymmetry.

  1. Scalable video coding in frequency domain

    NASA Astrophysics Data System (ADS)

    Civanlar, Mehmet R.; Puri, Atul

    1992-11-01

    Scalable video coding is important in a number of applications where video needs to be decoded and displayed at a variety of resolution scales. It is more efficient than simulcasting, in which all desired resolution scales are coded totally independent of one another within the constraint of a fixed available bandwidth. In this paper, we focus on scalability using the frequency domain approach. We employ the framework proposed for the ongoing second phase of Motion Picture Experts Group (MPEG-2) standard to study the performance of one such scheme and investigate improvements aimed at increasing its efficiency. Practical issues related to multiplexing of encoded data of various resolution scales to facilitate decoding are considered. Simulations are performed to investigate the potential of a chosen frequency domain scheme. Various prospects and limitations are also discussed.

  2. Inhomogeneous rotation in ferroelastic domain patterns

    NASA Astrophysics Data System (ADS)

    Jacobs, A. E.; Curnoe, S. H.; Desai, R. C.

    2004-03-01

    We study static, two-dimensional domain patterns obtained by numerical minimization of the strain energy for proper triangular→centered-rectangular (T-CR) and square→rectangular ferroelastics. Applications are made to hexagonal→orthorhombic and related materials (lead orthovanadate, Mg_3Cd, Ta_4N, etc) and YBa_2Cu_3O_7-δ. Examinatin of the local rotation, the local energy density and the non-order-parameter strains reveals wedge and other disclinations responsible for the complexity of the patterns. The rotation might be observed in birefringence imaging. We report also unusual structures obtained near Tc in T-CR systems, including trapped high-T phase and pencil-like domains.

  3. 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

  4. Entropy gives rise to topologically associating domains.

    PubMed

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

    2016-07-01

    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

  5. LHC RF System Time-Domain Simulation

    SciTech Connect

    Mastorides, T.; Rivetta, C.; /SLAC

    2010-09-14

    Non-linear time-domain simulations have been developed for the Positron-Electron Project (PEP-II) and the Large Hadron Collider (LHC). These simulations capture the dynamic behavior of the RF station-beam interaction and are structured to reproduce the technical characteristics of the system (noise contributions, non-linear elements, and more). As such, they provide useful results and insight for the development and design of future LLRF feedback systems. They are also a valuable tool for the study of diverse longitudinal beam dynamics effects such as coupled-bunch impedance driven instabilities and single bunch longitudinal emittance growth. Results from these studies and related measurements from PEP-II and LHC have been presented in multiple places. This report presents an example of the time-domain simulation implementation for the LHC.

  6. Further insight into BRUTUS domain composition and functionality.

    PubMed

    Matthiadis, Anna; Long, Terri A

    2016-08-01

    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

  7. Highly Efficient Domain Walls Injection in Perpendicular Magnetic Anisotropy Nanowire

    NASA Astrophysics Data System (ADS)

    Zhang, S. F.; Gan, W. L.; Kwon, J.; Luo, F. L.; Lim, G. J.; Wang, J. B.; Lew, W. S.

    2016-04-01

    Electrical injection of magnetic domain walls in perpendicular magnetic anisotropy nanowire is crucial for data bit writing in domain wall-based magnetic memory and logic devices. Conventionally, the current pulse required to nucleate a domain wall is approximately ~1012 A/m2. Here, we demonstrate an energy efficient structure to inject domain walls. Under an applied electric potential, our proposed Π-shaped stripline generates a highly concentrated current distribution. This creates a highly localized magnetic field that quickly initiates the nucleation of a magnetic domain. The formation and motion of the resulting domain walls can then be electrically detected by means of Ta Hall bars across the nanowire. Our measurements show that the Π-shaped stripline can deterministically write a magnetic data bit in 15 ns even with a relatively low current density of 5.34 × 1011 A/m2. Micromagnetic simulations reveal the evolution of the domain nucleation – first, by the formation of a pair of magnetic bubbles, then followed by their rapid expansion into a single domain. Finally, we also demonstrate experimentally that our injection geometry can perform bit writing using only about 30% of the electrical energy as compared to a conventional injection line.

  8. Highly Efficient Domain Walls Injection in Perpendicular Magnetic Anisotropy Nanowire

    PubMed Central

    Zhang, S. F.; Gan, W. L.; Kwon, J.; Luo, F. L.; Lim, G. J.; Wang, J. B.; Lew, W. S.

    2016-01-01

    Electrical injection of magnetic domain walls in perpendicular magnetic anisotropy nanowire is crucial for data bit writing in domain wall-based magnetic memory and logic devices. Conventionally, the current pulse required to nucleate a domain wall is approximately ~1012 A/m2. Here, we demonstrate an energy efficient structure to inject domain walls. Under an applied electric potential, our proposed Π-shaped stripline generates a highly concentrated current distribution. This creates a highly localized magnetic field that quickly initiates the nucleation of a magnetic domain. The formation and motion of the resulting domain walls can then be electrically detected by means of Ta Hall bars across the nanowire. Our measurements show that the Π-shaped stripline can deterministically write a magnetic data bit in 15 ns even with a relatively low current density of 5.34 × 1011 A/m2. Micromagnetic simulations reveal the evolution of the domain nucleation – first, by the formation of a pair of magnetic bubbles, then followed by their rapid expansion into a single domain. Finally, we also demonstrate experimentally that our injection geometry can perform bit writing using only about 30% of the electrical energy as compared to a conventional injection line. PMID:27098108

  9. Highly Efficient Domain Walls Injection in Perpendicular Magnetic Anisotropy Nanowire.

    PubMed

    Zhang, S F; Gan, W L; Kwon, J; Luo, F L; Lim, G J; Wang, J B; Lew, W S

    2016-01-01

    Electrical injection of magnetic domain walls in perpendicular magnetic anisotropy nanowire is crucial for data bit writing in domain wall-based magnetic memory and logic devices. Conventionally, the current pulse required to nucleate a domain wall is approximately ~10(12) A/m(2). Here, we demonstrate an energy efficient structure to inject domain walls. Under an applied electric potential, our proposed Π-shaped stripline generates a highly concentrated current distribution. This creates a highly localized magnetic field that quickly initiates the nucleation of a magnetic domain. The formation and motion of the resulting domain walls can then be electrically detected by means of Ta Hall bars across the nanowire. Our measurements show that the Π-shaped stripline can deterministically write a magnetic data bit in 15 ns even with a relatively low current density of 5.34 × 10(11) A/m(2). Micromagnetic simulations reveal the evolution of the domain nucleation - first, by the formation of a pair of magnetic bubbles, then followed by their rapid expansion into a single domain. Finally, we also demonstrate experimentally that our injection geometry can perform bit writing using only about 30% of the electrical energy as compared to a conventional injection line. PMID:27098108

  10. Latent subspace sparse representation-based unsupervised domain adaptation

    NASA Astrophysics Data System (ADS)

    Shuai, Liu; Sun, Hao; Zhao, Fumin; Zhou, Shilin

    2015-12-01

    In this paper, we introduce and study a novel unsupervised domain adaptation (DA) algorithm, called latent subspace sparse representation based domain adaptation, based on the fact that source and target data that lie in different but related low-dimension subspaces. The key idea is that each point in a union of subspaces can be constructed by a combination of other points in the dataset. In this method, we propose to project the source and target data onto a common latent generalized subspace which is a union of subspaces of source and target domains and learn the sparse representation in the latent generalized subspace. By employing the minimum reconstruction error and maximum mean discrepancy (MMD) constraints, the structure of source and target domain are preserved and the discrepancy is reduced between the source and target domains and thus reflected in the sparse representation. We then utilize the sparse representation to build a weighted graph which reflect the relationship of points from the different domains (source-source, source- target, and target-target) to predict the labels of the target domain. We also proposed an efficient optimization method for the algorithm. Our method does not need to combine with any classifiers and therefore does not need train the test procedures. Various experiments show that the proposed method perform better than the competitive state of art subspace-based domain adaptation.

  11. 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.

  12. Localization of resistive domains in inhomogeneous superconductors

    SciTech Connect

    Gurevich, A.V.; Mints, R.G.

    1981-01-01

    The properties of resistive domains due to the Joule heating in inhomogeneous superconductors with transport currents are studied. The equilibrium of a domain at an inhomogeneity of arbitrary type and with dimensions much smaller than the dimensions of the domain is investigated. It is shown that resistive domains can become localized at inhomogeneities. The temperature distribution in a domain and the current--voltage characteristic of the domain are determined. The stability of localized domains is discussed. It is shown that such domains give rise to a hysteresis in the destruction (recovery) of the superconductivity by the transport current.

  13. Unconstrained invoice processing in the health insurance domain

    NASA Astrophysics Data System (ADS)

    Hurst, Matthew; Barney, Dave

    2003-01-01

    We present an overview of an information extraction application in the health insurance invoice processing domain. The system is novel in that it is not constrained by the document type - it has no explicit document model or document type classification phase. The system relies on constraints derived from a domain model, constraints derived from world state, and simple models of layout, including the use of labeled fields and the proximity of related information.

  14. Time domain referencing in intensity modulation fiber optic sensing systems

    NASA Technical Reports Server (NTRS)

    Adamovsky, Grigory

    1986-01-01

    Intensity modulation sensors are classified by the way in which the reference and signal channels are separated: in space, wavelength, or time domains. To implement the time-domain referencing, different types of fiber-optic loops have been used. A pulse of short duration sent into the loop results in a series of pulses of different amplitudes. The information about the measured parameter is retrieved from the relative amplitudes of pulses in the same train.

  15. Evolution of distinct EGF domains with specific functions

    PubMed Central

    Wouters, Merridee A.; Rigoutsos, Isidore; Chu, Carmen K.; Feng, Lina L.; Sparrow, Duncan B.; Dunwoodie, Sally L.

    2005-01-01

    EGF domains are extracellular protein modules cross-linked by three intradomain disulfides. Past studies suggest the existence of two types of EGF domain with three-disulfides, human EGF-like (hEGF) domains and complement C1r-like (cEGF) domains, but to date no functional information has been related to the two different types, and they are not differentiated in sequence or structure databases. We have developed new sequence patterns based on the different C-termini to search specifically for the two types of EGF domains in sequence databases. The exhibited sensitivity and specificity of the new pattern-based method represents a significant advancement over the currently available sequence detection techniques. We re-annotated EGF sequences in the latest release of Swiss-Prot looking for functional relationships that might correlate with EGF type. We show that important post-translational modifications of three-disulfide EGFs, including unusual forms of glycosylation and post-translational proteolytic processing, are dependent on EGF subtype. For example, EGF domains that are shed from the cell surface and mediate intercellular signaling are all hEGFs, as are all human EGF receptor family ligands. Additional experimental data suggest that functional specialization has accompanied subtype divergence. Based on our structural analysis of EGF domains with three-disulfide bonds and comparison to laminin and integrin-like EGF domains with an additional inter-domain disulfide, we propose that these hEGF and cEGF domains may have arisen from a four-disulfide ancestor by selective loss of different cysteine residues. PMID:15772310

  16. Predicting cognitive change within domains

    PubMed Central

    Duff, Kevin; Beglinger, Leigh J.; Moser, David J.; Paulsen, Jane S.

    2010-01-01

    Standardized regression based (SRB) formulas, a method for predicting cognitive change across time, traditionally use baseline performance on a neuropsychological measure to predict future performance on that same measure. However, there are instances in which the same tests may not be given at follow-up assessments (e.g., lack of continuity of provider, avoiding practice effects). The current study sought to expand this methodology by developing SRBs to predict performance on different tests within the same cognitive domain. Using a sample of 127 non-demented community-dwelling older adults assessed at baseline and after one year, two sets of SRBs were developed: 1. those predicting performance on the same test, and 2. those predicting performance on a different test within the same cognitive domain. The domains examined were learning and memory, processing speed, and language. Across both sets of SRBs, one year scores were significantly predicted by baseline scores, especially for the learning and memory and processing speed measures. Although SRBs developed for the same test were comparable to those developed for different tests within the same domain, less variance was accounted for as tests became less similar. The current results lend preliminary support for additional development of SRBs, both for same- and different-tests, as well as beginning to examine domain-based SRBs. PMID:20358479

  17. Expansion and Functional Divergence of Jumonji C-Containing Histone Demethylases: Significance of Duplications in Ancestral Angiosperms and Vertebrates1[OPEN

    PubMed Central

    Qian, Shengzhan; Wang, Yingxiang; Ma, Hong; Zhang, Liangsheng

    2015-01-01

    Histone modifications, such as methylation and demethylation, are crucial mechanisms altering chromatin structure and gene expression. Recent biochemical and molecular studies have uncovered a group of histone demethylases called Jumonji C (JmjC) domain proteins. However, their evolutionary history and patterns have not been examined systematically. Here, we report extensive analyses of eukaryotic JmjC genes and define 14 subfamilies, including the Lysine-Specific Demethylase3 (KDM3), KDM5, JMJD6, Putative-Lysine-Specific Demethylase11 (PKDM11), and PKDM13 subfamilies, shared by plants, animals, and fungi. Other subfamilies are detected in plants and animals but not in fungi (PKDM12) or in animals and fungi but not in plants (KDM2 and KDM4). PKDM7, PKDM8, and PKDM9 are plant-specific groups, whereas Jumonji, AT-Rich Interactive Domain2, KDM6, and PKDM10 are animal specific. In addition to known domains, most subfamilies have characteristic conserved amino acid motifs. Whole-genome duplication (WGD) was likely an important mechanism for JmjC duplications, with four pairs from an angiosperm-wide WGD and others from subsequent WGDs. Vertebrates also experienced JmjC duplications associated with the vertebrate ancestral WGDs, with additional mammalian paralogs from tandem duplication and possible transposition. The sequences of paralogs have diverged in both known functional domains and other regions, showing evidence of selection pressure. The increases of JmjC copy number and the divergences in sequence and expression might have contributed to the divergent functions of JmjC genes, allowing the angiosperms and vertebrates to adapt to a great number of ecological niches and contributing to their evolutionary successes. PMID:26059336

  18. Expansion and Functional Divergence of Jumonji C-Containing Histone Demethylases: Significance of Duplications in Ancestral Angiosperms and Vertebrates.

    PubMed

    Qian, Shengzhan; Wang, Yingxiang; Ma, Hong; Zhang, Liangsheng

    2015-08-01

    Histone modifications, such as methylation and demethylation, are crucial mechanisms altering chromatin structure and gene expression. Recent biochemical and molecular studies have uncovered a group of histone demethylases called Jumonji C (JmjC) domain proteins. However, their evolutionary history and patterns have not been examined systematically. Here, we report extensive analyses of eukaryotic JmjC genes and define 14 subfamilies, including the Lysine-Specific Demethylase3 (KDM3), KDM5, JMJD6, Putative-Lysine-Specific Demethylase11 (PKDM11), and PKDM13 subfamilies, shared by plants, animals, and fungi. Other subfamilies are detected in plants and animals but not in fungi (PKDM12) or in animals and fungi but not in plants (KDM2 and KDM4). PKDM7, PKDM8, and PKDM9 are plant-specific groups, whereas Jumonji, AT-Rich Interactive Domain2, KDM6, and PKDM10 are animal specific. In addition to known domains, most subfamilies have characteristic conserved amino acid motifs. Whole-genome duplication (WGD) was likely an important mechanism for JmjC duplications, with four pairs from an angiosperm-wide WGD and others from subsequent WGDs. Vertebrates also experienced JmjC duplications associated with the vertebrate ancestral WGDs, with additional mammalian paralogs from tandem duplication and possible transposition. The sequences of paralogs have diverged in both known functional domains and other regions, showing evidence of selection pressure. The increases of JmjC copy number and the divergences in sequence and expression might have contributed to the divergent functions of JmjC genes, allowing the angiosperms and vertebrates to adapt to a great number of ecological niches and contributing to their evolutionary successes. PMID:26059336

  19. 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."

  20. Birdsong dialect patterns explained using magnetic domains.

    PubMed

    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." PMID:27415293

  1. Faraday instability in deformable domains

    NASA Astrophysics Data System (ADS)

    Pucci, Giuseppe; Ben Amar, Martine; Couder, Yves

    2014-11-01

    We investigate the Faraday instability in floating liquid lenses, as an example of hydrodynamic instability that develops in a domain with flexible boundaries. We show that a mutual adaptation of the instability pattern and the domain shape occurs, as a result of the competition between the wave radiation pressure and the capillary response of the lens border. Two archetypes of behaviour are observed. In the first, stable shapes are obtained experimentally and predicted theoretically as the exact solutions of a Riccati equation, and they result from the equilibrium between wave radiation pressure and capillarity. In the second, the radiation pressure exceeds the capillary response of the lens border and leads to non-equilibrium behaviours, with breaking into smaller domains that have a complex dynamics including spontaneous propagation. The authors are grateful to Université Franco-Italienne (UFI) for financial support.

  2. Domain walls inside localised orientifolds

    NASA Astrophysics Data System (ADS)

    Blåbäck, J.; van der Woerd, E.; Van Riet, T.; Williams, M.

    2015-12-01

    The equations of motion of toroidal orientifold compactifications with fluxes are in one-to-one correspondence with gauged supergravity if the orientifold (and D-brane) sources are smeared over the compact space. This smeared limit is identical to the approximation that ignores warping. It is therefore relevant to compare quantities obtained from the gauged supergravity with the true 10d solution with localised sources. In this paper we find the correspondence between BPS domain walls in gauged SUGRA and 10D SUGRA with localised sources. Our model is the simplest orientifold with fluxes we are aware of: an O6/D6 compactification on {T}^3/{Z}_2 in massive IIA with H 3-flux. The BPS domain walls correspond to a O6/D6/NS5/D8 bound state. Our analysis reveals that the domain wall energy computed in gauged SUGRA is unaffected by the localisation of the O6/D6 sources.

  3. 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.

  4. Kinetics of enzymatic reactions in lipid membranes containing domains

    NASA Astrophysics Data System (ADS)

    Zhdanov, Vladimir P.; Höök, Fredrik

    2015-04-01

    An appreciable part of enzymes operating in vivo is associated with lipid membranes. The function of such enzymes can be influenced by the presence of domains containing proteins and/or composed of different lipids. The corresponding experimental model-system studies can be performed under well controlled conditions, e.g., on a planar supported lipid bilayer or surface-immobilized vesicles. To clarify what may happen in such systems, we propose general kinetic equations describing the enzyme-catalyzed substrate conversion occurring via the Michaelis-Menten (MM) mechanism on a membrane with domains which do not directly participate in reaction. For two generic situations when a relatively slow reaction takes place primarily in or outside domains, we take substrate saturation and lateral substrate-substrate interactions at domains into account and scrutinize the dependence of the reaction rate on the average substrate coverage. With increasing coverage, depending on the details, the reaction rate reaches saturation via an inflection point or monotonously as in the conventional MM case. In addition, we show analytically the types of reaction kinetics occurring primarily at domain boundaries. In the physically interesting situation when the domain growth is fast on the reaction time scale, the latter kinetics are far from conventional. The opposite situation when the reaction is fast and controlled by diffusion has been studied by using the Monte Carlo technique. The corresponding results indicate that the dependence of the reaction kinetics on the domain size may be weak.

  5. A position-dependent transcription-activating domain in TFIIIA.

    PubMed

    Mao, X; Darby, M K

    1993-12-01

    Transcription of the Xenopus 5S RNA gene by RNA polymerase III requires the gene-specific factor TFIIIA. To identify domains within TFIIIA that are essential for transcriptional activation, we have expressed C-terminal deletion, substitution, and insertion mutants of TFIIIA in bacteria as fusions with maltose-binding protein (MBP). The MBP-TFIIIA fusion protein specifically binds to the 5S RNA gene internal control region and complements transcription in a TFIIIA-depleted oocyte nuclear extract. Random, cassette-mediated mutagenesis of the carboxyl region of TFIIIA, which is not required for promoter binding, has defined a 14-amino-acid region that is critical for transcriptional activation. In contrast to activators of RNA polymerase II, the activity of the TFIIIA activation domain is strikingly sensitive to its position relative to the DNA-binding domain. When the eight amino acids that separate the transcription-activating domain from the last zinc finger are deleted, transcriptional activity is lost. Surprisingly, diverse amino acids can replace these eight amino acids with restoration of full transcriptional activity, suggesting that the length and not the sequence of this region is important. Insertion of amino acids between the zinc finger region and the transcription-activating domain causes a reduction in transcription proportional to the number of amino acids introduced. We propose that to function, the transcription-activating domain of TFIIIA must be correctly positioned at a minimum distance from the DNA-binding domain. PMID:8246967

  6. X-ray study of aligned magnetic stripe domains in perpendicular multilayers

    SciTech Connect

    Hellwig, O.; Denbeaux, G.P.; Kortright, J.B.; Fullerton, Eric E.

    2003-03-03

    We have investigated the stripe domain structure and the magnetic reversal of perpendicular Co/Pt based multilayers at room temperature using magnetometry, magnetic imaging and magnetic x-ray scattering. In-plane field cycling aligns the stripe domains along the field direction. In magnetic x-ray scattering the parallel stripe domains act as a magnetic grating resulting in observed Bragg reflections up to 5th order. We model the scattering profile to extract and quantify the domain as well as domain wall widths. Applying fields up to {approx}1.2 kOe perpendicular to the film reversibly changes the relative width of up versus down domains while maintaining the overall stripe periodicity. Fields above 1.2 kOe introduce irreversible changes into the domain structure by contracting and finally annihilating individual stripe domains. We compare the current results with modeling and previous measurements of films with perpendicular anisotropy.

  7. ERPs and Domain Specificity: Beating a Straw Horse.

    ERIC Educational Resources Information Center

    Coulson, Seana; King, Jonathan W.; Kutas, Marta

    1998-01-01

    Discusses the importance, validity, and implications of the identity thesis that the P600 component of the scalp-recorded event-related potential is identical with the P3b, a domain-general component elicited by improbable task-related events. Explores epistemological complexities of the issue and discusses what the identity thesis does and does…

  8. A frequency domain method for the generation of partially coherent normal stationary time domain signals

    SciTech Connect

    Smallwood, D.O.; Paez, T.L.

    1991-01-01

    A procedure for generating vectors of time domain signals which are partially coherent in a prescribed manner is described. The procedure starts with the spectral density matrix, (G{sub xx}(f)), that relates pairs of elements of the vector random process (x(t), {minus}{infinity} < t < {infinity}). The spectral density matrix is decomposed into the form (G{sub xx}(f)) = (U(f)) (S(f)) (U(f)){prime} where (U(f)) is a matrix of complex frequency response functions, and (S(f)) is a diagonal matrix of real functions which can vary with frequency. The factors of the spectral density matrix, (U(f)) and (S(f)), are then used to generate a frame of random data in the frequency domain. The data is transformed into the time domain using an inverse FFT to generate a frame of data in the time domain. Successive frames of data are then windowed, overlapped, and added to form a vector of normal stationary sampled time histories, (x(t)), of arbitrary length. 11 refs., 4 figs., 1 tab.

  9. 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

  10. Propagating and reflecting of spin wave in permalloy nanostrip with 360° domain wall

    SciTech Connect

    Zhang, Senfu; Mu, Congpu; Zhu, Qiyuan; Zheng, Qi; Liu, Xianyin; Wang, Jianbo; Liu, Qingfang

    2014-01-07

    By micromagnetic simulation, we investigated the interaction between propagating spin wave (or magnonic) and a 360° domain wall in a nanostrip. It is found that propagating spin wave can drive a 360° domain wall motion, and the velocity and direction are closely related to the transmission coefficient of the spin wave of the domain wall. When the spin wave passes through the domain wall completely, the 360° domain wall moves toward the spin wave source. When the spin wave is reflected by the domain wall, the 360° domain wall moves along the spin wave propagation direction. Moreover, when the frequency of the spin wave is coincident with that of the 360° domain wall normal mode, the 360° domain wall velocity will be resonantly enhanced no matter which direction the 360 DW moves along. On the other hand, when the spin wave is reflected from the moving 360° domain wall, we observed the Doppler effect clearly. After passing through a 360° domain wall, the phase of the spin wave is changed, and the phase shift is related to the frequency. Nevertheless, phase shift could be manipulated by the number of 360° domain walls that spin wave passing through.

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

    SciTech Connect

    Venkatesan, Swaminathan; Chen, Jihua; Ngo, Evan C.; Dubey, Ashish; Khatiwada, Devendra; Zhang, Cheng; Qiao, Qiquan

    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 (PC60BM) and indene-C60 bis-adduct (IC60BA). 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:IC60BA solar cells while P3HT:PC60BM 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 diffraction (XRD) results showed that ICBA mixes with disordered P3HT much more readily than PC60BM which leads to lower short circuit current density and fill factor for P3HT:IC60BA cells annealed below 120°C. Annealing above 120°C improves the crystallinity of P3HT in case of P3HT:IC60BA whereas in P3HT:PC60BM 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.

  12. A Method to Examine Content Domain Structures

    ERIC Educational Resources Information Center

    D'Agostino, Jerome; Karpinski, Aryn; Welsh, Megan

    2011-01-01

    After a test is developed, most content validation analyses shift from ascertaining domain definition to studying domain representation and relevance because the domain is assumed to be set once a test exists. We present an approach that allows for the examination of alternative domain structures based on extant test items. In our example based on…

  13. Tensor distinction of domains in ferroic crystals

    NASA Astrophysics Data System (ADS)

    Litvin, D. B.

    2009-10-01

    Ferroic crystals contain two or more domains and may be distinguished by the values of components of tensorial physical properties of the domains. We have extended Aizu’s global tensor distinction by magnetization, polarization, and strain of all domains which arise in a ferroic phase transition to include distinction by toroidal moment, and from phases invariant under time reversal to domains which arise in transitions from all magnetic and non-magnetic phases. For determining possible switching of domains, a domain pair tensor distinction is also considered for all pairs of domains which arise in each ferroic phase transition.

  14. Protein structural domains: definition and prediction.

    PubMed

    Ezkurdia, Iakes; Tress, Michael L

    2011-11-01

    Recognition and prediction of structural domains in proteins is an important part of structure and function prediction. This unit lists the range of tools available for domain prediction, and describes sequence and structural analysis tools that complement domain prediction methods. Also detailed are the basic domain prediction steps, along with suggested strategies for different protein sequences and potential pitfalls in domain boundary prediction. The difficult problem of domain orientation prediction is also discussed. All the resources necessary for domain boundary prediction are accessible via publicly available Web servers and databases and do not require computational expertise. PMID:22045561

  15. Bayesian Models for Multiple Outcomes in Domains with Application to the Seychelles Child Development Study

    PubMed Central

    Xiao, Luo; Thurston, Sally W.; Ruppert, David; Love, Tanzy M.T.; Davidson, Philip W.

    2013-01-01

    The Seychelles Child Development Study (SCDS) examines the effects of prenatal exposure to methylmercury on the functioning of the central nervous system. The SCDS data include 20 outcomes measured on 9-year old children that can be classified broadly in four outcome classes or “domains”: cognition, memory, motor, and social behavior. Previous analyses and scientific theory suggest that these outcomes may belong to more than one of these domains, rather than only a single domain as is frequently assumed for modeling. We present a framework for examining the effects of exposure and other covariates when the outcomes may each belong to more than one domain and where we also want to learn about the assignment of outcomes to domains. Each domain is defined by a sentinel outcome which is preassigned to that domain only. All other outcomes can belong to multiple domains and are not preassigned. Our model allows exposure and covariate effects to differ across domains and across outcomes within domains, and includes random subject-specific effects which model correlations between outcomes within and across domains. We take a Bayesian MCMC approach. Results from the Seychelles study and from extensive simulations show that our model can effectively determine sparse domain assignment, and at the same time give increased power to detect overall, domain-specific and outcome-specific exposure and covariate effects relative to separate models for each endpoint. When fit to the Seychelles data, several outcomes were classified as partly belonging to domains other than their originally assigned domains. In retrospect, the new partial domain assignments are reasonable and, as we discuss, suggest important scientific insights about the nature of the outcomes. Checks of model misspecification were improved relative to a model that assumes each outcome is in a single domain. PMID:24729645

  16. Development in the Food Domain.

    ERIC Educational Resources Information Center

    Rozin, Paul

    1990-01-01

    Discusses problems of general interest in developmental psychology that can be successfully studied in the domain of food; these include (1) development of food likes and dislikes; (2) establishment of the edible/inedible distinction; (3) disgust and contagion; (4) transgenerational communication of preferences; and (5) transition to food…

  17. Cellulose binding domain fusion proteins

    DOEpatents

    Shoseyov, O.; Yosef, K.; Shpiegl, I.; Goldstein, M.A.; Doi, R.H.

    1998-02-17

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 16 figs.

  18. Cellulose binding domain fusion proteins

    DOEpatents

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc A.; Doi, Roy H.

    1998-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  19. Identification of alternative topological domains in chromatin

    PubMed Central

    2014-01-01

    Chromosome conformation capture experiments have led to the discovery of dense, contiguous, megabase-sized topological domains that are similar across cell types and conserved across species. These domains are strongly correlated with a number of chromatin markers and have since been included in a number of analyses. However, functionally-relevant domains may exist at multiple length scales. We introduce a new and efficient algorithm that is able to capture persistent domains across various resolutions by adjusting a single scale parameter. The ensemble of domains we identify allows us to quantify the degree to which the domain structure is hierarchical as opposed to overlapping, and our analysis reveals a pronounced hierarchical structure in which larger stable domains tend to completely contain smaller domains. The identified novel domains are substantially different from domains reported previously and are highly enriched for insulating factor CTCF binding and histone marks at the boundaries. PMID:24868242

  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. 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

  2. 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

  3. Diversity in protein recognition by PTB domains.

    PubMed

    Forman-Kay, J D; Pawson, T

    1999-12-01

    Phosphotyrosine-binding (PTB) domains were originally identified as modular domains that recognize phosphorylated Asn-Pro-Xxx-p Tyr-containing proteins. Recent binding and structural studies of PTB domain complexes with target peptides have revealed a number of deviations from the previously described mode of interaction, with respect to both the sequences of possible targets and their structures within the complexes. This diversity of recognition by PTB domains extends and strengthens our general understanding of modular binding domain recognition. PMID:10607674

  4. 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

  5. Toward a Taxonomy of Educational Objectives in the Relational Domain.

    ERIC Educational Resources Information Center

    Brandhorst, Allan R.

    A taxonomy of educational objectives which conceptualizes interpersonal skills in terms of measurable behavior is described. The categories represent six aspects of leadership capability--one of them cognitive (conceptualization), one of them cognitive-affective (evaluation), and four of them cognitive-affective-behavioral (leading, following,…

  6. 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

  7. 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. PMID:21319919

  8. 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.

  9. 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…

  10. 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…

  11. Gabor domain optical coherence microscopy

    NASA Astrophysics Data System (ADS)

    Murali, Supraja

    Time domain Optical Coherence Tomography (TD-OCT), first reported in 1991, makes use of the low temporal coherence properties of a NIR broadband laser to create depth sectioning of up to 2mm under the surface using optical interferometry and point to point scanning. Prior and ongoing work in OCT in the research community has concentrated on improving axial resolution through the development of broadband sources and speed of image acquisition through new techniques such as Spectral domain OCT (SD-OCT). In SD-OCT, an entire depth scan is acquired at once with a low numerical aperture (NA) objective lens focused at a fixed point within the sample. In this imaging geometry, a longer depth of focus is achieved at the expense of lateral resolution, which is typically limited to 10 to 20 mum. Optical Coherence Microscopy (OCM), introduced in 1994, combined the advantages of high axial resolution obtained in OCT with high lateral resolution obtained by increasing the NA of the microscope placed in the sample arm. However, OCM presented trade-offs caused by the inverse quadratic relationship between the NA and the DOF of the optics used. For applications requiring high lateral resolution, such as cancer diagnostics, several solutions have been proposed including the periodic manual re-focusing of the objective lens in the time domain as well as the spectral domain C-mode configuration in order to overcome the loss in lateral resolution outside the DOF. In this research, we report for the first time, high speed, sub-cellular imaging (lateral resolution of 2 mum) in OCM using a Gabor domain image processing algorithm with a custom designed and fabricated dynamic focus microscope interfaced to a Ti:Sa femtosecond laser centered at 800 nm within an SD-OCM configuration. It is envisioned that this technology will provide a non-invasive replacement for the current practice of multiple biopsies for skin cancer diagnosis. The research reported here presents three important advances

  12. Spline interpolation on unbounded domains

    NASA Astrophysics Data System (ADS)

    Skeel, Robert D.

    2016-06-01

    Spline interpolation is a splendid tool for multiscale approximation on unbounded domains. In particular, it is well suited for use by the multilevel summation method (MSM) for calculating a sum of pairwise interactions for a large set of particles in linear time. Outlined here is an algorithm for spline interpolation on unbounded domains that is efficient and elegant though not so simple. Further gains in efficiency are possible via quasi-interpolation, which compromises collocation but with minimal loss of accuracy. The MSM, which may also be of value for continuum models, embodies most of the best features of both hierarchical clustering methods (tree methods, fast multipole methods, hierarchical matrix methods) and FFT-based 2-level methods (particle-particle particle-mesh methods, particle-mesh Ewald methods).

  13. Frequency domain optical parametric amplification

    PubMed Central

    Schmidt, Bruno E.; Thiré, Nicolas; Boivin, Maxime; Laramée, Antoine; Poitras, François; Lebrun, Guy; Ozaki, Tsuneyuki; Ibrahim, Heide; Légaré, François

    2014-01-01

    Today’s ultrafast lasers operate at the physical limits of optical materials to reach extreme performances. Amplification of single-cycle laser pulses with their corresponding octave-spanning spectra still remains a formidable challenge since the universal dilemma of gain narrowing sets limits for both real level pumped amplifiers as well as parametric amplifiers. We demonstrate that employing parametric amplification in the frequency domain rather than in time domain opens up new design opportunities for ultrafast laser science, with the potential to generate single-cycle multi-terawatt pulses. Fundamental restrictions arising from phase mismatch and damage threshold of nonlinear laser crystals are not only circumvented but also exploited to produce a synergy between increased seed spectrum and increased pump energy. This concept was successfully demonstrated by generating carrier envelope phase stable, 1.43 mJ two-cycle pulses at 1.8 μm wavelength. PMID:24805968

  14. Pyramidal inversion domain boundaries revisited

    SciTech Connect

    Remmele, T.; Albrecht, M.; Irmscher, K.; Fornari, R.; Strassburg, M.

    2011-10-03

    The structure of pyramidal inversion domain boundaries in GaN:Mg was investigated by aberration corrected transmission electron microscopy. The analysis shows the upper (0001) boundary to consist of a single Mg layer inserted between polarity inverted GaN layers in an abcab stacking. The Mg bound in these defects is at least one order of magnitude lower than the chemical Mg concentration. Temperature dependent Hall effect measurements show that up to 27% of the Mg acceptors is electrically compensated.

  15. System time-domain simulation

    NASA Technical Reports Server (NTRS)

    Dawson, C. T.; Eggleston, T. W.; Goris, A. C.; Fashano, M.; Paynter, D.; Tranter, W. H.

    1980-01-01

    Complex systems are simulated by engineers without extensive computer experience. Analyst uses free-form engineering-oriented language to input "black box" description. System Time Domain (SYSTID) Simulation Program generates appropriate algorithms and proceeds with simulation. Program is easily linked to postprocessing routines. SYSTID program is written in FORTRAN IV for batch execution and has been implemented on UNIVAC 1110 under control of EXEC 8, Level 31.

  16. Flexible time domain averaging technique

    NASA Astrophysics Data System (ADS)

    Zhao, Ming; Lin, Jing; Lei, Yaguo; Wang, Xiufeng

    2013-09-01

    Time domain averaging(TDA) is essentially a comb filter, it cannot extract the specified harmonics which may be caused by some faults, such as gear eccentric. Meanwhile, TDA always suffers from period cutting error(PCE) to different extent. Several improved TDA methods have been proposed, however they cannot completely eliminate the waveform reconstruction error caused by PCE. In order to overcome the shortcomings of conventional methods, a flexible time domain averaging(FTDA) technique is established, which adapts to the analyzed signal through adjusting each harmonic of the comb filter. In this technique, the explicit form of FTDA is first constructed by frequency domain sampling. Subsequently, chirp Z-transform(CZT) is employed in the algorithm of FTDA, which can improve the calculating efficiency significantly. Since the signal is reconstructed in the continuous time domain, there is no PCE in the FTDA. To validate the effectiveness of FTDA in the signal de-noising, interpolation and harmonic reconstruction, a simulated multi-components periodic signal that corrupted by noise is processed by FTDA. The simulation results show that the FTDA is capable of recovering the periodic components from the background noise effectively. Moreover, it can improve the signal-to-noise ratio by 7.9 dB compared with conventional ones. Experiments are also carried out on gearbox test rigs with chipped tooth and eccentricity gear, respectively. It is shown that the FTDA can identify the direction and severity of the eccentricity gear, and further enhances the amplitudes of impulses by 35%. The proposed technique not only solves the problem of PCE, but also provides a useful tool for the fault symptom extraction of rotating machinery.

  17. Opposite Effects of KCTD Subunit Domains on GABAB Receptor-mediated Desensitization*

    PubMed Central

    Seddik, Riad; Jungblut, Stefan P.; Silander, Olin K.; Rajalu, Mathieu; Fritzius, Thorsten; Besseyrias, Valérie; Jacquier, Valérie; Fakler, Bernd; Gassmann, Martin; Bettler, Bernhard

    2012-01-01

    GABAB receptors assemble from principle and auxiliary subunits. The principle subunits GABAB1 and GABAB2 form functional heteromeric GABAB(1,2) receptors that associate with homotetramers of auxiliary KCTD8, -12, -12b, or -16 (named after their K+ channel tetramerization domain) subunits. These auxiliary subunits constitute receptor subtypes with distinct functional properties. KCTD12 and -12b generate desensitizing receptor responses while KCTD8 and -16 generate largely non-desensitizing receptor responses. The structural elements of the KCTDs underlying these differences in desensitization are unknown. KCTDs are modular proteins comprising a T1 tetramerization domain, which binds to GABAB2, and a H1 homology domain. KCTD8 and -16 contain an additional C-terminal H2 homology domain that is not sequence-related to the H1 domains. No functions are known for the H1 and H2 domains. Here we addressed which domains and sequence motifs in KCTD proteins regulate desensitization of the receptor response. We found that the H1 domains in KCTD12 and -12b mediate desensitization through a particular sequence motif, T/NFLEQ, which is not present in the H1 domains of KCTD8 and -16. In addition, the H2 domains in KCTD8 and -16 inhibit desensitization when expressed C-terminal to the H1 domains but not when expressed as a separate protein in trans. Intriguingly, the inhibitory effect of the H2 domain is sequence-independent, suggesting that the H2 domain sterically hinders desensitization by the H1 domain. Evolutionary analysis supports that KCTD12 and -12b evolved desensitizing properties by liberating their H1 domains from antagonistic H2 domains and acquisition of the T/NFLEQ motif. PMID:23035119

  18. Subharmonic Fourier domain mode locking.

    PubMed

    Eigenwillig, Christoph M; Wieser, Wolfgang; Biedermann, Benjamin R; Huber, Robert

    2009-03-15

    We demonstrate a subharmonically Fourier domain mode-locked wavelength-swept laser source with a substantially reduced cavity fiber length. In contrast to a standard Fourier domain mode-locked configuration, light is recirculated repetitively in the delay line with the optical bandpass filter used as switch. The laser has a fundamental optical round trip frequency of 285 kHz and can be operated at integer fractions thereof (subharmonics). Sweep ranges up to 95 nm full width centred at 1317 nm are achieved at the 1/5th subharmonic. A maximum sensitivity of 116 dB and an axial resolution of 12 microm in air are measured at an average sweep power of 12 mW. A sensitivity roll-off of 11 dB over 4 mm and 25 dB over 10 mm is observed and optical coherence tomography imaging is demonstrated. Besides the advantage of a reduced fiber length, subharmonic Fourier domain mode locking (shFDML) enables simple scaling of the sweep speed by extracting light from the delay part of the resonator. A sweep rate of 570 kHz is achieved. Characteristic features of shFDML operation, such as power leakage during fly-back and cw breakthrough, are investigated. PMID:19282912

  19. Compassion and professional care: exploring the domain.

    PubMed

    van der Cingel, Margreet

    2009-04-01

    Compassion unites people during times of suffering and distress. Unfortunately, compassion cannot take away suffering. Why then, is compassion important for people who suffer? Nurses work in a domain where human suffering is evidently present. In order to give meaning to compassion in the domain of professional care, it is necessary to describe what compassion is. The purpose of this paper is to explore questions and contradictions in the debate on compassion related to nursing care. The paper reviews classical philosophers as well as contemporary scientists' main arguments on compassion. First, I will examine the relationship between compassion and suffering. Second, how does one recognize serious suffering? This issue raises questions about the role of imagination and the need for identification. Third, literature describes compassion as an emotion. Some philosophers consider emotions uncontrollable feelings; others see a clear rational dimension in emotions. In order to determine what compassion is, it is necessary to weigh these contradictional arguments. Fourth, I will discuss motives for compassion. Is compassion an act of altruism or egoism? In this debate Nietzsche and Schopenhauer are well-known opponents. Today, analysis of their arguments leads to some surprising conclusions. Fifth, there is the issue of fault and compassion. Can we only feel compassionate when people who suffer are not to blame for their own suffering? Such a condition faces professional caretakers with a dilemma which needs a thorough analysis if compassion is to be of use in the field of professional care. Finally, I will explore the moral meaning of compassion. Compassion, described as a concept with cognitive as well as affective dimensions, also has volitional and behavioural aspects. These aspects specifically are of importance to nursing care and further research of compassion in the nursing domain. PMID:19291200

  20. Micro- and nano-domain engineering in lithium niobate

    NASA Astrophysics Data System (ADS)

    Shur, V. Ya.; Akhmatkhanov, A. R.; Baturin, I. S.

    2015-12-01

    The physical basis of the domain engineering in ferroelectrics and its application to lithium niobate crystals were reviewed. The unified kinetic approach to the domain structure evolution in electric field was formulated and its validity for understanding the variety of observed domain evolution scenarios was demonstrated. The kinetics and statics of the domain structure in the crystals of lithium niobate family including congruent, stoichiometric, and MgO doped ones have been discussed. The main stages of the periodical poling process and related problems have been pointed out. The basic poling techniques applied for creation of the periodical domain structures in bulk crystals and waveguides were compared. The recent applications of the periodically poled lithium niobate for light frequency conversion using second harmonic generation and optical parametric oscillation, excitation of the surface acoustic waves, and generation of terahertz radiation have been discussed. The special attention has been paid for achievements in fabrication of high-power optical parametric oscillation and integrated optical devices with periodically poled lithium niobate. The future trends in periodical poling and development of the nanodomain engineering which will allow to create the nanoscale domain patterns necessary for utilization of the new nonlinear interactions were reviewed.

  1. 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. PMID:25943580

  2. Micro- and nano-domain engineering in lithium niobate

    SciTech Connect

    Shur, V. Ya.; Akhmatkhanov, A. R.; Baturin, I. S.

    2015-12-15

    The physical basis of the domain engineering in ferroelectrics and its application to lithium niobate crystals were reviewed. The unified kinetic approach to the domain structure evolution in electric field was formulated and its validity for understanding the variety of observed domain evolution scenarios was demonstrated. The kinetics and statics of the domain structure in the crystals of lithium niobate family including congruent, stoichiometric, and MgO doped ones have been discussed. The main stages of the periodical poling process and related problems have been pointed out. The basic poling techniques applied for creation of the periodical domain structures in bulk crystals and waveguides were compared. The recent applications of the periodically poled lithium niobate for light frequency conversion using second harmonic generation and optical parametric oscillation, excitation of the surface acoustic waves, and generation of terahertz radiation have been discussed. The special attention has been paid for achievements in fabrication of high-power optical parametric oscillation and integrated optical devices with periodically poled lithium niobate. The future trends in periodical poling and development of the nanodomain engineering which will allow to create the nanoscale domain patterns necessary for utilization of the new nonlinear interactions were reviewed.

  3. 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.

  4. ACTN1 rod domain mutation associated with congenital macrothrombocytopenia.

    PubMed

    Yasutomi, Motoko; Kunishima, Shinji; Okazaki, Shintaro; Tanizawa, Akihiko; Tsuchida, Shinya; Ohshima, Yusei

    2016-01-01

    Mutations in ACTN1, the gene encoding the actin-crosslinking protein α-actinin-1, cause autosomal dominant macrothrombocytopenia. α-Actinin-1 exists as antiparallel dimers, composed of an N-terminal actin-binding domain (ABD), four spectrin-like repeats (SLRs), which form the spacer rod, and a C-terminal calmodulin-like (CaM) domain. All of the previously reported ACTN1 mutations associated with macrothrombocytopenia reside within the ABD and the CaM domain and not within the SLR domain. In this report, we describe a mutation in SLR2 of α-actinin-1 (p.Leu395Gln) associated with familial macrothrombocytopenia. A 3-year-old boy and his mother both had this mutation. They showed a mild form of thrombocytopenia without severe bleeding, accompanied by an elevated mean platelet volume. Consistent with the previous reports of mutations that reside in the ABD or the CaM domain, immunofluorescence examination revealed disorganization of the actin cytoskeleton in Gln395 mutant-transduced Chinese hamster ovary cells. Our findings suggest a novel mechanism for the pathogenesis of ACTN1-related macrothrombocytopenia that does not involve functional domain mutations. PMID:26453073

  5. 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

  6. Ferroelectric domain inversion and its stability in lithium niobate thin film on insulator with different thicknesses

    NASA Astrophysics Data System (ADS)

    Shao, Guang-hao; Bai, Yu-hang; Cui, Guo-xin; Li, Chen; Qiu, Xiang-biao; Geng, De-qiang; Wu, Di; Lu, Yan-qing

    2016-07-01

    Ferroelectric domain inversion and its effect on the stability of lithium niobate thin films on insulator (LNOI) are experimentally characterized. Two sets of specimens with different thicknesses varying from submicron to microns are selected. For micron thick samples (˜28 μm), domain structures are achieved by pulsed electric field poling with electrodes patterned via photolithography. No domain structure deterioration has been observed for a month as inspected using polarizing optical microscopy and etching. As for submicron (540 nm) films, large-area domain inversion is realized by scanning a biased conductive tip in a piezoelectric force microscope. A graphic processing method is taken to evaluate the domain retention. A domain life time of 25.0 h is obtained and possible mechanisms are discussed. Our study gives a direct reference for domain structure-related applications of LNOI, including guiding wave nonlinear frequency conversion, nonlinear wavefront tailoring, electro-optic modulation, and piezoelectric devices.

  7. 3D domain swapping in a chimeric c-Src SH3 domain takes place through two hinge loops.

    PubMed

    Cámara-Artigas, Ana; Martínez-Rodríguez, Sergio; Ortiz-Salmerón, Emilia; Martín-García, José M

    2014-04-01

    In the Src Homology 3 domain (SH3) the RT and n-Src loops form a pocket that accounts for the specificity and affinity in binding of proline rich motifs (PRMs), while the distal and diverging turns play a key role in the folding of the protein. We have solved the structure of a chimeric mutant c-Src-SH3 domain where specific residues at the RT- and n-Src-loops have been replaced by those present in the corresponding Abl-SH3 domain. Crystals of the chimeric protein show a single molecule in the asymmetric unit, which appears in an unfolded-like structure that upon generation of the symmetry related molecules reveals the presence of a domain swapped dimer where both, RT- and n-Src loops, act as hinge loops. In contrast, the fold of the diverging type II β-turn and the distal loop are well conserved. Our results are the first evidence for the presence of a structured diverging type II β-turn in an unfolded-like intermediate of the c-Src-SH3 domain, which can be stabilized by interactions from the β-strands of the same polypeptide chain or from a neighboring one. Futhermore, this crystallographic structure opens a unique opportunity to study the effect of the amino acid sequence of the hinge loops on the 3D domain swapping process of c-Src-SH3. PMID:24556574

  8. Elastic Domain Architectures in Constrained Layers

    NASA Astrophysics Data System (ADS)

    Slutsker, J.; Artemev, A.; Roytburd, A. L.

    2002-08-01

    The formation of elastic domains in transforming constrained films is a mechanism of relaxation of internal stresses caused by the misfit between a film and a substrate. The formation and evolution of polydomain microstructure as a result of the cubic-tetragonal transformation in a constrained layer are investigated by phase-field simulation. It has been shown that the three-domain hierarchical structure can be formed in the epitaxial films. With changing a fraction of out-of-plane domain there are two types of morphological transitions: from the three-domain structure to the two-domain one and from the hierarchical three-domain structure to the cellular three-domain structure. The results of the phase-field simulation are compared with available experimental data on 90deg domain structures in epitaxial ferroelectric films.

  9. Cellulose-binding domains: biotechnological applications.

    PubMed

    Levy, Ilan; Shoseyov, Oded

    2002-11-01

    Many researchers have acknowledged the fact that there exists an immense potential for the application of the cellulose-binding domains (CBDs) in the field of biotechnology. This becomes apparent when the phrase "cellulose-binding domain" is used as the key word for a computerized patent search; more then 150 hits are retrieved. Cellulose is an ideal matrix for large-scale affinity purification procedures. This chemically inert matrix has excellent physical properties as well as low affinity for nonspecific protein binding. It is available in a diverse range of forms and sizes, is pharmaceutically safe, and relatively inexpensive. Present studies into the application of CBDs in industry have established that they can be applied in the modification of physical and chemical properties of composite materials and the development of modified materials with improved properties. In agro-biotechnology, CBDs can be used to modify polysaccharide materials both in vivo and in vitro. The CBDs exert nonhydrolytic fiber disruption on cellulose-containing materials. The potential applications of "CBD technology" range from modulating the architecture of individual cells to the modification of an entire organism. Expressing these genes under specific promoters and using appropriate trafficking signals, can be used to alter the nutritional value and texture of agricultural crops and their final products. PMID:14550028

  10. Frequency Domain Calculations Of Acoustic Propagation

    NASA Technical Reports Server (NTRS)

    Lockard, David P.

    2004-01-01

    Two complex geometry problems are solved using the linearized Euler equations. The impedance mismatch method1 is used to impose the solid surfaces without the need to use a body-fitted grid. The problem is solved in the frequency domain to avoid long run times. Although the harmonic assumption eliminates all time dependence, a pseudo-time term is added to allow conventional iterative methods to be employed. A Jameson type, Runge-Kutta scheme is used to advance the solution in pseudo time. The spatial operator is based on a seven-point, sixth-order finite difference. Constant coefficient, sixth-derivative artificial dissipation is used throughout the domain. A buffer zone technique employing a complex frequency to damp all waves near the boundaries is used to minimize reflections. The results show that the method is capable of capturing the salient features of the scattering, but an excessive number of grid points are required to resolve the phenomena in the vicinity of the solid bodies because the wavelength of the acoustics is relatively short compared with the size of the bodies. Smoothly transitioning into the immersed boundary condition alleviates the difficulties, but a fine mesh is still required.

  11. Speckle size in optical Fourier domain imaging

    NASA Astrophysics Data System (ADS)

    Lamouche, G.; Vergnole, S.; Bisaillon, C.-E.; Dufour, M.; Maciejko, R.; Monchalin, J.-P.

    2007-06-01

    As in conventional time-domain optical coherence tomography (OCT), speckle is inherent to any Optical Fourier Domain Imaging (OFDI) of biological tissue. OFDI is also known as swept-source OCT (SS-OCT). The axial speckle size is mainly determined by the OCT resolution length and the transverse speckle size by the focusing optics illuminating the sample. There is also a contribution from the sample related to the number of scatterers contained within the probed volume. In the OFDI data processing, there is some liberty in selecting the range of wavelengths used and this allows variation in the OCT resolution length. Consequently the probed volume can be varied. By performing measurements on an optical phantom with a controlled density of discrete scatterers and by changing the probed volume with different range of wavelengths in the OFDI data processing, there is an obvious change in the axial speckle size, but we show that there is also a less obvious variation in the transverse speckle size. This work contributes to a better understanding of speckle in OCT.

  12. Effects of Intramolecular Distance between Amyloidogenic Domains on Amyloid Aggregation

    PubMed Central

    Ko, Ahra; Kim, Jin Ryoun

    2012-01-01

    Peptide/protein aggregation is implicated in many amyloid diseases. Some amyloidogenic peptides/proteins, such as those implicated in Alzheimer’s and Parkinson’s diseases, contain multiple amyloidogenic domains connected by “linker” sequences displaying high propensities to form turn structures. Recent studies have demonstrated the importance of physicochemical properties of each amino acid contained in the polypeptide sequences in amyloid aggregation. However, effects on aggregation related to the intramolecular distance between amyloidogenic domains, which may be determined by a linker length, have yet to be examined. In the study presented here, we created peptides containing two copies of KFFE, a simple four-residue amyloidogenic domain, connected by GS-rich linker sequences with different lengths yet similar physicochemical properties. Our experimental results indicate that aggregation occurred most rapidly when KFFE domains were connected by a linker of an intermediate length. Our experimental findings were consistent with estimated entropic contribution of a linker length toward formation of (partially) structured intermediates on the aggregation pathway. Moreover, inclusion of a relatively short linker was found to inhibit formation of aggregates with mature fibril morphology. When the results are assimilated, our study demonstrates that intramolecular distance between amyloidogenic domains is an important yet overlooked factor affecting amyloid aggregation. PMID:23202890

  13. Children’s Experience of Posttraumatic Growth: Distinguishing General from Domain-Specific Correlates

    PubMed Central

    Laceulle, Odilia M.; Kleber, Rolf J.; Alisic, Eva

    2015-01-01

    Although the five domains of posttraumatic growth (new possibilities, relating to others, personal strength, spiritual change and appreciation of life) have been studied extensively in adults, little is known about these domains and their correlates in children. We aimed to examine whether demographic and/or social characteristics are related to children’s reports of overall posttraumatic growth and of growth in specific domains. In a general population study, children aged 8–12 years who had been exposed to adverse events (N = 1290) filled out questionnaires on their experiences, demographic characteristics (gender, age, time lag since event), stress reactions, peer support, religiosity and posttraumatic growth. All demographic and social characteristics were related to overall posttraumatic growth, except time lag. Associations varied across the five domains with the strongest effects being found for stress reactions and religiosity. A higher level of stress reactions was related to more growth in all domains (general effect), whereas religious children experienced more spiritual growth than non-religious children without differences on other domains (domain specific effect). Other effects were small, and some did not remain significant after Bonferroni corrections. These findings suggest the presence of both general and domain-specific correlates of child posttraumatic growth. Although effects were generally small, the current findings show the need to differentiate between the domains of posttraumatic growth in both further research and clinical practice. This will allow a better understanding of the mechanisms of posttraumatic growth in children as well as more tailored assessment and intervention. PMID:26714193

  14. Structure of a two-CAP-domain protein from the human hookworm parasite Necator americanus

    SciTech Connect

    Asojo, Oluwatoyin A.

    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 structure 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.

  15. p15RS/RPRD1A (p15INK4b-related sequence/regulation of nuclear pre-mRNA domain-containing protein 1A) interacts with HDAC2 in inhibition of the Wnt/β-catenin signaling pathway.

    PubMed

    Liu, Chunxiao; Zhang, Yanquan; Li, Jun; Wang, Yinyin; Ren, Fangli; Zhou, Yifan; Wu, Yinyuan; Feng, Yarui; Zhou, Yu; Su, Fuqin; Jia, Baoqing; Wang, Dong; Chang, Zhijie

    2015-04-10

    We previously reported that p15RS (p15INK4b-related sequence), a regulation of nuclear pre-mRNA domain containing protein, inhibited Wnt signaling by interrupting the formation of the β-catenin·TCF4 complex. However, how p15RS functions as an intrinsic repressor to repress transcription remains unclear. In this study, we show that p15RS, through a specific interaction with HDAC2 (histone deacetylase 2), a deacetylase that regulates gene transcription, maintains histone H3 in a deacetylated state in the promoter region of Wnt-targeted genes where β-catenin·TCF4 is bound. We observed that histone deacetylase inhibitors impair the ability of p15RS in inhibiting Wnt/β-catenin signaling. Depletion of HDAC2 markedly disabled p15RS inhibition of Wnt/β-catenin-mediated transcription. Interestingly, overexpression of p15RS decreases the level of acetylated histone H3 in the c-MYC promoter. Finally, we demonstrate that p15RS significantly enhances the association of HDAC2 and TCF4 and enhances the occupancy of HDAC2 to DNA, resulting in the deacetylation of histone H3 and the failure of β-catenin interaction. We propose that p15RS acts as an intrinsic transcriptional repressor for Wnt/β-catenin-mediated gene transcription at least partially through recruiting HDAC2 to occupy the promoter and maintaining deacetylated histone H3. PMID:25697359

  16. Frequency domain photoacoustic and fluorescence microscopy

    PubMed Central

    Langer, Gregor; Buchegger, Bianca; Jacak, Jaroslaw; Klar, Thomas A.; Berer, Thomas

    2016-01-01

    We report on simultaneous frequency domain optical-resolution photoacoustic and fluorescence microscopy with sub-µm lateral resolution. With the help of a blood smear, we show that photoacoustic and fluorescence images provide complementary information. Furthermore, we compare theoretically predicted signal-to-noise ratios of sinusoidal modulation in frequency domain with pulsed excitation in time domain. PMID:27446698

  17. Frequency domain photoacoustic and fluorescence microscopy.

    PubMed

    Langer, Gregor; Buchegger, Bianca; Jacak, Jaroslaw; Klar, Thomas A; Berer, Thomas

    2016-07-01

    We report on simultaneous frequency domain optical-resolution photoacoustic and fluorescence microscopy with sub-µm lateral resolution. With the help of a blood smear, we show that photoacoustic and fluorescence images provide complementary information. Furthermore, we compare theoretically predicted signal-to-noise ratios of sinusoidal modulation in frequency domain with pulsed excitation in time domain. PMID:27446698

  18. Pectin Homogalacturonans: Nanostructural Characterization of Methylesterified Domains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Functionality of pectic hydrocolloids is largely dependent on the two major domains commonly found in their homogalacturonan (HG) regions, i.e., methylester protected domains (MPDs)and non methylesterified domains (NMDs). MPDs can participate in hydrogen bonding and hydrophobic interactions but unli...

  19. The Promise of Domain Adaptation

    NASA Astrophysics Data System (ADS)

    Mahabal, Ashish A.; Li, Jingling; Vaijanapurkar, Samarth; Bue, Brian; Miller, Adam; Donalek, Ciro; Djorgovski, Stanislav G.; Drake, Andrew J.; Graham, Matthew; CRTS, iPTF

    2016-01-01

    Most new surveys spend an appreciable time in collecting data on which to train classifiers before they can be used on future observations from the same dataset. The result generating phase can start much earlier if the training could incorporate data accumulated from older surveys enhanced with a small set from the new survey. This is exactly what Domain Adaptation (DA) allows us to do. The main idea behind DAs can be summarized thus: if we have two classes of separable objects in some feature space of a Source survey (S), we can define a hyperplane to separate the two types. In a second Target survey (T), for the same features the hyperplane would be inclined differently. DA methods get the mapping between the two hyperplanes using a small fraction of data from the Target (T) survey and can then be used to predict the classes of the remaining majority of data in T. We discuss the parameters that need to be tuned, the difficulties involved, and ways to improve the results. As we move towards bigger, and deeper surveys, being able to use existing labelled information to conduct classification in future surveys will be more cost-effective and promote time efficiency as well. Starting with the light curve data of 50,000 periodic objects from Catalina Real-Time Transient Survey (CRTS), we have applied domain adaptation techniques such as Geodesic Flow Kernel (GFK) with Random forest classifier and Co-training for domain adaptation (CODA) to the CRTS data which has 35,000 points overlapping with Palomar Transient Factory (PTF), and 12,000 with Lincoln Near-Earth Asteroid Research (LINEAR). The results suggest that domain adaptation is an area worth exploring as the knowledge between these surveys is transferable and the approaches to find the mappings between these surveys can be applied to the remaining data as well as for near future surveys such as CRTS-II, Zwicky Transient Facility (ZTF) and the Large Synoptic Survey Telescope (LSST) to name a few at the optical

  20. 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…

  1. 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…

  2. 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…

  3. 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…

  4. Domains of Chronic Stress and Suicidal Behaviors among Inpatient Adolescents

    ERIC Educational Resources Information Center

    Pettit, Jeremy W.; Green, Kelly L.; Grover, Kelly E.; Schatte, Dawnelle J.; Morgan, Sharon T.

    2011-01-01

    Little is known about the role of chronic stress in youth suicidal behaviors. This study examined the relations between specific domains of chronic stress and suicidal behaviors among 131 inpatient youth (M age = 15.02 years) who completed measures of stress, suicidal ideation, suicide attempt, and suicide intent. After controlling for…

  5. Domain 4: Growth and Development National Standards for Sport Coaches

    ERIC Educational Resources Information Center

    Shimon, Jane; Darden, Gibson

    2004-01-01

    This article, the third in a series of articles from the National Association for Sport and Physical Education (NASPE) sport structures, explains how the following two scenarios relate to Domain 4 Standards: (1) two adolescent boys have different baseball throwing skill levels, even though they have been on the same team for the past four years;…

  6. Content Area Reading Pedagogy and Domain Knowledge: A Bourdieusian Analysis

    ERIC Educational Resources Information Center

    Alvermann, Donna; Friese, Elizabeth; Beckmann, Sybilla; Rezak, Achariya

    2011-01-01

    The twofold purpose of this study was to trace prospective and practicing mathematics teachers' understandings of content area reading instruction in relation to domain knowledge in mathematics, and to examine the extent to which online pedagogical mentoring supported the integration of such instruction and knowledge. The design called for two…

  7. Three-Dimensional Domain Swapping Changes the Folding Mechanism of the Forkhead Domain of FoxP1.

    PubMed

    Medina, Exequiel; Córdova, Cristóbal; Villalobos, Pablo; Reyes, Javiera; Komives, Elizabeth A; Ramírez-Sarmiento, César A; Babul, Jorge

    2016-06-01

    The forkhead family of transcription factors (Fox) controls gene transcription during key processes such as regulation of metabolism, embryogenesis, and immunity. Structurally, Fox proteins feature a conserved DNA-binding domain known as forkhead. Interestingly, solved forkhead structures of members from the P subfamily (FoxP) show that they can oligomerize by three-dimensional domain swapping, whereby structural elements are exchanged between adjacent subunits, leading to an intertwined dimer. Recent evidence has largely stressed the biological relevance of domain swapping in FoxP, as several disease-causing mutations have been related to impairment of this process. Here, we explore the equilibrium folding and binding mechanism of the forkhead domain of wild-type FoxP1, and of two mutants that hinder DNA-binding (R53H) and domain swapping (A39P), using size-exclusion chromatography, circular dichroism, and hydrogen-deuterium exchange mass spectrometry. Our results show that domain swapping of FoxP1 occurs at micromolar protein concentrations within hours of incubation and is energetically favored, in contrast to classical domain-swapping proteins. Also, DNA-binding mutations do not significantly affect domain swapping. Remarkably, equilibrium unfolding of dimeric FoxP1 follows a three-state N2 ↔ 2I ↔ 2U folding mechanism in which dimer dissociation into a monomeric intermediate precedes protein unfolding, in contrast to the typical two-state model described for most domain-swapping proteins, whereas the A39P mutant follows a two-state N ↔ U folding mechanism consistent with the second transition observed for dimeric FoxP1. Also, the free-energy change of the N ↔ U in A39P FoxP1 is ∼2 kcal⋅mol(-1) larger than the I ↔ U transition of both wild-type and R53H FoxP1. Finally, hydrogen-deuterium exchange mass spectrometry reveals that the intermediate strongly resembles the native state. Our results suggest that domain swapping in FoxP1 is at least

  8. Domain wall fermion quenched spectroscopy

    NASA Astrophysics Data System (ADS)

    Malureanu, Catalin Ionut

    We measure y and the hadron spectrum on quenched ensembles using the domain wall fermion formulation. For the first time a 1/mf behavior of y for small valence masses has been observed. Our measurements of y on two different volumes of 83 x 32 and 163 x 32 at β = 5.85 suggest the behavior goes away on large enough volumes. Extensive spectrum calculations were done on 8 3 x 32 lattices at β = 5.7 and 5.85 corresponding roughly to a box size of 1.6 fm and 1.0 fm respectively. We have investigated five values of the extent of the fifth dimension Ls = 10, 16, 24, 32 and 48 with valence masses in the range 0.02 to 0.2 for the β = 5.7 ensemble and two values of Ls = 10 and 16 with valence masses in the range 0.02 to 0.08 for the β = 5.85 ensemble. Our pion remains massive in the infinite Ls extrapolation. This may be a finite volume effect. The nucleon to rho mass ratio stays constant at 1.4(1). Scaling violations for domain wall fermions are smaller roughly by a factor of four compared to the scaling violations in similar calculations done with staggered fermions.

  9. Frequency-domain Hadamard spectroscopy

    NASA Astrophysics Data System (ADS)

    Kupče, Ēriks; Freeman, Ray

    2003-05-01

    A new technique is proposed for multichannel excitation and detection of NMR signals in the frequency domain, an alternative to the widely used pulse-excited Fourier transform method. An extensive array of N radiofrequency irradiation channels covers the spectrum of interest. A selective radiofrequency pulse sequence is applied to each channel, generating a steady-state NMR response acquired one-point-at-a-time in the intervals between pulses. The excitation pattern is repeated N times, phase-encoded according to a Hadamard matrix, and the corresponding N composite responses are decoded by reference to the same matrix. This multiplex technique offers the same sensitivity advantage as conventional Fourier transform spectroscopy. The irradiation pattern may be tailored to concentrate on interesting spectral regions, to facilitate homonuclear double resonance, or to avoid exciting strong solvent peaks. As no free induction decay is involved, the new method avoids problems of pulse breakthrough or lineshape distortion by premature termination of the time-domain signal.

  10. Interfaces between Block Copolymer Domains

    NASA Astrophysics Data System (ADS)

    Kim, Jaeup; Jeong, Seong-Jun; Kim, Sang Ouk

    2011-03-01

    Block copolymers naturally form nanometer scale structures which repeat their geometry on a larger scale. Such a small scale periodic pattern can be used for various applications such as storage media, nano-circuits and optical filters. However, perfect alignment of block copolymer domains in the macroscopic scale is still a distant dream. The nanostructure formation usually occurs with spontaneously broken symmetry; hence it is easily infected by topological defects which sneak in due to entropic fluctuation and incomplete annealing. Careful annealing can gradually reduce the number of defects, but once kinetically trapped, it is extremely difficult to remove all the defects. One of the main reasons is that the defect finds a locally metastable morphology whose potential depth is large enough to prohibit further morphology evolution. In this work, the domain boundaries between differently oriented lamellar structures in thin film are studied. For the first time, it became possible to quantitatively study the block copolymer morphology in the transitional region, and it was shown that the twisted grain boundary is energetically favorable compared to the T-junction grain boundary. [Nano Letters, 9, 2300 (2010)]. This theoretical method successfully explained the experimental results.

  11. Word Domain Disambiguation via Word Sense Disambiguation

    SciTech Connect

    Sanfilippo, Antonio P.; Tratz, Stephen C.; Gregory, Michelle L.

    2006-06-04

    Word subject domains have been widely used to improve the perform-ance of word sense disambiguation al-gorithms. However, comparatively little effort has been devoted so far to the disambiguation of word subject do-mains. The few existing approaches have focused on the development of al-gorithms specific to word domain dis-ambiguation. In this paper we explore an alternative approach where word domain disambiguation is achieved via word sense disambiguation. Our study shows that this approach yields very strong results, suggesting that word domain disambiguation can be ad-dressed in terms of word sense disam-biguation with no need for special purpose algorithms.

  12. Single-domain antibodies for biomedical applications.

    PubMed

    Krah, Simon; Schröter, Christian; Zielonka, Stefan; Empting, Martin; Valldorf, Bernhard; Kolmar, Harald

    2016-01-01

    Single-domain antibodies are the smallest antigen-binding units of antibodies, consisting either only of one variable domain or one engineered constant domain that solely facilitates target binding. This class of antibody derivatives comprises naturally occurring variable domains derived from camelids and sharks as well as engineered human variable or constant antibody domains of the heavy or light chain. Because of their high affinity and specificity as well as stability, small size and benefit of multiple re-formatting opportunities, those molecules emerged as promising candidates for biomedical applications and some of these entities have already proven to be successful in clinical development. PMID:26551147

  13. Domain swapping: entangling alliances between proteins.

    PubMed Central

    Bennett, M J; Choe, S; Eisenberg, D

    1994-01-01

    The comparison of monomeric and dimeric diphtheria toxin (DT) reveals a mode for protein association which we call domain swapping. The structure of dimeric DT has been extensively refined against data to 2.0-A resolution and a three-residue loop has been corrected as compared with our published 2.5-A-resolution structure. The monomeric DT structure has also been determined, at 2.3-A resolution. Monomeric DT is a Y-shaped molecule with three domains: catalytic (C), transmembrane (T), and receptor binding (R). Upon freezing in phosphate buffer, DT forms a long-lived, metastable dimer. The protein chain tracing discloses that upon dimerization an unprecedented conformational rearrangement occurs: the entire R domain from each molecule of the dimer is exchanged for the R domain from the other. This involves breaking the noncovalent interactions between the R domain and the C and T domains, rotating the R domain by 180 degrees with atomic movements up to 65 A, and re-forming the same noncovalent interactions between the R domain and the C and T domains of the other chain of the dimer. This conformational transition explains the long life and metastability of the DT dimer. Several other intertwined, dimeric protein structures satisfy our definition of domain swapping and suggest that domain swapping may be the molecular mechanism for evolution of these oligomers and possibly of oligomeric proteins in general. Images PMID:8159715

  14. Domain adaptive boosting method and its applications

    NASA Astrophysics Data System (ADS)

    Geng, Jie; Miao, Zhenjiang

    2015-03-01

    Differences of data distributions widely exist among datasets, i.e., domains. For many pattern recognition, nature language processing, and content-based analysis systems, a decrease in performance caused by the domain differences between the training and testing datasets is still a notable problem. We propose a domain adaptation method called domain adaptive boosting (DAB). It is based on the AdaBoost approach with extensions to cover the domain differences between the source and target domains. Two main stages are contained in this approach: source-domain clustering and source-domain sample selection. By iteratively adding the selected training samples from the source domain, the discrimination model is able to achieve better domain adaptation performance based on a small validation set. The DAB algorithm is suitable for the domains with large scale samples and easy to extend for multisource adaptation. We implement this method on three computer vision systems: the skin detection model in single images, the video concept detection model, and the object classification model. In the experiments, we compare the performances of several commonly used methods and the proposed DAB. Under most situations, the DAB is superior.

  15. Domain wall conduction in multiaxial ferroelectrics

    SciTech Connect

    Eliseev, E. A.; Morozovska, A. N.; Svechnikov, S. V.; Maksymovych, Petro; Kalinin, Sergei V

    2012-01-01

    The conductance of domain wall structures consisting of either stripes or cylindrical domains in multiaxial ferroelectric-semiconductors is analyzed. The effects of the flexoelectric coupling, domain size, wall tilt, and curvature on charge accumulation are analyzed using the Landau-Ginsburg Devonshire theory for polarization vector combined with the Poisson equation for charge distributions. The proximity and size effect of the electron and donor accumulation/depletion by thin stripe domains and cylindrical nanodomains are revealed. In contrast to thick domain stripes and wider cylindrical domains, in which the carrier accumulation (and so the static conductivity) sharply increases at the domain walls only, small nanodomains of radii less than 5-10 correlation lengths appeared conducting across the entire cross-section. Implications of such conductive nanosized channels may be promising for nanoelectronics.

  16. Functional innovation from changes in protein domains and their combinations.

    PubMed

    Lees, Jonathan G; Dawson, Natalie L; Sillitoe, Ian; Orengo, Christine A

    2016-06-01

    Domains are the functional building blocks of proteins. In this work we discuss how domains can contribute to the evolution of new functions. Domains themselves can evolve through various mechanisms, altering their intrinsic function. Domains can also facilitate functional innovations by combining with other domains to make novel proteins. We discuss the mechanisms by which domain and domain combinations support functional innovations. We highlight interesting examples where changes in domain combination promote changes at the domain level. PMID:27309309

  17. 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.

  18. Towards a Domain Specific Software Architecture for Scientific Data Distribution

    NASA Astrophysics Data System (ADS)

    Wilson, A.; Lindholm, D. M.

    2011-12-01

    A reference architecture is a "design that satisfies a clearly distinguished subset of the functional capabilities identified in the reference requirements within the boundaries of certain design and implementation constraints, also identified in reference requirements." [Tracz, 1995] Recognizing the value of a reference architecture, NASA's ESDSWG's Standards Process Group (SPG) is introducing a multi-disciplinary science data systems (SDS) reference architecture in order to provide an implementation neutral, template solution for an architecture to support scientific data systems in general [Burnett, et al, 2011]. This reference architecture describes common features and patterns in scientific data systems, and can thus provide guidelines in building and improving such systems. But, guidelines alone may not be sufficient to actually build a system. A domain specific software architecture (DSSA) is "an assemblage of software components, specialized for a particular type of task (domain), generalized for effective use across that domain, composed in a standardized structure (topology) effective for building successful applications." [Tracz, 1995]. It can be thought of as relatively specific reference architecture. The "DSSA Process" is a software life cycle developed at Carnegie Melon's Software Engineering Institute that is based on the development and use of domain-specific software architectures, components, and tools. The process has four distinct activities: 1) develop a domain specific base/model, 2) populate and maintain the library, 3) build applications, 4) operate and maintain applications [Armitage, 1993]. The DSSA process may provide the missing link between guidelines and actual system construction. In this presentation we focus specifically on the realm of scientific data access and distribution. Assuming the role of domain experts in building data access systems, we report the results of creating a DSSA for scientific data distribution. We describe

  19. Structure and Function of KH Domains

    SciTech Connect

    Valverde, R.; Regan, E

    2008-01-01

    The hnRNP K homology (KH) domain was first identified in the protein human heterogeneous nuclear ribonucleoprotein K (hnRNP K) 14 years ago. Since then, KH domains have been identified as nucleic acid recognition motifs in proteins that perform a wide range of cellular functions. KH domains bind RNA or ssDNA, and are found in proteins associated with transcriptional and translational regulation, along with other cellular processes. Several diseases, e.g. fragile X mental retardation syndrome and paraneoplastic disease, are associated with the loss of function of a particular KH domain. Here we discuss the progress made towards understanding both general and specific features of the molecular recognition of nucleic acids by KH domains. The typical binding surface of KH domains is a cleft that is versatile but that can typically accommodate only four unpaired bases. Van der Waals forces and hydrophobic interactions and, to a lesser extent, electrostatic interactions, contribute to the nucleic acid binding affinity. 'Augmented' KH domains or multiple copies of KH domains within a protein are two strategies that are used to achieve greater affinity and specificity of nucleic acid binding. Isolated KH domains have been seen to crystallize as monomers, dimers and tetramers, but no published data support the formation of noncovalent higher-order oligomers by KH domains in solution. Much attention has been given in the literature to a conserved hydrophobic residue (typically Ile or Leu) that is present in most KH domains. The interest derives from the observation that an individual with this Ile mutated to Asn, in the KH2 domain of fragile X mental retardation protein, exhibits a particularly severe form of the syndrome. The structural effects of this mutation in the fragile X mental retardation protein KH2 domain have recently been reported. We discuss the use of analogous point mutations at this position in other KH domains to dissect both structure and function.

  20. Inversion domains in GaN grown on sapphire

    SciTech Connect

    Romano, L.T.; Northrup, J.E.; OKeefe, M.A.

    1996-10-01

    Planar defects observed in GaN films grown on (0001) sapphire have been identified as inversion domain boundaries (IDBs) by a combination of high resolution transmission electron microscopy, multiple dark field imaging, and convergent beam electron diffraction techniques. Films grown by molecular beam epitaxy (MBE), metalorganic vapor deposition (MOCVD), and hydride vapor phase epitaxy (HVPE) were investigated and all were found to contain IDBs. The IDBs in the MBE and HVPE films extended from the interface to the film surface and formed columnar domains that ranged in width from 3 to 20 nm in the MBE films and up to 100 nm in the HVPE films. For the films investigated, the MBE films had the highest density, and the MOCVD films had the lowest density of IDBs. The nucleation of inversion domains (IDs) may result from step-related inhomogeneities of the GaN/sapphire interface. {copyright} {ital 1996 American Institute of Physics.}

  1. Goldstone bosons versus domain walls bounded by cosmic strings

    NASA Astrophysics Data System (ADS)

    Dvali, G. R.

    1991-08-01

    It is shown that two possible schemes of string bounded domain wall formation are closely related. Walls can be avoided if a certain type of couplings between scalars, responsible for string and wall formation, is excluded from the potential. This enlarges the continous global symmetry of the model which, being broken, instead of domain walls gives rise to global strings and Gold-stone bosons. A realistic example of spontaneously broken family symmetry is considered. It is shown that the existence of the axion in the model with local chiral flavour symmetry SU(3)H can solve the domain wall problem. I would very much like to thank Z. Berezhiani, T. Bibilashvili, J. Chkareuli, E. Gurvich, O. Kancheli and S.M. Mahajan for very useful discussions.

  2. The structural mechanism of KCNH-channel regulation by the eag domain

    PubMed Central

    Haitin, Yoni; Carlson, Anne E.; Zagotta, William N.

    2013-01-01

    The KCNH voltage-dependent potassium channels (ether-á-go-go, EAG; EAG-related gene, ERG; EAG-like channels, ELK) are important regulators of cellular excitability1-3 and have key roles in diseases such as cardiac long QT syndrome type 2 (LQT2)4, epilepsy5, schizophrenia6 and cancer7. The intracellular domains of KCNH channels are structurally distinct from other voltage-gated channels. The amino-terminal region contains an eag domain, which is comprised of a Per-Arnt-Sim (PAS) domain and a PAS-cap domain8, while the carboxy-terminal region contains a cyclic nucleotide-binding homology domain (CNBHD) which is connected to the pore through a C-linker domain. Many disease-causing mutations localize to these specialized intracellular domains, which underlie the unique gating and regulation of KCNH channels9. It has been suggested that the eag domain may regulate the channel by interacting with either the S4-S5 linker or the CNBHD8,10. Here we present a 2-Å resolution crystal structure of the eag domain-CNBHD complex of the mouse EAG1 (mEAG1) channel. It displays extensive interactions between the eag domain and the CNBHD, indicating that the regulatory mechanism of the eag domain involves primarily the CNBHD. Surprisingly, the structure reveals that a number of LQT2 mutations at homologous positions in hERG, and cancer-associated mutations in EAG channels, localize to the eag domain-CNBHD interface. Furthermore, mutations at the interface produced dramatic effects on channel gating demonstrating the important physiological role of the eag domain-CNBHD interaction. Our structure of the eag domain-CNBHD complex of mEAG1 provides unique insights into the physiological and pathophysiological mechanisms of KCNH channels. PMID:23975098

  3. The structural mechanism of KCNH-channel regulation by the eag domain.

    PubMed

    Haitin, Yoni; Carlson, Anne E; Zagotta, William N

    2013-09-19

    The KCNH voltage-dependent potassium channels (ether-à-go-go, EAG; EAG-related gene, ERG; EAG-like channels, ELK) are important regulators of cellular excitability and have key roles in diseases such as cardiac long QT syndrome type 2 (LQT2), epilepsy, schizophrenia and cancer. The intracellular domains of KCNH channels are structurally distinct from other voltage-gated channels. The amino-terminal region contains an eag domain, which is composed of a Per-Arnt-Sim (PAS) domain and a PAS-cap domain, whereas the carboxy-terminal region contains a cyclic nucleotide-binding homology domain (CNBHD), which is connected to the pore through a C-linker domain. Many disease-causing mutations localize to these specialized intracellular domains, which underlie the unique gating and regulation of KCNH channels. It has been suggested that the eag domain may regulate the channel by interacting with either the S4-S5 linker or the CNBHD. Here we present a 2 Å resolution crystal structure of the eag domain-CNBHD complex of the mouse EAG1 (also known as KCNH1) channel. It displays extensive interactions between the eag domain and the CNBHD, indicating that the regulatory mechanism of the eag domain primarily involves the CNBHD. Notably, the structure reveals that a number of LQT2 mutations at homologous positions in human ERG, in addition to cancer-associated mutations in EAG channels, localize to the eag domain-CNBHD interface. Furthermore, mutations at the interface produced marked effects on channel gating, demonstrating the important physiological role of the eag domain-CNBHD interaction. Our structure of the eag domain-CNBHD complex of mouse EAG1 provides unique insights into the physiological and pathophysiological mechanisms of KCNH channels. PMID:23975098

  4. 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. PMID:25664627

  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. Domain decomposition approach to flexible multibody dynamics simulation

    NASA Astrophysics Data System (ADS)

    Kwak, JunYoung; Chun, TaeYoung; Shin, SangJoon; Bauchau, Olivier A.

    2014-01-01

    Finite element based formulations for flexible multibody systems are becoming increasingly popular and as the complexity of the configurations to be treated increases, so does the computational cost. It seems natural to investigate the applicability of parallel processing to this type of problems; domain decomposition techniques have been used extensively for this purpose. In this approach, the computational domain is divided into non-overlapping sub-domains, and the continuity of the displacement field across sub-domain boundaries is enforced via the Lagrange multiplier technique. In the finite element literature, this approach is presented as a mathematical algorithm that enables parallel processing. In this paper, the divided system is viewed as a flexible multibody system, and the sub-domains are connected by kinematic constraints. Consequently, all the techniques applicable to the enforcement of constraints in multibody systems become applicable to the present problem. In particular, it is shown that a combination of the localized Lagrange multiplier technique with the augmented Lagrange formulation leads to interesting solution strategies. The proposed algorithm is compared with the well-known FETI approach with regards to convergence and efficiency characteristics. The present algorithm is relatively simple and leads to improved convergence and efficiency characteristics. Finally, implementation on a parallel computer was conducted for the proposed approach.

  7. Real-time observation of epitaxial graphene domain reorientation

    PubMed Central

    Rogge, Paul C.; Thürmer, Konrad; Foster, Michael E.; McCarty, Kevin F.; Dubon, Oscar D.; Bartelt, Norman C.

    2015-01-01

    Graphene films grown by vapour deposition tend to be polycrystalline due to the nucleation and growth of islands with different in-plane orientations. Here, using low-energy electron microscopy, we find that micron-sized graphene islands on Ir(111) rotate to a preferred orientation during thermal annealing. We observe three alignment mechanisms: the simultaneous growth of aligned domains and dissolution of rotated domains, that is, ‘ripening'; domain boundary motion within islands; and continuous lattice rotation of entire domains. By measuring the relative growth velocity of domains during ripening, we estimate that the driving force for alignment is on the order of 0.1 meV per C atom and increases with rotation angle. A simple model of the orientation-dependent energy associated with the moiré corrugation of the graphene sheet due to local variations in the graphene–substrate interaction reproduces the results. This work suggests new strategies for improving the van der Waals epitaxy of 2D materials. PMID:25892219

  8. The Diversity and Evolution of Wolbachia Ankyrin Repeat Domain Genes

    PubMed Central

    Siozios, Stefanos; Ioannidis, Panagiotis; Klasson, Lisa; Andersson, Siv G. E.; Braig, Henk R.; Bourtzis, Kostas

    2013-01-01

    Ankyrin repeat domain-encoding genes are common in the eukaryotic and viral domains of life, but they are rare in bacteria, the exception being a few obligate or facultative intracellular Proteobacteria species. Despite having a reduced genome, the arthropod strains of the alphaproteobacterium Wolbachia contain an unusually high number of ankyrin repeat domain-encoding genes ranging from 23 in wMel to 60 in wPip strain. This group of genes has attracted considerable attention for their astonishing large number as well as for the fact that ankyrin proteins are known to participate in protein-protein interactions, suggesting that they play a critical role in the molecular mechanism that determines host-Wolbachia symbiotic interactions. We present a comparative evolutionary analysis of the wMel-related ankyrin repeat domain-encoding genes present in different Drosophila-Wolbachia associations. Our results show that the ankyrin repeat domain-encoding genes change in size by expansion and contraction mediated by short directly repeated sequences. We provide examples of intra-genic recombination events and show that these genes are likely to be horizontally transferred between strains with the aid of bacteriophages. These results confirm previous findings that the Wolbachia genomes are evolutionary mosaics and illustrate the potential that these bacteria have to generate diversity in proteins potentially involved in the symbiotic interactions. PMID:23390535

  9. Voltage-controlled domain wall traps in ferromagnetic nanowires.

    PubMed

    Bauer, Uwe; Emori, Satoru; Beach, Geoffrey S D

    2013-06-01

    Electrical control of magnetism has the potential to bring about revolutionary new spintronic devices, many of which rely on efficient manipulation of magnetic domain walls in ferromagnetic nanowires. Recently, it has been shown that voltage-induced charge accumulation at a metal-oxide interface can influence domain wall motion in ultrathin metallic ferromagnets, but the effects have been relatively modest and limited to the slow, thermally activated regime. Here we show that a voltage can generate non-volatile switching of magnetic properties at the nanoscale by modulating interfacial chemistry rather than charge density. Using a solid-state ionic conductor as a gate dielectric, we generate unprecedentedly strong voltage-controlled domain wall traps that function as non-volatile, electrically programmable and switchable pinning sites. Pinning strengths of at least 650 Oe can be readily achieved, enough to bring to a standstill domain walls travelling at speeds of at least ~20 m s(-1). We exploit this new magneto-ionic effect to demonstrate a prototype non-volatile memory device in which voltage-controlled domain wall traps facilitate electrical bit selection in a magnetic nanowire register. PMID:23708429

  10. Real-time observation of epitaxial graphene domain reorientation

    SciTech Connect

    Thuermer, Konrad; Foster, Michael E.; Bartelt, Norman Charles; Rogge, Paul C.; McCarty, Kevin F.; Dubon, Oscar D.; Bartelt, Norman C.

    2015-04-20

    Graphene films grown by vapour deposition tend to be polycrystalline due to the nucleation and growth of islands with different in-plane orientations. Here, using low-energy electron microscopy, we find that micron-sized graphene islands on Ir(111) rotate to a preferred orientation during thermal annealing. We observe three alignment mechanisms: the simultaneous growth of aligned domains and dissolution of rotated domains, that is, ‘ripening’; domain boundary motion within islands; and continuous lattice rotation of entire domains. By measuring the relative growth velocity of domains during ripening, we estimate that the driving force for alignment is on the order of 0.1 meV per C atom and increases with rotation angle. A simple model of the orientation-dependent energy associated with the moiré corrugation of the graphene sheet due to local variations in the graphene–substrate interaction reproduces the results. This study suggests new strategies for improving the van der Waals epitaxy of 2D materials.

  11. Real-time observation of epitaxial graphene domain reorientation

    DOE PAGESBeta

    Thuermer, Konrad; Foster, Michael E.; Bartelt, Norman Charles; Rogge, Paul C.; Lawrence Berkeley National Lab.; McCarty, Kevin F.; Dubon, Oscar D.; Lawrence Berkeley National Lab.; Bartelt, Norman C.

    2015-04-20

    Graphene films grown by vapour deposition tend to be polycrystalline due to the nucleation and growth of islands with different in-plane orientations. Here, using low-energy electron microscopy, we find that micron-sized graphene islands on Ir(111) rotate to a preferred orientation during thermal annealing. We observe three alignment mechanisms: the simultaneous growth of aligned domains and dissolution of rotated domains, that is, ‘ripening’; domain boundary motion within islands; and continuous lattice rotation of entire domains. By measuring the relative growth velocity of domains during ripening, we estimate that the driving force for alignment is on the order of 0.1 meV permore » C atom and increases with rotation angle. A simple model of the orientation-dependent energy associated with the moiré corrugation of the graphene sheet due to local variations in the graphene–substrate interaction reproduces the results. This study suggests new strategies for improving the van der Waals epitaxy of 2D materials.« less

  12. Inter-domain Communication of Human Cystathionine β-Synthase

    PubMed Central

    McCorvie, Thomas J.; Kopec, Jolanta; Hyung, Suk-Joon; Fitzpatrick, Fiona; Feng, Xidong; Termine, Daniel; Strain-Damerell, Claire; Vollmar, Melanie; Fleming, James; Janz, Jay M.; Bulawa, Christine; Yue, Wyatt W.

    2014-01-01

    Cystathionine β-synthase (CBS) is a key enzyme in sulfur metabolism, and its inherited deficiency causes homocystinuria. Mammalian CBS is modulated by the binding of S-adenosyl-l-methionine (AdoMet) to its regulatory domain, which activates its catalytic domain. To investigate the underlying mechanism, we performed x-ray crystallography, mutagenesis, and mass spectrometry (MS) on human CBS. The 1.7 Å structure of a AdoMet-bound CBS regulatory domain shows one AdoMet molecule per monomer, at the interface between two constituent modules (CBS-1, CBS-2). AdoMet binding is accompanied by a reorientation between the two modules, relative to the AdoMet-free basal state, to form interactions with AdoMet via residues verified by mutagenesis to be important for AdoMet binding (Phe443, Asp444, Gln445, and Asp538) and for AdoMet-driven inter-domain communication (Phe443, Asp538). The observed structural change is further supported by ion mobility MS, showing that as-purified CBS exists in two conformational populations, which converged to one in the presence of AdoMet. We therefore propose that AdoMet-induced conformational change alters the interface and arrangement between the catalytic and regulatory domains within the CBS oligomer, thereby increasing the accessibility of the enzyme active site for catalysis. PMID:25336647

  13. Cooperation of phosphoinositides and BAR domain proteins in endosomal tubulation.

    PubMed

    Shinozaki-Narikawa, Naeko; Kodama, Tatsuhiko; Shibasaki, Yoshikazu

    2006-11-01

    Phosphorylated derivatives of phosphatidylinositol (PtdIns) regulate many intracellular events, including vesicular trafficking and actin remodeling, by recruiting proteins to their sites of function. PtdIns(4,5)-bisphosphate [PI(4,5)P2] and related phosphoinositides are mainly synthesized by type I PtdIns-4-phosphate 5-kinases (PIP5Ks). We found that PIP5K induces endosomal tubules in COS-7 cells. ADP-ribosylation factor (ARF) 6 has been shown to act upstream of PIP5K and regulate endocytic transport and tubulation. ARF GAP with coiled-coil, ankyrin repeat, and pleckstrin homology domains 1 (ACAP1) has guanosine triphosphatase-activating protein (GAP) activity for ARF6. While there were few tubules induced by the expression of ACAP1 alone, numerous endosomal tubules were induced by coexpression of PIP5K and ACAP1. ACAP1 has a pleckstrin homology (PH) domain known to bind phosphoinositide and a Bin/amphiphysin/Rvs (BAR) domain that has been reported to detect membrane curvature. Truncated and point mutations in the ACAP1 BAR and PH domains revealed that both BAR and PH domains are required for tubulation. These results suggest that two ARF6 downstream molecules, PIP5K and ACAP1, function together in endosomal tubulation and that phosphoinositide levels may regulate endosomal dynamics. PMID:17010122

  14. Real-time observation of epitaxial graphene domain reorientation

    NASA Astrophysics Data System (ADS)

    Rogge, Paul C.; Thürmer, Konrad; Foster, Michael E.; McCarty, Kevin F.; Dubon, Oscar D.; Bartelt, Norman C.

    2015-04-01

    Graphene films grown by vapour deposition tend to be polycrystalline due to the nucleation and growth of islands with different in-plane orientations. Here, using low-energy electron microscopy, we find that micron-sized graphene islands on Ir(111) rotate to a preferred orientation during thermal annealing. We observe three alignment mechanisms: the simultaneous growth of aligned domains and dissolution of rotated domains, that is, `ripening' domain boundary motion within islands; and continuous lattice rotation of entire domains. By measuring the relative growth velocity of domains during ripening, we estimate that the driving force for alignment is on the order of 0.1 meV per C atom and increases with rotation angle. A simple model of the orientation-dependent energy associated with the moiré corrugation of the graphene sheet due to local variations in the graphene-substrate interaction reproduces the results. This work suggests new strategies for improving the van der Waals epitaxy of 2D materials.

  15. ASH structure alignment package: Sensitivity and selectivity in domain classification

    PubMed Central

    Standley, Daron M; Toh, Hiroyuki; Nakamura, Haruki

    2007-01-01

    Background Structure alignment methods offer the possibility of measuring distant evolutionary relationships between proteins that are not visible by sequence-based analysis. However, the question of how structural differences and similarities ought to be quantified in this regard remains open. In this study we construct a training set of sequence-unique CATH and SCOP domains, from which we develop a scoring function that can reliably identify domains with the same CATH topology and SCOP fold classification. The score is implemented in the ASH structure alignment package, for which the source code and a web service are freely available from the PDBj website . Results The new ASH score shows increased selectivity and sensitivity compared with values reported for several popular programs using the same test set of 4,298,905 structure pairs, yielding an area of .96 under the receiver operating characteristic (ROC) curve. In addition, weak sequence homologies between similar domains are revealed that could not be detected by BLAST sequence alignment. Also, a subset of domain pairs is identified that exhibit high similarity, even though their CATH and SCOP classification differs. Finally, we show that the ranking of alignment programs based solely on geometric measures depends on the choice of the quality measure. Conclusion ASH shows high selectivity and sensitivity with regard to domain classification, an important step in defining distantly related protein sequence families. Moreover, the CPU cost per alignment is competitive with the fastest programs, making ASH a practical option for large-scale structure classification studies. PMID:17407606

  16. Listening natively across perceptual domains?

    PubMed

    Langus, Alan; Seyed-Allaei, Shima; Uysal, Ertuğrul; Pirmoradian, Sahar; Marino, Caterina; Asaadi, Sina; Eren, Ömer; Toro, Juan M; Peña, Marcela; Bion, Ricardo A H; Nespor, Marina

    2016-07-01

    Our native tongue influences the way we perceive other languages. But does it also determine the way we perceive nonlinguistic sounds? The authors investigated how speakers of Italian, Turkish, and Persian group sequences of syllables, tones, or visual shapes alternating in either frequency or duration. We found strong native listening effects with linguistic stimuli. Speakers of Italian grouped the linguistic stimuli differently from speakers of Turkish and Persian. However, speakers of all languages showed the same perceptual biases when grouping the nonlinguistic auditory and the visual stimuli. The shared perceptual biases appear to be determined by universal grouping principles, and the linguistic differences caused by prosodic differences between the languages. Although previous findings suggest that acquired linguistic knowledge can either enhance or diminish the perception of both linguistic and nonlinguistic auditory stimuli, we found no transfer of native listening effects across auditory domains or perceptual modalities. (PsycINFO Database Record PMID:26820498

  17. Analysis of DCC domain structure

    SciTech Connect

    Randrup, J.; Thews, R.L.

    1997-10-01

    Wavelet-type methods are employed for the analysis of pion field configurations that have been obtained by dynamical simulations in idealized scenarios relevant to the formation of disoriented chiral condensates. It is illustrated how the measurement of the isospin domain structure depends on the ability to zoom in on limited parts of the phase space, due to the interplay between the pion correlation length and the effective source geometry. The need for advanced analysis methods is underscored by the fact that the extracted neutral-fraction distribution would differ significantly from the ideal form, even under perfect experimental conditions, and, moreover, by the circumstance that thermal sources with suitably adjusted temperatures can lead to distributions that may be practically indistinguishable from those arising from DCC-type nonequilibrium evolutions. {copyright} {ital 1997} {ital The American Physical Society}

  18. Analysis of DCC domain structure

    SciTech Connect

    Randrup, J.; Thews, R.L.

    1997-05-07

    Wavelet-type methods are employed for the analysis of pion field configurations that have been obtained by dynamical simulations in idealized scenarios relevant to the formation of disoriented chiral condensates. It is illustrated how the measurement of the isospin domain structure depends on the ability to zoom in on limited parts of the phase space, due to the interplay between the pion correlation length and the effective source geometry. The need for advanced analysis methods is underscored by the fact that the extracted neutral-fraction distribution would differ significantly from the ideal form, even under perfect experimental conditions, and, moreover, by the circumstance that thermal sources with suitably adjusted temperatures can lead to distributions that may be practically indistinguishable from those arising from DCC-type nonequilibrium evolutions.

  19. Time domain electromagnetic metal detectors

    SciTech Connect

    Hoekstra, P.

    1996-04-01

    This presentation focuses on illustrating by case histories the range of applications and limitations of time domain electromagnetic (TDEM) systems for buried metal detection. Advantages claimed for TDEM metal detectors are: independent of instrument response (Geonics EM61) to surrounding soil and rock type; simple anomaly shape; mitigation of interference by ambient electromagnetic noise; and responsive to both ferrous and non-ferrous metallic targets. The data in all case histories to be presented were acquired with the Geonics EM61 TDEM system. Case histories are a test bed site on Molokai, Hawaii; Fort Monroe, Virginia; and USDOE, Rocky Flats Plant. The present limitations of this technology are: discrimination capabilities in terms of type of ordnance, and depth of burial is limited, and ability of resolving targets with small metallic ambient needs to be improved.

  20. 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

    2007-01-01

    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. PMID:17174309

  1. The complex NOD-like receptor repertoire of the coral Acropora digitifera includes novel domain combinations.

    PubMed

    Hamada, Mayuko; Shoguchi, Eiichi; Shinzato, Chuya; Kawashima, Takeshi; Miller, David J; Satoh, Nori

    2013-01-01

    Innate immunity in corals is of special interest not only in the context of self-defense but also in relation to the establishment and collapse of their obligate symbiosis with dinoflagellates of the genus Symbiodinium. In innate immunity system of vertebrates, approximately 20 tripartite nucleotide oligomerization domain (NOD)-like receptor proteins that are defined by the presence of a NAIP, CIIA, HET-E and TP1 (NACHT) domain, a C-terminal leucine-rich repeat (LRR) domain, and one of three types of N-terminal effector domain, are known to function as the primary intracellular pattern recognition molecules. Surveying the coral genome revealed not only a larger number of NACHT- and related domain nucleotide-binding adaptor shared by APAF-1, R proteins, and CED-4 (NB-ARC)-encoding loci (~500) than in other metazoans but also surprising diversity of domain combinations among the coral NACHT/NB-ARC-containing proteins; N-terminal effector domains included the apoptosis-related domains caspase recruitment domain (CARD), death effector domain (DED), and Death, and C-terminal repeat domains included LRRs, tetratricopeptide repeats, ankyrin repeats, and WD40 repeats. Many of the predicted coral proteins that contain a NACHT/NB-ARC domain also contain a glycosyl transferase group 1 domain, a novel domain combination first found in metazoans. Phylogenetic analyses suggest that the NACHT/NB-ARC domain inventories of various metazoan lineages, including corals, are largely products of lineage-specific expansions. Many of the NACHT/NB-ARC loci are organized in pairs or triplets in the Acropora genome, suggesting that the large coral NACHT/NB-ARC repertoire has been generated at least in part by tandem duplication. In addition, shuffling of N-terminal effector domains may have occurred after expansions of specific NACHT/NB-ARC-repeat domain types. These results illustrate the extraordinary complexity of the innate immune repertoire of corals, which may in part reflect adaptive

  2. Frequency domain modelling of wind turbine structures

    SciTech Connect

    Soerensen, P.; Larsen, G.C.; Christensen, C.J.

    1995-09-01

    The present paper describes a frequency domain model of the structure of an operating horizontal axis wind turbine. The frequency domain model is implemented along with an analogous time domain modeling the Risoe PC code Design Basis 2, and a more detailed description of the model is offered in a Risoe report by Soerensen (1994). The structure of an operating wind turbine is affected by essential non-linearities between structural variables on blades and tower respectively. These non-linearities are caused by the rotation of the blades. The transformations between the blade coordinate systems and the tower coordinate system will depend on the instantaneous azimuth positions of the blades as they rotate. Frequency domain analysis are much faster than time simulations and in some respects they give more insight into the dynamics of the structure. However, the non-linear terms in the dynamic equations for a complex wind turbine structure are usually thought to preclude the use of frequency domain methods. Design Basis 2 is used to verify the frequency domain model comparing loads on the structure calculated with the frequency domain model both to loads calculated with the time domain model and to measured loads. Examples show that frequency and time domain calculations of typical PSD`s of loads are in very good agreement. Also the agreement between the calculated and measured PSD`s is good. Moreover, Design Basis 2 has shown that the frequency domain model results in an extremely fast calculation method.

  3. 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

  4. Conceptualizing and Re-Evaluating Resilience across Levels of Risk, Time, and Domains of Competence

    ERIC Educational Resources Information Center

    Vanderbilt-Adriance, Ella; Shaw, Daniel S.

    2008-01-01

    This article examines potential theoretical constraints on resilience across levels of risk, time, and domain of outcome. Studies of resilience are reviewed as they relate to the prevalence of resilience across levels of risk (e.g., single life events vs. cumulative risk), time, and domains of adjustment. Based on a thorough review of pertinent…

  5. 32 CFR 644.25 - Withdrawal of Public Domain for Defense Purposes.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 4 2014-07-01 2013-07-01 true Withdrawal of Public Domain for Defense Purposes... public domain land, water, or land and water, or restrictions on use of areas in the Continental Shelf... relative to outstanding mineral, grazing, water and other rights. (5) A statement as to the estimated...

  6. Materialism and Satisfaction with Over-All Quality of Life and Eight Life Domains

    ERIC Educational Resources Information Center

    Roberts, James A.; Clement, Aimee

    2007-01-01

    Previous research has shown that materialism relates negatively to satisfaction with many life domains. The present study broadens this body of research by examining the relationship between three dimensions of materialism and eight quality of life (QOL) domains in a large, diverse sample of U.S. respondents. Two hypotheses were tested: First,…

  7. 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…

  8. 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…

  9. 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.…

  10. 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.

  11. ELASTIC MEMBRANE DEFORMATIONS GOVERN INTERLEAFLET COUPLING OF LIPID-ORDERED DOMAINS

    PubMed Central

    Galimzyanov, Timur R.; Molotkovsky, Rodion J.; Bozdaganyan, Marine E.; Cohen, Fredric S.; Pohl, Peter; Akimov, Sergey A.

    2016-01-01

    The mechanism responsible for domain registration in two membrane leaflets has thus far remained enigmatic. Using continuum elasticity theory, we show that minimum line tension is achieved along the rim between thicker (ordered) and thinner (disordered) domains by shifting the rims in opposing leaflets by a few nanometers relative to each other. Increasing surface tension yields an increase in line tension, resulting in larger domains. Because domain registration is driven by lipid deformation energy, it does not require special lipid components nor interactions at the membrane midplane. PMID:26340212

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

    SciTech Connect

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

    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.

  13. Giant Effect of Uniaxial Pressure on Magnetic Domain Populations in Multiferroic Bismuth Ferrite

    NASA Astrophysics Data System (ADS)

    Ramazanoglu, M.; Ratcliff, W., II; Yi, H. T.; Sirenko, A. A.; Cheong, S.-W.; Kiryukhin, V.

    2011-08-01

    Neutron diffraction is used to show that small (˜7MPa, or 70 bar) uniaxial pressure produces significant changes in the populations of magnetic domains in a single crystal of 2% Nd-doped bismuth ferrite. The magnetic easy plane of the domains converted by the pressure is rotated 60° relative to its original position. These results demonstrate extreme sensitivity of the magnetic properties of multiferroic bismuth ferrite to tiny (less than 10-4) elastic strain, as well as weakness of the forces pinning the domain walls between the cycloidal magnetic domains in this material.

  14. Elastic Membrane Deformations Govern Interleaflet Coupling of Lipid-Ordered Domains.

    PubMed

    Galimzyanov, Timur R; Molotkovsky, Rodion J; Bozdaganyan, Marine E; Cohen, Fredric S; Pohl, Peter; Akimov, Sergey A

    2015-08-21

    The mechanism responsible for domain registration in two membrane leaflets has thus far remained enigmatic. Using continuum elasticity theory, we show that minimum line tension is achieved along the rim between thicker (ordered) and thinner (disordered) domains by shifting the rims in opposing leaflets by a few nanometers relative to each other. Increasing surface tension yields an increase in line tension, resulting in larger domains. Because domain registration is driven by lipid deformation energy, it does not require special lipid components or interactions at the membrane midplane. PMID:26340212

  15. Time domain scattering and radar cross section calculations for a thin, coated perfectly conducting plate

    NASA Technical Reports Server (NTRS)

    Luebbers, Raymond J.; Beggs, John H.

    1991-01-01

    Radar cross section (RCS) calculations for flat, perfectly conducting plates are readily available through the use of conventional frequency domain techniques such as the Method of Moments (MOM). However, if the plate is covered with a dielectric material that is relatively thick in comparison with the wavelength in the material, these frequency domain techniques become increasingly difficult to apply. We present the application of the Finite Difference Time Domain (FDTD) Technique to the problem of electromagnetic scattering and RCS calculations from a thin, perfectly conducting plate that is coated with a thick layer of lossless dielectric material. Both time domain and RCS calculations are presented and disclosed.

  16. Time domain scattering and radar cross section calculations for a thin, coated perfectly conducting plate

    NASA Technical Reports Server (NTRS)

    Luebbers, Raymond J.; Beggs, John H.

    1991-01-01

    Radar cross section (RCS) calculations for flat, perfectly conducting plates are readily available through the use of conventional frequency domain techniques such as the Method of Moments (MOM). However, if the plate is covered with a dielectric material that is relatively thick in comparison with the wavelength in the material, these frequency domain techniques become increasingly difficult to apply. The application is presented of the Finite Difference Time Domain (FDTD) technique to the problem of electromagnetic scattering and RCS calculations from a thin, perfectly conducting plate that is coated with a thick layer of lossless dielectric material. Both time domain and RCS calculations are presented and discussed.

  17. 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.

  18. Domain-Independent Scientific Function Finding

    NASA Astrophysics Data System (ADS)

    Schaffer, Cullen R.

    1990-01-01

    Programs such as Bacon, Abacus, Coper, Kepler and others are designed to find functional relationships of scientific significance in quantitative data without relying on the deep domain knowledge scientists normally bring to bear in analytic work. Whether these systems actually perform as intended is an open question, however. To date, they have been supported only by anecdotal evidence --reports that a desirable answer has been found in one or more selected and often artificial cases. In this dissertation, I thus attempt to develop, not only new approaches to domain -independent scientific function finding, but, equally, a rigorous methodology under which research into such methods can be conducted. A fundamental problem with previous work is that it has investigated scientific data analysis in the abstract --without referring to actual scientific data. By contrast, the work reported here is founded on a collection of 352 real scientific data sets. This empirical base supports a number of strong conclusions. First, while researchers working with artificial data have targeted complex multivariate relations, real data provides powerful evidence that even the simplest bivariate relationships are difficult to identify reliably. Second, despite its ubiquitous presence in previous work, the notion of heuristic search of a potentially explosive space of formulas appears to help very little with the problem of reliably identifying basic bivariate relationships. Instead, third, substantial performance improvement results from viewing function finding as a decision problem, the problem of classifying data sets reliably within a fixed--and quite limited--system of functional categories. This dissertation presents what I believe to be the strongest domain-independent scientific function-finding algorithm currently in existence and, certainly, the only one which has been rigorously demonstrated. At the same time, it suggests fundamental limitations in the power of such

  19. Floret-shaped solid domains on giant fluid lipid vesicles induced by pH

    NASA Astrophysics Data System (ADS)

    Sofou, Stavroula; Bandekar, Amey

    2012-02-01

    Lateral lipid phase separation and domain formation induced by changes in pH is significant in liposome-based drug delivery: environmentally responsive lipid heterogeneities can be tuned to alter collective membrane properties such as drug release and drug carrier reactivity impacting, therefore, the therapeutic outcomes. At the micron-meter scale, fluorescence microscopy on Giant Unilamellar fluid Vesicles (GUVs) shows that lowering pH (from 7.0 to 5.0) promotes the condensation of titratable PS or PA lipids into beautiful floret-shaped solid domains in which lipids are tightly packed via H-bonding and VdWs interactions. Solid domains phenomenologically comprise a circular ``core'' cap beyond which interfacial instabilities emerge resembling leaf-like stripes of almost vanishing Gaussian curvature independent of GUVs' preparation path and in agreement with a general condensation mechanism. Increasing incompressibility of domains is strongly correlated with larger number of thinner stripes per domain, and increasing relative rigidity of domains with smaller core cap areas. Line tension drives domain ripening, however the final domain shape is a result of enhanced incompressibility and rigidity maximized by domain coupling across the bilayer. Introduction of a transmembrane osmotic gradient (hyperosmotic on the outer lipid leaflet) allows the domain condensation process to reach its maximum extent which, however, is limited by the minimal expansivity of the continuous fluid membrane.

  20. The electrical Lithosphere of the Alboran Domain

    NASA Astrophysics Data System (ADS)

    Garcia, X. A.; Evans, R. L.; Elsenbeck, J.; Jegen, M. D.; Matsuno, T.

    2011-12-01

    On the Western edge of the Mediterranean, the slow convergence of the Iberian and African plates is marked by very intricate tectonic activity, marked by a combination of small-scale subduction and sub-lithospheric downwelling. Delamination or convective instability has also been proposed to have occurred beneath this domain during the past 25 My. And different geodynamic models have been proposed to explain the lithospheric structure of the arc-shaped belt (Betic and Rif orogenies) and the opening of the Alboran Basin. As part of several international projects carried out in this area, magnetotelluric (MT) methods have been used to explore the crust and upper mantle. The measurements of mantle electrical conductivity are a well known complement to measurements of seismic velocity. Conductivity is sensitive to temperature, composition and hydration of the mantle, and therefore MT is widely used to provide constraints on mantle processes. We present results of electromagnetic studies in the Western Mediterranean, focusing specially in the recently work on the Alboran sea as part of a marine MT survey. Land MT studies have already imaged an area of low resistivity coincident with an area of low velocities without earthquake hypocenters, interpreted as asthenospheric material intruded by the lateral lithospheric tearing and breaking-off of the east-directed subducting Ligurian slab under the Alboran Domain. The model suggests that the most likely scenario for the opening of the Alboran Basin is related to the westward rollback of the Ligurian subducting slab. The marine data show complex MT response functions with strong distortion due to seafloor topography and coast effect, suggesting a fairly resistive lithosphere beneath the seafloor.

  1. Phase transitions and domain structures in multiferroics

    NASA Astrophysics Data System (ADS)

    Vlahos, Eftihia

    2011-12-01

    Thin film ferroelectrics and multiferroics are two important classes of materials interesting both from a scientific and a technological prospective. The volatility of lead and bismuth as well as environmental issues regarding the toxicity of lead are two disadvantages of the most commonly used ferroelectric random access memory (FeRAM) materials such as Pb(Zr,Ti)O3 and SrBi2Ta2O9. Therefore lead-free thin film ferroelectrics are promising substitutes as long as (a) they can be grown on technologically important substrates such as silicon, and (b) their T c and Pr become comparable to that of well established ferroelectrics. On the other hand, the development of functional room temperature ferroelectric ferromagnetic multiferroics could lead to very interesting phenomena such as control of magnetism with electric fields and control of electrical polarization with magnetic fields. This thesis focuses on the understanding of material structure-property relations using nonlinear optical spectroscopy. Nonlinear spectroscopy is an excellent tool for probing the onset of ferroelectricity, and domain dynamics in strained ferroelectrics and multiferroics. Second harmonic generation was used to detect ferroelectricity and the antiferrodistortive phase transition in thin film SrTiO3. Incipient ferroelectric CaTiO3 has been shown to become ferroelectric when strained with a combination of SHG and dielectric measurements. The tensorial nature of the induced nonlinear polarization allows for probing of the BaTiO3 and SrTiO3 polarization contributions in nanoscale BaTiO3/SrTiO3 superlattices. In addition, nonlinear optics was used to demonstrate ferroelectricity in multiferroic EuTiO3. Finally, confocal SHG and Raman microscopy were utilized to visualize polar domains in incipient ferroelectric and ferroelastic CaTiO3.

  2. Transverse field-induced nucleation pad switching modes during domain wall injection

    SciTech Connect

    Bryan, M. T.; Fry, P. W.; Schrefl, T.; Gibbs, M. R. J.; Allwood, D. A.; Im, M.-Y.; Fischer, P.

    2010-03-12

    We have used magnetic transmission X-ray microscopy (M-TXM) to image in-field magnetization configurations of patterned Ni{sub 80}Fe{sub 20} domain wall 'injection pads' and attached planar nanowires. Comparison with micromagnetic simulations suggests that the evolution of magnetic domains in rectangular injection pads depends on the relative orientation of closure domains in the remanent state. The magnetization reversal pathway is also altered by the inclusion of transverse magnetic fields. These different modes explain previous results of domain wall injection into nanowires. Even more striking was the observation of domain walls injecting halfway across the width of wider (>400 nm wide) wires but over wire lengths of several micrometers. These extended Neel walls can interact with adjacent nanowires and cause a switching in the side of the wire undergoing reversal as the domain wall continues to expand.

  3. 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

  4. Structure of Concatenated HAMP Domains Provides a Mechanism for Signal Transduction

    SciTech Connect

    Airola, Michael V.; Watts, Kylie J.; Bilwes, Alexandrine M.; Crane, Brian R.

    2010-08-23

    HAMP domains are widespread prokaryotic signaling modules found as single domains or poly-HAMP chains in both transmembrane and soluble proteins. The crystal structure of a three-unit poly-HAMP chain from the Pseudomonas aeruginosa soluble receptor Aer2 defines a universal parallel four-helix bundle architecture for diverse HAMP domains. Two contiguous domains integrate to form a concatenated di-HAMP structure. The three HAMP domains display two distinct conformations that differ by changes in helical register, crossing angle, and rotation. These conformations are stabilized by different subsets of conserved residues. Known signals delivered to HAMP would be expected to switch the relative stability of the two conformations and the position of a coiled-coil phase stutter at the junction with downstream helices. We propose that the two conformations represent opposing HAMP signaling states and suggest a signaling mechanism whereby HAMP domains interconvert between the two states, which alternate down a poly-HAMP chain.

  5. Pinkbar is an epithelial-specific BAR domain protein that generates planar membrane structures

    SciTech Connect

    Pykäläinen, Anette; Boczkowska, Malgorzata; Zhao, Hongxia; Saarikangas, Juha; Rebowski, Grzegorz; Jansen, Maurice; Hakanen, Janne; Koskela, Essi V.; Peränen, Johan; Vihinen, Helena; Jokitalo, Eija; Salminen, Marjo; Ikonen, Elina; Dominguez, Roberto; Lappalainen, Pekka

    2013-05-29

    Bin/amphipysin/Rvs (BAR)-domain proteins sculpt cellular membranes and have key roles in processes such as endocytosis, cell motility and morphogenesis. BAR domains are divided into three subfamilies: BAR- and F-BAR-domain proteins generate positive membrane curvature and stabilize cellular invaginations, whereas I-BAR-domain proteins induce negative curvature and stabilize protrusions. We show that a previously uncharacterized member of the I-BAR subfamily, Pinkbar, is specifically expressed in intestinal epithelial cells, where it localizes to Rab13-positive vesicles and to the plasma membrane at intercellular junctions. Notably, the BAR domain of Pinkbar does not induce membrane tubulation but promotes the formation of planar membrane sheets. Structural and mutagenesis analyses reveal that the BAR domain of Pinkbar has a relatively flat lipid-binding interface and that it assembles into sheet-like oligomers in crystals and in solution, which may explain its unique membrane-deforming activity.

  6. 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. PMID:24680784

  7. The cloning of Grb10 reveals a new family of SH2 domain proteins.

    PubMed

    Ooi, J; Yajnik, V; Immanuel, D; Gordon, M; Moskow, J J; Buchberg, A M; Margolis, B

    1995-04-20

    SH2 domains function to bind proteins containing phosphotyrosine and are components of proteins that are important signal transducers for tyrosine kinases. We have cloned SH2 domain proteins by screening bacterial expression libraries with the tyrosine phosphorylated carboxyterminus of the epidermal growth factor (EGF) receptor. Here we report the identification of a new SH2 domain protein, Grb10. Grb10 is highly related to Grb7, an SH2 domain protein that we have previously identified. In addition to an SH2 domain, Grb7 and Grb10 have a central domain with similarity to a putative C. elegans gene likely to be involved in neuronal migration. At least three forms of Grb10 exist in fibroblasts apparently due to alternate translational start sites. Grb10 undergoes serine but not tyrosine phosphorylation after EGF treatment resulting in a shift mobility in a large fraction of Grb10 molecules. However Grb10 appears to bind poorly to EGF-Receptor and the true binding partner for the Grb10 SH2 domain is unclear. Grb10 maps to mouse chromosome 11 very close to the EGF-Receptor which is remarkably similar to Grb7 that maps near the EGF-Receptor related HER2 receptor. The finding of multiple family members with evolutionarily conserved domains indicates that these SH2 domain proteins are likely to have an important, although as of yet, unidentified function. PMID:7731717

  8. The formation of a generalized categorization repertoire: effect of training with multiple domains, samples, and comparisons.

    PubMed Central

    Fields, Lanny; Reeve, Kenneth F; Matneja, Priya; Varelas, Antonios; Belanich, James; Fitzer, Adrienne; Shamoun, Kim

    2002-01-01

    The present experiment explored the effects of three variables on the spontaneous categorization of stimuli in perceptually distinct and novel domains. Each of six stimulus domains was created by morphing two images that were the domain endpoints. The endpoints of the domains were male and female faces, two abstract drawings, a car and a truck, two banded-elevation satellite land images, a tree and a cat, and two false-color satellite images. The stimulus variants at each end of a domain defined two potential perceptual classes. Training was conducted in a matching-to-sample format and used stimuli from one or two domains, one or three variants per class as samples, and one or three variants per class as comparisons. The spontaneous categorization of stimuli in the untrained stimulus domains showed the emergence of a generalized categorization repertoire. The proportion of spontaneously categorized stimuli in the new domains was positively related to the number of domains and samples used in training, and was inversely related to the number of comparisons used in training. Differential reaction times demonstrated the discriminability of the stimuli in the emergent classes. This study is among the first to provide an empirical basis for a behavior-analytic model of the development of generalized categorization repertoires in natural settings. PMID:12507005

  9. Imaging Ferroelectric Domains and Domain Walls Using Charge Gradient Microscopy: Role of Screening Charges.

    PubMed

    Tong, Sheng; Jung, Il Woong; Choi, Yoon-Young; Hong, Seungbum; Roelofs, Andreas

    2016-02-23

    Advanced scanning probe microscopies (SPMs) open up the possibilities of the next-generation ferroic devices that utilize both domains and domain walls as active elements. However, current SPMs lack the capability of dynamically monitoring the motion of domains and domain walls in conjunction with the transport of the screening charges that lower the total electrostatic energy of both domains and domain walls. Charge gradient microscopy (CGM) is a strong candidate to overcome these shortcomings because it can map domains and domain walls at high speed and mechanically remove the screening charges. Yet the underlying mechanism of the CGM signals is not fully understood due to the complexity of the electrostatic interactions. Here, we designed a semiconductor-metal CGM tip, which can separate and quantify the ferroelectric domain and domain wall signals by simply changing its scanning direction. Our investigation reveals that the domain wall signals are due to the spatial change of polarization charges, while the domain signals are due to continuous removal and supply of screening charges at the CGM tip. In addition, we observed asymmetric CGM domain currents from the up and down domains, which are originated from the different debonding energies and the amount of the screening charges on positive and negative bound charges. We believe that our findings can help design CGM with high spatial resolution and lead to breakthroughs in information storage and energy-harvesting devices. PMID:26751281

  10. Miniature terahertz time-domain spectrometry

    NASA Astrophysics Data System (ADS)

    Schulkin, Brian

    This thesis focuses on the design, development and evaluation of novel concepts which enable the miniaturization of terahertz (THz) time-domain spectrometry. Portable THz spectrometry is applied to research and industrial domains for immediate, short and long term applications in nondestructive evaluation, homeland security, and biomedicine respectively. Due to the previous limitation of THz devices for public uses, in particular, the lack of access to a THz spectrometer, applications of THz science and technology have only recently expanded beyond the laboratory. There is an urgent need for compact, even handheld THz time-domain spectrometry (THz-TDS) platforms which can carry out proven-to-be-useful applications developed and tested in laboratory conditions. There are three major challenges restricting THz-TDS to laboratories. Atmospheric absorption severely limits the propagation distance of the THz beam and confines systems to low-moisture environments. The sample's surface roughness, grain size and geometry severely limit the bandwidth of the measurement. Physical size and weight of THz systems are generally limited by large laser sources and optomechanics. The sensitivity and selectivity of THz-TDS systems are the two most significant parameters used to describe the quality of the system. Sensitivity is directly related to the Signal-to-Noise Ratio (SNR) and dynamic range, which may be improved by either lowering the noise floor or increasing the THz signal. On the other hand, selectivity is far more complex as it is related to the sensitivity, sample preparation, baseline correction, and selection method. Sensitivity is gauged using industrial statistical methods, such as Gauge Repeatability and Reproducibility (GR&R), and can transform a not-so-useful SNR value to an extremely useful measure of the minimum detectable amount of a certain material. It is shown that the GR&R value is inversely proportional to the square root of the number of averaged waveforms

  11. Protein Domain Decomposition Using a Graph-Theoretic Approach

    SciTech Connect

    Xu, Y.; Xu, D.; Gabow, H.N.

    2000-08-20

    This paper presents a new algorithm for the decomposition of a multi-domain protein into individual structural domains. The underlying principle used is that residue-residue contacts are denser within a domain than between domains.

  12. AC driven magnetic domain quantification with 5 nm resolution.

    PubMed

    Li, Zhenghua; Li, Xiang; Dong, Dapeng; Liu, Dongping; Saito, H; Ishio, S

    2014-01-01

    As the magnetic storage density increases in commercial products, e.g. the hard disc drives, a full understanding of dynamic magnetism in nanometer resolution underpins the development of next-generation products. Magnetic force microscopy (MFM) is well suited to exploring ferromagnetic domain structures. However, atomic resolution cannot be achieved because data acquisition involves the sensing of long-range magnetostatic forces between tip and sample. Moreover, the dynamic magnetism cannot be characterized because MFM is only sensitive to the static magnetic fields. Here, we develop a side-band magnetic force microscopy (MFM) to locally observe the alternating magnetic fields in nanometer length scales at an operating distance of 1 nm. Variations in alternating magnetic fields and their relating time-variable magnetic domain reversals have been demonstrated by the side-band MFM. The magnetic domain wall motions, relating to the periodical rotation of sample magnetization, are quantified via micromagnetics. Based on the side-band MFM, the magnetic moment can be determined locally in a volume as small as 5 nanometers. The present technique can be applied to investigate the microscopic magnetic domain structures in a variety of magnetic materials, and allows a wide range of future applications, for example, in data storage and biomedicine. PMID:25011670

  13. Domain decomposition for the SPN solver MINOS

    SciTech Connect

    Jamelot, Erell; Baudron, Anne-Marie; Lautard, Jean-Jacques

    2012-07-01

    In this article we present a domain decomposition method for the mixed SPN equations, discretized with Raviart-Thomas-Nedelec finite elements. This domain decomposition is based on the iterative Schwarz algorithm with Robin interface conditions to handle communications. After having described this method, we give details on how to optimize the convergence. Finally, we give some numerical results computed in a realistic 3D domain. The computations are done with the MINOS solver of the APOLLO3 (R) code. (authors)

  14. Domain wall dynamics in cylindrical nanomagnet

    NASA Astrophysics Data System (ADS)

    Mukhopadhyay, Soumik; Singh, Amrita; Ghosh, Arindam

    2011-06-01

    The stochasticity associated with domain wall nucleation and propagation in a cylinderical nanowire has been studied using time resolved resistance measurement in presence of magnetic field. We have shown that the propagation stochasticity of domain wall in a cylindrical nanowire is reflected in the magnetic field dependent velocity distribution whereas the stochasticity involved in the domain wall nucleation can be effectively tuned by varying the angle between the direction of applied magnetic field and the long axis of the cylinder.

  15. 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

  16. Spread spectrum time domain reflectometry

    NASA Astrophysics Data System (ADS)

    Smith, Paul Samuel

    For many years, wiring has been treated as a system that could be installed and expected to work for the life of the aircraft. As aircraft age far beyond their original expected life span, this attitude is rapidly changing. Wiring problems have recently been identified as the cause of several tragic mishaps and hundreds of thousands of lost mission hours. Intermittent wiring faults have been and continue to be difficult to resolve. Test methods that pinpoint faults on the ground can miss intermittent failures. New test methods involving spread spectrum signals are investigated that could be used in flight to locate intermittent failures, including open circuits, short circuits, and arcs. Spread spectrum time domain reflectometry (SSTDR) and sequence time domain reflectometry (STDR) are analyzed in light of the signals commonly present on aircraft wiring. Pseudo noise codes used for the generation of STDR and SSTDR signals are analyzed for application in a STDR/SSTDR test system in the presence of noise. The effects of Mil-Std 1553 and white noise on the STDR and SSTDR signals are discussed analytically, through simulations, and with the use of test hardware. A test system using STDR and SSTDR is designed, built, and used to collect STDR and SSTDR test data. The data collected with the STDR/SSTDR test hardware is analyzed and compared to the theoretical results. Experimental data for open and short circuits collected using SSTDR and a curve fitting algorithm shows a maximum range estimation error of +/-0.2 ft for 75O coaxial cable up to 100ft, and +/-0.6ft for a sample 32.5ft non-controlled impedance aircraft cable. Mil-Std 1553 is specified to operate reliably with a signal-to-noise ratio of 17.5dB, and the SSTDR test system was able to locate an open circuit on a cable also carrying simulated Mil-Std 1553 data where the SSTDR signal was 50dB below the Mil-Std 1553 signal. STDR and SSTDR are shown to be effective in detecting and locating dry and wet arcs on wires.

  17. Cross-domain human action recognition.

    PubMed

    Bian, Wei; Tao, Dacheng; Rui, Yong

    2012-04-01

    Conventional human action recognition algorithms cannot work well when the amount of training videos is insufficient. We solve this problem by proposing a transfer topic model (TTM), which utilizes information extracted from videos in the auxiliary domain to assist recognition tasks in the target domain. The TTM is well characterized by two aspects: 1) it uses the bag-of-words model trained from the auxiliary domain to represent videos in the target domain; and 2) it assumes each human action is a mixture of a set of topics and uses the topics learned from the auxiliary domain to regularize the topic estimation in the target domain, wherein the regularization is the summation of Kullback-Leibler divergences between topic pairs of the two domains. The utilization of the auxiliary domain knowledge improves the generalization ability of the learned topic model. Experiments on Weizmann and KTH human action databases suggest the effectiveness of the proposed TTM for cross-domain human action recognition. PMID:21954214

  18. Transform domain steganography with blind source separation

    NASA Astrophysics Data System (ADS)

    Jouny, Ismail

    2015-05-01

    This paper applies blind source separation or independent component analysis for images that may contain mixtures of text, audio, or other images for steganography purposes. The paper focuses on separating mixtures in the transform domain such as Fourier domain or the Wavelet domain. The study addresses the effectiveness of steganography when using linear mixtures of multimedia components and the ability of standard blind sources separation techniques to discern hidden multimedia messages. Mixing in the space, frequency, and wavelet (scale) domains is compared. Effectiveness is measured using mean square error rate between original and recovered images.

  19. Origin and evolution of the cystic fibrosis transmembrane regulator protein R domain

    PubMed Central

    Sebastian, Aswathy; Rishishwar, Lavanya; Wang, Jianrong; Bernard, Karen F.; Conley, Andrew B.; McCarty, Nael A.; Jordan, I. King

    2013-01-01

    The Cystic Fibrosis Transmembrane Conductance Regulator protein (CFTR) is a member of the ABC transporter superfamily. CFTR is distinguished from all other members of this superfamily by its status as an ion channel as well as the presence of its unique regulatory (R) domain. We investigated the origin and subsequent evolution of the R domain along the CFTR evolutionary lineage. The R domain protein coding sequence originated via the loss of a splice donor site at the 3′ end of exon 14, leading to the subsequent read-through and capture of formerly intronic sequence as novel coding sequence. Inclusion of the remaining part of the R domain coding sequence in the CFTR transcript involved a lineage-specific gain of exonic sequence with no homology to protein coding sequences outside of CFTR and loss of two exons conserved among ABC family members. These events occurred at the base of the Gnathostome evolutionary lineage ~550–650 million years ago. The apparent origination of the R domain de novo from previously non-coding sequence is consistent with its lack of sequence similarity to other domains as well as its intrinsically disordered structure, which has important implications for its function. In particular, this lack of structure may provide for a dynamic and inducible regulatory activity based on transient physical interactions with more structured domains of the protein. Since its acquisition along the CFTR evolutionary lineage, the R domain has evolved more rapidly than any other CFTR domain; however, there is no evidence for positive (adaptive) selection in the evolution of the domain. The R domain does show a distinct pattern of relative evolutionary rates compared to other CFTR domains, which sheds additional light on the connection between its function and evolution. The regulatory function of the R domain is dependent upon a fairly small number of sites that are subject to phosphorylation, and these sites were fixed very early in R domain evolution

  20. Origin and evolution of the cystic fibrosis transmembrane regulator protein R domain.

    PubMed

    Sebastian, Aswathy; Rishishwar, Lavanya; Wang, Jianrong; Bernard, Karen F; Conley, Andrew B; McCarty, Nael A; Jordan, I King

    2013-07-10

    The Cystic Fibrosis Transmembrane Conductance Regulator protein (CFTR) is a member of the ABC transporter superfamily. CFTR is distinguished from all other members of this superfamily by its status as an ion channel as well as the presence of its unique regulatory (R) domain. We investigated the origin and subsequent evolution of the R domain along the CFTR evolutionary lineage. The R domain protein coding sequence originated via the loss of a splice donor site at the 3' end of exon 14, leading to the subsequent read-through and capture of formerly intronic sequence as novel coding sequence. Inclusion of the remaining part of the R domain coding sequence in the CFTR transcript involved a lineage-specific gain of exonic sequence with no homology to protein coding sequences outside of CFTR and loss of two exons conserved among ABC family members. These events occurred at the base of the Gnathostome evolutionary lineage ~550-650 million years ago. The apparent origination of the R domain de novo from previously non-coding sequence is consistent with its lack of sequence similarity to other domains as well as its intrinsically disordered structure, which has important implications for its function. In particular, this lack of structure may provide for a dynamic and inducible regulatory activity based on transient physical interactions with more structured domains of the protein. Since its acquisition along the CFTR evolutionary lineage, the R domain has evolved more rapidly than any other CFTR domain; however, there is no evidence for positive (adaptive) selection in the evolution of the domain. The R domain does show a distinct pattern of relative evolutionary rates compared to other CFTR domains, which sheds additional light on the connection between its function and evolution. The regulatory function of the R domain is dependent upon a fairly small number of sites that are subject to phosphorylation, and these sites were fixed very early in R domain evolution and