Sample records for domain previous work

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

    PubMed

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

    2016-01-01

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

  2. A Spoken Dialogue System for Command and Control

    DTIC Science & Technology

    2012-10-01

    Previous work in this domain focused on the formal representation of linguistic concepts in ontologies for data integration. His doctoral...20 2.8 Ongoing and Future Work .................................................................................... 20 2.8.1 Dynamic... work , we developed grammars with broader coverage for the domain of Livespace room-control. The goal was to provide commands and queries to be

  3. On the domain of the Nelson Hamiltonian

    NASA Astrophysics Data System (ADS)

    Griesemer, M.; Wünsch, A.

    2018-04-01

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

  4. An investigation of the effects of time and involvement in the relationship between stressors and work-family conflict.

    PubMed

    Fox, M L; Dwyer, D J

    1999-04-01

    Previous researchers have proposed that the time and energy involved in family and paid work should affect the relationship between stressors and conflict in both the work and family domains. Using a sample of 113 registered nurses, the authors hypothesized that the amount of time and involvement in both domains would moderate the stressor-conflict relationships. Results supported many of the interactions in predicting conflict in each domain, and implications for the health of working women with family responsibilities were discussed.

  5. Creativity and working memory capacity in sports: working memory capacity is not a limiting factor in creative decision making amongst skilled performers.

    PubMed

    Furley, Philip; Memmert, Daniel

    2015-01-01

    The goal of the study was to investigate the relationship between domain-general working memory capacity and domain-specific creativity amongst experienced soccer players. We administered the automated operation span task in combination with a domain-specific soccer creativity task to a group of 61 experienced soccer players to address the question whether an athlete's domain-specific creativity is restricted by their domain-general cognitive abilities (i.e., working memory capacity). Given that previous studies have either found a positive correlation, a negative correlation, or no correlation between working memory capacity and creativity, we analyzed the data in an exploratory manner by following recent recommendations to report effect-size estimations and their precision in form of 95% confidence intervals. The pattern of results provided evidence that domain-general working memory capacity is not associated with creativity in a soccer-specific creativity task. This pattern of results suggests that future research and theorizing on the role of working memory in everyday creative performance needs to distinguish between different types of creative performance while also taking the role of domain-specific experience into account.

  6. Creativity and working memory capacity in sports: working memory capacity is not a limiting factor in creative decision making amongst skilled performers

    PubMed Central

    Furley, Philip; Memmert, Daniel

    2015-01-01

    The goal of the study was to investigate the relationship between domain-general working memory capacity and domain-specific creativity amongst experienced soccer players. We administered the automated operation span task in combination with a domain-specific soccer creativity task to a group of 61 experienced soccer players to address the question whether an athlete’s domain-specific creativity is restricted by their domain-general cognitive abilities (i.e., working memory capacity). Given that previous studies have either found a positive correlation, a negative correlation, or no correlation between working memory capacity and creativity, we analyzed the data in an exploratory manner by following recent recommendations to report effect-size estimations and their precision in form of 95% confidence intervals. The pattern of results provided evidence that domain-general working memory capacity is not associated with creativity in a soccer-specific creativity task. This pattern of results suggests that future research and theorizing on the role of working memory in everyday creative performance needs to distinguish between different types of creative performance while also taking the role of domain-specific experience into account. PMID:25713552

  7. Achieving Consensus on Total Joint Replacement Trial Outcome Reporting Using the OMERACT Filter: Endorsement of the Final Core Domain Set for Total Hip and Total Knee Replacement Trials for Endstage Arthritis.

    PubMed

    Singh, Jasvinder A; Dowsey, Michelle M; Dohm, Michael; Goodman, Susan M; Leong, Amye L; Scholte Voshaar, Marieke M J H; Choong, Peter F

    2017-11-01

    Discussion and endorsement of the OMERACT total joint replacement (TJR) core domain set for total hip replacement (THR) and total knee replacement (TKR) for endstage arthritis; and next steps for selection of instruments. The OMERACT TJR working group met at the 2016 meeting at Whistler, British Columbia, Canada. We summarized the previous systematic reviews, the preliminary OMERACT TJR core domain set and results from previous surveys. We discussed preliminary core domains for TJR clinical trials, made modifications, and identified challenges with domain measurement. Working group participants (n = 26) reviewed, clarified, and endorsed each of the inner and middle circle domains and added a range of motion domain to the research agenda. TJR were limited to THR and TKR but included all endstage hip and knee arthritis refractory to medical treatment. Participants overwhelmingly endorsed identification and evaluation of top instruments mapping to the core domains (100%) and use of subscales of validated multidimensional instruments to measure core domains for the TJR clinical trial core measurement set (92%). An OMERACT core domain set for hip/knee TJR trials has been defined and we are selecting instruments to develop the TJR clinical trial core measurement set to serve as a common foundation for harmonizing measures in TJR clinical trials.

  8. How job demands affect partners' experience of exhaustion: integrating work-family conflict and crossover theory.

    PubMed

    Bakker, Arnold B; Demerouti, Evangelia; Dollard, Maureen F

    2008-07-01

    This study among 168 couples of dual-earner parents uses insights from previous work-family conflict and crossover research to propose an integrative model delineating how job demands experienced by men and women carry over to the home domain. The authors hypothesized that for both men and women, job demands foster their own work-family conflict (WFC), which in turn contributes to their partners' home demands, family-work conflict (FWC), and exhaustion. In addition, they hypothesized that social undermining mediates the relationship between individuals' WFC and their partners' home demands. The results of structural equation modeling analyses provided strong support for the proposed model. The hypothesis that gender would moderate the model relationships was rejected. These findings integrate previous findings on work-family conflict and crossover theories and suggest fluid boundaries between the work and home domains.

  9. Daily spillover from family to work: A test of the work-home resources model.

    PubMed

    Du, Danyang; Derks, Daantje; Bakker, Arnold B

    2018-04-01

    The present study examines a mediated moderation model of the day-level effects of family hassles and family-work spillover (affect and cognition) on the relationship between job resources and employees' flourishing at work. Based on the work-home resources model, the authors hypothesized that demands from one domain (family) induce repetitive thoughts or negative feelings about those problems, so that individuals are not able to function optimally and to make full use of contextual resources in the other domain (work). Multilevel analyses of 108 Chinese working parents' 366 daily surveys revealed that the relationship between morning job resources and afternoon flourishing was significantly positive when previous day family hassles were low; the relationship became nonsignificant when previous day family hassles were high. In addition, as predicted, daily rumination also attenuated the relationship between morning job resources and afternoon flourishing, whereas daily affect did not. Finally, the moderating effect of previous day family hassles was mediated by daily rumination. The findings contribute to spillover theories by revealing the roles of affective and cognitive spillover from family to work. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

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

    PubMed

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

    2014-01-01

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

  11. Combining MEDLINE and publisher data to create parallel corpora for the automatic translation of biomedical text

    PubMed Central

    2013-01-01

    Background Most of the institutional and research information in the biomedical domain is available in the form of English text. Even in countries where English is an official language, such as the United States, language can be a barrier for accessing biomedical information for non-native speakers. Recent progress in machine translation suggests that this technique could help make English texts accessible to speakers of other languages. However, the lack of adequate specialized corpora needed to train statistical models currently limits the quality of automatic translations in the biomedical domain. Results We show how a large-sized parallel corpus can automatically be obtained for the biomedical domain, using the MEDLINE database. The corpus generated in this work comprises article titles obtained from MEDLINE and abstract text automatically retrieved from journal websites, which substantially extends the corpora used in previous work. After assessing the quality of the corpus for two language pairs (English/French and English/Spanish) we use the Moses package to train a statistical machine translation model that outperforms previous models for automatic translation of biomedical text. Conclusions We have built translation data sets in the biomedical domain that can easily be extended to other languages available in MEDLINE. These sets can successfully be applied to train statistical machine translation models. While further progress should be made by incorporating out-of-domain corpora and domain-specific lexicons, we believe that this work improves the automatic translation of biomedical texts. PMID:23631733

  12. Lowered performance in working memory and attentional sub-processes are most prominent in multi-domain amnestic mild cognitive impairment subtypes.

    PubMed

    Klekociuk, Shannon Z; Summers, Mathew J

    2014-03-01

    Research suggests that working memory and attention deficits may be present in mild cognitive impairment (MCI). However, the functional status of these domains within revised MCI subtypes remains unclear, particularly because previous studies have examined these cognitive domains with the same tests that were used to classify MCI subtypes. The aim of this study was to examine working memory and attention function in MCI subtypes on a battery of neuropsychological tests that were distinct from those used to classify MCI subtypes A total of 122 adults aged 60-90 years were classified at baseline as amnestic MCI, non-amnestic MCI, and multi-domain amnestic (a-MCI+). The attentional and working memory capacity of participants was examined using a battery of tests distinct from those used to classify MCI at screening. The a-MCI+ group demonstrated the poorest performance on all working memory tasks and specific sub-processes of attention. The non-amnestic MCI group had lowered performance on visual span and complex sustained attention only. There was no evidence of either attentional or working memory impairment in the amnestic MCI participants. When MCI cohorts are assessed on measures distinct from those used at classification, a-MCI+ subjects had the most compromised working memory and attention function. These results support previous findings that suggest a-MCI+ more closely resembles early stage Alzheimer's disease and those with a-MCI+ may be at increased rate of future cognitive decline compared to those with other MCI subtypes. © 2014 The Authors. Psychogeriatrics © 2014 Japanese Psychogeriatric Society.

  13. Principle of minimal work fluctuations.

    PubMed

    Xiao, Gaoyang; Gong, Jiangbin

    2015-08-01

    Understanding and manipulating work fluctuations in microscale and nanoscale systems are of both fundamental and practical interest. For example, in considering the Jarzynski equality 〈e-βW〉=e-βΔF, a change in the fluctuations of e-βW may impact how rapidly the statistical average of e-βW converges towards the theoretical value e-βΔF, where W is the work, β is the inverse temperature, and ΔF is the free energy difference between two equilibrium states. Motivated by our previous study aiming at the suppression of work fluctuations, here we obtain a principle of minimal work fluctuations. In brief, adiabatic processes as treated in quantum and classical adiabatic theorems yield the minimal fluctuations in e-βW. In the quantum domain, if a system initially prepared at thermal equilibrium is subjected to a work protocol but isolated from a bath during the time evolution, then a quantum adiabatic process without energy level crossing (or an assisted adiabatic process reaching the same final states as in a conventional adiabatic process) yields the minimal fluctuations in e-βW, where W is the quantum work defined by two energy measurements at the beginning and at the end of the process. In the classical domain where the classical work protocol is realizable by an adiabatic process, then the classical adiabatic process also yields the minimal fluctuations in e-βW. Numerical experiments based on a Landau-Zener process confirm our theory in the quantum domain, and our theory in the classical domain explains our previous numerical findings regarding the suppression of classical work fluctuations [G. Y. Xiao and J. B. Gong, Phys. Rev. E 90, 052132 (2014)].

  14. COPRED: prediction of fold, GO molecular function and functional residues at the domain level.

    PubMed

    López, Daniel; Pazos, Florencio

    2013-07-15

    Only recently the first resources devoted to the functional annotation of proteins at the domain level started to appear. The next step is to develop specific methodologies for predicting function at the domain level based on these resources, and to implement them in web servers to be used by the community. In this work, we present COPRED, a web server for the concomitant prediction of fold, molecular function and functional sites at the domain level, based on a methodology for domain molecular function prediction and a resource of domain functional annotations previously developed and benchmarked. COPRED can be freely accessed at http://csbg.cnb.csic.es/copred. The interface works in all standard web browsers. WebGL (natively supported by most browsers) is required for the in-line preview and manipulation of protein 3D structures. The website includes a detailed help section and usage examples. pazos@cnb.csic.es.

  15. Examining Explanatory Biases in Young Children's Biological Reasoning

    ERIC Educational Resources Information Center

    Legare, Cristine H.; Gelman, Susan A.

    2014-01-01

    Despite the well-established literature on explanation in early childhood, little is known about what constrains children's explanations. State change and negative outcomes were examined as potential explanatory biases in the domain of naïve biology, extending upon previous work in the domain of naïve physics. In two studies, preschool children…

  16. Suppressing Irrelevant Information from Working Memory: Evidence for Domain-Specific Deficits in Poor Comprehenders

    ERIC Educational Resources Information Center

    Pimperton, Hannah; Nation, Kate

    2010-01-01

    Previous research has suggested that children with specific reading comprehension deficits (poor comprehenders) show an impaired ability to suppress irrelevant information from working memory, with this deficit detrimentally impacting on their working memory ability, and consequently limiting their reading comprehension performance. However, the…

  17. Development and initial evaluation of an enhanced measure of boundary flexibility for the work and family domains.

    PubMed

    Matthews, Russell A; Barnes-Farrell, Janet L

    2010-07-01

    This manuscript reports the development of a measure of work and family domain boundary flexibility. Building on previous research, we propose an expanded definition of boundary flexibility that includes two components-flexibility-ability and flexibility-willingness-and we develop a measure designed to capture this more comprehensive definition of boundary flexibility. Flexibility-ability is conceptualized as an individual's perception of personal and situational constraints that affect boundary management, and flexibility-willingness is conceptualized as an individual difference variable that captures the motivation to engage in boundary flexing. An additional feature of domain boundaries, permeability, is also examined. Data are presented from two studies. Study 1 (N = 244) describes the development of a multiscale measure that extends current conceptual definitions of boundary flexibility. Study 2 (N = 225) describes the refinement and evaluation of this measure. Confirmatory factor analysis, reliability evidence, interscale correlations, and correlations with important work-family constructs (e.g., domain centrality, work-family conflict) provide initial construct validity evidence for the measure.

  18. Outcomes in knowledge, attitudes and confidence of nursing staff working in nursing and residential care homes following a dementia training programme.

    PubMed

    Scerri, Anthony; Scerri, Charles

    2017-11-08

    Dementia training programmes for staff working in long-term care settings have been found to be effective in improving staff outcomes. This study investigated the impact of a dementia training programme for all Maltese nursing staff working in public nursing/residential homes on their knowledge, attitudes and confidence. Additionally, we identified the predictors of these domains before and after the programme. A 14-hour training programme focusing on dementia management, care and policy was developed for all nursing staff working in public nursing and residential homes in Malta. A pretest-posttest design was used to evaluate the participants' knowledge of dementia, attitudes and confidence in working with residents with dementia using validated tools. Demographic variables were measured and compared with each staff domain. The majority of nursing staff attended the training programme with 261 fully completed questionnaires being collected pre-training and 214 post-training. The programme significantly improved nursing staff knowledge, attitudes and confidence. Stepwise regression analysis of each staff domain showed that the strongest predictor in all models at pre-training was the intensity of previous training programmes. Furthermore, staff who attended previous training continued to improve in their attitudes and confidence following programme completion. The study continues to shed further evidence on the impact of dementia training programs on staff outcomes. It also indicated that the intensity of previous participation in dementia training programmes was related to the participants' knowledge, attitudes and confidence and that continual exposure to training had a cumulative effect.

  19. Domain-Specific Control of Selective Attention

    PubMed Central

    Lin, Szu-Hung; Yeh, Yei-Yu

    2014-01-01

    Previous research has shown that loading information on working memory affects selective attention. However, whether the load effect on selective attention is domain-general or domain-specific remains unresolved. The domain-general effect refers to the findings that load in one content (e.g. phonological) domain in working memory influences processing in another content (e.g., visuospatial) domain. Attentional control supervises selection regardless of information domain. The domain-specific effect refers to the constraint of influence only when maintenance and processing operate in the same domain. Selective attention operates in a specific content domain. This study is designed to resolve this controversy. Across three experiments, we manipulated the type of representation maintained in working memory and the type of representation upon which the participants must exert control to resolve conflict and select a target into the focus of attention. In Experiments 1a and 1b, participants maintained digits and nonverbalized objects, respectively, in working memory while selecting a target in a letter array. In Experiment 2, we presented auditory digits with a letter flanker task to exclude the involvement of resource competition within the same input modality. In Experiments 3a and 3b, we replaced the letter flanker task with an object flanker task while manipulating the memory load on object and digit representation, respectively. The results consistently showed that memory load modulated distractibility only when the stimuli of the two tasks were represented in the same domain. The magnitude of distractor interference was larger under high load than under low load, reflecting a lower efficacy of information prioritization. When the stimuli of the two tasks were represented in different domains, memory load did not modulate distractibility. Control of processing priority in selective attention demands domain-specific resources. PMID:24866977

  20. mlCAF: Multi-Level Cross-Domain Semantic Context Fusioning for Behavior Identification.

    PubMed

    Razzaq, Muhammad Asif; Villalonga, Claudia; Lee, Sungyoung; Akhtar, Usman; Ali, Maqbool; Kim, Eun-Soo; Khattak, Asad Masood; Seung, Hyonwoo; Hur, Taeho; Bang, Jaehun; Kim, Dohyeong; Ali Khan, Wajahat

    2017-10-24

    The emerging research on automatic identification of user's contexts from the cross-domain environment in ubiquitous and pervasive computing systems has proved to be successful. Monitoring the diversified user's contexts and behaviors can help in controlling lifestyle associated to chronic diseases using context-aware applications. However, availability of cross-domain heterogeneous contexts provides a challenging opportunity for their fusion to obtain abstract information for further analysis. This work demonstrates extension of our previous work from a single domain (i.e., physical activity) to multiple domains (physical activity, nutrition and clinical) for context-awareness. We propose multi-level Context-aware Framework (mlCAF), which fuses the multi-level cross-domain contexts in order to arbitrate richer behavioral contexts. This work explicitly focuses on key challenges linked to multi-level context modeling, reasoning and fusioning based on the mlCAF open-source ontology. More specifically, it addresses the interpretation of contexts from three different domains, their fusioning conforming to richer contextual information. This paper contributes in terms of ontology evolution with additional domains, context definitions, rules and inclusion of semantic queries. For the framework evaluation, multi-level cross-domain contexts collected from 20 users were used to ascertain abstract contexts, which served as basis for behavior modeling and lifestyle identification. The experimental results indicate a context recognition average accuracy of around 92.65% for the collected cross-domain contexts.

  1. mlCAF: Multi-Level Cross-Domain Semantic Context Fusioning for Behavior Identification

    PubMed Central

    Villalonga, Claudia; Lee, Sungyoung; Akhtar, Usman; Ali, Maqbool; Kim, Eun-Soo; Khattak, Asad Masood; Seung, Hyonwoo; Hur, Taeho; Kim, Dohyeong; Ali Khan, Wajahat

    2017-01-01

    The emerging research on automatic identification of user’s contexts from the cross-domain environment in ubiquitous and pervasive computing systems has proved to be successful. Monitoring the diversified user’s contexts and behaviors can help in controlling lifestyle associated to chronic diseases using context-aware applications. However, availability of cross-domain heterogeneous contexts provides a challenging opportunity for their fusion to obtain abstract information for further analysis. This work demonstrates extension of our previous work from a single domain (i.e., physical activity) to multiple domains (physical activity, nutrition and clinical) for context-awareness. We propose multi-level Context-aware Framework (mlCAF), which fuses the multi-level cross-domain contexts in order to arbitrate richer behavioral contexts. This work explicitly focuses on key challenges linked to multi-level context modeling, reasoning and fusioning based on the mlCAF open-source ontology. More specifically, it addresses the interpretation of contexts from three different domains, their fusioning conforming to richer contextual information. This paper contributes in terms of ontology evolution with additional domains, context definitions, rules and inclusion of semantic queries. For the framework evaluation, multi-level cross-domain contexts collected from 20 users were used to ascertain abstract contexts, which served as basis for behavior modeling and lifestyle identification. The experimental results indicate a context recognition average accuracy of around 92.65% for the collected cross-domain contexts. PMID:29064459

  2. Structure and function of the C-terminal domain of MrpA in the Bacillus subtilis Mrp-antiporter complex--the evolutionary progenitor of the long horizontal helix in complex I.

    PubMed

    Virzintiene, Egle; Moparthi, Vamsi K; Al-Eryani, Yusra; Shumbe, Leonard; Górecki, Kamil; Hägerhäll, Cecilia

    2013-10-11

    MrpA and MrpD are homologous to NuoL, NuoM and NuoN in complex I over the first 14 transmembrane helices. In this work, the C-terminal domain of MrpA, outside this conserved area, was investigated. The transmembrane orientation was found to correspond to that of NuoJ in complex I. We have previously demonstrated that the subunit NuoK is homologous to MrpC. The function of the MrpA C-terminus was tested by expression in a previously used Bacillus subtilis model system. At neutral pH, the truncated MrpA still worked, but at pH 8.4, where Mrp-complex formation is needed for function, the C-terminal domain of MrpA was absolutely required. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  3. Defining Outcome Measures for Psoriasis: The IDEOM Report from the GRAPPA 2016 Annual Meeting.

    PubMed

    Callis Duffin, Kristina; Gottlieb, Alice B; Merola, Joseph F; Latella, John; Garg, Amit; Armstrong, April W

    2017-05-01

    The International Dermatology Outcome Measures (IDEOM) psoriasis working group was established to develop core domains and measurements sets for psoriasis clinical trials and ultimately clinical practice. At the 2016 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis, the IDEOM psoriasis group presented an overview of its progress toward developing this psoriasis core domain set. First, it summarized the February 2016 meeting of all involved with the IDEOM, highlighting patient and payer perspectives on outcome measures. Second, the group presented an overview of the consensus process for developing the core domain set for psoriasis, including previous literature reviews, nominal group exercises, and meeting discussions. Future plans include the development of working groups to review candidate measures for at least 2 of the domains, including primary pathophysiologic manifestations and patient-reported outcomes, and Delphi surveys to gain consensus on the final psoriasis core domain set.

  4. Music training and working memory: an ERP study.

    PubMed

    George, Elyse M; Coch, Donna

    2011-04-01

    While previous research has suggested that music training is associated with improvements in various cognitive and linguistic skills, the mechanisms mediating or underlying these associations are mostly unknown. Here, we addressed the hypothesis that previous music training is related to improved working memory. Using event-related potentials (ERPs) and a standardized test of working memory, we investigated both neural and behavioral aspects of working memory in college-aged, non-professional musicians and non-musicians. Behaviorally, musicians outperformed non-musicians on standardized subtests of visual, phonological, and executive memory. ERPs were recorded in standard auditory and visual oddball paradigms (participants responded to infrequent deviant stimuli embedded in lists of standard stimuli). Electrophysiologically, musicians demonstrated faster updating of working memory (shorter latency P300s) in both the auditory and visual domains and musicians allocated more neural resources to auditory stimuli (larger amplitude P300), showing increased sensitivity to the auditory standard/deviant difference and less effortful updating of auditory working memory. These findings demonstrate that long-term music training is related to improvements in working memory, in both the auditory and visual domains and in terms of both behavioral and ERP measures. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Navigation and Comprehension of Digital Expository Texts: Hypertext Structure, Previous Domain Knowledge, and Working Memory Capacity

    ERIC Educational Resources Information Center

    Burin, Debora I.; Barreyro, Juan P.; Saux, Gastón; Irrazábal, Natalia C.

    2015-01-01

    Introduction: In contemporary information societies, reading digital text has become pervasive. One of the most distinctive features of digital texts is their internal connections via hyperlinks, resulting in non-linear hypertexts. Hypertext structure and previous knowledge affect navigation and comprehension of digital expository texts. From the…

  6. Effects of Three Diagram Instruction Methods on Transfer of Diagram Comprehension Skills: The Critical Role of Inference While Learning

    ERIC Educational Resources Information Center

    Cromley, Jennifer G.; Bergey, Bradley W.; Fitzhugh, Shannon; Newcombe, Nora; Wills, Theodore W.; Shipley, Thomas F.; Tanaka, Jacqueline C.

    2013-01-01

    Can students be taught to better comprehend the diagrams in their textbooks? Can such teaching transfer to uninstructed diagrams in the same domain or even in a new domain? What methods work best for these goals? Building on previous research showing positive results compared to control groups in both laboratory studies and short-term…

  7. Domain Nucleation Rates and Interfacial Line Tensions in Supported Bilayers of Ternary Mixtures Containing Galactosylceramide

    PubMed Central

    Blanchette, Craig D.; Lin, Wan-Chen; Orme, Christine A.; Ratto, Timothy V.; Longo, Marjorie L.

    2008-01-01

    Domains within the plane of the plasma membrane, referred to as membrane rafts, have been a topic of considerable interest in the field of membrane biophysics. Although model membrane systems have been used extensively to study lipid phase behavior as it relates to the existence of rafts, very little work has focused on either the initial stage of lipid domain nucleation, or the relevant physical parameters such as temperature and interfacial line tension which control nucleation. In this work, we utilize a method in which the kinetic process of lipid domain nucleation is imaged by atomic force microscopy and modeled using classical theory of nucleation to map interfacial line tension in ternary lipid mixtures. These mixtures consist of a fluid phase lipid component (1,2-dilauroyl-sn-glycero-3-phosphocholine, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, or 1,2-dioleoyl-sn-glycero-3-phosphocholine), a solid phase component (galactosylceramide), and cholesterol. Interfacial line tension measurements of galactosylceramide-rich domains track with our previously measured area/perimeter ratios and height mismatches measured here. Line tension also follows known trends in cholesterol interactions and partitioning, as we observed previously with area/perimeter ratios. Our line tension measurements are discussed in combination with recent line tension measurements to address line tension regulation by cholesterol and the dynamic nature of membrane rafts. PMID:18065459

  8. Optical digital chaos cryptography

    NASA Astrophysics Data System (ADS)

    Arenas-Pingarrón, Álvaro; González-Marcos, Ana P.; Rivas-Moscoso, José M.; Martín-Pereda, José A.

    2007-10-01

    In this work we present a new way to mask the data in a one-user communication system when direct sequence - code division multiple access (DS-CDMA) techniques are used. The code is generated by a digital chaotic generator, originally proposed by us and previously reported for a chaos cryptographic system. It is demonstrated that if the user's data signal is encoded with a bipolar phase-shift keying (BPSK) technique, usual in DS-CDMA, it can be easily recovered from a time-frequency domain representation. To avoid this situation, a new system is presented in which a previous dispersive stage is applied to the data signal. A time-frequency domain analysis is performed, and the devices required at the transmitter and receiver end, both user-independent, are presented for the optical domain.

  9. Characteristic of cognitive decline in Parkinson's disease: a 1-year follow-up.

    PubMed

    McKinlay, Audrey; Grace, Randolph C

    2011-10-01

    The aim of this study was to track the evolution of cognitive decline in Parkinson's disease (PD) patients 1 year after baseline testing. Thirty-three PD patients, divided according to three previously determined subgroups based on their initial cognitive performance, and a healthy comparison group were reassessed after a 1-year interval. Participants were assessed in the following five domains: Executive Function, Problem Solving, Working Memory/Attention, Memory, and Visuospatial Ability. The PD groups differed on the domains of Executive Function, Problem Solving, and Working Memory, with the most severe deficits being evident for the group that had previously shown the greatest level of impairment. Increased cognitive problems were also associated with decreased functioning in activities of daily living. The most severely impaired group had evidence of global cognitive decline, possibly reflecting a stage of preclinical dementia.

  10. Identification of an Amino Acid Domain Encoded by the Capsid Protein Gene of Porcine Circovirus Type 2 that Modulates Viral Protein Distribution During Replication

    USDA-ARS?s Scientific Manuscript database

    Previous work showed that distinct amino acid motifs are encoded by the Rep, Cap and ORF3 genes of two subgroups of porcine circoviruses (PCV), PCV2a and PCV2b. At a specific location of the gene, a certain amino acid residue or sequence is preferred. Specifically, two amino acid domains located in ...

  11. Elucidating nitric oxide synthase domain interactions by molecular dynamics.

    PubMed

    Hollingsworth, Scott A; Holden, Jeffrey K; Li, Huiying; Poulos, Thomas L

    2016-02-01

    Nitric oxide synthase (NOS) is a multidomain enzyme that catalyzes the production of nitric oxide (NO) by oxidizing L-Arg to NO and L-citrulline. NO production requires multiple interdomain electron transfer steps between the flavin mononucleotide (FMN) and heme domain. Specifically, NADPH-derived electrons are transferred to the heme-containing oxygenase domain via the flavin adenine dinucleotide (FAD) and FMN containing reductase domains. While crystal structures are available for both the reductase and oxygenase domains of NOS, to date there is no atomic level structural information on domain interactions required for the final FMN-to-heme electron transfer step. Here, we evaluate a model of this final electron transfer step for the heme-FMN-calmodulin NOS complex based on the recent biophysical studies using a 105-ns molecular dynamics trajectory. The resulting equilibrated complex structure is very stable and provides a detailed prediction of interdomain contacts required for stabilizing the NOS output state. The resulting equilibrated complex model agrees well with previous experimental work and provides a detailed working model of the final NOS electron transfer step required for NO biosynthesis. © 2015 The Protein Society.

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

    PubMed

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

    2006-04-15

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

  13. Noise Radiation From a Leading-Edge Slat

    NASA Technical Reports Server (NTRS)

    Lockard, David P.; Choudhari, Meelan M.

    2009-01-01

    This paper extends our previous computations of unsteady flow within the slat cove region of a multi-element high-lift airfoil configuration, which showed that both statistical and structural aspects of the experimentally observed unsteady flow behavior can be captured via 3D simulations over a computational domain of narrow spanwise extent. Although such narrow domain simulation can account for the spanwise decorrelation of the slat cove fluctuations, the resulting database cannot be applied towards acoustic predictions of the slat without invoking additional approximations to synthesize the fluctuation field over the rest of the span. This deficiency is partially alleviated in the present work by increasing the spanwise extent of the computational domain from 37.3% of the slat chord to nearly 226% (i.e., 15% of the model span). The simulation database is used to verify consistency with previous computational results and, then, to develop predictions of the far-field noise radiation in conjunction with a frequency-domain Ffowcs-Williams Hawkings solver.

  14. Risk and risk management for Australian sex workers.

    PubMed

    Harris, Margaret; Nilan, Pam; Kirby, Emma

    2011-03-01

    In this article, we address the experiences of female sex workers in urban Australia through analysis of interviews using a feminist approach. Although many previous studies have been conducted, our focus was on the voices of sex workers in an area that was rapidly gentrifying, leading to local community tensions. Intensive analysis of interview transcripts was employed to derive thematic codes for understanding how the women viewed and managed everyday risk in sex work. They were well aware of the health risks associated with sex work. For women working on premises, domain separation between sex work and other life domains was an important management strategy for maintaining self-esteem. For women working on the street, instincts honed by years of dangerous work provided a measure of safety. Our findings have implications for health and other agencies dealing with sex workers in situations in which community pressure is exerted to move sex workers away from the area.

  15. Understanding ferromagnetic hysteresis: A theoretical approach

    NASA Astrophysics Data System (ADS)

    Gangopadhyay, Bijan Kumar

    2018-05-01

    This work presents a theoretical-mathematical model for the ferromagnetic hysteresis. Theoretical understanding on ferromagnetism can be achieved through addressing the self-interaction propensity between the magnetic dipole moments associated with the magnetic domains, in conjunction with the pinning effects of the dipoles with the defects in the domain sites. An expression which relates ferromagnetic magnetization to the effective magnetic field was established in our previous work (AIP Conference Proceedings 1665, 130042 (2015)). Using this relation and solving for the reversible and the irreversible components of the magnetization, we successfully show that the magnetic saturation and the magnetic remanence can be achieved theoretically. This work also estimates the range of the external field that can be used to trace a reversible M-H curve.

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

    PubMed Central

    Wang, Xiao-Tao; Cui, Wang

    2017-01-01

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

  17. The Extent of Working Memory Deficits Associated with Williams Syndrome: Exploration of Verbal and Spatial Domains and Executively Controlled Processes

    ERIC Educational Resources Information Center

    Rhodes, Sinead M.; Riby, Deborah M.; Fraser, Emma; Campbell, Lorna Elise

    2011-01-01

    The present study investigated verbal and spatial working memory (WM) functioning in individuals with the neuro-developmental disorder Williams syndrome (WS) using WM component tasks. While there is strong evidence of WM impairments in WS, previous research has focused on short-term memory and has neglected assessment of executive components of…

  18. Effects of biases in domain wall network evolution. II. Quantitative analysis

    NASA Astrophysics Data System (ADS)

    Correia, J. R. C. C. C.; Leite, I. S. C. R.; Martins, C. J. A. P.

    2018-04-01

    Domain walls form at phase transitions which break discrete symmetries. In a cosmological context, they often overclose the Universe (contrary to observational evidence), although one may prevent this by introducing biases or forcing anisotropic evolution of the walls. In a previous work [Correia et al., Phys. Rev. D 90, 023521 (2014), 10.1103/PhysRevD.90.023521], we numerically studied the evolution of various types of biased domain wall networks in the early Universe, confirming that anisotropic networks ultimately reach scaling while those with a biased potential or biased initial conditions decay. We also found that the analytic decay law obtained by Hindmarsh was in good agreement with simulations of biased potentials, but not of biased initial conditions, and suggested that the difference was related to the Gaussian approximation underlying the analytic law. Here, we extend our previous work in several ways. For the cases of biased potential and biased initial conditions, we study in detail the field distributions in the simulations, confirming that the validity (or not) of the Gaussian approximation is the key difference between the two cases. For anisotropic walls, we carry out a more extensive set of numerical simulations and compare them to the canonical velocity-dependent one-scale model for domain walls, finding that the model accurately predicts the linear scaling regime after isotropization. Overall, our analysis provides a quantitative description of the cosmological evolution of these networks.

  19. Modeling Patient Treatment With Medical Records: An Abstraction Hierarchy to Understand User Competencies and Needs.

    PubMed

    St-Maurice, Justin D; Burns, Catherine M

    2017-07-28

    Health care is a complex sociotechnical system. Patient treatment is evolving and needs to incorporate the use of technology and new patient-centered treatment paradigms. Cognitive work analysis (CWA) is an effective framework for understanding complex systems, and work domain analysis (WDA) is useful for understanding complex ecologies. Although previous applications of CWA have described patient treatment, due to their scope of work patients were previously characterized as biomedical machines, rather than patient actors involved in their own care. An abstraction hierarchy that characterizes patients as beings with complex social values and priorities is needed. This can help better understand treatment in a modern approach to care. The purpose of this study was to perform a WDA to represent the treatment of patients with medical records. The methods to develop this model included the analysis of written texts and collaboration with subject matter experts. Our WDA represents the ecology through its functional purposes, abstract functions, generalized functions, physical functions, and physical forms. Compared with other work domain models, this model is able to articulate the nuanced balance between medical treatment, patient education, and limited health care resources. Concepts in the analysis were similar to the modeling choices of other WDAs but combined them in as a comprehensive, systematic, and contextual overview. The model is helpful to understand user competencies and needs. Future models could be developed to model the patient's domain and enable the exploration of the shared decision-making (SDM) paradigm. Our work domain model links treatment goals, decision-making constraints, and task workflows. This model can be used by system developers who would like to use ecological interface design (EID) to improve systems. Our hierarchy is the first in a future set that could explore new treatment paradigms. Future hierarchies could model the patient as a controller and could be useful for mobile app development. ©Justin D St-Maurice, Catherine M Burns. Originally published in JMIR Human Factors (http://humanfactors.jmir.org), 28.07.2017.

  20. Modeling Patient Treatment With Medical Records: An Abstraction Hierarchy to Understand User Competencies and Needs

    PubMed Central

    2017-01-01

    Background Health care is a complex sociotechnical system. Patient treatment is evolving and needs to incorporate the use of technology and new patient-centered treatment paradigms. Cognitive work analysis (CWA) is an effective framework for understanding complex systems, and work domain analysis (WDA) is useful for understanding complex ecologies. Although previous applications of CWA have described patient treatment, due to their scope of work patients were previously characterized as biomedical machines, rather than patient actors involved in their own care. Objective An abstraction hierarchy that characterizes patients as beings with complex social values and priorities is needed. This can help better understand treatment in a modern approach to care. The purpose of this study was to perform a WDA to represent the treatment of patients with medical records. Methods The methods to develop this model included the analysis of written texts and collaboration with subject matter experts. Our WDA represents the ecology through its functional purposes, abstract functions, generalized functions, physical functions, and physical forms. Results Compared with other work domain models, this model is able to articulate the nuanced balance between medical treatment, patient education, and limited health care resources. Concepts in the analysis were similar to the modeling choices of other WDAs but combined them in as a comprehensive, systematic, and contextual overview. The model is helpful to understand user competencies and needs. Future models could be developed to model the patient’s domain and enable the exploration of the shared decision-making (SDM) paradigm. Conclusion Our work domain model links treatment goals, decision-making constraints, and task workflows. This model can be used by system developers who would like to use ecological interface design (EID) to improve systems. Our hierarchy is the first in a future set that could explore new treatment paradigms. Future hierarchies could model the patient as a controller and could be useful for mobile app development. PMID:28754650

  1. Stochastic lattice model of synaptic membrane protein domains.

    PubMed

    Li, Yiwei; Kahraman, Osman; Haselwandter, Christoph A

    2017-05-01

    Neurotransmitter receptor molecules, concentrated in synaptic membrane domains along with scaffolds and other kinds of proteins, are crucial for signal transmission across chemical synapses. In common with other membrane protein domains, synaptic domains are characterized by low protein copy numbers and protein crowding, with rapid stochastic turnover of individual molecules. We study here in detail a stochastic lattice model of the receptor-scaffold reaction-diffusion dynamics at synaptic domains that was found previously to capture, at the mean-field level, the self-assembly, stability, and characteristic size of synaptic domains observed in experiments. We show that our stochastic lattice model yields quantitative agreement with mean-field models of nonlinear diffusion in crowded membranes. Through a combination of analytic and numerical solutions of the master equation governing the reaction dynamics at synaptic domains, together with kinetic Monte Carlo simulations, we find substantial discrepancies between mean-field and stochastic models for the reaction dynamics at synaptic domains. Based on the reaction and diffusion properties of synaptic receptors and scaffolds suggested by previous experiments and mean-field calculations, we show that the stochastic reaction-diffusion dynamics of synaptic receptors and scaffolds provide a simple physical mechanism for collective fluctuations in synaptic domains, the molecular turnover observed at synaptic domains, key features of the observed single-molecule trajectories, and spatial heterogeneity in the effective rates at which receptors and scaffolds are recycled at the cell membrane. Our work sheds light on the physical mechanisms and principles linking the collective properties of membrane protein domains to the stochastic dynamics that rule their molecular components.

  2. A Cross-Domain Collaborative Filtering Algorithm Based on Feature Construction and Locally Weighted Linear Regression

    PubMed Central

    Jiang, Feng; Han, Ji-zhong

    2018-01-01

    Cross-domain collaborative filtering (CDCF) solves the sparsity problem by transferring rating knowledge from auxiliary domains. Obviously, different auxiliary domains have different importance to the target domain. However, previous works cannot evaluate effectively the significance of different auxiliary domains. To overcome this drawback, we propose a cross-domain collaborative filtering algorithm based on Feature Construction and Locally Weighted Linear Regression (FCLWLR). We first construct features in different domains and use these features to represent different auxiliary domains. Thus the weight computation across different domains can be converted as the weight computation across different features. Then we combine the features in the target domain and in the auxiliary domains together and convert the cross-domain recommendation problem into a regression problem. Finally, we employ a Locally Weighted Linear Regression (LWLR) model to solve the regression problem. As LWLR is a nonparametric regression method, it can effectively avoid underfitting or overfitting problem occurring in parametric regression methods. We conduct extensive experiments to show that the proposed FCLWLR algorithm is effective in addressing the data sparsity problem by transferring the useful knowledge from the auxiliary domains, as compared to many state-of-the-art single-domain or cross-domain CF methods. PMID:29623088

  3. A Cross-Domain Collaborative Filtering Algorithm Based on Feature Construction and Locally Weighted Linear Regression.

    PubMed

    Yu, Xu; Lin, Jun-Yu; Jiang, Feng; Du, Jun-Wei; Han, Ji-Zhong

    2018-01-01

    Cross-domain collaborative filtering (CDCF) solves the sparsity problem by transferring rating knowledge from auxiliary domains. Obviously, different auxiliary domains have different importance to the target domain. However, previous works cannot evaluate effectively the significance of different auxiliary domains. To overcome this drawback, we propose a cross-domain collaborative filtering algorithm based on Feature Construction and Locally Weighted Linear Regression (FCLWLR). We first construct features in different domains and use these features to represent different auxiliary domains. Thus the weight computation across different domains can be converted as the weight computation across different features. Then we combine the features in the target domain and in the auxiliary domains together and convert the cross-domain recommendation problem into a regression problem. Finally, we employ a Locally Weighted Linear Regression (LWLR) model to solve the regression problem. As LWLR is a nonparametric regression method, it can effectively avoid underfitting or overfitting problem occurring in parametric regression methods. We conduct extensive experiments to show that the proposed FCLWLR algorithm is effective in addressing the data sparsity problem by transferring the useful knowledge from the auxiliary domains, as compared to many state-of-the-art single-domain or cross-domain CF methods.

  4. Cross-Species Analyses Identify the BNIP-2 and Cdc42GAP Homology (BCH) Domain as a Distinct Functional Subclass of the CRAL_TRIO/Sec14 Superfamily

    PubMed Central

    Gupta, Anjali Bansal; Wee, Liang En; Zhou, Yi Ting; Hortsch, Michael; Low, Boon Chuan

    2012-01-01

    The CRAL_TRIO protein domain, which is unique to the Sec14 protein superfamily, binds to a diverse set of small lipophilic ligands. Similar domains are found in a range of different proteins including neurofibromatosis type-1, a Ras GTPase-activating Protein (RasGAP) and Rho guanine nucleotide exchange factors (RhoGEFs). Proteins containing this structural protein domain exhibit a low sequence similarity and ligand specificity while maintaining an overall characteristic three-dimensional structure. We have previously demonstrated that the BNIP-2 and Cdc42GAP Homology (BCH) protein domain, which shares a low sequence homology with the CRAL_TRIO domain, can serve as a regulatory scaffold that binds to Rho, RhoGEFs and RhoGAPs to control various cell signalling processes. In this work, we investigate 175 BCH domain-containing proteins from a wide range of different organisms. A phylogenetic analysis with ∼100 CRAL_TRIO and similar domains from eight representative species indicates a clear distinction of BCH-containing proteins as a novel subclass within the CRAL_TRIO/Sec14 superfamily. BCH-containing proteins contain a hallmark sequence motif R(R/K)h(R/K)(R/K)NL(R/K)xhhhhHPs (‘h’ is large and hydrophobic residue and ‘s’ is small and weekly polar residue) and can be further subdivided into three unique subtypes associated with BNIP-2-N, macro- and RhoGAP-type protein domains. A previously unknown group of genes encoding ‘BCH-only’ domains is also identified in plants and arthropod species. Based on an analysis of their gene-structure and their protein domain context we hypothesize that BCH domain-containing genes evolved through gene duplication, intron insertions and domain swapping events. Furthermore, we explore the point of divergence between BCH and CRAL-TRIO proteins in relation to their ability to bind small GTPases, GAPs and GEFs and lipid ligands. Our study suggests a need for a more extensive analysis of previously uncharacterized BCH, ‘BCH-like’ and CRAL_TRIO-containing proteins and their significance in regulating signaling events involving small GTPases. PMID:22479462

  5. Macroscopic domain formation during cooling in the platelet plasma membrane: an issue of low cholesterol content

    PubMed Central

    Bali, Rachna; Savino, Laura; Ramirez, Diego A.; Tsvetkova, Nelly M.; Bagatolli, Luis; Tablin, Fern; Crowe, John H.; Leidy, Chad

    2009-01-01

    There has been ample debate on whether cell membranes can present macroscopic lipid domains as predicted by three-component phase diagrams obtained by fluorescence microscopy. Several groups have argued that membrane proteins and interactions with the cytoskeleton inhibit the formation of large domains. In contrast, some polarizable cells do show large regions with qualitative differences in lipid fluidity. It is important to ask more precisely, based on the current phase diagrams, under what conditions would large domains be expected to form in cells. In this work we study the thermotropic phase behavior of the platelet plasma membrane by FTIR, and compare it to a POPC/Sphingomyelin/Cholesterol model representing the outer leaflet composition. We find that this model closely reflects the platelet phase behavior. Previous work has shown that the platelet plasma membrane presents inhomogeneous distribution of DiI18:0 at 24°C, but not at 37°C, which suggests the formation of macroscopic lipid domains at low temperatures. We show by fluorescence microscopy, and by comparison with published phase diagrams, that the outer leaflet model system enters the macroscopic domain region only at the lower temperature. In addition, the low cholesterol content in platelets (~15 mol %), appears to be crucial for the formation of large domains during cooling. PMID:19341703

  6. An energy-consistent fracture model for ferroelectrics

    NASA Astrophysics Data System (ADS)

    Miao, Hongchen; Li, Faxin

    2017-02-01

    The fracture behavior of ferroelectrics has been intensively studied in recent decades, though currently a widely accepted fracture mechanism is still lacking. In this work, enlightened by previous experimental observations that crack propagation in ferroelectrics is always accompanied by domain switching, we propose a micromechanical model in which both crack propagation and domain switching are controlled by energy-based criteria. Both electric energy and mechanical energy can induce domain switching, while only mechanical energy can drive crack propagation. Furthermore, constrained domain switching is considered in this model, leading to the gradient domain switching zone near the crack tip. Analysis results show that stress-induced ferroelastic switching always has a toughening effect as the mechanical energy release rate serves as the driving force for both fracture and domain switching. In comparison, the electric-field-induced switching may have either a toughening or detoughening effect. The proposed model can qualitatively agree with the existing experimental results.

  7. Invited Article: Generation of one-million-mode continuous-variable cluster state by unlimited time-domain multiplexing

    NASA Astrophysics Data System (ADS)

    Yoshikawa, Jun-ichi; Yokoyama, Shota; Kaji, Toshiyuki; Sornphiphatphong, Chanond; Shiozawa, Yu; Makino, Kenzo; Furusawa, Akira

    2016-09-01

    In recent quantum optical continuous-variable experiments, the number of fully inseparable light modes has drastically increased by introducing a multiplexing scheme either in the time domain or in the frequency domain. Here, modifying the time-domain multiplexing experiment reported in the work of Yokoyama et al. [Nat. Photonics 7, 982 (2013)], we demonstrate the successive generation of fully inseparable light modes for more than one million modes. The resulting multi-mode state is useful as a dual-rail continuous variable cluster state. We circumvent the previous problem of optical phase drifts, which has limited the number of fully inseparable light modes to around ten thousands, by continuous feedback control of the optical system.

  8. Work stressors and partner social undermining: Comparing negative affect and psychological detachment as mechanisms.

    PubMed

    Meier, Laurenz L; Cho, Eunae

    2018-05-14

    With the mounting evidence that employees' work experiences spill over into the family domain and cross over to family members, it is important to understand the underlying mechanism through which work experiences affect the family domain and what factors may alleviate the adverse impact of work stress. Expanding previous research that mainly focused on the affect-based mechanism (negative affect), the present research investigated a resource-based mechanism (psychological detachment from work) in the relationship linking two work stressors (high workload and workplace incivility) with social undermining toward the partner at home. We also explored the relative strength of the mediating effects of the two mechanisms. In addition, we tested whether relationship satisfaction moderates the proposed effect of detachment on partner undermining. We tested these research questions using two studies with differing designs: a five-wave longitudinal study (N = 470) and a multisource study (N = 131). The results suggest that stressful work experiences affect the family domain via lack of detachment as well as negative affect, that the two pathways have comparable strength, and that high relationship satisfaction mitigates the negative effect of lack of detachment on partner undermining. In sum, this research extends the spillover-crossover model by establishing that poor psychological detachment from work during leisure time is an additional mechanism that links work and family. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  9. The C2'- and C3'-endo equilibrium for AMP molecules bound in the cystathionine-beta-synthase domain.

    PubMed

    Feng, Na; Qi, Chao; Hou, Yan-Jie; Zhang, Ying; Wang, Da-Cheng; Li, De-Feng

    2018-03-04

    The equilibrium between C2'- and C3'-endo conformations of nucleotides in solution, as well as their polymers DNA and RNA, has been well studied in previous work. However, this equilibrium of nucleotides in their binding state remains unclear. We observed two AMP molecules, in C3'- and C2'-endo conformations respectively, simultaneously bound to a cystathionine-beta-synthase (CBS) domain dimer of the magnesium and cobalt efflux protein CorC in the crystallographic study. The C2'-endo AMP molecule assumes the higher sugar pucker energy and one more hydrogen bond with the protein than the C3'-endo molecule does. The balance between the high sugar pucker energy and the low binding energy suggests an equilibrium or switch between C2'- and C3'-endo conformations of the bound nucleotides. Our work challenge the previous hypothesis that the ribose of the bound nucleotides would be locked in a fixed conformation. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. A token centric part-of-speech tagger for biomedical text.

    PubMed

    Barrett, Neil; Weber-Jahnke, Jens

    2014-05-01

    Difficulties with part-of-speech (POS) tagging of biomedical text is accessing and annotating appropriate training corpora. These difficulties may result in POS taggers trained on corpora that differ from the tagger's target biomedical text (cross-domain tagging). In such cases where training and target corpora differ tagging accuracy decreases. This paper presents a POS tagger for cross-domain tagging called TcT. TcT estimates a tag's likelihood for a given token by combining token collocation probabilities and the token's tag probabilities calculated using a Naive Bayes classifier. We compared TcT to three POS taggers used in the biomedical domain (mxpost, Brill and TnT). We trained each tagger on a non-biomedical corpus and evaluated it on biomedical corpora. TcT was more accurate in cross-domain tagging than mxpost, Brill and TnT (respective averages 83.9, 81.0, 79.5 and 78.8). Our analysis of tagger performance suggests that lexical differences between corpora have more effect on tagging accuracy than originally considered by previous research work. Biomedical POS tagging algorithms may be modified to improve their cross-domain tagging accuracy without requiring extra training or large training data sets. Future work should reexamine POS tagging methods for biomedical text. This differs from the work to date that has focused on retraining existing POS taggers. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. A Taxonomy of Instructional Objectives for Developmentally Disabled Persons: Vocational Domain. Working Paper 85-1. COMPETE: Community-Based Model for Public-School Exit and Transition to Employment.

    ERIC Educational Resources Information Center

    Dever, Richard B.

    The purpose of Project COMPETE is to use previous research and exemplary practices to develop and validate a model and training sequence to assist retarded youth to make the transition from school to employment in the most competitive environment possible. This project working paper lists vocational goals and objectives that individuals with…

  12. The Work Compatibility Improvement Framework: an integrated perspective of the human-at-work system.

    PubMed

    Genaidy, Ash; Salem, Sam; Karwowski, Waldemar; Paez, Omar; Tuncel, Setenay

    2007-01-15

    The industrial revolution demonstrated the limitations of a pure mechanistic approach towards work design. Human work is now seen as a complex entity that involves different scientific branches and blurs the line between mental and physical activities. Job design has been a traditional concern of applied psychology, which has provided insight into the interaction between the individual and the work environment. The goal of this paper is to introduce the human-at-work system as a holistic approach to organizational design. It postulates that the well-being of workers and work outcomes are issues that need to be addressed jointly, moving beyond traditional concepts of job satisfaction and work stress. The work compatibility model (WCM) is introduced as an engineering approach that seeks to integrate previous constructs of job and organizational design. The WCM seeks a balance between energy expenditure and replenishment. The implementation of the WCM in industrial settings is described within the context of the Work Compatibility Improvement Framework. A sample review of six models (motivation-hygiene theory; job characteristics theory; person-environment fit; demand-control model; and balance theory) provides the foundation for the interaction between the individual and the work environment. A review of three workload assessment methods (position analysis questionnaire, job task analysis and NASA task load index) gives an example of the foundation for the taxonomy of work environment domains. Previous models have sought to identify a balance state for the human-at-work system. They differentiated between the objective and subjective effects of the environment and the worker. An imbalance between the person and the environment has been proven to increase health risks. The WCM works with a taxonomy of 12 work domains classified in terms of the direct (acting) or indirect (experienced) effect on the worker. In terms of measurement, two quantitative methods are proposed to measure the state of the system. The first method introduced by Abdallah et al. (2004) identifies operating zones. The second method introduced by Salem et al. (2006) identifies the distribution of the work elements on the x/y coordinate plane. While previous efforts have identified some relevant elements of the systems, they failed to provide a holistic, quantitative approach combining organizational and human factors into a common framework. It is postulated that improving the well-being of workers will simultaneously improve organizational outcomes. The WCM moves beyond previous models by providing a hierarchical structure of work domains and a combination of methods to diagnose any organizational setting. The WCM is an attempt to achieve organizational excellence in human resource management, moving beyond job design to an integrated improvement strategy. A joint approach to organizational and job design will not only result in decreased prevalence of health risks, but in enhanced organizational effectiveness as well. The implementation of the WCM, that is, the Work Compatibility Improvement Framework, provides the basis for integrating different elements of the work environment into a single reliable construct. An improvement framework is essential to ensure that the measures of the WCM result in a system that is adaptive and self-regulated.

  13. Efficient and Extensible Quasi-Explicit Modular Nonlinear Multiscale Battery Model: GH-MSMD

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

    Kim, Gi-Heon; Smith, Kandler; Lawrence-Simon, Jake

    Complex physics and long computation time hinder the adoption of computer aided engineering models in the design of large-format battery cells and systems. A modular, efficient battery simulation model -- the multiscale multidomain (MSMD) model -- was previously introduced to aid the scale-up of Li-ion material and electrode designs to complete cell and pack designs, capturing electrochemical interplay with 3-D electronic current pathways and thermal response. Here, this paper enhances the computational efficiency of the MSMD model using a separation of time-scales principle to decompose model field variables. The decomposition provides a quasi-explicit linkage between the multiple length-scale domains andmore » thus reduces time-consuming nested iteration when solving model equations across multiple domains. In addition to particle-, electrode- and cell-length scales treated in the previous work, the present formulation extends to bus bar- and multi-cell module-length scales. We provide example simulations for several variants of GH electrode-domain models.« less

  14. Efficient and Extensible Quasi-Explicit Modular Nonlinear Multiscale Battery Model: GH-MSMD

    DOE PAGES

    Kim, Gi-Heon; Smith, Kandler; Lawrence-Simon, Jake; ...

    2017-03-24

    Complex physics and long computation time hinder the adoption of computer aided engineering models in the design of large-format battery cells and systems. A modular, efficient battery simulation model -- the multiscale multidomain (MSMD) model -- was previously introduced to aid the scale-up of Li-ion material and electrode designs to complete cell and pack designs, capturing electrochemical interplay with 3-D electronic current pathways and thermal response. Here, this paper enhances the computational efficiency of the MSMD model using a separation of time-scales principle to decompose model field variables. The decomposition provides a quasi-explicit linkage between the multiple length-scale domains andmore » thus reduces time-consuming nested iteration when solving model equations across multiple domains. In addition to particle-, electrode- and cell-length scales treated in the previous work, the present formulation extends to bus bar- and multi-cell module-length scales. We provide example simulations for several variants of GH electrode-domain models.« less

  15. Domains of unprofessional behavior during medical school associated with future disciplinary action by a state medical board.

    PubMed

    Teherani, Arianne; Hodgson, Carol S; Banach, Mary; Papadakis, Maxine A

    2005-10-01

    In a previous study, we showed that unprofessional behavior in medical school was associated with subsequent disciplinary action. This study expands on that work by identifying the domains of unprofessional behavior that are most problematic. In this retrospective case-control study, negative comments were extracted from student files for 68 case (disciplined) and 196 matched control (nondisciplined) physicians. Comments were analyzed qualitatively and subsequently quantified. The relationship between domains of behavior and disciplinary action was established through chi-square tests and multivariate analysis of variance. Three domains of unprofessional behavior emerged that were related significantly to later disciplinary outcome: (1) poor reliability and responsibility, (2) lack of self-improvement and adaptability, and (3) poor initiative and motivation. Three critical domains of professionalism associated with future disciplinary action have been defined. These findings could lead to focused remediation strategies and policy decisions.

  16. The Attraction Effect in Decision Making: Superior Performance by Older Adults

    PubMed Central

    Kim, Sunghan; Hasher, Lynn

    2006-01-01

    Previous work showed that older adults’ choice performance can be wiser than that of younger adults (Tentori, Osherson, Hasher, & May, 2001). We contrasted two possible interpretations: a general expertise/wisdom view that suggests that older adults are generally more skilled at making decisions than younger adults and a domain-specific expertise view that suggests that older adults are more skilled decision makers only in domains in which they have greater knowledge. These hypotheses were contrasted using attraction effect tasks in two different domains: earning extra credit in a course and grocery shopping, domains presumed to be of different levels of knowledge to younger and older adults. Older adults showed consistent choice for both domains; younger adults showed consistent choice only for the extra credit problem. Several explanations of these findings are considered, including Damasio’s somatic marker theory and age differences in reliance on heuristic versus analytic styles. PMID:15881294

  17. Sonification Design for Complex Work Domains: Dimensions and Distractors

    ERIC Educational Resources Information Center

    Anderson, Janet E.; Sanderson, Penelope

    2009-01-01

    Sonification--representing data in sound--is a potential method for supporting human operators who have to monitor dynamic processes. Previous research has investigated a limited number of sound dimensions and has not systematically investigated the impact of dimensional interactions on sonification effectiveness. In three experiments the authors…

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  19. A New Take on Program Planning: A Faculty Competencies Framework

    ERIC Educational Resources Information Center

    Sanford, Rania; Kinch, Amy Fowler

    2016-01-01

    Building on previous studies on the changing nature of faculty work, this article presents a conceptual framework for faculty professional success. The authors report on the perceptions of 300 faculty development professionals regarding the importance of skills in nine competency domains: teaching; research; leadership; diversity, inclusion and…

  20. Studying real-world perceptual expertise

    PubMed Central

    Shen, Jianhong; Mack, Michael L.; Palmeri, Thomas J.

    2014-01-01

    Significant insights into visual cognition have come from studying real-world perceptual expertise. Many have previously reviewed empirical findings and theoretical developments from this work. Here we instead provide a brief perspective on approaches, considerations, and challenges to studying real-world perceptual expertise. We discuss factors like choosing to use real-world versus artificial object domains of expertise, selecting a target domain of real-world perceptual expertise, recruiting experts, evaluating their level of expertise, and experimentally testing experts in the lab and online. Throughout our perspective, we highlight expert birding (also called birdwatching) as an example, as it has been used as a target domain for over two decades in the perceptual expertise literature. PMID:25147533

  1. Determinant representation of the domain-wall boundary condition partition function of a Richardson-Gaudin model containing one arbitrary spin

    NASA Astrophysics Data System (ADS)

    Faribault, Alexandre; Tschirhart, Hugo; Muller, Nicolas

    2016-05-01

    In this work we present a determinant expression for the domain-wall boundary condition partition function of rational (XXX) Richardson-Gaudin models which, in addition to N-1 spins \\frac{1}{2}, contains one arbitrarily large spin S. The proposed determinant representation is written in terms of a set of variables which, from previous work, are known to define eigenstates of the quantum integrable models belonging to this class as solutions to quadratic Bethe equations. Such a determinant can be useful numerically since systems of quadratic equations are much simpler to solve than the usual highly nonlinear Bethe equations. It can therefore offer significant gains in stability and computation speed.

  2. Time-discretized steady compressible Navier-Stokes equations with inflow and outflow boundaries

    NASA Astrophysics Data System (ADS)

    Yoon, Gangjoon; Yang, Sung-Dae; Song, Minsu; Gunzburger, Max

    2013-12-01

    The time-discretized steady compressible Navier-Stokes equations in n-dimensional bounded domains with the velocity specified only at the inflow boundary are considered. The existence and uniqueness of L p solutions are proved for p > n. For time-discretized steady flows, results of Kweon and Kellogg and of Kweon and Song are extended in a manner that allows for more general domains and for density-dependent viscosity coefficients. Moreover, we only require p > n which is a critical barrier in the previous works.

  3. Eyes-on training and radiological expertise: an examination of expertise development and its effects on visual working memory.

    PubMed

    Beck, Melissa R; Martin, Benjamin A; Smitherman, Emily; Gaschen, Lorrie

    2013-08-01

    Our aim was to examine the specificity of the effects of acquiring expertise on visual working memory (VWM) and the degree to which higher levels of experience within the domain of expertise are associated with more efficient use of VWM. Previous research is inconsistent on whether expertise effects are specific to the area of expertise or generalize to other tasks that also involve the same cognitive processes. It is also unclear whether more training and/or experience will lead to continued improvement on domain-relevant tasks or whether a plateau could be reached. In Experiment I, veterinary medicine students completed a one-shot visual change detection task. In Experiment 2, veterinarians completed a flicker change detection task. Both experiments involved stimuli specific to the domain of radiology and general stimuli. In Experiment I, veterinary medicine students who had completed an "eyes-on" radiological training demonstrated a domain-specific effect in which performance was better on the domain-specific stimuli than on the domain-general stimuli. In Experiment 2, veterinarians again showed a domain-specific effect, but performance was unrelated to the amount of experience veterinarians had accumulated. The effect of experience is domain specific and occurs during the first few years of training, after which a plateau is reached. VWM training in one domain may not lead to improved performance on other VWM tasks. In acquiring expertise, eyes-on training is important initially, but continued experience may not be associated with further improvements in the efficiency of VWM.

  4. R Script Approach to Infer Toxoplasma Infection Mechanisms From Microarrays and Domain-Domain Protein Interactions

    PubMed Central

    Arenas, Ailan F; Salcedo, Gladys E; Gomez-Marin, Jorge E

    2017-01-01

    Pathogen-host protein-protein interaction systems examine the interactions between the protein repertoires of 2 distinct organisms. Some of these pathogen proteins interact with the host protein system and may manipulate it for their own advantages. In this work, we designed an R script by concatenating 2 functions called rowDM and rowCVmed to infer pathogen-host interaction using previously reported microarray data, including host gene enrichment analysis and the crossing of interspecific domain-domain interactions. We applied this script to the Toxoplasma-host system to describe pathogen survival mechanisms from human, mouse, and Toxoplasma Gene Expression Omnibus series. Our outcomes exhibited similar results with previously reported microarray analyses, but we found other important proteins that could contribute to toxoplasma pathogenesis. We observed that Toxoplasma ROP38 is the most differentially expressed protein among toxoplasma strains. Enrichment analysis and KEGG mapping indicated that the human retinal genes most affected by Toxoplasma infections are those related to antiapoptotic mechanisms. We suggest that proteins PIK3R1, PRKCA, PRKCG, PRKCB, HRAS, and c-JUN could be the possible substrates for differentially expressed Toxoplasma kinase ROP38. Likewise, we propose that Toxoplasma causes overexpression of apoptotic suppression human genes. PMID:29317802

  5. MALDI-MS analysis and imaging of small molecule metabolites with 1,5-diaminonaphthalene (DAN).

    PubMed

    Korte, Andrew R; Lee, Young Jin

    2014-08-01

    1,5-Diaminonaphthalene (DAN) has previously been reported as an effective matrix for matrix-assisted laser desorption ionization-mass spectrometry of phospholipids. In the current work, we investigate the use of DAN as a matrix for small metabolite analysis in negative ion mode. DAN was found to provide superior ionization to the compared matrices for MW < ~400 Da; however, 9-aminoacridine (9-AA) was found to be superior for a uridine diphosphate standard (MW 566 Da). DAN was also found to provide a more representative profile of a natural phospholipid mixture than 9-AA. Finally, DAN and 9-AA were applied for imaging of metabolites directly from corn leaf sections. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  6. Competency-based Radiology Residency: A Survey of Expectations from Singapore's Perspective.

    PubMed

    Yang, Hui; Tan, Colin J X; Lau, Doreen A H; Lim, Winston E H; Tay, Kiang Hiong; Kei, Pin Lin

    2015-03-01

    In response to the demands of an ageing nation, the postgraduate medical education in Singapore is currently in the early stage of transition into the American-styled residency programme. This study assessed the expectations of both radiology trainees and faculty on their ideal clinical learning environment (CLE) which facilitates the programme development. A modified 23-item questionnaire was administered to both trainees and faculty at a local training hospital. All items were scored according to their envisioned level of importance and categorised into 5 main CLE domains-supervision, formal training programme, work-based learning, social atmosphere and workload. 'Supervision' was identified as the most important domain of the CLE by both trainees and faculty, followed by 'formal training programmes', 'work-based learning' and 'social atmosphere'. 'Workload' was rated as the least important domain. For all domains, the reported expectation between both trainees and faculty respondents did not differ significantly. Intragroup comparison also showed no significant difference within each group of respondents. This study has provided valuable insights on both respondents' expectations on their ideal CLE that can best train competency in future radiologists. Various approaches to address these concerns were also discussed. The similarities in findings between ours and previous studies suggest that the 'supervision', 'formal training programmes' and 'work-based learning' domains are crucial for the success of a postgraduate medical training and should be emphasised in future curriculum. 'Workload' remains a challenge in postgraduate medical training, but attempts to address this will have an impact in future radiology training.

  7. Quality of life benefits of paid work activity in schizophrenia.

    PubMed

    Bryson, Gary; Lysaker, Paul; Bell, Morris

    2002-01-01

    In a study of work rehabilitation, 97 participants with schizophrenia or schizoaffective disorder were randomized into either a Pay or a No Pay condition to determine the impact of work activity and pay on rehabilitation outcomes. This report specifically investigates the relationship between work rehabilitation and quality of life (QOL) measures for people with schizophrenia. Previous reports have described improvements in symptoms and work outcomes for participants in the Pay condition. Results in this report reveal that randomization to the Pay condition improved ratings on the Heinrichs Quality of Life Scale (QLS). The improvements are found both in overall QLS and in the domain of Intrapsychic Foundations (motivation, sense of purpose, anhedonia, and empathy). For a larger sample (n = 114) we assessed the relationship between amount of participation and QLS improvement. Degree of participation was related to improvement on the QLS total and Intrapsychic Foundations domain. Finally, improvement in the Interpersonal Relations scale was associated with weeks of participation for the most consistent participants. How participation in work rehabilitation and its interaction with pay improves motivation, interpersonal relatedness, and overall quality of life is discussed.

  8. Do Creativity Self-Beliefs Predict Literacy Achievement and Motivation?

    ERIC Educational Resources Information Center

    Putwain, David W.; Kearsley, Rebecca; Symes, Wendy

    2012-01-01

    Previous work has suggested that creativity self-beliefs show only small relations with academic achievement and may only be related to intrinsic, not extrinsic motivation. We set out to re-examine these relationships accounting for the multifaceted and process embedded nature of creativity self-beliefs and the full domain range of extrinsic…

  9. Coordination of Fractional Quantities: Cueing of Resources, Constraints, and Effect of Numeric Structure

    ERIC Educational Resources Information Center

    Ramful, Ajay; Nenduradu, Rajeev

    2013-01-01

    While previous work in the domain of proportional reasoning has primarily focused on the coordination of integer quantities, this study investigates how students coordinate fractional quantities. Fine-grained analysis of two seventh graders' responses to a set of systematically designed proportional tasks, shows how their knowledge of…

  10. Hypercube matrix computation task

    NASA Technical Reports Server (NTRS)

    Calalo, Ruel H.; Imbriale, William A.; Jacobi, Nathan; Liewer, Paulett C.; Lockhart, Thomas G.; Lyzenga, Gregory A.; Lyons, James R.; Manshadi, Farzin; Patterson, Jean E.

    1988-01-01

    A major objective of the Hypercube Matrix Computation effort at the Jet Propulsion Laboratory (JPL) is to investigate the applicability of a parallel computing architecture to the solution of large-scale electromagnetic scattering problems. Three scattering analysis codes are being implemented and assessed on a JPL/California Institute of Technology (Caltech) Mark 3 Hypercube. The codes, which utilize different underlying algorithms, give a means of evaluating the general applicability of this parallel architecture. The three analysis codes being implemented are a frequency domain method of moments code, a time domain finite difference code, and a frequency domain finite elements code. These analysis capabilities are being integrated into an electromagnetics interactive analysis workstation which can serve as a design tool for the construction of antennas and other radiating or scattering structures. The first two years of work on the Hypercube Matrix Computation effort is summarized. It includes both new developments and results as well as work previously reported in the Hypercube Matrix Computation Task: Final Report for 1986 to 1987 (JPL Publication 87-18).

  11. Zero-moment point determination of worst-case manoeuvres leading to vehicle wheel lift

    NASA Astrophysics Data System (ADS)

    Lapapong, S.; Brown, A. A.; Swanson, K. S.; Brennan, S. N.

    2012-01-01

    This paper proposes a method to evaluate vehicle rollover propensity based on a frequency-domain representation of the zero-moment point (ZMP). Unlike other rollover metrics such as the static stability factor, which is based on the steady-state behaviour, and the load transfer ratio, which requires the calculation of tyre forces, the ZMP is based on a simplified kinematic model of the vehicle and the analysis of the contact point of the vehicle relative to the edge of the support polygon. Previous work has validated the use of the ZMP experimentally in its ability to predict wheel lift in the time domain. This work explores the use of the ZMP in the frequency domain to allow a chassis designer to understand how operating conditions and vehicle parameters affect rollover propensity. The ZMP analysis is then extended to calculate worst-case sinusoidal manoeuvres that lead to untripped wheel lift, and the analysis is tested across several vehicle configurations and compared with that of the standard Toyota J manoeuvre.

  12. Non-3D domain swapped crystal structure of truncated zebrafish alphaA crystallin

    PubMed Central

    Laganowsky, A; Eisenberg, D

    2010-01-01

    In previous work on truncated alpha crystallins (Laganowsky et al., Protein Sci 2010; 19:1031–1043), we determined crystal structures of the alpha crystallin core, a seven beta-stranded immunoglobulin-like domain, with its conserved C-terminal extension. These extensions swap into neighboring cores forming oligomeric assemblies. The extension is palindromic in sequence, binding in either of two directions. Here, we report the crystal structure of a truncated alphaA crystallin (AAC) from zebrafish (Danio rerio) revealing C-terminal extensions in a non three-dimensional (3D) domain swapped, “closed” state. The extension is quasi-palindromic, bound within its own zebrafish core domain, lying in the opposite direction to that of bovine AAC, which is bound within an adjacent core domain (Laganowsky et al., Protein Sci 2010; 19:1031–1043). Our findings establish that the C-terminal extension of alpha crystallin proteins can be either 3D domain swapped or non-3D domain swapped. This duality provides another molecular mechanism for alpha crystallin proteins to maintain the polydispersity that is crucial for eye lens transparency. PMID:20669149

  13. Structural bioinformatics of the human spliceosomal proteome

    PubMed Central

    Korneta, Iga; Magnus, Marcin; Bujnicki, Janusz M.

    2012-01-01

    In this work, we describe the results of a comprehensive structural bioinformatics analysis of the spliceosomal proteome. We used fold recognition analysis to complement prior data on the ordered domains of 252 human splicing proteins. Examples of newly identified domains include a PWI domain in the U5 snRNP protein 200K (hBrr2, residues 258–338), while examples of previously known domains with a newly determined fold include the DUF1115 domain of the U4/U6 di-snRNP protein 90K (hPrp3, residues 540–683). We also established a non-redundant set of experimental models of spliceosomal proteins, as well as constructed in silico models for regions without an experimental structure. The combined set of structural models is available for download. Altogether, over 90% of the ordered regions of the spliceosomal proteome can be represented structurally with a high degree of confidence. We analyzed the reduced spliceosomal proteome of the intron-poor organism Giardia lamblia, and as a result, we proposed a candidate set of ordered structural regions necessary for a functional spliceosome. The results of this work will aid experimental and structural analyses of the spliceosomal proteins and complexes, and can serve as a starting point for multiscale modeling of the structure of the entire spliceosome. PMID:22573172

  14. Life satisfaction of women of working age shortly after breast cancer surgery.

    PubMed

    Olsson, Mariann; Nilsson, Marie; Fugl-Meyer, Kerstin; Petersson, Lena-Marie; Wennman-Larsen, Agneta; Kjeldgård, Linnea; Alexanderson, Kristina

    2017-03-01

    To explore, among women of working age, satisfaction with life as a whole and with different life domains, and its associations with social and health variables, shortly after breast cancer surgery. This cross-sectional study included 605 women, aged 20-63 years, who had had breast cancer surgery with no distant metastasis, pre-surgical chemotherapy, or previous breast cancer. Associations between LiSat-11 and demographic and social factors as well as health- and treatment-related variables were analysed by multivariable logistic regression. Compared with Swedish reference levels, the women were, after breast cancer surgery, less satisfied with life, particularly sexual life. Women working shortly after breast cancer surgery were more often satisfied with life in provision domains compared with the reference population. Although most included variables showed associations with satisfaction, after adjustment for all significantly associated variables, only six variables-having children, being in work, having emotional and informational social support, and having good physical and emotional functioning-were positively associated with satisfaction with life as a whole. The odds ratios for satisfaction were higher in most life domains if the woman had social support and good emotional and cognitive functioning. One month after breast cancer surgery, satisfaction with different life domains was associated primarily with social support and health-related functioning. However, this soon after surgery, treatment-related variables showed no significant associations with life satisfaction. These results are useful for planning interventions to enhance e.g. social support and emotional as well as cognitive functioning.

  15. Novel Mechanism of Hemin Capture by Hbp2, the Hemoglobin-binding Hemophore from Listeria monocytogenes*

    PubMed Central

    Malmirchegini, G. Reza; Sjodt, Megan; Shnitkind, Sergey; Sawaya, Michael R.; Rosinski, Justin; Newton, Salete M.; Klebba, Phillip E.; Clubb, Robert T.

    2014-01-01

    Iron is an essential nutrient that is required for the growth of the bacterial pathogen Listeria monocytogenes. In cell cultures, this microbe secretes hemin/hemoglobin-binding protein 2 (Hbp2; Lmo2185) protein, which has been proposed to function as a hemophore that scavenges heme from the environment. Based on its primary sequence, Hbp2 contains three NEAr transporter (NEAT) domains of unknown function. Here we show that each of these domains mediates high affinity binding to ferric heme (hemin) and that its N- and C-terminal domains interact with hemoglobin (Hb). The results of hemin transfer experiments are consistent with Hbp2 functioning as an Hb-binding hemophore that delivers hemin to other Hbp2 proteins that are attached to the cell wall. Surprisingly, our work reveals that the central NEAT domain in Hbp2 binds hemin even though its primary sequence lacks a highly conserved YXXXY motif that is used by all other previously characterized NEAT domains to coordinate iron in the hemin molecule. To elucidate the mechanism of hemin binding by Hbp2, we determined crystal structures of its central NEAT domain (Hbp2N2; residues 183–303) in its free and hemin-bound states. The structures reveal an unprecedented mechanism of hemin binding in which Hbp2N2 undergoes a major conformational rearrangement that facilitates metal coordination by a non-canonical tyrosine residue. These studies highlight previously unrecognized plasticity in the hemin binding mechanism of NEAT domains and provide insight into how L. monocytogenes captures heme iron. PMID:25315777

  16. Tire Changes, Fresh Air, and Yellow Flags: Challenges in Predictive Analytics for Professional Racing.

    PubMed

    Tulabandhula, Theja; Rudin, Cynthia

    2014-06-01

    Our goal is to design a prediction and decision system for real-time use during a professional car race. In designing a knowledge discovery process for racing, we faced several challenges that were overcome only when domain knowledge of racing was carefully infused within statistical modeling techniques. In this article, we describe how we leveraged expert knowledge of the domain to produce a real-time decision system for tire changes within a race. Our forecasts have the potential to impact how racing teams can optimize strategy by making tire-change decisions to benefit their rank position. Our work significantly expands previous research on sports analytics, as it is the only work on analytical methods for within-race prediction and decision making for professional car racing.

  17. Structure of the glucagon receptor in complex with a glucagon analogue.

    PubMed

    Zhang, Haonan; Qiao, Anna; Yang, Linlin; Van Eps, Ned; Frederiksen, Klaus S; Yang, Dehua; Dai, Antao; Cai, Xiaoqing; Zhang, Hui; Yi, Cuiying; Cao, Can; He, Lingli; Yang, Huaiyu; Lau, Jesper; Ernst, Oliver P; Hanson, Michael A; Stevens, Raymond C; Wang, Ming-Wei; Reedtz-Runge, Steffen; Jiang, Hualiang; Zhao, Qiang; Wu, Beili

    2018-01-03

    Class B G-protein-coupled receptors (GPCRs), which consist of an extracellular domain (ECD) and a transmembrane domain (TMD), respond to secretin peptides to play a key part in hormonal homeostasis, and are important therapeutic targets for a variety of diseases. Previous work has suggested that peptide ligands bind to class B GPCRs according to a two-domain binding model, in which the C-terminal region of the peptide targets the ECD and the N-terminal region of the peptide binds to the TMD binding pocket. Recently, three structures of class B GPCRs in complex with peptide ligands have been solved. These structures provide essential insights into peptide ligand recognition by class B GPCRs. However, owing to resolution limitations, the specific molecular interactions for peptide binding to class B GPCRs remain ambiguous. Moreover, these previously solved structures have different ECD conformations relative to the TMD, which introduces questions regarding inter-domain conformational flexibility and the changes required for receptor activation. Here we report the 3.0 Å-resolution crystal structure of the full-length human glucagon receptor (GCGR) in complex with a glucagon analogue and partial agonist, NNC1702. This structure provides molecular details of the interactions between GCGR and the peptide ligand. It reveals a marked change in the relative orientation between the ECD and TMD of GCGR compared to the previously solved structure of the inactive GCGR-NNC0640-mAb1 complex. Notably, the stalk region and the first extracellular loop undergo major conformational changes in secondary structure during peptide binding, forming key interactions with the peptide. We further propose a dual-binding-site trigger model for GCGR activation-which requires conformational changes of the stalk, first extracellular loop and TMD-that extends our understanding of the previously established two-domain peptide-binding model of class B GPCRs.

  18. Homeopathic potentization based on nanoscale domains.

    PubMed

    Czerlinski, George; Ypma, Tjalling

    2011-12-01

    The objectives of this study were to present a simple descriptive and quantitative model of how high potencies in homeopathy arise. The model begins with the mechanochemical production of hydrogen and hydroxyl radicals from water and the electronic stabilization of the resulting nanodomains of water molecules. The life of these domains is initially limited to a few days, but may extend to years when the electromagnetic characteristic of a homeopathic agent is copied onto the domains. This information is transferred between the original agent and the nanodomains, and also between previously imprinted nanodomains and new ones. The differential equations previously used to describe these processes are replaced here by exponential expressions, corresponding to simplified model mechanisms. Magnetic stabilization is also involved, since these long-lived domains apparently require the presence of the geomagnetic field. Our model incorporates this factor in the formation of the long-lived compound. Numerical simulation and graphs show that the potentization mechanism can be described quantitatively by a very simplified mechanism. The omitted factors affect only the fine structure of the kinetics. Measurements of pH changes upon absorption of different electromagnetic frequencies indicate that about 400 nanodomains polymerize to form one cooperating unit. Singlet excited states of some compounds lead to dramatic changes in their hydrogen ion dissociation constant, explaining this pH effect and suggesting that homeopathic information is imprinted as higher singlet excited states. A simple description is provided of the process of potentization in homeopathic dilutions. With the exception of minor details, this simple model replicates the results previously obtained from a more complex model. While excited states are short lived in isolated molecules, they become long lived in nanodomains that form coherent cooperative aggregates controlled by the geomagnetic field. These domains either slowly emit biophotons or perform specific biochemical work at their target.

  19. A Developmental Examination of the Conceptual Structure of Animal, Artifact, and Human Social Categories across Two Cultural Contexts

    ERIC Educational Resources Information Center

    Rhodes, Marjorie; Gelman, Susan A.

    2009-01-01

    Previous research indicates that the ontological status that adults attribute to categories varies systematically by domain. For example, adults view distinctions between different animal species as natural and objective, but view distinctions between different kinds of furniture as more conventionalized and subjective. The present work (N=435;…

  20. A Taxonomy of Instructional Objectives for Developmentally Disabled Persons: Personal Maintenance and Development: Homemaking and Community Life; Leisure; and Travel Domains. Working Paper 85-2. COMPETE: Community-Based Model for Public-School Exit and Transition to Employment.

    ERIC Educational Resources Information Center

    Dever, Richard B.

    The purpose of Project COMPETE is to use previous research and exemplary practices to develop and validate a model and training sequence to assist retarded youth to make the transition from school to employment in the most competitive environment possible. The taxonomy described in this project working paper focuses on instructional objectives in…

  1. The Myb-domain protein ULTRAPETALA1 INTERACTING FACTOR 1 controls floral meristem activities in Arabidopsis.

    PubMed

    Moreau, Fanny; Thévenon, Emmanuel; Blanvillain, Robert; Lopez-Vidriero, Irene; Franco-Zorrilla, Jose Manuel; Dumas, Renaud; Parcy, François; Morel, Patrice; Trehin, Christophe; Carles, Cristel C

    2016-04-01

    Higher plants continuously and iteratively produce new above-ground organs in the form of leaves, stems and flowers. These organs arise from shoot apical meristems whose homeostasis depends on coordination between self-renewal of stem cells and their differentiation into organ founder cells. This coordination is stringently controlled by the central transcription factor WUSCHEL (WUS), which is both necessary and sufficient for stem cell specification in Arabidopsis thaliana ULTRAPETALA1 (ULT1) was previously identified as a plant-specific, negative regulator of WUS expression. However, molecular mechanisms underlying this regulation remain unknown. ULT1 protein contains a SAND putative DNA-binding domain and a B-box, previously proposed as a protein interaction domain in eukaryotes. Here, we characterise a novel partner of ULT1, named ULT1 INTERACTING FACTOR 1 (UIF1), which contains a Myb domain and an EAR motif. UIF1 and ULT1 function in the same pathway for regulation of organ number in the flower. Moreover, UIF1 displays DNA-binding activity and specifically binds to WUS regulatory elements. We thus provide genetic and molecular evidence that UIF1 and ULT1 work together in floral meristem homeostasis, probably by direct repression of WUS expression. © 2016. Published by The Company of Biologists Ltd.

  2. Using neighborhood cohesiveness to infer interactions between protein domains.

    PubMed

    Segura, Joan; Sorzano, C O S; Cuenca-Alba, Jesus; Aloy, Patrick; Carazo, J M

    2015-08-01

    In recent years, large-scale studies have been undertaken to describe, at least partially, protein-protein interaction maps, or interactomes, for a number of relevant organisms, including human. However, current interactomes provide a somehow limited picture of the molecular details involving protein interactions, mostly because essential experimental information, especially structural data, is lacking. Indeed, the gap between structural and interactomics information is enlarging and thus, for most interactions, key experimental information is missing. We elaborate on the observation that many interactions between proteins involve a pair of their constituent domains and, thus, the knowledge of how protein domains interact adds very significant information to any interactomic analysis. In this work, we describe a novel use of the neighborhood cohesiveness property to infer interactions between protein domains given a protein interaction network. We have shown that some clustering coefficients can be extended to measure a degree of cohesiveness between two sets of nodes within a network. Specifically, we used the meet/min coefficient to measure the proportion of interacting nodes between two sets of nodes and the fraction of common neighbors. This approach extends previous works where homolog coefficients were first defined around network nodes and later around edges. The proposed approach substantially increases both the number of predicted domain-domain interactions as well as its accuracy as compared with current methods. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

    PubMed

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

    2016-09-01

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

  4. Visuo–spatial working memory is an important source of domain-general vulnerability in the development of arithmetic cognition

    PubMed Central

    Ashkenazi, Sarit; Rosenberg-Lee, Miriam; Metcalfe, Arron W.S.; Swigart, Anna G.; Menon, Vinod

    2014-01-01

    The study of developmental disorders can provide a unique window into the role of domain-general cognitive abilities and neural systems in typical and atypical development. Mathematical disabilities (MD) are characterized by marked difficulty in mathematical cognition in the presence of preserved intelligence and verbal ability. Although studies of MD have most often focused on the role of core deficits in numerical processing, domain-general cognitive abilities, in particular working memory (WM), have also been implicated. Here we identify specific WM components that are impaired in children with MD and then examine their role in arithmetic problem solving. Compared to typically developing (TD) children, the MD group demonstrated lower arithmetic performance and lower visuo-spatial working memory (VSWM) scores with preserved abilities on the phonological and central executive components of WM. Whole brain analysis revealed that, during arithmetic problem solving, left posterior parietal cortex, bilateral dorsolateral and ventrolateral prefrontal cortex, cingulate gyrus and precuneus, and fusiform gyrus responses were positively correlated with VSWM ability in TD children, but not in the MD group. Additional analyses using a priori posterior parietal cortex regions previously implicated in WM tasks, demonstrated a convergent pattern of results during arithmetic problem solving. These results suggest that MD is characterized by a common locus of arithmetic and VSWM deficits at both the cognitive and functional neuroanatomical levels. Unlike TD children, children with MD do not use VSWM resources appropriately during arithmetic problem solving. This work advances our understanding of VSWM as an important domain-general cognitive process in both typical and atypical mathematical skill development. PMID:23896444

  5. Domain Adaptation with Conditional Transferable Components

    PubMed Central

    Gong, Mingming; Zhang, Kun; Liu, Tongliang; Tao, Dacheng; Glymour, Clark; Schölkopf, Bernhard

    2017-01-01

    Domain adaptation arises in supervised learning when the training (source domain) and test (target domain) data have different distributions. Let X and Y denote the features and target, respectively, previous work on domain adaptation mainly considers the covariate shift situation where the distribution of the features P(X) changes across domains while the conditional distribution P(Y∣X) stays the same. To reduce domain discrepancy, recent methods try to find invariant components T(X) that have similar P(T(X)) on different domains by explicitly minimizing a distribution discrepancy measure. However, it is not clear if P(Y∣T(X)) in different domains is also similar when P(Y∣X) changes. Furthermore, transferable components do not necessarily have to be invariant. If the change in some components is identifiable, we can make use of such components for prediction in the target domain. In this paper, we focus on the case where P(X∣Y) and P(Y) both change in a causal system in which Y is the cause for X. Under appropriate assumptions, we aim to extract conditional transferable components whose conditional distribution P(T(X)∣Y) is invariant after proper location-scale (LS) transformations, and identify how P(Y) changes between domains simultaneously. We provide theoretical analysis and empirical evaluation on both synthetic and real-world data to show the effectiveness of our method. PMID:28239433

  6. A comprehensive assessment of memory, delay aversion, timing, inhibition, decision making and variability in attention deficit hyperactivity disorder: advancing beyond the three-pathway models.

    PubMed

    Coghill, D R; Seth, S; Matthews, K

    2014-07-01

    Although attention deficit hyperactivity disorder (ADHD) has been associated with a broad range of deficits across various neuropsychological domains, most studies have assessed only a narrow range of neuropsychological functions. Direct cross-domain comparisons are rare, with almost all studies restricted to less than four domains. Therefore, the relationships between these various domains remain undefined. In addition, almost all studies included previously medicated participants, limiting the conclusions that can be drawn. We present the first study to compare a large cohort of medication-naive boys with ADHD with healthy controls on a broad battery of neuropsychological tasks, assessing six key domains of neuropsychological functioning. The neuropsychological functioning of 83 medication-naive boys with well-characterized ADHD (mean age 8.9 years) was compared with that of 66 typically developing (TYP) boys (mean age 9.0 years) on a broad battery of validated neuropsychological tasks. Data reduction using complementary factor analysis (CFA) confirmed six distinct neuropsychological domains: working memory, inhibition, delay aversion, decision making, timing and response variability. Boys with ADHD performed less well across all six domains although, for each domain, only a minority of boys with ADHD had a deficit [effect size (% with deficit) ADHD versus TYP: working memory 0.95 (30.1), inhibition 0.61 (22.9), delay aversion 0.82 (36.1), decision making 0.55 (20.5), timing 0.71 (31.3), response variability 0.37 (18.1)]. The clinical syndrome of ADHD is neuropsychologically heterogeneous. These data highlight the complexity of the relationships between the different neuropsychological profiles associated with ADHD and the clinical symptoms and functional impairment.

  7. The influence of the glutamatergic system on cognition in schizophrenia: A systematic review.

    PubMed

    Thomas, Elizabeth H X; Bozaoglu, Kiymet; Rossell, Susan L; Gurvich, Caroline

    2017-06-01

    Previous literature showing the role of the glutamatergic system on cognition in schizophrenia has been inconclusive. 44 relevant pharmacological, candidate gene and neuroimaging studies were identified through systematic search following PRISMA guidelines. To be included, studies must have observed at least one objective measure of cognitive performance in patients with schizophrenia and either manipulated or measured the glutamatergic system. Of the cognitive domains observed, memory, working memory and executive functions appear to be most influenced by the glutamatergic pathway. In addition, evidence from the literature suggests that presynaptic components synthesis and uptake of glutamate is involved in memory, while postsynaptic signalling appears to be involved in working memory. In addition, it appears that the glutamatergic pathway is particularly involved in cognitive flexibility and learning potential in regards to executive functioning. The glutamatergic system appears to contribute to the cognitive deficits in schizophrenia, whereby different parts of the pathway are associated with different cognitive domains. This review demonstrates the necessity for cognition to be examined by domain as opposed to globally. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Social capital and burnout among mental healthcare providers.

    PubMed

    Eliacin, Johanne; Flanagan, Mindy; Monroe-DeVita, Maria; Wasmuth, Sarah; Salyers, Michelle P; Rollins, Angela L

    2018-01-06

    Provider burnout is a critical problem in mental health services. Contributing factors have been explicated across three domains: personal, job and organizational characteristics. Of these, organizational characteristics, including workplace environment, appear to be particularly important given that most interventions addressing burnout via the other domains (e.g. bolstering personal coping skills) have been modestly effective at best. This study builds on previous research by using social capital as a framework for the experience of work social milieu, and aims to provide a richer understanding of how workplace social environment might impact burnout and help create more effective ways to reduce burnout. Providers (n = 40) taking part in a larger burnout intervention study were randomly selected to take part in interviews regarding their workplace environment and burnout. Participant responses were analyzed thematically. Workplace social milieu revolved around two primary themes: workplace social capital in provider burnout and the protective qualities of social capital in cohesive work teams that appear to mitigate burnout. These results imply that work environments where managers support collaboration and social interaction among work teams may reduce burnout.

  9. Verification and validation of a Work Domain Analysis with turing machine task analysis.

    PubMed

    Rechard, J; Bignon, A; Berruet, P; Morineau, T

    2015-03-01

    While the use of Work Domain Analysis as a methodological framework in cognitive engineering is increasing rapidly, verification and validation of work domain models produced by this method are becoming a significant issue. In this article, we propose the use of a method based on Turing machine formalism named "Turing Machine Task Analysis" to verify and validate work domain models. The application of this method on two work domain analyses, one of car driving which is an "intentional" domain, and the other of a ship water system which is a "causal domain" showed the possibility of highlighting improvements needed by these models. More precisely, the step by step analysis of a degraded task scenario in each work domain model pointed out unsatisfactory aspects in the first modelling, like overspecification, underspecification, omission of work domain affordances, or unsuitable inclusion of objects in the work domain model. Copyright © 2014 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  10. Generalizing the correlated chromophore domain model of reversible photodegradation to include the effects of an applied electric field

    NASA Astrophysics Data System (ADS)

    Anderson, Benjamin; Kuzyk, Mark G.

    2014-03-01

    All observations of photodegradation and self-healing follow the predictions of the correlated chromophore domain model [Ramini et al., Polym. Chem. 4, 4948 (2013), 10.1039/c3py00263b]. In the present work, we generalize the domain model to describe the effects of an electric field by including induced dipole interactions between molecules in a domain by means of a self-consistent field approach. This electric field correction is added to the statistical mechanical model to calculate the distribution of domains that are central to healing. Also included in the model are the dynamics due to the formation of an irreversibly damaged species, which we propose involves damage to the polymer mediated through energy transfer from a dopant molecule after absorbing a photon. As in previous studies, the model with one-dimensional domains best explains all experimental data of the population as a function of time, temperature, intensity, concentration, and now applied electric field. Though the precise nature of a domain is yet to be determined, the fact that only one-dimensional domain models are consistent with observations suggests that they might be made of correlated dye molecules along polymer chains. Furthermore, the voltage-dependent measurements suggest that the largest polarizability axis of the molecules are oriented perpendicular to the chain.

  11. Equilibrium intermediate-state patterns in a type-I superconducting slab in an arbitrarily oriented applied magnetic field

    DOE PAGES

    Clem, John; Prozorov, Ruslan; Wijngaarden, Rinke J.

    2013-09-04

    The equilibrium topology of superconducting and normal domains in flat type-I superconductors is investigated. Important improvements with respect to previous work are that (1) the energy of the external magnetic field, as deformed by the presence of superconducting domains, is calculated in the same way for three different topologies and (2) calculations are made for arbitrary orientation of the applied field. A phase diagram is presented for the minimum-energy topology as a function of applied field magnitude and angle. For small (large) applied fields, normal (superconducting) tubes are found, while for intermediate fields, parallel domains have a lower energy. Themore » range of field magnitudes for which the superconducting-tubes structure is favored shrinks when the field is more in-plane oriented.« less

  12. Interactions of U24 from Roseolovirus with WW domains: canonical vs noncanonical.

    PubMed

    Sang, Yurou; Zhang, Rui; Creagh, A Louise; Haynes, Charles A; Straus, Suzana K

    2017-06-01

    U24 is a C-terminal membrane-anchored protein found in both human herpes virus type 6 and 7 (HHV-6 and HHV-7), with an N-terminal segment that is rich in prolines (PPxY motif in both HHV-6A and 7; PxxP motif in HHV-6A). Previous work has shown that U24 interacts strongly with Nedd4 WW domains, in particular, hNedd4L-WW3*. It was also shown that this interaction depends strongly on the nature of the amino acids that are upstream from the PY motif in U24. In this contribution, data was obtained from pull-downs, isothermal titration calorimetry, and NMR to further determine what modulates U24:WW domain interactions. Specifically, 3 non-canonical WW domains from human Smad ubiquitination regulatory factor (Smurf), namely hSmurf2-WW2, hSmurf2-WW3, and a tandem construct hSmurf2-WW2 + 3, were studied. Overall, the interactions between U24 and these Smurf WW domains were found to be weaker than those in U24:Nedd4 WW domain pairs, suggesting that U24 function is tightly linked to specific E3 ubiqitin ligases.

  13. Dicer uses distinct modules for recognizing dsRNA termini.

    PubMed

    Sinha, Niladri K; Iwasa, Janet; Shen, Peter S; Bass, Brenda L

    2018-01-19

    Invertebrates rely on Dicer to cleave viral double-stranded RNA (dsRNA), and Drosophila Dicer-2 distinguishes dsRNA substrates by their termini. Blunt termini promote processive cleavage, while 3' overhanging termini are cleaved distributively. To understand this discrimination, we used cryo-electron microscopy to solve structures of Drosophila Dicer-2 alone and in complex with blunt dsRNA. Whereas the Platform-PAZ domains have been considered the only Dicer domains that bind dsRNA termini, unexpectedly, we found that the helicase domain is required for binding blunt, but not 3' overhanging, termini. We further showed that blunt dsRNA is locally unwound and threaded through the helicase domain in an adenosine triphosphate-dependent manner. Our studies reveal a previously unrecognized mechanism for optimizing antiviral defense and set the stage for the discovery of helicase-dependent functions in other Dicers. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  14. Sensitivity study of heavy precipitation in Limited Area Model climate simulations: influence of the size of the domain and the use of the spectral nudging technique

    NASA Astrophysics Data System (ADS)

    Colin, Jeanne; Déqué, Michel; Radu, Raluca; Somot, Samuel

    2010-10-01

    We assess the impact of two sources of uncertainties in a limited area model (LAM) on the representation of intense precipitation: the size of the domain of integration and the use of the spectral nudging technique (driving of the large-scale within the domain of integration). We work in a perfect-model approach where the LAM is driven by a general circulation model (GCM) run at the same resolution and sharing the same physics and dynamics as the LAM. A set of three 50 km resolution simulations run over Western Europe with the LAM ALADIN-Climate and the GCM ARPEGE-Climate are performed to address this issue. Results are consistent with previous studies regarding the seasonal-mean fields. Furthermore, they show that neither the use of the spectral nudging nor the choice of a small domain are detrimental to the modelling of heavy precipitation in the present experiment.

  15. Achievement emotions in elementary, middle, and high school: how do students feel about specific contexts in terms of settings and subject-domains?

    PubMed

    Raccanello, Daniela; Brondino, Margherita; De Bernardi, Bianca

    2013-12-01

    The present work investigates students' representation of achievement emotions, focusing in context-specific situations in terms of settings and subject-domains, as a function of grade level. We involved 527 fourth-, seventh-, and eleventh-graders, who evaluated ten discrete emotions through questionnaires, with reference to verbal language and mathematics, and different settings (class, homework, tests). Confirmatory multitrait-multimethod analyses indicated higher salience of subject-domains rather than settings for all the emotions; however, complexity of reality was best explained when also settings were accounted for. Analyses of variance revealed higher intensity of positive emotions for younger students, and the opposite pattern for older students; significant differences for most of the emotions based on the evaluative nature of settings, moderated by class levels; more intense positive emotions for mathematics and more intense negative emotions for Italian. Results are discussed considering their theoretical and applied relevance, corroborating previous literature on domain-specificity. © 2013 The Scandinavian Psychological Associations.

  16. Pair correlation functions for identifying spatial correlation in discrete domains

    NASA Astrophysics Data System (ADS)

    Gavagnin, Enrico; Owen, Jennifer P.; Yates, Christian A.

    2018-06-01

    Identifying and quantifying spatial correlation are important aspects of studying the collective behavior of multiagent systems. Pair correlation functions (PCFs) are powerful statistical tools that can provide qualitative and quantitative information about correlation between pairs of agents. Despite the numerous PCFs defined for off-lattice domains, only a few recent studies have considered a PCF for discrete domains. Our work extends the study of spatial correlation in discrete domains by defining a new set of PCFs using two natural and intuitive definitions of distance for a square lattice: the taxicab and uniform metric. We show how these PCFs improve upon previous attempts and compare between the quantitative data acquired. We also extend our definitions of the PCF to other types of regular tessellation that have not been studied before, including hexagonal, triangular, and cuboidal. Finally, we provide a comprehensive PCF for any tessellation and metric, allowing investigation of spatial correlation in irregular lattices for which recognizing correlation is less intuitive.

  17. Generic Safety Requirements for Developing Safe Insulin Pump Software

    PubMed Central

    Zhang, Yi; Jetley, Raoul; Jones, Paul L; Ray, Arnab

    2011-01-01

    Background The authors previously introduced a highly abstract generic insulin infusion pump (GIIP) model that identified common features and hazards shared by most insulin pumps on the market. The aim of this article is to extend our previous work on the GIIP model by articulating safety requirements that address the identified GIIP hazards. These safety requirements can be validated by manufacturers, and may ultimately serve as a safety reference for insulin pump software. Together, these two publications can serve as a basis for discussing insulin pump safety in the diabetes community. Methods In our previous work, we established a generic insulin pump architecture that abstracts functions common to many insulin pumps currently on the market and near-future pump designs. We then carried out a preliminary hazard analysis based on this architecture that included consultations with many domain experts. Further consultation with domain experts resulted in the safety requirements used in the modeling work presented in this article. Results Generic safety requirements for the GIIP model are presented, as appropriate, in parameterized format to accommodate clinical practices or specific insulin pump criteria important to safe device performance. Conclusions We believe that there is considerable value in having the diabetes, academic, and manufacturing communities consider and discuss these generic safety requirements. We hope that the communities will extend and revise them, make them more representative and comprehensive, experiment with them, and use them as a means for assessing the safety of insulin pump software designs. One potential use of these requirements is to integrate them into model-based engineering (MBE) software development methods. We believe, based on our experiences, that implementing safety requirements using MBE methods holds promise in reducing design/implementation flaws in insulin pump development and evolutionary processes, therefore improving overall safety of insulin pump software. PMID:22226258

  18. Evaluation of Disulfide Bond Position to Enhance the Thermal Stability of a Highly Stable Single Domain Antibody

    PubMed Central

    Zabetakis, Dan; Olson, Mark A.; Anderson, George P.; Legler, Patricia M.; Goldman, Ellen R.

    2014-01-01

    Single domain antibodies are the small recombinant variable domains derived from camelid heavy-chain-only antibodies. They are renowned for their stability, in large part due to their ability to refold following thermal or chemical denaturation. In addition to refolding after heat denaturation, A3, a high affinity anti-Staphylococcal Enterotoxin B single domain antibody, possesses a melting temperature of ∼84°C, among the highest reported for a single domain antibody. In this work we utilized the recently described crystal structure of A3 to select locations for the insertion of a second disulfide bond and evaluated the impact that the addition of this second bond had on the melting temperature. Four double-disulfide versions of A3 were constructed and each was found to improve the melting temperature relative to the native structure without reducing affinity. Placement of the disulfide bond at a previously published position between framework regions 2 and 3 yielded the largest improvement (>6°C), suggesting this location is optimal, and seemingly provides a universal route to raise the melting temperature of single domain antibodies. This study further demonstrates that even single domain antibodies with extremely high melting points can be further stabilized by addition of disulfide bonds. PMID:25526640

  19. Prediction of heterotrimeric protein complexes by two-phase learning using neighboring kernels

    PubMed Central

    2014-01-01

    Background Protein complexes play important roles in biological systems such as gene regulatory networks and metabolic pathways. Most methods for predicting protein complexes try to find protein complexes with size more than three. It, however, is known that protein complexes with smaller sizes occupy a large part of whole complexes for several species. In our previous work, we developed a method with several feature space mappings and the domain composition kernel for prediction of heterodimeric protein complexes, which outperforms existing methods. Results We propose methods for prediction of heterotrimeric protein complexes by extending techniques in the previous work on the basis of the idea that most heterotrimeric protein complexes are not likely to share the same protein with each other. We make use of the discriminant function in support vector machines (SVMs), and design novel feature space mappings for the second phase. As the second classifier, we examine SVMs and relevance vector machines (RVMs). We perform 10-fold cross-validation computational experiments. The results suggest that our proposed two-phase methods and SVM with the extended features outperform the existing method NWE, which was reported to outperform other existing methods such as MCL, MCODE, DPClus, CMC, COACH, RRW, and PPSampler for prediction of heterotrimeric protein complexes. Conclusions We propose two-phase prediction methods with the extended features, the domain composition kernel, SVMs and RVMs. The two-phase method with the extended features and the domain composition kernel using SVM as the second classifier is particularly useful for prediction of heterotrimeric protein complexes. PMID:24564744

  20. The impact of premorbid and current intellect in schizophrenia: cognitive, symptom, and functional outcomes

    PubMed Central

    Wells, Ruth; Swaminathan, Vaidy; Sundram, Suresh; Weinberg, Danielle; Bruggemann, Jason; Jacomb, Isabella; Cropley, Vanessa; Lenroot, Rhoshel; Pereira, Avril M; Zalesky, Andrew; Bousman, Chad; Pantelis, Christos; Weickert, Cynthia Shannon; Weickert, Thomas W

    2015-01-01

    Background: Cognitive heterogeneity among people with schizophrenia has been defined on the basis of premorbid and current intelligence quotient (IQ) estimates. In a relatively large, community cohort, we aimed to independently replicate and extend cognitive subtyping work by determining the extent of symptom severity and functional deficits in each group. Methods: A total of 635 healthy controls and 534 patients with a diagnosis of schizophrenia or schizoaffective disorder were recruited through the Australian Schizophrenia Research Bank. Patients were classified into cognitive subgroups on the basis of the Wechsler Test of Adult Reading (a premorbid IQ estimate) and current overall cognitive abilities into preserved, deteriorated, and compromised groups using both clinical and empirical (k-means clustering) methods. Additional cognitive, functional, and symptom outcomes were compared among the resulting groups. Results: A total of 157 patients (29%) classified as ‘preserved’ performed within one s.d. of control means in all cognitive domains. Patients classified as ‘deteriorated’ (n=239, 44%) performed more than one s.d. below control means in all cognitive domains except estimated premorbid IQ and current visuospatial abilities. A separate 138 patients (26%), classified as ‘compromised,’ performed more than one s.d. below control means in all cognitive domains and displayed greater impairment than other groups on symptom and functional measures. Conclusions: In the present study, we independently replicated our previous cognitive classifications of people with schizophrenia. In addition, we extended previous work by demonstrating worse functional outcomes and symptom severity in the compromised group. PMID:27336046

  1. Engineered Human Antibody Constant Domains with Increased Stability*S⃞

    PubMed Central

    Gong, Rui; Vu, Bang K.; Feng, Yang; Prieto, DaRue A.; Dyba, Marzena A.; Walsh, Joseph D.; Prabakaran, Ponraj; Veenstra, Timothy D.; Tarasov, Sergey G.; Ishima, Rieko; Dimitrov, Dimiter S.

    2009-01-01

    The immunoglobulin (Ig) constant CH2 domain is critical for antibody effector functions. Isolated CH2 domains are promising as scaffolds for construction of libraries containing diverse binders that could also confer some effector functions. However, previous work has shown that an isolated murine CH2 domain is relatively unstable to thermally induced unfolding. To explore unfolding mechanisms of isolated human CH2 and increase its stability γ1 CH2 was cloned and a panel of cysteine mutants was constructed. Human γ1 CH2 unfolded at a higher temperature (Tm = 54.1 °C, as measured by circular dichroism) than that previously reported for a mouse CH2 (41 °C). One mutant (m01) was remarkably stable (Tm = 73.8 °C). Similar results were obtained by differential scanning calorimetry. This mutant was also significantly more stable than the wild-type CH2 against urea induced unfolding (50% unfolding at urea concentration of 6.8 m versus 4.2 m). The m01 was highly soluble and monomeric. The existence of the second disulfide bond in m01 and its correct position were demonstrated by mass spectrometry and nuclear magnetic resonance spectroscopy, respectively. The loops were on average more flexible than the framework in both CH2 and m01, and the overall secondary structure was not affected by the additional disulfide bond. These data suggest that a human CH2 domain is relatively stable to unfolding at physiological temperature, and that both CH2 and the highly stable mutant m01 are promising new scaffolds for the development of therapeutics against human diseases. PMID:19307178

  2. The uncertain trajectory of a pilot-wave

    NASA Astrophysics Data System (ADS)

    Nachbin, Andre

    2015-11-01

    Yves Couder (Paris 7) and coworkers reported on walking droplets on the surface of a vibrating bath. John Bush (MIT) and coworkers also produced laboratory experiments which were compared to theoretical predictions. Both groups discussed the pilot-wave properties previously thought to be peculiar to the microscopic, quantum realm. Of particular interest is the wavelike statistics for pilot-wave dynamics in a confined domain. We present a one dimensional water wave model for a droplet bouncing in a confined domain. The mathematical model makes use of conformal mapping which allows for the presence of submerged barriers. The computational simulations produce tunneling events. Work supported by CNPq grant 454027/2008-7 and by FAPERJ Cientistas do Nosso Estado grant 102917/2011.

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

    PubMed Central

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

    2012-01-01

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

  4. Testing domain general learning in an Australian lizard.

    PubMed

    Qi, Yin; Noble, Daniel W A; Fu, Jinzhong; Whiting, Martin J

    2018-06-02

    A key question in cognition is whether animals that are proficient in a specific cognitive domain (domain specific hypothesis), such as spatial learning, are also proficient in other domains (domain general hypothesis) or whether there is a trade-off. Studies testing among these hypotheses are biased towards mammals and birds. To understand constraints on the evolution of cognition more generally, we need broader taxonomic and phylogenetic coverage. We used Australian eastern water skinks (Eulamprus quoyii) with known spatial learning ability in three additional tasks: an instrumental and two discrimination tasks. Under domain specific learning we predicted that lizards that were good at spatial learning would perform less well in the discrimination tasks. Conversely, we predicted that lizards that did not meet our criterion for spatial learning would likewise perform better in discrimination tasks. Lizards with domain general learning should perform approximately equally well (or poorly) in these tasks. Lizards classified as spatial learners performed no differently to non-spatial learners in both the instrumental and discrimination learning tasks. Nevertheless, lizards were proficient in all tasks. Our results reveal two patterns: domain general learning in spatial learners and domain specific learning in non-spatial learners. We suggest that delineating learning into domain general and domain specific may be overly simplistic and we need to instead focus on individual variation in learning ability, which ultimately, is likely to play a key role in fitness. These results, in combination with previously published work on this species, suggests that this species has behavioral flexibility because they are competent across multiple cognitive domains and are capable of reversal learning.

  5. Structure of the mouse galectin-4 N-terminal carbohydrate-recognition domain reveals the mechanism of oligosaccharide recognition

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

    Krejciríková, Veronika; Pachl, Petr; Fábry, Milan

    2011-11-18

    Galectin-4, a member of the tandem-repeat subfamily of galectins, participates in cell-membrane interactions and plays an important role in cell adhesion and modulation of immunity and malignity. The oligosaccharide specificity of the mouse galectin-4 carbohydrate-recognition domains (CRDs) has been reported previously. In this work, the structure and binding properties of the N-terminal domain CRD1 were further investigated and the crystal structure of CRD1 in complex with lactose was determined at 2.1 {angstrom} resolution. The lactose-binding affinity was characterized by fluorescence measurements and two lactose-binding sites were identified: a high-affinity site with a K{sub d} value in the micromolar range (K{submore » d1} = 600 {+-} 70 {mu}M) and a low-affinity site with K{sub d2} = 28 {+-} 10 mM.« less

  6. Identification of novel Trypanosoma cruzi prolyl oligopeptidase inhibitors by structure-based virtual screening

    NASA Astrophysics Data System (ADS)

    de Almeida, Hugo; Leroux, Vincent; Motta, Flávia Nader; Grellier, Philippe; Maigret, Bernard; Santana, Jaime M.; Bastos, Izabela Marques Dourado

    2016-12-01

    We have previously demonstrated that the secreted prolyl oligopeptidase of Trypanosoma cruzi (POPTc80) is involved in the infection process by facilitating parasite migration through the extracellular matrix. We have built a 3D structural model where POPTc80 is formed by a catalytic α/β-hydrolase domain and a β-propeller domain, and in which the substrate docks at the inter-domain interface, suggesting a "jaw opening" gating access mechanism. This preliminary model was refined by molecular dynamics simulations and next used for a virtual screening campaign, whose predictions were tested by standard binding assays. This strategy was successful as all 13 tested molecules suggested from the in silico calculations were found out to be active POPTc80 inhibitors in the micromolar range (lowest K i at 667 nM). This work paves the way for future development of innovative drugs against Chagas disease.

  7. Time Use and Physical Activity: A Shift Away from Movement across the Globe

    PubMed Central

    Ng, Shu Wen; Popkin, Barry

    2012-01-01

    Technology linked with reduced physical activity (PA) in occupational work, home/domestic work, and travel and increased sedentary activities, especially television viewing, dominates the globe. Using detailed historical data on time allocation, occupational distributions, energy expenditures data by activity, and time-varying measures of metabolic equivalents of task (MET) for activities when available, we measure historical and current MET by four major PA domains (occupation, home production, travel, and active leisure) and sedentary time among adults (> 18 years). Trends by domain for the United States (1965–2009), the United Kingdom (1961–2005), Brazil (2002–2007), China (1991–2009), and India (2000–2005) are presented. We also project changes in energy expenditure by domain and sedentary time (excluding sleep and personal care) to 2020 and 2030 for each of these countries. The use of previously unexplored detailed time allocation and energy expenditures and other datasets represents a useful addition to our ability to document activity and inactivity globally. Given the potential impact on weight gain and other cardiometabolic health risks, the differential declines in MET of activity and increases in sedentary time across the globe represents a major threat to global health. PMID:22694051

  8. Work, Family and Community Support as Predictors of Work-Family Conflict: A Study of Low-Income Workers

    ERIC Educational Resources Information Center

    Griggs, Tracy Lambert; Casper, Wendy J.; Eby, Lillian T.

    2013-01-01

    This study examines relationships between support from work, family and community domains with time- and strain-based work-family conflict in a sample of low-income workers. Results reveal significant within-domain and cross-domain relationships between support from all three life domains with work--family conflict. With respect to family support,…

  9. Transient thermal stresses of work roll by coupled thermoelasticity

    NASA Astrophysics Data System (ADS)

    Lai, W. B.; Chen, T. C.; Weng, C. I.

    1991-01-01

    A numerical method, based on a two-dimensional plane strain model, is developed to predict the transient responses (that include distributions of temperature, thermal deformation, and thermal stress) of work roll during strip rolling by coupled thermoelasticity. The method consists of discretizing the space domain of the problem by finite element method first, and then treating the time domain by implicit time integration techniques. In order to avoid the difficulty in analysis due to relative movement between work roll and its thermal boundary, the energy equation is formulated with respect to a fixed Eulerian reference frame. The effect of thermoelastic coupling term, that is generally disregarded in strip rolling, can be considered and assessed. The influences of some important process parameters, such as rotational speed of the roll and intensity of heat flux, on transient solutions are also included and discussed. Furthermore, since the stress history at any point of the roll in both transient and steady state could be accurately evaluated, it is available to perform the analysis of thermal fatigue for the roll by means of previous data.

  10. Structural Studies on Cytosolic Domain of Magnesium Transporter MgtE from Enterococcus faecalis

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

    Ragumani, S.; Sauder, J; Burley, S

    2009-01-01

    Magnesium (Mg{sup 2+}) is an essential element for growth and maintenance of living cells. It acts as a cofactor for many enzymes and is also essential for stability of the plasma membrane. There are two distinct classes of magnesium transporters identified in bacteria that convey Mg{sup 2+} from periplasm to cytoplasm [ATPase-dependent (MgtA and MgtB) and constitutively active (CorA and MgtE)]. Previously published work on Mg{sup 2+} transporters yielded structures of full length MgtE from Thermus thermophilus, determined at 3.5 {angstrom} resolution, and its cytoplasmic domain with and without bond Mg{sup 2+} determined at 2.3 and 3.9 {angstrom} resolution, respectively.more » Here, they report the crystal structure of the Mg{sup 2+} bound form of the cytosolic portion of MgtE (residues 6-262) from Enterococcus faecalis at 2.2 {angstrom} resolution. The present structure and magnesium bound cytosolic domain structure from T. thermophilus (PDB ID: 2YVY) are structurally similar. Three magnesium binding sites are common to both MgtE full length and the present structure. Their work revealed an additional Mg{sup 2+} binding site in the E. faecalis structure. In this report, they discuss the functional significance of Mg{sup 2+} binding sites in the cytosolic domains of MgtE transporters.« less

  11. Phylogenomics and sequence-structure-function relationships in the GmrSD family of Type IV restriction enzymes.

    PubMed

    Machnicka, Magdalena A; Kaminska, Katarzyna H; Dunin-Horkawicz, Stanislaw; Bujnicki, Janusz M

    2015-10-23

    GmrSD is a modification-dependent restriction endonuclease that specifically targets and cleaves glucosylated hydroxymethylcytosine (glc-HMC) modified DNA. It is encoded either as two separate single-domain GmrS and GmrD proteins or as a single protein carrying both domains. Previous studies suggested that GmrS acts as endonuclease and NTPase whereas GmrD binds DNA. In this work we applied homology detection, sequence conservation analysis, fold recognition and homology modeling methods to study sequence-structure-function relationships in the GmrSD restriction endonucleases family. We also analyzed the phylogeny and genomic context of the family members. Results of our comparative genomics study show that GmrS exhibits similarity to proteins from the ParB/Srx fold which can have both NTPase and nuclease activity. In contrast to the previous studies though, we attribute the nuclease activity also to GmrD as we found it to contain the HNH endonuclease motif. We revealed residues potentially important for structure and function in both domains. Moreover, we found that GmrSD systems exist predominantly as a fused, double-domain form rather than as a heterodimer and that their homologs are often encoded in regions enriched in defense and gene mobility-related elements. Finally, phylogenetic reconstructions of GmrS and GmrD domains revealed that they coevolved and only few GmrSD systems appear to be assembled from distantly related GmrS and GmrD components. Our study provides insight into sequence-structure-function relationships in the yet poorly characterized family of Type IV restriction enzymes. Comparative genomics allowed to propose possible role of GmrD domain in the function of the GmrSD enzyme and possible active sites of both GmrS and GmrD domains. Presented results can guide further experimental characterization of these enzymes.

  12. A comparison of GluR-A-deficient and wild-type mice on a test battery assessing sensorimotor, affective, and cognitive behaviors.

    PubMed

    Bannerman, D M; Deacon, R M J; Brady, S; Bruce, A; Sprengel, R; Seeburg, P H; Rawlins, J N P

    2004-06-01

    Previous studies have demonstrated a spatial working memory deficit in glutamate receptor (GluR)-A (GluR1) AMPA receptor subunit knockout mice. The present study evaluated male and female wild-type and GluR-A-/- mice on a test battery that assessed sensorimotor, affective, and cognitive behaviors. Results revealed a behavioral phenotype more extensive than previously described. GluR-A-/- mice were hyperactive, displayed a subtle lack of motor coordination, and were generally more anxious than wild-type controls. In addition, they showed a deficit in spontaneous alternation, consistent with previous reports of a role for GluR-A-dependent plasticity in hippocampus-dependent, spatial working memory. Although changes in motor coordination or anxiety cannot explain the dissociations already reported within the spatial memory domain, it is clear that they could significantly affect interpretation of results obtained in other kinds of behavioral tasks. ((c) 2004 APA, all rights reserved)

  13. Copper Coordination in the Full-Length, Recombinant Prion Protein†

    PubMed Central

    Burns, Colin S.; Aronoff-Spencer, Eliah; Legname, Giuseppe; Prusiner, Stanley B.; Antholine, William E.; Gerfen, Gary J.; Peisach, Jack; Millhauser, Glenn L.

    2010-01-01

    The prion protein (PrP) binds divalent copper at physiologically relevant conditions and is believed to participate in copper regulation or act as a copper-dependent enzyme. Ongoing studies aim at determining the molecular features of the copper binding sites. The emerging consensus is that most copper binds in the octarepeat domain, which is composed of four or more copies of the fundamental sequence PHGGGWGQ. Previous work from our laboratory using PrP-derived peptides, in conjunction with EPR and X-ray crystallography, demonstrated that the HGGGW segment constitutes the fundamental binding unit in the octarepeat domain [Burns et al. (2002) Biochemistry 41, 3991–4001; Aronoff-Spencer et al. (2000) Biochemistry 39, 13760–13771]. Copper coordination arises from the His imidazole and sequential deprotonated glycine amides. In this present work, recombinant, full-length Syrian hamster PrP is investigated using EPR methodologies. Four copper ions are taken up in the octarepeat domain, which supports previous findings. However, quantification studies reveal a fifth binding site in the flexible region between the octarepeats and the PrP globular C-terminal domain. A series of PrP peptide constructs show that this site involves His96 in the PrP(92–96) segment GGGTH. Further examination by X-band EPR, S-band EPR, and electron spin–echo envelope spectroscopy, demonstrates coordination by the His96 imidazole and the glycine preceding the threonine. The copper affinity for this type of binding site is highly pH dependent, and EPR studies here show that recombinant PrP loses its affinity for copper below pH 6.0. These studies seem to provide a complete profile of the copper binding sites in PrP and support the hypothesis that PrP function is related to its ability to bind copper in a pH-dependent fashion. PMID:12779334

  14. 2017 Emerging Technology Domains Risk Survey

    DTIC Science & Technology

    2017-10-01

    REV-03.18.2016.0 2017 Emerging Technology Domains Risk Survey Daniel Klinedinst Joel Land Kyle O’Meara October 2017 TECHNICAL REPORT CMU/SEI...to the CERT/CC 2016 Emerging Technol- ogy Domains Risk Survey [King 2016]. This list does not supersede previous reports. Many of the previously... Survey [King 2016]. Table 1: New and Emerging Technologies Gartner’s 2015 List of New Technology CERT’s List of Emerging Domains Trust Boundary

  15. A complex ligase ribozyme evolved in vitro from a group I ribozyme domain

    NASA Technical Reports Server (NTRS)

    Jaeger, L.; Wright, M. C.; Joyce, G. F.; Bada, J. L. (Principal Investigator)

    1999-01-01

    Like most proteins, complex RNA molecules often are modular objects made up of distinct structural and functional domains. The component domains of a protein can associate in alternative combinations to form molecules with different functions. These observations raise the possibility that complex RNAs also can be assembled from preexisting structural and functional domains. To test this hypothesis, an in vitro evolution procedure was used to isolate a previously undescribed class of complex ligase ribozymes, starting from a pool of 10(16) different RNA molecules that contained a constant region derived from a large structural domain that occurs within self-splicing group I ribozymes. Attached to this constant region were three hypervariable regions, totaling 85 nucleotides, that gave rise to the catalytic motif within the evolved catalysts. The ligase ribozymes catalyze formation of a 3',5'-phosphodiester linkage between adjacent template-bound oligonucleotides, one bearing a 3' hydroxyl and the other a 5' triphosphate. Ligation occurs in the context of a Watson-Crick duplex, with a catalytic rate of 0.26 min(-1) under optimal conditions. The constant region is essential for catalytic activity and appears to retain the tertiary structure of the group I ribozyme. This work demonstrates that complex RNA molecules, like their protein counterparts, can share common structural domains while exhibiting distinct catalytic functions.

  16. 1H, 15N and 13C resonance assignments of the J-domain of co-chaperone Sis1 from Saccharomyces cerevisiae.

    PubMed

    Pinheiro, Glaucia M S; Amorim, Gisele C; Iqbal, Anwar; Ramos, C H I; Almeida, Fabio C L

    2018-04-30

    Protein folding in the cell is usually aided by molecular chaperones, from which the Hsp70 (Hsp = heat shock protein) family has many important roles, such as aiding nascent folding and participating in translocation. Hsp70 has ATPase activity which is stimulated by binding to the J-domain present in co-chaperones from the Hsp40 family. Hsp40s have many functions, as for instance the binding to partially folded proteins to be delivered to Hsp70. However, the presence of the J-domain characterizes Hsp40s or, by this reason, as J-proteins. The J-domain alone can stimulate Hsp70 ATPase activity. Apparently, it also maintains the same conformation as in the whole protein although structural information on full J-proteins is still missing. This work reports the 1 H, 15 N and 13 C resonance assignments of the J-domain of a Hsp40 from Saccharomyces cerevisiae, named Sis1. Secondary structure and order parameter prediction from chemical shifts are also reported. Altogether, the data show that Sis1 J-domain is highly structured and predominantly formed by α-helices, results that are in very good agreement with those previously reported for the crystallographic structure.

  17. A new crystal structure of the bifunctional antibiotic simocyclinone D8 bound to DNA gyrase gives fresh insight into the mechanism of inhibition.

    PubMed

    Hearnshaw, Stephen J; Edwards, Marcus J; Stevenson, Clare E; Lawson, David M; Maxwell, Anthony

    2014-05-15

    Simocyclinone D8 (SD8) is an antibiotic produced by Streptomyces antibioticus that targets DNA gyrase. A previous structure of SD8 complexed with the N-terminal domain of the DNA gyrase A protein (GyrA) suggested that four SD8 molecules stabilized a tetramer of the protein; subsequent mass spectrometry experiments suggested that a protein dimer with two symmetry-related SD8s was more likely. This work describes the structures of a further truncated form of the GyrA N-terminal domain fragment with and without SD8 bound. The structure with SD8 has the two SD8 molecules bound within the same GyrA dimer. This new structure is entirely consistent with the mutations in GyrA that confer SD8 resistance and, by comparison with a new apo structure of the GyrA N-terminal domain, reveals the likely conformation changes that occur upon SD8 binding and the detailed mechanism of SD8 inhibition of gyrase. Isothermal titration calorimetry experiments are consistent with the crystallography results and further suggest that a previously observed complex between SD8 and GyrB is ~1000-fold weaker than the interaction with GyrA. Copyright © 2014. Published by Elsevier Ltd.

  18. A New Crystal Structure of the Bifunctional Antibiotic Simocyclinone D8 Bound to DNA Gyrase Gives Fresh Insight into the Mechanism of Inhibition

    PubMed Central

    Hearnshaw, Stephen J.; Edwards, Marcus J.; Stevenson, Clare E.; Lawson, David M.; Maxwell, Anthony

    2014-01-01

    Simocyclinone D8 (SD8) is an antibiotic produced by Streptomyces antibioticus that targets DNA gyrase. A previous structure of SD8 complexed with the N-terminal domain of the DNA gyrase A protein (GyrA) suggested that four SD8 molecules stabilized a tetramer of the protein; subsequent mass spectrometry experiments suggested that a protein dimer with two symmetry-related SD8s was more likely. This work describes the structures of a further truncated form of the GyrA N-terminal domain fragment with and without SD8 bound. The structure with SD8 has the two SD8 molecules bound within the same GyrA dimer. This new structure is entirely consistent with the mutations in GyrA that confer SD8 resistance and, by comparison with a new apo structure of the GyrA N-terminal domain, reveals the likely conformation changes that occur upon SD8 binding and the detailed mechanism of SD8 inhibition of gyrase. Isothermal titration calorimetry experiments are consistent with the crystallography results and further suggest that a previously observed complex between SD8 and GyrB is ~ 1000-fold weaker than the interaction with GyrA. PMID:24594357

  19. Ultrasonic isolation of the outer membrane of Escherichia coli with autodisplayed Z-domains.

    PubMed

    Bong, Ji-Hong; Yoo, Gu; Park, Min; Kang, Min-Jung; Jose, Joachim; Pyun, Jae-Chul

    2014-11-01

    The outer membrane of Escherichia coli was previously isolated as a liposome-like outer membrane particle using an enzymatic treatment for lysozymes; for immunoassays, the particles were subsequently layered on solid supports via hydrophobic interactions. This work presents an enzyme-free isolation method for the E. coli outer membrane with autodisplayed Z-domains using ultrasonication. First, the properties of the outer membrane particle, such as the particle size, zeta potential, and total protein, were compared with the properties of particles obtained using the previous preparation methods. Compared with the conventional isolation method using an enzyme treatment, the ultrasonic method exhibited a higher efficiency at isolating the outer membrane and less contamination by cytosolic proteins. The isolated outer membrane particles were layered on a gold surface, and the roughness and thickness of the layered outer membrane layers were subsequently analyzed using AFM analysis. Finally, the antibody-binding activity of two outer membrane layers with autodisplayed Z-domains created from particles that were isolated using the enzymatic and ultrasonic isolation methods was measured using fluorescein-labeled antibody as a model analyte, and the activity of the outer membrane layer that was isolated from the ultrasonic method was estimated to be more than 20% higher than that from the conventional enzymatic method. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Differential Associations of UPPS-P Impulsivity Traits With Alcohol Problems.

    PubMed

    McCarty, Kayleigh N; Morris, David H; Hatz, Laura E; McCarthy, Denis M

    2017-07-01

    The UPPS-P model posits that impulsivity comprises five factors: positive urgency, negative urgency, lack of planning, lack of perseverance, and sensation seeking. Negative and positive urgency are the traits most consistently associated with alcohol problems. However, previous work has examined alcohol problems either individually or in the aggregate, rather than examining multiple problem domains simultaneously. Recent work has also questioned the utility of distinguishing between positive and negative urgency, as this distinction did not meaningfully differ in predicting domains of psychopathology. The aims of this study were to address these issues by (a) testing unique associations of UPPS-P with specific domains of alcohol problems and (b) determining the utility of distinguishing between positive and negative urgency as risk factors for specific alcohol problems. Associations between UPPS-P traits and alcohol problem domains were examined in two cross-sectional data sets using negative binomial regression models. In both samples, negative urgency was associated with social/interpersonal, self-perception, risky behaviors, and blackout drinking problems. Positive urgency was associated with academic/occupational and physiological dependence problems. Both urgency traits were associated with impaired control and self-care problems. Associations for other UPPS-P traits did not replicate across samples. Results indicate that negative and positive urgency have differential associations with alcohol problem domains. Results also suggest a distinction between the type of alcohol problems associated with these traits-negative urgency was associated with problems experienced during a drinking episode, whereas positive urgency was associated with alcohol problems that result from longer-term drinking trends.

  1. Distinct Ubiquitin Binding Modes Exhibited by SH3 Domains: Molecular Determinants and Functional Implications

    PubMed Central

    Ortega Roldan, Jose L.; Casares, Salvador; Ringkjøbing Jensen, Malene; Cárdenes, Nayra; Bravo, Jerónimo; Blackledge, Martin; Azuaga, Ana I.; van Nuland, Nico A. J.

    2013-01-01

    SH3 domains constitute a new type of ubiquitin-binding domains. We previously showed that the third SH3 domain (SH3-C) of CD2AP binds ubiquitin in an alternative orientation. We have determined the structure of the complex between first CD2AP SH3 domain and ubiquitin and performed a structural and mutational analysis to decipher the determinants of the SH3-C binding mode to ubiquitin. We found that the Phe-to-Tyr mutation in CD2AP and in the homologous CIN85 SH3-C domain does not abrogate ubiquitin binding, in contrast to previous hypothesis and our findings for the first two CD2AP SH3 domains. The similar alternative binding mode of the SH3-C domains of these related adaptor proteins is characterised by a higher affinity to C-terminal extended ubiquitin molecules. We conclude that CD2AP/CIN85 SH3-C domain interaction with ubiquitin constitutes a new ubiquitin-binding mode involved in a different cellular function and thus changes the previously established mechanism of EGF-dependent CD2AP/CIN85 mono-ubiquitination. PMID:24039852

  2. Empowerment variables for rehabilitation clients on perceived beliefs concerning work quality of life domains.

    PubMed

    Tschopp, Molly K; Frain, Michael P; Bishop, Malachy

    2009-01-01

    This article describes and presents an initial analysis of variables generally associated with empowerment towards perceived beliefs concerning quality of life work domains for individuals with disabilities. The model examines the domains of importance, satisfaction, control and degree of interference of disability that an individual feels towards work. The internet based study used results from 70 individuals with disabilities in varying aspects of work. The variables composing empowerment that correlated strongly with the work domains include: self-advocacy, self-efficacy, perceived stigma, and family resiliency as measured through coping. Quality of Life concerning work was measured through the DSC-C a domain specific QOL instrument.

  3. Molecular cloning and characterization of two novel genes from hexaploid wheat that encode double PR-1 domains coupled with a receptor-like protein kinase

    USDA-ARS?s Scientific Manuscript database

    Hexaploid wheat (Triticum aestivum L.) contains at least 23 TaPr-1 genes encoding the group 1 pathogenesis-related (PR-1) proteins as identified in our previous work. Here we report the cloning and characterization of TaPr-1-rk1 and TaPr-1-rk2, two novel genes closely related to the wheat PR-1 famil...

  4. Reaction-diffusion systems and external morphogen gradients: the two-dimensional case, with an application to skeletal pattern formation.

    PubMed

    Glimm, Tilmann; Zhang, Jianying; Shen, Yun-Qiu; Newman, Stuart A

    2012-03-01

    We investigate a reaction-diffusion system consisting of an activator and an inhibitor in a two-dimensional domain. There is a morphogen gradient in the domain. The production of the activator depends on the concentration of the morphogen. Mathematically, this leads to reaction-diffusion equations with explicitly space-dependent terms. It is well known that in the absence of an external morphogen, the system can produce either spots or stripes via the Turing bifurcation. We derive first-order expansions for the possible patterns in the presence of an external morphogen and show how both stripes and spots are affected. This work generalizes previous one-dimensional results to two dimensions. Specifically, we consider the quasi-one-dimensional case of a thin rectangular domain and the case of a square domain. We apply the results to a model of skeletal pattern formation in vertebrate limbs. In the framework of reaction-diffusion models, our results suggest a simple explanation for some recent experimental findings in the mouse limb which are much harder to explain in positional-information-type models.

  5. Crystal structure of heterotetrameric sarcosine oxidase from Corynebacterium sp. U-96

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

    Ida, Koh; E-mail: idakoh@sci.kitasato-u.ac.jp; Moriguchi, Tomotaka

    2005-07-29

    Sarcosine oxidase from Corynebacterium sp. U-96 is a heterotetrameric enzyme. Here we report the crystal structures of the enzyme in complex with dimethylglycine and folinic acid. The {alpha} subunit is composed of two domains, contains NAD{sup +}, and binds folinic acid. The {beta} subunit contains dimethylglycine, FAD, and FMN, and these flavins are approximately 10 A apart. The {gamma} subunit is in contact with two domains of {alpha} subunit and has possibly a folate-binding structure. The {delta} subunit contains a single atom of zinc and has a Cys{sub 3}His zinc finger structure. Based on the structures determined and on themore » previous works, the structure-function relationship on the heterotetrameric sarcosine oxidase is discussed.« less

  6. Geophysical framework of the southwestern Nevada volcanic field and hydrogeologic implications

    USGS Publications Warehouse

    Grauch, V.J.; Sawyer, David A.; Fridrich, Chris J.; Hudson, Mark R.

    1999-01-01

    Gravity and magnetic data, when integrated with other geophysical, geological, and rock-property data, provide a regional framework to view the subsurface geology in the southwestern Nevada volcanic field. The region has been loosely divided into six domains based on structural style and overall geophysical character. For each domain, the subsurface tectonic and magmatic features that have been inferred or interpreted from previous geophysical work has been reviewed. Where possible, abrupt changes in geophysical fields as evidence for potential structural lithologic control on ground-water flow has been noted. Inferred lithology is used to suggest associated hydrogeologic units in the subsurface. The resulting framework provides a basis for investigators to develop hypotheses from regional ground-water pathways where no drill-hole information exists.

  7. Structured prediction models for RNN based sequence labeling in clinical text.

    PubMed

    Jagannatha, Abhyuday N; Yu, Hong

    2016-11-01

    Sequence labeling is a widely used method for named entity recognition and information extraction from unstructured natural language data. In clinical domain one major application of sequence labeling involves extraction of medical entities such as medication, indication, and side-effects from Electronic Health Record narratives. Sequence labeling in this domain, presents its own set of challenges and objectives. In this work we experimented with various CRF based structured learning models with Recurrent Neural Networks. We extend the previously studied LSTM-CRF models with explicit modeling of pairwise potentials. We also propose an approximate version of skip-chain CRF inference with RNN potentials. We use these methodologies for structured prediction in order to improve the exact phrase detection of various medical entities.

  8. Structured prediction models for RNN based sequence labeling in clinical text

    PubMed Central

    Jagannatha, Abhyuday N; Yu, Hong

    2016-01-01

    Sequence labeling is a widely used method for named entity recognition and information extraction from unstructured natural language data. In clinical domain one major application of sequence labeling involves extraction of medical entities such as medication, indication, and side-effects from Electronic Health Record narratives. Sequence labeling in this domain, presents its own set of challenges and objectives. In this work we experimented with various CRF based structured learning models with Recurrent Neural Networks. We extend the previously studied LSTM-CRF models with explicit modeling of pairwise potentials. We also propose an approximate version of skip-chain CRF inference with RNN potentials. We use these methodologies1 for structured prediction in order to improve the exact phrase detection of various medical entities. PMID:28004040

  9. Lexicon-enhanced sentiment analysis framework using rule-based classification scheme.

    PubMed

    Asghar, Muhammad Zubair; Khan, Aurangzeb; Ahmad, Shakeel; Qasim, Maria; Khan, Imran Ali

    2017-01-01

    With the rapid increase in social networks and blogs, the social media services are increasingly being used by online communities to share their views and experiences about a particular product, policy and event. Due to economic importance of these reviews, there is growing trend of writing user reviews to promote a product. Nowadays, users prefer online blogs and review sites to purchase products. Therefore, user reviews are considered as an important source of information in Sentiment Analysis (SA) applications for decision making. In this work, we exploit the wealth of user reviews, available through the online forums, to analyze the semantic orientation of words by categorizing them into +ive and -ive classes to identify and classify emoticons, modifiers, general-purpose and domain-specific words expressed in the public's feedback about the products. However, the un-supervised learning approach employed in previous studies is becoming less efficient due to data sparseness, low accuracy due to non-consideration of emoticons, modifiers, and presence of domain specific words, as they may result in inaccurate classification of users' reviews. Lexicon-enhanced sentiment analysis based on Rule-based classification scheme is an alternative approach for improving sentiment classification of users' reviews in online communities. In addition to the sentiment terms used in general purpose sentiment analysis, we integrate emoticons, modifiers and domain specific terms to analyze the reviews posted in online communities. To test the effectiveness of the proposed method, we considered users reviews in three domains. The results obtained from different experiments demonstrate that the proposed method overcomes limitations of previous methods and the performance of the sentiment analysis is improved after considering emoticons, modifiers, negations, and domain specific terms when compared to baseline methods.

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

    PubMed

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

    2011-04-01

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

  11. Is the association between high strain work and depressive symptoms modified by private life social support: a cohort study of 1,074 Danish employees?

    PubMed Central

    2014-01-01

    Background Previous studies have shown that psychosocial working conditions characterized by high psychological demands and low decision latitude (i.e., high strain work) are associated with increased risk of depressive symptoms. Little is known, however, concerning how this association may be modified by factors outside the working environment. This article examines the modifying role of private life social support in the relation between high strain work and the development of severe depressive symptoms. Methods Data were questionnaire-based, collected from a cross-occupational sample of 1,074 Danish employees. At baseline, all participants were free of severe depressive symptoms, measured by the Mental Health Inventory. High strain work was defined by the combination of high psychological demands at work and low control, measured with multi-dimensional scales. Private life social support was operationalized as the number of life domains with confidants and dichotomized as low (0–1 domains) or high (2 or more domains). Using logistic regression we examined the risk of onset of severe depressive symptoms, adjusting for sex, age, occupational position, and prior depressive symptoms. Results Separately, neither high strain work nor low private life social support statistically significantly predicted depressive symptoms. However, participants with joint exposure to high strain work and low private life social support had an Odds ratio (OR) for severe depressive symptoms of 3.41 (95% CI: 1.36-8.58), compared to participants with no work strain and high private life social support. There was no increased risk for participants with high strain work and high private life social support (OR = 1.32, 95% CI: 0.65-2.68). The interaction term for departure from additivity was, however, not statistically significant (p = 0.18). Conclusions Our findings suggest that high strain work may increase risk of depressive symptoms in individuals with low private life social support, although the effect-modification was statistically non-significant. Larger studies are needed to further establish the role of private life social support in the relation between high strain work and depression. PMID:25005843

  12. Is the association between high strain work and depressive symptoms modified by private life social support: a cohort study of 1,074 Danish employees?

    PubMed

    Madsen, Ida E H; Jorgensen, Anette F B; Borritz, Marianne; Nielsen, Martin L; Rugulies, Reiner

    2014-07-08

    Previous studies have shown that psychosocial working conditions characterized by high psychological demands and low decision latitude (i.e., high strain work) are associated with increased risk of depressive symptoms. Little is known, however, concerning how this association may be modified by factors outside the working environment. This article examines the modifying role of private life social support in the relation between high strain work and the development of severe depressive symptoms. Data were questionnaire-based, collected from a cross-occupational sample of 1,074 Danish employees. At baseline, all participants were free of severe depressive symptoms, measured by the Mental Health Inventory. High strain work was defined by the combination of high psychological demands at work and low control, measured with multi-dimensional scales. Private life social support was operationalized as the number of life domains with confidants and dichotomized as low (0-1 domains) or high (2 or more domains). Using logistic regression we examined the risk of onset of severe depressive symptoms, adjusting for sex, age, occupational position, and prior depressive symptoms. Separately, neither high strain work nor low private life social support statistically significantly predicted depressive symptoms. However, participants with joint exposure to high strain work and low private life social support had an Odds ratio (OR) for severe depressive symptoms of 3.41 (95% CI: 1.36-8.58), compared to participants with no work strain and high private life social support. There was no increased risk for participants with high strain work and high private life social support (OR = 1.32, 95% CI: 0.65-2.68). The interaction term for departure from additivity was, however, not statistically significant (p = 0.18). Our findings suggest that high strain work may increase risk of depressive symptoms in individuals with low private life social support, although the effect-modification was statistically non-significant. Larger studies are needed to further establish the role of private life social support in the relation between high strain work and depression.

  13. Fitting hidden Markov models of protein domains to a target species: application to Plasmodium falciparum

    PubMed Central

    2012-01-01

    Background Hidden Markov Models (HMMs) are a powerful tool for protein domain identification. The Pfam database notably provides a large collection of HMMs which are widely used for the annotation of proteins in new sequenced organisms. In Pfam, each domain family is represented by a curated multiple sequence alignment from which a profile HMM is built. In spite of their high specificity, HMMs may lack sensitivity when searching for domains in divergent organisms. This is particularly the case for species with a biased amino-acid composition, such as P. falciparum, the main causal agent of human malaria. In this context, fitting HMMs to the specificities of the target proteome can help identify additional domains. Results Using P. falciparum as an example, we compare approaches that have been proposed for this problem, and present two alternative methods. Because previous attempts strongly rely on known domain occurrences in the target species or its close relatives, they mainly improve the detection of domains which belong to already identified families. Our methods learn global correction rules that adjust amino-acid distributions associated with the match states of HMMs. These rules are applied to all match states of the whole HMM library, thus enabling the detection of domains from previously absent families. Additionally, we propose a procedure to estimate the proportion of false positives among the newly discovered domains. Starting with the Pfam standard library, we build several new libraries with the different HMM-fitting approaches. These libraries are first used to detect new domain occurrences with low E-values. Second, by applying the Co-Occurrence Domain Discovery (CODD) procedure we have recently proposed, the libraries are further used to identify likely occurrences among potential domains with higher E-values. Conclusion We show that the new approaches allow identification of several domain families previously absent in the P. falciparum proteome and the Apicomplexa phylum, and identify many domains that are not detected by previous approaches. In terms of the number of new discovered domains, the new approaches outperform the previous ones when no close species are available or when they are used to identify likely occurrences among potential domains with high E-values. All predictions on P. falciparum have been integrated into a dedicated website which pools all known/new annotations of protein domains and functions for this organism. A software implementing the two proposed approaches is available at the same address: http://www.lirmm.fr/∼terrapon/HMMfit/ PMID:22548871

  14. Fitting hidden Markov models of protein domains to a target species: application to Plasmodium falciparum.

    PubMed

    Terrapon, Nicolas; Gascuel, Olivier; Maréchal, Eric; Bréhélin, Laurent

    2012-05-01

    Hidden Markov Models (HMMs) are a powerful tool for protein domain identification. The Pfam database notably provides a large collection of HMMs which are widely used for the annotation of proteins in new sequenced organisms. In Pfam, each domain family is represented by a curated multiple sequence alignment from which a profile HMM is built. In spite of their high specificity, HMMs may lack sensitivity when searching for domains in divergent organisms. This is particularly the case for species with a biased amino-acid composition, such as P. falciparum, the main causal agent of human malaria. In this context, fitting HMMs to the specificities of the target proteome can help identify additional domains. Using P. falciparum as an example, we compare approaches that have been proposed for this problem, and present two alternative methods. Because previous attempts strongly rely on known domain occurrences in the target species or its close relatives, they mainly improve the detection of domains which belong to already identified families. Our methods learn global correction rules that adjust amino-acid distributions associated with the match states of HMMs. These rules are applied to all match states of the whole HMM library, thus enabling the detection of domains from previously absent families. Additionally, we propose a procedure to estimate the proportion of false positives among the newly discovered domains. Starting with the Pfam standard library, we build several new libraries with the different HMM-fitting approaches. These libraries are first used to detect new domain occurrences with low E-values. Second, by applying the Co-Occurrence Domain Discovery (CODD) procedure we have recently proposed, the libraries are further used to identify likely occurrences among potential domains with higher E-values. We show that the new approaches allow identification of several domain families previously absent in the P. falciparum proteome and the Apicomplexa phylum, and identify many domains that are not detected by previous approaches. In terms of the number of new discovered domains, the new approaches outperform the previous ones when no close species are available or when they are used to identify likely occurrences among potential domains with high E-values. All predictions on P. falciparum have been integrated into a dedicated website which pools all known/new annotations of protein domains and functions for this organism. A software implementing the two proposed approaches is available at the same address: http://www.lirmm.fr/~terrapon/HMMfit/

  15. Hydrodynamic and Membrane Binding Properties of Purified Rous Sarcoma Virus Gag Protein

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

    Dick, Robert A.; Datta, Siddhartha A. K.; Nanda, Hirsh

    2016-05-06

    Previously, no retroviral Gag protein has been highly purified in milligram quantities and in a biologically relevant and active form. We have purified Rous sarcoma virus (RSV) Gag protein and in parallel several truncation mutants of Gag and have studied their biophysical properties and membrane interactionsin vitro. RSV Gag is unusual in that it is not naturally myristoylated. From its ability to assemble into virus-like particlesin vitro, we infer that RSV Gag is biologically active. By size exclusion chromatography and small-angle X-ray scattering, Gag in solution appears extended and flexible, in contrast to previous reports on unmyristoylated HIV-1 Gag, whichmore » is compact. However, by neutron reflectometry measurements of RSV Gag bound to a supported bilayer, the protein appears to adopt a more compact, folded-over conformation. At physiological ionic strength, purified Gag binds strongly to liposomes containing acidic lipids. This interaction is stimulated by physiological levels of phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2] and by cholesterol. However, unlike HIV-1 Gag, RSV Gag shows no sensitivity to acyl chain saturation. In contrast with full-length RSV Gag, the purified MA domain of Gag binds to liposomes only weakly. Similarly, both an N-terminally truncated version of Gag that is missing the MA domain and a C-terminally truncated version that is missing the NC domain bind only weakly. These results imply that NC contributes to membrane interactionin vitro, either by directly contacting acidic lipids or by promoting Gag multimerization. Retroviruses like HIV assemble at and bud from the plasma membrane of cells. Assembly requires the interaction between thousands of Gag molecules to form a lattice. Previous work indicated that lattice formation at the plasma membrane is influenced by the conformation of monomeric HIV. We have extended this work to the more tractable RSV Gag. Our results show that RSV Gag is highly flexible and can adopt a folded-over conformation on a lipid bilayer, implicating both the N and C termini in membrane binding. In addition, binding of Gag to membranes is diminished when either terminal domain is truncated. RSV Gag membrane association is significantly less sensitive than HIV Gag membrane association to lipid acyl chain saturation. These findings shed light on Gag assembly and membrane binding, critical steps in the viral life cycle and an untapped target for antiretroviral drugs.« less

  16. Native Alanine Substitution in the Glycine Hinge Modulates Conformational Flexibility of Heme Nitric Oxide/Oxygen (H-NOX) Sensing Proteins.

    PubMed

    Hespen, Charles W; Bruegger, Joel J; Guo, Yirui; Marletta, Michael A

    2018-06-15

    Heme nitric oxide/oxygen sensing (H-NOX) domains are direct NO sensors that regulate a variety of biological functions in both bacteria and eukaryotes. Previous work on H-NOX proteins has shown that upon NO binding, a conformational change occurs along two glycine residues on adjacent helices (termed the glycine hinge). Despite the apparent importance of the glycine hinge, it is not fully conserved in all H-NOX domains. Several H-NOX sensors from the family Flavobacteriaceae contain a native alanine substitution in one of the hinge residues. In this work, the effect of the increased steric bulk within the Ala-Gly hinge on H-NOX function was investigated. The hinge in Kordia algicida OT-1 ( Ka H-NOX) is composed of A71 and G145. Ligand-binding properties and signaling function for this H-NOX were characterized. The variant A71G was designed to convert the hinge region of Ka H-NOX to the typical Gly-Gly motif. In activity assays with its cognate histidine kinase (HnoK), the wild type displayed increased signal specificity compared to A71G. Increasing titrations of unliganded A71G gradually inhibits HnoK autophosphorylation, while increasing titrations of unliganded wild type H-NOX does not inhibit HnoK. Crystal structures of both wild type and A71G Ka H-NOX were solved to 1.9 and 1.6 Å, respectively. Regions of H-NOX domains previously identified as involved in protein-protein interactions with HnoK display significantly higher b-factors in A71G compared to wild-type H-NOX. Both biochemical and structural data indicate that the hinge region controls overall conformational flexibility of the H-NOX, affecting NO complex formation and regulation of its HnoK.

  17. Minor long-term effects 3-4 years after the ReDO™ intervention for women with stress-related disorders: A focus on sick leave rate, everyday occupations and well-being.

    PubMed

    Eklund, Mona

    2017-01-01

    The Redesigning Daily Occupations (ReDO™) work rehabilitation method has been found effective, compared with care as usual (CAU), for women with stress-related disorders. To conduct a long-term follow-up of former ReDO™ and CAU participants with respect to sick leave, well-being and everyday occupations 3-4 years after completed work rehabilitation. Forty-two women in each group participated. An index day was decided to estimate sick-leave rate, retrieved from register data. Fifty-five women also participated in a telephone interview addressing well-being, everyday occupations and life events. Both groups had reduced their sick-leave rate further, but no difference between the groups was established. The ReDO™ women perceived a better balance in the work domain of everyday occupations, whereas the CAU group reported more over-occupation. No differences were found on well-being. The groups had experienced similar important life events, affecting the women's work and private lives. Previous stress and anxiety predicted sick leave at the long-term follow-up. Although the ReDO™ intervention had speeded up return to work in the immediate follow-up perspective, the CAU had caught up in the longer term. Still, the ReDO™ women exhibited better balance in the work domain.

  18. Personal Decision-Making Criteria Related to Seasonal and Pandemic A(H1N1) Influenza-Vaccination Acceptance among French Healthcare Workers

    PubMed Central

    Bouadma, Lila; Barbier, François; Biard, Lucie; Esposito-Farèse, Marina; Le Corre, Bertrand; Macrez, Annick; Salomon, Laurence; Bonnal, Christine; Zanker, Caroline; Najem, Christophe; Mourvillier, Bruno; Lucet, Jean Christophe; Régnier, Bernard; Wolff, Michel; Tubach, Florence

    2012-01-01

    Background Influenza-vaccination rates among healthcare workers (HCW) remain low worldwide, even during the 2009 A(H1N1) pandemic. In France, this vaccination is free but administered on a voluntary basis. We investigated the factors influencing HCW influenza vaccination. Methods In June–July 2010, HCW from wards of five French hospitals completed a cross-sectional survey. A multifaceted campaign aimed at improving vaccination coverage in this hospital group was conducted before and during the 2009 pandemic. Using an anonymous self-administered questionnaire, we assessed the relationships between seasonal (SIV) and pandemic (PIV) influenza vaccinations, and sociodemographic and professional characteristics, previous and current vaccination statuses, and 33 statements investigating 10 sociocognitive domains. The sociocognitive domains describing HCWs' SIV and PIV profiles were analyzed using the classification-and-regression–tree method. Results Of the HCWs responding to our survey, 1480 were paramedical and 401 were medical with 2009 vaccination rates of 30% and 58% for SIV and 21% and 71% for PIV, respectively (p<0.0001 for both SIV and PIV vaccinations). Older age, prior SIV, working in emergency departments or intensive care units, being a medical HCW and the hospital they worked in were associated with both vaccinations; while work shift was associated only with PIV. Sociocognitive domains associated with both vaccinations were self-perception of benefits and health motivation for all HCW. For medical HCW, being a role model was an additional domain associated with SIV and PIV. Conclusions Both vaccination rates remained low. Vaccination mainly depended on self-determined factors and for medical HCW, being a role model. PMID:22848342

  19. Cognitive work analysis to evaluate the problem of patient falls in an inpatient setting

    PubMed Central

    Lopez, Karen Dunn; Cary, Michael P; Kanak, Mary F

    2010-01-01

    Objective To identify factors in the nursing work domain that contribute to the problem of inpatient falls, aside from patient risk, using cognitive work analysis. Design A mix of qualitative and quantitative methods were used to identify work constraints imposed on nurses, which may underlie patient falls. Measurements Data collection was done on a neurology unit staffed by 27 registered nurses and utilized field observations, focus groups, time–motion studies and written surveys (AHRQ Hospital Survey on Patient Culture, NASA-TLX, and custom Nursing Knowledge of Fall Prevention Subscale). Results Four major constraints were identified that inhibit nurses' ability to prevent patient falls. All constraints relate to work processes and the physical work environment, opposed to safety culture or nursing knowledge, as currently emphasized. The constraints were: cognitive ‘head data’, temporal workload, inconsistencies in written and verbal transfer of patient data, and limitations in the physical environment. To deal with these constraints, the nurses tend to employ four workarounds: written and mental chunking schemas, bed alarms, informal querying of the previous care nurse, and informal video and audio surveillance. These workarounds reflect systemic design flaws and may only be minimally effective in decreasing risk to patients. Conclusion Cognitive engineering techniques helped identify seemingly hidden constraints in the work domain that impact the problem of patient falls. System redesign strategies aimed at improving work processes and environmental limitations hold promise for decreasing the incidence of falls in inpatient nursing units. PMID:20442150

  20. Cognitive work analysis to evaluate the problem of patient falls in an inpatient setting.

    PubMed

    Lopez, Karen Dunn; Gerling, Gregory J; Cary, Michael P; Kanak, Mary F

    2010-01-01

    To identify factors in the nursing work domain that contribute to the problem of inpatient falls, aside from patient risk, using cognitive work analysis. A mix of qualitative and quantitative methods were used to identify work constraints imposed on nurses, which may underlie patient falls. Data collection was done on a neurology unit staffed by 27 registered nurses and utilized field observations, focus groups, time-motion studies and written surveys (AHRQ Hospital Survey on Patient Culture, NASA-TLX, and custom Nursing Knowledge of Fall Prevention Subscale). Four major constraints were identified that inhibit nurses' ability to prevent patient falls. All constraints relate to work processes and the physical work environment, opposed to safety culture or nursing knowledge, as currently emphasized. The constraints were: cognitive 'head data', temporal workload, inconsistencies in written and verbal transfer of patient data, and limitations in the physical environment. To deal with these constraints, the nurses tend to employ four workarounds: written and mental chunking schemas, bed alarms, informal querying of the previous care nurse, and informal video and audio surveillance. These workarounds reflect systemic design flaws and may only be minimally effective in decreasing risk to patients. Cognitive engineering techniques helped identify seemingly hidden constraints in the work domain that impact the problem of patient falls. System redesign strategies aimed at improving work processes and environmental limitations hold promise for decreasing the incidence of falls in inpatient nursing units.

  1. Irrelevant Features of a Stimulus Can Either Facilitate or Disrupt Performance in a Working Memory Task: The Role of Fluid Intelligence

    PubMed Central

    Perfetti, Bernardo; Tesse, Marcello; Varanese, Sara; Saggino, Aristide; Onofrj, Marco

    2011-01-01

    It has been shown that fluid intelligence (gf) is fundamental to overcome interference due to information of a previously encoded item along a task-relevant domain. However, the biasing effect of task-irrelevant dimensions is still unclear as well as its relation with gf. The present study aimed at clarifying these issues. Gf was assessed in 60 healthy subjects. In a different session, the same subjects performed two versions (letter-detection and spatial) of a three-back working memory task with a set of physically identical stimuli (letters) presented at different locations on the screen. In the letter-detection task, volunteers were asked to match stimuli on the basis of their identity whereas, in the spatial task, they were required to match items on their locations. Cross-domain bias was manipulated by pseudorandomly inserting a match between the current and the three back items on the irrelevant domain. Our findings showed that a task-irrelevant feature of a salient stimulus can actually bias the ongoing performance. We revealed that, at trials in which the current and the three-back items matched on the irrelevant domain, group accuracy was lower (interference). On the other hand, at trials in which the two items matched on both the relevant and irrelevant domains, the group showed an enhancement of the performance (facilitation). Furthermore, we demonstrated that individual differences in fluid intelligence covaries with the ability to override cross-domain interference in that higher gf subjects showed better performance at interference trials than low gf subjects. Altogether, our findings suggest that stimulus features irrelevant to the task can affect cognitive performance along the relevant domain and that gf plays an important role in protecting relevant memory contents from the hampering effect of such a bias. PMID:22022580

  2. Enhancement of DNaseI Salt Tolerance by Mimicking the Domain Structure of DNase from an Extremely Halotolerant Bacterium Thioalkalivibrio sp. K90mix

    PubMed Central

    Alzbutas, Gediminas; Kaniusaite, Milda; Lagunavicius, Arunas

    2016-01-01

    In our previous work we showed that DNaseI-like protein from an extremely halotolerant bacterium Thioalkalivibrio sp. K90mix retained its activity at salt concentrations as high as 4 M NaCl and the key factor allowing this was the C-terminal DNA-binding domain, which comprised two HhH (helix-hairpin-helix) motifs. The further investigations revealed that this domain originated from proteins related to bacterial competence ComEA/ComE proteins. It is likely that in the course of evolution the DNA-binding domain from these proteins was fused to a metallo-β-lactamase superfamily domain. Very likely such domain organization having proteins subsequently “donated” the DNA-binding domain to bacterial DNases. In this study we have mimicked this evolutionary step by fusing bovine DNaseI and DNA-binding domains. We have created two fusions: one harboring the DNA-binding domain of DNaseI-like protein from Thioalkalivibrio sp. K90mix and the second one harboring the DNA-binding domain of bacterial competence protein ComEA from Bacillus subtilis. Both domains enhanced salt tolerance of DNaseI, albeit to different extent. Molecular modeling revealed the essential differences between their interaction with DNA shedding some light on the differences in salt tolerance. In this study we have enhanced salt tolerance of bovine DNaseI; thus, we successfully mimicked the Nature’s evolutionary engineering that created the extremely halotolerant bacterial DNase. We have demonstrated that the newly engineered DNaseI variants can be successfully used in applications where activity of the wild type bovine DNaseI is impeded by buffers used. PMID:26939122

  3. Functional Pathways of Social Support for Mental Health in Work and Family Domains Among Chinese Scientific and Technological Professionals.

    PubMed

    Gan, Yiqun; Gan, Tingting; Chen, Zhiyan; Miao, Miao; Zhang, Kan

    2015-10-01

    This study investigated the role of social support in the complex pattern of associations among stressors, work-family interferences and depression in the domains of work and family. A questionnaire was administered to a nationwide sample of 11,419 Chinese science and technology professionals. Several structural equation models were specified to determine whether social support functioned as a predictor or a mediator. Using Mplus 5.0, we compared the moderation model, the independence model, the antecedent model and the mediation model. The results revealed that the relationship between work-family interference and social support was domain specific. The independence model fit the data best in the work domain. Both the moderation model and the antecedent model fit the family domain data equally well. The current study was conducted to answer the need for comprehensive investigations of cultural uniqueness in the antecedents of work-family interference. The domain specificity, i.e. the multiple channels of the functions of support in the family domain and not in the work domain, ensures that this study is unique and culturally specific. Copyright © 2014 John Wiley & Sons, Ltd.

  4. Met expectations and the wellbeing of diaspora immigrants: a longitudinal study.

    PubMed

    Mähönen, Tuuli Anna; Leinonen, Elina; Jasinskaja-Lahti, Inga

    2013-01-01

    Previous research has pointed to the importance of expectations for the adaptation of immigrants. However, most studies have been methodologically retrospective with only limited possibilities to show the optimal relationship between migrants' expectations and actual acculturation experiences for their wellbeing and other aspects of psychological adaptation. Moreover, previous research has been conducted mostly among sojourners and students. This longitudinal study focused on the relationship between premigration expectations and postmigration experiences of diaspora immigrants from Russia to Finland (N = 153). We examined how the fulfillment of premigration expectations in social (i.e., family relations, friendships, and free time) and economic (i.e., occupational position, working conditions, and economic and career situation) domains affects immigrants' wellbeing (i.e., satisfaction with life and general mood) after migration. Three alternative models of expectation confirmation (i.e., disconfirmation model, ideal point model, and the importance of experiences only) derived from previous organizational psychological research were tested with polynomial regression and response surface analysis. In the economic domain, immigrants' expectations, experiences, and their interrelationship did not affect wellbeing in the postmigration stage. However, in the social domain, the more expectations were exceeded by actual experiences, the better were life satisfaction and the general mood of immigrants. The results underline the importance of social relationships and the context-dependent nature of immigrants' wellbeing. Interventions in the preacculturation stage should create positive but realistic expectations for diaspora immigrants and other groups of voluntary (re)migrants. Furthermore, policies concerning the postmigration stage should facilitate the fulfillment of these expectations and support the social adaptation of immigrants.

  5. D Semantic Labeling of ALS Data Based on Domain Adaption by Transferring and Fusing Random Forest Models

    NASA Astrophysics Data System (ADS)

    Wu, J.; Yao, W.; Zhang, J.; Li, Y.

    2018-04-01

    Labeling 3D point cloud data with traditional supervised learning methods requires considerable labelled samples, the collection of which is cost and time expensive. This work focuses on adopting domain adaption concept to transfer existing trained random forest classifiers (based on source domain) to new data scenes (target domain), which aims at reducing the dependence of accurate 3D semantic labeling in point clouds on training samples from the new data scene. Firstly, two random forest classifiers were firstly trained with existing samples previously collected for other data. They were different from each other by using two different decision tree construction algorithms: C4.5 with information gain ratio and CART with Gini index. Secondly, four random forest classifiers adapted to the target domain are derived through transferring each tree in the source random forest models with two types of operations: structure expansion and reduction-SER and structure transfer-STRUT. Finally, points in target domain are labelled by fusing the four newly derived random forest classifiers using weights of evidence based fusion model. To validate our method, experimental analysis was conducted using 3 datasets: one is used as the source domain data (Vaihingen data for 3D Semantic Labelling); another two are used as the target domain data from two cities in China (Jinmen city and Dunhuang city). Overall accuracies of 85.5 % and 83.3 % for 3D labelling were achieved for Jinmen city and Dunhuang city data respectively, with only 1/3 newly labelled samples compared to the cases without domain adaption.

  6. Hydrogeology from 10,000 ft below: lessons learned in applying pulse testing for leakage detection in a carbon sequestration formation

    NASA Astrophysics Data System (ADS)

    Sun, A. Y.; Lu, J.; Hovorka, S. D.; Freifeld, B. M.; Islam, A.

    2015-12-01

    Monitoring techniques capable of deep subsurface detection are desirable for early warning and leakage pathway identification in geologic carbon storage formations. This work investigates the feasibility of a leakage detection technique based on pulse testing, which is a traditional hydrogeological characterization tool. In pulse testing, the monitoring reservoir is stimulated at a fixed frequency and the acquired pressure perturbation signals are analyzed in the frequency domain to detect potential deviations in the reservoir's frequency domain response function. Unlike traditional time-domain analyses, the frequency-domain analysis aims to minimize the interference of reservoir noise by imposing coded injection patterns such that the reservoir responses to injection can be uniquely determined. We have established the theoretical basis of the approach in previous work. Recently, field validation of this pressure-based, leakage detection technique was conducted at a CO2-EOR site located in Mississippi, USA. During the demonstration, two sets of experiments were performed using 90-min and 150-min pulsing periods, for both with and without leak scenarios. Because of the lack of pre-existing leakage pathways, artificial leakage CO2 was simulated by rate-controlled venting from one of the monitoring wells. Our results show that leakage events caused a significant deviation in the amplitude of the frequency response function, indicating that pulse testing may be used as a cost-effective monitoring technique with a strong potential for automation.

  7. Using Cognitive Work Analysis to Fit Decision Support Tools to Nurse Managers’ Work Flow

    PubMed Central

    Brewer, Barbara B.; Logue, Melanie D.; Gephart, Sheila; Verran, Joyce A.

    2011-01-01

    Purpose To better understand the environmental constraints on nurse managers that impact their need for and use of decision support tools, we conducted a Cognitive Work Analysis (CWA). A complete CWA includes system analyses at five levels: work domain, decision-making procedures, decision-making strategies, social organization/collaboration, and worker skill level. Here we describe the results of the Work Domain Analysis (WDA) portion in detail then integrate the WDA with other portions of the CWA, reported previously, to generate a more complete picture of the nurse manager’s work domain. Methods Data for the WDA were obtained from semi-structured interviews with nurse managers, division directors, CNOs, and other managers (n = 20) on 10 patient care units in 3 Arizona hospitals. The WDA described the nurse manager’s environment in terms of the constraints it imposes on the nurse manager’s ability to achieve targeted outcomes through organizational goals and priorities, functions, processes, as well as work objects and resources (e.g., people, equipment, technology, and data). Constraints were identified and summarized through qualitative thematic analysis. Results The results highlight the competing priorities, and external and internal constraints that today’s nurse managers must satisfy as they try to improve quality and safety outcomes on their units. Nurse managers receive a great deal of data, much in electronic format. Although dashboards were perceived as helpful because they integrated some data elements, no decision support tools were available to help nurse managers with planning or answering “what if” questions. The results suggest both the need for additional decision support to manage the growing complexity of the environment, and the constraints the environment places on the design of that technology if it is to be effective. Limitations of the study include the small homogenous sample and the reliance on interview data targeting safety and quality. PMID:21862397

  8. Using Cognitive Work Analysis to fit decision support tools to nurse managers' work flow.

    PubMed

    Effken, Judith A; Brewer, Barbara B; Logue, Melanie D; Gephart, Sheila M; Verran, Joyce A

    2011-10-01

    To better understand the environmental constraints on nurse managers that impact their need for and use of decision support tools, we conducted a Cognitive Work Analysis (CWA). A complete CWA includes system analyses at five levels: work domain, decision-making procedures, decision-making strategies, social organization/collaboration, and worker skill level. Here we describe the results of the Work Domain Analysis (WDA) portion in detail then integrate the WDA with other portions of the CWA, reported previously, to generate a more complete picture of the nurse manager's work domain. Data for the WDA were obtained from semi-structured interviews with nurse managers, division directors, CNOs, and other managers (n = 20) on 10 patient care units in three Arizona hospitals. The WDA described the nurse manager's environment in terms of the constraints it imposes on the nurse manager's ability to achieve targeted outcomes through organizational goals and priorities, functions, processes, as well as work objects and resources (e.g., people, equipment, technology, and data). Constraints were identified and summarized through qualitative thematic analysis. The results highlight the competing priorities, and external and internal constraints that today's nurse managers must satisfy as they try to improve quality and safety outcomes on their units. Nurse managers receive a great deal of data, much in electronic format. Although dashboards were perceived as helpful because they integrated some data elements, no decision support tools were available to help nurse managers with planning or answering "what if" questions. The results suggest both the need for additional decision support to manage the growing complexity of the environment, and the constraints the environment places on the design of that technology if it is to be effective. Limitations of the study include the small homogeneous sample and the reliance on interview data targeting safety and quality. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  9. Automated Scheduling of Personnel to Staff Operations for the Mars Science Laboratory

    NASA Technical Reports Server (NTRS)

    Knight, Russell; Mishkin, Andrew; Allbaugh, Alicia

    2014-01-01

    Leveraging previous work on scheduling personnel for space mission operations, we have adapted ASPEN (Activity Scheduling and Planning Environment) [1] to the domain of scheduling personnel for operations of the Mars Science Laboratory. Automated scheduling of personnel is not new. We compare our representations to a sampling of employee scheduling systems available with respect to desired features. We described the constraints required by MSL personnel schedulers and how each is handled by the scheduling algorithm.

  10. Linking Team Resources to Work-Family Enrichment and Satisfaction

    ERIC Educational Resources Information Center

    Hunter, Emily M.; Perry, Sara Jansen; Carlson, Dawn S.; Smith, Steven A.

    2010-01-01

    Work-family scholars now recognize the potential positive effects of participation in one life domain (i.e., work or family) on performance in other life domains. We examined how employees might benefit from team resources, which are highly relevant to the modern workplace, in both work and nonwork domains via work-family enrichment. Using the…

  11. Optimal vibration control of a rotating plate with self-sensing active constrained layer damping

    NASA Astrophysics Data System (ADS)

    Xie, Zhengchao; Wong, Pak Kin; Lo, Kin Heng

    2012-04-01

    This paper proposes a finite element model for optimally controlled constrained layer damped (CLD) rotating plate with self-sensing technique and frequency-dependent material property in both the time and frequency domain. Constrained layer damping with viscoelastic material can effectively reduce the vibration in rotating structures. However, most existing research models use complex modulus approach to model viscoelastic material, and an additional iterative approach which is only available in frequency domain has to be used to include the material's frequency dependency. It is meaningful to model the viscoelastic damping layer in rotating part by using the anelastic displacement fields (ADF) in order to include the frequency dependency in both the time and frequency domain. Also, unlike previous ones, this finite element model treats all three layers as having the both shear and extension strains, so all types of damping are taken into account. Thus, in this work, a single layer finite element is adopted to model a three-layer active constrained layer damped rotating plate in which the constraining layer is made of piezoelectric material to work as both the self-sensing sensor and actuator under an linear quadratic regulation (LQR) controller. After being compared with verified data, this newly proposed finite element model is validated and could be used for future research.

  12. An iterative sinogram gap-filling method with object- and scanner-dedicated discrete cosine transform (DCT)-domain filters for high resolution PET scanners.

    PubMed

    Kim, Kwangdon; Lee, Kisung; Lee, Hakjae; Joo, Sungkwan; Kang, Jungwon

    2018-01-01

    We aimed to develop a gap-filling algorithm, in particular the filter mask design method of the algorithm, which optimizes the filter to the imaging object by an adaptive and iterative process, rather than by manual means. Two numerical phantoms (Shepp-Logan and Jaszczak) were used for sinogram generation. The algorithm works iteratively, not only on the gap-filling iteration but also on the mask generation, to identify the object-dedicated low frequency area in the DCT-domain that is to be preserved. We redefine the low frequency preserving region of the filter mask at every gap-filling iteration, and the region verges on the property of the original image in the DCT domain. The previous DCT2 mask for each phantom case had been manually well optimized, and the results show little difference from the reference image and sinogram. We observed little or no difference between the results of the manually optimized DCT2 algorithm and those of the proposed algorithm. The proposed algorithm works well for various types of scanning object and shows results that compare to those of the manually optimized DCT2 algorithm without perfect or full information of the imaging object.

  13. Identifying state-level policy and provision domains for physical education and physical activity in high school

    PubMed Central

    2013-01-01

    Background It is important to quickly and efficiently identify policies that are effective at changing behavior; therefore, we must be able to quantify and evaluate the effect of those policies and of changes to those policies. The purpose of this study was to develop state-level physical education (PE) and physical activity (PA) policy domain scores at the high-school level. Policy domain scores were developed with a focus on measuring policy change. Methods Exploratory factor analysis was used to group items from the state-level School Health Policies and Programs Study (SHPPS) into policy domains. Items that related to PA or PE at the High School level were identified from the 7 SHPPS health program surveys. Data from 2000 and 2006 were used in the factor analysis. RESULTS: From the 98 items identified, 17 policy domains were extracted. Average policy domain change scores were positive for 12 policy domains, with the largest increases for “Discouraging PA as Punishment”, “Collaboration”, and “Staff Development Opportunities”. On average, states increased scores in 4.94 ± 2.76 policy domains, decreased in 3.53 ± 2.03, and had no change in 7.69 ± 2.09 policy domains. Significant correlations were found between several policy domain scores. Conclusions Quantifying policy change and its impact is integral to the policy making and revision process. Our results build on previous research offering a way to examine changes in state-level policies related to PE and PA of high-school students and the faculty and staff who serve them. This work provides methods for combining state-level policies relevant to PE or PA in youth for studies of their impact. PMID:23815860

  14. Early predictors of occupational back reinjury: results from a prospective study of workers in Washington State.

    PubMed

    Keeney, Benjamin J; Turner, Judith A; Fulton-Kehoe, Deborah; Wickizer, Thomas M; Chan, Kwun Chuen Gary; Franklin, Gary M

    2013-01-15

    Prospective population-based cohort study. To identify early predictors of self-reported occupational back reinjury within 1 year after work-related back injury. Back injuries are the costliest and most prevalent disabling occupational injuries in the United States. A substantial proportion of workers with back injuries have reinjuries after returning to work, yet there are few studies of risk factors for occupational back reinjuries. We aimed to identify the incidence and early (in the claim) predictors of self-reported back reinjury by approximately 1 year after the index injury among Washington State workers with new work disability claims for back injuries. The Washington Workers' Compensation Disability Risk Identification Study Cohort provided a large, population-based sample with information on variables in 7 domains: sociodemographic, employment-related, pain and function, clinical status, health care, health behavior, and psychological. We conducted telephone interviews with workers 3 weeks and 1 year after submission of a time-loss claim for the injury. We first identified predictors (P < 0.10) of self-reported reinjury within 1 year in bivariate analyses. Those variables were then included in a multivariate logistic regression model predicting occupational back reinjury. A total of 290 (25.8%) of 1123 (70.0% response rate) workers who completed the 1-year follow-up interview and had returned to work reported having reinjured their back at work. Baseline variables significantly associated with reinjury (P < 0.05) in the multivariate model included male sex, constant whole-body vibration at work, previous similar injury, 4 or more previous claims of any type, possessing health insurance, and high fear-avoidance scores. Baseline obesity was associated with reduced odds of reinjury. No other employment-related or psychological variables were significant. One-fourth of the workers who received work disability compensation for a back injury self-reported reinjury after returning to work. Baseline variables in multiple domains predicted occupational back reinjury. Increased knowledge of early risk factors for reinjury may help to lead to interventions, such as efforts to reduce fear avoidance and graded activity to promote recovery, effective in lowering the risk of reinjury.

  15. Prediction of small molecule binding property of protein domains with Bayesian classifiers based on Markov chains.

    PubMed

    Bulashevska, Alla; Stein, Martin; Jackson, David; Eils, Roland

    2009-12-01

    Accurate computational methods that can help to predict biological function of a protein from its sequence are of great interest to research biologists and pharmaceutical companies. One approach to assume the function of proteins is to predict the interactions between proteins and other molecules. In this work, we propose a machine learning method that uses a primary sequence of a domain to predict its propensity for interaction with small molecules. By curating the Pfam database with respect to the small molecule binding ability of its component domains, we have constructed a dataset of small molecule binding and non-binding domains. This dataset was then used as training set to learn a Bayesian classifier, which should distinguish members of each class. The domain sequences of both classes are modelled with Markov chains. In a Jack-knife test, our classification procedure achieved the predictive accuracies of 77.2% and 66.7% for binding and non-binding classes respectively. We demonstrate the applicability of our classifier by using it to identify previously unknown small molecule binding domains. Our predictions are available as supplementary material and can provide very useful information to drug discovery specialists. Given the ubiquitous and essential role small molecules play in biological processes, our method is important for identifying pharmaceutically relevant components of complete proteomes. The software is available from the author upon request.

  16. Time domain multiplexed spatial division multiplexing receiver.

    PubMed

    van Uden, Roy G H; Okonkwo, Chigo M; Chen, Haoshuo; de Waardt, Hugo; Koonen, Antonius M J

    2014-05-19

    A novel time domain multiplexed (TDM) spatial division multiplexing (SDM) receiver which allows for the reception of >1 dual polarization mode with a single coherent receiver, and corresponding 4-port oscilloscope, is experimentally demonstrated. Received by two coherent receivers and respective 4-port oscilloscopes, a 3 mode transmission of 28GBaud QPSK, 8, 16, and 32QAM over 41.7km of few-mode fiber demonstrates the performance of the TDM-SDM receiver with respect to back-to-back. In addition, by using carrier phase estimation employing one digital phase locked loop per output, the frequency offset between the transmitter laser and local oscillator is shown to perform similar to previous work which employs 3 coherent receivers and 4-port oscilloscopes which are dedicated to the reception of each the three modes.

  17. Impasse-driven tutoring for reactive skill acquisition

    NASA Technical Reports Server (NTRS)

    Hill, Randall W., Jr.; Johnson, W. Lewis

    1993-01-01

    We are interested in developing effective performance-oriented training for the operation of systems that are used for monitor and control purposes. We have focused on one such system, the communications Link Monitor and Control (LMC) system used in NASA's Deep Space Network (DSN), which is a worldwide system for navigating, tracking and communicating with unmanned interplanetary spacecraft. The tasks in this domain are procedural in nature and require reactive, goal-oriented skills; we have previously described a cognitive model for problem solving that accounts for both novice and expert levels of behavior as well as how skill is acquired. Our cognitive modeling work in this task domain led us to make a number of predictions about tutoring that have influenced the design of the system described in this paper.

  18. A developmental examination of the conceptual structure of animal, artifact, and human social categories across two cultural contexts

    PubMed Central

    Rhodes, Marjorie; Gelman, Susan A.

    2009-01-01

    Previous research indicates that the ontological status that adults attribute to categories varies systematically by domain. For example, adults view distinctions between different animal species as natural and objective, but view distinctions between different kinds of furniture as more conventionalized and subjective. The present work (N = 435; ages 5-18) examined the effects of domain, age, and cultural context on beliefs about the naturalness vs. conventionality of categories. Results demonstrate that young children, like adults, view animal categories as natural kinds, but artifact categories as more conventionalized. For human social categories (gender and race), beliefs about naturalness and conventionality were predicted by interactions between cultural context and age. Implications for the origins of social categories and theories of conceptual development will be discussed. PMID:19524886

  19. Magnon-induced non-Markovian friction of a domain wall in a ferromagnet

    NASA Astrophysics Data System (ADS)

    Kim, Se Kwon; Tchernyshyov, Oleg; Galitski, Victor; Tserkovnyak, Yaroslav

    2018-05-01

    Motivated by the recent study on the quasiparticle-induced friction of solitons in superfluids, we theoretically study magnon-induced intrinsic friction of a domain wall in a one-dimensional ferromagnet. To this end, we start by obtaining the hitherto overlooked dissipative interaction of a domain wall and its quantum magnon bath to linear order in the domain-wall velocity and to quadratic order in magnon fields. An exact expression for the pertinent scattering matrix is obtained with the aid of supersymmetric quantum mechanics. We then derive the magnon-induced frictional force on a domain wall in two different frameworks: time-dependent perturbation theory in quantum mechanics and the Keldysh formalism, which yield identical results. The latter, in particular, allows us to verify the fluctuation-dissipation theorem explicitly by providing both the frictional force and the correlator of the associated stochastic Langevin force. The potential for magnons induced by a domain wall is reflectionless, and thus the resultant frictional force is non-Markovian similar to the case of solitons in superfluids. They share an intriguing connection to the Abraham-Lorentz force that is well known for its causality paradox. The dynamical responses of a domain wall are studied under a few simple circumstances, where the non-Markovian nature of the frictional force can be probed experimentally. Our work, in conjunction with the previous study on solitons in superfluids, shows that the macroscopic frictional force on solitons can serve as an effective probe of the microscopic degrees of freedom of the system.

  20. Individual Importance Weighting of Domain Satisfaction Ratings does Not Increase Validity

    PubMed Central

    Rohrer, Julia M.; Schmukle, Stefan C.

    2018-01-01

    Bottom-up models of life satisfaction are based on the assumption that individuals judge the overall quality of their lives by aggregating information across various life domains, such as health, family, and income. This aggregation supposedly involves a weighting procedure because individuals care about different parts of their lives to varying degrees. Thus, composite measures of well-being should be more accurate if domain satisfaction scores are weighted by the importance that respondents assign to the respective domains. Previous studies have arrived at mixed conclusions about whether such a procedure actually works. In the present study, importance weighting was investigated in the Panel Study of Income Dynamics (PSID; N = 5,049). Both weighted composite scores and moderated regression analyses converged in producing the conclusion that individual importance weights did not result in higher correlations with the outcome variable, a global measure of life satisfaction. By contrast, using weights that vary normatively across domains (e.g., assigning a larger weight to family satisfaction than to housing satisfaction for all respondents) significantly increased the correlation with global life satisfaction (although incremental validity was rather humble). These results converge with findings from other fields such as self-concept research, where evidence for individual importance weighting seems elusive as best. PMID:29652406

  1. Individual Importance Weighting of Domain Satisfaction Ratings does Not Increase Validity.

    PubMed

    Rohrer, Julia M; Schmukle, Stefan C

    2018-01-01

    Bottom-up models of life satisfaction are based on the assumption that individuals judge the overall quality of their lives by aggregating information across various life domains, such as health, family, and income. This aggregation supposedly involves a weighting procedure because individuals care about different parts of their lives to varying degrees. Thus, composite measures of well-being should be more accurate if domain satisfaction scores are weighted by the importance that respondents assign to the respective domains. Previous studies have arrived at mixed conclusions about whether such a procedure actually works. In the present study, importance weighting was investigated in the Panel Study of Income Dynamics (PSID; N = 5,049). Both weighted composite scores and moderated regression analyses converged in producing the conclusion that individual importance weights did not result in higher correlations with the outcome variable, a global measure of life satisfaction. By contrast, using weights that vary normatively across domains (e.g., assigning a larger weight to family satisfaction than to housing satisfaction for all respondents) significantly increased the correlation with global life satisfaction (although incremental validity was rather humble). These results converge with findings from other fields such as self-concept research, where evidence for individual importance weighting seems elusive as best.

  2. Bisphenol A (BPA) binding on full-length architectures of estrogen receptor.

    PubMed

    Liu, Yaquan; Qu, Kaili; Hai, Ying; Zhao, Chunyan

    2018-08-01

    Previous research has shown that the major toxicity mechanism for many environment chemicals is binding with estrogen receptor (ER) and blocking endogenous estrogen access, including bisphenol A (BPA). However, the molecular level understanding the global consequence of BPA binding on the full-length architectures of ER is largely unknown, which is a necessary stage to evaluate estrogen-like toxicity of BPA. In the present work, the consequence of BPA on full-length architectures of ER was firstly modeled based on molecular dynamics, focusing on the cross communication between multi-domains including ligand binding domain (LBD) and DNA binding domain (DBD). The study proved consequence of BPA upon full-length ER structure was dependent on long-range communications between multiple protein domains. The allosteric effects occurring in LBD units could alter dimerization formation through a crucial change in residue-residue connections, which resulted in relaxation of DBD. It indicated BPA could present consequence on the full-size receptor, not only on the separate domains, but also on the cross communication among LBD, DBD, and DNA molecules. It might provide detailed insight into the knowledge about the structural characteristics of ER and its role in gene regulation, which eventually helped us evaluate the estrogen-like toxicity upon BPA binding with full-length ER. © 2018 Wiley Periodicals, Inc.

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

    PubMed

    Eu, Byung Chan

    2008-09-07

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

  4. The Success of Linear Bootstrapping Models: Decision Domain-, Expertise-, and Criterion-Specific Meta-Analysis

    PubMed Central

    Kaufmann, Esther; Wittmann, Werner W.

    2016-01-01

    The success of bootstrapping or replacing a human judge with a model (e.g., an equation) has been demonstrated in Paul Meehl’s (1954) seminal work and bolstered by the results of several meta-analyses. To date, however, analyses considering different types of meta-analyses as well as the potential dependence of bootstrapping success on the decision domain, the level of expertise of the human judge, and the criterion for what constitutes an accurate decision have been missing from the literature. In this study, we addressed these research gaps by conducting a meta-analysis of lens model studies. We compared the results of a traditional (bare-bones) meta-analysis with findings of a meta-analysis of the success of bootstrap models corrected for various methodological artifacts. In line with previous studies, we found that bootstrapping was more successful than human judgment. Furthermore, bootstrapping was more successful in studies with an objective decision criterion than in studies with subjective or test score criteria. We did not find clear evidence that the success of bootstrapping depended on the decision domain (e.g., education or medicine) or on the judge’s level of expertise (novice or expert). Correction of methodological artifacts increased the estimated success of bootstrapping, suggesting that previous analyses without artifact correction (i.e., traditional meta-analyses) may have underestimated the value of bootstrapping models. PMID:27327085

  5. Comprehensive Binary Interaction Mapping of SH2 Domains via Fluorescence Polarization Reveals Novel Functional Diversification of ErbB Receptors

    PubMed Central

    Ciaccio, Mark F.; Chuu, Chih-pin; Jones, Richard B.

    2012-01-01

    First-generation interaction maps of Src homology 2 (SH2) domains with receptor tyrosine kinase (RTK) phosphosites have previously been generated using protein microarray (PM) technologies. Here, we developed a large-scale fluorescence polarization (FP) methodology that was able to characterize interactions between SH2 domains and ErbB receptor phosphosites with higher fidelity and sensitivity than was previously achieved with PMs. We used the FP assay to query the interaction of synthetic phosphopeptides corresponding to 89 ErbB receptor intracellular tyrosine sites against 93 human SH2 domains and 2 phosphotyrosine binding (PTB) domains. From 358,944 polarization measurements, the affinities for 1,405 unique biological interactions were determined, 83% of which are novel. In contrast to data from previous reports, our analyses suggested that ErbB2 was not more promiscuous than the other ErbB receptors. Our results showed that each receptor displays unique preferences in the affinity and location of recruited SH2 domains that may contribute to differences in downstream signaling potential. ErbB1 was enriched versus the other receptors for recruitment of domains from RAS GEFs whereas ErbB2 was enriched for recruitment of domains from tyrosine and phosphatidyl inositol phosphatases. ErbB3, the kinase inactive ErbB receptor family member, was predictably enriched for recruitment of domains from phosphatidyl inositol kinases and surprisingly, was enriched for recruitment of domains from tyrosine kinases, cytoskeletal regulatory proteins, and RHO GEFs but depleted for recruitment of domains from phosphatidyl inositol phosphatases. Many novel interactions were also observed with phosphopeptides corresponding to ErbB receptor tyrosines not previously reported to be phosphorylated by mass spectrometry, suggesting the existence of many biologically relevant RTK sites that may be phosphorylated but below the detection threshold of standard mass spectrometry procedures. This dataset represents a rich source of testable hypotheses regarding the biological mechanisms of ErbB receptors. PMID:22973453

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

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

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

  7. The Ω-loop lid domain of phosphoenolpyruvate carboxykinase is essential for catalytic function

    PubMed Central

    Johnson, Troy A.; Holyoak, Todd

    2012-01-01

    Phosphoenolpyruvate carboxykinase (PEPCK) is an essential metabolic enzyme operating in the gluconeogenesis and glyceroneogenesis pathways. Recent studies have demonstrated that the enzyme contains a mobile active site lid domain that transitions between an open/disorded conformation to a closed/ordered conformation as the enzyme progresses through the catalytic cycle. The understanding of how this mobile domain functions in catalysis is incomplete. Previous studies show that the closure of the lid domain stabilizes the reaction intermediate and protects the reactive intermediate from spurious protonation and thus contributes to the fidelity of the enzyme. In order to more fully investigate the roles of the lid domain in PEPCK function we created three mutations that replaced the 11-residue lid domain with one, two or three glycine residues. Kinetic analysis of the mutant enzymes demonstrates that none of the enzyme constructs exhibit any measurable kinetic activity resulting in a decrease in the catalytic parameters by at least 106. Structural characterization of the mutants in complexes representing the catalytic cycle suggest that the inactivity is due to a role for the lid domain in the formation of the fully closed state of the enzyme that is required for catalytic function. In the absence of the lid domain, the enzyme is unable to achieve the fully closed state and is rendered inactive despite possessing all of the residues and substrates required for catalytic function. This work demonstrates how enzyme catalytic function can be abolished through the alteration of conformational equilibria despite all elements required for chemical conversion of substrates to products remaining intact. PMID:23127136

  8. Role of CBS and Bateman Domains in Phosphorylation-Dependent Regulation of a CLC Anion Channel.

    PubMed

    Yamada, Toshiki; Krzeminski, Mickael; Bozoky, Zoltan; Forman-Kay, Julie D; Strange, Kevin

    2016-11-01

    Eukaryotic CLC anion channels and transporters are homodimeric proteins composed of multiple α-helical membrane domains and large cytoplasmic C-termini containing two cystathionine-β-synthase domains (CBS1 and CBS2) that dimerize to form a Bateman domain. The Bateman domains of adjacent CLC subunits interact to form a Bateman domain dimer. The functions of CLC CBS and Bateman domains are poorly understood. We utilized the Caenorhabditis elegans CLC-1/2/Ka/Kb anion channel homolog CLH-3b to characterize the regulatory roles of CLC cytoplasmic domains. CLH-3b activity is reduced by phosphorylation or deletion of a 14-amino-acid activation domain (AD) located on the linker connecting CBS1 and CBS2. We demonstrate here that phosphorylation-dependent reductions in channel activity require an intact Bateman domain dimer and concomitant phosphorylation or deletion of both ADs. Regulation of a CLH-3b AD deletion mutant is reconstituted by intracellular perfusion with recombinant 14-amino-acid AD peptides. The sulfhydryl reactive reagent 2-(trimethylammonium)ethyl methanethiosulfonate bromide (MTSET) alters in a phosphorylation-dependent manner the activity of channels containing single cysteine residues that are engineered into the short intracellular loop connecting membrane α-helices H and I (H-I loop), the AD, CBS1, and CBS2. In contrast, MTSET has no effect on channels in which cysteine residues are engineered into intracellular regions that are dispensable for regulation. These studies together with our previous work suggest that binding and unbinding of the AD to the Bateman domain dimer induces conformational changes that are transduced to channel membrane domains via the H-I loop. Our findings provide new, to our knowledge, insights into the roles of CLC Bateman domains and the structure-function relationships that govern the regulation of CLC protein activity by diverse ligands and signaling pathways. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  9. Factor structure of a standards-based inventory of competencies in social work with groups.

    PubMed

    Macgowan, Mark J; Dillon, Frank R; Spadola, Christine E

    2018-01-01

    This study extends previous findings on a measure of competencies based on Standards for Social Work Practice with Groups. The Inventory of Competencies in Social Work with Groups (ICSWG) measures confidence in performing the Standards. This study examines the latent structure of the Inventory, while illuminating the underlying structure of the Standards. A multinational sample of 586 persons completed the ICSWG. Exploratory factor analysis (EFA), reliability estimates, standard error of measurement estimates, and a range of validity tests were conducted. The EFA yielded a six-factor solution consisting of core values, mutuality/connectivity, collaboration, and three phases of group development (planning, beginnings/middles, endings). The alphas were .98 for the scale and ranged from .85 to .95 for the subscales. Correlations between the subscales and validators supported evidence of construct validity. The findings suggest key group work domains that should be taught and practiced in social work with groups.

  10. Work-related stress is associated with impaired neuropsychological test performance: a clinical cross-sectional study.

    PubMed

    Eskildsen, Anita; Andersen, Lars Peter; Pedersen, Anders Degn; Vandborg, Sanne Kjær; Andersen, Johan Hviid

    2015-01-01

    Patients on sick leave due to work-related stress often complain about impaired concentration and memory. However, it is undetermined how widespread these impairments are, and which cognitive domains are most long-term stress sensitive. Previous studies show inconsistent results and are difficult to synthesize. The primary aim of this study was to examine whether patients with work-related stress complaints have cognitive impairments compared to a matched control group without stress. Our secondary aim was to examine whether the level of self-reported perceived stress is associated with neuropsychological test performance. We used a broad neuropsychological test battery to assess 59 outpatients with work-related stress complaints (without major depression) and 59 healthy controls. We matched the patients and controls pairwise by sex, age and educational level. Compared to controls, patients generally showed mildly reduced performance across all the measured domains of the neuropsychological test battery. However, only three comparisons reached statistical significance (p < 0.05). Effect sizes (Cohen's d) were generally small to medium. The most pronounced differences between patients and controls were seen on tests of prospective memory, speed and complex working memory. There were no statistical significant associations between self-reported perceived stress level and neuropsychological test performance. In conclusion, we recommend that cognitive functions should be considered when evaluating patients with work-related stress complaints, especially when given advice regarding return to work. Since this study had a cross-sectional design, it is still uncertain whether the impairments are permanent. Further study is required to establish causal links between work-related stress and cognitive deficits.

  11. Proteolytic processing of lysyl oxidase-like-2 in the extracellular matrix is required for crosslinking of basement membrane collagen IV.

    PubMed

    López-Jiménez, Alberto J; Basak, Trayambak; Vanacore, Roberto M

    2017-10-13

    Lysyl oxidase-like-2 (LOXL2) is an enzyme secreted into the extracellular matrix that crosslinks collagens by mediating oxidative deamination of lysine residues. Our previous work demonstrated that this enzyme crosslinks the 7S domain, a structural domain that stabilizes collagen IV scaffolds in the basement membrane. Despite its relevant role in extracellular matrix biosynthesis, little is known about the structural requirements of LOXL2 that enable collagen IV crosslinking. In this study, we demonstrate that LOXL2 is processed extracellularly by serine proteases, generating a 65-kDa form lacking the first two scavenger receptor cysteine-rich domains. Site-specific mutagenesis to prevent proteolytic processing generated a full-length enzyme that is active in vitro toward a soluble substrate, but fails to crosslink insoluble collagen IV within the extracellular matrix. In contrast, the processed form of LOXL2 binds to collagen IV and crosslinks the 7S domain. Together, our data demonstrate that proteolytic processing is an important event that allows LOXL2-mediated crosslinking of basement membrane collagen IV. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. The formin DAD domain plays dual roles in autoinhibition and actin nucleation

    PubMed Central

    Gould, Christopher J.; Maiti, Sankar; Michelot, Alphée; Graziano, Brian R.; Blanchoin, Laurent; Goode, Bruce L.

    2011-01-01

    Summary Formins are a large family of actin assembly-promoting proteins with many important biological roles [1-3]. However, it has remained unclear how formins nucleate actin polymerization. All other nucleators are known to recruit actin monomers as a central part of their mechanisms [3-5]. However, the actin-nucleating FH2 domain of formins lacks appreciable affinity for monomeric actin [6, 7]. Here, we found that yeast and mammalian formins bind actin monomers, but this activity requires their C-terminal DAD domains. Further, we observed that the DAD works in concert with the FH2 to enhance nucleation without affecting the rate of filament elongation. We dissected this mechanism in mDia1, mapped nucleation activity to conserved residues in the DAD, and demonstrated that DAD roles in nucleation and autoinhibition are separable. Further, DAD enhancement of nucleation was independent of contributions from the FH1 domain to nucleation [8]. Together, our data show that: (i) the DAD has dual functions in autoinhibition and nucleation, (ii) the FH1, FH2 and DAD form a tri-partite nucleation machine, and (iii) formins nucleate by recruiting actin monomers, and therefore are more similar to other nucleators than previously thought. PMID:21333540

  13. SdAb heterodimer formation using leucine zippers

    NASA Astrophysics Data System (ADS)

    Goldman, Ellen R.; Anderson, George P.; Brozozog-Lee, P. Audrey; Zabetakis, Dan

    2013-05-01

    Single domain antibodies (sdAb) are variable domains cloned from camel, llama, or shark heavy chain only antibodies, and are among the smallest known naturally derived antigen binding fragments. SdAb derived from immunized llamas are able to bind antigens with high affinity, and most are capable of refolding after heat or chemical denaturation to bind antigen again. We hypothesized that the ability to produce heterodimeric sdAb would enable reagents with the robust characteristics of component sdAb, but with dramatically improved overall affinity through increased avidity. Previously we had constructed multimeric sdAb by genetically linking sdAb that bind non-overlapping epitopes on the toxin, ricin. In this work we explored a more flexible approach; the construction of multivalent binding reagents using multimerization domains. We expressed anti-ricin sdAb that recognize different epitopes on the toxin as fusions with differently charged leucine zippers. When the initially produced homodimers are mixed the leucine zipper domains will pair to produce heterodimers. We used fluorescence resonance energy transfer to confirm heterodimer formation. Surface plasmon resonance, circular dichroism, enzyme linked immunosorbent assays, and fluid array assays were used to characterize the multimer constructs, and evaluate their utility in toxin detection.

  14. Identification of novel protein domains required for the expression of an active dehydratase fragment from a polyunsaturated fatty acid synthase.

    PubMed

    Oyola-Robles, Delise; Gay, Darren C; Trujillo, Uldaeliz; Sánchez-Parés, John M; Bermúdez, Mei-Ling; Rivera-Díaz, Mónica; Carballeira, Néstor M; Baerga-Ortiz, Abel

    2013-07-01

    Polyunsaturated fatty acids (PUFAs) are made in some strains of deep-sea bacteria by multidomain proteins that catalyze condensation, ketoreduction, dehydration, and enoyl-reduction. In this work, we have used the Udwary-Merski Algorithm sequence analysis tool to define the boundaries that enclose the dehydratase (DH) domains in a PUFA multienzyme. Sequence analysis revealed the presence of four areas of high structure in a region that was previously thought to contain only two DH domains as defined by FabA-homology. The expression of the protein fragment containing all four protein domains resulted in an active enzyme, while shorter protein fragments were not soluble. The tetradomain fragment was capable of catalyzing the conversion of crotonyl-CoA to β-hydroxybutyryl-CoA efficiently, as shown by UV absorbance change as well as by chromatographic retention of reaction products. Sequence alignments showed that the two novel domains contain as much sequence conservation as the FabA-homology domains, suggesting that they too may play a functional role in the overall reaction. Structure predictions revealed that all domains belong to the hotdog protein family: two of them contain the active site His70 residue present in FabA-like DHs, while the remaining two do not. Replacing the active site His residues in both FabA domains for Ala abolished the activity of the tetradomain fragment, indicating that the DH activity is contained within the FabA-homology regions. Taken together, these results provide a first glimpse into a rare arrangement of DH domains which constitute a defining feature of the PUFA synthases. Copyright © 2013 The Protein Society.

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

    PubMed

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

    2005-03-17

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

  16. Identification of novel protein domains required for the expression of an active dehydratase fragment from a polyunsaturated fatty acid synthase

    PubMed Central

    Oyola-Robles, Delise; Gay, Darren C; Trujillo, Uldaeliz; Sánchez-Parés, John M; Bermúdez, Mei-Ling; Rivera-Díaz, Mónica; Carballeira, Néstor M; Baerga-Ortiz, Abel

    2013-01-01

    Polyunsaturated fatty acids (PUFAs) are made in some strains of deep-sea bacteria by multidomain proteins that catalyze condensation, ketoreduction, dehydration, and enoyl-reduction. In this work, we have used the Udwary-Merski Algorithm sequence analysis tool to define the boundaries that enclose the dehydratase (DH) domains in a PUFA multienzyme. Sequence analysis revealed the presence of four areas of high structure in a region that was previously thought to contain only two DH domains as defined by FabA-homology. The expression of the protein fragment containing all four protein domains resulted in an active enzyme, while shorter protein fragments were not soluble. The tetradomain fragment was capable of catalyzing the conversion of crotonyl-CoA to β-hydroxybutyryl-CoA efficiently, as shown by UV absorbance change as well as by chromatographic retention of reaction products. Sequence alignments showed that the two novel domains contain as much sequence conservation as the FabA-homology domains, suggesting that they too may play a functional role in the overall reaction. Structure predictions revealed that all domains belong to the hotdog protein family: two of them contain the active site His70 residue present in FabA-like DHs, while the remaining two do not. Replacing the active site His residues in both FabA domains for Ala abolished the activity of the tetradomain fragment, indicating that the DH activity is contained within the FabA-homology regions. Taken together, these results provide a first glimpse into a rare arrangement of DH domains which constitute a defining feature of the PUFA synthases. PMID:23696301

  17. Absence of post-translational aspartyl beta-hydroxylation of epidermal growth factor domains in mice leads to developmental defects and an increased incidence of intestinal neoplasia.

    PubMed

    Dinchuk, Joseph E; Focht, Richard J; Kelley, Jennifer A; Henderson, Nancy L; Zolotarjova, Nina I; Wynn, Richard; Neff, Nicola T; Link, John; Huber, Reid M; Burn, Timothy C; Rupar, Mark J; Cunningham, Mark R; Selling, Bernard H; Ma, Jianhong; Stern, Andrew A; Hollis, Gregory F; Stein, Robert B; Friedman, Paul A

    2002-04-12

    The BAH genomic locus encodes three distinct proteins: junctin, humbug, and BAH. All three proteins share common exons, but differ significantly based upon the use of alternative terminal exons. The biological roles of BAH and humbug and their functional relationship to junctin remain unclear. To evaluate the role of BAH in vivo, the catalytic domain of BAH was specifically targeted such that the coding regions of junctin and humbug remained undisturbed. BAH null mice lack measurable BAH protein in several tissues, lack aspartyl beta-hydroxylase activity in liver preparations, and exhibit no hydroxylation of the epidermal growth factor (EGF) domain of clotting Factor X. In addition to reduced fertility in females, BAH null mice display several developmental defects including syndactyly, facial dysmorphology, and a mild defect in hard palate formation. The developmental defects present in BAH null mice are similar to defects observed in knock-outs and hypomorphs of the Notch ligand Serrate-2. In this work, beta-hydroxylation of Asp residues in EGF domains is demonstrated for a soluble form of a Notch ligand, human Jagged-1. These results along with recent reports that another post-translational modification of EGF domains in Notch gene family members (glycosylation by Fringe) alters Notch pathway signaling, lends credence to the suggestion that aspartyl beta-hydroxylation may represent another post-translational modification of EGF domains that can modulate Notch pathway signaling. Previous work has demonstrated increased levels of BAH in certain tumor tissues and a role for BAH in tumorigenesis has been proposed. The role of hydroxylase in tumor formation was tested directly by crossing BAH KO mice with an intestinal tumor model, APCmin mice. Surprisingly, BAH null/APCmin mice show a statistically significant increase in both intestinal polyp size and number when compared with BAH wild-type/APCmin controls. These results suggest that, in contrast to expectations, loss of BAH catalytic activity may promote tumor formation.

  18. An N-terminal nuclear localization sequence but not the calmodulin-binding domain mediates nuclear localization of nucleomorphin, a protein that regulates nuclear number in Dictyostelium

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

    Myre, Michael A.; O'Day, Danton H.

    2005-06-24

    Nucleomorphin is a novel nuclear calmodulin (CaM)-binding protein (CaMBP) containing an extensive DEED (glu/asp repeat) domain that regulates nuclear number. GFP-constructs of the 38 kDa NumA1 isoform localize as intranuclear patches adjacent to the inner nuclear membrane. The translocation of CaMBPs into nuclei has previously been shown by others to be mediated by both classic nuclear localization sequences (NLSs) and CaM-binding domains (CaMBDs). Here we show that NumA1 possesses a CaMBD ({sup 171}EDVSRFIKGKLLQKQQKIYKDLERF{sup 195}) containing both calcium-dependent-binding motifs and an IQ-like motif for calcium-independent binding. GFP-constructs containing only NumA1 residues 1-129, lacking the DEED and CaMBDs, still localized as patchesmore » at the internal periphery of nuclei thus ruling out a direct role for the CaMBD in nuclear import. These constructs contained the amino acid residues {sup 48}KKSYQDPEIIAHSRPRK{sup 64} that include both a putative bipartite and classical NLS. GFP-bipartite NLS constructs localized uniformly within nuclei but not as patches. As with previous work, removal of the DEED domain resulted in highly multinucleate cells. However as shown here, multinuclearity only occurred when the NLS was present allowing the protein to enter nuclei. Site-directed mutation analysis in which the NLS was changed to {sup 48}EF{sup 49} abolished the stability of the GFP fusion at the protein but not RNA level preventing subcellular analyses. Cells transfected with the {sup 48}EF{sup 49} construct exhibited slowed growth when compared to parental AX3 cells and other GFP-NumA1 deletion mutants. In addition to identifying an NLS that is sufficient for nuclear translocation of nucleomorphin and ruling out CaM-binding in this event, this work shows that the nuclear localization of NumA1 is crucial to its ability to regulate nuclear number in Dictyostelium.« less

  19. Identifying student mental models from their response pattern to a physics multiple-choice test

    NASA Astrophysics Data System (ADS)

    Montenegro Maggio, Maximiliano Jose

    Previous work has shown that students present different misconceptions across different but similar physical situations, but the cause of these differences is still not clear. In this study, a novel analysis method was introduced to help to gain a better understanding of how different physical situations affect students' responses and learning. This novel analysis groups students into mental model groups (MMG) by similarities in their responses to multiple-choice test items, under the assumption that they have similar mental models. The Mass and Energy Conservation test was developed to probe the common misconception that objects with greater mass fall faster than objects with lesser mass across four physical situations and four knowledge sub-domains: information, dynamics, work, and energy. The test was applied before and after energy instruction to 144 college students in a large Midwestern university attending a calculus-based introductory physics course. Test time along with instruction and physical situation were the two factors. It was found that physical situation did not have a significant effect on mental models: The number of MMGs identified and the fraction of students belonging to the same MMG were not significantly different (p > .05) across physical situations. However, there was a significant effect of test time on mental models (p < .05): the fraction of students belonging to the same MMG changed from the pretest to the posttest, in that the MMG representing higher performance became predominant than the MMG with lower performance for the posttest results. A MANOVA for the average scores for each sub-domain and physical situation combination was applied to validate the previous results. It was found that a significant effect (p < .01) by physical situation resulted due to a lower average dynamics sub-domain score for the friction physical-situation attribute when compared to the no-friction physical-situation attribute. A significant effect (p < .01) was found for test time. This was due to an increase of the average energy sub-domain score from the pretest to the posttest. No significant interaction effect ( p > .05) was found. The MANOVA results obtained can be explained through the change in proportion of the MMGs present in the sample.

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

    ERIC Educational Resources Information Center

    Spilich, George J.; And Others

    1979-01-01

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

  1. Effects of domain knowledge, working memory capacity, and age on cognitive performance: an investigation of the knowledge-is-power hypothesis.

    PubMed

    Hambrick, David Z; Engle, Randall W

    2002-06-01

    Domain knowledge facilitates performance in many cognitive tasks. However, very little is known about the interplay between domain knowledge and factors that are believed to reflect general, and relatively stable, characteristics of the individual. The primary goal of this study was to investigate the interplay between domain knowledge and one such factor: working memory capacity. Adults from wide ranges of working memory capacity, age, and knowledge about the game of baseball listened to, and then answered questions about, simulated radio broadcasts of baseball games. There was a strong facilitative effect of preexisting knowledge of baseball on memory performance, particularly for information judged to be directly relevant to the baseball games. However, there was a positive effect of working memory capacity on memory performance as well, and there was no indication that domain knowledge attenuated this effect. That is, working memory capacity contributed to memory performance even at high levels of domain knowledge. Similarly, there was no evidence that domain knowledge attenuated age-related differences (favoring young adults) in memory performance. We discuss implications of the results for understanding proficiency in cognitive domains from an individual-differences perspective. Copyright 2001 Elsevier Science (USA).

  2. The GreenCut: re-evaluation of physiological role of previously studied proteins and potential novel protein functions.

    PubMed

    Heinnickel, Mark L; Grossman, Arthur R

    2013-10-01

    Based on comparative genomics, a list of proteins present in the green algal, flowering and nonflowering plant lineages, but not detected in nonphotosynthetic organisms, was assembled (Merchant et al., Science 318:245-250, 2007; Karpowicz et al., J Biol Chem 286:21427-21439, 2011). This protein grouping, previously designated the GreenCut, was established using stringent comparative genomic criteria; they are those Chlamydomonas reinhardtii proteins with orthologs in Arabidopsis thaliana, Physcomitrella patens, Oryza sativa, Populus tricocarpa and at least one of the three Ostreococcus species with fully sequenced genomes, but not in bacteria, yeast, fungi or mammals. Many GreenCut proteins are also present in red algae and diatoms and a subset of 189 have been identified as encoded on nearly all cyanobacterial genomes. Of the current GreenCut proteins (597 in total), approximately half have been studied previously. The functions or activities of a number of these proteins have been deduced from phenotypic analyses of mutants (defective for genes encoding specific GreenCut proteins) of A. thaliana, and in many cases the assigned functions do not exist in C. reinhardtii. Therefore, precise physiological functions of several previously studied GreenCut proteins are still not clear. The GreenCut also contains a number of proteins with certain conserved domains. Three of the most highly conserved domains are the FK506 binding, cyclophilin and PAP fibrillin domains; most members of these gene families are not well characterized. In general, our analysis of the GreenCut indicates that many processes critical to green lineage organisms remain unstudied or poorly characterized. We have begun to examine the functions of some GreenCut proteins in detail. For example, our work on the CPLD38 protein has demonstrated that it has an essential role in photosynthetic function and the stability of the cytochrome b 6 f complex.

  3. A STUDY ON TEMPORAL DISTRIBUTION OF FREIGHT TRANSPORTATION IN CONSIDERATION OF DAILY WORK-LIFE CYCLE

    NASA Astrophysics Data System (ADS)

    Kitaoka, Daiki; Hara, Hidetaka; Oeda, Yoshinao; Sumi, Tomonori

    As advanced freight service is demanded, the time related requirements fo r freight transportation becomes more and more significant. This study, focusing on temporal distribution of freight transportation responding to the travel time, developed a shipment departure time decision model for each item, aiming at quantitatively grasping social requirement in the time domain. The model takes account of the daily work cycle of both work cy cles of shippers and carriers along with the travel time. The proposed model has a similar structure as that derived from the previous studies taking account of the daily living cycle of individuals. This model properly reproduced temporal distribution of shipment departure time that changes depending on the length of necessary lead time for each item.

  4. Fluency and belief bias in deductive reasoning: new indices for old effects

    PubMed Central

    Trippas, Dries; Handley, Simon J.; Verde, Michael F.

    2014-01-01

    Models based on signal detection theory (SDT) have occupied a prominent role in domains such as perception, categorization, and memory. Recent work by Dube et al. (2010) suggests that the framework may also offer important insights in the domain of deductive reasoning. Belief bias in reasoning has traditionally been examined using indices based on raw endorsement rates—indices that critics have claimed are highly problematic. We discuss a new set of SDT indices fit for the investigation belief bias and apply them to new data examining the effect of perceptual disfluency on belief bias in syllogisms. In contrast to the traditional approach, the SDT indices do not violate important statistical assumptions, resulting in a decreased Type 1 error rate. Based on analyses using these novel indices we demonstrate that perceptual disfluency leads to decreased reasoning accuracy, contrary to predictions. Disfluency also appears to eliminate the typical link found between cognitive ability and the effect of beliefs on accuracy. Finally, replicating previous work, we demonstrate that cognitive ability leads to an increase in reasoning accuracy and a decrease in the response bias component of belief bias. PMID:25009515

  5. Delphi consensus of an expert committee in oncogeriatrics regarding comprehensive geriatric assessment in seniors with cancer in Spain.

    PubMed

    Molina-Garrido, Maria-Jose; Guillén-Ponce, Carmen; Blanco, Remei; Saldaña, Juana; Feliú, Jaime; Antonio, Maite; López-Mongil, Rosa; Ramos Cordero, Primitivo; Gironés, Regina

    2018-07-01

    The aim of this work was to reach a national consensus in Spain regarding the Comprehensive Geriatric Assessment (CGA) domains in older oncological patients and the CGA scales to be used as a foundation for widespread use. The Delphi method was implemented to attain consensus. Representatives of the panel were chosen from among the members of the Oncogeriatric Working Group of the Spanish Society of Medical Oncology (SEOM). Consensus was defined as ≥66.7% coincidence in responses and by the stability of said coincidence (changes ≤15% between rounds). The study was conducted between July and December 2016. Of the 17 people invited to participate, 16 agreed. The panel concluded by consensus that the following domains should be included in the CGA:(and the scales to evaluate them): functional (Barthel Index, Lawton-Brody scale, gait speed), cognitive (Pfeiffer questionnaire), nutritional (Mini Nutritional Assessment - MNA), psychological/mood (Yesavage scale), social-familial (Gijon scale), comorbidity (Charlson index), medications, and geriatric syndromes (urinary and/or fecal incontinence, low auditory and/or visual acuity, presence of falls, pressure sores, insomnia, and abuse). Also by consensus, the CGA should be administered to older patients with cancer for whom there is a subsequent therapeutic intent and who scored positive on a previous frailty-screening questionnaire. After 3 rounds, consensus was reached regarding CGA domains to be used in older patients with cancer, the scales to be administered for each of these domains, as well as the timeline to be followed during consultation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Characterizing Novel Archaeal Lineages in Salton Sea Sediments

    NASA Astrophysics Data System (ADS)

    Tarn, J.; Valentine, D. L.

    2016-12-01

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

  7. Preliminary Work Domain Analysis for Human Extravehicular Activity

    NASA Technical Reports Server (NTRS)

    McGuire, Kerry; Miller, Matthew; Feigh, Karen

    2015-01-01

    A work domain analysis (WDA) of human extravehicular activity (EVA) is presented in this study. A formative methodology such as Cognitive Work Analysis (CWA) offers a new perspective to the knowledge gained from the past 50 years of living and working in space for the development of future EVA support systems. EVA is a vital component of human spaceflight and provides a case study example of applying a work domain analysis (WDA) to a complex sociotechnical system. The WDA presented here illustrates how the physical characteristics of the environment, hardware, and life support systems of the domain guide the potential avenues and functional needs of future EVA decision support system development.

  8. Pulsed ENDOR Determination of Relative Orientation of g- and Molecular-Frames of Imidazole-Coordinated Heme Center of iNOS

    PubMed Central

    Astashkin, Andrei V.; Fan, Weihong; Elmore, Bradley O.; Guillemette, J. Guy; Feng, Changjian

    2011-01-01

    Mammalian nitric oxide synthase (NOS) is a flavo-hemoprotein that catalyzes the oxidation of L-arginine to nitric oxide. Information about the relative alignment of the heme and FMN domains of NOS is important for understanding the electron transfer between the heme and FMN centers, but no crystal structure data for NOS holoenzyme are available. In our previous work [Astashkin, A. V.; Elmore, B. O.; Fan, W.; Guillemette, J. G.; Feng, C. J. Am. Chem. Soc. 2010, 132, 12059–12067], the distance between the imidazole-coordinated low-spin Fe(III) heme and FMN semiquinone in a human inducible NOS (iNOS) oxygenase/FMN construct has been determined by pulsed electron paramagnetic resonance (EPR). The orientation of the Fe – FMN radius-vector, RFe-FMN, with respect to the heme g-frame was also determined. In the present study, pulsed electron-nuclear double resonance (ENDOR) investigation of the deuterons at carbons C2 and C5 in the deuterated coordinated imidazole was used to determine the relative orientation of the heme g- and molecular frames, from which RFe-FMN can be referenced to the heme molecular frame. Numerical simulations of the ENDOR spectra showed that the g-factor axis corresponding to the low-field EPR turning point is perpendicular to the heme plane, while the axis corresponding to the high-field turning point is in the heme plane and makes an angle of about 80° with the coordinated imidazole plane. The FMN-heme domain docking model obtained in the previous work was found to be in qualitative agreement with the combined experimental results of the two pulsed EPR works. PMID:21834532

  9. [Examination of calibrated item banks for the assessment of work capacity in an outpatient sample of cardiological patients].

    PubMed

    Haschke, A; Abberger, B; Schröder, K; Wirtz, M; Bengel, J; Baumeister, H

    2013-12-01

    Work capacity is a major outcome variable in cardiological rehabilitation. However, there is a lacks of capacious and economic assessment instruments for work capacity. By developing item response theory based item banks a first step to close this gap is done. The present study aims to validate the work capacity item banks for cardiovascular rehabilitation inpatients (WCIB-Cardio) in a sample of cardiovascular rehabilitation outpatients. Additionally, we examined differences between in- and outpatients with regard to their work capacity. Data of 283 cardiovascular rehabilitation inpatients and 77 cardiovascular rehabilitation outpatients were collected in 15 rehabilitation centres. The WCIB-Cardio contains the 2 domains of "cognitive work capacity"(20 items) and "physical work capacity"(18 items). Validation of the item bank for cardiological outpatients was conducted with separate Rasch analysis for each domain. For the domain of cognitive work capacity 10 items showed satisfying quality criteria (Rasch reliability=0.71; overall model fit=0.07). For the domain of physical work capacity good values for Rasch-reliability (0.83) and overall -model fit (0.65) could be proven after exclusion of 3 items. Unidimensionality and a broad ability spectrum could be covered for both domains. With regard to content, outpatients evaluate themselves less burdened than inpatients for the domain of cognitive work capacity (‾X outpatient =-2.06 vs. ‾X inpatient =-2.49; p<0.07) similarly for the domain of physical work capacity (‾X outpatient =-3.68 vs. ‾X inpatient =-2.88; p<0.01). With the WCIB-Cardio II there is a precondition to develop self-report instruments of work capacity in cardiological in- and outpatients. © Georg Thieme Verlag KG Stuttgart · New York.

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

    PubMed Central

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

    2016-01-01

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

  11. A FAST ITERATIVE METHOD FOR SOLVING THE EIKONAL EQUATION ON TETRAHEDRAL DOMAINS

    PubMed Central

    Fu, Zhisong; Kirby, Robert M.; Whitaker, Ross T.

    2014-01-01

    Generating numerical solutions to the eikonal equation and its many variations has a broad range of applications in both the natural and computational sciences. Efficient solvers on cutting-edge, parallel architectures require new algorithms that may not be theoretically optimal, but that are designed to allow asynchronous solution updates and have limited memory access patterns. This paper presents a parallel algorithm for solving the eikonal equation on fully unstructured tetrahedral meshes. The method is appropriate for the type of fine-grained parallelism found on modern massively-SIMD architectures such as graphics processors and takes into account the particular constraints and capabilities of these computing platforms. This work builds on previous work for solving these equations on triangle meshes; in this paper we adapt and extend previous two-dimensional strategies to accommodate three-dimensional, unstructured, tetrahedralized domains. These new developments include a local update strategy with data compaction for tetrahedral meshes that provides solutions on both serial and parallel architectures, with a generalization to inhomogeneous, anisotropic speed functions. We also propose two new update schemes, specialized to mitigate the natural data increase observed when moving to three dimensions, and the data structures necessary for efficiently mapping data to parallel SIMD processors in a way that maintains computational density. Finally, we present descriptions of the implementations for a single CPU, as well as multicore CPUs with shared memory and SIMD architectures, with comparative results against state-of-the-art eikonal solvers. PMID:25221418

  12. Crossover between two- and three-dimensional turbulence in spatial mixing layers

    NASA Astrophysics Data System (ADS)

    Biancofiore, Luca

    2016-11-01

    We investigate how the domain depth affects the turbulent behaviour in spatially developing mixing layers by means of large-eddy simulations (LES) based on a spectral vanishing viscosity technique. Analyses of spectra of the vertical velocity, of Lumley's diagrams, of the turbulent kinetic energy and of the vortex stretching show that a two-dimensional behaviour of the turbulence is promoted in spatial mixing layers by constricting the fluid motion in one direction. This finding is in agreement with previous works on turbulent systems constrained by a geometric anisotropy, pioneered by Smith, Chasnov & Waleffe. We observe that the growth of the momentum thickness along the streamwise direction is damped in a confined domain. A full two-dimensional turbulent behaviour is observed when the momentum thickness is of the same order of magnitude as the confining scale.

  13. Impact of Virtual Work Environment on Traditional Team Domains.

    ERIC Educational Resources Information Center

    Geroy, Gary D.; Olson, Joel; Hartman, Jackie

    2002-01-01

    Examines a virtual work team to determine the domains of the team and the effect the virtual work environment had on the domains. Discusses results of a literature review and a phenomenological heuristic case study, including the effects of post-modern philosophy and postindustrial society on changes in the marketplace. (Contains 79 references.)…

  14. Human-level control through deep reinforcement learning.

    PubMed

    Mnih, Volodymyr; Kavukcuoglu, Koray; Silver, David; Rusu, Andrei A; Veness, Joel; Bellemare, Marc G; Graves, Alex; Riedmiller, Martin; Fidjeland, Andreas K; Ostrovski, Georg; Petersen, Stig; Beattie, Charles; Sadik, Amir; Antonoglou, Ioannis; King, Helen; Kumaran, Dharshan; Wierstra, Daan; Legg, Shane; Hassabis, Demis

    2015-02-26

    The theory of reinforcement learning provides a normative account, deeply rooted in psychological and neuroscientific perspectives on animal behaviour, of how agents may optimize their control of an environment. To use reinforcement learning successfully in situations approaching real-world complexity, however, agents are confronted with a difficult task: they must derive efficient representations of the environment from high-dimensional sensory inputs, and use these to generalize past experience to new situations. Remarkably, humans and other animals seem to solve this problem through a harmonious combination of reinforcement learning and hierarchical sensory processing systems, the former evidenced by a wealth of neural data revealing notable parallels between the phasic signals emitted by dopaminergic neurons and temporal difference reinforcement learning algorithms. While reinforcement learning agents have achieved some successes in a variety of domains, their applicability has previously been limited to domains in which useful features can be handcrafted, or to domains with fully observed, low-dimensional state spaces. Here we use recent advances in training deep neural networks to develop a novel artificial agent, termed a deep Q-network, that can learn successful policies directly from high-dimensional sensory inputs using end-to-end reinforcement learning. We tested this agent on the challenging domain of classic Atari 2600 games. We demonstrate that the deep Q-network agent, receiving only the pixels and the game score as inputs, was able to surpass the performance of all previous algorithms and achieve a level comparable to that of a professional human games tester across a set of 49 games, using the same algorithm, network architecture and hyperparameters. This work bridges the divide between high-dimensional sensory inputs and actions, resulting in the first artificial agent that is capable of learning to excel at a diverse array of challenging tasks.

  15. Human-level control through deep reinforcement learning

    NASA Astrophysics Data System (ADS)

    Mnih, Volodymyr; Kavukcuoglu, Koray; Silver, David; Rusu, Andrei A.; Veness, Joel; Bellemare, Marc G.; Graves, Alex; Riedmiller, Martin; Fidjeland, Andreas K.; Ostrovski, Georg; Petersen, Stig; Beattie, Charles; Sadik, Amir; Antonoglou, Ioannis; King, Helen; Kumaran, Dharshan; Wierstra, Daan; Legg, Shane; Hassabis, Demis

    2015-02-01

    The theory of reinforcement learning provides a normative account, deeply rooted in psychological and neuroscientific perspectives on animal behaviour, of how agents may optimize their control of an environment. To use reinforcement learning successfully in situations approaching real-world complexity, however, agents are confronted with a difficult task: they must derive efficient representations of the environment from high-dimensional sensory inputs, and use these to generalize past experience to new situations. Remarkably, humans and other animals seem to solve this problem through a harmonious combination of reinforcement learning and hierarchical sensory processing systems, the former evidenced by a wealth of neural data revealing notable parallels between the phasic signals emitted by dopaminergic neurons and temporal difference reinforcement learning algorithms. While reinforcement learning agents have achieved some successes in a variety of domains, their applicability has previously been limited to domains in which useful features can be handcrafted, or to domains with fully observed, low-dimensional state spaces. Here we use recent advances in training deep neural networks to develop a novel artificial agent, termed a deep Q-network, that can learn successful policies directly from high-dimensional sensory inputs using end-to-end reinforcement learning. We tested this agent on the challenging domain of classic Atari 2600 games. We demonstrate that the deep Q-network agent, receiving only the pixels and the game score as inputs, was able to surpass the performance of all previous algorithms and achieve a level comparable to that of a professional human games tester across a set of 49 games, using the same algorithm, network architecture and hyperparameters. This work bridges the divide between high-dimensional sensory inputs and actions, resulting in the first artificial agent that is capable of learning to excel at a diverse array of challenging tasks.

  16. The Mental Health Impact of Physical Appearance Concerns in the Context of Other Life Domains Among Australian Gay Men.

    PubMed

    Hosking, Warwick; Lyons, Anthony; van der Rest, Brittany

    2017-07-01

    Previous studies have identified gay men as a high-risk population for body image disturbances. However, little research has examined the mental health impact of gay men's physical appearance concerns in the context of other major life domains. The present study addressed this gap by investigating how mental health outcomes (satisfaction with life, self-esteem, positive well-being, and psychological distress) were associated with satisfaction with and importance of physical appearance, work, family relationships, friendships, health and fitness, and sex life among Australian gay men aged 18-39. The possible moderating role of intimate relationship status was also examined. Results from an online survey revealed that greater satisfaction with physical appearance, work, family, and friendships all had similar positive associations with mental health. However, more importance placed on physical appearance was more consistently associated with poorer mental health compared with the subjective importance of other domains. Findings also indicated the associations between physical appearance satisfaction and life satisfaction, and between physical appearance importance and positive well-being, were weaker for those in relationships. Thus, physical appearance matters in gay men's lives, but was only one factor when considered in the broader context of other life areas that contributed to overall well-being. These findings suggest the need for a nuanced and contextualized understanding of how physical appearance concerns fit into gay men's lives.

  17. Fibromyalgia Syndrome Module at OMERACT 9

    PubMed Central

    Mease, Philip; Arnold, Lesley M; Choy, Ernest H; Clauw, Daniel J.; Crofford, Leslie; Glass, Jennifer M; Martin, Susan A; Morea, Jessica; Simon, Lee; Strand, Vibeke; Williams, David A

    2012-01-01

    Objectives (1) Establish a core domain set for fibromyalgia (FM) assessment in clinical trials and practice, (2) review outcome measures’ performance characteristics, (3) discuss development of a responder index for the assessment of FM in clinical trials, (4) review objective markers, (5) review the domain of cognitive dysfunction, (6) establish a research agenda for work regarding outcomes research. Methods (1) Results of univariate and multivariate analysis of 10 different FM clinical trials of four different drugs, mapping key domains identified in previously presented patient focus group: Delphi exercises and a clinician/researcher Delphi exercise, breakout discussions to vote on possible essential domains and reliable measures. (2) Updates presented regarding outcome measures’ status. (3) Presented update on objective markers to measure FM disease state. 4) The issue of cognitive dysfunction (dyscognition) in FM was reviewed. Results (1) Greater than 70% of OMERACT participants agreed that pain, tenderness, fatigue, patient global, multidimensional function and sleep disturbance domains should be measured in all FM clinical trials, dyscognition and depression in some trial, and domains of research interest include stiffness, anxiety, functional imaging, and cerebrospinal fluid biomarkers. (2) FM domains’ outcome measures have generally proven to be reliable, discriminative, and feasible. More sophisticated and comprehensive measures are in development, as is a responder index for FM. (3) Increasing number of objective markers are being developed for FM assessment. (4) Cognitive dysfunction assessment by self-assessed and applied outcome measures is being developed. Conclusions A multidimensional symptom core set is proposed for the evaluation of FM in clinical trials. There is ongoing research on improved measures of single domains and composite measures. PMID:19820221

  18. Crystal Structure of the Passenger Domain of the Escherichia coli Autotransporter EspP

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

    Khan, Shekeb; Mian, Hira S.; Sandercock, Linda E.

    2013-03-07

    Autotransporters represent a large superfamily of known and putative virulence factors produced by Gram-negative bacteria. They consist of an N-terminal 'passenger domain' responsible for the specific effector functions of the molecule and a C-terminal '{beta}-domain' responsible for translocation of the passenger across the bacterial outer membrane. Here, we present the 2.5-{angstrom} crystal structure of the passenger domain of the extracellular serine protease EspP, produced by the pathogen Escherichia coli O157:H7 and a member of the serine protease autotransporters of Enterobacteriaceae (SPATEs). Like the previously structurally characterized SPATE passenger domains, the EspP passenger domain contains an extended right-handed parallel {beta}-helix precededmore » by an N-terminal globular domain housing the catalytic function of the protease. Of note, however, is the absence of a second globular domain protruding from this {beta}-helix. We describe the structure of the EspP passenger domain in the context of previous results and provide an alternative hypothesis for the function of the {beta}-helix within SPATEs.« less

  19. Crystal Structure of a Two-domain Fragment of Hepatocyte Growth Factor Activator Inhibitor-1: FUNCTIONAL INTERACTIONS BETWEEN THE KUNITZ-TYPE INHIBITOR DOMAIN-1 AND THE NEIGHBORING POLYCYSTIC KIDNEY DISEASE-LIKE DOMAIN.

    PubMed

    Hong, Zebin; De Meulemeester, Laura; Jacobi, Annemarie; Pedersen, Jan Skov; Morth, J Preben; Andreasen, Peter A; Jensen, Jan K

    2016-07-01

    Hepatocyte growth factor activator inhibitor-1 (HAI-1) is a type I transmembrane protein and inhibitor of several serine proteases, including hepatocyte growth factor activator and matriptase. The protein is essential for development as knock-out mice die in utero due to placental defects caused by misregulated extracellular proteolysis. HAI-1 contains two Kunitz-type inhibitor domains (Kunitz), which are generally thought of as a functionally self-contained protease inhibitor unit. This is not the case for HAI-1, where our results reveal how interdomain interactions have evolved to stimulate the inhibitory activity of an integrated Kunitz. Here we present an x-ray crystal structure of an HAI-1 fragment covering the internal domain and Kunitz-1. The structure reveals not only that the previously uncharacterized internal domain is a member of the polycystic kidney disease domain family but also how the two domains engage in interdomain interactions. Supported by solution small angle x-ray scattering and a combination of site-directed mutagenesis and functional assays, we show that interdomain interactions not only stabilize the fold of the internal domain but also stimulate the inhibitory activity of Kunitz-1. By completing our structural characterization of the previously unknown N-terminal region of HAI-1, we provide new insight into the interplay between tertiary structure and the inhibitory activity of a multidomain protease inhibitor. We propose a previously unseen mechanism by which the association of an auxiliary domain stimulates the inhibitory activity of a Kunitz-type inhibitor (i.e. the first structure of an intramolecular interaction between a Kunitz and another domain). © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Search for ultra high energy astrophysical neutrinos with the ANITA experiment

    NASA Astrophysics Data System (ADS)

    Romero-Wolf, Andrew

    2010-12-01

    This work describes a search for cosmogenic neutrinos at energies above 1018 eV with the Antarctic Impulsive Transient Antenna (ANITA). ANITA is a balloon-borne radio interferometer designed to measure radio impulsive emission from particle showers produced in the Antarctic ice-sheet by ultra-high energy neutrinos (UHEnu). Flying at 37 km altitude the ANITA detector is sensitive to 1M km3 of ice and is expected to produce the highest exposure to ultra high energy neutrinos to date. The design, flight performance, and analysis of the first flight of ANITA in 2006 are the subject of this dissertation. Due to sparse anthropogenic backgrounds throughout the Antarctic continent, the ANITA analysis depends on high resolution directional reconstruction. An interferometric method was developed that not only provides high resolution but is also sensitive to very weak radio emissions. The results of ANITA provide the strongest constraints on current ultra-high energy neutrino models. In addition there was a serendipitous observation of ultra-high energy cosmic ray geosynchrotron emissions that are of distinct character from the expected neutrino signal. This thesis includes a study of the radio Cherenkov emission from ultra-high energy electromagnetic showers in ice in the time-domain. All previous simulations computed the radio pulse frequency spectrum. I developed a purely time-domain algorithm for computing radiation using the vector potentials of charged particle tracks. The results are fully consistent with previous frequency domain calculations and shed new light into the properties of the radio pulse in the time domain. The shape of the pulse in the time domain is directly related to the depth development of the excess charge in the shower and its width to the observation angle with respect to the Cherenkov direction. This information can be of great practical importance for interpreting actual data.

  1. Combination Across Domains: An MEG Investigation into the Relationship between Mathematical, Pictorial, and Linguistic Processing

    PubMed Central

    Bemis, Douglas K.; Pylkkänen, Liina

    2013-01-01

    Debates surrounding the evolution of language often hinge upon its relationship to cognition more generally and many investigations have attempted to demark the boundary between the two. Though results from these studies suggest that language may recruit domain-general mechanisms during certain types of complex processing, the domain-generality of basic combinatorial mechanisms that lie at the core of linguistic processing is still unknown. Our previous work (Bemis and Pylkkänen, 2011, 2012) used magnetoencephalography to isolate neural activity associated with the simple composition of an adjective and a noun (“red boat”) and found increased activity during this processing localized to the left anterior temporal lobe (lATL), ventro-medial prefrontal cortex (vmPFC), and left angular gyrus (lAG). The present study explores the domain-generality of these effects and their associated combinatorial mechanisms through two parallel non-linguistic combinatorial tasks designed to be as minimal and natural as the linguistic paradigm. In the first task, we used pictures of colored shapes to elicit combinatorial conceptual processing similar to that evoked by the linguistic expressions and find increased activity again localized to the vmPFC during combinatorial processing. This result suggests that a domain-general semantic combinatorial mechanism operates during basic linguistic composition, and that activity generated by its processing localizes to the vmPFC. In the second task, we recorded neural activity as subjects performed simple addition between two small numerals. Consistent with a wide array of recent results, we find no effects related to basic addition that coincide with our linguistic effects and instead find increased activity localized to the intraparietal sulcus. This result suggests that the scope of the previously identified linguistic effects is restricted to compositional operations and does not extend generally to all tasks that are merely similar in form. PMID:23293621

  2. Compressional reactivation of hyperextended domains on a rifted margin: a requirement for a reappraisal of traditional restoration procedures?

    NASA Astrophysics Data System (ADS)

    Cadenas Martínez, P.; Fernandez Viejo, G.; Pulgar, J. A.

    2017-12-01

    The North Iberian margin is an inverted hyperextended rifted margin that preserves the initial stages of compressional reactivation. Rift inheritance conditioned in a determinant way the contractional reactivation. The underthrusting of the hyperextended distal domains beneath the platform and the formation of an accretionary wedge at the toe of the slope focused most of the compression. The underthrusting gave place to the formation of a crustal root and the uplifting of the Cantabrian Mountains onshore. Meanwhile, the main rift basins within the continental platform were slightly inverted. Plate kinematic reconstructions and palinspatic restorations have provided different shortening values. Thereby, the amount of shortening linked with the Cenozoic compression is still unclear and a matter of debate on this area.In this work, we present a full cross-section at the central part of the North Iberian margin developed from the restoration of a high quality depth migrated seismic profile running from the continental platform to the Biscay abyssal plain. A shortening calculation gives an estimate of about 1 km within the Asturian Basin, in the continental platform, while in the accretionary wedge at the bottom of the slope, shortening values ranges between 12 km and 15 km. The limited values estimated within the Asturian Basin support the mild inversion observed within this basin, which preserves most of the extensional imprint. Within the abyssal plain, shortening values differ from previous estimations and cannot account for a high amount of compression in the upper crust. Deformation of the hyperextended crust and the exhumed mantle domains inherited from the rifting processes would have accommodated most of the compression. Restoration of these domains seems to be the key to decipher the structure and the tectonic evolution of the reactivated rifted margin but cannot be solved accurately using traditional restoration methods. This leads to a reappraisal of the traditional way of restoring compressional belt transects and particularly, when previous hyperextended domains within the rifted margins are involved.

  3. Structure of the SPRY domain of the human RNA helicase DDX1, a putative interaction platform within a DEAD-box protein

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

    Kellner, Julian N.; Meinhart, Anton, E-mail: anton.meinhart@mpimf-heidelberg.mpg.de

    The structure of the SPRY domain of the human RNA helicase DDX1 was determined at 2.0 Å resolution. The SPRY domain provides a putative protein–protein interaction platform within DDX1 that differs from other SPRY domains in its structure and conserved regions. The human RNA helicase DDX1 in the DEAD-box family plays an important role in RNA processing and has been associated with HIV-1 replication and tumour progression. Whereas previously described DEAD-box proteins have a structurally conserved core, DDX1 shows a unique structural feature: a large SPRY-domain insertion in its RecA-like consensus fold. SPRY domains are known to function as protein–proteinmore » interaction platforms. Here, the crystal structure of the SPRY domain of human DDX1 (hDSPRY) is reported at 2.0 Å resolution. The structure reveals two layers of concave, antiparallel β-sheets that stack onto each other and a third β-sheet beneath the β-sandwich. A comparison with SPRY-domain structures from other eukaryotic proteins showed that the general β-sandwich fold is conserved; however, differences were detected in the loop regions, which were identified in other SPRY domains to be essential for interaction with cognate partners. In contrast, in hDSPRY these loop regions are not strictly conserved across species. Interestingly, though, a conserved patch of positive surface charge is found that may replace the connecting loops as a protein–protein interaction surface. The data presented here comprise the first structural information on DDX1 and provide insights into the unique domain architecture of this DEAD-box protein. By providing the structure of a putative interaction domain of DDX1, this work will serve as a basis for further studies of the interaction network within the hetero-oligomeric complexes of DDX1 and of its recruitment to the HIV-1 Rev protein as a viral replication factor.« less

  4. Work domain constraints for modelling surgical performance.

    PubMed

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

    2015-10-01

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

  5. Predictors of life disability in trichotillomania.

    PubMed

    Tung, Esther S; Flessner, Christopher A; Grant, Jon E; Keuthen, Nancy J

    2015-01-01

    Limited research has investigated disability and functional impairment in trichotillomania (TTM) subjects. This study examined the relationships between hair pulling (HP) style and severity and disability while controlling for mood severity. Disability was measured in individual life areas (work, social, and family/home life) instead of as a total disability score as in previous studies. One hundred fifty three adult hair pullers completed several structured interviews and self-report instruments. HP style and severity, as well as depression, anxiety, and stress were correlated with work, social, and family/home life impairment on the Sheehan Disability Scale (SDS). Multiple regression analyses were performed to determine significant predictors of life impairment. Depressive severity was a significant predictor for all SDS life areas. In addition, interference/avoidance associated with HP was a predictor for work and social life disability. Distress from HP was a significant predictor of social and family/home life disability. Focused HP score and anxiety were significant predictors of family/home life disability. As expected, depression in hair pullers predicted disability across life domains. Avoiding work and social situations can seriously impair functioning in those life domains. Severity of distress and worry about HP may be most elevated in social situations with friends and family and thus predict impairment in those areas. Finally, since HP often occurs at home, time spent in focused hair pulling would have a greater negative impact on family and home responsibilities than social and work life. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. A conserved tryptophan within the WRDPLVDID domain of yeast Pah1 phosphatidate phosphatase is required for its in vivo function in lipid metabolism.

    PubMed

    Park, Yeonhee; Han, Gil-Soo; Carman, George M

    2017-12-01

    PAH1 -encoded phosphatidate phosphatase, which catalyzes the dephosphorylation of phosphatidate to produce diacylglycerol at the endoplasmic reticulum membrane, plays a major role in controlling the utilization of phosphatidate for the synthesis of triacylglycerol or membrane phospholipids. The conserved N-LIP and haloacid dehalogenase-like domains of Pah1 are required for phosphatidate phosphatase activity and the in vivo function of the enzyme. Its non-conserved regions, which are located between the conserved domains and at the C terminus, contain sites for phosphorylation by multiple protein kinases. Truncation analyses of the non-conserved regions showed that they are not essential for the catalytic activity of Pah1 and its physiological functions ( e.g. triacylglycerol synthesis). This analysis also revealed that the C-terminal region contains a previously unrecognized WRDPLVDID domain (residues 637-645) that is conserved in yeast, mice, and humans. The deletion of this domain had no effect on the catalytic activity of Pah1 but caused the loss of its in vivo function. Site-specific mutational analyses of the conserved residues within WRDPLVDID indicated that Trp-637 plays a crucial role in Pah1 function. This work also demonstrated that the catalytic activity of Pah1 is required but is not sufficient for its in vivo functions. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Functional specialization in nucleotide sugar transporters occurred through differentiation of the gene cluster EamA (DUF6) before the radiation of Viridiplantae

    PubMed Central

    2011-01-01

    Background The drug/metabolite transporter superfamily comprises a diversity of protein domain families with multiple functions including transport of nucleotide sugars. Drug/metabolite transporter domains are contained in both solute carrier families 30, 35 and 39 proteins as well as in acyl-malonyl condensing enzyme proteins. In this paper, we present an evolutionary analysis of nucleotide sugar transporters in relation to the entire superfamily of drug/metabolite transporters that considers crucial intra-protein duplication events that have shaped the transporters. We use a method that combines the strengths of hidden Markov models and maximum likelihood to find relationships between drug/metabolite transporter families, and branches within families. Results We present evidence that the triose-phosphate transporters, domain unknown function 914, uracil-diphosphate glucose-N-acetylglucosamine, and nucleotide sugar transporter families have evolved from a domain duplication event before the radiation of Viridiplantae in the EamA family (previously called domain unknown function 6). We identify previously unknown branches in the solute carrier 30, 35 and 39 protein families that emerged simultaneously as key physiological developments after the radiation of Viridiplantae, including the "35C/E" branch of EamA, which formed in the lineage of T. adhaerens (Animalia). We identify a second cluster of DMTs, called the domain unknown function 1632 cluster, which has non-cytosolic N- and C-termini, and thus appears to have been formed from a different domain duplication event. We identify a previously uncharacterized motif, G-X(6)-G, which is overrepresented in the fifth transmembrane helix of C-terminal domains. We present evidence that the family called fatty acid elongases are homologous to transporters, not enzymes as had previously been thought. Conclusions The nucleotide sugar transporters families were formed through differentiation of the gene cluster EamA (domain unknown function 6) before Viridiplantae, showing for the first time the significance of EamA. PMID:21569384

  8. Homo-trimerization is essential for the transcription factor function of Myrf for oligodendrocyte differentiation.

    PubMed

    Kim, Dongkyeong; Choi, Jin-Ok; Fan, Chuandong; Shearer, Randall S; Sharif, Mohamed; Busch, Patrick; Park, Yungki

    2017-05-19

    Myrf is a key transcription factor for oligodendrocyte differentiation and central nervous system myelination. We and others have previously shown that Myrf is generated as a membrane protein in the endoplasmic reticulum (ER), and that it undergoes auto-processing to release its N-terminal fragment from the ER, which enters the nucleus to work as a transcription factor. These previous studies allow a glimpse into the unusual complexity behind the biogenesis and function of the transcription factor domain of Myrf. Here, we report that Myrf N-terminal fragments assemble into stable homo-trimers before ER release. Consequently, Myrf N-terminal fragments are released from the ER only as homo-trimers. Our re-analysis of a previous genetic screening result in Caenorhabditis elegans shows that homo-trimerization is essential for the biological functions of Myrf N-terminal fragment, and that the region adjacent to the DNA-binding domain is pivotal to its homo-trimerization. Further, our computational analysis uncovered a novel homo-trimeric DNA motif that mediates the homo-trimeric DNA binding of Myrf N-terminal fragments. Importantly, we found that homo-trimerization defines the DNA binding specificity of Myrf N-terminal fragments. In sum, our study elucidates the molecular mechanism governing the biogenesis and function of Myrf N-terminal fragments and its physiological significance. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. Work and Family Characteristics as Predictors of Early Retirement in Married Men and Women

    PubMed Central

    Kubicek, Bettina; Korunka, Christian; Hoonakker, Peter; Raymo, James M.

    2010-01-01

    This study presents an integrative model of early retirement using data from the Wisconsin Longitudinal Study. The model extends prior work by incorporating work-family conflict to capture the interaction between the work and family domains and by assuming proximal and distal predictors of early retirement. More precisely, the model suggests that family and job demands and resources predict family-to-work and work-to-family conflict, respectively. All of these factors are presumed to have only indirect effects on retirement timing via the intervening effect of quality of life measures, that is, marital satisfaction, job satisfaction and health. The authors assume that these three factors constitute predictors of early retirement in addition to socioeconomic status and the availability of a pension plan and health insurance. The model was tested with structural equation modeling techniques, and the results were supportive. Therefore, the proposed model offers a general framework for the integration of previous research findings. PMID:21430790

  10. Does Domain Knowledge Moderate Involvement of Working Memory Capacity in Higher-Level Cognition? A Test of Three Models

    ERIC Educational Resources Information Center

    Hambrick, D.Z.; Oswald, F.L.

    2005-01-01

    Research suggests that both working memory capacity and domain knowledge contribute to individual differences in higher-level cognition. This study evaluated three hypotheses concerning the interplay between these factors. The compensation hypothesis predicts that domain knowledge attenuates the influence of working memory capacity on higher-level…

  11. Effects of Proactive Interference on Non-Verbal Working Memory

    PubMed Central

    Cyr, Marilyn; Nee, Derek E.; Nelson, Eric; Senger, Thea; Jonides, John; Malapani, Chara

    2016-01-01

    Working memory (WM) is a cognitive system responsible for actively maintaining and processing relevant information and is central to successful cognition. A process critical to WM is the resolution of proactive interference (PI), which involves suppressing memory intrusions from prior memories that are no longer relevant. Most studies that have examined resistance to PI in a process-pure fashion used verbal material. By contrast, studies using non-verbal material are scarce, and it remains unclear whether the effect of PI is domain-general or whether it applies solely to the verbal domain. The aim of the present study was to examine the effect of PI in visual working memory using both objects with high and low nameability. Using a Directed-Forgetting paradigm, we varied discriminability between WM items on two dimensions, one verbal (high-nameability vs. low-nameability objects) and one perceptual (colored vs. gray objects). As in previous studies using verbal material, effects of PI were found with object stimuli, even after controlling for verbal labels being used (i.e., Low-Nameability condition). We also found that the addition of distinctive features (color, verbal label) increased performance in rejecting intrusion probes, most likely through an increase in discriminability between content-context bindings in WM. PMID:27838866

  12. Modality specificity and integration in working memory: Insights from visuospatial bootstrapping.

    PubMed

    Allen, Richard J; Havelka, Jelena; Falcon, Thomas; Evans, Sally; Darling, Stephen

    2015-05-01

    The question of how meaningful associations between verbal and spatial information might be utilized to facilitate working memory performance is potentially highly instructive for models of memory function. The present study explored how separable processing capacities within specialized domains might each contribute to this, by examining the disruptive impacts of simple verbal and spatial concurrent tasks on young adults' recall of visually presented digit sequences encountered either in a single location or within a meaningful spatial "keypad" configuration. The previously observed advantage for recall in the latter condition (the "visuospatial bootstrapping effect") consistently emerged across 3 experiments, indicating use of familiar spatial information in boosting verbal memory. The magnitude of this effect interacted with concurrent activity; articulatory suppression during encoding disrupted recall to a greater extent when digits were presented in single locations (Experiment 1), while spatial tapping during encoding had a larger impact on the keypad condition and abolished the visuospatial bootstrapping advantage (Experiment 2). When spatial tapping was performed during recall (Experiment 3), no task by display interaction was observed. Outcomes are discussed within the context of the multicomponent model of working memory, with a particular emphasis on cross-domain storage in the episodic buffer (Baddeley, 2000). (c) 2015 APA, all rights reserved).

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

    PubMed

    Rusli, Yazmin Ahmad; Montgomery, James W

    2017-10-17

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

  14. Postoperative Perfection: Ceiling Effects and Lack of Discrimination With Both SRS-22 and -24 Outcomes Instruments in Patients With Adolescent Idiopathic Scoliosis.

    PubMed

    Bastrom, Tracey P; Bartley, Carrie; Marks, Michelle C; Yaszay, Burt; Newton, Peter O

    2015-12-01

    Review of a prospective database registry. To compare the Scoliosis Research Society (SRS)-22 and SRS-24 outcomes instruments in terms of scores, rate of ceiling effects, and discriminant ability in patients with pre- and postoperative adolescent idiopathic scoliosis. Despite improvements noted with the SRS-22, the SRS-24 is still occasionally used prospectively and for comparisons with previous studies reporting SRS-24 scores. Previous work has demonstrated that postoperative scores from the 2 versions are not interchangeable. A multicenter prospective registry of patients who underwent surgical correction of adolescent idiopathic scoliosis was queried for preoperative and 2-year postoperative SRS-22 and SRS-24 scores. Scores were compared between versions and ceiling effects were identified. Groups of deformity severity were created to evaluate discriminant ability. 829 patients were identified. The SRS-22 scores for pain and general function were significantly greater than SRS-24 scores (P < 0.001), whereas the SRS-22 scores were significantly lower than the SRS-24 for self-image (P < 0.001). Preoperative ceiling effect was only noted in 1 domain each. Both versions were able to discriminate between large (80°+) and small (<45°) preoperative curves in all domains and total scores (P < 0.05). Postoperatively, the SRS-22 scores for all shared domains and total score were significantly greater than SRS-24 scores (P < 0.001). Ceiling effects in 5 of 5 domain scores were noted postoperatively for SRS-22 and in 4 of 7 for SRS-24. With a smaller range of deformity postoperatively, only the SRS-22 self-image domain was able to discriminate between large (29°+) and small (≤11°) residual curves (P < 0.05). Scores obtained by the SRS-22 and the SRS-24 are not translatable despite shared domains. Whereas both versions demonstrated preoperative discriminant ability, postoperative discrimination of residual deformity is lacking in both. Patient-reported outcomes of treatment are crucial in advancing treatment, and improvement in the ability to assess subjective outcomes is essential. 3.

  15. Intellectual Growth in Children as a Function of Domain Specific and Domain General Working Memory Subgroups

    ERIC Educational Resources Information Center

    Swanson, H. Lee

    2011-01-01

    This study examined whether children's growth on measures of fluid (Raven Colored Progressive Matrices) and crystallized (reading and math achievement) intelligence was attributable to domain-specific or domain-general functions of working memory (WM). A sample of 290 elementary school children was tested on measures of intelligence across three…

  16. Dielectric Study of Alcohols Using Broadband Terahertz Time Domain Spectroscopy (THz-TDS).

    NASA Astrophysics Data System (ADS)

    Sarkar, Sohini; Saha, Debasis; Banerjee, Sneha; Mukherjee, Arnab; Mandal, Pankaj

    2016-06-01

    Broadband Terahertz-Time Domain Spectroscopy (THz-TDS) (1-10 THz) has been utilized to study the complex dielectric properties of methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, and 1-octanol. Previous reports on dielectric study of alcohols were limited to 5 THz. At THz (1 THz = 33.33 wn = 4 meV) frequency range (0.1 to 15 THz), the molecular reorientation and several intermolecular vibrations (local oscillation of dipoles) may coexist and contribute to the overall liquid dynamics. We find that the Debye type relaxations barely contribute beyond 1 THz, rather three harmonic oscillators dominate the entire spectral range. To get insights on the modes responsible for the observed absorption in THz frequency range, we performed all atom molecular dynamics (MD) using OPLS force field and ab initio quantum calculations. Combined experimental and theoretical study reveal that the complex dielectric functions of alcohols have contribution from a) alkyl group oscillation within H-bonded network ( 1 THz), b) intermolecular H-bond stretching ( 5 THz) , and c) librational motions in alcohols. The present work, therefore, complements all previous studies on alcohols at lower frequencies and provides a clear picture on them in a broad spectral range from microwave to 10 THz.

  17. Predicting repeat protein folding kinetics from an experimentally determined folding energy landscape

    PubMed Central

    Street, Timothy O; Barrick, Doug

    2009-01-01

    The Notch ankyrin domain is a repeat protein whose folding has been characterized through equilibrium and kinetic measurements. In previous work, equilibrium folding free energies of truncated constructs were used to generate an experimentally determined folding energy landscape (Mello and Barrick, Proc Natl Acad Sci USA 2004;101:14102–14107). Here, this folding energy landscape is used to parameterize a kinetic model in which local transition probabilities between partly folded states are based on energy values from the landscape. The landscape-based model correctly predicts highly diverse experimentally determined folding kinetics of the Notch ankyrin domain and sequence variants. These predictions include monophasic folding and biphasic unfolding, curvature in the unfolding limb of the chevron plot, population of a transient unfolding intermediate, relative folding rates of 19 variants spanning three orders of magnitude, and a change in the folding pathway that results from C-terminal stabilization. These findings indicate that the folding pathway(s) of the Notch ankyrin domain are thermodynamically selected: the primary determinants of kinetic behavior can be simply deduced from the local stability of individual repeats. PMID:19177351

  18. Predicting chroma from luma with frequency domain intra prediction

    NASA Astrophysics Data System (ADS)

    Egge, Nathan E.; Valin, Jean-Marc

    2015-03-01

    This paper describes a technique for performing intra prediction of the chroma planes based on the reconstructed luma plane in the frequency domain. This prediction exploits the fact that while RGB to YUV color conversion has the property that it decorrelates the color planes globally across an image, there is still some correlation locally at the block level.1 Previous proposals compute a linear model of the spatial relationship between the luma plane (Y) and the two chroma planes (U and V).2 In codecs that use lapped transforms this is not possible since transform support extends across the block boundaries3 and thus neighboring blocks are unavailable during intra- prediction. We design a frequency domain intra predictor for chroma that exploits the same local correlation with lower complexity than the spatial predictor and which works with lapped transforms. We then describe a low- complexity algorithm that directly uses luma coefficients as a chroma predictor based on gain-shape quantization and band partitioning. An experiment is performed that compares these two techniques inside the experimental Daala video codec and shows the lower complexity algorithm to be a better chroma predictor.

  19. Performance Dependences of Multiplication Layer Thickness for InP/InGaAs Avalanche Photodiodes Based on Time Domain Modeling

    NASA Technical Reports Server (NTRS)

    Xiao, Yegao; Bhat, Ishwara; Abedin, M. Nurul

    2005-01-01

    InP/InGaAs avalanche photodiodes (APDs) are being widely utilized in optical receivers for modern long haul and high bit-rate optical fiber communication systems. The separate absorption, grading, charge, and multiplication (SAGCM) structure is an important design consideration for APDs with high performance characteristics. Time domain modeling techniques have been previously developed to provide better understanding and optimize design issues by saving time and cost for the APD research and development. In this work, performance dependences on multiplication layer thickness have been investigated by time domain modeling. These performance characteristics include breakdown field and breakdown voltage, multiplication gain, excess noise factor, frequency response and bandwidth etc. The simulations are performed versus various multiplication layer thicknesses with certain fixed values for the areal charge sheet density whereas the values for the other structure and material parameters are kept unchanged. The frequency response is obtained from the impulse response by fast Fourier transformation. The modeling results are presented and discussed, and design considerations, especially for high speed operation at 10 Gbit/s, are further analyzed.

  20. Physical working conditions as covered in European monitoring questionnaires.

    PubMed

    Tynes, Tore; Aagestad, Cecilie; Thorsen, Sannie Vester; Andersen, Lars Louis; Perkio-Makela, Merja; García, Francisco Javier Pinilla; Blanco, Luz Galiana; Vermeylen, Greet; Parent-Thirion, Agnes; Hooftman, Wendela; Houtman, Irene; Liebers, Falk; Burr, Hermann; Formazin, Maren

    2017-06-05

    The prevalence of workers with demanding physical working conditions in the European work force remains high, and occupational physical exposures are considered important risk factors for musculoskeletal disorders (MSD), a major burden for both workers and society. Exposures to physical workloads are therefore part of the European nationwide surveys to monitor working conditions and health. An interesting question is to what extent the same domains, dimensions and items referring to the physical workloads are covered in the surveys. The purpose of this paper is to determine 1) which domains and dimensions of the physical workloads are monitored in surveys at the national level and the EU level and 2) the degree of European consensus among these surveys regarding coverage of individual domains and dimensions. Items on physical workloads used in one European wide/Spanish and five other European nationwide work environment surveys were classified into the domains and dimensions they cover, using a taxonomy agreed upon among all participating partners. The taxonomy reveals that there is a modest overlap between the domains covered in the surveys, but when considering dimensions, the results indicate a lower agreement. The phrasing of items and answering categories differs between the surveys. Among the domains, the three domains covered by all surveys are "lifting, holding & carrying of loads/pushing & pulling of loads", "awkward body postures" and "vibrations". The three domains covered less well, that is only by three surveys or less, are "physical work effort", "working sitting", and "mixed exposure". This is the fırst thorough overview to evaluate the coverage of domains and dimensions of self-reported physical workloads in a selection of European nationwide surveys. We hope the overview will provide input to the revisions and updates of the individual countries' surveys in order to enhance coverage of relevant domains and dimensions in all surveys and to increase the informational value of the surveys.

  1. Finite Element Analysis of Poroelastic Composites Undergoing Thermal and Gas Diffusion

    NASA Technical Reports Server (NTRS)

    Salamon, N. J. (Principal Investigator); Sullivan, Roy M.; Lee, Sunpyo

    1995-01-01

    A theory for time-dependent thermal and gas diffusion in mechanically time-rate-independent anisotropic poroelastic composites has been developed. This theory advances previous work by the latter two authors by providing for critical transverse shear through a three-dimensional axisymmetric formulation and using it in a new hypothesis for determining the Biot fluid pressure-solid stress coupling factor. The derived governing equations couple material deformation with temperature and internal pore pressure and more strongly couple gas diffusion and heat transfer than the previous theory. Hence the theory accounts for the interactions between conductive heat transfer in the porous body and convective heat carried by the mass flux through the pores. The Bubnov Galerkin finite element method is applied to the governing equations to transform them into a semidiscrete finite element system. A numerical procedure is developed to solve the coupled equations in the space and time domains. The method is used to simulate two high temperature tests involving thermal-chemical decomposition of carbon-phenolic composites. In comparison with measured data, the results are accurate. Moreover unlike previous work, for a single set of poroelastic parameters, they are consistent with two measurements in a restrained thermal growth test.

  2. Paid and unpaid work, and its relation to low back and neck/shoulder disorders among women.

    PubMed

    Josephson, Malin; Ahlberg, Gunnel; Härenstam, Annika; Svensson, Helena; Theorell, Töres; Wiktorin, Christina; Vingård, Eva

    2003-01-01

    The aim of the present study was to estimate the influence of total work hours, paid work in the labor market and unpaid work in the family domain, on care-seeking for low back and neck/shoulder disorders in the female population. The exposure assessments considered a typical working' day during the previous twelve months and were assessed by interviews and questionnaires; 704 cases and 984 referents were examined. The cases had sought professional care during the study period; the referents were randomly selected from the same source population. There was no increased relative risk for care-seeking for low back and neck/shoulder disorders for gainfully employed women compared to those not employed, or for full-time compared to part-time working women. At least 60 hours per week of paid work, or at least 40 hours per week of unpaid work, separately, indicated an increased relative risk for care-seeking. The present results did not strengthen the hypothesis that a high amount of hours of work is an independent risk factor for musculoskeletal disorders.

  3. Crystal Structure of a Two-domain Fragment of Hepatocyte Growth Factor Activator Inhibitor-1

    PubMed Central

    Hong, Zebin; De Meulemeester, Laura; Jacobi, Annemarie; Pedersen, Jan Skov; Morth, J. Preben; Andreasen, Peter A.; Jensen, Jan K.

    2016-01-01

    Hepatocyte growth factor activator inhibitor-1 (HAI-1) is a type I transmembrane protein and inhibitor of several serine proteases, including hepatocyte growth factor activator and matriptase. The protein is essential for development as knock-out mice die in utero due to placental defects caused by misregulated extracellular proteolysis. HAI-1 contains two Kunitz-type inhibitor domains (Kunitz), which are generally thought of as a functionally self-contained protease inhibitor unit. This is not the case for HAI-1, where our results reveal how interdomain interactions have evolved to stimulate the inhibitory activity of an integrated Kunitz. Here we present an x-ray crystal structure of an HAI-1 fragment covering the internal domain and Kunitz-1. The structure reveals not only that the previously uncharacterized internal domain is a member of the polycystic kidney disease domain family but also how the two domains engage in interdomain interactions. Supported by solution small angle x-ray scattering and a combination of site-directed mutagenesis and functional assays, we show that interdomain interactions not only stabilize the fold of the internal domain but also stimulate the inhibitory activity of Kunitz-1. By completing our structural characterization of the previously unknown N-terminal region of HAI-1, we provide new insight into the interplay between tertiary structure and the inhibitory activity of a multidomain protease inhibitor. We propose a previously unseen mechanism by which the association of an auxiliary domain stimulates the inhibitory activity of a Kunitz-type inhibitor (i.e. the first structure of an intramolecular interaction between a Kunitz and another domain). PMID:27189939

  4. Transcriptomic Signature of the SHATTERPROOF2 Expression Domain Reveals the Meristematic Nature of Arabidopsis Gynoecial Medial Domain1[OPEN

    PubMed Central

    Villarino, Gonzalo H.; Hu, Qiwen; Flores-Vergara, Miguel; Sehra, Bhupinder; Brumos, Javier; Stepanova, Anna N.; Sundberg, Eva; Heber, Steffen

    2016-01-01

    Plant meristems, like animal stem cell niches, maintain a pool of multipotent, undifferentiated cells that divide and differentiate to give rise to organs. In Arabidopsis (Arabidopsis thaliana), the carpel margin meristem is a vital meristematic structure that generates ovules from the medial domain of the gynoecium, the female floral reproductive structure. The molecular mechanisms that specify this meristematic region and regulate its organogenic potential are poorly understood. Here, we present a novel approach to analyze the transcriptional signature of the medial domain of the Arabidopsis gynoecium, highlighting the developmental stages that immediately proceed ovule initiation, the earliest stages of seed development. Using a floral synchronization system and a SHATTERPROOF2 (SHP2) domain-specific reporter, paired with FACS and RNA sequencing, we assayed the transcriptome of the gynoecial medial domain with temporal and spatial precision. This analysis reveals a set of genes that are differentially expressed within the SHP2 expression domain, including genes that have been shown previously to function during the development of medial domain-derived structures, including the ovules, thus validating our approach. Global analyses of the transcriptomic data set indicate a similarity of the pSHP2-expressing cell population to previously characterized meristematic domains, further supporting the meristematic nature of this gynoecial tissue. Our method identifies additional genes including novel isoforms, cis-natural antisense transcripts, and a previously unrecognized member of the REPRODUCTIVE MERISTEM family of transcriptional regulators that are potential novel regulators of medial domain development. This data set provides genome-wide transcriptional insight into the development of the carpel margin meristem in Arabidopsis. PMID:26983993

  5. I-domain of lymphocyte function-associated antigen-1 mediates rolling of polystyrene particles on ICAM-1 under flow.

    PubMed

    Eniola, A Omolola; Krasik, Ellen F; Smith, Lee A; Song, Gang; Hammer, Daniel A

    2005-11-01

    In their active state, beta(2)-integrins, such as LFA-1, mediate the firm arrest of leukocytes by binding intercellular adhesion molecules (ICAMs) expressed on endothelium. Although the primary function of LFA-1 is assumed to be the ability to mediate firm adhesion, recent work has shown that LFA-1 can contribute to cell tethering and rolling under hydrodynamic flow, a role previously largely attributed to the selectins. The inserted (I) domain of LFA-1 has recently been crystallized in the wild-type (wt) and locked-open conformations and has been shown to, respectively, support rolling and firm adhesion under flow when expressed in alpha(L)beta(2) heterodimers or as isolated domains on cells. Here, we report results from cell-free adhesion assays where wt I-domain-coated polystyrene particles were allowed to interact with ICAM-1-coated surfaces in shear flow. We show that wt I-domain can independently mediate the capture of particles from flow and support their rolling on ICAM-1 surfaces in a manner similar to how carbohydrate-selectin interactions mediate rolling. Adhesion is specific and blocked by appropriate antibodies. We also show that the rolling velocity of I-domain-coated particles depends on the wall shear stress in flow chamber, I-domain site density on microsphere surfaces, and ICAM-1 site density on substrate surfaces. Furthermore, we show that rolling is less sensitive to wall shear stress and ICAM-1 substrate density at high density of I-domain on the microsphere surface. Computer simulations using adhesive dynamics can recreate bead rolling dynamics and show that the mechanochemical properties of ICAM-1-I-domain interactions are similar to those of carbohydrate-selectin interactions. Understanding the biophysics of adhesion mediated by the I-domain of LFA-1 can elucidate the complex roles this integrin plays in leukocyte adhesion in inflammation.

  6. Visual and spatial working memory are not that dissociated after all: a time-based resource-sharing account.

    PubMed

    Vergauwe, Evie; Barrouillet, Pierre; Camos, Valérie

    2009-07-01

    Examinations of interference between visual and spatial materials in working memory have suggested domain- and process-based fractionations of visuo-spatial working memory. The present study examined the role of central time-based resource sharing in visuo-spatial working memory and assessed its role in obtained interference patterns. Visual and spatial storage were combined with both visual and spatial on-line processing components in computer-paced working memory span tasks (Experiment 1) and in a selective interference paradigm (Experiment 2). The cognitive load of the processing components was manipulated to investigate its impact on concurrent maintenance for both within-domain and between-domain combinations of processing and storage components. In contrast to both domain- and process-based fractionations of visuo-spatial working memory, the results revealed that recall performance was determined by the cognitive load induced by the processing of items, rather than by the domain to which those items pertained. These findings are interpreted as evidence for a time-based resource-sharing mechanism in visuo-spatial working memory.

  7. Early Predictors of Occupational Back Re-Injury: Results from a Prospective Study of Workers in Washington State

    PubMed Central

    Keeney, Benjamin J.; Turner, Judith A.; Fulton-Kehoe, Deborah; Wickizer, Thomas M.; Chan, Kwun Chuen Gary; Franklin, Gary M.

    2014-01-01

    Study Design Prospective population-based cohort study Objective To identify early predictors of self-reported occupational back re-injury within 1 year after work-related back injury Summary of Background Data Back injuries are the costliest and most prevalent disabling occupational injuries in the United States. A substantial proportion of workers with back injuries have re-injuries after returning to work, yet there are few studies of risk factors for occupational back re-injuries. Methods We aimed to identify the incidence and early (in the claim) predictors of self-reported back re-injury by approximately 1 year after the index injury among Washington State workers with new work disability claims for back injuries. The Washington Workers’ Compensation Disability Risk Identification Study Cohort (D-RISC) provided a large, population-based sample with information on variables in seven domains: sociodemographic, employment-related, pain and function, clinical status, health care, health behavior, and psychological. We conducted telephone interviews with workers 3 weeks and 1 year after submission of a time-loss claim for the injury. We first identified predictors (p-values < 0.10) of self-reported re-injury within 1 year in bivariate analyses. Those variables were then included in a multivariate logistic regression model predicting occupational back re-injury. Results 290 (25.8%) of 1,123 (70.0% response rate) workers who completed the one-year follow-up interview and had returned to work reported having re-injured their back at work. Baseline variables significantly associated with re-injury (p-value < 0.05) in the multivariate model included male gender, constant whole body vibration at work, a history of previous similar injury, 4 or more previous claims of any type, possessing health insurance, and high fear-avoidance scores. Baseline obesity was associated with reduced odds of re-injury. No other employment-related or psychological variables were significant. Conclusion One-fourth of workers who received work disability compensation for a back injury self-reported re-injury after returning to work. Baseline variables in multiple domains predicted occupational back re-injury. Increased knowledge of early risk factors for re-injury may help lead to interventions, such as efforts to reduce fear-avoidance and graded activity to promote recovery, effective in lowering the risk of re-injury. PMID:22772568

  8. Racial bias in sport medical staff's perceptions of others' pain.

    PubMed

    Druckman, James N; Trawalter, Sophie; Montes, Ivonne; Fredendall, Alexandria; Kanter, Noah; Rubenstein, Allison Paige

    2017-11-27

    Unequal treatment based on race is well documented in higher education and healthcare settings. In the present work, we examine racial bias at the intersection of these domains: racial bias in pain-related perceptions among National Collegiate Athletic Association (NCAA) Division 1 sport medical staff. Using experimental vignettes about a student-athlete who injured his/her anterior cruciate ligament (ACL), we find, like prior work, that respondents perceived Black (vs. White) targets as having higher initial pain tolerance. Moreover, this bias was mediated by perceptions of social class. We extend prior work by showing racial bias was not evident on other outcome measures, including perception of recovery process pain, likelihood of over-reporting pain, and over-use of drugs to combat pain. This suggests stricter boundary conditions on bias in pain perceptions than had been previously recognized.

  9. How Does Processing Affect Storage in Working Memory Tasks? Evidence for Both Domain-General and Domain-Specific Effects

    ERIC Educational Resources Information Center

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

    2011-01-01

    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.…

  10. Quality of life of coal dust workers without pneumoconiosis in mainland China.

    PubMed

    Yu, Hong-Mei; Ren, Xiao-Wei; Chen, Qian; Zhao, Jing-Yi; Zhu, Ting-Juan; Guo, Zhi-Xi

    2008-01-01

    The purpose of this cross-sectional study was to evaluate the quality of life (QOL) of coal dust workers without pneumoconiosis in mainland China. Three hundred five coal dust workers and 200 non-dust workers without pneumoconiosis from five coal mines in Shanxi province were enrolled in this study. The Chinese World Health Organization Quality of Life-brief version (WHOQOL-BREF) questionnaire was used. Socio-demographic, working, and health factors were also collected. Multiple stepwise regression analysis was used to identify significant factors related to the four domain scores of WHOQOL-BREF. All functional domains of the Chinese WHOQOL-BREF were significantly worse in coal dust workers compared to non-dust workers except for psychological health. For the physical domain of QOL, educational level, working hours, and work danger were the significant factors. In the psychological domain, types of job, welfare satisfaction, work danger, hobbies, smoking, one-child family, and marital status were the predictive factors. Working hours, welfare satisfaction, educational level, and birthplace were the predictive factors for the social domain of QOL. Finally, the predictors for the environmental domain of QOL were types of job, working hours, welfare satisfaction, work danger, self-reported social status, smoking, and drinking. Coal dust workers without pneumoconiosis had worse QOL than non-dust workers but their subjective feelings were positive. There were four distinct models for the various domains of QOL. Corresponding health policies could be developed to improve their QOL.

  11. Structural basis for ligand-dependent dimerization of phenylalanine hydroxylase regulatory domain

    PubMed Central

    Patel, Dipali; Kopec, Jolanta; Fitzpatrick, Fiona; McCorvie, Thomas J.; Yue, Wyatt W.

    2016-01-01

    The multi-domain enzyme phenylalanine hydroxylase (PAH) catalyzes the hydroxylation of dietary I-phenylalanine (Phe) to I-tyrosine. Inherited mutations that result in PAH enzyme deficiency are the genetic cause of the autosomal recessive disorder phenylketonuria. Phe is the substrate for the PAH active site, but also an allosteric ligand that increases enzyme activity. Phe has been proposed to bind, in addition to the catalytic domain, a site at the PAH N-terminal regulatory domain (PAH-RD), to activate the enzyme via an unclear mechanism. Here we report the crystal structure of human PAH-RD bound with Phe at 1.8 Å resolution, revealing a homodimer of ACT folds with Phe bound at the dimer interface. This work delivers the structural evidence to support previous solution studies that a binding site exists in the RD for Phe, and that Phe binding results in dimerization of PAH-RD. Consistent with our structural observation, a disease-associated PAH mutant impaired in Phe binding disrupts the monomer:dimer equilibrium of PAH-RD. Our data therefore support an emerging model of PAH allosteric regulation, whereby Phe binds to PAH-RD and mediates the dimerization of regulatory modules that would bring about conformational changes to activate the enzyme. PMID:27049649

  12. Broad-Enrich: functional interpretation of large sets of broad genomic regions.

    PubMed

    Cavalcante, Raymond G; Lee, Chee; Welch, Ryan P; Patil, Snehal; Weymouth, Terry; Scott, Laura J; Sartor, Maureen A

    2014-09-01

    Functional enrichment testing facilitates the interpretation of Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) data in terms of pathways and other biological contexts. Previous methods developed and used to test for key gene sets affected in ChIP-seq experiments treat peaks as points, and are based on the number of peaks associated with a gene or a binary score for each gene. These approaches work well for transcription factors, but histone modifications often occur over broad domains, and across multiple genes. To incorporate the unique properties of broad domains into functional enrichment testing, we developed Broad-Enrich, a method that uses the proportion of each gene's locus covered by a peak. We show that our method has a well-calibrated false-positive rate, performing well with ChIP-seq data having broad domains compared with alternative approaches. We illustrate Broad-Enrich with 55 ENCODE ChIP-seq datasets using different methods to define gene loci. Broad-Enrich can also be applied to other datasets consisting of broad genomic domains such as copy number variations. http://broad-enrich.med.umich.edu for Web version and R package. Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press.

  13. Not-so-social learning strategies.

    PubMed

    Heyes, Cecilia; Pearce, John M

    2015-03-07

    Social learning strategies (SLSs) are rules specifying the conditions in which it would be adaptive for animals to copy the behaviour of others rather than to persist with a previously established behaviour or to acquire a new behaviour through asocial learning. In behavioural ecology, cultural evolutionary theory and economics, SLSs are studied using a 'phenotypic gambit'-from a purely functional perspective, without reference to their underlying psychological mechanisms. However, SLSs are described in these fields as if they were implemented by complex, domain-specific, genetically inherited mechanisms of decision-making. In this article, we suggest that it is time to begin investigating the psychology of SLSs, and we initiate this process by examining recent experimental work relating to three groups of strategies: copy when alternative unsuccessful, copy when model successful and copy the majority. In each case, we argue that the reported behaviour could have been mediated by domain-general and taxonomically general psychological mechanisms; specifically, by mechanisms, identified through conditioning experiments, that make associative learning selective. We also suggest experimental manipulations that could be used in future research to resolve more fully the question whether, in non-human animals, SLSs are mediated by domain-general or domain-specific psychological mechanisms. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  14. Work-to-Family Conflict, Positive Spillover, and Boundary Management: A Person-Environment Fit Approach

    ERIC Educational Resources Information Center

    Chen, Zheng; Powell, Gary N.; Greenhaus, Jeffrey H.

    2009-01-01

    This study adopted a person-environment fit approach to examine whether greater congruence between employees' preferences for segmenting their work domain from their family domain (i.e., keeping work matters at work) and what their employers' work environment allowed would be associated with lower work-to-family conflict and higher work-to-family…

  15. Simulations of Turbulence in Tokamak Edge and Effects of Self-Consistent Zonal Flows

    NASA Astrophysics Data System (ADS)

    Cohen, Bruce; Umansky, Maxim

    2013-10-01

    Progress is reported on simulations of electromagnetic drift-resistive ballooning turbulence in the tokamak edge. This extends previous work to include self-consistent zonal flows and their effects. The previous work addressed simulation of L-mode tokamak edge turbulence using the turbulence code BOUT that solves Braginskii-based plasma fluid equations in tokamak edge domain. The calculations use realistic single-null geometry and plasma parameters of the DIII-D tokamak and produce fluctuation amplitudes, fluctuation spectra, and particle and thermal fluxes that compare favorably to experimental data. In the effect of sheared ExB poloidal rotation is included with an imposed static radial electric field fitted to experimental data. In the new work here we include the radial electric field self-consistently driven by the microturbulence, which contributes to the sheared ExB poloidal rotation (zonal flow generation). We present simulations with/without zonal flows for both cylindrical geometry, as in the UCLA Large Plasma Device, and for the DIII-D tokamak L-mode cases in to quantify the influence of self-consistent zonal flows on the microturbulence and the concomitant transport. This work was performed under the auspices of the U.S. Department of Energy under contract DE-AC52-07NA27344 at the Lawrence Livermore National Laboratory.

  16. Steady RANS methodology for calculating pressure drop in an in-line molten salt compact crossflow heat exchanger

    DOE PAGES

    Carasik, Lane B.; Shaver, Dillon R.; Haefner, Jonah B.; ...

    2017-08-21

    We report the development of molten salt cooled reactors (MSR) and fluoride-salt cooled high temperature reactors (FHR) requires the use of advanced design tools for the primary heat exchanger design. Due to geometric and flow characteristics, compact (pitch to diameter ratios equal to or less than 1.25) heat exchangers with a crossflow flow arrangement can become desirable for these reactors. Unfortunately, the available experimental data is limited for compact tube bundles or banks in crossflow. Computational Fluid Dynamics can be used to alleviate the lack of experimental data in these tube banks. Previous computational efforts have been primarily focused onmore » large S/D ratios (larger than 1.4) using unsteady Reynolds averaged Navier-Stokes and Large Eddy Simulation frameworks. These approaches are useful, but have large computational requirements that make comprehensive design studies impractical. A CFD study was conducted with steady RANS in an effort to provide a starting point for future design work. The study was performed for an in-line tube bank geometry with FLiBe (LiF-BeF2), a frequently selected molten salt, as the working fluid. Based on the estimated pressure drops, the pressure and velocity distributions in the domain, an appropriate meshing strategy was determined and presented. Periodic boundaries in the spanwise direction transverse flow were determined to be an appropriate boundary condition for reduced computational domains. The domain size was investigated and a minimum of 2-flow channels for a domain is recommended to ensure the behavior is accounted for. Finally, the standard low Re κ-ε (Lien) turbulence model was determined to be the most appropriate for steady RANS of this case at the time of writing.« less

  17. Steady RANS methodology for calculating pressure drop in an in-line molten salt compact crossflow heat exchanger

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

    Carasik, Lane B.; Shaver, Dillon R.; Haefner, Jonah B.

    We report the development of molten salt cooled reactors (MSR) and fluoride-salt cooled high temperature reactors (FHR) requires the use of advanced design tools for the primary heat exchanger design. Due to geometric and flow characteristics, compact (pitch to diameter ratios equal to or less than 1.25) heat exchangers with a crossflow flow arrangement can become desirable for these reactors. Unfortunately, the available experimental data is limited for compact tube bundles or banks in crossflow. Computational Fluid Dynamics can be used to alleviate the lack of experimental data in these tube banks. Previous computational efforts have been primarily focused onmore » large S/D ratios (larger than 1.4) using unsteady Reynolds averaged Navier-Stokes and Large Eddy Simulation frameworks. These approaches are useful, but have large computational requirements that make comprehensive design studies impractical. A CFD study was conducted with steady RANS in an effort to provide a starting point for future design work. The study was performed for an in-line tube bank geometry with FLiBe (LiF-BeF2), a frequently selected molten salt, as the working fluid. Based on the estimated pressure drops, the pressure and velocity distributions in the domain, an appropriate meshing strategy was determined and presented. Periodic boundaries in the spanwise direction transverse flow were determined to be an appropriate boundary condition for reduced computational domains. The domain size was investigated and a minimum of 2-flow channels for a domain is recommended to ensure the behavior is accounted for. Finally, the standard low Re κ-ε (Lien) turbulence model was determined to be the most appropriate for steady RANS of this case at the time of writing.« less

  18. Dynamin1 is a novel target for IRSp53 protein and works with mammalian enabled (Mena) protein and Eps8 to regulate filopodial dynamics.

    PubMed

    Chou, Ai Mei; Sem, Kai Ping; Wright, Graham Daniel; Sudhaharan, Thankiah; Ahmed, Sohail

    2014-08-29

    Filopodia are dynamic actin-based structures that play roles in processes such as cell migration, wound healing, and axonal guidance. Cdc42 induces filopodial formation through IRSp53, an Inverse-Bin-Amphiphysins-Rvs (I-BAR) domain protein. Previous work from a number of laboratories has shown that IRSp53 generates filopodia by coupling membrane protrusion with actin dynamics through its Src homology 3 domain binding partners. Here, we show that dynamin1 (Dyn1), the large guanosine triphosphatase, is an interacting partner of IRSp53 through pulldown and Förster resonance energy transfer analysis, and we explore its role in filopodial formation. In neuroblastoma cells, Dyn1 localizes to filopodia, associated tip complexes, and the leading edge just behind the anti-capping protein mammalian enabled (Mena). Dyn1 knockdown reduces filopodial formation, which can be rescued by overexpressing wild-type Dyn1 but not the GTPase mutant Dyn1-K44A and the loss-of-function actin binding domain mutant Dyn1-K/E. Interestingly, dynasore, an inhibitor of Dyn GTPase, also reduced filopodial number and increased their lifetime. Using rapid time-lapse total internal reflection fluorescence microscopy, we show that Dyn1 and Mena localize to filopodia only during initiation and assembly. Dyn1 actin binding domain mutant inhibits filopodial formation, suggesting a role in actin elongation. In contrast, Eps8, an actin capping protein, is seen most strongly at filopodial tips during disassembly. Taken together, the results suggest IRSp53 partners with Dyn1, Mena, and Eps8 to regulate filopodial dynamics. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Health Concerns of Transgender and Gender Nonconforming Youth and Their Parents Upon Presentation to a Transgender Clinic.

    PubMed

    Lawlis, Shauna M; Donkin, Hillary R; Bates, Justin R; Britto, Maria T; Conard, Lee Ann E

    2017-11-01

    The purpose of the study was to determine the frequency of specific health concerns identified by transgender and gender nonconforming patients and their parents at initial clinic visit. Checklists were developed in an iterative process and distributed to both patients and parents at their initial visit to a transgender clinic. Retrospective chart review and secondary data analyses were performed to determine the number of items endorsed, frequency with which each item was endorsed, and provider domain of each item endorsed: physician, social work, or both physician and social work. Checklists were collected from 118 patients and 103 parents. Patients endorsed a mean of 8.4 concerns (range 0-22) and parents 7.9 concerns (range 0-20). The most commonly endorsed patient concerns included use of gender-affirming hormones, steps for transition, gender-affirming surgery, restroom/dressing room use, and legal issues. Common parent concerns included general resources, child safety at school, acute mental health concerns, restroom/dressing room use, and steps for transition. Of the concerns endorsed by patients, 44% were in the social work domain, 37% in the physician domain, and 19% in both the social work and physician domain. Of the concerns endorsed by parents, 40% were in the social work domain, 31% in the physician domain, and 29% in the social work and physician domain. Although patients and parents had similar numbers of concerns, they primarily focused on different topics. Youth were more interested in hormones and transition, while parents were more interested with transition and acceptance. Many concerns for both patients and parents fell within the social work domain. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

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

    ERIC Educational Resources Information Center

    Rusli, Yazmin Ahmad; Montgomery, James W.

    2017-01-01

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

  1. A General Architecture for Intelligent Tutoring of Diagnostic Classification Problem Solving

    PubMed Central

    Crowley, Rebecca S.; Medvedeva, Olga

    2003-01-01

    We report on a general architecture for creating knowledge-based medical training systems to teach diagnostic classification problem solving. The approach is informed by our previous work describing the development of expertise in classification problem solving in Pathology. The architecture envelops the traditional Intelligent Tutoring System design within the Unified Problem-solving Method description Language (UPML) architecture, supporting component modularity and reuse. Based on the domain ontology, domain task ontology and case data, the abstract problem-solving methods of the expert model create a dynamic solution graph. Student interaction with the solution graph is filtered through an instructional layer, which is created by a second set of abstract problem-solving methods and pedagogic ontologies, in response to the current state of the student model. We outline the advantages and limitations of this general approach, and describe it’s implementation in SlideTutor–a developing Intelligent Tutoring System in Dermatopathology. PMID:14728159

  2. Array of Synchronized Nano-Oscillators Based on Repulsion between Domain Wall and Skyrmion

    NASA Astrophysics Data System (ADS)

    Jin, Chendong; Wang, Jianbo; Wang, Weiwei; Song, Chengkun; Wang, Jinshuai; Xia, Haiyan; Liu, Qingfang

    2018-04-01

    Spin-transfer nano-oscillators (STNOs) are nanosized microwave signal generators based on spin-transfer torque and the magnetoresistance effect. So far, the low output power of STNOs is one of the key restrictive factors. Fabrication and synchronization of a multiple STNO array in one device is a promising way to increase the output power. However, previous studies have shown that only a limited number of STNOs achieve synchronization due to the complex coupling mechanism. In this work, we propose an alternative structure of STNOs based on the repulsion between the domain wall and the Skyrmion. It is found that the frequency tunability of this kind of STNO reaches up to 1.9 GHz. Moreover, we numerically demonstrate that the integrated arrays of STNOs can export synchronous signals, which is promising to potentially increase their total power. Our results provide alternatives for designing of Skyrmion-based devices and further improving the output power of STNOs.

  3. Plan recognition and generalization in command languages with application to telerobotics

    NASA Technical Reports Server (NTRS)

    Yared, Wael I.; Sheridan, Thomas B.

    1991-01-01

    A method for pragmatic inference as a necessary accompaniment to command languages is proposed. The approach taken focuses on the modeling and recognition of the human operator's intent, which relates sequences of domain actions ('plans') to changes in some model of the task environment. The salient feature of this module is that it captures some of the physical and linguistic contextual aspects of an instruction. This provides a basis for generalization and reinterpretation of the instruction in different task environments. The theoretical development is founded on previous work in computational linguistics and some recent models in the theory of action and intention. To illustrate these ideas, an experimental command language to a telerobot is implemented. The program consists of three different components: a robot graphic simulation, the command language itself, and the domain-independent pragmatic inference module. Examples of task instruction processes are provided to demonstrate the benefits of this approach.

  4. Robust Audio Watermarking by Using Low-Frequency Histogram

    NASA Astrophysics Data System (ADS)

    Xiang, Shijun

    In continuation to earlier work where the problem of time-scale modification (TSM) has been studied [1] by modifying the shape of audio time domain histogram, here we consider the additional ingredient of resisting additive noise-like operations, such as Gaussian noise, lossy compression and low-pass filtering. In other words, we study the problem of the watermark against both TSM and additive noises. To this end, in this paper we extract the histogram from a Gaussian-filtered low-frequency component for audio watermarking. The watermark is inserted by shaping the histogram in a way that the use of two consecutive bins as a group is exploited for hiding a bit by reassigning their population. The watermarked signals are perceptibly similar to the original one. Comparing with the previous time-domain watermarking scheme [1], the proposed watermarking method is more robust against additive noise, MP3 compression, low-pass filtering, etc.

  5. Report from the third international consensus meeting to harmonise core outcome measures for atopic eczema/dermatitis clinical trials (HOME)

    PubMed Central

    Chalmers, JR; Schmitt, J; Apfelbacher, C; Dohil, M; Eichenfield, LF; Simpson, EL; Singh, J; Spuls, P; Thomas, KS; Admani, S; Aoki, V; Ardeleanu, M; Barbarot, S; Berger, T; Bergman, JN; Block, J; Borok, N; Burton, T; Chamlin, SL; Deckert, S; DeKlotz, CC; Graff, LB; Hanifin, JM; Hebert, AA; Humphreys, R; Katoh, N; Kisa, RM; Margolis, DJ; Merhand, S; Minnillo, R; Mizutani, H; Nankervis, H; Ohya, Y; Rodgers, P; Schram, ME; Stalder, JF; Svensson, A; Takaoka, R; Teper, A; Tom, WL; von Kobyletzki, L; Weisshaar, E; Zelt, S; Williams, HC

    2014-01-01

    Summary This report provides a summary of the third meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in San Diego, CA, U.S.A., 6–7 April 2013 (HOME III). The meeting addressed the four domains that had previously been agreed should be measured in every eczema clinical trial: clinical signs, patient-reported symptoms, long-term control and quality of life. Formal presentations and nominal group techniques were used at this working meeting, attended by 56 voting participants (31 of whom were dermatologists). Significant progress was made on the domain of clinical signs. Without reference to any named scales, it was agreed that the intensity and extent of erythema, excoriation, oedema/papulation and lichenification should be included in the core outcome measure for the scale to have content validity. The group then discussed a systematic review of all scales measuring the clinical signs of eczema and their measurement properties, followed by a consensus vote on which scale to recommend for inclusion in the core outcome set. Research into the remaining three domains was presented, followed by discussions. The symptoms group and quality of life groups need to systematically identify all available tools and rate the quality of the tools. A definition of long-term control is needed before progress can be made towards recommending a core outcome measure. What's already known about this topic? Many different scales have been used to measure eczema, making it difficult to compare trials in meta-analyses and hampering improvements in clinical practice. HOME core outcome measures must pass the OMERACT (Outcome Measures in Rheumatology) filter of truth (validity), discrimination (sensitivity to change and responsiveness) and feasibility (ease of use, costs, time to perform and interpret). It has been previously agreed as part of the consensus process that four domains should be measured by the core outcomes: clinical signs, patient-reported symptoms, long-term control and health-related quality of life. What does this study add? Progress was made towards developing a core outcome set for measuring eczema in clinical trials. The group established the essential items to be included in the outcome measure for the clinical signs of eczema and was able to recommend a scale for the core set. The remaining three domains of patient-reported symptoms, long-term control and health-related quality of life require further work and meetings to determine the core outcome measures. PMID:24980543

  6. Oxidative stress mediated aldehyde adduction of Grp78 in a mouse model of alcoholic liver disease: Functional independence of ATPase activity and chaperone function

    PubMed Central

    Galligan, James J.; Fritz, Kristofer S.; Backos, Donald S.; Shearn, Colin T.; Smathers, Rebecca L.; Jiang, Hua; MacLean, Kenneth N.; Reigan, Philip R.; Petersen, Dennis R.

    2015-01-01

    Pathogenesis in alcoholic liver disease (ALD) is complicated and multifactorial but clearly involves oxidative stress and inflammation. Currently, conflicting reports exist regarding the role of endoplasmic reticulum (ER) stress in the etiology of ALD. The glucose regulated protein 78 (GRP78) is the ER homologue of HSP70 and plays a critical role in the cellular response to ER stress by serving as a chaperone assisting protein folding and by regulating the signaling of the unfolded protein response (UPR). Comprised of three functional domains, an ATPase, peptide-binding, and lid domain, GRP78 folds nascent polypeptides via the substrate-binding domain. Earlier work has indicated that the ATPase function of GRP78 is intrinsically linked and essential to its chaperone activity. Previous work in our laboratory has indicated that Grp78 and the UPR are not induced in a mouse model of ALD but that Grp78 is adducted by the lipid electrophiles 4-hydroxynonenal (4-HNE) and 4-oxononenal (4-ONE) in vivo. As impairment of Grp78 has the potential to contribute to pathogenesis in ALD, we investigated the functional consequences of aldehyde adduction upon Grp78 function. Identification of 4-HNE and 4-ONE target residues in purified human GRP78 revealed a marked propensity for Lys and His adduction within the ATPase domain and a relative paucity of adduct formation within the peptide-binding domain. Consistent with these findings, we observed a concomitant dose-dependent decrease in ATP-binding and ATPase activity without any discernible impairment of chaperone function. Collectively, our data indicate that ATPase activity is not essential for Grp78 mediated chaperone activity and is consistent with the hypothesis that ER stress does not play a primary initiating role in the early stages of ALD. PMID:24924946

  7. Clostridium perfringens epsilon toxin H149A mutant as a platform for receptor binding studies.

    PubMed

    Bokori-Brown, Monika; Kokkinidou, Maria C; Savva, Christos G; Fernandes da Costa, Sérgio; Naylor, Claire E; Cole, Ambrose R; Moss, David S; Basak, Ajit K; Titball, Richard W

    2013-05-01

    Clostridium perfringens epsilon toxin (Etx) is a pore-forming toxin responsible for a severe and rapidly fatal enterotoxemia of ruminants. The toxin is classified as a category B bioterrorism agent by the U.S. Government Centres for Disease Control and Prevention (CDC), making work with recombinant toxin difficult. To reduce the hazard posed by work with recombinant Etx, we have used a variant of Etx that contains a H149A mutation (Etx-H149A), previously reported to have reduced, but not abolished, toxicity. The three-dimensional structure of H149A prototoxin shows that the H149A mutation in domain III does not affect organisation of the putative receptor binding loops in domain I of the toxin. Surface exposed tyrosine residues in domain I of Etx-H149A (Y16, Y20, Y29, Y30, Y36 and Y196) were mutated to alanine and mutants Y30A and Y196A showed significantly reduced binding to MDCK.2 cells relative to Etx-H149A that correlated with their reduced cytotoxic activity. Thus, our study confirms the role of surface exposed tyrosine residues in domain I of Etx in binding to MDCK cells and the suitability of Etx-H149A for further receptor binding studies. In contrast, binding of all of the tyrosine mutants to ACHN cells was similar to that of Etx-H149A, suggesting that Etx can recognise different cell surface receptors. In support of this, the crystal structure of Etx-H149A identified a glycan (β-octyl-glucoside) binding site in domain III of Etx-H149A, which may be a second receptor binding site. These findings have important implications for developing strategies designed to neutralise toxin activity. Copyright © 2013 The Protein Society.

  8. Structural and Histone Binding Ability Characterizations of Human PWWP Domains

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

    Wu, Hong; Zeng, Hong; Lam, Robert

    2013-09-25

    The PWWP domain was first identified as a structural motif of 100-130 amino acids in the WHSC1 protein and predicted to be a protein-protein interaction domain. It belongs to the Tudor domain 'Royal Family', which consists of Tudor, chromodomain, MBT and PWWP domains. While Tudor, chromodomain and MBT domains have long been known to bind methylated histones, PWWP was shown to exhibit histone binding ability only until recently. The PWWP domain has been shown to be a DNA binding domain, but sequence analysis and previous structural studies show that the PWWP domain exhibits significant similarity to other 'Royal Family' members,more » implying that the PWWP domain has the potential to bind histones. In order to further explore the function of the PWWP domain, we used the protein family approach to determine the crystal structures of the PWWP domains from seven different human proteins. Our fluorescence polarization binding studies show that PWWP domains have weak histone binding ability, which is also confirmed by our NMR titration experiments. Furthermore, we determined the crystal structures of the BRPF1 PWWP domain in complex with H3K36me3, and HDGF2 PWWP domain in complex with H3K79me3 and H4K20me3. PWWP proteins constitute a new family of methyl lysine histone binders. The PWWP domain consists of three motifs: a canonical {beta}-barrel core, an insertion motif between the second and third {beta}-strands and a C-terminal {alpha}-helix bundle. Both the canonical {beta}-barrel core and the insertion motif are directly involved in histone binding. The PWWP domain has been previously shown to be a DNA binding domain. Therefore, the PWWP domain exhibits dual functions: binding both DNA and methyllysine histones.« less

  9. Femtosecond Polarization Phase Selective (PPS) High Magnetic Field Studies of Electron-Spin-Hole (ESH) Dynamics: New Tools for Ultrafast Imaging Fe-centered ESH Transfer Mechanisms Steps

    NASA Astrophysics Data System (ADS)

    Rupnik, Kresimir; Cooper, Benjamin; Dunne, Taylor; Gerosa, Katherine; Mercer, Kaitlyn; McGill, Stephen

    In previous work, new Nanoparticle-enzyme Based Hybrids (NEBH) synthesis methods were investigated for nanoparticles of different shapes and electron energies. These hybrids can provide electromagnetic-field-driven ESH separations and transfers to desired molecular locations. Of paramount biomedical interest are the activity centers (including Fe-clusters) in proteins that perform their intended function and help synthesize other molecules. In this work we discuss results of our recent in situ ESH dynamics measurements: we use <15fs (Vitara) PPS broad band pulses and ultrahigh, 25T, magnetic fields from Split-helix magnet at NHMFL. Work included multi-spectral domain PPS harmonic generations and PPS sum frequency generations. Model compounds, including cytochromes, were used for testing and calibrations and previously studied Fe-S enzymes were prepared for measurements. While PPS opto-magnetic methods are known for their insight into electronic structure, our femtosecond measurements can provide ultrafast dynamic imaging of ESH mechanisms decision making steps. UF-PPS Project, performed in part at NHMFL, supported by NSF CA No. DMR-1157490, and 0654118 and U.S. DOE.

  10. Domain-Specific and Domain-General Learning Factors Are Expressed in Genetically Heterogeneous CD-1 Mice

    ERIC Educational Resources Information Center

    Kolata, Stefan; Light, Kenneth; Matzel, Louis D.

    2008-01-01

    It has been established that both domain-specific (e.g. spatial) as well as domain-general (general intelligence) factors influence human cognition. However, the separation of these processes has rarely been attempted in studies using laboratory animals. Previously, we have found that the performances of outbred mice across a wide range of…

  11. A chirality-based metrics for free-energy calculations in biomolecular systems.

    PubMed

    Pietropaolo, Adriana; Branduardi, Davide; Bonomi, Massimiliano; Parrinello, Michele

    2011-09-01

    In this work, we exploit the chirality index introduced in (Pietropaolo et al., Proteins 2008, 70, 667) as an effective descriptor of the secondary structure of proteins to explore their complex free-energy landscape. We use the chirality index as an alternative metrics in the path collective variables (PCVs) framework and we show in the prototypical case of the C-terminal domain of immunoglobulin binding protein GB1 that relevant configurations can be efficiently sampled in combination with well-tempered metadynamics. While the projections of the configurations found onto a variety of different descriptors are fully consistent with previously reported calculations, this approach provides a unifying perspective of the folding mechanism which was not possible using metadynamics with the previous formulation of PCVs. Copyright © 2011 Wiley Periodicals, Inc.

  12. Identification of the kinase that activates a nonmetazoan STAT gives insights into the evolution of phosphotyrosine-SH2 domain signaling.

    PubMed

    Araki, Tsuyoshi; Kawata, Takefumi; Williams, Jeffrey G

    2012-07-10

    SH2 domains are integral to many animal signaling pathways. By interacting with specific phosphotyrosine residues, they provide regulatable protein-protein interaction domains. Dictyostelium is the only nonmetazoan with functionally characterized SH2 domains, but the cognate tyrosine kinases are unknown. There are no orthologs of the animal tyrosine kinases, but there are very many tyrosine kinase-like kinases (TKLs), a group of kinases which, despite their family name, are classified mainly as serine-threonine kinases. STATs are transcription factors that dimerize via phosphotyrosine-SH2 domain interactions. STATc is activated by phosphorylation on Tyr922 when cells are exposed to the prestalk inducer differentiation inducing factor (DIF-1), a chlorinated hexaphenone. We show that in a null mutant for Pyk2, a tyrosine-specific TKL, exposure to DIF-1 does not activate STATc. Conversely, overexpression of Pyk2 causes constitutive STATc activation. Pyk2 phosphorylates STATc on Tyr922 in vitro and complexes with STATc both in vitro and in vivo. This demonstration that a TKL directly activates a STAT has significant implications for understanding the evolutionary origins of SH2 domain-phosphotyrosine signaling. It also has mechanistic implications. Our previous work suggested that a predicted constitutive STATc tyrosine kinase activity is counterbalanced in vivo by the DIF-1-regulated activity of PTP3, a Tyr922 phosphatase. Here we show that the STATc-Pyk2 complex is formed constitutively by an interaction between the STATc SH2 domain and phosphotyrosine residues on Pyk2 that are generated by autophosphorylation. Also, as predicted, Pyk2 is constitutively active as a STATc kinase. This observation provides further evidence for this highly atypical, possibly ancestral, STAT regulation mechanism.

  13. The Crystal Structure of the Ubiquitin-like Domain of Ribosome Assembly Factor Ytm1 and Characterization of Its Interaction with the AAA-ATPase Midasin*

    PubMed Central

    Romes, Erin M.; Sobhany, Mack; Stanley, Robin E.

    2016-01-01

    The synthesis of eukaryotic ribosomes is a complex, energetically demanding process requiring the aid of numerous non-ribosomal factors, such as the PeBoW complex. The mammalian PeBoW complex, composed of Pes1, Bop1, and WDR12, is essential for the processing of the 32S preribosomal RNA. Previous work in Saccharomyces cerevisiae has shown that release of the homologous proteins in this complex (Nop7, Erb1, and Ytm1, respectively) from preribosomal particles requires Rea1 (midasin or MDN1 in humans), a large dynein-like protein. Midasin contains a C-terminal metal ion-dependent adhesion site (MIDAS) domain that interacts with the N-terminal ubiquitin-like (UBL) domain of Ytm1/WDR12 as well as the UBL domain of Rsa4/Nle1 in a later step in the ribosome maturation pathway. Here we present the crystal structure of the UBL domain of the WDR12 homologue from S. cerevisiae at 1.7 Å resolution and demonstrate that human midasin binds to WDR12 as well as Nle1 through their respective UBL domains. Midasin contains a well conserved extension region upstream of the MIDAS domain required for binding WDR12 and Nle1, and the interaction is dependent upon metal ion coordination because removal of the metal or mutation of residues that coordinate the metal ion diminishes the interaction. Mammalian WDR12 displays prominent nucleolar localization that is dependent upon active ribosomal RNA transcription. Based upon these results, we propose that release of the PeBoW complex and subsequent release of Nle1 by midasin is a well conserved step in the ribosome maturation pathway in both yeast and mammalian cells. PMID:26601951

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

    PubMed

    Buljan, Marija; Frankish, Adam; Bateman, Alex

    2010-01-01

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

  15. OMERACT Endorsement of Patient-reported Outcome Instruments in Antineutrophil Cytoplasmic Antibody–associated Vasculitis

    PubMed Central

    Robson, Joanna C.; Tomasson, Gunnar; Milman, Nataliya; Ashdown, Sue; Boonen, Annelies; Casey, George C.; Cronholm, Peter F.; Cuthbertson, David; Dawson, Jill; Direskeneli, Haner; Easley, Ebony; Kermani, Tanaz A.; Farrar, John T.; Gebhart, Don; Lanier, Georgia; Luqmani, Raashid A.; Mahr, Alfred; McAlear, Carol A.; Peck, Jacqueline; Shea, Beverley; Shea, Judy A.; Sreih, Antoine G.; Tugwell, Peter S.; Merkel, Peter A.

    2018-01-01

    Objective The antineutrophil cytoplasmic antibody–associated vasculitides (AAV) are multiorgan diseases. Patients with AAV report impairment in their health-related quality of life (HRQOL) and have different priorities regarding disease assessment compared with physicians. The Outcome Measures in Rheumatology (OMERACT) Vasculitis Working Group previously received endorsement for a core set of domains in AAV. Two approaches to measure patient-reported outcomes (PRO) were presented at OMERACT 2016. Methods A novel 5-step tool was used to facilitate assessment of the instruments by delegates: the OMERACT Filter 2.0 Instrument Selection Algorithm, with a red-amber-green checklist of questions, including (1) good match with domain (face and content validity), (2) feasibility, (3) do numeric scores make sense (construct validity)?, (4) overall ratings of discrimination, and (5) can individual thresholds of meaning be defined? Delegates gave an overall endorsement. Three generic Patient-Reported Outcomes Measurement Information System (PROMIS) instruments (fatigue, physical functioning, and pain interference) and a disease-specific PRO, the AAV-PRO (6 domains related to symptoms and HRQOL), were presented. Results OMERACT delegates endorsed the use of the PROMIS instruments for fatigue, physical functioning, and pain interference (87.6% overall endorsement) and the disease-specific AAV-PRO instrument (89.4% overall endorsement). Conclusion The OMERACT Vasculitis Working Group gained endorsement by OMERACT for use of the PROMIS and the AAV-PRO in clinical trials of vasculitis. These instruments are complementary to each other. The PROMIS and the AAV-PRO need further work to assess their utility in longitudinal settings, including their ability to discriminate between treatments of varying efficacy in the setting of a randomized controlled trial. PMID:28864650

  16. Evidenced-Based Cognitive Rehabilitation for Persons With Multiple Sclerosis: An Updated Review of the Literature From 2007 to 2016.

    PubMed

    Goverover, Yael; Chiaravalloti, Nancy D; O'Brien, Amanda R; DeLuca, John

    2018-02-01

    To update the clinical recommendations for cognitive rehabilitation of people with multiple sclerosis (MS), based on a systematic review of the literature from 2007 through 2016. Searches of MEDLINE, PsycINFO, and CINAHL were conducted with a combination of the following terms: attention, awareness, cognition, cognitive, communication, executive, executive function, language, learning, memory, perception, problem solving, reasoning, rehabilitation, remediation, training, processing speed, and working memory. One hundred twenty-nine articles were identified and underwent initial screening. Fifty-nine articles were selected for inclusion after initial screening. Nineteen studies were excluded after further detailed review. Forty studies were fully reviewed and evaluated. Articles were assigned to 1 of 6 categories: attention, learning and memory, processing speed and working memory, executive functioning, metacognition, or nonspecified/combined cognitive domains. Articles were abstracted and levels of evidence were decided using specific criteria. The current review yielded 6 class I studies, 10 class II studies, and 24 class III studies. One intervention in the area of verbal learning and memory received support for a practice standard, 2 computer programs received support as practice guidelines (in the area of attention and multicognitive domains), and several studies provided support for 5 practice options in the domains of attention and learning and memory. Substantial progress has been made since our previous review regarding the identification of effective treatments for cognitive impairments in persons with MS. However, much work remains to be done to optimize rehabilitation potential by applying the most methodologically rigorous research designs to provide class I evidence in support of a given treatment strategy. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  17. A profile of communication in primary care physician telephone consultations: application of the Roter Interaction Analysis System.

    PubMed

    Innes, Michael; Skelton, John; Greenfield, Sheila

    2006-05-01

    Telephone consultations are a part of everyday practice, there is surprisingly little research on the subject. To describe the variation of consulting skills within a body of telephone consultations in primary care, highlighting the performance of one method of assessing the process of the consultation-- the Roter Interaction Analysis System-- with telephone consultations. Cross sectional study of 43 recordings of telephone consultations with GPs. One rural county in the Midlands. Recordings were made of 8 GPs, purposively selected for maximum variance in one region of the UK. Forty-three consultations were coded using the Roter Interaction Analysis System. From the descriptive categories, six composite categories were compiled reflecting a number of domains of interaction in a consultation: rapport, data gathering, patient education and counselling, partnership building, doctor dominance and patient-centredness. Analysis of variance was undertaken to explain variations between consultations for the different domains. Comparison was made to findings from similar work for face-to-face consultations. These telephone consultations feature more biomedical information exchange than psychosocial or affective communication. Length of interaction accounts for much of the variation seen between consultations in the domains of rapport, data gathering, patient education and counselling and partnership. Male doctors are more patient centred in this study. There is the suggestion of more doctor dominance and a less patient-centred approach when comparisons are made with previous work on face-to-face consultations. Although the telephone is increasingly being used to provide care, this study highlights the fact that telephone consultations cannot be taken as equivalent to those conducted face to face. More work needs to be done to delineate the features of telephone consultations.

  18. Participation in daytime activities among people with mild or moderate intellectual disability.

    PubMed

    Dusseljee, J C E; Rijken, P M; Cardol, M; Curfs, L M G; Groenewegen, P P

    2011-01-01

    Community participation has been defined as performing daytime activities by people while interacting with others. Previous studies on community participation among people with intellectual disability (ID) have mainly focused on the domestic life aspect. This study investigates the variation in community participation in the domains work, social contacts and leisure activities among people with ID in the Netherlands. A number of categories of people with ID were distinguished by: (1) gender; (2) age; (3) type of education; (4) severity of ID; and (5) accommodation type. Data were gathered on 653 people with mild or moderate ID, of whom 513 by oral interviews and 140 by structured questionnaires filled in by representatives of those who could not be interviewed. Pearson chi-square tests were used to test differences between categories of people with ID in the distributions of the participation variables. Additional logistic regression analyses were conducted to correct for differences between the categories in other variables. Most people with mild or moderate ID in the Netherlands have work or other daytime activities, have social contacts and have leisure activities. However, people aged 50 years and over and people with moderate ID participate less in these domains than those under 50 years and people with mild ID. Moreover, people with ID hardly participate in activities with people without ID. High participation among people with a mild or moderate ID within the domains of work, social contact and leisure activities does not necessarily indicate a high level of interaction with the community, because the majority hardly interact with people without ID. Furthermore, older people with ID and people with a more severe level of ID seem to be more at risk for social exclusion. © 2010 The Authors. Journal of Intellectual Disability Research © 2010 Blackwell Publishing Ltd.

  19. Molecular and functional analyses of a maize autoactive NB-LRR protein identify precise structural requirements for activity.

    PubMed

    Wang, Guan-Feng; Ji, Jiabing; El-Kasmi, Farid; Dangl, Jeffery L; Johal, Guri; Balint-Kurti, Peter J

    2015-02-01

    Plant disease resistance is often mediated by nucleotide binding-leucine rich repeat (NLR) proteins which remain auto-inhibited until recognition of specific pathogen-derived molecules causes their activation, triggering a rapid, localized cell death called a hypersensitive response (HR). Three domains are recognized in one of the major classes of NLR proteins: a coiled-coil (CC), a nucleotide binding (NB-ARC) and a leucine rich repeat (LRR) domains. The maize NLR gene Rp1-D21 derives from an intergenic recombination event between two NLR genes, Rp1-D and Rp1-dp2 and confers an autoactive HR. We report systematic structural and functional analyses of Rp1 proteins in maize and N. benthamiana to characterize the molecular mechanism of NLR activation/auto-inhibition. We derive a model comprising the following three main features: Rp1 proteins appear to self-associate to become competent for activity. The CC domain is signaling-competent and is sufficient to induce HR. This can be suppressed by the NB-ARC domain through direct interaction. In autoactive proteins, the interaction of the LRR domain with the NB-ARC domain causes de-repression and thus disrupts the inhibition of HR. Further, we identify specific amino acids and combinations thereof that are important for the auto-inhibition/activity of Rp1 proteins. We also provide evidence for the function of MHD2, a previously uncharacterized, though widely conserved NLR motif. This work reports several novel insights into the precise structural requirement for NLR function and informs efforts towards utilizing these proteins for engineering disease resistance.

  20. The development and application of a quantitative peptide microarray platform to SH2 domain specificity space

    NASA Astrophysics Data System (ADS)

    Engelmann, Brett Warren

    The Src homology 2 (SH2) domains evolved alongside protein tyrosine kinases (PTKs) and phosphatases (PTPs) in metazoans to recognize the phosphotyrosine (pY) post-translational modification. The human genome encodes 121 SH2 domains within 111 SH2 domain containing proteins that represent the primary mechanism for cellular signal transduction immediately downstream of PTKs. Despite pY recognition contributing to roughly half of the binding energy, SH2 domains possess substantial binding specificity, or affinity discrimination between phosphopeptide ligands. This specificity is largely imparted by amino acids (AAs) adjacent to the pY, typically from positions +1 to +4 C-terminal to the pY. Much experimental effort has been undertaken to construct preferred binding motifs for many SH2 domains. However, due to limitations in previous experimental methodologies these motifs do not account for the interplay between AAs. It was therefore not known how AAs within the context of individual peptides function to impart SH2 domain specificity. In this work we identified the critical role context plays in defining SH2 domain specificity for physiological ligands. We also constructed a high quality interactome using 50 SH2 domains and 192 physiological ligands. We next developed a quantitative high-throughput (Q-HTP) peptide microarray platform to assess the affinities four SH2 domains have for 124 physiological ligands. We demonstrated the superior characteristics of our platform relative to preceding approaches and validated our results using established biophysical techniques, literature corroboration, and predictive algorithms. The quantitative information provided by the arrays was leveraged to investigate SH2 domain binding distributions and identify points of binding overlap. Our microarray derived affinity estimates were integrated to produce quantitative interaction motifs capable of predicting interactions. Furthermore, our microarrays proved capable of resolving subtle contextual differences within motifs that modulate interaction affinities. We conclude that contextually informed specificity profiling of protein interaction domains using the methodologies developed in this study can inform efforts to understand the interconnectivity of signaling networks in normal and aberrant states. Three supplementary tables containing detailed lists of peptides, interactions, and sources of corroborative information are provided.

  1. Calcium binding to Procambarus clarkii sarcoplasmic calcium binding protein splice variants.

    PubMed

    Rohrback, Suzanne E; Wheatly, Michele G; Gillen, Christopher M

    2015-01-01

    Sarcoplasmic calcium binding protein (SCP) is a high-affinity calcium buffering protein expressed in muscle of crayfish and other invertebrates. In previous work, we identified three splice variants of Procambarus clarkii SCP (pcSCP1a, pcSCP1b, and pcSCP1c) that differ in a 37 amino acid region that lies mainly between the 2nd and 3ed EF-hand calcium binding domain. To evaluate the function of the proteins encoded by the pcSCP1 transcripts, we produced recombinant pcSCP1 and used tryptophan fluorescence to characterize calcium binding. Tryptophan fluorescence of pcSCP1a decreased in response to increased calcium, while tryptophan fluorescence of the pcSCP1b and pcSCP1c variants increased. We estimated calcium binding constants and Hill coefficients with two different equations: the standard Hill equation and a modified Hill equation that accounts for contributions from two different tryptophans. The approaches gave similar results. Steady-state calcium binding constants (Kd) ranged from 2.7±0.7×10(-8)M to 5.6±0.1×10(-7)M, consistent with previous work. Variants displayed significantly different apparent calcium affinities, which were decreased in the presence of magnesium. Calcium Kd was lowest for pcSCP1a and highest for pcSCP1c. Site-directed mutagenesis of pcSCP1c residues to the amino acids of pcSCP1b decreased the calcium Kd, identifying residues outside the EF-hand domains that contribute to calcium binding in crayfish SCP. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Learning to Rank Figures within a Biomedical Article

    PubMed Central

    Liu, Feifan; Yu, Hong

    2014-01-01

    Hundreds of millions of figures are available in biomedical literature, representing important biomedical experimental evidence. This ever-increasing sheer volume has made it difficult for scientists to effectively and accurately access figures of their interest, the process of which is crucial for validating research facts and for formulating or testing novel research hypotheses. Current figure search applications can't fully meet this challenge as the “bag of figures” assumption doesn't take into account the relationship among figures. In our previous study, hundreds of biomedical researchers have annotated articles in which they serve as corresponding authors. They ranked each figure in their paper based on a figure's importance at their discretion, referred to as “figure ranking”. Using this collection of annotated data, we investigated computational approaches to automatically rank figures. We exploited and extended the state-of-the-art listwise learning-to-rank algorithms and developed a new supervised-learning model BioFigRank. The cross-validation results show that BioFigRank yielded the best performance compared with other state-of-the-art computational models, and the greedy feature selection can further boost the ranking performance significantly. Furthermore, we carry out the evaluation by comparing BioFigRank with three-level competitive domain-specific human experts: (1) First Author, (2) Non-Author-In-Domain-Expert who is not the author nor co-author of an article but who works in the same field of the corresponding author of the article, and (3) Non-Author-Out-Domain-Expert who is not the author nor co-author of an article and who may or may not work in the same field of the corresponding author of an article. Our results show that BioFigRank outperforms Non-Author-Out-Domain-Expert and performs as well as Non-Author-In-Domain-Expert. Although BioFigRank underperforms First Author, since most biomedical researchers are either in- or out-domain-experts for an article, we conclude that BioFigRank represents an artificial intelligence system that offers expert-level intelligence to help biomedical researchers to navigate increasingly proliferated big data efficiently. PMID:24625719

  3. Learning to rank figures within a biomedical article.

    PubMed

    Liu, Feifan; Yu, Hong

    2014-01-01

    Hundreds of millions of figures are available in biomedical literature, representing important biomedical experimental evidence. This ever-increasing sheer volume has made it difficult for scientists to effectively and accurately access figures of their interest, the process of which is crucial for validating research facts and for formulating or testing novel research hypotheses. Current figure search applications can't fully meet this challenge as the "bag of figures" assumption doesn't take into account the relationship among figures. In our previous study, hundreds of biomedical researchers have annotated articles in which they serve as corresponding authors. They ranked each figure in their paper based on a figure's importance at their discretion, referred to as "figure ranking". Using this collection of annotated data, we investigated computational approaches to automatically rank figures. We exploited and extended the state-of-the-art listwise learning-to-rank algorithms and developed a new supervised-learning model BioFigRank. The cross-validation results show that BioFigRank yielded the best performance compared with other state-of-the-art computational models, and the greedy feature selection can further boost the ranking performance significantly. Furthermore, we carry out the evaluation by comparing BioFigRank with three-level competitive domain-specific human experts: (1) First Author, (2) Non-Author-In-Domain-Expert who is not the author nor co-author of an article but who works in the same field of the corresponding author of the article, and (3) Non-Author-Out-Domain-Expert who is not the author nor co-author of an article and who may or may not work in the same field of the corresponding author of an article. Our results show that BioFigRank outperforms Non-Author-Out-Domain-Expert and performs as well as Non-Author-In-Domain-Expert. Although BioFigRank underperforms First Author, since most biomedical researchers are either in- or out-domain-experts for an article, we conclude that BioFigRank represents an artificial intelligence system that offers expert-level intelligence to help biomedical researchers to navigate increasingly proliferated big data efficiently.

  4. Imaging the magnetic nanodomains in Nd 2 Fe 14 B

    DOE PAGES

    Huang, Lunan; Taufour, Valentin; Lamichhane, T. N.; ...

    2016-03-08

    Here, we study magnetic domains in Nd 2Fe 14B single crystals using high resolution magnetic force microscopy (MFM). Previous MFM studies and small angle neutron scattering experiments suggested the presence of nanoscale domains in addition to optically detected micrometer-scale ones. We find, in addition to the elongated, wavy nanodomains reported by a previous MFM study, that the micrometer-sized, star-shaped fractal pattern is constructed of an elongated network of nanodomains ~20 nm in width, with resolution-limited domain walls thinner than 2 nm. While the microscopic domains exhibit significant resilience to an external magnetic field, some of the nanodomains are sensitive tomore » the magnetic field of the MFM tip.« less

  5. Chemical vapor deposition growth of boron-carbon-nitrogen layers from methylamine borane thermolysis products

    NASA Astrophysics Data System (ADS)

    Leardini, Fabrice; Flores, Eduardo; Galvis E, Andrés R.; Ferrer, Isabel J.; Ramón Ares, José; Sánchez, Carlos; Molina, Pablo; van der Meulen, Herko P.; Gómez Navarro, Cristina; López Polin, Guillermo; Urbanos, Fernando J.; Granados, Daniel; García-García, F. Javier; Demirci, Umit B.; Yot, Pascal G.; Mastrangelo, Filippo; Grazia Betti, Maria; Mariani, Carlo

    2018-01-01

    This work investigates the growth of B-C-N layers by chemical vapor deposition using methylamine borane (MeAB) as the single-source precursor. MeAB has been synthesized and characterized, paying particular attention to the analysis of its thermolysis products, which are the gaseous precursors for B-C-N growth. Samples have been grown on Cu foils and transferred onto different substrates for their morphological, structural, chemical, electronic and optical characterizations. The results of these characterizations indicate a segregation of h-BN and graphene-like (Gr) domains. However, there is an important presence of B and N interactions with C at the Gr borders, and of C interacting at the h-BN-edges, respectively, in the obtained nano-layers. In particular, there is a significant presence of C-N bonds, at Gr/h-BN borders and in the form of N doping of Gr domains. The overall B:C:N contents in the layers is close to 1:3:1.5. A careful analysis of the optical bandgap determination of the obtained B-C-N layers is presented, discussed and compared with previous seminal works with samples of similar composition.

  6. Crowdsourcing Knowledge Discovery and Innovations in Medicine

    PubMed Central

    2014-01-01

    Clinicians face difficult treatment decisions in contexts that are not well addressed by available evidence as formulated based on research. The digitization of medicine provides an opportunity for clinicians to collaborate with researchers and data scientists on solutions to previously ambiguous and seemingly insolvable questions. But these groups tend to work in isolated environments, and do not communicate or interact effectively. Clinicians are typically buried in the weeds and exigencies of daily practice such that they do not recognize or act on ways to improve knowledge discovery. Researchers may not be able to identify the gaps in clinical knowledge. For data scientists, the main challenge is discerning what is relevant in a domain that is both unfamiliar and complex. Each type of domain expert can contribute skills unavailable to the other groups. “Health hackathons” and “data marathons”, in which diverse participants work together, can leverage the current ready availability of digital data to discover new knowledge. Utilizing the complementary skills and expertise of these talented, but functionally divided groups, innovations are formulated at the systems level. As a result, the knowledge discovery process is simultaneously democratized and improved, real problems are solved, cross-disciplinary collaboration is supported, and innovations are enabled. PMID:25239002

  7. Applying research to practice: generalist and specialist (visual ergonomics) consultancy.

    PubMed

    Long, Jennifer; Long, Airdrie

    2012-01-01

    Ergonomics is a holistic discipline encompassing a wide range of special interest groups. The role of an ergonomics consultant is to provide integrated solutions to improve comfort, safety and productivity. In Australia, there are two types of consultants--generalists and specialists. Both have training in ergonomics but specialist knowledge may be the result of previous education or work experience. This paper presents three projects illustrating generalist and specialist (visual ergonomics) consultancy: development of a vision screening protocol, solving visual discomfort in an office environment and solving postural discomfort in heavy industry. These case studies demonstrate how multiple ergonomics consultants may work together to solve ergonomics problems. It also describes some of the challenges for consultants, for those engaging their services and for the ergonomics profession, e.g. recognizing the boundaries of expertise, sharing information with business competitors, the costs-benefits of engaging multiple consultants and the risk of fragmentation of ergonomics knowledge and solutions. Since ergonomics problems are often multifaceted, ergonomics consultants should have a solid grounding in all domains of ergonomics, even if they ultimately only practice in one specialty or domain. This will benefit the profession and ensure that ergonomics remains a holistic discipline.

  8. Crowdsourcing knowledge discovery and innovations in medicine.

    PubMed

    Celi, Leo Anthony; Ippolito, Andrea; Montgomery, Robert A; Moses, Christopher; Stone, David J

    2014-09-19

    Clinicians face difficult treatment decisions in contexts that are not well addressed by available evidence as formulated based on research. The digitization of medicine provides an opportunity for clinicians to collaborate with researchers and data scientists on solutions to previously ambiguous and seemingly insolvable questions. But these groups tend to work in isolated environments, and do not communicate or interact effectively. Clinicians are typically buried in the weeds and exigencies of daily practice such that they do not recognize or act on ways to improve knowledge discovery. Researchers may not be able to identify the gaps in clinical knowledge. For data scientists, the main challenge is discerning what is relevant in a domain that is both unfamiliar and complex. Each type of domain expert can contribute skills unavailable to the other groups. "Health hackathons" and "data marathons", in which diverse participants work together, can leverage the current ready availability of digital data to discover new knowledge. Utilizing the complementary skills and expertise of these talented, but functionally divided groups, innovations are formulated at the systems level. As a result, the knowledge discovery process is simultaneously democratized and improved, real problems are solved, cross-disciplinary collaboration is supported, and innovations are enabled.

  9. Electrical and well log study of the Plio-Quaternary deposits of the southern part of the Rharb Basin, northern Morocco

    NASA Astrophysics Data System (ADS)

    El Bouhaddioui, Mohamed; Mridekh, Abdelaziz; Kili, Malika; El Mansouri, Bouabid; El Gasmi, El Houssine; Magrane, Bouchaib

    2016-11-01

    The Rharb Basin is located in the NW of Morocco. It is the onshore extension of a lager offshore basin between Kenitra and Moulay Bousselham. The Rharb plain (properly called) extends over an area of 4200 Km2 between two very different structural entities: the unstable Rif domain in the NE and the East and the ''relatively stable'' Meseta domain in the south. The distribution of Pliocene-Quaternary deposits under this plain is complex and was controlled by both tectonics and climatic factors. The main objective of the present work is to define the spatiotemporal evolution of these deposits in the onshore part of the basin and to make a comparison with a sequence analysis defined, for equivalent deposits in the offshore basin, by a previous work. The proposed model allows thus to characterize the geometry of these deposits in the extension of continental shelf under the present day onshore basin, and to explain there is genesis in terms of interactions between eustatic sea level fluctuations, tectonics and sedimentary rates at the mouths of paleo-rivers that had drained the Rharb plain during Pliocene to Quaternary Times.

  10. Helios: Understanding Solar Evolution Through Text Analytics

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

    Randazzese, Lucien

    This proof-of-concept project focused on developing, testing, and validating a range of bibliometric, text analytic, and machine-learning based methods to explore the evolution of three photovoltaic (PV) technologies: Cadmium Telluride (CdTe), Dye-Sensitized solar cells (DSSC), and Multi-junction solar cells. The analytical approach to the work was inspired by previous work by the same team to measure and predict the scientific prominence of terms and entities within specific research domains. The goal was to create tools that could assist domain-knowledgeable analysts in investigating the history and path of technological developments in general, with a focus on analyzing step-function changes in performance,more » or “breakthroughs,” in particular. The text-analytics platform developed during this project was dubbed Helios. The project relied on computational methods for analyzing large corpora of technical documents. For this project we ingested technical documents from the following sources into Helios: Thomson Scientific Web of Science (papers), the U.S. Patent & Trademark Office (patents), the U.S. Department of Energy (technical documents), the U.S. National Science Foundation (project funding summaries), and a hand curated set of full-text documents from Thomson Scientific and other sources.« less

  11. Effects of proactive interference on non-verbal working memory.

    PubMed

    Cyr, Marilyn; Nee, Derek E; Nelson, Eric; Senger, Thea; Jonides, John; Malapani, Chara

    2017-02-01

    Working memory (WM) is a cognitive system responsible for actively maintaining and processing relevant information and is central to successful cognition. A process critical to WM is the resolution of proactive interference (PI), which involves suppressing memory intrusions from prior memories that are no longer relevant. Most studies that have examined resistance to PI in a process-pure fashion used verbal material. By contrast, studies using non-verbal material are scarce, and it remains unclear whether the effect of PI is domain-general or whether it applies solely to the verbal domain. The aim of the present study was to examine the effect of PI in visual WM using both objects with high and low nameability. Using a Directed-Forgetting paradigm, we varied discriminability between WM items on two dimensions, one verbal (high-nameability vs. low-nameability objects) and one perceptual (colored vs. gray objects). As in previous studies using verbal material, effects of PI were found with object stimuli, even after controlling for verbal labels being used (i.e., low-nameability condition). We also found that the addition of distinctive features (color, verbal label) increased performance in rejecting intrusion probes, most likely through an increase in discriminability between content-context bindings in WM.

  12. High-performance finite-difference time-domain simulations of C-Mod and ITER RF antennas

    NASA Astrophysics Data System (ADS)

    Jenkins, Thomas G.; Smithe, David N.

    2015-12-01

    Finite-difference time-domain methods have, in recent years, developed powerful capabilities for modeling realistic ICRF behavior in fusion plasmas [1, 2, 3, 4]. When coupled with the power of modern high-performance computing platforms, such techniques allow the behavior of antenna near and far fields, and the flow of RF power, to be studied in realistic experimental scenarios at previously inaccessible levels of resolution. In this talk, we present results and 3D animations from high-performance FDTD simulations on the Titan Cray XK7 supercomputer, modeling both Alcator C-Mod's field-aligned ICRF antenna and the ITER antenna module. Much of this work focuses on scans over edge density, and tailored edge density profiles, to study dispersion and the physics of slow wave excitation in the immediate vicinity of the antenna hardware and SOL. An understanding of the role of the lower-hybrid resonance in low-density scenarios is emerging, and possible implications of this for the NSTX launcher and power balance are also discussed. In addition, we discuss ongoing work centered on using these simulations to estimate sputtering and impurity production, as driven by the self-consistent sheath potentials at antenna surfaces.

  13. High-performance finite-difference time-domain simulations of C-Mod and ITER RF antennas

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

    Jenkins, Thomas G., E-mail: tgjenkins@txcorp.com; Smithe, David N., E-mail: smithe@txcorp.com

    Finite-difference time-domain methods have, in recent years, developed powerful capabilities for modeling realistic ICRF behavior in fusion plasmas [1, 2, 3, 4]. When coupled with the power of modern high-performance computing platforms, such techniques allow the behavior of antenna near and far fields, and the flow of RF power, to be studied in realistic experimental scenarios at previously inaccessible levels of resolution. In this talk, we present results and 3D animations from high-performance FDTD simulations on the Titan Cray XK7 supercomputer, modeling both Alcator C-Mod’s field-aligned ICRF antenna and the ITER antenna module. Much of this work focuses on scansmore » over edge density, and tailored edge density profiles, to study dispersion and the physics of slow wave excitation in the immediate vicinity of the antenna hardware and SOL. An understanding of the role of the lower-hybrid resonance in low-density scenarios is emerging, and possible implications of this for the NSTX launcher and power balance are also discussed. In addition, we discuss ongoing work centered on using these simulations to estimate sputtering and impurity production, as driven by the self-consistent sheath potentials at antenna surfaces.« less

  14. Crystal Structure of the Escherichia coli 23S rRNA: m{5}C Methyltransferase RlmI (YccW) Reveals Evolutionary Links Between RNA Modification Enzymes

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

    Sunita, S.; Tkaczuk, K; Purta, E

    2008-01-01

    Methylation is the most common RNA modification in the three domains of life. Transfer of the methyl group from S-adenosyl-l-methionine (AdoMet) to specific atoms of RNA nucleotides is catalyzed by methyltransferase (MTase) enzymes. The rRNA MTase RlmI (rRNA large subunit methyltransferase gene I; previously known as YccW) specifically modifies Escherichia coli 23S rRNA at nucleotide C1962 to form 5-methylcytosine. Here, we report the crystal structure of RlmI refined at 2 {angstrom} to a final R-factor of 0.194 (R{sub free} = 0.242). The RlmI molecule comprises three domains: the N-terminal PUA domain; the central domain, which resembles a domain previously foundmore » in RNA:5-methyluridine MTases; and the C-terminal catalytic domain, which contains the AdoMet-binding site. The central and C-terminal domains are linked by a {Beta}-hairpin structure that has previously been observed in several MTases acting on nucleic acids or proteins. Based on bioinformatics analyses, we propose a model for the RlmI-AdoMet-RNA complex. Comparative structural analyses of RlmI and its homologs provide insight into the potential function of several structures that have been solved by structural genomics groups and furthermore indicate that the evolutionary paths of RNA and DNA 5-methyluridine and 5-methylcytosine MTases have been closely intertwined.« less

  15. Using theories of behaviour to understand transfusion prescribing in three clinical contexts in two countries: development work for an implementation trial.

    PubMed

    Francis, Jill J; Tinmouth, Alan; Stanworth, Simon J; Grimshaw, Jeremy M; Johnston, Marie; Hyde, Chris; Stockton, Charlotte; Brehaut, Jamie C; Fergusson, Dean; Eccles, Martin P

    2009-10-24

    Blood transfusion is an essential part of healthcare and can improve patient outcomes. However, like most therapies, it is also associated with significant clinical risks. In addition, there is some evidence of overuse. Understanding the potential barriers and enablers to reduced prescribing of blood products will facilitate the selection of intervention components likely to be effective, thereby reducing the number of costly trials evaluating different implementation strategies. Using a theoretical basis to understand behaviours targeted for change will contribute to a 'basic science' relating to determinants of professional behaviour and how these inform the selection of techniques for changing behaviour. However, it is not clear which theories of behaviour are relevant to clinicians' transfusing behaviour. The aim of this study is to use a theoretical domains framework to identify relevant theories, and to use these theories to identify factors that predict the decision to transfuse. The study involves two steps: interview study and questionnaire study. Using a previously identified framework, we will conduct semi-structured interviews with clinicians to elicit their views about which factors are associated with waiting and further monitoring the patient rather than transfusing red blood cells. Interviews will cover the following theoretical domains: knowledge; skills; social/professional role and identity; beliefs about capabilities; beliefs about consequences; motivation and goals; memory, attention, and decision processes; environmental context and resources; social influences; emotion; behavioural regulation; nature of the behaviour. The interviews will take place independently in Canada and the UK and involve two groups of physicians in each country (UK: adult and neonatal intensive care physicians; Canada: intensive care physicians and orthopaedic surgeons). We will: analyse interview transcript content to select relevant theoretical domains; use consensus processes to map these domains on to theories of behaviour; develop questionnaires based on these theories; and mail them to each group of physicians in the two countries. From our previous work, it is likely that the theories will include: theory of planned behaviour, social cognitive theory and the evidence-based strategy, implementation intention. The questionnaire data will measure predictor variables (theoretical constructs) and outcome variables (intention and clinical decision), and will be analysed using multiple regression analysis. We aim to achieve 150 respondents in each of the four groups for each postal survey.

  16. Birth, evolution, and transmission of satellite-free mammalian centromeric domains.

    PubMed

    Nergadze, Solomon G; Piras, Francesca M; Gamba, Riccardo; Corbo, Marco; Cerutti, Federico; McCarter, Joseph G W; Cappelletti, Eleonora; Gozzo, Francesco; Harman, Rebecca M; Antczak, Douglas F; Miller, Donald; Scharfe, Maren; Pavesi, Giulio; Raimondi, Elena; Sullivan, Kevin F; Giulotto, Elena

    2018-06-01

    Mammalian centromeres are associated with highly repetitive DNA (satellite DNA), which has so far hindered molecular analysis of this chromatin domain. Centromeres are epigenetically specified, and binding of the CENPA protein is their main determinant. In previous work, we described the first example of a natural satellite-free centromere on Equus caballus Chromosome 11. Here, we investigated the satellite-free centromeres of Equus asinus by using ChIP-seq with anti-CENPA antibodies. We identified an extraordinarily high number of centromeres lacking satellite DNA (16 of 31). All of them lay in LINE- and AT-rich regions. A subset of these centromeres is associated with DNA amplification. The location of CENPA binding domains can vary in different individuals, giving rise to epialleles. The analysis of epiallele transmission in hybrids (three mules and one hinny) showed that centromeric domains are inherited as Mendelian traits, but their position can slide in one generation. Conversely, centromere location is stable during mitotic propagation of cultured cells. Our results demonstrate that the presence of more than half of centromeres void of satellite DNA is compatible with genome stability and species survival. The presence of amplified DNA at some centromeres suggests that these arrays may represent an intermediate stage toward satellite DNA formation during evolution. The fact that CENPA binding domains can move within relatively restricted regions (a few hundred kilobases) suggests that the centromeric function is physically limited by epigenetic boundaries. © 2018 Nergadze et al.; Published by Cold Spring Harbor Laboratory Press.

  17. MPP1 directly interacts with flotillins in erythrocyte membrane - Possible mechanism of raft domain formation.

    PubMed

    Biernatowska, Agnieszka; Augoff, Katarzyna; Podkalicka, Joanna; Tabaczar, Sabina; Gajdzik-Nowak, Weronika; Czogalla, Aleksander; Sikorski, Aleksander F

    2017-11-01

    Flotillins are prominent, oligomeric protein components of erythrocyte (RBC) membrane raft domains and are considered to play an important structural role in lateral organization of the plasma membrane. In our previous work on erythroid membranes and giant plasma membrane vesicles (GPMVs) derived from them we have shown that formation of functional domains (resting state rafts) depends on the presence of membrane palmitoylated protein 1 (MPP1/p55), pointing to its new physiological role. Exploration of the molecular mechanism of MPP1 function in organizing membrane domains described here, through searching for its molecular partners in RBC membrane by using different methods, led to the identification of the raft-marker proteins, flotillin 1 and flotillin 2, as hitherto unreported direct MPP1 binding-partners in the RBC membrane. These proteins are found in high molecular-weight complexes in native RBC membrane and, significantly, their presence was shown to be separate from the well-known protein 4.1-dependent interactions of MPP1 with membrane proteins. Furthermore, FLIM analysis revealed that loss of the endogenous MPP1-flotillins interactions resulted in significant changes in RBC membrane-fluidity, emphasizing the physiological importance of such interactions in vivo. Therefore, our data establish a new perspective on the role of MPP1 in erythroid cells and suggests that direct MPP1-flotillins interactions could be the major driving-force behind the formation of raft domains in RBC. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  18. Shape Transitions and Lattice Structuring of Ceramide-Enriched Domains Generated by Sphingomyelinase in Lipid Monolayers

    PubMed Central

    Härtel, Steffen; Fanani, María Laura; Maggio, Bruno

    2005-01-01

    Sphingomyelinases (SMases) hydrolyze the membrane constituent sphingomyelin (SM) to phosphocholine and ceramide (Cer). Growing evidence supports that SMase-induced SM→Cer conversion leads to the formation of lateral Cer-enriched domains which drive structural reorganization in lipid membranes. We previously provided visual evidence in real-time for the formation of Cer-enriched domains in SM monolayers through the action of the neutral Bacillus cereus SMase. In this work, we disclose a succession of discrete morphologic transitions and lateral organization of Cer-enriched domains that underlay the SMase-generated surface topography. We further reveal how these structural parameters couple to the generation of two-dimensional electrostatic fields, based upon the specific orientation of the lipid dipole moments in the Cer-enriched domains. Advanced image processing routines in combination with time-resolved epifluorescence microscopy on Langmuir monolayers revealed: 1), spontaneous nucleation and circular growth of Cer-enriched domains after injection of SMase into the subphase of the SM monolayer; 2), domain-intrinsic discrete transitions from circular to periodically undulating shapes followed by a second transition toward increasingly branched morphologies; 3), lateral superstructure organization into predominantly hexagonal domain lattices; 4), formation of super-superstructures by the hexagonal lattices; and 5), rotationally and laterally coupled domain movement before domain border contact. All patterns proved to be specific for the SMase-driven system since they could not be observed with Cer-enriched domains generated by defined mixtures of SM/Cer in enzyme-free monolayers at the same surface pressure (Π = 10 mN/m). Following the theories of lateral shape transitions, dipolar electrostatic interactions of lipid domains, and direct determinations of the monolayer dipole potential, our data show that SMase induces a domain-specific packing and orientation of the molecular dipole moments perpendicular to the air/water interface. In consequence, protein-driven generation of specific out-of-equilibrium states, an accepted concept for maintenance of transmembrane lipid asymmetry, must also be considered on the lateral level. Lateral enzyme-specific out-of-equilibrium organization of lipid domains represents a new level of signal transduction from local (nm) to long-range (μm) scales. The cross-talk between lateral domain structures and dipolar electrostatic fields adds new perspectives to the mechanisms of SMase-mediated signal transduction in biological membranes. PMID:15489298

  19. Spending Time: The Impact of Hours Worked on Work-Family Conflict

    ERIC Educational Resources Information Center

    Adkins, Cheryl L.; Premeaux, Sonya F.

    2012-01-01

    Scholars have long assumed that as workers spend more time at work fewer hours are available for their non-work lives leading to negative effects in both domains, and most studies examining the impact of work hours on work and life domains have supported this viewpoint. However, the majority of these studies have used one-dimensional measures of…

  20. Decision Support System Requirements Definition for Human Extravehicular Activity Based on Cognitive Work Analysis

    PubMed Central

    Miller, Matthew James; McGuire, Kerry M.; Feigh, Karen M.

    2016-01-01

    The design and adoption of decision support systems within complex work domains is a challenge for cognitive systems engineering (CSE) practitioners, particularly at the onset of project development. This article presents an example of applying CSE techniques to derive design requirements compatible with traditional systems engineering to guide decision support system development. Specifically, it demonstrates the requirements derivation process based on cognitive work analysis for a subset of human spaceflight operations known as extravehicular activity. The results are presented in two phases. First, a work domain analysis revealed a comprehensive set of work functions and constraints that exist in the extravehicular activity work domain. Second, a control task analysis was performed on a subset of the work functions identified by the work domain analysis to articulate the translation of subject matter states of knowledge to high-level decision support system requirements. This work emphasizes an incremental requirements specification process as a critical component of CSE analyses to better situate CSE perspectives within the early phases of traditional systems engineering design. PMID:28491008

  1. Decision Support System Requirements Definition for Human Extravehicular Activity Based on Cognitive Work Analysis.

    PubMed

    Miller, Matthew James; McGuire, Kerry M; Feigh, Karen M

    2017-06-01

    The design and adoption of decision support systems within complex work domains is a challenge for cognitive systems engineering (CSE) practitioners, particularly at the onset of project development. This article presents an example of applying CSE techniques to derive design requirements compatible with traditional systems engineering to guide decision support system development. Specifically, it demonstrates the requirements derivation process based on cognitive work analysis for a subset of human spaceflight operations known as extravehicular activity . The results are presented in two phases. First, a work domain analysis revealed a comprehensive set of work functions and constraints that exist in the extravehicular activity work domain. Second, a control task analysis was performed on a subset of the work functions identified by the work domain analysis to articulate the translation of subject matter states of knowledge to high-level decision support system requirements. This work emphasizes an incremental requirements specification process as a critical component of CSE analyses to better situate CSE perspectives within the early phases of traditional systems engineering design.

  2. A mixed-methods study of interprofessional learning of resuscitation skills.

    PubMed

    Bradley, Paul; Cooper, Simon; Duncan, Fiona

    2009-09-01

    This study aimed to identify the effects of interprofessional resuscitation skills teaching on medical and nursing students' attitudes, leadership, team-working and performance skills. Year 2 medical and nursing students learned resuscitation skills in uniprofessional or interprofessional settings, prior to undergoing observational ratings of video-recorded leadership, teamwork and skills performance and subsequent focus group interviews. The Readiness for Interprofessional Learning Scale (RIPLS) was administered pre- and post-intervention and again 3-4 months later. There was no significant difference between interprofessional and uniprofessional teams for leadership, team dynamics or resuscitation tasks performance. Gender, previous interprofessional learning experience, professional background and previous leadership experience had no significant effect. Interview analysis showed broad support for interprofessional education (IPE) matched to clinical reality with perceived benefits for teamwork, communication and improved understanding of roles and perspectives. Concerns included inappropriate role adoption, hierarchy issues, professional identity and the timing of IPE episodes. The RIPLS subscales for professional identity and team-working increased significantly post-intervention for interprofessional groups but returned to pre-test levels by 3-4 months. However, interviews showed interprofessional groups retained a 'residual positivity' towards IPE, more so than uniprofessional groups. An intervention based on common, relevant, shared learning outcomes set in a realistic educational context can work with students who have differing levels of previous IPE and skills training experience. Qualitatively, positive attitudes outlast quantitative changes measured using the RIPLS. Further quantitative and qualitative work is required to examine other domains of learning, the timing of interventions and impact on attitudes towards IPE.

  3. The dynamic spillover of satisfaction between work and marriage: the role of time and mood.

    PubMed

    Heller, Daniel; Watson, David

    2005-11-01

    Previous research has indicated important linkages between work and family domains and roles. However, the nature of the dynamic spillover between job and marital satisfaction remains poorly understood. The current study tests both the concurrent and lagged associations between job and marital satisfaction at a within-individual level of analysis using a diary study of 76 fully employed, married adults. The authors further examine the mediating role of mood in this spillover process. Consistent with their hypotheses, findings indicate both a concurrent and a lagged (job to marital and marital to job) job satisfaction-marital satisfaction association at the within-subject level of analysis and lend some support for the mediating role of mood (most notably positive affect) in these associations. The authors hope these findings stimulate new research that uses more complex designs and comprehensive theoretical models to investigate work-family links. ((c) 2005 APA, all rights reserved).

  4. Modelling and simulation of “Free Cooling” process applied to building construction

    NASA Astrophysics Data System (ADS)

    Ousegui, A.; Asbik, M.

    2018-05-01

    Thermal energy storage systems (TES), using phase change material (PCM) in building walls, consists a hot topic within the research community currently. In the present work, a numerical model is developed to simulate free cooling of air-PCM heat exchanger in both charging and discharging steps. The studied case is taken from experimental work. The domain consists in two parallel plates made of Paraffin as PCM, separate by a gap where air circulates. The flow and temperature can be adjusted. The goal is to calculate the temperature of the air at the outlet, in order to analyse the performance of the device. A good agreement was founded between experimental and numerical results. The analysis of the influence of the flow rate on the efficiency of the process confirms a previous works, that the heating flow rate should be higher than cooling one.

  5. Sparse maps—A systematic infrastructure for reduced-scaling electronic structure methods. II. Linear scaling domain based pair natural orbital coupled cluster theory

    NASA Astrophysics Data System (ADS)

    Riplinger, Christoph; Pinski, Peter; Becker, Ute; Valeev, Edward F.; Neese, Frank

    2016-01-01

    Domain based local pair natural orbital coupled cluster theory with single-, double-, and perturbative triple excitations (DLPNO-CCSD(T)) is a highly efficient local correlation method. It is known to be accurate and robust and can be used in a black box fashion in order to obtain coupled cluster quality total energies for large molecules with several hundred atoms. While previous implementations showed near linear scaling up to a few hundred atoms, several nonlinear scaling steps limited the applicability of the method for very large systems. In this work, these limitations are overcome and a linear scaling DLPNO-CCSD(T) method for closed shell systems is reported. The new implementation is based on the concept of sparse maps that was introduced in Part I of this series [P. Pinski, C. Riplinger, E. F. Valeev, and F. Neese, J. Chem. Phys. 143, 034108 (2015)]. Using the sparse map infrastructure, all essential computational steps (integral transformation and storage, initial guess, pair natural orbital construction, amplitude iterations, triples correction) are achieved in a linear scaling fashion. In addition, a number of additional algorithmic improvements are reported that lead to significant speedups of the method. The new, linear-scaling DLPNO-CCSD(T) implementation typically is 7 times faster than the previous implementation and consumes 4 times less disk space for large three-dimensional systems. For linear systems, the performance gains and memory savings are substantially larger. Calculations with more than 20 000 basis functions and 1000 atoms are reported in this work. In all cases, the time required for the coupled cluster step is comparable to or lower than for the preceding Hartree-Fock calculation, even if this is carried out with the efficient resolution-of-the-identity and chain-of-spheres approximations. The new implementation even reduces the error in absolute correlation energies by about a factor of two, compared to the already accurate previous implementation.

  6. Pain, psychological distress and motor pattern in women with provoked vestibulodynia (PVD) - symptom characteristics and therapy suggestions.

    PubMed

    Haugstad, Gro Killi; Wojniusz, Slawomir; Kirste, Unni Merete; Kirschner, Rolf Steinar; Lilleheie, Ingvild; Haugstad, Tor Sigbjørn

    2018-04-25

    Provoked vestibulodynia (PVD) represent a longstanding pain syndrome that affects large numbers of women worldwide. However, no standardized guidelines for PVD treatment exist. In a cross-sectional pilot study we examined 30 PVD patients on multidimensional parameters including pain, psychological distress and quality of movement, in order to obtain a broader understanding of the somatic and psychological symptoms in PVD, and for the future to develop better interventions. Additionally, we compare the findings to previously published results regarding the same parameters in women with chronic pelvic pain (CPP). Thirty women with PVD recruited from a tertiary care university clinic of gynecology were assessed for demographic data, pain intensity (VAS), psychological distress (GHQ-30 and Tampa scale of Kinesophobia) and quality of movement (standardized Mensendieck test, SMT). Average age of the PVD women was 24.7±3.60 years, 60% of them were in permanent relationships, all were nulliparous, none had been subjected to surgical procedures, 100% were working full or part time and 90% were educated to at least undergraduate level. Mean VAS score was 7.77±1.97 (mean±SD), kinesiophobia 24.4±3.95 and anxiety domain of GHQ-30 9.73±4.06. SMT scores were particularly low for the domains of respiration and gait (less than 50% of optimal scores). PVD women display reduced quality of movement, especially for gait and respiration patterns, increased level of anxiety and high average pain scores. These findings are similar to what we have previously reported in CPP patients. However, in contrast to CPP group, PVD women are on average younger, have higher work participation, higher education level and have not been subjected to surgical procedures. Since PVD women display similar, although somewhat less severe, symptom profile than CPP, we suggest that a multidimensional approach to treatment, such as "somatocognitive therapy" should be investigated in this group as it has previously been shown to be promising in treatment of CPP.

  7. Episodic memory impairment in Addison's disease: results from a telephonic cognitive assessment.

    PubMed

    Henry, Michelle; Thomas, Kevin G F; Ross, Ian L

    2014-06-01

    Patients with Addison's disease frequently self-report memory and attention difficulties, even when on standard replacement therapy. However, few published studies examine, using objective measures and assessing across multiple domains, the cognitive functioning of Addison's disease patients relative to healthy controls. The primary aim of this study was to investigate whether the previously reported subjective cognitive deficits in Addison's disease are confirmed by objective measures. Conducting comprehensive neuropsychological assessments of patients with relatively rare clinical disorders, such as Addison's disease, is challenging because access to those patients is often limited, and because their medical condition might prevent extended testing sessions. Brief telephonic cognitive assessments are a useful tool in such circumstances. Hence, we administered the Brief Test of Adult Cognition by Telephone to 27 Addison's disease patients and 27 matched healthy controls. The instrument provides objective assessment of episodic memory, working memory, executive functioning, reasoning, and speed of processing. Statistical analyses confirmed that, as expected, patients performed significantly more poorly than controls on the episodic memory subtest. There were, however, no significant between-group differences on the attention, executive functioning, reasoning, and speed of processing subtests. Furthermore, patients with a longer duration of illness performed more poorly across all domains of cognition. We conclude that, for Addison's disease patients, previously reported subjective cognitive deficits are matched by objective impairment, but only in the domain of episodic memory. Future research might investigate (a) whether these memory deficits are material-specific (i.e., whether non-verbal memory is also affected), and (b) the neurobiological mechanisms underlying these deficits.

  8. Time perspective, personality and smoking, body mass, and physical activity: an empirical study.

    PubMed

    Adams, Jean; Nettle, Daniel

    2009-02-01

    Time perspective describes how individuals conceptualize and value future events, and may be related to health behaviours. Research to date has focused on addictive behaviours, used a variety of different measures of time perspective, and not explored the role of personality. This work aimed to: explore the relationships between: five previously used measures of time perspective; time perspective and the broad domains of the five-factor model of personality; and time perspective and smoking, body mass, and physical activity after controlling for socio-demographics and personality. Cross-sectional self-report data were collected using a web based survey. Participants (N=423) were recruited via local community internet message boards in US urban areas. The survey collected information on: delay discount rate, the Consideration of Future Consequences Scale (CFCS), the future scale of the Zimbardo Time Perspective Inventory (ZTPI), subjective probability of living to age 75, and time period for financial planning, the five-factor personality inventory, smoking, body mass index (BMI), and physical activity. After controlling for socio-demographics, most markers of time perspective were significantly correlated with each other, but the strength of correlations was rarely strong. Conscientiousness, Neuroticism, Agreeableness, and Openness were associated with some markers of time perspective. After controlling for socio-demographic and personality domains, only CFCS score was associated with smoking status and BMI. There is some overlap between previously used markers of time perspective and the five-factor personality domains but this is neither strong nor consistent. Smoking and BMI, but not physical activity, are associated with CFCS, but not other measures of time perspective.

  9. Work-family interface from a life and career stage perspective: the role of demands and resources.

    PubMed

    Demerouti, Evangelia; Peeters, Maria C W; van der Heijden, Beatrice I J M

    2012-01-01

    Work-family conflict and enrichment are experiences that occur daily and have substantial consequences for employees, their families, and the organizations that employ them. The aim of the current review is to make a link between life and career stage, work and family conditions, and the work-family interface. The basic proposition is that life stages partly determine career development, and consequently the specific working conditions (job demands and job resources) and family conditions (family demands and family resources) that individuals are exposed to. As a result, the specific demands and resources in the work and family domains determine to what extent individuals experience that work and family are conflicting or enriching life domains. In this review we suggest that individuals in early adulthood will experience high inter-role conflict and low facilitation due to high demands and low resources in both life domains, while individuals in late adulthood will experience the opposite pattern; that is, low conflict and high facilitation due to low demands and high resources in both domains. Individuals in middle adulthood will experience high work-family conflict but also high family-work facilitation due to the presence of high job demands and resources in both life domains. Integrating life and career stage perspectives and the experience of work-family interface is of notable practical utility because it provides a mechanism to make more informed decisions about the relative need for and corresponding benefits of work-family programs.

  10. Narrative and "anti-narrative" in science: How scientists tell stories, and don't.

    PubMed

    Padian, Kevin

    2018-06-04

    Narratives are common to all branches of science, not only to the humanities. Scientists tell stories about how the things we study work, develop, and evolve, and about how we come to be interested in them. Here I add a third domain (Secularity) to Gould's two "non-overlapping magisteria" of Science and Religion, and I review previous work on the parallels in elements between story-telling in literature and science. The stories of each domain have different criteria for judging them valid or useful. In science, especially historical sciences such as biology and geology, particular scientific methods and approaches both structure and test our narratives. Relying on the narrative assumptions of how certain processes, such as natural selection, are supposed to work is treacherous unless they are tested by appropriate historical patterns, such as phylogeny, and rooted in the process of natural mechanisms. The structure of scientific explanation seen in peer-reviewed papers and grant proposals obscures true narrative within a formulaic sequence of "question, methods, materials" and so on that is quite different from the classic narrative of folk-tales and novels, producing an "anti-narrative" that must be "un-learned" before it can be communicated to non-scientists. By adopting some of the techniques of classic story-telling, scientists can become more effective in making our ideas clear, educating the public, and even attracting funding.

  11. 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…

  12. Beyond Conflict: Functional Facets of the Work-Family Interplay

    ERIC Educational Resources Information Center

    Wiese, Bettina S.; Seiger, Christine P.; Schmid, Christian M.; Freund, Alexandra M.

    2010-01-01

    The present paper deals with three positive facets of the work-family interplay, i.e., transfer of competencies, transfer of positive mood, and cross-domain compensation. The latter refers to the experience that engagement in one domain helps dealing with failures in the other domain. In two correlational studies (N[subscript 1] = 107 working…

  13. Delayed Recall and Working Memory MMSE Domains Predict Delirium following Cardiac Surgery.

    PubMed

    Price, Catherine C; Garvan, Cynthia; Hizel, Loren P; Lopez, Marcos G; Billings, Frederic T

    2017-01-01

    Reduced preoperative cognition is a risk factor for postoperative delirium. The significance for type of preoperative cognitive deficit, however, has yet to be explored and could provide important insights into mechanisms and prediction of delirium. Our goal was to determine if certain cognitive domains from the general cognitive screener, the Mini-Mental State Exam (MMSE), predict delirium after cardiac surgery. Patients completed a preoperative MMSE prior to undergoing elective cardiac surgery. Following surgery, delirium was assessed throughout ICU stay using the Confusion Assessment Method for ICU delirium and the Richmond Agitation and Sedation Scale. Cardiac surgery patients who developed delirium (n = 137) had lower total MMSE scores than patients who did not develop delirium (n = 457). In particular, orientation to place, working memory, delayed recall, and language domain scores were lower. Of these, only the working memory and delayed recall domains predicted delirium in a regression model adjusting for history of chronic obstructive pulmonary disease, age, sex, and duration of cardiopulmonary bypass. For each word not recalled on the three-word delayed recall assessment, the odds of delirium increased by 50%. For each item missed on the working memory index, the odds of delirium increased by 36%. Of the patients who developed delirium, 47% had a primary impairment in memory, 21% in working memory, and 33% in both domains. The area under the receiver operating characteristics curve using only the working memory and delayed recall domains was 0.75, compared to 0.76 for total MMSE score. Delirium risk is greater for individuals with reduced MMSE scores on the delayed recall and working memory domains. Research should address why patients with memory and executive vulnerabilities are more prone to postoperative delirium than those with other cognitive limitations.

  14. Integrating Data From the UK National Reporting and Learning System With Work Domain Analysis to Understand Patient Safety Incidents in Community Pharmacy.

    PubMed

    Phipps, Denham L; Tam, W Vanessa; Ashcroft, Darren M

    2017-03-01

    To explore the combined use of a critical incident database and work domain analysis to understand patient safety issues in a health-care setting. A retrospective review was conducted of incidents reported to the UK National Reporting and Learning System (NRLS) that involved community pharmacy between April 2005 and August 2010. A work domain analysis of community pharmacy was constructed using observational data from 5 community pharmacies, technical documentation, and a focus group with 6 pharmacists. Reports from the NRLS were mapped onto the model generated by the work domain analysis. Approximately 14,709 incident reports meeting the selection criteria were retrieved from the NRLS. Descriptive statistical analysis of these reports found that almost all of the incidents involved medication and that the most frequently occurring error types were dose/strength errors, incorrect medication, and incorrect formulation. The work domain analysis identified 4 overall purposes for community pharmacy: business viability, health promotion and clinical services, provision of medication, and use of medication. These purposes were served by lower-order characteristics of the work system (such as the functions, processes and objects). The tasks most frequently implicated in the incident reports were those involving medication storage, assembly, or patient medication records. Combining the insights from different analytical methods improves understanding of patient safety problems. Incident reporting data can be used to identify general patterns, whereas the work domain analysis can generate information about the contextual factors that surround a critical task.

  15. What helps and hinders midwives in engaging with pregnant women about stopping smoking? A cross-sectional survey of perceived implementation difficulties among midwives in the North East of England.

    PubMed

    Beenstock, Jane; Sniehotta, Falko F; White, Martin; Bell, Ruth; Milne, Eugene Mg; Araujo-Soares, Vera

    2012-04-24

    Around 5,000 miscarriages and 300 perinatal deaths per year result from maternal smoking in the United Kingdom. In the northeast of England, 22% of women smoke at delivery compared to 14% nationally. Midwives have designated responsibilities to help pregnant women stop smoking. We aimed to assess perceived implementation difficulties regarding midwives' roles in smoking cessation in pregnancy. A self-completed, anonymous survey was sent to all midwives in northeast England (n = 1,358) that explores the theoretical explanations for implementation difficulties of four behaviours recommended in the National Institute for Health and Clinical Excellence (NICE) guidance: (a) asking a pregnant woman about her smoking behaviour, (b) referring to the stop-smoking service, (c) giving advice about smoking behaviour, and (d) using a carbon monoxide monitor. Questions covering Michie et al.'s theoretical domain framework (TDF), describing 11 domains of hypothesised behavioural determinants (i.e., 'knowledge', 'skills', 'social/professional role/identity', 'beliefs about capabilities', 'beliefs about consequences', 'motivation and goals', 'memory', 'attention and decision processes', 'environmental context and resources', 'social influences', 'emotion', and 'self-regulation/action planning'), were used to describe perceived implementation difficulties, predict self-reported implementation behaviours, and explore relationships with demographic and professional variables. The overall response rate was 43% (n = 589). The number of questionnaires analysed was 364, following removal of the delivery-unit midwives, who are not directly involved in providing smoking-cessation services. Participants reported few implementation difficulties, high levels of motivation for all four behaviours and identified smoking-cessation work with their role. Midwives were less certain about the consequences of, and the environmental context and resources available for, engaging in this work relative to other TDF domains. All domains were highly correlated. A principal component analysis showed that a single factor ('propensity to act'), derived from all domains, explained 66% of variance in theoretical domain measures. The 'propensity to act' was predictive of the self-reported behaviour 'Refer all women who smoke……to NHS Stop Smoking Services' and mediated the relationship between demographic variables, such as midwives' main place of work, and behaviour. Our findings advance understanding of what facilitates and inhibits midwives' guideline implementation behaviours in relation to smoking cessation and will inform the development of current practice and new interventions. Using the TDF as a self-completion questionnaire is innovative, and this study supports previous research that the TDF is an appropriate tool to understand the behaviour of healthcare professionals.

  16. Partial information decomposition as a spatiotemporal filter.

    PubMed

    Flecker, Benjamin; Alford, Wesley; Beggs, John M; Williams, Paul L; Beer, Randall D

    2011-09-01

    Understanding the mechanisms of distributed computation in cellular automata requires techniques for characterizing the emergent structures that underlie information processing in such systems. Recently, techniques from information theory have been brought to bear on this problem. Building on this work, we utilize the new technique of partial information decomposition to show that previous information-theoretic measures can confound distinct sources of information. We then propose a new set of filters and demonstrate that they more cleanly separate out the background domains, particles, and collisions that are typically associated with information storage, transfer, and modification in cellular automata.

  17. SemantEco: a semantically powered modular architecture for integrating distributed environmental and ecological data

    USGS Publications Warehouse

    Patton, Evan W.; Seyed, Patrice; Wang, Ping; Fu, Linyun; Dein, F. Joshua; Bristol, R. Sky; McGuinness, Deborah L.

    2014-01-01

    We aim to inform the development of decision support tools for resource managers who need to examine large complex ecosystems and make recommendations in the face of many tradeoffs and conflicting drivers. We take a semantic technology approach, leveraging background ontologies and the growing body of linked open data. In previous work, we designed and implemented a semantically enabled environmental monitoring framework called SemantEco and used it to build a water quality portal named SemantAqua. Our previous system included foundational ontologies to support environmental regulation violations and relevant human health effects. In this work, we discuss SemantEco’s new architecture that supports modular extensions and makes it easier to support additional domains. Our enhanced framework includes foundational ontologies to support modeling of wildlife observation and wildlife health impacts, thereby enabling deeper and broader support for more holistically examining the effects of environmental pollution on ecosystems. We conclude with a discussion of how, through the application of semantic technologies, modular designs will make it easier for resource managers to bring in new sources of data to support more complex use cases.

  18. A resource perspective on the work-home interface: the work-home resources model.

    PubMed

    ten Brummelhuis, Lieke L; Bakker, Arnold B

    2012-10-01

    The objective of this article is to provide a theoretical framework explaining positive and negative work-home processes integrally. Using insights from conservation of resources theory, we explain how personal resources (e.g., time, energy, and mood) link demanding and resourceful aspects of one domain to outcomes in the other domain. The resulting work-home resources (W-HR) model describes work-home conflict as a process whereby demands in one domain deplete personal resources and impede accomplishments in the other domain. Enrichment is described as a process of resource accumulation: Work and home resources increase personal resources. Those personal resources, in turn, can be utilized to improve home and work outcomes. Moreover, our resource approach to the work-home interface allows us to address two other issues that have thus far lacked a solid theoretical foundation. The W-HR model also explains how conditional factors such as personality and culture may influence the occurrence of work-home conflict and enrichment. Furthermore, the model allows us to examine how work-home conflict and enrichment develop over time. Finally, the model provides useful insights for other psychology subdisciplines, such as gender studies and developmental psychology.

  19. Cortical circuitry implementing graphical models.

    PubMed

    Litvak, Shai; Ullman, Shimon

    2009-11-01

    In this letter, we develop and simulate a large-scale network of spiking neurons that approximates the inference computations performed by graphical models. Unlike previous related schemes, which used sum and product operations in either the log or linear domains, the current model uses an inference scheme based on the sum and maximization operations in the log domain. Simulations show that using these operations, a large-scale circuit, which combines populations of spiking neurons as basic building blocks, is capable of finding close approximations to the full mathematical computations performed by graphical models within a few hundred milliseconds. The circuit is general in the sense that it can be wired for any graph structure, it supports multistate variables, and it uses standard leaky integrate-and-fire neuronal units. Following previous work, which proposed relations between graphical models and the large-scale cortical anatomy, we focus on the cortical microcircuitry and propose how anatomical and physiological aspects of the local circuitry may map onto elements of the graphical model implementation. We discuss in particular the roles of three major types of inhibitory neurons (small fast-spiking basket cells, large layer 2/3 basket cells, and double-bouquet neurons), subpopulations of strongly interconnected neurons with their unique connectivity patterns in different cortical layers, and the possible role of minicolumns in the realization of the population-based maximum operation.

  20. The Structure of Working Memory Abilities across the Adult Life Span

    PubMed Central

    Hale, Sandra; Rose, Nathan S.; Myerson, Joel; Strube, Michael J; Sommers, Mitchell; Tye-Murray, Nancy; Spehar, Brent

    2010-01-01

    The present study addresses three questions regarding age differences in working memory: (1) whether performance on complex span tasks decreases as a function of age at a faster rate than performance on simple span tasks; (2) whether spatial working memory decreases at a faster rate than verbal working memory; and (3) whether the structure of working memory abilities is different for different age groups. Adults, ages 20–89 (n=388), performed three simple and three complex verbal span tasks and three simple and three complex spatial memory tasks. Performance on the spatial tasks decreased at faster rates as a function of age than performance on the verbal tasks, but within each domain, performance on complex and simple span tasks decreased at the same rates. Confirmatory factor analyses revealed that domain-differentiated models yielded better fits than models involving domain-general constructs, providing further evidence of the need to distinguish verbal and spatial working memory abilities. Regardless of which domain-differentiated model was examined, and despite the faster rates of decrease in the spatial domain, age group comparisons revealed that the factor structure of working memory abilities was highly similar in younger and older adults and showed no evidence of age-related dedifferentiation. PMID:21299306

  1. Child Safety Reference Frameworks: a Policy Tool for Child Injury Prevention at the Sub-national Level.

    PubMed

    Scholtes, Beatrice; Schröder-Bäck, Peter; Mackay, Morag; Vincenten, Joanne; Brand, Helmut

    2017-06-01

    The aim of this paper is to present the Child Safety Reference Frameworks (CSRF), a policy advice tool that places evidence-based child safety interventions, applicable at the sub-national level, into a framework resembling the Haddon Matrix. The CSRF is based on work done in previous EU funded projects, which we have adapted to the field of child safety. The CSRF were populated following a literature review. Four CSRF were developed for four domains of child safety: road, water and home safety, and intentional injury prevention. The CSRF can be used as a reference, assessment and comparative tool by child safety practitioners and policy makers working at the sub-national level. Copyright© by the National Institute of Public Health, Prague 2017

  2. The allosteric communication pathways in KIX domain of CBP.

    PubMed

    Palazzesi, Ferruccio; Barducci, Alessandro; Tollinger, Martin; Parrinello, Michele

    2013-08-27

    Allosteric regulation plays an important role in a myriad of biomacromolecular processes. Specifically, in a protein, the process of allostery refers to the transmission of a local perturbation, such as ligand binding, to a distant site. Decades after the discovery of this phenomenon, models built on static images of proteins are being reconsidered with the knowledge that protein dynamics plays an important role in its function. Molecular dynamics simulations are a valuable tool for studying complex biomolecular systems, providing an atomistic description of their structure and dynamics. Unfortunately, their predictive power has been limited by the complexity of the biomolecule free-energy surface and by the length of the allosteric timescale (in the order of milliseconds). In this work, we are able to probe the origins of the allosteric changes that transcription factor mixed lineage leukemia (MLL) causes to the interactions of KIX domain of CREB-binding protein (CBP) with phosphorylated kinase inducible domain (pKID), by combing all-atom molecular dynamics with enhanced sampling methods recently developed in our group. We discuss our results in relation to previous NMR studies. We also develop a general simulations protocol to study allosteric phenomena and many other biological processes that occur in the micro/milliseconds timescale.

  3. Atmospheric Turbulence Modeling for Aero Vehicles: Fractional Order Fits

    NASA Technical Reports Server (NTRS)

    Kopasakis, George

    2015-01-01

    Atmospheric turbulence models are necessary for the design of both inlet/engine and flight controls, as well as for studying coupling between the propulsion and the vehicle structural dynamics for supersonic vehicles. Models based on the Kolmogorov spectrum have been previously utilized to model atmospheric turbulence. In this paper, a more accurate model is developed in its representative fractional order form, typical of atmospheric disturbances. This is accomplished by first scaling the Kolmogorov spectral to convert them into finite energy von Karman forms and then by deriving an explicit fractional circuit-filter type analog for this model. This circuit model is utilized to develop a generalized formulation in frequency domain to approximate the fractional order with the products of first order transfer functions, which enables accurate time domain simulations. The objective of this work is as follows. Given the parameters describing the conditions of atmospheric disturbances, and utilizing the derived formulations, directly compute the transfer function poles and zeros describing these disturbances for acoustic velocity, temperature, pressure, and density. Time domain simulations of representative atmospheric turbulence can then be developed by utilizing these computed transfer functions together with the disturbance frequencies of interest.

  4. Atmospheric Turbulence Modeling for Aero Vehicles: Fractional Order Fits

    NASA Technical Reports Server (NTRS)

    Kopasakis, George

    2010-01-01

    Atmospheric turbulence models are necessary for the design of both inlet/engine and flight controls, as well as for studying coupling between the propulsion and the vehicle structural dynamics for supersonic vehicles. Models based on the Kolmogorov spectrum have been previously utilized to model atmospheric turbulence. In this paper, a more accurate model is developed in its representative fractional order form, typical of atmospheric disturbances. This is accomplished by first scaling the Kolmogorov spectral to convert them into finite energy von Karman forms and then by deriving an explicit fractional circuit-filter type analog for this model. This circuit model is utilized to develop a generalized formulation in frequency domain to approximate the fractional order with the products of first order transfer functions, which enables accurate time domain simulations. The objective of this work is as follows. Given the parameters describing the conditions of atmospheric disturbances, and utilizing the derived formulations, directly compute the transfer function poles and zeros describing these disturbances for acoustic velocity, temperature, pressure, and density. Time domain simulations of representative atmospheric turbulence can then be developed by utilizing these computed transfer functions together with the disturbance frequencies of interest.

  5. Efficient reversible data hiding in encrypted image with public key cryptosystem

    NASA Astrophysics Data System (ADS)

    Xiang, Shijun; Luo, Xinrong

    2017-12-01

    This paper proposes a new reversible data hiding scheme for encrypted images by using homomorphic and probabilistic properties of Paillier cryptosystem. The proposed method can embed additional data directly into encrypted image without any preprocessing operations on original image. By selecting two pixels as a group for encryption, data hider can retrieve the absolute differences of groups of two pixels by employing a modular multiplicative inverse method. Additional data can be embedded into encrypted image by shifting histogram of the absolute differences by using the homomorphic property in encrypted domain. On the receiver side, legal user can extract the marked histogram in encrypted domain in the same way as data hiding procedure. Then, the hidden data can be extracted from the marked histogram and the encrypted version of original image can be restored by using inverse histogram shifting operations. Besides, the marked absolute differences can be computed after decryption for extraction of additional data and restoration of original image. Compared with previous state-of-the-art works, the proposed scheme can effectively avoid preprocessing operations before encryption and can efficiently embed and extract data in encrypted domain. The experiments on the standard image files also certify the effectiveness of the proposed scheme.

  6. Specific intermolecular interactions of conserved water molecules with amino acids in the Galectin-1 carbohydrate recognition domain

    NASA Astrophysics Data System (ADS)

    Di Lella, Santiago; Petruk, Ariel A.; Armiño, Diego J. Alonso de; Álvarez, Rosa M. S.

    2010-08-01

    Water molecules, rigidly associated to protein surfaces, play a key role in stabilizing biomolecules and participating in their biological functions. Recent studies on the solvation properties of the carbohydrate recognition domain of Galectin-1 by means of molecular dynamic simulations have revealed the existence of several water sites which were well correlated to both the bound water molecules observed in the crystal structure of the protein in the free state and to some of the hydroxyl groups of the carbohydrate ligand observed in the crystal structure of the complexed protein. In this work, we present a study using quantum mechanical methods (B3LYP/6-311++G(3df,3dp)//B3LYP/6-31+G(d)) to determine the energy involved in the binding of these water molecules to specific amino acids in the carbohydrate recognition domain of the protein. By modeling the hydroxyl groups of the carbohydrate by methanol, the energies associated to the local interactions between the ligand and the protein have been evaluated by replacing specific water molecules with methanol. The values of the binding energies have been compared to those previously obtained by the molecular dynamic method.

  7. Final Report: Subcontract B623868 Algebraic Multigrid solvers for coupled PDE systems

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

    Brannick, J.

    The Pennsylvania State University (“Subcontractor”) continued to work on the design of algebraic multigrid solvers for coupled systems of partial differential equations (PDEs) arising in numerical modeling of various applications, with a main focus on solving the Dirac equation arising in Quantum Chromodynamics (QCD). The goal of the proposed work was to develop combined geometric and algebraic multilevel solvers that are robust and lend themselves to efficient implementation on massively parallel heterogeneous computers for these QCD systems. The research in these areas built on previous works, focusing on the following three topics: (1) the development of parallel full-multigrid (PFMG) andmore » non-Galerkin coarsening techniques in this frame work for solving the Wilson Dirac system; (2) the use of these same Wilson MG solvers for preconditioning the Overlap and Domain Wall formulations of the Dirac equation; and (3) the design and analysis of algebraic coarsening algorithms for coupled PDE systems including Stokes equation, Maxwell equation and linear elasticity.« less

  8. Remembering faces and scenes: The mixed-category advantage in visual working memory.

    PubMed

    Jiang, Yuhong V; Remington, Roger W; Asaad, Anthony; Lee, Hyejin J; Mikkalson, Taylor C

    2016-09-01

    We examined the mixed-category memory advantage for faces and scenes to determine how domain-specific cortical resources constrain visual working memory. Consistent with previous findings, visual working memory for a display of 2 faces and 2 scenes was better than that for a display of 4 faces or 4 scenes. This pattern was unaffected by manipulations of encoding duration. However, the mixed-category advantage was carried solely by faces: Memory for scenes was not better when scenes were encoded with faces rather than with other scenes. The asymmetry between faces and scenes was found when items were presented simultaneously or sequentially, centrally, or peripherally, and when scenes were drawn from a narrow category. A further experiment showed a mixed-category advantage in memory for faces and bodies, but not in memory for scenes and objects. The results suggest that unique category-specific interactions contribute significantly to the mixed-category advantage in visual working memory. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  9. A qualitative study of the interactions among the psychosocial work environment and family, community and services for workers with low mental health.

    PubMed

    Mackenzie, Catherine R; Keuskamp, Dominic; Ziersch, Anna M; Baum, Fran E; Popay, Jennie

    2013-09-03

    The psychosocial work environment can benefit and harm mental health. Poor psychosocial work environments and high level work-family conflict are both associated with poor mental health, yet little is known about how people with poor mental health manage the interactions among multiple life domains. This study explores the interfaces among paid work, family, community and support services and their combined effects on mental health. We conducted 21 in-depth semi-structured interviews with people identified as having poor mental health to examine their experiences of paid employment and mental health and wellbeing in the context of their daily lives. The employment-related psychosocial work environment, particularly workplace relationships, employment security and degree of control over hours, strongly affected participants' mental health. The interfaces among the life domains of family, community and access to support services suggest that effects on mental health differ according to: time spent in each domain, the social, psychological and physical spaces where domain activities take place, life stage and the power available to participants in their multiple domains. This paper is based on a framework analysis of all the interviews, and vignettes of four cases. Cases were selected to represent different types of relationships among the domains and how interactions among them either mitigated and/or exacerbated mental health effects of psychosocial work environments. Examining domain interactions provides greater explanatory capacity for understanding how people with low mental health manage their lives than restricting the research to the separate impacts of the psychosocial work environment or work-family conflict. The extent to which people can change the conditions under which they engage in paid work and participate in family and social life is significantly affected by the extent to which their employment position affords them latitude. Policies that provide psychosocial protections to workers that enable them to make changes or complaints without detrimental repercussions (such as vilification or job loss) and increase access to welfare benefits and support services could improve mental health among people with paid work. These policies would have particularly important effects for those in lower socioeconomic status positions.

  10. A qualitative study of the interactions among the psychosocial work environment and family, community and services for workers with low mental health

    PubMed Central

    2013-01-01

    Background The psychosocial work environment can benefit and harm mental health. Poor psychosocial work environments and high level work-family conflict are both associated with poor mental health, yet little is known about how people with poor mental health manage the interactions among multiple life domains. This study explores the interfaces among paid work, family, community and support services and their combined effects on mental health. Methods We conducted 21 in-depth semi-structured interviews with people identified as having poor mental health to examine their experiences of paid employment and mental health and wellbeing in the context of their daily lives. Results The employment-related psychosocial work environment, particularly workplace relationships, employment security and degree of control over hours, strongly affected participants’ mental health. The interfaces among the life domains of family, community and access to support services suggest that effects on mental health differ according to: time spent in each domain, the social, psychological and physical spaces where domain activities take place, life stage and the power available to participants in their multiple domains. This paper is based on a framework analysis of all the interviews, and vignettes of four cases. Cases were selected to represent different types of relationships among the domains and how interactions among them either mitigated and/or exacerbated mental health effects of psychosocial work environments. Conclusions Examining domain interactions provides greater explanatory capacity for understanding how people with low mental health manage their lives than restricting the research to the separate impacts of the psychosocial work environment or work-family conflict. The extent to which people can change the conditions under which they engage in paid work and participate in family and social life is significantly affected by the extent to which their employment position affords them latitude. Policies that provide psychosocial protections to workers that enable them to make changes or complaints without detrimental repercussions (such as vilification or job loss) and increase access to welfare benefits and support services could improve mental health among people with paid work. These policies would have particularly important effects for those in lower socioeconomic status positions. PMID:24004446

  11. Morintides: cargo-free chitin-binding peptides from Moringa oleifera.

    PubMed

    Kini, Shruthi G; Wong, Ka H; Tan, Wei Liang; Xiao, Tianshu; Tam, James P

    2017-03-31

    Hevein-like peptides are a family of cysteine-rich and chitin-binding peptides consisting of 29-45 amino acids. Their chitin-binding property is essential for plant defense against fungi. Based on the number of cysteine residues in their sequences, they are divided into three sub-families: 6C-, 8C- and 10C-hevein-like peptides. All three subfamilies contain a three-domain precursor comprising a signal peptide, a mature hevein-like peptide and a C-terminal domain comprising a hinge region with protein cargo in 8C- and 10C-hevein-like peptides. Here we report the isolation and characterization of two novel 8C-hevein-like peptides, designated morintides (mO1 and mO2), from the drumstick tree Moringa oleifera, a drought-resistant tree belonging to the Moringaceae family. Proteomic analysis revealed that morintides comprise 44 amino acid residues and are rich in cysteine, glycine and hydrophilic amino acid residues such as asparagine and glutamine. Morintides are resistant to thermal and enzymatic degradation, able to bind to chitin and inhibit the growth of phyto-pathogenic fungi. Transcriptomic analysis showed that they contain a three-domain precursor comprising an endoplasmic reticulum (ER) signal sequence, a mature peptide domain and a C-terminal domain. A striking feature distinguishing morintides from other 8C-hevein-like peptides is a short and protein-cargo-free C-terminal domain. Previously, a similar protein-cargo-free C-terminal domain has been observed only in ginkgotides, the 8C-hevein-like peptides from a gymnosperm Ginkgo biloba. Thus, morintides, with a cargo-free C-terminal domain, are a stand-alone class of 8C-hevein-like peptides from angiosperms. Our results expand the existing library of hevein-like peptides and shed light on molecular diversity within the hevein-like peptide family. Our work also sheds light on the anti-fungal activity and stability of 8C-hevein-like peptides.

  12. Crystal structure of the Src family kinase Hck SH3-SH2 linker regulatory region supports an SH3-dominant activation mechanism.

    PubMed

    Alvarado, John J; Betts, Laurie; Moroco, Jamie A; Smithgall, Thomas E; Yeh, Joanne I

    2010-11-12

    Most mammalian cell types depend on multiple Src family kinases (SFKs) to regulate diverse signaling pathways. Strict control of SFK activity is essential for normal cellular function, and loss of kinase regulation contributes to several forms of cancer and other diseases. Previous x-ray crystal structures of the SFKs c-Src and Hck revealed that intramolecular association of their Src homology (SH) 3 domains and SH2 kinase linker regions has a key role in down-regulation of kinase activity. However, the amino acid sequence of the Hck linker represents a suboptimal ligand for the isolated SH3 domain, suggesting that it may form the polyproline type II helical conformation required for SH3 docking only in the context of the intact structure. To test this hypothesis directly, we determined the crystal structure of a truncated Hck protein consisting of the SH2 and SH3 domains plus the linker. Despite the absence of the kinase domain, the structures and relative orientations of the SH2 and SH3 domains in this shorter protein were very similar to those observed in near full-length, down-regulated Hck. However, the SH2 kinase linker adopted a modified topology and failed to engage the SH3 domain. This new structure supports the idea that these noncatalytic regions work together as a "conformational switch" that modulates kinase activity in a manner unique to the SH3 domain and linker topologies present in the intact Hck protein. Our results also provide fresh structural insight into the facile induction of Hck activity by HIV-1 Nef and other Hck SH3 domain binding proteins and implicate the existence of innate conformational states unique to individual Src family members that "fine-tune" their sensitivities to activation by SH3-based ligands.

  13. Wives Domain-Specific "Marriage Work" with Friends and Spouses: Links to Marital Quality

    ERIC Educational Resources Information Center

    Proulx, Christine M.; Helms, Heather M.; Payne, C. Chris

    2004-01-01

    This study examined the friendship experiences of 52 wives and mothers, with particular attention given to wives' marriage work (discussions about concerns and problems in the marriage) in 10 domains with friends and spouses. A series of within-subjects repeated measures analyses of variance (ANOVAs) indicated that in all but two domains, wives…

  14. Support at Work and Home: The Path to Satisfaction through Balance

    ERIC Educational Resources Information Center

    Ferguson, Merideth; Carlson, Dawn; Zivnuska, Suzanne; Whitten, Dwayne

    2012-01-01

    This study examines social support (from both coworkers and partners) and its path to satisfaction through work-family balance. This study fills a gap by explaining how support impacts satisfaction in the same domain, across domains, and how it crosses over to impact the partner's domain. Using a matched dataset of 270 job incumbents and their…

  15. Neurocognitive outcomes in neurofibromatosis clinical trials: Recommendations for the domain of attention.

    PubMed

    Walsh, Karin S; Janusz, Jennifer; Wolters, Pamela L; Martin, Staci; Klein-Tasman, Bonita P; Toledo-Tamula, Mary Anne; Thompson, Heather L; Payne, Jonathan M; Hardy, Kristina K; de Blank, Peter; Semerjian, Claire; Gray, Laura Schaffner; Solomon, Sondra E; Ullrich, Nicole

    2016-08-16

    Neurofibromatosis type 1 (NF1) is associated with neurocognitive deficits that can impact everyday functioning of children, adolescents, and adults with this disease. However, there is little agreement regarding measures to use as cognitive endpoints in clinical trials. This article describes the work of the Neurocognitive Committee of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration. The goal of this committee is to identify standardized and specific cognitive assessment tools for use in NF clinical trials. The committee first identified cognitive domains relevant to NF1 and prioritized attention as the first domain of focus given prior and current trends in NF1 cognitive clinical trials. Performance measures and behavioral rating questionnaires of attention were reviewed by the group using established criteria to assess patient characteristics, psychometric properties, and feasibility. The highest rated tests underwent side-by-side comparison. The Digit Span subtest from the Wechsler scales was given the highest ratings of the performance measures due to its good psychometrics, feasibility, utility across a wide age range, and extensive use in previous research. The Conners scales achieved the highest ratings of the behavioral questionnaires for similar reasons. Future articles will focus on other cognitive domains, with the ultimate goal of achieving agreement for cognitive endpoints that can be used across NF clinical trials. © 2016 American Academy of Neurology.

  16. Segmental front line dynamics of randomly pinned ferroelastic domain walls

    NASA Astrophysics Data System (ADS)

    Puchberger, S.; Soprunyuk, V.; Schranz, W.; Carpenter, M. A.

    2018-01-01

    Dynamic mechanical analysis (DMA) measurements as a function of temperature, frequency, and dynamic force amplitude are used to perform a detailed study of the domain wall motion in LaAlO3. In previous DMA measurements Harrison et al. [Phys. Rev. B 69, 144101 (2004), 10.1103/PhysRevB.69.144101] found evidence for dynamic phase transitions of ferroelastic domain walls in LaAlO3. In the present work we focus on the creep-to-relaxation region of domain wall motion using two complementary methods. We determine, in addition to dynamic susceptibility data, waiting time distributions of strain jerks during slowly increasing stress. These strain jerks, which result from self-similar avalanches close to the depinning threshold, follow a power-law behavior with an energy exponent ɛ =1.7 ±0.1 . Also, the distribution of waiting times between events follows a power law N (tw) ∝tw-(n +1 ) with an exponent n =0.9 , which transforms to a power law of susceptibility S (ω ) ∝ω-n . The present dynamic susceptibility data can be well fitted with a power law, with the same exponent (n =0.9 ) up to a characteristic frequency ω ≈ω* , where a crossover from stochastic DW motion to the pinned regime is well described using the scaling function of Fedorenko et al. [Phys. Rev. B 70, 224104 (2004), 10.1103/PhysRevB.70.224104].

  17. Dynamic Motion and Communication in the Streptococcal C1 Phage Lysin, PlyC

    PubMed Central

    Reboul, Cyril F.; Cowieson, Nathan P.; Costa, Mauricio G. S.; Kass, Itamar; Jackson, Colin; Perahia, David; Buckle, Ashley M.; McGowan, Sheena

    2015-01-01

    The growing problem of antibiotic resistance underlies the critical need to develop new treatments to prevent and control resistant bacterial infection. Exogenous application of bacteriophage lysins results in rapid and specific destruction of Gram-positive bacteria and therefore lysins represent novel antibacterial agents. The PlyC phage lysin is the most potent lysin characterized to date and can rapidly lyse Group A, C and E streptococci. Previously, we have determined the X-ray crystal structure of PlyC, revealing a complicated and unique arrangement of nine proteins. The scaffold features a multimeric cell-wall docking assembly bound to two catalytic domains that communicate and work synergistically. However, the crystal structure appeared to be auto-inhibited and raised important questions as to the mechanism underlying its extreme potency. Here we use small angle X-ray scattering (SAXS) and reveal that the conformational ensemble of PlyC in solution is different to that in the crystal structure. We also investigated the flexibility of the enzyme using both normal mode (NM) analysis and molecular dynamics (MD) simulations. Consistent with our SAXS data, MD simulations show rotational dynamics of both catalytic domains, and implicate inter-domain communication in achieving a substrate-ready conformation required for enzyme function. Our studies therefore provide insights into how the domains in the PlyC holoenzyme may act together to achieve its extraordinary potency. PMID:26470022

  18. Incorporation of rare earth elements in titanite: Stabilization of the A2/a dimorph by creation of antiphase boundaries

    USGS Publications Warehouse

    Hughes, J.M.; Bloodaxe, E.S.; Hanchar, J.M.; Foord, E.E.

    1997-01-01

    The atomic arrangement of a natural rare-earth-rich titanite and two synthetic rare-earth-doped titanites have been refined in space group A2/a, and the atomic arrangement of an undoped P21/a synthetic titanite was also refined for comparison. Previous work has shown that titanite possesses a domain structure, with domains formed of like-displaced Ti atoms in the [100] octahedral chains. P21/a titanite results when the crystal is formed of a single domain, but as Ti-reversal sites occur in the octahedral chain the apparent A2/a structure results from the average of antiphase domains. Antiphase boundaries occur at O1, which is alternately overbonded or underbonded at the boundaries, depending on the displacement of the neighboring Ti atoms. Type 2 antiphase boundaries exist where two Ti atoms are displaced away from the intervening O1 atom and are energetically unfavorable because of underbonding of that O1 atom. However, substitution of a trivalent rare earth element in the adjacent Ca2+ site relieves that underbonding, favoring the creation of type 2 antiphase boundaries and stabilization of the A2/a dimorph. The results of high-precision crystal structure analyses demonstrate that rare earth substituents for Ca stabilize the A2/a dimorph at lower substitution levels than required for octahedral substitutions.

  19. Differential pleiotropy and HOX functional organization.

    PubMed

    Sivanantharajah, Lovesha; Percival-Smith, Anthony

    2015-02-01

    Key studies led to the idea that transcription factors are composed of defined modular protein motifs or domains, each with separable, unique function. During evolution, the recombination of these modular domains could give rise to transcription factors with new properties, as has been shown using recombinant molecules. This archetypic, modular view of transcription factor organization is based on the analyses of a few transcription factors such as GAL4, which may represent extreme exemplars rather than an archetype or the norm. Recent work with a set of Homeotic selector (HOX) proteins has revealed differential pleiotropy: the observation that highly-conserved HOX protein motifs and domains make small, additive, tissue specific contributions to HOX activity. Many of these differentially pleiotropic HOX motifs may represent plastic sequence elements called short linear motifs (SLiMs). The coupling of differential pleiotropy with SLiMs, suggests that protein sequence changes in HOX transcription factors may have had a greater impact on morphological diversity during evolution than previously believed. Furthermore, differential pleiotropy may be the genetic consequence of an ensemble nature of HOX transcription factor allostery, where HOX proteins exist as an ensemble of states with the capacity to integrate an extensive array of developmental information. Given a new structural model for HOX functional domain organization, the properties of the archetypic TF may require reassessment. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. The CW domain, a structural module shared amongst vertebrates, vertebrate-infecting parasites and higher plants.

    PubMed

    Perry, Jason; Zhao, Yunde

    2003-11-01

    A previously undetected domain, named CW for its conserved cysteine and tryptophan residues, appears to be a four-cysteine zinc-finger motif found exclusively in vertebrates, vertebrate-infecting parasites and higher plants. Of the twelve distinct nuclear protein families that comprise the CW domain-containing superfamily, only the microrchida (MORC) family has begun to be characterized. However, several families contain other domains suggesting a relationship between the CW domain and either chromatin methylation status or early embryonic development.

  1. A targeted mutation within the feline leukemia virus (FeLV) envelope protein immunosuppressive domain to improve a canarypox virus-vectored FeLV vaccine.

    PubMed

    Schlecht-Louf, Géraldine; Mangeney, Marianne; El-Garch, Hanane; Lacombe, Valérie; Poulet, Hervé; Heidmann, Thierry

    2014-01-01

    We previously delineated a highly conserved immunosuppressive (IS) domain within murine and primate retroviral envelope proteins that is critical for virus propagation in vivo. The envelope-mediated immunosuppression was assessed by the ability of the proteins, when expressed by allogeneic tumor cells normally rejected by engrafted mice, to allow these cells to escape, at least transiently, immune rejection. Using this approach, we identified key residues whose mutation (i) specifically abolishes immunosuppressive activity without affecting the "mechanical" function of the envelope protein and (ii) significantly enhances humoral and cellular immune responses elicited against the virus. The objective of this work was to study the immunosuppressive activity of the envelope protein (p15E) of feline leukemia virus (FeLV) and evaluate the effect of its abolition on the efficacy of a vaccine against FeLV. Here we demonstrate that the FeLV envelope protein is immunosuppressive in vivo and that this immunosuppressive activity can be "switched off" by targeted mutation of a specific amino acid. As a result of the introduction of the mutated envelope sequence into a previously well characterized canarypox virus-vectored vaccine (ALVAC-FeLV), the frequency of vaccine-induced FeLV-specific gamma interferon (IFN-γ)-producing cells was increased, whereas conversely, the frequency of vaccine-induced FeLV-specific interleukin-10 (IL-10)-producing cells was reduced. This shift in the IFN-γ/IL-10 response was associated with a higher efficacy of ALVAC-FeLV against FeLV infection. This study demonstrates that FeLV p15E is immunosuppressive in vivo, that the immunosuppressive domain of p15E can modulate the FeLV-specific immune response, and that the efficacy of FeLV vaccines can be enhanced by inhibiting the immunosuppressive activity of the IS domain through an appropriate mutation.

  2. Quantitation of ortho-cresyl phosphate adducts to butyrylcholinesterase in human serum by immunomagnetic-UHPLC-MS/MS.

    PubMed

    Johnson, Darryl; Carter, Melissa D; Crow, Brian S; Isenberg, Samantha L; Graham, Leigh Ann; Erol, H Akin; Watson, Caroline M; Pantazides, Brooke G; van der Schans, Marcel J; Langenberg, Jan P; Noort, Daan; Blake, Thomas A; Thomas, Jerry D; Johnson, Rudolph C

    2015-04-01

    Tri-ortho-cresyl phosphate (ToCP) is an anti-wear, flame retardant additive used in industrial lubricants, hydraulic fluids and gasoline. The neurotoxic effects of ToCP arise from the liver-activated metabolite 2-(o-cresyl)-4H-1,3,2-benzodioxaphosphoran-2-one (cresyl saligenin phosphate or CBDP), which inhibits esterase enzymes including butyrylcholinesterase (BChE). Following BChE adduction, CBDP undergoes hydrolysis to form the aged adduct ortho-cresyl phosphoserine (oCP-BChE), thus providing a biomarker of CBDP exposure. Previous studies have identified ToCP in aircraft cabin and cockpit air, but assessing human exposure has been hampered by the lack of a laboratory assay to confirm exposure. This work presents the development of an immunomagnetic-UHPLC-MS/MS method for the quantitation of unadducted BChE and the long-term CBDP biomarker, oCP-BChE, in human serum. The method has a reportable range from 2.0 ng/ml to 150 ng/ml, which is consistent with the sensitivity of methods used to detect organophosphorus nerve agent protein adducts. The assay demonstrated high intraday and interday accuracy (≥85%) and precision (RSD ≤ 15%) across the calibration range. The method was developed for future analyses of potential human exposure to CBDP. Analysis of human serum inhibited in vitro with CBDP demonstrated that the oCP-BChE adduct was stable for at least 72 h at 4, 22 and 37 °C. Compared to a previously reported assay, this method requires 75% less sample volume, reduces analysis time by a factor of 20 and demonstrates a threefold improvement in sensitivity. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  3. Classification of intrinsic variables. IX - The Cepheid domain

    NASA Astrophysics Data System (ADS)

    Eggen, O. J.

    1983-03-01

    Intermediate band, Hβ and RI observations have been obtained throughout the cycle of variation for 135 high mass, long-period and short-period cepheids (LPC and SPC). This material, together with the observations previously discussed for some 100 ultrashort periods cepheids (USPC), is used to delineate the cepheid domain in the (β,[C1]) and (MBol,log Te) planes. The independently derived luminosity calibrations for bright giants and supergiants previously published are found to closely reproduce the luminosities derived from the Sandage-Tammann PL relation for most variables. The theoretical "fundamental blue edge," computed by Iben and Tuggle with Y = 0.38, closely represents the blue edge of the cepheid domain.

  4. Exact Solutions of Coupled Multispecies Linear Reaction–Diffusion Equations on a Uniformly Growing Domain

    PubMed Central

    Simpson, Matthew J.; Sharp, Jesse A.; Morrow, Liam C.; Baker, Ruth E.

    2015-01-01

    Embryonic development involves diffusion and proliferation of cells, as well as diffusion and reaction of molecules, within growing tissues. Mathematical models of these processes often involve reaction–diffusion equations on growing domains that have been primarily studied using approximate numerical solutions. Recently, we have shown how to obtain an exact solution to a single, uncoupled, linear reaction–diffusion equation on a growing domain, 0 < x < L(t), where L(t) is the domain length. The present work is an extension of our previous study, and we illustrate how to solve a system of coupled reaction–diffusion equations on a growing domain. This system of equations can be used to study the spatial and temporal distributions of different generations of cells within a population that diffuses and proliferates within a growing tissue. The exact solution is obtained by applying an uncoupling transformation, and the uncoupled equations are solved separately before applying the inverse uncoupling transformation to give the coupled solution. We present several example calculations to illustrate different types of behaviour. The first example calculation corresponds to a situation where the initially–confined population diffuses sufficiently slowly that it is unable to reach the moving boundary at x = L(t). In contrast, the second example calculation corresponds to a situation where the initially–confined population is able to overcome the domain growth and reach the moving boundary at x = L(t). In its basic format, the uncoupling transformation at first appears to be restricted to deal only with the case where each generation of cells has a distinct proliferation rate. However, we also demonstrate how the uncoupling transformation can be used when each generation has the same proliferation rate by evaluating the exact solutions as an appropriate limit. PMID:26407013

  5. Exact Solutions of Coupled Multispecies Linear Reaction-Diffusion Equations on a Uniformly Growing Domain.

    PubMed

    Simpson, Matthew J; Sharp, Jesse A; Morrow, Liam C; Baker, Ruth E

    2015-01-01

    Embryonic development involves diffusion and proliferation of cells, as well as diffusion and reaction of molecules, within growing tissues. Mathematical models of these processes often involve reaction-diffusion equations on growing domains that have been primarily studied using approximate numerical solutions. Recently, we have shown how to obtain an exact solution to a single, uncoupled, linear reaction-diffusion equation on a growing domain, 0 < x < L(t), where L(t) is the domain length. The present work is an extension of our previous study, and we illustrate how to solve a system of coupled reaction-diffusion equations on a growing domain. This system of equations can be used to study the spatial and temporal distributions of different generations of cells within a population that diffuses and proliferates within a growing tissue. The exact solution is obtained by applying an uncoupling transformation, and the uncoupled equations are solved separately before applying the inverse uncoupling transformation to give the coupled solution. We present several example calculations to illustrate different types of behaviour. The first example calculation corresponds to a situation where the initially-confined population diffuses sufficiently slowly that it is unable to reach the moving boundary at x = L(t). In contrast, the second example calculation corresponds to a situation where the initially-confined population is able to overcome the domain growth and reach the moving boundary at x = L(t). In its basic format, the uncoupling transformation at first appears to be restricted to deal only with the case where each generation of cells has a distinct proliferation rate. However, we also demonstrate how the uncoupling transformation can be used when each generation has the same proliferation rate by evaluating the exact solutions as an appropriate limit.

  6. Objective Work-Nonwork Conflict: From Incompatible Demands to Decreased Work Role Performance

    ERIC Educational Resources Information Center

    Haun, Sascha; Steinmetz, Holger; Dormann, Christian

    2011-01-01

    Research on work-nonwork conflict (WNC) is based on the assumption that incompatible demands from the work and the nonwork domain hamper role performance. This assumption implies that role demands from both domains interact in predicting role performance, but research has been largely limited to main effects. In this multi-source study, we analyze…

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

    PubMed Central

    2010-01-01

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

  8. Characterization of the RcsC sensor kinase from Erwinia amylovora and other enterobacteria

    USDA-ARS?s Scientific Manuscript database

    RcsC is a hybrid sensor kinase which contains a sensor domain, a histidine kinase domain and a receiver domain. We have previously demonstrated that, while the Erwinia amylovora rcsC mutant produces more amylovoran than the wild type strain in vitro, the mutant remains avirulent on both immature pea...

  9. Health Conditions and Factors Related to the Work Ability of Teachers

    PubMed Central

    VEDOVATO, Tatiana Giovanelli; MONTEIRO, Inês

    2014-01-01

    This is a cross-sectional study conducted with 258 teachers from nine state schools in two municipalities of São Paulo state with the purpose of assessing their work ability. A questionnaire with socio-demographic and health/work conditions data and the Work Ability Index (WAI) was performed. Most teachers were females, 41.9 yr old on average (SD 9.4), and with an undergraduate degree (95.7%). The work ability was considered good for 42.6% and moderate/low for 35.3%. In linear regressions models, which used the two domain model, the significant variables for a decrease in WAI were: individual perception of a worsening in the health situation (p<0001), having children (p=0.0003 / p=0.0001), difficulty in sleeping well at night (p=0.0009 / p=0.0014), history of physical pain in the previous six months (p<0.0001 / p<0.0001), being a teacher with a contract (p=0.0007) and working as a teacher for a longer time. (p=0.0183). Public investments on the work conditions of teachers are important to recover and to maintain their work ability. PMID:24429517

  10. Disentangling the Impact of Artistic Creativity on Creative Thinking, Working Memory, Attention, and Intelligence: Evidence for Domain-Specific Relationships with a New Self-Report Questionnaire

    PubMed Central

    Lunke, Katrin; Meier, Beat

    2016-01-01

    The goal of the present study was to take a new look at the relationship between creativity and cognitive functioning. Based on models that have postulated domain- and sub-domain-structures for different forms of creativity, like scientific, technical or artistic creativity with cognitive functions as important basis, we developed a new questionnaire. The Artistic Creativity Domains Compendium (ACDC) assesses interest, ability and performance in a distinct way for different domains of artistic creativity. We present the data of 270 adults tested with the ACDC, standard tests of divergent and convergent thinking, and tests of cognitive functions. We present fine-grained analyses on the internal and external validity of the ACDC and on the relationships between creativity, working memory, attention, and intelligence. Our results indicate domain-specific associations between creativity and attention as well as working memory. We conclude that the ACDC is a valid instrument to assess artistic creativity and that a fine-grained analysis reveals distinct patterns of relationships between separate domains of creativity and cognition. PMID:27516745

  11. Disentangling the Impact of Artistic Creativity on Creative Thinking, Working Memory, Attention, and Intelligence: Evidence for Domain-Specific Relationships with a New Self-Report Questionnaire.

    PubMed

    Lunke, Katrin; Meier, Beat

    2016-01-01

    The goal of the present study was to take a new look at the relationship between creativity and cognitive functioning. Based on models that have postulated domain- and sub-domain-structures for different forms of creativity, like scientific, technical or artistic creativity with cognitive functions as important basis, we developed a new questionnaire. The Artistic Creativity Domains Compendium (ACDC) assesses interest, ability and performance in a distinct way for different domains of artistic creativity. We present the data of 270 adults tested with the ACDC, standard tests of divergent and convergent thinking, and tests of cognitive functions. We present fine-grained analyses on the internal and external validity of the ACDC and on the relationships between creativity, working memory, attention, and intelligence. Our results indicate domain-specific associations between creativity and attention as well as working memory. We conclude that the ACDC is a valid instrument to assess artistic creativity and that a fine-grained analysis reveals distinct patterns of relationships between separate domains of creativity and cognition.

  12. Importance of Contextual Factors When Measuring Work Outcome in Ankylosing Spondylitis: A Systematic Review by the OMERACT Worker Productivity Group.

    PubMed

    Stolwijk, Carmen; Castillo-Ortiz, José-Dionisio; Gignac, Monique; Luime, Jolanda; Boonen, A

    2015-09-01

    To review the literature on contextual factors (CoFas) and their relationship to work outcomes in individuals with ankylosing spondylitis (AS). Articles that quantified the relationship between CoFas and employment status, sick leave, or presenteeism in individuals with AS were systematically identified. CoFas were classified into 5 domains for personal factors and 8 domains for environmental factors. We defined criteria for best-evidence synthesis for each CoFa domain based on the number of studies exploring that domain, and the quality of evidence of individual studies based on the risk of bias, adjustment of multivariable analyses for disease activity and physical function, and sample size. Twenty-five studies met our inclusion criteria: 20 addressed employment status, 6 examined sick leave, and 3 presenteeism. For employment, there was strong evidence for the role of age, moderate evidence for related skills/abilities, the absence of work accommodations, the nature of work and absence of workplace support, and poor evidence for the role of marital status. Evidence was insufficient for sex, education, and physical environment. For sick leave and presenteeism there were too few studies to perform a best-evidence synthesis for the role of CoFas. Using a newly proposed set of criteria for determining the best-evidence of the association between CoFa domains and work outcome, the following factors emerged: age, related skills/abilities, work accommodations, nature of work, and workplace support. In addition to disease-related variables, these CoFa domains seem important to include when designing and interpreting studies on work outcomes. © 2015, American College of Rheumatology.

  13. Visuospatial and verbal memory in mental arithmetic.

    PubMed

    Clearman, Jack; Klinger, Vojtěch; Szűcs, Dénes

    2017-09-01

    Working memory allows complex information to be remembered and manipulated over short periods of time. Correlations between working memory and mathematics achievement have been shown across the lifespan. However, only a few studies have examined the potentially distinct contributions of domain-specific visuospatial and verbal working memory resources in mental arithmetic computation. Here we aimed to fill this gap in a series of six experiments pairing addition and subtraction tasks with verbal and visuospatial working memory and interference tasks. In general, we found higher levels of interference between mental arithmetic and visuospatial working memory tasks than between mental arithmetic and verbal working memory tasks. Additionally, we found that interference that matched the working memory domain of the task (e.g., verbal task with verbal interference) lowered working memory performance more than mismatched interference (verbal task with visuospatial interference). Findings suggest that mental arithmetic relies on domain-specific working memory resources.

  14. 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.

  15. Repetition Suppression and Reactivation in Auditory–Verbal Short-Term Recognition Memory

    PubMed Central

    D'Esposito, Mark

    2009-01-01

    The neural response to stimulus repetition is not uniform across brain regions, stimulus modalities, or task contexts. For instance, it has been observed in many functional magnetic resonance imaging (fMRI) studies that sometimes stimulus repetition leads to a relative reduction in neural activity (repetition suppression), whereas in other cases repetition results in a relative increase in activity (repetition enhancement). In the present study, we hypothesized that in the context of a verbal short-term recognition memory task, repetition-related “increases” should be observed in the same posterior temporal regions that have been previously associated with “persistent activity” in working memory rehearsal paradigms. We used fMRI and a continuous recognition memory paradigm with short lags to examine repetition effects in the posterior and anterior regions of the superior temporal cortex. Results showed that, consistent with our hypothesis, the 2 posterior temporal regions consistently associated with working memory maintenance, also show repetition increases during short-term recognition memory. In contrast, a region in the anterior superior temporal lobe showed repetition suppression effects, consistent with previous research work on perceptual adaptation in the auditory–verbal domain. We interpret these results in light of recent theories of the functional specialization along the anterior and posterior axes of the superior temporal lobe. PMID:18987393

  16. Repetition suppression and reactivation in auditory-verbal short-term recognition memory.

    PubMed

    Buchsbaum, Bradley R; D'Esposito, Mark

    2009-06-01

    The neural response to stimulus repetition is not uniform across brain regions, stimulus modalities, or task contexts. For instance, it has been observed in many functional magnetic resonance imaging (fMRI) studies that sometimes stimulus repetition leads to a relative reduction in neural activity (repetition suppression), whereas in other cases repetition results in a relative increase in activity (repetition enhancement). In the present study, we hypothesized that in the context of a verbal short-term recognition memory task, repetition-related "increases" should be observed in the same posterior temporal regions that have been previously associated with "persistent activity" in working memory rehearsal paradigms. We used fMRI and a continuous recognition memory paradigm with short lags to examine repetition effects in the posterior and anterior regions of the superior temporal cortex. Results showed that, consistent with our hypothesis, the 2 posterior temporal regions consistently associated with working memory maintenance, also show repetition increases during short-term recognition memory. In contrast, a region in the anterior superior temporal lobe showed repetition suppression effects, consistent with previous research work on perceptual adaptation in the auditory-verbal domain. We interpret these results in light of recent theories of the functional specialization along the anterior and posterior axes of the superior temporal lobe.

  17. Insights into Strand Exchange in BTB Domain Dimers from the Crystal Structures of FAZF and Miz1

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

    Stogios, Peter J.; Cuesta-Seijo, Jose Antonio; Chen, Lu

    2010-09-22

    The BTB domain is a widely distributed protein-protein interaction motif that is often found at the N-terminus of zinc finger transcription factors. Previous crystal structures of BTB domains have revealed tightly interwound homodimers, with the N-terminus from one chain forming a two-stranded anti-parallel {beta}-sheet with a strand from the other chain. We have solved the crystal structures of the BTB domains from Fanconi anemia zinc finger (FAZF) and Miz1 (Myc-interacting zinc finger 1) to resolutions of 2.0 {angstrom} and 2.6 {angstrom}, respectively. Unlike previous examples of BTB domain structures, the FAZF BTB domain is a nonswapped dimer, with each N-terminalmore » {beta}-strand associated with its own chain. As a result, the dimerization interface in the FAZF BTB domain is about half as large as in the domain-swapped dimers. The Miz1 BTB domain resembles a typical swapped BTB dimer, although it has a shorter N-terminus that is not able to form the interchain sheet. Using cysteine cross-linking, we confirmed that the promyelocytic leukemia zinc finger (PLZF) BTB dimer is strand exchanged in solution, while the FAZF BTB dimer is not. A phylogenic tree of the BTB fold based on both sequence and structural features shows that the common ancestor of the BTB domain in BTB-ZF (bric a brac, tramtrack, broad-complex zinc finger) proteins was a domain-swapped dimer. The differences in the N-termini seen in the FAZF and Miz1 BTB domains appear to be more recent developments in the structural evolution of the domain.« less

  18. Domain structure of the ribozyme from eubacterial ribonuclease P.

    PubMed Central

    Loria, A; Pan, T

    1996-01-01

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

  19. Formal Language Design in the Context of Domain Engineering

    DTIC Science & Technology

    2000-03-28

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

  20. BLM promotes the activation of Fanconi Anemia signaling pathway.

    PubMed

    Panneerselvam, Jayabal; Wang, Hong; Zhang, Jun; Che, Raymond; Yu, Herbert; Fei, Peiwen

    2016-05-31

    Mutations in the human RecQ helicase, BLM, causes Bloom Syndrome, which is a rare autosomal recessive disorder and characterized by genomic instability and an increased risk of cancer. Fanconi Anemia (FA), resulting from mutations in any of the 19 known FA genes and those yet to be known, is also characterized by chromosomal instability and a high incidence of cancer. BLM helicase and FA proteins, therefore, may work in a common tumor-suppressor signaling pathway. To date, it remains largely unclear as to how BLM and FA proteins work concurrently in the maintenance of genome stability. Here we report that BLM is involved in the early activation of FA group D2 protein (FANCD2). We found that FANCD2 activation is substantially delayed and attenuated in crosslinking agent-treated cells harboring deficient Blm compared to similarly treated control cells with sufficient BLM. We also identified that the domain VI of BLM plays an essential role in promoting FANCD2 activation in cells treated with DNA crosslinking agents, especially ultraviolet B. The similar biological effects performed by ΔVI-BLM and inactivated FANCD2 further confirm the relationship between BLM and FANCD2. Mutations within the domain VI of BLM detected in human cancer samples demonstrate the functional importance of this domain, suggesting human tumorigenicity resulting from mtBLM may be at least partly attributed to mitigated FANCD2 activation. Collectively, our data show a previously unknown regulatory liaison in advancing our understanding of how the cancer susceptibility gene products act in concert to maintain genome stability.

  1. Direct comparison of prefrontal cortex regions engaged by working and long-term memory tasks.

    PubMed

    Braver, T S; Barch, D M; Kelley, W M; Buckner, R L; Cohen, N J; Miezin, F M; Snyder, A Z; Ollinger, J M; Akbudak, E; Conturo, T E; Petersen, S E

    2001-07-01

    Neuroimaging studies have suggested the involvement of ventrolateral, dorsolateral, and frontopolar prefrontal cortex (PFC) regions in both working (WM) and long-term memory (LTM). The current study used functional magnetic resonance imaging (fMRI) to directly compare whether these PFC regions show selective activation associated with one memory domain. In a within-subjects design, subjects performed the n-back WM task (two-back condition) as well as LTM encoding (intentional memorization) and retrieval (yes-no recognition) tasks. Additionally, each task was performed with two different types of stimulus materials (familiar words, unfamiliar faces) in order to determine the influence of material-type vs task-type. A bilateral region of dorsolateral PFC (DL-PFC; BA 46/9) was found to be selectively activated during the two-back condition, consistent with a hypothesized role for this region in active maintenance and/or manipulation of information in WM. Left frontopolar PFC (FP-PFC) was also found to be selectively engaged during the two-back. Although FP-PFC activity has been previously associated with retrieval from LTM, no frontopolar regions were found to be selectively engaged by retrieval. Finally, lateralized ventrolateral PFC (VL-PFC) regions were found to be selectively engaged by material-type, but uninfluenced by task-type. These results highlight the importance of examining PFC activity across multiple memory domains, both for functionally differentiating PFC regions (e.g., task-selectivity vs material-selectivity in DL-PFC and VL-PFC) and for testing the applicability of memory domain-specific theories (e.g., FP-PFC in LTM retrieval).

  2. Content-specific evidence accumulation in inferior temporal cortex during perceptual decision-making

    PubMed Central

    Tremel, Joshua J.; Wheeler, Mark E.

    2015-01-01

    During a perceptual decision, neuronal activity can change as a function of time-integrated evidence. Such neurons may serve as decision variables, signaling a choice when activity reaches a boundary. Because the signals occur on a millisecond timescale, translating to human decision-making using functional neuroimaging has been challenging. Previous neuroimaging work in humans has identified patterns of neural activity consistent with an accumulation account. However, the degree to which the accumulating neuroimaging signals reflect specific sources of perceptual evidence is unknown. Using an extended face/house discrimination task in conjunction with cognitive modeling, we tested whether accumulation signals, as measured using functional magnetic resonance imaging (fMRI), are stimulus-specific. Accumulation signals were defined as a change in the slope of the rising edge of activation corresponding with response time (RT), with higher slopes associated with faster RTs. Consistent with an accumulation account, fMRI activity in face- and house-selective regions in the inferior temporal cortex increased at a rate proportional to decision time in favor of the preferred stimulus. This finding indicates that stimulus-specific regions perform an evidence integrative function during goal-directed behavior and that different sources of evidence accumulate separately. We also assessed the decision-related function of other regions throughout the brain and found that several regions were consistent with classifications from prior work, suggesting a degree of domain generality in decision processing. Taken together, these results provide support for an integration-to-boundary decision mechanism and highlight possible roles of both domain-specific and domain-general regions in decision evidence evaluation. PMID:25562821

  3. On the detection and monitoring of reduced water content in plants using spectral responses in the visible domain

    NASA Astrophysics Data System (ADS)

    Baranoski, Gladimir V. G.; Van Leeuwen, Spencer; Chen, Tenn F.

    2016-05-01

    The water status of cultivated plants can have a significant impact not only on food production, but also on the appropriate usage of increasingly scarce freshwater supplies. Accordingly, the cost-effective detection and monitoring of changes in their water content are longstanding remote sensing goals. Existing procedures employed to achieve these goals are largely based on the spectral responses of plant leaves in the infrared domain where the light absorption within the foliar tissues is dominated by water. Recently, it has been suggested that such procedures could be implemented using spectral responses, more specifically spectral subsurface reflectance to transmittance ratios, obtained in the visible domain. The basis for this proposition resides on the premise that a reduced water content (RWC) can result in histological changes whose effects on the foliar optical properties may not be limited to the infrared domain. However, the experiments leading to this proposition were performed on detached leaves, which were not influenced by the whole plant's adaptation mechanisms to water stress. In this work, we investigate whether the spectral responses of living plant leaves in the visible domain can lead to reliable RWC estimations. We employ measured biophysical data and predictive light transport simulations in order to extend qualitatively and quantitatively the scope of previous studies in this area. Our findings indicate that the living specimens' physiological responses to water stress should be taken into account in the design of new procedures for the cost-effective RWC estimation using visible subsurface reflectance to transmittance ratios.

  4. Identification of Extracellular Domain Residues Required for Epithelial Na+ Channel Activation by Acidic pH

    PubMed Central

    Collier, Daniel M.; Peterson, Zerubbabel J.; Blokhin, Ilya O.; Benson, Christopher J.; Snyder, Peter M.

    2012-01-01

    A growing body of evidence suggests that the extracellular domain of the epithelial Na+ channel (ENaC) functions as a sensor that fine tunes channel activity in response to changes in the extracellular environment. We previously found that acidic pH increases the activity of human ENaC, which results from a decrease in Na+ self-inhibition. In the current work, we identified extracellular domain residues responsible for this regulation. We found that rat ENaC is less sensitive to pH than human ENaC, an effect mediated in part by the γ subunit. We identified a group of seven residues in the extracellular domain of γENaC (Asp-164, Gln-165, Asp-166, Glu-292, Asp-335, His-439, and Glu-455) that, when individually mutated to Ala, decreased proton activation of ENaC. γE455 is conserved in βENaC (Glu-446); mutation of this residue to neutral amino acids (Ala, Cys) reduced ENaC stimulation by acidic pH, whereas reintroduction of a negative charge (by MTSES modification of Cys) restored pH regulation. Combination of the seven γENaC mutations with βE446A generated a channel that was not activated by acidic pH, but inhibition by alkaline pH was intact. Moreover, these mutations reduced the effect of pH on Na+ self-inhibition. Together, the data identify eight extracellular domain residues in human β- and γENaC that are required for regulation by acidic pH. PMID:23060445

  5. The role of charge and multiple faces of the CD8 alpha/alpha homodimer in binding to major histocompatibility complex class I molecules: support for a bivalent model.

    PubMed

    Giblin, P A; Leahy, D J; Mennone, J; Kavathas, P B

    1994-03-01

    The CD8 dimer interacts with the alpha 3 domain of major histocompatibility complex class I molecules through two immunoglobulin variable-like domains. In this study a crystal structure-informed mutational analysis has been performed to identify amino acids in the CD8 alpha/alpha homodimer that are likely to be involved in binding to class I. Several key residues are situated on the top face of the dimer within loops analogous to the complementarity-determining regions (CDRs) of immunoglobulin. In addition, other important amino acids are located in the A and B beta-strands on the sides of the dimer. The potential involvement of amino acids on both the top and the side faces of the molecule is consistent with a bivalent model for the interaction between a single CD8 alpha/alpha homodimer and two class I molecules and may have important implications for signal transduction in class I-expressing cells. This study also demonstrates a role for the positive surface potential of CD8 in class I binding and complements previous work demonstrating the importance of a negatively charged loop on the alpha 3 domain of class I for CD8 alpha/alpha-class I interaction. We propose a model whereby residues located on the CDR-like loops of the CD8 homodimer interact with the alpha 3 domain of MHC class I while amino acids on the side of the molecule containing the A and B beta-strands contact the alpha 2 domain of class I.

  6. Work-Related Goal Appraisals and Stress during the Transition from Education to Work

    ERIC Educational Resources Information Center

    Dietrich, Julia; Jokisaari, Markku; Nurmi, Jari-Erik

    2012-01-01

    People's personal goals interact with their life situations in many ways. This study examined the appraisals of personal goals during a transition from education to work and their interplay with stress in different domains of life. Finnish young adults (N = 265, 60% female) reported on their goals in the work domain, and related appraisals of…

  7. Neuropsychological function and past exposure to metallic mercury in female dental workers

    PubMed Central

    Sletvold, Helge; Svendsen, Kristin; Aas, Oddfrid; Syversen, Tore; Hilt, Bjørn

    2012-01-01

    The aim of this study was to see if dental personnel with previous exposure to metallic mercury have later developed disturbances in cognitive function. Ninety-one female participants who had been selected from a previous health survey of dental personnel were investigated neuropsychologically within the following domains: motor function, short-term memory, working memory, executive function, mental flexibility, and visual and verbal long-term memory. The scores were mainly within normal ranges. Relationships between an exposure score, the duration of employment before 1990, and previously measured mercury in urine as independent variables and the neuropsychological findings as dependent variables, were analyzed by multiple linear regression controlling for age, general ability, length of education, alcohol consumption, and previous head injuries. The only relationship that was statistically significant in the hypothesized direction was between the previously measured urine mercury values and visual long-term memory, where the urine values explained 30% of the variability. As the study had a low statistical power and also some other methodological limitations, the results have to be interpreted with caution. Even so, we think it is right to conclude that neuropsychological findings indicative of subsequent cognitive injuries are difficult to find in groups of otherwise healthy dental personnel with previous occupational exposure to mercury. PMID:22092046

  8. Spillover of interpersonal conflicts from work into nonwork: A daily diary study.

    PubMed

    Martinez-Corts, Inés; Demerouti, Evangelia; Bakker, Arnold B; Boz, Marina

    2015-07-01

    [Correction Notice: An Erratum for this article was reported in Vol 20(3) of Journal of Occupational Health Psychology (see record 2015-15847-001). There was a misspelling in the figures. The legends for Figure 1 and Figure 2 should read "High Daily Resilience".] This study among a heterogeneous sample of employees expands the Job-Demands (JD-R) theory by examining how interpersonal conflicts at work-task and relationship conflict-spillover into the nonwork domain on a daily basis. We hypothesized that daily personal resources can buffer the daily negative spillover of interpersonal conflicts from work into the nonwork domain. A total of 113 employees (n = 565 occasions) filled in a daily diary questionnaire in the evening before bedtime over 5 consecutive working days. Results of multilevel analysis showed that the presence of daily personal resources is essential to buffer the spillover of interpersonal conflict at work to the nonwork domain. Specifically, on days that employees were not very optimistic or resilient, interpersonal conflicts resulted in higher strain-based work-life conflict experiences. These findings contribute to the JD-R theory and show how the unfavorable effects of daily interpersonal conflicts in the work domain may be avoided in the nonwork domain through enhancing personal resources. We discuss the implications for theory and practice. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  9. A dual change model of life satisfaction and functioning for individuals with schizophrenia

    PubMed Central

    Edmondson, Melissa; Pahwa, Rohini; Lee, Karen Kyeunghae; Hoe, Maanse; Brekke, John S.

    2013-01-01

    Despite the notion that increases in functioning should be associated with increases in life satisfaction in schizophrenia, research has often found no association between the two. Dual change models of global and domain-specific life satisfaction and functioning were examined in 145 individuals with schizophrenia receiving community-based services over 12 months. Functioning and satisfaction were measured using the Role Functioning Scale and Satisfaction with Life Scale. Data were analyzed using latent growth curve modeling. Improvement in global life satisfaction was associated with improvement in overall functioning over time. Satisfaction with living situation also improved as independent functioning improved. Work satisfaction did not improve as work functioning improved. Although social functioning improved, satisfaction with social relationships did not. The link between overall functioning and global life satisfaction provides support for a recovery-based orientation to community based psychosocial rehabilitation services. When examining sub-domains, the link between outcomes and subjective experience suggests a more complex picture than previously found. These findings are crucial to interventions and programs aimed at improving functioning and the subjective experiences of consumers recovering from mental illness. Interventions that show improvements in functional outcomes can assume that they will show concurrent improvements in global life satisfaction as well and in satisfaction with independent living. Interventions geared toward improving social functioning will need to consider the complexity of social relationships and how they affect satisfaction associated with personal relationships. Interventions geared towards improving work functioning will need to consider how the quality and level of work affect satisfaction with employment. PMID:22591780

  10. Effectiveness of Workplace Interventions in Return-to-Work for Musculoskeletal, Pain-Related and Mental Health Conditions: An Update of the Evidence and Messages for Practitioners.

    PubMed

    Cullen, K L; Irvin, E; Collie, A; Clay, F; Gensby, U; Jennings, P A; Hogg-Johnson, S; Kristman, V; Laberge, M; McKenzie, D; Newnam, S; Palagyi, A; Ruseckaite, R; Sheppard, D M; Shourie, S; Steenstra, I; Van Eerd, D; Amick, B C

    2018-03-01

    Purpose The objective of this systematic review was to synthesize evidence on the effectiveness of workplace-based return-to-work (RTW) interventions and work disability management (DM) interventions that assist workers with musculoskeletal (MSK) and pain-related conditions and mental health (MH) conditions with RTW. Methods We followed a systematic review process developed by the Institute for Work & Health and an adapted best evidence synthesis that ranked evidence as strong, moderate, limited, or insufficient. Results Seven electronic databases were searched from January 1990 until April 2015, yielding 8898 non-duplicate references. Evidence from 36 medium and high quality studies were synthesized on 12 different intervention categories across three broad domains: health-focused, service coordination, and work modification interventions. There was strong evidence that duration away from work from both MSK or pain-related conditions and MH conditions were significantly reduced by multi-domain interventions encompassing at least two of the three domains. There was moderate evidence that these multi-domain interventions had a positive impact on cost outcomes. There was strong evidence that cognitive behavioural therapy interventions that do not also include workplace modifications or service coordination components are not effective in helping workers with MH conditions in RTW. Evidence for the effectiveness of other single-domain interventions was mixed, with some studies reporting positive effects and others reporting no effects on lost time and work functioning. Conclusions While there is substantial research literature focused on RTW, there are only a small number of quality workplace-based RTW intervention studies that involve workers with MSK or pain-related conditions and MH conditions. We recommend implementing multi-domain interventions (i.e. with healthcare provision, service coordination, and work accommodation components) to help reduce lost time for MSK or pain-related conditions and MH conditions. Practitioners should also consider implementing these programs to help improve work functioning and reduce costs associated with work disability.

  11. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. The Big Three of Comparative Judgment: On the Effects of Social, Temporal, and Dimensional Comparisons on Academic Self-Concept

    ERIC Educational Resources Information Center

    Müller-Kalthoff, Hanno; Helm, Friederike; Möller, Jens

    2017-01-01

    Students evaluate their domain-specific abilities by comparing their own achievement in one domain to that of others (social comparison), to their own previous achievement (temporal comparison), as well as their own achievement in another domain (dimensional comparison). The theories underlying these three comparison processes each assume an…

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

    PubMed Central

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

    2016-01-01

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

  14. Attention allocation: Relationships to general working memory or specific language processing.

    PubMed

    Archibald, Lisa M D; Levee, Tyler; Olino, Thomas

    2015-11-01

    Attention allocation, updating working memory, and language processing are interdependent cognitive tasks related to the focused direction of limited resources, refreshing and substituting information in the current focus of attention, and receiving/sending verbal communication, respectively. The current study systematically examined the relationship among executive attention, working memory executive skills, and language abilities while adjusting for individual differences in short-term memory. School-age children completed a selective attention task requiring them to recall whether a presented shape was in the same place as a previous target shape shown in an array imposing a low or high working memory load. Results revealed a selective attention cost when working above but not within memory span capacity. Measures of general working memory were positively related to overall task performance, whereas language abilities were related to response time. In particular, higher language skills were associated with faster responses under low load conditions. These findings suggest that attentional control and storage demands have an additive impact on working memory resources but provide only limited evidence for a domain-general mechanism in language learning. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

  15. Ontology Design Patterns as Interfaces (invited)

    NASA Astrophysics Data System (ADS)

    Janowicz, K.

    2015-12-01

    In recent years ontology design patterns (ODP) have gained popularity among knowledge engineers. ODPs are modular but self-contained building blocks that are reusable and extendible. They minimize the amount of ontological commitments and thereby are easier to integrate than large monolithic ontologies. Typically, patterns are not directly used to annotate data or to model certain domain problems but are combined and extended to form data and purpose-driven local ontologies that serve the needs of specific applications or communities. By relying on a common set of patterns these local ontologies can be aligned to improve interoperability and enable federated queries without enforcing a top-down model of the domain. In previous work, we introduced ontological views as layer on top of ontology design patterns to ease the reuse, combination, and integration of patterns. While the literature distinguishes multiple types of patterns, e.g., content patterns or logical patterns, we propose to use them as interfaces here to guide the development of ontology-driven systems.

  16. Numerical investigation of velocity slip and temperature jump effects on unsteady flow over a stretching permeable surface

    NASA Astrophysics Data System (ADS)

    Hosseini, E.; Loghmani, G. B.; Heydari, M.; Rashidi, M. M.

    2017-02-01

    In this paper, the boundary layer flow and heat transfer of unsteady flow over a porous accelerating stretching surface in the presence of the velocity slip and temperature jump effects are investigated numerically. A new effective collocation method based on rational Bernstein functions is applied to solve the governing system of nonlinear ordinary differential equations. This method solves the problem on the semi-infinite domain without truncating or transforming it to a finite domain. In addition, the presented method reduces the solution of the problem to the solution of a system of algebraic equations. Graphical and tabular results are presented to investigate the influence of the unsteadiness parameter A , Prandtl number Pr, suction parameter fw, velocity slip parameter γ and thermal slip parameter φ on the velocity and temperature profiles of the fluid. The numerical experiments are reported to show the accuracy and efficiency of the novel proposed computational procedure. Comparisons of present results are made with those obtained by previous works and show excellent agreement.

  17. Drosophila Spire is an actin nucleation factor.

    PubMed

    Quinlan, Margot E; Heuser, John E; Kerkhoff, Eugen; Mullins, R Dyche

    2005-01-27

    The actin cytoskeleton is essential for many cellular functions including shape determination, intracellular transport and locomotion. Previous work has identified two factors--the Arp2/3 complex and the formin family of proteins--that nucleate new actin filaments via different mechanisms. Here we show that the Drosophila protein Spire represents a third class of actin nucleation factor. In vitro, Spire nucleates new filaments at a rate that is similar to that of the formin family of proteins but slower than in the activated Arp2/3 complex, and it remains associated with the slow-growing pointed end of the new filament. Spire contains a cluster of four WASP homology 2 (WH2) domains, each of which binds an actin monomer. Maximal nucleation activity requires all four WH2 domains along with an additional actin-binding motif, conserved among Spire proteins. Spire itself is conserved among metazoans and, together with the formin Cappuccino, is required for axis specification in oocytes and embryos, suggesting that multiple actin nucleation factors collaborate to construct essential cytoskeletal structures.

  18. Isotope-selective high-order interferometry with large organic molecules in free fall

    NASA Astrophysics Data System (ADS)

    Rodewald, Jonas; Dörre, Nadine; Grimaldi, Andrea; Geyer, Philipp; Felix, Lukas; Mayor, Marcel; Shayeghi, Armin; Arndt, Markus

    2018-03-01

    Interferometry in the time domain has proven valuable for matter-wave based measurements. This concept has recently been generalized to cold molecular clusters using short-pulse standing light waves which realized photo-depletion gratings, arranged in a time-domain Talbot–Lau interferometer (OTIMA). Here we extend this idea further to large organic molecules and demonstrate a new scheme to scan the emerging molecular interferogram in position space. The capability of analyzing different isotopes of the same monomer under identical conditions opens perspectives for studying the interference fringe shift as a function of time in gravitational free fall. The universality of OTIMA interferometry allows one to handle a large variety of particles. In our present work, quasi-continuous laser evaporation allows transferring fragile organic molecules into the gas phase, covering more than an order of magnitude in mass between 614 amu and 6509 amu, i.e. 300% more massive than in previous OTIMA experiments. For all masses, we find about 30% fringe visibility.

  19. Transcription start site associated RNAs (TSSaRNAs) are ubiquitous in all domains of life.

    PubMed

    Zaramela, Livia S; Vêncio, Ricardo Z N; ten-Caten, Felipe; Baliga, Nitin S; Koide, Tie

    2014-01-01

    A plethora of non-coding RNAs has been discovered using high-resolution transcriptomics tools, indicating that transcriptional and post-transcriptional regulation is much more complex than previously appreciated. Small RNAs associated with transcription start sites of annotated coding regions (TSSaRNAs) are pervasive in both eukaryotes and bacteria. Here, we provide evidence for existence of TSSaRNAs in several archaeal transcriptomes including: Halobacterium salinarum, Pyrococcus furiosus, Methanococcus maripaludis, and Sulfolobus solfataricus. We validated TSSaRNAs from the model archaeon Halobacterium salinarum NRC-1 by deep sequencing two independent small-RNA enriched (RNA-seq) and a primary-transcript enriched (dRNA-seq) strand-specific libraries. We identified 652 transcripts, of which 179 were shown to be primary transcripts (∼7% of the annotated genome). Distinct growth-associated expression patterns between TSSaRNAs and their cognate genes were observed, indicating a possible role in environmental responses that may result from RNA polymerase with varying pausing rhythms. This work shows that TSSaRNAs are ubiquitous across all domains of life.

  20. Consumers' Patient Portal Preferences and Health Literacy: A Survey Using Crowdsourcing.

    PubMed

    Zide, Mary; Caswell, Kaitlyn; Peterson, Ellen; Aberle, Denise R; Bui, Alex At; Arnold, Corey W

    2016-06-08

    eHealth apps have the potential to meet the information needs of patient populations and improve health literacy rates. However, little work has been done to document perceived usability of portals and health literacy of specific topics. Our aim was to establish a baseline of lung cancer health literacy and perceived portal usability. A survey based on previously validated instruments was used to assess a baseline of patient portal usability and health literacy within the domain of lung cancer. The survey was distributed via Amazon's Mechanical Turk to 500 participants. Our results show differences in preferences and literacy by demographic cohorts, with a trend of chronically ill patients having a more positive reception of patient portals and a higher health literacy rate of lung cancer knowledge (P<.05). This article provides a baseline of usability needs and health literacy that suggests that chronically ill patients have a greater preference for patient portals and higher level of health literacy within the domain of lung cancer.

  1. Auditory memory can be object based.

    PubMed

    Dyson, Benjamin J; Ishfaq, Feraz

    2008-04-01

    Identifying how memories are organized remains a fundamental issue in psychology. Previous work has shown that visual short-term memory is organized according to the object of origin, with participants being better at retrieving multiple pieces of information from the same object than from different objects. However, it is not yet clear whether similar memory structures are employed for other modalities, such as audition. Under analogous conditions in the auditory domain, we found that short-term memories for sound can also be organized according to object, with a same-object advantage being demonstrated for the retrieval of information in an auditory scene defined by two complex sounds overlapping in both space and time. Our results provide support for the notion of an auditory object, in addition to the continued identification of similar processing constraints across visual and auditory domains. The identification of modality-independent organizational principles of memory, such as object-based coding, suggests possible mechanisms by which the human processing system remembers multimodal experiences.

  2. Arabidopsis thaliana BTB/ POZ-MATH proteins interact with members of the ERF/AP2 transcription factor family.

    PubMed

    Weber, Henriette; Hellmann, Hanjo

    2009-11-01

    In Arabidopsis thaliana, the BTB/POZ-MATH (BPM) proteins comprise a small family of six members. They have been described previously to use their broad complex, tram track, bric-a-brac/POX virus and zinc finger (BTB/POZ) domain to assemble with CUL3a and CUL3b and potentially to serve as substrate adaptors to cullin-based E3-ligases in plants. In this article, we show that BPMs can also assemble with members of the ethylene response factor/Apetala2 transcription factor family, and that this is mediated by their meprin and TRAF (tumor necrosis factor receptor-associated factor) homology (MATH) domain. In addition, we provide a detailed description of BPM gene expression patterns in different tissues and on abiotic stress treatments, as well as their subcellular localization. This work connects, for the first time, BPM proteins with ethylene response factor/Apetala2 family members, which is likely to represent a novel regulatory mechanism of transcriptional control.

  3. Association of work productivity with clinical and patient-reported factors in patients infected with hepatitis C virus.

    PubMed

    Younossi, Z M; Stepanova, M; Henry, L; Younossi, I; Weinstein, A; Nader, F; Hunt, S

    2016-08-01

    Patients with HCV infection have reduced work productivity (WP), in terms of both presenteeism (impairment in work productivity while working) and absenteeism (productivity loss due to absence from work). The aim of this study was to identify clinical and patient-reported factors that are predictive of WP in HCV-infected patients. HCV-infected patients enrolled in clinical trials completed 3 PRO questionnaires (CLDQ-HCV, SF-36 and FACIT-F) and one work productivity (WPAI:SHP) questionnaire. In employed subjects, work productivity and its absenteeism and presenteeism components were calculated using WPAI:SHP instrument. Of 4121 HCV-infected patients with work productivity data, 2480 (60.2%) reported to be employed, and of those, 2190 had completed all PRO questionnaires before treatment initiation. Of the study cohort, 519/2190 (23.7%) had severe work impairment. In multiple linear regression analysis, work productivity was predicted by lower scores in activity/energy domain of CLDQ-HCV, physical well-being domain of FACIT-F, worry domain of CLDQ-HCV and role physical domain of SF-36 (all P < 0.0005). Furthermore, presenteeism was independently predicted by the activity/energy of CLDQ-HCV, physical well-being of FACIT-F, worry domain of CLDQ-HCV, role physical scale of SF-36 and fatigue scale of FACIT-F (P < 0.002). Finally, absenteeism was independently predicted by physical well-being scale of FACIT-F and role physical scale of SF-36 (all P < 0.002). Clinically, work productivity impairment was predicted by the presence of cirrhosis, anxiety, depression and clinically overt fatigue (P < 0.01). Thus, the most important drivers of WP in HCV are impairment of physical aspects of PROs and clinical history of depression, anxiety, fatigue and cirrhosis. © 2016 John Wiley & Sons Ltd.

  4. Cyber indicators of compromise: a domain ontology for security information and event management

    DTIC Science & Technology

    2017-03-01

    COMPROMISE: A DOMAIN ONTOLOGY FOR SECURITY INFORMATION AND EVENT MANAGEMENT by Marsha D. Rowell March 2017 Thesis Co-Advisors: J. D...to automate this work is Security Information and Event Management (SIEM). In short, SIEM technology works by aggregating log information , and then...Distribution is unlimited. CYBER INDICATORS OF COMPROMISE: A DOMAIN ONTOLOGY FOR SECURITY INFORMATION AND EVENT MANAGEMENT Marsha D. Rowell

  5. Mesozoic Crustal Thickening of the Longmenshan Belt (NE Tibet, China) by Imbrication of Basement Slices: Insights From Structural Analysis, Petrofabric and Magnetic Fabric Studies, and Gravity Modeling

    NASA Astrophysics Data System (ADS)

    Xue, Zhenhua; Martelet, Guillaume; Lin, Wei; Faure, Michel; Chen, Yan; Wei, Wei; Li, Shuangjian; Wang, Qingchen

    2017-12-01

    This work first presents field structural analysis, anisotropy of magnetic susceptibility (AMS) measurements, and kinematic and microstructural studies on the Neoproterozoic Pengguan complex located in the middle segment of the Longmenshan thrust belt (LMTB), NE Tibet. These investigations indicate that the Pengguan complex is a heterogeneous unit with a ductilely deformed NW domain and an undeformed SE domain, rather than a single homogeneous body as previously thought. The NW part of the Pengguan complex is constrained by top-to-the-NW shearing along its NW boundary and top-to-the-SE shearing along its SE boundary, where it imbricates and overrides the SE domain. Two orogen-perpendicular gravity models not only support the imbricated shape of the Pengguan complex but also reveal an imbrication of high-density material hidden below the Paleozoic rocks on the west of the LMTB. Regionally, this suggests a basement-slice-imbricated structure that developed along the margin of the Yangtze Block, as shown by the regional gravity anomaly map, together with the published nearby seismic profile and the distribution of orogen-parallel Neoproterozoic complexes. Integrating the previously published ages of the NW normal faulting and of the SE directed thrusting, the locally fast exhumation rate, and the lithological characteristics of the sediments in the LMTB front, we interpret the basement-slice-imbricated structure as the result of southeastward thrusting of the basement slices during the Late Jurassic-Early Cretaceous. This architecture makes a significant contribution to the crustal thickening of the LMTB during the Mesozoic, and therefore, the Cenozoic thickening of the Longmenshan belt might be less important than often suggested.

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

    PubMed

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

    2012-01-01

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

  7. Magnesium-dependent RNA binding to the PA endonuclease domain of the avian influenza polymerase.

    PubMed

    Xiao, Shiyan; Klein, Michael L; LeBard, David N; Levine, Benjamin G; Liang, Haojun; MacDermaid, Christopher M; Alfonso-Prieto, Mercedes

    2014-01-30

    Influenza A viruses are highly pathogenic and pose an unpredictable public health danger to humans. An attractive target for developing new antiviral drugs is the PA N-terminal domain (PAN) of influenza polymerase, which is responsible for the endonuclease activity and essential for viral replication. Recently, the crystal structures of the holo form of PAN as well as PAN bound to different inhibitors have been reported, but the potency and selectivity of these inhibitors still need to be improved. New drug design can be guided by a better understanding of the endonuclease activity of PAN. However, this requires the structure of PAN in complex with the host mRNA, which has not been determined yet. In particular, divalent metal ions are known to be essential for RNA cleavage, but it is not clear whether there is either one or two Mg ions in the PAN active site. In the present work, we have modeled the complex of the PAN endonuclease domain with the host mRNA in the presence of either one or two Mg(2+) by using all-atom molecular dynamics. These simulations identify crucial interactions between the enzyme and the nucleic acid. Moreover, they validate a previous hypothesis that a second metal ion binds in the presence of the RNA substrate and therefore support a two-metal ion mechanism, in which K134 decreases the pKa of the nucleophilic water. Nevertheless, at low Mg concentrations an alternative, one-metal ion mechanism is possible, with K137 as the catalytic lysine and H41 as the general base, rationalizing previous unexpected mutagenesis results. The RNA-enzyme interactions determined here could likely be used to design more specific endonuclease inhibitors to fight influenza viral infections.

  8. Primordial black hole and wormhole formation by domain walls

    NASA Astrophysics Data System (ADS)

    Deng, Heling; Garriga, Jaume; Vilenkin, Alexander

    2017-04-01

    In theories with a broken discrete symmetry, Hubble sized spherical domain walls may spontaneously nucleate during inflation. These objects are subsequently stretched by the inflationary expansion, resulting in a broad distribution of sizes. The fate of the walls after inflation depends on their radius. Walls smaller than a critical radius fall within the cosmological horizon early on and collapse due to their own tension, forming ordinary black holes. But if a wall is large enough, its repulsive gravitational field becomes dominant much before the wall can fall within the cosmological horizon. In this ``supercritical'' case, a wormhole throat develops, connecting the ambient exterior FRW universe with an interior baby universe, where the exponential growth of the wall radius takes place. The wormhole pinches off in a time-scale comparable to its light-crossing time, and black holes are formed at its two mouths. As discussed in previous work, the resulting black hole population has a wide distribution of masses and can have significant astrophysical effects. The mechanism of black hole formation has been previously studied for a dust-dominated universe. Here we investigate the case of a radiation-dominated universe, which is more relevant cosmologically, by using numerical simulations in order to find the initial mass of a black hole as a function of the wall size at the end of inflation. For large supercritical domain walls, this mass nearly saturates the upper bound according to which the black hole cannot be larger than the cosmological horizon. We also find that the subsequent accretion of radiation satisfies a scaling relation, resulting in a mass increase by about a factor of 2.

  9. Primordial black hole and wormhole formation by domain walls

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

    Deng, Heling; Garriga, Jaume; Vilenkin, Alexander, E-mail: heling.deng@tufts.edu, E-mail: garriga@cosmos.phy.tufts.edu, E-mail: vilenkin@cosmos.phy.tufts.edu

    In theories with a broken discrete symmetry, Hubble sized spherical domain walls may spontaneously nucleate during inflation. These objects are subsequently stretched by the inflationary expansion, resulting in a broad distribution of sizes. The fate of the walls after inflation depends on their radius. Walls smaller than a critical radius fall within the cosmological horizon early on and collapse due to their own tension, forming ordinary black holes. But if a wall is large enough, its repulsive gravitational field becomes dominant much before the wall can fall within the cosmological horizon. In this ''supercritical'' case, a wormhole throat develops, connectingmore » the ambient exterior FRW universe with an interior baby universe, where the exponential growth of the wall radius takes place. The wormhole pinches off in a time-scale comparable to its light-crossing time, and black holes are formed at its two mouths. As discussed in previous work, the resulting black hole population has a wide distribution of masses and can have significant astrophysical effects. The mechanism of black hole formation has been previously studied for a dust-dominated universe. Here we investigate the case of a radiation-dominated universe, which is more relevant cosmologically, by using numerical simulations in order to find the initial mass of a black hole as a function of the wall size at the end of inflation. For large supercritical domain walls, this mass nearly saturates the upper bound according to which the black hole cannot be larger than the cosmological horizon. We also find that the subsequent accretion of radiation satisfies a scaling relation, resulting in a mass increase by about a factor of 2.« less

  10. Conflict prevention, conflict mitigation, and manifestations of conflict during emergency department consultations.

    PubMed

    Chan, Teresa; Bakewell, Francis; Orlich, Donika; Sherbino, Jonathan

    2014-03-01

    The objective was to determine the causes of and mitigating factors for conflict between emergency physicians and other colleagues during consultations. From March to September 2010, a total of 61 physicians (31 residents and 30 attendings from emergency medicine [EM], internal medicine, and general surgery) were interviewed about how junior learners should be taught about emergency department (ED) consultations. During these interviews, they were asked if and how conflict manifests during the ED consultation process. Two investigators reviewed the transcripts independently to generate themes related to conflict until saturation was reached. Disagreements were resolved by consensus. The trustworthiness of the analysis was ensured by generating an audit trail, which was subsequently audited by an investigator not involved with the initial analysis. This analysis was compared to previously proposed models of trust and conflict from the sociology and business literature. All participants recalled some manifestation of conflict. There were 12 negative conflict-producing themes and 10 protective conflict-mitigating themes. When comparing these themes to a previously developed model of the domains of trust, each theme mapped to domains of the model. Conflict affects the ED consultation process. Areas that lead to conflict are identified that map to previous models of trust and conflict. This work extends the current understanding about intradisciplinary conflict in the clinical realm. These new findings may improve the understanding of the nature of conflicts that occur and form the foundation for interventions that may decrease conflict during ED consultations. © 2014 by the Society for Academic Emergency Medicine.

  11. Dispositional Predictors of Problem Solving in the Field of Office Work

    ERIC Educational Resources Information Center

    Rausch, Andreas

    2017-01-01

    It was investigated how domain-specific knowledge, fluid intelligence, vocational interest and work-related self-efficacy predicted domain-specific problem-solving performance in the field of office work. The participants included 100 German VET (vocational education and training) students nearing the end of a 3-year apprenticeship program as an…

  12. Globally optimal, minimum stored energy, double-doughnut superconducting magnets.

    PubMed

    Tieng, Quang M; Vegh, Viktor; Brereton, Ian M

    2010-01-01

    The use of the minimum stored energy current density map-based methodology of designing closed-bore symmetric superconducting magnets was described recently. The technique is further developed to cater for the design of interventional-type MRI systems, and in particular open symmetric magnets of the double-doughnut configuration. This extends the work to multiple magnet domain configurations. The use of double-doughnut magnets in MRI scanners has previously been hindered by the ability to deliver strong magnetic fields over a sufficiently large volume appropriate for imaging, essentially limiting spatial resolution, signal-to-noise ratio, and field of view. The requirement of dedicated interventional space restricts the manner in which the coils can be arranged and placed. The minimum stored energy optimal coil arrangement ensures that the field strength is maximized over a specific region of imaging. The design method yields open, dual-domain magnets capable of delivering greater field strengths than those used prior to this work, and at the same time it provides an increase in the field-of-view volume. Simulation results are provided for 1-T double-doughnut magnets with at least a 50-cm 1-ppm (parts per million) field of view and 0.7-m gap between the two doughnuts. Copyright (c) 2009 Wiley-Liss, Inc.

  13. The contribution of working memory to divided attention.

    PubMed

    Santangelo, Valerio; Macaluso, Emiliano

    2013-01-01

    Previous studies have indicated that increasing working memory (WM) load can affect the attentional selection of signals originating from one object/location. Here we assessed whether WM load affects also the selection of multiple objects/locations (divided attention). Participants monitored either two object-categories (vs. one category; object-based divided attention) or two locations (vs. one location; space-based divided attention) while maintaining in WM either a variable number of objects (object-based WM load) or locations (space-based WM load). Behavioural results showed that WM load affected attentional performance irrespective of divided or focused attention. However, fMRI results showed that the activity associated with object-based divided attention increased linearly with increasing object-based WM load in the left and right intraparietal sulcus (IPS); while, in the same areas, activity associated with space-based divided attention was not affected by any type of WM load. These findings support the hypothesis that WM contributes to the maintenance of resource-demanding attentional sets in a domain-specific manner. Moreover, the dissociable impact of WM load on performance and brain activity suggests that increased IPS activation reflects a recruitment of additional, domain-specific processing resources that enable dual-task performance under conditions of high WM load and high attentional demand. Copyright © 2011 Wiley Periodicals, Inc.

  14. Structure-based approach to rationally design a chimeric protein for an effective vaccine against Group B Streptococcus infections.

    PubMed

    Nuccitelli, Annalisa; Cozzi, Roberta; Gourlay, Louise J; Donnarumma, Danilo; Necchi, Francesca; Norais, Nathalie; Telford, John L; Rappuoli, Rino; Bolognesi, Martino; Maione, Domenico; Grandi, Guido; Rinaudo, C Daniela

    2011-06-21

    Structural vaccinology is an emerging strategy for the rational design of vaccine candidates. We successfully applied structural vaccinology to design a fully synthetic protein with multivalent protection activity. In Group B Streptococcus, cell-surface pili have aroused great interest because of their direct roles in virulence and importance as protective antigens. The backbone subunit of type 2a pilus (BP-2a) is present in six immunogenically different but structurally similar variants. We determined the 3D structure of one of the variants, and experimentally demonstrated that protective antibodies specifically recognize one of the four domains that comprise the protein. We therefore constructed a synthetic protein constituted by the protective domain of each one of the six variants and showed that the chimeric protein protects mice against the challenge with all of the type 2a pilus-carrying strains. This work demonstrates the power of structural vaccinology and will facilitate the development of an optimized, broadly protective pilus-based vaccine against Group B Streptococcus by combining the uniquely generated chimeric protein with protective pilin subunits from two other previously identified pilus types. In addition, this work describes a template procedure that can be followed to develop vaccines against other bacterial pathogens.

  15. [A Validation Study of the Modified Korean Version of Ethical Leadership at Work Questionnaire (K-ELW)].

    PubMed

    Kim, Jeong-Eon; Park, Eun-Jun

    2015-04-01

    The purpose of this study was to validate the Korean version of the Ethical Leadership at Work questionnaire (K-ELW) that measures RNs' perceived ethical leadership of their nurse managers. The strong validation process suggested by Benson (1998), including translation and cultural adaptation stage, structural stage, and external stage, was used. Participants were 241 RNs who reported their perceived ethical leadership using both the pre-version of K-ELW and a previously known Ethical Leadership Scale, and interactional justice of their managers, as well as their own demographics, organizational commitment and organizational citizenship behavior. Data analyses included descriptive statistics, Pearson correlation coefficients, reliability coefficients, exploratory factor analysis, and confirmatory factor analysis. SPSS 19.0 and Amos 18.0 versions were used. A modified K-ELW was developed from construct validity evidence and included 31 items in 7 domains: People orientation, task responsibility fairness, relationship fairness, power sharing, concern for sustainability, ethical guidance, and integrity. Convergent validity, discriminant validity, and concurrent validity were supported according to the correlation coefficients of the 7 domains with other measures. The results of this study provide preliminary evidence that the modified K-ELW can be adopted in Korean nursing organizations, and reliable and valid ethical leadership scores can be expected.

  16. Potential determinants of health-care professionals' use of survivorship care plans: a qualitative study using the theoretical domains framework.

    PubMed

    Birken, Sarah A; Presseau, Justin; Ellis, Shellie D; Gerstel, Adrian A; Mayer, Deborah K

    2014-11-15

    Survivorship care plans are intended to improve coordination of care for the nearly 14 million cancer survivors in the United States. Evidence suggests that survivorship care plans (SCPs) have positive outcomes for survivors, health-care professionals, and cancer programs, and several high-profile organizations now recommend SCP use. Nevertheless, SCP use remains limited among health-care professionals in United States cancer programs. Knowledge of barriers to SCP use is limited in part because extant studies have used anecdotal evidence to identify determinants. This study uses the theoretical domains framework to identify relevant constructs that are potential determinants of SCP use among United States health-care professionals. We conducted semi-structured interviews to assess the relevance of 12 theoretical domains in predicting SCP use among 13 health-care professionals in 7 cancer programs throughout the United States with diverse characteristics. Relevant theoretical domains were identified through thematic coding of interview transcripts, identification of specific beliefs within coded text units, and mapping of specific beliefs onto theoretical constructs. We found the following theoretical domains (based on specific beliefs) to be potential determinants of SCP use: health-care professionals' beliefs about the consequences of SCP use (benefit to survivors, health-care professionals, and the system as a whole); motivation and goals regarding SCP use (advocating SCP use; extent to which using SCPs competed for health-care professionals' time); environmental context and resources (whether SCPs were delivered at a dedicated visit and whether a system, information technology, and funding facilitated SCP use); and social influences (whether using SCPs is an organizational priority, influential people support SCP use, and people who could assist with SCP use buy into using SCPs). Specific beliefs mapped onto the following psychological constructs: outcome expectancies, intrinsic motivation, goal priority, resources, leadership, and team working. Previous studies have explored a limited range of determinants of SCP use. Our findings suggest a more comprehensive list of potential determinants that could be leveraged to promote SCP use. These results are particularly timely as cancer programs face impending SCP use requirements. Future work should develop instruments to measure the potential determinants and assess their relative influence on SCP use.

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

    ERIC Educational Resources Information Center

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

    2017-01-01

    The contributions of domain-general abilities and domain-specific knowledge to subsequent mathematics achievement were longitudinally assessed (n = 167) through 8th grade. First grade intelligence and working memory and prior grade reading achievement indexed domain-general effects, and domain-specific effects were indexed by prior grade…

  18. The Measurement and Role of Ecological Resilience Systems Theory Across Domain-Specific Outcomes: The Domain-Specific Resilient Systems Scales.

    PubMed

    Maltby, John; Day, Liz; Hall, Sophie S; Chivers, Sally

    2017-10-01

    Research suggests that trait resilience may be best understood within an ecological resilient systems theory, comprising engineering, ecological, and adaptive capacity resilience. However, there is no evidence as to how this theory translates to specific life domains. Data from two samples (the United States, n = 1,278; the United Kingdom, n = 211) facilitated five studies that introduce the Domain-Specific Resilient Systems Scales for assessing ecological resilient systems theory within work, health, marriage, friendships, and education. The Domain-Specific Resilient Systems Scales are found to predict unique variance in job satisfaction, lower job burnout, quality-of-life following illness, marriage commitment, and educational engagement, while controlling for factors including sex, age, personality, cognitive ability, and trait resilience. The findings also suggest a distinction between the three resilience dimensions in terms of the types of systems to which they contribute. Engineering resilience may contribute most to life domains where an established system needs to be maintained, for example, one's health. Ecological resilience may contribute most to life domains where the system needs sustainability in terms of present and future goal orientation, for example, one's work. Adaptive Capacity may contribute most to life domains where the system needs to be retained, preventing it from reaching a crisis state, for example, work burnout.

  19. Intrinsically disordered RGG/RG domains mediate degenerate specificity in RNA binding

    PubMed Central

    Ozdilek, Bagdeser A.; Thompson, Valery F.; Ahmed, Nasiha S.; White, Connor I.

    2017-01-01

    Abstract RGG/RG domains are the second most common RNA binding domain in the human genome, yet their RNA-binding properties remain poorly understood. Here, we report a detailed analysis of the RNA binding characteristics of intrinsically disordered RGG/RG domains from Fused in Sarcoma (FUS), FMRP and hnRNPU. For FUS, previous studies defined RNA binding as mediated by its well-folded domains; however, we show that RGG/RG domains are the primary mediators of binding. RGG/RG domains coupled to adjacent folded domains can achieve affinities approaching that of full-length FUS. Analysis of RGG/RG domains from FUS, FMRP and hnRNPU against a spectrum of contrasting RNAs reveals that each display degenerate binding specificity, while still displaying different degrees of preference for RNA. PMID:28575444

  20. Cognitive predictors of adaptive functioning in children with symptomatic epilepsy.

    PubMed

    Kerr, Elizabeth N; Fayed, Nora

    2017-10-01

    The current study sought to understand the contribution of the attention and working memory challenges experienced by children with active epilepsy without an intellectual disability to adaptive functioning (AF) while taking into account intellectual ability, co-occurring brain-based psychosocial diagnoses, and epilepsy-related variables. The relationship of attention and working memory with AF was examined in 76 children with active epilepsy with intellectual ability above the 2nd percentile recruited from a tertiary care center. AF was measured using the Scales of Independent Behavior-Revised (SIB-R) and compared with norm-referenced data. Standardized clinical assessments of attention span, sustained attention, as well as basic and more complex working memory were administered to children. Commonality analysis was used to investigate the importance of the variables with respect to the prediction of AF and to construct parsimonious models to elucidate the factors most important in explaining AF. Seventy-one percent of parents reported that their child experienced mild to severe difficulties with overall AF. Similar proportions of children displayed limitations in domain-specific areas of AF (Motor, Social/Communication, Person Living, and Community Living). The reduced models for Broad and domain-specific AF produced a maximum of seven predictor variables, with little loss in overall explained variance compared to the full models. Intellectual ability was a powerful predictor of Broad and domain-specific AF. Complex working memory was the only other cognitive predictor retained in each of the parsimonious models of AF. Sustained attention and complex working memory explained a large amount of the total variance in Motor AF. Children with a previously diagnosed comorbidity displayed lower Social/Communication, Personal Living, and Broad AF than those without a diagnosis. At least one epilepsy-related variable appeared in each of the reduced models, with age of seizure onset and seizure type (generalized or partial) being the main predictors. Intellectual ability was the most powerful predictor of AF in children with epilepsy whose intellectual functioning was above the 2nd percentile. Co-occurring brain-based cognitive and psychosocial issues experienced by children with living epilepsy, particularly complex working memory and diagnosed comorbidities, contribute to AF and may be amenable to intervention. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  1. Direct interaction of Ski with either Smad3 or Smad4 is necessary and sufficient for Ski-mediated repression of transforming growth factor-beta signaling.

    PubMed

    Ueki, Nobuhide; Hayman, Michael J

    2003-08-29

    The oncoprotein Ski represses transforming growth factor (TGF)-beta signaling in an N-CoR-independent manner. However, the molecular mechanism(s) underlying this event has not been elucidated. Here, we identify an additional domain in Ski that mediates interaction with Smad3 which is important for this repression. This domain is distinct from the previously reported N-terminal Smad3 binding domain in Ski. Individual alanine substitution of several residues in the domain significantly affected Ski-Smad3 interaction. Furthermore, combined mutations within this domain, together with those in the previously identified Smad3 binding domain, can completely abolish the interaction of Ski with Smad3, while mutation in each domain alone retained partial interaction. By introducing those mutations that abolish direct interaction with Smad3 or Smad4 individually, or in combination, we show that interaction of Ski with either Smad3 or Smad4 is sufficient for Ski-mediated repression of TGF-beta signaling. Furthermore our results clearly demonstrate that Ski does not disrupt Smad3-Smad4 heteromer formation, and recruitment of Ski to the Smad3/4 complex through binding to either Smad3 or Smad4 is both necessary and sufficient for repression.

  2. Domain-Specific Knowledge and Why Teaching Generic Skills Does Not Work

    ERIC Educational Resources Information Center

    Tricot, André; Sweller, John

    2014-01-01

    Domain-general cognitive knowledge has frequently been used to explain skill when domain-specific knowledge held in long-term memory may provide a better explanation. An emphasis on domain-general knowledge may be misplaced if domain-specific knowledge is the primary factor driving acquired intellectual skills. We trace the long history of…

  3. Predicting PDZ domain mediated protein interactions from structure

    PubMed Central

    2013-01-01

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

  4. Demographic management in a federated healthcare environment.

    PubMed

    Román, I; Roa, L M; Reina-Tosina, J; Madinabeitia, G

    2006-09-01

    The purpose of this paper is to provide a further step toward the decentralization of identification and demographic information about persons by solving issues related to the integration of demographic agents in a federated healthcare environment. The aim is to identify a particular person in every system of a federation and to obtain a unified view of his/her demographic information stored in different locations. This work is based on semantic models and techniques, and pursues the reconciliation of several current standardization works including ITU-T's Open Distributed Processing, CEN's prEN 12967, OpenEHR's dual and reference models, CEN's General Purpose Information Components and CORBAmed's PID service. We propose a new paradigm for the management of person identification and demographic data, based on the development of an open architecture of specialized distributed components together with the incorporation of techniques for the efficient management of domain ontologies, in order to have a federated demographic service. This new service enhances previous correlation solutions sharing ideas with different standards and domains like semantic techniques and database systems. The federation philosophy enforces us to devise solutions to the semantic, functional and instance incompatibilities in our approach. Although this work is based on several models and standards, we have improved them by combining their contributions and developing a federated architecture that does not require the centralization of demographic information. The solution is thus a good approach to face integration problems and the applied methodology can be easily extended to other tasks involved in the healthcare organization.

  5. A rapid and rational approach to generating isomorphous heavy-atom phasing derivatives.

    PubMed

    Lu, Jinghua; Sun, Peter D

    2014-09-01

    In attempts to replace the conventional trial-and-error heavy-atom derivative search method with a rational approach, we previously defined heavy metal compound reactivity against peptide ligands. Here, we assembled a composite pH- and buffer-dependent peptide reactivity profile for each heavy metal compound to guide rational heavy-atom derivative search. When knowledge of the best-reacting heavy-atom compound is combined with mass spectrometry assisted derivatization, and with a quick-soak method to optimize phasing, it is likely that the traditional heavy-atom compounds could meet the demand of modern high-throughput X-ray crystallography. As an example, we applied this rational heavy-atom phasing approach to determine a previously unknown mouse serum amyloid A2 crystal structure. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  6. Habitat suitability criteria via parametric distributions: estimation, model selection and uncertainty

    USGS Publications Warehouse

    Som, Nicholas A.; Goodman, Damon H.; Perry, Russell W.; Hardy, Thomas B.

    2016-01-01

    Previous methods for constructing univariate habitat suitability criteria (HSC) curves have ranged from professional judgement to kernel-smoothed density functions or combinations thereof. We present a new method of generating HSC curves that applies probability density functions as the mathematical representation of the curves. Compared with previous approaches, benefits of our method include (1) estimation of probability density function parameters directly from raw data, (2) quantitative methods for selecting among several candidate probability density functions, and (3) concise methods for expressing estimation uncertainty in the HSC curves. We demonstrate our method with a thorough example using data collected on the depth of water used by juvenile Chinook salmon (Oncorhynchus tschawytscha) in the Klamath River of northern California and southern Oregon. All R code needed to implement our example is provided in the appendix. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  7. Correlates of sports practice, occupational and leisure-time physical activity in Brazilian adolescents.

    PubMed

    Silva, Danilo R P; Fernandes, Rômulo A; Ohara, David; Collings, Paul J; Souza, Mariana F; Tomeleri, Crisieli M; Ronque, Enio R V; Sardinha, Luís B; Cyrino, Edilson S

    2016-01-01

    To analyze the relationship between different physical activity (PA) domains and sociodemographic, psychological, behavioral and biological factors in Brazilian adolescents. 1,220 adolescents (55.1% female) aged between 10 and 16 years-old participated in this study. The Baecke questionnaire was used to evaluate different PA domains, namely occupational, sports and leisure-time. Socioeconomic status, number of siblings, friendships satisfaction, mother's and father's PA level and previous experience with sports were self-reported. Cardiorespiratory fitness, waist circumference, and somatic maturity were estimated by objective indicators. Linear regression was used for the main statistical analysis. The variables consistently related to all of the PA domains were gender (boys more active), friendship satisfaction (positive with sports and leisure-time PA and negative with occupational PA) and cardiorespiratory fitness (positive). There were also domain-specific relationships for occupational (number of siblings [β = 0.02] and father's PA [β = 0.13]), sport practice (previous experience with sports [β = 0.33], waist circumference [β = 0.01] and somatic maturity [β = -0.12]) and leisure-time PA (chronological age [β = -0.15], mother's PA [β = 0.47] and previous experience with sports [β = 0.17]). The different domains of PA are related to specific variables in adolescence. This information may be helpful in formulating strategies for physical activity promotion, particularly in adolescents from low-to-middle income countries. © 2015 Wiley Periodicals, Inc.

  8. Work and personal life boundary management: boundary strength, work/personal life balance, and the segmentation-integration continuum.

    PubMed

    Bulger, Carrie A; Matthews, Russell A; Hoffman, Mark E

    2007-10-01

    While researchers are increasingly interested in understanding the boundaries surrounding the work and personal life domains, few have tested the propositions set forth by theory. Boundary theory proposes that individuals manage the boundaries between work and personal life through processes of segmenting and/or integrating the domains. The authors investigated boundary management profiles of 332 workers in an investigation of the segmentation-integration continuum. Cluster analysis indicated consistent clusters of boundary management practices related to varying segmentation and integration of the work and personal life domains. But, the authors suggest that the segmentation-integration continuum may be more complicated. Results also indicated relationships between boundary management practices and work-personal life interference and work-personal life enhancement. Less flexible and more permeable boundaries were related to more interference, while more flexible and more permeable boundaries were related to more enhancement.

  9. The Latent Structure of Spatial Skills and Mathematics: A Replication of the Two-Factor Model

    ERIC Educational Resources Information Center

    Mix, Kelly S.; Levine, Susan C.; Cheng, Yi-Lang; Young, Christopher J.; Hambrick, David Z.; Konstantopoulos, Spyros

    2017-01-01

    In a previous study, Mix et al. (2016) reported that spatial skill and mathematics were composed of 2 highly correlated, domain-specific factors, with a few cross-domain loadings. The overall structure was consistent across grade (kindergarten, 3rd grade, 6th grade), but the cross-domain loadings varied with age. The present study sought to…

  10. Structural analyses of von Willebrand factor C domains of collagen 2A and CCN3 reveal an alternative mode of binding to bone morphogenetic protein-2.

    PubMed

    Xu, Emma-Ruoqi; Blythe, Emily E; Fischer, Gerhard; Hyvönen, Marko

    2017-07-28

    Bone morphogenetic proteins (BMPs) are secreted growth factors that promote differentiation processes in embryogenesis and tissue development. Regulation of BMP signaling involves binding to a variety of extracellular proteins, among which are many von Willebrand factor C (vWC) domain-containing proteins. Although the crystal structure of the complex of crossveinless-2 (CV-2) vWC1 and BMP-2 previously revealed one mode of the vWC/BMP-binding mechanism, other vWC domains may bind to BMP differently. Here, using X-ray crystallography, we present for the first time structures of the vWC domains of two proteins thought to interact with BMP-2: collagen IIA and matricellular protein CCN3. We found that these two vWC domains share a similar N-terminal fold that differs greatly from that in CV-2 vWC, which comprises its BMP-2-binding site. We analyzed the ability of these vWC domains to directly bind to BMP-2 and detected an interaction only between the collagen IIa vWC and BMP-2. Guided by the collagen IIa vWC domain crystal structure and conservation of surface residues among orthologous domains, we mapped the BMP-binding epitope on the subdomain 1 of the vWC domain. This binding site is different from that previously observed in the complex between CV-2 vWC and BMP-2, revealing an alternative mode of interaction between vWC domains and BMPs. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Chloroplast Dynamics and Photosynthetic Efficiency: Final Technical Report

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

    Hanson, Maureen

    This project investigated the mechanism by which chloroplasts position themselves to maximize solar energy utilization, to enhance gas exchange, to minimize environmental stress, and to promote efficient exchange of metabolites with other compartments within the plant cell. Chloroplasts move within leaf cells to optimize light levels, moving toward levels of light useful for photosynthesis while moving away from excess light. Plastids sometimes extend their reach by sending out projections (stromules) that can connect anchor chloroplasts in position within the cell or provide close contacts with plasma membrane, mitochondria, peroxisomes, endoplasmic reticulum, and the nucleus. The intracellular location of chloroplasts inmore » relation to other organelles with which they share biosynthetic pathways, such as peroxisomes and mitochondria in photorespiration, affects metabolite flow. This work contributed to the knowledge of the mechanisms of organelle movement and anchoring in specific locations in plant cells and how proteins traffic within the cell. We identified two domains on 12 of the 13 Arabidopsis myosins that were similar to the vacuole-binding (V) domain characterized in yeast and to the DIL domain characterized in yeast and mouse as required for secretory vesicle or melanosome movement, respectively. Because all of the Arabidopsis regions with homology to the V domain contain the amino acid sequence PAL, we refer to this region as the Arabidopsis PAL domain. We have used the yeast Myo2p tail structural information to model the 12 myosin XI tail domains containing the homologous PAL and DIL domains. Eight YFP::DIL domain fusions labeled peroxisomes; none labeled mitochondria or chloroplasts. Six myosin XI Vacuole domains labeled mitochondria and seven labeled Golgi bodies. The Arabidopsis myosin XI-F PAL domain and the homologous myosin XI-F PAL domain from N. benthamiana labels chloroplasts and stromules in N. benthamiana leaves. Using an Arabidopsis line containing hotoconvertible GFP, we observed transfer of protein from one plastid to another and within a stromule from single plastids. We provided time-lapse movies demonstrating movement of both the photoconvertible GFP and standard GFP between plastids. We previously demonstrated the lack of a plastid network within plant cells. We provided protocols explaining how to use fluorescent protein technology to track plastids and stromules within plant cells. We demonstrated that standard GFP unexpectedly could be photoconverted to a red form under certain conditions, allowing the use of GFP lines for studies that require photoconversion.« less

  12. Is the competence of Swedish Registered Nurses working in municipal care of older people merely a question of age and postgraduate education?

    PubMed

    Karlstedt, Michaela; Wadensten, Barbro; Fagerberg, Ingegerd; Pöder, Ulrika

    2015-06-01

    Previous studies suggest that not only education but also personal aspects such as experience of working as a registered nurse (RN) and age can influence competence. The objective was to explore the educational and self-rated competence of RNs and their duties within the care of older people. A cross-sectional descriptive design was used. All RNs in two counties in Sweden were asked to complete a written questionnaire: a study specific questionnaire with educational and work related questions using the Nurse Competence Scale. The response rate was 61% (n 344). Higher self-rated satisfaction with own professional competence was related to older age, more years after nursing education and possessing at least one postgraduate education in specialist nursing. Educational needs were related to younger age and fewer years since nursing graduation. Education within elder care, including education about drugs was rated the most urgently needed area of education. The most frequently reported tasks were found in the domain helping role, whereas ensuring quality was less present in their daily work. Educational level, age and years of experience had an impact on RNs' self-perceived competence, which is in accordance with previous descriptions of the concept competence. It seems imperative that RNs working in care of the old and with the demands placed on them are given the opportunity to take a postgraduate specialist education in order to gain a competence level in their desired area of work. It is also important that RNs working in care of the old get tailored education in line with the requirements the organisation places on them. © 2014 Nordic College of Caring Science.

  13. Validating Domains of Patient Contextual Factors Essential to Preventing Contextual Errors: A Qualitative Study Conducted at Chicago Area Veterans Health Administration Sites.

    PubMed

    Binns-Calvey, Amy E; Malhiot, Alex; Kostovich, Carol T; LaVela, Sherri L; Stroupe, Kevin; Gerber, Ben S; Burkhart, Lisa; Weiner, Saul J; Weaver, Frances M

    2017-09-01

    "Patient context" indicates patient circumstances and characteristics or states that are essential to address when planning patient care. Specific patient "contextual factors," if overlooked, result in an inappropriate plan of care, a medical error termed a "contextual error." The myriad contextual factors that constitute patient context have been grouped into broad domains to create a taxonomy of challenges to consider when planning care. This study sought to validate a previously identified list of contextual domains. This qualitative study used directed content analysis. In 2014, 19 Department of Veterans Affairs (VA) providers (84% female) and 49 patients (86% male) from two VA medical centers and four outpatient clinics in the Chicago area participated in semistructured interviews and focus groups. Topics included patient-specific, community, and resource-related factors that affect patients' abilities to manage their care. Transcripts were analyzed with a previously identified list of contextual domains as a framework. Analysis of responses revealed that patients and providers identified the same 10 domains previously published, plus 3 additional ones. Based on comments made by patients and providers, the authors created a revised list of 12 domains from themes that emerged. Six pertain to patient circumstances such as access to care and financial situation, and 6 to patient characteristics/states including skills, abilities, and knowledge. Contextual factors in patients' lives may be essential to address for effective care planning. The rubric developed can serve as a "contextual differential" for clinicians to consider when addressing challenges patients face when planning their care.

  14. Combinatorial DNA Damage Pairing Model Based on X-Ray-Induced Foci Predicts the Dose and LET Dependence of Cell Death in Human Breast Cells

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

    Vadhavkar, Nikhil; Pham, Christopher; Georgescu, Walter

    In contrast to the classic view of static DNA double-strand breaks (DSBs) being repaired at the site of damage, we hypothesize that DSBs move and merge with each other over large distances (m). As X-ray dose increases, the probability of having DSB clusters increases as does the probability of misrepair and cell death. Experimental work characterizing the X-ray dose dependence of radiation-induced foci (RIF) in nonmalignant human mammary epithelial cells (MCF10A) is used here to validate a DSB clustering model. We then use the principles of the local effect model (LEM) to predict the yield of DSBs at the submicronmore » level. Two mechanisms for DSB clustering, namely random coalescence of DSBs versus active movement of DSBs into repair domains are compared and tested. Simulations that best predicted both RIF dose dependence and cell survival after X-ray irradiation favored the repair domain hypothesis, suggesting the nucleus is divided into an array of regularly spaced repair domains of ~;;1.55 m sides. Applying the same approach to high-linear energy transfer (LET) ion tracks, we are able to predict experimental RIF/m along tracks with an overall relative error of 12percent, for LET ranging between 30 350 keV/m and for three different ions. Finally, cell death was predicted by assuming an exponential dependence on the total number of DSBs and of all possible combinations of paired DSBs within each simulated RIF. Relative biological effectiveness (RBE) predictions for cell survival of MCF10A exposed to high-LET showed an LET dependence that matches previous experimental results for similar cell types. Overall, this work suggests that microdosimetric properties of ion tracks at the submicron level are sufficient to explain both RIF data and survival curves for any LET, similarly to the LEM assumption. Conversely, high-LET death mechanism does not have to infer linear-quadratic dose formalism as done in the LEM. In addition, the size of repair domains derived in our model are based on experimental RIF and are three times larger than the hypothetical LEM voxel used to fit survival curves. Our model is therefore an alternative to previous approaches that provides a testable biological mechanism (i.e., RIF). In addition, we propose that DSB pairing will help develop more accurate alternatives to the linear cancer risk model (LNT) currently used for regulating exposure to very low levels of ionizing radiation.« less

  15. A Resource Perspective on the Work-Home Interface: The Work-Home Resources Model

    ERIC Educational Resources Information Center

    ten Brummelhuis, Lieke L.; Bakker, Arnold B.

    2012-01-01

    The objective of this article is to provide a theoretical framework explaining positive and negative work-home processes integrally. Using insights from conservation of resources theory, we explain how personal resources (e.g., time, energy, and mood) link demanding and resourceful aspects of one domain to outcomes in the other domain. The…

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

    ERIC Educational Resources Information Center

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

    2017-01-01

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

  17. Psychosocial stressors and cigarette smoking among African American adults in midlife.

    PubMed

    Slopen, Natalie; Dutra, Lauren M; Williams, David R; Mujahid, Mahasin S; Lewis, Tené T; Bennett, Gary G; Ryff, Carol D; Albert, Michelle A

    2012-10-01

    Psychosocial stress is a significant risk factor for smoking, and Blacks experience higher levels of psychosocial stress relative to other racial/ethnic groups. Limited research has comprehensively examined psychosocial stressors in relation to smoking among Blacks. We examined psychosocial stressors in relation to smoking status (current, previous, and never) in middle-aged Blacks (34-85 years, n = 592) from Milwaukee, Wisconsin, a subset of the Midlife in the United States Study II (2004-2006). Eleven stressor domains were assessed, including psychological and physical work stress, work-family conflict, perceived inequality, relationship stress, neighborhood stress, discrimination, financial stress, recent problems, stressful events, and childhood adversity. We also calculated a cumulative score. Multinomial models were adjusted for age, gender, education, and income. Seven of the 11 stressors and the cumulative score were associated with higher odds of being a current smoker compared with a never-smoker: neighborhood, financial, relationship, and psychological work stress, perceived inequality, stressful events, childhood adversity (p values <.05; ORs ranged from 1.28 to 1.77). Three stressors and the cumulative score were associated with higher odds of being a previous smoker versus a never-smoker (p < .05). Individuals who scored in the top quartile on 5 or more stressors were 3.74 (95% CI = 2.09-6.71) times as likely to be current smokers, and more than twice as likely to be previous smokers, compared with individuals with no high stressors. These results demonstrate a strong relationship between stress and smoking among urban middle-aged Blacks and suggest that cessation programs should address modifiable individual and community-level stressors.

  18. [STRESS DUE TO THE WORK-LIFE CONFLICT: ADVICES FROM APPLIED RESEARCH FOR COPING IT].

    PubMed

    Poerio, Vincenzo

    2015-01-01

    Unlike most of the work-related stress research, which emphasizes how to manage stressors and maximize the psychological well-being, the present article focuses on one particular kind of stressor: the experience of conflict or interference between demands at work and responsibilities and commitments outside of the work setting, especially in respect offamily life and one's personal life. Referred to as "work-family conflict" or (more recently) "work-life conflict", this stressor has been demonstrated in research since the 1990s to exert a considerable impact on individuals' well-being along with other areas such as family functioning and even performance on the job. In contrast to the intra-role conflict, which refers to interference between roles within a single domain (e.g., the work context), work-family (or work-life) conflict is a form of inter-role interference which occurs when there is conflict across domains. In the 1980s and 1990s, research and writing in this area focused predominantly on work versus family, but in recent years the "non-work" component has been expanded to include other aspects of people's lives. For simplicity, we will refer to the two major spheres as the "work domain" (i.e., a person's paid employment) and the "life domain" (which comprises all other dimensions of life, including family, recreation, community activities and personal life). Although this classification is not entirely appropriate, it enables differentiation between the two spheres.

  19. Non-native, N-terminal Hsp70 Molecular Motor Recognition Elements in Transit Peptides Support Plastid Protein Translocation*

    PubMed Central

    Chotewutmontri, Prakitchai; Bruce, Barry D.

    2015-01-01

    Previously, we identified the N-terminal domain of transit peptides (TPs) as a major determinant for the translocation step in plastid protein import. Analysis of Arabidopsis TP dataset revealed that this domain has two overlapping characteristics, highly uncharged and Hsp70-interacting. To investigate these two properties, we replaced the N-terminal domains of the TP of the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase and its reverse peptide with a series of unrelated peptides whose affinities to the chloroplast stromal Hsp70 have been determined. Bioinformatic analysis indicated that eight out of nine peptides in this series are not similar to the TP N terminus. Using in vivo and in vitro protein import assays, the majority of the precursors containing Hsp70-binding elements were targeted to plastids, whereas none of the chimeric precursors lacking an N-terminal Hsp70-binding element were targeted to the plastids. Moreover, a pulse-chase assay showed that two chimeric precursors with the most uncharged peptides failed to translocate into the stroma. The ability of multiple unrelated Hsp70-binding elements to support protein import verified that the majority of TPs utilize an N-terminal Hsp70-binding domain during translocation and expand the mechanistic view of the import process. This work also indicates that synthetic biology may be utilized to create de novo TPs that exceed the targeting activity of naturally occurring sequences. PMID:25645915

  20. What helps and hinders midwives in engaging with pregnant women about stopping smoking? A cross-sectional survey of perceived implementation difficulties among midwives in the North East of England

    PubMed Central

    2012-01-01

    Background Around 5,000 miscarriages and 300 perinatal deaths per year result from maternal smoking in the United Kingdom. In the northeast of England, 22% of women smoke at delivery compared to 14% nationally. Midwives have designated responsibilities to help pregnant women stop smoking. We aimed to assess perceived implementation difficulties regarding midwives’ roles in smoking cessation in pregnancy. Methods A self-completed, anonymous survey was sent to all midwives in northeast England (n = 1,358) that explores the theoretical explanations for implementation difficulties of four behaviours recommended in the National Institute for Health and Clinical Excellence (NICE) guidance: (a) asking a pregnant woman about her smoking behaviour, (b) referring to the stop-smoking service, (c) giving advice about smoking behaviour, and (d) using a carbon monoxide monitor. Questions covering Michie et al.’s theoretical domain framework (TDF), describing 11 domains of hypothesised behavioural determinants (i.e., ‘knowledge’, ‘skills’, ‘social/professional role/identity’, ‘beliefs about capabilities’, ‘beliefs about consequences’, ‘motivation and goals’, ‘memory’, ‘attention and decision processes’, ‘environmental context and resources’, ‘social influences’, ‘emotion’, and ‘self-regulation/action planning’), were used to describe perceived implementation difficulties, predict self-reported implementation behaviours, and explore relationships with demographic and professional variables. Results The overall response rate was 43% (n = 589). The number of questionnaires analysed was 364, following removal of the delivery-unit midwives, who are not directly involved in providing smoking-cessation services. Participants reported few implementation difficulties, high levels of motivation for all four behaviours and identified smoking-cessation work with their role. Midwives were less certain about the consequences of, and the environmental context and resources available for, engaging in this work relative to other TDF domains. All domains were highly correlated. A principal component analysis showed that a single factor (‘propensity to act’), derived from all domains, explained 66% of variance in theoretical domain measures. The ‘propensity to act’ was predictive of the self-reported behaviour ‘Refer all women who smoke……to NHS Stop Smoking Services’ and mediated the relationship between demographic variables, such as midwives’ main place of work, and behaviour. Conclusions Our findings advance understanding of what facilitates and inhibits midwives’ guideline implementation behaviours in relation to smoking cessation and will inform the development of current practice and new interventions. Using the TDF as a self-completion questionnaire is innovative, and this study supports previous research that the TDF is an appropriate tool to understand the behaviour of healthcare professionals. PMID:22531641

  1. A strand-passage conformation of DNA gyrase is required to allow the bacterial toxin, CcdB, to access its binding site

    PubMed Central

    Smith, Andrew B.; Maxwell, Anthony

    2006-01-01

    DNA gyrase is the only topoisomerase able to introduce negative supercoils into DNA. Absent in humans, gyrase is a successful target for antibacterial drugs. However, increasing drug resistance is a serious problem and new agents are urgently needed. The naturally-produced Escherichia coli toxin CcdB has been shown to target gyrase by what is predicted to be a novel mechanism. CcdB has been previously shown to stabilize the gyrase ‘cleavage complex’, but it has not been shown to inhibit the catalytic reactions of gyrase. We present data showing that CcdB does indeed inhibit the catalytic reactions of gyrase by stabilization of the cleavage complex and that the GyrA C-terminal DNA-wrapping domain and the GyrB N-terminal ATPase domain are dispensable for CcdB's action. We further investigate the role of specific GyrA residues in the action of CcdB by site-directed mutagenesis; these data corroborate a model for CcdB action based on a recent crystal structure of a CcdB–GyrA fragment complex. From this work, we are now able to present a model for CcdB action that explains all previous observations relating to CcdB–gyrase interaction. CcdB action requires a conformation of gyrase that is only revealed when DNA strand passage is taking place. PMID:16963775

  2. A strand-passage conformation of DNA gyrase is required to allow the bacterial toxin, CcdB, to access its binding site.

    PubMed

    Smith, Andrew B; Maxwell, Anthony

    2006-01-01

    DNA gyrase is the only topoisomerase able to introduce negative supercoils into DNA. Absent in humans, gyrase is a successful target for antibacterial drugs. However, increasing drug resistance is a serious problem and new agents are urgently needed. The naturally-produced Escherichia coli toxin CcdB has been shown to target gyrase by what is predicted to be a novel mechanism. CcdB has been previously shown to stabilize the gyrase 'cleavage complex', but it has not been shown to inhibit the catalytic reactions of gyrase. We present data showing that CcdB does indeed inhibit the catalytic reactions of gyrase by stabilization of the cleavage complex and that the GyrA C-terminal DNA-wrapping domain and the GyrB N-terminal ATPase domain are dispensable for CcdB's action. We further investigate the role of specific GyrA residues in the action of CcdB by site-directed mutagenesis; these data corroborate a model for CcdB action based on a recent crystal structure of a CcdB-GyrA fragment complex. From this work, we are now able to present a model for CcdB action that explains all previous observations relating to CcdB-gyrase interaction. CcdB action requires a conformation of gyrase that is only revealed when DNA strand passage is taking place.

  3. Oxidative Stress Induces Disruption of the Axon Initial Segment

    PubMed Central

    Clark, Kareem C.; Sword, Brooke A.; Dupree, Jeffrey L.

    2017-01-01

    The axon initial segment (AIS), the domain responsible for action potential initiation and maintenance of neuronal polarity, is targeted for disruption in a variety of central nervous system pathological insults. Previous work in our laboratory implicates oxidative stress as a potential mediator of structural AIS alterations in two separate mouse models of central nervous system inflammation, as these effects were attenuated following reactive oxygen species scavenging and NADPH oxidase-2 ablation. While these studies suggest a role for oxidative stress in modulation of the AIS, the direct effects of reactive oxygen and nitrogen species (ROS/RNS) on the stability of this domain remain unclear. Here, we demonstrate that oxidative stress, as induced through treatment with 3-morpholinosydnonimine (SIN-1), a spontaneous ROS/RNS generator, drives a reversible loss of AIS protein clustering in primary cortical neurons in vitro. Pharmacological inhibition of both voltage-dependent and intracellular calcium (Ca2+) channels suggests that this mechanism of AIS disruption involves Ca2+ entry specifically through L-type voltage-dependent Ca2+ channels and its release from IP3-gated intracellular stores. Furthermore, ROS/RNS-induced AIS disruption is dependent upon activation of calpain, a Ca2+-activated protease previously shown to drive AIS modulation. Overall, we demonstrate for the first time that oxidative stress, as induced through exogenously applied ROS/RNS, is capable of driving structural alterations in the AIS complex. PMID:29228786

  4. A mutation in human VAP-B--MSP domain, present in ALS patients, affects the interaction with other cellular proteins.

    PubMed

    Mitne-Neto, M; Ramos, C R R; Pimenta, D C; Luz, J S; Nishimura, A L; Gonzales, F A; Oliveira, C C; Zatz, M

    2007-09-01

    Amyotrophic Lateral Sclerosis (ALS) is the most common adult-onset Motor Neuron Disease (MND), characterized by motor neurons death in the cortex, brainstem and spinal cord. Ten loci linked to Familial ALS have been mapped. ALS8 is caused by a substitution of a proline by a serine in the Vesicle-Associated Membrane Protein-Associated protein-B/C (VAP-B/C). VAP-B belongs to a highly conserved family of proteins implicated in Endoplasmic Reticulum-Golgi and intra-Golgi transport and microtubules stabilization. Previous studies demonstrated that the P56S mutation disrupts the subcellular localization of VAP-B and that this position would be essential for Unfolded Protein Response (UPR) induced by VAP-B. In the present work we expressed and purified recombinant wild-type and P56S mutant VAP-B-MSP domain for the analysis of its interactions with other cellular proteins. Our findings suggest that the P56S mutation may lead to a less stable interaction of this endoplasmic reticulum protein with at least two other proteins: tubulin and GAPDH. These two proteins have been previously related to other forms of neurodegenerative diseases and are potential key points to understand ALS8 pathogenesis and other forms of MND. Understanding the role of these protein interactions may help the treatment of this devastating disease in the future.

  5. Improving Cyber-Security of Smart Grid Systems via Anomaly Detection and Linguistic Domain Knowledge

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

    Ondrej Linda; Todd Vollmer; Milos Manic

    The planned large scale deployment of smart grid network devices will generate a large amount of information exchanged over various types of communication networks. The implementation of these critical systems will require appropriate cyber-security measures. A network anomaly detection solution is considered in this work. In common network architectures multiple communications streams are simultaneously present, making it difficult to build an anomaly detection solution for the entire system. In addition, common anomaly detection algorithms require specification of a sensitivity threshold, which inevitably leads to a tradeoff between false positives and false negatives rates. In order to alleviate these issues, thismore » paper proposes a novel anomaly detection architecture. The designed system applies the previously developed network security cyber-sensor method to individual selected communication streams allowing for learning accurate normal network behavior models. Furthermore, the developed system dynamically adjusts the sensitivity threshold of each anomaly detection algorithm based on domain knowledge about the specific network system. It is proposed to model this domain knowledge using Interval Type-2 Fuzzy Logic rules, which linguistically describe the relationship between various features of the network communication and the possibility of a cyber attack. The proposed method was tested on experimental smart grid system demonstrating enhanced cyber-security.« less

  6. Experimental observation of spatial quantum noise reduction below the standard quantum limit with bright twin beams of light

    NASA Astrophysics Data System (ADS)

    Kumar, Ashok; Nunley, Hayden; Marino, Alberto

    2016-05-01

    Quantum noise reduction (QNR) below the standard quantum limit (SQL) has been a subject of interest for the past two to three decades due to its wide range of applications in quantum metrology and quantum information processing. To date, most of the attention has focused on the study of QNR in the temporal domain. However, many areas in quantum optics, specifically in quantum imaging, could benefit from QNR not only in the temporal domain but also in the spatial domain. With the use of a high quantum efficiency electron multiplier charge coupled device (EMCCD) camera, we have observed spatial QNR below the SQL in bright narrowband twin light beams generated through a four-wave mixing (FWM) process in hot rubidium atoms. Owing to momentum conservation in this process, the twin beams are momentum correlated. This leads to spatial quantum correlations and spatial QNR. Our preliminary results show a spatial QNR of over 2 dB with respect to the SQL. Unlike previous results on spatial QNR with faint and broadband photon pairs from parametric down conversion (PDC), we demonstrate spatial QNR with spectrally and spatially narrowband bright light beams. The results obtained will be useful for atom light interaction based quantum protocols and quantum imaging. Work supported by the W.M. Keck Foundation.

  7. Computational study of the heterodimerization between μ and δ receptors

    NASA Astrophysics Data System (ADS)

    Liu, Xin; Kai, Ming; Jin, Lian; Wang, Rui

    2009-06-01

    A growing body of evidence indicated that the G protein coupled receptors exist as homo- or hetero-dimers in the living cell. The heterodimerization between μ and δ opioid receptors has attracted researchers' particular interests, it is reported to display novel pharmacological and signalling regulation properties. In this study, we construct the full-length 3D-model of μ and δ opioid receptors using the homology modelling method. Threading program was used to predict the possible templates for the N- and C-terminus domains. Then, a 30 ns molecular dynamics simulations was performed with each receptor embedded in an explicit membrane-water environment to refine and explore the conformational space. Based on the structures extracted from the molecular dynamics, the likely interface of μ-δ heterodimer was investigated through the analysis of protein-protein docking, cluster, shape complementary and interaction energy. The computational modelling works revealed that the most likely interface of heterodimer was formed between the transmembrane1,7 (TM1,7) domains of μ receptor and the TM(4,5) domains of δ receptor, with emphasis on μ-TM1 and δ-TM4, the next likely interface was μ(TM6,7)-δ(TM4,5), with emphasis on μ-TM6 and δ-TM4. Our results were consistent with previous reports.

  8. Opposing Shh and Fgf signals initiate nasotemporal patterning of the zebrafish retina.

    PubMed

    Hernández-Bejarano, María; Gestri, Gaia; Spawls, Lana; Nieto-López, Francisco; Picker, Alexander; Tada, Masazumi; Brand, Michael; Bovolenta, Paola; Wilson, Stephen W; Cavodeassi, Florencia

    2015-11-15

    The earliest known determinants of retinal nasotemporal identity are the transcriptional regulators Foxg1, which is expressed in the prospective nasal optic vesicle, and Foxd1, which is expressed in the prospective temporal optic vesicle. Previous work has shown that, in zebrafish, Fgf signals from the dorsal forebrain and olfactory primordia are required to specify nasal identity in the dorsal, prospective nasal, optic vesicle. Here, we show that Hh signalling from the ventral forebrain is required for specification of temporal identity in the ventral optic vesicle and is sufficient to induce temporal character when activated in the prospective nasal retina. Consequently, the evaginating optic vesicles become partitioned into prospective nasal and temporal domains by the opposing actions of Fgfs and Shh emanating from dorsal and ventral domains of the forebrain primordium. In absence of Fgf activity, foxd1 expression is established irrespective of levels of Hh signalling, indicating that the role of Shh in promoting foxd1 expression is only required in the presence of Fgf activity. Once the spatially complementary expression of foxd1 and foxg1 is established, the boundary between expression domains is maintained by mutual repression between Foxd1 and Foxg1. © 2015. Published by The Company of Biologists Ltd.

  9. Coiled-coil intermediate filament stutter instability and molecular unfolding.

    PubMed

    Arslan, Melis; Qin, Zhao; Buehler, Markus J

    2011-05-01

    Intermediate filaments (IFs) are the key components of cytoskeleton in eukaryotic cells and are critical for cell mechanics. The building block of IFs is a coiled-coil alpha-helical dimer, consisting of several domains that include linkers and other structural discontinuities. One of the discontinuities in the dimer's coiled-coil region is the so-called 'stutter' region. The stutter is a region where a variation of the amino acid sequence pattern from other parts of the alpha-helical domains of the protein is found. It was suggested in earlier works that due to this sequence variation, the perfect coiled-coil arrangement ceases to exist. Here, we show using explicit water molecular dynamics and well-tempered metadynamics that for the coil2 domain of vimentin IFs the stutter is more stable in a non-alpha-helical, unfolded state. This causes a local structural disturbance in the alpha helix, which has a global effect on the nanomechanics of the structure. Our analysis suggests that the stutter features an enhanced tendency to unfolding even under the absence of external forces, implying a much greater structural instability than previously assumed. As a result it features a smaller local bending stiffness than other segments and presents a seed for the initiation of molecular bending and unfolding at large deformation.

  10. Measurement of in vivo basal-turn vibrations of the organ of Corti using phase-sensitive Fourier domain optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Ramamoorthy, Sripriya; Zhang, Yuan; Petrie, Tracy; Chen, Fangyi; Subhash, Hrebesh M.; Choudhury, Niloy; Wang, Ruikang; Jacques, Steven L.; Nuttall, Alfred L.

    2013-03-01

    A major reason we can perceive faint sounds and communicate in noisy environments is that the outer hair cells of the organ of Corti enhance the sound-evoked motions inside the cochlea. To understand how the organ of Corti works, we have built and tested the phase-sensitive Fourier domain optical coherence tomography (PSFDOCT) system. This system has key advantages over our previous time domain OCT system [1]. The PSFDOCT system has better signal to noise and simultaneously acquires vibration data from all points along the optical-axis [2]. Feasibility of this system to measure in vitro cochlear vibrations in the apex was demonstrated earlier [3]. In this study, we measure the in vivo vibrations of the organ of Corti via round window in live anaesthetized guinea pigs using PSFDOCT. This region of the guinea pig cochlea responds to very high frequencies (10 - 40 kHz). The current vibration noise floor for native organ of Corti tissue is 0.03 nm in this frequency range. Sound-induced vibrations of the stapes, which delivers input to the cochlea, are also measured. The measured vibrations of the organ of Corti demonstrate non-linear compression and active amplification characteristic of sensitive mammalian cochlea.

  11. Td4IN2: A drought-responsive durum wheat (Triticum durum Desf.) gene coding for a resistance like protein with serine/threonine protein kinase, nucleotide binding site and leucine rich domains.

    PubMed

    Rampino, Patrizia; De Pascali, Mariarosaria; De Caroli, Monica; Luvisi, Andrea; De Bellis, Luigi; Piro, Gabriella; Perrotta, Carla

    2017-11-01

    Wheat, the main food source for a third of world population, appears strongly under threat because of predicted increasing temperatures coupled to drought. Plant complex molecular response to drought stress relies on the gene network controlling cell reactions to abiotic stress. In the natural environment, plants are subjected to the combination of abiotic and biotic stresses. Also the response of plants to biotic stress, to cope with pathogens, involves the activation of a molecular network. Investigations on combination of abiotic and biotic stresses indicate the existence of cross-talk between the two networks and a kind of overlapping can be hypothesized. In this work we describe the isolation and characterization of a drought-related durum wheat (Triticum durum Desf.) gene, identified in a previous study, coding for a protein combining features of NBS-LRR type resistance protein with a S/TPK domain, involved in drought stress response. This is one of the few examples reported where all three domains are present in a single protein and, to our knowledge, it is the first report on a gene specifically induced by drought stress and drought-related conditions, with this particular structure. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  12. Vessel classification in overhead satellite imagery using weighted "bag of visual words"

    NASA Astrophysics Data System (ADS)

    Parameswaran, Shibin; Rainey, Katie

    2015-05-01

    Vessel type classification in maritime imagery is a challenging problem and has applications to many military and surveillance applications. The ability to classify a vessel correctly varies significantly depending on its appearance which in turn is affected by external factors such as lighting or weather conditions, viewing geometry and sea state. The difficulty in classifying vessels also varies among different ship types as some types of vessels show more within-class variation than others. In our previous work, we showed that the bag of visual words" (V-BoW) was an effective feature representation for this classification task in the maritime domain. The V-BoW feature representation is analogous to the bag of words" (BoW) representation used in information retrieval (IR) application in text or natural language processing (NLP) domain. It has been shown in the textual IR applications that the performance of the BoW feature representation can be improved significantly by applying appropriate term-weighting such as log term frequency, inverse document frequency etc. Given the close correspondence between textual BoW (T-BoW) and V-BoW feature representations, we propose to apply several well-known term weighting schemes from the text IR domain on V-BoW feature representation to increase its ability to discriminate between ship types.

  13. The stability of working memory: do previous tasks influence complex span?

    PubMed

    Healey, M Karl; Hasher, Lynn; Danilova, Elena

    2011-11-01

    Schmeichel (2007) reported that performing an initial task before completing a working memory span task can lower span scores and suggested that the effect was due to depleted cognitive resources. We showed that the detrimental effect of prior tasks depends on a match between the stimuli used in the span task and the preceding task. A task requiring participants to ignore words reduced performance on a subsequent word-based verbal span task but not on an arrow-based spatial span task. Ignoring arrows had the opposite pattern of effects: reducing performance on the spatial span task but not on the word-based span task. Finally, we showed that antisaccade, a nonverbal task that taxes domain-general processes implicated in working memory, did not influence subsequent performance of either a verbal or a spatial span task. Together these results suggest that while span is sensitive to prior tasks, that sensitivity does not stem from depleted resources. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

  14. Planning Under Continuous Time and Resource Uncertainty: A Challenge for AI

    NASA Technical Reports Server (NTRS)

    Bresina, John; Dearden, Richard; Meuleau, Nicolas; Smith, David; Washington, Rich; Clancy, Daniel (Technical Monitor)

    2002-01-01

    There has been considerable work in Al on decision-theoretic planning and planning under uncertainty. Unfortunately, all of this work suffers from one or more of the following limitations: 1) it relies on very simple models of actions and time, 2) it assumes that uncertainty is manifested in discrete action outcomes, and 3) it is only practical for very small problems. For many real world problems, these assumptions fail to hold. A case in point is planning the activities for a Mars rover. For this domain none of the above assumptions are valid: 1) actions can be concurrent and have differing durations, 2) there is uncertainty concerning action durations and consumption of continuous resources like power, and 3) typical daily plans involve on the order of a hundred actions. We describe the rover problem, discuss previous work on planning under uncertainty, and present a detailed. but very small, example illustrating some of the difficulties of finding good plans.

  15. Scalable Domain Decomposed Monte Carlo Particle Transport

    NASA Astrophysics Data System (ADS)

    O'Brien, Matthew Joseph

    In this dissertation, we present the parallel algorithms necessary to run domain decomposed Monte Carlo particle transport on large numbers of processors (millions of processors). Previous algorithms were not scalable, and the parallel overhead became more computationally costly than the numerical simulation. The main algorithms we consider are: • Domain decomposition of constructive solid geometry: enables extremely large calculations in which the background geometry is too large to fit in the memory of a single computational node. • Load Balancing: keeps the workload per processor as even as possible so the calculation runs efficiently. • Global Particle Find: if particles are on the wrong processor, globally resolve their locations to the correct processor based on particle coordinate and background domain. • Visualizing constructive solid geometry, sourcing particles, deciding that particle streaming communication is completed and spatial redecomposition. These algorithms are some of the most important parallel algorithms required for domain decomposed Monte Carlo particle transport. We demonstrate that our previous algorithms were not scalable, prove that our new algorithms are scalable, and run some of the algorithms up to 2 million MPI processes on the Sequoia supercomputer.

  16. Structure of the dimerization domain of DiGeorge Critical Region 8

    PubMed Central

    Senturia, Rachel; Faller, Michael; Yin, Sheng; Loo, Joseph A; Cascio, Duilio; Sawaya, Michael R; Hwang, Daniel; Clubb, Robert T; Guo, Feng

    2010-01-01

    Maturation of microRNAs (miRNAs, ∼22nt) from long primary transcripts [primary miRNAs (pri-miRNAs)] is regulated during development and is altered in diseases such as cancer. The first processing step is a cleavage mediated by the Microprocessor complex containing the Drosha nuclease and the RNA-binding protein DiGeorge critical region 8 (DGCR8). We previously reported that dimeric DGCR8 binds heme and that the heme-bound DGCR8 is more active than the heme-free form. Here, we identified a conserved dimerization domain in DGCR8. Our crystal structure of this domain (residues 298–352) at 1.7 Å resolution demonstrates a previously unknown use of a WW motif as a platform for extensive dimerization interactions. The dimerization domain of DGCR8 is embedded in an independently folded heme-binding domain and directly contributes to association with heme. Heme-binding-deficient DGCR8 mutants have reduced pri-miRNA processing activity in vitro. Our study provides structural and biochemical bases for understanding how dimerization and heme binding of DGCR8 may contribute to regulation of miRNA biogenesis. PMID:20506313

  17. Ferroelectric and multiferroic domain imaging by Laser-induced photoemission microscopy

    NASA Astrophysics Data System (ADS)

    Hoefer, Anke; Fechner, Michael; Duncker, Klaus; Mertig, Ingrid; Widdra, Wolf

    2013-03-01

    The ferroelectric as well as multiferroic surface domain structures of BaTiO3(001) and BiFeO3(001) are imaged based on photoemission electron microscopy (PEEM) by femtosecond laser threshold excitation under UHV conditions. For well-prepared BaTiO3(001), three ferroelectric domain types are clearly discriminable due to work function differences. At room temperature, the surface domains resemble the known ferroelectric domain structure of the bulk. Upon heating above the Curie point of 400 K, the specific surface domain pattern remains up to 500 K. Ab-initio calculations explain this observation by a remaining tetragonal distortion of the topmost unit cells stabilized by a surface relaxation. The (001) surface of the single-phase multiferroic BiFeO3 which is ferroelectric and antiferromagnetic, shows clear ferroelectric work function contrast in PEEM. Additionally, the multiferroic domains show significant linear dichroism. The observation of a varying dichroism for different ferroelectric domains can be explained based on the coupled ferroelectric-antiferromagnetic order in BiFeO3. It demonstrates multiferroic imaging of different domain types within a single, lab-based experiment.

  18. Family, Employment, and Individual Resource-Based Antecedents of Maternal Work-Family Enrichment from Infancy through Middle Childhood

    PubMed Central

    Zhou, Nan; Buehler, Cheryl

    2015-01-01

    This study used data from the NICHD Study of Early Child Care and Youth Development (N = 1,019) to examine family, employment, and individual antecedents of maternal work-family enrichment from infancy through middle childhood. Work-family conflict and important confounding factors were controlled. From the family domain, higher income-to-needs ratio and social support were associated with higher work-family enrichment. From the employment domain, greater job rewards, benefits of employment for children, and work commitment were associated with higher work-family enrichment. From the individual domain, higher maternal education and extroversion were associated with higher work-family enrichment. No family, employment, and individual characteristics were associated with work-family conflict across time except for partner intimacy. In general, the results supported antecedents of work-family enrichment that supply needed resources. The present study contributed to the literature by identifying antecedents of maternal work-family enrichment across early child developmental stages, which goes beyond examinations of particular life stages and a work-family conflict perspective. Implications for theory and practice are discussed. PMID:26641483

  19. Supramodal parametric working memory processing in humans.

    PubMed

    Spitzer, Bernhard; Blankenburg, Felix

    2012-03-07

    Previous studies of delayed-match-to-sample (DMTS) frequency discrimination in animals and humans have succeeded in delineating the neural signature of frequency processing in somatosensory working memory (WM). During retention of vibrotactile frequencies, stimulus-dependent single-cell and population activity in prefrontal cortex was found to reflect the task-relevant memory content, whereas increases in occipital alpha activity signaled the disengagement of areas not relevant for the tactile task. Here, we recorded EEG from human participants to determine the extent to which these mechanisms can be generalized to frequency retention in the visual and auditory domains. Subjects performed analogous variants of a DMTS frequency discrimination task, with the frequency information presented either visually, auditorily, or by vibrotactile stimulation. Examining oscillatory EEG activity during frequency retention, we found characteristic topographical distributions of alpha power over visual, auditory, and somatosensory cortices, indicating systematic patterns of inhibition and engagement of early sensory areas, depending on stimulus modality. The task-relevant frequency information, in contrast, was found to be represented in right prefrontal cortex, independent of presentation mode. In each of the three modality conditions, parametric modulations of prefrontal upper beta activity (20-30 Hz) emerged, in a very similar manner as recently found in vibrotactile tasks. Together, the findings corroborate a view of parametric WM as supramodal internal scaling of abstract quantity information and suggest strong relevance of previous evidence from vibrotactile work for a more general framework of quantity processing in human working memory.

  20. Supporting Mechanistic Reasoning in Domain-Specific Contexts

    ERIC Educational Resources Information Center

    Weinberg, Paul J.

    2017-01-01

    Mechanistic reasoning is an epistemic practice central within science, technology, engineering, and mathematics disciplines. Although there has been some work on mechanistic reasoning in the research literature and standards documents, much of this work targets domain-general characterizations of mechanistic reasoning; this study provides…

  1. Scalable Domain Decomposed Monte Carlo Particle Transport

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

    O'Brien, Matthew Joseph

    2013-12-05

    In this dissertation, we present the parallel algorithms necessary to run domain decomposed Monte Carlo particle transport on large numbers of processors (millions of processors). Previous algorithms were not scalable, and the parallel overhead became more computationally costly than the numerical simulation.

  2. The content of the work of clinical nurse specialists described by use of daily activity diaries.

    PubMed

    Oddsdóttir, Elín Jakobína; Sveinsdóttir, Herdís

    2011-05-01

    Evaluate the usefulness of the role of clinical nurse specialists and the content of their work by mapping their activities. The clinical work of advanced practice nursing differs in different countries, and a clear picture is lacking on what exactly advanced practice nurses do. Prospective exploratory study. The setting of the study was the largest hospital in Iceland where over half of the country's active nursing workforce are employed, including the only clinical nurse specialists. Of 19 clinical nurse specialists working at the hospital, 15 participated. Data were collected over seven days with a structured activity diary that lists 65 activities, classified into six roles and three domains. In 17 instances, the 'role activities' and 'domain activities' overlap and form 17 categories of practice. The clinical nurse specialists coded their activities at 15-minutes interval and could code up to four activities simultaneously. Daily, the clinical nurse specialists evaluated their clinical nurse specialist background. The roles that occupied the greatest proportion of the clinical nurse specialists' time were education, expert practice and 'other' activities, while the smallest proportions were in counselling, research and practice development. The domain they worked in most was the institutional domain, followed by the client/family domain and the clinical outcome management domain. All of the clinical nurse specialists reported working on two activities simultaneously, 11 of them on three activities and six on four activities. They self-assessed their background as clinical nurse specialists as being very useful. The activity diary is a useful tool for assessing the content of practice. Clinical nurse specialists spend too much time on activities related to the institution. Nurse managers are advised to provide clinical nurse specialists with ample time to develop the direct practice role in the client/family domain. The development of advanced nursing practice requires that clinical nurse specialists take an active and visible part in direct patient care. © 2011 Blackwell Publishing Ltd.

  3. The contributions of human factors and ergonomics to a sustainable minerals industry.

    PubMed

    Horberry, Tim; Burgess-Limerick, Robin; Fuller, Ruth

    2013-01-01

    This article describes examples of the application of human factors research and development work to a sustainable minerals industry. It begins by outlining human-related aspects of the minerals industry and the key human factors work previously undertaken in this domain. The focus then switches to sustainability in the minerals industry. Sustainability principles are introduced and illustrations provided of how human factors research and development work fits within such a framework. Three case studies of human factors in the minerals industry research are presented and the sustainability implications in each case study are highlighted. Finally, future trends related to human factors work in a sustainable minerals industry are addressed, in particular the opportunities and possible adverse consequences that increasing deployment of mining automation might bring. Minerals industries are a major global activity with significant sustainability implications. Aspects of sustainability in mining are examined using three case studies. These illustrate the contribution of human factors/ergonomics in reducing risks; developing emergency response management systems; and the value of participatory ergonomics in improving the design of mining equipment.

  4. The Role of Working Memory Gating in Task Switching: A Procedural Version of the Reference-Back Paradigm

    PubMed Central

    Kessler, Yoav

    2017-01-01

    Models of working memory (WM) suggest that the contents of WM are separated from perceptual input by a gate, that enables shielding information against interference when closed, and allows for rapid updating when open. Recent work in the declarative WM domain provided evidence for this notion, demonstrating the behavioral cost of opening and closing the gate. The goal of the present work was to examine gating in procedural WM, namely in a task-switching experiment. In each trial, participants were presented with a digit and a task cue, indicating whether the required task was a parity or a magnitude decision. Critically, a colored frame around the stimulus indicated whether the task cue was relevant (attend trials), or whether it had to be ignored, and the previous task set should be applied regardless of the present cue (ignore trials). Switching between tasks, and between ignore and attend trials, was manipulated. The results of two experiments demonstrated that the cost of gate opening was eliminated in task switching trials, implying that both processes operate in parallel. PMID:29312095

  5. Do Workers Who Experience Conflict between the Work and Family Domains Hit a "Glass Ceiling?": A Meta-Analytic Examination

    ERIC Educational Resources Information Center

    Hoobler, Jenny M.; Hu, Jia; Wilson, Morgan

    2010-01-01

    Based in Conservation of Resources (COR; Hobfoll, 1989) and self-verification (Swann, 1987) theories, we argue that when workers experience conflict between the work and family domains, this should have implications for evaluations of their work performance and ultimately affect more "objective" career outcomes such as salary and hierarchical…

  6. A Time Domain Impedance Probe For Ultra-Fast Measurements of Electron Parameters in the Ionosphere: Results From A NASA USIP Experiment

    NASA Astrophysics Data System (ADS)

    Clark, D. C.; Spencer, E. A.; Gollapalli, R.; Kerrigan, B.

    2016-12-01

    A plasma impedance probe is used to obtain plasma parameters in the ionosphere by measuring the magnitude, shape and location of resonances in the frequency spectrum when a probe structure is driven with RF excitation. We have designed and developed a new Time Domain Impedance Probe (TDIP) capable of making measurements of absolute electron density and electron neutral collision frequency at temporal and spatial resolutions not previously attained. A single measurement can be made in a time as short as 100 microseconds, which yields much higher spatial resolution than a frequency sweep method. This method essentially consists of applying a small amplitude time limited voltage signal into a probe and measuring the resulting current response. The frequency bandwidth of the voltage signal is selected in order that the electron plasma resonances are observable. A prototype of the new instrument was flown at 08:45 EST on March 1 2016 on a NASA Undergraduate Student Instrument Progam (USIP) sounding rocket launched out of Wallops Flight Facility (Flight time was around 20 minutes). Here we analyze the data from the sounding rocket experiment, using an adaptive system identification technique to compare the measured data with analytical formulas obtained from a theoretical consideration of the time domain response. The analytical formula is calibrated to a plasma fluid finite difference time domain (PFFDTD) numerical computation before using it to analyze the rocket data from 85 km to 170 km on both upleg and downleg. Our results show that the technique works as advertised, but several issues including payload charging and signal rectification remains to be resolved. A plasma impedance probe is used to obtain plasma parameters in the ionosphere by measuring the magnitude, shape and location of resonances in the frequency spectrum when a probe structure is driven with RF excitation. We have designed and developed a new Time Domain Impedance Probe (TDIP) capable of making measurements of absolute electron density and electron neutral collision frequency at temporal and spatial resolutions not previously attained. A single measurement can be made in a time as short as 100 microseconds, which yields much higher spatial resolution than a frequency sweep method. This method essentially consists of applying a small amplitude time limited voltage signal into a probe and measuring the resulting current response. The frequency bandwidth of the voltage signal is selected in order that the electron plasma resonances are observable. A prototype of the new instrument was flown at 08:45 EST on March 1 2016 on a NASA Undergraduate Student Instrument Progam (USIP) sounding rocket launched out of Wallops Flight Facility (Flight time was around 20 minutes). Here we analyze the data from the sounding rocket experiment, using an adaptive system identification technique to compare the measured data with analytical formulas obtained from a theoretical consideration of the time domain response. The analytical formula is calibrated to a plasma fluid finite difference time domain (PFFDTD) numerical computation before using it to analyze the rocket data from 85 km to 170 km on both upleg and downleg. Our results show that the technique works as advertised, but several issues including payload charging and signal rectification remains to be resolved.

  7. CD and NMR conformational studies of a peptide encompassing the Mid Loop interface of Ship2-Sam.

    PubMed

    Mercurio, Flavia A; Scognamiglio, Pasqualina L; Di Natale, Concetta; Marasco, Daniela; Pellecchia, Maurizio; Leone, Marilisa

    2014-11-01

    The lipid phosphatase Ship2 is a protein that intervenes in several diseases such as diabetes, cancer, neurodegeneration, and atherosclerosis. It is made up of a catalytic domain and several protein docking modules such as a C-terminal Sam (Sterile alpha motif) domain. The Sam domain of Ship2 (Ship2-Sam) binds to the Sam domains of the EphA2 receptor (EphA2-Sam) and the PI3K effector protein Arap3 (Arap3-Sam). These heterotypic Sam-Sam interactions occur through formation of dimers presenting the canonical "Mid Loop/End Helix" binding mode. The central region of Ship2-Sam, spanning the C-terminal end of α2, the α3 and α4 helices together with the α2α3 and α3α4 interhelical loops, forms the Mid Loop surface that is needed to bind partners Sam domains. A peptide encompassing most of the Ship2-Sam Mid Loop interface (Shiptide) capable of binding to both EphA2-Sam and Arap3-Sam, was previously identified. Here we investigated the conformational features of this peptide, through solution CD and NMR studies in different conditions. These studies reveal that the peptide is highly flexible in aqueous buffer, while it adopts a helical conformation in presence of 2,2,2-trifluoroethanol. The discovered structural insights and in particular the identification of a helical motif, may lead to the design of more constrained and possibly cell permeable Shiptide analogs that could work as efficient antagonists of Ship2-Sam heterotypic interactions and embrace therapeutic applications. © 2014 Wiley Periodicals, Inc.

  8. 3DIANA: 3D Domain Interaction Analysis: A Toolbox for Quaternary Structure Modeling

    PubMed Central

    Segura, Joan; Sanchez-Garcia, Ruben; Tabas-Madrid, Daniel; Cuenca-Alba, Jesus; Sorzano, Carlos Oscar S.; Carazo, Jose Maria

    2016-01-01

    Electron microscopy (EM) is experiencing a revolution with the advent of a new generation of Direct Electron Detectors, enabling a broad range of large and flexible structures to be resolved well below 1 nm resolution. Although EM techniques are evolving to the point of directly obtaining structural data at near-atomic resolution, for many molecules the attainable resolution might not be enough to propose high-resolution structural models. However, accessing information on atomic coordinates is a necessary step toward a deeper understanding of the molecular mechanisms that allow proteins to perform specific tasks. For that reason, methods for the integration of EM three-dimensional maps with x-ray and NMR structural data are being developed, a modeling task that is normally referred to as fitting, resulting in the so called hybrid models. In this work, we present a novel application—3DIANA—specially targeted to those cases in which the EM map resolution is medium or low and additional experimental structural information is scarce or even lacking. In this way, 3DIANA statistically evaluates proposed/potential contacts between protein domains, presents a complete catalog of both structurally resolved and predicted interacting regions involving these domains and, finally, suggests structural templates to model the interaction between them. The evaluation of the proposed interactions is computed with DIMERO, a new method that scores physical binding sites based on the topology of protein interaction networks, which has recently shown the capability to increase by 200% the number of domain-domain interactions predicted in interactomes as compared to previous approaches. The new application displays the information at a sequence and structural level and is accessible through a web browser or as a Chimera plugin at http://3diana.cnb.csic.es. PMID:26772592

  9. Structural Features of the Pseudomonas fluorescens Biofilm Adhesin LapA Required for LapG-Dependent Cleavage, Biofilm Formation, and Cell Surface Localization

    PubMed Central

    Boyd, Chelsea D.; Smith, T. Jarrod; El-Kirat-Chatel, Sofiane; Newell, Peter D.; Dufrêne, Yves F.

    2014-01-01

    The localization of the LapA protein to the cell surface is a key step required by Pseudomonas fluorescens Pf0-1 to irreversibly attach to a surface and form a biofilm. LapA is a member of a diverse family of predicted bacterial adhesins, and although lacking a high degree of sequence similarity, family members do share common predicted domains. Here, using mutational analysis, we determine the significance of each domain feature of LapA in relation to its export and localization to the cell surface and function in biofilm formation. Our previous work showed that the N terminus of LapA is required for cleavage by the periplasmic cysteine protease LapG and release of the adhesin from the cell surface under conditions unfavorable for biofilm formation. We define an additional critical region of the N terminus of LapA required for LapG proteolysis. Furthermore, our results suggest that the domains within the C terminus of LapA are not absolutely required for biofilm formation, export, or localization to the cell surface, with the exception of the type I secretion signal, which is required for LapA export and cell surface localization. In contrast, deletion of the central repetitive region of LapA, consisting of 37 repeats of 100 amino acids, results in an inability to form a biofilm. We also used single-molecule atomic force microscopy to further characterize the role of these domains in biofilm formation on hydrophobic and hydrophilic surfaces. These studies represent the first detailed analysis of the domains of the LapA family of biofilm adhesin proteins. PMID:24837291

  10. Ferroionic states: coupling between surface electrochemical and bulk ferroelectric functionalities on the nanoscale.

    NASA Astrophysics Data System (ADS)

    Kalinin, Sergei

    Ferroelectricity on the nanoscale has remained a subject of much fascination in condensed matter physics for the last several decades. It is well-recognized that stability of the ferroelectric state necessitates effective polarization screening, and hence screening mechanism and screening charge dynamics become strongly coupled to ferroelectric phase stability and domain behavior. Previously, the role of the screening charge in macroscopic ferroelectrics was observed in phenomena such as potential retention above Curie temperature, back switching of ferroelectric domains, and chaos and intermittency during domain switching. In the last several years, multiple reports claiming ferroelectricity in ultrathin ferroelectrics based on formation of remanent polarization states, local hysteresis loops, and pressure induced switching were made. However, similar phenomena were reported for traditionally non-ferroelectric materials, creating significant level of uncertainty in the field. We pose that in the nanoscale systems, the ferroelectric state is fundamentally inseparable from electrochemical state of the surface, leading to emergence of coupled electrochemical-ferroelectric states. I will present the results of experimental and theoretical work exploring the basic mechanisms of emergence of these coupled states including the basic theory and phase-field formulation for domain evolution. I further discuss the thermodynamics and thickness evolution of this state, and demonstrate the experimental pathway to establish its presence based on spectroscopic version of piezoresponse force microscopy. Finally, the role of chemical screening on domain dynamics is explored using phase-field modelling. This analysis reconciles multiple prior studies, and set forward the predictive pathways for new generations of ferroelectric devices and applications. This research was sponsored by the Division of Materials Sciences and Engineering, BES, DOE, and was conducted at the Center for Nanophase Materials Sciences, sponsored at Oak Ridge National Laboratory by the Scientific User Facilities Division.

  11. Peer Review-Based Scripted Collaboration to Support Domain-Specific and Domain-General Knowledge Acquisition in Computer Science

    ERIC Educational Resources Information Center

    Demetriadis, Stavros; Egerter, Tina; Hanisch, Frank; Fischer, Frank

    2011-01-01

    This study investigates the effectiveness of using peer review in the context of scripted collaboration to foster both domain-specific and domain-general knowledge acquisition in the computer science domain. Using a one-factor design with a script and a control condition, students worked in small groups on a series of computer science problems…

  12. Integration of Pragmatic and Phonetic Cues in Spoken Word Recognition

    PubMed Central

    Rohde, Hannah; Ettlinger, Marc

    2015-01-01

    Although previous research has established that multiple top-down factors guide the identification of words during speech processing, the ultimate range of information sources that listeners integrate from different levels of linguistic structure is still unknown. In a set of experiments, we investigate whether comprehenders can integrate information from the two most disparate domains: pragmatic inference and phonetic perception. Using contexts that trigger pragmatic expectations regarding upcoming coreference (expectations for either he or she), we test listeners' identification of phonetic category boundaries (using acoustically ambiguous words on the/hi/∼/∫i/continuum). The results indicate that, in addition to phonetic cues, word recognition also reflects pragmatic inference. These findings are consistent with evidence for top-down contextual effects from lexical, syntactic, and semantic cues, but they extend this previous work by testing cues at the pragmatic level and by eliminating a statistical-frequency confound that might otherwise explain the previously reported results. We conclude by exploring the time-course of this interaction and discussing how different models of cue integration could be adapted to account for our results. PMID:22250908

  13. Combining biophysical methods to analyze the disulfide bond in SH2 domain of C-terminal Src kinase.

    PubMed

    Liu, Dongsheng; Cowburn, David

    2016-01-01

    The Src Homology 2 (SH2) domain is a structurally conserved protein domain that typically binds to a phosphorylated tyrosine in a peptide motif from the target protein. The SH2 domain of C-terminal Src kinase (Csk) contains a single disulfide bond, which is unusual for most SH2 domains. Although the global motion of SH2 domain regulates Csk function, little is known about the relationship between the disulfide bond and binding of the ligand. In this study, we combined X-ray crystallography, solution NMR, and other biophysical methods to reveal the interaction network in Csk. Denaturation studies have shown that disulfide bond contributes significantly to the stability of SH2 domain, and crystal structures of the oxidized and C122S mutant showed minor conformational changes. We further investigated the binding of SH2 domain to a phosphorylated peptide from Csk-binding protein upon reduction and oxidation using both NMR and fluorescence approaches. This work employed NMR, X-ray cryptography, and other biophysical methods to study a disulfide bond in Csk SH2 domain. In addition, this work provides in-depth understanding of the structural dynamics of Csk SH2 domain.

  14. Artifact interactions retard technological improvement: An empirical study

    PubMed Central

    Magee, Christopher L.

    2017-01-01

    Empirical research has shown performance improvement of many different technological domains occurs exponentially but with widely varying improvement rates. What causes some technologies to improve faster than others do? Previous quantitative modeling research has identified artifact interactions, where a design change in one component influences others, as an important determinant of improvement rates. The models predict that improvement rate for a domain is proportional to the inverse of the domain’s interaction parameter. However, no empirical research has previously studied and tested the dependence of improvement rates on artifact interactions. A challenge to testing the dependence is that any method for measuring interactions has to be applicable to a wide variety of technologies. Here we propose a novel patent-based method that is both technology domain-agnostic and less costly than alternative methods. We use textual content from patent sets in 27 domains to find the influence of interactions on improvement rates. Qualitative analysis identified six specific keywords that signal artifact interactions. Patent sets from each domain were then examined to determine the total count of these 6 keywords in each domain, giving an estimate of artifact interactions in each domain. It is found that improvement rates are positively correlated with the inverse of the total count of keywords with Pearson correlation coefficient of +0.56 with a p-value of 0.002. The results agree with model predictions, and provide, for the first time, empirical evidence that artifact interactions have a retarding effect on improvement rates of technological domains. PMID:28777798

  15. Putative calcium-binding domains of the Caenorhabditis elegans BK channel are dispensable for intoxication and ethanol activation

    PubMed Central

    Davis, S. J.; Scott, L. L.; Ordemann, G.; Philpo, A.; Cohn, J.; Pierce-Shimomura, J. T.

    2016-01-01

    Alcohol modulates the highly conserved, voltage- and calcium-activated potassium (BK) channel, which contributes to alcohol-mediated behaviors in species from worms to humans. Previous studies have shown that the calcium-sensitive domains, RCK1 and the Ca2+ bowl, are required for ethanol activation of the mammalian BK channel in vitro. In the nematode Caenorhabditis elegans, ethanol activates the BK channel in vivo, and deletion of the worm BK channel, SLO-1, confers strong resistance to intoxication. To determine if the conserved RCK1 and calcium bowl domains were also critical for intoxication and basal BK channel-dependent behaviors in C. elegans, we generated transgenic worms that express mutated SLO-1 channels predicted to have the RCK1, Ca2+ bowl or both domains rendered insensitive to calcium. As expected, mutating these domains inhibited basal function of SLO-1 in vivo as neck and body curvature of these mutants mimicked that of the BK null mutant. Unexpectedly, however, mutating these domains singly or together in SLO-1 had no effect on intoxication in C. elegans. Consistent with these behavioral results, we found that ethanol activated the SLO-1 channel in vitro with or without these domains. By contrast, in agreement with previous in vitro findings, C. elegans harboring a human BK channel with mutated calcium-sensing domains displayed resistance to intoxication. Thus, for the worm SLO-1 channel, the putative calcium-sensitive domains are critical for basal in vivo function but unnecessary for in vivo ethanol action. PMID:26113050

  16. Relationship of psychosocial work factors and health-related quality of life in male automotive assembly workers in Malaysia.

    PubMed

    Edimansyah, Bin Abdin; Rusli, Bin Nordin; Naing, Lin; Mohamed Rusli, Bin Abdullah; Winn, Than

    2007-06-01

    The present study investigates the relationship between psychosocial work factors and health-related quality of life (HRQOL) in male automotive assembly plant workers in Malaysia. A total of 728 male workers were recruited in March-July 2005 from 2 major automotive assembly plants in Selangor and Pahang. In this cross-sectional study, information on socio-demography, psychosocial work factors using the 97-item Job Content Questionnaire (JCQ) and an abbreviated 26-item version of the World Health Organization Quality of Life-Brief Version (WHOQOL-BREF) questionnaire containing 4 domains (physical health, psychological, social relationship, and environment) was self-administered to all workers involved. The prevalence of reported good or very good overall HRQOL and general health was 64.9% and 53.7%, respectively. Multiple linear regression analysis indicated that created skill was positively associated with physical health and psychological domains; whilst, skill discretion was positively associated with social relationship and environment domains. Social support was positively associated with physical health and environment domains; whilst, co-worker support was positively associated with psychological and social relationship domains. Job insecurity and hazardous condition were negatively associated with all domains, whilst psychological job demands was negatively associated with the environment domain of HRQOL.

  17. Role of Plant-Specific N-Terminal Domain of Maize CK2β1 Subunit in CK2β Functions and Holoenzyme Regulation

    PubMed Central

    Vélez-Bermúdez, Isabel C.; Carretero-Paulet, Lorenzo; Lumbreras, Victoria; Pagès, Montserrat

    2011-01-01

    Protein kinase CK2 is a highly pleiotropic Ser/Thr kinase ubiquituous in eukaryotic organisms. CK2 is organized as a heterotetrameric enzyme composed of two types of subunits: the catalytic (CK2α) and the regulatory (CK2β). The CK2β subunits enhance the stability, activity and specificity of the holoenzyme, but they can also perform functions independently of the CK2 tetramer. CK2β regulatory subunits in plants differ from their animal or yeast counterparts, since they present an additional specific N-terminal extension of about 90 aminoacids that shares no homology with any previously characterized functional domain. Sequence analysis of the N-terminal domain of land plant CK2β subunit sequences reveals its arrangement through short, conserved motifs, some of them including CK2 autophosphorylation sites. By using maize CK2β1 and a deleted version (ΔNCK2β1) lacking the N-terminal domain, we have demonstrated that CK2β1 is autophosphorylated within the N-terminal domain. Moreover, the holoenzyme composed with CK2α1/ΔNCK2β1 is able to phosphorylate different substrates more efficiently than CK2α1/CK2β1 or CK2α alone. Transient overexpression of CK2β1 and ΔNCK2β1 fused to GFP in different plant systems show that the presence of N-terminal domain enhances aggregation in nuclear speckles and stabilizes the protein against proteasome degradation. Finally, bimolecular fluorescence complementation (BiFC) assays show the nuclear and cytoplasmic location of the plant CK2 holoenzyme, in contrast to the individual CK2α/β subunits mainly observed in the nucleus. All together, our results support the hypothesis that the plant-specific N-terminal domain of CK2β subunits is involved in the down-regulation of the CK2 holoenzyme activity and in the stabilization of CK2β1 protein. In summary, the whole amount of data shown in this work suggests that this domain was acquired by plants for regulatory purposes. PMID:21789193

  18. Polarity of the ascidian egg cortex and relocalization of cER and mRNAs in the early embryo.

    PubMed

    Prodon, François; Dru, Philippe; Roegiers, Fabrice; Sardet, Christian

    2005-06-01

    The mature ascidian oocyte is a large cell containing cytoplasmic and cortical domains polarized along a primary animal-vegetal (a-v) axis. The oocyte cortex is characterized by a gradient distribution of a submembrane monolayer of cortical rough endoplasmic reticulum (cER) and associated maternal postplasmic/PEM mRNAs (cER-mRNA domain). Between fertilization and first cleavage, this cER-mRNA domain is first concentrated vegetally and then relocated towards the posterior pole via microfilament-driven cortical contractions and spermaster-microtubule-driven translocations. The cER-mRNA domain further concentrates in a macroscopic cortical structure called the centrosome attracting body (CAB), which mediates a series of asymmetric divisions starting at the eight-cell stage. This results in the segregation of determinant mRNAs and their products in posterior cells of the embryo precursors of the muscle and germ line. Using two species of ascidians (Ciona intestinalis and Phallusia mammillata), we have pursued and amplified the work initiated in Halocynthia roretzi. We have analysed the cortical reorganizations in whole cells and in cortical fragments isolated from oocytes and from synchronously developing zygotes and embryos. After fertilization, we observe that a cortical patch rich in microfilaments encircles the cER-mRNA domain, concentrated into a cortical cap at the vegetal/contraction pole (indicating the future dorsal pole). Isolated cortices also retain microtubule asters rich in cER (indicating the future posterior pole). Before mitosis, parts of the cER-mRNA domain are detected, together with short microtubules, in isolated posterior (but not anterior) cortices. At the eight-cell stage, the posteriorly located cER-mRNA domain undergoes a cell-cycle-dependant compaction into the CAB. The CAB with embedded centrosomal microtubules can be isolated with cortical fragments from eight-cell-stage embryos. These and previous observations indicate that cytoskeleton-driven repositioning and compaction of a polarized cortical domain made of rough ER is a conserved mechanism used for polarization and segregation of cortical maternal mRNAs in embryos of evolutionarily distant species of ascidians.

  19. A Unified Approach to Intra-Domain Security

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

    Shue, Craig A; Kalafut, Andrew J.; Gupta, Prof. Minaxi

    2009-01-01

    While a variety of mechanisms have been developed for securing individual intra-domain protocols, none address the issue in a holistic manner. We develop a unified framework to secure prominent networking protocols within a single domain. We begin with a secure version of the DHCP protocol, which has the additional feature of providing each host with a certificate. We then leverage these certificates to secure ARP, prevent spoofing within the domain, and secure SSH and VPN connections between the domain and hosts which have previously interacted with it locally. In doing so, we also develop an incrementally deployable public key infrastructuremore » which can later be leveraged to support inter-domain authentication.« less

  20. Two-Phase Contiguous Supported Lipid Bilayer Model for Membrane Rafts via Polymer Blotting and Stenciling.

    PubMed

    Richards, Mark J; Daniel, Susan

    2017-02-07

    The supported lipid bilayer has been portrayed as a useful model of the cell membrane compatible with many biophysical tools and techniques that demonstrate its appeal in learning about the basic features of the plasma membrane. However, some of its potential has yet to be realized, particularly in the area of bilayer patterning and phase/composition heterogeneity. In this work, we generate contiguous bilayer patterns as a model system that captures the general features of membrane domains and lipid rafts. Micropatterned polymer templates of two types are investigated for generating patterned bilayer formation: polymer blotting and polymer lift-off stenciling. While these approaches have been used previously to create bilayer arrays by corralling bilayers patches with various types of boundaries impenetrable to bilayer diffusion, unique to the methods presented here, there are no physical barriers to diffusion. In this work, interfaces between contiguous lipid phases define the pattern shapes, with continuity between them allowing transfer of membrane-bound biomolecules between the phases. We examine effectors of membrane domain stability including temperature and cholesterol content to investigate domain dynamics. Contiguous patterning of supported bilayers as a model of lipid rafts expands the application of the SLB to an area with current appeal and brings with it a useful toolset for characterization and analysis. These combined tools should be helpful to researchers investigating lipid raft dynamics and function and biomolecule partitioning studies. Additionally, this patterning technique may be useful for applications such as bioseparations that exploit differences in lipid phase partitioning or creation of membranes that bind species like viruses preferentially at lipid phase boundaries, to name a few.

  1. EVEREST: a virtual research environment for the Earth Sciences

    NASA Astrophysics Data System (ADS)

    Glaves, H. M.; Marelli, F.; Albani, M.

    2015-12-01

    There is an increasing requirement for researchers to work collaboratively using common resources whilst being geographically dispersed. By creating a virtual research environment (VRE) using a service oriented architecture (SOA) tailored to the needs of Earth Science (ES) communities, the EVEREST project will provide a range of both generic and domain specific data management services to support a dynamic approach to collaborative research. EVER-EST will provide the means to overcome existing barriers to sharing of Earth Science data and information allowing research teams to discover, access, share and process heterogeneous data, algorithms, results and experiences within and across their communities, including those domains beyond Earth Science. Data providers will be also able to monitor user experiences and collect feedback through the VRE, improving their capacity to adapt to the changing requirements of their end-users. The EVER-EST e-infrastructure will be validated by four virtual research communities (VRC) covering different multidisciplinary ES domains: including ocean monitoring, selected natural hazards (flooding, ground instability and extreme weather events), land monitoring and risk management (volcanoes and seismicity). Each of the VRC represents a different collaborative use case for the VRE according to its own specific requirements for data, software, best practice and community engagement. The diverse use cases will demonstrate how the VRE can be used for a range of activities from straight forward data/software sharing to investigating ways to improve cooperative working. Development of the EVEREST VRE will leverage on the results of several previous projects which have produced state-of-the-art technologies for scientific data management and curation as well those initiatives which have developed models, techniques and tools for the preservation of scientific methods and their implementation in computational forms such as scientific workflows.

  2. Cognitive impairment in patients clinically recovered from central nervous system depressant drug overdose.

    PubMed

    Dassanayake, Tharaka L; Michie, Patricia T; Jones, Alison; Carter, Gregory; Mallard, Trevor; Whyte, Ian

    2012-08-01

    Central nervous system depressant drugs (CNS-Ds) are known to impair cognitive functions. Overdose of these drugs is common, and most of the hospital-treated patients are discharged within 24 to 48 hours. No previous studies have examined whether they have residual impairment at the time of discharge. Our aim was to evaluate whether patients with CNS-D overdose are impaired in cognitive domains important in daily activities at that time. We compared visuomotor skills (Trail-Making Test A and Choice Reaction Time), executive functions (viz attentional set-shifting: Trail-Making Test B; and planning: Stockings of Cambridge Task from the Cambridge Neuropsychological Test Automated Battery), working memory (Letter-Number Sequencing), and impulsivity and decision making (Cambridge Neuropsychological Test Automated Battery Information Sampling) in 107 patients with CNS-D overdose (benzodiazepines, opioids, or antipsychotics) with a control group of 68 with non-CNS-D overdose (acetaminophen, selective serotonin reuptake inhibitors, and serotonin noradrenaline reuptake inhibitors) on discharge from hospital. Outcome measures were adjusted for demographic and clinical covariates in multivariate regression models. Compared with the controls, patients in the CNS-D group were significantly impaired in all domains: they had prolonged Trail-Making completion times and reaction times, poorer working memory and planning and were more impulsive in decision making. Their Stockings of Cambridge Task performance was comparable to that of the control group for simple problems but worsened with increasing task complexity. The results show that patients with CNS-D overdose could be impaired in multiple cognitive domains underlying everyday functioning even at the time they are deemed medically fit to be discharged. Such impairments could adversely affect social and professional lives of this relatively young population during the immediate postdischarge period.

  3. Neuropsychological function in individuals with morbid obesity: a cross-sectional study.

    PubMed

    Sargénius, Hanna L; Lydersen, Stian; Hestad, Knut

    2017-01-01

    Previous research has shown cognitive dysfunction to be present in a significant number of individuals with obesity. The objective of this study was to assess the neuropsychological profile of morbidly obese patients referred to weight-loss treatment. An extensive battery of neuropsychological tests with well-known normative data covering various cognitive domains was administered to 96 patients. The test results were transformed to z-scores for comparisons with normative data. As a means of determining level of cognitive impairment within the group, deficit scores were applied. Group comparisons on the different cognitive domains were conducted between patients with depressive symptoms and patients reporting no such symptoms. As illustrated in mean z-scores, the patients demonstrated lower performance compared to normative data on visual memory (mean -.26, CI -.43 to -.09, p  = .003), speed of information processing (mean -.22, CI -.34 to -.09, p  = .001), executive functions (mean -.28, CI -.40 to -.16, p  < .001), and attention/vigilance (mean -.25, CI -.37 to -.13, p  < .001). Their performance was good on verbal fluency (mean .24, CI .04 to .44, p  = .016) and verbal memory (mean .55, CI .38 to .72, p  < .001). No significant performance differences were observed in the cognitive domains of visuospatial ability, motor function, and working memory. The deficit scores, however, revealed working memory and motor function to be significantly impaired within the group as well. Patients with depressive symptoms differed from patients without such symptoms on visual memory (mean .43, CI .07 to .80, p  = .021). Some characteristic cognitive weaknesses and strengths were evident at the group level, although pronounced variation was observed. Deficits in executive functions, information processing, and attention should be taken into consideration in clinical practice.

  4. Development of a Theory-Based Intervention to Increase Clinical Measurement of Reactive Balance in Adults at Risk of Falls.

    PubMed

    Sibley, Kathryn M; Brooks, Dina; Gardner, Paula; Janaudis-Ferreira, Tania; McGlynn, Mandy; OʼHoski, Sachi; McEwen, Sara; Salbach, Nancy M; Shaffer, Jennifer; Shing, Paula; Straus, Sharon E; Jaglal, Susan B

    2016-04-01

    Effective balance reactions are essential for avoiding falls, but are not regularly measured by physical therapists. Physical therapists report wanting to improve reactive balance assessment, and theory-based approaches are recommended as the foundation for the development of interventions. This article describes how a behavior change theory for health care providers, the theoretical domains framework (TDF), was used to develop an intervention to increase reactive balance measurement among physical therapists who work in rehabilitation settings and treat adults who are at risk of falls. We employed published recommendations for using the TDF-guided intervention development. We identified what health care provider behavior is in need of change, relevant barriers and facilitators, strategies to address them, and how we would measure behavior change. In this case, identifying strategies required selecting both a reactive balance measure and behavior change techniques. Previous research had determined that physical therapists need to increase reactive balance measurement, and identified barriers and facilitators that corresponded to 8 TDF domains. A published review informed the selection of the Balance Evaluation Systems Test (Reactive Postural Responses Section) as addressing the barriers and facilitators, and existing research informed the selection of 9 established behavior change techniques corresponding to each identified TDF domain. The TDF framework were incorporated into a 12-month intervention with interactive group sessions, local champions, and health record modifications. Intervention effect can be evaluated using health record abstraction, questionnaires, and qualitative semistructured interviews. Although future research will evaluate the intervention in a controlled study, the process of theory-based intervention development can be applied to other rehabilitation research contexts, maximizing the impact of this work.Video Abstract is available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A123).

  5. Dominant gain-of-function mutations in transmembrane domain III of ERS1 and ETR1 suggest a novel role for this domain in regulating the magnitude of ethylene response in Arabidopsis.

    PubMed

    Deslauriers, Stephen D; Alvarez, Ashley A; Lacey, Randy F; Binder, Brad M; Larsen, Paul B

    2015-10-01

    Prior work resulted in identification of an Arabidopsis mutant, eer5-1, with extreme ethylene response in conjunction with failure to induce a subset of ethylene-responsive genes, including AtEBP. EER5, which is a TREX-2 homolog that is part of a nucleoporin complex, functions as part of a cryptic aspect of the ethylene signaling pathway that is required for regulating the magnitude of ethylene response. A suppressor mutagenesis screen was carried out to identify second site mutations that could restore the growth of ethylene-treated eer5-1 to wild-type levels. A dominant gain-of-function mutation in the ethylene receptor ETHYLENE RESPONSE SENSOR 1 (ERS1) was identified, with the ers1-4 mutation being located in transmembrane domain III at a point nearly equivalent to the previously described etr1-2 mutation in the other Arabidopsis subfamily I ethylene receptor, ETHYLENE RESPONSE 1 (ETR1). Although both ers1-4 and etr1-2 partially suppress the ethylene hypersensitivity of eer5-1 and are at least in part REVERSION TO ETHYLENE SENSITIVITY 1 (RTE1)-dependent, ers1-4 was additionally found to restore the expression of AtEBP in ers1-4;eer5-1 etiolated seedlings after ethylene treatment in an EIN3-dependent manner. Our work indicates that ERS1-regulated expression of a subset of ethylene-responsive genes is related to controlling the magnitude of ethylene response, with hyperinduction of these genes correlated with reduced ethylene-dependent growth inhibition. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

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

    PubMed Central

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

    2018-01-01

    Previous studies have reported that music training not only improves children's musical skills, but also enhances their cognitive functions. However, there is a disagreement about what domain(s) might be affected. Moreover, effects of short-term (

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

    PubMed

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

    2017-01-01

    Previous studies have reported that music training not only improves children's musical skills, but also enhances their cognitive functions. However, there is a disagreement about what domain(s) might be affected. Moreover, effects of short-term (

  8. Why older workers work beyond the retirement age: a qualitative study.

    PubMed

    Sewdas, Ranu; de Wind, Astrid; van der Zwaan, Lennart G L; van der Borg, Wieke E; Steenbeek, Romy; van der Beek, Allard J; Boot, Cécile R L

    2017-08-22

    The aims of the present study were to: 1) gain insight into reasons for working beyond the statutory retirement age from older workers' perspectives, and 2) explore how the domains of the research framework Study on Transitions in Employment, Ability and Motivation (STREAM) can be applied to working beyond retirement age. A qualitative research design included individual interviews (n = 15) and three focus groups (n = 18 participants) conducted with older workers aged 65 years and older continuing in a paid job or self-employment. Interview participants were recruited from an existing STREAM cohort study. Focus group participants were recruited from companies and employment agencies. The data were subjected to thematic analysis. The most important motives for working beyond retirement age were maintaining daily routines and financial benefit. Good health and flexible work arrangements were mentioned as important preconditions. The themes emerging from the categorization of the motives and preconditions corresponded to the domains of health, work characteristics, skills and knowledge, and social and financial factors from the STREAM research framework. However, our analysis revealed one additional theme-purpose in life. This study offers important new insights into the various preconditions and motives that influence working beyond retirement age. In addition, the five domains of the STREAM research framework, including the additional domain of 'purpose in life', seem to be applicable to working beyond retirement age. This knowledge contributes to the development of work-related interventions that enhance older workers' motivation to prolong their working lives.

  9. Blind Forensics of Successive Geometric Transformations in Digital Images Using Spectral Method: Theory and Applications.

    PubMed

    Chen, Chenglong; Ni, Jiangqun; Shen, Zhaoyi; Shi, Yun Qing

    2017-06-01

    Geometric transformations, such as resizing and rotation, are almost always needed when two or more images are spliced together to create convincing image forgeries. In recent years, researchers have developed many digital forensic techniques to identify these operations. Most previous works in this area focus on the analysis of images that have undergone single geometric transformations, e.g., resizing or rotation. In several recent works, researchers have addressed yet another practical and realistic situation: successive geometric transformations, e.g., repeated resizing, resizing-rotation, rotation-resizing, and repeated rotation. We will also concentrate on this topic in this paper. Specifically, we present an in-depth analysis in the frequency domain of the second-order statistics of the geometrically transformed images. We give an exact formulation of how the parameters of the first and second geometric transformations influence the appearance of periodic artifacts. The expected positions of characteristic resampling peaks are analytically derived. The theory developed here helps to address the gap left by previous works on this topic and is useful for image security and authentication, in particular, the forensics of geometric transformations in digital images. As an application of the developed theory, we present an effective method that allows one to distinguish between the aforementioned four different processing chains. The proposed method can further estimate all the geometric transformation parameters. This may provide useful clues for image forgery detection.

  10. Characterization of a novel domain ‘GATE’ in the ABC protein DrrA and its role in drug efflux by the DrrAB complex

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

    Zhang, Han; Rahman, Sadia; Li, Wen

    2015-03-27

    A novel domain, GATE (Glycine-loop And Transducer Element), is identified in the ABC protein DrrA. This domain shows sequence and structural conservation among close homologs of DrrA as well as distantly-related ABC proteins. Among the highly conserved residues in this domain are three glycines, G215, G221 and G231, of which G215 was found to be critical for stable expression of the DrrAB complex. Other conserved residues, including E201, G221, K227 and G231, were found to be critical for the catalytic and transport functions of the DrrAB transporter. Structural analysis of both the previously published crystal structure of the DrrA homologmore » MalK and the modeled structure of DrrA showed that G215 makes close contacts with residues in and around the Walker A motif, suggesting that these interactions may be critical for maintaining the integrity of the ATP binding pocket as well as the complex. It is also shown that G215A or K227R mutation diminishes some of the atomic interactions essential for ATP catalysis and overall transport function. Therefore, based on both the biochemical and structural analyses, it is proposed that the GATE domain, located outside of the previously identified ATP binding and hydrolysis motifs, is an additional element involved in ATP catalysis. - Highlights: • A novel domain ‘GATE’ is identified in the ABC protein DrrA. • GATE shows high sequence and structural conservation among diverse ABC proteins. • GATE is located outside of the previously studied ATP binding and hydrolysis motifs. • Conserved GATE residues are critical for stability of DrrAB and for ATP catalysis.« less

  11. Watermarking scheme for authentication of compressed image

    NASA Astrophysics Data System (ADS)

    Hsieh, Tsung-Han; Li, Chang-Tsun; Wang, Shuo

    2003-11-01

    As images are commonly transmitted or stored in compressed form such as JPEG, to extend the applicability of our previous work, a new scheme for embedding watermark in compressed domain without resorting to cryptography is proposed. In this work, a target image is first DCT transformed and quantised. Then, all the coefficients are implicitly watermarked in order to minimize the risk of being attacked on the unwatermarked coefficients. The watermarking is done through registering/blending the zero-valued coefficients with a binary sequence to create the watermark and involving the unembedded coefficients during the process of embedding the selected coefficients. The second-order neighbors and the block itself are considered in the process of the watermark embedding in order to thwart different attacks such as cover-up, vector quantisation, and transplantation. The experiments demonstrate the capability of the proposed scheme in thwarting local tampering, geometric transformation such as cropping, and common signal operations such as lowpass filtering.

  12. Testing HyDE on ADAPT

    NASA Technical Reports Server (NTRS)

    Sweet, Adam

    2008-01-01

    The IVHM Project in the Aviation Safety Program has funded research in electrical power system (EPS) health management. This problem domain contains both discrete and continuous behavior, and thus is directly relevant for the hybrid diagnostic tool HyDE. In FY2007 work was performed to expand the HyDE diagnosis model of the ADAPT system. The work completed resulted in a HyDE model with the capability to diagnose five times the number of ADAPT components previously tested. The expanded diagnosis model passed a corresponding set of new ADAPT fault injection scenario tests with no incorrect faults reported. The time required for the HyDE diagnostic system to isolate the fault varied widely between tests; this variance was reduced by tuning HyDE input parameters. These results and other diagnostic design trade-offs are discussed. Finally, possible future improvements for both the HyDE diagnostic model and HyDE itself are presented.

  13. Avian Models for Human Cognitive Neuroscience: A Proposal.

    PubMed

    Clayton, Nicola S; Emery, Nathan J

    2015-06-17

    Research on avian cognitive neuroscience over the past two decades has revealed the avian brain to be a better model for understanding human cognition than previously thought, despite differences in the neuroarchitecture of avian and mammalian brains. The brain, behavior, and cognition of songbirds have provided an excellent model of human cognition in one domain, namely learning human language and the production of speech. There are other important behavioral candidates of avian cognition, however, notably the capacity of corvids to remember the past and plan for the future, as well as their ability to think about another's perspective, and physical reasoning. We review this work and assess the evidence that the corvid brain can support such a cognitive architecture. We propose potential applications of these behavioral paradigms for cognitive neuroscience, including recent work on single-cell recordings and neuroimaging in corvids. Finally, we discuss their impact on understanding human developmental cognition. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Assessing the Linguistic Productivity of Unsupervised Deep Neural Networks

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

    Phillips, Lawrence A.; Hodas, Nathan O.

    Increasingly, cognitive scientists have demonstrated interest in applying tools from deep learning. One use for deep learning is in language acquisition where it is useful to know if a linguistic phenomenon can be learned through domain-general means. To assess whether unsupervised deep learning is appropriate, we first pose a smaller question: Can unsupervised neural networks apply linguistic rules productively, using them in novel situations. We draw from the literature on determiner/noun productivity by training an unsupervised, autoencoder network measuring its ability to combine nouns with determiners. Our simple autoencoder creates combinations it has not previously encountered, displaying a degree ofmore » overlap similar to actual children. While this preliminary work does not provide conclusive evidence for productivity, it warrants further investigation with more complex models. Further, this work helps lay the foundations for future collaboration between the deep learning and cognitive science communities.« less

  15. Transferring x-ray based automated threat detection between scanners with different energies and resolution

    NASA Astrophysics Data System (ADS)

    Caldwell, M.; Ransley, M.; Rogers, T. W.; Griffin, L. D.

    2017-10-01

    A significant obstacle to developing high performance Deep Learning algorithms for Automated Threat Detection (ATD) in security X-ray imagery, is the difficulty of obtaining large training datasets. In our previous work, we circumvented this problem for ATD in cargo containers, using Threat Image Projection and data augmentation. In this work, we investigate whether data scarcity for other modalities, such as parcels and baggage, can be ameliorated by transforming data from one domain so that it approximates the appearance of another. We present an ontology of ATD datasets to assess where transfer learning may be applied. We define frameworks for transfer at the training and testing stages, and compare the results for both methods against ATD where a common data source is used for training and testing. Our results show very poor transfer, which we attribute to the difficulty of accurately matching the blur and contrast characteristics of different scanners.

  16. Structure-function analysis of the auxilin J-domain reveals an extended Hsc70 interaction interface.

    PubMed

    Jiang, Jianwen; Taylor, Alexander B; Prasad, Kondury; Ishikawa-Brush, Yumiko; Hart, P John; Lafer, Eileen M; Sousa, Rui

    2003-05-20

    J-domains are widespread protein interaction modules involved in recruiting and stimulating the activity of Hsp70 family chaperones. We have determined the crystal structure of the J-domain of auxilin, a protein which is involved in uncoating clathrin-coated vesicles. Comparison to the known structures of J-domains from four other proteins reveals that the auxilin J-domain is the most divergent of all J-domain structures described to date. In addition to the canonical J-domain features described previously, the auxilin J-domain contains an extra N-terminal helix and a long loop inserted between helices I and II. The latter loop extends the positively charged surface which forms the Hsc70 binding site, and is shown by directed mutagenesis and surface plasmon resonance to contain side chains important for binding to Hsc70.

  17. A two-dimensional time domain near zone to far zone transformation

    NASA Technical Reports Server (NTRS)

    Luebbers, Raymond J.; Ryan, Deirdre; Beggs, John H.; Kunz, Karl S.

    1991-01-01

    In a previous paper, a time domain transformation useful for extrapolating 3-D near zone finite difference time domain (FDTD) results to the far zone was presented. In this paper, the corresponding 2-D transform is outlined. While the 3-D transformation produced a physically observable far zone time domain field, this is not convenient to do directly in 2-D, since a convolution would be required. However, a representative 2-D far zone time domain result can be obtained directly. This result can then be transformed to the frequency domain using a Fast Fourier Transform, corrected with a simple multiplicative factor, and used, for example, to calculate the complex wideband scattering width of a target. If an actual time domain far zone result is required it can be obtained by inverse Fourier transform of the final frequency domain result.

  18. The periplasmic domain of Escherichia coli outer membrane protein A can undergo a localized temperature dependent structural transition.

    PubMed

    Ishida, Hiroaki; Garcia-Herrero, Alicia; Vogel, Hans J

    2014-12-01

    Gram-negative bacteria such as Escherichia coli are surrounded by two membranes with a thin peptidoglycan (PG)-layer located in between them in the periplasmic space. The outer membrane protein A (OmpA) is a 325-residue protein and it is the major protein component of the outer membrane of E. coli. Previous structure determinations have focused on the N-terminal fragment (residues 1-171) of OmpA, which forms an eight stranded transmembrane β-barrel in the outer membrane. Consequently it was suggested that OmpA is composed of two independently folded domains in which the N-terminal β-barrel traverses the outer membrane and the C-terminal domain (residues 180-325) adopts a folded structure in the periplasmic space. However, some reports have proposed that full-length OmpA can instead refold in a temperature dependent manner into a single domain forming a larger transmembrane pore. Here, we have determined the NMR solution structure of the C-terminal periplasmic domain of E. coli OmpA (OmpA(180-325)). Our structure reveals that the C-terminal domain folds independently into a stable globular structure that is homologous to the previously reported PG-associated domain of Neisseria meningitides RmpM. Our results lend credence to the two domain structure model and a PG-binding function for OmpA, and we could indeed localize the PG-binding site on the protein through NMR chemical shift perturbation experiments. On the other hand, we found no evidence for binding of OmpA(180-325) with the TonB protein. In addition, we have also expressed and purified full-length OmpA (OmpA(1-325)) to study the structure of the full-length protein in micelles and nanodiscs by NMR spectroscopy. In both membrane mimetic environments, the recombinant OmpA maintains its two domain structure that is connected through a flexible linker. A series of temperature-dependent HSQC experiments and relaxation dispersion NMR experiments detected structural destabilization in the bulge region of the periplasmic domain of OmpA above physiological temperatures, which may induce dimerization and play a role in triggering the previously reported larger pore formation. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. The generality of working memory capacity: a latent-variable approach to verbal and visuospatial memory span and reasoning.

    PubMed

    Kane, Michael J; Hambrick, David Z; Tuholski, Stephen W; Wilhelm, Oliver; Payne, Tabitha W; Engle, Randall W

    2004-06-01

    A latent-variable study examined whether verbal and visuospatial working memory (WM) capacity measures reflect a primarily domain-general construct by testing 236 participants in 3 span tests each of verbal WM. visuospatial WM, verbal short-term memory (STM), and visuospatial STM. as well as in tests of verbal and spatial reasoning and general fluid intelligence (Gf). Confirmatory' factor analyses and structural equation models indicated that the WM tasks largely reflected a domain-general factor, whereas STM tasks, based on the same stimuli as the WM tasks, were much more domain specific. The WM construct was a strong predictor of Gf and a weaker predictor of domain-specific reasoning, and the reverse was true for the STM construct. The findings support a domain-general view of WM capacity, in which executive-attention processes drive the broad predictive utility of WM span measures, and domain-specific storage and rehearsal processes relate more strongly to domain-specific aspects of complex cognition. ((c) 2004 APA, all rights reserved)

  20. Positioning continuing education: boundaries and intersections between the domains continuing education, knowledge translation, patient safety and quality improvement.

    PubMed

    Kitto, Simon; Bell, Mary; Peller, Jennifer; Sargeant, Joan; Etchells, Edward; Reeves, Scott; Silver, Ivan

    2013-03-01

    Public and professional concern about health care quality, safety and efficiency is growing. Continuing education, knowledge translation, patient safety and quality improvement have made concerted efforts to address these issues. However, a coordinated and integrated effort across these domains is lacking. This article explores and discusses the similarities and differences amongst the four domains in relation to their missions, stakeholders, methods, and limitations. This paper highlights the potential for a more integrated and collaborative partnership to promote networking and information sharing amongst the four domains. This potential rests on the premise that an integrated approach may result in the development and implementation of more holistic and effective interdisciplinary interventions. In conclusion, an outline of current research that is informed by the preliminary findings in this paper is also briefly discussed. The research concerns a comprehensive mapping of the relationships between the domains to gain an understanding of potential dissonances between how the domains represent themselves, their work and the work of their 'partner' domains.

  1. Time Domain Reflectometry for Damage Detection of Laminated CFRP plate

    DTIC Science & Technology

    2011-08-18

    Final Report PROJECT ID: AOARD-10-4112 Title: Time Domain Reflectometry for damage detection of laminated CFRP plate Researcher: Professor Akira...From July/2010 To July/2011 Abstract Recently, high toughness Carbon Fiber Reinforced Polymer (CFRP) laminates are used to primary structures. The...large laminated CFRP structures. In the previous study, Time Domain Reflectometry (TDR) method is adopted for the detection of the fiber breakages of

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

    PubMed

    Ponte, Aline Sarturi; Fedosse, Elenir

    2016-10-01

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

  3. "Decisions, decisions, decisions": transfer and specificity of decision-making skill between sports.

    PubMed

    Causer, Joe; Ford, Paul R

    2014-08-01

    The concept of transfer of learning holds that previous practice or experience in one task or domain will enable successful performance in another related task or domain. In contrast, specificity of learning holds that previous practice or experience in one task or domain does not transfer to other related tasks or domains. The aim of the current study is to examine whether decision-making skill transfers between sports that share similar elements, or whether it is specific to a sport. Participants (n = 205) completed a video-based temporal occlusion decision-making test in which they were required to decide on which action to execute across a series of 4 versus 4 soccer game situations. A sport engagement questionnaire was used to identify 106 soccer players, 43 other invasion sport players and 58 other sport players. Positive transfer of decision-making skill occurred between soccer and other invasion sports, which are related and have similar elements, but not from volleyball, supporting the concept of transfer of learning.

  4. Functional dependence of neuroligin on a new non-PDZ intracellular domain

    PubMed Central

    Shipman, Seth L; Schnell, Eric; Hirai, Takaaki; Chen, Bo-Shiun; Roche, Katherine W; Nicoll, Roger A

    2011-01-01

    Neuroligins, a family of postsynaptic adhesion molecules, are important in synaptogenesis through a well-characterized trans-synaptic interaction with neurexin. In addition, neuroligins are thought to drive postsynaptic assembly through binding of their intracellular domain to PSD-95. However, there is little direct evidence to support the functional necessity of the neuroligin intracellular domain in postsynaptic development. We found that presence of endogenous neuroligin obscured the study of exogenous mutated neuroligin. We therefore used chained microRNAs in rat organotypic hippocampal slices to generate a reduced background of endogenous neuroligin. On this reduced background, we found that neuroligin function was critically dependent on the cytoplasmic tail. However, this function required neither the PDZ ligand nor any other previously described cytoplasmic binding domain, but rather required a previously unknown conserved region. Mutation of a single critical residue in this region inhibited neuroligin-mediated excitatory synaptic potentiation. Finally, we found a functional distinction between neuroligins 1 and 3. PMID:21532576

  5. Closed-form estimates of the domain of attraction for nonlinear systems via fuzzy-polynomial models.

    PubMed

    Pitarch, José Luis; Sala, Antonio; Ariño, Carlos Vicente

    2014-04-01

    In this paper, the domain of attraction of the origin of a nonlinear system is estimated in closed form via level sets with polynomial boundaries, iteratively computed. In particular, the domain of attraction is expanded from a previous estimate, such as a classical Lyapunov level set. With the use of fuzzy-polynomial models, the domain of attraction analysis can be carried out via sum of squares optimization and an iterative algorithm. The result is a function that bounds the domain of attraction, free from the usual restriction of being positive and decrescent in all the interior of its level sets.

  6. A bacterial toxin-antitoxin module is the origin of inter-bacterial and inter-kingdom effectors of Bartonella.

    PubMed

    Harms, Alexander; Liesch, Marius; Körner, Jonas; Québatte, Maxime; Engel, Philipp; Dehio, Christoph

    2017-10-01

    Host-targeting type IV secretion systems (T4SS) evolved from conjugative T4SS machineries that mediate interbacterial plasmid transfer. However, the origins of effectors secreted by these virulence devices have remained largely elusive. Previous work showed that some effectors exhibit homology to toxins of bacterial toxin-antitoxin modules, but the evolutionary trajectories underlying these ties had not been resolved. We previously reported that FicT toxins of FicTA toxin-antitoxin modules disrupt cellular DNA topology via their enzymatic FIC (filamentation induced by cAMP) domain. Intriguingly, the FIC domain of the FicT toxin VbhT of Bartonella schoenbuchensis is fused to a type IV secretion signal-the BID (Bep intracellular delivery) domain-similar to the Bartonella effector proteins (Beps) that are secreted into eukaryotic host cells via the host-targeting VirB T4SS. In this study, we show that the VbhT toxin is an interbacterial effector protein secreted via the conjugative Vbh T4SS that is closely related to the VirB T4SS and encoded by plasmid pVbh of B. schoenbuchensis. We therefore propose that the Vbh T4SS together with its effector VbhT represent an evolutionary missing link on a path that leads from a regular conjugation system and FicTA toxin-antitoxin modules to the VirB T4SS and the Beps. Intriguingly, phylogenetic analyses revealed that the fusion of FIC and BID domains has probably occurred independently in VbhT and the common ancestor of the Beps, suggesting parallel evolutionary paths. Moreover, several other examples of TA module toxins that are bona fide substrates of conjugative T4SS indicate that their recruitment as interbacterial effectors is prevalent and serves yet unknown biological functions in the context of bacterial conjugation. We propose that the adaptation for interbacterial transfer favors the exaptation of FicT and other TA module toxins as inter-kingdom effectors and may thus constitute an important stepping stone in the evolution of host-targeted effector proteins.

  7. Identification of discrete sites in Yip1A necessary for regulation of endoplasmic reticulum structure.

    PubMed

    Dykstra, Kaitlyn M; Ulengin, Idil; Delrose, Nicholas; Lee, Tina H

    2013-01-01

    The endoplasmic reticulum (ER) of specialized cells can undergo dramatic changes in structural organization, including formation of concentric whorls. We previously reported that depletion of Yip1A, an integral membrane protein conserved between yeast and mammals, caused ER whorl formation reminiscent of that seen in specialized cells. Yip1A and its yeast homologue Yip1p cycle between the ER and early Golgi, have been implicated in a number of distinct trafficking steps, and interact with a conserved set of binding partners including Yif1p/Yif1A and the Ypt1/Ypt31 Rab GTPases. Here, we carried out a mutational analysis of Yip1A to obtain insight into how it regulates ER whorl formation. Most of the Yip1A cytoplasmic domain was dispensable, whereas the transmembrane (TM) domain, especially residues within predicted TM helices 3 and 4, were sensitive to mutagenesis. Comprehensive analysis revealed two discrete functionally required determinants. One was E95 and flanking residues L92 and L96 within the cytoplasmic domain; the other was K146 and nearby residue V152 within the TM domain. Notably, the identified determinants correspond closely to two sites previously found to be essential for yeast viability (E76 and K130 in Yip1p corresponding to E95 and K146 in Yip1A, respectively). In contrast, a third site (E89) also essential for yeast viability (E70 in Yip1p) was dispensable for regulation of whorl formation. Earlier work showed that E76 (E95) was dispensable for binding Yif1p or Ypt1p/Ypt31p, whereas E70 (E89) was required. Collectively, these findings suggest that the ability of Yip1A to bind its established binding partners may be uncoupled from its ability to control ER whorl formation. In support, Yif1A knockdown did not cause ER whorl formation. Thus Yip1A may use the sites identified herein to interact with a novel binding partner to regulate ER membrane organization.

  8. The SANT2 domain of the murine tumor cell DnaJ-like protein 1 human homologue interacts with alpha1-antichymotrypsin and kinetically interferes with its serpin inhibitory activity.

    PubMed

    Kroczynska, Barbara; Evangelista, Christina M; Samant, Shalaka S; Elguindi, Ebrahim C; Blond, Sylvie Y

    2004-03-19

    The murine tumor cell DnaJ-like protein 1 or MTJ1/ERdj1 is a membrane J-domain protein enriched in microsomal and nuclear fractions. We previously showed that its lumenal J-domain stimulates the ATPase activity of the molecular chaperone BiP/GRP78 (Chevalier, M., Rhee, H., Elguindi, E. C., and Blond, S. Y. (2000) J. Biol. Chem. 275, 19620-19627). MTJ1/ERdj1 also contains a large carboxyl-terminal cytosolic extension composed of two tryptophan-mediated repeats or SANT domains for which the function(s) is unknown. Here we describe the cloning of the human homologue HTJ1 and its interaction with alpha(1)-antichymotrypsin (ACT), a member of the serine proteinase inhibitor (serpin) family. The interaction was initially identified in a two-hybrid screening and further confirmed in vitro by dot blots, native electrophoresis, and fluorescence studies. The second SANT domain of HTJ1 (SANT2) was found to be sufficient for binding to ACT, both in yeast and in vitro. Single tryptophan-alanine substitutions at two strictly conserved residues significantly (Trp-497) or totally (Trp-520) abolished the interaction with ACT. SANT2 binds to human ACT with an intrinsic affinity equal to 0.5 nm. Preincubation of ACT with nearly stoichiometric concentrations of SANT2 wild-type but not SANT2: W520A results in an apparent loss of ACT inhibitory activity toward chymotrypsin. Kinetic analysis indicates that the formation of the covalent inhibitory complex ACT-chymotrypsin is significantly delayed in the presence of SANT2 with no change on the catalytic efficiency of the enzyme. This work demonstrates for the first time that the SANT2 domain of MTJ1/HTJ1/ERdj1 mediates stable and high affinity protein-protein interactions.

  9. Transmembrane Domains of Highly Pathogenic Viral Fusion Proteins Exhibit Trimeric Association In Vitro

    PubMed Central

    Webb, Stacy R.; Smith, Stacy E.; Fried, Michael G.

    2018-01-01

    ABSTRACT Enveloped viruses require viral fusion proteins to promote fusion of the viral envelope with a target cell membrane. To drive fusion, these proteins undergo large conformational changes that must occur at the right place and at the right time. Understanding the elements which control the stability of the prefusion state and the initiation of conformational changes is key to understanding the function of these important proteins. The construction of mutations in the fusion protein transmembrane domains (TMDs) or the replacement of these domains with lipid anchors has implicated the TMD in the fusion process. However, the structural and molecular details of the role of the TMD in these fusion events remain unclear. Previously, we demonstrated that isolated paramyxovirus fusion protein TMDs associate in a monomer-trimer equilibrium, using sedimentation equilibrium analytical ultracentrifugation. Using a similar approach, the work presented here indicates that trimeric interactions also occur between the fusion protein TMDs of Ebola virus, influenza virus, severe acute respiratory syndrome coronavirus (SARS CoV), and rabies virus. Our results suggest that TM-TM interactions are important in the fusion protein function of diverse viral families. IMPORTANCE Many important human pathogens are enveloped viruses that utilize membrane-bound glycoproteins to mediate viral entry. Factors that contribute to the stability of these glycoproteins have been identified in the ectodomain of several viral fusion proteins, including residues within the soluble ectodomain. Although it is often thought to simply act as an anchor, the transmembrane domain of viral fusion proteins has been implicated in protein stability and function as well. Here, using a biophysical approach, we demonstrated that the fusion protein transmembrane domains of several deadly pathogens—Ebola virus, influenza virus, SARS CoV, and rabies virus—self-associate. This observation across various viral families suggests that transmembrane domain interactions may be broadly relevant and serve as a new target for therapeutic development. PMID:29669880

  10. The signaling helix: a common functional theme in diverse signaling proteins

    PubMed Central

    Anantharaman, Vivek; Balaji, S; Aravind, L

    2006-01-01

    Background The mechanism by which the signals are transmitted between receptor and effector domains in multi-domain signaling proteins is poorly understood. Results Using sensitive sequence analysis methods we identify a conserved helical segment of around 40 residues in a wide range of signaling proteins, including numerous sensor histidine kinases such as Sln1p, and receptor guanylyl cyclases such as the atrial natriuretic peptide receptor and nitric oxide receptors. We term this helical segment the signaling (S)-helix and present evidence that it forms a novel parallel coiled-coil element, distinct from previously known helical segments in signaling proteins, such as the Dimerization-Histidine phosphotransfer module of histidine kinases, the intra-cellular domains of the chemotaxis receptors, inter-GAF domain helical linkers and the α-helical HAMP module. Analysis of domain architectures allowed us to reconstruct the domain-neighborhood graph for the S-helix, which showed that the S-helix almost always occurs between two signaling domains. Several striking patterns in the domain neighborhood of the S-helix also became evident from the graph. It most often separates diverse N-terminal sensory domains from various C-terminal catalytic signaling domains such as histidine kinases, cNMP cyclase, PP2C phosphatases, NtrC-like AAA+ ATPases and diguanylate cyclases. It might also occur between two sensory domains such as PAS domains and occasionally between a DNA-binding HTH domain and a sensory domain. The sequence conservation pattern of the S-helix revealed the presence of a unique constellation of polar residues in the dimer-interface positions within the central heptad of the coiled-coil formed by the S-helix. Conclusion Combining these observations with previously reported mutagenesis studies on different S-helix-containing proteins we suggest that it functions as a switch that prevents constitutive activation of linked downstream signaling domains. However, upon occurrence of specific conformational changes due to binding of ligand or other sensory inputs in a linked upstream domain it transmits the signal to the downstream domain. Thus, the S-helix represents one of the most prevalent functional themes involved in the flow of signals between modules in diverse prokaryote-type multi-domain signaling proteins. Reviewers This article was reviewed by Frank Eisenhaber, Arcady Mushegian and Sandor Pongor. PMID:16953892

  11. Modelling and Simulation for Requirements Engineering and Options Analysis

    DTIC Science & Technology

    2010-05-01

    should be performed to work successfully in the domain; and process-based techniques model the processes that occur in the work domain. There is a crisp ...acad/sed/sedres/ dm /erg/cwa. DRDC Toronto CR 2010-049 39 23. Can the current technique for developing simulation models for assessments

  12. Family, employment, and individual resource-based antecedents of maternal work-family enrichment from infancy through middle childhood.

    PubMed

    Zhou, Nan; Buehler, Cheryl

    2016-07-01

    This study used data from the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care and Youth Development (N = 1,019) to examine family, employment, and individual antecedents of maternal work-family enrichment from infancy through middle childhood. Work-family conflict and important confounding factors were controlled. From the family domain, higher income-to-needs ratio and social support were associated with higher work-family enrichment. From the employment domain, greater job rewards, benefits of employment for children, and work commitment were associated with higher work-family enrichment. From the individual domain, higher maternal education and extroversion were associated with higher work-family enrichment. No family, employment, and individual characteristics were associated with work-family conflict across time except for partner intimacy. In general, the results supported antecedents of work-family enrichment that supply needed resources. The present study contributed to the literature by identifying antecedents of maternal work-family enrichment across early child developmental stages, which goes beyond examinations of particular life stages and a work-family conflict perspective. Implications for theory and practice are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  13. A Nodal Domain Integration Model of Two-Dimensional Heat and Soil-Water Flow Coupled by Soil-Water Phase Change.

    DTIC Science & Technology

    1987-06-01

    WORK UNIT ELEMENT NO. NO NO ACCESSION NO I I ICWIS 31711 11 TITLE (Include Security Classification) A Nodal Domain Integration Model of Two...t.5% Unclassified."- .-,,. PREFACE This report was prepared by Ted Hromadka, Director of Water Re- sources, Williamson and Schmid. The work was...performed for CRREL under Contract 84-M-1691 and was funded by the Directorate of Civil Works , Office of the Chief of Engineers, under Civil Works Order No

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

    PubMed

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

    2014-04-01

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

  15. Abacus Training Affects Math and Task Switching Abilities and Modulates Their Relationships in Chinese Children

    PubMed Central

    Yao, Yuan; Weng, Jian; Hu, Yuzheng; Chen, Feiyan

    2015-01-01

    Our previous work demonstrated that abacus-based mental calculation (AMC), a traditional Chinese calculation method, could help children improve their math abilities (e.g. basic arithmetical ability) and executive function (e.g. working memory). This study further examined the effects of long-term AMC training on math ability in visual-spatial domain and the task switching component of executive function. More importantly, this study investigated whether AMC training modulated the relationship between math abilities and task switching. The participants were seventy 7-year-old children who were randomly assigned into AMC and control groups at primary school entry. Children in AMC group received 2-hour AMC training every week since primary school entry. On the contrary, children in the control group had never received any AMC training. Math and task switching abilities were measured one year and three years respectively after AMC training began. The results showed that AMC children performed better than their peers on math abilities in arithmetical and visual-spatial domains. In addition, AMC group responded faster than control group in the switching task, while no group difference was found in switch cost. Most interestingly, group difference was present in the relationships between math abilities and switch cost. These results implied the effect of AMC training on math abilities as well as its relationship with executive function. PMID:26444689

  16. Abacus Training Affects Math and Task Switching Abilities and Modulates Their Relationships in Chinese Children.

    PubMed

    Wang, Chunjie; Geng, Fengji; Yao, Yuan; Weng, Jian; Hu, Yuzheng; Chen, Feiyan

    2015-01-01

    Our previous work demonstrated that abacus-based mental calculation (AMC), a traditional Chinese calculation method, could help children improve their math abilities (e.g. basic arithmetical ability) and executive function (e.g. working memory). This study further examined the effects of long-term AMC training on math ability in visual-spatial domain and the task switching component of executive function. More importantly, this study investigated whether AMC training modulated the relationship between math abilities and task switching. The participants were seventy 7-year-old children who were randomly assigned into AMC and control groups at primary school entry. Children in AMC group received 2-hour AMC training every week since primary school entry. On the contrary, children in the control group had never received any AMC training. Math and task switching abilities were measured one year and three years respectively after AMC training began. The results showed that AMC children performed better than their peers on math abilities in arithmetical and visual-spatial domains. In addition, AMC group responded faster than control group in the switching task, while no group difference was found in switch cost. Most interestingly, group difference was present in the relationships between math abilities and switch cost. These results implied the effect of AMC training on math abilities as well as its relationship with executive function.

  17. Stress, depression, quality of life and salivary cortisol levels in community health agents.

    PubMed

    Knuth, Berenice Scaletzky; Cocco, Rafaela Abreu; Radtke, Vinicius Augusto; Medeiros, João Ricardo Carvalho; Oses, Jean Pierre; Wiener, Carolina David; Jansen, Karen

    2016-06-01

    To determine the prevalence of and factors associated with depression and stress with perceived quality of life and the salivary cortisol levels in Community Health Agent (CHA). Materials and Methods Cross-sectional descriptive study of CHAs in Pelotas-RS, Brazil. Data collection, including sociodemographic information and factors related to work and health. Beck Depression Inventory (BDI) II was used to assess depressive symptoms, Inventory of Stress Symptoms Lipp (ISSL) was used for the analysis of stress and the WHOQOL-BREF was used to investigate quality of life. Salivary cortisol was quantified via ELISA test. The assessments showed that 71.0% are in a state of stress resistance, 30.5% were in the alert state of stress and 32.8% were in the stress state of exhaustion. Depressive episodes (BDI≥12) were observed in 28.2%. The environmental domain had the lowest score for quality of life. We observed significantly higher salivary cortisol levels in CHAs with less than 1 year of service and with the lowest quality of life scores in the environmental subsection. A high prevalence of stress and depression was observed in this sample of CHAs. In addition, the worst levels of quality of life were identified in the environmental subsection. Cortisol levels corroborate these findings regarding quality of life within the environmental domain and began working less than a year previously.

  18. Quality by design approach of a pharmaceutical gel manufacturing process, part 1: determination of the design space.

    PubMed

    Rosas, Juan G; Blanco, Marcel; González, Josep M; Alcalá, Manel

    2011-10-01

    This work was conducted in the framework of a quality by design project involving the production of a pharmaceutical gel. Preliminary work included the identification of the quality target product profiles (QTPPs) from historical values for previously manufactured batches, as well as the critical quality attributes for the process (viscosity and pH), which were used to construct a D-optimal experimental design. The experimental design comprised 13 gel batches, three of which were replicates at the domain center intended to assess the reproducibility of the target process. The viscosity and pH models established exhibited very high linearity and negligible lack of fit (LOF). Thus, R(2) was 0.996 for viscosity and 0.975 for pH, and LOF was 0.53 for the former parameter and 0.84 for the latter. The process proved reproducible at the domain center. Water content and temperature were the most influential factors for viscosity, and water content and acid neutralized fraction were the most influential factors for pH. A desirability function was used to find the best compromise to optimize the QTPPs. The body of information was used to identify and define the design space for the process. A model capable of combining the two response variables into a single one was constructed to facilitate monitoring of the process. Copyright © 2011 Wiley-Liss, Inc.

  19. FCS diffusion laws in two-phase lipid membranes: determination of domain mean size by experiments and Monte Carlo simulations.

    PubMed

    Favard, Cyril; Wenger, Jérôme; Lenne, Pierre-François; Rigneault, Hervé

    2011-03-02

    Many efforts have been undertaken over the last few decades to characterize the diffusion process in model and cellular lipid membranes. One of the techniques developed for this purpose, fluorescence correlation spectroscopy (FCS), has proved to be a very efficient approach, especially if the analysis is extended to measurements on different spatial scales (referred to as FCS diffusion laws). In this work, we examine the relevance of FCS diffusion laws for probing the behavior of a pure lipid and a lipid mixture at temperatures below, within and above the phase transitions, both experimentally and numerically. The accuracy of the microscopic description of the lipid mixtures found here extends previous work to a more complex model in which the geometry is unknown and the molecular motion is driven only by the thermodynamic parameters of the system itself. For multilamellar vesicles of both pure lipid and lipid mixtures, the FCS diffusion laws recorded at different temperatures exhibit large deviations from pure Brownian motion and reveal the existence of nanodomains. The variation of the mean size of these domains with temperature is in perfect correlation with the enthalpy fluctuation. This study highlights the advantages of using FCS diffusion laws in complex lipid systems to describe their temporal and spatial structure. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  20. Polarization of IRON-REGULATED TRANSPORTER 1 (IRT1) to the plant-soil interface plays crucial role in metal homeostasis.

    PubMed

    Barberon, Marie; Dubeaux, Guillaume; Kolb, Cornelia; Isono, Erika; Zelazny, Enric; Vert, Grégory

    2014-06-03

    In plants, the controlled absorption of soil nutrients by root epidermal cells is critical for growth and development. IRON-REGULATED TRANSPORTER 1 (IRT1) is the main root transporter taking up iron from the soil and is also the main entry route in plants for potentially toxic metals such as manganese, zinc, cobalt, and cadmium. Previous work demonstrated that the IRT1 protein localizes to early endosomes/trans-Golgi network (EE/TGN) and is constitutively endocytosed through a monoubiquitin- and clathrin-dependent mechanism. Here, we show that the availability of secondary non-iron metal substrates of IRT1 (Zn, Mn, and Co) controls the localization of IRT1 between the outer polar domain of the plasma membrane and EE/TGN in root epidermal cells. We also identify FYVE1, a phosphatidylinositol-3-phosphate-binding protein recruited to late endosomes, as an important regulator of IRT1-dependent metal transport and metal homeostasis in plants. FYVE1 controls IRT1 recycling to the plasma membrane and impacts the polar delivery of this transporter to the outer plasma membrane domain. This work establishes a functional link between the dynamics and the lateral polarity of IRT1 and the transport of its substrates, and identifies a molecular mechanism driving polar localization of a cell surface protein in plants.

  1. Trait liabilities and specific promotive processes in psychopathology: The example of suicidal behavior.

    PubMed

    Buchman-Schmitt, Jennifer M; Brislin, Sarah J; Venables, Noah C; Joiner, Thomas E; Patrick, Christopher J

    2017-07-01

    The RDoC matrix framework calls for investigation of mental health problems through analysis of core biobehavioral processes quantified and studied across multiple domains of measurement. Critics have raised concerns about RDoC, including overemphasis on biological concepts/measures and disregard for the principle of multifinality, which holds that identical biological predispositions can give rise to differing behavioral outcomes. The current work illustrates an ontogenetic process approach to addressing these concerns, focusing on biobehavioral traits corresponding to RDoC constructs as predictors, and suicidal behavior as the outcome variable. Data were collected from a young adult sample (N=105), preselected to enhance rates of suicidality. Participants completed self-report measures of traits (threat sensitivity, response inhibition) and suicide-specific processes. We show that previously reported associations for traits of threat sensitivity and weak inhibitory control with suicidal behavior are mediated by more specific suicide-promoting processes-namely, thwarted belongingness, perceived burdensomeness, and capability for suicide. The sample was relatively small and the data were cross-sectional, limiting conclusions that can be drawn from the mediation analyses. Given prior research documenting neurophysiological as well as psychological bases to these trait dispositions, the current work sets the stage for an intensive RDoC-oriented investigation of suicidal tendencies in which both traits and suicide-promoting processes are quantified using indicators from different domains of measurement. More broadly, this work illustrates how an RDoC research approach can contribute to a nuanced understanding of specific clinical problems, through consideration of how general biobehavioral liabilities interface with distinct problem-promoting processes. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Connectome Signatures of Neurocognitive Abnormalities in Euthymic Bipolar I Disorder

    PubMed Central

    Ajilore, Olusola; Vizueta, Nathalie; Walshaw, Patricia; Zhan, Liang; Leow, Alex; Altshuler, Lori L.

    2015-01-01

    Objectives Connectomics have allowed researchers to study integrative patterns of neural connectivity in humans. Yet, it is unclear how connectomics may elucidate structure-function relationships in bipolar I disorder (BPI). Expanding on our previous structural connectome study, here we used an overlapping sample with additional psychometric and fMRI data to relate structural connectome properties to both fMRI signals and cognitive performance. Methods 42 subjects completed a neuropsychological (NP) battery covering domains of processing speed, verbal memory, working memory, and cognitive flexibility. 32 subjects also had fMRI data performing a Go/NoGo task. Results Bipolar participants had lower NP performance across all domains, but only working memory reached statistical significance. In BPI participants, processing speed was significantly associated with both white matter integrity (WMI) in the corpus callosum and interhemispheric network integration. Mediation models further revealed that the relationship between interhemispheric integration and processing speed was mediated by WMI, and processing speed mediated the relationship between WMI and working memory. Bipolar subjects had significantly decreased BA47 activation during NoGo vs. Go. Significant predictors of BA47 fMRI activations during the Go/NoGo task were its nodal path length (left hemisphere) and its nodal clustering coefficient (right hemisphere). Conclusions This study suggests that structural connectome changes underlie abnormalities in fMRI activation and cognitive performance in euthymic BPI subjects. Results support that BA47 structural connectome changes may be a trait marker for BPI. Future studies are needed to determine if these “connectome signatures” may also confer a biological risk and/or serve as predictors of relapse. PMID:26228398

  3. Nationwide Buildings Energy Research enabled through an integrated Data Intensive Scientific Workflow and Advanced Analysis Environment

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

    Kleese van Dam, Kerstin; Lansing, Carina S.; Elsethagen, Todd O.

    2014-01-28

    Modern workflow systems enable scientists to run ensemble simulations at unprecedented scales and levels of complexity, allowing them to study system sizes previously impossible to achieve, due to the inherent resource requirements needed for the modeling work. However as a result of these new capabilities the science teams suddenly also face unprecedented data volumes that they are unable to analyze with their existing tools and methodologies in a timely fashion. In this paper we will describe the ongoing development work to create an integrated data intensive scientific workflow and analysis environment that offers researchers the ability to easily create andmore » execute complex simulation studies and provides them with different scalable methods to analyze the resulting data volumes. The integration of simulation and analysis environments is hereby not only a question of ease of use, but supports fundamental functions in the correlated analysis of simulation input, execution details and derived results for multi-variant, complex studies. To this end the team extended and integrated the existing capabilities of the Velo data management and analysis infrastructure, the MeDICi data intensive workflow system and RHIPE the R for Hadoop version of the well-known statistics package, as well as developing a new visual analytics interface for the result exploitation by multi-domain users. The capabilities of the new environment are demonstrated on a use case that focusses on the Pacific Northwest National Laboratory (PNNL) building energy team, showing how they were able to take their previously local scale simulations to a nationwide level by utilizing data intensive computing techniques not only for their modeling work, but also for the subsequent analysis of their modeling results. As part of the PNNL research initiative PRIMA (Platform for Regional Integrated Modeling and Analysis) the team performed an initial 3 year study of building energy demands for the US Eastern Interconnect domain, which they are now planning to extend to predict the demand for the complete century. The initial study raised their data demands from a few GBs to 400GB for the 3year study and expected tens of TBs for the full century.« less

  4. Radiosity diffusion model in 3D

    NASA Astrophysics Data System (ADS)

    Riley, Jason D.; Arridge, Simon R.; Chrysanthou, Yiorgos; Dehghani, Hamid; Hillman, Elizabeth M. C.; Schweiger, Martin

    2001-11-01

    We present the Radiosity-Diffusion model in three dimensions(3D), as an extension to previous work in 2D. It is a method for handling non-scattering spaces in optically participating media. We present the extension of the model to 3D including an extension to the model to cope with increased complexity of the 3D domain. We show that in 3D more careful consideration must be given to the issues of meshing and visibility to model the transport of light within reasonable computational bounds. We demonstrate the model to be comparable to Monte-Carlo simulations for selected geometries, and show preliminary results of comparisons to measured time-resolved data acquired on resin phantoms.

  5. Wavelet tree structure based speckle noise removal for optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Yuan, Xin; Liu, Xuan; Liu, Yang

    2018-02-01

    We report a new speckle noise removal algorithm in optical coherence tomography (OCT). Though wavelet domain thresholding algorithms have demonstrated superior advantages in suppressing noise magnitude and preserving image sharpness in OCT, the wavelet tree structure has not been investigated in previous applications. In this work, we propose an adaptive wavelet thresholding algorithm via exploiting the tree structure in wavelet coefficients to remove the speckle noise in OCT images. The threshold for each wavelet band is adaptively selected following a special rule to retain the structure of the image across different wavelet layers. Our results demonstrate that the proposed algorithm outperforms conventional wavelet thresholding, with significant advantages in preserving image features.

  6. Self-adjoint realisations of the Dirac-Coulomb Hamiltonian for heavy nuclei

    NASA Astrophysics Data System (ADS)

    Gallone, Matteo; Michelangeli, Alessandro

    2018-02-01

    We derive a classification of the self-adjoint extensions of the three-dimensional Dirac-Coulomb operator in the critical regime of the Coulomb coupling. Our approach is solely based upon the Kreĭn-Višik-Birman extension scheme, or also on Grubb's universal classification theory, as opposite to previous works within the standard von Neumann framework. This let the boundary condition of self-adjointness emerge, neatly and intrinsically, as a multiplicative constraint between regular and singular part of the functions in the domain of the extension, the multiplicative constant giving also immediate information on the invertibility property and on the resolvent and spectral gap of the extension.

  7. Effects of sources on time-domain finite difference models.

    PubMed

    Botts, Jonathan; Savioja, Lauri

    2014-07-01

    Recent work on excitation mechanisms in acoustic finite difference models focuses primarily on physical interpretations of observed phenomena. This paper offers an alternative view by examining the properties of models from the perspectives of linear algebra and signal processing. Interpretation of a simulation as matrix exponentiation clarifies the separate roles of sources as boundaries and signals. Boundary conditions modify the matrix and thus its modal structure, and initial conditions or source signals shape the solution, but not the modal structure. Low-frequency artifacts are shown to follow from eigenvalues and eigenvectors of the matrix, and previously reported artifacts are predicted from eigenvalue estimates. The role of source signals is also briefly discussed.

  8. Propagation of Boundary-Induced Discontinuity in Stationary Radiative Transfer

    NASA Astrophysics Data System (ADS)

    Kawagoe, Daisuke; Chen, I.-Kun

    2018-01-01

    We consider the boundary value problem of the stationary transport equation in the slab domain of general dimensions. In this paper, we discuss the relation between discontinuity of the incoming boundary data and that of the solution to the stationary transport equation. We introduce two conditions posed on the boundary data so that discontinuity of the boundary data propagates along positive characteristic lines as that of the solution to the stationary transport equation. Our analysis does not depend on the celebrated velocity averaging lemma, which is different from previous works. We also introduce an example in two dimensional case which shows that piecewise continuity of the boundary data is not a sufficient condition for the main result.

  9. A Meta-Analysis of Mathematics and Working Memory: Moderating Effects of Working Memory Domain, Type of Mathematics Skill, and Sample Characteristics

    ERIC Educational Resources Information Center

    Peng, Peng; Namkung, Jessica; Barnes, Marcia; Sun, Congying

    2016-01-01

    The purpose of this meta-analysis was to determine the relation between mathematics and working memory (WM) and to identify possible moderators of this relation including domains of WM, types of mathematics skills, and sample type. A meta-analysis of 110 studies with 829 effect sizes found a significant medium correlation of mathematics and WM, r…

  10. Using cognitive work analysis to explore activity allocation within military domains.

    PubMed

    Jenkins, D P; Stanton, N A; Salmon, P M; Walker, G H; Young, M S

    2008-06-01

    Cognitive work analysis (CWA) is frequently advocated as an approach for the analysis of complex socio-technical systems. Much of the current CWA literature within the military domain pays particular attention to its initial phases; work domain analysis and contextual task analysis. Comparably, the analysis of the social and organisational constraints receives much less attention. Through the study of a helicopter mission planning system software tool, this paper describes an approach for investigating the constraints affecting the distribution of work. The paper uses this model to evaluate the potential benefits of the social and organisational analysis phase within a military context. The analysis shows that, through its focus on constraints, the approach provides a unique description of the factors influencing the social organisation within a complex domain. This approach appears to be compatible with existing approaches and serves as a validation of more established social analysis techniques. As part of the ergonomic design of mission planning systems, the social organisation and cooperation analysis phase of CWA provides a constraint-based description informing allocation of function between key actor groups. This approach is useful because it poses questions related to the transfer of information and optimum working practices.

  11. The structural role of the zinc ion can be dispensable in prokaryotic zinc-finger domains

    PubMed Central

    Baglivo, Ilaria; Russo, Luigi; Esposito, Sabrina; Malgieri, Gaetano; Renda, Mario; Salluzzo, Antonio; Di Blasio, Benedetto; Isernia, Carla; Fattorusso, Roberto; Pedone, Paolo V.

    2009-01-01

    The recent characterization of the prokaryotic Cys2His2 zinc-finger domain, identified in Ros protein from Agrobacterium tumefaciens, has demonstrated that, although possessing a similar zinc coordination sphere, this domain is structurally very different from its eukaryotic counterpart. A search in the databases has identified ≈300 homologues with a high sequence identity to the Ros protein, including the amino acids that form the extensive hydrophobic core in Ros. Surprisingly, the Cys2His2 zinc coordination sphere is generally poorly conserved in the Ros homologues, raising the question of whether the zinc ion is always preserved in these proteins. Here, we present a functional and structural study of a point mutant of Ros protein, Ros56–142C82D, in which the second coordinating cysteine is replaced by an aspartate, 5 previously-uncharacterized representative Ros homologues from Mesorhizobium loti, and 2 mutants of the homologues. Our results indicate that the prokaryotic zinc-finger domain, which in Ros protein tetrahedrally coordinates Zn(II) through the typical Cys2His2 coordination, in Ros homologues can either exploit a CysAspHis2 coordination sphere, previously never described in DNA binding zinc finger domains to our knowledge, or lose the metal, while still preserving the DNA-binding activity. We demonstrate that this class of prokaryotic zinc-finger domains is structurally very adaptable, and surprisingly single mutations can transform a zinc-binding domain into a nonzinc-binding domain and vice versa, without affecting the DNA-binding ability. In light of our findings an evolutionary link between the prokaryotic and eukaryotic zinc-finger domains, based on bacteria-to-eukaryota horizontal gene transfer, is discussed. PMID:19369210

  12. Characterization and Measurement of Passive and Active Metamaterial Devices

    DTIC Science & Technology

    2010-03-01

    A periodic bound- ary mirrors the computational domain along an axis. Unit cell boundary conditions mirror the computational domain along two axes... mirrored a number of times in each direction to create a square matrix of ring resonators. Figure 33(b) shows a 4× 4 array. The frequency domain...created by mirroring the previous structure three times. Thus, the dimensions of the particles are identical. The same boundary conditions and spacing

  13. A Meta-analysis of Cerebellar Contributions to Higher Cognition from PET and fMRI studies

    PubMed Central

    Keren-Happuch, E; Chen, Shen-Hsing Annabel; Ho, Moon-Ho Ringo; Desmond, John E.

    2013-01-01

    A growing interest in cerebellar function and its involvement in higher cognition have prompted much research in recent years. Cerebellar presence in a wide range of cognitive functions examined within an increasing body of neuroimaging literature has been observed. We applied a meta-analytic approach, which employed the activation likelihood estimate method, to consolidate results of cerebellar involvement accumulated in different cognitive tasks of interest and systematically identified similarities among the studies. The current analysis included 88 neuroimaging studies demonstrating cerebellar activations in higher cognitive domains involving emotion, executive function, language, music, timing and working memory. While largely consistent with a prior meta-analysis by Stoodley and Schmahmann (2009), our results extended their findings to include music and timing domains to provide further insights into cerebellar involvement and elucidate its role in higher cognition. In addition, we conducted inter- and intra-domain comparisons for the cognitive domains of emotion, language and working memory. We also considered task differences within the domain of verbal working memory by conducting a comparison of the Sternberg with the n-back task, as well as an analysis of the differential components within the Sternberg task. Results showed a consistent cerebellar presence in the timing domain, providing evidence for a role in time keeping. Unique clusters identified within the domain further refine the topographic organization of the cerebellum. PMID:23125108

  14. Correlation between the ripple phase and stripe domains in membranes.

    PubMed

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

    2011-12-01

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

  15. Coreference annotation and resolution in the Colorado Richly Annotated Full Text (CRAFT) corpus of biomedical journal articles.

    PubMed

    Cohen, K Bretonnel; Lanfranchi, Arrick; Choi, Miji Joo-Young; Bada, Michael; Baumgartner, William A; Panteleyeva, Natalya; Verspoor, Karin; Palmer, Martha; Hunter, Lawrence E

    2017-08-17

    Coreference resolution is the task of finding strings in text that have the same referent as other strings. Failures of coreference resolution are a common cause of false negatives in information extraction from the scientific literature. In order to better understand the nature of the phenomenon of coreference in biomedical publications and to increase performance on the task, we annotated the Colorado Richly Annotated Full Text (CRAFT) corpus with coreference relations. The corpus was manually annotated with coreference relations, including identity and appositives for all coreferring base noun phrases. The OntoNotes annotation guidelines, with minor adaptations, were used. Interannotator agreement ranges from 0.480 (entity-based CEAF) to 0.858 (Class-B3), depending on the metric that is used to assess it. The resulting corpus adds nearly 30,000 annotations to the previous release of the CRAFT corpus. Differences from related projects include a much broader definition of markables, connection to extensive annotation of several domain-relevant semantic classes, and connection to complete syntactic annotation. Tool performance was benchmarked on the data. A publicly available out-of-the-box, general-domain coreference resolution system achieved an F-measure of 0.14 (B3), while a simple domain-adapted rule-based system achieved an F-measure of 0.42. An ensemble of the two reached F of 0.46. Following the IDENTITY chains in the data would add 106,263 additional named entities in the full 97-paper corpus, for an increase of 76% percent in the semantic classes of the eight ontologies that have been annotated in earlier versions of the CRAFT corpus. The project produced a large data set for further investigation of coreference and coreference resolution in the scientific literature. The work raised issues in the phenomenon of reference in this domain and genre, and the paper proposes that many mentions that would be considered generic in the general domain are not generic in the biomedical domain due to their referents to specific classes in domain-specific ontologies. The comparison of the performance of a publicly available and well-understood coreference resolution system with a domain-adapted system produced results that are consistent with the notion that the requirements for successful coreference resolution in this genre are quite different from those of the general domain, and also suggest that the baseline performance difference is quite large.

  16. Conformational Changes of an Interdomain Linker Mediate Mechanical Signal Transmission in Sensor Kinase BvgS

    PubMed Central

    Lesne, Elodie; Dupré, Elian; Locht, Camille

    2017-01-01

    ABSTRACT The whooping cough agent, Bordetella pertussis, controls the expression of its large virulence regulon in a coordinated manner through the two-component system BvgAS. BvgS is a dimeric, multidomain sensor kinase. Each monomer comprises, in succession, tandem periplasmic Venus flytrap (VFT) domains, a transmembrane segment, a cytoplasmic Per-Arnt-Sim (PAS) domain, a kinase module, and additional phosphorelay domains. BvgS shifts between kinase and phosphatase modes of activity in response to chemical modulators that modify the clamshell motions of the VFT domains. We have shown previously that this regulation involves a shift between distinct states of conformation and dynamics of the two-helix coiled-coil linker preceding the enzymatic module. In this work, we determined the mechanism of signal transduction across the membrane via a first linker, which connects the VFT and PAS domains of BvgS, using extensive cysteine cross-linking analyses and other approaches. Modulator perception by the periplasmic domains appears to trigger a small, symmetrical motion of the transmembrane segments toward the periplasm, causing rearrangements of the noncanonical cytoplasmic coiled coil that follows. As a consequence, the interface of the PAS domains is modified, which affects the second linker and eventually causes the shift of enzymatic activity. The major features of this first linker are well conserved among BvgS homologs, indicating that the mechanism of signal transduction unveiled here is likely to be generally relevant for this family of sensor kinases. IMPORTANCE Bordetella pertussis produces virulence factors coordinately regulated by the two-component system BvgAS. BvgS is a sensor kinase, and BvgA is a response regulator that activates gene transcription when phosphorylated by BvgS. Sensor kinases homologous to BvgS are also found in other pathogens. Our goal is to decipher the mechanisms of BvgS signaling, since these sensor kinases may represent new targets for antibacterial agents. Signal perception by the sensor domains of BvgS triggers small motions of the helical linker region underneath. The protein domain that follows this linker undergoes a large conformational change that amplifies the initial signal, causing a shift of activity from kinase to phosphatase. Because BvgS homologs harbor similar regions, these signaling mechanisms are likely to apply generally to that family of sensor kinases. PMID:28507245

  17. Cognitive and psychomotor effects of risperidone in schizophrenia and schizoaffective disorder.

    PubMed

    Houthoofd, Sofie A M K; Morrens, Manuel; Sabbe, Bernard G C

    2008-09-01

    The aim of this review was to discuss data from double-blind, randomized controlled trials (RCTs) that have investigated the effects of oral and long-acting injectable risperidone on cognitive and psychomotor functioning in patients with schizophrenia or schizoaffective disorder. PubMed/MEDLINE and the Institute of Scientific Information Web of Science database were searched for relevant English-language double-blind RCTs published between March 2000 and July 2008, using the terms schizophrenia, schizoaffective disorder, cognition, risperidone, psychomotor, processing speed, attention, vigilance, working memory, verbal learning, visual learning, reasoning, problem solving, social cognition, MATRICS, and long-acting. Relevant studies included patients with schizophrenia or schizoaffective disorder. Cognitive domains were delineated at the Consensus Conferences of the National Institute of Mental Health-Measurement And Treatment Research to Improve Cognition in Schizophrenia (NIMH-MATRICS). The tests employed to assess each domain and psychomotor functioning, and the within-group and between-group comparisons of risperidone with haloperidol and other atypical antipsychotics, are presented. The results of individual tests were included when they were individually presented and interpretable for either drug; outcomes that were presented as cluster scores or factor structures were excluded. A total of 12 articles were included in this review. Results suggested that the use of oral risperidone appeared to be associated with within-group improvements on the cognitive domains of processing speed, attention/vigilance, verbal and visual learning and memory, and reasoning and problem solving in patients with schizophrenia or schizoaffective disorder. Risperidone and haloperidol seemed to generate similar beneficial effects (on the domains of processing speed, attention/vigilance, [verbal and nonverbal] working memory, and visual learning and memory, as well as psychomotor functioning), although the results for verbal fluency, verbal learning and memory, and reasoning and problem solving were not unanimous, and no comparative data on social cognition were available. Similar cognitive effects were found with risperidone, olanzapine, and quetiapine on the domains of verbal working memory and reasoning and problem solving, as well as verbal fluency. More research is needed on the domains in which study results were contradictory. For olanzapine versus risperidone, these were verbal and visual learning and memory and psychomotor functioning. No comparative data for olanzapine and risperidone were available for the social cognition domain. For quetiapine versus risperidone, the domains in which no unanimity was found were processing speed, attention/vigilance, nonverbal working memory, and verbal learning and memory. The limited available reports on risperidone versus clozapine suggest that: risperidone was associated with improved, and clozapine with worsened, performance on the nonverbal working memory domain; risperidone improved and clozapine did not improve reasoning and problem-solving performance; clozapine improved, and risperidone did not improve, social cognition performance. Use of long-acting injectable risperidone seemed to be associated with improved performance in the domains of attention/vigilance, verbal learning and memory, and reasoning and problem solving, as well as psychomotor functioning. The results for the nonverbal working memory domain were indeterminate, and no clear improvement was seen in the social cognition domain. The domains of processing speed, verbal working memory, and visual learning and memory, as well as verbal fluency, were not assessed. The results of this review of within-group comparisons of oral risperidone suggest that the agent appeared to be associated with improved functioning in the cognitive domains of processing speed, attention/vigilance, verbal and visual learning and memory, and reasoning and problem solving in patients with schizophrenia or schizoaffective disorder. Long-acting injectable risperidone seemed to be associated with improved functioning in the domains of attention/vigilance, verbal learning and memory, and reasoning and problem solving, as well as psychomotor functioning, in patients with schizophrenia or schizoaffective disorder.

  18. Ecto-Fc MS identifies ligand-receptor interactions through extracellular domain Fc fusion protein baits and shotgun proteomic analysis

    PubMed Central

    Savas, Jeffrey N.; De Wit, Joris; Comoletti, Davide; Zemla, Roland; Ghosh, Anirvan

    2015-01-01

    Ligand-receptor interactions represent essential biological triggers which regulate many diverse and important cellular processes. We have developed a discovery-based proteomic biochemical protocol which couples affinity purification with multidimensional liquid chromatographic tandem mass spectrometry (LCLC-MS/MS) and bioinformatic analysis. Compared to previous approaches, our analysis increases sensitivity, shortens analysis duration, and boosts comprehensiveness. In this protocol, receptor extracellular domains are fused with the Fc region of IgG to generate fusion proteins that are purified from transfected HEK293T cells. These “ecto-Fcs” are coupled to protein A beads and serve as baits for binding assays with prey proteins extracted from rodent brain. After capture, the affinity purified proteins are digested into peptides and comprehensively analyzed by LCLC-MS/MS with ion trap mass spectrometers. In four working days, this protocol can generate shortlists of candidate ligand-receptor protein-protein interactions. Our “Ecto-Fc MS” approach outperforms antibody-based approaches and provides a reproducible and robust framework to identify extracellular ligand – receptor interactions. PMID:25101821

  19. A laboratory validation study of the time-lapse oscillatory pumping test concept for leakage detection in geological repositories

    NASA Astrophysics Data System (ADS)

    Sun, A. Y.; Islam, A.; Lu, J.

    2017-12-01

    Time-lapse oscillatory pumping test (OPT) has been introduced recently as a pressure-based monitoring technique for detecting potential leakage in geologic repositories. By routinely conducting OPT at a number of pulsing frequencies, a site operator may identify the potential anomalies in the frequency domain, alleviating the ambiguity caused by reservoir noise and improving the signal-to-noise ratio. Building on previous theoretical and field studies, this work performed a series of laboratory experiments to validate the concept of time-lapse OPT using a custom made, stainless steel tank under relatively high pressures ( 120psi). The experimental configuration simulates a miniature geologic storage repository consisting of three layers (i.e., injection zone, caprock, and above-zone aquifer). Results show that leakage in the injection zone led to deviations in the power spectrum of observed pressure data, and the amplitude of which also increases with decreasing pulsing frequencies. The experimental results were further analyzed by developing a 3D flow model, using which the model parameters were estimated through frequency domain inversion.

  20. Use of media and public-domain Internet sources for detection and assessment of plant health threats

    PubMed Central

    Thomas, Carla S.; Nelson, Noele P.; Jahn, Gary C.; Niu, Tianchan; Hartley, David M.

    2011-01-01

    Event-based biosurveillance is a recognized approach to early warning and situational awareness of emerging health threats. In this study, we build upon previous human and animal health work to develop a new approach to plant pest and pathogen surveillance. We show that monitoring public domain electronic media for indications and warning of epidemics and associated social disruption can provide information about the emergence and progression of plant pest infestation or disease outbreak. The approach is illustrated using a case study, which describes a plant pest and pathogen epidemic in China and Vietnam from February 2006 to December 2007, and the role of ducks in contributing to zoonotic virus spread in birds and humans. This approach could be used as a complementary method to traditional plant pest and pathogen surveillance to aid global and national plant protection officials and political leaders in early detection and timely response to significant biological threats to plant health, economic vitality, and social stability. This study documents the inter-relatedness of health in human, animal, and plant populations and emphasizes the importance of plant health surveillance. PMID:24149031

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