Sample records for domain dependent knowing

  1. Sizes of lipid domains: What do we know from artificial lipid membranes? What are the possible shared features with membrane rafts in cells?

    PubMed

    Rosetti, Carla M; Mangiarotti, Agustín; Wilke, Natalia

    2017-05-01

    In model lipid membranes with phase coexistence, domain sizes distribute in a very wide range, from the nanometer (reported in vesicles and supported films) to the micrometer (observed in many model membranes). Domain growth by coalescence and Ostwald ripening is slow (minutes to hours), the domain size being correlated with the size of the capture region. Domain sizes thus strongly depend on the number of domains which, in the case of a nucleation process, depends on the oversaturation of the system, on line tension and on the perturbation rate in relation to the membrane dynamics. Here, an overview is given of the factors that affect nucleation or spinodal decomposition and domain growth, and their influence on the distribution of domain sizes in different model membranes is discussed. The parameters analyzed respond to very general physical rules, and we therefore propose a similar behavior for the rafts in the plasma membrane of cells, but with obstructed mobility and with a continuously changing environment. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Who Knows? Metacognitive Social Learning Strategies.

    PubMed

    Heyes, Cecilia

    2016-03-01

    To make good use of learning from others (social learning), we need to learn from the right others; from agents who know better than we do. Research on social learning strategies (SLSs) has identified rules that focus social learning on the right agents, and has shown that the behaviour of many animals conforms to these rules. However, it has not asked what the rules are made of, that is, about the cognitive processes implementing SLSs. Here, I suggest that most SLSs depend on domain-general, sensorimotor processes. However, some SLSs have the characteristics tacitly ascribed to all of them. These metacognitive SLSs represent 'who knows' in a conscious, reportable way, and have the power to promote cultural evolution. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    ERIC Educational Resources Information Center

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

    2017-01-01

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

  4. If You Don’t Know Where You Are Going, You Probably Will End Up Somewhere Else: Computer Network Operations Force Presentation

    DTIC Science & Technology

    2009-06-01

    Engineering Graduate School of Engineering and Management Air Force Institute of Technology Air University Air Education and Training Command In...control of cross-domain dependencies, and management of Title 10 relationships. This literature review of joint doctrine indicates USSTRATCOM...24 III: How Do Combatant Commands Manage

  5. How Do We Go about "Knowing" the Culture of Our School?

    ERIC Educational Resources Information Center

    Achilles, C. M.

    Research on learning styles has shown that students learn better when teachers plan class learning activities to fit students' learning styles. This paper describes three "ways of knowing" and discusses the role they play in "knowing the culture" of a school. The first part relates ways of knowing to the usual three domains of learning--cognitive,…

  6. Functional Implications of Domain Organization Within Prokaryotic Rhomboid Proteases.

    PubMed

    Panigrahi, Rashmi; Lemieux, M Joanne

    2015-01-01

    Intramembrane proteases are membrane embedded enzymes that cleave transmembrane substrates. This interesting class of enzyme and its water mediated substrate cleavage mechanism occurring within the hydrophobic lipid bilayer has drawn the attention of researchers. Rhomboids are a family of ubiquitous serine intramembrane proteases. Bacterial forms of rhomboid proteases are mainly composed of six transmembrane helices that are preceded by a soluble N-terminal domain. Several crystal structures of the membrane domain of the E. coli rhomboid protease ecGlpG have been solved. Independently, the ecGlpG N-terminal cytoplasmic domain structure was solved using both NMR and protein crystallography. Despite these structures, we still do not know the structure of the full-length protein, nor do we know the functional role of these domains in the cell. This chapter will review the structural and functional roles of the different domains associated with prokaryotic rhomboid proteases. Lastly, we will address questions remaining in the field.

  7. Susan Loucks-Horsley learning model in light pollution theme: based on a new taxonomy for science education

    NASA Astrophysics Data System (ADS)

    Liliawati, W.; Utama, J. A.; Fauziah, H.

    2016-08-01

    The curriculum in Indonesia recommended that science teachers in the elementary and intermediate schools should have interdisciplinary ability in science. However, integrated learning still has not been implemented optimally. This research is designing and applying integrated learning with Susan Loucks-Horsley model in light pollution theme. It can be showed how the student's achievements based on new taxonomy of science education with five domains: knowing & understanding, science process skill, creativity, attitudinal and connecting & applying. This research use mixed methods with concurrent embedded design. The subject is grade 8 of junior high school students in Bandung as many as 27 students. The Instrument have been employed has 28 questions test mastery of concepts, observations sheet and moral dilemma test. The result shows that integrated learning with model Susan Loucks-Horsley is able to increase student's achievement and positive characters on light pollution theme. As the results are the average normalized gain of knowing and understanding domain reach in lower category, the average percentage of science process skill domain reach in good category, the average percentage of creativity and connecting domain reach respectively in good category and attitudinal domain the average percentage is over 75% in moral knowing and moral feeling.

  8. Domain Engineering

    NASA Astrophysics Data System (ADS)

    Bjørner, Dines

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

  9. A structure for maturing intelligent tutoring system student models

    NASA Technical Reports Server (NTRS)

    Holmes, Willard M.

    1990-01-01

    A special structure is examined for evolving a detached model of the user of an intelligent tutoring system. Tutoring is used in the context of education and training devices. A detached approach to populating the student model data structure is examined in the context of the need for time dependent reasoning about what the student knows about a particular concept in the domain of interest. This approach, to generating a data structure for the student model, allows an inference engine separate from the tutoring strategy determination to be used. This methodology has advantages in environments requiring real-time operation.

  10. "We Know What to Say, We Know What to Write, but We Don't Know How": The Challenges of Becoming Academically Literate in a New Linguistic and Socio-Cultural Space

    ERIC Educational Resources Information Center

    Sibomana, Emmanuel

    2016-01-01

    Historically, some languages and discourses which were initially localised subsequently became regionally or even globally dominant. Currently, English is the dominant global language in all domains, including the academic. Thus academics and scholars from non-English backgrounds are at a disadvantage: they have to adhere to academic literacy…

  11. Knowing How We Know: Evidentiality and Cognitive Development

    ERIC Educational Resources Information Center

    Matsui, Tomoko; Fitneva, Stanka A.

    2009-01-01

    Evidentials are grammatical elements such as affixes and particles indicating the source of knowledge. We provide an overview of this grammatical category and consider three research domains to which developmental studies on evidentiality contribute: the acquisition of linguistic means to characterize knowledge, the conceptual understanding of…

  12. Communicating Physics and the Design of Textbooks.

    ERIC Educational Resources Information Center

    Barojas, Jorge; Trigueros, Maria

    1991-01-01

    The planning of an introductory calculus textbook in classical mechanics is shown as an example of an approach to textbook design that uses four main cognitive categories: sources of learning, instruments of learning, processes of knowing, and mechanisms of knowing. The aspects, domains, description, and elements of each section of the textbook…

  13. Handwriting: What Do We Know and What Do We Need to Know?

    ERIC Educational Resources Information Center

    Medwell, Jane; Wray, David

    2007-01-01

    Handwriting has a low status and profile in literacy education in England and in recent years has attracted little attention from teachers, policy-makers or researchers into mainstream educational processes. This article identifies a substantial programme of research into handwriting, including studies located in the domains of special needs…

  14. THE LIABILITY FORMS OF THE MEDICAL PERSONNEL.

    PubMed

    Bărcan, Cristian

    2015-01-01

    Current legislation, namely Law no. 95/2006 on healthcare reform in the medical malpractice domain stipulates that medical staff can be held accountable in the following forms: disciplinary liability, administrative liability, civil liability and criminal liability. Each form of legal liability presents its features, aspects that are found mainly in the procedural rules. However, the differences between the various legal forms of liability are not met only in the procedural rules but also in their effects and consequences. It is necessary to know what the procedure for disciplinary responsibility, administrative liability, civil liability, or criminal liability is. In addition to the differentiation determined by the consequences that may arise from the different forms of legal liability, it is important to know the competent authorities to investigate a case further and the solutions which various public institutions can take regarding the medical staff. Depending on the type of legal liability, authorities have a specialized authority. If the Disciplinary Committee is encountered at the College of Physicians, it may not intervene in cases before the monitoring and competence for malpractice cases Committee. The latter two committees cannot intervene directly in the legal assessment of civil or criminal cases, as no criminal investigation authorities cannot intervene in strictly civilian cases. Therefore, the importance of knowing the competent institutions is imperative.

  15. 41 CFR 102-173.80 - How will I know if my request is approved?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-INTERNET GOV DOMAIN Registration § 102-173.80 How will I know if my request is approved? A registration... your registration information was received. If all of your information is accurate and complete, a second notice will be sent to you within one business day, informing you that all of your information is...

  16. Teaching the Net: Innovative Techniques in Internet Training.

    ERIC Educational Resources Information Center

    Brandt, D. Scott

    Teaching the Internet is hard because the technology keeps changing, the system is complex, the environment is relatively unstable, and it is hard to know how much one needs to know in order to successfully use the Internet. The Internet is a pseudo-complex knowledge domain--the "rules" vary, and it is hard to tell which are the…

  17. Knowing Who Knows: Laypersons' Capabilities to Judge Experts' Pertinence for Science Topics

    ERIC Educational Resources Information Center

    Bromme, Rainer; Thomm, Eva

    2016-01-01

    Because modern societies are built on elaborate divisions of cognitive labor, individuals remain laypersons in most knowledge domains. Hence, they have to rely on others' expertise when deciding on many science-related issues in private and public life. Even children already locate and discern expertise in the minds of others (e.g., Danovitch…

  18. Cognitive Analysis of Chinese-English Metaphors of Animal and Human Body Part Words

    ERIC Educational Resources Information Center

    Song, Meiying

    2009-01-01

    Metaphorical cognition arises from the mapping of two conceptual domains onto each other. According to the "Anthropocentrism", people tend to know the world first by learning about their bodies including Apparatuses. Based on that, people begin to know the material world, and the human body part metaphorization emerges as the times…

  19. College Student Epistemological Perspectives across Knowledge Domains: A Proposed Grounded Theory

    ERIC Educational Resources Information Center

    Palmer, Betsy; Marra, Rose M.

    2004-01-01

    Scholars have studied epistemological development--or how one understands knowledge and knowing--of college students for many years. Research in this domain has included benchmarking studies of epistemological development, examinations of how curricular innovations impact epistemology, and some studies of differences in epistemological development…

  20. Cross-Dependency Inference in Multi-Layered Networks: A Collaborative Filtering Perspective.

    PubMed

    Chen, Chen; Tong, Hanghang; Xie, Lei; Ying, Lei; He, Qing

    2017-08-01

    The increasingly connected world has catalyzed the fusion of networks from different domains, which facilitates the emergence of a new network model-multi-layered networks. Examples of such kind of network systems include critical infrastructure networks, biological systems, organization-level collaborations, cross-platform e-commerce, and so forth. One crucial structure that distances multi-layered network from other network models is its cross-layer dependency, which describes the associations between the nodes from different layers. Needless to say, the cross-layer dependency in the network plays an essential role in many data mining applications like system robustness analysis and complex network control. However, it remains a daunting task to know the exact dependency relationships due to noise, limited accessibility, and so forth. In this article, we tackle the cross-layer dependency inference problem by modeling it as a collective collaborative filtering problem. Based on this idea, we propose an effective algorithm Fascinate that can reveal unobserved dependencies with linear complexity. Moreover, we derive Fascinate-ZERO, an online variant of Fascinate that can respond to a newly added node timely by checking its neighborhood dependencies. We perform extensive evaluations on real datasets to substantiate the superiority of our proposed approaches.

  1. Factors associated with attitudes toward the elderly in a sample of elderly caregivers.

    PubMed

    Luchesi, Bruna Moretti; Alexandre, Tiago da Silva; de Oliveira, Nathalia Alves; Brigola, Allan Gustavo; Kusumota, Luciana; Pavarini, Sofia Cristina Iost; Marques, Sueli

    2016-12-01

    The number of elderly caregivers is increasing in the world. It is important to know the attitudes toward the elderly, because they can influence a range of behaviors. Our aim was to determine factors associated with attitudes toward the elderly in a sample of older carers. Three hundred and thirteen elderly caregivers (75.4% women, mean age 69.7 ± 7.1) who cared for a dependent older person at home completed a cross-sectional household interview. In addition to the four domains of the Neri Scale to Assess Attitudes Toward the Elderly, participants were evaluated regarding the demographics, care recipient (CR) characteristics, functional and cognitive status, general health, life satisfaction, perceived stress, and depressive symptoms. Overall, attitudes toward the elderly were neutral in this sample. More negative attitudes in some Neri Scale domains were associated with being older, living in an urban setting, taking more medications per day, caring for an elderly dependent in basic Activities of Daily Living (ADLs), being "more or less" satisfied with life, and having higher levels of perceived stress. There was a negative association between positive attitudes and educational level. The results highlight the need for public policies to promote more positive attitudes toward aging and change negative stereotypes usually used to designate older people. These public policies can try to modify some predictors of negative attitudes, such as perceived stress, which was associated with all four domains of Neri Scale.

  2. Structural intermediates and directionality of the swiveling motion of Pyruvate Phosphate Dikinase

    NASA Astrophysics Data System (ADS)

    Minges, Alexander; Ciupka, Daniel; Winkler, Christian; Höppner, Astrid; Gohlke, Holger; Groth, Georg

    2017-03-01

    Pyruvate phosphate dikinase (PPDK) is a vital enzyme in cellular energy metabolism catalyzing the ATP- and Pi-dependent formation of phosphoenolpyruvate from pyruvate in C4 -plants, but the reverse reaction forming ATP in bacteria and protozoa. The multi-domain enzyme is considered an efficient molecular machine that performs one of the largest single domain movements in proteins. However, a comprehensive understanding of the proposed swiveling domain motion has been limited by not knowing structural intermediates or molecular dynamics of the catalytic process. Here, we present crystal structures of PPDKs from Flaveria, a model genus for studying the evolution of C4 -enzymes from phylogenetic ancestors. These structures resolve yet unknown conformational intermediates and provide the first detailed view on the large conformational transitions of the protein in the catalytic cycle. Independently performed unrestrained MD simulations and configurational free energy calculations also identified these intermediates. In all, our experimental and computational data reveal strict coupling of the CD swiveling motion to the conformational state of the NBD. Moreover, structural asymmetries and nucleotide binding states in the PPDK dimer support an alternate binding change mechanism for this intriguing bioenergetic enzyme.

  3. Domain Specificity of Personal Epistemology: Resolved Questions, Persistent Issues, New Models

    ERIC Educational Resources Information Center

    Hofer, Barbara K.

    2006-01-01

    Beliefs that individuals hold about knowledge and knowing, or what has been termed ''personal epistemology'', are related to learning and achievement in complex ways. These beliefs are also differentiated by discipline (e.g., math, science, history) as well as by judgment domains (e.g., personal taste, morality, meaning). This commentary on five…

  4. Closing the Obesity Achievement Gap: Evidence-Based Practices that School Counselors Can Help Implement

    ERIC Educational Resources Information Center

    Perusse, Rachelle; Kailimang, Lukas; Krell, Megan

    2009-01-01

    School counselors are charged with helping students in the personal/social, academic, and career development domains. Obesity creates adverse educational outcomes for students along these three domains, suggesting an obesity achievement gap. Thus, school counselors can benefit from knowing which interventions have been shown to be successful in…

  5. Development of an instructional expert system for hole drilling processes

    NASA Technical Reports Server (NTRS)

    Al-Mutawa, Souhaila; Srinivas, Vijay; Moon, Young Bai

    1990-01-01

    An expert system which captures the expertise of workshop technicians in the drilling domain was developed. The expert system is aimed at novice technicians who know how to operate the machines but have not acquired the decision making skills that are gained with experience. This paper describes the domain background and the stages of development of the expert system.

  6. IEA's TIMSS 2003 International Report on Achievement in the Mathematics Cognitive Domains: Findings from a Developmental Project

    ERIC Educational Resources Information Center

    Mullis, Ina V. S.; Martin, Michael O.; Foy, Pierre

    2005-01-01

    This report documents the process undertaken to produce scales in three cognitive domains: knowing, applying, and reasoning. Included are the final scales showing differences among countries, as well as within countries. TIMSS 2003 is the third and most recently completed round of IEA's Trends in International Mathematics and Science Study, a…

  7. Recognition memory and awareness: occurrence of perceptual effects in remembering or in knowing depends on conscious resources at encoding, but not at retrieval.

    PubMed

    Gardiner, John M; Gregg, Vernon H; Karayianni, Irene

    2006-03-01

    We report four experiments in which a remember-know paradigm was combined with a response deadline procedure in order to assess memory awareness in fast, as compared with slow,recognition judgments. In the experiments, we also investigated the perceptual effects of study-test congruence, either for picture size or for speaker's voice, following either full or divided attention at study. These perceptual effects occurred in remembering with full attention and in knowing with divided attention, but they were uninfluenced by recognition speed, indicating that their occurrence in remembering or knowing depends more on conscious resources at encoding than on those at retrieval. The results have implications for theoretical accounts of remembering and knowing that assume that remembering is more consciously controlled and effortful, whereas knowing is more automatic and faster.

  8. Switching from Bloom to the Medicine Wheel: Creating Learning Outcomes That Support Indigenous Ways of Knowing in Post-Secondary Education

    ERIC Educational Resources Information Center

    LaFever, Marcella

    2016-01-01

    Based on a review of works by Indigenous educators, this paper suggests a four-domain framework for developing course outcome statements that will serve all students, with a focus on better supporting the educational empowerment of Indigenous students. The framework expands the three domains of learning, pioneered by Bloom to a four-domain…

  9. What do mothers want to know about teens' activities? Levels, trajectories, and correlates.

    PubMed

    Smetana, Judith G; Rote, Wendy M

    2015-01-01

    Middle class mothers (n = 169) of middle adolescents (M = 15.69 years old) in the U.S. rated how much they want to know and responded qualitatively about what they "always" and "never" want to know about adolescents' risky prudential (e.g., drinking alcohol, using illegal drugs), personal (e.g., teens' private conversations), and multifaceted (involving overlapping prudential and personal concerns) activities. Latent growth curve modeling over one year showed that mothers wanted to know most about prudential, less about multifaceted, and least about personal activities; wanting to know declined over time for each type of activity, but less for prudential than for other activities. With teen problem behavior controlled, psychologically controlling parenting, supportive and negative interactions with teens, knowledge of adolescents' activities, and teens' age were associated with individual differences in mothers' initial ratings and trajectories of wanting to know, although results varied by domain and were moderated by teen gender. Copyright © 2014 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  10. Disciplinary knowledge of K-3 teachers and their knowledge calibration in the domain of early literacy.

    PubMed

    Cunningham, Anne E; Perry, Kathryn E; Stanovich, Keith E; Stanovich, Paula J

    2004-06-01

    Recently, investigators have begun to pay increasing attention to the role of teachers' domain specific knowledge in the area of reading, and its implications for both classroom practice and student learning. The aims of the present study were to assess kindergarten to third-grade teachers' actual and perceived reading-related subject matter knowledge, and to investigate the extent to which teachers calibrate their reading related subject matter knowledge by examining relationships between actual and perceived knowledge. Results indicated that while teachers demonstrated limited knowledge of children's literature, phoneme awareness, and phonics, the majority of these same teachers evaluated their knowledge levels quite positively. Teachers demonstrated some ability to calibrate their own knowledge levels in the area of children's literature, yet they were poorly calibrated in the domains of phoneme awareness and phonics. These findings suggest that teachers tend to overestimate their reading related subject matter knowledge and are often unaware of what they know and do not know. Implications for the design of teacher education at both the preservice and inservice levels are discussed.

  11. Education-based disparities in knowledge of novel health risks: The case of knowledge gaps in HIV risk perceptions.

    PubMed

    Kiviniemi, Marc T; Orom, Heather; Waters, Erika A; McKillip, Megan; Hay, Jennifer L

    2018-05-01

    Risk perception is a key determinant of preventive health behaviour, but when asked, some individuals indicate they do not know their health risk. Low education is associated with both lack of knowledge about health risk and with the persistence and exacerbation of gaps in knowledge about health issues. This study uses the context of an emerging infectious disease threat to explore the hypothesis that the education-don't know risk relation results from differences in knowledge about the health issue of interest. Specifically, we examine whether patterns of change over time follow theoretical predictions that disparities in risk knowledge would increase over time in less educated sectors of the population (knowledge gap hypothesis). Secondary analysis of population-representative behavioural surveillance survey. We analysed data from the 1993 to 2000 Behavior Risk Factor Surveillance System surveys, which measured education and perceived HIV/AIDS risk in a population sample collected separately in each survey year; don't know responses were coded. In each year, individuals with higher education were less likely to respond don't know. The absolute prevalence of don't know responding dropped over time; nonetheless, there was an increase over time in the magnitude of the pattern of lower education being associated with greater don't know responding. We found support for the knowledge gap hypothesis. Over time, populations with greater education gained more knowledge about their HIV risk than populations with lower education. Results highlight the need to carefully consider health communication strategies to reach and address those individuals with low education and health knowledge. Statement of contribution What is already known on this subject? A meaningful potion of the population answers 'don't know' when asked to report their risk for health problems, indicating a lack of risk perception in the domain. Previous studies have shown that level of education is associated with don't know responding - those with lower educational attainment are more likely to respond don't know. The education-don't know responding relation suggests that lack of health information and health domain knowledge might be a factor in lacking risk perception, but this mechanism has not been previously tested. What does this study add? Patterns of changes in don't know responding over time as population-level knowledge of a health risk increase are consistent with the health information/health knowledge hypothesis outlined above. As population knowledge of HIV/AIDS risk in the United States increased over time (indicated by declining overall rates of don't know responses), the relation of education level to don't know responding actually became stronger. The pattern of change over time is the classic 'knowledge gap hypothesis' pattern, which has not been previously demonstrated for knowledge of personal health risk. The knowledge gap response pattern supports the health information/health knowledge hypothesis. © 2018 The British Psychological Society.

  12. Health behaviour procrastination: a novel reasoned route towards self-regulatory failure.

    PubMed

    Kroese, Floor M; de Ridder, Denise T D

    2016-09-01

    In this paper, we highlight a novel perspective on health behaviour failure by considering reasoned procrastination as a contributing factor. We argue that the failure to enact intentions does not necessarily occur because people are victims of their strong impulses, but that people may also knowingly and wilfully postpone their intended actions. While procrastination is acknowledged as a factor associated with intention-behaviour gaps in other domains, it has surprisingly received only very little attention in the domain of health behaviour. We argue that it is particularly important to recognise the waxing and waning of intentions: rather than being truly abandoned, intentions may sometimes be temporarily put aside. This paper describes how the procrastination account relates to the intention-behaviour gap as we know it, what is known about procrastination and health behaviour, and what theoretical and practical implications can be derived from the addition of this novel perspective to our understanding of health behaviour change.

  13. Organic unity theory: an integrative mind-body theory for psychiatry.

    PubMed

    Goodman, A

    1997-12-01

    The potential of psychiatry as an integrative science has been impeded by an internal schism that derives from the duality of mental and physical. Organic unity theory is proposed as a conceptual framework that brings together the terms of the mind-body duality in one coherent perspective. Organic unity theory is braided of three strands: identity, which describes the relationship between mentally described events and corresponding physically described events; continuity, which describes the linguistic-conceptual system that contains both mental and physical terms; and dialectic, which describes the relationship between the empirical way of knowing that is associated with the physical domain of the linguistic-conceptual system and the hermeneutic way of knowing that is associated with the mental domain. Each strand represents an integrative formulation that resolves an aspect of mental-physical dualism into an underlying unity. After the theory is presented, its implications for psychiatry are briefly considered.

  14. Knowing Who Knows: Laypersons' Capabilities to Judge Experts' Pertinence for Science Topics.

    PubMed

    Bromme, Rainer; Thomm, Eva

    2016-01-01

    Because modern societies are built on elaborate divisions of cognitive labor, individuals remain laypersons in most knowledge domains. Hence, they have to rely on others' expertise when deciding on many science-related issues in private and public life. Even children already locate and discern expertise in the minds of others (e.g., Danovitch & Keil, 2004). This study examines how far university students accurately judge experts' pertinence for science topics even when they lack proficient knowledge of the domain. Participants judged the pertinence of experts from diverse disciplines based on the experts' assumed contributions to texts adapted from original articles from Science and Nature. Subjective pertinence judgments were calibrated by comparing them with bibliometrics of the original articles. Furthermore, participants' general science knowledge was controlled. Results showed that participants made well-calibrated pertinence judgments regardless of their level of general science knowledge. Copyright © 2015 Cognitive Science Society, Inc.

  15. [Empowerment and power: their relationship in the proces of caring for the chronically ill in primary care].

    PubMed

    Riba Bellera, Lydia; Boixadera Vendrell, Mireia; Buendía Surroca, Carmen; Martorell Poveda, Maria Antònia; Piñeiro Méndez, Pilar; Zamora Sánchez, Juan José

    2014-06-01

    The concepts of "power" and "empowerment" are used in various disciplines, both political and social. Now are these terms frequently in the field of health. Our goal is to know its meaning as a synonym of expressions: "energy", "force", "domain", "vigour", "power", "capacity", "authority" and "control", which have been always within our practice nurse's own lexicon. Semantically analyzing them will help us in the understanding of its nuance. The literature review facilitates their understanding and allows us to link these words within the management of care. In this way we can propose diagnoses, interventions and outcomes specifically related to these concepts, which will help us optimize the efficiency in the management of care plans. The purpose of various collective nurses from different institutions is that the person is able to not generate dependencies and have the option of choosing your own lifestyle according to their culture and environment, independently or with the help. Generate knowledge is to generate power. The person should be educated and informed, to be expert and active and taking action to help control and minimize the progression of your health problem chronic and its possible complications. We are in the process of reformulation of the health system, whether it is private or public, and is necessary to know the power of the various actors involved in the management of the care to us. Each of these main actors--person ill, family/caregiver or nurse--has to know what is his role in this process.

  16. What people with PTSD symptoms do (and do not) know about PTSD: A national survey.

    PubMed

    Harik, Juliette M; Matteo, Rebecca A; Hermann, Barbara A; Hamblen, Jessica L

    2017-04-01

    If people do not recognize posttraumatic stress disorder (PTSD) symptoms, they may not realize they are suffering from the disorder. Likewise, if people do not know that effective treatments exist, they may be unlikely to seek care. This study examined what people with PTSD symptoms know about PTSD and its treatment. We hypothesized that military service and prior receipt of PTSD treatment would be associated with greater PTSD knowledge. We conducted an online survey assessing knowledge in three domains: trauma, PTSD symptoms, and effective PTSD treatments. Participants were 301 adults (50% veterans) who were drawn from a national research panel and screened positive for PTSD. When asked to identify items from a list, participants had better recognition for traumatic events (M = 72.2% of items correct) and PTSD symptoms (M = 62.3%) than for effective PTSD treatments (M = 37.9%). Across domains, participants often identified false items as true. Most participants thought divorce was a trauma that could cause PTSD, that drug addiction was a PTSD symptom, and that support groups are effective PTSD treatments. Prior receipt of PTSD treatment was associated with better symptom recognition (b = .86, P = .003). Being a military veteran was associated with better trauma recognition (b = .56, P = .025), but poorer treatment recognition (b = -.65, P = .034). People with PTSD symptoms lack knowledge about the disorder, especially regarding effective treatments. Public education about PTSD is needed so that people recognize when to seek care and which treatments to choose. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  17. Opinion mining feature-level using Naive Bayes and feature extraction based analysis dependencies

    NASA Astrophysics Data System (ADS)

    Sanda, Regi; Baizal, Z. K. Abdurahman; Nhita, Fhira

    2015-12-01

    Development of internet and technology, has major impact and providing new business called e-commerce. Many e-commerce sites that provide convenience in transaction, and consumers can also provide reviews or opinions on products that purchased. These opinions can be used by consumers and producers. Consumers to know the advantages and disadvantages of particular feature of the product. Procuders can analyse own strengths and weaknesses as well as it's competitors products. Many opinions need a method that the reader can know the point of whole opinion. The idea emerged from review summarization that summarizes the overall opinion based on sentiment and features contain. In this study, the domain that become the main focus is about the digital camera. This research consisted of four steps 1) giving the knowledge to the system to recognize the semantic orientation of an opinion 2) indentify the features of product 3) indentify whether the opinion gives a positive or negative 4) summarizing the result. In this research discussed the methods such as Naï;ve Bayes for sentiment classification, and feature extraction algorithm based on Dependencies Analysis, which is one of the tools in Natural Language Processing (NLP) and knowledge based dictionary which is useful for handling implicit features. The end result of research is a summary that contains a bunch of reviews from consumers on the features and sentiment. With proposed method, accuration for sentiment classification giving 81.2 % for positive test data, 80.2 % for negative test data, and accuration for feature extraction reach 90.3 %.

  18. An analysis of women's ways of knowing in a 10th grade integrated science classroom

    NASA Astrophysics Data System (ADS)

    Kochheiser, Karen Lynn

    All students can learn science, but how they learn science may differ. This study is about learning science and its relationship to gender. Women need to develop and establish connections with the objects that they are learning and be able to establish a voice in a science classroom. Unfortunately, traditional science classrooms still view science as a male domain and tend to discourage women from pursuing higher levels of science or science related careers. The ways that women learn science are a very complex set of interactions. In order to describe these interactions, this study explored how women's ways of knowing are represented in a high school science classroom. Nine women from an enriched integrated biology and earth science class contributed to this study. The women contributed to this study by participating in individual and group interviews, questionnaires, journals, observations and participant review of the interviews. The ways that these women learn science were described in terms of Belenky, Clinchy, Goldberger, and Tarule's Women's Ways of Knowing: The Development of Self, Voice, and Mind (1997). The women's ways of learning in this classroom tended to be situational with the women fitting different categories of knowing depending on the situation. Most of the women demonstrated periods of time where they wanted to be heard or tried to establish a voice in the classroom. The study helps to provide a theory for how women make choices in their learning of science and the struggle to be successful in a male dominated discipline. The women participating in this study gained an awareness of how they learn science and how that can be used to make them even more successful in the classroom. The awareness of how women learn science will also be of great benefit to other teachers and educators as the work for science reform continues to make science a 'science for all'.

  19. Personal Computer and Workstation Operating Systems Tutorial

    DTIC Science & Technology

    1994-03-01

    to a RAM area where it is executed by the CPU. The program consists of instructions that perform operations on data. The CPU will perform two basic...memory to improve system performance. More often the user will buy a new fixed disk so the computer will hold more programs internally. The trend today...MHZ. Another way to view how fast the information is going into the register is in a time domain rather than a frequency domain knowing that time and

  20. Molecular dynamics simulation unveils the conformational flexibility of the interdomain linker in the bacterial transcriptional regulator GabR from Bacillus subtilis bound to pyridoxal 5’-phosphate

    PubMed Central

    Narzi, Daniele; Guidoni, Leonardo

    2017-01-01

    GabR from Bacillus subtilis is a transcriptional regulator belonging to the MocR subfamily of the GntR regulators. The structure of the MocR regulators is characterized by the presence of two domains: i) a N-terminal domain, about 60 residue long, possessing the winged-Helix-Turn-Helix (wHTH) architecture with DNA recognition and binding capability; ii) a C-terminal domain (about 350 residue) folded as the pyridoxal 5’-phosphate (PLP) dependent aspartate aminotransferase (AAT) with dimerization and effector binding functions. The two domains are linked to each other by a peptide bridge. Although structural and functional characterization of MocRs is proceeding at a fast pace, virtually nothing is know about the molecular changes induced by the effector binding and on how these modifications influence the properties of the regulator. An extensive molecular dynamics simulation on the crystallographic structure of the homodimeric B. subtilis GabR has been undertaken with the aim to envisage the role and the importance of conformational flexibility in the action of GabR. Molecular dynamics has been calculated for the apo (without PLP) and holo (with PLP bound) forms of the GabR. A comparison between the molecular dynamics trajectories calculated for the two GabR forms suggested that one of the wHTH domain detaches from the AAT-like domain in the GabR PLP-bound form. The most evident conformational change in the holo PLP-bound form is represented by the rotation and the subsequent detachment from the subunit surface of one of the wHTH domains. The movement is mediated by a rearrangement of the linker connecting the AAT domain possibly triggered by the presence of the negative charge of the PLP cofactor. This is the second most significant conformational modification. The C-terminal section of the linker docks into the “active site” pocket and establish stabilizing contacts consisting of hydrogen-bonds, salt-bridges and hydrophobic interactions. PMID:29253008

  1. Emotional Intelligence: Directing a Child's Emotional Education.

    ERIC Educational Resources Information Center

    Richburg, Melanie; Fletcher, Teresa

    2002-01-01

    Describes the domains of emotional intelligence and proposes that there may be a significant relationship between emotional intelligence and life success. Provides examples of knowing one's emotions, managing emotions, motivating oneself, recognizing emotions in others, and handling relationships. Applies the theory to the case conceptualization…

  2. Investigating TPACK: Knowledge Growth in Teaching with Technology

    ERIC Educational Resources Information Center

    Niess, Margaret L.

    2011-01-01

    Technological pedagogical and content knowledge (TPACK) presents a dynamic framework for describing teachers' knowledge required for designing, implementing, and evaluating curriculum and instruction with technology. TPACK strategic thinking includes knowing when, where, and how to use domain-specific knowledge and strategies for guiding students'…

  3. Modeling of Floating Time Domain Electromagnetic Method to Detect Dissolved Sediment

    NASA Astrophysics Data System (ADS)

    Nurjanah, Siti; Widodo

    2017-04-01

    In hydrology context, sediment can be interpreted as inorganic and organic material that is transported by, suspended in, or deposited by streams. It is important to know the function of soil, stream discharge, land-cover features, weather conditions and land-use activities. Sediment load carried by streams and rivers can be composed either of fine materials, mostly silts, and clays, or coarse materials such as sand. One product of sediment is dissolved load consists of indistinct material in solution moving downstream. It is produced by chemical weathering processes and does not move out of the water. To investigate the dissolved sediment, we have applied the floating of Time Domain Electromagnetic (TDEM) method. The acquisition of TDEM data has been performed use tires and small ship as innovation measurements. The calculated data model using Occam and Marquardt Algorithms. The responses of data show the sedimentation has less resistive compare the surrounding structures. This innovation is very helpful to know the environmental condition, especially in the water.

  4. Spotlight on Brain Tumors: Do You Know the Symptoms?

    MedlinePlus

    ... Subscribe October 2017 Print this issue Spotlight on Brain Tumors Do You Know the Symptoms? En español ... at Epilepsy Wise Choices Possible Symptoms of a Brain Tumor The symptoms of a brain tumor depend ...

  5. Structure and inference in annotated networks

    PubMed Central

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

    2016-01-01

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

  6. Structure and inference in annotated networks

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

  7. Estimating the signal-to-noise ratio of AVIRIS data

    NASA Technical Reports Server (NTRS)

    Curran, Paul J.; Dungan, Jennifer L.

    1988-01-01

    To make the best use of narrowband airborne visible/infrared imaging spectrometer (AVIRIS) data, an investigator needs to know the ratio of signal to random variability or noise (signal-to-noise ratio or SNR). The signal is land cover dependent and varies with both wavelength and atmospheric absorption; random noise comprises sensor noise and intrapixel variability (i.e., variability within a pixel). The three existing methods for estimating the SNR are inadequate, since typical laboratory methods inflate while dark current and image methods deflate the SNR. A new procedure is proposed called the geostatistical method. It is based on the removal of periodic noise by notch filtering in the frequency domain and the isolation of sensor noise and intrapixel variability using the semi-variogram. This procedure was applied easily and successfully to five sets of AVIRIS data from the 1987 flying season and could be applied to remotely sensed data from broadband sensors.

  8. Homo Ignorans: Deliberately Choosing Not to Know.

    PubMed

    Hertwig, Ralph; Engel, Christoph

    2016-05-01

    Western history of thought abounds with claims that knowledge is valued and sought. Yet people often choose not to know. We call the conscious choice not to seek or use knowledge (or information) deliberate ignorance. Using examples from a wide range of domains, we demonstrate that deliberate ignorance has important functions. We systematize types of deliberate ignorance, describe their functions, discuss their normative desirability, and consider how they can be modeled. To date, psychologists have paid relatively little attention to the study of ignorance, let alone the deliberate kind. Yet the desire not to know is no anomaly. It is a choice to seek rather than reduce uncertainty whose reasons require nuanced cognitive and economic theories and whose consequences-for the individual and for society-require analyses of both actor and environment. © The Author(s) 2016.

  9. Flexibility in Problem Solving: The Case of Equation Solving

    ERIC Educational Resources Information Center

    Star, Jon R.; Rittle-Johnson, Bethany

    2008-01-01

    A key learning outcome in problem-solving domains is the development of flexible knowledge, where learners know multiple strategies and adaptively choose efficient strategies. Two interventions hypothesized to improve flexibility in problem solving were experimentally evaluated: prompts to discover multiple strategies and direct instruction on…

  10. Pause, play, repeat

    PubMed Central

    Sansó, Miriam; Fisher, Robert P

    2013-01-01

    Cyclin-dependent kinases (CDKs) play a central role in governing eukaryotic cell division. It is becoming clear that the transcription cycle of RNA polymerase II (RNAP II) is also regulated by CDKs; in metazoans, the cell cycle and transcriptional CDK networks even share an upstream activating kinase, which is itself a CDK. From recent chemical-genetic analyses we know that CDKs and their substrates control events both early in transcription (the transition from initiation to elongation) and late (3′ end formation and transcription termination). Moreover, mutual dependence on CDK activity might couple the “beginning” and “end” of the cycle, to ensure the fidelity of mRNA maturation and the efficient recycling of RNAP II from sites of termination to the transcription start site (TSS). As is the case for CDKs involved in cell cycle regulation, different transcriptional CDKs act in defined sequence on multiple substrates. These phosphorylations are likely to influence gene expression by several mechanisms, including direct, allosteric effects on the transcription machinery, co-transcriptional recruitment of proteins needed for mRNA-capping, splicing and 3′ end maturation, dependent on multisite phosphorylation of the RNAP II C-terminal domain (CTD) and, perhaps, direct regulation of RNA-processing or histone-modifying machinery. Here we review these recent advances, and preview the emerging challenges for transcription-cycle research. PMID:23756342

  11. What Everyone Should Know about Archeans

    ERIC Educational Resources Information Center

    Freeland, Peter

    2013-01-01

    For many years biologists supposed that one group of microorganisms, which they called archaebacteria, were an ancient and primitive type of bacteria. Following biochemical analysis of their RNA and other cell components, it soon became clear that their distinct features merited classification in a separate domain, the archea. From an evolutionary…

  12. Know Your Laws.

    ERIC Educational Resources Information Center

    Watson, Joan Q.

    These 24 self-contained competency-based modules are designed to acquaint Florida adult students with laws they will meet in everyday life; fundamentals of local, state, and federal governments; and the criminal and juvenile justice systems. (The 130 objectives are categorized in the first three levels of the Cognitive Domain and parallel the…

  13. Estimating Linear Size and Scale: Body Rulers

    ERIC Educational Resources Information Center

    Jones, Gail; Taylor, Amy; Broadwell, Bethany

    2009-01-01

    The National Science Education Standards emphasise the use of concepts and skills that cut across the science domains. One of these cross-cutting areas is measurement. Students should know measurement systems, units of measurement, tools and error in measurement as well as the importance of measurement to scientific endeavours. Even though…

  14. Bible Knowledge and Moral Judgment: Knowing Scripture and Using Ethical Reasoning

    ERIC Educational Resources Information Center

    Nelson, Daniel

    2004-01-01

    The relationship between moral judgment and religious knowledge was investigated, with an analysis of the impact of academic skill on both domains. Fifty-six Bible college seniors completed measures of moral judgment (Defining Issues Test), Bible knowledge (Standardized Bible Content Test), and academic skill (Academic Profile). Results indicate…

  15. Cognitive Correlates of Math Skills in Third-Grade Students

    ERIC Educational Resources Information Center

    Mannamaa, Mairi; Kikas, Eve; Peets, Katlin; Palu, Anu

    2012-01-01

    Math achievement is not a unidimensional construct but includes different skills that require different cognitive abilities. The focus of this study was to examine associations between a number of cognitive abilities and three domains of math skills (knowing, applying and problem solving) simultaneously in a multivariate framework. Participants…

  16. Decoding Representations: How Children with Autism Understand Drawings

    ERIC Educational Resources Information Center

    Allen, Melissa L.

    2009-01-01

    Young typically developing children can reason about abstract depictions if they know the intention of the artist. Children with autism spectrum disorder (ASD), who are notably impaired in social, "intention monitoring" domains, may have great difficulty in decoding vague representations. In Experiment 1, children with ASD are unable to use…

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

    PubMed

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

    2017-01-01

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

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

    PubMed Central

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

    2017-01-01

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

  19. What Every Social Studies Teacher Should Know about Simulations

    ERIC Educational Resources Information Center

    Wright-Maley, Cory

    2015-01-01

    Simulations are of growing interest within the social studies in terms of research and practice. Although the findings of early research were unfavorable to simulations in terms of student learning, recent research has revealed new and interesting findings related to different domains of student learning that earlier research did not. In light of…

  20. AIDS: It's Not What You Know, It's What You Do.

    ERIC Educational Resources Information Center

    Hochhauser, Mark

    This document reviews five psychological domains of prevention of the behavioral disease of Acquired Immune Deficiency Syndrome (AIDS). First the limits of AIDS education are discussed, noting that increasing amounts of education will not necessarily reduce the spread of the virus, since information and education do not control behavior. Research…

  1. Awareness of Malicious Social Engineering among Facebook Users

    ERIC Educational Resources Information Center

    Slonka, Kevin J.

    2014-01-01

    With the rapid growth of Facebook, the social networking website is becoming a lucrative target for malicious activity. Users of Facebook therefore should be aware of various malicious attacks and know how to identify them. This research analyzed Facebook users' level of understanding in the domain of malicious social engineering on Facebook. The…

  2. ReACT!: An Interactive Educational Tool for AI Planning for Robotics

    ERIC Educational Resources Information Center

    Dogmus, Zeynep; Erdem, Esra; Patogulu, Volkan

    2015-01-01

    This paper presents ReAct!, an interactive educational tool for artificial intelligence (AI) planning for robotics. ReAct! enables students to describe robots' actions and change in dynamic domains without first having to know about the syntactic and semantic details of the underlying formalism, and to solve planning problems using…

  3. Epistemic Metacognition in Context: Evaluating and Learning Online Information

    ERIC Educational Resources Information Center

    Mason, Lucia; Boldrin, Angela; Ariasi, Nicola

    2010-01-01

    This study examined epistemic metacognition as a reflective activity about knowledge and knowing in the context of online information searching on the Web, and whether it was related to prior knowledge on the topic, study approach, and domain-specific beliefs about science. In addition, we investigated whether Internet-based learning was…

  4. Alignment in Early Movement Education: Remembering What We Know

    ERIC Educational Resources Information Center

    Oliver, Suzanne

    2009-01-01

    This article addresses postural awareness and efficiency as a fundamental but often overlooked aspect of movement training that falls naturally into the domain of HPERD pedagogical practice. Beginning with a brief overview and discussion on the anatomical "cost" of poor organization, the body of the article describes activities that can be…

  5. Net Neutrality: What Librarians Should Know

    ERIC Educational Resources Information Center

    Anderson, Byron

    2007-01-01

    The openness of the Internet has greatly facilitated scholarly communication and led to creative developments in many fields. The Internet has been called the most democratic of media. In many countries, one does not need permission to post a new Web page. Public domain information flows freely and is widely accessible on an impartial basis to…

  6. Developing Procedural Flexibility: Are Novices Prepared to Learn from Comparing Procedures?

    ERIC Educational Resources Information Center

    Rittle-Johnson, Bethany; Star, Jon R.; Durkin, Kelley

    2012-01-01

    Background: A key learning outcome in problem-solving domains is the development of procedural flexibility, where learners know multiple procedures and use them appropriately to solve a range of problems (e.g., Verschaffel, Luwel, Torbeyns, & Van Dooren, 2009). However, students often fail to become flexible problem solvers in mathematics. To…

  7. Beliefs about Knowledge, Knowing, and Learning: Differences across Knowledge Types in Physics

    ERIC Educational Resources Information Center

    Muis, Krista R.; Gierus, Bogusia

    2014-01-01

    The authors examined whether students' epistemic and learning beliefs varied across different knowledge types in physics. On the basis of various beliefs frameworks, the authors predicted that individuals' beliefs would vary within a domain across the same content when presented conceptually versus procedurally. Participants were 81 high…

  8. Expertise, Ethics Expertise, and Clinical Ethics Consultation: Achieving Terminological Clarity

    PubMed Central

    Iltis, Ana S.; Sheehan, Mark

    2016-01-01

    The language of ethics expertise has become particularly important in bioethics in light of efforts to establish the value of the clinical ethics consultation (CEC), to specify who is qualified to function as a clinical ethics consultant, and to characterize how one should evaluate whether or not a person is so qualified. Supporters and skeptics about the possibility of ethics expertise use the language of ethics expertise in ways that reflect competing views about what ethics expertise entails. We argue for clarity in understanding the nature of expertise and ethics expertise. To be an ethics expert, we argue, is to be an expert in knowing what ought to be done. Any attempt to articulate expertise with respect to knowing what ought to be done must include an account of ethics that specifies the nature of moral truth and the means by which we access this truth or a theoretical account of ethics such that expertise in another domain is linked to knowing or being better at judging what ought to be done and the standards by which this “knowing” or “being better at judging” is determined. We conclude with a discussion of the implications of our analysis for the literature on ethics expertise in CEC. We do think that there are clear domains in which a clinical ethics consultant might be expert but we are skeptical about the possibility that this includes ethics expertise. Clinical ethics consultants should not be referred to as ethics experts. PMID:27256848

  9. Does the care dependency of nursing home residents influence their health-related quality of life?-A cross-sectional study

    PubMed Central

    2013-01-01

    Background Studies on health-related quality of life (HRQOL) are missing for nursing home residents independent from their health conditions or interventions after admission. Our aim was to analyse if the care dependency of nursing home residents influence their HRQOL and to describe HRQOL of nursing home residents at the time of admission. Method Eleven German nursing homes were randomly selected for a cross-sectional multicentre study from April 2008 until December 2009. HRQOL was measured with the Nottingham Health Profile (NHP) in the six domains “Physical Mobility”, ”Energy”, “Pain”, “Social Isolation”, “Emotional Reaction” and “Sleep”. Domain scores range from zero (good subjective health status) to 100 (poor subjective health status). Care dependency was evaluated using the Care Dependency Scale, age, sex, cognitive status and diseases were documented by the research assistants. Multivariate regression analysis was performed to quantify the influence of care dependency on HRQOL. Results 120 residents were included in total. HRQOL was mostly reduced in the domains “Physical Mobility” and ”Energy“ (mean scores >43.0), while impairment differences in the domains “Pain”, “Social Isolation”, “Emotional Reaction” and “Sleep” were only moderate (≤25.0). HRQOL was not influenced by the age. Women (n = 85) had a significantly poorer HRQOL in the domain “Pain” than men (mean score women: 29.5 ± 31.5; males: 14.9 ± 17.2; p = 0.011). Care dependency had an influence on the domain “Sleep” (ß = −0.195, p = 0.031), while the other domains were not influenced by care dependency. Residents with a low care dependency scored significantly lower (better HRQOL) in the domain “Sleep” than residents with a high care dependency (mean score 15.3; SD ± 19.0 versus mean score 32.8 SD ± 33.2; p < 0.02). Conclusion The level of care dependency has no influence on the HRQOL from the nursing home residents’ perspective apart from the domain “Sleep”. High care dependency residents have a lower HRQOL in the domain “Sleep” compared to moderate and low care dependency residents. We found a significantly lower HRQOL in women compared to men in the domain “Pain“. PMID:23497216

  10. Does the care dependency of nursing home residents influence their health-related quality of life?-A cross-sectional study.

    PubMed

    Tabali, Manuela; Ostermann, Thomas; Jeschke, Elke; Dassen, Theo; Heinze, Cornelia

    2013-03-11

    Studies on health-related quality of life (HRQOL) are missing for nursing home residents independent from their health conditions or interventions after admission. Our aim was to analyse if the care dependency of nursing home residents influence their HRQOL and to describe HRQOL of nursing home residents at the time of admission. Eleven German nursing homes were randomly selected for a cross-sectional multicentre study from April 2008 until December 2009. HRQOL was measured with the Nottingham Health Profile (NHP) in the six domains "Physical Mobility", "Energy", "Pain", "Social Isolation", "Emotional Reaction" and "Sleep". Domain scores range from zero (good subjective health status) to 100 (poor subjective health status). Care dependency was evaluated using the Care Dependency Scale, age, sex, cognitive status and diseases were documented by the research assistants. Multivariate regression analysis was performed to quantify the influence of care dependency on HRQOL. 120 residents were included in total. HRQOL was mostly reduced in the domains "Physical Mobility" and "Energy" (mean scores >43.0), while impairment differences in the domains "Pain", "Social Isolation", "Emotional Reaction" and "Sleep" were only moderate (≤25.0). HRQOL was not influenced by the age. Women (n = 85) had a significantly poorer HRQOL in the domain "Pain" than men (mean score women: 29.5 ± 31.5; males: 14.9 ± 17.2; p = 0.011). Care dependency had an influence on the domain "Sleep" (ß = -0.195, p = 0.031), while the other domains were not influenced by care dependency. Residents with a low care dependency scored significantly lower (better HRQOL) in the domain "Sleep" than residents with a high care dependency (mean score 15.3; SD ± 19.0 versus mean score 32.8 SD ± 33.2; p < 0.02). The level of care dependency has no influence on the HRQOL from the nursing home residents' perspective apart from the domain "Sleep". High care dependency residents have a lower HRQOL in the domain "Sleep" compared to moderate and low care dependency residents. We found a significantly lower HRQOL in women compared to men in the domain "Pain".

  11. Random domain name and address mutation (RDAM) for thwarting reconnaissance attacks

    PubMed Central

    Chen, Xi; Zhu, Yuefei

    2017-01-01

    Network address shuffling is a novel moving target defense (MTD) that invalidates the address information collected by the attacker by dynamically changing or remapping the host’s network addresses. However, most network address shuffling methods are limited by the limited address space and rely on the host’s static domain name to map to its dynamic address; therefore these methods cannot effectively defend against random scanning attacks, and cannot defend against an attacker who knows the target’s domain name. In this paper, we propose a network defense method based on random domain name and address mutation (RDAM), which increases the scanning space of the attacker through a dynamic domain name method and reduces the probability that a host will be hit by an attacker scanning IP addresses using the domain name system (DNS) query list and the time window methods. Theoretical analysis and experimental results show that RDAM can defend against scanning attacks and worm propagation more effectively than general network address shuffling methods, while introducing an acceptable operational overhead. PMID:28489910

  12. Toxic and nontoxic components of botulinum neurotoxin complex are evolved from a common ancestral zinc protein

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

    Inui, Ken; Japan Society for the Promotion of Science, 1-8 Chiyoda-ku, Tokyo 102-8472; Sagane, Yoshimasa

    2012-03-16

    Highlights: Black-Right-Pointing-Pointer BoNT and NTNHA proteins share a similar protein architecture. Black-Right-Pointing-Pointer NTNHA and BoNT were both identified as zinc-binding proteins. Black-Right-Pointing-Pointer NTNHA does not have a classical HEXXH zinc-coordinating motif similar to that found in all serotypes of BoNT. Black-Right-Pointing-Pointer Homology modeling implied probable key residues involved in zinc coordination. -- Abstract: Zinc atoms play an essential role in a number of enzymes. Botulinum neurotoxin (BoNT), the most potent toxin known in nature, is a zinc-dependent endopeptidase. Here we identify the nontoxic nonhemagglutinin (NTNHA), one of the BoNT-complex constituents, as a zinc-binding protein, along with BoNT. A protein structuremore » classification database search indicated that BoNT and NTNHA share a similar domain architecture, comprising a zinc-dependent metalloproteinase-like, BoNT coiled-coil motif and concanavalin A-like domains. Inductively coupled plasma-mass spectrometry analysis demonstrated that every single NTNHA molecule contains a single zinc atom. This is the first demonstration of a zinc atom in this protein, as far as we know. However, the NTNHA molecule does not possess any known zinc-coordinating motif, whereas all BoNT serotypes possess the classical HEXXH motif. Homology modeling of the NTNHA structure implied that a consensus K-C-L-I-K-X{sub 35}-D sequence common among all NTNHA serotype molecules appears to coordinate a single zinc atom. These findings lead us to propose that NTNHA and BoNT may have evolved distinct functional specializations following their branching out from a common ancestral zinc protein.« less

  13. Online Activities and Writing Practices of Urban Malaysian Adolescents

    ERIC Educational Resources Information Center

    Tan, Kok Eng; Ng, Melissa L. Y.; Saw, Kim Guan

    2010-01-01

    Among a number of urban adolescents in Malaysia, going online is a much valued practice. They are regularly drawn to the Internet to engage in activities across school, nonschool, mainstream and alternative domains. The aim of this study is to know more about what these adolescents do online. Data on the online activities were collected from 535…

  14. A Cognitive Map of Human Performance Technology: A Study of Domain Expertise.

    ERIC Educational Resources Information Center

    Villachica, Steven W.; Lohr, Linda L.; Summers, Laura; Lowell, Nate; Roberts, Stephanie; Javeri, Manisha; Hunt, Erin; Mahoney, Chris; Conn, Cyndie

    Most representations of academic disciplines have been created when experts depict or report what they know; however, there are potential problems that can arise when practitioners rely on expert self-report. One way to avoid potential problems associated with expert self-report is to employ cognitive task analysis methods. The Pathfinder Scaling…

  15. A Comparison of Elementary, Middle, and High School Teachers' Orientations toward Motivating Students

    ERIC Educational Resources Information Center

    Hansen, Mark David

    2010-01-01

    Developmental psychologists have long known that students are less interested in school and academic tasks with each additional year in school (Eccles & Midgely, 1989). In addition, they know that the most effective predictor of motivation at any age is self-efficacy, a student's perception of his/her academic ability in a specific domain. Factors…

  16. Pre-Service Physics Teachers' Ideas on Size, Visibility and Structure of the Atom

    ERIC Educational Resources Information Center

    Unlu, Pervin

    2010-01-01

    Understanding the atom gives the opportunity to both understand and conceptually unify the various domains of science, such as physics, chemistry, biology, astronomy and geology. Among these disciplines, physics teachers are expected to be particularly well educated in this topic. It is important that pre-service physics teachers know what sort of…

  17. Students' Conceptions of Radiation and What to Do about Them

    ERIC Educational Resources Information Center

    Plotz, Thomas

    2017-01-01

    For good science teaching, it is necessary to have knowledge of your students' preconceptions. Numerous studies have been conducted about typical ideas that students bring to the science classroom in science education research. Unfortunately the domains of which we know preconceptions are not distributed evenly and there is a lack of studies about…

  18. Cognitive Structure and the Affective Domain: On Knowing and Feeling in Biology.

    ERIC Educational Resources Information Center

    Thompson, Tressa L.; Mintzes, Joel J.

    2002-01-01

    Explores the structural complexity and propositional validity of knowledge about and attitudes toward sharks and the relationships among knowledge and attitudes. Uses concept mapping and a Likert-type attitude inventory for assessment and involves (n=238) participants from 5th, 8th, and 11th grades and college-level and senior citizens. Reports…

  19. Science of Learning Is Learning of Science: Why We Need a Dialectical Approach to Science Education Research

    ERIC Educational Resources Information Center

    Roth, Wolff-Michael

    2012-01-01

    Research on learning science in informal settings and the formal (sometimes experimental) study of learning in classrooms or psychological laboratories tend to be separate domains, even drawing on different theories and methods. These differences make it difficult to compare knowing and learning observed in one paradigm/context with those observed…

  20. 41 CFR 102-173.80 - How will I know if my request is approved?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... appropriate Chief Information Officer (CIO). Once your domain name has been activated, a notice will be sent... your registration information was received. If all of your information is accurate and complete, a second notice will be sent to you within one business day, informing you that all of your information is...

  1. 41 CFR 102-173.80 - How will I know if my request is approved?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... appropriate Chief Information Officer (CIO). Once your domain name has been activated, a notice will be sent... your registration information was received. If all of your information is accurate and complete, a second notice will be sent to you within one business day, informing you that all of your information is...

  2. 41 CFR 102-173.80 - How will I know if my request is approved?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... appropriate Chief Information Officer (CIO). Once your domain name has been activated, a notice will be sent... your registration information was received. If all of your information is accurate and complete, a second notice will be sent to you within one business day, informing you that all of your information is...

  3. 41 CFR 102-173.80 - How will I know if my request is approved?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... appropriate Chief Information Officer (CIO). Once your domain name has been activated, a notice will be sent... your registration information was received. If all of your information is accurate and complete, a second notice will be sent to you within one business day, informing you that all of your information is...

  4. STS Education: International Perspectives on Reform. Ways of Knowing Science Series.

    ERIC Educational Resources Information Center

    Solomon, Joan, Ed.; Aikenhead, Glen, Ed.

    This book is a collection of essays about science-technology-society (STS) education for school science that examines new challenges and new questions in the domain of STS education. The book does not employ a purely academic approach found in science studies, yet almost every chapter shows some reflection on the historical, philosophical, or…

  5. High School Biology Students' Transfer of the Concept of Natural Selection: A Mixed-Methods Approach

    ERIC Educational Resources Information Center

    Pugh, Kevin J.; Koskey, Kristin L. K.; Linnenbrink-Garcia, Lisa

    2014-01-01

    The concept of natural selection serves as a foundation for understanding diverse biological concepts and has broad applicability to other domains. However, we know little about students' abilities to transfer (i.e. apply to a new context or use generatively) this concept and the relation between students' conceptual understanding and transfer…

  6. Relationship among Iranian EFL Students' Foreign Language Anxiety, Foreign Language Listening Anxiety and Their Listening Comprehension

    ERIC Educational Resources Information Center

    Serraj, Samaneh; Noordin, Noreen Bt.

    2013-01-01

    Anxiety is an influential factor in a foreign language learning domain and plays a crucial role in language learners' performance. The following study was conducted to explore the possible impact of Foreign Language Anxiety and Foreign Language Listening Anxiety on language learners' listening skill. The researcher was interested to know the…

  7. Escherichia coli survival in waters: Temperature dependence

    EPA Science Inventory

    Knowing the survival rates of water-borne Escherichia coli is important in evaluating microbial contamination and making appropriate management decisions. E. coli survival rates are dependent on temperature, a dependency that is routinely expressed using an analogue of the Q10 mo...

  8. Optical characterizations of silver nanoprisms embedded in polymer thin film layers

    NASA Astrophysics Data System (ADS)

    Carlberg, Miriam; Pourcin, Florent; Margeat, Olivier; Le Rouzo, Judikael; Berginc, Gerard; Sauvage, Rose-Marie; Ackermann, Jorg; Escoubas, Ludovic

    2017-10-01

    The precise control of light-matter interaction has a wide range of applications and is currently driven by the use of nanoparticles (NPs) by the recent advances in nanotechnology. Taking advantage of the material, size, shape, and surrounding media dependence of the optical properties of plasmonic NPs, thin film layers with tunable optical properties are achieved. The NPs are synthesized by wet chemistry and embedded in a polyvinylpyrrolidone (PVP) polymer thin film layer. Spectrophotometer and spectroscopic ellipsometry measurements are coupled to finite-difference time domain numerical modeling to optically characterize the heterogeneous thin film layers. Silver nanoprisms of 10 to 50 nm edge size exhibit high absorption through the visible wavelength range. A simple optical model composed of a Cauchy law and a Lorentz law, accounting for the optical properties of the nonabsorbing polymer and the absorbing property of the nanoprisms, fits the spectroscopic ellipsometry measurements. Knowing the complex optical indices of heterogeneous thin film layers let us design layers of any optical properties.

  9. Rotation and strain rate of Sulawesi from geometrical velocity field

    NASA Astrophysics Data System (ADS)

    Sarsito, D. A.; Susilo, Simons, W. J. F.; Abidin, H. Z.; Sapiie, B.; Triyoso, W.; Andreas, H.

    2017-07-01

    One of methods that can be used to determine the tectonic deformation status is rate estimation from geometric rotation and strain using quantitative velocity data from GPS observations. Microplate Sulawesi region located in the zone of triple junction (Eurasia, Australia and Philippine Sea Plates) has very complex tectonic and seismic condition, which is why become very important to know its recent deformation status in order to study neo-tectonic and disaster mitigation. Deformation rate quantification is estimated in two parameters: rotation and geodetic strain rate of each GPS station Delaunay triangle in the study area. The analysis in this study is not done using the grids since there is no rheological information at location that can be used as the interpolation-extrapolation constraints. Our analysis reveals that Sulawesi is characterized by rapid rotation in several different domains and compression-strain pattern that varies depending on the type and boundary conditions of microplate. This information is useful for studying neo tectonic deformation status and earthquake disaster mitigation.

  10. Tyrosine Phosphorylation in Toll-Like Receptor Signaling

    PubMed Central

    Chattopadhyay, Saurabh; Sen, Ganes C.

    2014-01-01

    There is a wealth of knowledge about how different Ser/Thr protein kinases participate in Toll-like receptor (TLR) signaling. In many cases, we know the identities of the Ser/Thr residues of various components of the TLR-signaling pathways that are phosphorylated, the functional consequences of the phosphorylation and the responsible protein kinases. In contrast, the analysis of Tyr-phosphorylation of TLRs and their signaling proteins is currently incomplete, because several existing analyses are not systematic or they do not rely on robust experimental data. Nevertheless, it is clear that many TLRs require, for signaling, ligand-dependent phosphorylation of specific Tyr residues in their cytoplasmic domains; the list includes TLR2, TLR3, TLR4, TLR5, TLR8 and TLR9. In this article, we discuss the current status of knowledge on the effect of Tyr-phosphorylation of TLRs and their signaling proteins on their biochemical and biological functions, the possible identities of the relevant protein tyrosine kinases (PTKs) and the nature of regulations of PTK-mediated activation of TLR signaling pathways. PMID:25022196

  11. We Know the Yin—But Where Is the Yang? Toward a Balanced Approach on Common Source Bias in Public Administration Scholarship

    PubMed Central

    George, Bert; Pandey, Sanjay K.

    2017-01-01

    Surveys have long been a dominant instrument for data collection in public administration. However, it has become widely accepted in the last decade that the usage of a self-reported instrument to measure both the independent and dependent variables results in common source bias (CSB). In turn, CSB is argued to inflate correlations between variables, resulting in biased findings. Subsequently, a narrow blinkered approach on the usage of surveys as single data source has emerged. In this article, we argue that this approach has resulted in an unbalanced perspective on CSB. We argue that claims on CSB are exaggerated, draw upon selective evidence, and project what should be tentative inferences as certainty over large domains of inquiry. We also discuss the perceptual nature of some variables and measurement validity concerns in using archival data. In conclusion, we present a flowchart that public administration scholars can use to analyze CSB concerns. PMID:29046599

  12. We Know the Yin-But Where Is the Yang? Toward a Balanced Approach on Common Source Bias in Public Administration Scholarship.

    PubMed

    George, Bert; Pandey, Sanjay K

    2017-06-01

    Surveys have long been a dominant instrument for data collection in public administration. However, it has become widely accepted in the last decade that the usage of a self-reported instrument to measure both the independent and dependent variables results in common source bias (CSB). In turn, CSB is argued to inflate correlations between variables, resulting in biased findings. Subsequently, a narrow blinkered approach on the usage of surveys as single data source has emerged. In this article, we argue that this approach has resulted in an unbalanced perspective on CSB. We argue that claims on CSB are exaggerated, draw upon selective evidence, and project what should be tentative inferences as certainty over large domains of inquiry. We also discuss the perceptual nature of some variables and measurement validity concerns in using archival data. In conclusion, we present a flowchart that public administration scholars can use to analyze CSB concerns.

  13. Consumer awareness, satisfaction, motivation and perceived benefits from using an after-hours GP helpline - A mixed methods study.

    PubMed

    McKenzie, Rosemary

    2016-07-01

    The 'after hours GP helpline' (AGPH) was added to the nurse triage and advice services in Australia in July 2011 with the intention of improving access to general practitioner (GP) advice in the after-hours period. The objectives of the article are to examine consumer awareness, satisfaction, motivation for use and perceived benefits of using the AGPH. A mixed-methods approach used secondary data on population awareness and caller satisfaction, and an in-depth qualitative study of consumers. Awareness of the service was low but satisfaction was high. Users called the service because they did not know what to do, were afraid and/or could not access a health service after hours. Users derived reassurance and increased confidence in managing their health. A conceptual model identifying three experiential domains of dependence, access and health literacy illustrates the relationship between motivation for use and perceived benefits. The model may help to target the service to those who will benefit most.

  14. Membrane Localization is Critical for Activation of the PICK1 BAR Domain

    PubMed Central

    Madsen, Kenneth L.; Eriksen, Jacob; Milan-Lobo, Laura; Han, Daniel S.; Niv, Masha Y.; Ammendrup-Johnsen, Ina; Henriksen, Ulla; Bhatia, Vikram K.; Stamou, Dimitrios; Sitte, Harald H.; McMahon, Harvey T.; Weinstein, Harel; Gether, Ulrik

    2013-01-01

    The PSD-95/Discs-large/ZO-1 homology (PDZ) domain protein, protein interacting with C kinase 1 (PICK1) contains a C-terminal Bin/amphiphysin/Rvs (BAR) domain mediating recognition of curved membranes; however, the molecular mechanisms controlling the activity of this domain are poorly understood. In agreement with negative regulation of the BAR domain by the N-terminal PDZ domain, PICK1 distributed evenly in the cytoplasm, whereas truncation of the PDZ domain caused BAR domain-dependent redistribution to clusters colocalizing with markers of recycling endosomal compartments. A similar clustering was observed both upon truncation of a short putative α-helical segment in the linker between the PDZ and the BAR domains and upon coexpression of PICK1 with a transmembrane PDZ ligand, including the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluR2 subunit, the GluR2 C-terminus transferred to the single transmembrane protein Tac or the dopamine transporter C-terminus transferred to Tac. In contrast, transfer of the GluR2 C-terminus to cyan fluorescent protein, a cytosolic protein, did not elicit BAR domain-dependent clustering. Instead, localizing PICK1 to the membrane by introducing an N-terminal myristoylation site produced BAR domain-dependent, but ligand-independent, PICK1 clustering. The data support that in the absence of PDZ ligand, the PICK1 BAR domain is inhibited through a PDZ domain-dependent and linker-dependent mechanism. Moreover, they suggest that unmasking of the BAR domain’s membrane-binding capacity is not a consequence of ligand binding to the PDZ domain per se but results from, and coincides with, recruitment of PICK1 to a membrane compartment. PMID:18466293

  15. E. coli survival in waters: temperature dependence

    USDA-ARS?s Scientific Manuscript database

    Knowing the survival rates of water-borne Escherichia coli is important for evaluating microbial contamination and in making appropriate management decisions. E. coli survival rates are dependent on temperature; this dependency is routinely expressed using an analog of the Q10 model. This suggestion...

  16. The relative contribution of ferroelastic and ferroelectric texture to the character of a hard PZT ceramic

    NASA Astrophysics Data System (ADS)

    Key, Thomas Stallings

    The development of ferroelastic (90°) texture in addition to ferroelectric (180°) texture is essential to maximizing the piezoelectric properties of many hard tetragonal PZTs, including Piezoetechnologies K270. Ferroelastic texture results from motion of domain walls that is dependent on an individual crystals orientation. Increases in ferroelastic texture raises the maximum net polarization that can be achieved by changes in ferroelectric texture. By studying a hard PZT poled under various temperature conditions, insight was gained into factors affecting the development of ferroelastic texture and how ferroelastic texture contributes to piezoelectric properties. Depinning proved to be the major barrier to preventing ferroelastic domain wall motion where strain based domain interactions and polar defect complexes on the domain level appear to be the dominant factors. Insight into the affect of increased domain texture on the relationship between the increasing magnitude of the remnant polarization (|Pr|) and the magnitude of the coercive field (|EC|) was gained by plotting |EC| vs. |Pr| as a function of poling time for a variety of poling temperatures. At low |Pr| values, |EC| increased rapidly as a function of increases in |Pr| regardless of the poling temperature. This relationship was characteristic of samples poled at 25 °C where increases in ferroelastic texture were largely suppressed. Because increases in polarization were still observable changes in ferroelectric texture most responsible for the polarization increase and like play a strong role in the initial |EC| vs. |Pr| relationship. As |Pr| increased beyond 5 to 8 iC/cm2, the slope of |EC| vs. |Pr| decreased where the reduction in slope increased with poling temperature. This only occurred in samples poled at elevated temperatures where ferroelastic texture was know to ultimately develop during the poling process, leading to the suggestion that the change in slope was due to increases in combined ferroelectric and ferroelastic texture. Lastly, it was found that electric field induced increases in ferroelectric texture by poling at 25 °C occurs while ferroelastic domain wall motion is largely suppressed. This change in ferroelectric texture severely hinders the rate at which subsequent ferroelastic domain wall motion can be induced during poling at elevated temperatures below TC, suggesting that hard PZT samples should be preheated to the poling temperature before poling begins.

  17. Menthol's potential effects on nicotine dependence: a tobacco industry perspective.

    PubMed

    Yerger, Valerie B

    2011-05-01

    To examine what the tobacco industry knows about the potential effects menthol may have on nicotine dependence. A snowball strategy was used to systematically search the Legacy Tobacco Documents Library (http://legacy.library.ucsf.edu/) between 22 February and 29 April, 2010. Of the approximately 11 million documents available in the Legacy Tobacco Documents Library, the iterative searches returned tens of thousands of results. We qualitatively analysed a final collection of 309 documents relevant the effects of menthol on nicotine dependence. The tobacco industry knows that menthol overrides the harsh taste of tobacco and alleviates nicotine's irritating effects, synergistically interacts with nicotine, stimulates the trigeminal nerve to elicit a 'liking' response for a tobacco product, and makes low tar, low nicotine tobacco products more acceptable to smokers than non-mentholated low delivery products. Menthol is not only used in cigarettes as a flavour additive; tobacco companies know that menthol also has sensory effects and interacts with nicotine to produce tobacco products that are easier to smoke, thereby making it easier to expose smokers, especially those who are new and uninitiated, to the addictive power of nicotine.

  18. Can ill-structured problems reveal beliefs about medical knowledge and knowing? A focus-group approach

    PubMed Central

    Roex, Ann; Clarebout, Geraldine; Dory, Valerie; Degryse, Jan

    2009-01-01

    Background Epistemological beliefs (EB) are an individual's cognitions about knowledge and knowing. In several non-medical domains, EB have been found to contribute to the way individuals reason when faced with ill-structured problems (i.e. problems with no clear-cut, right or wrong solutions). Such problems are very common in medical practice. Determining whether EB are also influential in reasoning processes with regard to medical issues to which there is no straightforward answer, could have implications for medical education. This study focused on 2 research questions: 1. Can ill-structured problems be used to elicit general practice trainees' and trainers' EB? and 2. What are the views of general practice trainees and trainers about knowledge and how do they justify knowing? Methods 2 focus groups of trainees (n = 18) were convened on 3 occasions during their 1st year of postgraduate GP training. 2 groups of GP trainers (n = 11) met on one occasion. Based on the methodology of the Reflective Judgement Interview (RJI), participants were asked to comment on 11 ill-structured problems. The sessions were audio taped and transcribed and an adapted version of the RJI scoring rules was used to assess the trainees' reasoning about ill-structured problems. Results Participants made a number of statements illustrating their EB and their importance in clinical reasoning. The level of EB varied widely form one meeting to another and depending on the problem addressed. Overall, the EB expressed by trainees did not differ from those of trainers except on a particular ill-structured problem regarding shoulder pain. Conclusion The use of focus groups has entailed some difficulties in the interpretation of the results, but a number of preliminary conclusions can be drawn. Ill-structured medical problems can be used to elicit EB. Most trainees and trainers displayed pre-reflective and quasi-reflective EB. The way trainees and doctors view and justify knowledge are likely to be involved in medical reasoning processes. PMID:19775425

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

    PubMed

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

    2015-05-01

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

  20. Functional domains of plant chimeric calcium/calmodulin-dependent protein kinase: regulation by autoinhibitory and visinin-like domains

    NASA Technical Reports Server (NTRS)

    Ramachandiran, S.; Takezawa, D.; Wang, W.; Poovaiah, B. W.

    1997-01-01

    A novel calcium-binding calcium/calmodulin-dependent protein kinase (CCaMK) with a catalytic domain, calmodulin-binding domain, and a neural visinin-like domain was cloned and characterized from plants [Patil et al., (1995) Proc. Natl. Acad. Sci. USA 92, 4797-4801; Takezawa et al. (1996) J. Biol. Chem. 271, 8126-8132]. The mechanisms of CCaMK activation by calcium and calcium/calmodulin were investigated using various deletion mutants. The use of deletion mutants of CCaMK lacking either one, two, or all three calcium-binding EF hands indicated that all three calcium-binding sites in the visinin-like domain were crucial for the full calcium/calmodulin-dependent kinase activity. As each calcium-binding EF hand was deleted, there was a gradual reduction in calcium/calmodulin-dependent kinase activity from 100 to 4%. Another mutant (amino acids 1-322) which lacks both the visinin-like domain containing three EF hands and the calmodulin-binding domain was constitutively active, indicating the presence of an autoinhibitory domain around the calmodulin-binding domain. By using various synthetic peptides and the constitutively active mutant, we have shown that CCaMK contains an autoinhibitory domain within the residues 322-340 which overlaps its calmodulin-binding domain. Kinetic studies with both ATP and the GS peptide substrate suggest that the autoinhibitory domain of CCaMK interacts only with the peptide substrate binding motif of the catalytic domain, but not with the ATP-binding motif.

  1. Creative Expression as a Way of Knowing in Diabetes Adult Health Education: An Action Research Study

    ERIC Educational Resources Information Center

    Stuckey, Heather L.

    2009-01-01

    This action research study explores the meaning-making process using forms of creative expression for eight women with insulin-dependent diabetes. The study is theoretically informed by arts-based ways of knowing and aspects of feminist poststructuralism, and explains the process of creativity used in the action research process. The findings…

  2. Developing expectations regarding the boundaries of expertise.

    PubMed

    Landrum, Asheley R; Mills, Candice M

    2015-01-01

    Three experiments examined elementary school-aged children's and adults' expectations regarding what specialists (i.e., those with narrow domains of expertise) and generalists (i.e., those with broad domains of expertise) are likely to know. Experiment 1 demonstrated developmental differences in the ability to differentiate between generalists and specialists, with younger children believing generalists have more specific trivia knowledge than older children and adults believed. Experiment 2 demonstrated that children and adults expected generalists to have more underlying principles knowledge than specific trivia knowledge about unfamiliar animals. However, they believed that generalists would have more of both types of knowledge than themselves. Finally, Experiment 3 demonstrated that children and adults recognized that underlying principles knowledge can be generalized between topics closely related to the specialists' domains of expertise. However, they did not recognize when this knowledge was generalizable to topics slightly less related, expecting generalists to know only as much as they would. Importantly, this work contributes to the literature by showing how much of and what kinds of knowledge different types of experts are expected to have. In sum, this work provides insight into some of the ways children's notions of expertise change over development. The current research demonstrates that between the ages of 5 and 10, children are developing the ability to recognize how experts' knowledge is likely to be limited. That said, even older children at times struggle to determine the breadth of an experts' knowledge. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Evolutionary analysis of the TPP-dependent enzyme family.

    PubMed

    Costelloe, Seán J; Ward, John M; Dalby, Paul A

    2008-01-01

    The evolutionary relationships of the thiamine pyrophosphate (TPP)-dependent family of enzymes was investigated by generation of a neighbor joining phylogenetic tree using sequences from the conserved pyrophosphate (PP) and pyrimidine (Pyr) binding domains of 17 TPP-dependent enzymes. This represents the most comprehensive analysis of TPP-dependent enzyme evolution to date. The phylogeny was shown to be robust by comparison with maximum likelihood trees generated for each individual enzyme and also broadly confirms the evolutionary history proposed recently from structural comparisons alone (Duggleby 2006). The phylogeny is most parsimonious with the TPP enzymes having arisen from a homotetramer which subsequently diverged into an alpha(2)beta(2) heterotetramer. The relationship between the PP- and Pyr-domains and the recruitment of additional protein domains was examined using the transketolase C-terminal (TKC)-domain as an example. This domain has been recruited by several members of the family and yet forms no part of the active site and has unknown function. Removal of the TKC-domain was found to increase activity toward beta-hydroxypyruvate and glycolaldehyde. Further truncations of the Pyr-domain yielded several variants with retained activity. This suggests that the influence of TKC-domain recruitment on the evolution of the mechanism and specificity of transketolase (TK) has been minor, and that the smallest functioning unit of TK comprises the PP- and Pyr-domains, whose evolutionary histories extend to all TPP-dependent enzymes.

  4. Parents' Emotion-Related Beliefs, Behaviours, and Skills Predict Children's Recognition of Emotion

    ERIC Educational Resources Information Center

    Castro, Vanessa L.; Halberstadt, Amy G.; Lozada, Fantasy T.; Craig, Ashley B.

    2015-01-01

    Children who are able to recognize others' emotions are successful in a variety of socioemotional domains, yet we know little about how school-aged children's abilities develop, particularly in the family context. We hypothesized that children develop emotion recognition skill as a function of parents' own emotion-related beliefs,…

  5. "Every Child Ready": Exposure to a Comprehensive Instructional Model Improves Students' Growth Trajectories in Multiple Early Learning Domains

    ERIC Educational Resources Information Center

    Carlson, Abby G.; Curby, Timothy W.; Brown, Chavaughn A.; Truong, Felicia R.

    2017-01-01

    The current study investigates the impact of Every Child Ready (ECR), a comprehensive instructional model that includes: "What to teach, how to teach and how to know instruction is effective." The ECR instructional model is designed to provide high quality instruction to children via a play-based, thematic curriculum. Participants…

  6. Impact of Different Levels of Epistemic Beliefs on Learning Processes and Outcomes in Vocational Education and Training

    ERIC Educational Resources Information Center

    Berding, Florian; Rolf-Wittlake, Katharina; Buschenlange, Janes

    2017-01-01

    Epistemic beliefs are individuals' beliefs about knowledge and knowing. Modelling them is currently based on two central assumptions. First, epistemic beliefs are conceptualized as a multi-level construct, i.e. they exist on a general, academic, domain-specific and/or topic-specific level. Second, research assumes that their more concrete levels…

  7. Supporting Youth Transitioning out of Foster Care. Issue Brief 3: Employment Programs. OPRE Report No. 2014-70

    ERIC Educational Resources Information Center

    Edelstein, Sara; Lowenstein, Christopher

    2014-01-01

    This issue brief is one of three that focus on programs providing services to youth transitioning out of foster care in three common service domains: education, employment, and financial literacy and asset building. This brief highlights why employment services are important to youth currently or formerly in foster care, what we know about the…

  8. Knowing and Learning about Science in Primary School "Communities of Science Practice": The Views of Participating Scientists in the "MyScience" Initiative

    ERIC Educational Resources Information Center

    Forbes, Anne; Skamp, Keith

    2013-01-01

    "MyScience" is a primary science education initiative in which being in a community of practice is integral to the learning process. One component of this initiative involves professional scientists interacting with primary school communities which are navigating their way towards sustainable "communities of practice" around the "domain" of…

  9. "You Know Spanish, Right?": Language for Specific Purposes and the Challenge of Teaching Content Areas and Lexical Domain

    ERIC Educational Resources Information Center

    Jackson, Douglas A.; Polchow, Shannon M.

    2015-01-01

    In a typically monolingual state, those students who do possess a second language are poised to better integrate themselves into the international business community, yet, possessing (for example) a Spanish degree does not indicate proficiency. Unless students have been exposed to a variety of subjects relating to law, health care, business, and…

  10. The Art of Teaching Children the Arts: Music, Dance and Poetry with Children Aged 2-8 Years Old

    ERIC Educational Resources Information Center

    Samuelsson, Ingrid Pramling; Carlsson, Maj Asplund; Olsson, Bengt; Pramling, Niklas; Wallerstedt, Cecilia

    2009-01-01

    In this article, the theoretical framework of developmental pedagogy is presented as a tool in studying and developing children's knowing within the arts. The domains of art focused on are music, poetry and dance/aesthetic movement. Through empirical examples from a large-scale research project, we illustrate the tools of developmental pedagogy…

  11. Third graders' understanding of core political concepts (law, nation-state, government) before and after teaching.

    PubMed

    Berti, A E; Andriolo, A

    2001-11-01

    A curriculum of about 22 hr distributed over 3 months on some core political notions (law, the main Italian political offices, the state) was implemented in an Italian 3rd-grade class of 23 children. Another class of 20 children formed the comparison group. The workings of the executive system were exemplified by explaining the running of the school (which in Italy is state-run). Children's learning and retention of these notions were tested twice, 1 month and 10 months after the end of the curriculum. At pre-test, before implementation of the curriculum, the majority of the children did not have a concept of the political domain: They did not know of parliament and government, hardly distinguished between the law and other types of rules, and did not know that teachers, policemen, and judges are public servants. At post- and delayed post-test, most of the children in the experimental group had mastered the concepts, performing significantly better than the comparison group. Thus, the development of political understanding appears to be due to the acquisition of relevant domain-specific knowledge rather than the emergence of across-the-board logic ability.

  12. Plant chimeric Ca2+/Calmodulin-dependent protein kinase. Role of the neural visinin-like domain in regulating autophosphorylation and calmodulin affinity

    NASA Technical Reports Server (NTRS)

    Sathyanarayanan, P. V.; Cremo, C. R.; Poovaiah, B. W.

    2000-01-01

    Chimeric Ca(2+)/calmodulin-dependent protein kinase (CCaMK) is characterized by a serine-threonine kinase domain, an autoinhibitory domain, a calmodulin-binding domain and a neural visinin-like domain with three EF-hands. The neural visinin-like Ca(2+)-binding domain at the C-terminal end of the CaM-binding domain makes CCaMK unique among all the known calmodulin-dependent kinases. Biological functions of the plant visinin-like proteins or visinin-like domains in plant proteins are not well known. Using EF-hand deletions in the visinin-like domain, we found that the visinin-like domain regulated Ca(2+)-stimulated autophosphorylation of CCaMK. To investigate the effects of Ca(2+)-stimulated autophosphorylation on the interaction with calmodulin, the equilibrium binding constants of CCaMK were measured by fluorescence emission anisotropy using dansylated calmodulin. Binding was 8-fold tighter after Ca(2+)-stimulated autophosphorylation. This shift in affinity did not occur in CCaMK deletion mutants lacking Ca(2+)-stimulated autophosphorylation. A variable calmodulin affinity regulated by Ca(2+)-stimulated autophosphorylation mediated through the visinin-like domain is a new regulatory mechanism for CCaMK activation and calmodulin-dependent protein kinases. Our experiments demonstrate the existence of two functional molecular switches in a protein kinase regulating the kinase activity, namely a visinin-like domain acting as a Ca(2+)-triggered switch and a CaM-binding domain acting as an autophosphorylation-triggered molecular switch.

  13. Rethinking Familiarity: Remember/Know Judgments in Free Recall

    PubMed Central

    Mickes, Laura; Seale-Carlisle, Travis M.; Wixted, John T.

    2013-01-01

    Although frequently used with recognition, a few studies have used the Remember/Know procedure with free recall. In each case, participants gave Know judgments to a significant number of recalled items (items that were presumably not remembered on the basis of familiarity). What do these Know judgments mean? We investigated this issue using a source memory/free-recall procedure. For each word that was recalled, participants were asked to (a) make a confidence rating on a 5-point scale, (b) make a Remember/Know judgment, and (c) recollect a source detail. The large majority of both Remember judgments and Know judgments were made with high confidence and high accuracy, but source memory was nevertheless higher for Remember judgments than for Know judgments. These source memory results correspond to what is found using recognition, and they raise the possibility that Know judgments in free recall identify the cue-dependent retrieval of item-only information from an episodic memory search set. In agreement with this idea, we also found that the temporal dynamics of free recall were similar for high-confidence Remember and high-confidence Know judgments (as if both judgments reflected retrieval from the same search set). If Know judgments in free recall do in fact reflect the episodic retrieval of item-only information, it seems reasonable to suppose that the same might be true of high-confidence Know judgments in recognition. If so, then a longstanding debate about the role of the hippocampus in recollection and familiarity may have a natural resolution. PMID:23637470

  14. Cross-domain question classification in community question answering via kernel mapping

    NASA Astrophysics Data System (ADS)

    Su, Lei; Hu, Zuoliang; Yang, Bin; Li, Yiyang; Chen, Jun

    2015-10-01

    An increasingly popular method for retrieving information is via the community question answering (CQA) systems such as Yahoo! Answers and Baidu Knows. In CQA, question classification plays an important role to find the answers. However, the labeled training examples for statistical question classifier are fairly expensive to obtain, as they require the experienced human efforts. Meanwhile, unlabeled data are readily available. This paper employs the method of domain adaptation via kernel mapping to solve this problem. In detail, the kernel approach is utilized to map the target-domain data and the source-domain data into a common space, where the question classifiers are trained under the closer conditional probabilities. The kernel mapping function is constructed by domain knowledge. Therefore, domain knowledge could be transferred from the labeled examples in the source domain to the unlabeled ones in the targeted domain. The statistical training model can be improved by using a large number of unlabeled data. Meanwhile, the Hadoop Platform is used to construct the mapping mechanism to reduce the time complexity. Map/Reduce enable kernel mapping for domain adaptation in parallel in the Hadoop Platform. Experimental results show that the accuracy of question classification could be improved by the method of kernel mapping. Furthermore, the parallel method in the Hadoop Platform could effective schedule the computing resources to reduce the running time.

  15. Metamemory in a Familiar Place: The Effects of Environmental Context on Feeling of Knowing

    ERIC Educational Resources Information Center

    Hanczakowski, Maciej; Zawadzka, Katarzyna; Collie, Harriet; Macken, Bill

    2017-01-01

    Feeling-of-knowing (FOK) judgments are judgments of future recognizability of currently inaccessible information. They are known to depend both on the access to partial information about a target of retrieval and on the familiarity of the cue that is used as a memory probe. In the present study we assessed whether FOK judgments could also be…

  16. Knowing Me, Knowing You: Professional Development for Support Staff

    ERIC Educational Resources Information Center

    Coulbeck, Joy

    2009-01-01

    Meeting the challenges of delivering a 21st-century curriculum and a world-class quality education ultimately depends on the willingness of the staff on the ground to give 100% effort to their jobs. Although many people in schools work very hard, some staff members are way down on the scale with regard to performance. All too often, a significant…

  17. Practical benefits of knowing the enemy: Modern molecular tools for diagnosing the etiology of bacterial diseases and understanding the taxonomy and diversity of plant pathogenic bacteria

    USDA-ARS?s Scientific Manuscript database

    Knowing the identity of bacterial plant pathogens is essential to strategic and sustainable disease management. However, such identifications are linked to bacterial taxonomy, a complicated and changing discipline that depends on methods and information that often are not used by those who are diagn...

  18. Students' Conscious Unknowns about Artefacts and Natural Objects

    ERIC Educational Resources Information Center

    Vaz-Rebelo, Piedade; Fernandes, Paula; Morgado, Julia; Monteiro, António; Otero, José

    2016-01-01

    This study attempts to characterise what 7th- and 12th-grade students believe they do not know about artefacts and natural objects, as well as the dependence of what is unknown on a knowledge of these objects. The students were asked to make explicit through questioning what they did not know about a sample of objects. The unknowns generated were…

  19. Defense Small Business Innovation Research Program (SBIR) Abstracts of Phase 1 Awards 1983.

    DTIC Science & Technology

    1984-04-06

    STRATEGY, THE INTERPLAY BETWEEN ELECTROMAGNETIC EMISSION CON- TROL AND FLEET OPERATION. THE TECHNICAL APPROACH IS BASED ON AN ANALYSIS OF EMCON...THEM AND A BOTTOM UP APPROACH . THE REQUIREMENTS AND ARCHITECTURAL ASPECTS WILL BE EXPLORED FROM THE MORE ENCOMPASSING PERSPECTIVE OF THE TOTAL...AN AI APPROACH TO INFORMATION FUSION INCLUDING KNOW- LEDGE ORGANIZATION, HYPOTHESIS REPRESENTATIVES, DOMAIN KNOWLEDGE RE- PRESENTATION, HYPOTHESIS

  20. Report of the Advisory Panel to the Mathematical and Information Science Directorate

    DTIC Science & Technology

    1988-04-01

    how to program S computers so that...Engineering, to expand the domain of behaviors we know how to program computers to perform to include more behaviors that previously only humans could do...technology? It is not easy to make clear the difference between making an advance in discovering how to program a behavior that no one knew how to program

  1. Health Sensitivity: Age Differences in the Within-Person Coupling of Individuals' Physical Health and Well-Being

    ERIC Educational Resources Information Center

    Schöllgen, Ina; Morack, Jennifer; Infurna, Frank J.; Ram, Nilam; Gerstorf, Denis

    2016-01-01

    Well-being and physical health are central indicators of quality of life in old age. Research from a between-person difference perspective finds that people in better health than their peers also report higher well-being than their peers. However, we know very little about whether changes in one domain are accompanied by changes in the other…

  2. Considering IIOT and security for the DoD

    NASA Astrophysics Data System (ADS)

    Klawon, Kevin; Gold, Josh; Bachman, Kristen; Landoll, Darren

    2016-05-01

    The Internet of Things (IoT) has come of age and domestic and industrial devices are all "smart". But how can they be universally classified and queried? How do we know that the underlying architecture is secure enough to deploy on a defense network? By leverage existing platforms designed for interoperability, extensibility, and security that can manage data across multiple domains and runs on any platform.

  3. Case for Building Informal Ontology of a Subject Matter at School Level Science Education with Community Collaboration

    ERIC Educational Resources Information Center

    Datt, Sachin

    2015-01-01

    School science textbooks are an amalgamation of concepts collected from different fields of Science like Physics, Chemistry and Biology. The actual number of concepts in the different domains of science are enormous. Educationists have to make a decision of choosing some concept that they think are necessary for students to know at a certain age.…

  4. The Future Is Bright: How Can We Optimize Online Counseling, and How Can We Know Whether We Have Done So?

    ERIC Educational Resources Information Center

    Caspar, Franz; Berger, Thomas

    2005-01-01

    This article analyzes three original articles that include a wealth of information and ideas stimulating even for readers familiar with the domain as a springboard for further discussion. The areas covered include aspects related to the field's technical possibilities and problems in general and the use of online therapy for counseling …

  5. Promoting Motivation through Mode of Instruction: The Relationship between Use of Affective Teaching Techniques and Motivation to Learn Science

    ERIC Educational Resources Information Center

    Sanchez Rivera, Yamil

    2010-01-01

    The purpose of this study is to add to what we know about the affective domain and to create a valid instrument for future studies. The Motivation to Learn Science (MLS) Inventory is based on Krathwohl's Taxonomy of Affective Behaviors (Krathwohl et. al., 1964). The results of the Exploratory Factor Analysis (EFA) and Confirmatory Factor…

  6. Impaired Performance on See-Know Tasks amongst Children with Autism: Evidence of Specific Difficulties with Theory of Mind or Domain-General Task Factors?

    ERIC Educational Resources Information Center

    Lind, Sophie E.; Bowler, Dermot M.

    2010-01-01

    It is widely assumed that children with autism have a diminished understanding of the perception-knowledge relationship, as a specific manifestation of a theory of mind (ToM) impairment. However, such a conclusion may not be justified on the basis of previous studies, which have suffered from significant methodological weaknesses. The current…

  7. Field-Polarity-Dependent Domain Growth in Epitaxial BaTiO 3 Films

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

    Roth, Robert; Guo, Er-Jia; Rafique, Mohsin

    The growth of circular tip-induced domains has been studied in epitaxial BaTiO 3 (BTO) films as a function of writing voltage and time using piezoresponse force microscopy (PFM). While abundant for Pb(Zr,Ti)O 3 (PZT) films, such studies are rare for BTO. Strong relaxation of written domains is observed in the form of reduction of the PFM amplitude inside the area of written domains which occurs additionally to a decrease of the domain radius. The domain wall velocity observed for negative tip voltage is systematically smaller than that for positive tip voltage. Based on maps of the positive and negative switchingmore » fields, the effective driving field for both polarities has been estimated. The polarity-dependent effective field cannot account for the different velocities, indicating a polarity-dependent mobility of the domain walls.« less

  8. Field-Polarity-Dependent Domain Growth in Epitaxial BaTiO 3 Films

    DOE PAGES

    Roth, Robert; Guo, Er-Jia; Rafique, Mohsin; ...

    2018-03-23

    The growth of circular tip-induced domains has been studied in epitaxial BaTiO 3 (BTO) films as a function of writing voltage and time using piezoresponse force microscopy (PFM). While abundant for Pb(Zr,Ti)O 3 (PZT) films, such studies are rare for BTO. Strong relaxation of written domains is observed in the form of reduction of the PFM amplitude inside the area of written domains which occurs additionally to a decrease of the domain radius. The domain wall velocity observed for negative tip voltage is systematically smaller than that for positive tip voltage. Based on maps of the positive and negative switchingmore » fields, the effective driving field for both polarities has been estimated. The polarity-dependent effective field cannot account for the different velocities, indicating a polarity-dependent mobility of the domain walls.« less

  9. Menthol's potential effects on nicotine dependence: a tobacco industry perspective

    PubMed Central

    2011-01-01

    Objective To examine what the tobacco industry knows about the potential effects menthol may have on nicotine dependence. Methods A snowball strategy was used to systematically search the Legacy Tobacco Documents Library (http://legacy.library.ucsf.edu/) between 22 February and 29 April, 2010. Of the approximately 11 million documents available in the Legacy Tobacco Documents Library, the iterative searches returned tens of thousands of results. We qualitatively analysed a final collection of 309 documents relevant the effects of menthol on nicotine dependence. Results The tobacco industry knows that menthol overrides the harsh taste of tobacco and alleviates nicotine's irritating effects, synergistically interacts with nicotine, stimulates the trigeminal nerve to elicit a ‘liking’ response for a tobacco product, and makes low tar, low nicotine tobacco products more acceptable to smokers than non-mentholated low delivery products. Conclusion Menthol is not only used in cigarettes as a flavour additive; tobacco companies know that menthol also has sensory effects and interacts with nicotine to produce tobacco products that are easier to smoke, thereby making it easier to expose smokers, especially those who are new and uninitiated, to the addictive power of nicotine. PMID:21504929

  10. Toward a domain-specific approach to the study of parental psychological control: distinguishing between dependency-oriented and achievement-oriented psychological control.

    PubMed

    Soenens, Bart; Vansteenkiste, Maarten; Luyten, Patrick

    2010-02-01

    Theory and research suggest that psychologically controlling parenting can be driven by parental concerns in two different domains, that is, interpersonal closeness and achievement. Three studies addressing this hypothesis are presented. Study 1 provides evidence for the validity of the Dependency-Oriented and Achievement-Oriented Psychological Control Scale (DAPCS), a new measure assessing psychological control in these two domains. Study 2 showed that dependency-oriented and achievement-oriented psychological control were related in expected ways to parental separation anxiety and perfectionism in a sample of mothers and fathers. Finally, Study 3 showed that dependency-oriented and achievement-oriented psychological control were differentially related to middle adolescent dependency and self-criticism and that these personality features act as specific intervening variables between the domain-specific expressions of psychological control and depressive symptoms. It is argued that the distinction between two domain-specific expressions of psychological control may allow for a more intricate analysis of the processes involved in intrusive parenting.

  11. On the dependence of the domain of values of functionals of hypersonic aerodynamics on controls

    NASA Astrophysics Data System (ADS)

    Bilchenko, Grigory; Bilchenko, Nataly

    2018-05-01

    The properties of mathematical model of control of heat and mass transfer in laminar boundary layer on permeable cylindrical and spherical surfaces of the hypersonic aircraft are considered. Dependences of hypersonic aerodynamics functionals (the total heat flow and the total Newton friction force) on controls (the blowing into boundary layer, the temperature factor, the magnetic field) are investigated. The domains of allowed values of functionals of hypersonic aerodynamics are obtained. The results of the computational experiments are presented: the dependences of total heat flow on controls; the dependences of total Newton friction force on controls; the mutual dependences of functionals (as the domains of allowed values "Heat and Friction"); the dependences of blowing system power on controls. The influences of magnetic field and dissociation on the domain of "Heat and Friction" allowed values are studied. It is proved that for any fixed constant value of magnetic field the blowing system power is a symmetric function of constant dimensionless controls (the blowing into boundary layer and the temperature factor). It is shown that the obtained domain of allowed values of functionals of hypersonic aerodynamics depending on permissible range of controls may be used in engineering.

  12. Applicability of the lattice Boltzmann method to determine the ohmic resistance in equivalent resistor connections

    NASA Astrophysics Data System (ADS)

    Espinoza-Andaluz, Mayken; Barzola, Julio; Guarochico-Moreira, Víctor H.; Andersson, Martin

    2017-12-01

    Knowing the ohmic resistance in the materials allow to know in advance its electrical behavior when a potential difference is applied, and therefore the prediction of the electrical performance can be achieved in a most certain manner. Although the Lattice Boltzmann method (LBM) has been applied to solve several physical phenomena in complex geometries, it has only been used to describe the fluid phase, but applicability studies of LBM on the solid-electric-conducting material have not been carried out yet. The purpose of this paper is to demonstrate the accuracy of calculating the equivalent resistor connections using LBM. Several series and parallel resistor connections are effected. All the computations are carried out with 3D models, and the domain materials are designed by the authors.

  13. Psychosocial determinants and outcomes of chemotherapy in older women with breast cancer: what do we know? What do we need to know?

    PubMed

    Tallarico, Michelle; Figueiredo, Melissa; Goodman, Michelle; Kreling, Barbara; Mandelblatt, Jeanne

    2005-01-01

    With the aging of the U.S. population and rising breast cancer incidence with advancing age, the absolute number of women aged 65 years and older diagnosed with and surviving breast cancer will dramatically increase over the coming decades. Despite this demographic imperative, we know little about the impact of adjuvant therapies in this age group. We synthesized data to describe key findings and gaps in knowledge about the outcomes of adjuvant breast cancer treatment in women aged 65 years and and older ("older women"). We reviewed research published between 1995 and June 2005 on breast cancer outcomes among older women treated with adjuvant therapy for breast cancer. Outcomes included communication, emotional distress, satisfaction, and multiple quality-of-life domains. Only 16 articles focused exclusively on older women and chemotherapy; and only one included a large sample of older women (N = 1755). Most common domains included comorbidities, symptoms, and survival. Of the 13 clinical trials and three observational studies we reviewed, only one clinical trial measured quality of life and psychological factors such as coping. None of the studies examined patient preferences or patient-physician communication (processes of care) in older women. Few studies have been designed to specifically evaluate adjuvant therapy processes and outcomes among older women, especially interactions between treatment and comorbidity, and the impact of the processes of care on outcomes. In addition, only narrow segments of the older population with breast cancer (e.g., well-educated, nonminority women) have been included in trials to date. Thus, at present we do not have sufficient data to assist physicians and their older patients in developing adjuvant treatment decisions and plans tailored to older women's needs, preferences, and concerns.

  14. Intelligent systems for human resources.

    PubMed

    Kline, K B

    1988-11-01

    An intelligent system contains knowledge about some domain; it has sophisticated decision-making processes and the ability to explain its actions. The most important aspect of an intelligent system is its ability to effectively interact with humans to teach or assist complex information processing. Two intelligent systems are Intelligent Tutoring Systems (ITs) and Expert Systems. The ITSs provide instruction to a student similar to a human tutor. The ITSs capture individual performance and tutor deficiencies. These systems consist of an expert module, which contains the knowledge or material to be taught; the student module, which contains a representation of the knowledge the student knows and does not know about the domain; and the instructional or teaching module, which selects specific knowledge to teach, the instructional strategy, and provides assistance to the student to tutor deficiencies. Expert systems contain an expert's knowledge about some domain and perform specialized tasks or aid a novice in the performance of certain tasks. The most important part of an expert system is the knowledge base. This knowledge base contains all the specialized and technical knowledge an expert possesses. For an expert system to interact effectively with humans, it must have the ability to explain its actions. Use of intelligent systems can have a profound effect on human resources. The ITSs can provide better training by tutoring on an individual basis, and the expert systems can make better use of human resources through job aiding and performing complex tasks. With increasing training requirements and "doing more with less," intelligent systems can have a positive effect on human resources.

  15. Magnetization reversal in ferromagnetic spirals via domain wall motion

    NASA Astrophysics Data System (ADS)

    Schumm, Ryan D.; Kunz, Andrew

    2016-11-01

    Domain wall dynamics have been investigated in a variety of ferromagnetic nanostructures for potential applications in logic, sensing, and recording. We present a combination of analytic and simulated results describing the reliable field driven motion of a domain wall through the arms of a ferromagnetic spiral nanowire. The spiral geometry is capable of taking advantage of the benefits of both straight and circular wires. Measurements of the in-plane components of the spirals' magnetization can be used to determine the angular location of the domain wall, impacting the magnetoresistive applications dependent on the domain wall location. The spirals' magnetization components are found to depend on the spiral parameters: the initial radius and spacing between spiral arms, along with the domain wall location. The magnetization is independent of the parameters of the rotating field used to move the domain wall, and therefore the model is valid for current induced domain wall motion as well. The speed of the domain wall is found to depend on the frequency of the rotating driving field, and the domain wall speeds can be reliably varied over several orders of magnitude. We further demonstrate a technique capable of injecting multiple domain walls and show the reliable and unidirectional motion of domain walls through the arms of the spiral.

  16. Dual Regulation of a Chimeric Plant Serine/Threonine Kinase by Calcium and Calcium/Calmodulin

    NASA Technical Reports Server (NTRS)

    Takezawa, D.; Ramachandiran, S.; Paranjape, V.; Poovaiah, B. W.

    1996-01-01

    A chimeric Ca(2+)/calmodulin-dependent protein kinase (CCaMK) gene characterized by a catalytic domain, a calmodulin-binding domain, and a neural visinin-like Ca(2+)-binding domain was recently cloned from plants. The Escherichia coli-expressed CCaMK phosphorylates various protein and peptide substrates in a Ca(2+)/calmodulin-dependent manner. The calmodulin-binding region of CCAMK has similarity to the calmodulin-binding region of the alpha-subunit of multifunctional Ca(2+)/calmodulin-dependent protein kinase (CaMKII). CCaMK exhibits basal autophosphorylation at the threonine residue(s) (0.098 mol of P-32/mol) that is stimulated 3.4-fold by Ca(2+) (0.339 mol of P-32/mol), while calmodulin inhibits Ca(2+)-stimulated autophosphorylation to the basal level. A deletion mutant lacking the visinin-like domain did not show Ca(2+)-simulated autophosphorylation activity but retained Ca(2+)/calmodulin-dependent protein kinase activity at a reduced level. Ca(2+)-dependent mobility shift assays using E.coli-expressed protein from residues 358-520 revealed that Ca(2+) binds to the visinin-like domain. Studies with site-directed mutants of the visinin-like domain indicated that EF-hands II and III are crucial for Ca(2+)-induced conformational changes in the visinin-like domain. Autophosphorylation of CCaMK increases Ca(2+)/calmodulin-dependent protein kinase activity by about 5-fold, whereas it did not affect its C(2+)-independent activity. This report provides evidence for the existence of a protein kinase in plants that is modulated by Ca(2+) and Ca(2+)/calmodulin. The presence of a visinin-like Ca(2+)-binding domain in CCaMK adds an additional Ca(2+)-sensing mechanism not previously known to exist in the Ca(2+)/calmodulin-mediated signaling cascade in plants.

  17. Writing My Way to My Future | Poster

    Cancer.gov

    By Nathalie Walker, Guest Writer Editor’s note: This article is the second in a series describing one student’s perspective on her experiences as a Werner H. Kirsten student intern. “The future depends on what you do today.” Those wise words were spoken by Mahatma Gandhi. Before I started my Werner H. Kirsten (WHK) student internship, I did not know what I know now. I only

  18. Integrated Multi-Aperture Sensor and Navigation Fusion

    DTIC Science & Technology

    2010-02-01

    Visio, Springer-Verlag Inc., New York, 2004. [3] R. G. Brown and P. Y. C. Hwang , Introduction to Random Signals and Applied Kalman Filtering, Third...formulate Kalman filter vision/inertial measurement observables for other images without the need to know (or measure) their feature ranges. As compared...Internal Data Fusion Multi-aperture/INS data fusion is formulated in the feature domain using the complementary Kalman filter methodology [3]. In this

  19. The Program Management Challenges of Web 2.0

    DTIC Science & Technology

    2010-06-01

    identifying and keeping abreast of the newly emerging technologies; their fast pace of evolution or modification, changing domain focus areas, their varied...definitive experts. No one knows what the future holds for network-centric materiel development . We are in the early stages of the Information Age and...led to the development and evolution of online Web-based communities and services such as auction houses, knowledge portals, social networking sites

  20. A Meta-Analysis of Self-Regulated Learning in Work-Related Training and Educational Attainment: What We Know and Where We Need to Go

    ERIC Educational Resources Information Center

    Sitzmann, Traci; Ely, Katherine

    2011-01-01

    Researchers have been applying their knowledge of goal-oriented behavior to the self-regulated learning domain for more than 30 years. This review examines the current state of research on self-regulated learning and gaps in the field's understanding of how adults regulate their learning of work-related knowledge and skills. Self-regulation theory…

  1. Domain morphology, boundaries, and topological defects in biophotonic gyroid nanostructures of butterfly wing scales

    PubMed Central

    Singer, Andrej; Boucheron, Leandra; Dietze, Sebastian H.; Jensen, Katharine E.; Vine, David; McNulty, Ian; Dufresne, Eric R.; Prum, Richard O.; Mochrie, Simon G. J.; Shpyrko, Oleg G.

    2016-01-01

    Many organisms in nature have evolved sophisticated cellular mechanisms to produce photonic nanostructures and, in recent years, diverse crystalline symmetries have been identified and related to macroscopic optical properties. However, because we know little about the distributions of domain sizes, the orientations of photonic crystals, and the nature of defects in these structures, we are unable to make the connection between the nanostructure and its development and functionality. We report on nondestructive studies of the morphology of chitinous photonic crystals in butterfly wing scales. Using spatially and angularly resolved x-ray diffraction, we find that the domains are highly oriented with respect to the whole scale, indicating growth from scale boundaries. X-ray coherent diffractive imaging reveals two types of crystalline domain interfaces: abrupt changes between domains emerging from distinct nucleation sites and smooth transitions with edge dislocations presumably resulting from internal stresses during nanostructure development. Our study of the scale structure reveals new aspects of photonic crystal growth in butterfly wings and shows their similarity to block copolymer materials. It opens new avenues to exploration of fundamental processes underlying the growth of biological photonic nanostructures in a variety of species. PMID:27386575

  2. Domain morphology, boundaries, and topological defects in biophotonic gyroid nanostructures of butterfly wing scales.

    PubMed

    Singer, Andrej; Boucheron, Leandra; Dietze, Sebastian H; Jensen, Katharine E; Vine, David; McNulty, Ian; Dufresne, Eric R; Prum, Richard O; Mochrie, Simon G J; Shpyrko, Oleg G

    2016-06-01

    Many organisms in nature have evolved sophisticated cellular mechanisms to produce photonic nanostructures and, in recent years, diverse crystalline symmetries have been identified and related to macroscopic optical properties. However, because we know little about the distributions of domain sizes, the orientations of photonic crystals, and the nature of defects in these structures, we are unable to make the connection between the nanostructure and its development and functionality. We report on nondestructive studies of the morphology of chitinous photonic crystals in butterfly wing scales. Using spatially and angularly resolved x-ray diffraction, we find that the domains are highly oriented with respect to the whole scale, indicating growth from scale boundaries. X-ray coherent diffractive imaging reveals two types of crystalline domain interfaces: abrupt changes between domains emerging from distinct nucleation sites and smooth transitions with edge dislocations presumably resulting from internal stresses during nanostructure development. Our study of the scale structure reveals new aspects of photonic crystal growth in butterfly wings and shows their similarity to block copolymer materials. It opens new avenues to exploration of fundamental processes underlying the growth of biological photonic nanostructures in a variety of species.

  3. Unfolding of a Temperature-Sensitive Domain Controls Voltage-Gated Channel Activation.

    PubMed

    Arrigoni, Cristina; Rohaim, Ahmed; Shaya, David; Findeisen, Felix; Stein, Richard A; Nurva, Shailika Reddy; Mishra, Smriti; Mchaourab, Hassane S; Minor, Daniel L

    2016-02-25

    Voltage-gated ion channels (VGICs) are outfitted with diverse cytoplasmic domains that impact function. To examine how such elements may affect VGIC behavior, we addressed how the bacterial voltage-gated sodium channel (BacNa(V)) C-terminal cytoplasmic domain (CTD) affects function. Our studies show that the BacNa(V) CTD exerts a profound influence on gating through a temperature-dependent unfolding transition in a discrete cytoplasmic domain, the neck domain, proximal to the pore. Structural and functional studies establish that the BacNa(V) CTD comprises a bi-partite four-helix bundle that bears an unusual hydrophilic core whose integrity is central to the unfolding mechanism and that couples directly to the channel activation gate. Together, our findings define a general principle for how the widespread four-helix bundle cytoplasmic domain architecture can control VGIC responses, uncover a mechanism underlying the diverse BacNa(V) voltage dependencies, and demonstrate that a discrete domain can encode the temperature-dependent response of a channel. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Unfolding of a temperature-sensitive domain controls voltage-gated channel activation

    PubMed Central

    Arrigoni, Cristina; Rohaim, Ahmed; Shaya, David; Findeisen, Felix; Stein, Richard A.; Nurva, Shailika Reddy; Mishra, Smriti; Mchaourab, Hassane S.; Minor, Daniel L.

    2016-01-01

    Voltage-gated ion channels (VGICs) are outfitted with diverse cytoplasmic domains that impact function. To examine how such elements may affect VGIC behavior, we addressed how the bacterial voltage-gated sodium channel (BacNaV) C-terminal cytoplasmic domain (CTD) affects function. Our studies show that the BacNaV CTD exerts a profound influence on gating through a temperature-dependent unfolding transition in a discrete cytoplasmic domain, the neck domain, proximal to the pore. Structural and functional studies establish that the BacNaV CTD comprises a bi-partite four-helix bundle that bears an unusual hydrophilic core whose integrity is central to the unfolding mechanism and that couples directly to the channel activation gate. Together, our findings define a general principle for how the widespread four-helix bundle cytoplasmic domain architecture can control VGIC responses, uncover a mechanism underlying the diverse BacNaV voltage dependencies, and demonstrate that a discrete domain can encode the temperature dependent response of a channel. PMID:26919429

  5. An Analysis of Some Variables Affecting the Internet Dependency Level of Turkish Adolescents by Using Decision Tree Methods

    ERIC Educational Resources Information Center

    Kayri, Murat; Gunuc, Selim

    2010-01-01

    Internet dependency is going to expand into social life in wide area whereas it has been accepted as a pathological and psychological disease. Knowing the basic effects of internet dependency is an inevitable approach to use the internet technology healthy. In this study, internet dependency levels of 754 students were examined with the Internet…

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

    PubMed

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

    2013-05-01

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

  7. Modeling of dispersion and nonlinear characteristics of tapered photonic crystal fibers for applications in nonlinear optics

    NASA Astrophysics Data System (ADS)

    Pakarzadeh, H.; Rezaei, S. M.

    2016-01-01

    In this article, we investigate for the first time the dispersion and the nonlinear characteristics of the tapered photonic crystal fibers (PCFs) as a function of length z, via solving the eigenvalue equation of the guided mode using the finite-difference frequency-domain method. Since the structural parameters such as the air-hole diameter and the pitch of the microstructured cladding change along the tapered PCFs, dispersion and nonlinear properties change with the length as well. Therefore, it is important to know the exact behavior of such fiber parameters along z which is necessary for nonlinear optics applications. We simulate the z dependency of the zero-dispersion wavelength, dispersion slope, effective mode area, nonlinear parameter, and the confinement loss along the tapered PCFs and propose useful relations for describing dispersion and nonlinear parameters. The results of this article, which are in a very good agreement with the available experimental data, are important for simulating pulse propagation as well as investigating nonlinear effects such as supercontinuum generation and parametric amplification in tapered PCFs.

  8. Using NIAM to capture time dependencies in a domain of discourse

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

    Becker, S.D.

    1994-07-01

    This paper addresses the issues surrounding the use of NIAM to capture time dependencies in a domain of discourse. The NIAM concepts that support capturing time dependencies are in the event and process portions of the NIAM metamodel, which are the portions most poorly supported by a well-established methodology. This lack of methodological support is a potentially serious handicap in any attempt to apply NIAM to a domain of discourse in which time dependencies are a central issue. However, the capability that NIAM provides for validating and verifying the elementary facts in the domain may reduce the magnitude of themore » event/process-specification task to a level at which it could be effectively handled even without strong methodological support.« less

  9. Quantitative analysis of domain texture in polycrystalline barium titanate by polarized Raman microprobe spectroscopy

    NASA Astrophysics Data System (ADS)

    Sakashita, Tatsuo; Chazono, Hirokazu; Pezzotti, Giuseppe

    2007-12-01

    A quantitative determination of domain distribution in polycrystalline barium titanate (BaTiO3, henceforth BT) ceramics has been pursued with the aid of a microprobe polarized Raman spectrometer. The crystallographic texture and domain orientation distribution of BT ceramics, which switched upon applying stress according to ferroelasticity principles, were determined from the relative intensity of selected phonon modes, taking into consideration a theoretical analysis of the angular dependence of phonon mode intensity for the tetragonal BT phase. Furthermore, the angular dependence of Raman intensity measured in polycrystalline BT depended on the statistical distribution of domain angles in the laser microprobe, which was explicitly taken into account in this work for obtaining a quantitative analysis of domain orientation for in-plane textured BT polycrystalline materials.

  10. Using terahertz time-domain spectroscopical technique to monitor cocrystal formation between piracetam and 2,5-dihydroxybenzoic acid

    NASA Astrophysics Data System (ADS)

    Du, Yong; Xia, Yi; Zhang, Huili; Hong, Zhi

    2013-07-01

    Far-infrared vibrational absorption of cocrystal formation between 2,5-dihydroxybenzoic acid (2,5-DHBA) and piracetam compounds under solvent evaporation and grinding methods have been investigated using terahertz time-domain spectroscopy (THz-TDS) at room temperature. The experimental results show large difference among absorption spectra of the formed cocrystals and the involved individual parent molecules in 0.20-1.50 THz region, which probably originated from the intra-molecular and inter-molecular hydrogen bonds due to the presence of two hydroxyl groups in 2,5-DHBA and amide moieties in piracetam compound. The THz absorption spectra of two formed cocrystals with different methods are almost identical. With grinding method, the reaction process can be monitored directly from both time-domain and frequency-domain spectra using THz-TDS technique. The results indicate that THz-TDS technology can absolutely offer us a high potential method to identify and characterize the formed cocrystals, and also provide the rich information about their reaction dynamic process involving two or more molecular crystals in situ to better know the corresponding reaction mechanism in pharmaceutical fields.

  11. Human I-mfa domain proteins specifically interact with KSHV LANA and affect its regulation of Wnt signaling-dependent transcription

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

    Kusano, Shuichi, E-mail: skusano@m2.kufm.kagoshima-u.ac.jp; Eizuru, Yoshito

    2010-06-04

    Kaposi's sarcoma-associated herpes virus (KSHV)-encoded latency-associated nuclear antigen (LANA) protein has been reported to interact with glycogen synthase kinase 3{beta} (GSK-3{beta}) and to negatively regulate its activity, leading to stimulation of GSK-3{beta}-dependent {beta}-catenin degradation. We show here that the I-mfa domain proteins, HIC (human I-mfa domain-containing protein) and I-mfa (inhibitor of MyoD family a), interacted in vivo with LANA through their C-terminal I-mfa domains. This interaction affected the intracellular localization of HIC, inhibited the LANA-dependent transactivation of a {beta}-catenin-regulated reporter construct, and decreased the level of the LANA.GSK-3{beta} complex. These data reveal for the first time that I-mfa domain proteinsmore » interact with LANA and negatively regulate LANA-mediated activation of Wnt signaling-dependent transcription by inhibiting the formation of the LANA.GSK-3{beta} complex.« less

  12. Oligomerization-Dependent Regulation of Motility and Morphogenesis by the Collagen Xviii Nc1/Endostatin Domain

    PubMed Central

    Kuo, Calvin J.; LaMontagne, Kenneth R.; Garcia-Cardeña, Guillermo; Ackley, Brian D.; Kalman, Daniel; Park, Susan; Christofferson, Rolf; Kamihara, Junne; Ding, Yuan-Hua; Lo, Kin-Ming; Gillies, Stephen; Folkman, Judah; Mulligan, Richard C.; Javaherian, Kashi

    2001-01-01

    Collagen XVIII (c18) is a triple helical endothelial/epithelial basement membrane protein whose noncollagenous (NC)1 region trimerizes a COOH-terminal endostatin (ES) domain conserved in vertebrates, Caenorhabditis elegans and Drosophila. Here, the c18 NC1 domain functioned as a motility-inducing factor regulating the extracellular matrix (ECM)-dependent morphogenesis of endothelial and other cell types. This motogenic activity required ES domain oligomerization, was dependent on rac, cdc42, and mitogen-activated protein kinase, and exhibited functional distinction from the archetypal motogenic scatter factors hepatocyte growth factor and macrophage stimulatory protein. The motility-inducing and mitogen-activated protein kinase–stimulating activities of c18 NC1 were blocked by its physiologic cleavage product ES monomer, consistent with a proteolysis-dependent negative feedback mechanism. These data indicate that the collagen XVIII NC1 region encodes a motogen strictly requiring ES domain oligomerization and suggest a previously unsuspected mechanism for ECM regulation of motility and morphogenesis. PMID:11257123

  13. Familiarity Breeds Attempts: A Critical Review of Dual-Process Theories of Recognition.

    PubMed

    Mandler, George

    2008-09-01

    Recognition memory and recall/recollection are the major divisions of the psychology of human memory. Theories of recognition have shifted from a "strength" approach to a dual-process view, which distinguishes between knowing that one has experienced an object before and knowing what it was. In this article, I discuss the history of this approach and the two processes of familiarity and recollection and locate their origin in pattern matching and organization. I evaluate various theories in terms of their basic requirements and their defining research and propose the extension of the original two process theory to domains such as pictorial recognition. Finally, I present the main phenomena that a dual-process theory of recognition must account for and discuss future needs and directions of research and development. © 2008 Association for Psychological Science.

  14. A development optical course based on optical fiber white light interference

    NASA Astrophysics Data System (ADS)

    Jiang, Haili; Sun, Qiuhua; Zhao, Yancheng; Li, Qingbo

    2017-08-01

    The Michelson interferometer is a very important instrument in optical part for college physics teaching. But most students only know the instrument itself and don't know how to use it in practical engineering problems. A case about optical fiber white light interference based on engineering practice was introduced in the optical teaching of college physics and then designed a development course of university physical optics part. This system based on low-coherence white light interferometric technology can be used to measure distribution strain or temperature. It also could be used in the case of temperature compensation mode.This teaching design can use the knowledge transfer rule to enable students to apply the basic knowledge in the university physics to the new knowledge domain, which can promote the students' ability of using scientific methods to solve complex engineering problems.

  15. Characterization of DNA polymerase X from Thermus thermophilus HB8 reveals the POLXc and PHP domains are both required for 3'-5' exonuclease activity.

    PubMed

    Nakane, Shuhei; Nakagawa, Noriko; Kuramitsu, Seiki; Masui, Ryoji

    2009-04-01

    The X-family DNA polymerases (PolXs) comprise a highly conserved DNA polymerase family found in all kingdoms. Mammalian PolXs are known to be involved in several DNA-processing pathways including repair, but the cellular functions of bacterial PolXs are less known. Many bacterial PolXs have a polymerase and histidinol phosphatase (PHP) domain at their C-termini in addition to a PolX core (POLXc) domain, and possess 3'-5' exonuclease activity. Although both domains are highly conserved in bacteria, their molecular functions, especially for a PHP domain, are unknown. We found Thermus thermophilus HB8 PolX (ttPolX) has Mg(2+)/Mn(2+)-dependent DNA/RNA polymerase, Mn(2+)-dependent 3'-5' exonuclease and DNA-binding activities. We identified the domains of ttPolX by limited proteolysis and characterized their biochemical activities. The POLXc domain was responsible for the polymerase and DNA-binding activities but exonuclease activity was not detected for either domain. However, the POLXc and PHP domains interacted with each other and a mixture of the two domains had Mn(2+)-dependent 3'-5' exonuclease activity. Moreover, site-directed mutagenesis revealed catalytically important residues in the PHP domain for the 3'-5' exonuclease activity. Our findings provide a molecular insight into the functional domain organization of bacterial PolXs, especially the requirement of the PHP domain for 3'-5' exonuclease activity.

  16. Temporal phase mask encrypted optical steganography carried by amplified spontaneous emission noise.

    PubMed

    Wu, Ben; Wang, Zhenxing; Shastri, Bhavin J; Chang, Matthew P; Frost, Nicholas A; Prucnal, Paul R

    2014-01-13

    A temporal phase mask encryption method is proposed and experimentally demonstrated to improve the security of the stealth channel in an optical steganography system. The stealth channel is protected in two levels. In the first level, the data is carried by amplified spontaneous emission (ASE) noise, which cannot be detected in either the time domain or spectral domain. In the second level, even if the eavesdropper suspects the existence of the stealth channel, each data bit is covered by a fast changing phase mask. The phase mask code is always combined with the wide band noise from ASE. Without knowing the right phase mask code to recover the stealth data, the eavesdropper can only receive the noise like signal with randomized phase.

  17. The importance of the criteria of residential buildings from the perspective of future users

    NASA Astrophysics Data System (ADS)

    Sirochmanová, Lenka; Kozlovská, Mária; Bašková, Renáta

    2016-06-01

    The developers need to know what is important to their customers in preparation of new construction of residential buildings. The paper deals with finding the importance of structure, material, cost, time and environmental criteria of residential buildings from the perspective of the future owners. The research methodology that provided the information was questionnaire survey. Research was conducted in two lines. The first line is dedicated to the research of main construction domains of residential building. The second line of the research deals with the specific criteria of main construction domains. The order of importance of the main areas and the specific criteria is determined by analyzing of data through descriptive characteristics: median, modus, variance, average value and by weigh of importance.

  18. Automated Database Schema Design Using Mined Data Dependencies.

    ERIC Educational Resources Information Center

    Wong, S. K. M.; Butz, C. J.; Xiang, Y.

    1998-01-01

    Describes a bottom-up procedure for discovering multivalued dependencies in observed data without knowing a priori the relationships among the attributes. The proposed algorithm is an application of technique designed for learning conditional independencies in probabilistic reasoning; a prototype system for automated database schema design has…

  19. Moiré patterns in doubly differential electron-momentum distributions in atomic ionization by mid-infrared lasers

    NASA Astrophysics Data System (ADS)

    Dran, Martín; Arbó, Diego G.

    2018-05-01

    We analyze the doubly differential electron momentum distribution in above-threshold ionization of atomic hydrogen by a linearly polarized mid-infrared laser pulse. We reproduce side rings in the momentum distribution with forward-backward symmetry previously observed by Lemell et al. [Phys. Rev. A 87, 013421 (2013), 10.1103/PhysRevA.87.013421], whose origin, as far as we know, has not been explained so far. By developing a Fourier theory of moiré patterns, we demonstrate that such structures stem from the interplay between intra- and intercycle interference patterns which work as two separate grids in the two-dimensional momentum domain. We use a three-dimensional (3D) description based on the saddle-point approximation (SPA) to unravel the nature of these structures. When the periods of the two grids (intra- and intercycle) are similar, principal moiré patterns arise symmetrically as concentric rings in the forward and backward directions at high electron kinetic energy. Higher order moiré patterns are observed and characterized when the period of one grid is multiple of the other. We find a scale law for the position (in momentum space) of the center of the moiré rings in the tunneling regime. We verify the SPA predictions by comparison with time-dependent distorted-wave strong-field approximation calculations and the solutions of the full 3D time-dependent Schrödinger equation.

  20. Soil, Water, Plants and Preferred Flow in All Directions: A Biosphere-2 Experiment

    NASA Astrophysics Data System (ADS)

    McDonnell, J.; Evaristo, J. A.; Kim, M.; Van Haren, J. L. M.; Pangle, L. A.; Harman, C. J.; Troch, P. A. A.

    2016-12-01

    Measuring, understanding and predicting preferential flow in the critical zone is impossibly difficult, but we must try. While past work has focused on specific features of preferential flow pathways and model parameterizations, the resultant effect of preferential flow is often difficult to detect because we do not know the boundary conditions of our flow domain. Here we take a holistic view of preferential flow at the ecosystem level. We present new results from the tropical rainforest biome at Biosphere 2. We test the null hypothesis that the ecohydrological system is well mixed and that water forming groundwater recharge and plant transpiration is from a common pool. Our specific research question is what is the nature of preferential flow and partitioning of groundwater recharge, soil water recharge, and transpiration water after rainfall events? We performed a 10-week drought experiment and then added 66 mm of labelled rainfall with 152‰ deuterium (D), distributed over four events (mean 16.5 mm per event). This was followed by a total of 87 mm of rainfall (-60‰ D) distributed over 13 events that were spaced every 2-3 days. Our results show that flow in all ecohydrological domains (soil water, groundwater recharge and plant transpiration) was preferential. With known boundary conditions, we found that groundwater recharge was 3-8 times younger ( 8 days) than transpired water (range 24-64 days). The "age" of transpired water showed strong dependence on species and was intimately linked to driving force (difference between soil matric potential and midday leaf water potential). These results suggest that preferential flow in the critical zone is one whereby transpiration is strongly species-dependent, and groundwater recharge is controlled by inherent subsurface heterogeneity. The marked difference in the ages associated with these two fluxes supports the concept of ecohydrological separation—in this case, in a `time-based' context.

  1. Do Smokers Know What We're Talking about? The Construct Validity of Nicotine Dependence Questionnaire Measures

    ERIC Educational Resources Information Center

    Japuntich, Sandra J.; Piper, Megan E.; Schlam, Tanya R.; Bolt, Daniel M.; Baker, Timothy B.

    2009-01-01

    Few studies have examined whether nicotine dependence self-report questionnaires can predict specific behaviors and symptoms at specific points in time. The present study used data from a randomized clinical trial (N = 608; M. E. Piper et al., 2007) to assess the construct validity of scales and items from 3 nicotine dependence measures: the…

  2. Minimization of Ohmic Losses for Domain Wall Motion in a Ferromagnetic Nanowire

    NASA Astrophysics Data System (ADS)

    Tretiakov, O. A.; Liu, Y.; Abanov, Ar.

    2010-11-01

    We study current-induced domain-wall motion in a narrow ferromagnetic wire. We propose a way to move domain walls with a resonant time-dependent current which dramatically decreases the Ohmic losses in the wire and allows driving of the domain wall with higher speed without burning the wire. For any domain-wall velocity we find the time dependence of the current needed to minimize the Ohmic losses. Below a critical domain-wall velocity specified by the parameters of the wire the minimal Ohmic losses are achieved by dc current. Furthermore, we identify the wire parameters for which the losses reduction from its dc value is the most dramatic.

  3. Immunological and protective effects of Bordetella bronchiseptica subunit vaccines based on the recombinant N-terminal domain of dermonecrotic toxin.

    PubMed

    Wang, Chuanwen; Liu, Liping; Zhang, Zhen; Yan, Zhengui; Yu, Cuilian; Shao, Mingxu; Jiang, Xiaodong; Chi, Shanshan; Wei, Kai; Zhu, Ruiliang

    2015-10-01

    Dermonecrotic toxin (DNT) produced by Bordetella bronchiseptica (B. bronchiseptica) can cause clinical turbinate atrophy in swine and induce dermonecrotic lesions in model mice. We know that the N-terminal of DNT molecule contains the receptor-binding domain, which facilitates binding to the target cells. However, we do not know whether this domain has sufficient immunogenicity to resist B. bronchiseptica damage and thereby to develop a subunit vaccine for the swine industry. In this study, we prokaryotically expressed the recombinant N-terminal of DNT from B. bronchiseptica (named DNT-N) and prepared it for the subunit vaccine to evaluate its immunogenicity. Taishan Pinus massoniana pollen polysaccharide (TPPPS), a known immunomodulator, was used as the adjuvant to examine its immune-conditioning effects. At 49 d after inoculation, 10 mice from each group were challenged with B. bronchiseptica, and another 10 mice were intradermally challenged with native DNT, to examine the protection imparted by the vaccines. The immune parameters (T-lymphocyte counts, cytokine secretions, serum antibody titers, and survival rates) and skin lesions were determined. The results showed that pure DNT-N vaccine significantly induced immune responses and had limited ability to resist the B. bronchiseptica and DNT challenge, whereas the mice administered with TPPPS or Freund's incomplete adjuvant vaccine could induce higher levels of the above immune parameters. Remarkably, the DNT-N vaccine combined with TPPPS adjuvant protected the mice effectively to prevent B. bronchiseptica infection. Our findings indicated that DNT-N has potential for development as an effective subunit vaccine to counteract the damage of B. bronchiseptica infection, especially when used conjointly with TPPPS. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Some Lower Valence Vanadium Fluorides: Their Crystal Distortions, Domain Structures, Modulated Structures, Ferrimagnetism, and Composition Dependence.

    ERIC Educational Resources Information Center

    Hong, Y. S.; And Others

    1980-01-01

    Describes some contemporary concepts unique to the structure of advanced solids, i.e., their crystal distortions, domain structures, modulated structures, ferrimagnetism, and composition dependence. (Author/CS)

  5. ADAM disintegrin-like domain recognition by the lymphocyte integrins α4β1 and α4β7

    PubMed Central

    Bridges, Lance C.; Sheppard, Dean; Bowditch, Ron D.

    2004-01-01

    The ADAM (a disintegrin and metalloprotease) family of proteins possess both proteolytic and adhesive domains. We have established previously that the disintegrin domain of ADAM28, an ADAM expressed by human lymphocytes, is recognized by the integrin α4β1. The present study characterizes the integrin binding properties of the disintegrin-like domains of human ADAM7, ADAM28 and ADAM33 with the integrins α4β1, α4β7 and α9β1. Cell-adhesion assays demonstrated that, similar to ADAM28, the ADAM7 disintegrin domain supported α4β1-dependent Jurkat cell adhesion, whereas the ADAM33 disintegrin domain did not. The lymphocyte integrin α4β7 was also found to recognize both disintegrin domains of ADAM7 and ADAM28, but not of ADAM33. This is the first demonstration that mammalian disintegrins are capable of interacting with α4β7. All three disintegrin domains supported α9β1-dependent cell adhesion. Recognition by both α4β1 and α4β7 of ADAM7 and ADAM28 was activation-dependent, requiring either the presence of Mn2+ or an activating monoclonal antibody for cell attachment. Charge-to-alanine mutagenesis experiments revealed that the same residues within an individual ADAM disintegrin domain function in recognizing multiple integrins. However, the residues within a specific region of each ADAM disintegrin-like domain required for integrin binding were distinct. These results establish that ADAM7 and ADAM28 are recognized by the leucocyte integrins α4β1, α4β7 and α9β1. ADAM33 exclusively supported only α9β1-dependent adhesion. PMID:15504110

  6. Structural basis of redox-dependent substrate binding of protein disulfide isomerase

    PubMed Central

    Yagi-Utsumi, Maho; Satoh, Tadashi; Kato, Koichi

    2015-01-01

    Protein disulfide isomerase (PDI) is a multidomain enzyme, operating as an essential folding catalyst, in which the b′ and a′ domains provide substrate binding sites and undergo an open–closed domain rearrangement depending on the redox states of the a′ domain. Despite the long research history of this enzyme, three-dimensional structural data remain unavailable for its ligand-binding mode. Here we characterize PDI substrate recognition using α-synuclein (αSN) as the model ligand. Our nuclear magnetic resonance (NMR) data revealed that the substrate-binding domains of PDI captured the αSN segment Val37–Val40 only in the oxidized form. Furthermore, we determined the crystal structure of an oxidized form of the b′–a′ domains in complex with an undecapeptide corresponding to this segment. The peptide-binding mode observed in the crystal structure with NMR validation, was characterized by hydrophobic interactions on the b′ domain in an open conformation. Comparison with the previously reported crystal structure indicates that the a′ domain partially masks the binding surface of the b′ domain, causing steric hindrance against the peptide in the reduced form of the b′–a′ domains that exhibits a closed conformation. These findings provide a structural basis for the mechanism underlying the redox-dependent substrate binding of PDI. PMID:26350503

  7. Stewards of Digital Literacies

    ERIC Educational Resources Information Center

    Rheingold, Howard

    2012-01-01

    Participatory culture, in which citizens feel and exercise the agency of being cocreators of their culture and not just passive consumers of culture created by others, depends on widespread literacies of participation. One can't participate without knowing how. And cultural participation depends on a social component that is not easily learned…

  8. Training Social Work Students for Practice with Substance Abusers: An Ecological Approach.

    ERIC Educational Resources Information Center

    Van Wormer, Katherine

    1987-01-01

    The following questions are addressed: Why should general social work students need to know about alcoholism/addiction, chemical dependency? What skills are required for assessment of chemical dependency intervention? How can the social work curriculum provide adequate training for work with substance abusers? (Author/MH)

  9. Characterisation of optical filters for broadband UVA radiometer

    NASA Astrophysics Data System (ADS)

    Alves, Luciana C.; Coelho, Carla T.; Corrêa, Jaqueline S. P. M.; Menegotto, Thiago; Ferreira da Silva, Thiago; Aparecida de Souza, Muriel; Melo da Silva, Elisama; Simões de Lima, Maurício; Dornelles de Alvarenga, Ana Paula

    2016-07-01

    Optical filters were characterized in order to know its suitability for use in broadband UVA radiometer head for spectral irradiance measurements. The spectral transmittance, the angular dependence and the spatial uniformity of the spectral transmittance of the UVA optical filters were investigated. The temperature dependence of the transmittance was also studied.

  10. The confidential enquiry into maternal deaths: its role and importance for pathologists.

    PubMed Central

    Dawson, I

    1988-01-01

    Comparatively few pathologists seem to know of the existence of the confidential enquiry into maternal deaths and fewer still know anything of its aims or its methods of obtaining confidential information. As the success of any such enquiry depends greatly on the accuracy and completeness of necropsy, histological, and other laboratory reports a brief account of the report itself and the role of pathologists in it may not be out of place. PMID:3170768

  11. Altered mechanical properties of titin immunoglobulin domain 27 in the presence of calcium.

    PubMed

    DuVall, Michael M; Gifford, Jessica L; Amrein, Matthias; Herzog, Walter

    2013-04-01

    Titin (connectin) based passive force regulation has been an important physiological mechanism to adjust to varying muscle stretch conditions. Upon stretch, titin behaves as a spring capable of modulating its elastic response in accordance with changes in muscle biochemistry. One such mechanism has been the calcium-dependent stiffening of titin domains that renders the spring inherently more resistant to stretch. This transient titin-calcium interaction may serve a protective function in muscle, which could preclude costly unfolding of select domains when muscles elongate to great lengths. To test this idea, fluorescence spectroscopy was performed revealing a change in the microenvironment of the investigated immunoglobulin domain 27 (I27) of titin with calcium. Additionally, an atomic force microscope was used to evaluate the calcium-dependent regulation of passive force by stretching eight linked titin I27 domains until they unfolded. When stretching in the presence of calcium, the I27 homopolymer chain became stabilized, displaying three novel properties: (1) higher stretching forces were needed to unfold the domains, (2) the stiffness, measured as a persistence length (PL), increased and (3) the peak-to-peak distance between adjacent I27 domains increased. Furthermore, a peak order dependence became apparent for both force and PL, reflecting the importance of characterizing the dynamic unfolding history of a polymer with this approach. Together, this novel titin Ig-calcium interaction may serve to stabilize the I27 domain permitting titin to tune passive force within stretched muscle in a calcium-dependent manner.

  12. Molecular basis of the specific subcellular localization of the C2-like domain of 5-lipoxygenase.

    PubMed

    Kulkarni, Shilpa; Das, Sudipto; Funk, Colin D; Murray, Diana; Cho, Wonhwa

    2002-04-12

    The activation of 5-lipoxygenase (5-LO) involves its calcium-dependent translocation to the nuclear envelope, where it catalyzes the two-step transformation of arachidonic acid into leukotriene A(4), leading to the synthesis of various leukotrienes. To understand the mechanism by which 5-LO is specifically targeted to the nuclear envelope, we studied the membrane binding properties of the amino-terminal domain of 5-LO, which has been proposed to have a C2 domain-like structure. The model building, electrostatic potential calculation, and in vitro membrane binding studies of the isolated C2-like domain of 5-LO and selected mutants show that this Ca(2+)-dependent domain selectively binds zwitterionic phosphatidylcholine, which is conferred by tryptophan residues (Trp(13), Trp(75), and Trp(102)) located in the putative Ca(2+)-binding loops. The spatiotemporal dynamics of the enhanced green fluorescence protein-tagged C2-like domain of 5-LO and mutants in living cells also show that the phosphatidylcholine selectivity of the C2-like domain accounts for the specific targeting of 5-LO to the nuclear envelope. Together, these results show that the C2-like domain of 5-LO is a genuine Ca(2+)-dependent membrane-targeting domain and that the subcellular localization of the domain is governed in large part by its membrane binding properties.

  13. Dependence as a unifying construct in defining Alzheimer’s disease severity

    PubMed Central

    McLaughlin, Trent; Feldman, Howard; Fillit, Howard; Sano, Mary; Schmitt, Frederick; Aisen, Paul; Leibman, Christopher; Mucha, Lisa; Ryan, J. Michael; Sullivan, Sean D.; Spackman, D. Eldon; Neumann, Peter J.; Cohen, Joshua; Stern, Yaakov

    2012-01-01

    This article reviews measures of Alzheimer’s disease (AD) progression in relation to patient dependence and offers a unifying conceptual framework for dependence in AD. Clinicians typically characterize AD by symptomatic impairments in three domains: cognition, function, and behavior. From a patient’s perspective, changes in these domains, individually and in concert, ultimately lead to increased dependence and loss of autonomy. Examples of dependence in AD range from a need for reminders (early AD) to requiring safety supervision and assistance with basic functions (late AD). Published literature has focused on the clinical domains as somewhat separate constructs and has given limited attention to the concept of patient dependence as a descriptor of AD progression. This article presents the concept of dependence on others for care needs as a potential method for translating the effect of changes in cognition, function, and behavior into a more holistic, transparent description of AD progression. PMID:21044778

  14. Dependence as a unifying construct in defining Alzheimer's disease severity.

    PubMed

    McLaughlin, Trent; Feldman, Howard; Fillit, Howard; Sano, Mary; Schmitt, Frederick; Aisen, Paul; Leibman, Christopher; Mucha, Lisa; Ryan, J Michael; Sullivan, Sean D; Spackman, D Eldon; Neumann, Peter J; Cohen, Joshua; Stern, Yaakov

    2010-11-01

    This article reviews measures of Alzheimer's disease (AD) progression in relation to patient dependence and offers a unifying conceptual framework for dependence in AD. Clinicians typically characterize AD by symptomatic impairments in three domains: cognition, function, and behavior. From a patient's perspective, changes in these domains, individually and in concert, ultimately lead to increased dependence and loss of autonomy. Examples of dependence in AD range from a need for reminders (early AD) to requiring safety supervision and assistance with basic functions (late AD). Published literature has focused on the clinical domains as somewhat separate constructs and has given limited attention to the concept of patient dependence as a descriptor of AD progression. This article presents the concept of dependence on others for care needs as a potential method for translating the effect of changes in cognition, function, and behavior into a more holistic, transparent description of AD progression. Copyright © 2010. Published by Elsevier Inc.

  15. Polarity Control and Growth of Lateral Polarity Structures in AlN

    DTIC Science & Technology

    2013-05-10

    domains. Transmission electron microscopy shows mixed edge-screw type dislocations with polarity-dependent dislocation bending. Raman 1. REPORT DATE (DD-MM...polarity-dependent dislocation bending. Raman spectroscopy reveals compressively strained Al-polar and relaxed N-polar domains. The near band edge...dislocation bending. Raman spectroscopy reveals compressively strained Al-polar and relaxed N-polar domains. The near band edge luminescence consists of

  16. Munc13-4 reconstitutes calcium-dependent SNARE-mediated membrane fusion

    PubMed Central

    Boswell, Kristin L.; James, Declan J.; Esquibel, Joseph M.; Bruinsma, Stephen; Shirakawa, Ryutaro; Horiuchi, Hisanori

    2012-01-01

    Munc13-4 is a widely expressed member of the CAPS/Munc13 protein family proposed to function in priming secretory granules for exocytosis. Munc13-4 contains N- and C-terminal C2 domains (C2A and C2B) predicted to bind Ca2+, but Ca2+-dependent regulation of Munc13-4 activity has not been described. The C2 domains bracket a predicted SNARE-binding domain, but whether Munc13-4 interacts with SNARE proteins is unknown. We report that Munc13-4 bound Ca2+ and restored Ca2+-dependent granule exocytosis to permeable cells (platelets, mast, and neuroendocrine cells) dependent on putative Ca2+-binding residues in C2A and C2B. Munc13-4 exhibited Ca2+-stimulated SNARE interactions dependent on C2A and Ca2+-dependent membrane binding dependent on C2B. In an apparent coupling of membrane and SNARE binding, Munc13-4 stimulated SNARE-dependent liposome fusion dependent on putative Ca2+-binding residues in both C2A and C2B domains. Munc13-4 is the first priming factor shown to promote Ca2+-dependent SNARE complex formation and SNARE-mediated liposome fusion. These properties of Munc13-4 suggest its function as a Ca2+ sensor at rate-limiting priming steps in granule exocytosis. PMID:22508512

  17. Munc13-4 reconstitutes calcium-dependent SNARE-mediated membrane fusion.

    PubMed

    Boswell, Kristin L; James, Declan J; Esquibel, Joseph M; Bruinsma, Stephen; Shirakawa, Ryutaro; Horiuchi, Hisanori; Martin, Thomas F J

    2012-04-16

    Munc13-4 is a widely expressed member of the CAPS/Munc13 protein family proposed to function in priming secretory granules for exocytosis. Munc13-4 contains N- and C-terminal C2 domains (C2A and C2B) predicted to bind Ca(2+), but Ca(2+)-dependent regulation of Munc13-4 activity has not been described. The C2 domains bracket a predicted SNARE-binding domain, but whether Munc13-4 interacts with SNARE proteins is unknown. We report that Munc13-4 bound Ca(2+) and restored Ca(2+)-dependent granule exocytosis to permeable cells (platelets, mast, and neuroendocrine cells) dependent on putative Ca(2+)-binding residues in C2A and C2B. Munc13-4 exhibited Ca(2+)-stimulated SNARE interactions dependent on C2A and Ca(2+)-dependent membrane binding dependent on C2B. In an apparent coupling of membrane and SNARE binding, Munc13-4 stimulated SNARE-dependent liposome fusion dependent on putative Ca(2+)-binding residues in both C2A and C2B domains. Munc13-4 is the first priming factor shown to promote Ca(2+)-dependent SNARE complex formation and SNARE-mediated liposome fusion. These properties of Munc13-4 suggest its function as a Ca(2+) sensor at rate-limiting priming steps in granule exocytosis.

  18. Magnetic domain wall engineering in a nanoscale permalloy junction

    NASA Astrophysics Data System (ADS)

    Wang, Junlin; Zhang, Xichao; Lu, Xianyang; Zhang, Jason; Yan, Yu; Ling, Hua; Wu, Jing; Zhou, Yan; Xu, Yongbing

    2017-08-01

    Nanoscale magnetic junctions provide a useful approach to act as building blocks for magnetoresistive random access memories (MRAM), where one of the key issues is to control the magnetic domain configuration. Here, we study the domain structure and the magnetic switching in the Permalloy (Fe20Ni80) nanoscale magnetic junctions with different thicknesses by using micromagnetic simulations. It is found that both the 90-° and 45-° domain walls can be formed between the junctions and the wire arms depending on the thickness of the device. The magnetic switching fields show distinct thickness dependencies with a broad peak varying from 7 nm to 22 nm depending on the junction sizes, and the large magnetic switching fields favor the stability of the MRAM operation.

  19. Mechanism of Mediator recruitment by tandem Gcn4 activation domains and three Gal11 activator-binding domains.

    PubMed

    Herbig, Eric; Warfield, Linda; Fish, Lisa; Fishburn, James; Knutson, Bruce A; Moorefield, Beth; Pacheco, Derek; Hahn, Steven

    2010-05-01

    Targets of the tandem Gcn4 acidic activation domains in transcription preinitiation complexes were identified by site-specific cross-linking. The individual Gcn4 activation domains cross-link to three common targets, Gal11/Med15, Taf12, and Tra1, which are subunits of four conserved coactivator complexes, Mediator, SAGA, TFIID, and NuA4. The Gcn4 N-terminal activation domain also cross-links to the Mediator subunit Sin4/Med16. The contribution of the two Gcn4 activation domains to transcription was gene specific and varied from synergistic to less than additive. Gcn4-dependent genes had a requirement for Gal11 ranging from 10-fold dependence to complete Gal11 independence, while the Gcn4-Taf12 interaction did not significantly contribute to the expression of any gene studied. Complementary methods identified three conserved Gal11 activator-binding domains that bind each Gcn4 activation domain with micromolar affinity. These Gal11 activator-binding domains contribute additively to transcription activation and Mediator recruitment at Gcn4- and Gal11-dependent genes. Although we found that the conserved Gal11 KIX domain contributes to Gal11 function, we found no evidence of specific Gcn4-KIX interaction and conclude that the Gal11 KIX domain does not function by specific interaction with Gcn4. Our combined results show gene-specific coactivator requirements, a surprising redundancy in activator-target interactions, and an activator-coactivator interaction mediated by multiple low-affinity protein-protein interactions.

  20. The Effects of Item Format and Cognitive Domain on Students' Science Performance in TIMSS 2011

    NASA Astrophysics Data System (ADS)

    Liou, Pey-Yan; Bulut, Okan

    2017-12-01

    The purpose of this study was to examine eighth-grade students' science performance in terms of two test design components, item format, and cognitive domain. The portion of Taiwanese data came from the 2011 administration of the Trends in International Mathematics and Science Study (TIMSS), one of the major international large-scale assessments in science. The item difficulty analysis was initially applied to show the proportion of correct items. A regression-based cumulative link mixed modeling (CLMM) approach was further utilized to estimate the impact of item format, cognitive domain, and their interaction on the students' science scores. The results of the proportion-correct statistics showed that constructed-response items were more difficult than multiple-choice items, and that the reasoning cognitive domain items were more difficult compared to the items in the applying and knowing domains. In terms of the CLMM results, students tended to obtain higher scores when answering constructed-response items as well as items in the applying cognitive domain. When the two predictors and the interaction term were included together, the directions and magnitudes of the predictors on student science performance changed substantially. Plausible explanations for the complex nature of the effects of the two test-design predictors on student science performance are discussed. The results provide practical, empirical-based evidence for test developers, teachers, and stakeholders to be aware of the differential function of item format, cognitive domain, and their interaction in students' science performance.

  1. Minimization of Ohmic losses for domain wall motion in ferromagnetic nanowires

    NASA Astrophysics Data System (ADS)

    Abanov, Artem; Tretiakov, Oleg; Liu, Yang

    2011-03-01

    We study current-induced domain-wall motion in a narrow ferromagnetic wire. We propose a way to move domain walls with a resonant time-dependent current which dramatically decreases the Ohmic losses in the wire and allows driving of the domain wall with higher speed without burning the wire. For any domain wall velocity we find the time-dependence of the current needed to minimize the Ohmic losses. Below a critical domain-wall velocity specified by the parameters of the wire the minimal Ohmic losses are achieved by dc current. Furthermore, we identify the wire parameters for which the losses reduction from its dc value is the most dramatic. This work was supported by the NSF Grant No. 0757992 and Welch Foundation (A-1678).

  2. Developing guidelines for postgraduate dental educators in the UK.

    PubMed

    Bullock, A D; Firmstone, V R; Falcon, H C

    2010-01-09

    Commissioned by the UK Committee of Postgraduate Dental Deans and Directors (COPDEND), the purpose of this work was to establish UK guidelines for dental educators. The final document comprises 79 statements, in eight domains. Each domain has four zones related to what dental educators (1) know, (2) do with members of the dental team as learners, (3) do with other dental educators as learners and (4) lead on. Launched in November 2008, the document provides a framework of good practice for use in the employment, development and management of dental educators in the UK. The guidelines are readily available from the COPDEND website. A key purpose of this paper is to report on the process of development and a central part of that was the integration of feedback and consultation on early drafts. These processes elicited a total of 102 responses. Issues raised in consultation included: (1) how the zones interrelate; (2) differentiation between domains; (3) measurability; and (4) implementation challenges. This paper includes our responses to these issues.

  3. [Three-dimensional genome organization: a lesson from the Polycomb-Group proteins].

    PubMed

    Bantignies, Frédéric

    2013-01-01

    As more and more genomes are being explored and annotated, important features of three-dimensional (3D) genome organization are just being uncovered. In the light of what we know about Polycomb group (PcG) proteins, we will present the latest findings on this topic. The PcG proteins are well-conserved chromatin factors that repress transcription of numerous target genes. They bind the genome at specific sites, forming chromatin domains of associated histone modifications as well as higher-order chromatin structures. These 3D chromatin structures involve the interactions between PcG-bound regulatory regions at short- and long-range distances, and may significantly contribute to PcG function. Recent high throughput "Chromosome Conformation Capture" (3C) analyses have revealed many other higher order structures along the chromatin fiber, partitioning the genomes into well demarcated topological domains. This revealed an unprecedented link between linear epigenetic domains and chromosome architecture, which might be intimately connected to genome function. © Société de Biologie, 2013.

  4. Crystal structure of group II intron domain 1 reveals a template for RNA assembly

    DOE PAGES

    Zhao, Chen; Rajashankar, Kanagalaghatta R.; Marcia, Marco; ...

    2015-10-26

    Although the importance of large noncoding RNAs is increasingly appreciated, our understanding of their structures and architectural dynamics remains limited. In particular, we know little about RNA folding intermediates and how they facilitate the productive assembly of RNA tertiary structures. In this paper, we report the crystal structure of an obligate intermediate that is required during the earliest stages of group II intron folding. Composed of domain 1 from the Oceanobacillus iheyensis group II intron (266 nucleotides), this intermediate retains native-like features but adopts a compact conformation in which the active site cleft is closed. Transition between this closed andmore » the open (native) conformation is achieved through discrete rotations of hinge motifs in two regions of the molecule. Finally, the open state is then stabilized by sequential docking of downstream intron domains, suggesting a 'first come, first folded' strategy that may represent a generalizable pathway for assembly of large RNA and ribonucleoprotein structures.« less

  5. Identification of a magnesium-dependent NAD(P)(H)-binding domain in the nicotinoprotein methanol dehydrogenase from Bacillus methanolicus.

    PubMed

    Hektor, Harm J; Kloosterman, Harm; Dijkhuizen, Lubbert

    2002-12-06

    The Bacillus methanolicus methanol dehydrogenase (MDH) is a decameric nicotinoprotein alcohol dehydrogenase (family III) with one Zn(2+) ion, one or two Mg(2+) ions, and a tightly bound cofactor NAD(H) per subunit. The Mg(2+) ions are essential for binding of cofactor NAD(H) in MDH. A B. methanolicus activator protein strongly stimulates the relatively low coenzyme NAD(+)-dependent MDH activity, involving hydrolytic removal of the NMN(H) moiety of cofactor NAD(H) (Kloosterman, H., Vrijbloed, J. W., and Dijkhuizen, L. (2002) J. Biol. Chem. 277, 34785-34792). Members of family III of NAD(P)-dependent alcohol dehydrogenases contain three unique, conserved sequence motifs (domains A, B, and C). Domain C is thought to be involved in metal binding, whereas the functions of domains A and B are still unknown. This paper provides evidence that domain A constitutes (part of) a new magnesium-dependent NAD(P)(H)-binding domain. Site-directed mutants D100N and K103R lacked (most of the) bound cofactor NAD(H) and had lost all coenzyme NAD(+)-dependent MDH activity. Also mutants G95A and S97G were both impaired in cofactor NAD(H) binding but retained coenzyme NAD(+)-dependent MDH activity. Mutant G95A displayed a rather low MDH activity, whereas mutant S97G was insensitive to activator protein but displayed "fully activated" MDH reaction rates. The various roles of these amino acid residues in coenzyme and/or cofactor NAD(H) binding in MDH are discussed.

  6. Air Force and the Cyberspace Mission: Defending the Air Force’s Computer Network in the Future

    DTIC Science & Technology

    2007-12-01

    computers, their operating systems and software purchased by the Air Force are commercial off-the-shelf (COTS) components, often manufactured abroad due...crystal clear 2003 information security report: “The U.S. Department of Defense (DOD) relies too much on commercial software , doesn’t know who is...creating the software , and faces other significant cybersecurity problems.”11 This paper explores the topic of defense of the cyberspace domain by

  7. The neurobiology of the human memory.

    PubMed

    Fietta, Pierluigi; Fietta, Pieranna

    2011-01-01

    Memory can be defined as the ability to acquire, process, store, and retrieve information. Memory is indispensable for learning, adaptation, and survival of every living organism. In humans, the remembering process has acquired great flexibility and complexity, reaching close links with other mental functions, such as thinking and emotions. Changes in synaptic connectivity and interactions among multiple neural networks provide the neurobiological substrates for memory encoding, retention, and consolidation. Memory may be categorized as short-term and long-term memory (according to the storage temporal duration), as implicit and explicit memory (with respect to the consciousness of remembering), as declarative (knowing that [fact]) and procedural (knowing how [skill]) memory, or as sensory (echoic, iconic and haptil), semantic, and episodic memory (according to the various remembering domains). Significant advances have been obtained in understanding memory neurobiology, but much remains to be learned in its cognitive, psychological, and phenomenological aspects.

  8. Preliminary field trial of a putative research algorithm for diagnosing ICD-11 personality disorders in psychiatric patients: 2. Proposed trait domains.

    PubMed

    Kim, Youl-Ri; Tyrer, Peter; Lee, Hong-Seock; Kim, Sung-Gon; Hwang, Soon-Taek; Lee, Gi Young; Mulder, Roger

    2015-11-01

    This field trial examines the discriminant validity of five trait domains of the originally proposed research algorithm for diagnosing International Classification of Diseases (ICD)-11 personality disorders. This trial was carried out in South Korea where a total of 124 patients with personality disorder participated in the study. Participants were assessed using originally proposed monothetic trait domains of asocial-schizoid, antisocial-dissocial, anxious-dependent, emotionally unstable and anankastic-obsessional groups of the research algorithm in ICD-11. Their assessments were compared to those from the Personality Assessment Schedule interview, and the five-factor model (FFM). A total of 48.4% of patients were found to have pathology in two or more domains. In the discriminant analysis, 64.2% of the grouped cases of the originally proposed ICD-11 domains were correctly classified by the five domain categories using the Personality Assessment Schedule, with the highest accuracy in the anankastic-obsessional domain and the lowest accuracy in the emotionally unstable domain. In comparison, the asocial-schizoid, anxious-dependent and the emotionally unstable domains were moderately correlated with the FFM, whereas the anankastic-obsessional or antisocial-dissocial domains were not significantly correlated with the FFM. In this field trial, we demonstrated the limited discriminant and the convergent validities of the originally proposed trait domains of the research algorithm for diagnosing ICD-11 personality disorder. The results suggest that the anankastic, asocial and dissocial domains show good discrimination, whereas the anxious-dependent and emotionally unstable ones overlap too much and have been subsequently revised. Copyright © 2015 John Wiley & Sons, Ltd.

  9. Assembly and misassembly of cystic fibrosis transmembrane conductance regulator: folding defects caused by deletion of F508 occur before and after the calnexin-dependent association of membrane spanning domain (MSD) 1 and MSD2.

    PubMed

    Rosser, Meredith F N; Grove, Diane E; Chen, Liling; Cyr, Douglas M

    2008-11-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) is a polytopic membrane protein that functions as a Cl(-) channel and consists of two membrane spanning domains (MSDs), two cytosolic nucleotide binding domains (NBDs), and a cytosolic regulatory domain. Cytosolic 70-kDa heat shock protein (Hsp70), and endoplasmic reticulum-localized calnexin are chaperones that facilitate CFTR biogenesis. Hsp70 functions in both the cotranslational folding and posttranslational degradation of CFTR. Yet, the mechanism for calnexin action in folding and quality control of CFTR is not clear. Investigation of this question revealed that calnexin is not essential for CFTR or CFTRDeltaF508 degradation. We identified a dependence on calnexin for proper assembly of CFTR's membrane spanning domains. Interestingly, efficient folding of NBD2 was also found to be dependent upon calnexin binding to CFTR. Furthermore, we identified folding defects caused by deletion of F508 that occurred before and after the calnexin-dependent association of MSD1 and MSD2. Early folding defects are evident upon translation of the NBD1 and R-domain and are sensed by the RMA-1 ubiquitin ligase complex.

  10. Hydrogen–Deuterium Exchange and Mass Spectrometry Reveal the pH-Dependent Conformational Changes of Diphtheria Toxin T Domain

    PubMed Central

    2015-01-01

    The translocation (T) domain of diphtheria toxin plays a critical role in moving the catalytic domain across the endosomal membrane. Translocation/insertion is triggered by a decrease in pH in the endosome where conformational changes of T domain occur through several kinetic intermediates to yield a final trans-membrane form. High-resolution structural studies are only applicable to the static T-domain structure at physiological pH, and studies of the T-domain translocation pathway are hindered by the simultaneous presence of multiple conformations. Here, we report the application of hydrogen–deuterium exchange mass spectrometry (HDX-MS) for the study of the pH-dependent conformational changes of the T domain in solution. Effects of pH on intrinsic HDX rates were deconvolved by converting the on-exchange times at low pH into times under our “standard condition” (pH 7.5). pH-Dependent HDX kinetic analysis of T domain clearly reveals the conformational transition from the native state (W-state) to a membrane-competent state (W+-state). The initial transition occurs at pH 6 and includes the destabilization of N-terminal helices accompanied by the separation between N- and C-terminal segments. The structural rearrangements accompanying the formation of the membrane-competent state expose a hydrophobic hairpin (TH8–9) to solvent, prepare it to insert into the membrane. At pH 5.5, the transition is complete, and the protein further unfolds, resulting in the exposure of its C-terminal hydrophobic TH8–9, leading to subsequent aggregation in the absence of membranes. This solution-based study complements high resolution crystal structures and provides a detailed understanding of the pH-dependent structural rearrangement and acid-induced oligomerization of T domain. PMID:25290210

  11. Hydrogen-deuterium exchange and mass spectrometry reveal the pH-dependent conformational changes of diphtheria toxin T domain.

    PubMed

    Li, Jing; Rodnin, Mykola V; Ladokhin, Alexey S; Gross, Michael L

    2014-11-04

    The translocation (T) domain of diphtheria toxin plays a critical role in moving the catalytic domain across the endosomal membrane. Translocation/insertion is triggered by a decrease in pH in the endosome where conformational changes of T domain occur through several kinetic intermediates to yield a final trans-membrane form. High-resolution structural studies are only applicable to the static T-domain structure at physiological pH, and studies of the T-domain translocation pathway are hindered by the simultaneous presence of multiple conformations. Here, we report the application of hydrogen-deuterium exchange mass spectrometry (HDX-MS) for the study of the pH-dependent conformational changes of the T domain in solution. Effects of pH on intrinsic HDX rates were deconvolved by converting the on-exchange times at low pH into times under our "standard condition" (pH 7.5). pH-Dependent HDX kinetic analysis of T domain clearly reveals the conformational transition from the native state (W-state) to a membrane-competent state (W(+)-state). The initial transition occurs at pH 6 and includes the destabilization of N-terminal helices accompanied by the separation between N- and C-terminal segments. The structural rearrangements accompanying the formation of the membrane-competent state expose a hydrophobic hairpin (TH8-9) to solvent, prepare it to insert into the membrane. At pH 5.5, the transition is complete, and the protein further unfolds, resulting in the exposure of its C-terminal hydrophobic TH8-9, leading to subsequent aggregation in the absence of membranes. This solution-based study complements high resolution crystal structures and provides a detailed understanding of the pH-dependent structural rearrangement and acid-induced oligomerization of T domain.

  12. A Unified Framework for Creating Domain Dependent Polarity Lexicons from User Generated Reviews

    PubMed Central

    Asghar, Muhammad Zubair; Khan, Aurangzeb; Ahmad, Shakeel; Khan, Imran Ali; Kundi, Fazal Masud

    2015-01-01

    The exponential increase in the explosion of Web-based user generated reviews has resulted in the emergence of Opinion Mining (OM) applications for analyzing the users’ opinions toward products, services, and policies. The polarity lexicons often play a pivotal role in the OM, indicating the positivity and negativity of a term along with the numeric score. However, the commonly available domain independent lexicons are not an optimal choice for all of the domains within the OM applications. The aforementioned is due to the fact that the polarity of a term changes from one domain to other and such lexicons do not contain the correct polarity of a term for every domain. In this work, we focus on the problem of adapting a domain dependent polarity lexicon from set of labeled user reviews and domain independent lexicon to propose a unified learning framework based on the information theory concepts that can assign the terms with correct polarity (+ive, -ive) scores. The benchmarking on three datasets (car, hotel, and drug reviews) shows that our approach improves the performance of the polarity classification by achieving higher accuracy. Moreover, using the derived domain dependent lexicon changed the polarity of terms, and the experimental results show that our approach is more effective than the base line methods. PMID:26466101

  13. The attributes of successful de-escalation and restraint teams.

    PubMed

    Snorrason, Jón; Biering, Páll

    2018-06-04

    Inpatient violence is a widespread problem on psychiatric wards often with serious consequences, and psychiatric hospitals have set up teams to de-escalate and restrain patients with aggression (D-E&R teams) which are specially trained to respond to it in a safe manner. Successful de-escalation and restraining of patients with aggression depend not only on the methods learned in training but also on the confidence of the team. Therefore, it is of great importance to understand the factors that enhance D-E&R teams' competence in managing patients with aggression in a successful and safe manner. The aim of this hermeneutic study was to identify and understand those factors. Purposive-expert sampling was used and twelve D-E&R team members with significant experience participated in the study. The central theme found was a safe team. Ensuring the safety of the team and its members was found to be a prerequisite for successful teamwork in managing patients with aggression in a safe manner. This central theme falls into two interacting domains: the internal dynamics of the team and the team's interaction with patients. Several themes, such as mutual trust, flexibility, and knowing one's role, influence these domains and hence strengthen or weaken the confidence and safety of the team. The findings of the study will contribute to a better understanding of these factors; understanding which could be used to improve the training, supervision, and quality assessment of D-E&R teams and hence lead to more safety in psychiatric wards. © 2018 Australian College of Mental Health Nurses Inc.

  14. The Effects of Healthy Aging, Amnestic Mild Cognitive Impairment, and Alzheimer’s Disease on Recollection and Familiarity: A Meta-Analytic Review

    PubMed Central

    Yonelinas, Andrew P.

    2014-01-01

    It is well established that healthy aging, amnestic Mild Cognitive Impairment (aMCI), and Alzheimer’s Disease (AD) are associated with substantial declines in episodic memory. However, there is still debate as to how two forms of episodic memory – recollection and familiarity – are affected by healthy and pathological aging. To address this issue we conducted a meta-analytic review of the effect sizes reported in studies using remember/know (RK), receiver operating characteristic (ROC) and process dissociation (PD) methods to examine recollection and familiarity in healthy aging (25 published reports), aMCI (9 published reports), and AD (5 published reports). The results from the meta-analysis revealed that healthy aging is associated with moderate-to-large recollection impairments. Familiarity was not impaired in studies using ROC or PD methods but was impaired in studies that used the RK procedure. aMCI was associated with large decreases in recollection whereas familiarity only tended to show a decrease in studies with a patient sample comprised of both single-domain and multiple-domain aMCI patients. Lastly, AD was associated with large decreases in both recollection and familiarity. The results are consistent with neuroimaging evidence suggesting that the hippocampus is critical for recollection whereas familiarity is dependent on the integrity of the surrounding perirhinal cortex. Moreover, the results highlight the relevance of method selection when examining aging, and suggest that familiarity deficits might be a useful behavioral marker for identifying individuals that will develop dementia. PMID:25119304

  15. The clathrin-binding and J-domains of GAK support the uncoating and chaperoning of clathrin by Hsc70 in the brain

    PubMed Central

    Park, Bum-Chan; Yim, Yang-In; Zhao, Xiaohong; Olszewski, Maciej B.; Eisenberg, Evan; Greene, Lois E.

    2015-01-01

    ABSTRACT Cyclin-G-associated kinase (GAK), the ubiquitously expressed J-domain protein, is essential for the chaperoning and uncoating of clathrin that is mediated by Hsc70 (also known as HSPA8). Adjacent to the C-terminal J-domain that binds to Hsc70, GAK has a clathrin-binding domain that is linked to an N-terminal kinase domain through a PTEN-like domain. Knocking out GAK in fibroblasts caused inhibition of clathrin-dependent trafficking, which was rescued by expressing a 62-kDa fragment of GAK, comprising just the clathrin-binding and J-domains. Expressing this fragment as a transgene in mice rescued the lethality and the histological defects caused by knocking out GAK in the liver or in the brain. Furthermore, when both GAK and auxilin (also known as DNAJC6), the neuronal-specific homolog of GAK, were knocked out in the brain, mice expressing the 62-kDa GAK fragment were viable, lived a normal life-span and had no major behavior abnormalities. However, these mice were about half the size of wild-type mice. Therefore, the PTEN-like domains of GAK and auxilin are not essential for Hsc70-dependent chaperoning and uncoating of clathrin, but depending on the tissue, these domains appear to increase the efficiency of these co-chaperones. PMID:26345367

  16. Coupling between Current and Dynamic Magnetization : from Domain Walls to Spin Waves

    NASA Astrophysics Data System (ADS)

    Lucassen, M. E.

    2012-05-01

    So far, we have derived some general expressions for domain-wall motion and the spin motive force. We have seen that the β parameter plays a large role in both subjects. In all chapters of this thesis, there is an emphasis on the determination of this parameter. We also know how to incorporate thermal fluctuations for rigid domain walls, as shown above. In Chapter 2, we study a different kind of fluctuations: shot noise. This noise is caused by the fact that an electric current consists of electrons, and therefore has fluctuations. In the process, we also compute transmission and reflection coefficients for a rigid domain wall, and from them the linear momentum transfer. More work on fluctuations is done in Chapter 3. Here, we consider a (extrinsically pinned) rigid domain wall under the influence of thermal fluctuations that induces a current via spin motive force. We compute how the resulting noise in the current is related to the β parameter. In Chapter 4 we look into in more detail into the spin motive forces from field driven domain walls. Using micro magnetic simulations, we compute the spin motive force due to vortex domain walls explicitly. As mentioned before, this gives qualitatively different results than for a rigid domain wall. The final subject in Chapter 5 is the application of the general expression for spin motive forces to magnons. Although this might seem to be unrelated to domain-wall motion, this calculation allows us to relate the β parameter to macroscopic transport coefficients. This work was supported by Stichting voor Fundamenteel Onderzoek der Materie (FOM), the Netherlands Organization for Scientific Research (NWO), and by the European Research Council (ERC) under the Seventh Framework Program (FP7).

  17. Pectin Homogalacturonans: Nanostructural Characterization of Methylesterified Domains

    USDA-ARS?s Scientific Manuscript database

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

  18. Vantage point.

    PubMed

    Kay, Jenny

    2010-04-28

    A RECENT BBC Panorama television programme asked how we know which hospitals are 'good'. It argued that the hospital rating system cannot always be trusted because it depends in large part on self-assessment.

  19. System and technique for characterizing fluids using ultrasonic diffraction grating spectroscopy

    DOEpatents

    Greenwood, Margaret S [Richland, WA

    2008-07-08

    A system for determining property of multiphase fluids based on ultrasonic diffraction grating spectroscopy includes a diffraction grating on a solid in contact with the fluid. An interrogation device delivers ultrasound through the solid and a captures a reflection spectrum from the diffraction grating. The reflection spectrum exhibits peaks whose relative size depends on the properties of the various phases of the multiphase fluid. For example, for particles in a liquid, the peaks exhibit dependence on the particle size and the particle volume fraction. Where the exact relationship is know know a priori, data from different peaks of the same reflection spectrum or data from the peaks of different spectra obtained from different diffraction gratings can be used to resolve the size and volume fraction.

  20. Autophosphorylation-based calcium (Ca2+) sensitivity priming and Ca2+/Calmodulin inhibition of Arabidopsis thaliana Ca2+-dependent protein kinase 28 (CPK28)

    USDA-ARS?s Scientific Manuscript database

    Plant calcium (Ca2+) dependent protein kinases (CPKs) are composed of a dual specificity (Ser/Thr and Tyr) kinase domain tethered to a Calmodulin-like domain (CLD) via an autoinhibitory junction (J) and represent the primary Ca2+-dependent protein kinase activities in plant systems. While regulation...

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

    PubMed

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

    2009-01-01

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

  2. Using terahertz time-domain spectroscopical technique to monitor cocrystal formation between piracetam and 2,5-dihydroxybenzoic acid.

    PubMed

    Du, Yong; Xia, Yi; Zhang, Huili; Hong, Zhi

    2013-07-01

    Far-infrared vibrational absorption of cocrystal formation between 2,5-dihydroxybenzoic acid (2,5-DHBA) and piracetam compounds under solvent evaporation and grinding methods have been investigated using terahertz time-domain spectroscopy (THz-TDS) at room temperature. The experimental results show large difference among absorption spectra of the formed cocrystals and the involved individual parent molecules in 0.20-1.50 THz region, which probably originated from the intra-molecular and inter-molecular hydrogen bonds due to the presence of two hydroxyl groups in 2,5-DHBA and amide moieties in piracetam compound. The THz absorption spectra of two formed cocrystals with different methods are almost identical. With grinding method, the reaction process can be monitored directly from both time-domain and frequency-domain spectra using THz-TDS technique. The results indicate that THz-TDS technology can absolutely offer us a high potential method to identify and characterize the formed cocrystals, and also provide the rich information about their reaction dynamic process involving two or more molecular crystals in situ to better know the corresponding reaction mechanism in pharmaceutical fields. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. A Theory-Based Methodology for Analyzing Domain Suitability for Expert Systems Technology Applications

    DTIC Science & Technology

    1989-06-01

    amount of data now available as a result of these experiments, we are still unable to explain the "why" or " how " of successful systems or to predict for...order to better understand the potential contribution of this research, it is important to first discuss how expert systems are developed and the...task performance through internal and external feedback. 9. Knowing how to act upon the feedback received. 10. Implementing the action based on the

  4. Natural Language Processing Systems Evaluation Workshop Held in Berkely, California on 18 June 1991

    DTIC Science & Technology

    1991-12-01

    re~arded as -a fairly complete dictionary contains about 18,000 itemsw at soluition to the domain-restricted task at tzanlating present, and will be... dictionary access and so on, with an article. Unfortunately, the Weidner system did but as time goes on, one might imagine functionality not know that...superfast type. looped tht it A31l be built with taste by peo. writer ought to be possible in the monolingual case pie who understand languages and

  5. Deficiency in chromosome congression by the inhibition of Plk1 polo box domain-dependent recognition.

    PubMed

    Watanabe, Nobumoto; Sekine, Tomomi; Takagi, Masatoshi; Iwasaki, Jun-ichi; Imamoto, Naoko; Kawasaki, Hisashi; Osada, Hiroyuki

    2009-01-23

    Polo-like kinase 1 (Plk1) is one of the key regulators of mitotic cell division. In addition to an N-terminal protein kinase catalytic domain, Plk1 possesses a phosphopeptide binding domain named polo box domain (PBD) at its C terminus. PBD is postulated to be essential for Plk1 localization and substrate targeting. Here, we developed a high-throughput screening system to identify inhibitors of PBD-dependent binding and screened a chemical library. We isolated a benzotropolone-containing natural compound derived from nutgalls (purpurogallin (PPG)) that inhibited PBD-dependent binding in vitro and in vivo. PPG not only delayed the onset of mitosis but also prolonged the progression of mitosis in HeLa cells. Although apparently normal bipolar spindles were formed even in the presence of PPG, the perturbation of chromosome alignment at metaphase plates activated the spindle assembly checkpoint pathway. These results demonstrate the predominant role of PBD-dependent binding on smooth chromosome congression at metaphase.

  6. Ovarian Tumor (OTU)-domain Containing Viral Proteases Evade Ubiquitin- and ISG15-dependent Innate Immune Responses

    PubMed Central

    Frias-Staheli, Natalia; Giannakopoulos, Nadia V.; Kikkert, Marjolein; Taylor, Shannon L.; Bridgen, Anne; Paragas, Jason J.; Richt, Juergen A.; Rowland, Raymond R.; Schmaljohn, Connie S.; Lenschow, Deborah J.; Snijder, Eric J.; García-Sastre, Adolfo; Virgin, Herbert Whiting

    2007-01-01

    Summary Ubiquitin (Ub) and interferon stimulated gene product 15 (ISG15) reversibly conjugate to proteins via a conserved LRLRGG C-terminal motif, mediating important innate antiviral responses. The ovarian tumor (OTU) domain represents a superfamily of predicted proteases found in eukaryotic, bacterial and viral proteins, some of which have Ub-deconjugating activity. We show that the OTU domain-containing proteases of nairoviruses and arteriviruses hydrolyze Ub and ISG15 from cellular target proteins. This broad activity contrasts with the target specificity of known mammalian OTU domain-containing proteins. The biological significance of this activity of viral OTU domain-containing proteases was evidenced by their capacity to inhibit NF-κB dependent signaling and to antagonize the antiviral effects of ISG15 during Sindbis virus infection in vivo. The deconjugating activity of viral OTU proteases represents a novel viral immune evasion mechanism that inhibits Ub-and ISG15-dependent antiviral pathways. PMID:18078692

  7. Structures of apicomplexan calcium-dependent protein kinases reveal mechanism of activation by calcium

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

    Wernimont, Amy K; Artz, Jennifer D.; Jr, Patrick Finerty

    2010-09-21

    Calcium-dependent protein kinases (CDPKs) have pivotal roles in the calcium-signaling pathway in plants, ciliates and apicomplexan parasites and comprise a calmodulin-dependent kinase (CaMK)-like kinase domain regulated by a calcium-binding domain in the C terminus. To understand this intramolecular mechanism of activation, we solved the structures of the autoinhibited (apo) and activated (calcium-bound) conformations of CDPKs from the apicomplexan parasites Toxoplasma gondii and Cryptosporidium parvum. In the apo form, the C-terminal CDPK activation domain (CAD) resembles a calmodulin protein with an unexpected long helix in the N terminus that inhibits the kinase domain in the same manner as CaMKII. Calcium bindingmore » triggers the reorganization of the CAD into a highly intricate fold, leading to its relocation around the base of the kinase domain to a site remote from the substrate binding site. This large conformational change constitutes a distinct mechanism in calcium signal-transduction pathways.« less

  8. Structural Basis for Methylarginine-dependent Recognition of Aubergine by Tudor

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

    Liu, H.; Wang, J; Huang, Y

    2010-01-01

    Piwi proteins are modified by symmetric dimethylation of arginine (sDMA), and the methylarginine-dependent interaction with Tudor domain proteins is critical for their functions in germline development. Cocrystal structures of an extended Tudor domain (eTud) of Drosophila Tudor with methylated peptides of Aubergine, a Piwi family protein, reveal that sDMA is recognized by an asparagine-gated aromatic cage. Furthermore, the unexpected Tudor-SN/p100 fold of eTud is important for sensing the position of sDMA. The structural information provides mechanistic insights into sDMA-dependent Piwi-Tudor interaction, and the recognition of sDMA by Tudor domains in general.

  9. Generalized analytical solutions to sequentially coupled multi-species advective-dispersive transport equations in a finite domain subject to an arbitrary time-dependent source boundary condition

    NASA Astrophysics Data System (ADS)

    Chen, Jui-Sheng; Liu, Chen-Wuing; Liang, Ching-Ping; Lai, Keng-Hsin

    2012-08-01

    SummaryMulti-species advective-dispersive transport equations sequentially coupled with first-order decay reactions are widely used to describe the transport and fate of the decay chain contaminants such as radionuclide, chlorinated solvents, and nitrogen. Although researchers attempted to present various types of methods for analytically solving this transport equation system, the currently available solutions are mostly limited to an infinite or a semi-infinite domain. A generalized analytical solution for the coupled multi-species transport problem in a finite domain associated with an arbitrary time-dependent source boundary is not available in the published literature. In this study, we first derive generalized analytical solutions for this transport problem in a finite domain involving arbitrary number of species subject to an arbitrary time-dependent source boundary. Subsequently, we adopt these derived generalized analytical solutions to obtain explicit analytical solutions for a special-case transport scenario involving an exponentially decaying Bateman type time-dependent source boundary. We test the derived special-case solutions against the previously published coupled 4-species transport solution and the corresponding numerical solution with coupled 10-species transport to conduct the solution verification. Finally, we compare the new analytical solutions derived for a finite domain against the published analytical solutions derived for a semi-infinite domain to illustrate the effect of the exit boundary condition on coupled multi-species transport with an exponential decaying source boundary. The results show noticeable discrepancies between the breakthrough curves of all the species in the immediate vicinity of the exit boundary obtained from the analytical solutions for a finite domain and a semi-infinite domain for the dispersion-dominated condition.

  10. Efficient Time Propagation Technique for MAS NMR Simulation: Application to Quadrupolar Nuclei.

    PubMed

    Charpentier; Fermon; Virlet

    1998-06-01

    The quantum mechanical Floquet theory is investigated in order to derive an efficient way of performing numerical calculations of the dynamics of nuclear spin systems in MAS NMR experiments. Here, we take advantage of time domain integration of the quantum evolution over one period as proposed by Eden et al. (1). But a full investigation of the propagator U(t, t0), and especially its dependence with respect to t and t0 within a formalized approach, leads to further simplifications and to a substantial reduction in computation time when performing powder averaging for any complex sequence. Such an approximation is suitable for quadrupolar nuclei (I > 1/2) and can be applied to the simulation of the RIACT (rotational induced adiabatic coherence transfer) phenomenon that occurs under special experimental conditions in spin locking experiments (2-4). The present method is also compared to the usual infinite dimensional Floquet space approach (5, 6), which is shown to be rather inefficient. As far as we know, it has never been reported for quadrupolar nuclei with I >/= 3/2 in spin locking experiments. The method can also be easily extended to other areas of spectroscopy. Copyright 1998 Academic Press.

  11. Natural Immunity to Ebola Virus in the Syrian Hamster Requires Antibody Responses.

    PubMed

    Prescott, Joseph; Falzarano, Darryl; Feldmann, Heinz

    2015-10-01

    Most ebolaviruses can cause severe disease in humans and other primates, with high case fatality rates during human outbreaks. Although these viruses have been studied for almost 4 decades, little is know regarding the mechanisms by which they cause disease and what is important for protection or treatment after infection. Because of the sporadic nature of the outbreaks and difficulties accessing the populations affected by ebolaviruses, little is also known about what constitutes an appropriate immune response to infection in humans that survive infection. Such knowledge would allow a targeted approach to therapies. In contrast to humans, rodents are protected from disease on infection with ebolaviruses, although adapted versions of some of the viruses are lethal in mice, hamsters and guinea pigs. Using the recently described hamster model, along with T-cell depletion strategies, we show that CD4(+) T cells are required for natural immunity to Ebola virus infection and that CD4-dependent antibody responses are required for immunity in this model. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  12. Caveolae.

    PubMed

    Parton, Robert G; Tillu, Vikas A; Collins, Brett M

    2018-04-23

    Caveolae are one of the most abundant and striking features of the plasma membrane of many mammalian cell types. These surface pits have fascinated biologists since their discovery by the pioneers of electron microscopy in the middle of the last century, but we are only just starting to understand their multiple functions. Molecular understanding of caveolar formation is advancing rapidly and we now know that sculpting the membrane to generate the characteristic bulb-shaped caveolar pit involves the coordinated action of integral membrane proteins and peripheral membrane coat proteins in a process dependent on their multiple interactions with membrane lipids. The resulting structure is further stabilised by protein complexes at the caveolar neck. Caveolae can bud to generate an endocytic carrier but can also be disassembled in response to specific stimuli to function as a mechanoprotective device. These structures have also been linked to numerous signalling pathways. Here, we will briefly summarise the current molecular and structural understanding of caveolar formation and dynamics, discuss how the crucial structural components of caveolae work together to generate a dynamic sensing domain, and discuss the implications of recent studies on the diverse roles proposed for caveolae in different cells and tissues. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Inferring social ties from geographic coincidences.

    PubMed

    Crandall, David J; Backstrom, Lars; Cosley, Dan; Suri, Siddharth; Huttenlocher, Daniel; Kleinberg, Jon

    2010-12-28

    We investigate the extent to which social ties between people can be inferred from co-occurrence in time and space: Given that two people have been in approximately the same geographic locale at approximately the same time, on multiple occasions, how likely are they to know each other? Furthermore, how does this likelihood depend on the spatial and temporal proximity of the co-occurrences? Such issues arise in data originating in both online and offline domains as well as settings that capture interfaces between online and offline behavior. Here we develop a framework for quantifying the answers to such questions, and we apply this framework to publicly available data from a social media site, finding that even a very small number of co-occurrences can result in a high empirical likelihood of a social tie. We then present probabilistic models showing how such large probabilities can arise from a natural model of proximity and co-occurrence in the presence of social ties. In addition to providing a method for establishing some of the first quantifiable estimates of these measures, our findings have potential privacy implications, particularly for the ways in which social structures can be inferred from public online records that capture individuals' physical locations over time.

  14. We are what we eat: How food is represented in our mind/brain.

    PubMed

    Rumiati, Raffaella I; Foroni, Francesco

    2016-08-01

    Despite the essential role of food in our lives, we have little understanding of the way our knowledge about food is organized in the brain. At birth, human infants exhibit very few food preferences, and do not yet know much about what is edible and what is not. A multisensory learning development will eventually turn young infants into omnivore adults, for whom deciding what to eat becomes an effortful task. Recognizing food constitutes an essential step in this decisional process. In this paper we examine how concepts about food are represented in the human brain. More specifically, we first analyze how brain-damaged patients recognize natural and manufactured food, and then examine these patterns in the light of the sensory-functional hypothesis and the domain-specific hypothesis. Secondly, we discuss how concepts of food are represented depending on whether we embrace the embodied view or the disembodied view. We conclude that research on food recognition and on the organization of knowledge about food must also take into account some aspects specific to food category, the relevance of which has not been sufficiently recognized and investigated to date.

  15. Magnetic Susceptibility and Heavy Metals in Guano from South Sulawesi Caves

    NASA Astrophysics Data System (ADS)

    Rifai, H.; Putra, R.; Fadila, M. R.; Erni, E.; Wurster, C. M.

    2018-04-01

    Measurement of some magnetic properties have been performed on vertical profile from South Sulawesi caves (Mampu and Bubau) by using low cost, rapid, sensitive and non destructive magnetic method. The aim is to attempt to use magnetic characters as a fingerprint for anthropogenic pollution in the caves. Guano samples were collected every 5 cm at a certain section of Mampu and Bubau cave, South Sulawesi, starting from surface through 300 cm in depth of mampu Cave and 30 cm of Bubau Cave. The magnetic parameters such as magnetic susceptibility and percentage frequency dependence susceptibility were measured using the Bartington MS2-MS2B instruments and supported by X-Ray Fluoroscence (XRF) to know their element composition. The results show that the samples had variations in magnetic susceptibility from 3.5 to 242.6 x 10‑8 m3/kg for Mampu Cave and from 8.6 to 106.5 x 10‑8 m3/kg for Bubau Cave and also magnetic domain. Then, the XRF results show that the caves contain several heavy metals. Magnetic and heavy metal analyses showing that the magnetic minerals in caves are lithogenic (Fe-bearing minerals) in origin and anthropogenic (Zn content) in the caves.

  16. Switching Cyclic Nucleotide-Selective Activation of Cyclic Adenosine Monophosphate-Dependent Protein Kinase Holoenzyme Reveals Distinct Roles of Tandem Cyclic Nucleotide-Binding Domains.

    PubMed

    He, Daniel; Lorenz, Robin; Kim, Choel; Herberg, Friedrich W; Lim, Chinten James

    2017-12-15

    The cyclic adenosine monophosphate (cAMP)- and cyclic guanosine monophosphate (cGMP)-dependent protein kinases (PKA and PKG) are key effectors of cyclic nucleotide signaling. Both share structural features that include tandem cyclic nucleotide-binding (CNB) domains, CNB-A and CNB-B, yet their functions are separated through preferential activation by either cAMP or cGMP. Based on structural studies and modeling, key CNB contact residues have been identified for both kinases. In this study, we explored the requirements for conversion of PKA activation from cAMP-dependent to cGMP-dependent. The consequences of the residue substitutions T192R/A212T within CNB-A or G316R/A336T within CNB-B of PKA-RIα on cyclic nucleotide binding and holoenzyme activation were assessed in vitro using purified recombinant proteins, and ex vivo using RIα-deficient mouse embryonic fibroblasts genetically reconstituted with wild-type or mutant PKA-RIα. In vitro, a loss of binding and activation selectivity was observed when residues in either one of the CNB domains were mutated, while mutations in both CNB domains resulted in a complete switch of selectivity from cAMP to cGMP. The switch in selectivity was also recapitulated ex vivo, confirming their functional roles in cells. Our results highlight the importance of key cyclic nucleotide contacts within each CNB domain and suggest that these domains may have evolved from an ancestral gene product to yield two distinct cyclic nucleotide-dependent protein kinases.

  17. Do Cancer Patients Prefer to Know the Diagnosis? A Descriptive Study Among Iranian Patients.

    PubMed

    Samimi Ardestani, Seyed Mehdi; Faridhosseini, Farhad; Shirkhani, Fatemeh; Karamad, Ardeshir; Farid, Layla; Fayyazi Bordbar, Mohammad Reza; Motlagh, Ali

    2015-12-01

    There are important differences regarding cancer disclosure in various geographical populations (Europeans, Western Asia, Eastern Asia), depending on multiple sociocultural factors, and therefore, there is no standard protocol on this issue, especially in Iran. To evaluate the amount of information that Iranian patients have and their preference for the disclosure of the cancer diagnosis. In this cross sectional descriptive research, patients admitted in the oncology departments of 3 referral medical centers, Imam Hussein, Shohada-e-Tajrish and Modarres, in Tehran, from March 2007 to April 2008, were questioned about their awareness and knowledge regarding their diagnosis. Two different structured questionnaires were designed for the people who know and who didn't know their diagnosis. For the former, the survey concerned their psychological reactions to their situations, whether they would prefer to know about their diagnosis and by whom they are preferred to be informed .For the latter, the questionnaire included their preference whether to know the diagnosis and their current emotional state. Descriptive statistics and chi square test was applied to analyze gathering Data, using SPSS version 14. 60.3% of the patients knew their diagnosis. Among the subjects who did not know their diagnosis, 88% preferred to be more informed about their diagnosis and 68% had some psychological reaction to their situations. Among the subjects who knew their diagnosis, 92.1 % preferred to know their diagnosis, 73.6% preferred to be informed directly by their physicians. Following the diagnostic disclosure, 81.5% reported that they had felt nervous, anxious and worried. The majority of Iranian patients with malignancy want to know the truth and they prefer to be informed directly by their doctors.

  18. Kinase Associated-1 Domains Drive MARK/PAR1 Kinases to Membrane Targets by Binding Acidic Phospholipids

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

    Moravcevic, Katarina; Mendrola, Jeannine M.; Schmitz, Karl R.

    Phospholipid-binding modules such as PH, C1, and C2 domains play crucial roles in location-dependent regulation of many protein kinases. Here, we identify the KA1 domain (kinase associated-1 domain), found at the C terminus of yeast septin-associated kinases (Kcc4p, Gin4p, and Hsl1p) and human MARK/PAR1 kinases, as a membrane association domain that binds acidic phospholipids. Membrane localization of isolated KA1 domains depends on phosphatidylserine. Using X-ray crystallography, we identified a structurally conserved binding site for anionic phospholipids in KA1 domains from Kcc4p and MARK1. Mutating this site impairs membrane association of both KA1 domains and intact proteins and reveals the importancemore » of phosphatidylserine for bud neck localization of yeast Kcc4p. Our data suggest that KA1 domains contribute to coincidence detection, allowing kinases to bind other regulators (such as septins) only at the membrane surface. These findings have important implications for understanding MARK/PAR1 kinases, which are implicated in Alzheimer's disease, cancer, and autism.« less

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

    PubMed Central

    Hutcherson, Cendri A

    2018-01-01

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

  20. Structures of Bacterial Biosynthetic Arginine Decarboxylases

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

    F Forouhar; S Lew; J Seetharaman

    2011-12-31

    Biosynthetic arginine decarboxylase (ADC; also known as SpeA) plays an important role in the biosynthesis of polyamines from arginine in bacteria and plants. SpeA is a pyridoxal-5'-phosphate (PLP)-dependent enzyme and shares weak sequence homology with several other PLP-dependent decarboxylases. Here, the crystal structure of PLP-bound SpeA from Campylobacter jejuni is reported at 3.0 {angstrom} resolution and that of Escherichia coli SpeA in complex with a sulfate ion is reported at 3.1 {angstrom} resolution. The structure of the SpeA monomer contains two large domains, an N-terminal TIM-barrel domain followed by a {beta}-sandwich domain, as well as two smaller helical domains. Themore » TIM-barrel and {beta}-sandwich domains share structural homology with several other PLP-dependent decarboxylases, even though the sequence conservation among these enzymes is less than 25%. A similar tetramer is observed for both C. jejuni and E. coli SpeA, composed of two dimers of tightly associated monomers. The active site of SpeA is located at the interface of this dimer and is formed by residues from the TIM-barrel domain of one monomer and a highly conserved loop in the {beta}-sandwich domain of the other monomer. The PLP cofactor is recognized by hydrogen-bonding, {pi}-stacking and van der Waals interactions.« less

  1. Plasticity of BRCA2 Function in Homologous Recombination: Genetic Interactions of the PALB2 and DNA Binding Domains

    PubMed Central

    Siaud, Nicolas; Lam, Isabel; Christ, Nicole; Schlacher, Katharina; Xia, Bing; Jasin, Maria

    2011-01-01

    The breast cancer suppressor BRCA2 is essential for the maintenance of genomic integrity in mammalian cells through its role in DNA repair by homologous recombination (HR). Human BRCA2 is 3,418 amino acids and is comprised of multiple domains that interact with the RAD51 recombinase and other proteins as well as with DNA. To gain insight into the cellular function of BRCA2 in HR, we created fusions consisting of various BRCA2 domains and also introduced mutations into these domains to disrupt specific protein and DNA interactions. We find that a BRCA2 fusion peptide deleted for the DNA binding domain and active in HR is completely dependent on interaction with the PALB2 tumor suppressor for activity. Conversely, a BRCA2 fusion peptide deleted for the PALB2 binding domain is dependent on an intact DNA binding domain, providing a role for this conserved domain in vivo; mutagenesis suggests that both single-stranded and double-stranded DNA binding activities in the DNA binding domain are required for its activity. Given that PALB2 itself binds DNA, these results suggest alternative mechanisms to deliver RAD51 to DNA. In addition, the BRCA2 C terminus contains both RAD51-dependent and -independent activities which are essential to HR in some contexts. Finally, binding the small peptide DSS1 is essential for activity when its binding domain is present, but not when it is absent. Our results reveal functional redundancy within the BRCA2 protein and emphasize the plasticity of this large protein built for optimal HR function in mammalian cells. The occurrence of disease-causing mutations throughout BRCA2 suggests sub-optimal HR from a variety of domain modulations. PMID:22194698

  2. Child Care

    MedlinePlus

    Children's healthy development depends on safe and positive experiences when they are very young. If you work or go to school, you want to know that your child is in good hands while you are away. You may ...

  3. Caring for a Seriously Ill Child

    MedlinePlus

    ... medical situation, but also your child's age and maturity level. It's important to know, if possible, what ... process when possible. Depending on their ages and maturity level, visiting the hospital, meeting the nursing and ...

  4. LysK CHAP endopeptidase domain is required for lysis of live staphylococcal cells.

    USDA-ARS?s Scientific Manuscript database

    LysK is a staphylococcal bacteriophage endolysin composed of three domains, an N-terminal cysteine, histidine-dependent amidohydrolases/peptidases (CHAP) endopeptidase domain (cleaves between D-alanine of the stem peptide and glycine of the cross-bridge peptide) a mid-protein amidase 2 domain (N-ace...

  5. The role of glycosylation and domain interactions in the thermal stability of human angiotensin-converting enzyme.

    PubMed

    O'Neill, Hester G; Redelinghuys, Pierre; Schwager, Sylva L U; Sturrock, Edward D

    2008-09-01

    The N and C domains of somatic angiotensin-converting enzyme (sACE) differ in terms of their substrate specificity, inhibitor profiling, chloride dependency and thermal stability. The C domain is thermally less stable than sACE or the N domain. Since both domains are heavily glycosylated, the effect of glycosylation on their thermal stability was investigated by assessing their catalytic and physicochemical properties. Testis ACE (tACE) expressed in mammalian cells, mammalian cells in the presence of a glucosidase inhibitor and insect cells yielded proteins with altered catalytic and physicochemical properties, indicating that the more complex glycans confer greater thermal stabilization. Furthermore, a decrease in tACE and N-domain N-glycans using site-directed mutagenesis decreased their thermal stability, suggesting that certain N-glycans have an important effect on the protein's thermodynamic properties. Evaluation of the thermal stability of sACE domain swopover and domain duplication mutants, together with sACE expressed in insect cells, showed that the C domain contained in sACE is less dependent on glycosylation for thermal stabilization than a single C domain, indicating that stabilizing interactions between the two domains contribute to the thermal stability of sACE and are decreased in a C-domain-duplicating mutant.

  6. Chimeric Plant Calcium/Calmodulin-Dependent Protein Kinase Gene with a Neural Visinin-Like Calcium-Binding Domain

    NASA Technical Reports Server (NTRS)

    Patil, Shameekumar; Takezawa, D.; Poovaiah, B. W.

    1995-01-01

    Calcium, a universal second messenger, regulates diverse cellular processes in eukaryotes. Ca-2(+) and Ca-2(+)/calmodulin-regulated protein phosphorylation play a pivotal role in amplifying and diversifying the action of Ca-2(+)- mediated signals. A chimeric Ca-2(+)/calmodulin-dependent protein kinase (CCaMK) gene with a visinin-like Ca-2(+)- binding domain was cloned and characterized from lily. The cDNA clone contains an open reading frame coding for a protein of 520 amino acids. The predicted structure of CCaMK contains a catalytic domain followed by two regulatory domains, a calmodulin-binding domain and a visinin-like Ca-2(+)-binding domain. The amino-terminal region of CCaMK contains all 11 conserved subdomains characteristic of serine/threonine protein kinases. The calmodulin-binding region of CCaMK has high homology (79%) to alpha subunit of mammalian Ca-2(+)/calmodulin-dependent protein kinase. The calmodulin-binding region is fused to a neural visinin-like domain that contains three Ca-2(+)-binding EF-hand motifs and a biotin-binding site. The Escherichia coli-expressed protein (approx. 56 kDa) binds calmodulin in a Ca-2(+)-dependent manner. Furthermore, Ca-45-binding assays revealed that CCaMK directly binds Ca-2(+). The CCaMK gene is preferentially expressed in developing anthers. Southern blot analysis revealed that CCaMK is encoded by a single gene. The structural features of the gene suggest that it has multiple regulatory controls and could play a unique role in Ca-2(+) signaling in plants.

  7. Functional characterization of Arabidopsis thaliana transthyretin-like protein.

    PubMed

    Pessoa, João; Sárkány, Zsuzsa; Ferreira-da-Silva, Frederico; Martins, Sónia; Almeida, Maria R; Li, Jianming; Damas, Ana M

    2010-02-18

    Arabidopsis thaliana transthyretin-like (TTL) protein is a potential substrate in the brassinosteroid signalling cascade, having a role that moderates plant growth. Moreover, sequence homology revealed two sequence domains similar to 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU) decarboxylase (N-terminal domain) and 5-hydroxyisourate (5-HIU) hydrolase (C-terminal domain). TTL is a member of the transthyretin-related protein family (TRP), which comprises a number of proteins with sequence homology to transthyretin (TTR) and the characteristic C-terminal sequence motif Tyr-Arg-Gly-Ser. TRPs are single domain proteins that form tetrameric structures with 5-HIU hydrolase activity. Experimental evidence is fundamental for knowing if TTL is a tetrameric protein, formed by the association of the 5-HIU hydrolase domains and, in this case, if the structural arrangement allows for OHCU decarboxylase activity. This work reports about the biochemical and functional characterization of TTL. The TTL gene was cloned and the protein expressed and purified for biochemical and functional characterization. The results show that TTL is composed of four subunits, with a moderately elongated shape. We also found evidence for 5-HIU hydrolase and OHCU decarboxylase activities in vitro, in the full-length protein. The Arabidopsis thaliana transthyretin-like (TTL) protein is a tetrameric bifunctional enzyme, since it has 5-HIU hydrolase and OHCU decarboxylase activities, which were simultaneously observed in vitro.

  8. Use of the recognition heuristic depends on the domain's recognition validity, not on the recognition validity of selected sets of objects.

    PubMed

    Pohl, Rüdiger F; Michalkiewicz, Martha; Erdfelder, Edgar; Hilbig, Benjamin E

    2017-07-01

    According to the recognition-heuristic theory, decision makers solve paired comparisons in which one object is recognized and the other not by recognition alone, inferring that recognized objects have higher criterion values than unrecognized ones. However, success-and thus usefulness-of this heuristic depends on the validity of recognition as a cue, and adaptive decision making, in turn, requires that decision makers are sensitive to it. To this end, decision makers could base their evaluation of the recognition validity either on the selected set of objects (the set's recognition validity), or on the underlying domain from which the objects were drawn (the domain's recognition validity). In two experiments, we manipulated the recognition validity both in the selected set of objects and between domains from which the sets were drawn. The results clearly show that use of the recognition heuristic depends on the domain's recognition validity, not on the set's recognition validity. In other words, participants treat all sets as roughly representative of the underlying domain and adjust their decision strategy adaptively (only) with respect to the more general environment rather than the specific items they are faced with.

  9. Protein–Protein Interactions Modulate the Docking-Dependent E3-Ubiquitin Ligase Activity of Carboxy-Terminus of Hsc70-Interacting Protein (CHIP)*

    PubMed Central

    Narayan, Vikram; Landré, Vivien; Ning, Jia; Hernychova, Lenka; Muller, Petr; Verma, Chandra; Walkinshaw, Malcolm D.; Blackburn, Elizabeth A.; Ball, Kathryn L.

    2015-01-01

    CHIP is a tetratricopeptide repeat (TPR) domain protein that functions as an E3-ubiquitin ligase. As well as linking the molecular chaperones to the ubiquitin proteasome system, CHIP also has a docking-dependent mode where it ubiquitinates native substrates, thereby regulating their steady state levels and/or function. Here we explore the effect of Hsp70 on the docking-dependent E3-ligase activity of CHIP. The TPR-domain is revealed as a binding site for allosteric modulators involved in determining CHIP's dynamic conformation and activity. Biochemical, biophysical and modeling evidence demonstrate that Hsp70-binding to the TPR, or Hsp70-mimetic mutations, regulate CHIP-mediated ubiquitination of p53 and IRF-1 through effects on U-box activity and substrate binding. HDX-MS was used to establish that conformational-inhibition-signals extended from the TPR-domain to the U-box. This underscores inter-domain allosteric regulation of CHIP by the core molecular chaperones. Defining the chaperone-associated TPR-domain of CHIP as a manager of inter-domain communication highlights the potential for scaffolding modules to regulate, as well as assemble, complexes that are fundamental to protein homeostatic control. PMID:26330542

  10. A Robust Geometric Model for Argument Classification

    NASA Astrophysics Data System (ADS)

    Giannone, Cristina; Croce, Danilo; Basili, Roberto; de Cao, Diego

    Argument classification is the task of assigning semantic roles to syntactic structures in natural language sentences. Supervised learning techniques for frame semantics have been recently shown to benefit from rich sets of syntactic features. However argument classification is also highly dependent on the semantics of the involved lexicals. Empirical studies have shown that domain dependence of lexical information causes large performance drops in outside domain tests. In this paper a distributional approach is proposed to improve the robustness of the learning model against out-of-domain lexical phenomena.

  11. 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.

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

    PubMed

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

    2010-03-23

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

  13. Calcium binding to calmodulin mutants monitored by domain-specific intrinsic phenylalanine and tyrosine fluorescence.

    PubMed Central

    VanScyoc, Wendy S; Sorensen, Brenda R; Rusinova, Elena; Laws, William R; Ross, J B Alexander; Shea, Madeline A

    2002-01-01

    Cooperative calcium binding to the two homologous domains of calmodulin (CaM) induces conformational changes that regulate its association with and activation of numerous cellular target proteins. Calcium binding to the pair of high-affinity sites (III and IV in the C-domain) can be monitored by observing calcium-dependent changes in intrinsic tyrosine fluorescence intensity (lambda(ex)/lambda(em) of 277/320 nm). However, calcium binding to the low-affinity sites (I and II in the N-domain) is more difficult to measure with optical spectroscopy because that domain of CaM does not contain tryptophan or tyrosine. We recently demonstrated that calcium-dependent changes in intrinsic phenylalanine fluorescence (lambda(ex)/lambda(em) of 250/280 nm) of an N-domain fragment of CaM reflect occupancy of sites I and II (VanScyoc, W. S., and M. A. Shea, 2001, Protein Sci. 10:1758-1768). Using steady-state and time-resolved fluorescence methods, we now show that these excitation and emission wavelength pairs for phenylalanine and tyrosine fluorescence can be used to monitor equilibrium calcium titrations of the individual domains in full-length CaM. Calcium-dependent changes in phenylalanine fluorescence specifically indicate ion occupancy of sites I and II in the N-domain because phenylalanine residues in the C-domain are nonemissive. Tyrosine emission from the C-domain does not interfere with phenylalanine fluorescence signals from the N-domain. This is the first demonstration that intrinsic fluorescence may be used to monitor calcium binding to each domain of CaM. In this way, we also evaluated how mutations of two residues (Arg74 and Arg90) located between sites II and III can alter the calcium-binding properties of each of the domains. The mutation R74A caused an increase in the calcium affinity of sites I and II in the N-domain. The mutation R90A caused an increase in calcium affinity of sites III and IV in the C-domain whereas R90G caused an increase in calcium affinity of sites in both domains. This approach holds promise for exploring the linked energetics of calcium binding and target recognition. PMID:12414709

  14. Magnetic skin layer of NiO(100) probed by polarization-dependent spectromicroscopy

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

    Mandal, Suman, E-mail: suman.mandal@sscu.iisc.ernet.in; Menon, Krishnakumar S. R., E-mail: krishna.menon@saha.ac.in; Belkhou, Rachid

    2014-06-16

    Using polarization-dependent x-ray photoemission electron microscopy, we have investigated the surface effects on antiferromagnetic (AFM) domain formation. Depth-resolved information obtained from our study indicates the presence of strain-induced surface AFM domains on some of the cleaved NiO(100) crystals, which are unusually thinner than bulk AFM domain wall widths (∼150 nm). Existence of such magnetic skin layer is substantiated by exchange-coupled ferromagnetic Fe domains in Fe/NiO(100), thereby evidencing the influence of this surface AFM domains on interfacial magnetic coupling. Our observations demonstrate a depth evolution of AFM structure in presence of induced surface strain, while the surface symmetry-breaking in absence of inducedmore » strain does not modify the bulk AFM domain structure. Realization of such thin surface AFM layer will provide better microscopic understanding of the exchange bias phenomena.« less

  15. Thickness, humidity, and polarization dependent ferroelectric switching and conductivity in Mg doped lithium niobate

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

    Neumayer, Sabine M.; Rodriguez, Brian J., E-mail: brian.rodriguez@ucd.ie; Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4

    2015-12-28

    Mg doped lithium niobate (Mg:LN) exhibits several advantages over undoped LN such as resistance to photorefraction, lower coercive fields, and p-type conductivity that is particularly pronounced at domain walls and opens up a range of applications, e.g., in domain wall electronics. Engineering of precise domain patterns necessitates well founded knowledge of switching kinetics, which can differ significantly from that of undoped LN. In this work, the role of humidity and sample composition in polarization reversal has been investigated under application of the same voltage waveform. Control over domain sizes has been achieved by varying the sample thickness and initial polarizationmore » as well as atmospheric conditions. In addition, local introduction of proton exchanged phases allows for inhibition of domain nucleation or destabilization, which can be utilized to modify domain patterns. Polarization dependent current flow, attributed to charged domain walls and band bending, demonstrates the rectifying ability of Mg:LN in combination with suitable metal electrodes that allow for further tailoring of conductivity.« less

  16. Measuring determinants of career satisfaction of anesthesiologists: validation of a survey instrument.

    PubMed

    Afonso, Anoushka M; Diaz, James H; Scher, Corey S; Beyl, Robbie A; Nair, Singh R; Kaye, Alan David

    2013-06-01

    To measure the parameter of job satisfaction among anesthesiologists. Survey instrument. Academic anesthesiology departments in the United States. 320 anesthesiologists who attended the annual meeting of the ASA in 2009 (95% response rate). The anonymous 50-item survey collected information on 26 independent demographic variables and 24 dependent ranked variables of career satisfaction among practicing anesthesiologists. Mean survey scores were calculated for each demographic variable and tested for statistically significant differences by analysis of variance. Questions within each domain that were internally consistent with each other within domains were identified by Cronbach's alpha ≥ 0.7. P-values ≤ 0.05 were considered statistically significant. Cronbach's alpha analysis showed strong internal consistency for 10 dependent outcome questions in the practice factor-related domain (α = 0.72), 6 dependent outcome questions in the peer factor-related domain (α = 0.71), and 8 dependent outcome questions in the personal factor-related domain (α = 0.81). Although age was not a variable, full-time status, early satisfaction within the first 5 years of practice, working with respected peers, and personal choice factors were all significantly associated with anesthesiologist job satisfaction. Improvements in factors related to job satisfaction among anesthesiologists may lead to higher early and current career satisfaction. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. A filter-mediated communication model for design collaboration in building construction.

    PubMed

    Lee, Jaewook; Jeong, Yongwook; Oh, Minho; Hong, Seung Wan

    2014-01-01

    Multidisciplinary collaboration is an important aspect of modern engineering activities, arising from the growing complexity of artifacts whose design and construction require knowledge and skills that exceed the capacities of any one professional. However, current collaboration in the architecture, engineering, and construction industries often fails due to lack of shared understanding between different participants and limitations of their supporting tools. To achieve a high level of shared understanding, this study proposes a filter-mediated communication model. In the proposed model, participants retain their own data in the form most appropriate for their needs with domain-specific filters that transform the neutral representations into semantically rich ones, as needed by the participants. Conversely, the filters can translate semantically rich, domain-specific data into a neutral representation that can be accessed by other domain-specific filters. To validate the feasibility of the proposed model, we computationally implement the filter mechanism and apply it to a hypothetical test case. The result acknowledges that the filter mechanism can let the participants know ahead of time what will be the implications of their proposed actions, as seen from other participants' points of view.

  18. Recommendations from Transgender Healthcare Consumers in Rural Areas

    PubMed Central

    Knutson, Douglas; Martyr, Meredith A.; Mitchell, Travis A.; Arthur, Tori; Koch, Julie M.

    2018-01-01

    Abstract Purpose: Scholars indicate that rates of mental and physical health issues (e.g., substance use, anxiety, depression) may be much higher among transgender individuals relative to the general population. This disparity may be even greater for transgender individuals in rural areas. Clinical researchers suggest using affirmative therapeutic approaches and interventions to address the health concerns of transgender individuals, specifically to connect individuals with the transgender community. However, little is known about the content of information that is shared in transgender communities in rural areas. Method: For this qualitative study, researchers asked transgender individuals in rural areas (n=10) what recommendations they would offer to other transgender individuals in rural areas regarding healthcare access. Results: Results were organized into four domains: Access care, Quality control, Difficulties, and Mentorship. Within these domains, we identified 11 sub-domains: Get physical healthcare, Get mental healthcare, Provider search, Provider vetting, Treatment verification, It will be difficult, Know who you are, Believe in yourself, Move, Connect to community, and Other. Conclusions: We discuss implications of our findings for healthcare provision in rural areas, and we provide recommendations for future research.

  19. The PPARγ2 A/B-Domain Plays a Gene-Specific Role in Transactivation and Cofactor Recruitment

    PubMed Central

    Bugge, Anne; Grøntved, Lars; Aagaard, Mads M.; Borup, Rehannah; Mandrup, Susanne

    2009-01-01

    We have previously shown that adenoviral expression of peroxisome proliferator-activated receptors (PPARs) leads to rapid establishment of transcriptionally active complexes and activation of target gene expression within 5–8 h after transduction. Here we have used the adenoviral delivery system combined with expression array analysis to identify novel putative PPARγ target genes in murine fibroblasts and to determine the role of the A/B-domain in PPARγ-mediated transactivation of genomic target genes. Of the 257 genes found to be induced by PPARγ2 expression, only 25 displayed A/B-domain dependency, i.e. significantly reduced induction in the cells expressing the truncated PPARγ lacking the A/B-domain (PPARγCDE). Nine of the 25 A/B-domain-dependent genes were involved in lipid storage, and in line with this, triglyceride accumulation was considerably decreased in the cells expressing PPARγCDE compared with cells expressing full-length PPARγ2. Using chromatin immunoprecipitation, we demonstrate that PPARγ binding to genomic target sites and recruitment of the mediator component TRAP220/MED1/PBP/DRIP205 is not affected by the deletion of the A/B-domain. By contrast, the PPARγ-mediated cAMP response element-binding protein (CREB)-binding protein (CBP) and p300 recruitment to A/B-domain-dependent target genes is compromised by deletion of the A/B-domain. These results indicate that the A/B-domain of PPARγ2 is specifically involved in the recruitment or stabilization of CBP- and p300-containing cofactor complexes to a subset of target genes. PMID:19282365

  20. The Ecology of Technological Progress: How Symbiosis and Competition Affect the Growth of Technology Domains

    ERIC Educational Resources Information Center

    Carnabuci, Gianluca

    2010-01-01

    We show that the progress of technological knowledge is an inherently ecological process, wherein the growth rate of each technology domain depends on dynamics occurring in "other" technology domains. We identify two sources of ecological interdependence among technology domains. First, there are symbiotic interdependencies, implying…

  1. SH2 dependent autophosphorylation within the Tec family kinase Itk

    PubMed Central

    Joseph, Raji E.; Severin, Andrew; Min, Lie; Fulton, D. Bruce; Andreotti, Amy H.

    2009-01-01

    The Tec family kinase, Itk, undergoes an in cis autophosphorylation on Y180 within its SH3 domain. Autophosphorylation of the Itk SH3 domain by the Itk kinase domain is strictly dependent on the presence of the intervening SH2 domain. A direct docking interaction between the Itk kinase and SH2 domains brings the Itk SH3 domain into the active site where Y180 is then phosphorylated. We now identify the residues on the surface of the Itk SH2 domain responsible for substrate docking and show that this SH2 surface mediates autophosphorylation in the full length Itk molecule. The canonical phospholigand binding site on the SH2 domain is not involved in substrate docking, instead the docking site consists of side chains from three loop regions (AB, EF and BG) and part of the βD strand. These results are extended into Btk, a Tec family kinase linked to the B cell deficiency X-linked agammaglobulinemia (XLA). Our results suggest that some XLA causing mutations might impair Btk phosphorylation. PMID:19523959

  2. Field driven magnetic racetrack memory accompanied with the interfacial Dzyaloshinskii-Moriya interaction

    NASA Astrophysics Data System (ADS)

    Kim, June-Seo; Lee, Hyeon-Jun; Hong, Jung-Il; You, Chun-Yeol

    2018-06-01

    The in-plane magnetic field pulse driven domain wall motion on a perpendicularly magnetized nanowire is numerically investigated by performing micromagnetic simulations and magnetic domain wall dynamics are evaluated analytically with one-dimensional collective coordinate models including the interfacial Dzyaloshinskii-Moriya interaction. With the action of the precession torque, the chirality and the magnetic field direction dependent displacements of the magnetic domain walls are clearly observed. In order to move Bloch type and Neel type domain walls, a longitudinal and a transverse in-plane magnetic field pulse are required, respectively. The domain wall type (Bloch or Neel) can easily be determined by the dynamic motion of the domain walls under the applied pulse fields. By applying a temporally asymmetric in-plane field pulse and successive notches in the perpendicularly magnetized nanowire strip line with a proper interval, the concept of racetrack memory based on the synchronous displacements of the chirality dependent multiple domain walls is verified to be feasible. Requirement of multiple domain walls with homogeneous chirality is achieved with the help of Dzyaloshinskii-Moriya interaction.

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

    NASA Astrophysics Data System (ADS)

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

    2010-07-01

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

  4. SH2-dependent autophosphorylation within the Tec family kinase Itk.

    PubMed

    Joseph, Raji E; Severin, Andrew; Min, Lie; Fulton, D Bruce; Andreotti, Amy H

    2009-08-07

    The Tec family kinase, Itk (interleukin-2 tyrosine kinase), undergoes an in cis autophosphorylation on Y180 within its Src homology 3 (SH3) domain. Autophosphorylation of the Itk SH3 domain by the Itk kinase domain is strictly dependent on the presence of the intervening Src homology 2 (SH2) domain. A direct docking interaction between the Itk kinase and SH2 domains brings the Itk SH3 domain into the active site where Y180 is then phosphorylated. We now identify the residues on the surface of the Itk SH2 domain responsible for substrate docking and show that this SH2 surface mediates autophosphorylation in the full-length Itk molecule. The canonical phospholigand binding site on the SH2 domain is not involved in substrate docking, instead the docking site consists of side chains from three loop regions (AB, EF and BG) and part of the betaD strand. These results are extended into Btk (Bruton's tyrosine kinase), a Tec family kinase linked to the B-cell deficiency X-linked agammaglobulinemia (XLA). Our results suggest that some XLA-causing mutations might impair Btk phosphorylation.

  5. Phenotype Instance Verification and Evaluation Tool (PIVET): A Scaled Phenotype Evidence Generation Framework Using Web-Based Medical Literature.

    PubMed

    Henderson, Jette; Ke, Junyuan; Ho, Joyce C; Ghosh, Joydeep; Wallace, Byron C

    2018-05-04

    Researchers are developing methods to automatically extract clinically relevant and useful patient characteristics from raw healthcare datasets. These characteristics, often capturing essential properties of patients with common medical conditions, are called computational phenotypes. Being generated by automated or semiautomated, data-driven methods, such potential phenotypes need to be validated as clinically meaningful (or not) before they are acceptable for use in decision making. The objective of this study was to present Phenotype Instance Verification and Evaluation Tool (PIVET), a framework that uses co-occurrence analysis on an online corpus of publically available medical journal articles to build clinical relevance evidence sets for user-supplied phenotypes. PIVET adopts a conceptual framework similar to the pioneering prototype tool PheKnow-Cloud that was developed for the phenotype validation task. PIVET completely refactors each part of the PheKnow-Cloud pipeline to deliver vast improvements in speed without sacrificing the quality of the insights PheKnow-Cloud achieved. PIVET leverages indexing in NoSQL databases to efficiently generate evidence sets. Specifically, PIVET uses a succinct representation of the phenotypes that corresponds to the index on the corpus database and an optimized co-occurrence algorithm inspired by the Aho-Corasick algorithm. We compare PIVET's phenotype representation with PheKnow-Cloud's by using PheKnow-Cloud's experimental setup. In PIVET's framework, we also introduce a statistical model trained on domain expert-verified phenotypes to automatically classify phenotypes as clinically relevant or not. Additionally, we show how the classification model can be used to examine user-supplied phenotypes in an online, rather than batch, manner. PIVET maintains the discriminative power of PheKnow-Cloud in terms of identifying clinically relevant phenotypes for the same corpus with which PheKnow-Cloud was originally developed, but PIVET's analysis is an order of magnitude faster than that of PheKnow-Cloud. Not only is PIVET much faster, it can be scaled to a larger corpus and still retain speed. We evaluated multiple classification models on top of the PIVET framework and found ridge regression to perform best, realizing an average F1 score of 0.91 when predicting clinically relevant phenotypes. Our study shows that PIVET improves on the most notable existing computational tool for phenotype validation in terms of speed and automation and is comparable in terms of accuracy. ©Jette Henderson, Junyuan Ke, Joyce C Ho, Joydeep Ghosh, Byron C Wallace. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 04.05.2018.

  6. Phenotype Instance Verification and Evaluation Tool (PIVET): A Scaled Phenotype Evidence Generation Framework Using Web-Based Medical Literature

    PubMed Central

    Ke, Junyuan; Ho, Joyce C; Ghosh, Joydeep; Wallace, Byron C

    2018-01-01

    Background Researchers are developing methods to automatically extract clinically relevant and useful patient characteristics from raw healthcare datasets. These characteristics, often capturing essential properties of patients with common medical conditions, are called computational phenotypes. Being generated by automated or semiautomated, data-driven methods, such potential phenotypes need to be validated as clinically meaningful (or not) before they are acceptable for use in decision making. Objective The objective of this study was to present Phenotype Instance Verification and Evaluation Tool (PIVET), a framework that uses co-occurrence analysis on an online corpus of publically available medical journal articles to build clinical relevance evidence sets for user-supplied phenotypes. PIVET adopts a conceptual framework similar to the pioneering prototype tool PheKnow-Cloud that was developed for the phenotype validation task. PIVET completely refactors each part of the PheKnow-Cloud pipeline to deliver vast improvements in speed without sacrificing the quality of the insights PheKnow-Cloud achieved. Methods PIVET leverages indexing in NoSQL databases to efficiently generate evidence sets. Specifically, PIVET uses a succinct representation of the phenotypes that corresponds to the index on the corpus database and an optimized co-occurrence algorithm inspired by the Aho-Corasick algorithm. We compare PIVET’s phenotype representation with PheKnow-Cloud’s by using PheKnow-Cloud’s experimental setup. In PIVET’s framework, we also introduce a statistical model trained on domain expert–verified phenotypes to automatically classify phenotypes as clinically relevant or not. Additionally, we show how the classification model can be used to examine user-supplied phenotypes in an online, rather than batch, manner. Results PIVET maintains the discriminative power of PheKnow-Cloud in terms of identifying clinically relevant phenotypes for the same corpus with which PheKnow-Cloud was originally developed, but PIVET’s analysis is an order of magnitude faster than that of PheKnow-Cloud. Not only is PIVET much faster, it can be scaled to a larger corpus and still retain speed. We evaluated multiple classification models on top of the PIVET framework and found ridge regression to perform best, realizing an average F1 score of 0.91 when predicting clinically relevant phenotypes. Conclusions Our study shows that PIVET improves on the most notable existing computational tool for phenotype validation in terms of speed and automation and is comparable in terms of accuracy. PMID:29728351

  7. pH-dependent electron transfer reaction and direct bioelectrocatalysis of the quinohemoprotein pyranose dehydrogenase

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

    Takeda, Kouta; Matsumura, Hirotoshi; Ishida, Takuya

    A pyranose dehydrogenase from Coprinopsis cinerea (CcPDH) is an extracellular quinohemoeprotein, which consists a b-type cytochrome domain, a pyrroloquinoline-quinone (PQQ) domain, and a family 1-type carbohydrate-binding module. The electron transfer reaction of CcPDH was studied using some electron acceptors and a carbon electrode at various pH levels. Phenazine methosulfate (PMS) reacted directly at the PQQ domain, whereas cytochrome c (cyt c) reacted via the cytochrome domain of intact CcPDH. Thus, electrons are transferred from reduced PQQ in the catalytic domain of CcPDH to heme b in the N-terminal cytochrome domain, which acts as a built-in mediator and transfers electron tomore » a heterogenous electron transfer protein. The optimal pH values of the PMS reduction (pH 6.5) and the cyt c reduction (pH 8.5) differ. The catalytic currents for the oxidation of L-fucose were observed within a range of pH 4.5 to 11. Bioelectrocatalysis of CcPDH based on direct electron transfer demonstrated that the pH profile of the biocatalytic current was similar to the reduction activity of cyt c characters. - Highlights: • pH dependencies of activity were different for the reduction of cyt c and DCPIP. • DET-based bioelectrocatalysis of CcPDH was observed. • The similar pH-dependent profile was found with cyt c and electrode. • The present results suggested that IET reaction of CcPDH shows pH dependence.« less

  8. Knowledge vs. Action: Discrepancies in University Students' Knowledge about and Self-Reported Use of Self-Regulated Learning Strategies.

    PubMed

    Foerst, Nora M; Klug, Julia; Jöstl, Gregor; Spiel, Christiane; Schober, Barbara

    2017-01-01

    University students are supposed to be autonomous learners, able to adapt to an educational environment significantly less guided than school. Entering higher education poses a challenge of self-regulation, in which beginning students are often not prepared with self-regulation strategies needed. Since there are many studies assessing self-regulated learning (SRL) via classical self-reports, we know a lot about how students generally self-assess their SRL strategies. However, SRL and performance do not always correlate highly in these studies. The aim of the present study is to determine whether there are discrepancies between students' knowledge about SRL and their action in applying adequate SRL strategies in relevant learning situations. We also want to know whether such discrepancies generalize across domains and what the reasons for discrepancies are. The situation-specific Self-Regulated Learning Questionnaire for Action and Knowledge (SRL-QuAK) was used in a sample of 408 psychology and economic sciences students. Descriptive data analysis was conducted to determine potential discrepancies between SRL knowledge and action and differences between the study domains in an explorative way. The reasons for not using SRL-strategies were derived via qualitative content analysis. The results showed that although students had quite advanced knowledge of SRL strategies, they did not put this knowledge into action. This dissonance between SRL knowledge and action was found in both domains. In terms of reasons, students stated that they (a) lacked the time to use SRL strategies, (b) would not benefit from SRL strategies in the given situation, (c) would not be able to put the strategies to use effectively or (d) found it too arduous to use SRL strategies. The implications of these results will be discussed, e.g., the consequences for measures to overcome students' dissonance between knowledge and action and therefore to promote academic performance and well-being.

  9. Knowledge vs. Action: Discrepancies in University Students' Knowledge about and Self-Reported Use of Self-Regulated Learning Strategies

    PubMed Central

    Foerst, Nora M.; Klug, Julia; Jöstl, Gregor; Spiel, Christiane; Schober, Barbara

    2017-01-01

    University students are supposed to be autonomous learners, able to adapt to an educational environment significantly less guided than school. Entering higher education poses a challenge of self-regulation, in which beginning students are often not prepared with self-regulation strategies needed. Since there are many studies assessing self-regulated learning (SRL) via classical self-reports, we know a lot about how students generally self-assess their SRL strategies. However, SRL and performance do not always correlate highly in these studies. The aim of the present study is to determine whether there are discrepancies between students' knowledge about SRL and their action in applying adequate SRL strategies in relevant learning situations. We also want to know whether such discrepancies generalize across domains and what the reasons for discrepancies are. The situation-specific Self-Regulated Learning Questionnaire for Action and Knowledge (SRL-QuAK) was used in a sample of 408 psychology and economic sciences students. Descriptive data analysis was conducted to determine potential discrepancies between SRL knowledge and action and differences between the study domains in an explorative way. The reasons for not using SRL-strategies were derived via qualitative content analysis. The results showed that although students had quite advanced knowledge of SRL strategies, they did not put this knowledge into action. This dissonance between SRL knowledge and action was found in both domains. In terms of reasons, students stated that they (a) lacked the time to use SRL strategies, (b) would not benefit from SRL strategies in the given situation, (c) would not be able to put the strategies to use effectively or (d) found it too arduous to use SRL strategies. The implications of these results will be discussed, e.g., the consequences for measures to overcome students' dissonance between knowledge and action and therefore to promote academic performance and well-being. PMID:28798713

  10. Tyrosine Kinase 2-mediated Signal Transduction in T Lymphocytes Is Blocked by Pharmacological Stabilization of Its Pseudokinase Domain*

    PubMed Central

    Tokarski, John S.; Zupa-Fernandez, Adriana; Tredup, Jeffrey A.; Pike, Kristen; Chang, ChiehYing; Xie, Dianlin; Cheng, Lihong; Pedicord, Donna; Muckelbauer, Jodi; Johnson, Stephen R.; Wu, Sophie; Edavettal, Suzanne C.; Hong, Yang; Witmer, Mark R.; Elkin, Lisa L.; Blat, Yuval; Pitts, William J.; Weinstein, David S.; Burke, James R.

    2015-01-01

    Inhibition of signal transduction downstream of the IL-23 receptor represents an intriguing approach to the treatment of autoimmunity. Using a chemogenomics approach marrying kinome-wide inhibitory profiles of a compound library with the cellular activity against an IL-23-stimulated transcriptional response in T lymphocytes, a class of inhibitors was identified that bind to and stabilize the pseudokinase domain of the Janus kinase tyrosine kinase 2 (Tyk2), resulting in blockade of receptor-mediated activation of the adjacent catalytic domain. These Tyk2 pseudokinase domain stabilizers were also shown to inhibit Tyk2-dependent signaling through the Type I interferon receptor but not Tyk2-independent signaling and transcriptional cellular assays, including stimulation through the receptors for IL-2 (JAK1- and JAK3-dependent) and thrombopoietin (JAK2-dependent), demonstrating the high functional selectivity of this approach. A crystal structure of the pseudokinase domain liganded with a representative example showed the compound bound to a site analogous to the ATP-binding site in catalytic kinases with features consistent with high ligand selectivity. The results support a model where the pseudokinase domain regulates activation of the catalytic domain by forming receptor-regulated inhibitory interactions. Tyk2 pseudokinase stabilizers, therefore, represent a novel approach to the design of potent and selective agents for the treatment of autoimmunity. PMID:25762719

  11. Mutational analyses of Aquifex pyrophilus DNA ligase define essential domains for self-adenylation and DNA binding activity.

    PubMed

    Lim, J H; Choi, J; Kim, W; Ahn, B Y; Han, Y S

    2001-04-15

    We constructed nine deletion mutants of NAD+-dependent DNA ligase from Aquifex pyrophilus to characterize the functional domains. All of DNA ligase deletion mutants were analyzed in biochemical assays for NAD+-dependent self-adenylation, DNA binding, and nick-closing activity. Although the mutant lsub1 (91-362) included the active site lysine (KxDG), self-adenylation was not shown. However, the mutants lsub6 (1-362), lsub7 (1-516), and lsub9 (1-635) showed the same adenylation activity as that of wild type. The lsub5 (91-719), which has the C-terminal domain (487-719) as to lsub4 (91-486), showed minimal adenylation activity. These results suggest that the presence of N-terminal 90 residues is essential for the formation of an enzyme-AMP complex, while C-terminal domain (487-719) appears to play a minimal role in adenylation. It was found that the presence of C-terminal domain (487-719) is indispensable for DNA binding activity of lsub5 (91-719). The mutant lsub9 (1-635) showed reduced DNA binding activity compared to that of wild type, suggesting the contribution of the domain (636-719) for the DNA binding activity. Thus, we concluded that the N-terminal 90 residues and C-terminal domain (487-719) of NAD+-dependent DNA ligase from A. pyrophilus are mutually indispensable for binding of DNA substrate.

  12. Estrogen Receptor α L543A,L544A Mutation Changes Antagonists to Agonists, Correlating with the Ligand Binding Domain Dimerization Associated with DNA Binding Activity*

    PubMed Central

    Arao, Yukitomo; Hamilton, Katherine J.; Coons, Laurel A.; Korach, Kenneth S.

    2013-01-01

    A ligand-dependent nuclear transcription factor, ERα has two transactivating functional domains (AF), AF-1 and AF-2. AF-1 is localized in the N-terminal region, and AF-2 is distributed in the C-terminal ligand-binding domain (LBD) of the ERα protein. Helix 12 (H12) in the LBD is a component of the AF-2, and the configuration of H12 is ligand-inducible to an active or inactive form. We demonstrated previously that the ERα mutant (AF2ER) possessing L543A,L544A mutations in H12 disrupts AF-2 function and reverses antagonists such as fulvestrant/ICI182780 (ICI) or 4-hydoxytamoxifen (OHT) into agonists in the AF2ER knock-in mouse. Our previous in vitro studies suggested that the mode of AF2ER activation is similar to the partial agonist activity of OHT for WT-ERα. However, it is still unclear how antagonists activate ERα. To understand the molecular mechanism of antagonist reversal activity, we analyzed the correlation between the ICI-dependent estrogen-responsive element-mediated transcription activity of AF2ER and AF2ER-LBD dimerization activity. We report here that ICI-dependent AF2ER activation correlated with the activity of AF2ER-LBD homodimerization. Prevention of dimerization impaired the ICI-dependent ERE binding and transcription activity of AF2ER. The dislocation of H12 caused ICI-dependent LBD homodimerization involving the F-domain, the adjoining region of H12. Furthermore, F-domain truncation also strongly depressed the dimerization of WT-ERα-LBD with antagonists but not with E2. AF2ER activation levels with ICI, OHT, and raloxifene were parallel with the degree of AF2ER-LBD homodimerization, supporting a mechanism that antagonist-dependent LBD homodimerization involving the F-domain results in antagonist reversal activity of H12-mutated ERα. PMID:23733188

  13. Mesencephalic basolateral domain specification is dependent on Sonic Hedgehog

    PubMed Central

    Martinez-Lopez, Jesus E.; Moreno-Bravo, Juan A.; Madrigal, M. Pilar; Martinez, Salvador; Puelles, Eduardo

    2015-01-01

    In the study of central nervous system morphogenesis, the identification of new molecular markers allows us to identify domains along the antero-posterior and dorso-ventral (DV) axes. In the past years, the alar and basal plates of the midbrain have been divided into different domains. The precise location of the alar-basal boundary is still under discussion. We have identified Barhl1, Nhlh1 and Six3 as appropriate molecular markers to the adjacent domains of this transition. The description of their expression patterns and the contribution to the different mesencephalic populations corroborated their role in the specification of these domains. We studied the influence of Sonic Hedgehog on these markers and therefore on the specification of these territories. The lack of this morphogen produced severe alterations in the expression pattern of Barhl1 and Nhlh1 with consequent misspecification of the basolateral (BL) domain. Six3 expression was apparently unaffected, however its distribution changed leading to altered basal domains. In this study we confirmed the localization of the alar-basal boundary dorsal to the BL domain and demonstrated that the development of the BL domain highly depends on Shh. PMID:25741244

  14. Shared cultural knowledge: Effects of music on young children’s social preferences

    PubMed Central

    Soley, Gaye; Spelke, Elizabeth S.

    2016-01-01

    Adults use cultural markers to discern the structure of the social landscape. Such markers may also influence the social preferences of young children, who tend to conform to their own group and prefer others who do so. However, the forces that propel these preferences are unknown. Here, we use social preferences based on music to investigate these forces in four- and five-year-old children. First, we establish that children prefer other children whose favorite songs are familiar to them. Then we show that this effect depends on shared knowledge: children both prefer others who know songs they themselves know, and avoid others who know songs they do not know, irrespective of the target children’s liking of the songs. These results suggest that young children have a remarkably selective sensitivity to shared cultural knowledge. Shared knowledge may be a powerful determinant of children’s social preferences, both because it underpins effective communication and because it is conveyed by others through social interactions and therefore can serve as a marker of social group identity. PMID:26773967

  15. Shared cultural knowledge: Effects of music on young children's social preferences.

    PubMed

    Soley, Gaye; Spelke, Elizabeth S

    2016-03-01

    Adults use cultural markers to discern the structure of the social landscape. Such markers may also influence the social preferences of young children, who tend to conform to their own group and prefer others who do so. However, the forces that propel these preferences are unknown. Here, we use social preferences based on music to investigate these forces in four- and five-year-old children. First, we establish that children prefer other children whose favorite songs are familiar to them. Then we show that this effect depends on shared knowledge: children both prefer others who know songs they themselves know, and avoid others who know songs they do not know, irrespective of the target children's liking of the songs. These results suggest that young children have a remarkably selective sensitivity to shared cultural knowledge. Shared knowledge may be a powerful determinant of children's social preferences, both because it underpins effective communication and because it is conveyed by others through social interactions and therefore can serve as a marker of social group identity. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Coexistence of domains with distinct order and polarity in fluid bacterial membranes.

    PubMed

    Vanounou, Sharon; Pines, Dina; Pines, Ehud; Parola, Abraham H; Fishov, Itzhak

    2002-07-01

    In this study we sought the detection and characterization of bacterial membrane domains. Fluorescence generalized polarization (GP) spectra of laurdan-labeled Escherichia coli and temperature dependencies of both laurdan's GP and fluorescence anisotropy of 1,3-diphenyl-1,3,5-hexatriene (DPH) (rDPH) affirmed that at physiological temperatures, the E. coli membrane is in a liquid-crystalline phase. However, the strong excitation wavelength dependence of rlaurdan at 37 degrees C reflects membrane heterogeneity. Time-resolved fluorescence emission spectra, which display distinct biphasic redshift kinetics, verified the coexistence of two subpopulations of laurdan. In the initial phase, <50 ps, the redshift in the spectral mass center is much faster for laurdan excited at the blue edge (350 nm), whereas at longer time intervals, similar kinetics is observed upon excitation at either blue or red edge (400 nm). Excitation in the blue region selects laurdan molecules presumably located in a lipid domain in which fast intramolecular relaxation and low anisotropy characterize laurdan's emission. In the proteo-lipid domain, laurdan motion and conformation are restricted as exhibited by a slower relaxation rate, higher anisotropy and a lower GP value. Triple-Gaussian decomposition of laurdan emission spectra showed a sharp phase transition in the temperature dependence of individual components when excited in the blue but not in the red region. At least two kinds of domains of distinct polarity and order are suggested to coexist in the liquid-crystalline bacterial membrane: a lipid-enriched and a proteolipid domain. In bacteria with chloramphenicol (Cam)-inhibited protein synthesis, laurdan showed reduced polarity and restoration of an isoemissive point in the temperature-dependent spectra. These results suggest a decrease in membrane heterogeneity caused by Cam-induced domain dissipation.

  17. RapA2 Is a Calcium-binding Lectin Composed of Two Highly Conserved Cadherin-like Domains That Specifically Recognize Rhizobium leguminosarum Acidic Exopolysaccharides*

    PubMed Central

    Abdian, Patricia L.; Caramelo, Julio J.; Ausmees, Nora; Zorreguieta, Angeles

    2013-01-01

    In silico analyses have revealed a conserved protein domain (CHDL) widely present in bacteria that has significant structural similarity to eukaryotic cadherins. A CHDL domain was shown to be present in RapA, a protein that is involved in autoaggregation of Rhizobium cells, biofilm formation, and adhesion to plant roots as shown by us and others. Structural similarity to cadherins suggested calcium-dependent oligomerization of CHDL domains as a mechanistic basis for RapA action. Here we show by circular dichroism spectroscopy, light scattering, isothermal titration calorimetry, and other methods that RapA2 from Rhizobium leguminosarum indeed exhibits a cadherin-like β-sheet conformation and that its proper folding and stability are dependent on the binding of one calcium ion per protein molecule. By further in silico analysis we also reveal that RapA2 consists of two CHDL domains and expand the range of CHDL-containing proteins in bacteria and archaea. However, light scattering assays at various concentrations of added calcium revealed that RapA2 formed neither homo-oligomers nor hetero-oligomers with RapB (a distinct CHDL protein), indicating that RapA2 does not mediate cellular interactions through a cadherin-like mechanism. Instead, we demonstrate that RapA2 interacts specifically with the acidic exopolysaccharides (EPSs) produced by R. leguminosarum in a calcium-dependent manner, sustaining a role of these proteins in the development of the biofilm matrix made of EPS. Because EPS binding by RapA2 can only be attributed to its two CHDL domains, we propose that RapA2 is a calcium-dependent lectin and that CHDL domains in various bacterial and archaeal proteins confer carbohydrate binding activity to these proteins. PMID:23235153

  18. Pepino mosaic virus RNA-Dependent RNA Polymerase POL Domain Is a Hypersensitive Response-Like Elicitor Shared by Necrotic and Mild Isolates.

    PubMed

    Sempere, Raquel N; Gómez-Aix, Cristina; Ruíz-Ramón, Fabiola; Gómez, Pedro; Hasiów-Jaroszewska, Beata; Sánchez-Pina, María Amelia; Aranda, Miguel A

    2016-04-01

    Pepino mosaic virus (PepMV) is an emerging pathogen that represents a serious threat to tomato production worldwide. PepMV-induced diseases manifest with a wide range of symptoms, including systemic necrosis. Our results showed that PepMV accumulation depends on the virus isolate, tomato cultivar, and environmental conditions, and associates with the development of necrosis. Substitution of lysine for glutamic acid at position 67 in the triple gene block 3 (TGB3) protein, previously described as a necrosis determinant, led to increased virus accumulation and was necessary but not sufficient to induce systemic necrosis. Systemic necrosis both in tomato and Nicotiana benthamiana shared hypersensitive response (HR) features, allowing the assessment of the role of different genomic regions on necrosis induction. Overexpression of both TGB3 and the polymerase domain (POL) of the RNA-dependent RNA polymerase (RdRp) resulted in necrosis, although only local expression of POL triggered HR-like symptoms. Our results also indicated that the necrosis-eliciting activity of POL resides in its highly conserved "palm" domain, and that necrosis was jasmonic acid-dependent but not salicylic acid-dependent. Altogether, our data suggest that the RdRp-POL domain plays an important role in PepMV necrosis induction, with necrosis development depending on the virus accumulation level, which can be modulated by the nature of TGB3, host genotype and environmental conditions.

  19. Optimal boundary regularity for a singular Monge-Ampère equation

    NASA Astrophysics Data System (ADS)

    Jian, Huaiyu; Li, You

    2018-06-01

    In this paper we study the optimal global regularity for a singular Monge-Ampère type equation which arises from a few geometric problems. We find that the global regularity does not depend on the smoothness of domain, but it does depend on the convexity of the domain. We introduce (a , η) type to describe the convexity. As a result, we show that the more convex is the domain, the better is the regularity of the solution. In particular, the regularity is the best near angular points.

  20. Human HLTF mediates postreplication repair by its HIRAN domain-dependent replication fork remodelling

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

    Achar, Yathish Jagadheesh; Balogh, David; Neculai, Dante

    Defects in the ability to respond properly to an unrepaired DNA lesion blocking replication promote genomic instability and cancer. Human HLTF, implicated in error-free replication of damaged DNA and tumour suppression, exhibits a HIRAN domain, a RING domain, and a SWI/SNF domain facilitating DNA-binding, PCNA-polyubiquitin-ligase, and dsDNA-translocase activities, respectively. Here, we investigate the mechanism of HLTF action with emphasis on its HIRAN domain. We found that in cells HLTF promotes the filling-in of gaps left opposite damaged DNA during replication, and this postreplication repair function depends on its HIRAN domain. Our biochemical assays show that HIRAN domain mutant HLTF proteinsmore » retain their ubiquitin ligase, ATPase and dsDNA translocase activities but are impaired in binding to a model replication fork. These data and our structural study indicate that the HIRAN domain recruits HLTF to a stalled replication fork, and it also provides the direction for the movement of the dsDNA translocase motor domain for fork reversal. We suggest functional similarities between the HIRAN, the OB, the HARP2, and other domains found in certain motor proteins, which may explain why only a subset of DNA translocases can carry out fork reversal.« less

  1. Human HLTF mediates postreplication repair by its HIRAN domain-dependent replication fork remodelling

    DOE PAGES

    Achar, Yathish Jagadheesh; Balogh, David; Neculai, Dante; ...

    2015-09-08

    Defects in the ability to respond properly to an unrepaired DNA lesion blocking replication promote genomic instability and cancer. Human HLTF, implicated in error-free replication of damaged DNA and tumour suppression, exhibits a HIRAN domain, a RING domain, and a SWI/SNF domain facilitating DNA-binding, PCNA-polyubiquitin-ligase, and dsDNA-translocase activities, respectively. Here, we investigate the mechanism of HLTF action with emphasis on its HIRAN domain. We found that in cells HLTF promotes the filling-in of gaps left opposite damaged DNA during replication, and this postreplication repair function depends on its HIRAN domain. Our biochemical assays show that HIRAN domain mutant HLTF proteinsmore » retain their ubiquitin ligase, ATPase and dsDNA translocase activities but are impaired in binding to a model replication fork. These data and our structural study indicate that the HIRAN domain recruits HLTF to a stalled replication fork, and it also provides the direction for the movement of the dsDNA translocase motor domain for fork reversal. We suggest functional similarities between the HIRAN, the OB, the HARP2, and other domains found in certain motor proteins, which may explain why only a subset of DNA translocases can carry out fork reversal.« less

  2. Density-Dependent Recruitment and Diapause in the Spring-Feeding Generation of Hemlock Woolly Adelgid (Hemiptera: Adelgidae) in Western North America.

    PubMed

    Weed, Aaron S; Elkinton, Joseph S; Lany, Nina K

    2016-12-01

    Insect populations are affected by density-dependent and density-independent factors, and knowing how these factors affect long-term population growth is critical to pest management. In this study, we experimentally manipulated densities of the hemlock woolly adelgid on eastern and western hemlock trees in the western USA to evaluate the effects of density and host species on hemlock woolly adelgid crawler colonization. We then followed development of hemlock woolly adelgid on each hemlock species. Settlement of crawlers was strongly density-dependent and consistent between host species. In addition, a period of hot days that coincided with the settlement of hemlock woolly adelgid crawlers put our experimental and naturally occurring populations into diapause during April. Diapause resulted in one generation that yr in our experimental population. Analyses of long-term air temperature records indicated that diapause-inducing temperatures in April similar to those observed in our experiment have occurred rarely since 1909 and the frequency of these events has not changed over time. Prior work suggests that hemlock woolly adelgid completes two generations per yr in the western USA with a diapause occurring in the summer. This typical life history reflects the long-term influence of regional average seasonal temperature patterns on development and the timing of diapause-inducing temperatures. However, the timing of unseasonal weather, such as the hot days observed in our experiment, occasionally changes life history trajectories from this normal pattern. Our results show that density-dependent and density-independent factors have strong effects on generational mortality and life history of hemlock woolly adelgid that are important to its population dynamics and management. Published by Oxford University Press on behalf of Entomological Society of America 2016. This work is written by US Government employees and is in the public domain in the US.

  3. The SRC homology 2 domain of Rin1 mediates its binding to the epidermal growth factor receptor and regulates receptor endocytosis.

    PubMed

    Barbieri, M Alejandro; Kong, Chen; Chen, Pin-I; Horazdovsky, Bruce F; Stahl, Philip D

    2003-08-22

    Activated epidermal growth factor receptors (EGFRs) recruit intracellular proteins that mediate receptor signaling and endocytic trafficking. Rin1, a multifunctional protein, has been shown to regulate EGFR internalization (1). Here we show that EGF stimulation induces a specific, rapid, and transient membrane recruitment of Rin1 and that recruitment is dependent on the Src homology 2 (SH2) domain of Rin1. Immunoprecipitation of EGFR is accompanied by co-immunoprecipitation of Rin1 in a time- and ligand-dependent manner. Association of Rin1 and specifically the SH2 domain of Rin1 with the EGFR was dependent on tyrosine phosphorylation of the intracellular domain of the EGFR. The recruitment of Rin1, observed by light microscopy, indicated that although initially cytosolic, Rin1 was recruited to both plasma membrane and endosomes following EGF addition. Moreover, the expression of the SH2 domain of Rin1 substantially impaired the internalization of EGF without affecting internalization of transferrin. Finally, we found that Rin1 co-immunoprecipitated with a number of tyrosine kinase receptors but not with cargo endocytic receptors. These results indicate that Rin1 provides a link via its SH2 domain between activated tyrosine kinase receptors and the endocytic pathway through the recruitment and activation of Rab5a.

  4. ABCA1-dependent sterol release: sterol molecule specificity and potential membrane domain for HDL biogenesis

    PubMed Central

    Yamauchi, Yoshio; Yokoyama, Shinji; Chang, Ta-Yuan

    2016-01-01

    Mammalian cells synthesize various sterol molecules, including the C30 sterol, lanosterol, as cholesterol precursors in the endoplasmic reticulum. The build-up of precursor sterols, including lanosterol, displays cellular toxicity. Precursor sterols are found in plasma HDL. How these structurally different sterols are released from cells is poorly understood. Here, we show that newly synthesized precursor sterols arriving at the plasma membrane (PM) are removed by extracellular apoA-I in a manner dependent on ABCA1, a key macromolecule for HDL biogenesis. Analysis of sterol molecules by GC-MS and tracing the fate of radiolabeled acetate-derived sterols in normal and mutant Niemann-Pick type C cells reveal that ABCA1 prefers newly synthesized sterols, especially lanosterol, as the substrates before they are internalized from the PM. We also show that ABCA1 resides in a cholesterol-rich membrane domain resistant to the mild detergent, Brij 98. Blocking ACAT activity increases the cholesterol contents of this domain. Newly synthesized C29/C30 sterols are transiently enriched within this domain, but rapidly disappear from this domain with a half-life of less than 1 h. Our work shows that substantial amounts of precursor sterols are transported to a certain PM domain and are removed by the ABCA1-dependent pathway. PMID:26497474

  5. Geothermal Heat Flux and Upper Mantle Viscosity across West Antarctica: Insights from the UKANET and POLENET Seismic Networks

    NASA Astrophysics Data System (ADS)

    O'Donnell, J. P.; Dunham, C.; Stuart, G. W.; Brisbourne, A.; Nield, G. A.; Whitehouse, P. L.; Hooper, A. J.; Nyblade, A.; Wiens, D.; Aster, R. C.; Anandakrishnan, S.; Huerta, A. D.; Wilson, T. J.; Winberry, J. P.

    2017-12-01

    Quantifying the geothermal heat flux at the base of ice sheets is necessary to understand their dynamics and evolution. The heat flux is a composite function of concentration of upper crustal radiogenic elements and flow of heat from the mantle into the crust. Radiogenic element concentration varies with tectonothermal age, while heat flow across the crust-mantle boundary depends on crustal and lithospheric thicknesses. Meanwhile, accurately monitoring current ice mass loss via satellite gravimetry or altimetry hinges on knowing the upper mantle viscosity structure needed to account for the superimposed glacial isostatic adjustment (GIA) signal in the satellite data. In early 2016 the UK Antarctic Network (UKANET) of 10 broadband seismometers was deployed for two years across the southern Antarctic Peninsula and Ellsworth Land. Using UKANET data in conjunction with seismic records from our partner US Polar Earth Observing Network (POLENET) and the Antarctic Seismographic Argentinian Italian Network (ASAIN), we have developed a 3D shear wave velocity model of the West Antarctic crust and uppermost mantle based on Rayleigh and Love wave phase velocity dispersion curves extracted from ambient noise cross-correlograms. We combine seismic receiver functions with the shear wave model to help constrain the depth to the crust-mantle boundary across West Antarctica and delineate tectonic domains. The shear wave model is subsequently converted to temperature using a database of densities and elastic properties of minerals common in crustal and mantle rocks, while the various tectonic domains are assigned upper crustal radiogenic element concentrations based on their inferred tectonothermal ages. We combine this information to map the basal geothermal heat flux variation across West Antarctica. Mantle viscosity depends on factors including temperature, grain size, the hydrogen content of olivine and the presence of melt. Using published mantle xenolith and magnetotelluric data to constrain grain size and hydrogen content, respectively, we use the temperature model to estimate the regional upper mantle viscosity structure. The viscosity information will be incorporated in a 3D GIA model that will better constrain estimates of current ice loss from the West Antarctic Ice Sheet.

  6. Can Earth Sciences Help Alleviate Global Poverty?

    NASA Astrophysics Data System (ADS)

    Mutter, J. C.

    2004-12-01

    Poverty is not properly described solely in terms of economics. Certainly the billion people living on less than a dollar a day are the extreme poor and the two billion people who are living today on two dollars a day or less are poor also. One third of all humans live in poverty today. But poverty concerns deprivation - of good health, adequate nutrition, adequate education, properly paid employment, clean water, adequate housing and good sanitation. It is a fundamental denial of opportunity and a violation of basic human rights. Despite its prevalence and persistence of poverty and the attention given it by many scholars, the causes of poverty are not well understood and hence interventions to bring poor societies out of their condition often fail. One commonly missed component in the search for solutions to poverty is the fundamental co-dependence between the state of the Earth and the state of human well-being. These relationships, are compelling but often indirect and non-linear and sometimes deeply nuanced. They are also largely empirical in nature, lacking theory or models that describe the nature of the relationships. So while it is quite apparent that the poorest people are much more vulnerable than the rich to the Earths excesses and even to relatively small natural variations in places where the base conditions are poor, we do not presently know whether the recognized vulnerability is both an outcome of poverty and a contributing cause. Are societies poor, or held from development out of poverty because of their particular relationship to Earth's natural systems? Does how we live depend on where we live? Providing answers to these questions is one of the most fundamental research challenges of our time. That research lies in a domain squarely at the boundary between the natural and social sciences and cannot be answered by studies in either domain alone. What is clear even now, is that an understanding of the Earth gained from the natural sciences is essential and could hold the key to making gains toward alleviating the burden of global poverty.

  7. Domain switching kinetics in ferroelectric-resistive BiFeO3 thin film memories

    NASA Astrophysics Data System (ADS)

    Meng, Jianwei; Jiang, Jun; Geng, Wenping; Chen, Zhihui; Zhang, Wei; Jiang, Anquan

    2015-02-01

    We fabricated (00l) BiFeO3 (BFO) thin films in different growth modes on SrRuO3/SrTiO3 substrates using a pulsed laser deposition technique. X-ray diffraction patterns show an out-of-plane lattice constant of 4.03 Å and ferroelectric polarization of 82 µC/cm2 for the BFO thin film in a layer-by-layer growth mode (2D-BFO), larger than 3.96 Å and 51 µC/cm2 for the thin film in the 3D-island formation growth mode (3D-BFO). The 2D-BFO thin film at 300 K shows switchable on/off diode currents upon polarization flipping near a negative coercive voltage, which is nevertheless absent from the above 3D-BFO thin film. From a positive-up-negative-down pulse characterization technique, we measured domain switching current transients as well as polarization-voltage (Pf-Vf) hysteresis loops in both semiconducting thin films. Pf-Vf hysteresis loops after 1 µs-retention time show the preferred domain orientation pointing to bottom electrodes in a 3D-BFO thin film. The poor retention of the domains pointing to top electrodes can be improved considerably in a 2D-BFO thin film. From these measurements, we extracted domain switching time dependence of coercive voltage at temperatures of 78-300 K. From these dependences, we found coercive voltages in semiconducting ferroelectric thin films much higher than those in insulating thin films, disobeying the traditional Merz equation. Finally, an equivalent resistance model in description of free-carrier compensation of the front domain boundary charge is developed to interpret this difference. This equivalent resistance can be coincidently extracted either from domain switching time dependence of coercive voltage or from applied voltage dependence of domain switching current, which drops almost linearly with the temperature until down to 0 in a ferroelectric insulator at 78 K.

  8. Agile battle management efficiency for command, control, communications, computers and intelligence (C4I)

    NASA Astrophysics Data System (ADS)

    Blasch, Erik; Bélanger, Micheline

    2016-05-01

    Various operations such as civil-military co-operation (CIMIC) affairs require orchestration of communications, assets, and actors. A key component includes technology advancements to enable coordination among people and machines the ability to know where things are, who to coordinate with, and open and consistent lines of communication. In this paper, we explore concepts of battle management (BM) to support high-tempo emergency response scenarios such as a disaster action response team (DART). Three concepts highlighted of agile battle management (ABM) include source orchestration (e.g., sensors and domains), battle management language (BML) development (e.g., software and ontologies), and command and control (C2) coordination (e.g., people and visualization); which require correlation and de-confliction. These concepts of ABM support the physical, information, and cognitive domains for efficient command, control, communications, and information (C3I) to synchronize data and people for efficient and effective operations.

  9. [Nurse undergraduate students' perception of quality of life].

    PubMed

    Bampi, Luciana Neves da Silva; Baraldi, Solange; Guilhem, Dirce; Pompeu, Rafaella Bizzo; Campos, Ana Carolina de Oliveira

    2013-06-01

    The research objective was to know nurse undergraduate students' perception of quality of life. A cross-sectional study was conducted from August 2010 to August 2011 with 56 nursing students of the Faculty of Health Sciences, University of Brasilia, Brazil. A specific questionnaire was used (sociodemographic, academic and health profile) and the WHOQOL-BREF. Statistical analyzes included a description of frequency, central tendency and dispersion measures, and comparison between domains. The Psychological and Environment domains were assessed as the best and worst scores, respectively. The facets called Thinking, learning, memory and concentration, Sleep and rest Energy and fatigue, Activities of daily living, Work Capacity, Participation in and opportunities for recreation/leisure activities,financial resources and negative feelings were affected. The facets with the worst score influenced negatively the quality of life for students and might trigger negative feelings such as bad mood, desperation anxiety and depression.

  10. From Blank Canvas to Masterwork: Creating a Professional Practice Model at a Magnet Hospital

    PubMed Central

    Tydings, Donna M.; Nickoley, Sue; Nichols, Lynn W.; Krenzer, Maureen E.

    2016-01-01

    Objective. The purpose of this study was to engage registered nurses (RNs) in the creation of a Professional Practice Model (PPM). Background. PPMs are essential as the philosophical underpinnings for nursing practice. The study institution created a new PPM utilizing the voice of their RNs. Methods. Qualitative inquiry with focus groups was conducted to explore RNs values and beliefs about their professional practice. Constant-comparative analysis was used to code data and identify domains. Results. The 92 RN participants represented diverse roles and practice settings. The four domains identified were caring, knowing, navigating, and leading. Conclusions. Nurse leaders face the challenge of assisting nurses in articulating their practice using a common voice. In this study, nurses described their identity, their roles, and how they envisioned nursing should be practiced. The results align with the ANCC Magnet® Model, ANA standards, and important foundational and organization specific documents. PMID:28097022

  11. Capturing the Integration of Practice-Based Learning with Beliefs, Values, and Attitudes using Modified Concept Mapping.

    PubMed

    Mcnaughton, Susan; Barrow, Mark; Bagg, Warwick; Frielick, Stanley

    2016-01-01

    Practice-based learning integrates the cognitive, psychomotor, and affective domains and is influenced by students' beliefs, values, and attitudes. Concept mapping has been shown to effectively demonstrate students' changing concepts and knowledge structures. This article discusses how concept mapping was modified to capture students' perceptions of the connections between the domains of thinking and knowing, emotions, behavior, attitudes, values, and beliefs and the specific experiences related to these, over a period of eight months of practice-based clinical learning. The findings demonstrate that while some limitations exist, modified concept mapping is a manageable way to gather rich data about students' perceptions of their clinical practice experiences. These findings also highlight the strong integrating influence of beliefs and values on other areas of practice, suggesting that these need to be attended to as part of a student's educational program.

  12. Capturing the Integration of Practice-Based Learning with Beliefs, Values, and Attitudes using Modified Concept Mapping

    PubMed Central

    Mcnaughton, Susan; Barrow, Mark; Bagg, Warwick; Frielick, Stanley

    2016-01-01

    Practice-based learning integrates the cognitive, psychomotor, and affective domains and is influenced by students’ beliefs, values, and attitudes. Concept mapping has been shown to effectively demonstrate students’ changing concepts and knowledge structures. This article discusses how concept mapping was modified to capture students’ perceptions of the connections between the domains of thinking and knowing, emotions, behavior, attitudes, values, and beliefs and the specific experiences related to these, over a period of eight months of practice-based clinical learning. The findings demonstrate that while some limitations exist, modified concept mapping is a manageable way to gather rich data about students’ perceptions of their clinical practice experiences. These findings also highlight the strong integrating influence of beliefs and values on other areas of practice, suggesting that these need to be attended to as part of a student's educational program. PMID:29349311

  13. Associations between attention deficit hyperactivity disorder symptom domains and DSM-IV lifetime substance dependence.

    PubMed

    Ameringer, Katherine J; Leventhal, Adam M

    2013-01-01

    Most studies of attention deficit hyperactivity disorder (ADHD) in the substance dependence literature have assessed ADHD as a single, categorical entity. This approach limits characterization across the spectrum of ADHD symptomatology and may mask differences across the two core domains of ADHD symptoms-hyperactive-impulsive (HI) and inattention (IN). Further, it is unclear whether relations of HI and IN symptoms to substance dependence extend across drug classes and to the general population. This cross-sectional study investigated associations of lifetime ADHD HI and IN symptom levels to individual classes of lifetime substance dependence (alcohol, nicotine, depressants, opioids, stimulants, cannabis, hallucinogens, polysubstance) in a population-based sample of 34,653 American adults. HI and IN were associated with the majority of dependence diagnoses in a linear pattern, such that each additional symptom was associated with a proportional increase in odds of dependence. After adjusting for the overlap between symptom domains, both HI and IN uniquely associated with alcohol, nicotine, and polysubstance dependence, but only HI uniquely associated with dependence on illicit substances. These findings suggest that individuals in the general population with elevated levels of ADHD (particularly HI) symptoms are at risk for various forms of substance dependence and could benefit from preventive interventions. Copyright © American Academy of Addiction Psychiatry.

  14. Associations between Attention Deficit Hyperactivity Disorder Symptom Domains and DSM-IV Lifetime Substance Dependence

    PubMed Central

    Ameringer, Katherine J.; Leventhal, Adam M.

    2013-01-01

    Background and Objectives Most studies of attention deficit hyperactivity disorder (ADHD) in the substance dependence literature have assessed ADHD as a single, categorical entity. This approach limits characterization across the spectrum of ADHD symptomatology and may mask differences across the two core domains of ADHD symptoms—hyperactive-impulsive (HI) and inattention (IN). Further, it is unclear whether relations of HI and IN symptoms to substance dependence extend across drug classes and to the general population. Methods This cross-sectional study investigated associations of lifetime ADHD HI and IN symptom levels to individual classes of lifetime substance dependence (alcohol, nicotine, depressants, opioids, stimulants, cannabis, hallucinogens, polysubstance) in a population-based sample of 34,653 American adults. Results HI and IN were associated with the majority of dependence diagnoses in a linear pattern, such that each additional symptom was associated with a proportional increase in odds of dependence. After adjusting for the overlap between symptom domains, both HI and IN uniquely associated with alcohol, nicotine, and polysubstance dependence, but only HI uniquely associated with dependence on illicit substances. Conclusions and Scientific Significance These findings suggest that individuals in the general population with elevated levels of ADHD (particularly HI) symptoms are at risk for various forms of substance dependence and could benefit from preventive interventions. PMID:23398223

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

    PubMed Central

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

    2015-01-01

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

  16. Structural analysis of an oxygen-regulated diguanylate cyclase.

    PubMed

    Tarnawski, Miroslaw; Barends, Thomas R M; Schlichting, Ilme

    2015-11-01

    Cyclic di-GMP is a bacterial second messenger that is involved in switching between motile and sessile lifestyles. Given the medical importance of biofilm formation, there has been increasing interest in understanding the synthesis and degradation of cyclic di-GMPs and their regulation in various bacterial pathogens. Environmental cues are detected by sensing domains coupled to GGDEF and EAL or HD-GYP domains that have diguanylate cyclase and phosphodiesterase activities, respectively, producing and degrading cyclic di-GMP. The Escherichia coli protein DosC (also known as YddV) consists of an oxygen-sensing domain belonging to the class of globin sensors that is coupled to a C-terminal GGDEF domain via a previously uncharacterized middle domain. DosC is one of the most strongly expressed GGDEF proteins in E. coli, but to date structural information on this and related proteins is scarce. Here, the high-resolution structural characterization of the oxygen-sensing globin domain, the middle domain and the catalytic GGDEF domain in apo and substrate-bound forms is described. The structural changes between the iron(III) and iron(II) forms of the sensor globin domain suggest a mechanism for oxygen-dependent regulation. The structural information on the individual domains is combined into a model of the dimeric DosC holoprotein. These findings have direct implications for the oxygen-dependent regulation of the activity of the cyclase domain.

  17. AKT-dependent phosphorylation of the SAM domain induces oligomerization and activation of the scaffold protein CNK1.

    PubMed

    Fischer, Adrian; Weber, Wilfried; Warscheid, Bettina; Radziwill, Gerald

    2017-01-01

    Scaffold proteins are hubs for the coordination of intracellular signaling networks. The scaffold protein CNK1 promotes several signal transduction pathway. Here we demonstrate that sterile motif alpha (SAM) domain-dependent oligomerization of CNK1 stimulates CNK1-mediated signaling in growth factor-stimulated cells. We identified Ser22 located within the SAM domain as AKT-dependent phosphorylation site triggering CNK1 oligomerization. Oligomeric CNK1 increased the affinity for active AKT indicating a positive AKT feedback mechanism. A CNK1 mutant lacking the SAM domain and the phosphorylation-defective mutant CNK1 S22A antagonizes oligomerization and prevents CNK1-driven cell proliferation and matrix metalloproteinase 14 promoter activation. The phosphomimetic mutant CNK1 S22D constitutively oligomerizes and stimulates CNK1 downstream signaling. Searching the COSMIC database revealed Ser22 as putative target for oncogenic activation of CNK1. Like the phosphomimetic mutant CNK1 S22D , the oncogenic mutant CNK1 S22F forms clusters in serum-starved cells comparable to clusters of CNK1 in growth factor-stimulated cells. CNK1 clusters induced by activating Ser22 mutants correlate with enhanced cell invasion and binding to and activation of ADP ribosylation factor 1 associated with tumor formation. Mutational analysis indicate that EGF-triggered phosphorylation of Thr8 within the SAM domain prevents AKT binding and antagonizes CNK1-mediated AKT signaling. Our findings reveal SAM domain-dependent oligomerization by AKT as switch for CNK1 activation. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. A Plant Immune Receptor Detects Pathogen Effectors that Target WRKY Transcription Factors.

    PubMed

    Sarris, Panagiotis F; Duxbury, Zane; Huh, Sung Un; Ma, Yan; Segonzac, Cécile; Sklenar, Jan; Derbyshire, Paul; Cevik, Volkan; Rallapalli, Ghanasyam; Saucet, Simon B; Wirthmueller, Lennart; Menke, Frank L H; Sohn, Kee Hoon; Jones, Jonathan D G

    2015-05-21

    Defense against pathogens in multicellular eukaryotes depends on intracellular immune receptors, yet surveillance by these receptors is poorly understood. Several plant nucleotide-binding, leucine-rich repeat (NB-LRR) immune receptors carry fusions with other protein domains. The Arabidopsis RRS1-R NB-LRR protein carries a C-terminal WRKY DNA binding domain and forms a receptor complex with RPS4, another NB-LRR protein. This complex detects the bacterial effectors AvrRps4 or PopP2 and then activates defense. Both bacterial proteins interact with the RRS1 WRKY domain, and PopP2 acetylates lysines to block DNA binding. PopP2 and AvrRps4 interact with other WRKY domain-containing proteins, suggesting these effectors interfere with WRKY transcription factor-dependent defense, and RPS4/RRS1 has integrated a "decoy" domain that enables detection of effectors that target WRKY proteins. We propose that NB-LRR receptor pairs, one member of which carries an additional protein domain, enable perception of pathogen effectors whose function is to target that domain. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Thickness, humidity, and polarization dependent ferroelectric switching and conductivity in Mg doped lithium niobate

    DOE PAGES

    Neumayer, Sabine M.; Strelcov, Evgheni; Manzo, Michele; ...

    2015-12-28

    Mg doped lithium niobate (Mg:LN) exhibits several advantages over undoped LN such as resistance to photorefraction, lower coercive fields, and p-type conductivity that is particularly pronounced at domain walls and opens up a range of applications, e.g., in domain wall electronics. Engineering of precise domain patterns necessitates well founded knowledge of switching kinetics, which can differ significantly from that of undoped LN. In this work, the role of humidity and sample composition in polarization reversal has been investigated under application of the same voltage waveform. Control over domain sizes has been achieved by varying the sample thickness and initial polarizationmore » as well as atmospheric conditions. Additionally, local introduction of proton exchanged phases allows for inhibition of domain nucleation or destabilization, which can be utilized to modify domain patterns. In polarization dependent current flow, attributed to charged domain walls and band bending, it the rectifying ability of Mg: LN in combination with suitable metal electrodes that allow for further tailoring of conductivity is demonstrated.« less

  20. How Many Words Do We Know? Practical Estimates of Vocabulary Size Dependent on Word Definition, the Degree of Language Input and the Participant’s Age

    PubMed Central

    Brysbaert, Marc; Stevens, Michaël; Mandera, Paweł; Keuleers, Emmanuel

    2016-01-01

    Based on an analysis of the literature and a large scale crowdsourcing experiment, we estimate that an average 20-year-old native speaker of American English knows 42,000 lemmas and 4,200 non-transparent multiword expressions, derived from 11,100 word families. The numbers range from 27,000 lemmas for the lowest 5% to 52,000 for the highest 5%. Between the ages of 20 and 60, the average person learns 6,000 extra lemmas or about one new lemma every 2 days. The knowledge of the words can be as shallow as knowing that the word exists. In addition, people learn tens of thousands of inflected forms and proper nouns (names), which account for the substantially high numbers of ‘words known’ mentioned in other publications. PMID:27524974

  1. Tunable inertia of chiral magnetic domain walls

    PubMed Central

    Torrejon, Jacob; Martinez, Eduardo; Hayashi, Masamitsu

    2016-01-01

    The time it takes to accelerate an object from zero to a given velocity depends on the applied force and the environment. If the force ceases, it takes exactly the same time to completely decelerate. A magnetic domain wall is a topological object that has been observed to follow this behaviour. Here we show that acceleration and deceleration times of chiral Neel walls driven by current are different in a system with low damping and moderate Dzyaloshinskii–Moriya exchange constant. The time needed to accelerate a domain wall with current via the spin Hall torque is much faster than the time it needs to decelerate once the current is turned off. The deceleration time is defined by the Dzyaloshinskii–Moriya exchange constant whereas the acceleration time depends on the spin Hall torque, enabling tunable inertia of chiral domain walls. Such unique feature of chiral domain walls can be utilized to move and position domain walls with lower current, key to the development of storage class memory devices. PMID:27882932

  2. ManUniCast: A Community Weather and Air-Quality Forecasting Teaching Portal

    NASA Astrophysics Data System (ADS)

    Schultz, David M.; Anderson, Stuart; Fairman, Jonathan G.; Lowe, Douglas; McFiggans, Gordon; Lee, Elsa; Seo-Zindy, Ryo

    2014-05-01

    Manunicast was borne out of the needs of our teaching program: students were entering a world where environmental prediction via numerical model was an essential skill, but were not exposed to the production or output of such models. Our site is an educational testbed to explain to students and the public how weather, air-quality, and air-chemistry forecasts are made using real-time predictions as examples. As far as we know, this site provides the first freely available real-time predictions for the UK. We perform two simulations a day over three domains using the most popular, freely available, community atmospheric mesoscale and chemistry models WRF-ARW and WRF-Chem: 1. a WRF-ARW domain over the North Atlantic and western Europe (20-km horizontal grid spacing) 2. a WRF-ARW domain over the UK and Ireland (4-km grid spacing, nested within the 20-km domain) 3. a WRF-Chem domain over the UK and Ireland (12-km grid spacing) Called ManUniCast (Manchester University Forecast), we offer a suite of products from horizontal maps, time series at stations (meteograms), skew-T-logp charts, and cross sections to help students better visualize the weather and the relationships between the various fields more effectively, specifically through the ability to overlay and fade between different plotted products. This presentation discusses how we funded and built ManUniCast, the struggles we faced, and its use in our classes.

  3. Sharing Service Resource Information for Application Integration in a Virtual Enterprise - Modeling the Communication Protocol for Exchanging Service Resource Information

    NASA Astrophysics Data System (ADS)

    Yamada, Hiroshi; Kawaguchi, Akira

    Grid computing and web service technologies enable us to use networked resources in a coordinated manner. An integrated service is made of individual services running on coordinated resources. In order to achieve such coordinated services autonomously, the initiator of a coordinated service needs to know detailed service resource information. This information ranges from static attributes like the IP address of the application server to highly dynamic ones like the CPU load. The most famous wide-area service discovery mechanism based on names is DNS. Its hierarchical tree organization and caching methods take advantage of the static information managed. However, in order to integrate business applications in a virtual enterprise, we need a discovery mechanism to search for the optimal resources based on the given a set of criteria (search keys). In this paper, we propose a communication protocol for exchanging service resource information among wide-area systems. We introduce the concept of the service domain that consists of service providers managed under the same management policy. This concept of the service domain is similar to that for autonomous systems (ASs). In each service domain, the service information provider manages the service resource information of service providers that exist in this service domain. The service resource information provider exchanges this information with other service resource information providers that belong to the different service domains. We also verified the protocol's behavior and effectiveness using a simulation model developed for proposed protocol.

  4. Interaction between RING1 (R1) and the Ubiquitin-like (UBL) Domains Is Critical for the Regulation of Parkin Activity*

    PubMed Central

    Ham, Su Jin; Lee, Soo Young; Song, Saera; Chung, Ju-Ryung; Choi, Sekyu; Chung, Jongkyeong

    2016-01-01

    Parkin is an E3 ligase that contains a ubiquitin-like (UBL) domain in the N terminus and an R1-in-between-ring-RING2 motif in the C terminus. We showed that the UBL domain specifically interacts with the R1 domain and negatively regulates Parkin E3 ligase activity, Parkin-dependent mitophagy, and Parkin translocation to the mitochondria. The binding between the UBL domain and the R1 domain was suppressed by carbonyl cyanide m-chlorophenyl hydrazone treatment or by expression of PTEN-induced putative kinase 1 (PINK1), an upstream kinase that phosphorylates Parkin at the Ser-65 residue of the UBL domain. Moreover, we demonstrated that phosphorylation of the UBL domain at Ser-65 prevents its binding to the R1 domain and promotes Parkin activities. We further showed that mitochondrial translocation of Parkin, which depends on phosphorylation at Ser-65, and interaction between the R1 domain and a mitochondrial outer membrane protein, VDAC1, are suppressed by binding of the UBL domain to the R1 domain. Interestingly, Parkin with missense mutations associated with Parkinson disease (PD) in the UBL domain, such as K27N, R33Q, and A46P, did not translocate to the mitochondria and induce E3 ligase activity by m-chlorophenyl hydrazone treatment, which correlated with the interaction between the R1 domain and the UBL domain with those PD mutations. These findings provide a molecular mechanism of how Parkin recruitment to the mitochondria and Parkin activation as an E3 ubiquitin ligase are regulated by PINK1 and explain the previously unknown mechanism of how Parkin mutations in the UBL domain cause PD pathogenesis. PMID:26631732

  5. Interaction between RING1 (R1) and the Ubiquitin-like (UBL) Domains Is Critical for the Regulation of Parkin Activity.

    PubMed

    Ham, Su Jin; Lee, Soo Young; Song, Saera; Chung, Ju-Ryung; Choi, Sekyu; Chung, Jongkyeong

    2016-01-22

    Parkin is an E3 ligase that contains a ubiquitin-like (UBL) domain in the N terminus and an R1-in-between-ring-RING2 motif in the C terminus. We showed that the UBL domain specifically interacts with the R1 domain and negatively regulates Parkin E3 ligase activity, Parkin-dependent mitophagy, and Parkin translocation to the mitochondria. The binding between the UBL domain and the R1 domain was suppressed by carbonyl cyanide m-chlorophenyl hydrazone treatment or by expression of PTEN-induced putative kinase 1 (PINK1), an upstream kinase that phosphorylates Parkin at the Ser-65 residue of the UBL domain. Moreover, we demonstrated that phosphorylation of the UBL domain at Ser-65 prevents its binding to the R1 domain and promotes Parkin activities. We further showed that mitochondrial translocation of Parkin, which depends on phosphorylation at Ser-65, and interaction between the R1 domain and a mitochondrial outer membrane protein, VDAC1, are suppressed by binding of the UBL domain to the R1 domain. Interestingly, Parkin with missense mutations associated with Parkinson disease (PD) in the UBL domain, such as K27N, R33Q, and A46P, did not translocate to the mitochondria and induce E3 ligase activity by m-chlorophenyl hydrazone treatment, which correlated with the interaction between the R1 domain and the UBL domain with those PD mutations. These findings provide a molecular mechanism of how Parkin recruitment to the mitochondria and Parkin activation as an E3 ubiquitin ligase are regulated by PINK1 and explain the previously unknown mechanism of how Parkin mutations in the UBL domain cause PD pathogenesis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Allosteric activation of apicomplexan calcium-dependent protein kinases

    DOE PAGES

    Ingram, Jessica R.; Knockenhauer, Kevin E.; Markus, Benedikt M.; ...

    2015-08-24

    Calcium-dependent protein kinases (CDPKs) comprise the major group of Ca 2+-regulated kinases in plants and protists. It has long been assumed that CDPKs are activated, like other Ca 2+-regulated kinases, by derepression of the kinase domain (KD). However, we found that removal of the autoinhibitory domain from Toxoplasma gondii CDPK1 is not sufficient for kinase activation. From a library of heavy chain-only antibody fragments (VHHs), we isolated an antibody (1B7) that binds TgCDPK1 in a conformation-dependent manner and potently inhibits it. We uncovered the molecular basis for this inhibition by solving the crystal structure of the complex and simulating, throughmore » molecular dynamics, the effects of 1B7–kinase interactions. In contrast to other Ca 2+-regulated kinases, the regulatory domain of TgCDPK1 plays a dual role, inhibiting or activating the kinase in response to changes in Ca 2+ concentrations. We propose that the regulatory domain of TgCDPK1 acts as a molecular splint to stabilize the otherwise inactive KD. This dependence on allosteric stabilization reveals a novel susceptibility in this important class of parasite enzymes.« less

  7. Experts’ and Novices’ Perception of Ignorance and Knowledge in Different Research Disciplines and Its Relation to Belief in Certainty of Knowledge

    PubMed Central

    Hansson, Isabelle; Buratti, Sandra; Allwood, Carl Martin

    2017-01-01

    Assessments of the extent of knowledge in a domain can be important since non-identified lack of knowledge may lead to decisions that do not consider the effect of relevant factors. Two studies examined experts’ and novices’ perception of their own ignorance and knowledge out of everything there is to know within their own and other disciplines and their assessments of their discipline’s, and other disciplines’ knowledge of all there is to know in each discipline. In total 380 experts and 401 students from the disciplines of history, medicine, physics, and psychology participated. The results for ignorance and knowledge assessments of one’s own knowledge were similar. Novices reported more ignorance and less knowledge in their own discipline than experts, but no differences were found in the assessments of how much is known in each discipline. General belief in certainty of knowledge was associated with the knowledge assessments and level of expertise. Finally, disciplinary differences were found both for the knowledge assessments and for belief in certainty of knowledge. Historians and physicists assessed that less was known in their own discipline out of all there is to know (approximately 40%), compared to the medics (about 50%). Historians believed least in certainty of knowledge and physicists most. Our results have practical implications for higher educational teaching and interdisciplinary collaboration. PMID:28367132

  8. The role of biotin and oxamate in the carboxyl transferase reaction of pyruvate carboxylase

    PubMed Central

    Lietzan, Adam D.; Lin, Yi; St. Maurice, Martin

    2014-01-01

    Pyruvate carboxylase (PC) is a biotin-dependent enzyme that catalyzes the MgATP-dependent carboxylation of pyruvate to oxaloacetate, an important anaplerotic reaction in central metabolism. During catalysis, carboxybiotin is translocated to the carboxyltransferase domain where the carboxyl group is transferred to the acceptor substrate, pyruvate. Many studies on the carboxyltransferase domain of PC have demonstrated an enhanced oxaloacetate decarboxylation activity in the presence of oxamate and it has been shown that oxamate accepts a carboxyl group from carboxybiotin during oxaloacetate decarboxylation. The X-ray crystal structure of the carboxyltransferase domain from Rhizobium etli PC reveals that oxamate is positioned in the active site in an identical manner to the substrate, pyruvate, and kinetic data are consistent with the oxamate-stimulated decarboxylation of oxaloacetate proceeding through a simple ping-pong bi bi mechanism in the absence of the biotin carboxylase domain. Additionally, analysis of truncated PC enzymes indicates that the BCCP domain devoid of biotin does not contribute directly to the enzymatic reaction and conclusively demonstrates a biotin-independent oxaloacetate decarboxylation activity in PC. These findings advance the description of catalysis in PC and can be extended to the study of related biotin-dependent enzymes. PMID:25157442

  9. Discovery of cancer drug targets by CRISPR-Cas9 screening of protein domains.

    PubMed

    Shi, Junwei; Wang, Eric; Milazzo, Joseph P; Wang, Zihua; Kinney, Justin B; Vakoc, Christopher R

    2015-06-01

    CRISPR-Cas9 genome editing technology holds great promise for discovering therapeutic targets in cancer and other diseases. Current screening strategies target CRISPR-Cas9-induced mutations to the 5' exons of candidate genes, but this approach often produces in-frame variants that retain functionality, which can obscure even strong genetic dependencies. Here we overcome this limitation by targeting CRISPR-Cas9 mutagenesis to exons encoding functional protein domains. This generates a higher proportion of null mutations and substantially increases the potency of negative selection. We also show that the magnitude of negative selection can be used to infer the functional importance of individual protein domains of interest. A screen of 192 chromatin regulatory domains in murine acute myeloid leukemia cells identifies six known drug targets and 19 additional dependencies. A broader application of this approach may allow comprehensive identification of protein domains that sustain cancer cells and are suitable for drug targeting.

  10. One-Dimensional Singlet Exciton Diffusion in Poly(3-hexylthiophene) Crystalline Domains.

    PubMed

    Tamai, Yasunari; Matsuura, Yuu; Ohkita, Hideo; Benten, Hiroaki; Ito, Shinzaburo

    2014-01-16

    Singlet exciton dynamics in crystalline domains of regioregular poly(3-hexylthiophene) (P3HT) films was studied by transient absorption spectroscopy. Upon the selective excitation of crystalline P3HT at the absorption edge, no red shift of the singlet exciton band was observed with an elapse of time, suggesting singlet exciton dynamics in relatively homogeneous P3HT crystalline domains without downhill relaxation in the energetic disorder. Even under such selective excitation conditions, the annihilation rate coefficient γ(t) was still dependent on time, γ(t) ∝ t(-1/2), which is attributed to anisotropic exciton diffusion in P3HT crystalline domains. From the annihilation rate coefficient, the singlet exciton diffusion coefficient D and exciton diffusion length LD in the crystalline domains were evaluated to be 7.9 × 10(-3) cm(2) s(-1) and 20 nm, respectively. The origin of the time-dependent exciton dynamics is discussed in terms of dimensionality.

  11. Children’s Safety Initiative: A National Assessment of Pediatric Educational Needs amongEmergency Medical Services Providers

    PubMed Central

    Hansen, Matthew; Meckler, Garth; Dickinson, Caitlyn; Dickenson, Kathryn; Jui, Jonathan; Lambert, William; Guise, Jeanne-Marie

    2014-01-01

    Objective Emergency Medical Services (EMS) providers may have critical knowledge gaps in pediatric care due to lack of exposure and training. There is currently little evidence to guide educators to the knowledge gaps most likely to improve patient safety. The objective of this study was to identify educational needs of EMS providers related to pediatric care in various domains in order to inform development of curricula. Methods The Children’s Safety Initiative-EMS performed a three-phase Delphi survey on patient safety in pediatric emergencies among providers and content experts in pediatric emergency care including physicians, nurses and pre-hospital providers of all levels. Each round included questions related to educational needs of providers or the effect of training on patient safety events. We identified knowledge gaps in the following domains: case exposure, competency and knowledge, assessment and decision making, and critical thinking and proficiency. Individual knowledge gaps were ranked by portion of respondents who ranked them “highly likely” (likert-type score 7–10 out of 10) to contribute to safety events. Results There were 737 respondents who were included in analysis of the first phase of the survey. Paramedics were 50.8% of respondents; EMT-Basics/first responders were 22% and physicians 11.4%. The top educational priorities identified in the final round of the survey include: pediatric airway management, responder anxiety when working with children, and general pediatric skills among providers. The top three needs in decision-making include knowing when to alter plans mid-course, knowing when to perform and advanced airway, and assessing pain in children. The top 3 technical or procedural skills needs were pediatric advanced airway, neonatal resuscitation, and intravenous/intraosseos access. For neonates, specific educational needs identified included knowing appropriate vital signs and preventing hypothermia. Conclusions This is the first large-scale Delphi survey related to pediatric pre-hospital education. Our results provide foundational information related to the educational needs of pre-hospital providers. Medical directors and educators can use the results to shape future curricular development. PMID:25296191

  12. Children's safety initiative: a national assessment of pediatric educational needs among emergency medical services providers.

    PubMed

    Hansen, Matthew; Meckler, Garth; Dickinson, Caitlyn; Dickenson, Kathryn; Jui, Jonathan; Lambert, William; Guise, Jeanne-Marie

    2015-01-01

    Emergency medical services (EMS) providers may have critical knowledge gaps in pediatric care due to lack of exposure and training. There is currently little evidence to guide educators to the knowledge gaps that most need to be addressed to improve patient safety. The objective of this study was to identify educational needs of EMS providers related to pediatric care in various domains in order to inform development of curricula. The Children's Safety Initiative-EMS performed a three-phase Delphi survey on patient safety in pediatric emergencies among providers and content experts in pediatric emergency care, including physicians, nurses, and prehospital providers of all levels. Each round included questions related to educational needs of providers or the effect of training on patient safety events. We identified knowledge gaps in the following domains: case exposure, competency and knowledge, assessment and decision making, and critical thinking and proficiency. Individual knowledge gaps were ranked by portion of respondents who ranked them "highly likely" (Likert-type score 7-10 out of 10) to contribute to safety events. There were 737 respondents who were included in analysis of the first phase of the survey. Paramedics were 50.8% of respondents, EMT-basics/first responders were 22%, and physicians 11.4%. The top educational priorities identified in the final round of the survey include pediatric airway management, responder anxiety when working with children, and general pediatric skills among providers. The top three needs in decision-making include knowing when to alter plans mid-course, knowing when to perform an advanced airway, and assessing pain in children. The top 3 technical or procedural skills needs were pediatric advanced airway, neonatal resuscitation, and intravenous/intraosseous access. For neonates, specific educational needs identified included knowing appropriate vital signs and preventing hypothermia. This is the first large-scale Delphi survey related to pediatric prehospital education. Our results provide foundational information related to the educational needs of prehospital providers. Medical directors and educators can use the results to shape future curricular development.

  13. Emergency Department Patient Perspectives on the Risk of Addiction to Prescription Opioids.

    PubMed

    Conrardy, Michael; Lank, Patrick; Cameron, Kenzie A; McConnell, Ryan; Chevrier, Alison; Sears, Jill; Ahlstrom, Eric; Wolf, Michael S; Courtney, D Mark; McCarthy, Danielle M

    2016-01-01

    To characterize emergency department (ED) patients' knowledge and beliefs about the addictive potential of opioids. Mixed methods analysis of data from a randomized controlled trial. Urban academic ED (>88,000 visits). One hundred and seventy four discharged ED patients prescribed hydrocodone-acetaminophen for acute pain. The study analyzed data collected from a randomized controlled trial investigating patients' knowledge of opioids. ED patients discharged with hydrocodone-acetaminophen completed an audio-recorded phone interview 4–7 days later. This analysis focuses on responses about addiction. Responses were categorized using content analysis; thematic analysis identified broad themes common across different categories. Participants' mean age was 45.5 years (SD, 14.8), 58.6% female, 50.6% white, and the majority had an orthopedic diagnosis (24.1% back pain, 52.3% other injuries). Responses were categorized first based on whether the patient believed that opioids could be addictive (categorized as: yes, 58.7%; no, 19.5%; depends, 17.2%; or do not know, 4.6%), and second based on whether or not the patient discussed his/her own experience with the medication (categorized as: personalized, 35.6%; or not personalized, 64.4%). Cohen's Kappa was 0.84 for all categories. Three themes emerged in the thematic analysis: theme 1) patients expect to “feel” addicted if they are addicted, theme 2) patients fear addiction, and theme 3) side effects affected patient views of addiction. In this sample, patients had misconceptions about opioid addiction. Some patients did not know opioids could be addictive, others underestimated their personal risk of addiction, and others overtly feared addiction and, therefore, risked inadequate pain management. Despite limited data, we recommend providers discuss opioid addiction with their patients. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. 2016. This work is written by US Government employees and is in the public domain in the US.

  14. The Cr dependence problem of eigenvalues of the Laplace operator on domains in the plane

    NASA Astrophysics Data System (ADS)

    Haddad, Julian; Montenegro, Marcos

    2018-03-01

    The Cr dependence problem of multiple Dirichlet eigenvalues on domains is discussed for elliptic operators by regarding C r + 1-smooth one-parameter families of C1 perturbations of domains in Rn. As applications of our main theorem (Theorem 1), we provide a fairly complete description for all eigenvalues of the Laplace operator on disks and squares in R2 and also for its second eigenvalue on balls in Rn for any n ≥ 3. The central tool used in our proof is a degenerate implicit function theorem on Banach spaces (Theorem 2) of independent interest.

  15. Stabilization and control of distributed systems with time-dependent spatial domains

    NASA Technical Reports Server (NTRS)

    Wang, P. K. C.

    1990-01-01

    This paper considers the problem of the stabilization and control of distributed systems with time-dependent spatial domains. The evolution of the spatial domains with time is described by a finite-dimensional system of ordinary differential equations, while the distributed systems are described by first-order or second-order linear evolution equations defined on appropriate Hilbert spaces. First, results pertaining to the existence and uniqueness of solutions of the system equations are presented. Then, various optimal control and stabilization problems are considered. The paper concludes with some examples which illustrate the application of the main results.

  16. Oversimplifying quantum factoring.

    PubMed

    Smolin, John A; Smith, Graeme; Vargo, Alexander

    2013-07-11

    Shor's quantum factoring algorithm exponentially outperforms known classical methods. Previous experimental implementations have used simplifications dependent on knowing the factors in advance. However, as we show here, all composite numbers admit simplification of the algorithm to a circuit equivalent to flipping coins. The difficulty of a particular experiment therefore depends on the level of simplification chosen, not the size of the number factored. Valid implementations should not make use of the answer sought.

  17. Change of magnetic domain structure by mechanically induced twin boundary motion in Ni-Mn-Ga single crystal

    NASA Astrophysics Data System (ADS)

    Kopecký, Vít; Heczko, Oleg

    2017-10-01

    The single variant state exhibits usual labyrinth and band magnetic domains depending on orientation of easy magnetization axis. By the passage of single twin boundary induced by mechanical stress the rake and granular domain patterns are formed. These domain patterns are further modified by repeated passage of the twin boundary resulting in similar domain patterns in the sample even though the orientation of the magnetization is different.

  18. Focal adhesion kinase-dependent focal adhesion recruitment of SH2 domains directs SRC into focal adhesions to regulate cell adhesion and migration

    PubMed Central

    Wu, Jui-Chung; Chen, Yu-Chen; Kuo, Chih-Ting; Wenshin Yu, Helen; Chen, Yin-Quan; Chiou, Arthur; Kuo, Jean-Cheng

    2015-01-01

    Directed cell migration requires dynamical control of the protein complex within focal adhesions (FAs) and this control is regulated by signaling events involving tyrosine phosphorylation. We screened the SH2 domains present in tyrosine-specific kinases and phosphatases found within FAs, including SRC, SHP1 and SHP2, and examined whether these enzymes transiently target FAs via their SH2 domains. We found that the SRC_SH2 domain and the SHP2_N-SH2 domain are associated with FAs, but only the SRC_SH2 domain is able to be regulated by focal adhesion kinase (FAK). The FAK-dependent association of the SRC_SH2 domain is necessary and sufficient for SRC FA targeting. When the targeting of SRC into FAs is inhibited, there is significant suppression of SRC-mediated phosphorylation of paxillin and FAK; this results in an inhibition of FA formation and maturation and a reduction in cell migration. This study reveals an association between FAs and the SRC_SH2 domain as well as between FAs and the SHP2_N-SH2 domains. This supports the hypothesis that the FAK-regulated SRC_SH2 domain plays an important role in directing SRC into FAs and that this SRC-mediated FA signaling drives cell migration. PMID:26681405

  19. Focal adhesion kinase-dependent focal adhesion recruitment of SH2 domains directs SRC into focal adhesions to regulate cell adhesion and migration.

    PubMed

    Wu, Jui-Chung; Chen, Yu-Chen; Kuo, Chih-Ting; Wenshin Yu, Helen; Chen, Yin-Quan; Chiou, Arthur; Kuo, Jean-Cheng

    2015-12-18

    Directed cell migration requires dynamical control of the protein complex within focal adhesions (FAs) and this control is regulated by signaling events involving tyrosine phosphorylation. We screened the SH2 domains present in tyrosine-specific kinases and phosphatases found within FAs, including SRC, SHP1 and SHP2, and examined whether these enzymes transiently target FAs via their SH2 domains. We found that the SRC_SH2 domain and the SHP2_N-SH2 domain are associated with FAs, but only the SRC_SH2 domain is able to be regulated by focal adhesion kinase (FAK). The FAK-dependent association of the SRC_SH2 domain is necessary and sufficient for SRC FA targeting. When the targeting of SRC into FAs is inhibited, there is significant suppression of SRC-mediated phosphorylation of paxillin and FAK; this results in an inhibition of FA formation and maturation and a reduction in cell migration. This study reveals an association between FAs and the SRC_SH2 domain as well as between FAs and the SHP2_N-SH2 domains. This supports the hypothesis that the FAK-regulated SRC_SH2 domain plays an important role in directing SRC into FAs and that this SRC-mediated FA signaling drives cell migration.

  20. Electric-field-induced domain intersection in BaTiO3 single crystal

    NASA Astrophysics Data System (ADS)

    He, Ming; Wang, Mengxia; Zhang, Zhihua

    2017-03-01

    Large-angle convergent beam electron diffraction was used to determine the directions of polarization vectors in a BaTiO3 single crystal. Domain intersections driven by an electric field were investigated by in situ transmission electron microscopy. The dark triangles observed in the domain intersection region can be accounted for by dislocations and the strain field. Domains nucleate at the domain tip depending on the dislocations and strain field to relieve the accumulated stress. Schematic representations of the intersecting domains and the microscopic structure are given, clarifying the special electric-field-induced domain structure.

  1. Translocation of the Catalytic Domain of Diphtheria Toxin across Planar Phospholipid Bilayers by Its Own T Domain

    NASA Astrophysics Data System (ADS)

    Oh, Kyoung Joon; Senzel, Lisa; Collier, R. John; Finkelstein, Alan

    1999-07-01

    The T domain of diphtheria toxin is known to participate in the pH-dependent translocation of the catalytic C domain of the toxin across the endosomal membrane, but how it does so, and whether cellular proteins are also required for this process, remain unknown. Here, we report results showing that the T domain alone is capable of translocating the entire C domain across model, planar phospholipid bilayers in the absence of other proteins. The T domain therefore contains the entire molecular machinery for mediating transfer of the catalytic domain of diphtheria toxin across membranes.

  2. The Lived Experience of Knowing in Childbirth

    PubMed Central

    Savage, Jane Staton

    2006-01-01

    Research on knowing in childbirth has largely been a quantitative process. The purpose of this study was to understand the ways first-time mothers learn about birth. A phenomenological approach, using a feminist view, was used to analyze two in-depth interviews and journals to understand nine first-time expectant mothers' experiences of knowing in childbirth. The findings demonstrated a range of knowledge that contributed to issues of control and conflict. The participants also described an increased dependency on their mothers and a lack of their own intuition contiguous to the birth process. These findings contribute understanding to how expectant mothers know birth, suggesting that their knowing does not diminish conflict surrounding the event and may even exacerbate it when not combined with learning skills to manage conflict. Childbirth educators may want to include instruction on negotiating power differential in relationships encountered during childbirth in order to strengthen a first-time mother's ability to receive the care she wants. Educators may also want to assess the expectant mother's view of birth and her expectations for birth. Schools of nursing should consider the inclusion of women-centered care curricula at both the undergraduate and graduate levels. The mothers' responses in this study clearly reveal that the politics surrounding birthing remain in place and must be removed in order to provide a supportive environment for normal birth. PMID:17541456

  3. Medical negligence- meaning and scope in India.

    PubMed

    Kumar, L; Bastia, B K

    2011-01-01

    It is a principle recognized by our as well as by other legal systems that ignorance of the law is no excuse for violating it. The rule is also expressed in the form of a legal presumption that everyone knows the law. It is the duty of every man to know that part of it which concerns him. A doctor, in particular, is conclusively presumed to know the law, and is dealt with as if he did know it, because in general he can and ought to know it. In the matter of professional liability, the medical profession differs from other occupations for the reason that the former operates in spheres where success cannot be achieved in every case and very often success or failure depends upon factors beyond a medical man's control. Due to the increasing awareness of the rights of a patient in present day society, a medical man has become more vulnerable to being sued by a litigation suit of any kind, civil or criminal. The basis of a medical negligence suit is still alien to the majority of the practicing doctors in our country. Hence, the present article aims at discussing the various aspects of negligence, like the meaning and types of negligence, and the concept of duty of care, degree of care, and standard of care, as considered by the law.

  4. Complementary and alternative medicine (CAM) among hospitalised patients: reported use of CAM and reasons for use, CAM preferred during hospitalisation, and the socio-demographic determinants of CAM users.

    PubMed

    Shorofi, Seyed Afshin

    2011-11-01

    This paper reports a study to examine hospitalised patients' frequency and patterns of CAM use, their reasons for CAM use, their preferences of CAMs during hospitalisation, and the association between patients' socio-demographic variables and use of each individual CAM/CAM domain. A convenience sample of 353 patients hospitalised in 19 surgical wards at four metropolitan hospitals completed a questionnaire on CAM use and socio-demographic variables. The response rate was 73.5%, and over 90% of the sample acknowledged using CAMs. Non-herbal supplements (60.3%) and massage therapy (45%) were the most frequently used CAMs, with biologically based therapies (68.8%) as well as mind-body interventions (65.4%) being the most often used CAM domains. About 1 in 10 patients (9.6%) used CAMs from all five domains. With the exception of herbal-botanical therapies, self-prayer for health reasons/spiritual healing and music therapy, all CAMs were mainly used on an 'only when needed' basis. The most common reason nominated for using CAMs was that '[it] fits into my way of life/philosophy' (26%). The majority of patients declared interest in and support for the hospital providing CAMs. Patients were most inclined to choose therapies categorised as manipulative and body-based methods (65.4%) for use in hospital. Massage therapy (53.5%) and non-herbal supplements (43.1%) were the top two CAMs favoured for use in hospital. CAM use was also dependent of socio-demographic data (age, gender, marital status, place of residence, education level, religion, and income in hospitalised patients). The use of CAMs is pervasive amongst surgical in-patients, making it feasible to initially assess these patients for CAM use and provide them with clinically approved CAMs where possible. Notwithstanding that CAM use is fairly predictable by socio-demographic variables, further studies should be directed to know the variables useful for predicting the use of each CAM approach. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Deposition and growth of domains in one dimension

    NASA Astrophysics Data System (ADS)

    Rodgers, G. J.; Tavassoli, Z.

    1998-09-01

    A model of deposition and growth in one dimension is studied in which finite sized domains are deposited by the random sequential adsorption process. The domains then grow with a time dependent growth rate. When the initial deposited domains are monomers and dimers the coverage is found exactly for a number of different growth rates. A continuum version of this model is also considered.

  6. A Toll/interleukin (IL)-1 receptor domain protein from Yersinia pestis interacts with mammalian IL-1/Toll-like receptor pathways but does not play a central role in the virulence of Y. pestis in a mouse model of bubonic plague.

    PubMed

    Spear, Abigail M; Rana, Rohini R; Jenner, Dominic C; Flick-Smith, Helen C; Oyston, Petra C F; Simpson, Peter; Matthews, Stephen J; Byrne, Bernadette; Atkins, Helen S

    2012-06-01

    The Toll/interleukin (IL)-1 receptor (TIR) domain is an essential component of eukaryotic innate immune signalling pathways. Interaction between TIR domains present in Toll-like receptors and associated adaptors initiates and propagates an immune signalling cascade. Proteins containing TIR domains have also been discovered in bacteria. Studies have subsequently shown that these proteins are able to modulate mammalian immune signalling pathways dependent on TIR interactions and that this may represent an evasion strategy for bacterial pathogens. Here, we investigate a TIR domain protein from the highly virulent bacterium Yersinia pestis, the causative agent of plague. When overexpressed in vitro this protein is able to downregulate IL-1β- and LPS-dependent signalling to NFκB and to interact with the TIR adaptor protein MyD88. This interaction is dependent on a single proline residue. However, a Y. pestis knockout mutant lacking the TIR domain protein was not attenuated in virulence in a mouse model of bubonic plague. Minor alterations in the host cytokine response to the mutant were indicated, suggesting a potential subtle role in pathogenesis. The Y. pestis mutant also showed increased auto-aggregation and reduced survival in high-salinity conditions, phenotypes which may contribute to pathogenesis or survival.

  7. OnpA, an Unusual Flavin-Dependent Monooxygenase Containing a Cytochrome b5 Domain

    PubMed Central

    Xiao, Yi; Liu, Ting-Ting; Dai, Hui; Zhang, Jun-Jie; Liu, Hong; Tang, Huiru; Leak, David J.

    2012-01-01

    ortho-Nitrophenol 2-monooxygenase (EC 1.14.13.31) from Alcaligenes sp. strain NyZ215 catalyzes monooxygenation of ortho-nitrophenol to form catechol via ortho-benzoquinone. Sequence analysis of this onpA-encoded enzyme revealed that it contained a flavin-binding monooxygenase domain and a heme-binding cytochrome b5 domain. OnpA was purified to homogeneity as a His-tagged protein and was considered a monomer, as determined by gel filtration. FAD and heme were identified by high-performance liquid chromatography (HPLC) and HPLC-mass spectrometry (HPLC-MS) as cofactors in this enzyme, and quantitative analysis indicated that 1 mol of the purified recombinant OnpA contained 0.66 mol of FAD and 0.20 mol of heme. However, the enzyme activity of OnpA was increased by 60% and 450% after addition of FAD and hemin, respectively, suggesting that the optimal stoichiometry was 1:1:1. In addition, site-directed mutagenesis experiments confirmed that two highly conserved histidines located in the cytochrome b5 domain were associated with binding of the heme, and the cytochrome b5 domain was involved in the OnpA activity. These results indicate that OnpA is an unusual FAD-dependent monooxygenase containing a fused cytochrome b5 domain that is essential for its activity. Therefore, we here demonstrate a link between cytochrome b5 and flavin-dependent monooxygenases. PMID:22267507

  8. ABCA1-dependent sterol release: sterol molecule specificity and potential membrane domain for HDL biogenesis.

    PubMed

    Yamauchi, Yoshio; Yokoyama, Shinji; Chang, Ta-Yuan

    2016-01-01

    Mammalian cells synthesize various sterol molecules, including the C30 sterol, lanosterol, as cholesterol precursors in the endoplasmic reticulum. The build-up of precursor sterols, including lanosterol, displays cellular toxicity. Precursor sterols are found in plasma HDL. How these structurally different sterols are released from cells is poorly understood. Here, we show that newly synthesized precursor sterols arriving at the plasma membrane (PM) are removed by extracellular apoA-I in a manner dependent on ABCA1, a key macromolecule for HDL biogenesis. Analysis of sterol molecules by GC-MS and tracing the fate of radiolabeled acetate-derived sterols in normal and mutant Niemann-Pick type C cells reveal that ABCA1 prefers newly synthesized sterols, especially lanosterol, as the substrates before they are internalized from the PM. We also show that ABCA1 resides in a cholesterol-rich membrane domain resistant to the mild detergent, Brij 98. Blocking ACAT activity increases the cholesterol contents of this domain. Newly synthesized C29/C30 sterols are transiently enriched within this domain, but rapidly disappear from this domain with a half-life of less than 1 h. Our work shows that substantial amounts of precursor sterols are transported to a certain PM domain and are removed by the ABCA1-dependent pathway. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

  9. A Crystal Structure of Classical Swine Fever Virus NS5B Reveals a Novel N-terminal Domain.

    PubMed

    Li, Weiwei; Wu, Baixing; Soca, Wibowo Adian; An, Lei

    2018-05-02

    Classical swine fever virus (CSFV) is the ringleader of Classical swine fever (CSF). The non-structural protein 5B (NS5B) encodes an RNA-dependent RNA polymerase (RdRp) that is a key enzyme initiating viral RNA replication by a de novo mechanism. It is also an attractive target for the development of anti-CSFV drugs. To gain a better understanding on the mechanism of CSFV RNA synthesis, here we solved the first crystal structure of CSFV-NS5B. Our studies show that the CSFV-NS5B RdRp contains characteristic fingers, palm domain and thumb domain as well as a unique N-terminal domain (NTD) that had never been observed. Mutagenesis studies on NS5B validated the importance of NTD in the catalytic activity of this novel RNA-dependent RNA polymerase. Moreover, our results shed light on the understanding of CSFV infection. IMPORTANCE Pigs are important domestic animal. However, a highly contagious viral disease named Classical swine fever (CSF) causes devastating economic losses. Classical swine fever virus (CSFV) is the primary culprit of CSF, which is a positive-sense single-stranded RNA virus belonging to the Pestivirus genus, Flaviviridae family. Genome replication of CSFV depends on RNA-dependent RNA polymerase known as NS5B. However, the structure of CSFV-NS5B has never been reported, and the mechanism of CSFV replication is poorly understood. Here, we solved the first crystal structure of CSFV-NS5B, analyzed the function of characteristic fingers, palm, and thumb domains. Additionally, our structure also revealed the presence of a novel N-terminal domain (NTD). Biochemical studies demonstrated that the NTD of CSFV-NS5B is very important for RNA-dependent RNA polymerase (RdRp) activity. Collectively, our studies provide a structural basis for future rational design of anti-CSFV drugs which is critically important as no effective anti-CSFV drugs have been developed. Copyright © 2018 American Society for Microbiology.

  10. I-mfa domain proteins specifically interact with HTLV-1 Tax and repress its transactivating functions

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

    Kusano, Shuichi, E-mail: skusano@m2.kufm.kagoshima-u.ac.jp; Yoshimitsu, Makoto; Hachiman, Miho

    The I-mfa domain proteins HIC (also known as MDFIC) and I-mfa (also known as MDFI) are candidate tumor suppressor genes that are involved in cellular and viral transcriptional regulation. Here, we show that HIC and I-mfa directly interact with human T-cell leukemia virus type-1 (HTLV-1) Tax protein in vitro. In addition, HIC and I-mfa repress Tax-dependent transactivation of an HTLV-1 long terminal repeat (LTR) reporter construct in COS-1, Jurkat and high-Tax-producing HTLV-1-infected T cells. HIC also interacts with Tax through its I-mfa domain in vivo and represses Tax-dependent transactivation of HTLV-1 LTR and NF-κB reporter constructs in an interaction-dependent manner.more » Furthermore, we show that HIC decreases the nuclear distribution and stimulates the proteasomal degradation of Tax. These data reveal that HIC specifically interacts with HTLV-1 Tax and negatively regulates Tax transactivational activity by altering its subcellular distribution and stability. - Highlights: • I-mfa domain proteins, HIC and I-mfa, specifically interact with HTLV-1 Tax. • HIC and I-mfa repress the Tax-dependent transactivation of HTLV-1 LTR. • HIC represses the Tax-dependent transactivation of NF-κΒ. • HIC decreases the nuclear distribution of Tax. • HIC stimulates the proteasomal degradation of Tax.« less

  11. Echothymia: environmental dependency in the affective domain.

    PubMed

    Marin, Robert S; Gorovoy, Ian R

    2014-01-01

    Echothymia is stimulus-bound affective behavior, an echophenomenon in the domain of affect. Like echolalia and echopraxia, it is a concomitant of the environmental dependency associated with dysfunction of the frontal-striatal systems that mediate so-called frontal lobe functions. The authors introduce the definition and phenomenology of echothymia, overview its differential diagnosis and clinical significance, and suggest ways in which understanding echothymia may contribute to clinical management.

  12. Big Data: Are Biomedical and Health Informatics Training Programs Ready?

    PubMed Central

    Hersh, W.; Ganesh, A. U. Jai

    2014-01-01

    Summary Objectives The growing volume and diversity of health and biomedical data indicate that the era of Big Data has arrived for healthcare. This has many implications for informatics, not only in terms of implementing and evaluating information systems, but also for the work and training of informatics researchers and professionals. This article addresses the question: What do biomedical and health informaticians working in analytics and Big Data need to know? Methods We hypothesize a set of skills that we hope will be discussed among academic and other informaticians. Results The set of skills includes: Programming - especially with data-oriented tools, such as SQL and statistical programming languages; Statistics - working knowledge to apply tools and techniques; Domain knowledge - depending on one’s area of work, bioscience or health care; and Communication - being able to understand needs of people and organizations, and articulate results back to them. Conclusions Biomedical and health informatics educational programs must introduce concepts of analytics, Big Data, and the underlying skills to use and apply them into their curricula. The development of new coursework should focus on those who will become experts, with training aiming to provide skills in “deep analytical talent” as well as those who need knowledge to support such individuals. PMID:25123740

  13. Big Data: Are Biomedical and Health Informatics Training Programs Ready? Contribution of the IMIA Working Group for Health and Medical Informatics Education.

    PubMed

    Otero, P; Hersh, W; Jai Ganesh, A U

    2014-08-15

    The growing volume and diversity of health and biomedical data indicate that the era of Big Data has arrived for healthcare. This has many implications for informatics, not only in terms of implementing and evaluating information systems, but also for the work and training of informatics researchers and professionals. This article addresses the question: What do biomedical and health informaticians working in analytics and Big Data need to know? We hypothesize a set of skills that we hope will be discussed among academic and other informaticians. The set of skills includes: Programming - especially with data-oriented tools, such as SQL and statistical programming languages; Statistics - working knowledge to apply tools and techniques; Domain knowledge - depending on one's area of work, bioscience or health care; and Communication - being able to understand needs of people and organizations, and articulate results back to them. Biomedical and health informatics educational programs must introduce concepts of analytics, Big Data, and the underlying skills to use and apply them into their curricula. The development of new coursework should focus on those who will become experts, with training aiming to provide skills in "deep analytical talent" as well as those who need knowledge to support such individuals.

  14. Modeling Of Object- And Scene-Prototypes With Hierarchically Structured Classes

    NASA Astrophysics Data System (ADS)

    Ren, Z.; Jensch, P.; Ameling, W.

    1989-03-01

    The success of knowledge-based image analysis methodology and implementation tools depends largely on an appropriately and efficiently built model wherein the domain-specific context information about and the inherent structure of the observed image scene have been encoded. For identifying an object in an application environment a computer vision system needs to know firstly the description of the object to be found in an image or in an image sequence, secondly the corresponding relationships between object descriptions within the image sequence. This paper presents models of image objects scenes by means of hierarchically structured classes. Using the topovisual formalism of graph and higraph, we are currently studying principally the relational aspect and data abstraction of the modeling in order to visualize the structural nature resident in image objects and scenes, and to formalize. their descriptions. The goal is to expose the structure of image scene and the correspondence of image objects in the low level image interpretation. process. The object-based system design approach has been applied to build the model base. We utilize the object-oriented programming language C + + for designing, testing and implementing the abstracted entity classes and the operation structures which have been modeled topovisually. The reference images used for modeling prototypes of objects and scenes are from industrial environments as'well as medical applications.

  15. How temperament and character affect our career, relationships, and mental health.

    PubMed

    Gutiérrez, Fernando; Gárriz, Miguel; Peri, Josep M; Vall, Gemma; Torrubia, Rafael

    2016-10-01

    On the way toward an agreed dimensional taxonomy for personality disorders (PD), several pivotal questions remain unresolved. We need to know which dimensions produce problems and in what domains of life; whether impairment can be found at one or both extremes of each dimension; and whether, as is increasingly advocated, some dimensions measure personality functioning whereas others reflect style. To gain this understanding, we administered the Temperament and Character Inventory to a sample of 862 consecutively attended outpatients, mainly with PDs (61.2%). Using regression analysis, we examined the ability of personality to predict 39 variables from the Life Outcome Questionnaire concerning career, relationships, and mental health. Persistence stood out as the most important dimension regarding career success, with 24.2% of explained variance on average. Self-directedness was the best predictor of social functioning (21.1%), and harm avoidance regarding clinical problems (34.2%). Interpersonal dimensions such as reward dependence and cooperativeness were mostly inconsequential. In general, dimensions were detrimental only in one of their poles. Although personality explains 9.4% of life problems overall, dimensions believed to measure functioning (character) were not better predictors than those measuring style (temperament). The notion that PD diagnoses can be built upon the concept of "personality functioning" is unsupported. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Pathlength Determination for Gas in Scattering Media Absorption Spectroscopy

    PubMed Central

    Mei, Liang; Somesfalean, Gabriel; Svanberg, Sune

    2014-01-01

    Gas in scattering media absorption spectroscopy (GASMAS) has been extensively studied and applied during recent years in, e.g., food packaging, human sinus monitoring, gas diffusion studies, and pharmaceutical tablet characterization. The focus has been on the evaluation of the gas absorption pathlength in porous media, which a priori is unknown due to heavy light scattering. In this paper, three different approaches are summarized. One possibility is to simultaneously monitor another gas with known concentration (e.g., water vapor), the pathlength of which can then be obtained and used for the target gas (e.g., oxygen) to retrieve its concentration. The second approach is to measure the mean optical pathlength or physical pathlength with other methods, including time-of-flight spectroscopy, frequency-modulated light scattering interferometry and the frequency domain photon migration method. By utilizing these methods, an average concentration can be obtained and the porosities of the material are studied. The last method retrieves the gas concentration without knowing its pathlength by analyzing the gas absorption line shape, which depends upon the concentration of buffer gases due to intermolecular collisions. The pathlength enhancement effect due to multiple scattering enables also the use of porous media as multipass gas cells for trace gas monitoring. All these efforts open up a multitude of different applications for the GASMAS technique. PMID:24573311

  17. Advancing nursing practice: redefining the theoretical and practical integration of knowledge.

    PubMed

    Christensen, Martin

    2011-03-01

    The aim of this paper is to offer an alternative knowing-how knowing-that framework of nursing knowledge, which in the past has been accepted as the provenance of advanced practice. The concept of advancing practice is central to the development of nursing practice and has been seen to take on many different forms depending on its use in context. To many it has become synonymous with the work of the advanced or expert practitioner; others have viewed it as a process of continuing professional development and skills acquisition. Moreover, it is becoming closely linked with practice development. However, there is much discussion as to what constitutes the knowledge necessary for advancing and advanced practice, and it has been suggested that theoretical and practical knowledge form the cornerstone of advanced knowledge. The design of this article takes a discursive approach as to the meaning and integration of knowledge within the context of advancing nursing practice. A thematic analysis of the current discourse relating to knowledge integration models in an advancing and advanced practice arena was used to identify concurrent themes relating to the knowing-how knowing-that framework which commonly used to classify the knowledge necessary for advanced nursing practice. There is a dichotomy as to what constitutes knowledge for advanced and advancing practice. Several authors have offered a variety of differing models, yet it is the application and integration of theoretical and practical knowledge that defines and develops the advancement of nursing practice. An alternative framework offered here may allow differences in the way that nursing knowledge important for advancing practice is perceived, developed and coordinated. What has inevitably been neglected is that there are various other variables which when transposed into the existing knowing-how knowing-that framework allows for advanced knowledge to be better defined. One of the more notable variables is pattern recognition, which became the focus of Benner's work on expert practice. Therefore, if this is included into the knowing-how knowing-that framework, the knowing-how becomes the knowledge that contributes to advancing and advanced practice and the knowing-that becomes the governing action based on a deeper understanding of the problem or issue. © 2011 Blackwell Publishing Ltd.

  18. Interaction Between the Biotin Carboxyl Carrier Domain and the Biotin Carboxylase Domain in Pyruvate Carboxylase from Rhizobium etli†

    PubMed Central

    Lietzan, Adam D.; Menefee, Ann L.; Zeczycki, Tonya N.; Kumar, Sudhanshu; Attwood, Paul V.; Wallace, John C.; Cleland, W. Wallace; Maurice, Martin St.

    2011-01-01

    Pyruvate carboxylase (PC) catalyzes the ATP-dependent carboxylation of pyruvate to oxaloacetate, an important anaplerotic reaction in mammalian tissues. To effect catalysis, the tethered biotin of PC must gain access to active sites in both the biotin carboxylase domain and the carboxyl transferase domain. Previous studies have demonstrated that a mutation of threonine 882 to alanine in PC from Rhizobium etli renders the carboxyl transferase domain inactive and favors the positioning of biotin in the biotin carboxylase domain. We report the 2.4 Å resolution X-ray crystal structure of the Rhizobium etli PC T882A mutant which reveals the first high-resolution description of the domain interaction between the biotin carboxyl carrier protein domain and the biotin carboxylase domain. The overall quaternary arrangement of Rhizobium etli PC remains highly asymmetrical and is independent of the presence of allosteric activator. While biotin is observed in the biotin carboxylase domain, its access to the active site is precluded by the interaction between Arg353 and Glu248, revealing a mechanism for regulating carboxybiotin access to the BC domain active site. The binding location for the biotin carboxyl carrier protein domain demonstrates that tethered biotin cannot bind in the biotin carboxylase domain active site in the same orientation as free biotin, helping to explain the difference in catalysis observed between tethered biotin and free biotin substrates in biotin carboxylase enzymes. Electron density located in the biotin carboxylase domain active site is assigned to phosphonoacetate, offering a probable location for the putative carboxyphosphate intermediate formed during biotin carboxylation. The insights gained from the T882A Rhizobium etli PC crystal structure provide a new series of catalytic snapshots in PC and offer a revised perspective on catalysis in the biotin-dependent enzyme family. PMID:21958016

  19. Crystal structure studies of NADP{sup +} dependent isocitrate dehydrogenase from Thermus thermophilus exhibiting a novel terminal domain

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

    Kumar, S.M.; Pampa, K.J.; Manjula, M.

    2014-06-20

    Highlights: • We determined the structure of isocitrate dehydrogenase with citrate and cofactor. • The structure reveals a unique novel terminal domain involved in dimerization. • Clasp domain shows significant difference, and catalytic residues are conserved. • Oligomerization of the enzyme is quantized with subunit-subunit interactions. • Novel domain of this enzyme is classified as subfamily of the type IV. - Abstract: NADP{sup +} dependent isocitrate dehydrogenase (IDH) is an enzyme catalyzing oxidative decarboxylation of isocitrate into oxalosuccinate (intermediate) and finally the product α-ketoglutarate. The crystal structure of Thermus thermophilus isocitrate dehydrogenase (TtIDH) ternary complex with citrate and cofactor NADP{supmore » +} was determined using X-ray diffraction method to a resolution of 1.80 Å. The overall fold of this protein was resolved into large domain, small domain and a clasp domain. The monomeric structure reveals a novel terminal domain involved in dimerization, very unique and novel domain when compared to other IDH’s. And, small domain and clasp domain showing significant differences when compared to other IDH’s of the same sub-family. The structure of TtIDH reveals the absence of helix at the clasp domain, which is mainly involved in oligomerization in other IDH’s. Also, helices/beta sheets are absent in the small domain, when compared to other IDH’s of the same sub family. The overall TtIDH structure exhibits closed conformation with catalytic triad residues, Tyr144-Asp248-Lys191 are conserved. Oligomerization of the protein is quantized using interface area and subunit–subunit interactions between protomers. Overall, the TtIDH structure with novel terminal domain may be categorized as a first structure of subfamily of type IV.« less

  20. Archaeal Genome Guardians Give Insights into Eukaryotic DNA Replication and Damage Response Proteins

    PubMed Central

    Shin, David S.; Pratt, Ashley J.; Tainer, John A.

    2014-01-01

    As the third domain of life, archaea, like the eukarya and bacteria, must have robust DNA replication and repair complexes to ensure genome fidelity. Archaea moreover display a breadth of unique habitats and characteristics, and structural biologists increasingly appreciate these features. As archaea include extremophiles that can withstand diverse environmental stresses, they provide fundamental systems for understanding enzymes and pathways critical to genome integrity and stress responses. Such archaeal extremophiles provide critical data on the periodic table for life as well as on the biochemical, geochemical, and physical limitations to adaptive strategies allowing organisms to thrive under environmental stress relevant to determining the boundaries for life as we know it. Specifically, archaeal enzyme structures have informed the architecture and mechanisms of key DNA repair proteins and complexes. With added abilities to temperature-trap flexible complexes and reveal core domains of transient and dynamic complexes, these structures provide insights into mechanisms of maintaining genome integrity despite extreme environmental stress. The DNA damage response protein structures noted in this review therefore inform the basis for genome integrity in the face of environmental stress, with implications for all domains of life as well as for biomanufacturing, astrobiology, and medicine. PMID:24701133

  1. Routine Support to Parents and Stressors in Everyday Domains: Associations With Negative Affect and Cortisol.

    PubMed

    Savla, Jyoti; Zarit, Steven H; Almeida, David M

    2018-03-02

    Adult children are involved a myriad of roles including providing routine (non-caregiving) support to a parent. Yet we know little about whether providing routine support to a parent is stressful and whether it has any associations with stressors in other life domains. We use daily diary data (N = 127; Study Days = 424) from the National Study of Daily Experiences to determine whether providing routine support to an older parent is associated with higher negative affect and salivary cortisol. Results confirm that providing routine support and experiencing stressors at work were independently associated with negative affect and greater cortisol output. Stress reactions were not amplified, however, on days when adult children concurrently provided support to a parent and reported work stressors. Cutting back usual activities at work or home elevated negative affect but were not associated with an upsurge of cortisol production. Findings lend support to the caregiving career framework for understanding even casual routine assistance provided to a parent. Published by Oxford University Press on behalf of The Gerontological Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  2. A Filter-Mediated Communication Model for Design Collaboration in Building Construction

    PubMed Central

    Oh, Minho

    2014-01-01

    Multidisciplinary collaboration is an important aspect of modern engineering activities, arising from the growing complexity of artifacts whose design and construction require knowledge and skills that exceed the capacities of any one professional. However, current collaboration in the architecture, engineering, and construction industries often fails due to lack of shared understanding between different participants and limitations of their supporting tools. To achieve a high level of shared understanding, this study proposes a filter-mediated communication model. In the proposed model, participants retain their own data in the form most appropriate for their needs with domain-specific filters that transform the neutral representations into semantically rich ones, as needed by the participants. Conversely, the filters can translate semantically rich, domain-specific data into a neutral representation that can be accessed by other domain-specific filters. To validate the feasibility of the proposed model, we computationally implement the filter mechanism and apply it to a hypothetical test case. The result acknowledges that the filter mechanism can let the participants know ahead of time what will be the implications of their proposed actions, as seen from other participants' points of view. PMID:25309958

  3. Diabetes and Cognitive Decline in Older Adults: The Ginkgo Evaluation of Memory Study.

    PubMed

    Palta, Priya; Carlson, Michelle C; Crum, Rosa M; Colantuoni, Elizabeth; Sharrett, A Richey; Yasar, Sevil; Nahin, Richard L; DeKosky, Steven T; Snitz, Beth; Lopez, Oscar; Williamson, Jeff D; Furberg, Curt D; Rapp, Stephen R; Golden, Sherita Hill

    2017-12-12

    Previous studies have shown that individuals with diabetes exhibit accelerated cognitive decline. However, methodological limitations have limited the quality of this evidence. Heterogeneity in study design, cognitive test administration, and methods of analysis of cognitive data have made it difficult to synthesize and translate findings to practice. We analyzed longitudinal data from the Ginkgo Evaluation of Memory Study to test our hypothesis that older adults with diabetes have greater test-specific and domain-specific cognitive declines compared to older adults without diabetes. Tests of memory, visuo-spatial construction, language, psychomotor speed, and executive function were administered. Test scores were standardized to z-scores and averaged to yield domain scores. Linear random effects models were used to compare baseline differences and changes over time in test and domain scores among individuals with and without diabetes. Among the 3,069 adults, aged 72-96 years, 9.3% reported diabetes. Over a median follow-up of 6.1 years, participants with diabetes exhibited greater baseline differences in a test of executive function (trail making test, Part B) and greater declines in a test of language (phonemic verbal fluency). For the composite cognitive domain scores, participants with diabetes exhibited lower baseline executive function and global cognition domain scores, but no significant differences in the rate of decline. Identifying cognitive domains most affected by diabetes can lead to targeted risk modification, possibly in the form of lifestyle interventions such as diet and physical activity, which we know to be beneficial for improving vascular risk factors, such as diabetes, and therefore may reduce the risk of executive dysfunction and possible dementia. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. The educational needs of people with systemic sclerosis: a cross-sectional study using the Dutch version of the Educational Needs Assessment Tool (D-ENAT).

    PubMed

    Schouffoer, Anne; Ndosi, Mwidimi E; Vliet Vlieland, Thea P M; Meesters, Jorit J L

    2016-02-01

    The Dutch Educational Needs Assessment Tool (D-ENAT) systematically assesses educational needs of patients with rheumatic diseases. The present study aims to describe the educational needs of Dutch patients with systemic sclerosis (SSc). The D-ENAT was sent to 155 SSc patients registered at the outpatient clinic of a university hospital. The D-ENAT consists of 39 items in seven domains. "Each domain has different number of items therefore we normalized each domain score: (domain score/maximum) × 100) and expressed in percentage to enable comparisons between domains." A total D-ENAT score (0-156) is calculated by summing all 39 items. In addition, age, disease duration, gender, educational level, present information need (yes/no) and information need (1-4; wanting to know nothing-everything) were recorded. Univariate regression analysis was used to examine factors associated with the D-ENAT scores. The response rate was 103 out of 155 (66 %). The mean % of educational needs scores (0-100 %; lowest-highest) were 49 % for "D-ENAT total score," 46 % for "Managing pain," 41 % for "Movement," 43 % for "Feelings," 59 % for "Disease process," 44 % for "Treatments from health professionals," 61 % for "Self-help measures" and 51 % for "Support systems." No associations between the D-ENAT total score and age, disease duration, gender and educational level were found. The D-ENAT demonstrated its ability to identify educational needs of Dutch SSc patients. SSc patients demonstrated substantial educational needs, especially in the domains: "Disease process" and "Self-help measures." The validity and practical applicability of the D-ENAT to make an inventory of SSc patients' educational needs require further investigation.

  5. Orientation of Myosin Binding Protein C in the Cardiac Muscle Sarcomere Determined by Domain-Specific Immuno-EM

    PubMed Central

    Lee, Kyounghwan; Harris, Samantha P.; Sadayappan, Sakthivel; Craig, Roger

    2014-01-01

    Myosin binding protein-C is a thick filament protein of vertebrate striated muscle. The cardiac isoform (cMyBP-C) is essential for normal cardiac function, and mutations in cMyBP-C cause cardiac muscle disease. The rod-shaped molecule is composed primarily of 11 immunoglobulin- or fibronectin-like domains, and is located at 9 sites, 43 nm apart, in each half of the A-band. To understand how cMyBP-C functions, it is important to know its structural organization in the sarcomere, as this will affect its ability to interact with other sarcomeric proteins. Several models have been proposed, in which cMyBP-C wraps around, extends radially from, or runs axially along the thick filament. Our goal was to define cMyBP-C orientation by determining the relative axial positions of different cMyBP-C domains. Immuno-electron microscopy was performed using mouse cardiac myofibrils labeled with antibodies specific to the N- and C-terminal domains and to the middle of cMyBP-C. Antibodies to all regions of the molecule, except the C-terminus, labeled at the same nine axial positions in each half A-band, consistent with a circumferential and/or radial rather than an axial orientation of the bulk of the molecule. The C-terminal antibody stripes were slightly displaced axially, demonstrating an axial orientation of the C-terminal 3 domains, with the C-terminus closer to the M-line. These results, combined with previous studies, suggest that the C-terminal domains of cMyBP-C run along the thick filament surface, while the N-terminus extends towards neighboring thin filaments. This organization provides a structural framework for understanding cMyBP-C’s modulation of cardiac muscle contraction. PMID:25451032

  6. Fatigue effect in ferroelectric crystals: Growth of the frozen domains

    NASA Astrophysics Data System (ADS)

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

    2012-06-01

    The model of the fatigue effect during cyclic switching caused by growth of the frozen domain area with charged domain walls has been proposed. It was claimed on the basis of the previous experimental results that for switching in increasing field the frozen domain area started to grow at the given sub-threshold field value and stopped at the threshold field. The influence of the shape and frequency of the field pulses used for cyclic switching has been considered. The uniaxial ferroelectric stoichiometric lithium tantalate single crystals produced by vapor transport equilibration with record low value of coercive field have been chosen as a model material for experimental verification of the model. The formation of the charged domain walls as a result of cyclic switching has been revealed by analysis of the domain images obtained by optical and Raman confocal microscopy. It has been shown that the fatigue degree is equal to the fraction of the frozen domain area. The experimental dependence of the switched charge on the cycle number has been successfully fitted by modified Kolmogorov-Avrami formula. The experimentally observed frequency independence of fatigue profile for rectangular pulses and frequency dependence for triangular pulses has been explained by proposed model.

  7. DC-SIGN neck domain is a pH-sensor controlling oligomerization: SAXS and hydrodynamic studies of extracellular domain.

    PubMed

    Tabarani, Georges; Thépaut, Michel; Stroebel, David; Ebel, Christine; Vivès, Corinne; Vachette, Patrice; Durand, Dominique; Fieschi, Franck

    2009-08-07

    DC-SIGN is a C-type lectin receptor of dendritic cells and is involved in the early stages of numerous infectious diseases. DC-SIGN is organized into a tetramer enabling multivalent interaction with pathogens. Once formed, the DC-SIGN-pathogen complex can be internalized into compartments of increasing acidity. We have studied the pH dependence of the oligomerization state and conformation of the entire extracellular domain and neck region. We present evidence for equilibrium between the monomeric and tetrameric states of the extracellular domain, which exhibits a marked dependence with respect to both pH and ionic strength. Using solution x-ray scattering we have obtained a molecular envelope of the extracellular domain in which a model has been built. Our results highlight the central role of the neck domain in the pH-sensitive control of the oligomerization state, in the extended conformation of the protein, and in carbohydrate recognition domain organization and presentation. This work opens new insight into the molecular mechanism of ligand release and points to new avenues to block the first step of this important infection pathway.

  8. The Role of Bacterial Enhancer Binding Proteins as Specialized Activators of σ54-Dependent Transcription

    PubMed Central

    2012-01-01

    Summary: Bacterial enhancer binding proteins (bEBPs) are transcriptional activators that assemble as hexameric rings in their active forms and utilize ATP hydrolysis to remodel the conformation of RNA polymerase containing the alternative sigma factor σ54. We present a comprehensive and detailed summary of recent advances in our understanding of how these specialized molecular machines function. The review is structured by introducing each of the three domains in turn: the central catalytic domain, the N-terminal regulatory domain, and the C-terminal DNA binding domain. The role of the central catalytic domain is presented with particular reference to (i) oligomerization, (ii) ATP hydrolysis, and (iii) the key GAFTGA motif that contacts σ54 for remodeling. Each of these functions forms a potential target of the signal-sensing N-terminal regulatory domain, which can act either positively or negatively to control the activation of σ54-dependent transcription. Finally, we focus on the DNA binding function of the C-terminal domain and the enhancer sites to which it binds. Particular attention is paid to the importance of σ54 to the bacterial cell and its unique role in regulating transcription. PMID:22933558

  9. Post-deposition control of ferroelastic stripe domains and internal electric field by thermal treatment

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

    Feigl, L.; Iwanowska, M.; Sandu, C. S.

    The dependence of the formation of ferroelastic stripe domain patterns on the thermal history is investigated by detailed piezoresponse force microscopy and X-ray diffraction experiments after and during annealing of tensile strained tetragonal Pb(Ti,Zr)O{sub 3} epitaxial thin films on DyScO{sub 3} substrates. In particular, the ferroelastic pattern is reversibly interchanged between a cross-hatched and a stripe domain pattern if the films are cooled at different rates after annealing above the formation temperature of a-domains. Different types of 180° and non-180° patterns can be created, depending on the thermal treatment. The changes in the 180° domain structure and lattice parameters aremore » attributed to a change of oxygen vacancy concentration, which results in a modification of the internal electric field and unit cell size, causing also a shift of T{sub C}. Thermal treatment is done on rhombohedral La:BiFeO{sub 3} thin films as well. It is observed that also in these films, appropriate heat treatment modifies the domain pattern and films with a stripe domain pattern can be created, confirming the general validity of the developed model.« less

  10. Post-deposition control of ferroelastic stripe domains and internal electric field by thermal treatment

    NASA Astrophysics Data System (ADS)

    Feigl, L.; Janolin, P.-E.; Yamada, T.; Iwanowska, M.; Sandu, C. S.; Setter, N.

    2015-01-01

    The dependence of the formation of ferroelastic stripe domain patterns on the thermal history is investigated by detailed piezoresponse force microscopy and X-ray diffraction experiments after and during annealing of tensile strained tetragonal Pb(Ti,Zr)O3 epitaxial thin films on DyScO3 substrates. In particular, the ferroelastic pattern is reversibly interchanged between a cross-hatched and a stripe domain pattern if the films are cooled at different rates after annealing above the formation temperature of a-domains. Different types of 180° and non-180° patterns can be created, depending on the thermal treatment. The changes in the 180° domain structure and lattice parameters are attributed to a change of oxygen vacancy concentration, which results in a modification of the internal electric field and unit cell size, causing also a shift of TC. Thermal treatment is done on rhombohedral La:BiFeO3 thin films as well. It is observed that also in these films, appropriate heat treatment modifies the domain pattern and films with a stripe domain pattern can be created, confirming the general validity of the developed model.

  11. Low pH-Induced Pore Formation by the T Domain of Botulinum Toxin Type A is Dependent upon NaCl Concentration

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

    Lai, B.; Swaminathan, S.; Agarwal, R.

    2010-07-19

    Botulinum neurotoxins (BoNTs) undergo low pH-triggered membrane insertion, resulting in the translocation of their light (catalytic) chains into the cytoplasm. The T (translocation) domain of the BoNT heavy chain is believed to carry out translocation. Here, the behavior of isolated T domain from BoNT type A has been characterized, both in solution and when associated with model membranes. When BoNT T domain prepared in the detergent dodecylmaltoside was diluted into aqueous solution, it exhibited a low pH-dependent conformational change below pH 6. At low pH the T domain associated with, and formed pores within, model membrane vesicles composed of 30more » mol% dioleoylphosphatidylglycerol/70 mol% dioleoylphosphatidylcholine. Although T domain interacted with vesicles at low (50 mM) and high (400 mM) NaCl concentrations, the interaction required much less lipid at low salt. However, even at high lipid concentrations pore formation was much more pronounced at low NaCl concentrations than at high NaCl concentration. Increasing salt concentration after insertion in the presence of 50 mM NaCl did not decrease pore formation. A similar effect of NaCl concentration upon pore formation was observed in vesicles composed solely of dioleoylphosphatidylcholine, showing that the effect of NaCl did not solely involve modulation of electrostatic interactions between protein and anionic lipids. These results indicate that some feature of membrane-bound T domain tertiary structure critical for pore formation is highly dependent upon salt concentration.« less

  12. Recognition of cyclic-di-GMP by a riboswitch conducts translational repression through masking the ribosome-binding site distant from the aptamer domain.

    PubMed

    Inuzuka, Saki; Kakizawa, Hitoshi; Nishimura, Kei-Ichiro; Naito, Takuto; Miyazaki, Katsushi; Furuta, Hiroyuki; Matsumura, Shigeyoshi; Ikawa, Yoshiya

    2018-06-01

    The riboswitch is a class of RNA-based gene regulatory machinery that is dependent on recognition of its target ligand by RNA tertiary structures. Ligand recognition is achieved by the aptamer domain, and ligand-dependent structural changes of the expression platform then usually mediate termination of transcription or translational initiation. Ligand-dependent structural changes of the aptamer domain and expression platform have been reported for several riboswitches with short (<40 nucleotides) expression platforms. In this study, we characterized structural changes of the Vc2 c-di-GMP riboswitch that represses translation of downstream open reading frames in a ligand-dependent manner. The Vc2 riboswitch has a long (97 nucleotides) expression platform, but its structure and function are largely unknown. Through mutational analysis and chemical probing, we identified its secondary structures that are possibly responsible for switch-OFF and switch-ON states of translational initiation. © 2018 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  13. IgG Fc domains that bind C1q but not effector Fcγ receptors delineate the importance of complement-mediated effector functions.

    PubMed

    Lee, Chang-Han; Romain, Gabrielle; Yan, Wupeng; Watanabe, Makiko; Charab, Wissam; Todorova, Biliana; Lee, Jiwon; Triplett, Kendra; Donkor, Moses; Lungu, Oana I; Lux, Anja; Marshall, Nicholas; Lindorfer, Margaret A; Goff, Odile Richard-Le; Balbino, Bianca; Kang, Tae Hyun; Tanno, Hidetaka; Delidakis, George; Alford, Corrine; Taylor, Ronald P; Nimmerjahn, Falk; Varadarajan, Navin; Bruhns, Pierre; Zhang, Yan Jessie; Georgiou, George

    2017-08-01

    Engineered crystallizable fragment (Fc) regions of antibody domains, which assume a unique and unprecedented asymmetric structure within the homodimeric Fc polypeptide, enable completely selective binding to the complement component C1q and activation of complement via the classical pathway without any concomitant engagement of the Fcγ receptor (FcγR). We used the engineered Fc domains to demonstrate in vitro and in mouse models that for therapeutic antibodies, complement-dependent cell-mediated cytotoxicity (CDCC) and complement-dependent cell-mediated phagocytosis (CDCP) by immunological effector molecules mediated the clearance of target cells with kinetics and efficacy comparable to those of the FcγR-dependent effector functions that are much better studied, while they circumvented certain adverse reactions associated with FcγR engagement. Collectively, our data highlight the importance of CDCC and CDCP in monoclonal-antibody function and provide an experimental approach for delineating the effect of complement-dependent effector-cell engagement in various therapeutic settings.

  14. The TIR domain of TIR-NB-LRR resistance proteins is a signaling domain involved in cell death induction.

    PubMed

    Swiderski, Michal R; Birker, Doris; Jones, Jonathan D G

    2009-02-01

    In plants, the TIR (toll interleukin 1 receptor) domain is found almost exclusively in nucleotide-binding (NB) leucine-rich repeat resistance proteins and their truncated homologs, and has been proposed to play a signaling role during resistance responses mediated by TIR containing R proteins. Transient expression in Nicotiana benthamiana leaves of "TIR + 80", the RPS4 truncation without the NB-ARC domain, leads to EDS1-, SGT1-, and HSP90-dependent cell death. Transgenic Arabidopsis plants expressing the RPS4 TIR+80 from either dexamethasone or estradiol-inducible promoters display inducer-dependent cell death. Cell death is also elicited by transient expression of similarly truncated constructs from two other R proteins, RPP1A and At4g19530, but is not elicited by similar constructs representing RPP2A and RPP2B proteins. Site-directed mutagenesis of the RPS4 TIR domain identified many loss-of-function mutations but also revealed several gain-of function substitutions. Lack of cell death induction by the E160A substitution suggests that amino acids outside of the TIR domain contribute to cell death signaling in addition to the TIR domain itself. This is consistent with previous observations that the TIR domain itself is insufficient to induce cell death upon transient expression.

  15. Non-local sub-characteristic zones of influence in unsteady interactive boundary-layers

    NASA Technical Reports Server (NTRS)

    Rothmayer, A. P.

    1992-01-01

    The properties of incompressible, unsteady, interactive, boundary layers are examined for a model hypersonic boundary layer and internal flow past humps or, equivalently, external flow past short-scaled humps. Using a linear high frequency analysis, it is shown that the domains of dependence within the viscous sublayer may be a strong function of position within the sublayer and may be strongly influenced by the pressure displacement interaction, or the prescribed displacement condition. Detailed calculations are presented for the hypersonic boundary layer. This effect is found to carry over directly to the fully viscous problem as well as the nonlinear problem. In the fully viscous problem, the non-local character of the domains of dependence manifests itself in the sub-characteristics. Potential implications of the domain of dependence structure on finite difference computations of unsteady boundary layers are briefly discussed.

  16. Time-domain representation of frequency-dependent foundation impedance functions

    USGS Publications Warehouse

    Safak, E.

    2006-01-01

    Foundation impedance functions provide a simple means to account for soil-structure interaction (SSI) when studying seismic response of structures. Impedance functions represent the dynamic stiffness of the soil media surrounding the foundation. The fact that impedance functions are frequency dependent makes it difficult to incorporate SSI in standard time-history analysis software. This paper introduces a simple method to convert frequency-dependent impedance functions into time-domain filters. The method is based on the least-squares approximation of impedance functions by ratios of two complex polynomials. Such ratios are equivalent, in the time-domain, to discrete-time recursive filters, which are simple finite-difference equations giving the relationship between foundation forces and displacements. These filters can easily be incorporated into standard time-history analysis programs. Three examples are presented to show the applications of the method.

  17. A Short Note on Rules and Higher Order Rules.

    ERIC Educational Resources Information Center

    Scandura, Joseph M.

    This brief paper argues that structural analysis--an extended form of cognitive task analysis--demonstrates that both domain dependent and domain independent knowledge can be derived from specific content domains. It is noted that the major difference between the two is that lower order rules (specific knowledge) are derived directly from specific…

  18. MT2-MMP-dependent release of collagen IV NC1 domains regulates submandibular gland branching morphogenesis.

    PubMed

    Rebustini, Ivan T; Myers, Christopher; Lassiter, Keyonica S; Surmak, Andrew; Szabova, Ludmila; Holmbeck, Kenn; Pedchenko, Vadim; Hudson, Billy G; Hoffman, Matthew P

    2009-10-01

    Proteolysis is essential during branching morphogenesis, but the roles of MT-MMPs and their proteolytic products are not clearly understood. Here, we discover that decreasing MT-MMP activity during submandibular gland branching morphogenesis decreases proliferation and increases collagen IV and MT-MMP expression. Specifically, reducing epithelial MT2-MMP profoundly decreases proliferation and morphogenesis, increases Col4a2 and intracellular accumulation of collagen IV, and decreases the proteolytic release of collagen IV NC1 domains. Importantly, we demonstrate the presence of collagen IV NC1 domains in developing tissue. Furthermore, recombinant collagen IV NC1 domains rescue branching morphogenesis after MT2-siRNA treatment, increasing MT-MMP and proproliferative gene expression via beta1 integrin and PI3K-AKT signaling. Additionally, HBEGF also rescues MT2-siRNA treatment, increasing NC1 domain release, proliferation, and MT2-MMP and Hbegf expression. Our studies provide mechanistic insight into how MT2-MMP-dependent release of bioactive NC1 domains from collagen IV is critical for integrating collagen IV synthesis and proteolysis with epithelial proliferation during branching morphogenesis.

  19. Regulator-dependent mechanisms of C3b processing by factor I allow differentiation of immune responses.

    PubMed

    Xue, Xiaoguang; Wu, Jin; Ricklin, Daniel; Forneris, Federico; Di Crescenzio, Patrizia; Schmidt, Christoph Q; Granneman, Joke; Sharp, Thomas H; Lambris, John D; Gros, Piet

    2017-08-01

    The complement system labels microbes and host debris for clearance. Degradation of surface-bound C3b is pivotal to direct immune responses and protect host cells. How the serine protease factor I (FI), assisted by regulators, cleaves either two or three distant peptide bonds in the CUB domain of C3b remains unclear. We present a crystal structure of C3b in complex with FI and regulator factor H (FH; domains 1-4 with 19-20). FI binds C3b-FH between FH domains 2 and 3 and a reoriented C3b C-terminal domain and docks onto the first scissile bond, while stabilizing its catalytic domain for proteolytic activity. One cleavage in C3b does not affect its overall structure, whereas two cleavages unfold CUB and dislodge the thioester-containing domain (TED), affecting binding of regulators and thereby determining the number of cleavages. These data explain how FI generates late-stage opsonins iC3b or C3dg in a context-dependent manner, to react to foreign, danger or healthy self signals.

  20. Cognitive remediation therapy during treatment for alcohol dependence.

    PubMed

    Rupp, Claudia I; Kemmler, Georg; Kurz, Martin; Hinterhuber, Hartmann; Fleischhacker, W Wolfgang

    2012-07-01

    Cognitive impairments in individuals with alcohol dependence may interfere with the progress of treatment and contribute to the progression of the disease. This study aimed to determine whether cognitive remediation (CR) therapy applied during treatment for alcohol dependence improves cognitive functioning in alcohol-dependent inpatients. A secondary aim was to evaluate whether the benefits of CR generalize to noncognitive clinically meaningful outcomes at the end of inpatient treatment. Forty-one alcohol-dependent patients entering inpatient treatment for alcohol dependence were randomly assigned to receive conventional treatment (n = 21) or an additional 12 sessions of computer-assisted CR focusing on cognitive enhancement in attention/executive function and memory domains (n = 20). Assessments of cognitive abilities in these domains as well as of psychological well-being and alcohol craving were conducted at baseline (at the beginning of inpatient treatment) and after CR (at the end of treatment). Results indicated that, relative to patients completing conventional treatment, those who received supplemental CR showed significant improvement in attention/executive function and memory domains, particularly in attention (alertness, divided attention), working memory, and delayed memory (recall). In addition, patients receiving CR during alcohol-dependence treatment showed significantly greater improvements in psychological well-being (Symptom Checklist-90-Revised) and in the compulsion aspect of craving (Obsessive Compulsive Drinking Scale-German version). CR during inpatient treatment for alcohol dependence is effective in improving cognitive impairments in alcohol-dependent patients. The benefits generalize to noncognitive outcomes, demonstrating that CR may be an efficacious adjunctive intervention for the treatment of alcohol dependence.

  1. Is there a domain-general cognitive structuring system? Evidence from structural priming across music, math, action descriptions, and language.

    PubMed

    Van de Cavey, Joris; Hartsuiker, Robert J

    2016-01-01

    Cognitive processing in many domains (e.g., sentence comprehension, music listening, and math solving) requires sequential information to be organized into an integrational structure. There appears to be some overlap in integrational processing across domains, as shown by cross-domain interference effects when for example linguistic and musical stimuli are jointly presented (Koelsch, Gunter, Wittfoth, & Sammler, 2005; Slevc, Rosenberg, & Patel, 2009). These findings support theories of overlapping resources for integrational processing across domains (cfr. SSIRH Patel, 2003; SWM, Kljajevic, 2010). However, there are some limitations to the studies mentioned above, such as the frequent use of unnaturalistic integrational difficulties. In recent years, the idea has risen that evidence for domain-generality in structural processing might also be yielded though priming paradigms (cfr. Scheepers, 2003). The rationale behind this is that integrational processing across domains regularly requires the processing of dependencies across short or long distances in the sequence, involving respectively less or more syntactic working memory resources (cfr. SWM, Kljajevic, 2010), and such processing decisions might persist over time. However, whereas recent studies have shown suggestive priming of integrational structure between language and arithmetics (though often dependent on arithmetic performance, cfr. Scheepers et al., 2011; Scheepers & Sturt, 2014), it remains to be investigated to what extent we can also find evidence for priming in other domains, such as music and action (cfr. SWM, Kljajevic, 2010). Experiment 1a showed structural priming from the processing of musical sequences onto the position in the sentence structure (early or late) to which a relative clause was attached in subsequent sentence completion. Importantly, Experiment 1b showed that a similar structural manipulation based on non-hierarchically ordered color sequences did not yield any priming effect, suggesting that the priming effect is not based on linear order, but integrational dependency. Finally, Experiment 2 presented primes in four domains (relative clause sentences, music, mathematics, and structured descriptions of actions), and consistently showed priming within and across domains. These findings provide clear evidence for domain-general structural processing mechanisms. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Voltage-sensing phosphatase modulation by a C2 domain.

    PubMed

    Castle, Paul M; Zolman, Kevin D; Kohout, Susy C

    2015-01-01

    The voltage-sensing phosphatase (VSP) is the first example of an enzyme controlled by changes in membrane potential. VSP has four distinct regions: the transmembrane voltage-sensing domain (VSD), the inter-domain linker, the cytosolic catalytic domain, and the C2 domain. The VSD transmits the changes in membrane potential through the inter-domain linker activating the catalytic domain which then dephosphorylates phosphatidylinositol phosphate (PIP) lipids. The role of the C2, however, has not been established. In this study, we explore two possible roles for the C2: catalysis and membrane-binding. The Ci-VSP crystal structures show that the C2 residue Y522 lines the active site suggesting a contribution to catalysis. When we mutated Y522 to phenylalanine, we found a shift in the voltage dependence of activity. This suggests hydrogen bonding as a mechanism of action. Going one step further, when we deleted the entire C2 domain, we found voltage-dependent enzyme activity was no longer detectable. This result clearly indicates the entire C2 is necessary for catalysis as well as for modulating activity. As C2s are known membrane-binding domains, we tested whether the VSP C2 interacts with the membrane. We probed a cluster of four positively charged residues lining the top of the C2 and suggested by previous studies to interact with phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] (Kalli et al., 2014). Neutralizing those positive charges significantly shifted the voltage dependence of activity to higher voltages. We tested membrane binding by depleting PI(4,5)P2 from the membrane using the 5HT2C receptor and found that the VSD motions as measured by voltage clamp fluorometry (VCF) were not changed. These results suggest that if the C2 domain interacts with the membrane to influence VSP function it may not occur exclusively through PI(4,5)P2. Together, this data advances our understanding of the VSP C2 by demonstrating a necessary and critical role for the C2 domain in VSP function.

  3. Voltage-sensing phosphatase modulation by a C2 domain

    PubMed Central

    Castle, Paul M.; Zolman, Kevin D.; Kohout, Susy C.

    2015-01-01

    The voltage-sensing phosphatase (VSP) is the first example of an enzyme controlled by changes in membrane potential. VSP has four distinct regions: the transmembrane voltage-sensing domain (VSD), the inter-domain linker, the cytosolic catalytic domain, and the C2 domain. The VSD transmits the changes in membrane potential through the inter-domain linker activating the catalytic domain which then dephosphorylates phosphatidylinositol phosphate (PIP) lipids. The role of the C2, however, has not been established. In this study, we explore two possible roles for the C2: catalysis and membrane-binding. The Ci-VSP crystal structures show that the C2 residue Y522 lines the active site suggesting a contribution to catalysis. When we mutated Y522 to phenylalanine, we found a shift in the voltage dependence of activity. This suggests hydrogen bonding as a mechanism of action. Going one step further, when we deleted the entire C2 domain, we found voltage-dependent enzyme activity was no longer detectable. This result clearly indicates the entire C2 is necessary for catalysis as well as for modulating activity. As C2s are known membrane-binding domains, we tested whether the VSP C2 interacts with the membrane. We probed a cluster of four positively charged residues lining the top of the C2 and suggested by previous studies to interact with phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] (Kalli et al., 2014). Neutralizing those positive charges significantly shifted the voltage dependence of activity to higher voltages. We tested membrane binding by depleting PI(4,5)P2 from the membrane using the 5HT2C receptor and found that the VSD motions as measured by voltage clamp fluorometry (VCF) were not changed. These results suggest that if the C2 domain interacts with the membrane to influence VSP function it may not occur exclusively through PI(4,5)P2. Together, this data advances our understanding of the VSP C2 by demonstrating a necessary and critical role for the C2 domain in VSP function. PMID:25904865

  4. A new window into nurse manager development: teaching for the practice.

    PubMed

    Cathcart, Eloise Balasco; Greenspan, Miriam

    2012-12-01

    An important domain that emerged from the interpretation of 91 nurse manager (NM) narratives was achieving the right relationship between a NM and a recalcitrant staff member. This article depicts the qualitative distinctions in 2 stages of NM practice to show the importance of reflection on experiential learning in the development of expertise. This work confirms that NM development is more complex than teaching a curriculum of business and management theory and should include teaching for mastery of the skilled know-how of clinical leadership practice and formation of the person as manager.

  5. Stereotype Threat Alters the Subjective Experience of Memory.

    PubMed

    Mazerolle, Marie; Régner, Isabelle; Rigalleau, François; Huguet, Pascal

    2015-01-01

    There is now evidence that negative age-related stereotypes about memory reduce older adults' memory performance, and inflate age differences in this domain. Here, we examine whether stereotype threat may also influence the basic feeling that one is more or less able to remember. Using the Remember/Know paradigm, we demonstrated that stereotype threat conducted older adults to a greater feeling of familiarity with events, while failing to retrieve any contextual detail. This finding indicates that stereotype threat alters older adults' subjective experience of memory, and strengthens our understanding of the mechanisms underlying stereotype threat effects.

  6. Fabrication of Large Domain YBa2Cu3O(x) for Magnetic Suspension Applications

    NASA Technical Reports Server (NTRS)

    Sengupta, S.; Corpus, J.; Gaines, J. R., Jr.; Todt, V. R.; Zhang, X.; Miller, D. J.

    1996-01-01

    Large domain YBa2Cu3O(x) levitators have been fabricated using a seeded melt processing technique. Depending upon the seed, either a single or five domained sample can be obtained. The grain boundaries separating each domains in the five domain levitator are found to be 90 degrees. Similar levitation forces can be observed for single and five domained samples. After thermal cycling, however, a small decrease in the levitation force of the five domain levitator was observed as a function of thermal cycles while nearly no change in force was observed in the single domain levitator. Finally, it is shown that both, single and five domain YBCO, behave similarly as a function of sample thickness.

  7. The time dependent magnetization of fine-grained iron in lunar breccias

    NASA Technical Reports Server (NTRS)

    Gose, W. A.; Carnes, J. G.

    1973-01-01

    Lunar breccias of low metamorphic grade offer a unique opportunity to investigate the magnetic properties of dispersed fine-grained iron. These rocks exhibit a pronounced time-dependent magnetization whose acquisition and decay are well explained by Neel's single-domain theory. The effect is due to iron grains in the range from 120 to 150 A in diameter, which covers the transition from superparamagnetic to stable single-domain behavior.

  8. Structure of the adenylation domain of NAD[superscript +]-dependent DNA ligase from Staphylococcus aureus

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

    Han, Seungil; Chang, Jeanne S.; Griffor, Matt

    DNA ligase catalyzes phosphodiester-bond formation between immediately adjacent 5'-phosphate and 3''-hydroxyl groups in double-stranded DNA and plays a central role in many cellular and biochemical processes, including DNA replication, repair and recombination. Bacterial NAD{sup +}-dependent DNA ligases have been extensively characterized as potential antibacterial targets because of their essentiality and their structural distinction from human ATP-dependent DNA ligases. The high-resolution structure of the adenylation domain of Staphylococcus aureus NAD{sup +}-dependent DNA ligase establishes the conserved domain architecture with other bacterial adenylation domains. Two apo crystal structures revealed that the active site possesses the preformed NAD{sup +}-binding pocket and the 'C2more » tunnel' lined with hydrophobic residues: Leu80, Phe224, Leu287, Phe295 and Trp302. The C2 tunnel is unique to bacterial DNA ligases and the Leu80 side chain at the mouth of the tunnel points inside the tunnel and forms a narrow funnel in the S. aureus DNA ligase structure. Taken together with other DNA ligase structures, the S. aureus DNA ligase structure provides a basis for a more integrated understanding of substrate recognition and catalysis and will be also be of help in the development of small-molecule inhibitors.« less

  9. Eicosapentaenoic acid reduces membrane fluidity, inhibits cholesterol domain formation, and normalizes bilayer width in atherosclerotic-like model membranes.

    PubMed

    Mason, R Preston; Jacob, Robert F; Shrivastava, Sandeep; Sherratt, Samuel C R; Chattopadhyay, Amitabha

    2016-12-01

    Cholesterol crystalline domains characterize atherosclerotic membranes, altering vascular signaling and function. Omega-3 fatty acids reduce membrane lipid peroxidation and subsequent cholesterol domain formation. We evaluated non-peroxidation-mediated effects of eicosapentaenoic acid (EPA), other TG-lowering agents, docosahexaenoic acid (DHA), and other long-chain fatty acids on membrane fluidity, bilayer width, and cholesterol domain formation in model membranes. In membranes prepared at 1.5:1 cholesterol-to-phospholipid (C/P) mole ratio (creating pre-existing domains), EPA, glycyrrhizin, arachidonic acid, and alpha linolenic acid promoted the greatest reductions in cholesterol domains (by 65.5%, 54.9%, 46.8%, and 45.2%, respectively) compared to controls; other treatments had modest effects. EPA effects on cholesterol domain formation were dose-dependent. In membranes with 1:1 C/P (predisposing domain formation), DHA, but not EPA, dose-dependently increased membrane fluidity. DHA also induced cholesterol domain formation without affecting temperature-induced changes in-bilayer unit cell periodicity relative to controls (d-space; 57Å-55Å over 15-30°C). Together, these data suggest simultaneous formation of distinct cholesterol-rich ordered domains and cholesterol-poor disordered domains in the presence of DHA. By contrast, EPA had no effect on cholesterol domain formation and produced larger d-space values relative to controls (60Å-57Å; p<0.05) over the same temperature range, suggesting a more uniform maintenance of lipid dynamics despite the presence of cholesterol. These data indicate that EPA and DHA had different effects on membrane bilayer width, membrane fluidity, and cholesterol crystalline domain formation; suggesting omega-3 fatty acids with differing chain length or unsaturation may differentially influence membrane lipid dynamics and structural organization as a result of distinct phospholipid/sterol interactions. Copyright © 2016. Published by Elsevier B.V.

  10. Inhibition of DAI-dependent necroptosis by the Z-DNA binding domain of the vaccinia virus innate immune evasion protein, E3.

    PubMed

    Koehler, Heather; Cotsmire, Samantha; Langland, Jeffrey; Kibler, Karen V; Kalman, Daniel; Upton, Jason W; Mocarski, Edward S; Jacobs, Bertram L

    2017-10-24

    Vaccinia virus (VACV) encodes an innate immune evasion protein, E3, which contains an N-terminal Z-nucleic acid binding (Zα) domain that is critical for pathogenicity in mice. Here we demonstrate that the N terminus of E3 is necessary to inhibit an IFN-primed virus-induced necroptosis. VACV deleted of the Zα domain of E3 (VACV-E3LΔ83N) induced rapid RIPK3-dependent cell death in IFN-treated L929 cells. Cell death was inhibited by the RIPK3 inhibitor, GSK872, and infection with this mutant virus led to phosphorylation and aggregation of MLKL, the executioner of necroptosis. In 293T cells, induction of necroptosis depended on expression of RIPK3 as well as the host-encoded Zα domain-containing DNA sensor, DAI. VACV-E3LΔ83N is attenuated in vivo, and pathogenicity was restored in either RIPK3- or DAI-deficient mice. These data demonstrate that the N terminus of the VACV E3 protein prevents DAI-mediated induction of necroptosis.

  11. Raft-based sphingomyelin interactions revealed by new fluorescent sphingomyelin analogs

    PubMed Central

    Kinoshita, Masanao; Suzuki, Kenichi G.N.; Takada, Misa; Ano, Hikaru; Abe, Mitsuhiro; Makino, Asami; Kobayashi, Toshihide; Hirosawa, Koichiro M.; Fujiwara, Takahiro K.; Murata, Michio

    2017-01-01

    Sphingomyelin (SM) has been proposed to form cholesterol-dependent raft domains and sphingolipid domains in the plasma membrane (PM). How SM contributes to the formation and function of these domains remains unknown, primarily because of the scarcity of suitable fluorescent SM analogs. We developed new fluorescent SM analogs by conjugating a hydrophilic fluorophore to the SM choline headgroup without eliminating its positive charge, via a hydrophilic nonaethylene glycol linker. The new analogs behaved similarly to the native SM in terms of their partitioning behaviors in artificial liquid order-disorder phase-separated membranes and detergent-resistant PM preparations. Single fluorescent molecule tracking in the live-cell PM revealed that they indirectly interact with each other in cholesterol- and sphingosine backbone–dependent manners, and that, for ∼10–50 ms, they undergo transient colocalization-codiffusion with a glycosylphosphatidylinositol (GPI)-anchored protein, CD59 (in monomers, transient-dimer rafts, and clusters), in CD59-oligomer size–, cholesterol-, and GPI anchoring–dependent manners. These results suggest that SM continually and rapidly exchanges between CD59-associated raft domains and the bulk PM. PMID:28330937

  12. Biophysical characterization of the calmodulin-like domain of Plasmodium falciparum calcium dependent protein kinase 3

    PubMed Central

    Andresen, Cecilia; Niklasson, Markus; Cassman Eklöf, Sofie; Wallner, Björn

    2017-01-01

    Calcium dependent protein kinases are unique to plants and certain parasites and comprise an N-terminal segment and a kinase domain that is regulated by a C-terminal calcium binding domain. Since the proteins are not found in man they are potential drug targets. We have characterized the calcium binding lobes of the regulatory domain of calcium dependent protein kinase 3 from the malaria parasite Plasmodium falciparum. Despite being structurally similar, the two lobes differ in several other regards. While the monomeric N-terminal lobe changes its structure in response to calcium binding and shows global dynamics on the sub-millisecond time-scale both in its apo and calcium bound states, the C-terminal lobe could not be prepared calcium-free and forms dimers in solution. If our results can be generalized to the full-length protein, they suggest that the C-terminal lobe is calcium bound even at basal levels and that activation is caused by the structural reorganization associated with binding of a single calcium ion to the N-terminal lobe. PMID:28746405

  13. A TPR domain-containing N-terminal module of MPS1 is required for its kinetochore localization by Aurora B.

    PubMed

    Nijenhuis, Wilco; von Castelmur, Eleonore; Littler, Dene; De Marco, Valeria; Tromer, Eelco; Vleugel, Mathijs; van Osch, Maria H J; Snel, Berend; Perrakis, Anastassis; Kops, Geert J P L

    2013-04-15

    The mitotic checkpoint ensures correct chromosome segregation by delaying cell cycle progression until all kinetochores have attached to the mitotic spindle. In this paper, we show that the mitotic checkpoint kinase MPS1 contains an N-terminal localization module, organized in an N-terminal extension (NTE) and a tetratricopeptide repeat (TPR) domain, for which we have determined the crystal structure. Although the module was necessary for kinetochore localization of MPS1 and essential for the mitotic checkpoint, the predominant kinetochore binding activity resided within the NTE. MPS1 localization further required HEC1 and Aurora B activity. We show that MPS1 localization to kinetochores depended on the calponin homology domain of HEC1 but not on Aurora B-dependent phosphorylation of the HEC1 tail. Rather, the TPR domain was the critical mediator of Aurora B control over MPS1 localization, as its deletion rendered MPS1 localization insensitive to Aurora B inhibition. These data are consistent with a model in which Aurora B activity relieves a TPR-dependent inhibitory constraint on MPS1 localization.

  14. Single-stranded nucleic acids promote SAMHD1 complex formation.

    PubMed

    Tüngler, Victoria; Staroske, Wolfgang; Kind, Barbara; Dobrick, Manuela; Kretschmer, Stefanie; Schmidt, Franziska; Krug, Claudia; Lorenz, Mike; Chara, Osvaldo; Schwille, Petra; Lee-Kirsch, Min Ae

    2013-06-01

    SAM domain and HD domain-containing protein 1 (SAMHD1) is a dGTP-dependent triphosphohydrolase that degrades deoxyribonucleoside triphosphates (dNTPs) thereby limiting the intracellular dNTP pool. Mutations in SAMHD1 cause Aicardi-Goutières syndrome (AGS), an inflammatory encephalopathy that mimics congenital viral infection and that phenotypically overlaps with the autoimmune disease systemic lupus erythematosus. Both disorders are characterized by activation of the antiviral cytokine interferon-α initiated by immune recognition of self nucleic acids. Here we provide first direct evidence that SAMHD1 associates with endogenous nucleic acids in situ. Using fluorescence cross-correlation spectroscopy, we demonstrate that SAMHD1 specifically interacts with ssRNA and ssDNA and establish that nucleic acid-binding and formation of SAMHD1 complexes are mutually dependent. Interaction with nucleic acids and complex formation do not require the SAM domain, but are dependent on the HD domain and the C-terminal region of SAMHD1. We finally demonstrate that mutations associated with AGS exhibit both impaired nucleic acid-binding and complex formation implicating that interaction with nucleic acids is an integral aspect of SAMHD1 function.

  15. Both internalization and AIP1 association are required for tumor necrosis factor receptor 2-mediated JNK signaling.

    PubMed

    Ji, Weidong; Li, Yonghao; Wan, Ting; Wang, Jing; Zhang, Haifeng; Chen, Hong; Min, Wang

    2012-09-01

    The proinflammtory cytokine tumor necrosis factor (TNF), primarily via TNF receptor 1 (TNFR1), induces nuclear factor-κB (NF-κB)-dependent cell survival, and c-Jun N-terminal kinase (JNK) and caspase-dependent cell death, regulating vascular endothelial cell (EC) activation and apoptosis. However, signaling by the second receptor, TNFR2, is poorly understood. The goal of this study was to dissect how TNFR2 mediates NF-κB and JNK signaling in vascular EC, and its relevance to in vivo EC function. We show that TNFR2 contributes to TNF-induced NF-κB and JNK signaling in EC as TNFR2 deletion or knockdown reduces the TNF responses. To dissect the critical domains of TNFR2 that mediate the TNF responses, we examine the activity of TNFR2 mutant with a specific deletion of the TNFR2 intracellular region, which contains conserved domain I, domain II, domain III, and 2 TNFR-associated factor-2-binding sites. Deletion analyses indicate that different sequences on TNFR2 have distinct roles in NF-κB and JNK activation. Specifically, deletion of the TNFR-associated factor-2-binding sites (TNFR2-59) diminishes the TNFR2-mediated NF-κB, but not JNK activation; whereas, deletion of domain II or domain III blunts TNFR2-mediated JNK but not NF-κB activation. Interestingly, we find that the TNFR-associated factor-2-binding sites ensure TNFR2 on the plasma membrane, but the di-leucine LL motif within the domain II and aa338-355 within the domain III are required for TNFR2 internalization as well as TNFR2-dependent JNK signaling. Moreover, domain III of TNFR2 is responsible for association with ASK1-interacting protein-1, a signaling adaptor critical for TNF-induced JNK signaling. While TNFR2 containing the TNFR-associated factor-2-binding sites prevents EC cell death, a specific activation of JNK without NF-κB activation by TNFR2-59 strongly induces caspase activation and EC apoptosis. Our data reveal that both internalization and ASK1-interacting protein-1 association are required for TNFR2-dependent JNK and apoptotic signaling. Controlling TNFR2-mediated JNK and apoptotic signaling in EC may provide a novel strategy for the treatment of vascular diseases.

  16. The Zombie Instability: Using Numerical Simulation to Design a Laboratory Experiment

    NASA Astrophysics Data System (ADS)

    Wang, Meng; Pei, Suyang; Jiang, Chung-Hsiang; Hassanzadeh, Pedram; Marcus, Philip

    2014-11-01

    A new type of finite amplitude-instability has been found in numerical simulations of stratified, rotating, shear flows. The instability occurs via baroclinic critical layers that create linearly unstable vortex layers, which roll-up into vortices. Under the right conditions, those vortices can form a new generation of vortices, resulting in ``vortex self-replication'' that fills the fluid with vortices. Creating this instability in a laboratory would provide further evidence for the existence of the instability, which we first found in numerical simulations of protoplanetary disks. To design a laboratory experiment we need to know how the flow parameters-- shear, rotation and stratification, etc. affect the instability. To build an experiment economically, we also need to know how the finite-amplitude trigger of the instability scales with viscosity and the size of the domain. In this talk, we summarize our findings. We present a map, in terms of the experimentally controllable parameters, that shows where the instability occurs and whether the instability creates a few isolated transient vortices, a few long-lived vortices, or long-lived, self-replicating vortices that fill the entire flow.

  17. Characterization of new regulatory elements within the Drosophila bithorax complex.

    PubMed

    Pérez-Lluch, Sílvia; Cuartero, Sergi; Azorín, Fernando; Espinàs, M Lluïsa

    2008-12-01

    The homeotic Abdominal-B (Abd-B) gene expression depends on a modular cis-regulatory region divided into discrete functional domains (iab) that control the expression of the gene in a particular segment of the fly. These domains contain regulatory elements implicated in both initiation and maintenance of homeotic gene expression and elements that separate the different domains. In this paper we have performed an extensive analysis of the iab-6 regulatory region, which regulates Abd-B expression at abdominal segment A6 (PS11), and we have characterized two new polycomb response elements (PREs) within this domain. We report that PREs at Abd-B cis-regulatory domains present a particular chromatin structure which is nuclease accessible all along Drosophila development and both in active and repressed states. We also show that one of these regions contains a dCTCF and CP190 dependent activity in transgenic enhancer-blocking assays, suggesting that it corresponds to the Fab-6 boundary element of the Drosophila bithorax complex.

  18. Effect of externally applied electrostatic fields on the surface topography of ceramide-enriched domains in mixed monolayers with sphingomyelin.

    PubMed

    Wilke, Natalia; Maggio, Bruno

    2006-06-20

    Lipid and protein molecules anisotropically oriented at a hydrocarbon-aqueous interface configure a dynamic array of self-organized molecular dipoles. Electrostatic fields applied to lipid monolayers have been shown to induce in-plane migration of domains or phase separation in a homogeneous system. In this work, we have investigated the effect of externally applied electrostatic fields on the distribution of the condensed ceramide-enriched domains in mixed monolayers with sphingomyelin. In these monolayers, the lipids segregate in different phases at all pressures. This allows analyzing by epifluorescence microscopy the effect of the electrostatic field at all lateral pressure because coexistence of lipid domains in condensed state are always present. Our observations indicate that a positive potential applied to an electrode placed over the monolayer promotes a repulsion of the ceramide-enriched domains which is rather insensitive to the film composition, depends inversely on the lateral pressure and exhibits threshold dependence on the in-plane elasticity.

  19. Betel-quid dependence domains and syndrome associated with betel-quid ingredients among chewers: an Asian multi-country evidence.

    PubMed

    Lee, Chien-Hung; Chiang, Shang-Lun; Ko, Albert Min-Shan; Hua, Chun-Hung; Tsai, Ming-Hsui; Warnakulasuriya, Saman; Ibrahim, Salah Osman; Sunarjo; Zain, Rosnah Binti; Ling, Tian-You; Huang, Chieh-Liang; Lane, Hsien-Yuan; Lin, Cheng-Chieh; Ko, Ying-Chin

    2014-07-01

    Betel-quid (BQ) contains biologically psychoactive ingredients; however, data are limited concerning the symptoms and syndrome of BQ dependence among chewers. The aims of this study were to evaluate the ingredients-associated BQ dependence syndrome and country-specific chewing features and behaviour for BQ dependence among chewers from six Asian communities. An intercountry Asian Betel-quid Consortium study. Six Asian general communities in Taiwan, Mainland China, Indonesia, Malaysia, Sri Lanka and Nepal. Six multi-stage random samples of BQ chewers in the Asian Betel-quid Consortium study (n = 2078). All chewers were evaluated for BQ dependence using the DSM-IV and ICD-10 criteria. The 12-month BQ dependence rate was 12.5-92.6% and 47.9-99.3% (P = 0.023) among tobacco-free and tobacco-added BQ chewers across the six Asian communities, with a higher dependence rate in chewers who used tobacco-free BQ with lime added than without (23.3-95.6% versus 4.0%, P ≤ 0.001). Taiwanese and Hunanese BQ chewers both notably endorsed the dependency domain of 'time spent chewing'. 'Tolerance' and 'withdrawal' were the major dependence domains associated with the Nepalese and Indonesian chewers, with high BQ dependence rates. Malaysian and Sri Lankan chewers formed a BQ dependence cluster linked closely to 'craving'. In Sri Lanka, the quantity consumed explained 90.5% (P < 0.001) of the excess dependence risk for tobacco-added use, and could be a mediator between tobacco-derived psychoactive effect and BQ dependence development. DSM-IV criteria for dependence apply to a significant proportion of betel quid users in Asian communities, more so if they use it with tobacco or lime. © 2014 Society for the Study of Addiction.

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

    T Yeh; C Lee; L Amzel

    Fission yeast protein Sre1, the homolog of the mammalian sterol regulatory element-binding protein (SREBP), is a hypoxic transcription factor required for sterol homeostasis and low-oxygen growth. Nro1 regulates the stability of the N-terminal transcription factor domain of Sre1 (Sre1N) by inhibiting the action of the prolyl 4-hydroxylase-like Ofd1 in an oxygen-dependent manner. The crystal structure of Nro1 determined at 2.2 {angstrom} resolution shows an all-{alpha}-helical fold that can be divided into two domains: a small N-terminal domain, and a larger C-terminal HEAT-repeat domain. Follow-up studies showed that Nro1 defines a new class of nuclear import adaptor that functions both inmore » Ofd1 nuclear localization and in the oxygen-dependent inhibition of Ofd1 to control the hypoxic response.« less

  1. The conserved RNA recognition motif and C3H1 domain of the Not4 ubiquitin ligase regulate in vivo ligase function.

    PubMed

    Chen, Hongfeng; Sirupangi, Tirupataiah; Wu, Zhao-Hui; Johnson, Daniel L; Laribee, R Nicholas

    2018-05-25

    The Ccr4-Not complex controls RNA polymerase II (Pol II) dependent gene expression and proteasome function. The Not4 ubiquitin ligase is a Ccr4-Not subunit that has both a RING domain and a conserved RNA recognition motif and C3H1 domain (referred to as the RRM-C domain) with unknown function. We demonstrate that while individual Not4 RING or RRM-C mutants fail to replicate the proteasomal defects found in Not4 deficient cells, mutation of both exhibits a Not4 loss of function phenotype. Transcriptome analysis revealed that the Not4 RRM-C affects a specific subset of Pol II-regulated genes, including those involved in transcription elongation, cyclin-dependent kinase regulated nutrient responses, and ribosomal biogenesis. The Not4 RING, RRM-C, or RING/RRM-C mutations cause a generalized increase in Pol II binding at a subset of these genes, yet their impact on gene expression does not always correlate with Pol II recruitment which suggests Not4 regulates their expression through additional mechanisms. Intriguingly, we find that while the Not4 RRM-C is dispensable for Ccr4-Not association with RNA Pol II, the Not4 RING domain is required for these interactions. Collectively, these data elucidate previously unknown roles for the conserved Not4 RRM-C and RING domains in regulating Ccr4-Not dependent functions in vivo.

  2. Cholesterol trafficking and raft-like membrane domain composition mediate scavenger receptor class B type 1-dependent lipid sensing in intestinal epithelial cells.

    PubMed

    Morel, Etienne; Ghezzal, Sara; Lucchi, Géraldine; Truntzer, Caroline; Pais de Barros, Jean-Paul; Simon-Plas, Françoise; Demignot, Sylvie; Mineo, Chieko; Shaul, Philip W; Leturque, Armelle; Rousset, Monique; Carrière, Véronique

    2018-02-01

    Scavenger receptor Class B type 1 (SR-B1) is a lipid transporter and sensor. In intestinal epithelial cells, SR-B1-dependent lipid sensing is associated with SR-B1 recruitment in raft-like/ detergent-resistant membrane domains and interaction of its C-terminal transmembrane domain with plasma membrane cholesterol. To clarify the initiating events occurring during lipid sensing by SR-B1, we analyzed cholesterol trafficking and raft-like domain composition in intestinal epithelial cells expressing wild-type SR-B1 or the mutated form SR-B1-Q445A, defective in membrane cholesterol binding and signal initiation. These features of SR-B1 were found to influence both apical cholesterol efflux and intracellular cholesterol trafficking from plasma membrane to lipid droplets, and the lipid composition of raft-like domains. Lipidomic analysis revealed likely participation of d18:0/16:0 sphingomyelin and 16:0/0:0 lysophosphatidylethanolamine in lipid sensing by SR-B1. Proteomic analysis identified proteins, whose abundance changed in raft-like domains during lipid sensing, and these included molecules linked to lipid raft dynamics and signal transduction. These findings provide new insights into the role of SR-B1 in cellular cholesterol homeostasis and suggest molecular links between SR-B1-dependent lipid sensing and cell cholesterol and lipid droplet dynamics. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Imagining and Imaging Borders: Understanding Borderlands for Global Sustainability

    NASA Astrophysics Data System (ADS)

    Konrad, V.

    2013-11-01

    Borders are increasingly complex human responses and social constructions in a world where globalizing forces confront basic human concerns for security and certainty. In an effort to provide a background to assess research directions for imaging borders, this paper explores what we know about borders, and what we do not know well about borders. Borders in globalization are the meeting points of globalizing forces of security, trade and migration flows with emerging technologies, self determination and regionalization around the world. We need to know more about how: self determination fuels secessions and new borders; borders result from complex rather than simple policy and governance issues; borders depend on the political clout of borderland communities; market and migration flows impact borders; and borders are always in motion. The paper shows how these organizing principles underlie the basic themes of border governance, flows, culture, history, security and sustainability. Finally, the paper offers two brief illustrations of border imaging to link this presentation to the following discussion of the workshop.

  4. Functional relationship between CABIT, SAM and 14-3-3 binding domains of GAREM1 that play a role in its subcellular localization

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

    Nishino, Tasuku; Matsunaga, Ryota; Konishi, Hiroaki, E-mail: hkonishi@pu-hiroshima.ac.jp

    2015-08-21

    GAREM1 (Grb2-associated regulator of Erk/MAPK1) is an adaptor protein that is involved in the epidermal growth factor (EGF) pathway. The nuclear localization of GAREM1 depends on the nuclear localization sequence (NLS), which is located at the N-terminal CABIT (cysteine-containing, all in Themis) domain. Here, we identified 14-3-3ε as a GAREM-binding protein, and its binding site is closely located to the NLS. This 14-3-3 binding site was of the atypical type and independent of GAREM phosphorylation. Moreover, the binding of 14-3-3 had an effect on the nuclear localization of GAREM1. Unexpectedly, we observed that the CABIT domain had intramolecular association withmore » the C-terminal SAM (sterile alpha motif) domain. This association might be inhibited by binding of 14-3-3 at the CABIT domain. Our results demonstrate that the mechanism underlying the nuclear localization of GAREM1 depends on its NLS in the CABIT domain, which is controlled by the binding of 14-3-3 and the C-terminal SAM domain. We suggest that the interplay between 14-3-3, SAM domain and CABIT domain might be responsible for the distribution of GAREM1 in mammalian cells. - Highlights: • 14-3-3ε regulated the nuclear localization of GAREM1 as its binding partner. • The atypical 14-3-3 binding site of GAREM1 is located near the NLS in CABIT domain. • The CABIT domain had intramolecular association with the SAM domain in GAREM1. • Subcellular localization of GAREM1 is affected with its CABIT-SAM interaction.« less

  5. The mechanical response of talin

    NASA Astrophysics Data System (ADS)

    Yao, Mingxi; Goult, Benjamin T.; Klapholz, Benjamin; Hu, Xian; Toseland, Christopher P.; Guo, Yingjian; Cong, Peiwen; Sheetz, Michael P.; Yan, Jie

    2016-07-01

    Talin, a force-bearing cytoplasmic adapter essential for integrin-mediated cell adhesion, links the actin cytoskeleton to integrin-based cell-extracellular matrix adhesions at the plasma membrane. Its C-terminal rod domain, which contains 13 helical bundles, plays important roles in mechanosensing during cell adhesion and spreading. However, how the structural stability and transition kinetics of the 13 helical bundles of talin are utilized in the diverse talin-dependent mechanosensing processes remains poorly understood. Here we report the force-dependent unfolding and refolding kinetics of all talin rod domains. Using experimentally determined kinetics parameters, we determined the dynamics of force fluctuation during stretching of talin under physiologically relevant pulling speeds and experimentally measured extension fluctuation trajectories. Our results reveal that force-dependent stochastic unfolding and refolding of talin rod domains make talin a very effective force buffer that sets a physiological force range of only a few pNs in the talin-mediated force transmission pathway.

  6. Frequency dependent polarisation switching in h-ErMnO3

    NASA Astrophysics Data System (ADS)

    Ruff, Alexander; Li, Ziyu; Loidl, Alois; Schaab, Jakob; Fiebig, Manfred; Cano, Andres; Yan, Zewu; Bourret, Edith; Glaum, Julia; Meier, Dennis; Krohns, Stephan

    2018-04-01

    We report an electric-field poling study of the geometrically-driven improper ferroelectric h-ErMnO3. From a detailed dielectric analysis, we deduce the temperature and the frequency dependent range for which single-crystalline h-ErMnO3 exhibits purely intrinsic dielectric behaviour, i.e., free from the extrinsic so-called Maxwell-Wagner polarisations that arise, for example, from surface barrier layers. In this regime, ferroelectric hysteresis loops as a function of frequency, temperature, and applied electric fields are measured, revealing the theoretically predicted saturation polarisation on the order of 5-6 μC/cm2. Special emphasis is put on frequency dependent polarisation switching, which is explained in terms of domain-wall movement similar to proper ferroelectrics. Controlling the domain walls via electric fields brings us an important step closer to their utilization in domain-wall-based electronics.

  7. How Knowledge Powers Reading

    ERIC Educational Resources Information Center

    Lemov, Doug

    2017-01-01

    Recent research shows that reading comprehension relies heavily on prior knowledge. Far more than generic "reading skills" like drawing inferences, making predictions, and knowing the function of subheads, how well students learn from a nonfiction text depends on their background knowledge of the text's subject matter. And in a cyclical…

  8. Elevating Engagement and Community in Online Courses

    ERIC Educational Resources Information Center

    Cuthbertson, William; Falcone, Andrea

    2014-01-01

    Community, while inherent in assumptions about online education, rarely materializes as an integral component of the experience. Misconceptions and misguided motivations can derail participation and engagement in the online setting. Creating a successful online community is dependent on knowing what works in the face-to-face environment and…

  9. Automated Geospatial Watershed Assessment (AGWA)Documentation Version 2.0

    EPA Science Inventory

    What are the human impacts of environmental change? How might land be used and what would be the potential benefits or consequences? Numerous questions arise as the world we know becomes smaller in our perception and the human population it supports becomes more dependent on the ...

  10. Translation to Brazilian Portuguese, cultural adaptation and reproducibility of the questionnaire "Ankylosing Spondylitis: What do you know?"

    PubMed

    Orlandi, Aline; Brumini, Christine; Jones, Anamaria; Natour, Jamil

    2016-09-26

    Ankylosing spondylitis (AS) generates inflammation and pain in entheses, peripheral joints and the spine. Education regarding AS can improve patients' disability. Thus, it is important to assess patients' knowledge. There is no instrument in the literature for assessing knowledge of AS in Portuguese. The aim here was to translate to the Brazilian Portuguese language, culturally adapt and test the reliability of the questionnaire "Ankylosing Spondylitis: What do you know?" and to correlate the findings with other factors. Original article regarding validation of questionnaire, produced at the Federal University of Sao Paulo (Unifesp). For translation and cultural adaptation, Guilleman methodology was used. After the first phase, the reliability was tested on 30 patients. Correlations between these scores and other factors were examined. In the interobserver assessment, the Pearson correlation coefficient and Cronbach's alpha were 0.831 and 0.895, respectively. In the intraobserver evaluation, the intraclass correlation coefficient and Cronbach's alpha were 0.79 and 0.883, respectively. At this stage, the score for area of knowledge A showed correlations with ethnicity and education; the score for area D, with age; the total score and scores for areas A and B with "social aspects" of SF-36; and the score for area D with "pain", "vitality" and "emotional aspects" of SF-36. The Brazilian version of the questionnaire "Ankylosing Spondylitis: What do you know?" was created. It is reproducible and correlates with education level, ethnicity and the SF-36 domains "social aspects" and "emotional aspects".

  11. Adult Demography and Larval Processes in Coastal Benthic Populations: Intertidal Barnacles in Southern California and Baja California

    DTIC Science & Technology

    2005-09-01

    mechanism for near-shore concentration and estuarine recruitment of post-larval Penaeus plebejus Hess ( Decapoda , Penaeidae). Estuarine, Coastal and...the physical The dynamics of coastal populations is highly processes that are likely to affect the distribution dependent on the mechanisms and...help. I was lucky to land on a lab where, depending on the lunar phase, time of year, and who knows what other environmental variables, I would find a

  12. 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

  13. Precise Aperture-Dependent Motion Compensation with Frequency Domain Fast Back-Projection Algorithm.

    PubMed

    Zhang, Man; Wang, Guanyong; Zhang, Lei

    2017-10-26

    Precise azimuth-variant motion compensation (MOCO) is an essential and difficult task for high-resolution synthetic aperture radar (SAR) imagery. In conventional post-filtering approaches, residual azimuth-variant motion errors are generally compensated through a set of spatial post-filters, where the coarse-focused image is segmented into overlapped blocks concerning the azimuth-dependent residual errors. However, image domain post-filtering approaches, such as precise topography- and aperture-dependent motion compensation algorithm (PTA), have difficulty of robustness in declining, when strong motion errors are involved in the coarse-focused image. In this case, in order to capture the complete motion blurring function within each image block, both the block size and the overlapped part need necessary extension leading to degeneration of efficiency and robustness inevitably. Herein, a frequency domain fast back-projection algorithm (FDFBPA) is introduced to deal with strong azimuth-variant motion errors. FDFBPA disposes of the azimuth-variant motion errors based on a precise azimuth spectrum expression in the azimuth wavenumber domain. First, a wavenumber domain sub-aperture processing strategy is introduced to accelerate computation. After that, the azimuth wavenumber spectrum is partitioned into a set of wavenumber blocks, and each block is formed into a sub-aperture coarse resolution image via the back-projection integral. Then, the sub-aperture images are straightforwardly fused together in azimuth wavenumber domain to obtain a full resolution image. Moreover, chirp-Z transform (CZT) is also introduced to implement the sub-aperture back-projection integral, increasing the efficiency of the algorithm. By disusing the image domain post-filtering strategy, robustness of the proposed algorithm is improved. Both simulation and real-measured data experiments demonstrate the effectiveness and superiority of the proposal.

  14. The C-terminal domain of the betaine carrier BetP of Corynebacterium glutamicum is directly involved in sensing K+ as an osmotic stimulus.

    PubMed

    Schiller, Dirk; Rübenhagen, René; Krämer, Reinhard; Morbach, Susanne

    2004-05-18

    The glycine betaine carrier BetP of Corynebacterium glutamicum was recently shown to function both as an osmosensor and as an osmoregulator in proteoliposomes by sensing changes in the internal K(+) concentration as a measure of hyperosmotic stress. In vivo analysis of mutants carrying deletions at the C-terminal extension of BetP indicated that this domain participates in osmostress-dependent activity regulation. To address the question, whether a putative K(+) sensor is located within the C-terminal domain, several mutants with truncations in this domain were purified and reconstituted in proteoliposomes of Escherichia coli phospholipids, since this in vitro system allowed variation of the K(+) concentration at the lumenal side. Truncation of 12 amino acids led to a partly deregulated BetP in terms of osmoregulation; however, K(+) sensitivity was not impaired in this mutant. The deletion of 25 amino acid residues at the C-terminal end of BetP led to both deregulation of the carrier activity, i.e., high activity independent of external osmolality, and loss of K(+)-dependent transport stimulation, indicating that this region of the C-terminal domain is necessary for K(+) sensing and/or K(+)-dependent carrier activation. Immunological and proteolysis analyses showed that BetP and its recombinant forms were reconstituted in a right-side-out orientation, i.e., the C-terminal domain faces the lumen of the proteoliposomes and is thus able to detect the K(+) signal at the inside. This is the first experimental demonstration of a direct connection between an osmotic stimulus, i.e., the change in internal K(+), and a putative sensor domain.

  15. Contributions of physical and cognitive impairments to self-reported driving difficulty in chronic whiplash-associated disorders.

    PubMed

    Takasaki, Hiroshi; Treleaven, Julia; Johnston, Venerina; Jull, Gwendolen

    2013-08-15

    Cross-sectional. To conduct a preliminary analysis of the physical, cognitive, and psychological domains contributing to self-reported driving difficulty after adjusting for neck pain, dizziness, and relevant demographics in chronic whiplash-associated disorders (WAD) using hierarchical regression modeling. Pain is a risk factor for car crashes, and dizziness may affect fitness to drive. Both symptoms are common in chronic WAD and difficulty driving is a common complaint in this group. Chronic WAD is often accompanied by physical, cognitive, and psychological impairments. These impairments may contribute to self-reported driving difficulty beyond neck pain, dizziness, and relevant demographics. Forty individuals with chronic WAD participated. Dependent variables were the magnitude of self-reported driving difficulty assessed in the strategic, tactical, and operational levels of the Neck Pain Driving Index. Three models were developed to assess the contributions of independent variables (physical, cognitive, and psychological domains) to each of the 3 dependent variables after adjusting for neck pain intensity, dizziness, and driving demographics. The measures included were: physical domain-range and maximum speed of head rotation, performances during gaze stability, eye-head coordination, and visual dependency tests; cognitive domain-self-reported cognitive symptoms including fatigue and the trail making tests; and psychological domain-general stress, traumatic stress, depression, and fear of neck movements and driving. Symptom duration was relevant to driving difficulty in the strategic and tactical levels. The cognitive domain increased statistical power to estimate the strategic and operational levels (P < 0.1) beyond other contributors. The physical domain increased statistical power to estimate the tactical level (P < 0.1) beyond other contributors. Physical and cognitive impairments independently contributed to self-reported driving difficulty in chronic WAD beyond neck pain, dizziness, and symptom duration. 3.

  16. 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

  17. Distinct roles of beta1 metal ion-dependent adhesion site (MIDAS), adjacent to MIDAS (ADMIDAS), and ligand-associated metal-binding site (LIMBS) cation-binding sites in ligand recognition by integrin alpha2beta1.

    PubMed

    Valdramidou, Dimitra; Humphries, Martin J; Mould, A Paul

    2008-11-21

    Integrin-ligand interactions are regulated in a complex manner by divalent cations, and previous studies have identified ligand-competent, stimulatory, and inhibitory cation-binding sites. In collagen-binding integrins, such as alpha2beta1, ligand recognition takes place exclusively at the alpha subunit I domain. However, activation of the alphaI domain depends on its interaction with a structurally similar domain in the beta subunit known as the I-like or betaI domain. The top face of the betaI domain contains three cation-binding sites: the metal-ion dependent adhesion site (MIDAS), the ADMIDAS (adjacent to MIDAS), and LIMBS (ligand-associated metal-binding site). The role of these sites in controlling ligand binding to the alphaI domain has yet to be elucidated. Mutation of the MIDAS or LIMBS completely blocked collagen binding to alpha2beta1; in contrast mutation of the ADMIDAS reduced ligand recognition but this effect could be overcome by the activating monoclonal antibody TS2/16. Hence, the MIDAS and LIMBS appear to be essential for the interaction between alphaI and betaI, whereas occupancy of the ADMIDAS has an allosteric effect on the conformation of betaI. An activating mutation in the alpha2 I domain partially restored ligand binding to the MIDAS and LIMBS mutants. Analysis of the effects of Ca(2+), Mg(2+), and Mn(2+) on ligand binding to these mutants showed that the MIDAS is a ligand-competent site through which Mn(2+) stimulates ligand binding, whereas the LIMBS is a stimulatory Ca(2+)-binding site, occupancy of which increases the affinity of Mg(2+) for the MIDAS.

  18. Growth dependent magnetization reversal in Co2MnAl full Heusler alloy thin films

    NASA Astrophysics Data System (ADS)

    Barwal, Vineet; Husain, Sajid; Behera, Nilamani; Goyat, Ekta; Chaudhary, Sujeet

    2018-02-01

    Angular dependent magnetization reversal has been investigated in Co2MnAl (CMA) full Heusler alloy thin films grown on Si(100) at different growth temperatures (Ts) by DC-magnetron sputtering. An M -shaped curve is observed in the in-plane angular (0°-360°) dependent coercivity (ADC) by magneto-optical Kerr effect measurements. The dependence of the magnetization reversal on Ts is investigated in detail to bring out the structure-property correlation with regards to ADC in these polycrystalline CMA thin films. This magnetization reversal ( M -shaped ADC behavior) is well described by the two-phase model, which is a combination of Kondorsky (domain wall motion) and Stoner Wohlfarth (coherent rotation) models. In this model, magnetization reversal starts with depinning of domain walls, with their gradual displacement explained by the Kondorsky model, and at a higher field (when the domain walls merge), the system follows coherent rotation before reaching its saturation following the Stoner Wohlfarth model. Further, the analysis of angular dependent squareness ratio (Mr/Ms) indicates that our films clearly exhibited twofold uniaxial anisotropy, which is related to self-steering effect arising due to the obliquely incident flux during the film-growth.

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

    PubMed

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

    2006-09-01

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

  20. Generalization of the Schwarz–Christoffel mapping to multiply connected polygonal domains

    PubMed Central

    Vasconcelos, Giovani L.

    2014-01-01

    A generalization of the Schwarz–Christoffel mapping to multiply connected polygonal domains is obtained by making a combined use of two preimage domains, namely, a rectilinear slit domain and a bounded circular domain. The conformal mapping from the circular domain to the polygonal region is written as an indefinite integral whose integrand consists of a product of powers of the Schottky-Klein prime functions, which is the same irrespective of the preimage slit domain, and a prefactor function that depends on the choice of the rectilinear slit domain. A detailed derivation of the mapping formula is given for the case where the preimage slit domain is the upper half-plane with radial slits. Representation formulae for other canonical slit domains are also obtained but they are more cumbersome in that the prefactor function contains arbitrary parameters in the interior of the circular domain. PMID:24910523

  1. Generalization of the Schwarz-Christoffel mapping to multiply connected polygonal domains.

    PubMed

    Vasconcelos, Giovani L

    2014-06-08

    A generalization of the Schwarz-Christoffel mapping to multiply connected polygonal domains is obtained by making a combined use of two preimage domains, namely, a rectilinear slit domain and a bounded circular domain. The conformal mapping from the circular domain to the polygonal region is written as an indefinite integral whose integrand consists of a product of powers of the Schottky-Klein prime functions, which is the same irrespective of the preimage slit domain, and a prefactor function that depends on the choice of the rectilinear slit domain. A detailed derivation of the mapping formula is given for the case where the preimage slit domain is the upper half-plane with radial slits. Representation formulae for other canonical slit domains are also obtained but they are more cumbersome in that the prefactor function contains arbitrary parameters in the interior of the circular domain.

  2. [Managing focal incidental renal lesions].

    PubMed

    Nicolau, C; Paño, B; Sebastià, C

    2016-01-01

    Incidental renal lesions are relatively common in daily radiological practice. It is important to know the different diagnostic possibilities for incidentally detected lesions, depending on whether they are cystic or solid. The management of cystic lesions is guided by the Bosniak classification. In solid lesions, the goal is to differentiate between renal cancer and benign tumors such as fat-poor angiomyolipoma and oncocytoma. Radiologists need to know the recommendations for the management of these lesions and the usefulness of the different imaging techniques and interventional procedures in function of the characteristics of the incidental lesion and the patient's life expectancy. Copyright © 2015 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

  3. Hospital quality choice and market structure in a regulated duopoly.

    PubMed

    Beitia, Arantza

    2003-11-01

    This paper analyzes the optimal structure of a regulated health care industry in a model in which the regulator cannot enforce what hospitals do (unverifiable quality of health) or does not know what hospitals know (incomplete information about production costs) or both. We show that if quality is unverifiable the choice between monopoly and duopoly does not change with respect to the verifiable case but, if there are fixed costs (assumed to be quality dependent) and the monopoly is the optimal market structure, the quality level of the operative hospital decreases. Asymmetry of information introduces informational rents that can be reduced by increasing the most efficient hospital's market share. A monopoly is chosen more often.

  4. Memory, thinking, and aging. What we know about what we know.

    PubMed Central

    Teri, L; McCurry, S M; Logsdon, R G

    1997-01-01

    Cognition is the foundation that underlies all daily activities, from the most basic to the most complex. Successful aging depends, in large part, on maintaining a level of cognitive ability that allows a person to interact effectively and appropriately with the environment. In the following article we provide an overview of the effects of aging on cognition; discuss physical, social, and psychological factors that have been shown to influence cognition in old age; and review current literature on interventions that may optimize successful cognitive aging. We conclude with a discussion of abnormal cognitive aging and review current research on risk factors and treatments of Alzheimer's disease and other dementing illnesses. PMID:9348759

  5. Writing My Way to My Future | Poster

    Cancer.gov

    By Nathalie Walker, Guest Writer Editor’s note: This article is the second in a series describing one student’s perspective on her experiences as a Werner H. Kirsten student intern. “The future depends on what you do today.” Those wise words were spoken by Mahatma Gandhi. Before I started my Werner H. Kirsten (WHK) student internship, I did not know what I know now. I only knew what each of Gandhi’s words meant individually. I now understand the full meaning of the phrase. To me, Gandhi’s words mean that nothing in life is handed to you. You have to work hard today to get the results you want tomorrow.

  6. Structure-guided Mutational Analysis of the OB, HhH, and BRCT Domains of Escherichia coli DNA Ligase*S⃞

    PubMed Central

    Wang, Li Kai; Nair, Pravin A.; Shuman, Stewart

    2008-01-01

    NAD+-dependent DNA ligases (LigAs) are ubiquitous in bacteria and essential for growth. LigA enzymes have a modular structure in which a central catalytic core composed of nucleotidyltransferase and oligonucleotide-binding (OB) domains is linked via a tetracysteine zinc finger to distal helix-hairpin-helix (HhH) and BRCT (BRCA1-like C-terminal) domains. The OB and HhH domains contribute prominently to the protein clamp formed by LigA around nicked duplex DNA. Here we conducted a structure-function analysis of the OB and HhH domains of Escherichia coli LigA by alanine scanning and conservative substitutions, entailing 43 mutations at 22 amino acids. We thereby identified essential functional groups in the OB domain that engage the DNA phosphodiester backbone flanking the nick (Arg333); penetrate the minor grove and distort the nick (Val383 and Ile384); or stabilize the OB fold (Arg379). The essential constituents of the HhH domain include: four glycines (Gly455, Gly489, Gly521, Gly553), which bind the phosphate backbone across the minor groove at the outer margins of the LigA-DNA interface; Arg487, which penetrates the minor groove at the outer margin on the 3 ®-OH side of the nick; and Arg446, which promotes protein clamp formation via contacts to the nucleotidyltransferase domain. We find that the BRCT domain is required in its entirety for effective nick sealing and AMP-dependent supercoil relaxation. PMID:18515356

  7. Structure-guided mutational analysis of the OB, HhH, and BRCT domains of Escherichia coli DNA ligase.

    PubMed

    Wang, Li Kai; Nair, Pravin A; Shuman, Stewart

    2008-08-22

    NAD(+)-dependent DNA ligases (LigAs) are ubiquitous in bacteria and essential for growth. LigA enzymes have a modular structure in which a central catalytic core composed of nucleotidyltransferase and oligonucleotide-binding (OB) domains is linked via a tetracysteine zinc finger to distal helix-hairpin-helix (HhH) and BRCT (BRCA1-like C-terminal) domains. The OB and HhH domains contribute prominently to the protein clamp formed by LigA around nicked duplex DNA. Here we conducted a structure-function analysis of the OB and HhH domains of Escherichia coli LigA by alanine scanning and conservative substitutions, entailing 43 mutations at 22 amino acids. We thereby identified essential functional groups in the OB domain that engage the DNA phosphodiester backbone flanking the nick (Arg(333)); penetrate the minor grove and distort the nick (Val(383) and Ile(384)); or stabilize the OB fold (Arg(379)). The essential constituents of the HhH domain include: four glycines (Gly(455), Gly(489), Gly(521), Gly(553)), which bind the phosphate backbone across the minor groove at the outer margins of the LigA-DNA interface; Arg(487), which penetrates the minor groove at the outer margin on the 3 (R)-OH side of the nick; and Arg(446), which promotes protein clamp formation via contacts to the nucleotidyltransferase domain. We find that the BRCT domain is required in its entirety for effective nick sealing and AMP-dependent supercoil relaxation.

  8. Effect of dipolar moments in domain sizes of lipid bilayers and monolayers

    NASA Astrophysics Data System (ADS)

    Travesset, A.

    2006-08-01

    Lipid domains are found in systems such as multicomponent bilayer membranes and single component monolayers at the air-water interface. It was shown by Keller et al. [J. Phys. Chem. 91, 6417 (1987)] that in monolayers, the size of the domains results from balancing the line tension, which favors the formation of a large single circular domain, against the electrostatic cost of assembling the dipolar moments of the lipids. In this paper, we present an exact analytical expression for the electric potential, ion distribution, and electrostatic free energy for different problems consisting of three different slabs with different dielectric constants and Debye lengths, with a circular homogeneous dipolar density in the middle slab. From these solutions, we extend the calculation of domain sizes for monolayers to include the effects of finite ionic strength, dielectric discontinuities (or image charges), and the polarizability of the dipoles and further generalize the calculations to account for domains in lipid bilayers. In monolayers, the size of the domains is dependent on the different dielectric constants but independent of ionic strength. In asymmetric bilayers, where the inner and outer leaflets have different dipolar densities, domains show a strong size dependence with ionic strength, with molecular-sized domains that grow to macroscopic phase separation with increasing ionic strength. We discuss the implications of the results for experiments and briefly consider their relation to other two dimensional systems such as Wigner crystals or heteroepitaxial growth.

  9. SH2 domains of the p85 alpha subunit of phosphatidylinositol 3-kinase regulate binding to growth factor receptors.

    PubMed Central

    McGlade, C J; Ellis, C; Reedijk, M; Anderson, D; Mbamalu, G; Reith, A D; Panayotou, G; End, P; Bernstein, A; Kazlauskas, A

    1992-01-01

    The binding of cytoplasmic signaling proteins such as phospholipase C-gamma 1 and Ras GTPase-activating protein to autophosphorylated growth factor receptors is directed by their noncatalytic Src homology region 2 (SH2) domains. The p85 alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase, which associates with several receptor protein-tyrosine kinases, also contains two SH2 domains. Both p85 alpha SH2 domains, when expressed individually as fusion proteins in bacteria, bound stably to the activated beta receptor for platelet-derived growth factor (PDGF). Complex formation required PDGF stimulation and was dependent on receptor tyrosine kinase activity. The bacterial p85 alpha SH2 domains recognized activated beta PDGF receptor which had been immobilized on a filter, indicating that SH2 domains contact autophosphorylated receptors directly. Several receptor tyrosine kinases within the PDGF receptor subfamily, including the colony-stimulating factor 1 receptor and the Steel factor receptor (Kit), also associate with PI 3-kinase in vivo. Bacterially expressed SH2 domains derived from the p85 alpha subunit of PI 3-kinase bound in vitro to the activated colony-stimulating factor 1 receptor and to Kit. We infer that the SH2 domains of p85 alpha bind to high-affinity sites on these receptors, whose creation is dependent on receptor autophosphorylation. The SH2 domains of p85 are therefore primarily responsible for the binding of PI 3-kinase to activated growth factor receptors. Images PMID:1372092

  10. Crystal structure of SAM-dependent methyltransferase from Pyrococcus horikoshii.

    PubMed

    Pampa, K J; Madan Kumar, S; Hema, M K; Kumara, Karthik; Naveen, S; Kunishima, Naoki; Lokanath, N K

    2017-12-01

    Methyltransferases (MTs) are enzymes involved in methylation that are needed to perform cellular processes such as biosynthesis, metabolism, gene expression, protein trafficking and signal transduction. The cofactor S-adenosyl-L-methionine (SAM) is used for catalysis by SAM-dependent methyltransferases (SAM-MTs). The crystal structure of Pyrococcus horikoshii SAM-MT was determined to a resolution of 2.1 Å using X-ray diffraction. The monomeric structure consists of a Rossmann-like fold (domain I) and a substrate-binding domain (domain II). The cofactor (SAM) molecule binds at the interface between adjacent subunits, presumably near to the active site(s) of the enzyme. The observed dimeric state might be important for the catalytic function of the enzyme.

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

    PubMed

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

    2012-04-20

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

  12. Transformation by oncogenic mutants and ligand-dependent activation of FLT3 wild-type requires the tyrosine residues 589 and 591.

    PubMed

    Vempati, Sridhar; Reindl, Carola; Wolf, Ulla; Kern, Ruth; Petropoulos, Konstantin; Naidu, Vegi M; Buske, Christian; Hiddemann, Wolfgang; Kohl, Tobias M; Spiekermann, Karsten

    2008-07-15

    Mutations in the receptor tyrosine kinase FLT3 are found in up to 30% of acute myelogenous leukemia patients and are associated with an inferior prognosis. In this study, we characterized critical tyrosine residues responsible for the transforming potential of active FLT3-receptor mutants and ligand-dependent activation of FLT3-WT. We performed a detailed structure-function analysis of putative autophosphorylation tyrosine residues in the FLT3-D835Y tyrosine kinase domain (TKD) mutant. All tyrosine residues in the juxtamembrane domain (Y566, Y572, Y589, Y591, Y597, and Y599), interkinase domain (Y726 and Y768), and COOH-terminal domain (Y955 and Y969) of the FLT3-D835Y construct were successively mutated to phenylalanine and the transforming activity of these mutants was analyzed in interleukin-3-dependent Ba/F3 cells. Tyrosine residues critical for the transforming potential of FLT3-D835Y were also analyzed in FLT3 internal tandem duplication mutants (FLT3-ITD)and the FLT3 wild-type (FLT3-WT) receptor. The substitution of the tyrosine residues by phenylalanine in the juxtamembrane, interkinase, and COOH-terminal domains resulted in a complete loss of the transforming potential of FLT3-D835Y-expressing cells which can be attributed to a significant reduction of signal tranducer and activator of transcription 5 (STAT5) phosphorylation at the molecular level. Reintroduction of single tyrosine residues revealed the critical role of Y589 and Y591 in reconstituting interleukin-3-independent growth of FLT3-TKD-expressing cells. Combined mutation of Y589 and Y591 to phenylalanine also abrogated ligand-dependent proliferation of FLT3-WT and the transforming potential of FLT3-ITD-with a subsequent abrogation of STAT5 phosphorylation. We identified two tyrosine residues, Y589 and Y591, in the juxtamembrane domain that are critical for the ligand-dependent activation of FLT3-WT and the transforming potential of oncogenic FLT3 mutants.

  13. Safety concerns and hidden agenda behind HPV vaccines: another generation of drug-dependent society?

    PubMed

    Khatami, Mahin

    2016-12-01

    Analyses of data and hidden agenda behind repeated failed outcomes of cancer research and therapy, status of American health, safety concerns for HPV vaccines and future research considerations are summarized in this commentary. A closer look at cancer science reveals that highly power structure (system) in medical establishment vs. anti-system and chaos in cancer research ('medical/scientific ponzi schemes') is potent recipe for failed therapeutics that kills patients but generates huge corporate profit. American health status ranks last among other developed nations despite the highest amount that USA invests in healthcare. This is a wake-up call to make sure that the evil part of human being does not prevent the health services that the public deserves. Otherwise, 'it does not matter how many resources you have, if you don't know, or don't want to know, how to use them, they will never be enough'. Answer to cancer and improved public health is possible only by switching the current corruptive and abusive culture of 'who you know' to a culture of 'what you know'. Policy makers and professionals in decision making roles are urged to return to common sense and logics that our Forefathers used to serve the public.

  14. Universal Ferroelectric Switching Dynamics of Vinylidene Fluoride-trifluoroethylene Copolymer Films

    PubMed Central

    Hu, Wei Jin; Juo, Deng-Ming; You, Lu; Wang, Junling; Chen, Yi-Chun; Chu, Ying-Hao; Wu, Tom

    2014-01-01

    In this work, switching dynamics of poly(vinylidene fluoride-trifluoroethylene) [P(VDF-TrFE)] copolymer films are investigated over unprecedentedly wide ranges of temperature and electric field. Remarkably, domain switching of copolymer films obeys well the classical domain nucleation and growth model although the origin of ferroelectricity in organic ferroelectric materials inherently differs from the inorganic counterparts. A lower coercivity limit of 50 MV/m and 180° domain wall energy of 60 mJ/m2 are determined for P(VDF-TrFE) films. Furthermore, we discover in copolymer films an anomalous temperature-dependent crossover behavior between two power-law scaling regimes of frequency-dependent coercivity, which is attributed to the transition between flow and creep motions of domain walls. Our observations shed new light on the switching dynamics of semi-crystalline ferroelectric polymers, and such understandings are critical for realizing their reliable applications. PMID:24759786

  15. The Thiamin Pyrophosphate-Motif

    NASA Technical Reports Server (NTRS)

    Dominiak, P.; Ciszak, E.

    2003-01-01

    Using databases the authors have identified a common thiamin pyrophosphate (TPP)-motif in the family of functionally diverse TPP-dependent enzymes. This common motif consists of multimeric organization of subunits and two catalytic centers. Each catalytic center (PP:PYR) is formed at the interface of the PP-domain binding the magnesium ion, pyrophosphate and amhopyrimidine ring of TPP, and the PYR-domain binding the aminopyrimidine ring of that cofactor. A pair of these catalytic centers constitutes the catalytic core (PP:PYR)(sub 2) within these enzymes. Analysis of the structural elements of this catalytic core reveals novel definition of the common amino acid sequences, which are GXPhiX(sub 4)(G)PhiXXGQ and GDGX(sub 25-30)NN in the PP-domain, and the EX(sub 4)(G)PhiXXGPhi in the PYR-domain, where Phi corresponds to a hydrophobic amino acid. This TPP-motif provides a novel tool for annotation of TPP-dependent enzymes useful in advancing functional proteomics.

  16. Endothermic decompositions of inorganic monocrystalline thin plates. I. Shape of polycrystalline product domains versus constraints and time

    NASA Astrophysics Data System (ADS)

    Bertrand, G.; Comperat, M.; Lallemant, M.; Watelle, G.

    1980-03-01

    Copper sulfate pentahydrate dehydration into trihydrate was investigated using monocrystalline platelets with varying crystallographic orientations. The morphological and kinetic features of the trihydrate domains were examined. Different shapes were observed: polygons (parallelograms, hexagons) and ellipses; their conditions of occurrence are reported in the (P, T) diagram. At first (for about 2 min), the ratio of the long to the short axes of elliptical domains changes with time; these subsequently develop homothetically and the rate ratio is then only pressure dependent. Temperature influence is inferred from that of pressure. Polygonal shapes are time dependent and result in ellipses. So far, no model can be put forward. Yet, qualitatively, the polygonal shape of a domain may be explained by the prevalence of the crystal arrangement and the elliptical shape by that of the solid tensorial properties. The influence of those factors might be modulated versus pressure, temperature, interface extent, and, thus, time.

  17. Dynamic spectrin/ankyrin-G microdomains promote lateral membrane assembly by opposing endocytosis

    PubMed Central

    Jenkins, Paul M.; He, Meng; Bennett, Vann

    2015-01-01

    Current physical models for plasma membranes emphasize dynamic 10- to 300-nm compartments at thermodynamic equilibrium but subject to thermal fluctuations. However, epithelial lateral membranes contain micrometer-sized domains defined by an underlying membrane skeleton composed of spectrin and its partner ankyrin-G. We demonstrate that these spectrin/ankyrin-G domains exhibit local microtubule-dependent movement on a time scale of minutes and encounter most of the lateral membranes within an hour. Spectrin/ankyrin-G domains exclude clathrin and clathrin-dependent cargo, and inhibit both receptor-mediated and bulk endocytosis. Moreover, inhibition of endocytosis fully restores lateral membrane height in spectrin- or ankyrin-G–depleted cells. These findings support a non-equilibrium cellular-scale model for epithelial lateral membranes, where spectrin/ankyrin-G domains actively patrol the plasma membrane, analogous to “window washers,” and promote columnar morphology by blocking membrane uptake. PMID:26523289

  18. Gating mechanism of Kv11.1 (hERG) K+ channels without covalent connection between voltage sensor and pore domains.

    PubMed

    de la Peña, Pilar; Domínguez, Pedro; Barros, Francisco

    2018-03-01

    Kv11.1 (hERG, KCNH2) is a voltage-gated potassium channel crucial in setting the cardiac rhythm and the electrical behaviour of several non-cardiac cell types. Voltage-dependent gating of Kv11.1 can be reconstructed from non-covalently linked voltage sensing and pore modules (split channels), challenging classical views of voltage-dependent channel activation based on a S4-S5 linker acting as a rigid mechanical lever to open the gate. Progressive displacement of the split position from the end to the beginning of the S4-S5 linker induces an increasing negative shift in activation voltage dependence, a reduced z g value and a more negative ΔG 0 for current activation, an almost complete abolition of the activation time course sigmoid shape and a slowing of the voltage-dependent deactivation. Channels disconnected at the S4-S5 linker near the S4 helix show a destabilization of the closed state(s). Furthermore, the isochronal ion current mode shift magnitude is clearly reduced in the different splits. Interestingly, the progressive modifications of voltage dependence activation gating by changing the split position are accompanied by a shift in the voltage-dependent availability to a methanethiosulfonate reagent of a Cys introduced at the upper S4 helix. Our data demonstrate for the first time that alterations in the covalent connection between the voltage sensor and the pore domains impact on the structural reorganizations of the voltage sensor domain. Also, they support the hypothesis that the S4-S5 linker integrates signals coming from other cytoplasmic domains that constitute either an important component or a crucial regulator of the gating machinery in Kv11.1 and other KCNH channels.

  19. pH-dependent structural change of the extracellular sensor domain of the DraK histidine kinase from Streptomyces coelicolor

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

    Yeo, Kwon Joo; Kim, Eun Hye; Hwang, Eunha

    2013-02-15

    Highlights: ► We described the biochemical and biophysical properties of the extracellular sensory domain (ESD) of DraK histidine kinase. ► The ESD of DraK showed a reversible pH-dependent conformational change in a wide pH range. ► The E83 is an important residue for the pH-dependent conformational change. -- Abstract: Recently, the DraR/DraK (Sco3063/Sco3062) two-component system (TCS) of Streptomycescoelicolor has been reported to be involved in the differential regulation of antibiotic biosynthesis. However, it has not been shown that under which conditions and how the DraR/DraK TCS is activated to initiate the signal transduction process. Therefore, to understand the sensing mechanism,more » structural study of the sensory domain of DraK is highly required. Here, we report the biochemical and biophysical properties of the extracellular sensory domain (ESD) of DraK. We observed a reversible pH-dependent conformational change of the ESD in a pH range of 2.5–10. Size-exclusion chromatography and AUC (analytical ultracentrifugation) data indicated that the ESD is predominantly monomeric in solution and exists in equilibrium between monomer and dimer states in acidic condition. Using NMR (nuclear magnetic resonance) and CD (circular dichroism) spectroscopy, our findings suggest that the structure of the ESD at low pH is more structured than that at high pH. In particular, the glutamate at position 83 is an important residue for the pH-dependent conformational change. These results suggest that this pH-dependent conformational change of ESD may be involved in signal transduction process of DraR/DraK TCS.« less

  20. Cadherin Domains in the Polysaccharide-Degrading Marine Bacterium Saccharophagus degradans 2-40 Are Carbohydrate-Binding Modules▿

    PubMed Central

    Fraiberg, Milana; Borovok, Ilya; Bayer, Edward A.; Weiner, Ronald M.; Lamed, Raphael

    2011-01-01

    The complex polysaccharide-degrading marine bacterium Saccharophagus degradans strain 2-40 produces putative proteins that contain numerous cadherin and cadherin-like domains involved in intercellular contact interactions. The current study reveals that both domain types exhibit reversible calcium-dependent binding to different complex polysaccharides which serve as growth substrates for the bacterium. PMID:21036994

  1. Benchmarking and Enrollment Management

    ERIC Educational Resources Information Center

    Duniway, Robert L.

    2012-01-01

    Every college and university, whether public or private; two-year, four-year, or graduate; traditional or online, depends on recruiting and enrolling new students and strives to have as many of those students as possible complete their educational programs. Knowing how effectively an institution is managing the various stages of enrollment is…

  2. Lobbying for Contingent Faculty Interests

    ERIC Educational Resources Information Center

    Byrd, Nicole

    2008-01-01

    Lobbying has become a dirty word thanks to well-publicized cases involving lobbyists such as Jack Abramoff. However, advocating for one's positions is a positive act of civic engagement. The right to petition the government is enshrined in the Constitution, and lawmakers depend on interaction with constituents to know what the people they…

  3. Campus Architecture Is Campus Marketing

    ERIC Educational Resources Information Center

    Padjen, Elizabeth S.

    2002-01-01

    College and university administrators, especially the directors of admissions, who are on the frontline of the competition for prospective students, understand that college today is much more than an education: it is a lifestyle. They know that the size of the applicant pool and the eventual admissions yield frequently depend on one factor: the…

  4. 2013 Student Science Jeopardy Tournament a Big Success | Poster

    Cancer.gov

    By Robin Meckley, Contributing Writer The category was “General Science,” and the clue read: “Named for an Italian scientist, it is the scientific number of molecules in 1 gram mole of any substance.” Everything depended on knowing the correct response and wagering enough points.  

  5. AN OVERVIEW OF PARTITIONING AND BIOAVAILABILITY OF PAHS IN SEDIMENTS AND SOILS

    EPA Science Inventory

    Understanding and predicting any adverse effects of PAHs depends on generating a reliable measure or estimate of how much PAH is available for uptake. Simply knowing the total amount of PAH in soil, water or sediment is insufficient for determining whether or not these compounds ...

  6. Developing ecosystem service indicators: Experiences and lessons learned from sub-global assessments and other initiatives - new

    EPA Science Inventory

    People depend upon ecosystems to supply a range of services necessary for their survival and well-being. Ecosystem service indicators are critical for knowing whether or not these essential services are being maintained and used in a sustainable manner, thus enabling policy maker...

  7. Reconceptualizing the motive/environment link in recreation choice behavior

    Treesearch

    Richard Schreyer; Richard C. Knopf; Daniel R. Williams

    1985-01-01

    Effective inventory, management, and planning for recreation resources depend upon knowing why persons choose certain environments to attain specific goals, and what elements in those environments facilitate goal-attainment. Research focused on relating motives for participation to specific components in the environment has had only limited success. This paper proposes...

  8. What to Know about Brachytherapy (A Type of Internal Radiation Therapy)

    MedlinePlus

    ... understand what was going to happen.” About the treatment: ■ ■ Brachytherapy uses radiation to destroy cancer cells and shrink tumors. ■ ■ The ... may have. These differ depending on where the radiation is ... starting treatment. During treatment: ■ ■ Your doctor will place a small ...

  9. "That Hurts!": Humor and Sadomasochism in "Lolita."

    ERIC Educational Resources Information Center

    Bick, Ilsa J.

    1994-01-01

    States that humor is dependent on individual perspective, and that the subject matter of "Lolita" (1962), which concerns child abuse and molestation, is difficult to treat with humor. Argues that despite its subject, "Lolita" continues to be funny. Concludes that viewers know the subject matter is not funny, but while watching,…

  10. Coordinated autoinhibition of F-BAR domain membrane binding and WASp activation by Nervous Wreck.

    PubMed

    Stanishneva-Konovalova, Tatiana B; Kelley, Charlotte F; Eskin, Tania L; Messelaar, Emily M; Wasserman, Steven A; Sokolova, Olga S; Rodal, Avital A

    2016-09-20

    Membrane remodeling by Fes/Cip4 homology-Bin/Amphiphysin/Rvs167 (F-BAR) proteins is regulated by autoinhibitory interactions between their SRC homology 3 (SH3) and F-BAR domains. The structural basis of autoregulation, and whether it affects interactions of SH3 domains with other cellular ligands, remain unclear. Here we used single-particle electron microscopy to determine the structure of the F-BAR protein Nervous Wreck (Nwk) in both soluble and membrane-bound states. On membrane binding, Nwk SH3 domains do not completely dissociate from the F-BAR dimer, but instead shift from its concave surface to positions on either side of the dimer. Unexpectedly, along with controlling membrane binding, these autoregulatory interactions inhibit the ability of Nwk-SH3a to activate Wiskott-Aldrich syndrome protein (WASp)/actin related protein (Arp) 2/3-dependent actin filament assembly. In Drosophila neurons, Nwk autoregulation restricts SH3a domain-dependent synaptopod formation, synaptic growth, and actin organization. Our results define structural rearrangements in Nwk that control F-BAR-membrane interactions as well as SH3 domain activities, and suggest that these two functions are tightly coordinated in vitro and in vivo.

  11. MT2-MMP-dependent release of collagen IV NC1 domains regulates submandibular gland branching morphogenesis

    PubMed Central

    Rebustini, Ivan T.; Myers, Christopher; Lassiter, Keyonica S.; Surmak, Andrew; Szabova, Ludmila; Holmbeck, Kenn; Pedchenko, Vadim; Hudson, Billy G.; Hoffman, Matthew P.

    2009-01-01

    Summary Proteolysis is essential during branching morphogenesis, but the roles of MT-MMPs and their proteolytic products are not clearly understood. Here we discover that decreasing MT-MMP activity during submandibular gland branching morphogenesis decreases proliferation and increases collagen IV and MT-MMP expression. Importantly, reducing epithelial MT2-MMP profoundly decreases proliferation and morphogenesis, increases Col4a2 and intracellular accumulation of collagen IV, and decreases the proteolytic release of collagen IV NC1 domains. Importantly, we demonstrate the presence of collagen IV NC1 domains in developing tissue. Furthermore, recombinant collagen IV NC1 domains rescue branching morphogenesis after MT2-siRNA-treatment, increasing MT-MMP and pro-proliferative gene expression via β1 integrin and PI3K-AKT signaling. Additionally, HBEGF also rescues MT2-siRNA-treatment, increasing NC1 domain release, proliferation, and MT2-MMP and Hbegf expression. Our studies provide mechanistic insight into how MT2-MMP-dependent release of bioactive NC1 domains from collagen IV is critical for integrating collagen IV synthesis and proteolysis with epithelial proliferation during branching morphogenesis. PMID:19853562

  12. The soluble extracellular domain of E-cadherin interferes with EPEC adherence via interaction with the Tir:intimin complex.

    PubMed

    Login, Frédéric H; Jensen, Helene H; Pedersen, Gitte A; Amieva, Manuel R; Nejsum, Lene N

    2018-06-19

    Enteropathogenic Escherichia coli (EPEC) causes watery diarrhea when colonizing the surface of enterocytes. The translocated intimin receptor (Tir):intimin receptor complex facilitates tight adherence to epithelial cells and formation of actin pedestals beneath EPEC. We found that the host cell adherens junction protein E-cadherin (Ecad) was recruited to EPEC microcolonies. Live-cell and confocal imaging revealed that Ecad recruitment depends on, and occurs after, formation of the Tir:intimin complex. Combinatorial binding experiments using wild-type EPEC, isogenic mutants lacking Tir or intimin, and E. coli expressing intimin showed that the extracellular domain of Ecad binds the bacterial surface in a Tir:intimin-dependent manner. Finally, addition of the soluble extracellular domain of Ecad to the infection medium or depletion of Ecad extracellular domain from the cell surface reduced EPEC adhesion to host cells. Thus, the soluble extracellular domain of Ecad may be used in the design of intervention strategies targeting EPEC adherence to host cells.-Login, F. H., Jensen, H. H., Pedersen, G. A., Amieva, M. R., Nejsum, L. N. The soluble extracellular domain of E-cadherin interferes with EPEC adherence via interaction with the Tir:intimin complex.

  13. Region and Domain Dependent Action of Nomifensine

    PubMed Central

    Shu, Zhan; Taylor, I. Mitch; Walters, Seth H.; Michael, Adrian C.

    2014-01-01

    The dopamine (DA) terminal fields in the rat dorsal striatum (DS) and nucleus accumbens core (NAcc) are organized as patchworks of domains that exhibit distinct kinetics of DA release and clearance. The present study used fast-scan cyclic voltammetry recordings of electrically evoked DA overflow to test the hypothesis that nomifensine might exhibit domain-dependent actions within the NAcc, as we previously found to be the case within the DS. Within the NAcc, nomifensine preferentially enhanced evoked dopamine overflow in the slow compared to the fast domains. To seek a kinetic explanation for nomifensine’s selective actions, we quantified the apparent KM of DA clearance by numerically evaluating the derivative of the descending phase of the DA signal after the end of the stimulus. For comparison, we likewise quantified apparent KM in the domains of the DS. As expected because it is a competitive inhibitor, nomifensine significantly increased the apparent KM in both the fast and slow domains of both the NAcc and DS. However, our analysis also leads to the novel finding that nomifensine preferentially increases the apparent KM in the NAcc compared to the DS: apparent KM increased by ~500% in the NAcc and ~200% in the DS. PMID:24766210

  14. The hepatitis B virus large surface protein (LHBs) is a transcriptional activator.

    PubMed

    Hildt, E; Saher, G; Bruss, V; Hofschneider, P H

    1996-11-01

    It has been shown that a C-terminally truncated form of the middle-sized hepatitis B virus (HBV) surface protein (MHBst) functions as a transcriptional activator. This function is dependent on the cytosolic orientation of the N-terminal PreS2 domain of MHBst, but in the case of wild-type MHBs, the PreS2 domain is contranslationally translocated into the ER lumen. Recent reports demonstrated that the PreS2 domain of the large HBV surface protein (LHBs) initially remains on the cytosolic side of the ER membrane after translation. Therefore, the question arose as to whether the LHBs protein exhibits the same transcriptional activator function as MHBst. We show that LHBs, like MHBst, is indeed able to activate a variety of promoter elements. There is evidence for a PKC-dependent activation of AP-1 and NF-kappa B by LHBs. Downstream of the PKC the functionality of c-Raf-1 kinase is a prerequisite for LHBs-dependent activation of AP-1 and NF-kappa B since inhibition of c-Raf-1 kinase abolishes LHBs-dependent transcriptional activation of AP-1 and NF-kappa B.

  15. RIBEYE(B)-domain binds to lipid components of synaptic vesicles in an NAD(H)-dependent, redox-sensitive manner.

    PubMed

    Schwarz, Karin; Schmitz, Frank

    2017-03-20

    Synaptic ribbons are needed for fast and continuous exocytosis in ribbon synapses. RIBEYE is a main protein component of synaptic ribbons and is necessary to build the synaptic ribbon. RIBEYE consists of a unique A-domain and a carboxyterminal B-domain, which binds NAD(H). Within the presynaptic terminal, the synaptic ribbons are in physical contact with large numbers of synaptic vesicle (SV)s. How this physical contact between ribbons and synaptic vesicles is established at a molecular level is not well understood. In the present study, we demonstrate that the RIBEYE(B)-domain can directly interact with lipid components of SVs using two different sedimentation assays with liposomes of defined chemical composition. Similar binding results were obtained with a SV-containing membrane fraction. The binding of liposomes to RIBEYE(B) depends upon the presence of a small amount of lysophospholipids present in the liposomes. Interestingly, binding of liposomes to RIBEYE(B) depends on NAD(H) in a redox-sensitive manner. The binding is enhanced by NADH, the reduced form, and is inhibited by NAD + , the oxidized form. Lipid-mediated attachment of vesicles is probably part of a multi-step process that also involves additional, protein-dependent processes. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  16. Social recognition is context dependent in single male prairie voles

    PubMed Central

    Zheng, Da-Jiang; Foley, Lauren; Rehman, Asad; Ophir, Alexander G.

    2013-01-01

    Single males might benefit from knowing the identity of neighbouring males when establishing and defending boundaries. Similarly, males should discriminate between individual females if this leads to more reproductive opportunities. Contextual social cues may alter the value of learning identity. Knowing the identity of competitors that intrude into an animal’s territory may be more salient than knowing the identity of individuals on whose territory an animal is trespassing. Hence, social and environmental context could affect social recognition in many ways. Here we test social recognition of socially monogamous single male prairie voles, Microtus ochrogaster. In experiment 1 we tested recognition of male or female conspecifics and found that males discriminated between different males but not between different females. In experiment 2 we asked whether recognition of males is influenced when males are tested in their own cage (familiar), in a clean cage (neutral) or in the home cage of another male (unfamiliar). Although focal males discriminated between male conspecifics in all three contexts, individual variation in recognition was lower when males were tested in their home cage (in the presence of familiar social cues) compared to when the context lacked social cues (neutral). Experiment 1 indicates that selective pressures may have operated to enhance male territorial behaviour and indiscriminate mate selection. Experiment 2 suggests that the presence of a conspecific cue heightens social recognition and that home-field advantages might extend to social cognition. Taken together, our results indicate social recognition depends on the social and possibly territorial context. PMID:24273328

  17. Social recognition is context dependent in single male prairie voles.

    PubMed

    Zheng, Da-Jiang; Foley, Lauren; Rehman, Asad; Ophir, Alexander G

    2013-11-01

    Single males might benefit from knowing the identity of neighbouring males when establishing and defending boundaries. Similarly, males should discriminate between individual females if this leads to more reproductive opportunities. Contextual social cues may alter the value of learning identity. Knowing the identity of competitors that intrude into an animal's territory may be more salient than knowing the identity of individuals on whose territory an animal is trespassing. Hence, social and environmental context could affect social recognition in many ways. Here we test social recognition of socially monogamous single male prairie voles, Microtus ochrogaster . In experiment 1 we tested recognition of male or female conspecifics and found that males discriminated between different males but not between different females. In experiment 2 we asked whether recognition of males is influenced when males are tested in their own cage (familiar), in a clean cage (neutral) or in the home cage of another male (unfamiliar). Although focal males discriminated between male conspecifics in all three contexts, individual variation in recognition was lower when males were tested in their home cage (in the presence of familiar social cues) compared to when the context lacked social cues (neutral). Experiment 1 indicates that selective pressures may have operated to enhance male territorial behaviour and indiscriminate mate selection. Experiment 2 suggests that the presence of a conspecific cue heightens social recognition and that home-field advantages might extend to social cognition. Taken together, our results indicate social recognition depends on the social and possibly territorial context.

  18. Comparative analysis of ferroelectric domain statistics via nonlinear diffraction in random nonlinear materials.

    PubMed

    Wang, B; Switowski, K; Cojocaru, C; Roppo, V; Sheng, Y; Scalora, M; Kisielewski, J; Pawlak, D; Vilaseca, R; Akhouayri, H; Krolikowski, W; Trull, J

    2018-01-22

    We present an indirect, non-destructive optical method for domain statistic characterization in disordered nonlinear crystals having homogeneous refractive index and spatially random distribution of ferroelectric domains. This method relies on the analysis of the wave-dependent spatial distribution of the second harmonic, in the plane perpendicular to the optical axis in combination with numerical simulations. We apply this technique to the characterization of two different media, Calcium Barium Niobate and Strontium Barium Niobate, with drastically different statistical distributions of ferroelectric domains.

  19. Time-Domain Computation Of Electromagnetic Fields In MMICs

    NASA Technical Reports Server (NTRS)

    Lansing, Faiza S.; Rascoe, Daniel L.

    1995-01-01

    Maxwell's equations solved on three-dimensional, conformed orthogonal grids by finite-difference techniques. Method of computing frequency-dependent electrical parameters of monolithic microwave integrated circuit (MMIC) involves time-domain computation of propagation of electromagnetic field in response to excitation by single pulse at input terminal, followed by computation of Fourier transforms to obtain frequency-domain response from time-domain response. Parameters computed include electric and magnetic fields, voltages, currents, impedances, scattering parameters, and effective dielectric constants. Powerful and efficient means for analyzing performance of even complicated MMIC.

  20. Solution Structure of the cGMP Binding GAF Domain from Phosphodiesterase 5: Insights into Nucleotide Specificity, Dimerization, and cGMP-Dependent Conformational Change

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

    Heikaus, Clemens C.; Stout, Joseph R.; Sekharan, Monica R.

    2008-08-15

    Phosphodiesterase 5 (PDE5) controls intracellular levels of cGMP through its regulation of cGMP hydrolysis. Hydrolytic activity of the C-terminal catalytic domain is increased by cGMP binding to the N-terminal GAF A domain. We present the NMR solution structure of the cGMP-bound PDE5A GAF A domain. The cGMP orientation in the buried binding pocket was defined through 37 intermolecular NOEs.

  1. Interacting particle systems in time-dependent geometries

    NASA Astrophysics Data System (ADS)

    Ali, A.; Ball, R. C.; Grosskinsky, S.; Somfai, E.

    2013-09-01

    Many complex structures and stochastic patterns emerge from simple kinetic rules and local interactions, and are governed by scale invariance properties in combination with effects of the global geometry. We consider systems that can be described effectively by space-time trajectories of interacting particles, such as domain boundaries in two-dimensional growth or river networks. We study trajectories embedded in time-dependent geometries, and the main focus is on uniformly expanding or decreasing domains for which we obtain an exact mapping to simple fixed domain systems while preserving the local scale invariance properties. This approach was recently introduced in Ali et al (2013 Phys. Rev. E 87 020102(R)) and here we provide a detailed discussion on its applicability for self-affine Markovian models, and how it can be adapted to self-affine models with memory or explicit time dependence. The mapping corresponds to a nonlinear time transformation which converges to a finite value for a large class of trajectories, enabling an exact analysis of asymptotic properties in expanding domains. We further provide a detailed discussion of different particle interactions and generalized geometries. All our findings are based on exact computations and are illustrated numerically for various examples, including Lévy processes and fractional Brownian motion.

  2. Collagen insulated from tensile damage by domains that unfold reversibly: in situ X-ray investigation of mechanical yield and damage repair in the mussel byssus

    PubMed Central

    Harrington, Matthew J.; Gupta, Himadri S.; Fratzl, Peter; Waite, J. Herbert

    2009-01-01

    The byssal threads of the California mussel, Mytilus californianus, are highly hysteretic, elastomeric fibers that collectively perform a holdfast function in wave-swept rocky seashore habitats. Following cyclic loading past the mechanical yield point, threads exhibit a damage-dependent reduction in mechanical performance. However, the distal portion of the byssal thread is capable of recovering initial material properties through a time-dependent healing process in the absence of active cellular metabolism. Byssal threads are composed almost exclusively of multi-domain hybrid collagens known as preCols, which largely determine the mechanical properties of the thread. Here, the structure-property relationships that govern thread mechanical performance are further probed. The molecular rearrangements that occur during yield and damage repair were investigated using time-resolved in situ wide angle X-ray diffraction (WAXD) coupled with cyclic tensile loading of threads and through thermally enhanced damage-repair studies. Results indicate that the collagen domains in byssal preCols are mechanically protected by the unfolding of sacrificial non-collagenous domains that refold on a slower time-scale. Time-dependent healing is primarily attributed to stochastic recoupling of broken histidine-metal coordination complexes. PMID:19275941

  3. TopBP1 functions with 53BP1 in the G1 DNA damage checkpoint

    PubMed Central

    Cescutti, Rachele; Negrini, Simona; Kohzaki, Masaoki; Halazonetis, Thanos D

    2010-01-01

    TopBP1 is a checkpoint protein that colocalizes with ATR at sites of DNA replication stress. In this study, we show that TopBP1 also colocalizes with 53BP1 at sites of DNA double-strand breaks (DSBs), but only in the G1-phase of the cell cycle. Recruitment of TopBP1 to sites of DNA replication stress was dependent on BRCT domains 1–2 and 7–8, whereas recruitment to sites of DNA DSBs was dependent on BRCT domains 1–2 and 4–5. The BRCT domains 4–5 interacted with 53BP1 and recruitment of TopBP1 to sites of DNA DSBs in G1 was dependent on 53BP1. As TopBP1 contains a domain important for ATR activation, we examined whether it contributes to the G1 cell cycle checkpoint. By monitoring the entry of irradiated G1 cells into S-phase, we observed a checkpoint defect after siRNA-mediated depletion of TopBP1, 53BP1 or ATM. Thus, TopBP1 may mediate the checkpoint function of 53BP1 in G1. PMID:20871591

  4. TopBP1 functions with 53BP1 in the G1 DNA damage checkpoint.

    PubMed

    Cescutti, Rachele; Negrini, Simona; Kohzaki, Masaoki; Halazonetis, Thanos D

    2010-11-03

    TopBP1 is a checkpoint protein that colocalizes with ATR at sites of DNA replication stress. In this study, we show that TopBP1 also colocalizes with 53BP1 at sites of DNA double-strand breaks (DSBs), but only in the G1-phase of the cell cycle. Recruitment of TopBP1 to sites of DNA replication stress was dependent on BRCT domains 1-2 and 7-8, whereas recruitment to sites of DNA DSBs was dependent on BRCT domains 1-2 and 4-5. The BRCT domains 4-5 interacted with 53BP1 and recruitment of TopBP1 to sites of DNA DSBs in G1 was dependent on 53BP1. As TopBP1 contains a domain important for ATR activation, we examined whether it contributes to the G1 cell cycle checkpoint. By monitoring the entry of irradiated G1 cells into S-phase, we observed a checkpoint defect after siRNA-mediated depletion of TopBP1, 53BP1 or ATM. Thus, TopBP1 may mediate the checkpoint function of 53BP1 in G1.

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

    PubMed Central

    McHugh, R. Kathryn; Otto, Michael W.

    2011-01-01

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

  6. Temperature Dependence of Electrical and Thermal Conduction in Single Silver Nanowire

    DTIC Science & Technology

    2015-06-02

    Methods section. After knowing the geometrical sizes of the films, the electrical resistivity can be calculated . The temper- ature dependent electrical...plane spacing for peaks (111), (220) and (311) are 2.3616 Å, 1.4518 Å and 1.2287 Å respectively. The corresponding lattice constant can be calculated ...21 nm). So the upper limit of the thermal conductivity ( C vl 3ph vκ = /, ) is calculated as 12.3 W/K·m at 36 K. The phonon mean free path should

  7. Student evaluation of clickers in a dental pathology course.

    PubMed

    Llena, Carmen; Forner, Leopoldo; Cueva, Roger

    2015-07-01

    The purpose of this study was to evaluate the degree of satisfaction of students and teachers, and to determine whether the students notice improvements in learning and in the learning environment as a result of the use of clicker. Descriptive study. Fifty-one students and 8 teachers participated in the use of clicker technology in 8 preclinical seminars in dental pathology. Students and teachers filled a three-domain questionnaire at the end of the preclinical course. We used the Mann-Whitney U-test to compare the results between the two groups. The domain "perception and expectation" showed the use of clickers to be simple and convenient for 80% of the students, who expressed interest in extending the practice to other teaching areas. In the domain "active learning", over 70% of the students found the technique to be dynamic, participative and motivating. In the domain "improved learning", over 70% considered it useful to know their level of knowledge before the seminar and found the contents of the lesson to be clear. Thirty percent considered the items of the examination to be of a complexity similar to that of the first and second tests. Only in this latter aspect were significant differences found between the teachers and students (p=0.001). Participants described the use of clickers as simple and useful, motivating and participative. Both the students and teachers considered the technique to improve teaching and the learning environment. Key words:Dental education, audience response system, clickers, classroom response system, student´s perception.

  8. [Relationship between exercise dependence and big five personality].

    PubMed

    Kern, L

    2010-06-01

    Despite the increased interest in exercise dependence, there is limited research examining the personality characteristics of exercise dependent individuals. Furthermore, researchers examining the relationship between exercise dependence and personality have found inconsistent results. This maybe the result of the varying methods used by researchers to assess exercise dependence and personality. The purpose of this study was to examine the relationship between exercise dependence and personality, and that determine whether there is an addictive personality type. Participants were 484 university students (M=21.24, SD=3.03), and 322 sport leisure participants (M=30.08, Sd=13.58) who completed multidimensional assessments of exercise dependence and personality. to assess exercise dependence, the EDS-R (French version, Kern, L, 2007, Validation de l'adaptation française de l'échelle de dépendance à l'exercice physique : l'EDS-R Pratiques Psychologiques, 13, 4, 425-441) was undertaken. This scale is based on the DSM_IV criteria for substance dependence which are: withdrawal effects, intention effects, lack of control, time, reductions in other activities, continuance. The D5D was chosen to assess the big five personality dimensions (Rolland, J.-P., & Mogenet, J.-L. (1994). Manuel du système d5d. Paris: ECPA.). These dimensions are: Extraversion, Emotional Stability, Agreeableness, Conscientiousness, and Openness to Experience. To examine the predictive relationship of personality for exercise dependence symptoms, a series of multiple regressions was carried out. Results show that, according to the status of the people under scrutiny, it is either openness to experience and emotional stability or openness to experience and agreeableness which explain the greatest variance of exercise dependence. Then, the description of a personality type seemed very difficult to obtain. We feel it's important to know the personality type, but not sufficient; it is more pertinent to know the type of personality. Then, further research could examine the relationship between personality disorder and exercise dependence. In contrast with the literature, we did not find a relationship between exercise dependence and extraversion. Copyright (c) 2009 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

  9. Domain wall magnetoresistance in BiFeO3 thin films measured by scanning probe microscopy

    NASA Astrophysics Data System (ADS)

    Domingo, N.; Farokhipoor, S.; Santiso, J.; Noheda, B.; Catalan, G.

    2017-08-01

    We measure the magnetotransport properties of individual 71° domain walls in multiferroic BiFeO3 by means of conductive—atomic force microscopy (C-AFM) in the presence of magnetic fields up to one Tesla. The results suggest anisotropic magnetoresistance at room temperature, with the sign of the magnetoresistance depending on the relative orientation between the magnetic field and the domain wall plane. A consequence of this finding is that macroscopically averaged magnetoresistance measurements for domain wall bunches are likely to underestimate the magnetoresistance of each individual domain wall.

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

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

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

  11. Improvement of single domain antibody stability by disulfide bond introduction.

    PubMed

    Hagihara, Yoshihisa; Saerens, Dirk

    2012-01-01

    The successful medical application of single domain antibodies largely depends on their functionality. This feature is partly determined by the intrinsic stability of the single domain. Therefore a lot of research has gone into the elucidation of rules to uniformly increase stability of antibodies. Recently, a novel intra-domain disulfide bond was independently discovered by two research groups, after either rational design or careful investigation of the naturally occurring camelid antibody repertoire. By introducing this particular disulfide bond within a single domain antibody, the conformational stability can be increased in general. In this chapter it is described how to introduce this extra intra-domain disulfide bond and how to estimate the biophysical and biochemical impact of this cystine on the domain.

  12. [Perception of obesity in university students and in patients with eating disorders].

    PubMed

    Jáuregui Lobera, I; Polo, I M López; González, M T Montaña; Millán, M T Morales

    2008-01-01

    In order to approach in a multidisciplinary way obesity and eating disorders it is necessary to know the implicit theories of personality, the stereotypes, and the current stigmatization of overweight, as well as making the obese individual guilty by attributing his/her state to a "way of being". The objective was to know the perception that students and patients with eating disorders may have about obese people and analyze the differences that might exist between both groups. Setting, population, and interventions: we selected 138 students and 50 patients with anorexia or bulimia that assigned qualifying adjectives to obese people from a given list. We analyzed the most used adjectives and the corresponding personality scales by using the c2 test to determine the differences between the adjectives used and the scales in both samples. A p value < 0.05 was considered to be statistically significant, using the SPSS software, v.13. Obese people were essentially qualified as introverted, inhibited, and cooperative. About the latter scale, we found differences due to the most frequent use of the terms "affectionate", "helping", "obliging", "dependent", and "obedient" by the patients. As a whole, there exists a negative perception of obese people. Among the most commonly used adjectives we may highlight: "excluded", "shy", "touchy", "anxious", "rejected", "insecure", and "passive", the latter being the most repeated one in both groups. The patients tend to preferentially choose some adjectives, which expresses a paradoxical fact: they seem to have a more lenient perception of obese people but they more often choose the terms "anxious", "solitary", "lazy", "lifeless", "dependent", "easily frightened", "lonely", "childish", or "impulsive". To know the perception of obesity is essential for the psycho-educative work and prevention of associated psychopathological impairments. In eating disorders obesity represents "the most feared" condition so knowing the underlying theories about obesity and overweight in these patients is essential for their management.

  13. FBI-1 can stimulate HIV-1 Tat activity and is targeted to a novel subnuclear domain that includes the Tat-P-TEFb-containing nuclear speckles.

    PubMed

    Pendergrast, P Shannon; Wang, Chen; Hernandez, Nouria; Huang, Sui

    2002-03-01

    FBI-1 is a cellular POZ-domain-containing protein that binds to the HIV-1 LTR and associates with the HIV-1 transactivator protein Tat. Here we show that elevated levels of FBI-1 specifically stimulate Tat activity and that this effect is dependent on the same domain of FBI-1 that mediates Tat-FBI-1 association in vivo. FBI-1 also partially colocalizes with Tat and Tat's cellular cofactor, P-TEFb (Cdk9 and cyclin T1), at the splicing-factor-rich nuclear speckle domain. Further, a less-soluble population of FBI-1 distributes in a novel peripheral-speckle pattern of localization as well as in other nuclear regions. This distribution pattern is dependent on the FBI-1 DNA binding domain, on the presence of cellular DNA, and on active transcription. Taken together, these results suggest that FBI-1 is a cellular factor that preferentially associates with active chromatin and that can specifically stimulate Tat-activated HIV-1 transcription.

  14. H4 replication-dependent diacetylation and Hat1 promote S-phase chromatin assembly in vivo

    PubMed Central

    Ejlassi-Lassallette, Aïda; Mocquard, Eloïse; Arnaud, Marie-Claire; Thiriet, Christophe

    2011-01-01

    While specific posttranslational modification patterns within the H3 and H4 tail domains are associated with the S-phase, their actual functions in replication-dependent chromatin assembly have not yet been defined. Here we used incorporation of trace amounts of recombinant proteins into naturally synchronous macroplasmodia of Physarum polycephalum to examine the function of H3 and H4 tail domains in replication-coupled chromatin assembly. We found that the H3/H4 complex lacking the H4 tail domain was not efficiently recovered in nuclei, whereas depletion of the H3 tail domain did not impede nuclear import but chromatin assembly failed. Furthermore, our results revealed that the proper pattern of acetylation on the H4 tail domain is required for nuclear import and chromatin assembly. This is most likely due to binding of Hat1, as coimmunoprecipitation experiments showed Hat1 associated with predeposition histones in the cytoplasm and with replicating chromatin. These results suggest that the type B histone acetyltransferase assists in shuttling the H3/H4 complex from cytoplasm to the replication forks. PMID:21118997

  15. The Diaphanous-related Formin FHOD1 associates with ROCK1 and promotes Src-dependent plasma membrane blebbing.

    PubMed

    Hannemann, Sebastian; Madrid, Ricardo; Stastna, Jana; Kitzing, Thomas; Gasteier, Judith; Schönichen, André; Bouchet, Jerome; Jimenez, Alberto; Geyer, Matthias; Grosse, Robert; Benichou, Serge; Fackler, Oliver T

    2008-10-10

    Diaphanous-related formins (DRFs) mediate GTPase-triggered actin rearrangements to regulate central cellular processes, such as cell motility and cytokinesis. The DRF FHOD1 interacts with the Rho-GTPase Rac1 and mediates formation of actin stress fibers in its deregulated form; the physiologically relevant activities and molecular mechanisms of endogenous FHOD1, however, are still unknown. Here we report that FHOD1 physically associates via the N-terminal part of its FH2 domain with the central domain of ROCK1. Although FHOD1 does not affect the kinase activity of ROCK1, the DRF is an efficient substrate for phosphorylation by ROCK1. Co-expression of FHOD1 and ROCK1 results in the generation of nonapoptotic plasma membrane (PM) blebs, to which the DRF is efficiently recruited. Blebbing induced by FHOD1 and ROCK1 depends on F-actin integrity, the Rho-ROCK cascade, and Src activity and is reminiscent of the recently described PM blebs triggered by expression of Src homology 4 (SH4) domain PM targeting signals. Consistently, endogenous FHOD1 is required in SH4 domain expressing cells for efficient PM blebbing and rounded cell morphology in two-dimensional cultures or three-dimensional matrices, respectively. Efficient association of FHOD1 with ROCK1, as well as recruitment of the DRF to blebs, depends on Src activity, suggesting that the functional interaction between both proteins is regulated by Src. These results define a role for endogenous FHOD1 in SH4 domain-induced blebbing and suggest that its activity is regulated by ROCK1 in a Src-dependent manner.

  16. Non-interpretive mechanisms in psychoanalytic therapy. The 'something more' than interpretation. The Process of Change Study Group.

    PubMed

    Stern, D N; Sander, L W; Nahum, J P; Harrison, A M; Lyons-Ruth, K; Morgan, A C; Bruschweiler-Stern, N; Tronick, E Z

    1998-10-01

    It is by now generally accepted that something more than interpretation is necessary to bring about therapeutic change. Using an approach based on recent studies of mother-infant interaction and non-linear dynamic systems and their relation to theories of mind, the authors propose that the something more resides in interactional intersubjective process that give rise to what they will call 'implicit relational knowing'. This relational procedural domain is intrapsychically distinct from the symbolic domain. In the analytic relationship it comprises intersubjective moments occurring between patient and analyst that can create new organisations in, or reorganise not only the relationship between the interactants, but more importantly the patient's implicit procedural knowledge, his ways of being with others. The distinct qualities and consequences of these moments (now moments, 'moments of meeting') are modelled and discussed in terms of a sequencing process that they call moving along. Conceptions of the shared implicit relationship, transference and countertransference are discussed within the parameters of this perspective, which is distinguished from other relational theories and self-psychology. In sum, powerful therapeutic action occurs within implicit relational knowledge. They propose that much of what is observed to be lasting therapeutic effect results from such changes in this intersubjective relational domain.

  17. The Role of Functional Amyloids in Multicellular Growth and Development of Gram-Positive Bacteria.

    PubMed

    Dragoš, Anna; Kovács, Ákos T; Claessen, Dennis

    2017-08-07

    Amyloid fibrils play pivotal roles in all domains of life. In bacteria, these fibrillar structures are often part of an extracellular matrix that surrounds the producing organism and thereby provides protection to harsh environmental conditions. Here, we discuss the role of amyloid fibrils in the two distant Gram-positive bacteria, Streptomyces coelicolor and Bacillus subtilis . We describe how amyloid fibrils contribute to a multitude of developmental processes in each of these systems, including multicellular growth and community development. Despite this variety of tasks, we know surprisingly little about how their assembly is organized to fulfill all these roles.

  18. What's in a Name? Interlocutors Dynamically Update Expectations about Shared Names.

    PubMed

    Gegg-Harrison, Whitney M; Tanenhaus, Michael K

    2016-01-01

    In order to refer using a name, speakers must believe that their addressee knows about the link between the name and the intended referent. In cases where speakers and addressees learned a subset of names together, speakers are adept at using only the names their partner knows. But speakers do not always share such learning experience with their conversational partners. In these situations, what information guides speakers' choice of referring expression? A speaker who is uncertain about a names' common ground (CG) status often uses a name and description together. This N+D form allows speakers to demonstrate knowledge of a name, and could provide, even in the absence of miscommunication, useful evidence to the addressee regarding the speaker's knowledge. In cases where knowledge of one name is associated with knowledge of other names, this could provide indirect evidence regarding knowledge of other names that could support generalizations used to update beliefs about CG. Using Bayesian approaches to language processing as a guiding framework, we predict that interlocutors can use their partner's choice of referring expression, in particular their use of an N+D form, to generate more accurate beliefs regarding their partner's knowledge of other names. In Experiment 1, we find that domain experts are able to use their partner's referring expression choices to generate more accurate estimates of CG. In Experiment 2, we find that interlocutors are able to infer from a partner's use of an N+D form which other names that partner is likely to know or not know. Our results suggest that interlocutors can use the information conveyed in their partner's choice of referring expression to make generalizations that contribute to more accurate beliefs about what is shared with their partner, and further, that models of CG for reference need to account not just for the status of referents, but the status of means of referring to those referents.

  19. What's in a Name? Interlocutors Dynamically Update Expectations about Shared Names

    PubMed Central

    Gegg-Harrison, Whitney M.; Tanenhaus, Michael K.

    2016-01-01

    In order to refer using a name, speakers must believe that their addressee knows about the link between the name and the intended referent. In cases where speakers and addressees learned a subset of names together, speakers are adept at using only the names their partner knows. But speakers do not always share such learning experience with their conversational partners. In these situations, what information guides speakers' choice of referring expression? A speaker who is uncertain about a names' common ground (CG) status often uses a name and description together. This N+D form allows speakers to demonstrate knowledge of a name, and could provide, even in the absence of miscommunication, useful evidence to the addressee regarding the speaker's knowledge. In cases where knowledge of one name is associated with knowledge of other names, this could provide indirect evidence regarding knowledge of other names that could support generalizations used to update beliefs about CG. Using Bayesian approaches to language processing as a guiding framework, we predict that interlocutors can use their partner's choice of referring expression, in particular their use of an N+D form, to generate more accurate beliefs regarding their partner's knowledge of other names. In Experiment 1, we find that domain experts are able to use their partner's referring expression choices to generate more accurate estimates of CG. In Experiment 2, we find that interlocutors are able to infer from a partner's use of an N+D form which other names that partner is likely to know or not know. Our results suggest that interlocutors can use the information conveyed in their partner's choice of referring expression to make generalizations that contribute to more accurate beliefs about what is shared with their partner, and further, that models of CG for reference need to account not just for the status of referents, but the status of means of referring to those referents. PMID:26955361

  20. Eavesdropping on spin waves inside the domain-wall nanochannel via three-magnon processes

    NASA Astrophysics Data System (ADS)

    Zhang, Beining; Wang, Zhenyu; Cao, Yunshan; Yan, Peng; Wang, X. R.

    2018-03-01

    One recent breakthrough in the field of magnonics is the experimental realization of reconfigurable spin-wave nanochannels formed by a magnetic domain wall with a width of 10-100 nm [Wagner et al., Nat. Nano. 11, 432 (2016), 10.1038/nnano.2015.339]. This remarkable progress enables an energy-efficient spin-wave propagation with a well-defined wave vector along its propagating path inside the wall. In the mentioned experiment, a microfocus Brillouin light scattering spectroscopy was taken in a line-scans manner to measure the frequency of the bounded spin wave. Due to their localization nature, the confined spin waves can hardly be detected from outside the wall channel, which guarantees the information security to some extent. In this work, we theoretically propose a scheme to detect/eavesdrop on the spin waves inside the domain-wall nanochannel via nonlinear three-magnon processes. We send a spin wave (ωi,ki) in one magnetic domain to interact with the bounded mode (ωb,kb) in the wall, where kb is parallel with the domain-wall channel defined as the z ̂ axis. Two kinds of three-magnon processes, i.e., confluence and splitting, are expected to occur. The confluence process is conventional: conservation of energy and momentum parallel with the wall indicates a transmitted wave in the opposite domain with ω (k ) =ωi+ωb and (ki+kb-k ) .z ̂=0 , while the momentum perpendicular to the domain wall is not necessary to be conserved due to the nonuniform internal field near the wall. We predict a stimulated three-magnon splitting (or "magnon laser") effect: the presence of a bound magnon propagating along the domain wall channel assists the splitting of the incident wave into two modes, one is ω1=ωb,k1=kb identical to the bound mode in the channel, and the other one is ω2=ωi-ωb with (ki-kb-k2) .z ̂=0 propagating in the opposite magnetic domain. Micromagnetic simulations confirm our theoretical analysis. These results demonstrate that one is able to uniquely infer the spectrum of the spin wave in the domain-wall nanochannel once we know both the injection and the transmitted waves.

  1. Driving chiral domain walls in antiferromagnets using rotating magnetic fields

    NASA Astrophysics Data System (ADS)

    Pan, Keming; Xing, Lingdi; Yuan, H. Y.; Wang, Weiwei

    2018-05-01

    We show theoretically and numerically that an antiferromagnetic domain wall can be moved by a rotating magnetic field in the presence of Dzyaloshinskii-Moriya interaction (DMI). Two motion modes are found: rigid domain wall motion at low frequency (corresponding to the perfect frequency synchronization) and the oscillating motion at high frequency. In the full synchronized region, the steady velocity of the domain wall is universal, in the sense that it depends only on the frequency of the rotating field and the ratio between DMI strength and exchange constant. The domain wall velocity is independent of the Gilbert damping and the rotating field strength. Moreover, a rotating field in megahertz is sufficient to move the antiferromagnetic domain wall.

  2. Domain requirements for the Dock adapter protein in growth- cone signaling.

    PubMed

    Rao, Y; Zipursky, S L

    1998-03-03

    Tyrosine phosphorylation has been implicated in growth-cone guidance through genetic, biochemical, and pharmacological studies. Adapter proteins containing src homology 2 (SH2) domains and src homology 3 (SH3) domains provide a means of linking guidance signaling through phosphotyrosine to downstream effectors regulating growth-cone motility. The Drosophila adapter, Dreadlocks (Dock), the homolog of mammalian Nck containing three N-terminal SH3 domains and a single SH2 domain, is highly specialized for growth-cone guidance. In this paper, we demonstrate that Dock can couple signals in either an SH2-dependent or an SH2-independent fashion in photoreceptor (R cell) growth cones, and that Dock displays different domain requirements in different neurons.

  3. Working at the nexus between public health policy, practice and research. Dynamics of knowledge sharing in The Netherlands.

    PubMed

    Jansen, Maria W; De Leeuw, Evelyne; Hoeijmakers, Marjan; De Vries, Nanne K

    2012-10-17

    Joining the domains of practice, research and policy is an important aspect of boosting the quality performance required to tackle complex public health problems. "Joining domains" implies a departure from the linear and technocratic knowledge-translation approach. Integrating the practice, research and policy triangle means knowing its elements, appreciating the barriers, identifying possible cooperation strategies and studying strategy effectiveness under specified conditions.This article examines the dynamic process of developing an Academic Collaborative Centre for Public Health in the Netherlands, with the objective of achieving that the three domains of policy, practice and research become working partners on an equal footing. An interpretative hermeneutic approach was used to interpret the phenomenon of collaboration at the nexus between the three domains. The project was explicitly grounded in current organizational culture and routines, applied to nexus action. In the process of examination, we used both quantitative (e.g. records) and qualitative data (e.g., interviews and observations). The data were interpreted using the Actor-Network, Institutional Re-Design and Blurring the Boundaries theories. Results show commitment at strategic level. At the tactical level, however, managers were inclined to prioritize daily routine, while the policy domain remained absent. At the operational level, practitioners learned to do PhD research in real-life practice and researchers became acquainted with problems of practice and policy, resulting in new research initiatives. We conclude that working at the nexus is an ongoing process of formation and reformation. Strategies based on Institutional Re-Design theories in particular might help to more actively stimulate managers' involvement to establish mutually supportive networks.

  4. Domain size polydispersity effects on the structural and dynamical properties in lipid monolayers with phase coexistence

    NASA Astrophysics Data System (ADS)

    Rufeil-Fiori, Elena; Banchio, Adolfo J.

    Lipid monolayers with phase coexistence are a frequently used model for lipid membranes. In these systems, domains of the liquid-condensed phase always present size polydispersity. However, very few theoretical works consider size distribution effects on the monolayer properties. Because of the difference in surface densities, domains have excess dipolar density with respect to the surrounding liquid expanded phase, originating a dipolar inter-domain interaction. This interaction depends on the domain area, and hence the presence of a domain size distribution is associated with interaction polydispersity. Inter-domain interactions are fundamental to understanding the structure and dynamics of the monolayer. For this reason, it is expected that polydispersity significantly alters monolayer properties. By means of Brownian dynamics simulations, we study the radial distribution function (RDF), the average mean square displacement and the average time-dependent self-diffusion coefficient, D(t), of lipid monolayers with normal distributed size domains. It was found that polydispersity strongly affects the value of the interaction strength obtained, which is greatly underestimated if polydispersity is not considered. However, within a certain range of parameters, the RDF obtained from a polydisperse model can be well approximated by that of a monodisperse model, suitably fitting the interaction strength, even for 40% polydispersities. For small interaction strengths or small polydispersities, the polydisperse systems obtained from fitting the experimental RDF have an average mean square displacement and D(t) in good agreement with that of the monodisperse system.

  5. 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

  6. Rab9-dependent retrograde transport and endosomal sorting of the endopeptidase furin

    PubMed Central

    Chia, Pei Zhi Cheryl; Gasnereau, Isabelle; Lieu, Zi Zhao; Gleeson, Paul A.

    2011-01-01

    The endopeptidase furin and the trans-Golgi network protein TGN38 are membrane proteins that recycle between the TGN and plasma membrane. TGN38 is transported by a retromer-dependent pathway from early endosomes to the TGN, whereas the intracellular transport of furin is poorly defined. Here we have identified the itinerary and transport requirements of furin. Using internalisation assays, we show that furin transits the early and late endosomes en route to the TGN. The GTPase Rab9 and the TGN golgin GCC185, components of the late endosome-to-TGN pathway, were required for efficient TGN retrieval of furin. By contrast, TGN38 trafficking was independent of Rab9 and GCC185. To identify the sorting signals for the early endosome-to-TGN pathway, the trafficking of furin–TGN38 chimeras was investigated. The diversion of furin from the Rab9-dependent late-endosome-to-TGN pathway to the retromer-dependent early-endosome-to-TGN pathway required both the transmembrane domain and cytoplasmic tail of TGN38. We present evidence to suggest that the length of the transmembrane domain is a contributing factor in endosomal sorting. Overall, these data show that furin uses the Rab9-dependent pathway from late endosomes and that retrograde transport directly from early endosomes is dependent on both the transmembrane domain and the cytoplasmic tail. PMID:21693586

  7. Induction of nuclear factor kappaB by the CD30 receptor is mediated by TRAF1 and TRAF2.

    PubMed Central

    Duckett, C S; Gedrich, R W; Gilfillan, M C; Thompson, C B

    1997-01-01

    CD30 is a lymphoid cell-specific surface receptor which was originally identified as an antigen expressed on Hodgkin's lymphoma cells. Activation of CD30 induces the nuclear factor kappaB (NF-kappaB) transcription factor. In this study, we define the domains in CD30 which are required for NF-kappaB activation. Two separate elements of the cytoplasmic domain which were capable of inducing NF-kappaB independently of one another were identified. The first domain (domain 1) mapped to a approximately 120-amino-acid sequence in the membrane-proximal region of the CD30 cytoplasmic tail, between residues 410 and 531. A second, more carboxy-terminal region (domain 2) was identified between residues 553 and 595. Domain 2 contains two 5- to 10-amino-acid elements which can mediate the binding of CD30 to members of the tumor necrosis factor receptor-associated factor (TRAF) family of signal transducing proteins. Coexpression of CD30 with TRAF1 or TRAF2 but not TRAF3 augmented NF-kappaB activation through domain 2 but not domain 1. NF-kappaB induction through domain 2 was inhibited by coexpression of either full-length TRAF3 or dominant negative forms of TRAF1 or TRAF2. In contrast, NF-kappaB induction by domain 1 was not affected by alterations in TRAF protein levels. Together, these data support a model in which CD30 can induce NF-kappaB by both TRAF-dependent and -independent mechanisms. TRAF-dependent induction of NF-kappaB appears to be regulated by the relative levels of individual TRAF proteins in the cell. PMID:9032281

  8. Illuminating a neglected clinical issue: societal costs of interpersonal dependency and dependent personality disorder.

    PubMed

    Bornstein, Robert F

    2012-07-01

    To determine the degree to which patients with high levels of trait dependency or dependent personality disorder (DPD) engage in behaviors that harm themselves and others (e.g., domestic violence, child abuse). Six domains of literature were reviewed: (a) dependency as a risk factor for physical illness; (b) health care utilization and expenditures; (c) global and domain-specific functional impairment; (d) violence toward others; (e) victimization by others; and (f) self-harm. High levels of trait dependency and DPD are associated with elevated risk for physical illness, partner and child abuse, and suicidality, as well as with high levels of functional impairment and increased health care expenditure. Contrary to clinical lore, trait dependency and DPD are associated with behaviors that lead to myriad negative consequences for the dependent person, those close to them, and society as a whole. These patterns have noteworthy implications for assessment and treatment of dependent patients and suggest that DPD should be included as a diagnostic category in the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition. © 2012 Wiley Periodicals, Inc.

  9. The ShcA SH2 domain engages a 14-3-3/PI3'K signaling complex and promotes breast cancer cell survival.

    PubMed

    Ursini-Siegel, J; Hardy, W R; Zheng, Y; Ling, C; Zuo, D; Zhang, C; Podmore, L; Pawson, T; Muller, W J

    2012-11-29

    The ShcA adapter protein transmits activating signals downstream of receptor and cytoplasmic tyrosine kinases through the establishment of phosphotyrosine-dependent complexes. In this regard, ShcA possesses both a phosphotyrosine-binding domain (PTB) and Src homology 2 domain (SH2), which bind phosphotyrosine residues in a sequence-specific manner. Although the majority of receptor tyrosine kinases expressed in breast cancer cells bind the PTB domain, very little is known regarding the biological importance of SH2-driven ShcA signaling during mammary tumorigenesis. To address this, we employed transgenic mice expressing a mutant ShcA allele harboring a non-functional SH2 domain (ShcR397K) under the transcriptional control of the endogenous ShcA promoter. Using transplantation approaches, we demonstrate that SH2-dependent ShcA signaling within the mammary epithelial compartment is essential for breast tumor outgrowth, survival and the development of lung metastases. We further show that the ShcA SH2 domain activates the AKT pathway, potentially through a novel SH2-mediated complex between ShcA, 14-3-3ζ and the p85 regulatory subunit of phosphatidylinositol 3 (PI3') kinase. This study is the first to demonstrate that the SH2 domain of ShcA is critical for tumor survival during mammary tumorigenesis.

  10. Intracultural variation of knowledge about wild plant uses in the Biosphere Reserve Grosses Walsertal (Austria)

    PubMed Central

    2012-01-01

    Background Leading scholars in ethnobiology and ethnomedicine continuously stress the need for moving beyond the bare description of local knowledge and to additionally analyse and theorise about the characteristics and dynamics of human interactions with plants and related local knowledge. Analyses of the variation of local knowledge are thereby perceived as minimal standard. In this study we investigate the distribution and variation of wild plant knowledge in five domains: food, drinks, human medicine, veterinary medicine and customs. We assess relations between the wild plant knowledge of informants and their socio-demographic as well as geographic background. Method Research was conducted in the Biosphere Reserve Grosses Walsertal, Austria. Structured questionnaires were used to inquire wild plant knowledge from 433 informants with varying socio-demographic and geographic background. Children assisted in the data collection. Data was analysed using descriptive statistics and generalized linear models. Results and discussion A majority of respondents is familiar with wild plant uses, however to varying degrees. Knowledge variations depend on the socio-demographic and geographic background of the informants as well as on the domains of knowledge under investigation: women, older informants and homegardeners report more human medicinal applications and applications in drinks than men, younger informants and non-homegardeners; farmers know a greater variety of veterinary medicinal applications than non-farmers; the place of residence relates significantly to food and veterinary uses. Customs are difficult to investigate in standardized matrices. The household-related distribution of work and the general socio-cultural context are especially helpful in order to explain intracultural variation of knowledge in the Grosses Walsertal. Conclusions Research on the intracultural variation of local knowledge exposes cultural characteristics and highlights the cultural embeddedness of local knowledge. The impact of socio-cultural developments on local knowledge may be anticipated from understanding the intracultural variation of knowledge. PMID:22770375

  11. Familiar Person Recognition: Is Autonoetic Consciousness More Likely to Accompany Face Recognition Than Voice Recognition?

    NASA Astrophysics Data System (ADS)

    Barsics, Catherine; Brédart, Serge

    2010-11-01

    Autonoetic consciousness is a fundamental property of human memory, enabling us to experience mental time travel, to recollect past events with a feeling of self-involvement, and to project ourselves in the future. Autonoetic consciousness is a characteristic of episodic memory. By contrast, awareness of the past associated with a mere feeling of familiarity or knowing relies on noetic consciousness, depending on semantic memory integrity. Present research was aimed at evaluating whether conscious recollection of episodic memories is more likely to occur following the recognition of a familiar face than following the recognition of a familiar voice. Recall of semantic information (biographical information) was also assessed. Previous studies that investigated the recall of biographical information following person recognition used faces and voices of famous people as stimuli. In this study, the participants were presented with personally familiar people's voices and faces, thus avoiding the presence of identity cues in the spoken extracts and allowing a stricter control of frequency exposure with both types of stimuli (voices and faces). In the present study, the rate of retrieved episodic memories, associated with autonoetic awareness, was significantly higher from familiar faces than familiar voices even though the level of overall recognition was similar for both these stimuli domains. The same pattern was observed regarding semantic information retrieval. These results and their implications for current Interactive Activation and Competition person recognition models are discussed.

  12. Knowing your friends and foes--plant receptor-like kinases as initiators of symbiosis or defence.

    PubMed

    Antolín-Llovera, Meritxell; Petutsching, Elena Kristin; Ried, Martina Katharina; Lipka, Volker; Nürnberger, Thorsten; Robatzek, Silke; Parniske, Martin

    2014-12-01

    The decision between defence and symbiosis signalling in plants involves alternative and modular plasma membrane-localized receptor complexes. A critical step in their activation is ligand-induced homo- or hetero-oligomerization of leucine-rich repeat (LRR)- and/or lysin motif (LysM) receptor-like kinases (RLKs). In defence signalling, receptor complexes form upon binding of pathogen-associated molecular patterns (PAMPs), including the bacterial flagellin-derived peptide flg22, or chitin. Similar mechanisms are likely to operate during the perception of microbial symbiont-derived (lipo)-chitooligosaccharides. The structurally related chitin-oligomer ligands chitooctaose and chitotetraose trigger defence and symbiosis signalling, respectively, and their discrimination involves closely related, if not identical, LysM-RLKs. This illustrates the demand for and the challenges imposed on decision mechanisms that ensure appropriate signal initiation. Appropriate signalling critically depends on abundance and localization of RLKs at the cell surface. This is regulated by internalization, which also provides a mechanism for the removal of activated signalling RLKs. Abundance of the malectin-like domain (MLD)-LRR-RLK Symbiosis Receptor-like Kinase (SYMRK) is additionally controlled by cleavage of its modular ectodomain, which generates a truncated and rapidly degraded RLK fragment. This review explores LRR- and LysM-mediated signalling, the involvement of MLD-LRR-RLKs in symbiosis and defence, and the role of endocytosis in RLK function. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

  13. What Do We Know about Civic Engagement?

    ERIC Educational Resources Information Center

    Levine, Peter

    2011-01-01

    A decade ago, research on the civic engagement and learning of young people was still in a "bear market" (Cook 1985). The body of literature was strikingly small, considering that the future of democracy depends on the preparation of young citizens. Today, the situation is dramatically different. There is a torrent of research on youth civic…

  14. Accounting and Financial Planning--Top Priorities for School Business Administrators.

    ERIC Educational Resources Information Center

    Walters, Donald L.

    Success for the business administrator depends largely on ability to identify priorities and to direct time, energy, and know-how accordingly. This study attempted to find out the priorities of the tasks of accounting and financial planning for school business administrators and the precise nature of the school business administrator's…

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

    Diwaker, E-mail: diwakerphysics@gmail.com; Chakraborty, Aniruddha

    The Smoluchowski equation with a time-dependent sink term is solved exactly. In this method, knowing the probability distribution P(0, s) at the origin, allows deriving the probability distribution P(x, s) at all positions. Exact solutions of the Smoluchowski equation are also provided in different cases where the sink term has linear, constant, inverse, and exponential variation in time.

  16. It's Who You Know: Leveraging Social Networks for College and Careers

    ERIC Educational Resources Information Center

    González Canché, Manuel S.; D'Amico, Mark M.; Rios-Aguilar, Cecilia; Salas, Spencer

    2014-01-01

    There is increasing concern that community college student success should not only consider how many students earn degrees, but also how and to what extent the degrees enhance individuals' professional livelihoods. Whether that happens depends on students' ability to make strategic and well-informed choices. Looking through the lens of a…

  17. Getting to Know You: The Prospect of Challenging Ableism through Adult Learning

    ERIC Educational Resources Information Center

    McLean, Margaret A.

    2011-01-01

    Ableism is discrimination on the grounds that being able bodied is the normal and superior human condition. In contrast, being "disabled" is linked to ill health, incapacity, and dependence. These understandings become institutionalized in the beliefs, language, and practices of nondisabled people and create barriers to equitable social…

  18. School Teachers' Knowledge about Autism in Saudi Arabia

    ERIC Educational Resources Information Center

    Haimour, Abdulhade I.; Obaidat, Yahia F.

    2013-01-01

    The purpose of this study was to find out what school teachers know about Autism. In addition, this study attempted to find out if there any significant differences in school teachers' knowledge about Autism depending on teachers' (gender, position, education level, teaching experience, and contact with students with Autism) variables. A total of…

  19. Bayesian statistics: estimating plant demographic parameters

    Treesearch

    James S. Clark; Michael Lavine

    2001-01-01

    There are times when external information should be brought tobear on an ecological analysis. experiments are never conducted in a knowledge-free context. The inference we draw from an observation may depend on everything else we know about the process. Bayesian analysis is a method that brings outside evidence into the analysis of experimental and observational data...

  20. Exploring the Power of Solo, Silence, and Solitude

    ERIC Educational Resources Information Center

    Knapp, Clifford E., Ed.; Smith, Thomas E., Ed.

    2005-01-01

    What do solitude experiences offer in this increasingly high-speed, technically dependent world? As this book inspiringly reveals, solo quests can provide powerful reconnection with the natural world, the true self, and the great mystery beyond. As Parker Palmer writes in "To Know as We Are Known," "Solitude calls us to confront…

  1. An Azulene-Based Discovery Experiment: Challenging Students to Watch for the "False Assumption"

    ERIC Educational Resources Information Center

    Garner, Charles M.

    2005-01-01

    A discovery-based experiment is developed depending on a "false assumption" that the students mistakenly assume they know the structure of a reaction product and are forced to reconcile observations that are inconsistent with this assumption. This experiment involves the chemistry of azulenes, an interesting class of intensely colored aromatic…

  2. An Ecologic Characterization and Landscape Assessment of the Humboldt River Basin

    EPA Science Inventory

    The Humboldt River Basin covers a large part of northern Nevada. Very little is known about the water quality of the entire Basin. The people living in this area depend on clean water. Not knowing about water quality is a concern because people will need to manage the negative...

  3. How Do We Know? The Face of Government: Education

    ERIC Educational Resources Information Center

    US Census Bureau, 2012

    2012-01-01

    State and local government employees provide critical services that citizens depend on every day including police and fire protection, roads and public transit systems, social services, public health and hospitals, and education services. The U.S. Census Bureau collects statistics on the nation's governments every five years in the Census of…

  4. The Importance of Design Thinking for Technological Literacy: A Phenomenological Perspective

    ERIC Educational Resources Information Center

    Wells, Alastair

    2013-01-01

    "We know that progress depends on discovery, inventions, creativity and design, but we have simply supposed that it happens anyway," de Bono (1999 p. 43). Technology education is ostensibly a foundation for future designers and creative thinking. However evidence of good design or creative thinking in outcomes displayed in school…

  5. Determination of Self Efficacy Perception Levels of Teachers' Attending an Online Course toward Web Pedagogical Content Knowledge

    ERIC Educational Resources Information Center

    Oskay, Özge Özyalçin; Odabasi, Zuhal

    2016-01-01

    The effects of technological developments occurred new requirements in educational area. Today's teachers should know the content knowledge they teach, have pedagogical knowledge about teaching and learning methods and besides should use the technological tools effectively. Depending on these, new concepts such as Technological Pedagogical Content…

  6. Current induced incoherent magnetization dynamics in ferromagnetic/non-magnetic metallic multilayer nanowires

    NASA Astrophysics Data System (ADS)

    Al-Rashid, Md Mamun; Maqableh, Mazin; Stadler, Bethanie; Atulasimha, Jayasimha

    High density arrays of electrodeposited nanowires consisting of ferromagnetic/non-magnetic (Co/Cu) multilayers are promising as magnetic memory devices. For individual nanowires containing multiple (Co/Cu) bilayers, the stable magnetization orientations of the Co layers (with respect to each other and the nanowire axis) are dependent on the Cu layer thickness, even when the Co layer dimensions are fixed. This dependence is a result of the competition between shape anisotropy, magneto-crystalline anisotropy and intra-wire dipole coupling. However, when the nanowires are closely packed in arrays, inter-wire dipole coupling can result in complex and tunable domain structures comprising segments of multiple nanowires. This work explores the dependence of these domain structures and their switching on the non-magnetic layer thickness and intra-wire spacing both experimentally and via rigorous micromagnetic simulation. These domain structures play a crucial role in determining the current and time required for STT switching. NSF CAREER Grant CCF-1253370.

  7. A time-dependent model to determine the thermal conductivity of a nanofluid

    NASA Astrophysics Data System (ADS)

    Myers, T. G.; MacDevette, M. M.; Ribera, H.

    2013-07-01

    In this paper, we analyse the time-dependent heat equations over a finite domain to determine expressions for the thermal diffusivity and conductivity of a nanofluid (where a nanofluid is a fluid containing nanoparticles with average size below 100 nm). Due to the complexity of the standard mathematical analysis of this problem, we employ a well-known approximate solution technique known as the heat balance integral method. This allows us to derive simple analytical expressions for the thermal properties, which appear to depend primarily on the volume fraction and liquid properties. The model is shown to compare well with experimental data taken from the literature even up to relatively high concentrations and predicts significantly higher values than the Maxwell model for volume fractions approximately >1 %. The results suggest that the difficulty in reproducing the high values of conductivity observed experimentally may stem from the use of a static heat flow model applied over an infinite domain rather than applying a dynamic model over a finite domain.

  8. The tetraspanin CD63 regulates ESCRT-independent and dependent endosomal sorting during melanogenesis

    PubMed Central

    van Niel, Guillaume; Charrin, Stéphanie; Simoes, Sabrina; Romao, Maryse; Rochin, Leila; Saftig, Paul; Marks, Michael S.; Rubinstein, Eric; Raposo, Graça

    2011-01-01

    Summary Cargo sorting to intraluminal vesicles (ILVs) of multivesicular endosomes is required for numerous physiological processes including lysosome-related organelle (LRO) biogenesis. PMEL – a component of melanocyte LROs (melanosomes) – is sorted to ILVs in an ESCRT-independent manner, where it is proteolytically processed and assembled into functional amyloid fibrils during melanosome maturation. Here we show that the tetraspanin CD63 directly participates in ESCRT-independent sorting of the PMEL luminal domain, but not of traditional ESCRT-dependent cargoes, to ILVs. Inactivating CD63 in cell culture or in mice impairs amyloidogenesis and downstream melanosome morphogenesis. Whereas CD63 is required for normal PMEL luminal domain sorting, the disposal of the remaining PMEL transmembrane fragment requires functional ESCRTs but not CD63. In the absence of CD63, the PMEL luminal domain follows this fragment and is targeted for ESCRT-dependent degradation. Our data thus reveal a tight interplay regulated by CD63 between two distinct endosomal ILV sorting processes for a single cargo during LRO biogenesis. PMID:21962903

  9. I-mfa domain proteins specifically interact with HTLV-1 Tax and repress its transactivating functions.

    PubMed

    Kusano, Shuichi; Yoshimitsu, Makoto; Hachiman, Miho; Ikeda, Masanori

    2015-12-01

    The I-mfa domain proteins HIC (also known as MDFIC) and I-mfa (also known as MDFI) are candidate tumor suppressor genes that are involved in cellular and viral transcriptional regulation. Here, we show that HIC and I-mfa directly interact with human T-cell leukemia virus type-1 (HTLV-1) Tax protein in vitro. In addition, HIC and I-mfa repress Tax-dependent transactivation of an HTLV-1 long terminal repeat (LTR) reporter construct in COS-1, Jurkat and high-Tax-producing HTLV-1-infected T cells. HIC also interacts with Tax through its I-mfa domain in vivo and represses Tax-dependent transactivation of HTLV-1 LTR and NF-κB reporter constructs in an interaction-dependent manner. Furthermore, we show that HIC decreases the nuclear distribution and stimulates the proteasomal degradation of Tax. These data reveal that HIC specifically interacts with HTLV-1 Tax and negatively regulates Tax transactivational activity by altering its subcellular distribution and stability. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Magnetization Processes in Ribbons of Soft Magnetic Amorphous Alloys

    NASA Astrophysics Data System (ADS)

    Skulkina, N. A.; Ivanov, O. A.; Mazeeva, A. K.; Kuznetsov, P. A.; Stepanova, E. A.; Blinova, O. V.; Mikhalitsyna, E. A.

    2018-02-01

    Using iron-based (Fe-B-Si-C; Fe-Ni-Si-B) and cobalt-based (Co-Fe-Ni-Cr-Mn-Si-B) soft magnetic alloys as examples, we have studied the dependences of the remanence measured using minor hysteresis loops on the maximum induction. The different degrees of stabilization of the 180° and 90° domain walls allows these dependences to be used to analyze the magnetization processes that occur in the rapidly quenched soft magnetic alloys. It has been established from the B r( B m) dependences that, in the ribbons of soft magnetic amorphous alloys, the processes of the rotation of the magnetization oriented perpendicular to the ribbon plane start before the end of the processes of the displacement of the walls of domains with planar magnetization. After the end of the magnetization rotation processes, the magnetization processes can be interpreted as the displacement of the domain walls with a planar magnetization accompanied by a decrease in their number and a transition to a bistable state.

  11. Impact of Tortuosity on Charge-Carrier Transport in Organic Bulk Heterojunction Blends

    NASA Astrophysics Data System (ADS)

    Heiber, Michael C.; Kister, Klaus; Baumann, Andreas; Dyakonov, Vladimir; Deibel, Carsten; Nguyen, Thuc-Quyen

    2017-11-01

    The impact of the tortuosity of the charge-transport pathways through a bulk heterojunction film on the charge-carrier mobility is theoretically investigated using model morphologies and kinetic Monte Carlo simulations. The tortuosity descriptor provides a quantitative metric to characterize the quality of the charge-transport pathways, and model morphologies with controlled domain size and tortuosity are created using an anisotropic domain growth procedure. The tortuosity is found to be dependent on the anisotropy of the domain structure and is highly tunable. Time-of-flight charge-transport simulations on morphologies with a range of tortuosity values reveal that tortuosity can significantly reduce the magnitude of the mobility and the electric-field dependence relative to a neat material. These reductions are found to be further controlled by the energetic disorder and temperature. Most significantly, the sensitivity of the electric-field dependence to the tortuosity can explain the different experimental relationships previously reported, and exploiting this sensitivity could lead to simpler methods for characterizing and optimizing charge transport in organic solar cells.

  12. Dependence of the Thermal Conductivity of BiFeO3 Thin Films on Polarization and Structure

    NASA Astrophysics Data System (ADS)

    Ning, Shuai; Huberman, Samuel C.; Zhang, Chen; Zhang, Zhengjun; Chen, Gang; Ross, Caroline A.

    2017-11-01

    The role of the ferroelectric polarization state and crystal structure in determining the room-temperature thermal conductivity of epitaxial BiFeO3 thin films is investigated. The ferroelectric domain configuration is varied by changing the oxygen partial pressure during growth, as well as by polarizing the samples by the application of an in situ electric field during the thermal conductivity measurement. However, little or no dependence of thermal conductivity on the ferroelectric domain structure is observed. In contrast, the thermal conductivity significantly depends on the morphotropic phase structure, being about 2 /3 as large in tetragonal-like compared to rhombohedral-like BiFeO3 film. The substantial structural dependence of thermal conductivity found here may provide a route to reversible manipulation of thermal properties.

  13. Stress dependence of the Raman spectrum of polycrystalline barium titanate in presence of localized domain texture

    NASA Astrophysics Data System (ADS)

    Sakashita, Tatsuo; Deluca, Marco; Yamamoto, Shinsuke; Chazono, Hirokazu; Pezzotti, Giuseppe

    2007-06-01

    The stress dependence of the Raman spectrum of polycrystalline barium titanate (BaTiO3, BT) ceramics has been examined with microprobe polarized Raman spectroscopy. The angular dependence of the Raman spectrum of the tetragonal BT crystal has been theoretically established, enabling us to assess the stress dependence of selected spectral modes without the influence of crystallographic domain orientation. Upon considering the frequency shift of selected Raman modes as a function of orientation between the crystallographic axis and the polarization vector of incident and scattered light, a suitable instrumental configuration has been selected, which allowed a direct residual stress measurement according to a modified piezospectroscopic procedure. The analysis is based on the selection of mixed photostimulated spectral modes in two perpendicular angular orientations.

  14. Effects of Negative Affect, Urge to Smoke, and Working Memory Performance (n-back) on Nicotine Dependence.

    PubMed

    Lechner, William V; L Gunn, Rachel; Minto, Alexia; Philip, Noah S; Brown, Richard A; Uebelacker, Lisa A; Price, Lawrence H; Abrantes, Ana M

    2018-06-07

    Three key domains including negative emotionality, incentive salience, and executive function form the core functional elements of addictive behaviors. Variables related to these broader domains have been studied extensively in relation to one another; however, no studies to date, have examined models including variables from all three domains, in relation to nicotine dependence. Smokers (N = 117), 65.8% female, 78% white, mean age of 44.4 (SD = 10.8), enrolled in a smoking cessation program completed measures of negative affect (a component of negative emotionality), urge to smoke (incentive salience), and working memory (WM; a core executive function), during a baseline assessment period prior to initiating treatment. Negative affect was associated with greater urge to smoke, and this elevated urge to smoke was associated with higher levels of nicotine dependence. Further, a significant moderated mediation indicated that WM moderated the relationship between increased urge to smoke and nicotine dependence. For those with low to average WM, urge to smoke was significantly related to nicotine dependence; however, for those with higher WM (+1 SD), urge to smoke stemming from negative affect was not associated with nicotine dependence. To our knowledge, this is the first reported relationship between negative affect, urge to smoke, WM, and nicotine dependence. Although preliminary, results indicate that WM may moderate the relationship between urge to smoke associated with negative affect and nicotine dependence. Treatments targeting WM may be particularly useful for individuals with average to low WM who experience urge to smoke related to negative affect.

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

    PubMed

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

    2001-11-09

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

  16. 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.

  17. Binding of high molecular weight kininogen to human endothelial cells is mediated via a site within domains 2 and 3 of the urokinase receptor.

    PubMed Central

    Colman, R W; Pixley, R A; Najamunnisa, S; Yan, W; Wang, J; Mazar, A; McCrae, K R

    1997-01-01

    The urokinase receptor (uPAR) binds urokinase-type plasminogen activator (u-PA) through specific interactions with uPAR domain 1, and vitronectin through interactions with a site within uPAR domains 2 and 3. These interactions promote the expression of cell surface plasminogen activator activity and cellular adhesion to vitronectin, respectively. High molecular weight kininogen (HK) also stimulates the expression of cell surface plasminogen activator activity through its ability to serve as an acquired receptor for prekallikrein, which, after its activation, may directly activate prourokinase. Here, we report that binding of the cleaved form of HK (HKa) to human umbilical vein endothelial cells (HUVEC) is mediated through zinc-dependent interactions with uPAR. These occur through a site within uPAR domains 2 and 3, since the binding of 125I-HKa to HUVEC is inhibited by vitronectin, anti-uPAR domain 2 and 3 antibodies and soluble, recombinant uPAR (suPAR), but not by antibody 7E3, which recognizes the beta chain of the endothelial cell vitronectin receptor (integrin alphavbeta3), or fibrinogen, another alphavbeta3 ligand. We also demonstrate the formation of a zinc-dependent complex between suPAR and HKa. Interactions of HKa with endothelial cell uPAR may underlie its ability to promote kallikrein-dependent cell surface plasmin generation, and also explain, in part, its antiadhesive properties. PMID:9294114

  18. Vulnerability-specific stress generation: An examination of negative cognitive and interpersonal styles

    PubMed Central

    Liu, Richard T.; Alloy, Lauren B.; Mastin, Becky M.; Choi, Jimmy Y.; Boland, Elaine M.; Jenkins, Abby L.

    2014-01-01

    Although there is substantial evidence documenting the stress generation effect in depression (i.e., the tendency for depression-prone individuals to experience higher rates of life stress to which they contribute), additional research is required to advance current understanding of the specific types of dependent stress (i.e., events influenced by characteristics and attendant behaviors of the individual) relevant to this effect. The present study tested an extension of the stress generation hypothesis, in which the content of dependent stress that is produced by depression-prone individuals is contingent upon, and matches, the nature of their particular vulnerabilities. This extension was tested within the context of two cognitive models (i.e., hopelessness theory [Abramson, Metalsky, & Alloy, 1989] and Cole’s [1990, 1991] competency-based model) and two interpersonal models (i.e., Swann’s [1987] self-verification theory and Coyne’s [1976] interpersonal theory) of depression. Overall, support was obtained for vulnerability-specific stress generation. Specifically, in analyses across vulnerability domains, evidence of stress-generation specificity was found for all domain-specific cognitive vulnerabilities except self-perceived social competence. The within-domain analyses for cognitive vulnerabilities produced more mixed results, but were largely supportive. Additionally, excessive reassurance-seeking was specifically predictive of dependent stress in the social domain, and moderated, but did not mediate, the relation between negative inferential styles overall and in the interpersonal domain and their corresponding generated stress. Finally, no evidence was found for a stress generation effect with negative feedback-seeking. PMID:24679143

  19. Structures of Ca(V) Ca**2+/CaM-IQ Domain Complexes Reveal Binding Modes That Underlie Calcium-Dependent Inactivation And Facilitation

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

    Kim, E.Y.; Rumpf, C.H.; Fujiwara, Y.

    2009-05-20

    Calcium influx drives two opposing voltage-activated calcium channel (Ca{sub V}) self-modulatory processes: calcium-dependent inactivation (CDI) and calcium-dependent facilitation (CDF). Specific Ca{sup 2+}/calmodulin (Ca{sup 2+}/CaM) lobes produce CDI and CDF through interactions with the Ca{sub V}{alpha}{sub 1} subunit IQ domain. Curiously, Ca{sup 2+}/CaM lobe modulation polarity appears inverted between Ca{sub V}1s and Ca{sub V}2s. Here, we present crystal structures of Ca{sub V}2.1, Ca{sub V}2.2, and Ca{sub V}2.3 Ca{sup 2+}/CaM-IQ domain complexes. All display binding orientations opposite to Ca{sub V}1.2 with a physical reversal of the CaM lobe positions relative to the IQ {alpha}-helix. Titration calorimetry reveals lobe competition for a high-affinitymore » site common to Ca{sub V}1 and Ca{sub V}2 IQ domains that is occupied by the CDI lobe in the structures. Electrophysiological experiments demonstrate that the N-terminal Ca{sub V}2 Ca{sup 2+}/C-lobe anchors affect CDF. Together, the data unveil the remarkable structural plasticity at the heart of Ca{sub V} feedback modulation and indicate that Ca{sub V}1 and Ca{sub V}2 IQ domains bear a dedicated CDF site that exchanges Ca{sup 2+}/CaM lobe occupants.« less

  20. Some Exact Results for the Schroedinger Wave Equation with a Time Dependent Potential

    NASA Technical Reports Server (NTRS)

    Campbell, Joel

    2009-01-01

    The time dependent Schroedinger equation with a time dependent delta function potential is solved exactly for many special cases. In all other cases the problem can be reduced to an integral equation of the Volterra type. It is shown that by knowing the wave function at the origin, one may derive the wave function everywhere. Thus, the problem is reduced from a PDE in two variables to an integral equation in one. These results are used to compare adiabatic versus sudden changes in the potential. It is shown that adiabatic changes in the p otential lead to conservation of the normalization of the probability density.

  1. Do different types of school mathematics development depend on different constellations of numerical versus general cognitive abilities?

    PubMed

    Fuchs, Lynn S; Geary, David C; Compton, Donald L; Fuchs, Douglas; Hamlett, Carol L; Seethaler, Pamela M; Bryant, Joan D; Schatschneider, Christopher

    2010-11-01

    The purpose of this study was to examine the interplay between basic numerical cognition and domain-general abilities (such as working memory) in explaining school mathematics learning. First graders (N = 280; mean age = 5.77 years) were assessed on 2 types of basic numerical cognition, 8 domain-general abilities, procedural calculations, and word problems in fall and then reassessed on procedural calculations and word problems in spring. Development was indexed by latent change scores, and the interplay between numerical and domain-general abilities was analyzed by multiple regression. Results suggest that the development of different types of formal school mathematics depends on different constellations of numerical versus general cognitive abilities. When controlling for 8 domain-general abilities, both aspects of basic numerical cognition were uniquely predictive of procedural calculations and word problems development. Yet, for procedural calculations development, the additional amount of variance explained by the set of domain-general abilities was not significant, and only counting span was uniquely predictive. By contrast, for word problems development, the set of domain-general abilities did provide additional explanatory value, accounting for about the same amount of variance as the basic numerical cognition variables. Language, attentive behavior, nonverbal problem solving, and listening span were uniquely predictive.

  2. Do Different Types of School Mathematics Development Depend on Different Constellations of Numerical versus General Cognitive Abilities?

    PubMed Central

    Fuchs, Lynn S.; Geary, David C.; Compton, Donald L.; Fuchs, Douglas; Hamlett, Carol L.; Seethaler, Pamela M.; Bryant, Joan D.; Schatschneider, Christopher

    2010-01-01

    The purpose of this study was to examine the interplay between basic numerical cognition and domain-general abilities (such as working memory) in explaining school mathematics learning. First graders (n=280; 5.77 years) were assessed on 2 types of basic numerical cognition, 8 domain-general abilities, procedural calculations (PCs), and word problems (WPs) in fall and then reassessed on PCs and WPs in spring. Development was indexed via latent change scores, and the interplay between numerical and domain-general abilities was analyzed via multiple regression. Results suggest that the development of different types of formal school mathematics depends on different constellations of numerical versus general cognitive abilities. When controlling for 8 domain-general abilities, both aspects of basic numerical cognition were uniquely predictive of PC and WP development. Yet, for PC development, the additional amount of variance explained by the set of domain-general abilities was not significant, and only counting span was uniquely predictive. By contrast, for WP development, the set of domain- general abilities did provide additional explanatory value, accounting for about the same amount of variance as the basic numerical cognition variables. Language, attentive behavior, nonverbal problem solving, and listening span were uniquely predictive. PMID:20822213

  3. Interconnected magnetic tunnel junctions for spin-logic applications

    NASA Astrophysics Data System (ADS)

    Manfrini, Mauricio; Vaysset, Adrien; Wan, Danny; Raymenants, Eline; Swerts, Johan; Rao, Siddharth; Zografos, Odysseas; Souriau, Laurent; Gavan, Khashayar Babaei; Rassoul, Nouredine; Radisic, Dunja; Cupak, Miroslav; Dehan, Morin; Sayan, Safak; Nikonov, Dmitri E.; Manipatruni, Sasikanth; Young, Ian A.; Mocuta, Dan; Radu, Iuliana P.

    2018-05-01

    With the rapid progress of spintronic devices, spin-logic concepts hold promises of energy-delay conscious computation for efficient logic gate operations. We report on the electrical characterization of domain walls in interconnected magnetic tunnel junctions. By means of spin-transfer torque effect, domains walls are produced at the common free layer and its propagation towards the output pillar sensed by tunneling magneto-resistance. Domain pinning conditions are studied quasi-statically showing a strong dependence on pillar size, ferromagnetic free layer width and inter-pillar distance. Addressing pinning conditions are detrimental for cascading and fan-out of domain walls across nodes, enabling the realization of domain-wall-based logic technology.

  4. Domain-wall guided nucleation of superconductivity in hybrid ferromagnet-superconductor-ferromagnet layered structures.

    PubMed

    Gillijns, W; Aladyshkin, A Yu; Lange, M; Van Bael, M J; Moshchalkov, V V

    2005-11-25

    Domain-wall superconductivity is studied in a superconducting Nb film placed between two ferromagnetic Co/Pd multilayers with perpendicular magnetization. The parameters of top and bottom ferromagnetic films are chosen to provide different coercive fields, so that the magnetic domain structure of the ferromagnets can be selectively controlled. From the dependence of the critical temperature Tc on the applied magnetic field H, we have found evidence for domain-wall superconductivity in this three-layered F/S/F structure for different magnetic domain patterns. The phase boundary, calculated numerically for this structure from the linearized Ginzburg-Landau equation, is in good agreement with the experimental data.

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

    PubMed

    Ghosal, Gargi; Yuan, Jingsong; Chen, Junjie

    2011-06-01

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

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

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

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

    2013-12-09

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

  7. The heterodimeric sweet taste receptor has multiple potential ligand binding sites.

    PubMed

    Cui, Meng; Jiang, Peihua; Maillet, Emeline; Max, Marianna; Margolskee, Robert F; Osman, Roman

    2006-01-01

    The sweet taste receptor is a heterodimer of two G protein coupled receptors, T1R2 and T1R3. This discovery has increased our understanding at the molecular level of the mechanisms underlying sweet taste. Previous experimental studies using sweet receptor chimeras and mutants show that there are at least three potential binding sites in this heterodimeric receptor. Receptor activity toward the artificial sweeteners aspartame and neotame depends on residues in the amino terminal domain of human T1R2. In contrast, receptor activity toward the sweetener cyclamate and the sweet taste inhibitor lactisole depends on residues within the transmembrane domain of human T1R3. Furthermore, receptor activity toward the sweet protein brazzein depends on the cysteine rich domain of human T1R3. Although crystal structures are not available for the sweet taste receptor, useful homology models can be developed based on appropriate templates. The amino terminal domain, cysteine rich domain and transmembrane helix domain of T1R2 and T1R3 have been modeled based on the crystal structures of metabotropic glutamate receptor type 1, tumor necrosis factor receptor, and bovine rhodopsin, respectively. We have used homology models of the sweet taste receptors, molecular docking of sweet ligands to the receptors, and site-directed mutagenesis of the receptors to identify potential ligand binding sites of the sweet taste receptor. These studies have led to a better understanding of the structure and function of this heterodimeric receptor, and can act as a guide for rational structure-based design of novel non-caloric sweeteners, which can be used in the fighting against obesity and diabetes.

  8. Extracellular Membrane-proximal Domain of HAb18G/CD147 Binds to Metal Ion-dependent Adhesion Site (MIDAS) Motif of Integrin β1 to Modulate Malignant Properties of Hepatoma Cells*

    PubMed Central

    Li, Yong; Wu, Jiao; Song, Fei; Tang, Juan; Wang, Shi-Jie; Yu, Xiao-Ling; Chen, Zhi-Nan; Jiang, Jian-Li

    2012-01-01

    Several lines of evidence suggest that HAb18G/CD147 interacts with the integrin variants α3β1 and α6β1. However, the mechanism of the interaction remains largely unknown. In this study, mammalian protein-protein interaction trap (MAPPIT), a mammalian two-hybrid method, was used to study the CD147-integrin β1 subunit interaction. CD147 in human hepatocellular carcinoma (HCC) cells was interfered with by small hairpin RNA. Nude mouse xenograft model and metastatic model of HCC were used to detect the role of CD147 in carcinogenesis and metastasis. We found that the extracellular membrane-proximal domain of HAb18G/CD147 (I-type domain) binds at the metal ion-dependent adhesion site in the βA domain of the integrin β1 subunit, and Asp179 in the I-type domain of HAb18G/CD147 plays an important role in the interaction. The levels of the proteins that act downstream of integrin, including focal adhesion kinase (FAK) and phospho-FAK, were decreased, and the cytoskeletal structures of HCC cells were rearranged bearing the HAb18G/CD147 deletion. Simultaneously, the migration and invasion capacities, secretion of matrix metalloproteinases, colony formation rate in vitro, and tumor growth and metastatic potential in vivo were decreased. These results indicate that the interaction of HAb18G/CD147 extracellular I-type domain with the integrin β1 metal ion-dependent adhesion site motif activates the downstream FAK signaling pathway, subsequently enhancing the malignant properties of HCC cells. PMID:22130661

  9. Food risks and consumer trust. Avian influenza and the knowing and non-knowing on UK shopping floors.

    PubMed

    de Krom, Michiel P M M; Mol, Arthur P J

    2010-12-01

    Irrespective of major food crises in the 2000s consumer trust in food seems to remain high in Western Europe. Transparent information provision to consumers on food risks is a central strategy of the EU, its Member States and private food providers to build food trust among consumers. But can the interpretation of such information by consumers explain high levels of trust in food safety? Following recent outbreaks of avian influenza in the UK, this paper investigates the constitution of food trust among UK poultry consumers by focusing on the place where consumer decisions are made: the shopping floor. In-store qualitative interviews with consumers of a variety of poultry products at different shops are used to reveal the use of information in constructing trust. Besides on knowledge inducted from information provision, trust depends as much on consumer strategies to handle non-knowing of food risks. Three main forms of trust relations are distinguished, which together at a system level result in high levels of consumer trust in food. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. Structural elucidation of transmembrane domain zero (TMD0) of EcdL: A multidrug resistance-associated protein (MRP) family of ATP-binding cassette transporter protein revealed by atomistic simulation.

    PubMed

    Bera, Krishnendu; Rani, Priyanka; Kishor, Gaurav; Agarwal, Shikha; Kumar, Antresh; Singh, Durg Vijay

    2017-09-20

    ATP-Binding cassette (ABC) transporters play an extensive role in the translocation of diverse sets of biologically important molecules across membrane. EchnocandinB (antifungal) and EcdL protein of Aspergillus rugulosus are encoded by the same cluster of genes. Co-expression of EcdL and echinocandinB reflects tightly linked biological functions. EcdL belongs to Multidrug Resistance associated Protein (MRP) subfamily of ABC transporters with an extra transmembrane domain zero (TMD0). Complete structure of MRP subfamily comprising of TMD0 domain, at atomic resolution is not known. We hypothesized that the transportation of echonocandinB is mediated via EcdL protein. Henceforth, it is pertinent to know the topological arrangement of TMD0, with other domains of protein and its possible role in transportation of echinocandinB. Absence of effective template for TMD0 domain lead us to model by I-TASSER, further structure has been refined by multiple template modelling using homologous templates of remaining domains (TMD1, NBD1, TMD2, NBD2). The modelled structure has been validated for packing, folding and stereochemical properties. MD simulation for 0.1 μs has been carried out in the biphasic environment for refinement of modelled protein. Non-redundant structures have been excavated by clustering of MD trajectory. The structural alignment of modelled structure has shown Z-score -37.9; 31.6, 31.5 with RMSD; 2.4, 4.2, 4.8 with ABC transporters; PDB ID 4F4C, 4M1 M, 4M2T, respectively, reflecting the correctness of structure. EchinocandinB has been docked to the modelled as well as to the clustered structures, which reveals interaction of echinocandinB with TMD0 and other TM helices in the translocation path build of TMDs.

  11. Cardiac tissue enriched factors serum response factor and GATA-4 are mutual coregulators

    NASA Technical Reports Server (NTRS)

    Belaguli, N. S.; Sepulveda, J. L.; Nigam, V.; Charron, F.; Nemer, M.; Schwartz, R. J.

    2000-01-01

    Combinatorial interaction among cardiac tissue-restricted enriched transcription factors may facilitate the expression of cardiac tissue-restricted genes. Here we show that the MADS box factor serum response factor (SRF) cooperates with the zinc finger protein GATA-4 to synergistically activate numerous myogenic and nonmyogenic serum response element (SRE)-dependent promoters in CV1 fibroblasts. In the absence of GATA binding sites, synergistic activation depends on binding of SRF to the proximal CArG box sequence in the cardiac and skeletal alpha-actin promoter. GATA-4's C-terminal activation domain is obligatory for synergistic coactivation with SRF, and its N-terminal domain and first zinc finger are inhibitory. SRF and GATA-4 physically associate both in vivo and in vitro through their MADS box and the second zinc finger domains as determined by protein A pullout assays and by in vivo one-hybrid transfection assays using Gal4 fusion proteins. Other cardiovascular tissue-restricted GATA factors, such as GATA-5 and GATA-6, were equivalent to GATA-4 in coactivating SRE-dependent targets. Thus, interaction between the MADS box and C4 zinc finger proteins, a novel regulatory paradigm, mediates activation of SRF-dependent gene expression.

  12. Methods and principles for determining task dependent interface content

    NASA Technical Reports Server (NTRS)

    Shalin, Valerie L.; Geddes, Norman D.; Mikesell, Brian G.

    1992-01-01

    Computer generated information displays provide a promising technology for offsetting the increasing complexity of the National Airspace System. To realize this promise, however, we must extend and adapt the domain-dependent knowledge that informally guides the design of traditional dedicated displays. In our view, the successful exploitation of computer generated displays revolves around the idea of information management, that is, the identification, organization, and presentation of relevant and timely information in a complex task environment. The program of research that is described leads to methods and principles for information management in the domain of commercial aviation. The multi-year objective of the proposed program of research is to develop methods and principles for determining task dependent interface content.

  13. Syntactic dependency parsers for biomedical-NLP.

    PubMed

    Cohen, Raphael; Elhadad, Michael

    2012-01-01

    Syntactic parsers have made a leap in accuracy and speed in recent years. The high order structural information provided by dependency parsers is useful for a variety of NLP applications. We present a biomedical model for the EasyFirst parser, a fast and accurate parser for creating Stanford Dependencies. We evaluate the models trained in the biomedical domains of EasyFirst and Clear-Parser in a number of task oriented metrics. Both parsers provide stat of the art speed and accuracy in the Genia of over 89%. We show that Clear-Parser excels at tasks relating to negation identification while EasyFirst excels at tasks relating to Named Entities and is more robust to changes in domain.

  14. Angular dependence of coercivity derived from alignment dependence of coercivity in Nd-Fe-B sintered magnets

    NASA Astrophysics Data System (ADS)

    Matsuura, Yutaka; Nakamura, Tetsuya; Sumitani, Kazushi; Kajiwara, Kentaro; Tamura, Ryuji; Osamura, Kozo

    2018-01-01

    Experimental results of the alignment dependence of the coercivity in Nd-Fe-B sintered magnets showed that the angle of magnetization reversal for anisotropically aligned magnets was bigger than that obtained from the theoretical results calculated using the postulation that every grain independently reverses its magnetization direction following the 1/cos θ law. The angles of reversed magnetization (θ1) for Nd13.48Co0.55B5.76Febal. with alignment α=0.95 and for Nd12.75Dy0.84B5.81Co0.55Febal. with α=0.96 were 30° and 36°, respectively, which were very similar to that of an ideal magnet with a Gaussian distribution (σ=31° and 44°, respectively) of the grain alignment. In this model, we postulated that every grain independently reversed according to the 1/cos θ law. The calculation results for the angular dependence of the coercivity using the values θ1=ω1(0°)=30°, σ=31° and θ1=ω1(0°)=36°, σ=44° could qualitatively and convincingly explain the observed angular dependence of the coercivity of Nd14.2B6.2Co1.0Febal. and Nd14.2Dy0.3B6.2Co1.0Febal.. It is speculated that the magnetic domain wall is pinned at grains tilted away from the easy magnetization direction, and when the magnetic domain wall de-pins from the tilted grains, the magnetic domain wall jumps through several grains. We suggest that the coercive force of the aligned magnet behaves like a low-aligned magnet owing to the magnetization reversal of the crust of the grains induced by the pinning and subsequent jumping of the magnetic domain wall.

  15. Domain requirements for the Dock adapter protein in growth- cone signaling

    PubMed Central

    Rao, Yong; Zipursky, S. Lawrence

    1998-01-01

    Tyrosine phosphorylation has been implicated in growth-cone guidance through genetic, biochemical, and pharmacological studies. Adapter proteins containing src homology 2 (SH2) domains and src homology 3 (SH3) domains provide a means of linking guidance signaling through phosphotyrosine to downstream effectors regulating growth-cone motility. The Drosophila adapter, Dreadlocks (Dock), the homolog of mammalian Nck containing three N-terminal SH3 domains and a single SH2 domain, is highly specialized for growth-cone guidance. In this paper, we demonstrate that Dock can couple signals in either an SH2-dependent or an SH2-independent fashion in photoreceptor (R cell) growth cones, and that Dock displays different domain requirements in different neurons. PMID:9482841

  16. 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.

  17. Creation of a Ligand-Dependent Enzyme by Fusing Circularly Permuted Antibody Variable Region Domains.

    PubMed

    Iwai, Hiroto; Kojima-Misaizu, Miki; Dong, Jinhua; Ueda, Hiroshi

    2016-04-20

    Allosteric control of enzyme activity with exogenous substances has been hard to achieve, especially using antibody domains that potentially allow control by any antigens of choice. Here, in order to attain this goal, we developed a novel antibody variable region format introduced with circular permutations, called Clampbody. The two variable-region domains of the antibone Gla protein (BGP) antibody were each circularly permutated to have novel termini at the loops near their domain interface. Through their attachment to the N- and C-termini of a circularly permutated TEM-1 β-lactamase (cpBLA), we created a molecular switch that responds to the antigen peptide. The fusion protein specifically recognized the antigen, and in the presence of some detergent or denaturant, its catalytic activity was enhanced up to 4.7-fold in an antigen-dependent manner, due to increased resistance to these reagents. Hence, Clampbody will be a powerful tool for the allosteric regulation of enzyme and other protein activities and especially useful to design robust biosensors.

  18. UBXD Proteins: A Family of Proteins with Diverse Functions in Cancer.

    PubMed

    Rezvani, Khosrow

    2016-10-14

    The UBXD family is a diverse group of UBX (ubiquitin-regulatory X) domain-containing proteins in mammalian cells. Members of this family contain a UBX domain typically located at the carboxyl-terminal of the protein. In contrast to the UBX domain shared by all members of UBXD family, the amino-terminal domains are diverse and appear to carry out different roles in a subcellular localization-dependent manner. UBXD proteins are principally associated with the endoplasmic reticulum (ER), where they positively or negatively regulate the ER-associated degradation machinery (ERAD). The distinct protein interaction networks of UBXD proteins allow them to have specific functions independent of the ERAD pathway in a cell type- and tissue context-dependent manner. Recent reports have illustrated that a number of mammalian members of the UBXD family play critical roles in several proliferation and apoptosis pathways dysregulated in selected types of cancer. This review covers recent advances that elucidate the therapeutic potential of selected members of the UBXD family that can contribute to tumor growth.

  19. Distinct roles for extracellular and intracellular domains in neuroligin function at inhibitory synapses.

    PubMed

    Nguyen, Quynh-Anh; Horn, Meryl E; Nicoll, Roger A

    2016-11-02

    Neuroligins (NLGNs) are postsynaptic cell adhesion molecules that interact trans-synaptically with neurexins to mediate synapse development and function. NLGN2 is only at inhibitory synapses while NLGN3 is at both excitatory and inhibitory synapses. We found that NLGN3 function at inhibitory synapses in rat CA1 depends on the presence of NLGN2 and identified a domain in the extracellular region that accounted for this functional difference between NLGN2 and 3 specifically at inhibitory synapses. We further show that the presence of a cytoplasmic tail (c-tail) is indispensible, and identified two domains in the c-tail that are necessary for NLGN function at inhibitory synapses. These domains point to a gephyrin-dependent mechanism that is disrupted by an autism-associated mutation at R705 and a gephyrin-independent mechanism reliant on a putative phosphorylation site at S714. Our work highlights unique and separate roles for the extracellular and intracellular regions in specifying and carrying out NLGN function respectively.

  20. 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

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