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Sample records for address increasingly complex

  1. Exploring the Utilization of Complex Algal Communities to Address Algal Pond Crash and Increase Annual Biomass Production for Algal Biofuels

    SciTech Connect

    Hamilton, Cyd E.

    2014-03-25

    This white paper briefly reviews the research literature exploring complex algal communities as a means of increasing algal biomass production via increased tolerance, resilience, and resistance to a variety of abiotic and biotic perturbations occurring within harvesting timescales. This paper identifies what data are available and whether more research utilizing complex communities is needed to explore the potential of complex algal community stability (CACS) approach as a plausible means to increase biomass yields regardless of ecological context and resulting in decreased algal-based fuel prices by reducing operations costs. By reviewing the literature for what we do and do not know, in terms of CACS methodologies, this report will provide guidance for future research addressing pond crash phenomena.

  2. Increasing hope by addressing clients' outcome expectations.

    PubMed

    Swift, Joshua K; Derthick, Annie O

    2013-09-01

    Addressing clients' outcome expectations is an important clinical process that can lead to a strong therapeutic alliance, more positive treatment outcomes, and decreased rates of premature termination from psychotherapy. Five interventions designed to foster appropriate outcome expectations are discussed, including presenting a convincing treatment rationale, increasing clients' faith in their therapists, expressing faith in clients, providing outcome education, and comparing progress with expectations. Clinical examples and research support are provided for each. PMID:24000836

  3. Addressing childhood obesity through increased physical activity.

    PubMed

    Hills, Andrew P; Okely, Anthony D; Baur, Louise A

    2010-10-01

    Obesity is affecting an increasing proportion of children globally. Despite an appreciation that physical activity is essential for the normal growth and development of children and prevents obesity and obesity-related health problems, too few children are physically active. A concurrent problem is that today's young people spend more time than previous generations did in sedentary pursuits, including watching television and engaging in screen-based games. Active behavior has been displaced by these inactive recreational choices, which has contributed to reductions in activity-related energy expenditure. Implementation of multifactorial solutions considered to offer the best chance of combating these trends is urgently required to redress the energy imbalance that characterizes obesity. The counterproductive 'shame and blame' mentality that apportions responsibility for the childhood obesity problem to sufferers, their parents, teachers or health-care providers needs to be changed. Instead, these groups should offer constant support and encouragement to promote appropriate physical activity in children. Failure to provide activity opportunities will increase the likelihood that the children of today will live less healthy (and possibly shorter) lives than their parents. PMID:20736922

  4. Addressing the Complexity of the Earth System

    SciTech Connect

    Nobre, Carlos; Brasseur, Guy P.; Shapiro, Melvyn; Lahsen, Myanna; Brunet, Gilbert; Busalacchi, Antonio; Hibbard, Kathleen A.; Seitzinger, Sybil; Noone, Kevin; Ometto, Jean P.

    2010-10-01

    This paper highlights the role of the Earth-system biosphere and illustrates the complex: biosphere-atmosphere interactions in the Amazon Basin, changes in nitrogen cycling, ocean chemistry, and land use. It introduces three important requirements for accelerating the development and use of Earth system information. The first requirement is to develop Earth system analysis and prediction models that account for multi-scale physical, chemical and biological processes, including their interactions in the coupled atmosphere-ocean-land-ice system. The development of these models requires partnerships between academia, national research centers, and operational prediction facilities, and builds upon accomplishments in weather and climate predictions. They will highlight the regional aspects of global change, and include modules for water system, agriculture, forestry, energy, air quality, health, etc. The second requirement is to model the interactions between humans and the weather-climate-biogeochemical system. The third requirement is to introduce novel methodologies to account for societal drivers, impacts and feedbacks. This is a challenging endeavor requiring creative solutions and some compromising because human behavior cannot be fully represented within the framework of present-day physical prediction systems.

  5. Interweaving Knowledge Resources to Address Complex Environmental Health Challenges

    PubMed Central

    Anderson, Beth Ellen; Suk, William A.

    2015-01-01

    Background Complex problems do not respect academic disciplinary boundaries. Environmental health research is complex and often moves beyond these boundaries, integrating diverse knowledge resources to solve such challenges. Here we describe an evolving paradigm for interweaving approaches that integrates widely diverse resources outside of traditional academic environments in full partnerships of mutual respect and understanding. We demonstrate that scientists, social scientists, and engineers can work with government agencies, industry, and communities to interweave their expertise into metaphorical knowledge fabrics to share understanding, resources, and enthusiasm. Objective Our goal is to acknowledge and validate how interweaving research approaches can contribute to research-driven, solution-oriented problem solving in environmental health, and to inspire more members of the environmental health community to consider this approach. Discussion The National Institutes of Health’s National Institute of Environmental Health Sciences Superfund Research Program (SRP), as mandated by Congress, has evolved to become a program that reaches across a wide range of knowledge resources. SRP fosters interweaving multiple knowledge resources to develop innovative multidirectional partnerships for research and training. Here we describe examples of how motivation, ideas, knowledge, and expertise from different people, institutions, and agencies can integrate to tackle challenges that can be as complex as the resources they bring to bear on it. Conclusions By providing structure for interweaving science with its stakeholders, we are better able to leverage resources, increase potential for innovation, and proactively ensure a more fully developed spectrum of beneficial outcomes of research investments. Citation Anderson BE, Naujokas MF, Suk WA. 2015. Interweaving knowledge resources to address complex environmental health challenges. Environ Health Perspect 123:1095–1099

  6. Nutritional metabolomics: Progress in addressing complexity in diet and health

    PubMed Central

    Jones, Dean P.; Park, Youngja; Ziegler, Thomas R.

    2013-01-01

    Nutritional metabolomics is rapidly maturing to use small molecule chemical profiling to support integration of diet and nutrition in complex biosystems research. These developments are critical to facilitate transition of nutritional sciences from population-based to individual-based criteria for nutritional research, assessment and management. This review addresses progress in making these approaches manageable for nutrition research. Important concept developments concerning the exposome, predictive health and complex pathobiology, serve to emphasize the central role of diet and nutrition in integrated biosystems models of health and disease. Improved analytic tools and databases for targeted and non-targeted metabolic profiling, along with bioinformatics, pathway mapping and computational modeling, are now used for nutrition research on diet, metabolism, microbiome and health associations. These new developments enable metabolome-wide association studies (MWAS) and provide a foundation for nutritional metabolomics, along with genomics, epigenomics and health phenotyping, to support integrated models required for personalized diet and nutrition forecasting. PMID:22540256

  7. Connectivity and complex systems in geomorphology: addressing some key challenges

    NASA Astrophysics Data System (ADS)

    Pöppl, Ronald; Turnbull-Lloyd, Laura; Parsons, Anthony; Bracken, Louise; Keesstra, Saskia; Masselink, Rens

    2016-04-01

    "Connectivity thinking" and related concepts have a long history in geomorphology. Since the beginning of the 21st century connectivity research experienced a huge boom in geomorphology as geomorphologists started to develop new concepts on connectivity to better understand the complexity of geomorphic systems and system response to change. However, progress in the field of connectivity in geomorphology has mostly been developing in a parallel manner, resulting in a multiplicity of definitions, concepts and methodological approaches. Nevertheless, a set of common key challenges amongst the different connectivity concepts and approaches used to understand complex geomorphic systems are also evident. In the course of a theory think tank of the COST Action ES1306 (CONNECTEUR - Connecting European Connectivity Research) the following five different key challenges were detected (Turnbull et al., in prep.): (i) defining the fundamental unit, (ii) distinguishing between structural and functional boundaries, (iii) emergent behavior, (iv) memory effects, (v) measuring connectivity. In this presentation we will a) discuss how these key challenges are addressed and approached in connectivity research in geomorphology, b) evaluate ways in which cross-disciplinary advances may be made by exploring potential for a common toolbox approach to the study of connectivity.

  8. Applied social and behavioral science to address complex health problems.

    PubMed

    Livingood, William C; Allegrante, John P; Airhihenbuwa, Collins O; Clark, Noreen M; Windsor, Richard C; Zimmerman, Marc A; Green, Lawrence W

    2011-11-01

    Complex and dynamic societal factors continue to challenge the capacity of the social and behavioral sciences in preventive medicine and public health to overcome the most seemingly intractable health problems. This paper proposes a fundamental shift from a research approach that presumes to identify (from highly controlled trials) universally applicable interventions expected to be implemented "with fidelity" by practitioners, to an applied social and behavioral science approach similar to that of engineering. Such a shift would build on and complement the recent recommendations of the NIH Office of Behavioral and Social Science Research and require reformulation of the research-practice dichotomy. It would also require disciplines now engaged in preventive medicine and public health practice to develop a better understanding of systems thinking and the science of application that is sensitive to the complexity, interactivity, and unique elements of community and practice settings. Also needed is a modification of health-related education to ensure that those entering the disciplines develop instincts and capacities as applied scientists. PMID:22011425

  9. Increased textural complexity in food enhances satiation.

    PubMed

    Larsen, Danaé S; Tang, Jingyuan; Ferguson, Lynnette R; James, Bryony J

    2016-10-01

    For the first time this study has shown a direct effect of food textural complexity on satiation. Independent of oral processing time, increasing the textural complexity of a food significantly decreased food intake. Foods with complex textures stimulate many sensory perceptions during oral processing, with a succession of textures perceived between first bite and swallow. Previously the impact of texture on satiation (commonly tested by increasing viscosities of semi-solids) has been explained by texture's influence on oral processing time; a long oral processing time enhances satiation. The results of the current study show that subjects in a randomised cross-over trial who consumed a "starter" (preload) model food with high textural complexity went on to eat significantly less of a two course ad libitum meal. Subjects who consumed a "starter" model food with low textural complexity, but with the same flavour, energy density and oral processing time, ate significantly more of the same ad libitum meal. The results show that increasing the number of textures perceived during chewing of a solid food triggers the satiation response earlier than when chewing a less texturally complex food. Increasing textural complexity of manufactured foods, to allow for greater sensory stimulation per bite, could potentially be used as a tool to enhance the satiation response and decrease food intake. PMID:27235823

  10. Does increased hydrochemical model complexity decrease robustness?

    NASA Astrophysics Data System (ADS)

    Medici, C.; Wade, A. J.; Francés, F.

    2012-05-01

    SummaryThe aim of this study was, within a sensitivity analysis framework, to determine if additional model complexity gives a better capability to model the hydrology and nitrogen dynamics of a small Mediterranean forested catchment or if the additional parameters cause over-fitting. Three nitrogen-models of varying hydrological complexity were considered. For each model, general sensitivity analysis (GSA) and Generalized Likelihood Uncertainty Estimation (GLUE) were applied, each based on 100,000 Monte Carlo simulations. The results highlighted the most complex structure as the most appropriate, providing the best representation of the non-linear patterns observed in the flow and streamwater nitrate concentrations between 1999 and 2002. Its 5% and 95% GLUE bounds, obtained considering a multi-objective approach, provide the narrowest band for streamwater nitrogen, which suggests increased model robustness, though all models exhibit periods of inconsistent good and poor fits between simulated outcomes and observed data. The results confirm the importance of the riparian zone in controlling the short-term (daily) streamwater nitrogen dynamics in this catchment but not the overall flux of nitrogen from the catchment. It was also shown that as the complexity of a hydrological model increases over-parameterisation occurs, but the converse is true for a water quality model where additional process representation leads to additional acceptable model simulations. Water quality data help constrain the hydrological representation in process-based models. Increased complexity was justifiable for modelling river-system hydrochemistry. Increased complexity was justifiable for modelling river-system hydrochemistry.

  11. Developing integrated methods to address complex resource and environmental issues

    USGS Publications Warehouse

    2016-01-01

    IntroductionThis circular provides an overview of selected activities that were conducted within the U.S. Geological Survey (USGS) Integrated Methods Development Project, an interdisciplinary project designed to develop new tools and conduct innovative research requiring integration of geologic, geophysical, geochemical, and remote-sensing expertise. The project was supported by the USGS Mineral Resources Program, and its products and acquired capabilities have broad applications to missions throughout the USGS and beyond.In addressing challenges associated with understanding the location, quantity, and quality of mineral resources, and in investigating the potential environmental consequences of resource development, a number of field and laboratory capabilities and interpretative methodologies evolved from the project that have applications to traditional resource studies as well as to studies related to ecosystem health, human health, disaster and hazard assessment, and planetary science. New or improved tools and research findings developed within the project have been applied to other projects and activities. Specifically, geophysical equipment and techniques have been applied to a variety of traditional and nontraditional mineral- and energy-resource studies, military applications, environmental investigations, and applied research activities that involve climate change, mapping techniques, and monitoring capabilities. Diverse applied geochemistry activities provide a process-level understanding of the mobility, chemical speciation, and bioavailability of elements, particularly metals and metalloids, in a variety of environmental settings. Imaging spectroscopy capabilities maintained and developed within the project have been applied to traditional resource studies as well as to studies related to ecosystem health, human health, disaster assessment, and planetary science. Brief descriptions of capabilities and laboratory facilities and summaries of some

  12. The increasing complexity of the ubiquitin code.

    PubMed

    Yau, Richard; Rape, Michael

    2016-05-27

    Ubiquitylation is essential for signal transduction as well as cell division and differentiation in all eukaryotes. Substrate modifications range from a single ubiquitin molecule to complex polymeric chains, with different types of ubiquitylation often eliciting distinct outcomes. The recent identification of novel chain topologies has improved our understanding of how ubiquitylation establishes precise communication within cells. Here, we discuss how the increasing complexity of ubiquitylation is employed to ensure robust and faithful signal transduction in eukaryotic cells. PMID:27230526

  13. Addressing the Needs of Adolescents with Autism Spectrum Disorder: Considerations and Complexities for High School Interventions

    ERIC Educational Resources Information Center

    Kucharczyk, Suzanne; Reutebuch, Colleen K.; Carter, Erik W.; Hedges, Susan; El Zein, Farah; Fan, Hannah; Gustafson, Jenny R.

    2015-01-01

    The outcomes of students with autism spectrum disorder (ASD) are driving the field to address how secondary education might be optimally designed and delivered. We conducted 28 focus groups across four states to explore the contexts, considerations, and complexities associated with delivering and combining evidence-based interventions to meet the…

  14. Race and Science: Using a Comprehensive Interdisciplinary Approach To Address Complex Issues.

    ERIC Educational Resources Information Center

    Eisen, Arri; Cimino, Ashley; Aparicio, Hugo; Marsteller, Patricia; Kushner, Howard

    2003-01-01

    Describes an interdisciplinary approach that integrates the strengths of a research and teaching institution to address issues in a complex problem: the study of race, science, and health. The model involved a feedback loop among two undergraduate courses and a weekly seminar. (SLD)

  15. On Using Meta-Modeling and Multi-Modeling to Address Complex Problems

    ERIC Educational Resources Information Center

    Abu Jbara, Ahmed

    2013-01-01

    Models, created using different modeling techniques, usually serve different purposes and provide unique insights. While each modeling technique might be capable of answering specific questions, complex problems require multiple models interoperating to complement/supplement each other; we call this Multi-Modeling. To address the syntactic and…

  16. Addressing the Increasing Burden of Sexually Transmitted Infections in Rhode Island

    PubMed Central

    Chan, Philip A.; Maher, Justine; Poole, Danielle; Alexander-Scott, Nicole; Ducharme, R. Bobby; Yates, Gail; Benben, Stacey; Nunn, Amy; Comella, Jaime; Bandy, Utpala; Montague, Brian T.; Kojic, Erna; Chapin, Kimberle; Flanigan, Timothy P.

    2016-01-01

    The rates of sexually transmitted infections (STI) including chlamydia, gonorrhea, and syphilis, are increasing across the United States, including in Rhode Island (RI). These STIs affect many otherwise healthy adolescents and young adults, and represent a significant source of morbidity. The Centers for Disease Control and Prevention encourages states to develop strategies for addressing increasing STI rates in the setting of diminishing public health resources. The RI Department of Health (DOH) works with providers and funded community-based organizations to promote STI screening, expedited partner therapy, and partner services to reduce STI rates. The Miriam Hospital Immunology Center opened a public HIV/STI Clinic, which offers free and confidential testing for HIV, viral hepatitis, chlamydia, gonorrhea, and syphilis, as well as post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP) services to prevent HIV. In collaboration with the RI DOH, the Clinic serves as a referral source across the state for complicated STI cases. PMID:25562058

  17. Safety nets can help address the risks to nutrition from increasing climate variability.

    PubMed

    Alderman, Harold

    2010-01-01

    Models of climate change predict increased variability of weather as well as changes in agro-ecology. The increased variability will pose special challenges for nutrition. This study reviews evidence on climate shocks and nutrition and estimates the economic consequences in terms of reduced schooling and economic productivity stemming from nutritional insults in childhood. Panel data covering up to 20 y indicate that that short-term climate shocks have long-term impacts on children that persist, often into their adult lives. Other studies document the potential for relief programs to offset these shocks providing that the programs can be implemented with flexible financing, rapid identification of those affected by the shock, and timely scale-up. The last of these presumes that programs are already in place with contingency plans drawn up. Arguably, direct food distribution, including that of ready-to-use therapeutic food, may be part of the overall strategy. Even if such programs are too expensive for sustainable widespread use in the prevention of malnutrition, scalable food distribution programs may be cost effective to address the heightened risk of malnutrition following weather-related shocks. PMID:19923387

  18. Addressing health concerns of pregnant African American women using the lens of complexity theory.

    PubMed

    Sims, Traci

    2014-01-01

    Pregnant African American women are at higher risk for multiple complex health issues, including depression, than their European American counterparts (Canady, Bullen, Holzman, Broman, & Tian, 2008; Martin et al, 2011; Mathews & MacDorman, 2007; Orr, Blazer, & James, 2006; Segre, Losch, & O'Hara, 2006). Various strategies must be used to address depression through preventive care and promotion of access to appropriate mental health services. Nurses and other health care providers need to examine the relationships between the multifactorial problems to improve the health and well-being of pregnant African American women and their unborn children. This article presents a case study demonstrating the use of complexity science theory to understand and prevent poor health outcomes for pregnant African American women with depression and their unborn children. PMID:26050422

  19. Megacities and Large Urban Complexes - WMO Role in Addressing Challenges and Opportunities

    NASA Astrophysics Data System (ADS)

    Terblanche, Deon; Jalkanen, Liisa

    2013-04-01

    Megacities and Large Urban Complexes - WMO Role in Addressing Challenges and Opportunities Deon E. Terblanche and Liisa Jalkanen dterblanche@wmo.int ljalkanen@wmo.int World Meteorological Organization, Geneva, Switzerland The 21st Century could amongst others, become known as the century in which our species has evolved from Homo sapiens to Homo urbanus. By now the urban population has surpassed the rural population and the rate of urbanization will continue at such a pace that by 2050 urban dwellers could outnumber their rural counterpart by more than two to one. Most of this growth in urban population will occur in developing countries and along coastal areas. Urbanization is to a large extent the outcome of humans seeking a better life through improved opportunities presented by high-density communities. Megacities and large urban complexes provide more job opportunities and social structures, better transport and communication links and a relative abundance of physical goods and services when compared to most rural areas. Unfortunately these urban complexes also present numerous social and environmental challenges. Urban areas differ from their surroundings by morphology, population density, and with high concentration of industrial activities, energy consumption and transport. They also pose unique challenges to atmospheric modelling and monitoring and create a multi-disciplinary spectrum of potential threats, including air pollution, which need to be addressed in an integrated way. These areas are also vulnerable to the changing climate and its implications to sea-level and extreme events, air quality and related health impacts. Many urban activities are significantly impacted by weather events that would not be considered to be of high impact in less densely populated areas. For instance, moderate precipitation events can cause flooding and landslides as modified urban catchments generally have higher run-off to rainfall ratios than their more pristine rural

  20. Large system change challenges: addressing complex critical issues in linked physical and social domains

    NASA Astrophysics Data System (ADS)

    Waddell, Steve; Cornell, Sarah; Hsueh, Joe; Ozer, Ceren; McLachlan, Milla; Birney, Anna

    2015-04-01

    Most action to address contemporary complex challenges, including the urgent issues of global sustainability, occurs piecemeal and without meaningful guidance from leading complex change knowledge and methods. The potential benefit of using such knowledge is greater efficacy of effort and investment. However, this knowledge and its associated tools and methods are under-utilized because understanding about them is low, fragmented between diverse knowledge traditions, and often requires shifts in mindsets and skills from expert-led to participant-based action. We have been engaged in diverse action-oriented research efforts in Large System Change for sustainability. For us, "large" systems can be characterized as large-scale systems - up to global - with many components, of many kinds (physical, biological, institutional, cultural/conceptual), operating at multiple levels, driven by multiple forces, and presenting major challenges for people involved. We see change of such systems as complex challenges, in contrast with simple or complicated problems, or chaotic situations. In other words, issues and sub-systems have unclear boundaries, interact with each other, and are often contradictory; dynamics are non-linear; issues are not "controllable", and "solutions" are "emergent" and often paradoxical. Since choices are opportunity-, power- and value-driven, these social, institutional and cultural factors need to be made explicit in any actionable theory of change. Our emerging network is sharing and building a knowledge base of experience, heuristics, and theories of change from multiple disciplines and practice domains. We will present our views on focal issues for the development of the field of large system change, which include processes of goal-setting and alignment; leverage of systemic transitions and transformation; and the role of choice in influencing critical change processes, when only some sub-systems or levels of the system behave in purposeful ways

  1. Increased temporolimbic cortical folding complexity in temporal lobe epilepsy

    PubMed Central

    Voets, N.L.; Bernhardt, B.C.; Kim, H.; Yoon, U.

    2011-01-01

    Objective: Converging evidence suggests that abnormalities of brain development may play a role in the pathogenesis of temporal lobe epilepsy (TLE). As sulco-gyral patterns are thought to be a footprint of cortical development, we set out to quantitatively map folding complexity across the neocortex in TLE. Additionally, we tested whether there was a relationship between cortical complexity and features of hippocampal maldevelopment, commonly referred to as malrotation. Methods: To quantify folding complexity, we obtained whole-brain surface-based measures of absolute mean cortical curvature from MRI scans acquired in 43 drug-resistant patients with TLE with unilateral hippocampal atrophy, and 40 age- and sex-matched healthy controls. In patients, we correlated changes in cortical curvature with 3-dimensional measures of hippocampal positioning. Results: We found increased folding complexity in the temporolimbic cortices encompassing parahippocampal, temporopolar, insular, and fronto-opercular regions. Increased complexity was observed ipsilateral to the seizure focus in patients with left TLE (LTLE), whereas these changes were bilateral in patients with right TLE (RTLE). In both TLE groups, increased temporolimbic complexity was associated with increased hippocampal malrotation. We found tendencies for increased complexity in bilateral posterior temporal cortices in LTLE and contralateral parahippocampal cortices in RTLE to be predictive of unfavorable seizure outcome after surgery. Conclusion: The anatomic distribution of increased cortical complexity overlapping with limbic seizure networks in TLE and its association with hippocampal maldevelopment further imply that neurodevelopmental factors may play a role in the epileptogenic process of TLE. PMID:21148116

  2. Complexity Increases Predictability in Allometrically Constrained Food Webs.

    PubMed

    Iles, Alison C; Novak, Mark

    2016-07-01

    All ecosystems are subjected to chronic disturbances, such as harvest, pollution, and climate change. The capacity to forecast how species respond to such press perturbations is limited by our imprecise knowledge of pairwise species interaction strengths and the many direct and indirect pathways along which perturbations can propagate between species. Network complexity (size and connectance) has thereby been seen to limit the predictability of ecological systems. Here we demonstrate a counteracting mechanism in which the influence of indirect effects declines with increasing network complexity when species interactions are governed by universal allometric constraints. With these constraints, network size and connectance interact to produce a skewed distribution of interaction strengths whose skew becomes more pronounced with increasing complexity. Together, the increased prevalence of weak interactions and the increased relative strength and rarity of strong interactions in complex networks limit disturbance propagation and preserve the qualitative predictability of net effects even when pairwise interaction strengths exhibit substantial variation or uncertainty. PMID:27322124

  3. Addressing antimicrobial resistance in China: policy implementation in a complex context.

    PubMed

    Wang, Li; Zhang, Xiulan; Liang, Xiaoyun; Bloom, Gerald

    2016-01-01

    The effectiveness of antibiotics in treating bacterial infections is decreasing in China because of the widespread development of resistant organisms. Although China has enacted a number of regulations to address this problem, but the impact is very limited. This paper investigates the implementation of these regulations through the lens of complex adaptive systems (CAS). It presents the findings from reviews of relevant policy documents and published papers. The paper identifies different types of agent and explores their interaction with regard to the use of antibiotics and their responses to changes of the regulations. It focuses particularly on the impact of perverse financial incentives on overall patterns of use of antibiotics. Implications for the possibilities of nonlinear results, interactive relationships, and new pathways of policy implementation are discussed. The paper concludes that policy-makers need to better understand the objectives, incentives and potential adaptive behaviors of the agents when they implement interventions to improve antibiotic use and reduce the risk of emergence of resistant organisms. PMID:27267876

  4. Activities for Challenging Gifted Learners by Increasing Complexity in the Common Core

    ERIC Educational Resources Information Center

    McKeone, Alyssa; Caruso, Lenora; Bettle, Kailyn; Chase, Ashley; Bryson, Bridget; Schneider, Jean S.; Rule, Audrey C.

    2015-01-01

    Gifted learners need opportunities for critical and creative thinking to stretch their minds and imaginations. Strategies for increasing complexity in the four core areas of language arts, mathematics, science, and social studies were addressed using the Common Core and Iowa Core Standards through several methods. Descriptive adjective object…

  5. Increasing Accessibility: Using Universal Design Principles to Address Disability Impairments in the Online Learning Environment

    ERIC Educational Resources Information Center

    Pittman, Candice N.; Heiselt, April K.

    2014-01-01

    With the increasing number of students enrolling in distance education, there is a need to consider the accessibility of course materials in online learning environments. Four major groups of disabilities: mobility, auditory, visual, and cognitive are explored as they relate to their implementation into instructional design and their impact on…

  6. Monitoring hypoxia: approaches to addressing a complex phenomenon in the Black Sea

    NASA Astrophysics Data System (ADS)

    Friedrich, Jana; Janssen, Felix; He, Yunchang; Holtappels, Moritz; Konovalov, Sergey; Prien, Ralf; Rehder, Gregor; Stanev, Emil

    2014-05-01

    , and proved highly suitable to resolve oxygen intrusions into highly stratified systems and hence, to identify and localize processes in complex redoxclines. We also present an example of novel technology applied in the Baltic Sea, which would be highly suitable for the Black Sea. The time series recordings of the profiling instrumentation platform GODESS in the Gotland Basin allowed a thorough characterization of oscillating redoxclines as temporally dynamic, three-dimensional systems. Stand-alone static moorings equipped with optical oxygen sensors, current meters, and turbidity sensors allowed to resolve fast oxygen fluctuations at the sediment-water interface due to, e.g., internal waves and Ekman pumping on the Crimean shelf and identified the formation of seasonal (summer) hypoxia as an highly dynamic process on the north-western Black Sea shelf. This comprehensive study within the EU-FP7 project HYPOX ("In situ monitoring of oxygen depletion in hypoxic ecosystems of coastal and open seas, and land-locked water bodies", www.hypox.net) was able to address many aspects of hypoxia, e.g., in the Black Sea, and revealed the vital need for dedicated oxygen monitoring programs to adequately address the risk of hypoxia formation and ecosystem response. The challenge in any kind of monitoring is to choose the appropriate approach and technology that is suited to resolve the temporal and spatial scales on which the phenomenon occurs.

  7. Fort Collins Science Center Ecosystem Dynamics branch--interdisciplinary research for addressing complex natural resource issues across landscapes and time

    USGS Publications Warehouse

    Bowen, Zachary H.; Melcher, Cynthia P.; Wilson, Juliette T.

    2013-01-01

    The Ecosystem Dynamics Branch of the Fort Collins Science Center offers an interdisciplinary team of talented and creative scientists with expertise in biology, botany, ecology, geology, biogeochemistry, physical sciences, geographic information systems, and remote-sensing, for tackling complex questions about natural resources. As demand for natural resources increases, the issues facing natural resource managers, planners, policy makers, industry, and private landowners are increasing in spatial and temporal scope, often involving entire regions, multiple jurisdictions, and long timeframes. Needs for addressing these issues include (1) a better understanding of biotic and abiotic ecosystem components and their complex interactions; (2) the ability to easily monitor, assess, and visualize the spatially complex movements of animals, plants, water, and elements across highly variable landscapes; and (3) the techniques for accurately predicting both immediate and long-term responses of system components to natural and human-caused change. The overall objectives of our research are to provide the knowledge, tools, and techniques needed by the U.S. Department of the Interior, state agencies, and other stakeholders in their endeavors to meet the demand for natural resources while conserving biodiversity and ecosystem services. Ecosystem Dynamics scientists use field and laboratory research, data assimilation, and ecological modeling to understand ecosystem patterns, trends, and mechanistic processes. This information is used to predict the outcomes of changes imposed on species, habitats, landscapes, and climate across spatiotemporal scales. The products we develop include conceptual models to illustrate system structure and processes; regional baseline and integrated assessments; predictive spatial and mathematical models; literature syntheses; and frameworks or protocols for improved ecosystem monitoring, adaptive management, and program evaluation. The descriptions

  8. Recent seismicity detection increase in the Santorini volcanic island complex

    NASA Astrophysics Data System (ADS)

    Chouliaras, G.; Drakatos, G.; Makropoulos, K.; Melis, N. S.

    2012-04-01

    Santorini is the most active volcanic complex in the South Aegean Volcanic Arc. To improve the seismological network detectability of the seismicity in this region, the Institute of Geodynamics of the National Observatory of Athens (NOA) recently installed 4 portable seismological stations supplementary to the 3 permanent stations operating in the region. The addition of these stations has significantly improved the detectability and reporting of the local seismic activity in the NOA instrumental seismicity catalogue. In this study we analyze quantitatively the seismicity of the Santorini volcanic complex. The results indicate a recent significant reporting increase mainly for events of small magnitude and an increase in the seismicity rate by more than 100%. The mapping of the statistical significance of the rate change with the z-value method reveals that the rate increase exists primarily in the active fault zone perpendicular to the extensional tectonic stress regime that characterizes this region. The spatial distribution of the b-value around the volcanic complex indicates a low b-value distribution parallel to the extensional stress field, while the b-value cross section of the volcanic complex indicates relatively high b-values under the caldera and a significant b-value decrease with depth. These results are found to be in general agreement with the results from other volcanic regions and they encourage further investigations concerning the seismic and volcanic hazard and risk estimates for the Santorini volcanic complex using the NOA earthquake catalogue.

  9. Increasing task complexity and ice hockey skills of youth athletes.

    PubMed

    Fait, Philippe E; McFadyen, Bradford J; Zabjek, Karl; Reed, Nick; Taha, Tim; Keightley, Michelle

    2011-02-01

    The objective of this pilot study was to investigate the effects on cognitive performance of progressively adding tasks specific to ice hockey (skating, stick handling, and obstacle avoidance) during a visual interference task (Stroop Color Word Test-interference condition). In addition, the effects on locomotor performance of progressively adding tasks of stickhandling, visual interference, and obstacle avoidance related to maximal skating speed and minimal obstacle clearance were investigated in eight male athletes ages 10 to 12 years. Results revealed decreased performance on both cognitive and physical measures with increased task complexity, suggesting that adding complexity to an environment influences hockey skill performance. PMID:21466078

  10. Teaching Water: Connecting across Disciplines and into Daily Life to Address Complex Societal Issues

    ERIC Educational Resources Information Center

    Eisen, Arri; Hall, Anne; Lee, Tong Soon; Zupko, Jack

    2009-01-01

    A central problem in higher education is how to best develop in students interdisciplinary thinking and application skills necessary to work and engage effectively in the twenty-first century. Traditional university structures make addressing this problem especially challenging. Using as a model courses with diverse perspectives on water taught by…

  11. Increased ventilatory variability and complexity in patients with hyperventilation disorder.

    PubMed

    Bokov, Plamen; Fiamma, Marie-Noëlle; Chevalier-Bidaud, Brigitte; Chenivesse, Cécile; Straus, Christian; Similowski, Thomas; Delclaux, Christophe

    2016-05-15

    It has been hypothesized that hyperventilation disorders could be characterized by an abnormal ventilatory control leading to enhanced variability of resting ventilation. The variability of tidal volume (VT) often depicts a nonnormal distribution that can be described by the negative slope characterizing augmented breaths formed by the relationship between the probability density distribution of VT and VT on a log-log scale. The objectives of this study were to describe the variability of resting ventilation [coefficient of variation (CV) of VT and slope], the stability in respiratory control (loop, controller and plant gains characterizing ventilatory-chemoresponsiveness interactions) and the chaotic-like dynamics (embedding dimension, Kappa values characterizing complexity) of resting ventilation in patients with a well-defined dysfunctional breathing pattern characterized by air hunger and constantly decreased PaCO2 during a cardiopulmonary exercise test. Compared with 14 healthy subjects with similar anthropometrics, 23 patients with hyperventilation were characterized by increased variability of resting tidal ventilation (CV of VT median [interquartile]: 26% [19-35] vs. 36% [28-48], P = 0.020; slope: -6.63 [-7.65; -5.36] vs. -3.88 [-5.91; -2.66], P = 0.004) that was not related to increased chemical drive (loop gain: 0.051 [0.039-0.221] vs. 0.044 [0.012-0.087], P = 0.149) but that was related to an increased ventilatory complexity (Kappa values, P < 0.05). Plant gain was decreased in patients and correlated with complexity (with Kappa 5 - degree 5: Rho = -0.48, P = 0.006). In conclusion, well-defined patients suffering from hyperventilation disorder are characterized by increased variability of their resting ventilation due to increased ventilatory complexity with stable ventilatory-chemoresponsiveness interactions. PMID:26869707

  12. Morphine Increases Acetylcholine Release in the Trigeminal Nuclear Complex

    PubMed Central

    Zhu, Zhenghong; Bowman, Heather R.; Baghdoyan, Helen A.; Lydic, Ralph

    2008-01-01

    Study Objectives: The trigeminal nuclear complex (V) contains cholinergic neurons and includes the principal sensory trigeminal nucleus (PSTN) which receives sensory input from the face and jaw, and the trigeminal motor nucleus (MoV) which innervates the muscles of mastication. Pain associated with pathologies of V is often managed with opioids but no studies have characterized the effect of opioids on acetylcholine (ACh) release in PSTN and MoV. Opioids can increase or decrease ACh release in brainstem nuclei. Therefore, the present experiments tested the 2-tailed hypothesis that microdialysis delivery of opioids to the PSTN and MoV significantly alters ACh release. Design: Using a within-subjects design and isoflurane-anesthetized Wistar rats (n = 53), ACh release in PSTN during microdialysis with Ringer's solution (control) was compared to ACh release during dialysis delivery of the sodium channel blocker tetrodotoxin, muscarinic agonist bethanechol, opioid agonist morphine, mu opioid agonist DAMGO, antagonists for mu (naloxone) and kappa (nor-binaltorphimine; nor-BNI) opioid receptors, and GABAA antagonist bicuculline. Measurements and Results: Tetrodotoxin decreased ACh, confirming action potential-dependent ACh release. Bethanechol and morphine caused a concentration-dependent increase in PSTN ACh release. The morphine-induced increase in ACh release was blocked by nor-BNI but not by naloxone. Bicuculline delivered to the PSTN also increased ACh release. ACh release in the MoV was increased by morphine, and this increase was not blocked by naloxone or nor-BNI. Conclusions: These data comprise the first direct measures of ACh release in PSTN and MoV and suggest synaptic disinhibition as one possible mechanism by which morphine increases ACh release in the trigeminal nuclei. Citation: Zhu Z; Bowman HR; Baghdoyan HA; Lydic R. Morphine increases acetylcholine release in the trigeminal nuclear complex. SLEEP 2008;31(12):1629–1637. PMID:19090318

  13. Using fuzzy operators to address the complexity in decision making of water resources redistribution in two neighboring river basins

    NASA Astrophysics Data System (ADS)

    Chen, Ho-Wen; Chang, Ni-Bin

    2010-06-01

    This paper emphasizes the use of fuzzy sets for incorporating objective and subjective uncertainties to address coevolutionary alignment of a suite of water resources redistribution alternatives in a transboundary channel-reservoir system. The highlighted decision making complexity arises from the interactions between two neighboring water systems (i.e., the Tseng-Wen and Kao-Ping River Basins, South Taiwan) where a pending diversion plan has been under intensive debate for over a decade. While the local stakeholders make uncertain science linked with uncertain politics resulting in endless delay of the diversion plan, the environmental advocacy groups stress the increasing concern of loss of biological integrity due to changes of land use when sharing water resources across the boundary. Consequently, there is a need to generate a novel integration that enables us to consider a vast number of internal weirs, water intakes, reservoirs, drainage ditches, and transfer pipelines within the basin and bring out the connectivity via diversion between these two neighboring river basins under uncertainty. To explore the managerial implications with varying risk perception and risk attitude, four types of fuzzy operators tailored for the fuzzy multi-objective decision analysis depict greater flexibility in representing the complexity of possible trade-offs among those alternatives. These trade-offs in the multi-objective evaluation context are constrained by physical, chemical, socioeconomic, managerial, and technical factors reflecting the needs for adaptive water resources management. Findings indicates that the use of fuzzy operators is instructive, which could provide unique guidance for enlightening the potential barriers in sustainable water resources management at the regional scale.

  14. Addressing the Complexities of Literacy and Urban Teaching in the USA: Strategic Professional Development as Intervention

    ERIC Educational Resources Information Center

    Sulentic Dowell, Margaret-Mary

    2012-01-01

    Teaching quality impacts classroom instruction. Teaching is difficult, demanding and draining work; teaching in urban environs exacerbates the difficulties, the demands and the complexities of teaching. Through the eyes of an assistant superintendent, charged with implementing a new vision for literacy teaching and learning, this manuscript…

  15. Ecosystem services and cooperative fisheries research to address a complex fishery problem

    EPA Science Inventory

    The St. Louis River represents a complex fishery management problem. Current fishery management goals have to be developed taking into account bi-state commercial, subsistence and recreational fisheries which are valued for different characteristics by a wide range of anglers, as...

  16. When Time Makes a Difference: Addressing Ergodicity and Complexity in Education

    ERIC Educational Resources Information Center

    Koopmans, Matthijs

    2015-01-01

    The detection of complexity in behavioral outcomes often requires an estimation of their variability over a prolonged time spectrum to assess processes of stability and transformation. Conventional scholarship typically relies on time-independent measures, "snapshots", to analyze those outcomes, assuming that group means and their…

  17. Intervention Fidelity for a Complex Behaviour Change Intervention in Community Pharmacy Addressing Cardiovascular Disease Risk

    ERIC Educational Resources Information Center

    McNamara, K. P.; O'Reilly, S. L.; George, J.; Peterson, G. M.; Jackson, S. L.; Duncan, G.; Howarth, H.; Dunbar, J. A.

    2015-01-01

    Background: Delivery of cardiovascular disease (CVD) prevention programs by community pharmacists appears effective and enhances health service access. However, their capacity to implement complex behavioural change processes during patient counselling remains largely unexplored. This study aims to determine intervention fidelity by pharmacists…

  18. The Advantages of Structural Equation Modeling to Address the Complexity of Spatial Reference Learning

    PubMed Central

    Moreira, Pedro S.; Sotiropoulos, Ioannis; Silva, Joana; Takashima, Akihiko; Sousa, Nuno; Leite-Almeida, Hugo; Costa, Patrício S.

    2016-01-01

    Background: Cognitive performance is a complex process influenced by multiple factors. Cognitive assessment in experimental animals is often based on longitudinal datasets analyzed using uni- and multi-variate analyses, that do not account for the temporal dimension of cognitive performance and also do not adequately quantify the relative contribution of individual factors onto the overall behavioral outcome. To circumvent these limitations, we applied an Autoregressive Latent Trajectory (ALT) to analyze the Morris water maze (MWM) test in a complex experimental design involving four factors: stress, age, sex, and genotype. Outcomes were compared with a traditional Mixed-Design Factorial ANOVA (MDF ANOVA). Results: In both the MDF ANOVA and ALT models, sex, and stress had a significant effect on learning throughout the 9 days. However, on the ALT approach, the effects of sex were restricted to the learning growth. Unlike the MDF ANOVA, the ALT model revealed the influence of single factors at each specific learning stage and quantified the cross interactions among them. In addition, ALT allows us to consider the influence of baseline performance, a critical and unsolved problem that frequently yields inaccurate interpretations in the classical ANOVA model. Discussion: Our findings suggest the beneficial use of ALT models in the analysis of complex longitudinal datasets offering a better biological interpretation of the interrelationship of the factors that may influence cognitive performance. PMID:26955327

  19. Increased complexity of gene structure and base composition in vertebrates.

    PubMed

    Wu, Ying; Yuan, Huizhong; Tan, Shengjun; Chen, Jian-Qun; Tian, Dacheng; Yang, Haiwang

    2011-07-20

    How the structure and base composition of genes changed with the evolution of vertebrates remains a puzzling question. Here we analyzed 895 orthologous protein-coding genes in six multicellular animals: human, chicken, zebrafish, sea squirt, fruit fly, and worm. Our analyses reveal that many gene regions, particularly intron and 3' UTR, gradually expanded throughout the evolution of vertebrates from their invertebrate ancestors, and that the number of exons per gene increased. Studies based on all protein-coding genes in each genome provide consistent results. We also find that GC-content increased in many gene regions (especially 5' UTR) in the evolution of endotherms, except in coding-exons. Analysis of individual genomes shows that 3' UTR demonstrated stronger length and GC-content correlation with intron than 5' UTR, and gene with large intron in all six species demonstrated relatively similar GC-content. Our data indicates a great increase in complexity in vertebrate genes and we propose that the requirement for morphological and functional changes is probably the driving force behind the evolution of structure and base composition complexity in multicellular animal genes. PMID:21777854

  20. [The increase in receptor-mediated endocytosis of drugs in the composition of nanoparticles with the address fragment].

    PubMed

    Kostryukova, L V; Sanzhakov, M A; Ignatov, D V; Prozorovskyi, V N; Druzhilovskaya, O S; Kasatkina, E S; Medvedeva, N V; Ipatova, O M

    2016-03-01

    It is known that disorders in the cell functioning of the organs/tissues is accompanied by increased expression of certain receptors. A modern approach to improve the specificity of the drug accumulation in the affected area is to construct the delivery nanosystems with the address fragments. Active tagged transport may help to reduce the dose of the drug, minimizing the impact on healthy cells and organs (reduced adverse events). This approach is particularly important in oncology because of the high toxicity of the drugs used. In this work we have obtained and characterized the pharmaceutical composition of doxorubicin and chlorine e6 into colloidal nanoparticles with synthesized previously targeted conjugates based on folic acid and biotin. On the cell culture Hep G2 it was shown an increase in the internalization of drugs when they were introduced in the incubation medium in the form of drug compositions with transport nanosystems and targeted fragments. PMID:27420624

  1. Geometric complexity is increased in in vitro activated platelets.

    PubMed

    Bianciardi, Giorgio

    2015-06-01

    This article investigates the use of computerized fractal analysis for objective characterization of the complexity of platelets in vitro stimulated by low level thrombin (0.02 U mL(-1) ), collected from healthy individuals and observed by means of transmission electron microscopy. Platelet boundaries were extracted by means of automatically image analysis. Local fractal dimension was evaluated by the box-counting technique (measure of geometric complexity of the platelet outline). The results showed that the platelet boundary is fractal when observed by transmission electron microscopy and that, after an in vitro platelet activation test, the shape of platelets present increased geometric complexity in comparison to the no stimulated platelets (P < 0.001), with 100% correct classification. Computerized fractal analysis of platelet shape by transmission electron microscopy can provide accurate, quantitative, data to study platelet activation. The results may play important roles in the evaluation of the platelets status in pathological conditions, like as atherosclerosis and diabetes mellitus, where in in vivo activated platelets have been described. PMID:25808036

  2. Tool for evaluating research implementation challenges: A sense-making protocol for addressing implementation challenges in complex research settings

    PubMed Central

    2013-01-01

    Background Many challenges arise in complex organizational interventions that threaten research integrity. This article describes a Tool for Evaluating Research Implementation Challenges (TECH), developed using a complexity science framework to assist research teams in assessing and managing these challenges. Methods During the implementation of a multi-site, randomized controlled trial (RCT) of organizational interventions to reduce resident falls in eight nursing homes, we inductively developed, and later codified the TECH. The TECH was developed through processes that emerged from interactions among research team members and nursing home staff participants, including a purposive use of complexity science principles. Results The TECH provided a structure to assess challenges systematically, consider their potential impact on intervention feasibility and fidelity, and determine actions to take. We codified the process into an algorithm that can be adopted or adapted for other research projects. We present selected examples of the use of the TECH that are relevant to many complex interventions. Conclusions Complexity theory provides a useful lens through which research procedures can be developed to address implementation challenges that emerge from complex organizations and research designs. Sense-making is a group process in which diverse members interpret challenges when available information is ambiguous; the groups’ interpretations provide cues for taking action. Sense-making facilitates the creation of safe environments for generating innovative solutions that balance research integrity and practical issues. The challenges encountered during implementation of complex interventions are often unpredictable; however, adoption of a systematic process will allow investigators to address them in a consistent yet flexible manner, protecting fidelity. Research integrity is also protected by allowing for appropriate adaptations to intervention protocols that

  3. Investigating hypoxia in aquatic environments: diverse approaches to addressing a complex phenomenon

    NASA Astrophysics Data System (ADS)

    Friedrich, J.; Janssen, F.; Aleynik, D.; Bange, H. W.; Boltacheva, N.; Çağatay, M. N.; Dale, A. W.; Etiope, G.; Erdem, Z.; Geraga, M.; Gilli, A.; Gomoiu, M. T.; Hall, P. O. J.; Hansson, D.; He, Y.; Holtappels, M.; Kirf, M. K.; Kononets, M.; Konovalov, S.; Lichtschlag, A.; Livingstone, D. M.; Marinaro, G.; Mazlumyan, S.; Naeher, S.; North, R. P.; Papatheodorou, G.; Pfannkuche, O.; Prien, R.; Rehder, G.; Schubert, C. J.; Soltwedel, T.; Sommer, S.; Stahl, H.; Stanev, E. V.; Teaca, A.; Tengberg, A.; Waldmann, C.; Wehrli, B.; Wenzhöfer, F.

    2013-08-01

    In this paper we synthesize the new knowledge on oxygen and oxygen-related phenomena in aquatic systems, resulting from the EU-FP7 project HYPOX ("In situ monitoring of oxygen depletion in hypoxic ecosystems of coastal and open seas, and land-locked water bodies", www.hypox.net). In view of the anticipated oxygen loss in aquatic systems due to eutrophication and climate change, HYPOX was set up to improve capacities to monitor hypoxia as well as to understand its causes and consequences. Temporal dynamics and spatial patterns of hypoxia were analysed in field studies in various aquatic environments, including the Baltic Sea, the Black Sea, Scottish and Scandinavian fjords, Ionian Sea lagoons and embayments, and in Swiss lakes. Examples of episodic and rapid (hours) occurrences of hypoxia as well as seasonal changes in bottom-water oxygenation in stratified systems are discussed. Geologically-driven hypoxia caused by gas seepage is demonstrated. Using novel technologies, temporal and spatial patterns of water-column oxygenation, from basin-scale seasonal patterns to meter-scale submicromolar oxygen distributions were resolved. Existing multi-decadal monitoring data were used to demonstrate the imprint of climate change and eutrophication on long-term oxygen distributions. Organic and inorganic proxies were used to extend investigations on past oxygen conditions to centennial and even longer timescales not resolved by monitoring. The effects of hypoxia on faunal communities and biogeochemical processes were also addressed in the project. An investigation of benthic fauna is presented as an example of hypoxia-devastated benthic communities that slowly recover upon a reduction in eutrophication in a system where natural and anthropogenic hypoxia overlap. Biogeochemical investigations reveal that oxygen intrusions have a strong effect on microbially-mediated redox cycling of elements. Observations and modeling studies of

  4. Investigating hypoxia in aquatic environments: diverse approaches to addressing a complex phenomenon

    NASA Astrophysics Data System (ADS)

    Friedrich, J.; Janssen, F.; Aleynik, D.; Bange, H. W.; Boltacheva, N.; Çagatay, M. N.; Dale, A. W.; Etiope, G.; Erdem, Z.; Geraga, M.; Gilli, A.; Gomoiu, M. T.; Hall, P. O. J.; Hansson, D.; He, Y.; Holtappels, M.; Kirf, M. K.; Kononets, M.; Konovalov, S.; Lichtschlag, A.; Livingstone, D. M.; Marinaro, G.; Mazlumyan, S.; Naeher, S.; North, R. P.; Papatheodorou, G.; Pfannkuche, O.; Prien, R.; Rehder, G.; Schubert, C. J.; Soltwedel, T.; Sommer, S.; Stahl, H.; Stanev, E. V.; Teaca, A.; Tengberg, A.; Waldmann, C.; Wehrli, B.; Wenzhöfer, F.

    2014-02-01

    In this paper we provide an overview of new knowledge on oxygen depletion (hypoxia) and related phenomena in aquatic systems resulting from the EU-FP7 project HYPOX ("In situ monitoring of oxygen depletion in hypoxic ecosystems of coastal and open seas, and landlocked water bodies", http://www.hypox.net). In view of the anticipated oxygen loss in aquatic systems due to eutrophication and climate change, HYPOX was set up to improve capacities to monitor hypoxia as well as to understand its causes and consequences. Temporal dynamics and spatial patterns of hypoxia were analyzed in field studies in various aquatic environments, including the Baltic Sea, the Black Sea, Scottish and Scandinavian fjords, Ionian Sea lagoons and embayments, and Swiss lakes. Examples of episodic and rapid (hours) occurrences of hypoxia, as well as seasonal changes in bottom-water oxygenation in stratified systems, are discussed. Geologically driven hypoxia caused by gas seepage is demonstrated. Using novel technologies, temporal and spatial patterns of water-column oxygenation, from basin-scale seasonal patterns to meter-scale sub-micromolar oxygen distributions, were resolved. Existing multidecadal monitoring data were used to demonstrate the imprint of climate change and eutrophication on long-term oxygen distributions. Organic and inorganic proxies were used to extend investigations on past oxygen conditions to centennial and even longer timescales that cannot be resolved by monitoring. The effects of hypoxia on faunal communities and biogeochemical processes were also addressed in the project. An investigation of benthic fauna is presented as an example of hypoxia-devastated benthic communities that slowly recover upon a reduction in eutrophication in a system where naturally occurring hypoxia overlaps with anthropogenic hypoxia. Biogeochemical investigations reveal that oxygen intrusions have a strong effect on the microbially mediated

  5. Addressing the Complexity of Tourette's Syndrome through the Use of Animal Models.

    PubMed

    Nespoli, Ester; Rizzo, Francesca; Boeckers, Tobias M; Hengerer, Bastian; Ludolph, Andrea G

    2016-01-01

    Tourette's syndrome (TS) is a neurodevelopmental disorder characterized by fluctuating motor and vocal tics, usually preceded by sensory premonitions, called premonitory urges. Besides tics, the vast majority-up to 90%-of TS patients suffer from psychiatric comorbidities, mainly attention deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). The etiology of TS remains elusive. Genetics is believed to play an important role, but it is clear that other factors contribute to TS, possibly altering brain functioning and architecture during a sensitive phase of neural development. Clinical brain imaging and genetic studies have contributed to elucidate TS pathophysiology and disease mechanisms; however, TS disease etiology still is poorly understood. Findings from genetic studies led to the development of genetic animal models, but they poorly reflect the pathophysiology of TS. Addressing the role of neurotransmission, brain regions, and brain circuits in TS disease pathomechanisms is another focus area for preclinical TS model development. We are now in an interesting moment in time when numerous innovative animal models are continuously brought to the attention of the public. Due to the diverse and largely unknown etiology of TS, there is no single preclinical model featuring all different aspects of TS symptomatology. TS has been dissected into its key symptomst hat have been investigated separately, in line with the Research Domain Criteria concept. The different rationales used to develop the respective animal models are critically reviewed, to discuss the potential of the contribution of animal models to elucidate TS disease mechanisms. PMID:27092043

  6. Addressing the Complexity of Tourette's Syndrome through the Use of Animal Models

    PubMed Central

    Nespoli, Ester; Rizzo, Francesca; Boeckers, Tobias M.; Hengerer, Bastian; Ludolph, Andrea G.

    2016-01-01

    Tourette's syndrome (TS) is a neurodevelopmental disorder characterized by fluctuating motor and vocal tics, usually preceded by sensory premonitions, called premonitory urges. Besides tics, the vast majority—up to 90%—of TS patients suffer from psychiatric comorbidities, mainly attention deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). The etiology of TS remains elusive. Genetics is believed to play an important role, but it is clear that other factors contribute to TS, possibly altering brain functioning and architecture during a sensitive phase of neural development. Clinical brain imaging and genetic studies have contributed to elucidate TS pathophysiology and disease mechanisms; however, TS disease etiology still is poorly understood. Findings from genetic studies led to the development of genetic animal models, but they poorly reflect the pathophysiology of TS. Addressing the role of neurotransmission, brain regions, and brain circuits in TS disease pathomechanisms is another focus area for preclinical TS model development. We are now in an interesting moment in time when numerous innovative animal models are continuously brought to the attention of the public. Due to the diverse and largely unknown etiology of TS, there is no single preclinical model featuring all different aspects of TS symptomatology. TS has been dissected into its key symptomst hat have been investigated separately, in line with the Research Domain Criteria concept. The different rationales used to develop the respective animal models are critically reviewed, to discuss the potential of the contribution of animal models to elucidate TS disease mechanisms. PMID:27092043

  7. Addressing the complexity of water chemistry in environmental fate modeling for engineered nanoparticles.

    PubMed

    Sani-Kast, Nicole; Scheringer, Martin; Slomberg, Danielle; Labille, Jérôme; Praetorius, Antonia; Ollivier, Patrick; Hungerbühler, Konrad

    2015-12-01

    Engineered nanoparticle (ENP) fate models developed to date - aimed at predicting ENP concentration in the aqueous environment - have limited applicability because they employ constant environmental conditions along the modeled system or a highly specific environmental representation; both approaches do not show the effects of spatial and/or temporal variability. To address this conceptual gap, we developed a novel modeling strategy that: 1) incorporates spatial variability in environmental conditions in an existing ENP fate model; and 2) analyzes the effect of a wide range of randomly sampled environmental conditions (representing variations in water chemistry). This approach was employed to investigate the transport of nano-TiO2 in the Lower Rhône River (France) under numerous sets of environmental conditions. The predicted spatial concentration profiles of nano-TiO2 were then grouped according to their similarity by using cluster analysis. The analysis resulted in a small number of clusters representing groups of spatial concentration profiles. All clusters show nano-TiO2 accumulation in the sediment layer, supporting results from previous studies. Analysis of the characteristic features of each cluster demonstrated a strong association between the water conditions in regions close to the ENP emission source and the cluster membership of the corresponding spatial concentration profiles. In particular, water compositions favoring heteroaggregation between the ENPs and suspended particulate matter resulted in clusters of low variability. These conditions are, therefore, reliable predictors of the eventual fate of the modeled ENPs. The conclusions from this study are also valid for ENP fate in other large river systems. Our results, therefore, shift the focus of future modeling and experimental research of ENP environmental fate to the water characteristic in regions near the expected ENP emission sources. Under conditions favoring heteroaggregation in these

  8. Gold(I) biscarbene complexes derived from vascular-disrupting combretastatin A-4 address different targets and show antimetastatic potential.

    PubMed

    Muenzner, Julienne K; Biersack, Bernhard; Kalie, Hussein; Andronache, Ion C; Kaps, Leonard; Schuppan, Detlef; Sasse, Florenz; Schobert, Rainer

    2014-06-01

    Gold N-heterocyclic carbene (NHC) complexes are an emerging class of anticancer drugs. We present a series of gold(I) biscarbene complexes with NHC ligands derived from the plant metabolite combretastatin A-4 (CA-4) that retain its vascular-disrupting effect, yet address different cellular and protein targets. Unlike CA-4, these complexes did not interfere with tubulin, but with the actin cytoskeleton of endothelial and cancer cells. For the highly metastatic 518A2 melanoma cell line this effect was accompanied by a marked accumulation of cells in the G1 phase of the cell cycle and a suppression of active prometastatic matrix metalloproteinase-2. Despite these mechanistic differences the complexes were as strongly antivascular as CA-4 both in vitro in tube formation assays with human umbilical vein endothelial cells, and in vivo as to blood vessel disruption in the chorioallantoic membrane of chicken eggs. The antiproliferative effect of the new gold biscarbene complexes in a panel of six human cancer cell lines was impressive, with low sub-micromolar IC50 values (72 h) even against CA-4-refractory HT-29 colon and multidrug-resistant MCF-7 breast carcinoma cells. In preliminary studies with a mouse melanoma xenograft model the complexes led to significant decreases in tumor volume while being very well tolerated. PMID:24648184

  9. Using Next Generation Science Standards (NGSS) Practices to Address Scientific Misunderstandings Around Complex Environmental Issues

    NASA Astrophysics Data System (ADS)

    Turrin, M.; Kenna, T. C.

    2014-12-01

    The new NGSS provide an important opportunity for scientists to develop curriculum that links the practice of science to research-based data in order to improve understanding in areas of science that are both complex and confusing. Our curriculum focuses in particular on the fate and transport of anthropogenic radionuclides. Radioactivity, both naturally occurring and anthropogenic, is highly debated and largely misunderstood, and for large sections of the population is a source of scientific misunderstanding. Developed as part of the international GEOTRACES project which focuses on identifying ocean processes and quantifying fluxes that control the distributions of selected trace elements and isotopes in the ocean, and on establishing the sensitivity of these distributions to changing environmental conditions, the curriculum topic fits nicely into the applied focus of NGSS with both environmental and topical relevance. Our curriculum design focuses on small group discussion driven by questions, yet unlike more traditional curriculum pieces these are not questions posed to the students, rather they are questions posed by the students to facilitate their deeper understanding. Our curriculum design challenges the traditional question/answer memorization approach to instruction as we strive to develop an educational approach that supports the practice of science as well as the NGSS Cross Cutting Concepts and the Science & Engineering Practices. Our goal is for students to develop a methodology they can employ when faced with a complex scientific issue. Through background readings and team discussions they identify what type of information is important for them to know and where to find a reliable source for that information. Framing their discovery around key questions such as "What type of radioactive decay are we dealing with?", "What is the potential half-life of the isotope?", and "What are the pathways of transport of radioactivity?" allows students to evaluate a

  10. On the road to a stronger public health workforce: visual tools to address complex challenges.

    PubMed

    Drehobl, Patricia; Stover, Beth H; Koo, Denise

    2014-11-01

    The public health workforce is vital to protecting the health and safety of the public, yet for years, state and local governmental public health agencies have reported substantial workforce losses and other challenges to the workforce that threaten the public's health. These challenges are complex, often involve multiple influencing or related causal factors, and demand comprehensive solutions. However, proposed solutions often focus on selected factors and might be fragmented rather than comprehensive. This paper describes approaches to characterizing the situation more comprehensively and includes two visual tools: (1) a fishbone, or Ishikawa, diagram that depicts multiple factors affecting the public health workforce; and (2) a roadmap that displays key elements-goals and strategies-to strengthen the public health workforce, thus moving from the problems depicted in the fishbone toward solutions. The visual tools aid thinking about ways to strengthen the public health workforce through collective solutions and to help leverage resources and build on each other's work. The strategic roadmap is intended to serve as a dynamic tool for partnership, prioritization, and gap assessment. These tools reflect and support CDC's commitment to working with partners on the highest priorities for strengthening the workforce to improve the public's health. PMID:25439245

  11. EqualChance: Addressing Intra-set Write Variation to Increase Lifetime of Non-volatile Caches

    SciTech Connect

    Mittal, Sparsh; Vetter, Jeffrey S

    2014-01-01

    To address the limitations of SRAM such as high-leakage and low-density, researchers have explored use of non-volatile memory (NVM) devices, such as ReRAM (resistive RAM) and STT-RAM (spin transfer torque RAM) for designing on-chip caches. A crucial limitation of NVMs, however, is that their write endurance is low and the large intra-set write variation introduced by existing cache management policies may further exacerbate this problem, thereby reducing the cache lifetime significantly. We present EqualChance, a technique to increase cache lifetime by reducing intra-set write variation. EqualChance works by periodically changing the physical cache-block location of a write-intensive data item within a set to achieve wear-leveling. Simulations using workloads from SPEC CPU2006 suite and HPC (high-performance computing) field show that EqualChance improves the cache lifetime by 4.29X. Also, its implementation overhead is small, and it incurs very small performance and energy loss.

  12. Evolution in students' understanding of thermal physics with increasing complexity

    NASA Astrophysics Data System (ADS)

    Langbeheim, Elon; Safran, Samuel A.; Livne, Shelly; Yerushalmi, Edit

    2013-12-01

    We analyze the development in students’ understanding of fundamental principles in the context of learning a current interdisciplinary research topic—soft matter—that was adapted to the level of high school students. The topic was introduced in a program for interested 11th grade high school students majoring in chemistry and/or physics, in an off-school setting. Soft matter was presented in a gradual increase in the degree of complexity of the phenomena as well as in the level of the quantitative analysis. We describe the evolution in students’ use of fundamental thermodynamics principles to reason about phase separation—a phenomenon that is ubiquitous in soft matter. In particular, we examine the impact of the use of free energy analysis, a common approach in soft matter, on the understanding of the fundamental principles of thermodynamics. The study used diagnostic questions and classroom observations to gauge the student’s learning. In order to gain insight on the aspects that shape the understanding of the basic principles, we focus on the responses and explanations of two case-study students who represent two trends of evolution in conceptual understanding in the group. We analyze changes in the two case studies’ management of conceptual resources used in their analysis of phase separation, and suggest how their prior knowledge and epistemological framing (a combination of their personal tendencies and their prior exposure to different learning styles) affect their conceptual evolution. Finally, we propose strategies to improve the instruction of these concepts.

  13. A comparative study of actinide complexation in three ligand systems with increasing complexity

    NASA Astrophysics Data System (ADS)

    Jeanson, A.; Dahou, S.; Guillaumont, D.; Moisy, P.; Den Auwer, C.; Scheinost, A.; Hennig, C.; Vidaud, C.; Subra, G.; Solari, P. L.

    2009-11-01

    The complexation of thorium, neptunium and plutonium at oxidation state +IV with three ligands of increasing complexity has been investigated. These ligands are relevant for bio inorganic systems. The first ligand is the small nitrilotriacetic acid that often play the role of protecting ligands against hydrolysis. EXAFS results for the Th to Pu series have been correlated to quantum chemical calculations and show an homogeneous behavior of the actinide at oxidation state +IV. For larger ligands, steric effects may become significant and one can ask how the ligand may accommodate the large actinide cation coordination sphere. Model pentapeptides have been synthesized and tested as complexing agents. Comparison with NTA shows that the molecular arrangements are radically different. The third ligand system is transferrin, a diferric metalloptrotein that is well known to coordinate a large variety of cations from transition metals of f-elements. Metalloproteins bear primary, secondary and tertiary structures that all play a crucial role in bonding. At a given oxidation state (+IV), but for various atomic numbers (Th, Np, Pu) EXAFS data at the cation LIII edge exhibit significant coordination discrepancies that are related to a changes in protein geometry. In that sense, the metalloprotein may be viewed as a complex system.

  14. New and improved proteomics technologies for understanding complex biological systems: Addressing a grand challenge in the life sciences

    PubMed Central

    Hood, Leroy E.; Omenn, Gilbert S.; Moritz, Robert L.; Aebersold, Ruedi; Yamamoto, Keith R.; Amos, Michael; Hunter-Cevera, Jennie; Locascio, Laurie

    2014-01-01

    This White Paper sets out a Life Sciences Grand Challenge for Proteomics Technologies to enhance our understanding of complex biological systems, link genomes with phenotypes, and bring broad benefits to the biosciences and the US economy. The paper is based on a workshop hosted by the National Institute of Standards and Technology (NIST) in Gaithersburg, MD, 14–15 February 2011, with participants from many federal R&D agencies and research communities, under the aegis of the US National Science and Technology Council (NSTC). Opportunities are identified for a coordinated R&D effort to achieve major technology-based goals and address societal challenges in health, agriculture, nutrition, energy, environment, national security, and economic development. PMID:22807061

  15. Evolving paradigms in the treatment of relapsed/refractory multiple myeloma: increased options and increased complexity.

    PubMed

    Cornell, R F; Kassim, A A

    2016-04-01

    The use of modern therapies such as thalidomide, bortezomib and lenalidomide coupled with upfront high-dose therapy and autologous stem cell transplant (ASCT) has resulted in improved survival in patients with newly diagnosed multiple myeloma (MM). However, patients with relapsed/refractory multiple myeloma (RRMM) often have poorer clinical outcomes and might benefit from novel therapeutic strategies. Emerging therapies, such as deacetylase inhibitors, monoclonal antibodies and new proteasome inhibitors, appear promising and may change the therapeutic landscape in RRMM. A limited number of studies has shown a benefit with salvage ASCT in patients with RRMM, although there remains ongoing debate about its timing and effectiveness. Improvement in transplant outcomes has re-ignited a debate on the timing and possible role for salvage ASCT and allogeneic stem cell transplant in RRMM. As the treatment options for management of patients with RRMM become increasingly complex, physicians must consider both disease- and patient-related factors in choosing the appropriate therapeutic approach, with the goal of improving efficacy while minimizing toxicity. PMID:26726946

  16. Evolving paradigms in the treatment of relapsed/refractory multiple myeloma: increased options and increased complexity

    PubMed Central

    Cornell, R F; Kassim, A A

    2016-01-01

    The use of modern therapies such as thalidomide, bortezomib and lenalidomide coupled with upfront high-dose therapy and autologous stem cell transplant (ASCT) has resulted in improved survival in patients with newly diagnosed multiple myeloma (MM). However, patients with relapsed/refractory multiple myeloma (RRMM) often have poorer clinical outcomes and might benefit from novel therapeutic strategies. Emerging therapies, such as deacetylase inhibitors, monoclonal antibodies and new proteasome inhibitors, appear promising and may change the therapeutic landscape in RRMM. A limited number of studies has shown a benefit with salvage ASCT in patients with RRMM, although there remains ongoing debate about its timing and effectiveness. Improvement in transplant outcomes has re-ignited a debate on the timing and possible role for salvage ASCT and allogeneic stem cell transplant in RRMM. As the treatment options for management of patients with RRMM become increasingly complex, physicians must consider both disease- and patient-related factors in choosing the appropriate therapeutic approach, with the goal of improving efficacy while minimizing toxicity. PMID:26726946

  17. A responsive evaluation of mental health treatment in Cambodia: Intentionally addressing poverty to increase cultural responsiveness in therapy.

    PubMed

    Seponski, Desiree M; Lewis, Denise C; Megginson, Maegan C

    2014-01-01

    Mental health issues are significant contributors to the global burden of disease with the highest incidence in resource poor countries; 90% of those in need of mental health treatment reside in low resource countries but receive only 10% of the world's resources. Cambodia, the eighth least developed country in the world, serves as one example of the need to address mental health concerns in low-income, resource poor countries. The current study utilises responsive evaluation methodology to explore how poverty-stricken Cambodian clients, therapists and supervisors experience Western models of therapy as culturally responsive to their unique needs. Quantitative and qualitative data were triangulated across multiple stakeholders using numerous methods including a focus group, interviews, surveys, case illustrations and live supervision observation and analysed using constant comparative analysis. Emerging findings suggest that poverty, material needs, therapy location and financial situations greatly impact the daily lives and mental health conditions of Cambodians and hinder clients' therapeutic progress. The local community needs and context of poverty greatly hinder clients' therapeutic progress in therapy treatment and when therapy does not directly address the culture of poverty, clients did not experience therapy as valuable despite some temporary decreases in mental health symptoms. PMID:25204750

  18. Future prospects for prophylactic immune stimulation in crustacean aquaculture - the need for improved metadata to address immune system complexity.

    PubMed

    Hauton, Chris; Hudspith, Meggie; Gunton, Laetitia

    2015-02-01

    Future expansion of the crustacean aquaculture industry will be required to ensure global food security. However, this expansion must ensure: (a) that natural resources (including habitat use and fish meal) are sustainably exploited, (b) that the socio-economic development of producing nations is safeguarded, and (c) that the challenge presented by crustacean diseases is adequately met. Conventionally, the problem of disease in crustacean aquaculture has been addressed through prophylactic administration of stimulants, additives or probiotics. However, these approaches have been questioned both experimentally and philosophically. In this review, we argue that real progress in the field of crustacean immune stimulants has now slowed, with only incremental advances now being made. We further contend that an overt focus on the immune effector response has been misguided. In light of the wealth of new data reporting immune system complexity, a more refined approach is necessary - one that must consider the important role played by pattern recognition proteins. In support of this more refined approach, there is now a much greater requirement for the reporting of essential metadata. We propose a broad series of recommendations regarding the 'Minimum Information required to support a Stimulant Assessment experiment' (MISA guidelines) to foster new progression within the field. PMID:24796867

  19. Increasing quality and managing complexity in neuroinformatics software development with continuous integration

    PubMed Central

    Zaytsev, Yury V.; Morrison, Abigail

    2013-01-01

    High quality neuroscience research requires accurate, reliable and well maintained neuroinformatics applications. As software projects become larger, offering more functionality and developing a denser web of interdependence between their component parts, we need more sophisticated methods to manage their complexity. If complexity is allowed to get out of hand, either the quality of the software or the speed of development suffer, and in many cases both. To address this issue, here we develop a scalable, low-cost and open source solution for continuous integration (CI), a technique which ensures the quality of changes to the code base during the development procedure, rather than relying on a pre-release integration phase. We demonstrate that a CI-based workflow, due to rapid feedback about code integration problems and tracking of code health measures, enabled substantial increases in productivity for a major neuroinformatics project and additional benefits for three further projects. Beyond the scope of the current study, we identify multiple areas in which CI can be employed to further increase the quality of neuroinformatics projects by improving development practices and incorporating appropriate development tools. Finally, we discuss what measures can be taken to lower the barrier for developers of neuroinformatics applications to adopt this useful technique. PMID:23316158

  20. Functional group diversity increases with modularity in complex food webs

    PubMed Central

    Montoya, D.; Yallop, M.L.; Memmott, J.

    2015-01-01

    Biodiversity increases the ability of ecosystems to provide multiple functions. Most studies report a positive relationship between species richness and the number of ecosystem functions. However, it is not known whether the number of functional groups is related to the structure of the underlying species interaction network. Here we present food web data from 115 salt marsh islands and show that network structure is associated with the number of functional groups present. Functional group diversity is heterogeneously distributed across spatial scales, with some islands hosting more functional groups than others. Functional groups form modules within the community so that food webs with more modular architectures have more functional group diversity. Further, in communities with different interaction types, modularity can be seen as the multifunctional equivalent of trophic complementarity. Collectively, these findings reveal spatial heterogeneity in the number of functional groups that emerges from patterns in the structure of the food web. PMID:26059871

  1. Ecological community integration increases with added trophic complexity

    USGS Publications Warehouse

    Wright, C.K.

    2008-01-01

    The existence of functional biological organization at the level of multi-species communities has long been contested in ecology and evolutionary biology. I found that adding a trophic level to simulated ecological communities enhanced their ability to compete at the community level, increasing the likelihood of one community forcing all or most species in a second community to extinction. Community-level identity emerged within systems of interacting ecological networks, while competitive ability at the community level was enhanced by intense within-community selection pressure. These results suggest a reassessment of the nature of biological organization above the level of species, indicating that the drive toward biological integration, so prominent throughout the history of life, might extend to multi-species communities. ?? 2007 Elsevier B.V. All rights reserved.

  2. Does Increasing Treatment Frequency Address Suboptimal Responses to Ivermectin for the Control and Elimination of River Blindness?

    PubMed Central

    Frempong, Kwadwo K.; Walker, Martin; Cheke, Robert A.; Tetevi, Edward Jenner; Gyan, Ernest Tawiah; Owusu, Ebenezer O.; Wilson, Michael D.; Boakye, Daniel A.; Taylor, Mark J.; Biritwum, Nana-Kwadwo; Osei-Atweneboana, Mike; Basáñez, María-Gloria

    2016-01-01

    Background. Several African countries have adopted a biannual ivermectin distribution strategy in some foci to control and eliminate onchocerciasis. In 2010, the Ghana Health Service started biannual distribution to combat transmission hotspots and suboptimal responses to treatment. We assessed the epidemiological impact of the first 3 years of this strategy and quantified responses to ivermectin over 2 consecutive rounds of treatment in 10 sentinel communities. Methods. We evaluated Onchocerca volvulus community microfilarial intensity and prevalence in persons aged ≥20 years before the first, second, and fifth (or sixth) biannual treatment rounds using skin snip data from 956 participants. We used longitudinal regression modeling to estimate rates of microfilarial repopulation of the skin in a cohort of 217 participants who were followed up over the first 2 rounds of biannual treatment. Results. Biannual treatment has had a positive impact, with substantial reductions in infection intensity after 4 or 5 rounds in most communities. We identified 3 communities—all having been previously recognized as responding suboptimally to ivermectin—with statistically significantly high microfilarial repopulation rates. We did not find any clear association between microfilarial repopulation rate and the number of years of prior intervention, coverage, or the community level of infection. Conclusions. The strategy of biannual ivermectin treatment in Ghana has reduced O. volvulus microfilarial intensity and prevalence, but suboptimal responses to treatment remain evident in a number of previously and consistently implicated communities. Whether increasing the frequency of treatment will be sufficient to meet the World Health Organization's 2020 elimination goals remains uncertain. PMID:27001801

  3. COMPONENT-BASED AND WHOLE-MIXTURE ASSESSMENTS IN ADDRESSING THE UNIDENTIFIED FRACTION OF COMPLEX MIXTURES: DRINKING WATER AS AN EXAMPLE

    EPA Science Inventory


    Component-Based and Whole-Mixtures Assessments in Addressing the Unidentified Fraction of Complex Mixtures: Drinking Water as an Example

    J. E. Simmons; L. K. Teuschler; C. Gennings; T. F. Speth; S. D. Richardson; R. J. Miltner; M. G. Narotsky; K. D. Schenck; G. Rice

  4. Social workers' roles in addressing the complex end-of-life care needs of elders with advanced chronic disease.

    PubMed

    Kramer, Betty J

    2013-01-01

    This study examined social workers' roles in caring for low-income elders with advanced chronic disease in an innovative, community-based managed care program, from the perspective of elders, family, team members, and social workers. The results are drawn from a larger longitudinal, multimethod case study. Sources of data include survey reports of needs addressed by social workers for 120 deceased elders, five focus groups with interdisciplinary team members, and in-depth interviews with 14 elders and 10 of their family caregivers. A thematic conceptual matrix was developed to detail 32 distinctive social work roles that address divergent needs of elders, family, and team members. Distinctive perceptions of social workers' roles were identified for the different stakeholder groups (i.e., elders, family caregivers, team members, and social workers). Findings from this study may inform supervisors and educators regarding training needs of those preparing to enter the rapidly growing workforce of gerontological social workers who may be called upon to care for elders at the end of life. Training is particularly warranted to help social workers gain the skills needed to more successfully treat symptom management, depression, anxiety, agitation, grief, funeral planning, and spiritual needs that are common to the end of life. PMID:24295099

  5. Re-imagining decision making: addressing a discrete social driver of HIV/AIDS through the lens of complexity science.

    PubMed

    Burman, Christopher J; Moerschell, Linda; Mamabolo, Robert; Aphane, Marota; Delobelle, Peter

    2015-01-01

    This article argues that decision making is a discrete social driver that can be associated with the HIV/AIDS epidemic in the Limpopo province in South Africa. The authors argue that complexity science can inform future research and interventions by presenting two decision making frameworks arising out of complexity science that have the potential to enable young people to better negotiate decision-making contexts whilst simultaneously opening spaces of dialogue that can mitigate the impact of HIV-risk in specific, punctuated contexts. The methodological design was prompted by findings from youth-oriented community engagement projects that include Communication Conversations and Sex & Relationships Education. The proposed methods have the potential to exploit the phenomenon of leadership emergence as a product of decision making at critical moments. This has the potential to promote the growth of home-grown leadership skill sets that make sense to young people and to enable them better manage their own health, thus reducing risk and vulnerability to HIV infection and sexual violence. PMID:25920986

  6. An enzyme complex increases in vitro dry matter digestibility of corn and wheat in pigs.

    PubMed

    Park, Kyu Ree; Park, Chan Sol; Kim, Beob Gyun

    2016-01-01

    Two experiments were conducted to determine the effects of enzyme complex on in vitro dry matter (DM) digestibility for feed ingredients. The objective of experiment 1 was to screen feed ingredients that can be effective substrates for an enzyme complex, mainly consisted of β-pentosanase, β-glucanase and α-amylase, using in vitro digestibility methods. In experiment 1, the test ingredients were three grain sources (barley, corn and wheat) and six protein supplements (canola meal, copra expellers, cottonseed meal, distillers dried grains with solubles, palm kernel expellers and soybean meal). In vitro ileal and total tract digestibility (IVID and IVTTD, respectively) of DM for test ingredients were determined. In vitro digestibility methods consisted of two- or three-step procedure simulating in vivo digestion in the pig gastrointestinal tracts with or without enzyme complex. As the enzyme complex added, the IVID of DM for corn and wheat increased (p < 0.05) by 5.0 and 2.6 percentage unit, respectively. The IVTTD of DM for corn increased (p < 0.05) by 3.1 percentage unit with enzyme complex addition. As the effect of enzyme complex was the greatest in corn digestibility, corn grains were selected to determine the in vitro digestibility of the fractions (starch, germ, hull and gluten) that maximally respond to the enzyme complex in experiment 2. The IVID of DM for corn starch, germ and hull increased (p < 0.05) by 16.0, 2.8 and 1.2 percentage unit, respectively. The IVTTD of DM for corn starch and hull also increased (p < 0.05) by 8.6 and 0.9 percentage unit, respectively, with enzyme complex addition. In conclusion, the enzyme complex increases in vitro DM digestibility of corn and wheat, and the digestibility increments of corn are mainly attributed to the increased digestibility of corn starch. PMID:27247894

  7. Presidential address.

    PubMed

    Vohra, U

    1993-07-01

    The Secretary of India's Ministry of Health and Family Welfare serves as Chair of the Executive Council of the International Institute for Population Sciences in Bombay. She addressed its 35th convocation in 1993. Global population stands at 5.43 billion and increases by about 90 million people each year. 84 million of these new people are born in developing countries. India contributes 17 million new people annually. The annual population growth rate in India is about 2%. Its population size will probably surpass 1 billion by the 2000. High population growth rates are a leading obstacle to socioeconomic development in developing countries. Governments of many developing countries recognize this problem and have expanded their family planning programs to stabilize population growth. Asian countries that have done so and have completed the fertility transition include China, Japan, Singapore, South Korea, and Thailand. Burma, Malaysia, North Korea, Sri Lanka, and Vietnam have not yet completed the transition. Afghanistan, Bangladesh, Iran, Nepal, and Pakistan are half-way through the transition. High population growth rates put pressure on land by fragmenting finite land resources, increasing the number of landless laborers and unemployment, and by causing considerable rural-urban migration. All these factors bring about social stress and burden civic services. India has reduced its total fertility rate from 5.2 to 3.9 between 1971 and 1991. Some Indian states have already achieved replacement fertility. Considerable disparity in socioeconomic development exists among states and districts. For example, the states of Bihar, Madhya Pradesh, Rajasthan, and Uttar Pradesh have female literacy rates lower than 27%, while that for Kerala is 87%. Overall, infant mortality has fallen from 110 to 80 between 1981 and 1990. In Uttar Pradesh, it has fallen from 150 to 98, while it is at 17 in Kerala. India needs innovative approaches to increase contraceptive prevalence rates

  8. Addressing the Complexity of Mobile App Design in Hospital Setting with a Tailored Software Development Life Cycle Model.

    PubMed

    Ehrler, Frederic; Lovis, Christian; Blondon, Katherine

    2016-01-01

    Recent studies on workflow processes in hospital settings have shown that, since the introduction of EHRs, care-providers spend an increasing amount of their time on documentation rather than on bedside patient care. In order to improve the bedside work process and facilitate bedside documentation, we are developing an evidence-based mobile app for healthcare providers. In this paper, we present a tailored software development life cycle model that we created and validated during the design and development of this smartphone application. PMID:27577371

  9. Disruption of the Class IIa HDAC Corepressor Complex Increases Energy Expenditure and Lipid Oxidation.

    PubMed

    Gaur, Vidhi; Connor, Timothy; Sanigorski, Andrew; Martin, Sheree D; Bruce, Clinton R; Henstridge, Darren C; Bond, Simon T; McEwen, Kevin A; Kerr-Bayles, Lyndal; Ashton, Trent D; Fleming, Cassandra; Wu, Min; Pike Winer, Lisa S; Chen, Denise; Hudson, Gregg M; Schwabe, John W R; Baar, Keith; Febbraio, Mark A; Gregorevic, Paul; Pfeffer, Frederick M; Walder, Ken R; Hargreaves, Mark; McGee, Sean L

    2016-09-13

    Drugs that recapitulate aspects of the exercise adaptive response have the potential to provide better treatment for diseases associated with physical inactivity. We previously observed reduced skeletal muscle class IIa HDAC (histone deacetylase) transcriptional repressive activity during exercise. Here, we find that exercise-like adaptations are induced by skeletal muscle expression of class IIa HDAC mutants that cannot form a corepressor complex. Adaptations include increased metabolic gene expression, mitochondrial capacity, and lipid oxidation. An existing HDAC inhibitor, Scriptaid, had similar phenotypic effects through disruption of the class IIa HDAC corepressor complex. Acute Scriptaid administration to mice increased the expression of metabolic genes, which required an intact class IIa HDAC corepressor complex. Chronic Scriptaid administration increased exercise capacity, whole-body energy expenditure and lipid oxidation, and reduced fasting blood lipids and glucose. Therefore, compounds that disrupt class IIa HDAC function could be used to enhance metabolic health in chronic diseases driven by physical inactivity. PMID:27626651

  10. Protein Targeting and Transport as a Necessary Consequence of Increased Cellular Complexity

    PubMed Central

    Sommer, Maik S.; Schleiff, Enrico

    2014-01-01

    With increasing intracellular complexity, a new cell-biological problem that is the allocation of cytoplasmically synthesized proteins to their final destinations within the cell emerged. A special challenge is thereby the translocation of proteins into or across cellular membranes. The underlying mechanisms are only in parts well understood, but it can be assumed that the course of cellular evolution had a deep impact on the design of the required molecular machines. In this article, we aim to summarize the current knowledge and concepts of the evolutionary development of protein trafficking as a necessary premise and consequence of increased cellular complexity. PMID:25085907

  11. Positive Psychology Interventions Addressing Pleasure, Engagement, Meaning, Positive Relationships, and Accomplishment Increase Well-Being and Ameliorate Depressive Symptoms: A Randomized, Placebo-Controlled Online Study

    PubMed Central

    Gander, Fabian; Proyer, René T.; Ruch, Willibald

    2016-01-01

    Seligman (2002) suggested three paths to well-being, the pursuit of pleasure, the pursuit of meaning, and the pursuit of engagement, later adding two more, positive relationships and accomplishment, in his 2011 version. The contribution of these new components to well-being has yet to be addressed. In an online positive psychology intervention study, we randomly assigned 1624 adults aged 18–78 (M = 46.13; 79.2% women) to seven conditions. Participants wrote down three things they related to either one of the five components of Seligman's Well-Being theory (Conditions 1–5), all of the five components (Condition 6) or early childhood memories (placebo control condition). We assessed happiness (AHI) and depression (CES-D) before and after the intervention, and 1-, 3-, and 6 months afterwards. Additionally, we considered moderation effects of well-being levels at baseline. Results confirmed that all interventions were effective in increasing happiness and most ameliorated depressive symptoms. The interventions worked best for those in the middle-range of the well-being continuum. We conclude that interventions based on pleasure, engagement, meaning, positive relationships, and accomplishment are effective strategies for increasing well-being and ameliorating depressive symptoms and that positive psychology interventions are most effective for those people in the middle range of the well-being continuum. PMID:27242600

  12. Positive Psychology Interventions Addressing Pleasure, Engagement, Meaning, Positive Relationships, and Accomplishment Increase Well-Being and Ameliorate Depressive Symptoms: A Randomized, Placebo-Controlled Online Study.

    PubMed

    Gander, Fabian; Proyer, René T; Ruch, Willibald

    2016-01-01

    Seligman (2002) suggested three paths to well-being, the pursuit of pleasure, the pursuit of meaning, and the pursuit of engagement, later adding two more, positive relationships and accomplishment, in his 2011 version. The contribution of these new components to well-being has yet to be addressed. In an online positive psychology intervention study, we randomly assigned 1624 adults aged 18-78 (M = 46.13; 79.2% women) to seven conditions. Participants wrote down three things they related to either one of the five components of Seligman's Well-Being theory (Conditions 1-5), all of the five components (Condition 6) or early childhood memories (placebo control condition). We assessed happiness (AHI) and depression (CES-D) before and after the intervention, and 1-, 3-, and 6 months afterwards. Additionally, we considered moderation effects of well-being levels at baseline. Results confirmed that all interventions were effective in increasing happiness and most ameliorated depressive symptoms. The interventions worked best for those in the middle-range of the well-being continuum. We conclude that interventions based on pleasure, engagement, meaning, positive relationships, and accomplishment are effective strategies for increasing well-being and ameliorating depressive symptoms and that positive psychology interventions are most effective for those people in the middle range of the well-being continuum. PMID:27242600

  13. Simulation study on effects of signaling network structure on the developmental increase in complexity

    SciTech Connect

    Keranen, Soile V.E.

    2003-04-02

    The developmental increase in structural complexity in multicellular life forms depends on local, often non-periodic differences in gene expression. These depend on a network of gene-gene interactions coded within the organismal genome. To better understand how genomic information generates complex expression patterns, I have modeled the pattern forming behavior of small artificial genomes in virtual blastoderm embryos. I varied several basic properties of these genomic signaling networks, such as the number of genes, the distributions of positive (inductive) and negative (repressive) interactions, and the strengths of gene-gene interactions, and analyzed their effects on developmental pattern formation. The results show how even simple genomes can generate complex non-periodic patterns under suitable conditions. They also show how the frequency of complex patterns depended on the numbers and relative arrangements of positive and negative interactions. For example, negative co-regulation of signaling pathway components increased the likelihood of (complex) patterns relative to differential negative regulation of the pathway components. Interestingly, neither quantitative differences either in strengths of signaling interactions nor multiple response thresholds to signal concentration (as in morphogen gradients) were essential for formation of multiple, spatially unique cell types. Thus, with combinatorial code of gene regulation and hierarchical signaling interactions, it is theoretically possible to organize metazoan embryogenesis with just a small fraction of the metazoan genome. Because even small networks can generate complex patterns when they contain a suitable set of connections, evolution of metazoan complexity may have depended more on selection for favourable configurations of signaling interactions than on the increase in numbers of regulatory genes.

  14. Effect of thermal stability/complex terrain on wind turbine model(s): a wind tunnel study to address complex atmospheric conditions

    NASA Astrophysics Data System (ADS)

    Guala, M.; Hu, S. J.; Chamorro, L. P.

    2011-12-01

    Turbulent boundary layer measurements in both wind tunnel and in the near-neutral atmospheric surface layer revealed in the last decade the significant contribution of the large scales of motions to both turbulent kinetic energy and Reynolds stresses, for a wide range of Reynolds number. These scales are known to grow throughout the logarithmic layer and to extend several boundary layer heights in the streamwise direction. Potentially, they are a source of strong unsteadiness in the power output of wind turbines and in the aerodynamic loads of wind turbine blades. However, the large scales in realistic atmospheric conditions deserves further study, with well controlled boundary conditions. In the atmospheric wind tunnel of the St. Anthony Falls Laboratory, with a 16 m long test section and independently controlled incoming flow and floor temperatures, turbulent boundary layers in a range of stability conditions, from the stratified to the convective case, can be reproduced and monitored. Measurements of fluctuating temperature, streamwise and wall normal velocity components are simultaneously obtained by an ad hoc calibrated and customized triple-wire sensor. A wind turbine model with constant loading DC motor, constant tip speed ratio, and a rotor diameter of 0.128m is used to mimic a large full scale turbine in the atmospheric boundary layer. Measurements of the fluctuating voltage generated by the DC motor are compared with measurements of the blade's angular velocity by laser scanning, and eventually related to velocity measurements from the triple-wire sensor. This study preliminary explores the effect of weak stability and complex terrain (through a set of spanwise aligned topographic perturbations) on the large scales of the flow and on the fluctuations in the wind turbine(s) power output.

  15. Systems Thinking as a Competency for Community College Leaders in an Era of Increasing Complexity

    ERIC Educational Resources Information Center

    Davis, Anne Powel

    2013-01-01

    The pluralistic and often competing goals of myriad constituents, the changing demographics of students, the uncertainty of funding, and the growing demands for accountability from stakeholders have increased the complexity of systems which community college leaders must manage. Emerging from the recent literature on community colleges is a call…

  16. Mitochondrial Complex 1 Inhibition Increases 4-Repeat Isoform Tau by SRSF2 Upregulation

    PubMed Central

    De Andrade, Anderson; Höglinger, Günter

    2014-01-01

    Progressive Supranuclear Palsy (PSP) is a neurodegenerative disorder characterised by intracellular aggregation of the microtubule-associated protein tau. The tau protein exists in 6 predominant isoforms. Depending on alternative splicing of exon 10, three of these isoforms have four microtubule-binding repeat domains (4R), whilst the others only have three (3R). In PSP there is an excess of the 4R tau isoforms, which are thought to contribute significantly to the pathological process. The cause of this 4R increase is so far unknown. Several lines of evidence link mitochondrial complex I inhibition to the pathogenesis of PSP. We demonstrate here for the first time that annonacin and MPP+, two prototypical mitochondrial complex I inhibitors, increase the 4R isoforms of tau in human neurons. We show that the splicing factor SRSF2 is necessary to increase 4R tau with complex I inhibition. We also found SRSF2, as well as another tau splicing factor, TRA2B, to be increased in brains of PSP patients. Thereby, we provide new evidence that mitochondrial complex I inhibition may contribute as an upstream event to the pathogenesis of PSP and suggest that splicing factors may represent an attractive therapeutic target to intervene in the disease process. PMID:25402454

  17. Addressing the complexity and diversity of agricultural plant volatiles: a call for the integration of laboratory- and field-based analyses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    As the sophistication and sensitivity of chemical instrumentation increases so do the number of applications. Correspondingly, new questions and opportunities for systems previously studied also arise. As with most plants, the emission of volatiles from agricultural products is complex and varies am...

  18. Lessons from Red Data Books: Plant Vulnerability Increases with Floral Complexity.

    PubMed

    Stefanaki, Anastasia; Kantsa, Aphrodite; Tscheulin, Thomas; Charitonidou, Martha; Petanidou, Theodora

    2015-01-01

    The architectural complexity of flower structures (hereafter referred to as floral complexity) may be linked to pollination by specialized pollinators that can increase the probability of successful seed set. As plant-pollinator systems become fragile, a loss of such specialized pollinators could presumably result in an increased likelihood of pollination failure. This is an issue likely to be particularly evident in plants that are currently rare. Using a novel index describing floral complexity we explored whether this aspect of the structure of flowers could be used to predict vulnerability of plant species to extinction. To do this we defined plant vulnerability using the Red Data Book of Rare and Threatened Plants of Greece, a Mediterranean biodiversity hotspot. We also tested whether other intrinsic (e.g. life form, asexual reproduction) or extrinsic (e.g. habitat, altitude, range-restrictedness) factors could affect plant vulnerability. We found that plants with high floral complexity scores were significantly more likely to be vulnerable to extinction. Among all the floral complexity components only floral symmetry was found to have a significant effect, with radial-flower plants appearing to be less vulnerable. Life form was also a predictor of vulnerability, with woody perennial plants having significantly lower risk of extinction. Among the extrinsic factors, both habitat and maximum range were significantly associated with plant vulnerability (coastal plants and narrow-ranged plants are more likely to face higher risk). Although extrinsic and in particular anthropogenic factors determine plant extinction risk, intrinsic traits can indicate a plant's proneness to vulnerability. This raises the potential threat of declining global pollinator diversity interacting with floral complexity to increase the vulnerability of individual plant species. There is potential scope for using plant-pollinator specializations to identify plant species particularly at

  19. Lessons from Red Data Books: Plant Vulnerability Increases with Floral Complexity

    PubMed Central

    Stefanaki, Anastasia; Kantsa, Aphrodite; Tscheulin, Thomas; Charitonidou, Martha; Petanidou, Theodora

    2015-01-01

    The architectural complexity of flower structures (hereafter referred to as floral complexity) may be linked to pollination by specialized pollinators that can increase the probability of successful seed set. As plant—pollinator systems become fragile, a loss of such specialized pollinators could presumably result in an increased likelihood of pollination failure. This is an issue likely to be particularly evident in plants that are currently rare. Using a novel index describing floral complexity we explored whether this aspect of the structure of flowers could be used to predict vulnerability of plant species to extinction. To do this we defined plant vulnerability using the Red Data Book of Rare and Threatened Plants of Greece, a Mediterranean biodiversity hotspot. We also tested whether other intrinsic (e.g. life form, asexual reproduction) or extrinsic (e.g. habitat, altitude, range-restrictedness) factors could affect plant vulnerability. We found that plants with high floral complexity scores were significantly more likely to be vulnerable to extinction. Among all the floral complexity components only floral symmetry was found to have a significant effect, with radial-flower plants appearing to be less vulnerable. Life form was also a predictor of vulnerability, with woody perennial plants having significantly lower risk of extinction. Among the extrinsic factors, both habitat and maximum range were significantly associated with plant vulnerability (coastal plants and narrow-ranged plants are more likely to face higher risk). Although extrinsic and in particular anthropogenic factors determine plant extinction risk, intrinsic traits can indicate a plant’s proneness to vulnerability. This raises the potential threat of declining global pollinator diversity interacting with floral complexity to increase the vulnerability of individual plant species. There is potential scope for using plant—pollinator specializations to identify plant species particularly

  20. Radiation increases the cellular uptake of exosomes through CD29/CD81 complex formation

    SciTech Connect

    Hazawa, Masaharu; Tomiyama, Kenichi; Saotome-Nakamura, Ai; Obara, Chizuka; Yasuda, Takeshi; Gotoh, Takaya; Tanaka, Izumi; Yakumaru, Haruko; Ishihara, Hiroshi; Tajima, Katsushi

    2014-04-18

    Highlights: • Radiation increases cellular uptake of exosomes. • Radiation induces colocalization of CD29 and CD81. • Exosomes selectively bind the CD29/CD81 complex. • Radiation increases the cellular uptake of exosomes through CD29/CD81 complex formation. - Abstract: Exosomes mediate intercellular communication, and mesenchymal stem cells (MSC) or their secreted exosomes affect a number of pathophysiologic states. Clinical applications of MSC and exosomes are increasingly anticipated. Radiation therapy is the main therapeutic tool for a number of various conditions. The cellular uptake mechanisms of exosomes and the effects of radiation on exosome–cell interactions are crucial, but they are not well understood. Here we examined the basic mechanisms and effects of radiation on exosome uptake processes in MSC. Radiation increased the cellular uptake of exosomes. Radiation markedly enhanced the initial cellular attachment to exosomes and induced the colocalization of integrin CD29 and tetraspanin CD81 on the cell surface without affecting their expression levels. Exosomes dominantly bound to the CD29/CD81 complex. Knockdown of CD29 completely inhibited the radiation-induced uptake, and additional or single knockdown of CD81 inhibited basal uptake as well as the increase in radiation-induced uptake. We also examined possible exosome uptake processes affected by radiation. Radiation-induced changes did not involve dynamin2, reactive oxygen species, or their evoked p38 mitogen-activated protein kinase-dependent endocytic or pinocytic pathways. Radiation increased the cellular uptake of exosomes through CD29/CD81 complex formation. These findings provide essential basic insights for potential therapeutic applications of exosomes or MSC in combination with radiation.

  1. Addressing healthcare.

    PubMed

    Daly, Rich

    2013-02-11

    Though President Barack Obama has rarely made healthcare references in his State of the Union addresses, health policy experts are hoping he changes that strategy this year. "The question is: Will he say anything? You would hope that he would, given that that was the major issue he started his presidency with," says Dr. James Weinstein, left, of the Dartmouth-Hitchcock health system. PMID:23487896

  2. Mild Airflow Limitation during N2 Sleep Increases K-complex Frequency and Slows Electroencephalographic Activity

    PubMed Central

    Nguyen, Chinh D.; Wellman, Andrew; Jordan, Amy S.; Eckert, Danny J.

    2016-01-01

    Study Objectives: To determine the effects of mild airflow limitation on K-complex frequency and morphology and electroencephalogram (EEG) spectral power. Methods: Transient reductions in continuous positive airway pressure (CPAP) during stable N2 sleep were performed to induce mild airflow limitation in 20 patients with obstructive sleep apnea (OSA) and 10 healthy controls aged 44 ± 13 y. EEG at C3 and airflow were measured in 1-min windows to quantify K-complex properties and EEG spectral power immediately before and during transient reductions in CPAP. The frequency and morphology (amplitude and latency of P200, N550 and N900 components) of K-complexes and EEG spectral power were compared between conditions. Results: During mild airflow limitation (18% reduction in peak inspiratory airflow from baseline, 0.38 ± 0.11 versus 0.31 ± 0.1 L/sec) insufficient to cause American Academy of Sleep Medicine-defined cortical arousal, K-complex frequency (9.5 ± 4.5 versus 13.7 ± 6.4 per min, P < 0.01), N550 amplitude (25 ± 3 versus 27 ± 3 μV, P < 0.01) and EEG spectral power (delta: 147 ± 48 versus 230 ± 99 μV2, P < 0.01 and theta bands: 31 ± 14 versus 34 ± 13 μV2, P < 0.01) significantly increased whereas beta band power decreased (14 ± 5 versus 11 ± 4 μV2, P < 0.01) compared to the preceding non flow-limited period on CPAP. K-complex frequency, morphology, and timing did not differ between patients and controls. Conclusion: Mild airflow limitation increases K-complex frequency, N550 amplitude, and spectral power of delta and theta bands. In addition to providing mechanistic insight into the role of mild airflow limitation on K-complex characteristics and EEG activity, these findings may have important implications for respiratory conditions in which airflow limitation during sleep is common (e.g., snoring and OSA). Citation: Nguyen CD, Wellman A, Jordan AS, Eckert DJ. Mild airflow limitation during N2 sleep increases k-complex frequency and slows

  3. Chemometric and Statistical Analyses of ToF-SIMS Spectra of Increasingly Complex Biological Samples

    SciTech Connect

    Berman, E S; Wu, L; Fortson, S L; Nelson, D O; Kulp, K S; Wu, K J

    2007-10-24

    Characterizing and classifying molecular variation within biological samples is critical for determining fundamental mechanisms of biological processes that will lead to new insights including improved disease understanding. Towards these ends, time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used to examine increasingly complex samples of biological relevance, including monosaccharide isomers, pure proteins, complex protein mixtures, and mouse embryo tissues. The complex mass spectral data sets produced were analyzed using five common statistical and chemometric multivariate analysis techniques: principal component analysis (PCA), linear discriminant analysis (LDA), partial least squares discriminant analysis (PLSDA), soft independent modeling of class analogy (SIMCA), and decision tree analysis by recursive partitioning. PCA was found to be a valuable first step in multivariate analysis, providing insight both into the relative groupings of samples and into the molecular basis for those groupings. For the monosaccharides, pure proteins and protein mixture samples, all of LDA, PLSDA, and SIMCA were found to produce excellent classification given a sufficient number of compound variables calculated. For the mouse embryo tissues, however, SIMCA did not produce as accurate a classification. The decision tree analysis was found to be the least successful for all the data sets, providing neither as accurate a classification nor chemical insight for any of the tested samples. Based on these results we conclude that as the complexity of the sample increases, so must the sophistication of the multivariate technique used to classify the samples. PCA is a preferred first step for understanding ToF-SIMS data that can be followed by either LDA or PLSDA for effective classification analysis. This study demonstrates the strength of ToF-SIMS combined with multivariate statistical and chemometric techniques to classify increasingly complex biological samples

  4. Increasing phonological complexity reveals heightened instability in inter-articulatory coordination in adults who stutter

    PubMed Central

    Smith, Anne; Sadagopan, Neeraja; Walsh, Bridget; Weber-Fox, Christine

    2010-01-01

    The potential role of phonological complexity in destabilizing the speech motor systems of adults who stutter was explored by assessing the performance of 17 adults who stutter and 17 matched control participants on a nonword repetition task. The nonwords varied in length and phonological complexity. Behavioral results revealed no differences between the stuttering and normally fluent groups on accuracy of nonword repetition. In contrast, dramatic differences between groups were observed in the kinematic data. Indices of the consistency of inter-articulator coordination revealed that adults who stutter were much less consistent in their coordinative patterns over repeated productions. With increasing length and complexity of the nonwords, between-group differences in coordinative consistency were more pronounced. Coordination consistency measures revealed that adults who stutter (but not normally fluent adults) showed within-session practice effects; their coordinative consistency improved in five later compared to five earlier productions. Adults who stutter produced the nonwords at a slower rate, but both groups showed increased rates of production on the later trials, indicating a practice effect for duration for both groups. We conclude that, though the adults who stutter performed behaviorally with the same accuracy as normally fluent adults, the nonword repetition task reveals remarkable differences in the speech motor dynamics underlying fluent speech production in adults who stutter compared to their normally fluent peers. These results support a multifactorial, dynamic model of stuttering in which linguistic complexity and utterance length are factors that contribute to the probability of breakdown of the speech motor system. PMID:20412979

  5. Adaptation and information in ontogenesis and phylogenesis. Increase of complexity and efficiency.

    PubMed

    Azzone, G F

    1997-01-01

    Adaptations during phylogenesis or ontogenesis can occur either by maintaining constant or by increasing the informational content of the organism. In the former case the increasing adaptations to external perturbation are achieved by increasing the rate of genome replication; the increased amount of DNA reflects an increase of total but not of law informational content. In the latter case the adaptations are achieved by either istructionist or evolutionary mechanism or a combination of both. Evolutionary adaptations occur during ontogenesis mainly in the brain-mind, immunological and receptor systems and involve a repertoire of receptors that are., clonally distributed, genome-conditioned and amplified by somatic mutation. Specificity and intensity of responses are achieved a posteriori as a result of natural selection of the clones. The major adaptations during phylogenesis are accompanied by increased complexity. They have been attributed to shifts, short in time and space, against the entropic drive and thus occur notwithstanding the entropic drive and the second law of thermodynamics. The alternative view, is that the generation of complexity is due to the second law of thermodynamics in its extended formulation which includes Prigogine's theorem of minimum entropy production. This view requires however that natural selection provides the biological system with structures that bring the reactions within Onsager's range. The hierarchical organization of the natural world thus reflects a stratified thermodynamic stability. As the evolutionary adaptations generate new information they may be assimilated to Maxwell demon type of processes. PMID:9646724

  6. Complex I and complex III inhibition specifically increase cytosolic hydrogen peroxide levels without inducing oxidative stress in HEK293 cells

    PubMed Central

    Forkink, Marleen; Basit, Farhan; Teixeira, José; Swarts, Herman G.; Koopman, Werner J.H.; Willems, Peter H.G.M.

    2015-01-01

    Inhibitor studies with isolated mitochondria demonstrated that complex I (CI) and III (CIII) of the electron transport chain (ETC) can act as relevant sources of mitochondrial reactive oxygen species (ROS). Here we studied ROS generation and oxidative stress induction during chronic (24 h) inhibition of CI and CIII using rotenone (ROT) and antimycin A (AA), respectively, in intact HEK293 cells. Both inhibitors stimulated oxidation of the ROS sensor hydroethidine (HEt) and increased mitochondrial NAD(P)H levels without major effects on cell viability. Integrated analysis of cells stably expressing cytosolic- or mitochondria-targeted variants of the reporter molecules HyPer (H2O2-sensitive and pH-sensitive) and SypHer (H2O2-insensitive and pH-sensitive), revealed that CI- and CIII inhibition increased cytosolic but not mitochondrial H2O2 levels. Total and mitochondria-specific lipid peroxidation was not increased in the inhibited cells as reported by the C11-BODIPY581/591 and MitoPerOx biosensors. Also expression of the superoxide-detoxifying enzymes CuZnSOD (cytosolic) and MnSOD (mitochondrial) was not affected. Oxyblot analysis revealed that protein carbonylation was not stimulated by CI and CIII inhibition. Our findings suggest that chronic inhibition of CI and CIII: (i) increases the levels of HEt-oxidizing ROS and (ii) specifically elevates cytosolic but not mitochondrial H2O2 levels, (iii) does not induce oxidative stress or substantial cell death. We conclude that the increased ROS levels are below the stress-inducing level and might play a role in redox signaling. PMID:26516986

  7. Increasing the bioavailability of Ru(III) anticancer complexes through hydrophobic albumin interactions.

    PubMed

    Webb, Michael I; Wu, Boris; Jang, Thalia; Chard, Ryan A; Wong, Edwin W Y; Wong, May Q; Yapp, Donald T T; Walsby, Charles J

    2013-12-01

    A series of pyridine-based derivatives of the clinically successful Ru(III)-based complexes indazolium [trans-RuCl4(1H-indazole)2] (KP1019) and sodium [trans-RuCl4(1H-indazole)2] (KP1339) have been synthesized to probe the effect of hydrophobic interactions with human serum albumin (hsA) on anticancer activity. The solution behavior and protein interactions of the new compounds were characterized by using electron paramagnetic resonance (EPR) and UV/Vis spectroscopy. These studies have revealed that incorporation of hydrophobic substituents at the 4'-position of the axial pyridine ligand stabilizes non-coordinate interactions with hsA. As a consequence, direct coordination to the protein is inhibited, which is expected to increase the bioavailability of the complexes, thus potentially leading to improved anticancer activity. By using this approach, the lifetimes of hydrophobic protein interactions were extended from 2 h for the unsubstituted pyridine complex, to more than 24 h for several derivatives. Free complexes were tested for their anticancer activity against the SW480 human colon carcinoma cell line, exhibiting low cytotoxicity. Pre-treatment with hsA improved the solubility of every compound and led to some changes in activity. Particularly notable was the difference in activity between the methyl- and dibenzyl-functionalized complexes. The former shows reduced activity after incubation with hsA, indicating reduced bioavailability due to protein coordination. The latter exhibits little activity on its own but, following treatment with hsA, exhibited significant cytotoxicity, which is consistent with its ability to form non-coordinate interactions with the protein. Overall, our studies demonstrate that non-coordinate interactions with hsA are a viable target for enhancing the activity of Ru(III)-based complexes in vivo. PMID:24203647

  8. Increasing solubility of red bell pepper carotenoids by complexation with 2-hydroxypropyl-β-cyclodextrin.

    PubMed

    de Lima Petito, Nicolly; da Silva Dias, Daiana; Costa, Valéria Gonçalves; Falcão, Deborah Quintanilha; de Lima Araujo, Kátia Gome

    2016-10-01

    Red bell pepper carotenoids were complexed with 2-hydroxypropyl-β-cyclodextrin (2-HPβCD) in different mass ratios (1:4, 1:6, 1:8 and 1:10) through ultrasonic homogenization in order to increase carotenoid solubility and their use as natural pigment in food. Inclusion complexes, red bell pepper extract and physical mixtures were analyzed by DSC, FT-IR, (1)H NMR and DLS. Solubility assay was performed to identify the effect of complexation on the solubility of carotenoids. From characterization assays, results showed that inclusion process occurred for all tested ratios. Results for water solubility assays demonstrated clear differences between solubility index of inclusion complexes (8.06±2.59-16.55±4.40mg/mL) and physical mixtures (3.53±1.44-7.3±1.88mg/mL), while carotenoid extract was no water soluble, as expected. These results indicated that molecular inclusion of carotenoids in 2-HPβCD was efficient to enhance their solubility in water, enabling application of red bell pepper carotenoid as natural pigment and/or bioactive substances in food. PMID:27132832

  9. Ensuring Access to Safe, Legal Abortion in an Increasingly Complex Regulatory Environment.

    PubMed

    Paul, Maureen; Norton, Mary E

    2016-07-01

    Restrictions on access to abortion in the United States have reached proportions unprecedented since the nationwide legalization of abortion in 1973. Although some restrictions aim to discourage women from having abortions, many others impede access by affecting the timeliness, affordability, or availability of services. Evidence indicates that these restrictions do not increase abortion safety; rather, they create logistic barriers for women seeking abortion, and they have the greatest effect on women with the fewest resources. In this commentary, we recall the important role that obstetrician-gynecologists (ob-gyns) have played, both before and after Roe v. Wade, in facilitating access to safe abortion care. Using the literature on abortion safety and access as a foundation, we propose several practical ideas about what we as ob-gyns can do to address the current threat to abortion access, whether or not we provide abortion services in practice. We hope that this commentary will encourage discourse within our profession and prompt other suggestions. As ob-gyns who are dedicated to addressing health disparities and promoting the health and well-being of our patients, we can make a difference. PMID:27275804

  10. Inaugural address

    NASA Astrophysics Data System (ADS)

    Joshi, P. S.

    2014-03-01

    From jets to cosmos to cosmic censorship P S Joshi Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400005, India E-mail: psj@tifr.res.in 1. Introduction At the outset, I should like to acknowledge that part of the title above, which tries to capture the main flavour of this meeting, and has been borrowed from one of the plenary talks at the conference. When we set out to make the programme for the conference, we thought of beginning with observations on the Universe, but then we certainly wanted to go further and address deeper questions, which were at the very foundations of our inquiry, and understanding on the nature and structure of the Universe. I believe, we succeeded to a good extent, and it is all here for you in the form of these Conference Proceedings, which have been aptly titled as 'Vishwa Mimansa', which could be possibly translated as 'Analysis of the Universe'! It is my great pleasure and privilege to welcome you all to the ICGC-2011 meeting at Goa. The International Conference on Gravitation and Cosmology (ICGC) series of meetings are being organized by the Indian Association for General Relativity and Gravitation (IAGRG), and the first such meeting was planned and conducted in Goa in 1987, with subsequent meetings taking place at a duration of about four years at various locations in India. So, it was thought appropriate to return to Goa to celebrate the 25 years of the ICGC meetings. The recollections from that first meeting have been recorded elsewhere here in these Proceedings. The research and teaching on gravitation and cosmology was initiated quite early in India, by V V Narlikar at the Banares Hindu University, and by N R Sen in Kolkata in the 1930s. In course of time, this activity grew and gained momentum, and in early 1969, at the felicitation held for the 60 years of V V Narlikar at a conference in Ahmedabad, P C Vaidya proposed the formation of the IAGRG society, with V V Narlikar being the first President. This

  11. Evolution of Integrated Causal Structures in Animats Exposed to Environments of Increasing Complexity

    PubMed Central

    Albantakis, Larissa; Hintze, Arend; Koch, Christof; Adami, Christoph; Tononi, Giulio

    2014-01-01

    Natural selection favors the evolution of brains that can capture fitness-relevant features of the environment's causal structure. We investigated the evolution of small, adaptive logic-gate networks (“animats”) in task environments where falling blocks of different sizes have to be caught or avoided in a ‘Tetris-like’ game. Solving these tasks requires the integration of sensor inputs and memory. Evolved networks were evaluated using measures of information integration, including the number of evolved concepts and the total amount of integrated conceptual information. The results show that, over the course of the animats' adaptation, i) the number of concepts grows; ii) integrated conceptual information increases; iii) this increase depends on the complexity of the environment, especially on the requirement for sequential memory. These results suggest that the need to capture the causal structure of a rich environment, given limited sensors and internal mechanisms, is an important driving force for organisms to develop highly integrated networks (“brains”) with many concepts, leading to an increase in their internal complexity. PMID:25521484

  12. Interactions between default mode and control networks as a function of increasing cognitive reasoning complexity.

    PubMed

    Hearne, Luke; Cocchi, Luca; Zalesky, Andrew; Mattingley, Jason B

    2015-07-01

    Successful performance of challenging cognitive tasks depends on a consistent functional segregation of activity within the default-mode network, on the one hand, and control networks encompassing frontoparietal and cingulo-opercular areas on the other. Recent work, however, has suggested that in some cognitive control contexts nodes within the default-mode and control networks may actually cooperate to achieve optimal task performance. Here, we used functional magnetic resonance imaging to examine whether the ability to relate variables while solving a cognitive reasoning problem involves transient increases in connectivity between default-mode and control regions. Participants performed a modified version of the classic Wason selection task, in which the number of variables to be related is systematically varied across trials. As expected, areas within the default-mode network showed a parametric deactivation with increases in relational complexity, compared with neural activity in null trials. Critically, some of these areas also showed enhanced connectivity with task-positive control regions. Specifically, task-based connectivity between the striatum and the angular gyri, and between the thalamus and right temporal pole, increased as a function of relational complexity. These findings challenge the notion that functional segregation between regions within default-mode and control networks invariably support cognitive task performance, and reveal previously unknown roles for the striatum and thalamus in managing network dynamics during cognitive reasoning. PMID:25833189

  13. Opening addresses.

    PubMed

    Chukudebelu, W O; Lucas, A O; Ransome-kuti, O; Akinla, O; Obayi, G U

    1988-01-01

    The theme of the 3rd International Conference of the Society of Gynecology and Obstetrics of Nigeria (SOGON) held October 26, 1986 in Enugu was maternal morbidity and mortality in Africa. The opening addresses emphasize the high maternal mortality rate in Africa and SOGON's dedication to promoting women's health and welfare. In order to reduce maternal mortality, the scope of this problem must be made evident by gathering accurate mortality rates through maternity care monitoring and auditing. Governments, health professionals, educators, behavioral scientists, and communication specialists have a responsibility to improve maternal health services in this country. By making the population aware of this problem through education, measures can be taken to reduce the presently high maternal mortality rates. Nigerian women are physically unprepared for childbirth; therefore, balanced diets and disease prevention should be promoted. Since about 40% of deliveries are unmanaged, training for traditional birth attendants should be provided. Furthermore, family planning programs should discourage teenage pregnancies, encourage birth spacing and small families, and promote the use of family planning techniques among men. The problem of child bearing and rearing accompanied by hard work should also be investigated. For practices to change so that maternal mortality rates can be reduced, attitudes must be changed such that the current rates are viewed as unacceptable. PMID:12179275

  14. Opening Address

    NASA Astrophysics Data System (ADS)

    Yamada, T.

    2014-12-01

    Ladies and Gentlemen, it is my great honor and pleasure to present an opening address of the 3rd International Workshop on "State of the Art in Nuclear Cluster Physics"(SOTANCP3). On the behalf of the organizing committee, I certainly welcome all your visits to KGU Kannai Media Center belonging to Kanto Gakuin University, and stay in Yokohama. In particular, to whom come from abroad more than 17 countries, I would appreciate your participations after long long trips from your homeland to Yokohama. The first international workshop on "State of the Art in Nuclear Cluster Physics", called SOTANCP, was held in Strasbourg, France, in 2008, and the second one was held in Brussels, Belgium, in 2010. Then the third workshop is now held in Yokohama. In this period, we had the traditional 10th cluster conference in Debrecen, Hungary, in 2012. Thus we have the traditional cluster conference and SOTANCP, one after another, every two years. This obviously shows our field of nuclear cluster physics is very active and flourishing. It is for the first time in about 10 years to hold the international workshop on nuclear cluster physics in Japan, because the last cluster conference held in Japan was in Nara in 2003, about 10 years ago. The president in Nara conference was Prof. K. Ikeda, and the chairpersons were Prof. H. Horiuchi and Prof. I. Tanihata. I think, quite a lot of persons in this room had participated at the Nara conference. Since then, about ten years passed. So, this workshop has profound significance for our Japanese colleagues. The subjects of this workshop are to discuss "the state of the art in nuclear cluster physics" and also discuss the prospect of this field. In a couple of years, we saw significant progresses of this field both in theory and in experiment, which have brought better and new understandings on the clustering aspects in stable and unstable nuclei. I think, the concept of clustering has been more important than ever. This is true also in the

  15. Parasites affect food web structure primarily through increased diversity and complexity

    USGS Publications Warehouse

    Dunne, Jennifer A.; Lafferty, Kevin D.; Dobson, Andrew P.; Hechinger, Ryan F.; Kuris, Armand M.; Martinez, Neo D.; McLaughlin, John P.; Mouritsen, Kim N.; Poulin, Robert; Reise, Karsten; Stouffer, Daniel B.; Thieltges, David W.; Williams, Richard J.; Zander, Claus Dieter

    2013-01-01

    Comparative research on food web structure has revealed generalities in trophic organization, produced simple models, and allowed assessment of robustness to species loss. These studies have mostly focused on free-living species. Recent research has suggested that inclusion of parasites alters structure. We assess whether such changes in network structure result from unique roles and traits of parasites or from changes to diversity and complexity. We analyzed seven highly resolved food webs that include metazoan parasite data. Our analyses show that adding parasites usually increases link density and connectance (simple measures of complexity), particularly when including concomitant links (links from predators to parasites of their prey). However, we clarify prior claims that parasites ‘‘dominate’’ food web links. Although parasites can be involved in a majority of links, in most cases classic predation links outnumber classic parasitism links. Regarding network structure, observed changes in degree distributions, 14 commonly studied metrics, and link probabilities are consistent with scale-dependent changes in structure associated with changes in diversity and complexity. Parasite and free-living species thus have similar effects on these aspects of structure. However, two changes point to unique roles of parasites. First, adding parasites and concomitant links strongly alters the frequency of most motifs of interactions among three taxa, reflecting parasites’ roles as resources for predators of their hosts, driven by trophic intimacy with their hosts. Second, compared to free-living consumers, many parasites’ feeding niches appear broader and less contiguous, which may reflect complex life cycles and small body sizes. This study provides new insights about generic versus unique impacts of parasites on food web structure, extends the generality of food web theory, gives a more rigorous framework for assessing the impact of any species on trophic

  16. Ibutilide Increases the Variability and Complexity of Atrial Fibrillation Electrograms: Antiarrhythmic Insights Using Signal Analyses

    PubMed Central

    Biviano, Angelo B.; Ciaccio, Edward J.; Whang, William; Garan, Hasan

    2013-01-01

    Introduction Intravenous ibutilide is used to convert atrial fibrillation (AF) to sinus rhythm due to its Class III antiarrhythmic mechanisms. However, the effects of ibutilide on local electrograms during AF have not been elucidated. Methods and Results We used electrogram (EGM) analysis techniques to characterize how ibutilide administration changes the frequency, morphology, and repeatability of AF EGM signals, thereby providing insight into ibutilide’s antiarrhythmic mechanism of action. AF recordings were collected from 21 patients with AF both before and after ibutilide administration. The effects of ibutilide on the following AF EGM parameters were assessed: 1) dominant frequency, 2) variations in EGM amplitude and overall morphology, 3) repetition of electrogram patterns, and 4) complexity of the AF frequency spectra. When comparing pre- vs. post-ibutilide administration EGMs, DF decreased from 5.45 to 4.02 Hz (p<0.0001). There was an increase both in the variability of AF EGM amplitudes (p=0.003) and variability of overall AF EGM morphologies (p=0.003). AF EGM pattern repetitiveness decreased (p=0.01), and the AF frequency spectral profile manifested greater complexity (p=0.02). Conclusions Novel electrogram signal analysis techniques reveal that ibutilide administration causes increased complexity in the atrial electrical activation pattern while decreasing rate. These findings may be explained by the progressive destabilization of higher frequency, more homogeneous primary drivers of AF over the course of ibutilide administration and/or less uniform propagation of atrial activation, until AF maintenance becomes more difficult and either transforms to atrial tachycardia or terminates to sinus rhythm. PMID:23875908

  17. Welcome Address

    NASA Astrophysics Data System (ADS)

    Kiku, H.

    2014-12-01

    Ladies and Gentlemen, It is an honor for me to present my welcome address in the 3rd International Workshop on "State of the Art in Nuclear Cluster Physics"(SOTANCP3), as the president of Kanto Gakuin University. Particularly to those from abroad more than 17 countries, I am very grateful for your participation after long long trips from your home to Yokohama. On the behalf of the Kanto Gakuin University, we certainly welcome your visit to our university and stay in Yokohama. First I would like to introduce Kanto Gakuin University briefly. Kanto Gakuin University, which is called KGU, traces its roots back to the Yokohama Baptist Seminary founded in 1884 in Yamate, Yokohama. The seminary's founder was Albert Arnold Bennett, alumnus of Brown University, who came to Japan from the United States to establish a theological seminary for cultivating and training Japanese missionaries. Now KGU is a major member of the Kanto Gakuin School Corporation, which is composed of two kindergartens, two primary schools, two junior high schools, two senior high schools as well as KGU. In this university, we have eight faculties with graduate school including Humanities, Economics, Law, Sciences and Engineering, Architecture and Environmental Design, Human and Environmental Studies, Nursing, and Law School. Over eleven thousands students are currently learning in our university. By the way, my major is the geotechnical engineering, and I belong to the faculty of Sciences and Engineering in my university. Prof. T. Yamada, here, is my colleague in the same faculty. I know that the nuclear physics is one of the most active academic fields in the world. In fact, about half of the participants, namely, more than 50 scientists, come from abroad in this conference. Moreover, I know that the nuclear physics is related to not only the other fundamental physics such as the elementary particle physics and astrophysics but also chemistry, medical sciences, medical cares, and radiation metrology

  18. Phenylbutyrate increases pyruvate dehydrogenase complex activity in cells harboring a variety of defects

    PubMed Central

    Ferriero, Rosa; Boutron, Audrey; Brivet, Michele; Kerr, Douglas; Morava, Eva; Rodenburg, Richard J; Bonafé, Luisa; Baumgartner, Matthias R; Anikster, Yair; Braverman, Nancy E; Brunetti-Pierri, Nicola

    2014-01-01

    Objective Deficiency of pyruvate dehydrogenase complex (PDHC) is the most common genetic disorder leading to lactic acidosis. PDHC deficiency is genetically heterogenous and most patients have defects in the X-linked E1-α gene but defects in the other components of the complex encoded by PDHB, PDHX, DLAT, DLD genes or in the regulatory enzyme encoded by PDP1 have also been found. Phenylbutyrate enhances PDHC enzymatic activity in vitro and in vivo by increasing the proportion of unphosphorylated enzyme through inhibition of pyruvate dehydrogenase kinases and thus, has potential for therapy of patients with PDHC deficiency. In the present study, we investigated response to phenylbutyrate of multiple cell lines harboring all known gene defects resulting in PDHC deficiency. Methods Fibroblasts of patients with PDHC deficiency were studied for their enzyme activity at baseline and following phenylbutyrate incubation. Drug responses were correlated with genotypes and protein levels by Western blotting. Results Large deletions affecting PDHA1 that result in lack of detectable protein were unresponsive to phenylbutyrate, whereas increased PDHC activity was detected in most fibroblasts harboring PDHA1 missense mutations. Mutations affecting the R349-α residue were directed to proteasome degradation and were consistently unresponsive to short-time drug incubation but longer incubation resulted in increased levels of enzyme activity and protein that may be due to an additional effect of phenylbutyrate as a molecular chaperone. Interpretation PDHC enzyme activity was enhanced by phenylbutyrate in cells harboring missense mutations in PDHB, PDHX, DLAT, DLD, and PDP1 genes. In the prospect of a clinical trial, the results of this study may allow prediction of in vivo response in patients with PDHC deficiency harboring a wide spectrum of molecular defects. PMID:25356417

  19. MOZ increases p53 acetylation and premature senescence through its complex formation with PML.

    PubMed

    Rokudai, Susumu; Laptenko, Oleg; Arnal, Suzzette M; Taya, Yoichi; Kitabayashi, Issay; Prives, Carol

    2013-03-01

    Monocytic leukemia zinc finger (MOZ)/KAT6A is a MOZ, Ybf2/Sas3, Sas2, Tip60 (MYST)-type histone acetyltransferase that functions as a coactivator for acute myeloid leukemia 1 protein (AML1)- and Ets family transcription factor PU.1-dependent transcription. We previously reported that MOZ directly interacts with p53 and is essential for p53-dependent selective regulation of p21 expression. We show here that MOZ is an acetyltransferase of p53 at K120 and K382 and colocalizes with p53 in promyelocytic leukemia (PML) nuclear bodies following cellular stress. The MOZ-PML-p53 interaction enhances MOZ-mediated acetylation of p53, and this ternary complex enhances p53-dependent p21 expression. Moreover, we identified an Akt/protein kinase B recognition sequence in the PML-binding domain of MOZ protein. Akt-mediated phosphorylation of MOZ at T369 has a negative effect on complex formation between PML and MOZ. As a result of PML-mediated suppression of Akt, the increased PML-MOZ interaction enhances p21 expression and induces p53-dependent premature senescence upon forced PML expression. Our research demonstrates that MOZ controls p53 acetylation and transcriptional activity via association with PML. PMID:23431171

  20. Convocation address.

    PubMed

    Alexander, P C

    1994-07-01

    Total world population is growing at the annual rate of 2%. While this rate of growth represents a decline from the annual growth rate of 2.5% during the early 1960s, world population still continues to grow rapidly in absolute terms as a result of the already enormous population base. Experts predict world population to grow to 12-14 billion before it stabilizes. Most of this growth will be due to high fertility amid declining mortality in developing countries; 80% of world population by the year 2000 will be in developing countries. India, for example, had a population of 358 million people in 1950. That population, however, should grow to more than one billion by the year 2000. The author, governor of Maharashtra, congratulates all who have successfully completed courses at the International Institute for Population Sciences during the year and voices his expectation that graduates will use their newfound knowledge and expertise in research and teaching as well as in developing meaningful and effective population policies in their respective countries. He also describes some of India's current population-related problems and future prospects. India has thus far kept its rate of food production above the rate of population growth. Even so, the average caloric intake in India needs to be increased by at least 50% in order for the population to maintain adequate health standards. The current scarcity of additional arable land, the need to halt further deforestation, and the ongoing absolute growth in population, however, suggest that India will be unable to raise the level of caloric intake for its people. India may even become dependent upon other countries to provide food for its population. PMID:12346131

  1. Opening address

    NASA Astrophysics Data System (ADS)

    Castagnoli, C.

    1994-01-01

    Ladies and Gentlemen My cordial thanks to you for participating in our workshop and to all those who have sponsored it. When in 1957 I attended the International Congress on Fundamental Constants held in Turin on the occasion of the first centenary of the death of Amedeo Avogadro, I did not expect that about thirty-five years later a small but representative number of distinguished scientists would meet here again, to discuss how to go beyond the sixth decimal figure of the Avogadro constant. At that time, the uncertainty of the value of this constant was linked to the fourth decimal figure, as reported in the book by DuMond and Cohen. The progress made in the meantime is universally acknowledged to be due to the discovery of x-ray interferometry. We are honoured that one of the two founding fathers, Prof. Ulrich Bonse, is here with us, but we regret that the other, Prof. Michael Hart, is not present. After Bonse and Hart's discovery, the x-ray crystal density method triggered, as in a chain reaction, the investigation of two other quantities related to the Avogadro constant—density and molar mass. Scientists became, so to speak, resonant and since then have directed their efforts, just to mention a few examples, to producing near-perfect silicon spheres and determining their density, to calibrating, with increasing accuracy, mass spectrometers, and to studying the degree of homogeneity of silicon specimens. Obviously, I do not need to explain to you why the Avogadro constant is important. I wish, however, to underline that it is not only because of its position among fundamental constants, as we all know very well its direct links with the fine structure constant, the Boltzmann and Faraday constants, the h/e ratio, but also because when a new value of NA is obtained, the whole structure of the fundamental constants is shaken to a lesser or greater extent. Let me also remind you that the second part of the title of this workshop concerns the silicon

  2. Genome-enabled Modeling of Microbial Biogeochemistry using a Trait-based Approach. Does Increasing Metabolic Complexity Increase Predictive Capabilities?

    NASA Astrophysics Data System (ADS)

    King, E.; Karaoz, U.; Molins, S.; Bouskill, N.; Anantharaman, K.; Beller, H. R.; Banfield, J. F.; Steefel, C. I.; Brodie, E.

    2015-12-01

    The biogeochemical functioning of ecosystems is shaped in part by genomic information stored in the subsurface microbiome. Cultivation-independent approaches allow us to extract this information through reconstruction of thousands of genomes from a microbial community. Analysis of these genomes, in turn, gives an indication of the organisms present and their functional roles. However, metagenomic analyses can currently deliver thousands of different genomes that range in abundance/importance, requiring the identification and assimilation of key physiologies and metabolisms to be represented as traits for successful simulation of subsurface processes. Here we focus on incorporating -omics information into BioCrunch, a genome-informed trait-based model that represents the diversity of microbial functional processes within a reactive transport framework. This approach models the rate of nutrient uptake and the thermodynamics of coupled electron donors and acceptors for a range of microbial metabolisms including heterotrophs and chemolithotrophs. Metabolism of exogenous substrates fuels catabolic and anabolic processes, with the proportion of energy used for cellular maintenance, respiration, biomass development, and enzyme production based upon dynamic intracellular and environmental conditions. This internal resource partitioning represents a trade-off against biomass formation and results in microbial community emergence across a fitness landscape. Biocrunch was used here in simulations that included organisms and metabolic pathways derived from a dataset of ~1200 non-redundant genomes reflecting a microbial community in a floodplain aquifer. Metagenomic data was directly used to parameterize trait values related to growth and to identify trait linkages associated with respiration, fermentation, and key enzymatic functions such as plant polymer degradation. Simulations spanned a range of metabolic complexities and highlight benefits originating from simulations

  3. Academic Institutions and One Health: Building Capacity for Transdisciplinary Research Approaches to Address Complex Health Issues at the Animal–Human–Ecosystem Interface

    PubMed Central

    Allen-Scott, Lisa K.; Buntain, Bonnie; Hatfield, Jennifer M.; Meisser, Andrea

    2015-01-01

    To improve health at the human, animal, and ecosystem interface, defined as One Health, training of researchers must transcend individual disciplines to develop a new process of collaboration. The transdisciplinary research approach integrates frameworks and methodologies beyond academic disciplines and includes involvement of and input from policy makers and members of the community. The authors argue that there should be a significant shift in academic institutions’ research capacity to achieve the added value of a transdisciplinary approach for addressing One Health problems. This Perspective is a call to action for academic institutions to provide the foundations for this salient shift. The authors begin by describing the transdisciplinary approach, propose methods for building transdisciplinary research capacity, and highlight three value propositions that support the case. Examples are provided to illustrate how the transdisciplinary approach to research adds value through improved sustainability of impact, increased cost-effectiveness, and enhanced abilities to mitigate potentially harmful unintended consequences. The authors conclude with three key recommendations for academic institutions: (1) a focus on creating enabling environments for One Health and transdisciplinary research, (2) the development of novel funding structures for transdisciplinary research, and (3) training of “transmitters” using real-world-oriented educational programs that break down research silos through collaboration across disciplines. PMID:25650827

  4. Anomalously increased lifetimes of biological complexes at zero force due to the protein-water interface.

    PubMed

    Pereverzev, Yuriy V; Prezhdo, Oleg V; Sokurenko, Evgeni V

    2008-09-11

    A number of biological bonds show dramatically increased lifetimes at zero-force conditions, compared to lifetimes when even a small tensile force is applied to the ligand. The discrepancy is so great that it cannot be explained by the traditional receptor-ligand binding models. This generic phenomenon is rationalized here by considering the interaction of water with the receptor-ligand complex. It is argued that the water-protein interaction creates an energy barrier that prevents the ligand unbinding in the absence of the force. The properties of the interaction are such that even application of a relatively low force results in a dramatic drop of the bond lifetime due to the alteration of the water-receptor and water-ligand interaction network. The phenomenon is described by the presence of a second shallow interaction energy minimum for the bound ligand followed by a wide receptor-ligand dissociation barrier. The general analysis is applied quantitatively to the actin-myosin system, which demonstrates the gigantic drop of the bond lifetime at small forces and catch behavior (an increase in the lifetime) at moderate forces. The base hypothesis proposed to explain the small-force abnormal drop in the bond lifetime suggests that the majority of biological bonds may exhibit this phenomenon irrespectively whether they behave as slip or catch-slip bonds. PMID:18710275

  5. Modeling Increased Complexity and the Reliance on Automation: FLightdeck Automation Problems (FLAP) Model

    NASA Technical Reports Server (NTRS)

    Ancel, Ersin; Shih, Ann T.

    2014-01-01

    This paper highlights the development of a model that is focused on the safety issue of increasing complexity and reliance on automation systems in transport category aircraft. Recent statistics show an increase in mishaps related to manual handling and automation errors due to pilot complacency and over-reliance on automation, loss of situational awareness, automation system failures and/or pilot deficiencies. Consequently, the aircraft can enter a state outside the flight envelope and/or air traffic safety margins which potentially can lead to loss-of-control (LOC), controlled-flight-into-terrain (CFIT), or runway excursion/confusion accidents, etc. The goal of this modeling effort is to provide NASA's Aviation Safety Program (AvSP) with a platform capable of assessing the impacts of AvSP technologies and products towards reducing the relative risk of automation related accidents and incidents. In order to do so, a generic framework, capable of mapping both latent and active causal factors leading to automation errors, is developed. Next, the framework is converted into a Bayesian Belief Network model and populated with data gathered from Subject Matter Experts (SMEs). With the insertion of technologies and products, the model provides individual and collective risk reduction acquired by technologies and methodologies developed within AvSP.

  6. β-Amyloid-aluminum complex alters cytoskeletal stability and increases ROS production in cortical neurons.

    PubMed

    Bolognin, Silvia; Zatta, Paolo; Lorenzetto, Erika; Valenti, Maria Teresa; Buffelli, Mario

    2013-04-01

    Several lines of evidence have supported the potential involvement of metal ions in the etiology of Alzheimer's Disease (AD). However, the molecular mechanisms underlying this interaction are still partially unknown. Previous work from our laboratory has shown that β-amyloid peptide (Aβ) aggregation was strongly influenced by the conjugation of the peptide with few metal ions (aluminum, copper, zinc, and iron) that are found in high concentrations in the senile plaque core. The binding of aluminum (Al) to Aβ specifically stabilized the peptide in an oligomeric conformation. Here, we show that the aggregation of Aβ-Al was boosted by sodium dodecyl sulfate, a detergent that mimics some characteristics of biological membrane, suggesting a potential role for membrane components in the Aβ aggregation process. Notably, we also found that Aβ-Al caused mitochondrial dysfunction and reactive oxygen species production in primary cortical neurons. Aβ-Al strongly promoted also alterations in cytoskeleton network as shown by the increased F-actin expression and the occurrence of neuritic beading. Interestingly, the neurotoxic effect of this metal complex was associated with a decreased mRNA expression of ubiquitin thiolesterase, an ubiquitin-dependent protein involved in catabolic process, and by the increased expression of glutaminyl cyclase, responsible for pathological post-translational modification of Aβ. These results suggest that, in neuronal cells, Aβ-Al can induce relevant detrimental changes that resemble pathological hallmarks of AD. PMID:23416043

  7. Chlorogenic acid ameliorates intestinal mitochondrial injury by increasing antioxidant effects and activity of respiratory complexes.

    PubMed

    Zhou, Yan; Zhou, Lili; Ruan, Zheng; Mi, Shumei; Jiang, Min; Li, Xiaolan; Wu, Xin; Deng, Zeyuan; Yin, Yulong

    2016-05-01

    Dietary polyphenols are thought to be beneficial for human health by acting as antioxidants. Chlorogenic acid (CGA) is abundant in plant-based foods as an ester of caffeic acid and quinic acid. In this study, we investigated the effects of CGA on mitochondrial protection. Our results demonstrated that pretreatment with CGA ameliorated the intestinal mitochondrial injury induced by H2O2; membrane potential was increased, mitochondrial swelling, levels of reactive oxygen species, contents of 8-hydroxy-2-deoxyguanosine, and cytochrome c released were decreased. The beneficial effects of CGA were accompanied by an increase in antioxidant and respiratory-chain complex I, IV, and V activities. In trinitrobenzene-sulfonic acid-induced colitic rats indicated that CGA supplementation improved mitochondria ultrastructure and decreased mitochondrial injury. Our results suggest a promising role for CGA as a mitochondria-targeted antioxidant in combating intestinal oxidative injury. Daily intake of diets containing CGA, such as coffee and honeysuckle, may be useful for prevention of intestinal diseases. PMID:26824685

  8. Impacts of increasing the aerosol complexity in the Met Office global numerical weather prediction model

    NASA Astrophysics Data System (ADS)

    Mulcahy, J. P.; Walters, D. N.; Bellouin, N.; Milton, S. F.

    2014-05-01

    The inclusion of the direct and indirect radiative effects of aerosols in high-resolution global numerical weather prediction (NWP) models is being increasingly recognised as important for the improved accuracy of short-range weather forecasts. In this study the impacts of increasing the aerosol complexity in the global NWP configuration of the Met Office Unified Model (MetUM) are investigated. A hierarchy of aerosol representations are evaluated including three-dimensional monthly mean speciated aerosol climatologies, fully prognostic aerosols modelled using the CLASSIC aerosol scheme and finally, initialised aerosols using assimilated aerosol fields from the GEMS project. The prognostic aerosol schemes are better able to predict the temporal and spatial variation of atmospheric aerosol optical depth, which is particularly important in cases of large sporadic aerosol events such as large dust storms or forest fires. Including the direct effect of aerosols improves model biases in outgoing long-wave radiation over West Africa due to a better representation of dust. However, uncertainties in dust optical properties propagate to its direct effect and the subsequent model response. Inclusion of the indirect aerosol effects improves surface radiation biases at the North Slope of Alaska ARM site due to lower cloud amounts in high-latitude clean-air regions. This leads to improved temperature and height forecasts in this region. Impacts on the global mean model precipitation and large-scale circulation fields were found to be generally small in the short-range forecasts. However, the indirect aerosol effect leads to a strengthening of the low-level monsoon flow over the Arabian Sea and Bay of Bengal and an increase in precipitation over Southeast Asia. Regional impacts on the African Easterly Jet (AEJ) are also presented with the large dust loading in the aerosol climatology enhancing of the heat low over West Africa and weakening the AEJ. This study highlights the

  9. Impacts of increasing the aerosol complexity in the Met Office global NWP model

    NASA Astrophysics Data System (ADS)

    Mulcahy, J. P.; Walters, D. N.; Bellouin, N.; Milton, S. F.

    2013-11-01

    Inclusion of the direct and indirect radiative effects of aerosols in high resolution global numerical weather prediction (NWP) models is being increasingly recognised as important for the improved accuracy of short-range weather forecasts. In this study the impacts of increasing the aerosol complexity in the global NWP configuration of the Met Office Unified Model (MetUM) are investigated. A hierarchy of aerosol representations are evaluated including three dimensional monthly mean speciated aerosol climatologies, fully prognostic aerosols modelled using the CLASSIC aerosol scheme and finally, initialised aerosols using assimilated aerosol fields from the GEMS project. The prognostic aerosol schemes are better able to predict the temporal and spatial variation of atmospheric aerosol optical depth, which is particularly important in cases of large sporadic aerosol events such as large dust storms or forest fires. Including the direct effect of aerosols improves model biases in outgoing longwave radiation over West Africa due to a better representation of dust. However, uncertainties in dust optical properties propogate to its direct effect and the subsequent model response. Inclusion of the indirect aerosol effects improves surface radiation biases at the North Slope of Alaska ARM site due to lower cloud amounts in high latitude clean air regions. This leads to improved temperature and height forecasts in this region. Impacts on the global mean model precipitation and large-scale circulation fields were found to be generally small in the short range forecasts. However, the indirect aerosol effect leads to a strengthening of the low level monsoon flow over the Arabian Sea and Bay of Bengal and an increase in precipitation over Southeast Asia. Regional impacts on the African Easterly Jet (AEJ) are also presented with the large dust loading in the aerosol climatology enhancing of the heat low over West Africa and weakening the AEJ. This study highlights the importance

  10. Impacts of increasing the aerosol complexity in the Met Office global NWP model

    NASA Astrophysics Data System (ADS)

    Mulcahy, Jane; Walters, David; Bellouin, Nicolas; Milton, Sean

    2014-05-01

    Inclusion of the direct and indirect radiative effects of aerosols in high resolution global numerical weather prediction (NWP) models is being increasingly recognised as important for the improved accuracy of short-range weather forecasts. In this study the impacts of increasing the aerosol complexity in the global NWP configuration of the Met Office Unified Model (MetUM) are investigated. A hierarchy of aerosol representations are evaluated including three dimensional monthly mean speciated aerosol climatologies, fully prognostic aerosols modelled using the CLASSIC aerosol scheme and finally, initialised aerosols using assimilated aerosol fields from the GEMS project. The prognostic aerosol schemes are better able to predict the temporal and spatial variation of atmospheric aerosol optical depth, which is particularly important in cases of large sporadic aerosol events such as large dust storms or forest fires. Including the direct effect of aerosols improves model biases in outgoing longwave radiation over West Africa due to a better representation of dust. Inclusion of the indirect aerosol effects has significant impacts on the SW radiation particularly at high latitudes due to lower cloud amounts in high latitude clean air regions. This leads to improved surface radiation biases at the North Slope of Alaska ARM site. Verification of temperature and height forecasts is also improved in this region. Impacts on the global mean model precipitation and large-scale circulation fields were found to be generally small in the short range forecasts. However, the indirect aerosol effect leads to a strengthening of the low level monsoon flow over the Arabian Sea and Bay of Bengal and an increase in precipitation over Southeast Asia. This study highlights the importance of including a more realistic treatment of aerosol-cloud interactions in global NWP models and the potential for improved global environmental prediction systems through the incorporation of more complex

  11. Increasing complexity and versatility: how the calcium signaling toolkit was shaped during plant land colonization.

    PubMed

    Edel, Kai H; Kudla, Jörg

    2015-03-01

    Calcium serves as a versatile messenger in adaptation reactions and developmental processes in plants and animals. Eukaryotic cells generate cytosolic Ca(2+) signals via Ca(2+) conducting channels. Ca(2+) signals are represented in form of stimulus-specific spatially and temporally defined Ca(2+) signatures. These Ca(2+) signatures are detected, decoded and transmitted to downstream responses by an elaborate toolkit of Ca(2+) binding proteins that function as Ca(2+) sensors. In this article, we examine the distribution and evolution of Ca(2+)-conducting channels and Ca(2+) decoding proteins in the plant lineage. To this end, we have in addition to previously studied genomes of plant species, identified and analyzed the Ca(2+)-signaling components from species that hold key evolutionary positions like the filamentous terrestrial algae Klebsormidium flaccidum and Amborella trichopoda, the single living representative of the sister lineage to all other extant flowering plants. Plants and animals exhibit substantial differences in their complements of Ca(2+) channels and Ca(2+) binding proteins. Within the plant lineage, remarkable differences in the evolution of complexity between different families of Ca(2+) signaling proteins are observable. Using the CBL/CIPK Ca(2+) sensor/kinase signaling network as model, we attempt to link evolutionary tendencies to functional predictions. Our analyses, for example, suggest Ca(2+) dependent regulation of Na(+) homeostasis as an evolutionary most ancient function of this signaling network. Overall, gene families of Ca(2+) signaling proteins have significantly increased in their size during plant evolution reaching an extraordinary complexity in angiosperms. PMID:25477139

  12. Peptidoglycan recognition protein-peptidoglycan complexes increase monocyte/macrophage activation and enhance the inflammatory response.

    PubMed

    De Marzi, Mauricio C; Todone, Marcos; Ganem, María B; Wang, Qian; Mariuzza, Roy A; Fernández, Marisa M; Malchiodi, Emilio L

    2015-07-01

    Peptidoglycan recognition proteins (PGRP) are pattern recognition receptors that can bind or hydrolyse peptidoglycan (PGN). Four human PGRP have been described: PGRP-S, PGRP-L, PGRP-Iα and PGRP-Iβ. Mammalian PGRP-S has been implicated in intracellular destruction of bacteria by polymorphonuclear cells, PGRP-Iα and PGRP-Iβ have been found in keratinocytes and epithelial cells, and PGRP-L is a serum protein that hydrolyses PGN. We have expressed recombinant human PGRP and observed that PGRP-S and PGRP-Iα exist as monomer and disulphide dimer proteins. The PGRP dimers maintain their biological functions. We detected the PGRP-S dimer in human serum and polymorphonuclear cells, from where it is secreted after degranulation; these cells being a possible source of serum PGRP-S. Recombinant PGRP do not act as bactericidal or bacteriostatic agents in the assayed conditions; however, PGRP-S and PGRP-Iα cause slight damage in the bacterial membrane. Monocytes/macrophages increase Staphylococcus aureus phagocytosis in the presence of PGRP-S, PGRP-Iα and PGRP-Iβ. All PGRP bind to monocyte/macrophage membranes and are endocytosed by them. In addition, all PGRP protect cells from PGN-induced apoptosis. PGRP increase THP-1 cell proliferation and enhance activation by PGN. PGRP-S-PGN complexes increase the membrane expression of CD14, CD80 and CD86, and enhance secretion of interleukin-8, interleukin-12 and tumour necrosis factor-α, but reduce interleukin-10, clearly inducing an inflammatory profile. PMID:25752767

  13. Increased RNA-Induced Silencing Complex (RISC) Activity Contributes to Hepatocellular Carcinoma

    PubMed Central

    Yoo, Byoung Kwon; Santhekadur, Prasanna K.; Gredler, Rachel; Chen, Dong; Emdad, Luni; Bhutia, Sujit; Pannell, Lewis; Fisher, Paul B.; Sarkar, Devanand

    2011-01-01

    There is virtually no effective treatment for advanced hepatocellular carcinoma (HCC) and novel targets need to be identified to develop effective treatment. We recently documented that the oncogene Astrocyte elevated gene-1 (AEG-1) plays a seminal role in hepatocarcinogenesis. Employing yeast two-hybrid assay and co-immunoprecipitation followed by mass spectrometry we identified Staphylococcal nuclease domain containing 1 (SND1), a nuclease in the RNA-induced silencing complex (RISC) facilitating RNAi-mediated gene silencing, as an AEG-1 interacting protein. Co-immunoprecipitation and co-localization studies confirmed that AEG-1 is also a component of RISC and both AEG-1 and SND1 are required for optimum RISC activity facilitating siRNA and miRNA-mediated silencing of luciferase reporter gene. In 109 human HCC samples SND1 was overexpressed in ∼74% cases compared to normal liver. Correspondingly, significantly higher RISC activity was observed in human HCC cells compared to immortal normal hepatocytes. Increased RISC activity, conferred by AEG-1 or SND1, resulted in increased degradation of tumor suppressor mRNAs that are target of oncomiRs. Inhibition of enzymatic activity of SND1 significantly inhibited proliferation of human HCC cells. As a corollary, stable overexpression of SND1 augmented and siRNA-mediated inhibition of SND1 abrogated growth of human HCC cells in vitro and in vivo thus revealing a potential role of SND1 in hepatocarcinogenesis. Conclusion We unravel a novel mechanism that overexpression of AEG-1 and SND1 leading to increased RISC activity might contribute to hepatocarcinogenesis. Targeted inhibition of SND1 enzymatic activity might be developed as an effective therapy for HCC. PMID:21520169

  14. STUDIES TO ADDRESS THE ASSOCIATION BETWEEN PARTICULATE MATTER (PM) EXPOSURE AND DEVELOPMENT/EXACERBATION OF LUNG INJURY, INFLAMMATION, AND INCREASED AIRWAY RESPONSIVENESS.

    EPA Science Inventory

    Asthma, an inflammatory airways disease, has become an urgent health problem affecting an estimated 17 million persons in the United States alone (CDC 1998 MMWR 47). Since 1979, the death rate from asthma has increased by almost 56%. Epidemiologic studies have demonstrated posit...

  15. Do patients with tuberous sclerosis complex have an increased risk for malignancies?

    PubMed

    Peron, Angela; Vignoli, Aglaia; La Briola, Francesca; Volpi, Angela; Montanari, Emanuele; Morenghi, Emanuela; Ghelma, Filippo; Bulfamante, Gaetano; Cefalo, Graziella; Canevini, Maria Paola

    2016-06-01

    Tuberous Sclerosis Complex (TSC) is generally characterized by the presence of benign tumors, but some patients with malignancies have been reported in the literature. We examined a large Italian TSC population (240 individuals followed from 2001 to 2015, aged 3 months-74 years), assessing the frequency of malignancies to determine whether there is an increased risk for cancer in this disorder, and looking for possible features associated with the development of neoplasia. Fifteen patients had malignancies (6.25%); median age at diagnosis was 37.5 years (range of 1.6-58). Five of seven renal tumors were renal cell carcinomas. Eight patients had a non-renal malignancy (3.3%), but we did not find a more prevalent type of cancer. No patient developed more than one malignancy. The prevalence of all malignant tumors was compatible with the prevalence in the general population (5.6%, 95%CI 2.99-9.31%, vs. 4.4% in Italy). Median age at cancer diagnosis was lower (37.5 years, 95%CI 28.6-44.7, vs. 66.0 years). Two patients (13.3%) died of their cancer, while outcome was favorable in the remaining individuals. Malignant tumors were more frequently diagnosed in patients with mutations in TSC1 when compared to TSC2 and patients with no mutation identified (P = 0.032). Our study demonstrated that TSC patients do not seem to have an increased risk for malignancies besides renal cell carcinoma. However, when cancer develops, age at diagnosis is lower than in the general population, and malignant tumors are more frequently diagnosed in patients with mutations in TSC1. Further studies are needed to confirm these data. ©2016 Wiley Periodicals, Inc. PMID:27061015

  16. Complex interactions between climate change and toxicants: evidence that temperature variability increases sensitivity to cadmium.

    PubMed

    Kimberly, David A; Salice, Christopher J

    2014-07-01

    The Intergovernmental Panel on Climate Change projects that global climate change will have significant impacts on environmental conditions including potential effects on sensitivity of organisms to environmental contaminants. The objective of this study was to test the climate-induced toxicant sensitivity (CITS) hypothesis in which acclimation to altered climate parameters increases toxicant sensitivity. Adult Physa pomilia snails were acclimated to a near optimal 22 °C or a high-normal 28 °C for 28 days. After 28 days, snails from each temperature group were challenged with either low (150 μg/L) or high (300 μg/L) cadmium at each temperature (28 or 22 °C). In contrast to the CITS hypothesis, we found that acclimation temperature did not have a strong influence on cadmium sensitivity except at the high cadmium test concentration where snails acclimated to 28 °C were more cadmium tolerant. However, snails that experienced a switch in temperature for the cadmium challenge, regardless of the switch direction, were the most sensitive to cadmium. Within the snails that were switched between temperatures, snails acclimated at 28 °C and then exposed to high cadmium at 22 °C exhibited significantly greater mortality than those snails acclimated to 22 °C and then exposed to cadmium at 28 °C. Our results point to the importance of temperature variability in increasing toxicant sensitivity but also suggest a potentially complex cost of temperature acclimation. Broadly, the type of temporal stressor exposures we simulated may reduce overall plasticity in responses to stress ultimately rendering populations more vulnerable to adverse effects. PMID:24623389

  17. Maintaining Qubit Coherence in the face of Increased Superconducting Circuit Complexity

    NASA Astrophysics Data System (ADS)

    Hover, David; Weber, Steve; Rosenberg, Danna; Samach, Gabriel; Sears, Adam; Birenbaum, Jeffrey; Woods, Wayne; Yoder, Jonilyn; Racz, Livia; Kerman, Jamie; Oliver, William D.

    Maintaining qubit coherence in the face of increased superconducting circuit complexity is a challenge when designing an extensible quantum computing architecture. We consider this challenge in the context of inductively coupled, long-lived, capacitively-shunted flux qubits. Specifically, we discuss our efforts to mitigate the effects of radiation loss, parasitic chip-modes, cross-coupling, and Purcell decay. Our approach employs numerical modeling of the ideal Hamiltonian and electromagnetic analysis of the circuit, both of which are independently shown to be consistent with experimental results. This research was funded by the Office of the Director of National Intelligence (ODNI), Intelligence Advanced Research Projects Activity (IARPA) and by the Assistant Secretary of Defense for Research & Engineering under Air Force Contract No. FA8721-05-C-0002. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of ODNI, IARPA, or the US Government.

  18. Increasing complexity: which drug class to choose for treatment of hypertension in the elderly?

    PubMed

    Kaiser, Edelgard Anna; Lotze, Ulrich; Schäfer, Hans Hendrik

    2014-01-01

    Treatment of hypertension in the elderly is expected to become more complex in the coming decades. Based on the current landscape of clinical trials, guideline recommendations remain inconclusive. The present review discusses the latest evidence derived from studies available in 2013 and investigates optimal blood pressure (BP) and preferred treatment substances. Three common archetypes are discussed that hamper the treatment of hypertension in the very elderly. In addition, this paper presents the current recommendations of the NICE 2011, JNC7 2013-update, ESH/ESC 2013, CHEP 2013, JNC8 and ASH/ISH guidelines for elderly patients. Advantages of the six main substance classes, namely diuretics, beta-blockers (BBs), calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and direct renin inhibitors (DRIs) are discussed. Medical and economic implications of drug administration in the very elderly are presented. Avoidance of treatment-related adverse effects has become increasingly relevant. Current substance classes are equally effective, with similar effects on cardiovascular outcomes. Selection of substances should therefore also be based on collateral advantages of drugs that extend beyond BP reduction. The combination of ACEIs and diuretics appears to be favorable in managing systolic/diastolic hypertension. Diuretics are a preferred and cheap combination drug, and the combination with CCBs is recommended for patients with isolated systolic hypertension. ACEIs and CCBs are favorable for patients with dementia, while CCBs and ARBs imply substantial cost savings due to high adherence. PMID:24711696

  19. Mitochondrial Complex I Deficiency Increases Protein Acetylation and Accelerates Heart Failure

    PubMed Central

    Karamanlidis, Georgios; Lee, Chi Fung; Garcia-Menendez, Lorena; Kolwicz, Stephen C.; Suthammarak, Wichit; Gong, Guohua; Sedensky, Margaret M.; Morgan, Philip G.; Wang, Wang; Tian, Rong

    2013-01-01

    Summary Mitochondrial respiratory dysfunction is linked to the pathogenesis of multiple diseases including heart failure but the specific mechanisms for this link remain largely elusive. We modeled the impairment of mitochondrial respiration by inactivation of the Ndufs4 gene, a protein critical for Complex I (C-I) assembly, in the mouse heart (cKO). While C-I supported respiration decreased by >40%, the cKO mice maintained normal cardiac function in vivo and high-energy phosphate content in isolated perfused hearts. However, the cKO mice developed accelerated heart failure after pressure overload or repeated pregnancy. Decreased NAD+/NADH ratio by C-I deficiency inhibited Sirt3 activity, leading to increase in protein acetylation, and sensitization of the permeability transition in mitochondria (mPTP). NAD+ precursor supplementation to cKO mice partially normalized the NAD+/NADH ratio, protein acetylation and mPTP sensitivity. These findings describe a mechanism connecting mitochondrial dysfunction to the susceptibility to diseases and propose a potential therapeutic target. PMID:23931755

  20. A coordinated cross-disciplinary research initiative to address an increased incidence of narcolepsy following the 2009-2010 Pandemrix vaccination programme in Sweden.

    PubMed

    Feltelius, N; Persson, I; Ahlqvist-Rastad, J; Andersson, M; Arnheim-Dahlström, L; Bergman, P; Granath, F; Adori, C; Hökfelt, T; Kühlmann-Berenzon, S; Liljeström, P; Maeurer, M; Olsson, T; Örtqvist, Å; Partinen, M; Salmonson, T; Zethelius, B

    2015-10-01

    In response to the 2009-2010 influenza A(H1N1)pdm09 pandemic, a mass vaccination programme with the AS03-adjuvanted influenza A(H1N1) vaccine Pandemrix was initiated in Sweden. Unexpectedly, there were a number of narcolepsy cases amongst vaccinated children and adolescents reported. In this review, we summarize the results of a joint cross-disciplinary national research effort to investigate the adverse reaction signal from the spontaneous reporting system and to better understand possible causative mechanisms. A three- to fourfold increased risk of narcolepsy in vaccinated children and adolescents was verified by epidemiological studies. Of importance, no risk increase was observed for the other neurological and autoimmune diseases studied. Genetic studies confirmed the association with the allele HLA-DQB1*06:02, which is known to be related to sporadic narcolepsy. Furthermore, a number of studies using cellular and molecular experimental models investigated possible links between influenza vaccination and narcolepsy. Serum analysis, using a peptide microarray platform, showed that individuals who received Pandemrix exhibited a different epitope reactivity pattern to neuraminidase and haemagglutinin, as compared to individuals who were infected with H1N1. Patients with narcolepsy were also found to have increased levels of interferon-gamma production in response to streptococcus-associated antigens. The chain of patient-related events and the study results emerging over time were subjected to intense nationwide media attention. The importance of transparent communication and collaboration with patient representatives to maintain public trust in vaccination programmes is also discussed in the review. Organizational challenges due to this unexpected event delayed the initiation of some of the research projects, still the main objectives of this joint, cross-disciplinary research effort were reached, and important insights were acquired for future, similar

  1. Quantum Chemistry Meets Spectroscopy for Astrochemistry: Increasing Complexity toward Prebiotic Molecules.

    PubMed

    Barone, Vincenzo; Biczysko, Malgorzata; Puzzarini, Cristina

    2015-05-19

    For many years, scientists suspected that the interstellar medium was too hostile for organic species and that only a few simple molecules could be formed under such extreme conditions. However, the detection of approximately 180 molecules in interstellar or circumstellar environments in recent decades has changed this view dramatically. A rich chemistry has emerged, and relatively complex molecules such as C60 and C70 are formed. Recently, researchers have also detected complex organic and potentially prebiotic molecules, such as amino acids, in meteorites and in other space environments. Those discoveries have further stimulated the debate on the origin of the building blocks of life in the universe. Many efforts continue to focus on the physical, chemical, and astrophysical processes by which prebiotic molecules can be formed in the interstellar dust and dispersed to Earth or to other planets.Spectroscopic techniques, which are widely used to infer information about molecular structure and dynamics, play a crucial role in the investigation of planetary atmosphere and the interstellar medium. Increasingly these astrochemical investigations are assisted by quantum-mechanical calculations of structures as well as spectroscopic and thermodynamic properties, such as transition frequencies and reaction enthalpies, to guide and support observations, line assignments, and data analysis in these new and chemically complicated situations. However, it has proved challenging to extend accurate quantum-chemical computational approaches to larger systems because of the unfavorable scaling with the number of degrees of freedom (both electronic and nuclear).In this Account, we show that it is now possible to compute physicochemical properties of building blocks of biomolecules with an accuracy rivaling that of the most sophisticated experimental techniques, and we summarize specific contributions from our groups. As a test case, we present the underlying computational machinery

  2. Differential SAGE analysis in Arabidopsis uncovers increased transcriptome complexity in response to low temperature

    PubMed Central

    Robinson, Stephen J; Parkin, Isobel AP

    2008-01-01

    Background Abiotic stress, including low temperature, limits the productivity and geographical distribution of plants, which has led to significant interest in understanding the complex processes that allow plants to adapt to such stresses. The wide range of physiological, biochemical and molecular changes that occur in plants exposed to low temperature require a robust global approach to studying the response. We have employed Serial Analysis of Gene Expression (SAGE) to uncover changes in the transcriptome of Arabidopsis thaliana over a time course of low temperature stress. Results Five SAGE libraries were generated from A. thaliana leaf tissue collected at time points ranging from 30 minutes to one week of low temperature treatment (4°C). Over 240,000 high quality SAGE tags, corresponding to 16,629 annotated genes, provided a comprehensive survey of changes in the transcriptome in response to low temperature, from perception of the stress to acquisition of freezing tolerance. Interpretation of these data was facilitated by representing the SAGE data by gene identifier, allowing more robust statistical analysis, cross-platform comparisons and the identification of genes sharing common expression profiles. Simultaneous statistical calculations across all five libraries identified 920 low temperature responsive genes, only 24% of which overlapped with previous global expression analysis performed using microarrays, although similar functional categories were affected. Clustering of the differentially regulated genes facilitated the identification of novel loci correlated with the development of freezing tolerance. Analysis of their promoter sequences revealed subsets of genes that were independent of CBF and ABA regulation and could provide a mechanism for elucidating complementary signalling pathways. The SAGE data emphasised the complexity of the plant response, with alternate pre-mRNA processing events increasing at low temperatures and antisense transcription

  3. Survey on Addressing the Information and Support Needs of Jewish Women at Increased Risk for or Diagnosed with Breast Cancer: The Sharsheret Experience

    PubMed Central

    Tercyak, Kenneth P.; Silber, Elana; Johnson, Andrea C.; Fleischmann, Adina; Murphy, Sarah E.; Mays, Darren; O’Neill, Suzanne C.; Sharkey, Christina M.; Shoretz, Rochelle

    2015-01-01

    Approximately 12% of women living in the United States will be diagnosed with breast cancer during their lifetimes. While all women face formidable challenges posed by the threat of living with or at increased risk for breast cancer, those of Ashkenazi Jewish descent face additional challenges owing to higher BRCA1/2 mutation prevalence in this population. Amidst calls for population-based screening for hereditary breast cancer risk, much can be learned from the experiences of Jewish women about their needs. The present study is a secondary analysis of psychoeducational program satisfaction and evaluation data previously collected by a community organization dedicated to serving women of all Jewish backgrounds facing, or at risk for, breast cancer. Among respondents (n = 347), over one-third were referred to the organization by family or friends, most often after a cancer crisis. Of the information and support resources offered, the greatest level of engagement occurred with the one-on-one peer support and health care symposia resources. Respondents endorsed high levels of satisfaction with the programs and services, and a strong desire to give back to the community. These data suggest that culturally-relevant information and support services for Jewish women could be scaled-up for larger dissemination to meet the anticipated needs in this special population.

  4. Increasing HIV-1 molecular complexity among men who have sex with men in Bangkok.

    PubMed

    Leelawiwat, Wanna; Rutvisuttinunt, Wiriya; Arroyo, Miguel; Mueanpai, Famui; Kongpechsatit, Oranuch; Chonwattana, Wannee; Chaikummao, Supaporn; de Souza, Mark; vanGriensven, Frits; McNicholl, Janet M; Curlin, Marcel E

    2015-04-01

    In Thailand, new HIV-1 infections are largely concentrated in certain risk groups such as men who have sex with men (MSM), where annual incidence may be as high as 12% per year. The paucity of information on the molecular epidemiology of HIV-1 in Thai MSM limits progress in understanding the epidemic and developing new prevention methods. We evaluated HIV-1 subtypes in seroincident and seroprevalent HIV-1-infected men enrolled in the Bangkok MSM Cohort Study (BMCS) between 2006 and 2011. We characterized HIV-1 subtype in 231 seroprevalent and 194 seroincident subjects using the multihybridization assay (MHA). Apparent dual infections, recombinant strains, and isolates found to be nontypeable by MHA were further characterized by targeted genomic sequencing. Most subjects were infected with HIV-1 CRF01_AE (82%), followed by infections with recombinants (11%, primarily CRF01_AE/B recombinants), subtype B (5%), and dual infections (2%). More than 11 distinct chimeric patterns were observed among CRF01B_AE/B recombinants, most involving recombination within integrase. A significant increase in the proportion of nontypeable strains was observed among seroincident MSM between 2006 and 2011. CRF01_AE and subtype B were the most and least common infecting strains, respectively. The predominance of CRF01_AE among HIV-1 infections in Thai MSM participating in the BMCS parallels trends observed in Thai heterosexuals and injecting drug users. The presence of complex recombinants and a significant rise in nontypeable strains suggest ongoing changes in the genetic makeup of the HIV-1 epidemic in Thailand, which may pose challenges for HIV-1 prevention efforts and vaccine development. PMID:25366819

  5. Bounded rationality and voting decisions over 160 years: voter behavior and increasing complexity in decision-making.

    PubMed

    Stadelmann, David; Torgler, Benno

    2013-01-01

    Using a quasi-natural voting experiment encompassing a 160-year period (1848-2009) in Switzerland, we investigate whether a higher level of complexity leads to increased reliance on trusted parliamentary representatives. We find that when more referenda are held on the same day, constituents are more likely to refer to parliamentary recommendations when making their decisions. This finding holds true even when we narrow our focus to referenda with a relatively lower voter turnout on days on which more than one referendum is held. We also demonstrate that when constituents face a higher level of complexity, they follow the parliamentary recommendations rather than those of interest groups. "Viewed as a geometric figure, the ant's path is irregular, complex, hard to describe. But its complexity is really a complexity in the surface of the beach, not a complexity in the ant." ( [1] p. 51). PMID:24391888

  6. Bounded Rationality and Voting Decisions over 160 Years: Voter Behavior and Increasing Complexity in Decision-Making

    PubMed Central

    Stadelmann, David; Torgler, Benno

    2013-01-01

    Using a quasi-natural voting experiment encompassing a 160-year period (1848–2009) in Switzerland, we investigate whether a higher level of complexity leads to increased reliance on trusted parliamentary representatives. We find that when more referenda are held on the same day, constituents are more likely to refer to parliamentary recommendations when making their decisions. This finding holds true even when we narrow our focus to referenda with a relatively lower voter turnout on days on which more than one referendum is held. We also demonstrate that when constituents face a higher level of complexity, they follow the parliamentary recommendations rather than those of interest groups. “Viewed as a geometric figure, the ant’s path is irregular, complex, hard to describe. But its complexity is really a complexity in the surface of the beach, not a complexity in the ant.” ( [1] p. 51) PMID:24391888

  7. Increased Metabolic Flexibility and Complexity in a Long-Lived Growth Hormone Insensitive Mouse Model

    PubMed Central

    2014-01-01

    The goal of this study was to test whether the “loss of the complexity” hypothesis can be applied to compare the metabolic patterns of mouse models with known differences in metabolic and endocrine function as well as life span. Here, we compare the complexity of locomotor activity and metabolic patterns (energy expenditure, VO2, and respiratory quotient) of the long-lived growth hormone receptor gene deleted mice (GHR− /−) and their wild-type littermates. Using approximate entropy as a measure of complexity, we observed greater metabolic complexity, as indicated by greater irregularity in the physiological fluctuations of the GHR− /− mice. Further analysis of the data also revealed lower energy costs of locomotor activity and a stronger relationship between locomotor activity and respiratory quotient in the GHR− /− mice relative to controls. These findings suggest underlying differences in metabolic modulation in the GHR− /− mice revealed especially through measures of complexity of their time-dependent fluctuations. PMID:23788654

  8. Spectral determination of concentrations of functionally diverse pigments in increasingly complex arctic tundra canopies.

    PubMed

    Boelman, Natalie T; Magney, Troy S; Logan, Barry A; Griffin, Kevin L; Eitel, Jan U H; Greaves, Heather; Prager, Case M; Vierling, Lee A

    2016-09-01

    As the Arctic warms, tundra vegetation is becoming taller and more structurally complex, as tall deciduous shrubs become increasingly dominant. Emerging studies reveal that shrubs exhibit photosynthetic resource partitioning, akin to forests, that may need accounting for in the "big leaf" net ecosystem exchange models. We conducted a lab experiment on sun and shade leaves from S. pulchra shrubs to determine the influence of both constitutive (slowly changing bulk carotenoid and chlorophyll pools) and facultative (rapidly changing xanthophyll cycle) pigment pools on a suite of spectral vegetation indices, to devise a rapid means of estimating within canopy resource partitioning. We found that: (1) the PRI of dark-adapted shade leaves (PRIo) was double that of sun leaves, and that PRIo was sensitive to variation among sun and shade leaves in both xanthophyll cycle pool size (V + A + Z) (r (2) = 0.59) and Chla/b (r (2) = 0.64); (2) A corrected PRI (difference between dark and illuminated leaves, ΔPRI) was more sensitive to variation among sun and shade leaves in changes to the epoxidation state of their xanthophyll cycle pigments (dEPS) (r (2) = 0.78, RMSE = 0.007) compared to the uncorrected PRI of illuminated leaves (PRI) (r (2) = 0.34, RMSE = 0.02); and (3) the SR680 index was correlated with each of (V + A + Z), lutein, bulk carotenoids, (V + A + Z)/(Chla + b), and Chla/b (r (2) range = 0.52-0.69). We suggest that ΔPRI be employed as a proxy for facultative pigment dynamics, and the SR680 for the estimation of constitutive pigment pools. We contribute the first Arctic-specific information on disentangling PRI-pigment relationships, and offer insight into how spectral indices can assess resource partitioning within shrub tundra canopies. PMID:27193900

  9. Structural complexity and component type increase intertidal biodiversity independently of area.

    PubMed

    Loke, Lynette H L; Todd, Peter A

    2016-02-01

    Complexity is well accepted as one of the primary drivers of biodiversity, however, empirical support for such positive associations is often confounded with surface area and undermined by other potential explanatory factors, especially the type of structural component (e.g., pits, crevices, overhangs, etc.). In the present study, sample units (artificial substrates) of equal surface area (± 0.2%) were used to simultaneously examine the independent effects of complexity and different structural component types on species richness (S), abundance (N), and community composition. We created simple and complex concrete substrates of four different geometric designs using novel software. The substrates (n = 8) were mounted onto granite seawalls (at two tidal heights) on two islands south of Singapore Island. After 13 months of colonization, all 384 tiles were collected and their assemblages compared. A total of 53 744 individuals of 70 species/morphospecies were collected and identified. Our results show that greater complexity can support greater species richness and different communities that are independent of surface area. Furthermore, the type of structure (e.g., "pits," "grooves," "towers") can have an effect on richness and community composition that is independent of complexity. PMID:27145613

  10. The algorithmic complexity of neural spike trains increases during focal seizures.

    PubMed

    Rapp, P E; Zimmerman, I D; Vining, E P; Cohen, N; Albano, A M; Jiménez-Montaño, M A

    1994-08-01

    The interspike interval spike trains of spontaneously active cortical neurons can display nonrandom internal structure. The degree of nonrandom structure can be quantified and was found to decrease during focal epileptic seizures. Greater statistical discrimination between the two physiological conditions (normal vs seizure) was obtained with measurements of context-free grammar complexity than by measures of the distribution of the interspike intervals such as the mean interval, its standard deviation, skewness, or kurtosis. An examination of fixed epoch data sets showed that two factors contribute to the complexity: the firing rate and the internal structure of the spike train. However, calculations with randomly shuffled surrogates of the original data sets showed that the complexity is not completely determined by the firing rate. The sequence-sensitive structure of the spike train is a significant contributor. By combining complexity measurements with statistically related surrogate data sets, it is possible to classify neurons according to the dynamical structure of their spike trains. This classification could not have been made on the basis of conventional distribution-determined measures. Computations with more sophisticated kinds of surrogate data show that the structure observed using complexity measures cannot be attributed to linearly correlated noise or to linearly correlated noise transformed by a static monotonic nonlinearity. The patterns in spike trains appear to reflect genuine nonlinear structure. The limitations of these results are also discussed. The results presented in this article do not, of themselves, establish the presence of a fine-structure encoding of neural information. PMID:8046447

  11. Molecular phylogeny analysis of fiddler crabs: test of the hypothesis of increasing behavioral complexity in evolution.

    PubMed Central

    Sturmbauer, C; Levinton, J S; Christy, J

    1996-01-01

    The current phylogenetic hypothesis for the evolution and biogeography of fiddler crabs relies on the assumption that complex behavioral traits are assumed to also be evolutionary derived. Indo-west Pacific fiddler crabs have simpler reproductive social behavior and are more marine and were thought to be ancestral to the more behaviorally complex and more terrestrial American species. It was also hypothesized that the evolution of more complex social and reproductive behavior was associated with the colonization of the higher intertidal zones. Our phylogenetic analysis, based upon a set of independent molecular characters, however, demonstrates how widely entrenched ideas about evolution and biogeography led to a reasonable, but apparently incorrect, conclusion about the evolutionary trends within this pantropical group of crustaceans. Species bearing the set of "derived traits" are phylogenetically ancestral, suggesting an alternative evolutionary scenario: the evolution of reproductive behavioral complexity in fiddler crabs may have arisen multiple times during their evolution. The evolution of behavioral complexity may have arisen by coopting of a series of other adaptations for high intertidal living and antipredator escape. A calibration of rates of molecular evolution from populations on either side of the Isthmus of Panama suggest a sequence divergence rate for 16S rRNA of 0.9% per million years. The divergence between the ancestral clade and derived forms is estimated to be approximately 22 million years ago, whereas the divergence between the American and Indo-west Pacific is estimated to be approximately 17 million years ago. Images Fig. 1 PMID:11607711

  12. The IncP plasmid-encoded cell envelope-associated DNA transfer complex increases cell permeability.

    PubMed Central

    Daugelavicius, R; Bamford, J K; Grahn, A M; Lanka, E; Bamford, D H

    1997-01-01

    IncP-type plasmids are broad-host-range conjugative plasmids. DNA translocation requires DNA transfer-replication functions and additional factors required for mating pair formation (Mpf). The Mpf system is located in the cell membranes and is responsible for DNA transport from the donor to the recipient. The Mpf complex acts as a receptor for IncP-specific phages such as PRD1. In this investigation, we quantify the Mpf complexes on the cell surface by a phage receptor saturation technique. Electrochemical measurements are used to show that the Mpf complex increases cell envelope permeability to lipophilic compounds and ATP. In addition it reduces the ability of the cells to accumulate K+. However, the Mpf complex does not dissipate the membrane voltage. The Mpf complex is rapidly disassembled when intracellular ATP concentration is decreased, as measured by a PRD1 adsorption assay. PMID:9260964

  13. Mutations in TFIIIA that increase stability of the TFIIIA-5 S rRNA gene complex: unusual effects on the kinetics of complex assembly and dissociation.

    PubMed

    Brady, Kristina L; Ponnampalam, Stephen N; Bumbulis, Michael J; Setzer, David R

    2005-07-22

    We have identified four mutations in Xenopus TFIIIA that increase the stability of TFIIIA-5 S rRNA gene complexes. In each case, the mutation has a relatively modest effect on equilibrium binding affinity. In three cases, these equilibrium binding effects can be ascribed primarily to decreases in the rate constant for protein-DNA complex dissociation. In the fourth case, however, a substitution of phenylalanine for the wild-type leucine at position 148 in TFIIIA results in much larger compensating changes in the kinetics of complex assembly and dissociation. The data support a model in which a relatively unstable population of complexes with multi-component dissociation kinetics forms rapidly; complexes then undergo a slow conformational change that results in very stable, kinetically homogeneous TFIIIA-DNA complexes. The L148F mutant protein acts as a particularly potent transcriptional activator when it is fused to the VP16 activation domain and expressed in yeast cells. Substitution of L148 to tyrosine or tryptophan produces an equally strong transcriptional activator. Substitution to histidine results in genetic and biochemical effects that are more modest than, but similar to, those observed with the L148F mutation. We propose that an amino acid with a planar side chain at position 148 can intercalate between adjacent base pairs in the intermediate element of the 5 S rRNA gene. Intercalation occurs slowly but results in a very stable DNA-protein complex. These results suggest that transcriptional activation by a cis-acting sequence element is largely dependent on the kinetic, rather than the thermodynamic, stability of the complex formed with an activator protein. Thus, transcriptional activation is dependent in large part on the lifetime of the activator-DNA complex rather than on binding site occupancy at steady state. Introduction of intercalating amino acids into zinc finger proteins may be a useful tool for producing artificial transcription factors with

  14. A Systematic Review of Interventions to Increase Peer Interactions for Students with Complex Communication Challenges

    ERIC Educational Resources Information Center

    Chung, Yun-Ching; Carter, Erik W.; Sisco, Lynn G.

    2012-01-01

    Although positive peer relationships can facilitate the academic learning, skill development, and emotional well-being of students with complex communication challenges, few peer interactions are likely to take place in school settings apart from intentional intervention and support efforts. We conducted a systematic review to identify and examine…

  15. Increased Transcript Complexity in Genes Associated with Chronic Obstructive Pulmonary Disease.

    PubMed

    Lackey, Lela; McArthur, Evonne; Laederach, Alain

    2015-01-01

    Genome-wide association studies aim to correlate genotype with phenotype. Many common diseases including Type II diabetes, Alzheimer's, Parkinson's and Chronic Obstructive Pulmonary Disease (COPD) are complex genetic traits with hundreds of different loci that are associated with varied disease risk. Identifying common features in the genes associated with each disease remains a challenge. Furthermore, the role of post-transcriptional regulation, and in particular alternative splicing, is still poorly understood in most multigenic diseases. We therefore compiled comprehensive lists of genes associated with Type II diabetes, Alzheimer's, Parkinson's and COPD in an attempt to identify common features of their corresponding mRNA transcripts within each gene set. The SERPINA1 gene is a well-recognized genetic risk factor of COPD and it produces 11 transcript variants, which is exceptional for a human gene. This led us to hypothesize that other genes associated with COPD, and complex disorders in general, are highly transcriptionally diverse. We found that COPD-associated genes have a statistically significant enrichment in transcript complexity stemming from a disproportionately high level of alternative splicing, however, Type II Diabetes, Alzheimer's and Parkinson's disease genes were not significantly enriched. We also identified a subset of transcriptionally complex COPD-associated genes (~40%) that are differentially expressed between mild, moderate and severe COPD. Although the genes associated with other lung diseases are not extensively documented, we found preliminary data that idiopathic pulmonary disease genes, but not cystic fibrosis modulators, are also more transcriptionally complex. Interestingly, complex COPD transcripts are more often the product of alternative acceptor site usage. To verify the biological importance of these alternative transcripts, we used RNA-sequencing analyses to determine that COPD-associated genes are frequently expressed in

  16. Increased Transcript Complexity in Genes Associated with Chronic Obstructive Pulmonary Disease

    PubMed Central

    Lackey, Lela; McArthur, Evonne; Laederach, Alain

    2015-01-01

    Genome-wide association studies aim to correlate genotype with phenotype. Many common diseases including Type II diabetes, Alzheimer’s, Parkinson’s and Chronic Obstructive Pulmonary Disease (COPD) are complex genetic traits with hundreds of different loci that are associated with varied disease risk. Identifying common features in the genes associated with each disease remains a challenge. Furthermore, the role of post-transcriptional regulation, and in particular alternative splicing, is still poorly understood in most multigenic diseases. We therefore compiled comprehensive lists of genes associated with Type II diabetes, Alzheimer’s, Parkinson’s and COPD in an attempt to identify common features of their corresponding mRNA transcripts within each gene set. The SERPINA1 gene is a well-recognized genetic risk factor of COPD and it produces 11 transcript variants, which is exceptional for a human gene. This led us to hypothesize that other genes associated with COPD, and complex disorders in general, are highly transcriptionally diverse. We found that COPD-associated genes have a statistically significant enrichment in transcript complexity stemming from a disproportionately high level of alternative splicing, however, Type II Diabetes, Alzheimer’s and Parkinson’s disease genes were not significantly enriched. We also identified a subset of transcriptionally complex COPD-associated genes (~40%) that are differentially expressed between mild, moderate and severe COPD. Although the genes associated with other lung diseases are not extensively documented, we found preliminary data that idiopathic pulmonary disease genes, but not cystic fibrosis modulators, are also more transcriptionally complex. Interestingly, complex COPD transcripts are more often the product of alternative acceptor site usage. To verify the biological importance of these alternative transcripts, we used RNA-sequencing analyses to determine that COPD-associated genes are frequently

  17. More time for complex consultations in a high-deprivation practice is associated with increased patient enablement

    PubMed Central

    Mercer, Stewart W; Fitzpatrick, Bridie; Gourlay, Glen; Vojt, Gaby; McConnachie, Alex; Watt, Graham CM

    2007-01-01

    Background Evidence of the beneficial effects of longer consultations in general practice is limited. Aim To evaluate the effect of increasing consultation length on patient enablement in general practice in an area of extreme socioeconomic deprivation. Design of study Longitudinal study using a ‘before and after’ design. Setting Keppoch Medical Centre in Glasgow, which serves the most deprived practice area in Scotland. Method Participants were 300 adult patients at baseline, before the introduction of longer consultations, and 324 at follow-up, more than 1 year after the introduction of longer consultations. The intervention studied was more time in complex consultations. Patient satisfaction, perceptions of the GPs' empathy, GP stress, and patient enablement were collected by face-to-face interview. Additional qualitative data were obtained by individual interviews with the GPs, relating to their perceptions of the impact of the longer consultations. Results Response rates of 70% were obtained. Overall, 53% of consultations were complex. GP stress was higher in complex consultations. Patient satisfaction and perception of the GPs' empathy were consistently high. Average consultation length in complex consultations was increased by 2.5 minutes by the intervention. GP stress in consultations was decreased after the introduction of longer consultations, and patient enablement was increased. GPs' views endorsed these findings, with more anticipatory and coordinated care being possible in the longer consultations. Conclusion More resource to provide more time in complex consultations in an area of extreme deprivation is associated with an increase in patient enablement. PMID:18252071

  18. Increased Signal Complexity Improves the Breadth of Generalization in Auditory Perceptual Learning

    PubMed Central

    Brown, David J.; Proulx, Michael J.

    2013-01-01

    Perceptual learning can be specific to a trained stimulus or optimally generalized to novel stimuli with the breadth of generalization being imperative for how we structure perceptual training programs. Adapting an established auditory interval discrimination paradigm to utilise complex signals, we trained human adults on a standard interval for either 2, 4, or 10 days. We then tested the standard, alternate frequency, interval, and stereo input conditions to evaluate the rapidity of specific learning and breadth of generalization over the time course. In comparison with previous research using simple stimuli, the speed of perceptual learning and breadth of generalization were more rapid and greater in magnitude, including novel generalization to an alternate temporal interval within stimulus type. We also investigated the long term maintenance of learning and found that specific and generalized learning was maintained over 3 and 6 months. We discuss these findings regarding stimulus complexity in perceptual learning and how they can inform the development of effective training protocols. PMID:24349800

  19. Increased risk of preterm delivery in areas with cancer mortality problems from petrochemical complexes.

    PubMed

    Yang, Chun-Yuh; Chiu, Hui-Fen; Tsai, Shang-Shyue; Chang, Chih-Ching; Chuang, Hung-Yi

    2002-07-01

    The petrochemical and petroleum industries are the main sources of industrial air pollution in Taiwan. Data in this study concern outdoor air pollution and the health of individuals living in communities in close proximity to petrochemical industrial complexes. The prevalence of delivery of preterm birth infants was significantly higher in mothers living near petrochemical industrial complexes than in control mothers living elsewhere in Taiwan. After controlling for several possible confounders (including maternal age, season, marital status, maternal education, and infant sex), the adjusted odds ratio was 1.18 (95% CI=1.04-1.34) for delivery of preterm infants in the petrochemically polluted region. The data provide further support for the hypothesis that air pollution can affect the outcome of pregnancy. PMID:12176003

  20. Increased complexity in carcinomas: Analyzing and modeling the interaction of human cancer cells with their microenvironment.

    PubMed

    Stadler, Mira; Walter, Stefanie; Walzl, Angelika; Kramer, Nina; Unger, Christine; Scherzer, Martin; Unterleuthner, Daniela; Hengstschläger, Markus; Krupitza, Georg; Dolznig, Helmut

    2015-12-01

    Solid cancers are not simple accumulations of malignant tumor cells but rather represent complex organ-like structures. Despite a more chaotic general appearance as compared to the highly organized setup of healthy tissues, cancers still show highly differentiated structures and a close interaction with and dependency on the interwoven connective tissue. This complexity within cancers is not known in detail at the molecular level so far. The first part of this article will shortly describe the technology and strategies to quantify and dissect the heterogeneity in human solid cancers. Moreover, there is urgent need to better understand human cancer biology since the development of novel anti-cancer drugs is far from being efficient, predominantly due to the scarcity of predictive preclinical models. Hence, in vivo and in vitro models were developed, which better recapitulate the complexity of human cancers, by their intrinsic three-dimensional nature and the cellular heterogeneity and allow functional intervention for hypothesis testing. Therefore, in the second part 3D in vitro cancer models are presented that analyze and depict the heterogeneity in human cancers. Advantages and drawbacks of each model are highlighted and their suitability to preclinical drug testing is discussed. PMID:26320002

  1. Resveratrol Directly Binds to Mitochondrial Complex I and Increases Oxidative Stress in Brain Mitochondria of Aged Mice

    PubMed Central

    Chupin, Stéphanie; Baron, Stéphanie; Nivet-Antoine, Valérie; Vessières, Emilie; Ayer, Audrey; Henrion, Daniel; Lenaers, Guy; Reynier, Pascal; Procaccio, Vincent

    2015-01-01

    Resveratrol is often described as a promising therapeutic molecule for numerous diseases, especially in metabolic and neurodegenerative disorders. While the mechanism of action is still debated, an increasing literature reports that resveratrol regulates the mitochondrial respiratory chain function. In a recent study we have identified mitochondrial complex I as a direct target of this molecule. Nevertheless, the mechanisms and consequences of such an interaction still require further investigation. In this study, we identified in silico by docking study a binding site for resveratrol at the nucleotide pocket of complex I. In vitro, using solubilized complex I, we demonstrated a competition between NAD+ and resveratrol. At low doses (<5μM), resveratrol stimulated complex I activity, whereas at high dose (50 μM) it rather decreased it. In vivo, in brain mitochondria from resveratrol treated young mice, we showed that complex I activity was increased, whereas the respiration rate was not improved. Moreover, in old mice with low antioxidant defenses, we demonstrated that complex I activation by resveratrol led to oxidative stress. These results bring new insights into the mechanism of action of resveratrol on mitochondria and highlight the importance of the balance between pro- and antioxidant effects of resveratrol depending on its dose and age. These parameters should be taken into account when clinical trials using resveratrol or analogues have to be designed. PMID:26684010

  2. Causes versus effects: the increasing complexities of Alzheimer’s disease pathogenesis

    PubMed Central

    Mondragón-Rodríguez, Siddhartha; Basurto-Islas, Gustavo; Lee, Hyoung-gon; Perry, George; Zhu, Xiongwei; Castellani, Rudy J; Smith, Mark A

    2010-01-01

    Amyloid plaques and neurofibrillary tangles are the hallmarks of Alzheimer’s disease and have been the focus of disease etiology and pathogenesis. However, in the larger picture of a complex disease, the precise etiology of the lesions per se, as well as the clinical disease, remain to be defined. In this regard, to date no single process has been identified as a useful target and treatment efforts have shown no meaningful progress. Therefore, alternative ideas that may lead to new and effective treatment options are much needed. PMID:20420489

  3. Storage and bioavailability of molybdenum in soils increased by organic matter complexation

    NASA Astrophysics Data System (ADS)

    Wichard, Thomas; Mishra, Bhoopesh; Myneni, Satish C. B.; Bellenger, Jean-Philippe; Kraepiel, Anne M. L.

    2009-09-01

    The micronutrient molybdenum is a necessary component of the nitrogen-fixing enzyme nitrogenase. Molybdenum is very rare in soils, and is usually present in a highly soluble form, making it susceptible to leaching. However, it is generally thought that molybdenum attaches to mineral surfaces in acidic soils; this would prevent its escape into the groundwater, but would also impede uptake by microbes. Here we use X-ray spectroscopy to examine the chemical speciation of molybdenum in soil samples from forests in Arizona and New Jersey. We show that in the leaf litter layer, most of the molybdenum forms strong complexes with plant-derived tannins and tannin-like compounds; molybdenum binds to these organic ligands across a wide pH range. In deeper soils, molybdenum binds to both iron oxides and natural organic matter. We suggest that the molybdenum bound to organic matter can be captured by small complexing agents that are released by nitrogen-fixing bacteria; the molybdenum can then be incorporated into nitrogenase. We conclude that the binding of molybdenum to natural organic matter helps prevent leaching of molybdenum, and is thus a critical step in securing new nitrogen in terrestrial ecosystems.

  4. Systematic Analysis of Dimeric E3-RING Interactions Reveals Increased Combinatorial Complexity in Human Ubiquitination Networks*

    PubMed Central

    Woodsmith, Jonathan; Jenn, Robert C.; Sanderson, Chris M.

    2012-01-01

    Ubiquitination controls the stability or function of many human proteins, thereby regulating a wide range of physiological processes. In most cases the combinatorial pattern of protein interactions that facilitate substrate recognition or modification remain unclear. Moreover, the efficiency of ubiquitination reactions can be altered by the formation of homo- and heterotypic E3-RING complexes. To establish the prevalence and nature of binary E3-RING/E3-RING interactions systematic yeast two-hybrid screens were performed to test 7269 potential interactions between 124 human E3-RING proteins. These studies identified 228 dimeric interactions between 100 E3-RINGs, of which 205 were novel. Complementary co-immunoprecipitation studies were performed to test predicted network interactions, showing a high correlation (64%) with primary yeast two-hybrid data. This data was integrated with known E3-RING interactions, tissue expression profiles and proteomic ubiquitination datasets to facilitate identification of subnetworks in which E3-RING dimerization events have the potential to alter network structure. These results reveal a widespread yet selective pattern of E3-RING dimerization events, which have the potential to confer further combinatorial complexity within human ubiquitination cascades. PMID:22493164

  5. Storage and Bioavailability of Molybdenum in Soils Increased by Organic Matter Complexation

    SciTech Connect

    Wichard, T.; Mishra, B; Myneni, S; Bellenger, J; Kraepiel, A

    2009-01-01

    The micronutrient molybdenum is a necessary component of the nitrogen-fixing enzyme nitrogenase1, 2. Molybdenum is very rare in soils, and is usually present in a highly soluble form, making it susceptible to leaching3, 4. However, it is generally thought that molybdenum attaches to mineral surfaces in acidic soils; this would prevent its escape into the groundwater, but would also impede uptake by microbes3. Here we use X-ray spectroscopy to examine the chemical speciation of molybdenum in soil samples from forests in Arizona and New Jersey. We show that in the leaf litter layer, most of the molybdenum forms strong complexes with plant-derived tannins and tannin-like compounds; molybdenum binds to these organic ligands across a wide pH range. In deeper soils, molybdenum binds to both iron oxides and natural organic matter. We suggest that the molybdenum bound to organic matter can be captured by small complexing agents that are released by nitrogen-fixing bacteria; the molybdenum can then be incorporated into nitrogenase. We conclude that the binding of molybdenum to natural organic matter helps prevent leaching of molybdenum, and is thus a critical step in securing new nitrogen in terrestrial ecosystems.

  6. The Evolution and Increasing Complexity of the Resident Assistant Role in the United States from Colonial to Modern Times

    ERIC Educational Resources Information Center

    Boone, Katherine B.; Davidson, Denise L.; Bauman, Mark

    2016-01-01

    The evolution of the resident assistant position and its history are important to understanding its increasing complexities. In this article we examine how court cases and federal legislation, along with changes in popular culture, have altered and shaped the role of the resident assistant. Our premise is that this role, originally relatively…

  7. Dietary arginine silicate inositol complex increased bone healing: histologic and histomorphometric study

    PubMed Central

    Yaman, Ferhan; Acikan, Izzet; Dundar, Serkan; Simsek, Sercan; Gul, Mehmet; Ozercan, Ibrahim Hanifi; Komorowski, James; Sahin, Kazim

    2016-01-01

    Background Arginine silicate inositol complex (ASI; arginine 49.5%, silicon 8.2%, and inositol 25%) is a novel material that is a bioavailable source of silicon and arginine. ASI offers potential benefits for vascular and bone health. Objective The aim of this study was to evaluate the potential effects of ASI complex on bone healing of critical-sized defects in rats. Methods The rats were randomly assigned to two groups of 21 rats each. The control group was fed a standard diet for 12 weeks; after the first 8 weeks, a calvarial critical-sized defect was created, and the rats were sacrificed 7, 14, and 28 days later. The ASI group was fed a diet containing 1.81 g/kg of ASI for 12 weeks; after the first 8 weeks, a calvarial critical-sized defect was created, and the rats were sacrificed 7, 14, and 28 days later. The calvarial bones of all the rats were then harvested for evaluation. Results Osteoblasts and osteoclasts were detected at higher levels in the ASI group compared with the control group at days 7, 14, and 28 of the calvarial defect (P<0.05). New bone formation was detected at higher levels in the ASI group compared with the controls at day 28 (P<0.05). However, new bone formation was not detected at days 7 and 14 in both the groups (P>0.05). Conclusion ASI supplementation significantly improved bone tissue healing in rats with critical-sized defects. This study demonstrated that ASI can enhance bone repair and has potential as a therapeutic regimen in humans. PMID:27390517

  8. Adapting a Family-Based HIV Prevention Program for HIV-Infected Preadolescents and Their Families: Youth, Families and Health Care Providers Coming Together to Address Complex Needs

    PubMed Central

    McKay, Mary; Block, Megan; Mellins, Claude; Traube, Dorian E.; Brackis-Cott, Elizabeth; Minott, Desiree; Miranda, Claudia; Petterson, Jennifer; Abrams, Elaine J.

    2010-01-01

    SUMMARY This article describes a family-based HIV prevention and mental health promotion program specifically designed to meet the needs of perinatally-infected preadolescents and their families. This project represents one of the first attempts to involve perinatally HIV-infected youth in HIV prevention efforts while simultaneously addressing their mental health and health care needs. The program, entitled CHAMP+ (Collaborative HIV Prevention and Adolescent Mental Health Project-Plus), focuses on: (1) the impact of HIV on the family; (2) loss and stigma associated with HIV disease; (3) HIV knowledge and understanding of health and medication protocols; (4) family communication about puberty, sexuality and HIV; (5) social support and decision making related to disclosure; and (6) parental supervision and monitoring related to sexual possibility situations, sexual risk taking behavior and management of youth health and medication. Findings from a preliminary evaluation of CHAMP+ with six families are presented along with a discussion of challenges related to feasibility and implementation within a primary health care setting for perinatally infected youth. PMID:20852676

  9. Spatially Addressable Chemoselective C-terminal Ligation of an Intein Fusion Protein from a Complex Mixture to a Hydrazine-Terminated Surface

    PubMed Central

    Yang, Peng; Marinakos, Stella M.; Chilkoti, Ashutosh

    2011-01-01

    Protein immobilization on surfaces is useful in many areas of research, including biological characterization, antibody purification, and clinical diagnostics. A critical limitation in the development of protein microarrays and heterogeneous protein-based assays is the enormous work and associated costs in the purification of proteins prior to their immobilization on a surface; methods to address this problem would simplify the development of interfacial diagnostics that use a protein as the recognition element. Herein, we describe an approach for the facile, site-specific immobilization of proteins on a surface without any preprocessing or sample purification steps that ligates an intein fusion protein at its C-terminus by reaction with a hydrazine group presented by a surface. Furthermore, we demonstrate that this methodology can directly immobilize a protein directly from cell lysate on to a protein-resistant surface. This methodology is also compatible with soft lithography and inkjet printing, so that one or more proteins can be patterned on a surface without need for purification. PMID:21142101

  10. Mixed Heritage Said to Present Complex Issues: Multiracial Children Attracting Interest as Visibility Increases

    ERIC Educational Resources Information Center

    Viadero, Debra

    2009-01-01

    With Barack Obama making history by becoming the United States' first mixed-race president, his inauguration is calling attention to the nation's growing multiracial population, whose youngest members are showing up with increasing frequency at schoolhouse doors. Yet while the growth of the U.S. population of children with mixed-race backgrounds…

  11. Repeating a Monologue under Increasing Time Pressure: Effects on Fluency, Complexity, and Accuracy

    ERIC Educational Resources Information Center

    Thai, Chau; Boers, Frank

    2016-01-01

    Studies have shown that learners' task performance improves when they have the opportunity to repeat the task. Conditions for task repetition vary, however. In the 4/3/2 activity, learners repeat a monologue under increasing time pressure. The purpose is to foster fluency, but it has been suggested in the literature that it also benefits other…

  12. Prothrombin complex concentrate use in coagulopathy of lethal brain injuries increases organ donation.

    PubMed

    Joseph, Bellal; Aziz, Hassan; Pandit, Viraj; Hays, Daniel; Kulvatunyou, Narong; Tang, Andrew; Wynne, Julie; O' Keeffe, Terence; Green, Donald J; Friese, Randall S; Gruessner, Rainer; Rhee, Peter

    2014-04-01

    Coagulopathy is a defined barrier for organ donation in patients with lethal traumatic brain injuries. The purpose of this study was to document our experience with the use of prothrombin complex concentrate (PCC) to facilitate organ donation in patients with lethal traumatic brain injuries. We performed a 4-year retrospective analysis of all patients with devastating gunshot wounds to the brain. The data were analyzed for demographics, change in international normalized ratio (INR), and subsequent organ donation. The primary end point was organ donation. Eighty-eight patients with lethal traumatic brain injury were identified from the trauma registry of whom 13 were coagulopathic at the time of admission (mean INR 2.2 ± 0.8). Of these 13 patients, 10 patients received PCC in an effort to reverse their coagulopathy. Mean INR before PCC administration was 2.01 ± 0.7 and 1.1 ± 0.7 after administration (P < 0.006). Correction of coagulopathy was attained in 70 per cent (seven of 10) patients. Of these seven patients, consent for donation was obtained in six patients and resulted in 19 solid organs being procured. The cost of PCC per patient was $1022 ± 544. PCC effectively reveres coagulopathy associated with lethal traumatic brain injury and enabled patients to proceed to organ donation. Although various methodologies exist for the treatment of coagulopathy to facilitate organ donation, PCC provides a rapid and cost-effective therapy for reversal of coagulopathy in patients with lethal traumatic brain injuries. PMID:24887662

  13. Pharmaceutical companies and Italian Regional Governments: managing relationships in an increasing institutional complexity.

    PubMed

    Compagni, Amelia; Cavalli, Laura; Jommi, Claudio

    2008-09-01

    In Italy, the process of power decentralization to Regional Governments has particularly affected pharmaceutical care policies. Regions are experimenting with various strategies to govern drugs utilization and expenditure, and differentiating their approaches, leading to an ever-changing and complex institutional scenario. Pharmaceutical companies have created new professional roles, the Regional Affairs Managers (RAM), with the mandate to monitor the different regional contexts and measures, and to establish relationships with the public actors in charge of pharmaceutical policies. This analysis shows how public affairs/lobbying actions at regional level and the creation of a solid political competence within companies are still in an early phase. The activities carried out by RAMs remain limited to an exchange of information and only rarely are perceived by Regional public servants (RRs) as giving support to their work or influence decisions. The interaction with RAMs is often seen as little relevant and still too concentrated on products and a marketing/commercial approach rather than on broader issues of interest to RRs who need to manage the pharmaceutical care system at large. The level of acceptance of this type of activity is also variable and RRs' attitudes alternate between diffidence, polite tolerance, and openness to a constructive dialogue about pharmaceuticals and their management in a regional healthcare system. PMID:18384907

  14. Duration of Purkinje cell complex spikes increases with their firing frequency

    PubMed Central

    Warnaar, Pascal; Couto, Joao; Negrello, Mario; Junker, Marc; Smilgin, Aleksandra; Ignashchenkova, Alla; Giugliano, Michele; Thier, Peter; De Schutter, Erik

    2015-01-01

    Climbing fiber (CF) triggered complex spikes (CS) are massive depolarization bursts in the cerebellar Purkinje cell (PC), showing several high frequency spikelet components (±600 Hz). Since its early observations, the CS is known to vary in shape. In this study we describe CS waveforms, extracellularly recorded in awake primates (Macaca mulatta) performing saccades. Every PC analyzed showed a range of CS shapes with profoundly different duration and number of spikelets. The initial part of the CS was rather constant but the later part differed greatly, with a pronounced jitter of the last spikelets causing a large variation in total CS duration. Waveforms did not effect the following pause duration in the simple spike (SS) train, nor were SS firing rates predictive of the waveform shapes or vice versa. The waveforms did not differ between experimental conditions nor was there a preferred sequential order of CS shapes throughout the recordings. Instead, part of their variability, the timing jitter of the CS’s last spikelets, strongly correlated with interval length to the preceding CS: shorter CS intervals resulted in later appearance of the last spikelets in the CS burst, and vice versa. A similar phenomenon was observed in rat PCs recorded in vitro upon repeated extracellular stimulation of CFs at different frequencies in slice experiments. All together these results strongly suggest that the variability in the timing of the last spikelet is due to CS frequency dependent changes in PC excitability. PMID:25918500

  15. Complex genome evolution in Anopheles coluzzii associated with increased insecticide usage in Mali.

    PubMed

    Main, Bradley J; Lee, Yoosook; Collier, Travis C; Norris, Laura C; Brisco, Katherine; Fofana, Abdrahamane; Cornel, Anthony J; Lanzaro, Gregory C

    2015-10-01

    In certain cases, a species may have access to important genetic variation present in a related species via adaptive introgression. These novel alleles may interact with their new genetic background, resulting in unexpected phenotypes. In this study, we describe a selective sweep on standing variation on the X chromosome in the mosquito Anopheles coluzzii, a principal malaria vector in West Africa. This event may have been influenced by the recent adaptive introgression of the insecticide resistance gene known as kdr from the sister species Anopheles gambiae. Individuals carrying both kdr and a nearly fixed X-linked haplotype, encompassing at least four genes including the P450 gene CYP9K1 and the cuticular protein CPR125, have rapidly increased in relative frequency. In parallel, a reproductively isolated insecticide-susceptible A. gambiae population (Bamako form) has been driven to local extinction, likely due to strong selection from increased insecticide-treated bed net usage. PMID:26359110

  16. Visually complex foveal words increase the amount of parafoveal information acquired.

    PubMed

    Yan, Ming

    2015-06-01

    This study investigates the effect of foveal load (i.e., processing difficulty of currently fixated words) on parafoveal information processing. Contrary to the commonly accepted view that high foveal load leads to reduced parafoveal processing efficiency, results of the present study showed that increasing foveal visual (but not linguistic) processing load actually increased the amount of parafoveal information acquired, presumably due to the fact that longer fixation duration on the pretarget word provided more time for parafoveal processing of the target word. It is therefore proposed in the present study that foveal linguistic processing load is not the only factor that determines parafoveal processing; preview time (afforded by foveal word visual processing load) may jointly influence parafoveal processing. PMID:25911574

  17. Resveratrol Induces a Mitochondrial Complex I-dependent Increase in NADH Oxidation Responsible for Sirtuin Activation in Liver Cells*

    PubMed Central

    Desquiret-Dumas, Valérie; Gueguen, Naïg; Leman, Géraldine; Baron, Stéphanie; Nivet-Antoine, Valérie; Chupin, Stéphanie; Chevrollier, Arnaud; Vessières, Emilie; Ayer, Audrey; Ferré, Marc; Bonneau, Dominique; Henrion, Daniel; Reynier, Pascal; Procaccio, Vincent

    2013-01-01

    Resveratrol (RSV) has been shown to be involved in the regulation of energetic metabolism, generating increasing interest in therapeutic use. SIRT1 has been described as the main target of RSV. However, recent reports have challenged the hypothesis of its direct activation by RSV, and the signaling pathways remain elusive. Here, the effects of RSV on mitochondrial metabolism are detailed both in vivo and in vitro using murine and cellular models and isolated enzymes. We demonstrate that low RSV doses (1–5 μm) directly stimulate NADH dehydrogenases and, more specifically, mitochondrial complex I activity (EC50 ∼1 μm). In HepG2 cells, this complex I activation increases the mitochondrial NAD+/NADH ratio. This higher NAD+ level initiates a SIRT3-dependent increase in the mitochondrial substrate supply pathways (i.e. the tricarboxylic acid cycle and fatty acid oxidation). This effect is also seen in liver mitochondria of RSV-fed animals (50 mg/kg/day). We conclude that the increase in NADH oxidation by complex I is a crucial event for SIRT3 activation by RSV. Our results open up new perspectives in the understanding of the RSV signaling pathway and highlight the critical importance of RSV doses used for future clinical trials. PMID:24178296

  18. Towards scar-free surgery: An analysis of the increasing complexity from laparoscopic surgery to NOTES

    PubMed Central

    Chellali, Amine; Schwaitzberg, Steven D.; Jones, Daniel B.; Romanelli, John; Miller, Amie; Rattner, David; Roberts, Kurt E.; Cao, Caroline G.L.

    2014-01-01

    Background NOTES is an emerging technique for performing surgical procedures, such as cholecystectomy. Debate about its real benefit over the traditional laparoscopic technique is on-going. There have been several clinical studies comparing NOTES to conventional laparoscopic surgery. However, no work has been done to compare these techniques from a Human Factors perspective. This study presents a systematic analysis describing and comparing different existing NOTES methods to laparoscopic cholecystectomy. Methods Videos of endoscopic/laparoscopic views from fifteen live cholecystectomies were analyzed to conduct a detailed task analysis of the NOTES technique. A hierarchical task analysis of laparoscopic cholecystectomy and several hybrid transvaginal NOTES cholecystectomies was performed and validated by expert surgeons. To identify similarities and differences between these techniques, their hierarchical decomposition trees were compared. Finally, a timeline analysis was conducted to compare the steps and substeps. Results At least three variations of the NOTES technique were used for cholecystectomy. Differences between the observed techniques at the substep level of hierarchy and on the instruments being used were found. The timeline analysis showed an increase in time to perform some surgical steps and substeps in NOTES compared to laparoscopic cholecystectomy. Conclusion As pure NOTES is extremely difficult given the current state of development in instrumentation design, most surgeons utilize different hybrid methods – combination of endoscopic and laparoscopic instruments/optics. Results of our hierarchical task analysis yielded an identification of three different hybrid methods to perform cholecystectomy with significant variability amongst them. The varying degrees to which laparoscopic instruments are utilized to assist in NOTES methods appear to introduce different technical issues and additional tasks leading to an increase in the surgical time. The

  19. Botulinum toxin complex increases paracellular permeability in intestinal epithelial cells via activation of p38 mitogen-activated protein kinase.

    PubMed

    Miyashita, Shin-Ichiro; Sagane, Yoshimasa; Inui, Ken; Hayashi, Shintaro; Miyata, Keita; Suzuki, Tomonori; Ohyama, Tohru; Watanabe, Toshihiro; Niwa, Koichi

    2013-12-30

    Clostridium botulinum produces a large toxin complex (L-TC) that increases paracellular permeability in intestinal epithelial cells by a mechanism that remains unclear. Here, we show that mitogen-activated protein kinases (MAPKs) are involved in this permeability increase. Paracellular permeability was measured by FITC-dextran flux through a monolayer of rat intestinal epithelial IEC-6 cells, and MAPK activation was estimated from western blots. L-TC of C. botulinum serotype D strain 4947 increased paracellular dextran flux and activated extracellular signal-regulated kinase (ERK), p38, but not c-Jun N-terminal kinase (JNK) in IEC-6 cells. The permeability increase induced by L-TC was abrogated by the p38 inhibitor SB203580. These results indicate that L-TC increases paracellular permeability by activating p38, but not JNK and ERK. PMID:23884081

  20. Bioreactors Addressing Diabetes Mellitus

    PubMed Central

    Minteer, Danielle M.; Gerlach, Jorg C.

    2014-01-01

    The concept of bioreactors in biochemical engineering is a well-established process; however, the idea of applying bioreactor technology to biomedical and tissue engineering issues is relatively novel and has been rapidly accepted as a culture model. Tissue engineers have developed and adapted various types of bioreactors in which to culture many different cell types and therapies addressing several diseases, including diabetes mellitus types 1 and 2. With a rising world of bioreactor development and an ever increasing diagnosis rate of diabetes, this review aims to highlight bioreactor history and emerging bioreactor technologies used for diabetes-related cell culture and therapies. PMID:25160666

  1. Pentosan polysulfate increases affinity between ADAMTS-5 and TIMP-3 through formation of an electrostatically driven trimolecular complex.

    PubMed

    Troeberg, Linda; Mulloy, Barbara; Ghosh, Peter; Lee, Meng-Huee; Murphy, Gillian; Nagase, Hideaki

    2012-04-01

    The semi-synthetic sulfated polysaccharide PPS (pentosan polysulfate) increases affinity between the aggrecan-degrading ADAMTSs (adamalysins with thrombospondin motifs) and their endogenous inhibitor, TIMP (tissue inhibitor of metalloproteinases)-3. In the present study we demonstrate that PPS mediates the formation of a high-affinity trimolecular complex with ADAMTS-5 and TIMP-3. A TIMP-3 mutant that lacks extracellular-matrix-binding ability was insensitive to this affinity increase, and truncated forms of ADAMTS-5 that lack the Sp (spacer) domain had reduced PPS-binding ability and sensitivity to the affinity increase. PPS molecules composed of 11 or more saccharide units were 100-fold more effective than those of eight saccharide units, indicating the involvement of extended or multiple protein-interaction sites. The formation of a high-affinity trimolecular complex was completely abolished in the presence of 0.4 M NaCl. These results suggest that PPS enhances the affinity between ADAMTS-5 and TIMP-3 by forming electrostatically driven trimolecular complexes under physiological conditions. PMID:22299597

  2. Temperate Mountain Forest Biodiversity under Climate Change: Compensating Negative Effects by Increasing Structural Complexity

    PubMed Central

    Braunisch, Veronika; Coppes, Joy; Arlettaz, Raphaël; Suchant, Rudi; Zellweger, Florian; Bollmann, Kurt

    2014-01-01

    Species adapted to cold-climatic mountain environments are expected to face a high risk of range contractions, if not local extinctions under climate change. Yet, the populations of many endothermic species may not be primarily affected by physiological constraints, but indirectly by climate-induced changes of habitat characteristics. In mountain forests, where vertebrate species largely depend on vegetation composition and structure, deteriorating habitat suitability may thus be mitigated or even compensated by habitat management aiming at compositional and structural enhancement. We tested this possibility using four cold-adapted bird species with complementary habitat requirements as model organisms. Based on species data and environmental information collected in 300 1-km2 grid cells distributed across four mountain ranges in central Europe, we investigated (1) how species’ occurrence is explained by climate, landscape, and vegetation, (2) to what extent climate change and climate-induced vegetation changes will affect habitat suitability, and (3) whether these changes could be compensated by adaptive habitat management. Species presence was modelled as a function of climate, landscape and vegetation variables under current climate; moreover, vegetation-climate relationships were assessed. The models were extrapolated to the climatic conditions of 2050, assuming the moderate IPCC-scenario A1B, and changes in species’ occurrence probability were quantified. Finally, we assessed the maximum increase in occurrence probability that could be achieved by modifying one or multiple vegetation variables under altered climate conditions. Climate variables contributed significantly to explaining species occurrence, and expected climatic changes, as well as climate-induced vegetation trends, decreased the occurrence probability of all four species, particularly at the low-altitudinal margins of their distribution. These effects could be partly compensated by modifying

  3. Increasing fat content from 20 to 45 wt% in a complex diet induces lower endotoxemia in parallel with an increased number of intestinal goblet cells in mice.

    PubMed

    Benoit, Bérengère; Laugerette, Fabienne; Plaisancié, Pascale; Géloën, Alain; Bodennec, Jacques; Estienne, Monique; Pineau, Gaëlle; Bernalier-Donadille, Annick; Vidal, Hubert; Michalski, Marie-Caroline

    2015-04-01

    The impacts of high-fat diets (HFDs) on the onset of metabolic endotoxemia and low-grade inflammation are well established in rodent models. However, the dose-effect of dietary lipid intakes on these parameters is not known. We hypothesized that increasing dietary lipid amounts could be linked to parallel increases of endotoxemia, low-grade inflammation, and metabolic and intestinal alterations. Six-week-old male C57BL/6J mice were fed a low-fat diet (LFD, 2.6 wt% of lipids), a moderate HFD (mHFD, 22 wt% of lipids), or a very HFD (vHFD, 45 wt% of lipids) formulated mainly using chow ingredients and milk fat. After 12 weeks, white adipose tissues, liver, intestine, distal colon contents, and plasma were collected. Only vHFD mice significantly increased body weight and fat mass vs LFD mice. This was associated with increases of plasma concentrations of triglycerides, leptin and adiponectin, and liver lipids. No such differences were observed between LFD and mHFD mice. However, mHFD developed metabolic endotoxemia and inflammation, unlike vHFD mice. In turn, vHFD mice showed more goblet cells in all intestine segments vs both other groups and a decrease of Bacteroides-Prevotella in their microbiota vs LFD mice. Finally, mHFD mice colon exhibited a decrease in lactobacilli and in the levels of occludin phosphorylation. Altogether, using complex HFD, no associations were observed between dietary lipid amounts and the magnitude of endotoxemia, inflammation, and physiological alterations developed. These results reveal the impact of the diet composition on intestinal goblet cells and mucus coat, bringing new insights about further consequences on HFD-induced metabolic disorders. PMID:25687164

  4. Previous exposure to intact speech increases intelligibility of its digitally degraded counterpart as a function of stimulus complexity.

    PubMed

    Hakonen, Maria; May, Patrick J C; Alho, Jussi; Alku, Paavo; Jokinen, Emma; Jääskeläinen, Iiro P; Tiitinen, Hannu

    2016-01-15

    Recent studies have shown that acoustically distorted sentences can be perceived as either unintelligible or intelligible depending on whether one has previously been exposed to the undistorted, intelligible versions of the sentences. This allows studying processes specifically related to speech intelligibility since any change between the responses to the distorted stimuli before and after the presentation of their undistorted counterparts cannot be attributed to acoustic variability but, rather, to the successful mapping of sensory information onto memory representations. To estimate how the complexity of the message is reflected in speech comprehension, we applied this rapid change in perception to behavioral and magnetoencephalography (MEG) experiments using vowels, words and sentences. In the experiments, stimuli were initially presented to the subject in a distorted form, after which undistorted versions of the stimuli were presented. Finally, the original distorted stimuli were presented once more. The resulting increase in intelligibility observed for the second presentation of the distorted stimuli depended on the complexity of the stimulus: vowels remained unintelligible (behaviorally measured intelligibility 27%) whereas the intelligibility of the words increased from 19% to 45% and that of the sentences from 31% to 65%. This increase in the intelligibility of the degraded stimuli was reflected as an enhancement of activity in the auditory cortex and surrounding areas at early latencies of 130-160ms. In the same regions, increasing stimulus complexity attenuated mean currents at latencies of 130-160ms whereas at latencies of 200-270ms the mean currents increased. These modulations in cortical activity may reflect feedback from top-down mechanisms enhancing the extraction of information from speech. The behavioral results suggest that memory-driven expectancies can have a significant effect on speech comprehension, especially in acoustically adverse

  5. Exposure to Increased Environmental Complexity during Rearing Reduces Fearfulness and Increases Use of Three-Dimensional Space in Laying Hens (Gallus gallus domesticus)

    PubMed Central

    Brantsæter, Margrethe; Nordgreen, Janicke; Rodenburg, T. Bas; Tahamtani, Fernanda M.; Popova, Anastasija; Janczak, Andrew M.

    2016-01-01

    The complexity of the rearing environment is important for behavioral development and fearfulness. The aim of this study was to test the hypothesis that laying hens reared in a complex aviary system with exposure to mild intermittent stressors would be less fearful, less sensitive to stress, and would use elevated areas of the pen more often as adults than hens reared in a barren cage environment. Laying hens (N = 160) were housed in the same rearing house; half of the birds (n = 80) in an aviary and the other half (n = 80) in cages. At 16 weeks of age, the birds were transported to the experimental facilities. Their behavior was recorded at 19 and 23 weeks of age and analyzed by analysis of variance on individual scores for a fearfulness-related principal component generated using principal component analysis. The results indicate that aviary-reared birds have lower levels of fearfulness compared with cage-reared birds both at 19 weeks and at 23 weeks of age. When comparing the response induced by initial exposure to a novel object at 19 and 23 weeks of age, more aviary-reared birds tended to fly up at 19 weeks compared to the cage-reared birds, indicating a tendency toward a more active behavioral response in the aviary-reared birds than in cage-reared birds. There was no difference between treatments in the flight response at 23 weeks. The groups did not differ in defecation frequency or the concentration of fecal corticosterone metabolites at either age. At 19 weeks, observation of the spatial distribution in the home pens indicated that more aviary-reared birds spent time on the low perch, the elevated platform, and the upper perch, compared to the cage-reared birds. However, at 23 weeks of age, these differences were no longer detected. The results of this study support the hypothesis that increased environmental complexity during rearing reduces fearfulness of adult laying hens. PMID:26973843

  6. Exposure to Increased Environmental Complexity during Rearing Reduces Fearfulness and Increases Use of Three-Dimensional Space in Laying Hens (Gallus gallus domesticus).

    PubMed

    Brantsæter, Margrethe; Nordgreen, Janicke; Rodenburg, T Bas; Tahamtani, Fernanda M; Popova, Anastasija; Janczak, Andrew M

    2016-01-01

    The complexity of the rearing environment is important for behavioral development and fearfulness. The aim of this study was to test the hypothesis that laying hens reared in a complex aviary system with exposure to mild intermittent stressors would be less fearful, less sensitive to stress, and would use elevated areas of the pen more often as adults than hens reared in a barren cage environment. Laying hens (N = 160) were housed in the same rearing house; half of the birds (n = 80) in an aviary and the other half (n = 80) in cages. At 16 weeks of age, the birds were transported to the experimental facilities. Their behavior was recorded at 19 and 23 weeks of age and analyzed by analysis of variance on individual scores for a fearfulness-related principal component generated using principal component analysis. The results indicate that aviary-reared birds have lower levels of fearfulness compared with cage-reared birds both at 19 weeks and at 23 weeks of age. When comparing the response induced by initial exposure to a novel object at 19 and 23 weeks of age, more aviary-reared birds tended to fly up at 19 weeks compared to the cage-reared birds, indicating a tendency toward a more active behavioral response in the aviary-reared birds than in cage-reared birds. There was no difference between treatments in the flight response at 23 weeks. The groups did not differ in defecation frequency or the concentration of fecal corticosterone metabolites at either age. At 19 weeks, observation of the spatial distribution in the home pens indicated that more aviary-reared birds spent time on the low perch, the elevated platform, and the upper perch, compared to the cage-reared birds. However, at 23 weeks of age, these differences were no longer detected. The results of this study support the hypothesis that increased environmental complexity during rearing reduces fearfulness of adult laying hens. PMID:26973843

  7. Strong topographic sheltering effects lead to spatially complex treeline advance and increased forest density in a subtropical mountain region.

    PubMed

    Greenwood, Sarah; Chen, Jan-Chang; Chen, Chaur-Tzuhn; Jump, Alistair S

    2014-12-01

    Altitudinal treelines are typically temperature limited such that increasing temperatures linked to global climate change are causing upslope shifts of treelines worldwide. While such elevational increases are readily predicted based on shifting isotherms, at the regional level the realized response is often much more complex, with topography and local environmental conditions playing an important modifying role. Here, we used repeated aerial photographs in combination with forest inventory data to investigate changes in treeline position in the Central Mountain Range of Taiwan over the last 60 years. A highly spatially variable upslope advance of treeline was identified in which topography is a major driver of both treeline form and advance. The changes in treeline position that we observed occurred alongside substantial increases in forest density, and lead to a large increase in overall forest area. These changes will have a significant impact on carbon stocking in the high altitude zone, while the concomitant decrease in alpine grassland area is likely to have negative implications for alpine species. The complex and spatially variable changes that we report highlight the necessity for considering local factors such as topography when attempting to predict species distributional responses to warming climate. PMID:25141823

  8. Awards and Addresses Summary

    PubMed Central

    2008-01-01

    Each year at the annual ASHG meeting, addresses are given in honor of the society and a number of award winners. A summary of each of these addresses is given below. On the next pages, we have printed the Presidential Address and the addresses for the William Allan Award. The other addresses, accompanied by pictures of the speakers, can be found at www.ashg.org.

  9. Chlamydia trachomatis Tarp cooperates with the Arp2/3 complex to increase the rate of actin polymerization

    PubMed Central

    Jiwani, Shahanawaz; Ohr, Ryan J.; Fischer, Elizabeth R.; Hackstadt, Ted; Alvarado, Stephenie; Romero, Adriana; Jewett, Travis J.

    2012-01-01

    Actin polymerization is required for Chlamydia trachomatis entry into nonphagocytic host cells. Host and chlamydial actin nucleators are essential for internalization of chlamydiae by eukaryotic cells. The host cell Arp2/3 complex and the chlamydial translocated actin recruiting phosphoprotein (Tarp) are both required for entry. Tarp and the Arp2/3 complex exhibit unique actin polymerization kinetics individually, but the molecular details of how these two actin nucleators cooperate to promote bacterial entry is not understood. In this study we provide biochemical evidence that the two actin nucleators act synergistically by co-opting the unique attributes of each to enhance the dynamics of actin filament formation. This process is independent of Tarp phosphorylation. We further demonstrate that Tarp colocalization with actin filaments is independent of the Tarp phosphorylation domain. The results are consistent with a model in which chlamydial and host cell actin nucleators cooperate to increase the rate of actin filament formation. PMID:22465117

  10. Overexpression of the Arabidopsis anaphase promoting complex subunit CDC27a increases growth rate and organ size.

    PubMed

    Rojas, Cristian Antonio; Eloy, Nubia Barbosa; Lima, Marcelo de Freitas; Rodrigues, Roberta Lopes; Franco, Luciana Ozório; Himanen, Kristiina; Beemster, Gerrit T S; Hemerly, Adriana Silva; Ferreira, Paulo Cavalcanti Gomes

    2009-10-01

    The Anaphase Promoting Complex (APC) controls CDK activity by targeting the ubiquitin-dependent proteolysis of S-phase and mitosis-promoting cyclins. Here, we report that the ectopic expression of the Arabidopsis CDC27a, an APC subunit, accelerates plant growth and results in plants with increased biomass production. CDC27a overexpression was associated to apical meristem restructuration, protoplasts with higher (3)H-thimidine incorporation and altered cell-cycle marker expression. Total protein extracts immunoprecipitated with a CDC27a antibody showed ubiquitin ligase activity, indicating that the Arabidopsis CDC27a gets incorporated into APC complexes. These results indicate a role of AtCDC27a in regulation of plant growth and raise the possibility that the activity of the APC and the rates of plant cell division could be regulated by the concentration of the CDC27a subunit. PMID:19629716

  11. Increased platelet count and leucocyte–platelet complex formation in acute symptomatic compared with asymptomatic severe carotid stenosis

    PubMed Central

    McCabe, D; Harrison, P; Mackie, I; Sidhu, P; Purdy, G; Lawrie, A; Watt, H; Machin, S; Brown, M

    2005-01-01

    Objective: The risk of stroke in patients with recently symptomatic carotid stenosis is considerably higher than in patients with asymptomatic stenosis. In the present study it was hypothesised that excessive platelet activation might partly contribute to this difference. Methods: A full blood count was done and whole blood flow cytometry used to measure platelet surface expression of CD62P, CD63, and PAC1 binding and the percentage of leucocyte–platelet complexes in patients with acute (0–21 days, n = 19) and convalescent (79–365 days) symptomatic (n = 16) and asymptomatic (n = 16) severe (⩾70%) carotid stenosis. Most patients were treated with aspirin (37.5–300 mg daily) although alternative antithrombotic regimens were more commonly used in the symptomatic group. Results: The mean platelet count was higher in patients with acute and convalescent symptomatic compared with asymptomatic carotid stenosis. There were no significant differences in the median percentage expression of CD62P and CD63, or PAC1 binding between the acute or convalescent symptomatic and asymptomatic patients. The median percentages of neutrophil–platelet (p = 0.004), monocyte–platelet (p = 0.046), and lymphocyte–platelet complexes (p = 0.02) were higher in acute symptomatic than in asymptomatic patients. In patients on aspirin monotherapy, the percentages of neutrophil–platelet and monocyte–platelet complexes (p = 0.03) were higher in acute symptomatic (n = 11) than asymptomatic patients (n = 14). In the convalescent phase, the median percentages of all leucocyte–platelet complexes in the symptomatic group dropped to levels similar to those found in the asymptomatic group. Conclusion: Increased platelet count and leucocyte–platelet complex formation may contribute to the early excess risk of stroke in patients with recently symptomatic carotid stenosis. PMID:16107361

  12. Inhibition of Neuronal Cell Mitochondrial Complex I with Rotenone Increases Lipid β-Oxidation, Supporting Acetyl-Coenzyme A Levels*

    PubMed Central

    Worth, Andrew J.; Basu, Sankha S.; Snyder, Nathaniel W.; Mesaros, Clementina; Blair, Ian A.

    2014-01-01

    Rotenone is a naturally occurring mitochondrial complex I inhibitor with a known association with parkinsonian phenotypes in both human populations and rodent models. Despite these findings, a clear mechanistic link between rotenone exposure and neuronal damage remains to be determined. Here, we report alterations to lipid metabolism in SH-SY5Y neuroblastoma cells exposed to rotenone. The absolute levels of acetyl-CoA were found to be maintained despite a significant decrease in glucose-derived acetyl-CoA. Furthermore, palmitoyl-CoA levels were maintained, whereas the levels of many of the medium-chain acyl-CoA species were significantly reduced. Additionally, using isotopologue analysis, we found that β-oxidation of fatty acids with varying chain lengths helped maintain acetyl-CoA levels. Rotenone also induced increased glutamine utilization for lipogenesis, in part through reductive carboxylation, as has been found previously in other cell types. Finally, palmitoylcarnitine levels were increased in response to rotenone, indicating an increase in fatty acid import. Taken together, these findings show that alterations to lipid and glutamine metabolism play an important compensatory role in response to complex I inhibition by rotenone. PMID:25122772

  13. Low-dose ionizing radiation induces mitochondrial fusion and increases expression of mitochondrial complexes I and III in hippocampal neurons

    PubMed Central

    Chang, Chuang-Rung; Kao, Mou-Chieh; Chen, Kuan-Wei; Chiu, Shih-Che; Hsu, Ming-Ling; Hsiang, I-Chou; Chen, Yu-Jen; Chen, Linyi

    2015-01-01

    High energy ionizing radiation can cause DNA damage and cell death. During clinical radiation therapy, the radiation dose could range from 15 to 60 Gy depending on targets. While 2 Gy radiation has been shown to cause cancer cell death, studies also suggest a protective potential by low dose radiation. In this study, we examined the effect of 0.2-2 Gy radiation on hippocampal neurons. Low dose 0.2 Gy radiation treatment increased the levels of MTT. Since hippocampal neurons are post-mitotic, this result reveals a possibility that 0.2 Gy irradiation may increase mitochondrial activity to cope with stimuli. Maintaining neural plasticity is an energy-demanding process that requires high efficient mitochondrial function. We thus hypothesized that low dose radiation may regulate mitochondrial dynamics and function to ensure survival of neurons. Our results showed that five days after 0.2 Gy irradiation, no obvious changes on neuronal survival, neuronal synapses, membrane potential of mitochondria, reactive oxygen species levels, and mitochondrial DNA copy numbers. Interestingly, 0.2 Gy irradiation promoted the mitochondria fusion, resulting in part from the increased level of a mitochondrial fusion protein, Mfn2, and inhibition of Drp1 fission protein trafficking to the mitochondria. Accompanying with the increased mitochondrial fusion, the expressions of complexes I and III of the electron transport chain were also increased. These findings suggest that, hippocampal neurons undergo increased mitochondrial fusion to modulate cellular activity as an adaptive mechanism in response to low dose radiation. PMID:26415228

  14. Constraint of the limited information content of discharge measurements on the benefits of rating curve models with increased complexities

    NASA Astrophysics Data System (ADS)

    Van Eerdenbrugh, Katrien; Verhoest, Niko; De Mulder, Tom

    2015-04-01

    Discharge assessment through rating curves is a widespread technique in the field of hydrologic monitoring. In practical applications, this technique often consists of the use of one or multiple power laws, based on rather stringent assumptions concerning the nature of the prevailing flow conditions. In reality, those assumptions are regularly violated, inducing considerable uncertainties in the calculated discharges. It is thus important to estimate the effect of those simplifications when performing an overall uncertainty analysis of rating curve discharges. In this study, different rating curve formulations are compared based on both results of a hydrodynamic model and measured water levels and discharges. The results of a hydrodynamic model are used to justify the applicability of several rating curve models with increased complexity as an alternative for a single power law equation. With the hydrodynamic model, situations are simulated that correspond to steady state conditions and to minimal effect of downstream boundaries. Comparison of simulations results with those of measurement-driven simulations leads to an increased understanding of the rating curve dynamics. It allows for evaluation of rating curve formulations accounting for the influences of hysteresis and backwater effects which are neglected in power law rating curves. Subsequently, the performance of those rating curve models and the identifiability of their parameters are assessed based on available stage-discharge measurements and their accompanying uncertainties as described in literature. This assessment is performed based on the Generalised Likelihood Uncertainty Estimation (GLUE). Rejection criteria to distinguish behavioural from non-behavioural models are defined by uncertainties on both water levels and discharge measurements that envelop measured data points. The results of the hydrodynamic model clearly indicate benefits of adding complexity to the rating curve model, mainly by

  15. Dietary Tocotrienol/γ-Cyclodextrin Complex Increases Mitochondrial Membrane Potential and ATP Concentrations in the Brains of Aged Mice

    PubMed Central

    Schloesser, Anke; Esatbeyoglu, Tuba; Piegholdt, Stefanie; Dose, Janina; Ikuta, Naoko; Okamoto, Hinako; Ishida, Yoshiyuki; Terao, Keiji; Matsugo, Seiichi; Rimbach, Gerald

    2015-01-01

    Brain aging is accompanied by a decrease in mitochondrial function. In vitro studies suggest that tocotrienols, including γ- and δ-tocotrienol (T3), may exhibit neuroprotective properties. However, little is known about the effect of dietary T3 on mitochondrial function in vivo. In this study, we monitored the effect of a dietary T3/γ-cyclodextrin complex (T3CD) on mitochondrial membrane potential and ATP levels in the brain of 21-month-old mice. Mice were fed either a control diet or a diet enriched with T3CD providing 100 mg T3 per kg diet for 6 months. Dietary T3CD significantly increased mitochondrial membrane potential and ATP levels compared to those of controls. The increase in MMP and ATP due to dietary T3CD was accompanied by an increase in the protein levels of the mitochondrial transcription factor A (TFAM). Furthermore, dietary T3CD slightly increased the mRNA levels of superoxide dismutase, γ-glutamyl cysteinyl synthetase, and heme oxygenase 1 in the brain. Overall, the present data suggest that T3CD increases TFAM, mitochondrial membrane potential, and ATP synthesis in the brains of aged mice. PMID:26301044

  16. Acute Carnosine Administration Increases Respiratory Chain Complexes and Citric Acid Cycle Enzyme Activities in Cerebral Cortex of Young Rats.

    PubMed

    Macedo, Levy W; Cararo, José H; Maravai, Soliany G; Gonçalves, Cinara L; Oliveira, Giovanna M T; Kist, Luiza W; Guerra Martinez, Camila; Kurtenbach, Eleonora; Bogo, Maurício R; Hipkiss, Alan R; Streck, Emilio L; Schuck, Patrícia F; Ferreira, Gustavo C

    2016-10-01

    Carnosine (β-alanyl-L-histidine) is an imidazole dipeptide synthesized in excitable tissues of many animals, whose biochemical properties include carbonyl scavenger, anti-oxidant, bivalent metal ion chelator, proton buffer, and immunomodulating agent, although its precise physiological role(s) in skeletal muscle and brain tissues in vivo remain unclear. The aim of the present study was to investigate the in vivo effects of acute carnosine administration on various aspects of brain bioenergetics of young Wistar rats. The activity of mitochondrial enzymes in cerebral cortex was assessed using a spectrophotometer, and it was found that there was an increase in the activities of complexes I-III and II-III and succinate dehydrogenase in carnosine-treated rats, as compared to vehicle-treated animals. However, quantitative real-time RT-PCR (RT-qPCR) data on mRNA levels of mitochondrial biogenesis-related proteins (nuclear respiratory factor 1 (Nrf1), peroxisome proliferator-activated receptor-γ coactivator 1-α (Ppargc1α), and mitochondrial transcription factor A (Tfam)) were not altered significantly and therefore suggest that short-term carnosine administration does not affect mitochondrial biogenesis. It was in agreement with the finding that immunocontent of respiratory chain complexes was not altered in animals receiving carnosine. These observations indicate that acute carnosine administration increases the respiratory chain and citric acid cycle enzyme activities in cerebral cortex of young rats, substantiating, at least in part, a neuroprotector effect assigned to carnosine against oxidative-driven disorders. PMID:26476839

  17. Determination of local optical response functions of nanostructures with increasing complexity by using single and coupled Lorentzian oscillator models

    NASA Astrophysics Data System (ADS)

    Aeschlimann, Martin; Brixner, Tobias; Fischer, Alexander; Hensen, Matthias; Huber, Bernhard; Kilbane, Deirdre; Kramer, Christian; Pfeiffer, Walter; Piecuch, Martin; Thielen, Philip

    2016-07-01

    We reconstruct the optical response of nanostructures of increasing complexity by fitting interferometric time-resolved photoemission electron microscopy (PEEM) data from an ultrashort (21 fs) laser excitation source with different harmonic oscillator-based models. Due to its high spatial resolution of ~40 nm, PEEM is a true near-field imaging system and enables in normal incidence mode a mapping of plasmon polaritons and an intuitive interpretation of the plasmonic behaviour. Using an actively stabilized Mach-Zehnder interferometer, we record two-pulse correlation signals with 50 as time resolution that contain information about the temporal plasmon polariton evolution. Spectral amplitude and phase of excited plasmon polaritons are extracted from the recorded phase-resolved interferometric two-pulse correlation traces. We show that the optical response of a plasmon polariton generated at a gold nanoparticle can be reconstructed from the interferometric two-pulse correlation signal using a single harmonic oscillator model. In contrast, for a corrugated silver surface, a system with increased plasmonic complexity, in general an unambiguous reconstruction of the local optical response based on coupled and uncoupled harmonic oscillators, fails. Whereas for certain local responses different models can be discriminated, this is impossible for other positions. Multidimensional spectroscopy offers a possibility to overcome this limitation.

  18. Depleted energy charge and increased pulmonary endothelial permeability induced by mitochondrial complex I inhibition are mitigated by coenzyme Q1 in the isolated perfused rat lung.

    PubMed

    Bongard, Robert D; Yan, Ke; Hoffmann, Raymond G; Audi, Said H; Zhang, Xiao; Lindemer, Brian J; Townsley, Mary I; Merker, Marilyn P

    2013-12-01

    Mitochondrial dysfunction is associated with various forms of lung injury and disease that also involve alterations in pulmonary endothelial permeability, but the relationship, if any, between the two is not well understood. This question was addressed by perfusing isolated intact rat lung with a buffered physiological saline solution in the absence or presence of the mitochondrial complex I inhibitor rotenone (20 μM). Compared to control, rotenone depressed whole lung tissue ATP from 5.66 ± 0.46 (SEM) to 2.34 ± 0.15 µmol · g(-1) dry lung, with concomitant increases in the ADP:ATP and AMP:ATP ratios. Rotenone also increased lung perfusate lactate (from 12.36 ± 1.64 to 38.62 ± 3.14 µmol · 15 min(-1) perfusion · g(-1) dry lung) and the lactate:pyruvate ratio, but had no detectable impact on lung tissue GSH:GSSG redox status. The amphipathic quinone coenzyme Q1 (CoQ1; 50 μM) mitigated the impact of rotenone on the adenine nucleotide balance, wherein mitigation was blocked by NAD(P)H-quinone oxidoreductase 1 or mitochondrial complex III inhibitors. In separate studies, rotenone increased the pulmonary vascular endothelial filtration coefficient (Kf) from 0.043 ± 0.010 to 0.156 ± 0.037 ml · min(-1) · cm H2O(-1) · g(-1) dry lung, and CoQ1 protected against the effect of rotenone on Kf. A second complex I inhibitor, piericidin A, qualitatively reproduced the impact of rotenone on Kf and the lactate:pyruvate ratio. Taken together, the observations imply that pulmonary endothelial barrier integrity depends on mitochondrial bioenergetics as reflected in lung tissue ATP levels and that compensatory activation of whole lung glycolysis cannot protect against pulmonary endothelial hyperpermeability in response to mitochondrial blockade. The study further suggests that low-molecular-weight amphipathic quinones may have therapeutic utility in protecting lung barrier function in mitochondrial insufficiency. PMID:23912160

  19. Depleted energy charge and increased pulmonary endothelial permeability induced by mitochondrial complex I inhibition are mitigated by coenzyme Q1 in the isolated perfused rat lung

    PubMed Central

    Bongard, Robert D.; Yan, Ke; Hoffmann, Raymond G.; Audi, Said H.; Zhang, Xiao; Lindemer, Brian J.; Townsley, Mary I.; Merker, Marilyn P.

    2013-01-01

    Mitochondrial dysfunction is associated with various forms of lung injury and disease that also involve alterations in pulmonary endothelial permeability, but the relationship, if any, between the two is not well understood. This question was addressed by perfusing the isolated intact rat lung with a buffered physiological saline solution in the absence or presence of the mitochondrial complex I inhibitor rotenone (20 uM). As compared to control, rotenone depressed whole lung tissue ATP from 5.66 ± 0.46 (SEM) to 2.34 ± 0.15 (SEM) μmol·gram−1 dry lung, with concomitant increases in the ADP:ATP and AMP:ATP ratios. Rotenone also increased lung perfusate lactate (from 12.36 ± 1.64 (SEM) to 38.62 ± 3.14 μmol·15 min−1 perfusion·gm−1 dry lung) and the lactate:pyruvate ratio, but had no detectable impact on lung tissue GSH:GSSG redox status. The amphipathic quinone, coenzyme Q1 (CoQ1; 50 μM) mitigated the impact of rotenone on the adenine nucleotide balance, wherein mitigation was blocked by NAD(P)H:quinone oxidoreductase 1 (NQO1) or mitochondrial complex III inhibitors. In separate studies, rotenone increased the pulmonary vascular endothelial filtration coefficient (Kf) from 0.043 ± 0.010 (SEM) to 0.156 ± 0.037 (SEM) ml·min−1·cm H2O−1·gm−1 dry lung weight, and CoQ1 protected against the effect of rotenone on Kf. A second complex I inhibitor, piericidin A, qualitatively reproduced the impact of rotenone on Kf and the lactate/pyruvate ratio. Taken together, the observations imply that pulmonary endothelial barrier integrity depends on mitochondrial bioenergetics as reflected in lung tissue ATP levels and that compensatory activation of whole lung glycolysis cannot protect against pulmonary endothelial hyperpermeability in response to mitochondrial blockade. The study further suggests that low molecular weight amphipathic quinones may have therapeutic utility in protecting lung barrier function in mitochondrial insufficiency. PMID:23912160

  20. Dietary nitrate increases arginine availability and protects mitochondrial complex I and energetics in the hypoxic rat heart

    PubMed Central

    Ashmore, Tom; Fernandez, Bernadette O; Branco-Price, Cristina; West, James A; Cowburn, Andrew S; Heather, Lisa C; Griffin, Julian L; Johnson, Randall S; Feelisch, Martin; Murray, Andrew J

    2014-01-01

    Hypoxic exposure is associated with impaired cardiac energetics in humans and altered mitochondrial function, with suppressed complex I-supported respiration, in rat heart. This response might limit reactive oxygen species generation, but at the cost of impaired electron transport chain (ETC) activity. Dietary nitrate supplementation improves mitochondrial efficiency and can promote tissue oxygenation by enhancing blood flow. We therefore hypothesised that ETC dysfunction, impaired energetics and oxidative damage in the hearts of rats exposed to chronic hypoxia could be alleviated by sustained administration of a moderate dose of dietary nitrate. Male Wistar rats (n = 40) were given water supplemented with 0.7 mmol l−1 NaCl (as control) or 0.7 mmol l−1 NaNO3, elevating plasma nitrate levels by 80%, and were exposed to 13% O2 (hypoxia) or normoxia (n = 10 per group) for 14 days. Respiration rates, ETC protein levels, mitochondrial density, ATP content and protein carbonylation were measured in cardiac muscle. Complex I respiration rates and protein levels were 33% lower in hypoxic/NaCl rats compared with normoxic/NaCl controls. Protein carbonylation was 65% higher in hearts of hypoxic rats compared with controls, indicating increased oxidative stress, whilst ATP levels were 62% lower. Respiration rates, complex I protein and activity, protein carbonylation and ATP levels were all fully protected in the hearts of nitrate-supplemented hypoxic rats. Both in normoxia and hypoxia, dietary nitrate suppressed cardiac arginase expression and activity and markedly elevated cardiac l-arginine concentrations, unmasking a novel mechanism of action by which nitrate enhances tissue NO bioavailability. Dietary nitrate therefore alleviates metabolic abnormalities in the hypoxic heart, improving myocardial energetics. PMID:25172947

  1. Planting increases the abundance and structure complexity of soil core functional genes relevant to carbon and nitrogen cycling

    NASA Astrophysics Data System (ADS)

    Wang, Feng; Liang, Yuting; Jiang, Yuji; Yang, Yunfeng; Xue, Kai; Xiong, Jinbo; Zhou, Jizhong; Sun, Bo

    2015-09-01

    Plants have an important impact on soil microbial communities and their functions. However, how plants determine the microbial composition and network interactions is still poorly understood. During a four-year field experiment, we investigated the functional gene composition of three types of soils (Phaeozem, Cambisols and Acrisol) under maize planting and bare fallow regimes located in cold temperate, warm temperate and subtropical regions, respectively. The core genes were identified using high-throughput functional gene microarray (GeoChip 3.0), and functional molecular ecological networks (fMENs) were subsequently developed with the random matrix theory (RMT)-based conceptual framework. Our results demonstrated that planting significantly (P < 0.05) increased the gene alpha-diversity in terms of richness and Shannon - Simpson’s indexes for all three types of soils and 83.5% of microbial alpha-diversity can be explained by the plant factor. Moreover, planting had significant impacts on the microbial community structure and the network interactions of the microbial communities. The calculated network complexity was higher under maize planting than under bare fallow regimes. The increase of the functional genes led to an increase in both soil respiration and nitrification potential with maize planting, indicating that changes in the soil microbial communities and network interactions influenced ecological functioning.

  2. Planting increases the abundance and structure complexity of soil core functional genes relevant to carbon and nitrogen cycling

    PubMed Central

    Wang, Feng; Liang, Yuting; Jiang, Yuji; Yang, Yunfeng; Xue, Kai; Xiong, Jinbo; Zhou, Jizhong; Sun, Bo

    2015-01-01

    Plants have an important impact on soil microbial communities and their functions. However, how plants determine the microbial composition and network interactions is still poorly understood. During a four-year field experiment, we investigated the functional gene composition of three types of soils (Phaeozem, Cambisols and Acrisol) under maize planting and bare fallow regimes located in cold temperate, warm temperate and subtropical regions, respectively. The core genes were identified using high-throughput functional gene microarray (GeoChip 3.0), and functional molecular ecological networks (fMENs) were subsequently developed with the random matrix theory (RMT)-based conceptual framework. Our results demonstrated that planting significantly (P < 0.05) increased the gene alpha-diversity in terms of richness and Shannon – Simpson’s indexes for all three types of soils and 83.5% of microbial alpha-diversity can be explained by the plant factor. Moreover, planting had significant impacts on the microbial community structure and the network interactions of the microbial communities. The calculated network complexity was higher under maize planting than under bare fallow regimes. The increase of the functional genes led to an increase in both soil respiration and nitrification potential with maize planting, indicating that changes in the soil microbial communities and network interactions influenced ecological functioning. PMID:26396042

  3. Increased Platelet Reactivity Is Associated with Circulating Platelet-Monocyte Complexes and Macrophages in Human Atherosclerotic Plaques

    PubMed Central

    Vrijenhoek, Joyce E. P.; van Holten, Thijs C.; Elsenberg, Ellen H. A. M.; Mak-Nienhuis, Elske M.; de Borst, Gert Jan; Jukema, J. Wouter; Pijls, Nico H. J.; Waltenberger, Johannes; van Zonneveld, Anton Jan; Moll, Frans L.; McClellan, Elizabeth; Stubbs, Andrew; Pasterkamp, Gerard; Hoefer, Imo; de Groot, Philip G.; Roest, Mark

    2014-01-01

    Objective Platelet reactivity, platelet binding to monocytes and monocyte infiltration play a detrimental role in atherosclerotic plaque progression. We investigated whether platelet reactivity was associated with levels of circulating platelet-monocyte complexes (PMCs) and macrophages in human atherosclerotic carotid plaques. Methods Platelet reactivity was determined by measuring platelet P-selectin expression after platelet stimulation with increasing concentrations of adenosine diphosphate (ADP), in two independent cohorts: the Circulating Cells cohort (n = 244) and the Athero-Express cohort (n = 91). Levels of PMCs were assessed by flow cytometry in blood samples of patients who were scheduled for percutaneous coronary intervention (Circulating Cells cohort). Monocyte infiltration was semi-quantitatively determined by histological examination of atherosclerotic carotid plaques collected during carotid endarterectomy (Athero-Express cohort). Results We found increased platelet reactivity in patients with high PMCs as compared to patients with low PMCs (median (interquartile range): 4153 (1585–11267) area under the curve (AUC) vs. 9633 (3580–21565) AUC, P<0.001). Also, we observed increased platelet reactivity in patients with high macrophage levels in atherosclerotic plaques as compared to patients with low macrophage levels in atherosclerotic plaques (mean±SD; 8969±3485 AUC vs. 7020±3442 AUC, P = 0.02). All associations remained significant after adjustment for age, sex and use of drugs against platelet activation. Conclusion Platelet reactivity towards ADP is associated with levels of PMCs and macrophages in human atherosclerotic carotid plaques. PMID:25122139

  4. Increasing Regulatory T Cells With Interleukin-2 and Interleukin-2 Antibody Complexes Attenuates Lung Inflammation and Heart Failure Progression.

    PubMed

    Wang, Huan; Hou, Lei; Kwak, Dongmin; Fassett, John; Xu, Xin; Chen, Angela; Chen, Wei; Blazar, Bruce R; Xu, Yawei; Hall, Jennifer L; Ge, Jun-Bo; Bache, Robert J; Chen, Yingjie

    2016-07-01

    Congestive heart failure (CHF) is associated with an increase of leukocyte infiltration, proinflammatory cytokines, and fibrosis in the heart and lung. Regulatory T cells (Tregs, CD4(+)CD25(+)FoxP3(+)) suppress inflammatory responses in various clinical conditions. We postulated that expansion of Tregs attenuates CHF progression by reducing cardiac and lung inflammation. We investigated the effects of interleukin-2 (IL-2) plus IL-2 monoclonal antibody clone JES6-1 complexes (IL2/JES6-1) on induction of Tregs, transverse aortic constriction-induced cardiac and lung inflammation, and CHF progression in mice. We demonstrated that end-stage CHF caused a massive increase of lung macrophages and T cells, as well as relatively mild left ventricular (LV) leukocyte infiltration. Administration of IL2/JES6-1 caused an ≈6-fold increase of Tregs within CD4(+) T cells in the spleen, lung, and heart of mice. IL2/JES6-1 treatment of mice with existing transverse aortic constriction-induced LV failure markedly reduced lung and right ventricular weight and improved LV ejection fraction and LV end-diastolic pressure. Mechanistically, IL2/JES6-1 treatment significantly increased Tregs; suppressed CD4(+) T-cell accumulation; dramatically attenuated leukocyte infiltration, including decreasing CD45(+) cells, macrophages, CD8(+) T cells, and effector memory CD8(+); and reduced proinflammatory cytokine expressions and fibrosis in the lung of mice. Furthermore, IL2/JES6-1 administered before transverse aortic constriction attenuated the development of LV hypertrophy and dysfunction in mice. Our data indicate that increasing Tregs through administration of IL2/JES6-1 effectively attenuates pulmonary inflammation, right ventricular hypertrophy, and further LV dysfunction in mice with existing LV failure, suggesting that strategies to properly expand Tregs may be useful in reducing CHF progression. PMID:27160197

  5. The complex SNP and CNV genetic architecture of the increased risk of congenital heart defects in Down syndrome

    PubMed Central

    Sailani, M. Reza; Makrythanasis, Periklis; Valsesia, Armand; Santoni, Federico A.; Deutsch, Samuel; Popadin, Konstantin; Borel, Christelle; Migliavacca, Eugenia; Sharp, Andrew J.; Duriaux Sail, Genevieve; Falconnet, Emilie; Rabionet, Kelly; Serra-Juhé, Clara; Vicari, Stefano; Laux, Daniela; Grattau, Yann; Dembour, Guy; Megarbane, Andre; Touraine, Renaud; Stora, Samantha; Kitsiou, Sofia; Fryssira, Helena; Chatzisevastou-Loukidou, Chariklia; Kanavakis, Emmanouel; Merla, Giuseppe; Bonnet, Damien; Pérez-Jurado, Luis A.; Estivill, Xavier; Delabar, Jean M.; Antonarakis, Stylianos E.

    2013-01-01

    Congenital heart defect (CHD) occurs in 40% of Down syndrome (DS) cases. While carrying three copies of chromosome 21 increases the risk for CHD, trisomy 21 itself is not sufficient to cause CHD. Thus, additional genetic variation and/or environmental factors could contribute to the CHD risk. Here we report genomic variations that in concert with trisomy 21, determine the risk for CHD in DS. This case-control GWAS includes 187 DS with CHD (AVSD = 69, ASD = 53, VSD = 65) as cases, and 151 DS without CHD as controls. Chromosome 21–specific association studies revealed rs2832616 and rs1943950 as CHD risk alleles (adjusted genotypic P-values <0.05). These signals were confirmed in a replication cohort of 92 DS-CHD cases and 80 DS-without CHD (nominal P-value 0.0022). Furthermore, CNV analyses using a customized chromosome 21 aCGH of 135K probes in 55 DS-AVSD and 53 DS-without CHD revealed three CNV regions associated with AVSD risk (FDR ≤ 0.05). Two of these regions that are located within the previously identified CHD region on chromosome 21 were further confirmed in a replication study of 49 DS-AVSD and 45 DS- without CHD (FDR ≤ 0.05). One of these CNVs maps near the RIPK4 gene, and the second includes the ZBTB21 (previously ZNF295) gene, highlighting the potential role of these genes in the pathogenesis of CHD in DS. We propose that the genetic architecture of the CHD risk of DS is complex and includes trisomy 21, and SNP and CNV variations in chromosome 21. In addition, a yet-unidentified genetic variation in the rest of the genome may contribute to this complex genetic architecture. PMID:23783273

  6. Combining evidence of selection with association analysis increases power to detect regions influencing complex traits in dairy cattle

    PubMed Central

    2012-01-01

    Background Hitchhiking mapping and association studies are two popular approaches to map genotypes to phenotypes. In this study we combine both approaches to complement their specific strengths and weaknesses, resulting in a method with higher statistical power and fewer false positive signals. We applied our approach to dairy cattle as they underwent extremely successful selection for milk production traits and since an excellent phenotypic record is available. We performed whole genome association tests with a new mixed model approach to account for stratification, which we validated via Monte Carlo simulations. Selection signatures were inferred with the integrated haplotype score and a locus specific permutation based integrated haplotype score that works with a folded frequency spectrum and provides a formal test of signifance to identify selection signatures. Results About 1,600 out of 34,851 SNPs showed signatures of selection and the locus specific permutation based integrated haplotype score showed overall good accordance with the whole genome association study. Each approach provides distinct information about the genomic regions that influence complex traits. Combining whole genome association with hitchhiking mapping yielded two significant loci for the trait protein yield. These regions agree well with previous results from other selection signature scans and whole genome association studies in cattle. Conclusion We show that the combination of whole genome association and selection signature mapping based on the same SNPs increases the power to detect loci influencing complex traits. The locus specific permutation based integrated haplotype score provides a formal test of significance in selection signature mapping. Importantly it does not rely on knowledge of ancestral and derived allele states. PMID:22289501

  7. Adsorption and self-assembly of bio-organic molecules at model surfaces: A route towards increased complexity

    NASA Astrophysics Data System (ADS)

    Costa, Dominique; Pradier, Claire-Marie; Tielens, Frederik; Savio, Letizia

    2015-12-01

    attention will be drawn to the added value provided by the combination of several experimental surface science techniques and to the precious contribution of advanced complementary computational methods to resolve the details of systems of increased complexity. Finally, some hints on experiments performed in presence of water and then characterized in UHV and on the related theoretical work will be presented. This is a further step towards a better approximation of real biological systems. However, since the methods employed are often not typical of surface science, this topic is not developed in detail.

  8. Increasing Nitrogen Fixation and Seed Development in Soybean Requires Complex Adjustments of Nodule Nitrogen Metabolism and Partitioning Processes.

    PubMed

    Carter, Amanda M; Tegeder, Mechthild

    2016-08-01

    Legumes are able to access atmospheric di-nitrogen (N2) through a symbiotic relationship with rhizobia that reside within root nodules. In soybean, following N2 fixation by the bacteroids, ammonia is finally reduced in uninfected cells to allantoin and allantoic acid [1]. These ureides present the primary long-distance transport forms of nitrogen (N), and are exported from nodules via the xylem for shoot N supply. Transport of allantoin and allantoic acid out of nodules requires the function of ureide permeases (UPS1) located in cells adjacent to the vasculature [2, 3]. We expressed a common bean UPS1 transporter in cortex and endodermis cells of soybean nodules and found that delivery of N from nodules to shoot, as well as seed set, was significantly increased. In addition, the number of transgenic nodules was increased and symbiotic N2 fixation per nodule was elevated, indicating that transporter function in nodule N export is a limiting step in bacterial N acquisition. Further, the transgenic nodules showed considerable increases in nodule N assimilation, ureide synthesis, and metabolite levels. This suggests complex adjustments of nodule N metabolism and partitioning processes in support of symbiotic N2 fixation. We propose that the transgenic UPS1 plants display metabolic and allocation plasticity to overcome N2 fixation and seed yield limitations. Overall, it is demonstrated that transporter function in N export from nodules is a key step for enhancing atmospheric N2 fixation and nodule function and for improving shoot N nutrition and seed development in legumes. PMID:27451897

  9. Magnetic content addressable memories

    NASA Astrophysics Data System (ADS)

    Jiang, Zhenye

    Content Addressable Memories are designed with comparison circuits built into every bit cell. This parallel structure can increase the speed of searching from O(n) (as with Random Access Memories) to O(1), where n is the number of entries being searched. The high cost in hardware limits the application of CAM within situations where higher searching speed is extremely desired. Spintronics technology can build non-volatile Magnetic RAM with only one device for one bit cell. There are various technologies involved, like Magnetic Tunnel Junctions, off-easy-axis programming method, Synthetic Anti-Ferromagnetic tri-layers, Domain Wall displacement, Spin Transfer Torque tri-layers and etc. With them, particularly the Tunnel Magneto-Resistance variation in MTJ due to difference in magnetization polarity of the two magnets, Magnetic CAM can be developed with reduced hardware cost. And this is demonstrated by the discussion in this dissertation. Six MCAM designs are discussed. In the first design, comparand (C), local information (S) and their complements are stored into 4 MTJs connected in XOR gate pattern. The other five designs have one or two stacks for both information storage and comparison, and full TMR ratio can be taken advantage of. Two challenges for the five are specifically programming C without changing S and selectively programming a cell out of an array. The solutions to specific programming are: by confining the programming field for C in a ring structure design; by using field programming and spin polarized current programming respectively for C and S in the SAF+DW and SAF+STT tri-layer design; by making use of the difference in thresholds between direct mode and toggle mode switching in the SAF+SAF design. The problem of selective programming is addressed by off-easy-axis method and by including SAF tri-layers. Cell with STT tri-layers for both C and S can completely avoid the problems of specific and selective programming, but subject to the limit of

  10. The Need for a Counseling Psychology Model Training Values Statement Addressing Diversity

    ERIC Educational Resources Information Center

    Mintz, Laurie B.; Jackson, Aaron P.; Neville, Helen A.; Illfelder-Kaye, Joyce; Winterowd, Carrie L.; Loewy, Michael I.

    2009-01-01

    The authors articulate the need for a "Counseling Psychology Model Training Values Statement Addressing Diversity" (henceforth "Values Statement"). They discuss the historic unwillingness of the field to address values in a sophisticated or complex way and highlight the increasingly common training scenario in which trainees state that certain…

  11. Lack of nitric oxide synthases increases lipoprotein immune complex deposition in the aorta and elevates plasma sphingolipid levels in lupus

    PubMed Central

    Al Gadban, Mohammed M.; German, Jashalynn; Truman, Jean-Philip; Soodavar, Farzan; Riemer, Ellen C; Twal, Waleed O; Smith, Kent J; Heller, Demarcus; Hofbauer, Ann F; Oates, Jim C.; Hammad, Samar M.

    2012-01-01

    Systemic lupus erythematosus (SLE) patients display impaired endothelial nitric oxide synthase (eNOS) function required for normal vasodilatation. SLE patients express increased compensatory activity of inducible nitric oxide synthase (iNOS) generating excess nitric oxide that may result in inflammation. We examined the effects of genetic deletion of NOS2 and NOS3, encoding iNOS and eNOS respectively, on accelerated vascular disease in MRL/lpr lupus mouse model. NOS2 and NOS3 knockout (KO) MRL/lpr mice had higher plasma levels of triglycerides (23% and 35%, respectively), ceramide (45% and 21%, respectively), and sphingosine 1-phosphate (S1P) (21%) compared to counterpart MRL/lpr controls. Plasma levels of the anti-inflammatory cytokine interleukin 10 (IL-10) in NOS2 and NOS3 KO MRL/lpr mice were lower (53% and 80%, respectively) than counterpart controls. Nodule-like lesions in the adventitia were detected in aortas from both NOS2 and NOS3 KO MRL/lpr mice. Immunohistochemical evaluation of the lesions revealed activated endothelial cells and lipid-laden macrophages (foam cells), elevated sphingosine kinase 1 expression, and oxidized low-density lipoprotein immune complexes (oxLDL-IC). The findings suggest that advanced vascular disease in NOS2 and NOS3 KO MRL/lpr mice maybe mediated by increased plasma triglycerides, ceramide and S1P; decreased plasma IL-10; and accumulation of oxLDL-IC in the vessel wall. The results expose possible new targets to mitigate lupus-associated complications. PMID:22560558

  12. Between-year variation in population sex ratio increases with complexity of the breeding system in Hymenoptera.

    PubMed

    Kümmerli, Rolf; Keller, Laurent

    2011-06-01

    While adaptive adjustment of sex ratio in the function of colony kin structure and food availability commonly occurs in social Hymenoptera, long-term studies have revealed substantial unexplained between-year variation in sex ratio at the population level. In order to identify factors that contribute to increased between-year variation in population sex ratio, we conducted a comparative analysis across 47 Hymenoptera species differing in their breeding system. We found that between-year variation in population sex ratio steadily increased as one moved from solitary species, to primitively eusocial species, to single-queen eusocial species, to multiple-queen eusocial species. Specifically, between-year variation in population sex ratio was low (6.6% of total possible variation) in solitary species, which is consistent with the view that in solitary species, sex ratio can vary only in response to fluctuations in ecological factors such as food availability. In contrast, we found significantly higher (19.5%) between-year variation in population sex ratio in multiple-queen eusocial species, which supports the view that in these species, sex ratio can also fluctuate in response to temporal changes in social factors such as queen number and queen-worker control over sex ratio, as well as factors influencing caste determination. The simultaneous adjustment of sex ratio in response to temporal fluctuations in ecological and social factors seems to preclude the existence of a single sex ratio optimum. The absence of such an optimum may reflect an additional cost associated with the evolution of complex breeding systems in Hymenoptera societies. PMID:21597259

  13. Translocation of differently sized and charged polystyrene nanoparticles in in vitro intestinal cell models of increasing complexity.

    PubMed

    Walczak, Agata P; Kramer, Evelien; Hendriksen, Peter J M; Tromp, Peter; Helsper, Johannes P F G; van der Zande, Meike; Rietjens, Ivonne M C M; Bouwmeester, Hans

    2015-05-01

    Intestinal translocation is a key factor for determining bioavailability of nanoparticles (NPs) after oral uptake. Therefore, we evaluated three in vitro intestinal cell models of increasing complexity which might affect the translocation of NPs: a mono-culture (Caco-2 cells), a co-culture with mucus secreting HT29-MTX cells and a tri-culture with M-cells. Cell models were exposed to well characterized differently sized (50 and 100 nm) and charged (neutral, positively and negatively) polystyrene NPs. In addition, two types of negatively charged NPs with different surface chemistries were used. Size strongly affected the translocation of NPs, ranging up to 7.8% for the 50 nm NPs and 0.8% for the 100 nm NPs. Surface charge of NPs affected the translocation, however, surface chemistry seems more important, as the two types of negatively charged 50 nm NPs had an over 30-fold difference in translocation. Compared with the Caco-2 mono-culture, presence of mucus significantly reduced the translocation of neutral 50 nm NPs, but significantly increased the translocation of one type of negatively charged NPs. Incorporation of M-cells shifted the translocation rates for both NPs closer to those in the mono-culture model. The relative pattern of NP translocation in all three models was similar, but the absolute amounts of translocated NPs differed per model. We conclude that for comparing the relative translocation of different NPs, using one intestinal model is sufficient. To choose the most representative model for risk assessment, in vivo experiments are now needed to determine the in vivo translocation rates of the used NPs. PMID:25093449

  14. Keeping Up With The Planets: Scaling Kepler's Data Analysis Pipeline To Handle An Increasingly Complex Volume Of Astronomical Data.

    NASA Astrophysics Data System (ADS)

    Klaus, Todd C.; Cote, M. T.; Girouard, F.; McCauliff, S. D.; Henze, C.; Twicken, J. D.; Li, J.; Tenenbaum, P.; Seader, S.; Clarke, B. D.; Quintana, E. V.; Jenkins, J. M.; Caldwell, D. A.

    2012-05-01

    NASA’s Kepler Space Telescope has collected data on over 190,000 targets (and counting) since launch on March 6th, 2009, resulting in a growing dataset that must be processed by the Kepler Science Pipeline. The algorithms that make up the pipeline are responsible for clearing the chaff of instrumental and astrophysical noise to detect and model the transit-like signals hidden underneath. We discuss how the Kepler pipeline infrastructure has evolved to meet the growing computational needs of these algorithms. The algorithms and other support software that make up the pipeline were largely developed before launch and tested with simulated data. When confronted with flight data from the Kepler instrument, the pipeline revealed that the higher than expected thermal sensitivity of the instrument, electronics noise and operational procedures all introduced artifacts to the data at levels comparable to, or higher than the sought after transit signals. In the months after launch the team of pipeline developers at the Kepler Science Operations Center (SOC) at NASA Ames Research Center toiled to update the pipeline software to identify and mitigate these artifacts where possible, work that continues today. The increase in complexity caused by these algorithm changes, along with a need for regular reprocessing of a growing dataset to support scientific data analysis and pipeline development created an increasing demand for computing resources. This need in turn drove the need for changes to the pipeline infrastructure software to extend pipeline algorithm execution to NASA’s Advanced Supercomputer (NAS). Use of the NAS as a computing resource allows the pipeline operator to spread the planetary transit search and data validation jobs across tens of thousands of processing cores. With a possible extended mission on the horizon, this need will only grow, and work to port the rest of the pipeline to the NAS has already begun.

  15. Activation of protein phosphatase 2A is responsible for increased content and inactivation of respiratory chain complex i induced by all-trans retinoic acid in human keratinocytes.

    PubMed

    Papa, F; Sardaro, N; Lippolis, R; Panelli, D; Scacco, S

    2016-01-01

    This study presents the effect of all-trans retinoic acid (ATRA) on cell growth and respiratory chain complex I in human keratinocyte cultures. Keratinocyte treatment results in increased level of GRIM-19 and other subunits of complex I, in particular of their carbonylated forms, associated with inhibition of its enzymatic activity. The results show that in keratinocytes ATRA-promoted phosphatase activity controls the proteostasis and activity of complex I. PMID:27358125

  16. The Formation Of Glycerol Monodecanoate By A Dehydration Condensation Reaction: Increasing The Chemical Complexity Of Amphiphiles On The Early Earth

    NASA Astrophysics Data System (ADS)

    Apel, Charles L.; Deamer, David W.

    2005-08-01

    Dehydration/condensation reactions between organic molecules in the prebiotic environment increased the inventory and complexity of organic compounds available for self-assembly into primitive cellular organisms. As a model of such reactions and to demonstrate this principle, we have investigated the esterification reaction between glycerol and decanoic acid that forms glycerol monodecanoate (GMD). This amphiphile enhances robustness of self-assembled membranous structures of carboxylic acids to the potentially disruptive effects of pH, divalent cation binding and osmotic stress. Experimental variables included temperature, water activity and hydrolysis of the resulting ester product, providing insights into the environmental conditions that would favor the formation and stability of this more evolved amphiphile. At temperatures exceeding 50 ∘C, the ester product formed even in the presence of bulk water, suggesting that the reaction occurs at the liquid interface of the two reactants and that the products segregate in the two immiscible layers, thereby reducing hydrolytic back reactions. This implies that esterification reactions were likely to be common in the prebiotic environment as reactants underwent cycles of wetting and drying on rare early landmasses at elevated temperatures

  17. Gene expression analysis of tuberous sclerosis complex cortical tubers reveals increased expression of adhesion and inflammatory factors

    PubMed Central

    Boer, Karin; Crino, Peter B.; Gorter, Jan A.; Nellist, Mark; Jansen, Floor E.; Spliet, Wim G.M.; van Rijen, Peter C.; Wittink, Floyd R.A.; Breit, Timo M.; Troost, Dirk; Wadman, Wytse J.; Aronica, Eleonora

    2009-01-01

    Cortical tubers in patients with tuberous sclerosis complex are associated with disabling neurological manifestations, including intractable epilepsy. While these malformations are believed to result from the effects of TSC1 or TSC2 gene mutations, the molecular mechanisms leading to tuber formation, as well as the onset of seizures remain largely unknown. We used the Affymetrix Gene Chip platform to provide the first genome wide investigation of gene expression in surgically resected tubers, compared with histological normal perituberal tissue from the same patients or autopsy control tissue. We identified 2501 differentially expressed genes in cortical tubers compared with autopsy controls. Expression of genes associated with cell adhesion e.g., VCAM1, integrins and CD44, or with the inflammatory response, including complement factors, serpinA3, CCL2 and several cytokines, was increased in cortical tubers, whereas genes related to synaptic transmission e.g., the glial glutamate transporter GLT-1, and voltage-gated channel activity, exhibited lower expression. Gene expression in perituberal cortex was distinct from autopsy control cortex suggesting that even in the absence of tissue pathology the transcriptome is altered in TSC. Changes in gene expression yield insights into new candidate genes that may contribute to tuber formation or seizure onset, representing new targets for potential therapeutic development. PMID:19912235

  18. Addressivity in cogenerative dialogues

    NASA Astrophysics Data System (ADS)

    Hsu, Pei-Ling

    2014-03-01

    Ashraf Shady's paper provides a first-hand reflection on how a foreign teacher used cogens as culturally adaptive pedagogy to address cultural misalignments with students. In this paper, Shady drew on several cogen sessions to showcase his journey of using different forms of cogens with his students. To improve the quality of cogens, one strategy he used was to adjust the number of participants in cogens. As a result, some cogens worked and others did not. During the course of reading his paper, I was impressed by his creative and flexible use of cogens and at the same time was intrigued by the question of why some cogens work and not others. In searching for an answer, I found that Mikhail Bakhtin's dialogism, especially the concept of addressivity, provides a comprehensive framework to address this question. In this commentary, I reanalyze the cogen episodes described in Shady's paper in the light of dialogism. My analysis suggests that addressivity plays an important role in mediating the success of cogens. Cogens with high addressivity function as internally persuasive discourse that allows diverse consciousnesses to coexist and so likely affords productive dialogues. The implications of addressivity in teaching and learning are further discussed.

  19. Inhibition of the Tcf/beta-catenin complex increases apoptosis and impairs adrenocortical tumor cell proliferation and adrenal steroidogenesis

    PubMed Central

    Leal, Letícia F.; Bueno, Ana Carolina; Gomes, Débora C.; Abduch, Rafael; de Castro, Margaret; Antonini, Sonir R.

    2015-01-01

    Background To date, there is no effective therapy for patients with advanced/metastatic adrenocortical cancer (ACC). The activation of the Wnt/beta-catenin signaling is frequent in ACC and this pathway is a promising therapeutic target. Aim To investigate the effects of the inhibition of the Wnt/beta-catenin in ACC cells. Methods Adrenal (NCI-H295 and Y1) and non-adrenal (HeLa) cell lines were treated with PNU-74654 (5–200 μM) for 24–96 h to assess cell viability (MTS-based assay), apoptosis (Annexin V), expression/localization of beta-catenin (qPCR, immunofluorescence, immunocytochemistry and western blot), expression of beta-catenin target genes (qPCR and western blot), and adrenal steroidogenesis (radioimmunoassay, qPCR and western blot). Results In NCI-H295 cells, PNU-74654 significantly decreased cell proliferation 96 h after treatment, increased early and late apoptosis, decreased nuclear beta-catenin accumulation, impaired CTNNB1/beta-catenin expression and increased beta-catenin target genes 48 h after treatment. No effects were observed on HeLa cells. In NCI-H295 cells, PNU-74654 decreased cortisol, testosterone and androstenedione secretion 24 and 48 h after treatment. Additionally, in NCI-H295 cells, PNU-74654 decreased SF1 and CYP21A2 mRNA expression as well as the protein levels of STAR and aldosterone synthase 48 h after treatment. In Y1 cells, PNU-74654 impaired corticosterone secretion 24 h after treatment but did not decrease cell viability. Conclusions Blocking the Tcf/beta-catenin complex inhibits the Wnt/beta-catenin signaling in adrenocortical tumor cells triggering increased apoptosis, decreased cell viability and impairment of adrenal steroidogenesis. These promising findings pave the way for further experiments inhibiting the Wnt/beta-catenin pathway in pre-clinical models of ACC. The inhibition of this pathway may become a promising adjuvant therapy for patients with ACC. PMID:26515592

  20. Will Genetic Testing for Complex Diseases Increase Motivation to Quit Smoking? Anticipated Reactions in a Survey of Smokers

    ERIC Educational Resources Information Center

    Sanderson, Saskia C.; Wardle, Jane

    2005-01-01

    The aim of this study was to improve understanding of smokers' potential reactions to genetic testing for smoking-related diseases. One thousand twenty-four respondents completed a postal survey; 186 were smokers. Questions addressed anticipated psychological and behavioral reactions to genetic test results using hypothetical scenarios. Of…

  1. Dependency Resolution Difficulty Increases with Distance in Persian Separable Complex Predicates: Evidence for Expectation and Memory-Based Accounts.

    PubMed

    Safavi, Molood S; Husain, Samar; Vasishth, Shravan

    2016-01-01

    Delaying the appearance of a verb in a noun-verb dependency tends to increase processing difficulty at the verb; one explanation for this locality effect is decay and/or interference of the noun in working memory. Surprisal, an expectation-based account, predicts that delaying the appearance of a verb either renders it no more predictable or more predictable, leading respectively to a prediction of no effect of distance or a facilitation. Recently, Husain et al. (2014) suggested that when the exact identity of the upcoming verb is predictable (strong predictability), increasing argument-verb distance leads to facilitation effects, which is consistent with surprisal; but when the exact identity of the upcoming verb is not predictable (weak predictability), locality effects are seen. We investigated Husain et al.'s proposal using Persian complex predicates (CPs), which consist of a non-verbal element-a noun in the current study-and a verb. In CPs, once the noun has been read, the exact identity of the verb is highly predictable (strong predictability); this was confirmed using a sentence completion study. In two self-paced reading (SPR) and two eye-tracking (ET) experiments, we delayed the appearance of the verb by interposing a relative clause (Experiments 1 and 3) or a long PP (Experiments 2 and 4). We also included a simple Noun-Verb predicate configuration with the same distance manipulation; here, the exact identity of the verb was not predictable (weak predictability). Thus, the design crossed Predictability Strength and Distance. We found that, consistent with surprisal, the verb in the strong predictability conditions was read faster than in the weak predictability conditions. Furthermore, greater verb-argument distance led to slower reading times; strong predictability did not neutralize or attenuate the locality effects. As regards the effect of distance on dependency resolution difficulty, these four experiments present evidence in favor of working memory

  2. Dependency Resolution Difficulty Increases with Distance in Persian Separable Complex Predicates: Evidence for Expectation and Memory-Based Accounts

    PubMed Central

    Safavi, Molood S.; Husain, Samar; Vasishth, Shravan

    2016-01-01

    Delaying the appearance of a verb in a noun-verb dependency tends to increase processing difficulty at the verb; one explanation for this locality effect is decay and/or interference of the noun in working memory. Surprisal, an expectation-based account, predicts that delaying the appearance of a verb either renders it no more predictable or more predictable, leading respectively to a prediction of no effect of distance or a facilitation. Recently, Husain et al. (2014) suggested that when the exact identity of the upcoming verb is predictable (strong predictability), increasing argument-verb distance leads to facilitation effects, which is consistent with surprisal; but when the exact identity of the upcoming verb is not predictable (weak predictability), locality effects are seen. We investigated Husain et al.'s proposal using Persian complex predicates (CPs), which consist of a non-verbal element—a noun in the current study—and a verb. In CPs, once the noun has been read, the exact identity of the verb is highly predictable (strong predictability); this was confirmed using a sentence completion study. In two self-paced reading (SPR) and two eye-tracking (ET) experiments, we delayed the appearance of the verb by interposing a relative clause (Experiments 1 and 3) or a long PP (Experiments 2 and 4). We also included a simple Noun-Verb predicate configuration with the same distance manipulation; here, the exact identity of the verb was not predictable (weak predictability). Thus, the design crossed Predictability Strength and Distance. We found that, consistent with surprisal, the verb in the strong predictability conditions was read faster than in the weak predictability conditions. Furthermore, greater verb-argument distance led to slower reading times; strong predictability did not neutralize or attenuate the locality effects. As regards the effect of distance on dependency resolution difficulty, these four experiments present evidence in favor of working

  3. Inclusion complexes of chloramphenicol with β-cyclodextrin and aminoacids as a way to increase drug solubility and modulate ROS production.

    PubMed

    Aiassa, Virginia; Zoppi, Ariana; Albesa, Inés; Longhi, Marcela R

    2015-05-01

    The aim of this study was to improve the solubility of chloramphenicol and reduce the production of reactive oxygen species (ROS) in leucocytes induced by this drug, using complexation. Multicomponent complexes were prepared by the addition of β-cyclodextrin with glycine or cysteine. Nuclear magnetic resonance and phase solubility studies provided information at the molecular level on the structure of the complexes and their association binding constants, respectively. In the solid state, all systems were extensively characterized by Fourier-transform infrared spectroscopy, scanning electron microscopy, thermal analysis and X-ray powder diffraction. Antimicrobial activity of inclusion complexes was investigated by agar diffusion methods. Finally ROS determination by chemiluminescence was used to investigate the effect of complex formation on the potential toxicity in human leucocytes. These studies revealed that multicomponent complexes can increase the aqueous solubility of chloramphenicol as well as reducing the stress by ROS production in leucocytes and maintaining its microbiological activity. PMID:25659705

  4. Does Leisure Time as a Stress Coping Resource Increase Affective Complexity? Applying the Dynamic Model of Affect (DMA).

    PubMed

    Qian, Xinyi Lisa; Yarnal, Careen M; Almeida, David M

    2013-01-01

    Affective complexity, a manifestation of psychological well-being, refers to the relative independence between positive and negative affect (PA, NA). According to the Dynamic Model of Affect (DMA), stressful situations lead to highly inverse PA-NA relationship, reducing affective complexity. Meanwhile, positive events can sustain affective complexity by restoring PA-NA independence. Leisure, a type of positive events, has been identified as a coping resource. This study used the DMA to assess whether leisure time helps restore affective complexity on stressful days. We found that on days with more leisure time than usual, an individual experienced less negative PA-NA relationship after daily stressful events. The finding demonstrates the value of leisure time as a coping resource and the DMA's contribution to coping research. PMID:24659826

  5. Glucose, fructose and sucrose increase the solubility of protein-tannin complexes and at high concentration, glucose and sucrose interfere with bisulphite bleaching of wine pigments.

    PubMed

    Harbertson, James F; Yuan, Chunlong; Mireles, Maria S; Hanlin, Rachel L; Downey, Mark O

    2013-05-01

    Wines were modified with increasing sugar concentrations and decreasing tannin concentrations and analysed by a combination of protein precipitation and bisulphite bleaching. Increasing sugar concentration decreased the precipitation of tannin and protein-precipitable polymeric pigments (PPP). The use of a hydrogen bond disruptor (urea) to reduce protein-tannin and protein-pigment complex formation showed that the effect of sugar concentration occurred by increasing the solubility of the tannin-protein complex, not by interfering with protein-tannin complex formation. By increasing the solubility of pigment-protein complexes, non-protein-precipitable polymeric pigments (nPPP) appeared to increase. There was also an increase in total polymeric pigments at each tannin concentration with increasing glucose and sucrose concentration, indicating that sugar concentration might also affect bisulphite bleaching of wine pigments. While a significant effect of sugar concentration on tannin-protein complex solubility was observed, these effects were greatest at sugar concentrations far in excess of normal wine making conditions. Under normal wine making conditions, sugar concentration will have a negligible effect on protein-precipitable tannin, PPP and nPPP concentrations. PMID:23265524

  6. Addressing Social Issues.

    ERIC Educational Resources Information Center

    Schoebel, Susan

    1991-01-01

    Maintains that advertising can help people become more aware of social responsibilities. Describes a successful nationwide newspaper advertising competition for college students in which ads address social issues such as literacy, drugs, teen suicide, and teen pregnancy. Notes how the ads have helped grassroots programs throughout the United…

  7. States Address Achievement Gaps.

    ERIC Educational Resources Information Center

    Christie, Kathy

    2002-01-01

    Summarizes 2 state initiatives to address the achievement gap: North Carolina's report by the Advisory Commission on Raising Achievement and Closing Gaps, containing an 11-point strategy, and Kentucky's legislation putting in place 10 specific processes. The North Carolina report is available at www.dpi.state.nc.us.closingthegap; Kentucky's…

  8. Address of the President

    ERIC Educational Resources Information Center

    Ness, Frederic W.

    1976-01-01

    The president of the Association of American Colleges addresses at the 62nd annual meeting the theme of the conference: "Looking to the Future--Liberal Education in a Radically Changing Society." Contributions to be made by AAC are examined. (LBH)

  9. Addressing Sexual Harassment

    ERIC Educational Resources Information Center

    Young, Ellie L.; Ashbaker, Betty Y.

    2008-01-01

    This article discusses ways on how to address the problem of sexual harassment in schools. Sexual harassment--simply defined as any unwanted and unwelcome sexual behavior--is a sensitive topic. Merely providing students, parents, and staff members with information about the school's sexual harassment policy is insufficient; schools must take…

  10. Space sciences - Keynote address

    NASA Technical Reports Server (NTRS)

    Alexander, Joseph K.

    1990-01-01

    The present status and projected future developments of the NASA Space Science and Applications Program are addressed. Emphasis is given to biochemistry experiments that are planned for the Space Station. Projects for the late 1990s which will study the sun, the earth's magnetosphere, and the geosphere are briefly discussed.

  11. Excerpts from keynote address

    SciTech Connect

    Creel, G.C.

    1995-06-01

    Excerpts from the keynote principally address emissions issues in the fossil power industry as related to heat rate improvements. Stack emissions of both sulfur and nitrogen oxides are discussed, and a number of examples are given: (1) PEPCO`s Potomac River Station, and (2) Morgantown station`s NOX reduction efforts. Circulating water emissions are also briefly discussed, as are O & M costs of emission controls.

  12. Holographic content addressable storage

    NASA Astrophysics Data System (ADS)

    Chao, Tien-Hsin; Lu, Thomas; Reyes, George

    2015-03-01

    We have developed a Holographic Content Addressable Storage (HCAS) architecture. The HCAS systems consists of a DMD (Digital Micromirror Array) as the input Spatial Light Modulator (SLM), a CMOS (Complementary Metal-oxide Semiconductor) sensor as the output photodetector and a photorefractive crystal as the recording media. The HCAS system is capable of performing optical correlation of an input image/feature against massive reference data set stored in the holographic memory. Detailed system analysis will be reported in this paper.

  13. Exploring Innovation Processes from a Complexity Perspective. Part II. Experiences from the Subsea Increased Oil Recovery Case

    ERIC Educational Resources Information Center

    Aasen, Tone Merethe Berg; Johannessen, Stig

    2007-01-01

    In this second part of the papers, exploring innovation processes from a complexity perspective, we present an empirical example to strengthen further the relevance of the approach. The example draws on a longitudinal research initiative conducted in cooperation with the Norwegian petroleum company Statoil ASA. We conducted our research into the…

  14. Addressing epidemiological and public health analytic challenges in outcome and impact research: a commentary on 'Prechewing Infant Food, Consumption of Sweets and Dairy and Not Breastfeeding are Associated with Increased Diarrhea Risk of Ten Month Old Infants'.

    PubMed

    Habicht, Jean-Pierre; Pelto, Gretel H

    2016-07-01

    Based on a paper by Conkle et al 2016, in which the authors use a descriptive epidemiological design to examine the relationship of premastication and other dietary behavioral variables to childhood diarrhea in the US, we address larger issues of "plausible causality" and the challenges involved in moving from epidemiological studies to public health policy. Drawing on examples from breastfeeding research and water, sanitation and hygiene (WASH) research, we discuss the following propositions: 1. Effective outcome analyses require simultaneous investigation of different, even contradictory, pathways; 2. Outcome versus impact assessments require different analytic procedures including context analysis; 3. Impact analysis requires understanding the trade-offs between detrimental and beneficial outcomes in relation to potential interventions; 4. No estimates exist for the likely detrimental and beneficial impacts of banning premastication, much less for their trade-offs. PMID:27229538

  15. Experimental bacteriophage therapy increases survival of Galleria mellonella larvae infected with clinically relevant strains of the Burkholderia cepacia complex.

    PubMed

    Seed, Kimberley D; Dennis, Jonathan J

    2009-05-01

    The Burkholderia cepacia complex (BCC) is a group of bacterial pathogens that are highly antibiotic resistant and associated with debilitating respiratory infections. Although bacteriophages of the BCC have been isolated and characterized, no studies have yet examined phage therapy against the BCC in vivo. In a caterpillar infection model, we show that BCC phage therapy is an alternative treatment possibility and is highly effective under specific conditions. PMID:19223640

  16. Content addressable memory project

    NASA Technical Reports Server (NTRS)

    Hall, J. Storrs; Levy, Saul; Smith, Donald E.; Miyake, Keith M.

    1992-01-01

    A parameterized version of the tree processor was designed and tested (by simulation). The leaf processor design is 90 percent complete. We expect to complete and test a combination of tree and leaf cell designs in the next period. Work is proceeding on algorithms for the computer aided manufacturing (CAM), and once the design is complete we will begin simulating algorithms for large problems. The following topics are covered: (1) the practical implementation of content addressable memory; (2) design of a LEAF cell for the Rutgers CAM architecture; (3) a circuit design tool user's manual; and (4) design and analysis of efficient hierarchical interconnection networks.

  17. Development of a three component complex to increase isoniazid efficacy against isoniazid resistant and nonresistant Mycobacterium tuberculosis.

    PubMed

    Manning, Thomas; Plummer, Sydney; Baker, Tess; Wylie, Greg; Clingenpeel, Amy C; Phillips, Dennis

    2015-10-15

    The bacterium responsible for causing tuberculosis has evolved resistance to antibiotics used to treat the disease, resulting in new multidrug resistant Mycobacterium tuberculosis (MDR-TB) and extensively drug resistant M. tuberculosis (XDR-TB) strains. Analytical techniques (1)H and (13)C Nuclear Magnetic Resonance (NMR), Fourier Transform-Ion Cyclotron Resonance with Electrospray Ionization (FT-ICR/ESI), and Matrix Assisted Laser Desorption Ionization-Mass Spectrometry (MALDI-TOF-MS) were used to study different aspects of the Cu(II)-polyethylene glycol (PEG-3350)-sucrose-isoniazid and Cu(II)-polyethylene glycol (PEG3350)-glucose-isoniazid complexes. The Cu(II) cation, sucrose or glucose, and the aggregate formed by PEG primarily serve as a composite drug delivery agent for the frontline antibiotic, however the improvement in MIC values produced with the CU-PEG-SUC-INH complex suggest an additional effect. Several Cu-PEG-SUC-INH complex variations were tested against INH resistant and nonresistant strains of M. tuberculosis. PMID:26341133

  18. Addressing Environmental Health Inequalities.

    PubMed

    Gouveia, Nelson

    2016-01-01

    Environmental health inequalities refer to health hazards disproportionately or unfairly distributed among the most vulnerable social groups, which are generally the most discriminated, poor populations and minorities affected by environmental risks. Although it has been known for a long time that health and disease are socially determined, only recently has this idea been incorporated into the conceptual and practical framework for the formulation of policies and strategies regarding health. In this Special Issue of the International Journal of Environmental Research and Public Health (IJERPH), "Addressing Environmental Health Inequalities-Proceedings from the ISEE Conference 2015", we incorporate nine papers that were presented at the 27th Conference of the International Society for Environmental Epidemiology (ISEE), held in Sao Paulo, Brazil, in 2015. This small collection of articles provides a brief overview of the different aspects of this topic. Addressing environmental health inequalities is important for the transformation of our reality and for changing the actual development model towards more just, democratic, and sustainable societies driven by another form of relationship between nature, economy, science, and politics. PMID:27618906

  19. Plant Utility Improvements Increase Profits and Productivity at a Clothing Manufacturing Complex (MJ Soffee's Wastewater Heat Recovery System)

    SciTech Connect

    2000-11-01

    In response to increased marketplace competition and the need for expanded production capacity, MJ Soffee's manufacturing facility in Fayetteville, North Carolina implemented several energy improvement projects,

  20. Rapamycin reverses age-related increases in mitochondrial ROS production at complex I, oxidative stress, accumulation of mtDNA fragments inside nuclear DNA, and lipofuscin level, and increases autophagy, in the liver of middle-aged mice.

    PubMed

    Martínez-Cisuelo, V; Gómez, J; García-Junceda, I; Naudí, A; Cabré, R; Mota-Martorell, N; López-Torres, M; González-Sánchez, M; Pamplona, R; Barja, G

    2016-10-01

    Rapamycin consistently increases longevity in mice although the mechanism of action of this drug is unknown. In the present investigation we studied the effect of rapamycin on mitochondrial oxidative stress at the same dose that is known to increase longevity in mice (14mgofrapamycin/kg of diet). Middle aged mice (16months old) showed significant age-related increases in mitochondrial ROS production at complex I, accumulation of mtDNA fragments inside nuclear DNA, mitochondrial protein lipoxidation, and lipofuscin accumulation compared to young animals (4months old) in the liver. After 7weeks of dietary treatment all those increases were totally or partially (lipofuscin) abolished by rapamycin, middle aged rapamycin-treated animals showing similar levels in those parameters to young animals. The decrease in mitochondrial ROS production was due to qualitative instead of quantitative changes in complex I. The decrease in mitochondrial protein lipoxidation was not due to decreases in the amount of highly oxidizable unsaturated fatty acids. Rapamycin also decreased the amount of RAPTOR (of mTOR complex) and increased the amounts of the PGC1-α and ATG13 proteins. The results are consistent with the possibility that rapamycin increases longevity in mice at least in part by lowering mitochondrial ROS production and increasing autophagy, decreasing the derived final forms of damage accumulated with age which are responsible for increased longevity. The decrease in lipofuscin accumulation induced by rapamycin adds to previous information suggesting that the increase in longevity induced by this drug can be due to a decrease in the rate of aging. PMID:27498120

  1. Increasing the sensitivity of NMR diffusion measurements by paramagnetic longitudinal relaxation enhancement, with application to ribosome–nascent chain complexes

    PubMed Central

    Cassaignau, Anaïs M. E.; Cabrita, Lisa D.

    2016-01-01

    The translational diffusion of macromolecules can be examined non-invasively by stimulated echo (STE) NMR experiments to accurately determine their molecular sizes. These measurements can be important probes of intermolecular interactions and protein folding and unfolding, and are crucial in monitoring the integrity of large macromolecular assemblies such as ribosome–nascent chain complexes (RNCs). However, NMR studies of these complexes can be severely constrained by their slow tumbling, low solubility (with maximum concentrations of up to 10 μM), and short lifetimes resulting in weak signal, and therefore continuing improvements in experimental sensitivity are essential. Here we explore the use of the paramagnetic longitudinal relaxation enhancement (PLRE) agent NiDO2A on the sensitivity of 15N XSTE and SORDID heteronuclear STE experiments, which can be used to monitor the integrity of these unstable complexes. We exploit the dependence of the PLRE effect on the gyromagnetic ratio and electronic relaxation time to accelerate recovery of 1H magnetization without adversely affecting storage on Nz during diffusion delays or introducing significant transverse relaxation line broadening. By applying the longitudinal relaxation-optimized SORDID pulse sequence together with NiDO2A to 70S Escherichia coli ribosomes and RNCs, NMR diffusion sensitivity enhancements of up to 4.5-fold relative to XSTE are achieved, alongside ~1.9-fold improvements in two-dimensional NMR sensitivity, without compromising the sample integrity. We anticipate these results will significantly advance the use of NMR to probe dynamic regions of ribosomes and other large, unstable macromolecular assemblies. PMID:26253948

  2. Content addressable memory project

    NASA Technical Reports Server (NTRS)

    Hall, Josh; Levy, Saul; Smith, D.; Wei, S.; Miyake, K.; Murdocca, M.

    1991-01-01

    The progress on the Rutgers CAM (Content Addressable Memory) Project is described. The overall design of the system is completed at the architectural level and described. The machine is composed of two kinds of cells: (1) the CAM cells which include both memory and processor, and support local processing within each cell; and (2) the tree cells, which have smaller instruction set, and provide global processing over the CAM cells. A parameterized design of the basic CAM cell is completed. Progress was made on the final specification of the CPS. The machine architecture was driven by the design of algorithms whose requirements are reflected in the resulted instruction set(s). A few of these algorithms are described.

  3. Bax: Addressed to kill.

    PubMed

    Renault, Thibaud T; Manon, Stéphen

    2011-09-01

    The pro-apoptototic protein Bax (Bcl-2 Associated protein X) plays a central role in the mitochondria-dependent apoptotic pathway. In healthy mammalian cells, Bax is essentially cytosolic and inactive. Following a death signal, the protein is translocated to the outer mitochondrial membrane, where it promotes a permeabilization that favors the release of different apoptogenic factors, such as cytochrome c. The regulation of Bax translocation is associated to conformational changes that are under the control of different factors. The evidences showing the involvement of different Bax domains in its mitochondrial localization are presented. The interactions between Bax and its different partners are described in relation to their ability to promote (or prevent) Bax conformational changes leading to mitochondrial addressing and to the acquisition of the capacity to permeabilize the outer mitochondrial membrane. PMID:21641962

  4. Increasing evidence of the role of gene flow in animal evolution: hybrid speciation in the yellow-rumped warbler complex.

    PubMed

    Jacobsen, Frode; Omland, Kevin E

    2011-06-01

    In this issue of Molecular Ecology, Brelsford et al. (2011) present strong evidence for a case of hybrid speciation within the yellow-rumped warbler complex. Although homoploid hybrid speciation has now been documented in many animals (Mallet 2007), it seems rare in tetrapods (Mavárez & Linares 2008) and it has barely even been mentioned in birds (Price 2008). Brelsford and colleagues thus present the first detailed molecular evidence suggesting that hybrid speciation can occur in birds. Brelsford et al. (2011) posit that Audubon's warbler (Dendroica auduboni) constitutes a hybrid species originating from the admixture of two distinct parental lineages, represented today by myrtle warbler (D. coronata) and black-fronted warbler (D. nigrifrons). The authors present three major lines of molecular evidence suggesting that this is not simply a case of a hybrid swarm or limited introgression. PMID:21739625

  5. Identifying and Addressing Vaccine Hesitancy

    PubMed Central

    Kestenbaum, Lori A.; Feemster, Kristen A.

    2015-01-01

    In the 20th century, the introduction of multiple vaccines significantly reduced childhood morbidity, mortality, and disease outbreaks. Despite, and perhaps because of, their public health impact, an increasing number of parents and patients are choosing to delay or refuse vaccines. These individuals are described as vaccine hesitant. This phenomenon has developed due to the confluence of multiple social, cultural, political and personal factors. As immunization programs continue to expand, understanding and addressing vaccine hesitancy will be crucial to their successful implementation. This review explores the history of vaccine hesitancy, its causes, and suggested approaches for reducing hesitancy and strengthening vaccine acceptance. PMID:25875982

  6. Identifying and addressing vaccine hesitancy.

    PubMed

    Kestenbaum, Lori A; Feemster, Kristen A

    2015-04-01

    In the 20th century, the introduction of multiple vaccines significantly reduced childhood morbidity, mortality, and disease outbreaks. Despite, and perhaps because of, their public health impact, an increasing number of parents and patients are choosing to delay or refuse vaccines. These individuals are described as "vaccine hesitant." This phenomenon has developed due to the confluence of multiple social, cultural, political, and personal factors. As immunization programs continue to expand, understanding and addressing vaccine hesitancy will be crucial to their successful implementation. This review explores the history of vaccine hesitancy, its causes, and suggested approaches for reducing hesitancy and strengthening vaccine acceptance. PMID:25875982

  7. Neural Signals Evoked by Stimuli of Increasing Social Scene Complexity Are Detectable at the Single-Trial Level and Right Lateralized

    PubMed Central

    Amaral, Carlos P.; Simões, Marco A.; Castelo-Branco, Miguel S.

    2015-01-01

    Classification of neural signals at the single-trial level and the study of their relevance in affective and cognitive neuroscience are still in their infancy. Here we investigated the neurophysiological correlates of conditions of increasing social scene complexity using 3D human models as targets of attention, which may also be important in autism research. Challenging single-trial statistical classification of EEG neural signals was attempted for detection of oddball stimuli with increasing social scene complexity. Stimuli had an oddball structure and were as follows: 1) flashed schematic eyes, 2) simple 3D faces flashed between averted and non-averted gaze (only eye position changing), 3) simple 3D faces flashed between averted and non-averted gaze (head and eye position changing), 4) animated avatar alternated its gaze direction to the left and to the right (head and eye position), 5) environment with 4 animated avatars all of which change gaze and one of which is the target of attention. We found a late (> 300 ms) neurophysiological oddball correlate for all conditions irrespective of their complexity as assessed by repeated measures ANOVA. We attempted single-trial detection of this signal with automatic classifiers and obtained a significant balanced accuracy classification of around 79%, which is noteworthy given the amount of scene complexity. Lateralization analysis showed a specific right lateralization only for more complex realistic social scenes. In sum, complex ecological animations with social content elicit neurophysiological events which can be characterized even at the single-trial level. These signals are right lateralized. These finding paves the way for neuroscientific studies in affective neuroscience based on complex social scenes, and given the detectability at the single trial level this suggests the feasibility of brain computer interfaces that can be applied to social cognition disorders such as autism. PMID:25807525

  8. Retrieval Can Increase or Decrease Suggestibility Depending on How Memory Is Tested: The Importance of Source Complexity

    ERIC Educational Resources Information Center

    Chan, Jason C. K.; Wilford, Miko M.; Hughes, Katharine L.

    2012-01-01

    Taking an intervening test between learning episodes can enhance later source recollection. Paradoxically, testing can also increase people's susceptibility to the misinformation effect--a finding termed retrieval-enhanced suggestibility (RES, Chan, Thomas, & Bulevich, 2009). We conducted three experiments to examine this apparent contradiction.…

  9. Increase in complexation ability of humic acids with the addition of ligneous bulking agents during sewage sludge composting.

    PubMed

    Xiong, Xiong; Yan-Xia, Li; Ming, Yang; Feng-Song, Zhang; Wei, Li

    2010-12-01

    Wood sawdust and maize straw were selected to co-compost sewage sludge to investigate the effects of organic bulking agents on the formation and molecular transformation of humic substances. The results showed that composting process increased humic acids (HA) while decreased fulvic acids (FA), and the wood sawdust and maize straw promoted the formation of HA by 25.6% and 16.1%, respectively. Results from fluorescence titration demonstrated that organic bulking agents also increased the binding ability of HA with the heavy metal ions, Cu(II) and Cd(II), but had little influence on that of FA. These findings indicate that organic materials especially wood sawdust may be used as bulking agents to reduce the mobility and bioavailability of toxic metals in solid waste composts. PMID:20724147

  10. Complex coupled metabolic and prokaryotic community responses to increasing temperatures in anaerobic marine sediments: critical temperatures and substrate changes.

    PubMed

    Roussel, Erwan G; Cragg, Barry A; Webster, Gordon; Sass, Henrik; Tang, Xiaohong; Williams, Angharad S; Gorra, Roberta; Weightman, Andrew J; Parkes, R John

    2015-08-01

    The impact of temperature (0-80°C) on anaerobic biogeochemical processes and prokaryotic communities in marine sediments (tidal flat) was investigated in slurries for up to 100 days. Temperature had a non-linear effect on biogeochemistry and prokaryotes with rapid changes over small temperature intervals. Some activities (e.g. methanogenesis) had multiple 'windows' within a large temperature range (∼10 to 80°C). Others, including acetate oxidation, had maximum activities within a temperature zone, which varied with electron acceptor [metal oxide (up to ∼34°C) and sulphate (up to ∼50°C)]. Substrates for sulphate reduction changed from predominantly acetate below, and H2 above, a 43°C critical temperature, along with changes in activation energies and types of sulphate-reducing Bacteria. Above ∼43°C, methylamine metabolism ceased with changes in methanogen types and increased acetate concentrations (>1 mM). Abundances of uncultured Archaea, characteristic of deep marine sediments (e.g. MBGD Euryarchaeota, 'Bathyarchaeota') changed, indicating their possible metabolic activity and temperature range. Bacterial cell numbers were consistently higher than archaeal cells and both decreased above ∼15°C. Substrate addition stimulated activities, widened some activity temperature ranges (methanogenesis) and increased bacterial (×10) more than archaeal cell numbers. Hence, additional organic matter input from climate-related eutrophication may amplify the impact of temperature increases on sedimentary biogeochemistry. PMID:26207045

  11. Complex coupled metabolic and prokaryotic community responses to increasing temperatures in anaerobic marine sediments: critical temperatures and substrate changes

    PubMed Central

    Roussel, Erwan G.; Cragg, Barry A.; Webster, Gordon; Sass, Henrik; Tang, Xiaohong; Williams, Angharad S.; Gorra, Roberta; Weightman, Andrew J.; Parkes, R. John

    2015-01-01

    The impact of temperature (0–80°C) on anaerobic biogeochemical processes and prokaryotic communities in marine sediments (tidal flat) was investigated in slurries for up to 100 days. Temperature had a non-linear effect on biogeochemistry and prokaryotes with rapid changes over small temperature intervals. Some activities (e.g. methanogenesis) had multiple ‘windows’ within a large temperature range (∼10 to 80°C). Others, including acetate oxidation, had maximum activities within a temperature zone, which varied with electron acceptor [metal oxide (up to ∼34°C) and sulphate (up to ∼50°C)]. Substrates for sulphate reduction changed from predominantly acetate below, and H2 above, a 43°C critical temperature, along with changes in activation energies and types of sulphate-reducing Bacteria. Above ∼43°C, methylamine metabolism ceased with changes in methanogen types and increased acetate concentrations (>1 mM). Abundances of uncultured Archaea, characteristic of deep marine sediments (e.g. MBGD Euryarchaeota, ‘Bathyarchaeota’) changed, indicating their possible metabolic activity and temperature range. Bacterial cell numbers were consistently higher than archaeal cells and both decreased above ∼15°C. Substrate addition stimulated activities, widened some activity temperature ranges (methanogenesis) and increased bacterial (×10) more than archaeal cell numbers. Hence, additional organic matter input from climate-related eutrophication may amplify the impact of temperature increases on sedimentary biogeochemistry. PMID:26207045

  12. Use of multicriteria decision analysis to address conservation conflicts.

    PubMed

    Davies, A L; Bryce, R; Redpath, S M

    2013-10-01

    Conservation conflicts are increasing on a global scale and instruments for reconciling competing interests are urgently needed. Multicriteria decision analysis (MCDA) is a structured, decision-support process that can facilitate dialogue between groups with differing interests and incorporate human and environmental dimensions of conflict. MCDA is a structured and transparent method of breaking down complex problems and incorporating multiple objectives. The value of this process for addressing major challenges in conservation conflict management is that MCDA helps in setting realistic goals; entails a transparent decision-making process; and addresses mistrust, differing world views, cross-scale issues, patchy or contested information, and inflexible legislative tools. Overall we believe MCDA provides a valuable decision-support tool, particularly for increasing awareness of the effects of particular values and choices for working toward negotiated compromise, although an awareness of the effect of methodological choices and the limitations of the method is vital before applying it in conflict situations. PMID:23869557

  13. Managing the data deluge: data-driven GO category assignment improves while complexity of functional annotation increases.

    PubMed

    Gobeill, Julien; Pasche, Emilie; Vishnyakova, Dina; Ruch, Patrick

    2013-01-01

    The available curated data lag behind current biological knowledge contained in the literature. Text mining can assist biologists and curators to locate and access this knowledge, for instance by characterizing the functional profile of publications. Gene Ontology (GO) category assignment in free text already supports various applications, such as powering ontology-based search engines, finding curation-relevant articles (triage) or helping the curator to identify and encode functions. Popular text mining tools for GO classification are based on so called thesaurus-based--or dictionary-based--approaches, which exploit similarities between the input text and GO terms themselves. But their effectiveness remains limited owing to the complex nature of GO terms, which rarely occur in text. In contrast, machine learning approaches exploit similarities between the input text and already curated instances contained in a knowledge base to infer a functional profile. GO Annotations (GOA) and MEDLINE make possible to exploit a growing amount of curated abstracts (97 000 in November 2012) for populating this knowledge base. Our study compares a state-of-the-art thesaurus-based system with a machine learning system (based on a k-Nearest Neighbours algorithm) for the task of proposing a functional profile for unseen MEDLINE abstracts, and shows how resources and performances have evolved. Systems are evaluated on their ability to propose for a given abstract the GO terms (2.8 on average) used for curation in GOA. We show that since 2006, although a massive effort was put into adding synonyms in GO (+300%), our thesaurus-based system effectiveness is rather constant, reaching from 0.28 to 0.31 for Recall at 20 (R20). In contrast, thanks to its knowledge base growth, our machine learning system has steadily improved, reaching from 0.38 in 2006 to 0.56 for R20 in 2012. Integrated in semi-automatic workflows or in fully automatic pipelines, such systems are more and more efficient

  14. Cattle with increased severity of bovine respiratory disease complex exhibit decreased capacity to protect against histone cytotoxicity.

    PubMed

    Matera, J A; Wilson, B K; Hernandez Gifford, J A; Step, D L; Krehbiel, C R; Gifford, C A

    2015-04-01

    Bovine respiratory disease complex (BRDC) is the leading cause of morbidity and mortality in feedlot cattle. Significant inflammation and lesions are often observed in lungs of infected cattle. During acute inflammatory responses, histones contribute to mortality in rodents and humans and serum proteins can protect against histone-induced cytotoxicity. We hypothesized that cattle experiencing chronic or fatal cases of BRDC have reduced ability to protect against cytotoxic effects of histones. Serum samples were collected from 66 bull calves at the time of normal feedlot processing procedures. Animals were retrospectively assigned to groups consisting of calves never treated for BRDC (control [CONT]; n = 10), calves treated with antimicrobials once for BRDC (1T; n = 16), calves treated twice for BRDC (2T; n = 13), calves treated 3 times for BRDC (3T; n = 14), or calves treated 4 times for BRDC (4T; n = 13). Samples were also collected each time animals received antimicrobial treatment; animals within a group were further sorted by calves that recovered and calves that died to test histone cytotoxicity. Bovine kidney cells were cultured in duplicate in 96-well plates and exposed to 0 or 50 μg/mL of total histones for 18 h with 1% serum from each animal. Cell viability was assessed by the addition of resazurin for 6 h followed by fluorescent quantification. Fluorescent values from serum alone were subtracted from values obtained for histone treatment for each animal. Serum from CONT, 1T, and 2T at initial processing all exhibited a similar (P > 0.10) response to histone treatment with fluorescent values of -312 ± 557, -1,059 ± 441, and -975 ± 489, respectively. However, 3T and 4T demonstrated an impaired capacity (P < 0.05) to protect against histones (-2,778 ± 471 and -3,026 ± 489) at initial processing when compared to the other groups. When sorted by mortality within group, calves that were treated twice and recovered (-847 ± 331) demonstrated a greater (P

  15. Workshop Addresses Aviation Community

    NASA Astrophysics Data System (ADS)

    Meehan, Jennifer; Kunches, Joseph

    2012-08-01

    Delta Airlines had an unprecedented experience in 2011: For the first time, a flight was rerouted because of space weather activity. Flight 189 from Detroit, Mich., to Beijing, China, had to reroute due to solar activity that occurred 24-28 September 2011. Over the last decade most airlines that fly routes across the North Pole region have had diversions as a result of solar activity. As cross-polar air traffic increases, standing at 10,993 one-way crossings in 2011, the aviation industry is becoming more aware of the impacts that space weather can have on operations, communications, and navigation, as well as the issue of increased radiation exposure for passengers and flight crew on board.

  16. Human brain mapping under increasing cognitive complexity using regional cerebral blood flow measurements and positron emission tomography.

    PubMed

    Law, Ian

    2007-11-01

    Measurement of the regional cerebral blood flow (rCBF) is an important parameter in the evaluation of cerebral function. With positron emission tomography (PET) rCBF has predominantly been quantified using the short-lived radiotracer oxygen-15 labelled water (H 2 15 O) and an adaptation of the Kety one-tissue compartment autoradiographic model. The values attained in putative grey matter, however, are systematically underestimated because of the limited scanner resolution. For this reason we applied a dynamic kinetic two-tissue compartment model including a fast and a slow flow component each with a perfusable tissue fraction. In the fast component rCBF was 2-2.5 times greater than grey matter values using traditional autoradiography in both human and monkey. Visual stimulation in human gave a corrected rCBF increase of approximately 40%. Visual stimulation was also used to indirectly validate carbon-10 labelled carbondioxide ( 10 CO 2 ), a new very short-lived rCBF PET tracer with a half-life of only 19.3 seconds. This allowed an increase in the number of independent PET scans per subject from 12-14 using H 2 15 O to 64 using 10 CO 2 . The experiment demonstrated a maximal activation response in the visual cortex at a 10-15 Hz stimulation frequency. The use of the rCBF PET mapping technique is illustrated by studies of the organization of language and the oculomotor system. With respect to the former, we found confirmation of neuropsychological evidence of the involvement of the left supramarginal/angular gyrus in reading in Japanese of a phonologically based script system, Kana, and of the left posterior inferior temporal gyrus in reading of a morphogram based script system, Kanji. Concerning the organization of the oculomotor system we found overlapping areas in fronto-parietal cortex involved in maintaining visual fixation, and performing visually guided and imagined eye movements. These data show that overt eye movements are not a prerequisite of the

  17. Minority cytotypes in European populations of the Gymnadenia conopsea complex (Orchidaceae) greatly increase intraspecific and intrapopulation diversity

    PubMed Central

    Trávníček, Pavel; Jersáková, Jana; Kubátová, Barbora; Krejčíková, Jana; Bateman, Richard M.; Lučanová, Magdalena; Krajníková, Eva; Těšitelová, Tamara; Štípková, Zuzana; Amardeilh, Jean-Pierre; Brzosko, Emilia; Jermakowicz, Edyta; Cabanne, Olivier; Durka, Walter; Efimov, Peter; Hedrén, Mikael; Hermosilla, Carlos E.; Kreutz, Karel; Kull, Tiiu; Tali, Kadri; Marchand, Olivier; Rey, Manel; Schiestl, Florian P.; Čurn, Vladislav; Suda, Jan

    2012-01-01

    Background and Aims Patterns of ploidy variation among and within populations can provide valuable insights into the evolutionary mechanisms shaping the dynamics of plant systems showing ploidy diversity. Whereas data on majority ploidies are, by definition, often sufficiently extensive, much less is known about the incidence and evolutionary role of minority cytotypes. Methods Ploidy and proportions of endoreplicated genome were determined using DAPI (4',6-diamidino-2-phenylindole) flow cytometry in 6150 Gymnadenia plants (fragrant orchids) collected from 141 populations in 17 European countries. All widely recognized European species, and several taxa of less certain taxonomic status were sampled within Gymnadenia conopsea sensu lato. Key Results Most Gymnadenia populations were taxonomically and/or ploidy heterogeneous. Two majority (2x and 4x) and three minority (3x, 5x and 6x) cytotypes were identified. Evolution largely proceeded at the diploid level, whereas tetraploids were much more geographically and taxonomically restricted. Although minority ploidies constituted <2 % of the individuals sampled, they were found in 35 % of populations across the entire area investigated. The amount of nuclear DNA, together with the level of progressively partial endoreplication, separated all Gymnadenia species currently widely recognized in Europe. Conclusions Despite their low frequency, minority cytotypes substantially increase intraspecific and intrapopulation ploidy diversity estimates for fragrant orchids. The cytogenetic structure of Gymnadenia populations is remarkably dynamic and shaped by multiple evolutionary mechanisms, including both the ongoing production of unreduced gametes and heteroploid hybridization. Overall, it is likely that the level of ploidy heterogeneity experienced by most plant species/populations is currently underestimated; intensive sampling is necessary to obtain a holistic picture. PMID:23002267

  18. Ablation of the mitochondrial complex IV assembly protein Surf1 leads to increased expression of the UPR(MT) and increased resistance to oxidative stress in primary cultures of fibroblasts.

    PubMed

    Pharaoh, Gavin; Pulliam, Daniel; Hill, Shauna; Sataranatarajan, Kavithalakshmi; Van Remmen, Holly

    2016-08-01

    Mice deficient in the electron transport chain (ETC) complex IV assembly protein SURF1 have reduced assembly and activity of cytochrome c oxidase that is associated with an upregulation of components of the mitochondrial unfolded protein response (UPR(MT)) and increased mitochondrial number. We hypothesized that the upregulation of proteins associated with the UPR(MT) in response to reduced cytochrome c oxidase activity in Surf1(-/-) mice might contribute to increased stress resistance. To test this hypothesis we asked whether primary cultures of fibroblasts from Surf1(-/-) mice exhibit enhanced resistance to stressors compared to wild-type fibroblasts. Here we show that primary dermal fibroblasts isolated from Surf1(-/-) mice have increased expression of UPR(MT) components ClpP and Hsp60, and increased expression of Lon protease. Fibroblasts from Surf1(-/-) mice are significantly more resistant to cell death caused by oxidative stress induced by paraquat or tert-Butyl hydroperoxide compared to cells from wild-type mice. In contrast, Surf1(-/-) fibroblasts show no difference in sensitivity to hydrogen peroxide stress. The enhanced cell survival in response to paraquat or tert-Butyl hydroperoxide in Surf1(-/-) fibroblasts compared to wild-type fibroblasts is associated with induced expression of Lon, ClpP, and Hsp60, increased maximal respiration, and increased reserve capacity as measured using the Seahorse Extracellular Flux Analyzer. Overall these data support a protective role for the activation of the UPR(MT) in cell survival. PMID:27208630

  19. The Co-Operonic PE25/PPE41 Protein Complex of Mycobacterium tuberculosis Elicits Increased Humoral and Cell Mediated Immune Response

    PubMed Central

    Tundup, Smanla; Pathak, Niteen; Ramanadham, M.; Mukhopadhyay, Sangita; Murthy, K. J. R.; Ehtesham, Nasreen Z.; Hasnain, Seyed E.

    2008-01-01

    Background Many of the PE/PPE proteins are either surface localized or secreted outside and are thought to be a source of antigenic variation in the host. The exact role of these proteins are still elusive. We previously reported that the PPE41 protein induces high B cell response in TB patients. The PE/PPE genes are not randomly distributed in the genome but are organized as operons and the operon containing PE25 and PPE41 genes co-transcribe and their products interact with each other. Methodology/Principal Finding We now describe the antigenic properties of the PE25, PPE41 and PE25/PPE41 protein complex coded by a single operon. The PPE41 and PE25/PPE41 protein complex induces significant (p<0.0001) B cell response in sera derived from TB patients and in mouse model as compared to the PE25 protein. Further, mice immunized with the PE25/PPE41 complex and PPE41 proteins showed significant (p<0.00001) proliferation of splenocyte as compared to the mice immunized with the PE25 protein and saline. Flow cytometric analysis showed 15–22% enhancement of CD8+ and CD4+ T cell populations when immunized with the PPE41 or PE25/PPE41 complex as compared to a marginal increase (8–10%) in the mice immunized with the PE25 protein. The PPE41 and PE25/PPE41 complex can also induce higher levels of IFN-γ, TNF-α and IL-2 cytokines. Conclusion While this study documents the differential immunological response to the complex of PE and PPE vis-à-vis the individual proteins, it also highlights their potential as a candidate vaccine against tuberculosis. PMID:18974870

  20. Patterns of Address in Dili Tetum, East Timor

    ERIC Educational Resources Information Center

    Williams-van Klinken, Catharina; Hajek, John

    2006-01-01

    This article focuses on a detailed description of patterns of address in Dili Tetum today. It outlines the complexities of the address system and points to considerable variation in its evolving present-day use. We find, amongst other things, that a speaker may use a range of address strategies even to the same addressee, and that the use of…

  1. Addressing Increasing Demands on Australian Disability Support Workers

    ERIC Educational Resources Information Center

    Iacono, Teresa

    2010-01-01

    Disability support personnel within Australia include those who provide direct and daily care to people with intellectual disability (ID), largely in residential and day service contexts. Their roles and responsibilities are many, calling on far ranging skills. Yet, they come to these roles with levels of education that range from incomplete high…

  2. Increasing value and reducing waste: addressing inaccessible research

    PubMed Central

    Chan, An-Wen; Song, Fujian; Vickers, Andrew; Jefferson, Tom; Dickersin, Kay; Gøtzsche, Peter C.; Krumholz, Harlan M.; Ghersi, Davina; van der Worp, H. Bart

    2015-01-01

    The study protocol, publications, full study report detailing all analyses, and participant-level dataset constitute the main documentation of methods and results for health research. However, journal publications are available for only half of all studies and are plagued by selective reporting of methods and results. The protocol, full study report, and participant-level dataset are rarely available. The quality of information provided in study protocols and reports is variable and often incomplete. Inaccessibility of full information for the vast majority of studies wastes billions of dollars, introduces bias, and has a detrimental impact on patient care and research. To help improve this situation at a systemic level, three main actions are warranted. Firstly, it is important that academic institutions and funders reward investigators who fully disseminate their research protocols, reports, and participant-level datasets. Secondly, standards for the content of protocols, full study reports, and data sharing practices should be rigorously developed and adopted for all types of health research. Finally, journals, funders, sponsors, research ethics committees, regulators, and legislators should implement and enforce policies supporting study registration and availability of journal publications, full study reports, and participant-level datasets. PMID:24411650

  3. Increased production of mitochondrial superoxide in the spinal cord induces pain behaviors in mice: the effect of mitochondrial electron transport complex inhibitors.

    PubMed

    Kim, Hee Young; Chung, Jin Mo; Chung, Kyungsoon

    2008-12-01

    Scavengers of reactive oxygen species (ROS) have been shown to produce a strong antinociceptive effect on persistent pain, and mitochondria are suggested to be the main source of ROS in the spinal dorsal horn. To explore whether excessive generation of mitochondrial superoxide alone can induce pain, the effect of mitochondrial electron transport complex inhibitors on the development of mechanical hyperalgesia was examined in mice. Intrathecal injection of an electron transport complex inhibitor, antimycin A or rotenone, in normal mice resulted in a slowly developing but long-lasting and dose-dependent mechanical hyperalgesia. The levels of mechanical hyperalgesia after antimycin A, a complex III inhibitor, were higher than that with rotenone, a complex I inhibitor. A large increase of mitochondrial superoxide in the spinal dorsal horn and a strong antinociceptive effect of ROS scavengers, phenyl-N-tert-butylnitrone (PBN) and 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) were observed in antimycin A-treated mice. The study indicates that the enhanced production of spinal mitochondrial superoxide alone without nerve injury can produce mechanical hyperalgesia. PMID:18832013

  4. The Importance of Exposure in Addressing Current and Emerging Air Quality Issues

    EPA Science Inventory

    The air quality issues that we face today and will face in the future are becoming increasingly more complex and require an improved understanding of human exposure to be effectively addressed. The objectives of this paper are (1) to discuss how concepts of human exposure and ex...

  5. Visible-Light-Driven Photoisomerization and Increased Rotation Speed of a Molecular Motor Acting as a Ligand in a Ruthenium(II) Complex.

    PubMed

    Wezenberg, Sander J; Chen, Kuang-Yen; Feringa, Ben L

    2015-09-21

    Toward the development of visible-light-driven molecular rotary motors, an overcrowded alkene-based ligand and the corresponding ruthenium(II) complex is presented. In our design, a 4,5-diazafluorenyl coordination motif is directly integrated into the motor function. The photochemical and thermal isomerization behavior has been studied by UV/Vis and NMR spectroscopy. Upon coordination to a Ru(II) bipyridine complex, the photoisomerization process can be driven by visible (λmax = 450 nm) instead of UV light and furthermore, a large increase of the speed of rotation is noted. DFT calculations point to a contraction of the diazafluorenyl lower half upon metal-coordination resulting in reduced steric hindrance in the "fjord region" of the molecule. Consequently, it is shown that metal-ligand interactions can play an important role in the adjustment of both photophysical and thermodynamic properties of molecular motors. PMID:26271465

  6. 2014 ASHG Awards and Addresses

    PubMed Central

    2015-01-01

    Each year at the annual meeting of The American Society of Human Genetics (ASHG), addresses are given in honor of The Society and a number of award winners. A summary of each of these addresses is given below. On the following pages, we have printed the presidential address and the addresses for the William Allan Award, the Curt Stern Award, and the Victor A. McKusick Leadership Award. Webcasts of these addresses, as well as those of many other presentations, can be found at http://www.ashg.org.

  7. 2013 ASHG Awards and Addresses

    PubMed Central

    2014-01-01

    Each year at the annual meeting of The American Society of Human Genetics (ASHG), addresses are given in honor of The Society and a number of award winners. A summary of each of these addresses is given below. On the following pages, we have printed the Presidential Address and the addresses for the William Allan Award, the Curt Stern Award, and the Victor A. McKusick Leadership Award. Webcasts of these addresses, as well as those of many other presentations, can be found at http://www.ashg.org.

  8. Optically addressed multiband photodetector for infrared imaging applications

    NASA Astrophysics Data System (ADS)

    Cellek, O. O.; Zhang, Y.-H.

    2012-01-01

    Multiband infrared focal plane arrays (FPAs) with small pixel pitch have increased device processing complexity since they often need more than two terminals per pixel for readouts. Simpler FPAs are enabled by our newly demonstrated optically-addressed two-terminal multiband photodetector architecture. For long-wavelength infrared (LWIR) and midwavelength infrared (MWIR) imaging applications, the use of quantum well infrared photodetectors (QWIP) has been investigated. The results show that the utilization of unipolar QWIPs with bipolar near infrared (NIR) devices is feasible with this new optical-addressing scheme. Potential device performance is analyzed with an equivalent AC circuit model. Proposed design maximizes fill factor and enables small pixel-pitch FPA with single indium-bump per pixel for NIR/MWIR/LWIR multiband detection capability.

  9. Decrease and increase in brain activity during visual perceptual priming: an fMRI study on similar but perceptually different complex visual scenes.

    PubMed

    Blondin, François; Lepage, Martin

    2005-01-01

    A robust finding among functional neuroimaging studies on visual priming is decreased neural activity in extrastriate and inferior prefrontal cortices for the second presentation of an object relative to its first presentation. This effect can also be observed for different but perceptually similar objects that are alternative exemplars of the initially presented object (e.g. two different pencils). An unanswered question is whether this decrease in activity can be found for the successive presentation of similar complex visual scenes. We used a test in which landscape pictures were divided vertically into three segments. A first segment was presented and followed several stimuli later by a second related segment. Reaction times were faster for the presentation of the second segment relative to the first one. Although perceptually different from the first segment, the presentation of the second segment was nonetheless associated with reduced activity in late stage visual processing areas including parahippocampal/fusiform gyri bilaterally, left middle occipital and temporal gyri, right inferior temporal and superior occipital gyri, and in left inferior frontal gyrus. The observed decreases in activity in these regions replicate results on priming of different exemplars of single objects while further extending these results to similar complex visual scenes. The presentation of the second segment was also associated with increased activity mainly in frontal and parietal regions, two areas known to be associated with memory retrieval. In sum, priming effects can also occur for complex visual scenes that are intrinsically different from each other although similar in their composition. PMID:16168731

  10. A Phospholipid-Protein Complex from Antarctic Krill Reduced Plasma Homocysteine Levels and Increased Plasma Trimethylamine-N-Oxide (TMAO) and Carnitine Levels in Male Wistar Rats

    PubMed Central

    Bjørndal, Bodil; Ramsvik, Marie S.; Lindquist, Carine; Nordrehaug, Jan E.; Bruheim, Inge; Svardal, Asbjørn; Nygård, Ottar; Berge, Rolf K.

    2015-01-01

    Seafood is assumed to be beneficial for cardiovascular health, mainly based on plasma lipid lowering and anti-inflammatory effects of n-3 polyunsaturated fatty acids. However, other plasma risk factors linked to cardiovascular disease are less studied. This study aimed to penetrate the effect of a phospholipid-protein complex (PPC) from Antarctic krill on one-carbon metabolism and production of trimethylamine-N-oxide (TMAO) in rats. Male Wistar rats were fed isoenergetic control, 6%, or 11% PPC diets for four weeks. Rats fed PPC had reduced total homocysteine plasma level and increased levels of choline, dimethylglycine and cysteine, whereas the plasma level of methionine was unchanged compared to control. PPC feeding increased the plasma level of TMAO, carnitine, its precursors trimethyllysine and γ-butyrobetaine. There was a close correlation between plasma TMAO and carnitine, trimethyllysine, and γ-butyrobetaine, but not between TMAO and choline. The present data suggest that PPC has a homocysteine lowering effect and is associated with altered plasma concentrations of metabolites related to one-carbon metabolism and B-vitamin status in rats. Moreover, the present study reveals a non-obligatory role of gut microbiota in the increased plasma TMAO level as it can be explained by the PPC’s content of TMAO. The increased level of carnitine and carnitine precursors is interpreted to reflect increased carnitine biosynthesis. PMID:26371012

  11. Capping Protein Increases the Rate of Actin-based Motility by Promoting Filament Nucleation by the Arp2/3 Complex

    PubMed Central

    Akin, Orkun; Mullins, R. Dyche

    2008-01-01

    Summary Capping protein is an integral component of Arp2/3-nucleated actin networks that drive amoeboid motility. Increasing the concentration of capping protein, which caps barbed ends of actin filaments and prevents elongation, increases the rate of actin-based motility in vivo and in vitro. We studied the synergy between capping protein and Arp2/3 using an in vitro actin-based motility system reconstituted from purified proteins. We find that capping protein increases the rate of motility by promoting more frequent filament nucleation by the Arp2/3 complex, and not by increasing the rate of filament elongation as previously suggested. One consequence of this coupling between capping and nucleation is that, while the rate of motility depends strongly on the concentration of capping protein and Arp2/3, the net rate of actin assembly is insensitive to changes in either factor. By reorganizing their architecture, dendritic actin networks harness the same assembly kinetics to drive different rates of motility. PMID:18510928

  12. Epidermal growth factor increases the interaction between nucleolin and heterogeneous nuclear ribonucleoprotein K/poly(C) binding protein 1 complex to regulate the gastrin mRNA turnover.

    PubMed

    Lee, Pin-Tse; Liao, Pao-Chi; Chang, Wen-Chang; Tseng, Joseph T

    2007-12-01

    Gastrin, a gastrointestinal hormone responsible for gastric acid secretion, has been confirmed as a growth factor for gastrointestinal tract malignancies. High expression of gastrin mRNA was observed in pancreatic and colorectal cancer; however, the mechanism is unclear. Epidermal growth factor (EGF) was found to increase gastrin mRNA stability, indicating mRNA turnover regulation mechanism is involved in the control of gastrin mRNA expression. Using biotin-labeled RNA probe pull-down assay combined with mass spectrometry analysis, we identified the heterogeneous nuclear ribonucleoprotein K (hnRNP K) and poly(C) binding protein 1 (PCBP1) bound with the C-rich region in gastrin mRNA 3' untranslated region. Nucleolin bound with the AGCCCU motif and interacted with hnRNP K were also demonstrated. Under EGF treatment, we observed the amount of nucleolin interacting with hnRNP K and gastrin mRNA increased. Using small interfering RNA technology to define their functional roles, we found hnRNP K, PCBP1, and nucleolin were all responsible for stabilizing gastrin mRNA. Moreover, nucleolin plays a crucial role in mediating the increased gastrin mRNA stability induced by EGF signaling. Besides, we also observed hnRNP K/PCBP1 complex bound with the C-rich region in the gastrin mRNA increased nucleolin binding with gastrin mRNA. Finally, a novel binding model was proposed. PMID:17928403

  13. Addressing neurological disorders with neuromodulation.

    PubMed

    Oluigbo, Chima O; Rezai, Ali R

    2011-07-01

    Neurological disorders are becoming increasingly common in developed countries as a result of the aging population. In spite of medications, these disorders can result in progressive loss of function as well as chronic physical, cognitive, and emotional disability that ultimately places enormous emotional and economic on the patient, caretakers, and the society in general. Neuromodulation is emerging as a therapeutic option in these patients. Neuromodulation is a field, which involves implantable devices that allow for the reversible adjustable application of electrical, chemical, or biological agents to the central or peripheral nervous system with the objective of altering its functioning with the objective of achieving a therapeutic or clinically beneficial effect. It is a rapidly evolving field that brings together many different specialties in the fields of medicine, materials science, computer science and technology, biomedical, and neural engineering as well as the surgical or interventional specialties. It has multiple current and emerging indications, and an enormous potential for growth. The main challenges before it are in the need for effective collaboration between engineers, basic scientists, and clinicians to develop innovations that address specific problems resulting in new devices and clinical applications. PMID:21193369

  14. Enzymatic Dysfunction of Mitochondrial Complex I of the Candida albicans goa1 Mutant Is Associated with Increased Reactive Oxidants and Cell Death ▿

    PubMed Central

    Li, Dongmei; Chen, Hui; Florentino, Abigail; Alex, Deepu; Sikorski, Patricia; Fonzi, William A.; Calderone, Richard

    2011-01-01

    We have previously shown that deletion of GOA1 (growth and oxidant adaptation) of Candida albicans results in a loss of mitochondrial membrane potential, ATP synthesis, increased sensitivity to oxidants and killing by human neutrophils, and avirulence in a systemic model of candidiasis. We established that translocation of Goa1p to mitochondria occurred during peroxide stress. In this report, we show that the goa1Δ (GOA31), compared to the wild type (WT) and a gene-reconstituted (GOA32) strain, exhibits sensitivity to inhibitors of the classical respiratory chain (CRC), including especially rotenone (complex I [CI]) and salicylhydroxamic acid (SHAM), an inhibitor of the alternative oxidase pathway (AOX), while potassium cyanide (KCN; CIV) causes a partial inhibition of respiration. In the presence of SHAM, however, GOA31 has an enhanced respiration, which we attribute to the parallel respiratory (PAR) pathway and alternative NADH dehydrogenases. Interestingly, deletion of GOA1 also results in a decrease in transcription of the alternative oxidase gene AOX1 in untreated cells as well as negligible AOX1 and AOX2 transcription in peroxide-treated cells. To explain the rotenone sensitivity, we measured enzyme activities of complexes I to IV (CI to CIV) and observed a major loss of CI activity in GOA31 but not in control strains. Enzymatic data of CI were supported by blue native polyacrylamide gel electrophoresis (BN-PAGE) experiments which demonstrated less CI protein and reduced enzyme activity. The consequence of a defective CI in GOA31 is an increase in reactive oxidant species (ROS), loss of chronological aging, and programmed cell death ([PCD] apoptosis) in vitro compared to control strains. The increase in PCD was indicated by an increase in caspase activity and DNA fragmentation in GOA31. Thus, GOA1 is required for a functional CI and partially for the AOX pathway; loss of GOA1 compromises cell survival. Further, the loss of chronological aging is new to

  15. Increased risk of volume overload with plasma compared with four‐factor prothrombin complex concentrate for urgent vitamin K antagonist reversal

    PubMed Central

    Refaai, Majed A.; Goldstein, Joshua N.; Lee, Martin L.; Durn, Billie L.; Milling, Truman J.; Sarode, Ravi

    2015-01-01

    BACKGROUND Plasma is commonly used for vitamin K antagonist (VKA) reversal, but observational studies suggest that it is associated with transfusion‐related adverse reactions (e.g., volume overload). However, this issue has not previously been addressed in a randomized controlled trial (RCT). STUDY DESIGN AND METHODS Factors associated with volume overload were examined using data from two Phase IIIb RCTs comparing plasma with four‐factor prothrombin complex concentrate (4F‐PCC, Beriplex/Kcentra, CSL Behring) for urgent VKA reversal. VKA‐treated patients with major bleeding (NCT00708435) or requiring an urgent surgical or invasive procedure (NCT00803101) were randomly assigned (1:1) to receive either plasma or 4F‐PCC, concomitant with vitamin K. Adverse events (AEs) and serious AEs were prospectively captured up to Day 10 and 45, respectively. Volume overload predictors were evaluated on a univariate and multivariate basis. RESULTS A total of 388 patients (4F‐PCC, n = 191; plasma, n = 197) were enrolled. Volume overload occurred in 34 (9%) patients (4F‐PCC, n = 9; plasma, n = 25). In univariate analyses, use of plasma (vs. 4F‐PCC), use of nonstudy plasma and/or platelets, race, history of congestive heart failure (CHF), and history of renal disease were associated with volume overload. In multivariate analyses, use of plasma (vs. 4F‐PCC), history of CHF, and history of renal disease were independent volume overload predictors. In an additional analysis restricted to volume overload events recorded up to Day 7, only use of plasma (vs. 4F‐PCC) was an independent volume overload predictor. CONCLUSIONS After adjusting for other potential risk factors, plasma use was independently associated with a greater risk of volume overload than 4F‐PCC in patients requiring urgent VKA reversal. PMID:26135740

  16. Managing complexity of aerospace systems

    NASA Astrophysics Data System (ADS)

    Tamaskar, Shashank

    Growing complexity of modern aerospace systems has exposed the limits of conventional systems engineering tools and challenged our ability to design them in a timely and cost effective manner. According to the US Government Accountability Office (GAO), in 2009 nearly half of the defense acquisition programs are expecting 25% or more increase in unit acquisition cost. Increase in technical complexity has been identified as one of the primary drivers behind cost-schedule overruns. Thus to assure the affordability of future aerospace systems, it is increasingly important to develop tools and capabilities for managing their complexity. We propose an approach for managing the complexity of aerospace systems to address this pertinent problem. To this end, we develop a measure that improves upon the state-of-the-art metrics and incorporates key aspects of system complexity. We address the problem of system decomposition by presenting an algorithm for module identification that generates modules to minimize integration complexity. We demonstrate the framework on diverse spacecraft and show the impact of design decisions on integration cost. The measure and the algorithm together help the designer track and manage complexity in different phases of system design. We next investigate how complexity can be used as a decision metric in the model-based design (MBD) paradigm. We propose a framework for complexity enabled design space exploration that introduces the idea of using complexity as a non-traditional design objective. We also incorporate complexity with the component based design paradigm (a sub-field of MBD) and demonstrate it on several case studies. The approach for managing complexity is a small but significant contribution to the vast field of complexity management. We envision our approach being used in concert with a suite of complexity metrics to provide an ability to measure and track complexity through different stages of design and development. This will not

  17. Cyclodextrin-Complexed Ocimum basilicum Leaves Essential Oil Increases Fos Protein Expression in the Central Nervous System and Produce an Antihyperalgesic Effect in Animal Models for Fibromyalgia

    PubMed Central

    Nascimento, Simone S.; Araújo, Adriano A. S.; Brito, Renan G.; Serafini, Mairim R.; Menezes, Paula P.; DeSantana, Josimari M.; Lucca Júnior, Waldecy; Alves, Pericles B.; Blank, Arie F.; Oliveira, Rita C. M.; Oliveira, Aldeidia P.; Albuquerque-Júnior, Ricardo L. C.; Almeida, Jackson R. G. S.; Quintans-Júnior, Lucindo J.

    2014-01-01

    O. basilicum leaves produce essential oils (LEO) rich in monoterpenes. The short half-life and water insolubility are limitations for LEO medical uses. β-Cyclodextrin (β-CD) has been employed to improve the pharmacological properties of LEO. We assessed the antihyperalgesic profile of LEO, isolated or complexed in β-CD (LEO/β-CD), on an animal model for fibromyalgia. Behavioral tests: mice were treated every day with either LEO/β-CD (25, 50 or 100 mg/kg, p.o.), LEO (25 mg/kg, p.o.), tramadol (TRM 4 mg/kg, i.p.) or vehicle (saline), and 60 min after treatment behavioral parameters were assessed. Therefore, mice were evaluated for mechanical hyperalgesia (von Frey), motor coordination (Rota-rod) and muscle strength (Grip Strength Metter) in a mice fibromyalgia model. After 27 days, we evaluated the central nervous system (CNS) pathways involved in the effect induced by experimental drugs through immunofluorescence protocol to Fos protein. The differential scanning analysis (DSC), thermogravimetry/derivate thermogravimetry (TG/DTG) and infrared absorption spectroscopy (FTIR) curves indicated that the products prepared were able to incorporate the LEO efficiently. Oral treatment with LEO or LEO-βCD, at all doses tested, produced a significant reduction of mechanical hyperalgesia and we were able to significantly increase Fos protein expression. Together, our results provide evidence that LEO, isolated or complexed with β-CD, produces analgesic effects on chronic non-inflammatory pain as fibromyalgia. PMID:25551603

  18. Cyclodextrin-complexed Ocimum basilicum leaves essential oil increases Fos protein expression in the central nervous system and produce an antihyperalgesic effect in animal models for fibromyalgia.

    PubMed

    Nascimento, Simone S; Araújo, Adriano A S; Brito, Renan G; Serafini, Mairim R; Menezes, Paula P; DeSantana, Josimari M; Lucca, Waldecy; Alves, Pericles B; Blank, Arie F; Oliveira, Rita C M; Oliveira, Aldeidia P; Albuquerque, Ricardo L C; Almeida, Jackson R G S; Quintans, Lucindo J

    2015-01-01

    O. basilicum leaves produce essential oils (LEO) rich in monoterpenes. The short half-life and water insolubility are limitations for LEO medical uses. β-Cyclodextrin (β-CD) has been employed to improve the pharmacological properties of LEO. We assessed the antihyperalgesic profile of LEO, isolated or complexed in β-CD (LEO/β-CD), on an animal model for fibromyalgia. Behavioral tests: mice were treated every day with either LEO/β-CD (25, 50 or 100 mg/kg, p.o.), LEO (25 mg/kg, p.o.), tramadol (TRM 4 mg/kg, i.p.) or vehicle (saline), and 60 min after treatment behavioral parameters were assessed. Therefore, mice were evaluated for mechanical hyperalgesia (von Frey), motor coordination (Rota-rod) and muscle strength (Grip Strength Metter) in a mice fibromyalgia model. After 27 days, we evaluated the central nervous system (CNS) pathways involved in the effect induced by experimental drugs through immunofluorescence protocol to Fos protein. The differential scanning analysis (DSC), thermogravimetry/derivate thermogravimetry (TG/DTG) and infrared absorption spectroscopy (FTIR) curves indicated that the products prepared were able to incorporate the LEO efficiently. Oral treatment with LEO or LEO-βCD, at all doses tested, produced a significant reduction of mechanical hyperalgesia and we were able to significantly increase Fos protein expression. Together, our results provide evidence that LEO, isolated or complexed with β-CD, produces analgesic effects on chronic non-inflammatory pain as fibromyalgia. PMID:25551603

  19. Amine-functionalized task-specific ionic liquids: a mechanistic explanation for the dramatic increase in viscosity upon complexation with CO{sub 2} from molecular simulation

    SciTech Connect

    Gutowski, K.E.; Maginn, E.J.

    2008-11-15

    The capture of CO{sub 2} from fossil fuel combustion, particularly in coal-fired power plants, represents a critical component of efforts aimed at stabilizing greenhouse gas levels in the atmosphere. Recently, a series of second-generation task-specific ionic liquids (TSILs) containing amine functional groups have been synthesized and demonstrated to have much higher capacities for CO{sub 2} due to their reactivity with CO{sub 2}, as well unusually high viscosities in both the neat and complexed states. The current work extends the seminal studies of CO{sub 2} capture with ionic liquids (ILs) by providing insight from simulations into the mechanism responsible for the dramatic increase in viscosity upon complexation. Simulations conclusively demonstrate that the slow translational and rotational dynamics, which are manifest in the high viscosity, may be attributable to the formation of a strong, pervasive hydrogen-bonded network. Semiquantitative estimates of the cation and anion self-diffusion coefficients and rotational time constants, as well as detailed hydrogen bond analysis, are consistent with the experimentally observed formation of glassy or gel-like materials upon contact with CO{sub 2}. This has significant implications for the design of new approaches or materials involving ILs that take advantage of these preconceived limitations, in the synthesis or manipulation of new TSIL frameworks for CO{sub 2} capture, and in novel experimental studies of chemistries and dynamics in persistent heterogeneous environments.

  20. The protein phosphatase-1/inhibitor-2 complex differentially regulates GSK3 dephosphorylation and increases sarcoplasmic/endoplasmic reticulum calcium ATPase 2 levels

    SciTech Connect

    King, Taj D.; Gandy, Johanna C.; Bijur, Gautam N. . E-mail: gautam@uab.edu

    2006-11-01

    The ubiquitously expressed protein glycogen synthase kinase-3 (GSK3) is constitutively active, however its activity is markedly diminished following phosphorylation of Ser21 of GSK3{alpha} and Ser9 of GSK3{beta}. Although several kinases are known to phosphorylate Ser21/9 of GSK3, for example Akt, relatively much less is known about the mechanisms that cause the dephosphorylation of GSK3 at Ser21/9. In the present study KCl-induced plasma membrane depolarization of SH-SY5Y cells, which increases intracellular calcium concentrations caused a transient decrease in the phosphorylation of Akt at Thr308 and Ser473, and GSK3 at Ser21/9. Overexpression of the selective protein phosphatase-1 inhibitor protein, inhibitor-2, increased basal GSK3 phosphorylation at Ser21/9 and significantly blocked the KCl-induced dephosphorylation of GSK3{beta}, but not GSK3{alpha}. The phosphorylation of Akt was not affected by the overexpression of inhibitor-2. GSK3 activity is known to affect sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) levels. Overexpression of inhibitor-2 or treatment of cells with the GSK3 inhibitors lithium and SB216763 increased the levels of SERCA2. These results indicate that the protein phosphatase-1/inhibitor-2 complex differentially regulates GSK3 dephosphorylation induced by KCl and that GSK3 activity regulates SERCA2 levels.

  1. Increased expression of pentraxin 3 after in vivo and in vitro stimulation with gonadotropins in porcine oocyte-cumulus complexes and granulosa cells.

    PubMed

    Nagyova, E; Kalous, J; Nemcova, L

    2016-07-01

    It has been previously shown that multimeric pentraxin 3 (PTX3) is a key component of the cumulus oophorus extracellular matrix (ECM) in mice. In response to the ovulatory LH surge, the cumulus cells assemble a unique ECM that envelopes the oocyte and cumulus cell complex. Importantly, cumuli from PTX3(-/-) mice were defective in their ECM organization and their fertility was impaired. It has been demonstrated that tumor necrosis factor alpha-induced protein 6 catalyzes the formation of heavy chains of (inter-alpha-trypsin inhibitor) -hyaluronan complexes and these are then cross-linked via PTX3. This process is tightly regulated and requires the proteins to meet/interact in the correct order. Finally, in this way, the above-listed proteins form the cumulus oophorus ECM. We investigated whether PTX3 is expressed in the porcine preovulatory follicle. Porcine oocyte-cumulus complexes (OCC) and mural granulosa cells (MGC) from gilts were obtained either after stimulation in vivo with eCG/hCG (4, 8, 16, 24, and 32 h) or culture in vitro (4, 24, and 44 h) in FSH/LH-supplemented medium. The methods performed were real-time reverse transcriptase-polymerase chain reaction, Western blot analysis, and immunostaining. The expression of PTX3 transcripts was significantly increased 24 h after either in vivo hCG stimulation or in vitro FSH/LH treatment in both OCC and MGC. Western blot analysis with PTX3 antibody revealed that not only matrix extracts from in vivo-stimulated gilts contain high levels of PTX3 protein but also matrix extracts of FSH/LH-stimulated OCC cultured in medium supplemented either with follicular fluid or with porcine serum. The localization of PTX3 in the cumulus oocyte complex was confirmed by immunostaining. In conclusion, PTX3 is produced by porcine OCC and MGC both in vivo and in vitro with gonadotropin stimuli inducing cumulus expansion. PMID:26986845

  2. Increasing chlamydia screening tests in general practice: a modified Zelen prospective Cluster Randomised Controlled Trial evaluating a complex intervention based on the Theory of Planned Behaviour

    PubMed Central

    McNulty, Cliodna A M; Hogan, Angela H; Ricketts, Ellie J; Wallace, Louise; Oliver, Isabel; Campbell, Rona; Kalwij, Sebastian; O'Connell, Elaine; Charlett, Andre

    2014-01-01

    Objective To determine if a structured complex intervention increases opportunistic chlamydia screening testing of patients aged 15–24 years attending English general practitioner (GP) practices. Methods A prospective, Cluster Randomised Controlled Trial with a modified Zelen design involving 160 practices in South West England in 2010. The intervention was based on the Theory of Planned Behaviour (TPB). It comprised of practice-based education with up to two additional contacts to increase the importance of screening to GP staff and their confidence to offer tests through skill development (including videos). Practical resources (targets, posters, invitation cards, computer reminders, newsletters including feedback) aimed to actively influence social cognitions of staff, increasing their testing intention. Results Data from 76 intervention and 81 control practices were analysed. In intervention practices, chlamydia screening test rates were 2.43/100 15–24-year-olds registered preintervention, 4.34 during intervention and 3.46 postintervention; controls testing rates were 2.61/100 registered patients prior intervention, 3.0 during intervention and 2.82 postintervention. During the intervention period, testing in intervention practices was 1.76 times as great (CI 1.24 to 2.48) as controls; this persisted for 9 months postintervention (1.57 times as great, CI 1.27 to 2.30). Chlamydia infections detected increased in intervention practices from 2.1/1000 registered 15–24-year-olds prior intervention to 2.5 during the intervention compared with 2.0 and 2.3/1000 in controls (Estimated Rate Ratio intervention versus controls 1.4 (CI 1.01 to 1.93). Conclusions This complex intervention doubled chlamydia screening tests in fully engaged practices. The modified Zelen design gave realistic measures of practice full engagement (63%) and efficacy of this educational intervention in general practice; it should be used more often. Trial registration The trial was

  3. Increased complexity in interstellar chemistry: detection and chemical modeling of ethyl formate and n-propyl cyanide in Sagittarius B2(N)

    NASA Astrophysics Data System (ADS)

    Belloche, A.; Garrod, R. T.; Müller, H. S. P.; Menten, K. M.; Comito, C.; Schilke, P.

    2009-05-01

    Context: In recent years, organic molecules of increasing complexity have been found toward the prolific Galactic center source Sagittarius B2. Aims: We wish to explore the degree of complexity that the interstellar chemistry can reach in star-forming regions. Methods: We carried out a complete line survey of the hot cores Sgr B2(N) and (M) with the IRAM 30 m telescope in the 3 mm range, plus partial surveys at 2 and 1.3 mm. We analyzed this spectral survey in the local thermodynamical equilibrium approximation. We modeled the emission of all known molecules simultaneously, which allows us to search for less abundant, more complex molecules. We compared the derived column densities with the predictions of a coupled gas-phase and grain-surface chemical code. Results: We report the first detection in space of ethyl formate (C2H5OCHO) and n-propyl cyanide (C3H7CN) toward Sgr B2(N). The detection of n-propyl cyanide is based on refined spectroscopic parameters derived from combined analyses of available laboratory spectroscopic data. For each molecule, we identified spectral features at the predicted frequencies having intensities compatible with a unique rotation temperature. For an assumed source size of 3 arcsec, our modeling yields a column density of 5.4 × 1016 cm-2, a temperature of 100 K, and a linewidth of 7 km s-1 for ethyl formate. n-Propyl cyanide is detected with two velocity components having column densities of 1.5 × 1016 cm-2 and 6.6 × 1015 cm-2, respectively, for a source size of 3 arcsec, a temperature of 150 K, and a linewidth of 7 km s-1. The abundances of ethyl formate and n-propyl cyanide relative to H2 are estimated to be 3.6 × 10-9 and 1.0 × 10-9, respectively. We derived column density ratios of 0.8/15/1 for the related species t-HCOOH/CH3OCHO/C2H5OCHO and 108/80/1 for CH3CN/C2H5CN/C3H7CN. Our chemical modeling reproduces these ratios reasonably well. It suggests that the sequential, piecewise construction of ethyl and n-propyl cyanide from

  4. Violence Goes to School. Keynote Address.

    ERIC Educational Resources Information Center

    Levin, Jack

    1998-01-01

    Increased juvenile violence in schools has led to suggested solutions that are politically expedient but fail to address what makes violence so appealing. Instead of school uniforms, conflict resolution programs, or media rating systems, a grass roots approach of alternative programs, parental involvement, and youth support systems could repair…

  5. 2,3,7,8-Tetrachlorodibenzo-p-dioxin increases the expression of genes in the human epidermal differentiation complex and accelerates epidermal barrier formation.

    PubMed

    Sutter, Carrie Hayes; Bodreddigari, Sridevi; Campion, Christina; Wible, Ryan S; Sutter, Thomas R

    2011-11-01

    Chloracne is commonly observed in people exposed to dioxins, yet the mechanism of toxicity is not well understood. The pathology of chloracne is characterized by hyperkeratinization of the interfollicular squamous epithelium, hyperproliferation and hyperkeratinization of hair follicle cells as well as a metaplastic response of the ductular sebum secreting sebaceous glands. In vitro studies using normal human epidermal keratinocytes to model interfollicular human epidermis demonstrate a 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated acceleration of differentiation and increase in gene expression of several prodifferentiation genes, including filaggrin (FLG). Here, we demonstrated that the TCDD-activated aryl hydrocarbon receptor (AHR) bound a small fragment of DNA upstream of the transcriptional start sites of the FLG gene, containing one of two candidate xenobiotic response elements (XREs). Reporter assays using the promoter region of FLG containing the two putative XREs indicated that the increase in this messenger RNA (mRNA) was due to TCDD-mediated enhanced transcription, which was lost when both XREs were mutated. As FLG is part of the human epidermal differentiation complex (EDC) found on chromosome 1, we measured mRNAs from an additional 18 EDC genes for their regulation by TCDD. Of these genes, 14 were increased by TCDD. Immunoblot assays demonstrated that the proteins of FLG as well as that of another prodifferentiation gene, small proline rich protein 2, were increased by TCDD. In utero exposure to TCDD accelerated the formation of the epidermal barrier in the developing mouse fetus by approximately 1 day. These results indicate that the epidermal permeability barrier is a functional target of the TCDD-activated AHR. PMID:21835898

  6. Melatonin promotes the cumulus-oocyte complexes quality of vitrified-thawed murine ovaries; with increased mean number of follicles survival and ovary size following heterotopic transplantation.

    PubMed

    Hemadi, Masoud; Abolhassani, Farid; Akbari, Mohammad; Sobhani, Aligholi; Pasbakhsh, Parichehr; Ahrlund-Richter, Lars; Modaresi, Mohammad H; Salehnia, Mojdeh

    2009-09-15

    We have tested the protective effect of melatonin on neonate murine ovarian tissue after vitrification, thawing and heterotopic transplantation into ovariectomized recipient mice. Vitrified ovaries from neonate (CBA x C57Bl/6) F1 hybrid mice were thawed under standard condition with or without the addition of 100 microM melatonin. Following transplantation, melatonin (20 mg/kg/day) or saline solution (physiological saline) was injected i.p. to the treated and non-treated groups for 48 h respectively. Follicle survival and development, together with ovary size followed. Also, vaginal cytology was carried out for monitoring restored puberty. Histological and immunohistochemical studies showed that melatonin could promote the quality of the cumulus-oocyte complexes with uniform distribution of granulosa and stromal cells in the ovarian grafts. Furthermore, the mean follicles survival was improved and the ovary size increased (P< or = 0.001). The overall mean number of follicles entering the next maturation stage dramatically increased. However, the revascularization and restoration of puberty of ovarian grafts were similar between melatonin-treated and control groups. In conclusion, melatonin as a protection from ischemic injury and a reduce oxidative stress, was shown beneficial during the early days of transplantation. PMID:19622351

  7. Sexual maturation and administration of 17β-estradiol and testosterone induce complex gene expression changes in skin and increase resistance of Atlantic salmon to ectoparasite salmon louse.

    PubMed

    Krasnov, Aleksei; Wesmajervi Breiland, Mette S; Hatlen, Bjarne; Afanasyev, Sergey; Skugor, Stanko

    2015-02-01

    The crustacean ectoparasitic salmon louse (Lepeophtheirus salmonis) is a major problem of Atlantic salmon aquaculture in the Northern hemisphere. Host-pathogen interactions in this system are highly complex. Resistance to the parasite involves variations in genetic background, nutrition, properties of skin, and status of the endocrine and immune systems. This study addressed the relationship between sex hormones and lice infection. Field observation revealed a sharp reduction of lice prevalence during sexual maturation with no difference between male and female fish. To determine if higher resistance against lice was related to sex hormones, post-smolt salmon were administered control feed and feeds containing 17β-estradiol (20 mg/kg) and testosterone (25 mg/kg) during a 3-week pre-challenge period. After challenge with lice, counts were reduced 2-fold and 1.5-fold in fish that received 17β-estradiol and testosterone, respectively. Gene expression analyses were performed from skin of salmon collected in the field trial and from the controlled lab experiment at three time points (end of feeding-before challenge, 3 days post challenge (dpc) and 16 dpc) using oligonucleotide microarray and qPCR. Differential expression was observed in genes associated with diverse biological processes. Both studies revealed similar changes of several antibacterial acute phase proteins; of note was induction of cathelicidin and down-regulation of a defensin gene. Treatment with hormones revealed their ability to modulate T helper cell (Th)-mediated immunity in skin. Enhanced protection achieved by 17β-estradiol administration might in part be due to the skewing of Th responses away from the prototypic anti-parasitic Th2 immunity and towards the more effective Th1 responses. Multiple genes involved in wound healing, differentiation and remodelling of skin tissue were stimulated during maturation but suppressed with sex hormones. Such opposite regulation suggested that these processes

  8. The combined treatment with novel platinum(II) complex and anti-MUC1 increases apoptotic response in MDA-MB-231 breast cancer cells.

    PubMed

    Gornowicz, Agnieszka; Bielawska, Anna; Czarnomysy, Robert; Gabryel-Porowska, Halina; Muszyńska, Anna; Bielawski, Krzysztof

    2015-10-01

    New strategy of cancer's targeting treatment is combining monoclonal antibodies with chemotherapeutic agents. An important goal of targeted therapy appears to be a transmembrane glycoprotein type I-mucin 1 (MUC1), which is overexpressed in tumors of epithelial origin, especially in breast cancer. The goal of the study was to check the effect of monoclonal antibody against MUC1 with novel platinum(II) complex (Pt12) on selected aspects of apoptosis in human MDA-MB-231 breast cancer cells. The number of apoptotic and necrotic cells was measured using annexin V binding assay. The decrease of mitochondrial membrane potential (MMP) and DNA fragmentation was analyzed. Finally, the influence of novel platinum(II) complex (Pt12) used with anti-MUC1 on the concentration of selected markers of apoptosis such as Bax, caspase-8, -9, and caspase-3 was performed using ELISA. The results from combined treatment were compared with those obtained using monotherapy. In our study, we proved that anti-MUC1 used in combination with Pt12 strongly induced apoptosis in MDA-MB-231 breast cancer cell line. The effect was stronger than treatment with Pt12, cisplatin, anti-MUC1, and anti-MUC1 used with cisplatin. We also observed the highest decrease of MMP and the strongest DNA fragmentation after such a combined treatment. The results obtained from ELISA showed increased concentration of Bax, caspases-8, -9, -3 compared to monotherapy. Our study proved that Pt12 together with anti-MUC1 strongly induced apoptosis in estrogen-negative breast cancer cell line (MDA-MB-231). The apoptosis may go through extrinsic pathway associated with caspase-8 as well as intrinsic pathway connected with caspase-9. PMID:26112902

  9. Increasing the Depth of Mass-Spectrometry-Based Structural Analysis of Protein Complexes through the Use of Multiple Cross-Linkers.

    PubMed

    Ding, Yue-He; Fan, Sheng-Bo; Li, Shuang; Feng, Bo-Ya; Gao, Ning; Ye, Keqiong; He, Si-Min; Dong, Meng-Qiu

    2016-04-19

    Chemical cross-linking of proteins coupled with mass spectrometry (CXMS) is a powerful tool to study protein folding and to map the interfaces between interacting proteins. The most commonly used cross-linkers in CXMS are BS(3) and DSS, which have similar structures and generate the same linkages between pairs of lysine residues in spatial proximity. However, there are cases where no cross-linkable lysine pairs are present at certain regions of a protein or at the interface of two interacting proteins. In order to find the cross-linkers that can best complement the performance of BS(3) and DSS, we tested seven additional cross-linkers that either have different spacer arm structures or that target different amino acids (BS(2)G, EGS, AMAS, GMBS, Sulfo-GMBS, EDC, and TFCS). Using BSA, aldolase, the yeast H/ACA protein complex, and E. coli 70S ribosomes, we showed that, in terms of providing structural information not obtained through the use of BS(3) and DSS, EGS and Sulfo-GMBS worked better than the other cross-linkers that we tested. EGS generated a large number of cross-links not seen with the other amine-specific cross-linkers, possibly due to its hydrophilic spacer arm. We demonstrate that incorporating the cross-links contributed by the EGS and amine-sulfhydryl cross-linkers greatly increased the accuracy of Rosetta in docking the structure of the yeast H/ACA protein complex. Given the improved depth of useful information it can provide, we suggest that the multilinker CXMS approach should be used routinely when the amount of a sample permits. PMID:27010980

  10. Surgical Treatment of Diverticulitis: Hand-Assisted Laparoscopic Resection Is Predominantly Used for Complex Cases and Is Associated With Increased Postoperative Complications and Prolonged Hospitalization.

    PubMed

    Miyagaki, Hiromichi; Rhee, Rebecca; Shantha Kumara, H M C; Yan, Xiaohong; Njoh, Linda; Cekic, Vesna; Whelan, Richard L

    2016-06-01

    Introduction Laparoscopic (LAP) colectomy is now the "gold" standard for diverticulitis; the role of hand-assisted LAP (HAL) and Open methods today is unclear. This study assessed the elective use of these methods for diverticulitis. Methods A retrospective review of demographic, comorbidity (Carlson Comorbidity Index [CCI]), resection type, and short-term outcomes was carried out. Results There were 125 (44.5%) LAP, 125 (44.5%) HAL, and 31 (11%) Open cases (overall N = 281). The mean age, body mass index, and percentage of high-risk patients (CCI score >2) of the HAL group were greater (P < .05) than the LAP group (vs Open, P = ns). The Open group's mean age and percent with CCI >2 was greater when compared with the LAP group (P < .05). More Open (P < .05) and HAL patients had complex disease (Open, 63%; HAL, 40%, LAP, 22%) and were diverted (Open, 35%; HAL, 10%; LAP, 3%). Time to bowel movement was not different; however, there was a stepwise increase in median length of stay (LOS; days) from the LAP (5 days) to HAL (6 days) to Open group (7 days) (P < .05 for all). The LAP complication rate (22.4%) was lower (P < .05) than the HAL (42.4%) or Open groups' (45.2%) rates. The LAP surgical site infection rate (5.6%) was lower (P < .05) than the HAL (12.8%) or Open groups (19.6%). Conclusion The HAL and Open groups had more high risk, complex disease, diverted, and older patients than the LAP group; likewise, the overall complication rate and LOS was higher in the HAL and Open groups. Use of HAL methods likely contributed to the high minimally invasive surgery utilization rate (89%). PMID:26611789

  11. Trimethylation Enhancement Using (13)C-Diazomethane ((13)C-TrEnDi): Increased Sensitivity and Selectivity of Phosphatidylethanolamine, Phosphatidylcholine, and Phosphatidylserine Lipids Derived from Complex Biological Samples.

    PubMed

    Canez, Carlos R; Shields, Samuel W J; Bugno, Magdalena; Wasslen, Karl V; Weinert, Hillary P; Willmore, William G; Manthorpe, Jeffrey M; Smith, Jeffrey C

    2016-07-19

    Significant sensitivity enhancements in the tandem mass spectrometry-based analysis of complex mixtures of several phospholipid classes has been achieved via (13)C-TrEnDi. (13)C-TrEnDi-modified phosphatidylethanolamine (PE), phosphatidylserine (PS), and phosphatidylcholine (PC) lipids extracted from HeLa cells demonstrated greater sensitivity via precursor ion scans (PISs) than their unmodified counterparts. Sphingomyelin (SM) species exhibited neither an increased nor decreased sensitivity following modification. The use of isotopically labeled diazomethane enabled the distinction of modified PE and modified PC species that would yield isobaric species with unlabeled diazomethane. (13)C-TrEnDi created a PE-exclusive PIS of m/z 202.1, two PS-exclusive PISs of m/z 148.1 and m/z 261.1, and a PIS of m/z 199.1 for PC species (observed at odd m/z values) and SM species (observed at even m/z values). The standardized average area increase after TrEnDi modification was 10.72-fold for PE species, 2.36-fold for PC, and 1.05-fold for SM species. The sensitivity increase of PS species was not quantifiable, as there were no unmodified PS species identified prior to derivatization. (13)C-TrEnDi allowed for the identification of 4 PE and 7 PS species as well as the identification and quantitation of an additional 4 PE and 4 PS species that were below the limit of detection (LoD) prior to modification. (13)C-TrEnDi also pushed 24 PE and 6 PC lipids over the limit of quantitation (LoQ) that prior to modification were above the LoD only. PMID:27275841

  12. Evaluation of CO2 migration and formation storage capacity in the Dalders formations, Baltic Sea - Preliminary analysis by means of models of increasing complexity

    NASA Astrophysics Data System (ADS)

    Niemi, Auli; Yang, Zhibing; Tian, Liang; Jung, Byeongju; Fagerlund, Fritjof; Joodaki, Saba; Pasquali, Riccardo; O'Neill, Nick; Vernon, Richard

    2014-05-01

    We present preliminary data analysis and modeling of CO2 injection into selected parts of the Dalders Monocline and Dalders Structure, formations situated under the Baltic Sea and of potential interest for CO2 geological storage. The approach taken is to use models of increasing complexity successively, thereby increasing the confidence and reliability of the predictions. The objective is to get order-of-magnitude estimates of the behavior of the formations during potential industrial scale CO2 injection and subsequent storage periods. The focus has been in regions with best cap-rock characteristics, according to the present knowledge. Data has been compiled from various sources available, such as boreholes within the region. As the first approximation we use analytical solutions, in order to get an initial estimate the CO2 injection rates that can be used without causing unacceptable pressure increases. These preliminary values are then used as basis for more detailed numerical analyses with TOUGH2/TOUGH2-MP (e.g. Zhang et al, 2008) simulator and vertical equilibrium based (e.g. Gasda et al, 2009) models. With the numerical models the variations in material properties, formation thickness etc., as well as more processes such as CO2 dissolution can also be taken into account. The presentation discusses results from these preliminary analyses in terms of estimated storage capacity, CO2 and pressure plume extent caused by various injection scenarios, as well as CO2 travel time after the end of the injection. The effect of factors such as number of injection wells and the positioning of these, the effect of formation properties and the boundary conditions are discussed as are the benefits and disadvantages of the various modeling approaches used. References: Gasda S.E. et al, 2009. Computational Geosciences 13, 469-481. Zhang et al, 2008. Report LBNL-315E, Lawrence Berkeley National Laboratory.

  13. Aqueous solubility of calcium L-lactate, calcium D-gluconate, and calcium D-lactobionate: importance of complex formation for solubility increase by hydroxycarboxylate mixtures.

    PubMed

    Vavrusova, Martina; Munk, Merete Bøgelund; Skibsted, Leif H

    2013-08-28

    Among the calcium hydroxycarboxylates important for cheese quality, D-lactobionate [Ksp = (7.0 ± 0.3) × 10(-3) mol(3) L(-3)] and L-lactate [Ksp = (5.8 ± 0.2) × 10(-3) mol(3) L(-3)] were found more soluble than D-gluconate [Ksp = (7.1 ± 0.2) × 10(-4) mol(3) L(-3)], as indicated by the solubility products determined electrochemically for aqueous 1.0 M NaCl at 25.0 °C. Still, solubility of calcium L-lactate increases by 45% in the presence of 0.50 M sodium D-gluconate and by 37% in the presence of 0.50 M sodium D-lactobionate, while solubility of calcium D-gluconate increases by 66 and 85% in the presence of 0.50 M sodium L-lactate and 0.50 M sodium D-lactobionate, respectively, as determined by complexometric titration. Sodium L-lactate and sodium D-gluconate have only little influence on solubility of calcium D-lactobionate. The increased solubility is described quantitatively by calcium binding to D-gluconate (K1 = 14 ± 3 mol(-1) L) in 1.0 M NaCl at 25 °C, D-lactobionate (K1 = 11 ± 2 mol(-1) L), and L-lactate (K1 = 8 ± 2 mol(-1) L), as indicated by the association constants determined electrochemically. In mixed hydroxycarboxylate solutions, calcium binding is quantitatively described by the geometric mean of the individual association constants for both aqueous 1.0 and 0.20 M NaCl, indicating a 1:1 stoichiometry for complex formation. PMID:23906043

  14. Framework for Address Cooperative Extended Transactions

    1997-12-01

    The Framework for Addressing Cooperative Extended Transactions (FACET) is an object-oriented software framework for building models of complex, cooperative behaviors of agents. it can be used to implement simulation models of societal processes such as the complex interplay of participating individuals and organizations engaged in multiple concurrent transactions in pursuit of their various goals. These transactions can be patterned on, for example, clinical guidelines and procedures, business practices, government and corporate policies, etc. FACET canmore » also address other complex behaviors such as biological life cycles or manufacturing processes. FACET includes generic software objects representing the fundamental classes of agent -- Person and Organization - with mechanisms for resource management, including resolution of conflicting requests for participation and/or use of the agent's resources. The FACET infrastructure supports stochastic behavioral elements and coping mechanisms by which specified special conditions and events can cause an active cooperative process to be preempted, diverting the participants onto appropriate alternative behavioral pathways.« less

  15. Increased Awareness, Increased Appreciation

    ERIC Educational Resources Information Center

    Nightingale, Barbra

    2015-01-01

    This article provides a student's viewpoint in response to Larry Andrews' article, "The Humanities Are Dead! Long Live the Humanities!," which addresses and solidifies the notion that, at least from the standpoint of academicians, the humanities are alive and well. The author believes that a broader base of learning, an increased…

  16. Addressing problems of employee performance.

    PubMed

    McConnell, Charles R

    2011-01-01

    Employee performance problems are essentially of 2 kinds: those that are motivational in origin and those resulting from skill deficiencies. Both kinds of problems are the province of the department manager. Performance problems differ from problems of conduct in that traditional disciplinary processes ordinarily do not apply. Rather, performance problems are addressed through educational and remedial processes. The manager has a basic responsibility in ensuring that everything reasonable is done to help each employee succeed. There are a number of steps the manager can take to address employee performance problems. PMID:21537142

  17. Flexible Workflow Software enables the Management of an Increased Volume and Heterogeneity of Sensors, and evolves with the Expansion of Complex Ocean Observatory Infrastructures.

    NASA Astrophysics Data System (ADS)

    Tomlin, M. C.; Jenkyns, R.

    2015-12-01

    Ocean Networks Canada (ONC) collects data from observatories in the northeast Pacific, Salish Sea, Arctic Ocean, Atlantic Ocean, and land-based sites in British Columbia. Data are streamed, collected autonomously, or transmitted via satellite from a variety of instruments. The Software Engineering group at ONC develops and maintains Oceans 2.0, an in-house software system that acquires and archives data from sensors, and makes data available to scientists, the public, government and non-government agencies. The Oceans 2.0 workflow tool was developed by ONC to manage a large volume of tasks and processes required for instrument installation, recovery and maintenance activities. Since 2013, the workflow tool has supported 70 expeditions and grown to include 30 different workflow processes for the increasing complexity of infrastructures at ONC. The workflow tool strives to keep pace with an increasing heterogeneity of sensors, connections and environments by supporting versioning of existing workflows, and allowing the creation of new processes and tasks. Despite challenges in training and gaining mutual support from multidisciplinary teams, the workflow tool has become invaluable in project management in an innovative setting. It provides a collective place to contribute to ONC's diverse projects and expeditions and encourages more repeatable processes, while promoting interactions between the multidisciplinary teams who manage various aspects of instrument development and the data they produce. The workflow tool inspires documentation of terminologies and procedures, and effectively links to other tools at ONC such as JIRA, Alfresco and Wiki. Motivated by growing sensor schemes, modes of collecting data, archiving, and data distribution at ONC, the workflow tool ensures that infrastructure is managed completely from instrument purchase to data distribution. It integrates all areas of expertise and helps fulfill ONC's mandate to offer quality data to users.

  18. The C-terminal polyproline-containing region of ELMO contributes to an increase in the life-time of the ELMO-DOCK complex.

    PubMed

    Sévajol, Marion; Reiser, Jean-Baptiste; Chouquet, Anne; Pérard, Julien; Ayala, Isabel; Gans, Pierre; Kleman, Jean-Philippe; Housset, Dominique

    2012-03-01

    The eukaryotic Engulfment and CellMotility (ELMO) proteins form an evolutionary conserved family of key regulators which play a central role in Rho-dependent biological processes such as engulfment and cell motility/migration. ELMO proteins interact with a subset of Downstream of Crk (DOCK) family members, a new type of guanine exchange factors (GEF) for Rac and cdc42 GTPases. The physiological function of DOCK is to facilitate actin remodeling, a process which occurs only in presence of ELMO. Several studies have determined that the last 200 C-terminal residues of ELMO1 and the first 180 N-terminal residues of DOCK180 are responsible for the ELMO-DOCK interaction. However, the precise role of the different domains and motifs identified in these regions has remained elusive. Divergent functional, biochemical and structural data have been reported regarding the contribution of the C-terminal end of ELMO, comprising its polyproline motif, and of the DOCK SH3 domain. In the present study, we have investigated the contribution of the C-terminal end of ELMO1 to the interaction between ELMO1 and the SH3 domain of DOCK180 using nuclear magnetic resonance spectroscopy and surface plasmon resonance. Our data presented here demonstrate the ability of the SH3 domain of DOCK180 to interact with ELMO1, regardless of the presence of the polyproline-containing C-terminal end. However, the presence of the polyproline region leads to a significant increase in the half-life of the ELMO1-DOCK180 complex, along with a moderate increase on the affinity. PMID:22177965

  19. The Cytokine Response of U937-Derived Macrophages Infected through Antibody-Dependent Enhancement of Dengue Virus Disrupts Cell Apical-Junction Complexes and Increases Vascular Permeability

    PubMed Central

    Puerta-Guardo, Henry; Raya-Sandino, Arturo; González-Mariscal, Lorenza; Rosales, Victor H.; Ayala-Dávila, José; Chávez-Mungía, Bibiana; Martínez-Fong, Daniel; Medina, Fernando

    2013-01-01

    Severe dengue (SD) is a life-threatening complication of dengue that includes vascular permeability syndrome (VPS) and respiratory distress. Secondary infections are considered a risk factor for developing SD, presumably through a mechanism called antibody-dependent enhancement (ADE). Despite extensive studies, the molecular bases of how ADE contributes to SD and VPS are largely unknown. This work compares the cytokine responses of differentiated U937 human monocytic cells infected directly with dengue virus (DENV) or in the presence of enhancing concentrations of a humanized monoclonal antibody recognizing protein E (ADE-DENV infection). Using a cytometric bead assay, ADE-DENV-infected cells were found to produce significantly higher levels of the proinflammatory cytokines interleukin 6 (IL-6), IL-12p70, and tumor necrosis factor alpha (TNF-α), as well as prostaglandin E2 (PGE2), than cells directly infected. The capacity of conditioned supernatants (conditioned medium [CM]) to disrupt tight junctions (TJs) in MDCK cell cultures was evaluated. Exposure of MDCK cell monolayers to CM collected from ADE-DENV-infected cells (ADE-CM) but not from cells infected directly led to a rapid loss of transepithelial electrical resistance (TER) and to delocalization and degradation of apical-junction complex proteins. Depletion of either TNF-α, IL-6, or IL-12p70 from CM from ADE-DENV-infected cells fully reverted the disrupting effect on TJs. Remarkably, mice injected intraperitoneally with ADE-CM showed increased vascular permeability in sera and lungs, as indicated by an Evans blue quantification assay. These results indicate that the cytokine response of U937-derived macrophages to ADE-DENV infection shows an increased capacity to disturb TJs, while results obtained with the mouse model suggest that such a response may be related to the vascular plasma leakage characteristic of SD. PMID:23616663

  20. The formation of glycerol monodecanoate by a dehydration/condensation reaction: increasing the chemical complexity of amphiphiles on the early earth

    NASA Astrophysics Data System (ADS)

    Apel, C. L.; Deamer, D. W.

    Dehydration/condensation reactions between organic molecules in the prebiotic environment increased the inventory and complexity of organic compounds available for self-assembly into protocellular structures. As a model of such reactions, we have investigated the esterification reaction between glycerol and decanoic acid that forms glycerol monodecanoate. This amphiphile enhances robustness of self-assembled membranous structures of carboxylic acids to the potentially disruptive effects of pH, divalent cation binding and osmotic stress. Experimental variables included temperature, water activity and hydrolysis of the resulting ester product, providing insights into the environmental conditions that would favour the formation and stability of this more evolved amphiphile. At temperatures exceeding 500 C, the ester product formed even in the presence of bulk water, suggesting that the reaction occurs at the liquid interface of the two reactants and that the products segregate in the two immiscible layers, thereby reducing the rate of the hydrolytic back reaction. This suggests that esterification reactions were likely to commonly occur in the prebiotic environment as available reactants underwent cycles of wetting and drying on early landmasses at elevated temperatures.

  1. Selection of low cost materials for the sorption of copper and herbicides as single or mixed compounds in increasing complexity matrices.

    PubMed

    Huguenot, David; Bois, Paul; Jézéquel, Karine; Cornu, Jean-Yves; Lebeau, Thierry

    2010-10-15

    Low cost materials (sugar beet pulp, corncob, corncob char, perlite, vermiculite, sand, sediment) have been tested for their ability to quickly sorb copper, glyphosate, diuron and 3,4-dichloroaniline (3,4-DCA) as single or mixed compounds. Tests have been performed in increasingly complex liquid matrices: ultra pure water (UPW), runoff water (RW) and sediment extract medium (SEM). Highest sorption levels in UPW are achieved with corncob char for Cu (93%), glyphosate (74%), diuron (98%) and 3,4-DCA (99%). Other ready-to-use adequate sorbents are sugar beet pulp for Cu and sand for glyphosate, diuron and 3,4-DCA. Sorption levels obtained in UPW are significantly altered in SEM as a result of its higher dissolved organic carbon concentration, tenuous changes being obtained with RW. Interactions between herbicides and Cu are pointed out: higher sorption level is observed for glyphosate in mixture with Cu, as it is observed with diuron and 3,4-DCA when mixed with all other pollutants. Langmuir model has been found to better fit the data for copper, whereas Freundlich one has been found more relevant for diuron and 3,4-DCA. Our results stress the need for studying adsorption in different matrices when searching for sorbents to be used in field conditions. PMID:20594640

  2. Addressing the Complex Needs of Students with Attachment Disorders

    ERIC Educational Resources Information Center

    Losinski, Mickey; Katsiyannis, Antonis; White, Sherry; Wiseman, Nicole

    2016-01-01

    Attachment disorders are a relatively rare condition affecting children. This is particularly true for those who are adopted or living in foster care, and are thought to be attributed to an interruption in the bonding between a child and his or her caregiver. Attachment disorders are divided into two distinct categories: a predominately withdrawn…

  3. Addressing Phonological Questions with Ultrasound

    ERIC Educational Resources Information Center

    Davidson, Lisa

    2005-01-01

    Ultrasound can be used to address unresolved questions in phonological theory. To date, some studies have shown that results from ultrasound imaging can shed light on how differences in phonological elements are implemented. Phenomena that have been investigated include transitional schwa, vowel coalescence, and transparent vowels. A study of…

  4. Communities Address Barriers to Connectivity.

    ERIC Educational Resources Information Center

    Byers, Anne

    1996-01-01

    Rural areas lag behind urban areas in access to information technologies. Public institutions play a critical role in extending the benefits of information technologies to those who would not otherwise have access. The most successful rural telecommunications plans address barriers to use, such as unawareness of the benefits, technophobia, the…

  5. Keynote Address: Rev. Mark Massa

    ERIC Educational Resources Information Center

    Massa, Mark S.

    2011-01-01

    Rev. Mark S. Massa, S.J., is the dean and professor of Church history at the School of Theology and Ministry at Boston College. He was invited to give a keynote to begin the third Catholic Higher Education Collaborative Conference (CHEC), cosponsored by Boston College and Fordham University. Fr. Massa's address posed critical questions about…

  6. State of the Lab Address

    ScienceCinema

    King, Alex

    2013-03-01

    In his third-annual State of the Lab address, Ames Laboratory Director Alex King called the past year one of "quiet but strong progress" and called for Ames Laboratory to continue to build on its strengths while responding to changing expectations for energy research.

  7. State of the Lab Address

    SciTech Connect

    King, Alex

    2010-01-01

    In his third-annual State of the Lab address, Ames Laboratory Director Alex King called the past year one of "quiet but strong progress" and called for Ames Laboratory to continue to build on its strengths while responding to changing expectations for energy research.

  8. Films prepared from poly(vinyl alcohol) and amylose-fatty acid salt inclusion complexes with increased surface hydrophobicity and high elongation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this study, water-soluble amylose-inclusion complexes were prepared from high amylose corn starch and sodium salts of lauric, palmitic, and stearic acid by steam jet cooking. Cast films were prepared by combining the amylose complexes with poly(vinyl alcohol)(PVOH) solution at ratios varying from...

  9. Genomic duplication resulting in increased copy number of genes encoding the sister chromatid cohesion complex conveys clinical consequences distinct from Cornelia de Lange

    PubMed Central

    Yan, Jiong; Zhang, Feng; Brundage, Ellen; Scheuerle, Angela; Lanpher, Brendan; Erickson, Robert P.; Powis, Zoe; Robinson, Haynes B.; Trapane, Pamela L.; Stachiw-Hietpas, Danuta; Keppler-Noreuil, Kim M.; Lalani, Seema R.; Sahoo, Trilochan; Chinault, A. Craig; Patel, Ankita; Cheung, Sau Wai; Lupski, James R.

    2009-01-01

    Cornelia de Lange Syndrome (CdLS) is a multisystem congenital anomaly disorder. Heterozygous point mutations in three genes (NIPBL, SMC3 and SMC1A), encoding components of the sister chromatid cohesion apparatus, are responsible for ∼ 50-60% of CdLS cases. Recent studies have revealed a high degree of genomic rearrangements (e.g. deletions and duplications) in the human genome, which result in gene copy number variations (CNV). CNVs have been associated with a wide range of both Mendelian and complex traits including disease phenotypes such as Charcot-Marie-Tooth type 1A, Pelizaeus-Merzbacher, Parkinson, Alzheimer, autism and schizophrenia. Increased versus decreased copy number of the same gene can potentially cause either similar or different clinical features. We identified duplications on chromosomes 5 or X using genome wide array Comparative Genomic Hybridization (aCGH). The duplicated regions contain either the NIPBL or the SMC1A genes. Junction sequences analyses revealed the involvement of three genomic rearrangement mechanisms. The patients share some common features including mental retardation, developmental delay, sleep abnormalities, and crainofacial and limb defects. The systems affected are the same as in CdLS, but clinical manifestations are distinct from CdLS; particularly the absence of the CdLS facial gestalt. Our results confirm the notion that duplication CNV of genes can be a common mechanism for human genetic diseases. Defining the clinical consequences for a specific gene dosage alteration represents a new “reverse genomics” trend in medical genetics that is reciprocal to the traditional approach of delineation of the common clinical phenotype preceding the discovery of the genetic etiology. PMID:19052029

  10. Highly Soluble Tris-hydroxypyridonate Gd(III) Complexes with Increased Hydration Number, Fast Water Exchange, Slow Electronic Relaxation, and High Relaxivity1

    SciTech Connect

    Werner, Eric J.; Avedano, Stefano; Botta, Mauro; Hay, Benjamin P.; Moore, Evan G.; Aime, Silvio; Raymond, Kenneth N.

    2007-02-21

    The design, synthesis, and relaxivity properties of a highly soluble TACN-capped hydroxypyridonate Gd(III) complex are presented. Molecular mechanics modeling was used to help design a complex capable of possessing three water molecules in the inner metal coordination sphere, an attractive property for high-relaxivity MRI contrast agents. The measured relaxivity of 13.1 mM-1s-1 is consistent with three coordinated waters and represents one of the highest known relaxivities of any low-molecular weight Gd complex. An extremely fast water exchange rate, long electronic relaxation time, and unique pH dependent relaxivity of the complex are also discussed. B.P.H. acknowledges support from the Environmental Management Science Program, Office of Science, U.S. Department of Energy (grant 73759). Pacific Northwest National Laboratory is operated by Battelle for the U.S. Department of Energy.

  11. Nanoscale content-addressable memory

    NASA Technical Reports Server (NTRS)

    Davis, Bryan (Inventor); Principe, Jose C. (Inventor); Fortes, Jose (Inventor)

    2009-01-01

    A combined content addressable memory device and memory interface is provided. The combined device and interface includes one or more one molecular wire crossbar memories having spaced-apart key nanowires, spaced-apart value nanowires adjacent to the key nanowires, and configurable switches between the key nanowires and the value nanowires. The combination further includes a key microwire-nanowire grid (key MNG) electrically connected to the spaced-apart key nanowires, and a value microwire-nanowire grid (value MNG) electrically connected to the spaced-apart value nanowires. A key or value MNGs selects multiple nanowires for a given key or value.

  12. Addressing the workforce pipeline challenge

    SciTech Connect

    Leonard Bond; Kevin Kostelnik; Richard Holman

    2006-11-01

    A secure and affordable energy supply is essential for achieving U.S. national security, in continuing U.S. prosperity and in laying the foundations to enable future economic growth. To meet this goal the next generation energy workforce in the U.S., in particular those needed to support instrumentation, controls and advanced operations and maintenance, is a critical element. The workforce is aging and a new workforce pipeline, to support both current generation and new build has yet to be established. The paper reviews the challenges and some actions being taken to address this need.

  13. Aboriginal health promotion through addressing employment discrimination.

    PubMed

    Ferdinand, Angeline S; Paradies, Yin; Perry, Ryan; Kelaher, Margaret

    2014-01-01

    The Localities Embracing and Accepting Diversity (LEAD) program aimed to improve the mental health of Aboriginal Victorians by addressing racial discrimination and facilitating social and economic participation. As part of LEAD, Whittlesea Council adopted the Aboriginal Employment Pathways Strategy (AEPS) to increase Aboriginal employment and retention within the organisation. The Aboriginal Cultural Awareness Training Program was developed to build internal cultural competency and skills in recruiting and retaining Aboriginal staff. Analysis of surveys conducted before (pre; n=124) and after (post; n=107) the training program indicated a significant increase in participant understanding across all program objectives and in support of organisational policies to improve Aboriginal recruitment and retention. Participants ended the training with concrete ideas about intended changes, as well as how these changes could be supported by their supervisors and the wider organisation. Significant resources have since been allocated to implementing the AEPS over 5 years. In line with principles underpinning the National Aboriginal and Torres Strait Islander Health Plan 2013-23, particularly the focus on addressing racism as a determinant of health, this paper explores the AEPS and training program as promising approaches to health promotion through addressing barriers to Aboriginal employment. Possible implications for other large organisations are also considered. PMID:25155236

  14. Simulation with models of increasing complexity of CO2 emissions and nitrogen mineralisation, after soil application of labelled pig slurry and maize stalks

    NASA Astrophysics Data System (ADS)

    Bechini, Luca; Marino Gallina, Pietro; Geromel, Gabriele; Corti, Martina; Cavalli, Daniele

    2015-04-01

    High amounts of nitrogen are available per unit area in regions with intensive livestock operations. In swine farms, pig slurries are frequently incorporated in the soil together with maize stalks. Simulation models may help to understand nitrogen dynamics associated with animal manure and crop residue decomposition in the soil, and to support the definition of best management practices. The objective of this work was to test the ability of different models to simulate CO2 emissions and nitrogen mineralisation during a laboratory incubation (under optimal soil water content and constant temperature) of maize stalks (ST) and pig slurry (PS). A loam soil was amended with labelled (15N) or unlabelled maize stalks and pig slurries, in the presence of ammonium sulphate (AS). These treatments were established: unfertilised soil; ST15 + AS + PS; ST + AS15 + PS; and ST + AS + PS15. During 180 days, we measured CO2 emissions; microbial biomass C, N, and 15N; and soil mineral N (SMN and SM-15N). Three models of increasing complexity were calibrated using measured data. The models were two modifications of ICBM 2B/N (Kätterer and Andrén, 2001) and CN-SIM (Petersen et al., 2005). The three models simulated rather accurately the emissions of CO2 throughout the incubation period (Relative Root Mean Squared Error, RRMSE = 8-25). The simplest model (with one pool for ST and one for PS) strongly overestimated SMN immobilisation from day 3 to day 21, both in the treatments with AS15 and PS15 (RRMSE = 27-30%). The other two models represented rather well the dynamics of SMN in the soil (RRMSE = 21-25%), simulating a fast increase of nitrate concentration in the first days, and slower rates of nitrification thereafter. Worse performances were obtained with all models for the simulation of SM-15N in the treatment with ST15 (RRMSE = 64-104%): experimental data showed positive mineralization of stalk-derived N from the beginning of the incubation, while models strongly underestimated

  15. Hydrocomplexity: Addressing water security and emergent environmental risks

    NASA Astrophysics Data System (ADS)

    Kumar, Praveen

    2015-07-01

    Water security and emergent environmental risks are among the most significant societal concerns. They are highly interlinked to other global risks such as those related to climate, human health, food, human migration, biodiversity loss, urban sustainability, etc. Emergent risks result from the confluence of unanticipated interactions from evolving interdependencies between complex systems, such as those embedded in the water cycle. They are associated with the novelty of dynamical possibilities that have significant potential consequences to human and ecological systems, and not with probabilities based on historical precedence. To ensure water security we need to be able to anticipate the likelihood of risk possibilities as they present the prospect of the most impact through cascade of vulnerabilities. They arise due to a confluence of nonstationary drivers that include growing population, climate change, demographic shifts, urban growth, and economic expansion, among others, which create novel interdependencies leading to a potential of cascading network effects. Hydrocomplexity aims to address water security and emergent risks through the development of science, methods, and practices with the potential to foster a "Blue Revolution" akin to the Green revolution for food security. It blends both hard infrastructure based solution with soft knowledge driven solutions to increase the range of planning and design, management, mitigation and adaptation strategies. It provides a conceptual and synthetic framework to enable us to integrate discovery science and engineering, observational and information science, computational and communication systems, and social and institutional approaches to address consequential water and environmental challenges.

  16. Increased generation of intracellular reactive oxygen species initiates selective cytotoxicity against the MCF-7 cell line resultant from redox active combination therapy using copper-thiosemicarbazone complexes.

    PubMed

    Akladios, Fady N; Andrew, Scott D; Parkinson, Christopher J

    2016-06-01

    The combination of cytotoxic copper-thiosemicarbazone complexes with phenoxazines results in an up to 50-fold enhancement in the cytotoxic potential of the thiosemicarbazone against the MCF-7 human breast adenocarcinoma cell line over the effect attributable to drug additivity-allowing minimization of the more toxic copper-thiosemicarbazone component of the therapy. The combination of a benzophenoxazine with all classes of copper complex examined in this study proved more effective than combinations of the copper complexes with related isoelectronic azines. The combination approach results in rapid elevation of intracellular reactive oxygen levels followed by apoptotic cell death. Normal fibroblasts representative of non-cancerous cells (MRC-5) did not display a similar elevation of reactive oxygen levels when exposed to similar drug levels. The minimization of the copper-thiosemicarbazone component of the therapy results in an enhanced safety profile against normal fibroblasts. PMID:26951232

  17. Addressing viral resistance through vaccines

    PubMed Central

    Laughlin, Catherine; Schleif, Amanda; Heilman, Carole A

    2015-01-01

    Antimicrobial resistance is a serious healthcare concern affecting millions of people around the world. Antiviral resistance has been viewed as a lesser threat than antibiotic resistance, but it is important to consider approaches to address this growing issue. While vaccination is a logical strategy, and has been shown to be successful many times over, next generation viral vaccines with a specific goal of curbing antiviral resistance will need to clear several hurdles including vaccine design, evaluation and implementation. This article suggests that a new model of vaccination may need to be considered: rather than focusing on public health, this model would primarily target sectors of the population who are at high risk for complications from certain infections. PMID:26604979

  18. Addressing failures in exascale computing

    SciTech Connect

    Snir, Marc; Wisniewski, Robert W.; Abraham, Jacob A.; Adve, Sarita; Bagchi, Saurabh; Balaji, Pavan; Belak, Jim; Bose, Pradip; Cappello, Franck; Carlson, William; Chien, Andrew A.; Coteus, Paul; Debardeleben, Nathan A.; Diniz, Pedro; Engelmann, Christian; Erez, Mattan; Saverio, Fazzari; Geist, Al; Gupta, Rinku; Johnson, Fred; Krishnamoorthy, Sriram; Leyffer, Sven; Liberty, Dean; Mitra, Subhasish; Munson, Todd; Schreiber, Robert; Stearly, Jon; Van Hensbergen, Eric

    2014-05-01

    We present here a report produced by a workshop on “Addressing Failures in Exascale Computing” held in Park City, Utah, August 4–11, 2012. The charter of this workshop was to establish a common taxonomy about resilience across all the levels in a computing system; discuss existing knowledge on resilience across the various hardware and software layers of an exascale system; and build on those results, examining potential solutions from both a hardware and software perspective and focusing on a combined approach. The workshop brought together participants with expertise in applications, system software, and hardware; they came from industry, government, and academia; and their interests ranged from theory to implementation. The combination allowed broad and comprehensive discussions and led to this document, which summarizes and builds on those discussions.

  19. Light addressable photoelectrochemical cyanide sensor

    SciTech Connect

    Licht, S.; Myung, N.; Sun, Y.

    1996-03-15

    A sensor is demonstrated that is capable of spatial discrimination of cyanide with use of only a single stationary sensing element. Different spatial regions of the sensing element are light activated to reveal the solution cyanide concentration only at the point of illumination. In this light addressable photoelectrochemical (LAP) sensor the sensing element consists of an n-CdSe electrode immersed in solution, with the open-circuit potential determined under illumination. In alkaline ferro-ferri-cyanide solution, the open-circuit photopotential is highly responsive to cyanide, with a linear response of (120 mV) log [KCN]. LAP detection with a spatial resolution of {+-}1 mm for cyanide detection is demonstrated. The response is almost linear for 0.001-0.100 m cyanide with a resolution of 5 mV. 38 refs., 7 figs., 1 tab.

  20. Addressing Failures in Exascale Computing

    SciTech Connect

    Snir, Marc; Wisniewski, Robert; Abraham, Jacob; Adve, Sarita; Bagchi, Saurabh; Balaji, Pavan; Belak, J.; Bose, Pradip; Cappello, Franck; Carlson, Bill; Chien, Andrew; Coteus, Paul; DeBardeleben, Nathan; Diniz, Pedro; Engelmann, Christian; Erez, Mattan; Fazzari, Saverio; Geist, Al; Gupta, Rinku; Johnson, Fred; Krishnamoorthy, Sriram; Leyffer, Sven; Liberty, Dean; Mitra, Subhasish; Munson, Todd; Schreiber, Rob; Stearley, Jon; Van Hensbergen, Eric

    2014-01-01

    We present here a report produced by a workshop on Addressing failures in exascale computing' held in Park City, Utah, 4-11 August 2012. The charter of this workshop was to establish a common taxonomy about resilience across all the levels in a computing system, discuss existing knowledge on resilience across the various hardware and software layers of an exascale system, and build on those results, examining potential solutions from both a hardware and software perspective and focusing on a combined approach. The workshop brought together participants with expertise in applications, system software, and hardware; they came from industry, government, and academia, and their interests ranged from theory to implementation. The combination allowed broad and comprehensive discussions and led to this document, which summarizes and builds on those discussions.

  1. Design of phase-only, binary phase-only, and complex ternary matched filters with increased signal-to-noise ratios for colored noise

    NASA Technical Reports Server (NTRS)

    Kumar, B. V. K. V.; Juday, Richard D.

    1991-01-01

    An algorithm is provided for treating nonwhite additive noise in determining regions of support for phase-only filters, binary phase-only filters, and complex ternary matched filters. It is analytically shown to be optimal in the signal-to-noise ratio sense. It extends earlier research that assumed white noise.

  2. [Catalytic activity and the stability of horseradish peroxidase increase as a result of its incorporation into a polyelectrolyte complex with chitosan].

    PubMed

    Veselova, I A; Koreĭko, A V; Shekhovtsova, T N

    2009-01-01

    The incorporation of horseradish peroxidase into polyelectrolyte complexes with chitosans of different molecular weights (MW 5-150 kDa) yielded highly active and stable enzyme preparations. As a result of the selection of optimal conditions for the formation of peroxidase-chitosan complexes, it was found that 0.1% chitosan with a MW of 10 kDa had the strongest activatory effect on peroxidase (activation degree, > 70%) in the reaction of o-dianisidine oxidation by hydrogen peroxide. The complex formed by 0.001% chitosan with a molecular weight of 150 kDa was most stable: when immobilized on foamed polyurethane, it retained at least 50% of the initial activity for 550 days. The highest catalytic activity was exhibited in a 0.05 M phthalate buffer (pH 5.9-6.2) by the complex containing 0.006-0.009% chitosan in the indicator reaction. The activatory effect of the polysaccharide on the enzyme was determined by its influence on the binding and conversion of the reducting substrate peroxidase. PMID:19382699

  3. OPENING ADDRESS: Heterostructures in Semiconductors

    NASA Astrophysics Data System (ADS)

    Grimmeiss, Hermann G.

    1996-01-01

    Good morning, Gentlemen! On behalf of the Nobel Foundation, I should like to welcome you to the Nobel Symposium on "Heterostructures in Semiconductors". It gives me great pleasure to see so many colleagues and old friends from all over the world in the audience and, in particular, to bid welcome to our Nobel laureates, Prof. Esaki and Prof. von Klitzing. In front of a different audience I would now commend the scientific and technological importance of heterostructures in semiconductors and emphatically emphasise that heterostructures, as an important contribution to microelectronics and, hence, information technology, have changed societies all over the world. I would also mention that information technology is one of the most important global key industries which covers a wide field of important areas each of which bears its own character. Ever since the invention of the transistor, we have witnessed a fantastic growth in semiconductor technology, leading to more complex functions and higher densities of devices. This development would hardly be possible without an increasing understanding of semiconductor materials and new concepts in material growth techniques which allow the fabrication of previously unknown semiconductor structures. But here and today I will not do it because it would mean to carry coals to Newcastle. I will therefore not remind you that heterostructures were already suggested and discussed in detail a long time before proper technologies were available for the fabrication of such structures. Now, heterostructures are a foundation in science and part of our everyday life. Though this is certainly true, it is nevertheless fair to say that not all properties of heterostructures are yet understood and that further technologies have to be developed before a still better understanding is obtained. The organisers therefore hope that this symposium will contribute not only to improving our understanding of heterostructures but also to opening new

  4. Addressing the world water crisis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The world is facing an impinging crisis on water as population growth continues, energy use increases, and affluence (standard of living) increases all requiring more water. Agriculture must find ways to use water more productively while improving the impact of agriculture on the environment. Agri...

  5. Innovative Legal Approaches to Address Obesity

    PubMed Central

    Pomeranz, Jennifer L; Teret, Stephen P; Sugarman, Stephen D; Rutkow, Lainie; Brownell, Kelly D

    2009-01-01

    Context: The law is a powerful public health tool with considerable potential to address the obesity issue. Scientific advances, gaps in the current regulatory environment, and new ways of conceptualizing rights and responsibilities offer a foundation for legal innovation. Methods: This article connects developments in public health and nutrition with legal advances to define promising avenues for preventing obesity through the application of the law. Findings: Two sets of approaches are defined: (1) direct application of the law to factors known to contribute to obesity and (2) original and innovative legal solutions that address the weak regulatory stance of government and the ineffectiveness of existing policies used to control obesity. Specific legal strategies are discussed for limiting children's food marketing, confronting the potential addictive properties of food, compelling industry speech, increasing government speech, regulating conduct, using tort litigation, applying nuisance law as a litigation strategy, and considering performance-based regulation as an alternative to typical regulatory actions. Finally, preemption is an overriding issue and can play both a facilitative and a hindering role in obesity policy. Conclusions: Legal solutions are immediately available to the government to address obesity and should be considered at the federal, state, and local levels. New and innovative legal solutions represent opportunities to take the law in creative directions and to link legal, nutrition, and public health communities in constructive ways. PMID:19298420

  6. Addressing language barriers to healthcare in India.

    PubMed

    Narayan, Lalit

    2013-01-01

    In spite of a growing recognition of the importance of doctor-patient communication, the issue of language barriers to healthcare has received very little attention in India. The Indian population speaks over 22 major languages with English used as the lingua franca for biomedicine. Large-scale internal migration has meant that health workers are encountering increasing instances of language discordance within clinical settings. Research done predominantly in the West has shown language discordance to significantly affect access to care, cause problems of comprehension and adherence, and decrease the satisfaction and quality of care. Addressing language barriers to healthcare in India requires a stronger political commitment to providing non-discriminatory health services, especially to vulnerable groups such as illiterate migrant workers. Research will have to address three broad areas: the ways in which language barriers affect health and healthcare, the efficacy of interventions to overcome language barriers, and the costs of language barriers and efforts to overcome them. There is a need to address such barriers in health worker education and clinical practice. Proven strategies such as hiring multilingual healthcare workers, providing language training to health providers, employing in situ translators or using telephone interpretation services will have to be evaluated for their appropriateness to the Indian context. Internet-based initiatives, the proliferation of mobile phones and recent advances in machine translation promise to contribute to the solution. PMID:24758452

  7. Best Practices in Hiring: Addressing Unconscious Bias

    NASA Astrophysics Data System (ADS)

    Simpson, Caroline E.

    2012-01-01

    Research has shown that implementing certain hiring practices will increase diversity in the workplace while enhancing academic quality. All of these practices rely on addressing the issue of 'unconscious bias.' A brief overview of unconscious bias--what it is, how it works, and simple measures to counter it--will be presented. Successful strategies, actions, and recommendations for implementing best recruiting and hiring practices, which have been proven to enhance academic excellence by ensuring a deep and diverse applicant pool, will also be presented.

  8. Gender: addressing a critical focus.

    PubMed

    Thornton, L; Wegner, M N

    1995-01-01

    The definition of gender was addressed at the Fourth World Conference on Women (Beijing, China). After extensive debate, the definition developed by the UN Population Fund in 1995 was adopted: "a set of qualities and behaviors expected from a female or male by society." The sustainability of family planning (FP) programs depends on acknowledgment of the role gender plays in contraceptive decision-making and use. For example, programs must consider the fact that women in many cultures do not make FP decisions without the consent of their spouse. AVSC is examining providers' gender-based ideas about clients and the effects of these views on the quality of reproductive health services. Questions such as how service providers can encourage joint responsibility for contraception without requiring spousal consent or how they can make men feel comfortable about using a male method in a society where FP is considered a woman's issue are being discussed. Also relevant is how service providers can discuss sexual matters openly with female clients in cultures that do not allow women to enjoy their sexuality. Another concern is the potential for physical violence to a client as a result of the provision of FP services. PMID:12294397

  9. Vaccine hesitancy: understanding better to address better.

    PubMed

    Kumar, Dewesh; Chandra, Rahul; Mathur, Medha; Samdariya, Saurabh; Kapoor, Neelesh

    2016-01-01

    Vaccine hesitancy is an emerging term in the socio-medical literature which describes an approach to vaccine decision making. It recognizes that there is a continuum between full acceptance and outright refusal of some or all vaccines and challenges the previous understanding of individuals or groups, as being either anti-vaccine or pro-vaccine. The behaviours responsible for vaccine hesitancy can be related to confidence, convenience and complacency. The causes of vaccine hesitancy can be described by the epidemiological triad i.e. the complex interaction of environmental- (i.e. external), agent- (i.e. vaccine) and host (or parent)- specific factors. Vaccine hesitancy is a complex and dynamic issue; future vaccination programs need to reflect and address these context-specific factors in both their design and evaluation. Many experts are of the view that it is best to counter vaccine hesitancy at the population level. They believe that it can be done by introducing more transparency into policy decision-making before immunization programs, providing up-to-date information to the public and health providers about the rigorous procedures undertaken before introduction of new vaccines, and through diversified post-marketing surveillance of vaccine-related events. PMID:26839681

  10. Complexity and Health Coaching: Synergies in Nursing

    PubMed Central

    Mitchell, Gail J.; Wong, Winnie; Rush, Danica

    2013-01-01

    Health care professionals are increasingly aware that persons are complex and live in relation with other complex human communities and broader systems. Complex beings and systems are living and evolving in nonlinear ways through a process of mutual influence. Traditional standardized approaches in chronic disease management do not address these non-linear linkages and the meaning and changes that impact day-to-day life and caring for self and family. The RN health coach role described in this paper addresses the complexities and ambiguities for persons living with chronic illness in order to provide person-centered care and support that are unique and responsive to the context of persons' lives. Informed by complexity thinking and relational inquiry, the RN health coach is an emergent innovation of creative action with community and groups that support persons as they shape their health and patterns of living. PMID:24102025

  11. Acute Viral Escape Selectively Impairs Nef-Mediated Major Histocompatibility Complex Class I Downmodulation and Increases Susceptibility to Antiviral T Cells

    PubMed Central

    Weiler, Andrea M.; Das, Arpita; Akinyosoye, Oluwasayo; Cui, Sherry; O'Connor, Shelby L.; Scheef, Elizabeth A.; Reed, Jason S.; Panganiban, Antonito T.; Sacha, Jonah B.; Rakasz, Eva G.; Friedrich, Thomas C.

    2015-01-01

    Nef-specific CD8+ T lymphocytes (CD8TL) are associated with control of simian immunodeficiency virus (SIV) despite extensive nef variation between and within animals. Deep viral sequencing of the immunodominant Mamu-B*017:01-restricted Nef165–173IW9 epitope revealed highly restricted evolution. A common acute escape variant, T170I, unexpectedly and uniquely degraded Nef's major histocompatibility complex class I (MHC-I) downregulatory capacity, rendering the virus more vulnerable to CD8TL targeting other epitopes. These data aid in a mechanistic understanding of Nef functions and suggest means of immunity-mediated control of lentivirus replication. PMID:26637459

  12. Acute Viral Escape Selectively Impairs Nef-Mediated Major Histocompatibility Complex Class I Downmodulation and Increases Susceptibility to Antiviral T Cells.

    PubMed

    Weiler, Andrea M; Das, Arpita; Akinyosoye, Oluwasayo; Cui, Sherry; O'Connor, Shelby L; Scheef, Elizabeth A; Reed, Jason S; Panganiban, Antonito T; Sacha, Jonah B; Rakasz, Eva G; Friedrich, Thomas C; Maness, Nicholas J

    2016-02-01

    Nef-specific CD8(+) T lymphocytes (CD8TL) are associated with control of simian immunodeficiency virus (SIV) despite extensive nef variation between and within animals. Deep viral sequencing of the immunodominant Mamu-B*017:01-restricted Nef165-173IW9 epitope revealed highly restricted evolution. A common acute escape variant, T170I, unexpectedly and uniquely degraded Nef's major histocompatibility complex class I (MHC-I) downregulatory capacity, rendering the virus more vulnerable to CD8TL targeting other epitopes. These data aid in a mechanistic understanding of Nef functions and suggest means of immunity-mediated control of lentivirus replication. PMID:26637459

  13. Welfare Entitlements: Addressing New Realities.

    ERIC Educational Resources Information Center

    Belcher, Jon R.; Fandetti, Donald V.

    1995-01-01

    Because welfare entitlements are increasingly unpopular, social work advocates need to place greater emphasis on job growth and alternate mechanisms for wealth redistribution, including refundable tax credits for working poor people. The Internal Revenue Code can be an effective weapon in combating poverty if antipoverty approaches in the code are…

  14. Name-Based Address Mapping for Virtual Private Networks

    NASA Astrophysics Data System (ADS)

    Surányi, Péter; Shinjo, Yasushi; Kato, Kazuhiko

    IPv4 private addresses are commonly used in local area networks (LANs). With the increasing popularity of virtual private networks (VPNs), it has become common that a user connects to multiple LANs at the same time. However, private address ranges for LANs frequently overlap. In such cases, existing systems do not allow the user to access the resources on all LANs at the same time. In this paper, we propose name-based address mapping for VPNs, a novel method that allows connecting to hosts through multiple VPNs at the same time, even when the address ranges of the VPNs overlap. In name-based address mapping, rather than using the IP addresses used on the LANs (the real addresses), we assign a unique virtual address to each remote host based on its domain name. The local host uses the virtual addresses to communicate with remote hosts. We have implemented name-based address mapping for layer 3 OpenVPN connections on Linux and measured its performance. The communication overhead of our system is less than 1.5% for throughput and less than 0.2ms for each name resolution.

  15. Increased Mitochondrial Pro-oxidant Activity Mediates Up-regulation of Complex I S-glutathionylation via Protein Thiyl Radical in the Murine Heart of eNOS−/−

    PubMed Central

    Kang, Patrick T.; Chen, Chwen-Lih; Chen, Yeong-Renn

    2014-01-01

    In response to oxidative stress, mitochondrial Complex I is reversibly S-glutathionylated. We hypothesized that protein S-glutathionylation (PrSSG) of Complex I is mediated by a kinetic mechanism involving reactive protein thiyl radical (PrS•) and GSH in vivo. Previous studies have shown that in vitro S-glutathionylation of isolated Complex I at the 51 kDa and 75 kDa subunits was detected under the conditions of •O2− production, and mass spectrometry confirmed that formation of Complex I PrS• mediates PrSSG. Exposure of myocytes to menadione resulted in enhanced Complex I PrSSG and PrS• (Kang et al Free Radical Biol. Med. 2012; 52: 962–73). In this investigation, we tested our hypothesis in the murine heart of eNOS−/−. The eNOS−/− mouse is known to be hypertensive and develops the pathological phenotype of progressive cardiac hypertrophy. The mitochondria isolated from the eNOS−/− myocardium exhibited a marked dysfunction with impaired state 3 respiration, a declining respiratory control index, and decreasing enzymatic activities of ETC components. Further biochemical analysis and EPR measurement indicated defective aconitase activity, a marked increase in •O2− generation activity, and a more oxidized physiological setting. These results suggest increasing prooxidant activity and subsequent oxidative stress in the mitochondria of the eNOS−/− murine heart. When Complex I from the mitochondria of the eNOS−/− murine heart was analyzed by immuno-spin trapping and probed with anti-GSH antibody, both PrS• and PrSSG of Complex I were significantly enhanced. Overexpression of SOD2 in the murine heart dramatically diminished the detected PrS•, supporting the conclusion that mediation of Complex I PrSSG by oxidative stress-induced PrS• is a unique pathway for the redox regulation of mitochondrial function in vivo. PMID:25445401

  16. An address geocoding solution for Chinese cities

    NASA Astrophysics Data System (ADS)

    Zhang, Xuehu; Ma, Haoming; Li, Qi

    2006-10-01

    We introduce the challenges of address geocoding for Chinese cities and present a potential solution along with a prototype system that deal with these challenges by combining and extending current geocoding solutions developed for United States and Japan. The proposed solution starts by separating city addresses into "standard" addresses which meet a predefined address model and non-standard ones. The standard addresses are stored in a structured relational database in their normalized forms, while a selected portion of the non-standard addresses are stored as aliases to the standard addresses. An in-memory address index is then constructed from the address database and serves as the basis for real-time address matching. Test results were obtained from two trials conducted in the city Beijing. On average 80% matching rate were achieved. Possible improvements to the current design are also discussed.

  17. HspB5/αB-crystallin increases dendritic complexity and protects the dendritic arbor during heat shock in cultured rat hippocampal neurons.

    PubMed

    Bartelt-Kirbach, Britta; Moron, Margarethe; Glomb, Maximilian; Beck, Clara-Maria; Weller, Marie-Pascale; Golenhofen, Nikola

    2016-10-01

    The small heat shock protein ΗspΒ5 (αB-crystallin) exhibits generally cytoprotective functions and possesses powerful neuroprotective capacity in the brain. However, little is known about the mode of action of ΗspΒ5 or other members of the HspB family particularly in neurons. To get clues of the neuronal function of HspBs, we overexpressed several HspBs in cultured rat hippocampal neurons and investigated their effect on neuronal morphology and stress resistance. Whereas axon length and synapse density were not affected by any HspB, dendritic complexity was enhanced by HspB5 and, to a lesser extent, by HspB6. Furthermore, we could show that this process was dependent on phosphorylation, since a non-phosphorylatable mutant of HspB5 did not show this effect. Rarefaction of the dendritic arbor is one hallmark of several neurodegenerative diseases. To investigate if HspB5, which is upregulated at pathophysiological conditions, might be able to protect dendrites during such situations, we exposed HspB5 overexpressing neuronal cultures to heat shock. HspB5 prevented heat shock-induced rarefaction of dendrites. In conclusion, we identified regulation of dendritic complexity as a new function of HspB5 in hippocampal neurons. PMID:27085702

  18. On the lack of robustness of hydrologic models regarding water balance simulation - a diagnostic approach on 20 mountainous catchments using three models of increasing complexity

    NASA Astrophysics Data System (ADS)

    Coron, L.; Andréassian, V.; Perrin, C.; Bourqui, M.; Hendrickx, F.

    2013-09-01

    This paper investigates the robustness of rainfall-runoff models when their parameters are transferred in time. More specifically, we studied their ability to simulate water balance on periods with different hydroclimatic characteristics. The testing procedure consisted in a series of parameter transfers between 10-yr periods and the systematic analysis of mean-volume errors. This procedure was applied to three conceptual models of different structural complexity over 20 mountainous catchments in southern France. The results showed that robustness problems are common. Errors on 10-yr-mean flows were significant for all three models and calibration periods, even when the entire record was used for calibration. Various graphical and numerical tools were used to show strong similarities between the shapes of mean flow biases calculated on a 10-yr-long sliding window when various parameter sets are used. Unexpected behavioural similarities were observed between the three models tested, considering their large differences in structural complexity. While the actual causes for robustness problems in these models remain unclear, this work stresses the limited transferability in time of the water balance adjustments made through parameter optimization. Although absolute differences between simulations obtained with different calibrated parameter sets were sometimes substantial, relative differences in simulated mean flows between time periods remained similar regardless of the calibrated parameter sets.

  19. Addressing the Mathematics-Specific Needs of Beginning Mathematics Teachers

    ERIC Educational Resources Information Center

    Britton, Edward

    2012-01-01

    Beginning mathematics teachers at the secondary level (middle and high school grades) have mathematics-specific needs that induction programs should address more substantially. However, a number of issues in how programs can accomplish this are more complex than often framed in discussions occurring in the induction programs and the field of…

  20. Challenges in an Aging Society: Presidential Address to APPAM

    ERIC Educational Resources Information Center

    Swartz, Katherine

    2010-01-01

    The United States is at a critical crossroads in its history right now. The public policy problems that the people are facing are complex and interrelated, and the demographic changes that are about to significantly change their country are not well understood by large numbers of people. In this presidential address to the Association for Public…

  1. Complex Spatiotemporal Responses of Global Terrestrial Primary Production to Climate Change and Increasing Atmospheric CO2 in the 21st Century

    PubMed Central

    Pan, Shufen; Tian, Hanqin; Dangal, Shree R. S.; Zhang, Chi; Yang, Jia; Tao, Bo; Ouyang, Zhiyun; Wang, Xiaoke; Lu, Chaoqun; Ren, Wei; Banger, Kamaljit; Yang, Qichun; Zhang, Bowen; Li, Xia

    2014-01-01

    Quantitative information on the response of global terrestrial net primary production (NPP) to climate change and increasing atmospheric CO2 is essential for climate change adaptation and mitigation in the 21st century. Using a process-based ecosystem model (the Dynamic Land Ecosystem Model, DLEM), we quantified the magnitude and spatiotemporal variations of contemporary (2000s) global NPP, and projected its potential responses to climate and CO2 changes in the 21st century under the Special Report on Emission Scenarios (SRES) A2 and B1 of Intergovernmental Panel on Climate Change (IPCC). We estimated a global terrestrial NPP of 54.6 (52.8–56.4) PgC yr−1 as a result of multiple factors during 2000–2009. Climate change would either reduce global NPP (4.6%) under the A2 scenario or slightly enhance NPP (2.2%) under the B1 scenario during 2010–2099. In response to climate change, global NPP would first increase until surface air temperature increases by 1.5°C (until the 2030s) and then level-off or decline after it increases by more than 1.5°C (after the 2030s). This result supports the Copenhagen Accord Acknowledgement, which states that staying below 2°C may not be sufficient and the need to potentially aim for staying below 1.5°C. The CO2 fertilization effect would result in a 12%–13.9% increase in global NPP during the 21st century. The relative CO2 fertilization effect, i.e. change in NPP on per CO2 (ppm) bases, is projected to first increase quickly then level off in the 2070s and even decline by the end of the 2080s, possibly due to CO2 saturation and nutrient limitation. Terrestrial NPP responses to climate change and elevated atmospheric CO2 largely varied among biomes, with the largest increases in the tundra and boreal needleleaf deciduous forest. Compared to the low emission scenario (B1), the high emission scenario (A2) would lead to larger spatiotemporal variations in NPP, and more dramatic and counteracting impacts from climate and

  2. Complex spatiotemporal responses of global terrestrial primary production to climate change and increasing atmospheric CO2 in the 21st century.

    PubMed

    Pan, Shufen; Tian, Hanqin; Dangal, Shree R S; Zhang, Chi; Yang, Jia; Tao, Bo; Ouyang, Zhiyun; Wang, Xiaoke; Lu, Chaoqun; Ren, Wei; Banger, Kamaljit; Yang, Qichun; Zhang, Bowen; Li, Xia

    2014-01-01

    Quantitative information on the response of global terrestrial net primary production (NPP) to climate change and increasing atmospheric CO2 is essential for climate change adaptation and mitigation in the 21st century. Using a process-based ecosystem model (the Dynamic Land Ecosystem Model, DLEM), we quantified the magnitude and spatiotemporal variations of contemporary (2000s) global NPP, and projected its potential responses to climate and CO2 changes in the 21st century under the Special Report on Emission Scenarios (SRES) A2 and B1 of Intergovernmental Panel on Climate Change (IPCC). We estimated a global terrestrial NPP of 54.6 (52.8-56.4) PgC yr(-1) as a result of multiple factors during 2000-2009. Climate change would either reduce global NPP (4.6%) under the A2 scenario or slightly enhance NPP (2.2%) under the B1 scenario during 2010-2099. In response to climate change, global NPP would first increase until surface air temperature increases by 1.5 °C (until the 2030s) and then level-off or decline after it increases by more than 1.5 °C (after the 2030s). This result supports the Copenhagen Accord Acknowledgement, which states that staying below 2 °C may not be sufficient and the need to potentially aim for staying below 1.5 °C. The CO2 fertilization effect would result in a 12%-13.9% increase in global NPP during the 21st century. The relative CO2 fertilization effect, i.e. change in NPP on per CO2 (ppm) bases, is projected to first increase quickly then level off in the 2070s and even decline by the end of the 2080s, possibly due to CO2 saturation and nutrient limitation. Terrestrial NPP responses to climate change and elevated atmospheric CO2 largely varied among biomes, with the largest increases in the tundra and boreal needleleaf deciduous forest. Compared to the low emission scenario (B1), the high emission scenario (A2) would lead to larger spatiotemporal variations in NPP, and more dramatic and counteracting impacts from climate and increasing

  3. Addressing Heart Failure Challenges through Illness-Informed Social Work.

    PubMed

    Hopp, Faith Pratt; Camp, Jessica K; Perry, Tam E

    2015-08-01

    This article describes the role of social workers in addressing the needs of people with heart failure. Although previous studies have explored the role of social workers in health care settings, few studies have addressed the challenges of specific chronic diseases such as heart failure. To address this gap in the literature, this study used qualitative interviews with health care social workers (n = 8) to obtain in-depth information about activities and challenges related to heart failure care. Findings suggest that health care social workers perceive heart failure as characterized by an uncertain illness trajectory, frequent hospitalizations, and difficulties accessing formal and informal care. These findings suggest the importance of what we term illness-informed social work, a practice that combines heart failure knowledge with social work competencies to address the complex psychosocial issues in heart failure care. PMID:26285359

  4. Partial complex I deficiency due to the CNS conditional ablation of Ndufa5 results in a mild chronic encephalopathy but no increase in oxidative damage

    PubMed Central

    Peralta, Susana; Torraco, Alessandra; Wenz, Tina; Garcia, Sofia; Diaz, Francisca; Moraes, Carlos T.

    2014-01-01

    Deficiencies in the complex I (CI; NADH-ubiquinone oxidoreductase) of the respiratory chain are frequent causes of mitochondrial diseases and have been associated with other neurodegenerative disorders, such as Parkinson's disease. The NADH-ubiquinone oxidoreductase 1 alpha subcomplex subunit 5 (NDUFA5) is a nuclear-encoded structural subunit of CI, located in the peripheral arm. We inactivated Ndufa5 in mice by the gene-trap methodology and found that this protein is required for embryonic survival. Therefore, we have created a conditional Ndufa5 knockout (KO) allele by introducing a rescuing Ndufa5 cDNA transgene flanked by loxP sites, which was selectively ablated in neurons by the CaMKIIα-Cre. At the age of 11 months, mice with a central nervous system knockout of Ndufa5 (Ndufa5 CNS-KO) showed lethargy and loss of motor skills. In these mice cortices, the levels of NDUFA5 protein were reduced to 25% of controls. Fully assembled CI levels were also greatly reduced in cortex and CI activity in homogenates was reduced to 60% of controls. Despite the biochemical phenotype, no oxidative damage, neuronal death or gliosis were detected in the Ndufa5 CNS-KO brain at this age. These results showed that a partial defect in CI in neurons can lead to late-onset motor phenotypes without neuronal loss or oxidative damage. PMID:24154540

  5. A cellulose-binding module of the Trichoderma reesei beta-mannanase Man5A increases the mannan-hydrolysis of complex substrates.

    PubMed

    Hägglund, Per; Eriksson, Torny; Collén, Anna; Nerinckx, Wim; Claeyssens, Marc; Stålbrand, Henrik

    2003-02-27

    Endo-beta-1,4-D-mannanases (beta-mannanase; EC 3.2.1.78) are endohydrolases that participate in the degradation of hemicellulose, which is closely associated with cellulose in plant cell walls. The beta-mannanase from Trichoderma reesei (Man5A) is composed of an N-terminal catalytic module and a C-terminal carbohydrate-binding module (CBM). In order to study the properties of the CBM, a construct encoding a mutant of Man5A lacking the part encoding the CBM (Man5ADeltaCBM), was expressed in T. reesei under the regulation of the Aspergillus nidulans gpdA promoter. The wild-type enzyme was expressed in the same way and both proteins were purified to electrophoretic homogeneity using ion-exchange chromatography. Both enzymes hydrolysed mannopentaose, soluble locust bean gum galactomannan and insoluble ivory nut mannan with similar rates. With a mannan/cellulose complex, however, the deletion mutant lacking the CBM showed a significant decrease in hydrolysis. Binding experiments using activity detection of Man5A and Man5ADeltaCBM suggests that the CBM binds to cellulose but not to mannan. Moreover, the binding of Man5A to cellulose was compared with that of an endoglucanase (Cel7B) from T. reesei. PMID:12523968

  6. Computational strategies to address chromatin structure problems.

    PubMed

    Perišić, Ognjen; Schlick, Tamar

    2016-01-01

    While the genetic information is contained in double helical DNA, gene expression is a complex multilevel process that involves various functional units, from nucleosomes to fully formed chromatin fibers accompanied by a host of various chromatin binding enzymes. The chromatin fiber is a polymer composed of histone protein complexes upon which DNA wraps, like yarn upon many spools. The nature of chromatin structure has been an open question since the beginning of modern molecular biology. Many experiments have shown that the chromatin fiber is a highly dynamic entity with pronounced structural diversity that includes properties of idealized zig-zag and solenoid models, as well as other motifs. This diversity can produce a high packing ratio and thus inhibit access to a majority of the wound DNA. Despite much research, chromatin's dynamic structure has not yet been fully described. Long stretches of chromatin fibers exhibit puzzling dynamic behavior that requires interpretation in the light of gene expression patterns in various tissue and organisms. The properties of chromatin fiber can be investigated with experimental techniques, like in vitro biochemistry, in vivo imagining, and high-throughput chromosome capture technology. Those techniques provide useful insights into the fiber's structure and dynamics, but they are limited in resolution and scope, especially regarding compact fibers and chromosomes in the cellular milieu. Complementary but specialized modeling techniques are needed to handle large floppy polymers such as the chromatin fiber. In this review, we discuss current approaches in the chromatin structure field with an emphasis on modeling, such as molecular dynamics and coarse-grained computational approaches. Combinations of these computational techniques complement experiments and address many relevant biological problems, as we will illustrate with special focus on epigenetic modulation of chromatin structure. PMID:27345617

  7. Computational strategies to address chromatin structure problems

    NASA Astrophysics Data System (ADS)

    Perišić, Ognjen; Schlick, Tamar

    2016-06-01

    While the genetic information is contained in double helical DNA, gene expression is a complex multilevel process that involves various functional units, from nucleosomes to fully formed chromatin fibers accompanied by a host of various chromatin binding enzymes. The chromatin fiber is a polymer composed of histone protein complexes upon which DNA wraps, like yarn upon many spools. The nature of chromatin structure has been an open question since the beginning of modern molecular biology. Many experiments have shown that the chromatin fiber is a highly dynamic entity with pronounced structural diversity that includes properties of idealized zig-zag and solenoid models, as well as other motifs. This diversity can produce a high packing ratio and thus inhibit access to a majority of the wound DNA. Despite much research, chromatin’s dynamic structure has not yet been fully described. Long stretches of chromatin fibers exhibit puzzling dynamic behavior that requires interpretation in the light of gene expression patterns in various tissue and organisms. The properties of chromatin fiber can be investigated with experimental techniques, like in vitro biochemistry, in vivo imagining, and high-throughput chromosome capture technology. Those techniques provide useful insights into the fiber’s structure and dynamics, but they are limited in resolution and scope, especially regarding compact fibers and chromosomes in the cellular milieu. Complementary but specialized modeling techniques are needed to handle large floppy polymers such as the chromatin fiber. In this review, we discuss current approaches in the chromatin structure field with an emphasis on modeling, such as molecular dynamics and coarse-grained computational approaches. Combinations of these computational techniques complement experiments and address many relevant biological problems, as we will illustrate with special focus on epigenetic modulation of chromatin structure.

  8. Addressing the vaccine confidence gap.

    PubMed

    Larson, Heidi J; Cooper, Louis Z; Eskola, Juhani; Katz, Samuel L; Ratzan, Scott

    2011-08-01

    Vaccines--often lauded as one of the greatest public health interventions--are losing public confidence. Some vaccine experts have referred to this decline in confidence as a crisis. We discuss some of the characteristics of the changing global environment that are contributing to increased public questioning of vaccines, and outline some of the specific determinants of public trust. Public decision making related to vaccine acceptance is neither driven by scientific nor economic evidence alone, but is also driven by a mix of psychological, sociocultural, and political factors, all of which need to be understood and taken into account by policy and other decision makers. Public trust in vaccines is highly variable and building trust depends on understanding perceptions of vaccines and vaccine risks, historical experiences, religious or political affiliations, and socioeconomic status. Although provision of accurate, scientifically based evidence on the risk-benefit ratios of vaccines is crucial, it is not enough to redress the gap between current levels of public confidence in vaccines and levels of trust needed to ensure adequate and sustained vaccine coverage. We call for more research not just on individual determinants of public trust, but on what mix of factors are most likely to sustain public trust. The vaccine community demands rigorous evidence on vaccine efficacy and safety and technical and operational feasibility when introducing a new vaccine, but has been negligent in demanding equally rigorous research to understand the psychological, social, and political factors that affect public trust in vaccines. PMID:21664679

  9. GEOSS: Addressing Big Data Challenges

    NASA Astrophysics Data System (ADS)

    Nativi, S.; Craglia, M.; Ochiai, O.

    2014-12-01

    In the sector of Earth Observation, the explosion of data is due to many factors including: new satellite constellations, the increased capabilities of sensor technologies, social media, crowdsourcing, and the need for multidisciplinary and collaborative research to face Global Changes. In this area, there are many expectations and concerns about Big Data. Vendors have attempted to use this term for their commercial purposes. It is necessary to understand whether Big Data is a radical shift or an incremental change for the existing digital infrastructures. This presentation tries to explore and discuss the impact of Big Data challenges and new capabilities on the Global Earth Observation System of Systems (GEOSS) and particularly on its common digital infrastructure called GCI. GEOSS is a global and flexible network of content providers allowing decision makers to access an extraordinary range of data and information at their desk. The impact of the Big Data dimensionalities (commonly known as 'V' axes: volume, variety, velocity, veracity, visualization) on GEOSS is discussed. The main solutions and experimentation developed by GEOSS along these axes are introduced and analyzed. GEOSS is a pioneering framework for global and multidisciplinary data sharing in the Earth Observation realm; its experience on Big Data is valuable for the many lessons learned.

  10. Wireless address event representation system for biological sensor networks

    NASA Astrophysics Data System (ADS)

    Folowosele, Fopefolu; Tapson, Jonathan; Etienne-Cummings, Ralph

    2007-05-01

    We describe wireless networking systems for close proximity biological sensors, as would be encountered in artificial skin. The sensors communicate to a "base station" that interprets the data and decodes its origin. Using a large bundle of ultra thin metal wires from the sensors to the "base station" introduces significant technological hurdles for both the construction and maintenance of the system. Fortunately, the Address Event Representation (AER) protocol provides an elegant and biomorphic method for transmitting many impulses (i.e. neural spikes) down a single wire/channel. However, AER does not communicate any sensory information within each spike, other that the address of the origination of the spike. Therefore, each sensor must provide a number of spikes to communicate its data, typically in the form of the inter-spike intervals or spike rate. Furthermore, complex circuitry is required to arbitrate access to the channel when multiple sensors communicate simultaneously, which results in spike delay. This error is exacerbated as the number of sensors per channel increases, mandating more channels and more wires. We contend that despite the effectiveness of the wire-based AER protocol, its natural evolution will be the wireless AER protocol. A wireless AER system: (1) does not require arbitration to handle multiple simultaneous access of the channel, (2) uses cross-correlation delay to encode sensor data in every spike (eliminating the error due to arbitration delay), and (3) can be reorganized and expanded with little consequence to the network. The system uses spread spectrum communications principles, implemented with a low-power integrate-and-fire neurons. This paper discusses the design, operation and capabilities of such a system. We show that integrate-and-fire neurons can be used to both decode the origination of each spike and extract the data contained within in. We also show that there are many technical obstacles to overcome before this version

  11. Expansion of Voltage-dependent Na+ Channel Gene Family in Early Tetrapods Coincided with the Emergence of Terrestriality and Increased Brain Complexity

    PubMed Central

    Zakon, Harold H.; Jost, Manda C.; Lu, Ying

    2011-01-01

    Mammals have ten voltage-dependent sodium (Nav) channel genes. Nav channels are expressed in different cell types with different subcellular distributions and are critical for many aspects of neuronal processing. The last common ancestor of teleosts and tetrapods had four Nav channel genes, presumably on four different chromosomes. In the lineage leading to mammals, a series of tandem duplications on two of these chromosomes more than doubled the number of Nav channel genes. It is unknown when these duplications occurred and whether they occurred against a backdrop of duplication of flanking genes on their chromosomes or as an expansion of ion channel genes in general. We estimated key dates of the Nav channel gene family expansion by phylogenetic analysis using teleost, elasmobranch, lungfish, amphibian, avian, lizard, and mammalian Nav channel sequences, as well as chromosomal synteny for tetrapod genes. We tested, and exclude, the null hypothesis that Nav channel genes reside in regions of chromosomes prone to duplication by demonstrating the lack of duplication or duplicate retention of surrounding genes. We also find no comparable expansion in other voltage-dependent ion channel gene families of tetrapods following the teleost–tetrapod divergence. We posit a specific expansion of the Nav channel gene family in the Devonian and Carboniferous periods when tetrapods evolved, diversified, and invaded the terrestrial habitat. During this time, the amniote forebrain evolved greater anatomical complexity and novel tactile sensory receptors appeared. The duplication of Nav channel genes allowed for greater regional specialization in Nav channel expression, variation in subcellular localization, and enhanced processing of somatosensory input. PMID:21148285

  12. Expansion of voltage-dependent Na+ channel gene family in early tetrapods coincided with the emergence of terrestriality and increased brain complexity.

    PubMed

    Zakon, Harold H; Jost, Manda C; Lu, Ying

    2011-04-01

    Mammals have ten voltage-dependent sodium (Nav) channel genes. Nav channels are expressed in different cell types with different subcellular distributions and are critical for many aspects of neuronal processing. The last common ancestor of teleosts and tetrapods had four Nav channel genes, presumably on four different chromosomes. In the lineage leading to mammals, a series of tandem duplications on two of these chromosomes more than doubled the number of Nav channel genes. It is unknown when these duplications occurred and whether they occurred against a backdrop of duplication of flanking genes on their chromosomes or as an expansion of ion channel genes in general. We estimated key dates of the Nav channel gene family expansion by phylogenetic analysis using teleost, elasmobranch, lungfish, amphibian, avian, lizard, and mammalian Nav channel sequences, as well as chromosomal synteny for tetrapod genes. We tested, and exclude, the null hypothesis that Nav channel genes reside in regions of chromosomes prone to duplication by demonstrating the lack of duplication or duplicate retention of surrounding genes. We also find no comparable expansion in other voltage-dependent ion channel gene families of tetrapods following the teleost-tetrapod divergence. We posit a specific expansion of the Nav channel gene family in the Devonian and Carboniferous periods when tetrapods evolved, diversified, and invaded the terrestrial habitat. During this time, the amniote forebrain evolved greater anatomical complexity and novel tactile sensory receptors appeared. The duplication of Nav channel genes allowed for greater regional specialization in Nav channel expression, variation in subcellular localization, and enhanced processing of somatosensory input. PMID:21148285

  13. Prediction Models of Retention Indices for Increased Confidence in Structural Elucidation during Complex Matrix Analysis: Application to Gas Chromatography Coupled with High-Resolution Mass Spectrometry.

    PubMed

    Dossin, Eric; Martin, Elyette; Diana, Pierrick; Castellon, Antonio; Monge, Aurelien; Pospisil, Pavel; Bentley, Mark; Guy, Philippe A

    2016-08-01

    Monitoring of volatile and semivolatile compounds was performed using gas chromatography (GC) coupled to high-resolution electron ionization mass spectrometry, using both headspace and liquid injection modes. A total of 560 reference compounds, including 8 odd n-alkanes, were analyzed and experimental linear retention indices (LRI) were determined. These reference compounds were randomly split into training (n = 401) and test (n = 151) sets. LRI for all 552 reference compounds were also calculated based upon computational Quantitative Structure-Property Relationship (QSPR) models, using two independent approaches RapidMiner (coupled to Dragon) and ACD/ChromGenius software. Correlation coefficients for experimental versus predicted LRI values calculated for both training and test set compounds were calculated at 0.966 and 0.949 for RapidMiner and at 0.977 and 0.976 for ACD/ChromGenius, respectively. In addition, the cross-validation correlation was calculated at 0.96 from RapidMiner and the residual standard error value obtained from ACD/ChromGenius was 53.635. These models were then used to predict LRI values for several thousand compounds reported present in tobacco and tobacco-related fractions, plus a range of specific flavor compounds. It was demonstrated that using the mean of the LRI values predicted by RapidMiner and ACD/ChromGenius, in combination with accurate mass data, could enhance the confidence level for compound identification from the analysis of complex matrixes, particularly when the two predicted LRI values for a compound were in close agreement. Application of this LRI modeling approach to matrixes with unknown composition has already enabled the confirmation of 23 postulated compounds, demonstrating its ability to facilitate compound identification in an analytical workflow. The goal is to reduce the list of putative candidates to a reasonable relevant number that can be obtained and measured for confirmation. PMID:27403731

  14. Applying evolutionary biology to address global challenges

    PubMed Central

    Carroll, Scott P.; Jørgensen, Peter Søgaard; Kinnison, Michael T.; Bergstrom, Carl T.; Denison, R. Ford; Gluckman, Peter; Smith, Thomas B.; Strauss, Sharon Y.; Tabashnik, Bruce E.

    2014-01-01

    Two categories of evolutionary challenges result from escalating human impacts on the planet. The first arises from cancers, pathogens and pests that evolve too quickly, and the second from the inability of many valued species to adapt quickly enough. Applied evolutionary biology provides a suite of strategies to address these global challenges that threaten human health, food security, and biodiversity. This review highlights both progress and gaps in genetic, developmental and environmental manipulations across the life sciences that either target the rate and direction of evolution, or reduce the mismatch between organisms and human-altered environments. Increased development and application of these underused tools will be vital in meeting current and future targets for sustainable development. PMID:25213376

  15. Applying evolutionary biology to address global challenges.

    PubMed

    Carroll, Scott P; Jørgensen, Peter Søgaard; Kinnison, Michael T; Bergstrom, Carl T; Denison, R Ford; Gluckman, Peter; Smith, Thomas B; Strauss, Sharon Y; Tabashnik, Bruce E

    2014-10-17

    Two categories of evolutionary challenges result from escalating human impacts on the planet. The first arises from cancers, pathogens, and pests that evolve too quickly and the second, from the inability of many valued species to adapt quickly enough. Applied evolutionary biology provides a suite of strategies to address these global challenges that threaten human health, food security, and biodiversity. This Review highlights both progress and gaps in genetic, developmental, and environmental manipulations across the life sciences that either target the rate and direction of evolution or reduce the mismatch between organisms and human-altered environments. Increased development and application of these underused tools will be vital in meeting current and future targets for sustainable development. PMID:25213376

  16. Assessing what to address in science communication.

    PubMed

    Bruine de Bruin, Wändi; Bostrom, Ann

    2013-08-20

    As members of a democratic society, individuals face complex decisions about whether to support climate change mitigation, vaccinations, genetically modified food, nanotechnology, geoengineering, and so on. To inform people's decisions and public debate, scientific experts at government agencies, nongovernmental organizations, and other organizations aim to provide understandable and scientifically accurate communication materials. Such communications aim to improve people's understanding of the decision-relevant issues, and if needed, promote behavior change. Unfortunately, existing communications sometimes fail when scientific experts lack information about what people need to know to make more informed decisions or what wording people use to describe relevant concepts. We provide an introduction for scientific experts about how to use mental models research with intended audience members to inform their communication efforts. Specifically, we describe how to conduct interviews to characterize people's decision-relevant beliefs or mental models of the topic under consideration, identify gaps and misconceptions in their knowledge, and reveal their preferred wording. We also describe methods for designing follow-up surveys with larger samples to examine the prevalence of beliefs as well as the relationships of beliefs with behaviors. Finally, we discuss how findings from these interviews and surveys can be used to design communications that effectively address gaps and misconceptions in people's mental models in wording that they understand. We present applications to different scientific domains, showing that this approach leads to communications that improve recipients' understanding and ability to make informed decisions. PMID:23942122

  17. Programming chemistry in DNA-addressable bioreactors

    PubMed Central

    Fellermann, Harold; Cardelli, Luca

    2014-01-01

    We present a formal calculus, termed the chemtainer calculus, able to capture the complexity of compartmentalized reaction systems such as populations of possibly nested vesicular compartments. Compartments contain molecular cargo as well as surface markers in the form of DNA single strands. These markers serve as compartment addresses and allow for their targeted transport and fusion, thereby enabling reactions of previously separated chemicals. The overall system organization allows for the set-up of programmable chemistry in microfluidic or other automated environments. We introduce a simple sequential programming language whose instructions are motivated by state-of-the-art microfluidic technology. Our approach integrates electronic control, chemical computing and material production in a unified formal framework that is able to mimic the integrated computational and constructive capabilities of the subcellular matrix. We provide a non-deterministic semantics of our programming language that enables us to analytically derive the computational and constructive power of our machinery. This semantics is used to derive the sets of all constructable chemicals and supermolecular structures that emerge from different underlying instruction sets. Because our proofs are constructive, they can be used to automatically infer control programs for the construction of target structures from a limited set of resource molecules. Finally, we present an example of our framework from the area of oligosaccharide synthesis. PMID:25121647

  18. Assessing what to address in science communication

    PubMed Central

    Bruine de Bruin, Wändi; Bostrom, Ann

    2013-01-01

    As members of a democratic society, individuals face complex decisions about whether to support climate change mitigation, vaccinations, genetically modified food, nanotechnology, geoengineering, and so on. To inform people’s decisions and public debate, scientific experts at government agencies, nongovernmental organizations, and other organizations aim to provide understandable and scientifically accurate communication materials. Such communications aim to improve people’s understanding of the decision-relevant issues, and if needed, promote behavior change. Unfortunately, existing communications sometimes fail when scientific experts lack information about what people need to know to make more informed decisions or what wording people use to describe relevant concepts. We provide an introduction for scientific experts about how to use mental models research with intended audience members to inform their communication efforts. Specifically, we describe how to conduct interviews to characterize people’s decision-relevant beliefs or mental models of the topic under consideration, identify gaps and misconceptions in their knowledge, and reveal their preferred wording. We also describe methods for designing follow-up surveys with larger samples to examine the prevalence of beliefs as well as the relationships of beliefs with behaviors. Finally, we discuss how findings from these interviews and surveys can be used to design communications that effectively address gaps and misconceptions in people’s mental models in wording that they understand. We present applications to different scientific domains, showing that this approach leads to communications that improve recipients’ understanding and ability to make informed decisions. PMID:23942122

  19. 32 CFR 516.7 - Mailing addresses.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 3 2011-07-01 2009-07-01 true Mailing addresses. 516.7 Section 516.7 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC RELATIONS LITIGATION General § 516.7 Mailing addresses. Mailing addresses for organizations referenced...

  20. 47 CFR 97.23 - Mailing address.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 5 2012-10-01 2012-10-01 false Mailing address. 97.23 Section 97.23 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AMATEUR RADIO... name and mailing address. The mailing address must be in an area where the amateur service is...

  1. 47 CFR 97.23 - Mailing address.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 5 2014-10-01 2014-10-01 false Mailing address. 97.23 Section 97.23 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AMATEUR RADIO... name and mailing address. The mailing address must be in an area where the amateur service is...

  2. 47 CFR 97.23 - Mailing address.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 5 2013-10-01 2013-10-01 false Mailing address. 97.23 Section 97.23 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AMATEUR RADIO... name and mailing address. The mailing address must be in an area where the amateur service is...

  3. 47 CFR 97.23 - Mailing address.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Mailing address. 97.23 Section 97.23 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AMATEUR RADIO... name and mailing address. The mailing address must be in an area where the amateur service is...

  4. 47 CFR 97.23 - Mailing address.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 5 2011-10-01 2011-10-01 false Mailing address. 97.23 Section 97.23 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AMATEUR RADIO... name and mailing address. The mailing address must be in an area where the amateur service is...

  5. 47 CFR 13.10 - Licensee address.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Licensee address. 13.10 Section 13.10 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL COMMERCIAL RADIO OPERATORS General § 13.10 Licensee address. In accordance with § 1.923 of this chapter all applications must specify an address where...

  6. CCCC Chair's Address: Representing Ourselves, 2008

    ERIC Educational Resources Information Center

    Glenn, Cheryl

    2008-01-01

    This article presents the text of the author's address at the fifty-ninth annual convention of the Conference on College Composition and Communication (CCCC) in March 2008. In her address, the author picks up strands of previous Chairs' addresses and weaves them through the fabric of her remarks. What she hopes will give sheen to the fabric is her…

  7. 75 FR 49813 - Change of Address

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-16

    ... COMMISSION 11 CFR Parts 9405, 9407, 9409, 9410, 9420, and 9428 Change of Address AGENCY: United States... Assistance Commission (EAC) is amending its regulations to reflect a change of address for its headquarters. This technical amendment is a nomenclature change that updates and corrects the address for...

  8. 32 CFR 516.7 - Mailing addresses.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 3 2010-07-01 2010-07-01 true Mailing addresses. 516.7 Section 516.7 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC RELATIONS LITIGATION General § 516.7 Mailing addresses. Mailing addresses for organizations referenced...

  9. IP address management : augmenting Sandia's capabilities through open source tools.

    SciTech Connect

    Nayar, R. Daniel

    2005-08-01

    Internet Protocol (IP) address management is an increasingly growing concern at Sandia National Laboratories (SNL) and the networking community as a whole. The current state of the available IP addresses indicates that they are nearly exhausted. Currently SNL doesn't have the justification to obtain more IP address space from Internet Assigned Numbers Authority (IANA). There must exist a local entity to manage and allocate IP assignments efficiently. Ongoing efforts at Sandia have been in the form of a multifunctional database application notably known as Network Information System (NWIS). NWIS is a database responsible for a multitude of network administrative services including IP address management. This study will explore the feasibility of augmenting NWIS's IP management capabilities utilizing open source tools. Modifications of existing capabilities to better allocate available IP address space are studied.

  10. Increased Probability of Co-Occurrence of Two Rare Diseases in Consanguineous Families and Resolution of a Complex Phenotype by Next Generation Sequencing

    PubMed Central

    Lal, Dennis; Neubauer, Bernd A.; Toliat, Mohammad R.; Altmüller, Janine; Thiele, Holger; Nürnberg, Peter; Kamrath, Clemens; Schänzer, Anne; Sander, Thomas; Hahn, Andreas; Nothnagel, Michael

    2016-01-01

    Massively parallel sequencing of whole genomes and exomes has facilitated a direct assessment of causative genetic variation, now enabling the identification of genetic factors involved in rare diseases (RD) with Mendelian inheritance patterns on an almost routine basis. Here, we describe the illustrative case of a single consanguineous family where this strategy suffered from the difficulty to distinguish between two etiologically distinct disorders, namely the co-occurrence of hereditary hypophosphatemic rickets (HRR) and congenital myopathies (CM), by their phenotypic manifestation alone. We used parametric linkage analysis, homozygosity mapping and whole exome-sequencing to identify mutations underlying HRR and CM. We also present an approximate approach for assessing the probability of co-occurrence of two unlinked recessive RD in a single family as a function of the degree of consanguinity and the frequency of the disease-causing alleles. Linkage analysis and homozygosity mapping yielded elusive results when assuming a single RD, but whole-exome sequencing helped to identify two mutations in two genes, namely SLC34A3 and SEPN1, that segregated independently in this family and that have previously been linked to two etiologically different diseases. We assess the increase in chance co-occurrence of rare diseases due to consanguinity, i.e. under circumstances that generally favor linkage mapping of recessive disease, and show that this probability can increase by several orders of magnitudes. We conclude that such potential co-occurrence represents an underestimated risk when analyzing rare or undefined diseases in consanguineous families and should be given more consideration in the clinical and genetic evaluation. PMID:26789268

  11. Increased Probability of Co-Occurrence of Two Rare Diseases in Consanguineous Families and Resolution of a Complex Phenotype by Next Generation Sequencing.

    PubMed

    Lal, Dennis; Neubauer, Bernd A; Toliat, Mohammad R; Altmüller, Janine; Thiele, Holger; Nürnberg, Peter; Kamrath, Clemens; Schänzer, Anne; Sander, Thomas; Hahn, Andreas; Nothnagel, Michael

    2016-01-01

    Massively parallel sequencing of whole genomes and exomes has facilitated a direct assessment of causative genetic variation, now enabling the identification of genetic factors involved in rare diseases (RD) with Mendelian inheritance patterns on an almost routine basis. Here, we describe the illustrative case of a single consanguineous family where this strategy suffered from the difficulty to distinguish between two etiologically distinct disorders, namely the co-occurrence of hereditary hypophosphatemic rickets (HRR) and congenital myopathies (CM), by their phenotypic manifestation alone. We used parametric linkage analysis, homozygosity mapping and whole exome-sequencing to identify mutations underlying HRR and CM. We also present an approximate approach for assessing the probability of co-occurrence of two unlinked recessive RD in a single family as a function of the degree of consanguinity and the frequency of the disease-causing alleles. Linkage analysis and homozygosity mapping yielded elusive results when assuming a single RD, but whole-exome sequencing helped to identify two mutations in two genes, namely SLC34A3 and SEPN1, that segregated independently in this family and that have previously been linked to two etiologically different diseases. We assess the increase in chance co-occurrence of rare diseases due to consanguinity, i.e. under circumstances that generally favor linkage mapping of recessive disease, and show that this probability can increase by several orders of magnitudes. We conclude that such potential co-occurrence represents an underestimated risk when analyzing rare or undefined diseases in consanguineous families and should be given more consideration in the clinical and genetic evaluation. PMID:26789268

  12. Addressable Reconfigurable Technology (ART) for Building Sustainable Moon Bases

    NASA Astrophysics Data System (ADS)

    Clark, P. E.; Curtis, S. A.; Rilee, M. L.; Shaya, E. J.; Cheung, C. Y.; Floyd, S. R.

    2005-05-01

    NASA's Exploration Initiative requires approaches and tools to support of near future human activities on the lunar surface. A sustainable infrastructure and tools to support such activities must be developed using currently available ElectroMechanical Systems (EMS). Architecture based on Addressable Reconfigurable Technology (ART), which we are already developing for small rovers, should be well suited to this task. ART structures are highly addressable arrays of robust nodes interconnected by highly reconfigurable struts that, along with tethers and surfaces are autonomously and reversibly deployable. The basic building unit in this architecture is a tetrahedron, the most efficient space-filling form, consisting of nodes interconnected with struts that can be reversibly and/or partially deployed or stowed to allow the tetrahedron to change its size and shape on command in real-time. Tetrahedral units are interlinked in one (linear), two (planar), or three (space-filling) dimensions to create conformable objects. As more tetrahedra are interconnected, the degrees of freedom are increased and motions evolve from simple to complex, from stepped to continuous. This design allows movement to change shape and/or location revolutionizing the architecture for space structures by epitomizing portable `form follows function' at every level. Although the 3D network of actuators and structural elements is composed of nodes that are addressable as are pixels in an LCD screen. The full functionality of such a system requires fully autonomous operation, and will ultimately be realized through a neural basis function (NBF) we are currently developing, which possesses the capability for actuator-level autonomic response and heuristic-level decision-making. Two EMS level ART-based concepts are designed for sustainable autonomous operation on the Moon. The Autonomous Lunar Investigator (ALI) would consist of one or more 12tetrahedral walkers capable of rapid locomotion with the

  13. National Institutes of Health addresses the science of diversity

    PubMed Central

    Valantine, Hannah A.; Collins, Francis S.

    2015-01-01

    The US biomedical research workforce does not currently mirror the nation’s population demographically, despite numerous attempts to increase diversity. This imbalance is limiting the promise of our biomedical enterprise for building knowledge and improving the nation’s health. Beyond ensuring fairness in scientific workforce representation, recruiting and retaining a diverse set of minds and approaches is vital to harnessing the complete intellectual capital of the nation. The complexity inherent in diversifying the research workforce underscores the need for a rigorous scientific approach, consistent with the ways we address the challenges of science discovery and translation to human health. Herein, we identify four cross-cutting diversity challenges ripe for scientific exploration and opportunity: research evidence for diversity’s impact on the quality and outputs of science; evidence-based approaches to recruitment and training; individual and institutional barriers to workforce diversity; and a national strategy for eliminating barriers to career transition, with scientifically based approaches for scaling and dissemination. Evidence-based data for each of these challenges should provide an integrated, stepwise approach to programs that enhance diversity rapidly within the biomedical research workforce. PMID:26392553

  14. National Institutes of Health addresses the science of diversity.

    PubMed

    Valantine, Hannah A; Collins, Francis S

    2015-10-01

    The US biomedical research workforce does not currently mirror the nation's population demographically, despite numerous attempts to increase diversity. This imbalance is limiting the promise of our biomedical enterprise for building knowledge and improving the nation's health. Beyond ensuring fairness in scientific workforce representation, recruiting and retaining a diverse set of minds and approaches is vital to harnessing the complete intellectual capital of the nation. The complexity inherent in diversifying the research workforce underscores the need for a rigorous scientific approach, consistent with the ways we address the challenges of science discovery and translation to human health. Herein, we identify four cross-cutting diversity challenges ripe for scientific exploration and opportunity: research evidence for diversity's impact on the quality and outputs of science; evidence-based approaches to recruitment and training; individual and institutional barriers to workforce diversity; and a national strategy for eliminating barriers to career transition, with scientifically based approaches for scaling and dissemination. Evidence-based data for each of these challenges should provide an integrated, stepwise approach to programs that enhance diversity rapidly within the biomedical research workforce. PMID:26392553

  15. Increasing the complexity of chromatin: functionally distinct roles for replication-dependent histone H2A isoforms in cell proliferation and carcinogenesis

    PubMed Central

    Singh, Rajbir; Mortazavi, Amir; Telu, Kelly H.; Nagarajan, Prabakaran; Lucas, David M.; Thomas-Ahner, Jennifer M.; Clinton, Steven K.; Byrd, John C.; Freitas, Michael A.; Parthun, Mark R.

    2013-01-01

    Replication-dependent histones are encoded by multigene families found in several large clusters in the human genome and are thought to be functionally redundant. However, the abundance of specific replication-dependent isoforms of histone H2A is altered in patients with chronic lymphocytic leukemia. Similar changes in the abundance of H2A isoforms are also associated with the proliferation and tumorigenicity of bladder cancer cells. To determine whether these H2A isoforms can perform distinct functions, expression of several H2A isoforms was reduced by siRNA knockdown. Reduced expression of the HIST1H2AC locus leads to increased rates of cell proliferation and tumorigenicity. We also observe that regulation of replication-dependent histone H2A expression can occur on a gene-specific level. Specific replication-dependent histone H2A genes are either up- or downregulated in chronic lymphocytic leukemia tumor tissue samples. In addition, discreet elements are identified in the 5′ untranslated region of the HIST1H2AC locus that confer translational repression. Taken together, these results indicate that replication-dependent histone isoforms can possess distinct cellular functions and that regulation of these isoforms may play a role in carcinogenesis. PMID:23956221

  16. Addressing health literacy in patient decision aids

    PubMed Central

    2013-01-01

    Background Effective use of a patient decision aid (PtDA) can be affected by the user’s health literacy and the PtDA’s characteristics. Systematic reviews of the relevant literature can guide PtDA developers to attend to the health literacy needs of patients. The reviews reported here aimed to assess: 1. a) the effects of health literacy / numeracy on selected decision-making outcomes, and b) the effects of interventions designed to mitigate the influence of lower health literacy on decision-making outcomes, and 2. the extent to which existing PtDAs a) account for health literacy, and b) are tested in lower health literacy populations. Methods We reviewed literature for evidence relevant to these two aims. When high-quality systematic reviews existed, we summarized their evidence. When reviews were unavailable, we conducted our own systematic reviews. Results Aim 1: In an existing systematic review of PtDA trials, lower health literacy was associated with lower patient health knowledge (14 of 16 eligible studies). Fourteen studies reported practical design strategies to improve knowledge for lower health literacy patients. In our own systematic review, no studies reported on values clarity per se, but in 2 lower health literacy was related to higher decisional uncertainty and regret. Lower health literacy was associated with less desire for involvement in 3 studies, less question-asking in 2, and less patient-centered communication in 4 studies; its effects on other measures of patient involvement were mixed. Only one study assessed the effects of a health literacy intervention on outcomes; it showed that using video to improve the salience of health states reduced decisional uncertainty. Aim 2: In our review of 97 trials, only 3 PtDAs overtly addressed the needs of lower health literacy users. In 90% of trials, user health literacy and readability of the PtDA were not reported. However, increases in knowledge and informed choice were reported in those studies

  17. The importance of systems thinking to address obesity.

    PubMed

    Finegood, Diane T

    2012-01-01

    Obesity is clearly a complex problem for both the individual and for society. Complex or 'wicked' problems have common characteristics such as heterogeneity, nonlinearity, interdependence, and self-organization. As such they require solutions appropriate for complex problems, rather than a reductionist search for the causes. 'Systems thinking' provides new ways to consider how to collectively address complex societal problems like obesity, where biology interacts with social, cultural and built environmental factors in infinite permutations and combinations. The systems that give rise to the obesity epidemic function at multiple levels, and there are important interactions between these levels. At any given level, individual actors and organizations matter and system function is optimized when individual and organizational capacity to respond is well matched to the complexity of individual tasks. Providing system supports to help networks of individuals become 'communities of practice' and 'systems of influence' may also help to accelerate the pace of effective action against obesity. Research efforts need to move away from the relentless search for the specific isolated causes of obesity and focus on solutions that have been shown to work in addressing other 'wicked' problems. PMID:23128771

  18. Novel Duplicate Address Detection with Hash Function.

    PubMed

    Song, GuangJia; Ji, ZhenZhou

    2016-01-01

    Duplicate address detection (DAD) is an important component of the address resolution protocol (ARP) and the neighbor discovery protocol (NDP). DAD determines whether an IP address is in conflict with other nodes. In traditional DAD, the target address to be detected is broadcast through the network, which provides convenience for malicious nodes to attack. A malicious node can send a spoofing reply to prevent the address configuration of a normal node, and thus, a denial-of-service attack is launched. This study proposes a hash method to hide the target address in DAD, which prevents an attack node from launching destination attacks. If the address of a normal node is identical to the detection address, then its hash value should be the same as the "Hash_64" field in the neighboring solicitation message. Consequently, DAD can be successfully completed. This process is called DAD-h. Simulation results indicate that address configuration using DAD-h has a considerably higher success rate when under attack compared with traditional DAD. Comparative analysis shows that DAD-h does not require third-party devices and considerable computing resources; it also provides a lightweight security resolution. PMID:26991901

  19. Novel Duplicate Address Detection with Hash Function

    PubMed Central

    Song, GuangJia; Ji, ZhenZhou

    2016-01-01

    Duplicate address detection (DAD) is an important component of the address resolution protocol (ARP) and the neighbor discovery protocol (NDP). DAD determines whether an IP address is in conflict with other nodes. In traditional DAD, the target address to be detected is broadcast through the network, which provides convenience for malicious nodes to attack. A malicious node can send a spoofing reply to prevent the address configuration of a normal node, and thus, a denial-of-service attack is launched. This study proposes a hash method to hide the target address in DAD, which prevents an attack node from launching destination attacks. If the address of a normal node is identical to the detection address, then its hash value should be the same as the “Hash_64” field in the neighboring solicitation message. Consequently, DAD can be successfully completed. This process is called DAD-h. Simulation results indicate that address configuration using DAD-h has a considerably higher success rate when under attack compared with traditional DAD. Comparative analysis shows that DAD-h does not require third-party devices and considerable computing resources; it also provides a lightweight security resolution. PMID:26991901

  20. Battery Cell Voltage Sensing and Balancing Using Addressable Transformers

    NASA Technical Reports Server (NTRS)

    Davies, Francis

    2009-01-01

    A document discusses the use of saturating transformers in a matrix arrangement to address individual cells in a high voltage battery. This arrangement is able to monitor and charge individual cells while limiting the complexity of circuitry in the battery. The arrangement has inherent galvanic isolation, low cell leakage currents, and allows a single bad cell in a battery of several hundred cells to be easily spotted.

  1. Duplicate Address Detection Table in IPv6 Mobile Networks

    NASA Astrophysics Data System (ADS)

    Alisherov, Farkhod; Kim, Taihoon

    In IP networks, each computer or communication equipment needs an IP address. To supply enough IP addresses, the new Internet protocol IPv6 is used in next generatoion mobile communication. Although IPv6 improves the existing IPv4 Internet protocol, Duplicate Address Detection (DAD) mechanism may consume resources and suffer from long delay. DAD is used to ensure whether the IP address is unique or not. When a mobile node performs an inter-domain handoff, it will first generate a new IP and perform a DAD procedure. The DAD procedure not only wastes time but also increases the signaling load on Internet. In this paper, the author proposes a new DAD mechanism to speed up the DAD procedure. A DAD table is created in access or mobility routers in IP networks and record all IP addresses of the area. When a new IP address needs to perform DAD, it can just search in the DAD table to confirm the uniqueness of the address.

  2. Using chiral molecules as an approach to address low-druggability recognition sites.

    PubMed

    Lucas, Xavier; Günther, Stefan

    2014-11-01

    The content of chiral carbon atoms or structural complexity, which is known to correlate well with relevant physicochemical properties of small molecules, represents a promising descriptor that could fill the gap in existing drug discovery between ligand library filtering rules and the corresponding properties of the target's recognition site. Herein, we present an in silico study on the yet unclear underlying correlations between molecular complexity and other more sophisticated physicochemical and biological properties. By analyzing thousands of protein-ligand complexes from DrugBank, we show that increasing molecular complexity of drugs is an approach to addressing particularly low-druggability and polar recognition sites. We also show that biologically relevant protein classes characteristically bind molecules with a certain degree of structural complexity. Three distinct behaviors toward drug recognition are described. The reported results set the basis for a better understanding of protein-drug recognition, and open the possibility of including target information in the filtering of large ligand libraries for screening. PMID:25223950

  3. A vanadyl sulfate-bovine serum albumin complex stimulates the release of lipoprotein lipase activity from isolated rat fat pads through an increase in the cellular content of cAMP and myo-inositol 1,4,5-trisphosphate.

    PubMed

    Motoyashiki, T; Miyake, M; Yoshida, A; Morita, T; Ueki, H

    1999-08-01

    A vanadyl sulfate-bovine serum albumin complex (vanadyl-BSA) prolonged the stability of the V4+ oxidation state, although vanadyl alone can readily change the oxidation state from V4+ to V5+ under physiological conditions. Vanadyl-BSA stimulated the release of lipoprotein lipase (LPL) activity from isolated rat fat pads and increased the cellular LPL activity in a time-dependent manner. These effects were independent of protein synthesis. Propranolol, quin 2-AM, ruthenium red, and neomycin all inhibited LPL release more potently than the increase in activity. In contrast, potent inhibition of the increase effect was observed with genistein and wortmannin. Short-term incubation of the fat pads with vanadyl-BSA showed a transient increase in the cellular content of cAMP and myo-inositol 1,4,5-trisphosphate (IP3), which was inhibited by propranolol and neomycin, respectively. These results suggest that vanadyl-BSA stimulates the release of LPL activity through an increase in the cellular content of cAMP and IP3, leading to an increased intracellular Ca2+ concentration, and that it also increases cellular LPL activity via process(es) sensitive to genistein and wortmannin. PMID:10480313

  4. The increasingly complex regulation of adipocyte differentiation.

    PubMed

    Poulos, Sylvia P; Dodson, Michael V; Culver, Melinda F; Hausman, Gary J

    2016-03-01

    Adipose (AD) tissue development and function relies on the ability of adipocytes to proliferate and differentiate into lipid-containing cells that also have endocrine function. Research suggests that certain conditions can induce AD tissue stem cells to differentiate into various cell types and that the microenvironment of the cell, including the extracellular matrix (ECM), is essential in maintaining cell and tissue function. This review provides an overview of factors involved in the proliferation and differentiation of adipocytes. A brief review of the numerous factors that influence PPARγ, the transcription factor thought to be the master regulator of adipocyte differentiation, provides context of established pathways that regulate adipogenesis. Thought provoking findings from research with hypoxia that is supported by earlier research that vascular development is related to adipogenesis are reviewed. Finally, our understanding of the critical role of the ECM and environment in adipogenesis is discussed and compared with studies that suggest that adipocytes may dedifferentiate and can convert into other cell types. PMID:26645953

  5. Undergraduate Education in an Increasingly Complex World.

    ERIC Educational Resources Information Center

    Clinton, Bill

    1987-01-01

    Declines in the United States' competitive status in the world show that the nation needs a better educated, more creative, more flexible work force. Undergraduate education has an essential role to play in preparing students for both work and citizenship, requiring new collaboration between state, education, and community leaders. (MSE)

  6. Is increasing complexity of algorithms the price for higher accuracy? virtual comparison of three algorithms for tertiary level management of chronic cough in people living with HIV in a low-income country

    PubMed Central

    2012-01-01

    Background The algorithmic approach to guidelines has been introduced and promoted on a large scale since the 1970s. This study aims at comparing the performance of three algorithms for the management of chronic cough in patients with HIV infection, and at reassessing the current position of algorithmic guidelines in clinical decision making through an analysis of accuracy, harm and complexity. Methods Data were collected at the University Hospital of Kigali (CHUK) in a total of 201 HIV-positive hospitalised patients with chronic cough. We simulated management of each patient following the three algorithms. The first was locally tailored by clinicians from CHUK, the second and third were drawn from publications by Médecins sans Frontières (MSF) and the World Health Organisation (WHO). Semantic analysis techniques known as Clinical Algorithm Nosology were used to compare them in terms of complexity and similarity. For each of them, we assessed the sensitivity, delay to diagnosis and hypothetical harm of false positives and false negatives. Results The principal diagnoses were tuberculosis (21%) and pneumocystosis (19%). Sensitivity, representing the proportion of correct diagnoses made by each algorithm, was 95.7%, 88% and 70% for CHUK, MSF and WHO, respectively. Mean time to appropriate management was 1.86 days for CHUK and 3.46 for the MSF algorithm. The CHUK algorithm was the most complex, followed by MSF and WHO. Total harm was by far the highest for the WHO algorithm, followed by MSF and CHUK. Conclusions This study confirms our hypothesis that sensitivity and patient safety (i.e. less expected harm) are proportional to the complexity of algorithms, though increased complexity may make them difficult to use in practice. PMID:22260242

  7. Inhibition of Mitochondrial Complex I Leads to Decreased Motility and Membrane Integrity Related to Increased Hydrogen Peroxide and Reduced ATP Production, while the Inhibition of Glycolysis Has Less Impact on Sperm Motility

    PubMed Central

    Plaza Davila, María; Martin Muñoz, Patricia; Tapia, Jose A.; Ortega Ferrusola, Cristina; Balao da Silva C, Carolina; Peña, Fernando J.

    2015-01-01

    Mitochondria have been proposed as the major source of reactive oxygen species in somatic cells and human spermatozoa. However, no data regarding the role of mitochondrial ROS production in stallion spermatozoa are available. To shed light on the role of the mitochondrial electron transport chain in the origin of oxidative stress in stallion spermatozoa, specific inhibitors of complex I (rotenone) and III (antimycin-A) were used. Ejaculates from seven Andalusian stallions were collected and incubated in BWW media at 37°C in the presence of rotenone, antimycin-A or control vehicle. Incubation in the presence of these inhibitors reduced sperm motility and velocity (CASA analysis) (p<0.01), but the effect was more evident in the presence of rotenone (a complex I inhibitor). These inhibitors also decreased ATP content. The inhibition of complexes I and III decreased the production of reactive oxygen species (p<0.01) as assessed by flow cytometry after staining with CellRox deep red. This observation suggests that the CellRox probe mainly identifies superoxide and that superoxide production may reflect intense mitochondrial activity rather than oxidative stress. The inhibition of complex I resulted in increased hydrogen peroxide production (p<0.01). The inhibition of glycolysis resulted in reduced sperm velocities (p<0.01) without an effect on the percentage of total motile sperm. Weak and moderate (but statistically significant) positive correlations were observed between sperm motility, velocity and membrane integrity and the production of reactive oxygen species. These results indicate that stallion sperm rely heavily on oxidative phosphorylation (OXPHOS) for the production of ATP for motility but also require glycolysis to maintain high velocities. These data also indicate that increased hydrogen peroxide originating in the mitochondria is a mechanism involved in stallion sperm senescence. PMID:26407142

  8. 16 CFR 0.2 - Official address.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 1 2012-01-01 2012-01-01 false Official address. 0.2 Section 0.2 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE ORGANIZATION § 0.2 Official address. The principal office of the Commission is at Washington, DC. All communications to...

  9. 40 CFR 374.6 - Addresses.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 29 2012-07-01 2012-07-01 false Addresses. 374.6 Section 374.6 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SUPERFUND, EMERGENCY PLANNING, AND COMMUNITY RIGHT-TO-KNOW PROGRAMS PRIOR NOTICE OF CITIZEN SUITS § 374.6 Addresses. Administrator, U.S. Environmental Protection Agency, 1200...

  10. 16 CFR 0.2 - Official address.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Official address. 0.2 Section 0.2 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE ORGANIZATION § 0.2... 20580, unless otherwise specifically directed. The Commission's Web site address is www.ftc.gov....

  11. 16 CFR 0.2 - Official address.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Official address. 0.2 Section 0.2 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE ORGANIZATION § 0.2... 20580, unless otherwise specifically directed. The Commission's Web site address is www.ftc.gov....

  12. 10 CFR 218.34 - Addresses.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 3 2010-01-01 2010-01-01 false Addresses. 218.34 Section 218.34 Energy DEPARTMENT OF ENERGY OIL STANDBY MANDATORY INTERNATIONAL OIL ALLOCATION Procedures § 218.34 Addresses. All..., Economic Regulatory Administration, Department of Energy, 2000 M Street, NW., Washington, DC 20461, and...

  13. History Forum Addresses Creation/Evolution Controversy.

    ERIC Educational Resources Information Center

    Schweinsberg, John

    1997-01-01

    A series of programs entitled Creationism and Evolution: The History of a Controversy was presented at the University of Alabama in Huntsville. The controversy was addressed from an historical and sociological, rather than a scientific perspective. Speakers addressed the evolution of scientific creationism, ancient texts versus sedimentary rocks…

  14. Public Address Systems. Specifications - Installation - Operation.

    ERIC Educational Resources Information Center

    Palmer, Fred M.

    Provisions for public address in new construction of campus buildings (specifications, installations, and operation of public address systems), are discussed in non-technical terms. Consideration is given to microphones, amplifiers, loudspeakers and the placement and operation of various different combinations. (FS)

  15. 40 CFR 80.174 - Addresses.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 16 2011-07-01 2011-07-01 false Addresses. 80.174 Section 80.174... FUELS AND FUEL ADDITIVES Detergent Gasoline § 80.174 Addresses. (a) The detergent additive sample required under § 80.161(b)(2) shall be sent to: Manager, Fuels and Technical Analysis Group,...

  16. 7 CFR 1730.3 - RUS addresses.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 11 2014-01-01 2014-01-01 false RUS addresses. 1730.3 Section 1730.3 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE ELECTRIC SYSTEM OPERATIONS AND MAINTENANCE General § 1730.3 RUS addresses. (a) Persons wishing to obtain forms referred to in this part...

  17. Forms of Address in Chilean Spanish

    ERIC Educational Resources Information Center

    Bishop, Kelley; Michnowicz, Jim

    2010-01-01

    The present investigation examines possible social and linguistic factors that influence forms of address used in Chilean Spanish with various interlocutors. A characteristic of the Spanish of Chile is the use of a variety of forms of address for the second person singular, "tu", "vos", and "usted", with corresponding verb conjugations (Lipski…

  18. 40 CFR 374.6 - Addresses.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 28 2014-07-01 2014-07-01 false Addresses. 374.6 Section 374.6 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SUPERFUND, EMERGENCY PLANNING, AND COMMUNITY RIGHT-TO-KNOW PROGRAMS PRIOR NOTICE OF CITIZEN SUITS § 374.6 Addresses. Administrator, U.S. Environmental Protection Agency, 1200...

  19. 34 CFR 674.44 - Address searches.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false Address searches. 674.44 Section 674.44 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION FEDERAL PERKINS LOAN PROGRAM Due Diligence § 674.44 Address searches. (a) If...

  20. 34 CFR 674.44 - Address searches.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 3 2013-07-01 2013-07-01 false Address searches. 674.44 Section 674.44 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION FEDERAL PERKINS LOAN PROGRAM Due Diligence § 674.44 Address searches. (a) If...

  1. 34 CFR 674.44 - Address searches.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 3 2011-07-01 2011-07-01 false Address searches. 674.44 Section 674.44 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION FEDERAL PERKINS LOAN PROGRAM Due Diligence § 674.44 Address searches. (a) If...

  2. 34 CFR 674.44 - Address searches.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 3 2014-07-01 2014-07-01 false Address searches. 674.44 Section 674.44 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION FEDERAL PERKINS LOAN PROGRAM Due Diligence § 674.44 Address searches. (a) If...

  3. 34 CFR 674.44 - Address searches.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 3 2012-07-01 2012-07-01 false Address searches. 674.44 Section 674.44 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION FEDERAL PERKINS LOAN PROGRAM Due Diligence § 674.44 Address searches. (a) If...

  4. Image compression using address-vector quantization

    NASA Astrophysics Data System (ADS)

    Nasrabadi, Nasser M.; Feng, Yushu

    1990-12-01

    A novel vector quantization scheme, the address-vector quantizer (A-VQ), is proposed which exploits the interblock correlation by encoding a group of blocks together using an address-codebook (AC). The AC is a set of address-codevectors (ACVs), each representing a combination of addresses or indices. Each element of the ACV is an address of an entry in the LBG-codebook, representing a vector-quantized block. The AC consists of an active (addressable) region and an inactive (nonaddressable) region. During encoding the ACVs in the AC are reordered adaptively to bring the most probable ACVs into the active region. When encoding an ACV, the active region is checked, and if such an address combination exists, its index is transmitted to the receiver. Otherwise, the address of each block is transmitted individually. The SNR of the images encoded by the A-VQ method is the same as that of a memoryless vector quantizer, but the bit rate is by a factor of approximately two.

  5. Approaches for Resolving Dynamic IP Addressing.

    ERIC Educational Resources Information Center

    Foo, Schubert; Hui, Siu Cheung; Yip, See Wai; He, Yulan

    1997-01-01

    A problem with dynamic Internet protocol (IP) addressing arises when the Internet connection is through an Internet provider since the IP address is allocated only at connection time. This article examines a number of online and offline methods for resolving the problem. Suggests dynamic domain name system (DNS) and directory service look-up are…

  6. Tradition and Change in Swedish Address Forms.

    ERIC Educational Resources Information Center

    Mitchell, Stephen A.

    In most European languages, choice of address form classifies the relation between speakers. The first theoretical framework for analyzing address form usage was established by Brown and Gilman (1960) in their investigation of the semantics of pronoun use in a wide variety of Indo-European languages, which concluded that Europeans use the informal…

  7. 7 CFR 504.5 - Address.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 6 2014-01-01 2014-01-01 false Address. 504.5 Section 504.5 Agriculture Regulations... USER FEES § 504.5 Address. Deposits of and requests for microbial patent cultures should be directed to.... University St., Peoria, Illinois 61604; (309) 685-4011....

  8. 7 CFR 504.5 - Address.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 6 2012-01-01 2012-01-01 false Address. 504.5 Section 504.5 Agriculture Regulations... USER FEES § 504.5 Address. Deposits of and requests for microbial patent cultures should be directed to.... University St., Peoria, Illinois 61604; (309) 685-4011....

  9. 7 CFR 504.5 - Address.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Address. 504.5 Section 504.5 Agriculture Regulations... USER FEES § 504.5 Address. Deposits of and requests for microbial patent cultures should be directed to.... University St., Peoria, Illinois 61604; (309) 685-4011....

  10. 7 CFR 504.5 - Address.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 6 2011-01-01 2011-01-01 false Address. 504.5 Section 504.5 Agriculture Regulations... USER FEES § 504.5 Address. Deposits of and requests for microbial patent cultures should be directed to.... University St., Peoria, Illinois 61604; (309) 685-4011....

  11. 7 CFR 504.5 - Address.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 6 2013-01-01 2013-01-01 false Address. 504.5 Section 504.5 Agriculture Regulations... USER FEES § 504.5 Address. Deposits of and requests for microbial patent cultures should be directed to.... University St., Peoria, Illinois 61604; (309) 685-4011....

  12. 25 CFR 2.14 - Record address.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Record address. 2.14 Section 2.14 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR PROCEDURES AND PRACTICE APPEALS FROM ADMINISTRATIVE ACTIONS § 2.14 Record address. (a) Every interested party who files a document in connection with an...

  13. 25 CFR 2.14 - Record address.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Record address. 2.14 Section 2.14 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR PROCEDURES AND PRACTICE APPEALS FROM ADMINISTRATIVE ACTIONS § 2.14 Record address. (a) Every interested party who files a document in connection with an...

  14. An addressable cell array for a platform of biosensor chips

    NASA Astrophysics Data System (ADS)

    Yang, Seungkyoung; Choi, Soo-hee; Jung, Moon Youn; Song, Kibong; Park, Jeong Won

    2013-05-01

    In order to detect interested matters in fields, various lab-on-a-chips where chemical, physical, or biological sensors are loaded have been developed. eNOSE can be a representative example among them. Because animals can sense 300~1000 different chemicals by olfactory system - smell -, the olfactory system has been spotlighted as new materials in the field of sensing. Those investigations, however, are usually focused on how to detect signals from the olfactory neurons or receptors loaded on chips and enhance sensing efficacy of chips. Therefore, almost of those chips are designed for only one material sensing. Multi-sensing using multi-channels will be needed when the olfactory systems are adopted well on chips. For multiple sensing, we developed an addressable cell array. The chip has 38 cell-chambers arranged in a circle shape and different cell types of thirty eight can be allocated with specific addresses on the chip without any complex valve system. In order to confirm the cell addressing, we loaded EGFP-transfected and empty vector-transfected HEK293a cells into inlets of the cell array in a planned address and those cells were positioned into each chamber by brief aspiration. The arrayed cells were confirmed as a specific pattern through EGFP and nuclei staining. This cell array which can generate address of sensor materials like cells with their own specification is expected to be applied to a platform for a biosensor chip at various sensing fields.

  15. Wind vs. Biofuels: Addressing Climate, Health and Energy

    SciTech Connect

    Professor Mark Jacobson

    2007-01-29

    The favored approach today for addressing global warming is to promote a variety of options: biofuels, wind, solar thermal, solar photovoltaic, geothermal, hydroelectric, and nuclear energy and to improve efficiency. However, by far, most emphasis has been on biofuels. It is shown here, though, that current-technology biofuels cannot address global warming and may slightly increase death and illness due to ozone-related air pollution. Future biofuels may theoretically slow global warming, but only temporarily and with the cost of increased air pollution mortality. In both cases, the land required renders biofuels an impractical solution. Recent measurements and statistical analyses of U.S. and world wind power carried out at Stanford University suggest that wind combined with other options can substantially address global warming, air pollution mortality, and energy needs simultaneously.

  16. Wind versus Biofuels for Addressing Climate, Health, and Energy

    SciTech Connect

    Jacobson, Mark Z.

    2007-01-29

    The favored approach today for addressing global warming is to promote a variety of options: biofuels, wind, solar thermal, solar photovoltaic, geothermal, hydroelectric, and nuclear energy and to improve efficiency. However, by far, most emphasis has been on biofuels. It is shown here, though, that current-technology biofuels cannot address global warming and may slightly increase death and illness due to ozone-related air pollution. Future biofuels may theoretically slow global warming, but only temporarily and with the cost of increased air pollution mortality. In both cases, the land required renders biofuels an impractical solution. Recent measurements and statistical analyses of U.S. and world wind power carried out at Stanford University suggest that wind combined with other options can substantially address global warming, air pollution mortality, and energy needs simultaneously.

  17. Neutralizing a Surface Charge on the FMN Subdomain Increases the Activity of Neuronal Nitric-oxide Synthase by Enhancing the Oxygen Reactivity of the Enzyme Heme-Nitric Oxide Complex*

    PubMed Central

    Haque, Mohammad Mahfuzul; Fadlalla, Mohammed; Wang, Zhi-Qiang; Ray, Sougata Sinha; Panda, Koustubh; Stuehr, Dennis J.

    2009-01-01

    Nitric-oxide synthases (NOSs) are calmodulin-dependent flavoheme enzymes that oxidize l-Arg to nitric oxide (NO) and l-citrulline. Their catalytic behaviors are complex and are determined by their rates of heme reduction (kr), ferric heme-NO dissociation (kd), and ferrous heme-NO oxidation (kox). We found that point mutation (E762N) of a conserved residue on the enzyme's FMN subdomain caused the NO synthesis activity to double compared with wild type nNOS. However, in the absence of l-Arg, NADPH oxidation rates suggested that electron flux through the heme was slower in E762N nNOS, and this correlated with the mutant having a 60% slower kr. During NO synthesis, little heme-NO complex accumulated in the mutant, compared with ∼50–70% of the wild-type nNOS accumulating as this complex. This suggested that the E762N nNOS is hyperactive because it minimizes buildup of an inactive ferrous heme-NO complex during NO synthesis. Indeed, we found that kox was 2 times faster in the E762N mutant than in wild-type nNOS. The mutational effect on kox was independent of calmodulin. Computer simulation and experimental measures both indicated that the slower kr and faster kox of E762N nNOS combine to lower its apparent Km,O2 for NO synthesis by at least 5-fold, which in turn increases its V/Km value and enables it to be hyperactive in steady-state NO synthesis. Our work underscores how sensitive nNOS activity is to changes in the kox and reveals a novel means for the FMN module or protein-protein interactions to alter nNOS activity. PMID:19473991

  18. Climate change in China and China's policies and actions for addressing climate change

    NASA Astrophysics Data System (ADS)

    Qin, D.; Huang, J.; Luo, Y.

    2010-12-01

    Since the first assessment report (FAR) of Inter-Governmental Panel on Climate Change (IPCC) in 1990, the international scientific community has made substantial progresses in climate change sciences. Changes in components of climate system, including the atmosphere, oceans and cryosphere, indicate that global warming is unequivocal. Instrumental records demonstrate that the global mean temperature has a significant increasing trend during the 20th century and in the latest 50 years the warming become faster. In the meantime, the global sea level has a strong increasing trend, as well as the snow coverage of Northern Hemisphere showed an obvious downward trend. Moreover, the global warming plays a key role in significantly affecting the climate system and social-economy on both global and regional scales, such as sea level rise, melting of mountain glaciers and ice sheets, desertification, deforestation, increase of weather extremes (typhoon, hurricane and rainstorm) and so on. The state of the art understanding of IPCC Fourth Assessment Report (AR4) was most of the observed increase in global average temperatures since the mid-20th century is very likely due to the observed increase in the concentrations of anthropogenic greenhouse gases. Climate change issues, as a grave challenge to the sustainable development of the human society, have received ever greater attention from the international community. Deeply cognizant of the complexity and extensive influence of these issues and fully aware of the arduousness and urgency of the task of addressing climate change, the Chinese government is determined to address climate change in the process of pursuing sustainable development. The facts of climate change in China and its impacts, and China’s policies and actions for addressing climate change are introduced in this paper.

  19. Inductively Coupled Plasma Mass Spectrometry Study on the Increase in the Amount of Pr Atoms for Cs-Ion-Implanted Pd/CaO Multilayer Complex with Deuterium Permeation

    NASA Astrophysics Data System (ADS)

    Hioki, Tatsumi; Takahashi, Naoko; Kosaka, Satoru; Nishi, Teppei; Azuma, Hirozumi; Hibi, Shogo; Higuchi, Yuki; Murase, Atsushi; Motohiro, Tomoyoshi

    2013-10-01

    To investigate the nuclear transmutation of Cs into Pr reported in this journal by Iwamura and coworkers, we have measured the amount of Pr atoms in the range as low as ˜1×1010 cm-2 using inductively coupled plasma mass spectrometry for Cs-ion-implanted Pd/CaO multilayer complexes before and after deuterium permeation. The amount of Pr was initially at most 2.0×1011 cm-2 and it increased up to 1.6×1012 cm-2 after deuterium permeation. The increase in the amount of Pr could be explained neither by deuterium permeation-stimulated segregation of Pr impurities nor by external contamination from the experimental environment during the permeation. No increase in Pr was observed for permeation with hydrogen. These findings suggest that the observed increase in Pr with deuterium permeation can be attributed to a nuclear origin, as reported by Iwamura and coworkers, although the amount of the increase in Pr is two orders of magnitude less than that reported by them.

  20. mTOR Hyperactivation by Ablation of Tuberous Sclerosis Complex 2 in the Mouse Heart Induces Cardiac Dysfunction with the Increased Number of Small Mitochondria Mediated through the Down-Regulation of Autophagy

    PubMed Central

    Taneike, Manabu; Nishida, Kazuhiko; Omiya, Shigemiki; Zarrinpashneh, Elham; Misaka, Tomofumi; Kitazume-Taneike, Rika; Austin, Ruth; Takaoka, Minoru; Yamaguchi, Osamu; Gambello, Michael J.; Shah, Ajay M.; Otsu, Kinya

    2016-01-01

    Mammalian target of rapamycin complex 1 (mTORC1) is a key regulator of cell growth, proliferation and metabolism. mTORC1 regulates protein synthesis positively and autophagy negatively. Autophagy is a major system to manage bulk degradation and recycling of cytoplasmic components and organelles. Tuberous sclerosis complex (TSC) 1 and 2 form a heterodimeric complex and inactivate Ras homolog enriched in brain, resulting in inhibition of mTORC1. Here, we investigated the effects of hyperactivation of mTORC1 on cardiac function and structure using cardiac-specific TSC2-deficient (TSC2-/-) mice. TSC2-/- mice were born normally at the expected Mendelian ratio. However, the median life span of TSC2-/- mice was approximately 10 months and significantly shorter than that of control mice. TSC2-/- mice showed cardiac dysfunction and cardiomyocyte hypertrophy without considerable fibrosis, cell infiltration or apoptotic cardiomyocyte death. Ultrastructural analysis of TSC2-/- hearts revealed misalignment, aggregation and a decrease in the size and an increase in the number of mitochondria, but the mitochondrial function was maintained. Autophagic flux was inhibited, while the phosphorylation level of S6 or eukaryotic initiation factor 4E -binding protein 1, downstream of mTORC1, was increased. The upregulation of autophagic flux by trehalose treatment attenuated the cardiac phenotypes such as cardiac dysfunction and structural abnormalities of mitochondria in TSC2-/- hearts. The results suggest that autophagy via the TSC2-mTORC1 signaling pathway plays an important role in maintenance of cardiac function and mitochondrial quantity and size in the heart and could be a therapeutic target to maintain mitochondrial homeostasis in failing hearts. PMID:27023784

  1. 7 CFR 1730.3 - RUS addresses.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... ELECTRIC SYSTEM OPERATIONS AND MAINTENANCE General § 1730.3 RUS addresses. (a) Persons wishing to obtain... assigned RUS General Field Representative (GFR) or such other office as designated by RUS....

  2. 21 CFR 600.2 - Mailing addresses.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... BIOLOGICAL PRODUCTS: GENERAL General Provisions § 600.2 Mailing addresses. (a) Licensed biological products... applications (BLAs) and their amendments and supplements, adverse experience reports, biological product deviation reports, fatality reports, and other correspondence. Biological products samples must not be...

  3. 21 CFR 600.2 - Mailing addresses.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... BIOLOGICAL PRODUCTS: GENERAL General Provisions § 600.2 Mailing addresses. (a) Licensed biological products... applications (BLAs) and their amendments and supplements, adverse experience reports, biological product deviation reports, fatality reports, and other correspondence. Biological products samples must not be...

  4. 21 CFR 600.2 - Mailing addresses.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... BIOLOGICAL PRODUCTS: GENERAL General Provisions § 600.2 Mailing addresses. (a) Licensed biological products... applications (BLAs) and their amendments and supplements, adverse experience reports, biological product deviation reports, fatality reports, and other correspondence. Biological products samples must not be...

  5. Addressing Your Child's Weight at the Doctor

    MedlinePlus

    ... a Healthy Heart Healthy Kids Our Kids Programs Childhood Obesity What is childhood obesity? Overweight in Children BMI in Children Is Childhood Obesity an Issue in Your Home? Addressing your Child's ...

  6. 7 CFR 1730.3 - RUS addresses.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... ELECTRIC SYSTEM OPERATIONS AND MAINTENANCE General § 1730.3 RUS addresses. (a) Persons wishing to obtain... assigned RUS General Field Representative (GFR) or such other office as designated by RUS....

  7. 7 CFR 1730.3 - RUS addresses.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... ELECTRIC SYSTEM OPERATIONS AND MAINTENANCE General § 1730.3 RUS addresses. (a) Persons wishing to obtain... assigned RUS General Field Representative (GFR) or such other office as designated by RUS....

  8. 7 CFR 1730.3 - RUS addresses.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... ELECTRIC SYSTEM OPERATIONS AND MAINTENANCE General § 1730.3 RUS addresses. (a) Persons wishing to obtain... assigned RUS General Field Representative (GFR) or such other office as designated by RUS....

  9. Addressing the Public About Science and Religion

    NASA Astrophysics Data System (ADS)

    Peshkin, Murray

    2010-03-01

    Attacks on the integrity of science teaching in our public schools have recently become increasingly threatening. Geology and Darwinian evolution are the primary targets and cosmology is at risk. Up to now, the Supreme Court has excluded teachings based on religion from public schools for constitutional, not scientific, reasons. But now the incumbent Supreme Court seem less committed to strict separation of church and state than were their predecessors, and federal courts are beginning to judge the science itself. In this situation, we need to create a climate of public opinion favorable to the protection of good science by explaining the issues both to students and to others. I have been trying to do that by addressing audiences such as church groups, other community groups, and high school and college classes. I do not seek to convert committed anti-evolutionists. I am trying to inform the reasonable majority who do not really know what science is and does, or what a theory is and how we know when it's right, or why we tell them that all knowledge is provisional but still insist that we are teaching the right science. Many have been advised by their religious teachers that there is no conflict between science and their religious beliefs but do not see how that can be. I try to explain how they are disjoint discussions. I also discuss the likely consequences for our country if we degrade the teaching of science in the public schools. My audiences have generally been receptive. Here I will relate some lessons I have learned from my experience with such talks. Without doubt, the most important lesson is that most Americans have religious beliefs that are important to them and are willing to consider what I say only because they know I respect their beliefs. This work was partially supported by the U.S. Dept. of Energy, Office of Nuclear Physics, under contract DE-AC02-06CH11357.

  10. [Complex posttraumatic stress disorder].

    PubMed

    Green, Tamar; Kotler, Moshe

    2007-11-01

    The characteristic symptoms resulting from exposure to an extreme trauma include three clusters of symptoms: persistent experience of the traumatic event, persistent avoidance of stimuli associated with the trauma and persistent symptoms of increased arousal. Beyond the accepted clusters of symptoms for posttraumatic stress disorder exists a formation of symptoms related to exposure to extreme or prolonged stress e.g. childhood abuse, physical violence, rape, and confinement within a concentration camp. With accumulated evidence of the existence of these symptoms began a trail to classify a more complex syndrome, which included, but was not confined to the symptoms of posttraumatic stress disorder. This review addresses several subjects for study in complex posttraumatic stress disorder, which is a complicated and controversial topic. Firstly, the concept of complex posttraumatic stress disorder is presented. Secondly, the professional literature relevant to this disturbance is reviewed and finally, the authors present the polemic being conducted between the researchers of posttraumatic disturbances regarding validity, reliability and the need for separate diagnosis for these symptoms. PMID:18087837

  11. Catholic Social Teaching: Addressing Globalization in Catholic Business Education

    ERIC Educational Resources Information Center

    Ball, James B.; Martinez, Zaida; Toyne, Brian

    2009-01-01

    Although business schools are increasingly aware of the importance of globalization in educating future business leaders, their business programs have addressed globalization from a limited perspective that fails to provide students with a broader understanding of its impact on societies and its moral consequences. The conventional approach to the…

  12. 46 CFR 67.113 - Managing owner designation; address; requirement to report change of address.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Managing owner designation; address; requirement to... Required for Vessel Documentation § 67.113 Managing owner designation; address; requirement to report change of address. The owner of each vessel must designate a managing owner on the Application...

  13. 46 CFR 67.113 - Managing owner designation; address; requirement to report change of address.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Managing owner designation; address; requirement to... Required for Vessel Documentation § 67.113 Managing owner designation; address; requirement to report change of address. The owner of each vessel must designate a managing owner on the Application...

  14. 46 CFR 67.113 - Managing owner designation; address; requirement to report change of address.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Managing owner designation; address; requirement to... Required for Vessel Documentation § 67.113 Managing owner designation; address; requirement to report change of address. The owner of each vessel must designate a managing owner on the Application...

  15. 46 CFR 67.113 - Managing owner designation; address; requirement to report change of address.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Managing owner designation; address; requirement to... Required for Vessel Documentation § 67.113 Managing owner designation; address; requirement to report change of address. The owner of each vessel must designate a managing owner on the Application...

  16. 46 CFR 67.113 - Managing owner designation; address; requirement to report change of address.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Managing owner designation; address; requirement to... Required for Vessel Documentation § 67.113 Managing owner designation; address; requirement to report change of address. The owner of each vessel must designate a managing owner on the Application...

  17. Treatment of sickle cell anemia with 5-azacytidine results in increased fetal hemoglobin production and is associated with nonrandom hypomethylation of DNA around the gamma-delta-beta-globin gene complex.

    PubMed Central

    Charache, S; Dover, G; Smith, K; Talbot, C C; Moyer, M; Boyer, S

    1983-01-01

    Increased production of fetal hemoglobin (HbF) was observed in a patient with sickle cell anemia treated with 5-azacytidine. Each of four courses of therapy resulted in a rapid and prolonged increase in the percentage of HbF containing reticulocytes (F reticulocytes) and HbF containing erythrocytes (F cells). The percentage of HbF in peripheral blood rose from 1.8 to 8.9%. The rise in HbF production was accompanied by an increase in peripheral blood hemoglobin concentration from 8 to 12 g/dl and an increase in mean erythrocyte volume. Treatment with 5-azacytidine resulted in hypomethylation of total genomic and a Y-chromosome-specific DNA fragment isolated from both peripheral blood and bone marrow. Of 15 restriction enzyme sites around the gamma-delta-beta-globin gene complex, only 2 became hypomethylated: one 107 bases 5' to the gamma G and the other 107 bases 5' to the gamma A globin genes. Images PMID:6192443

  18. How to unify knowledge. Keynote address.

    PubMed

    Wilson, E O

    2001-05-01

    The central question of general scholarship is whether all of knowledge is intrinsically consilient, that is, whether it can be united by a continuous skein of cause-and-effect explanation and across levels of increasingly complex organization. The answer lies in the recognition that the traditional line separating the great branches of learning (natural sciences, social sciences, and humanities) is not a barrier or even a line, but rather a broad domain of poorly explored material phenomena now being cooperatively entered from all sides. The key to bridge-building is the discovery and analysis of human nature, which consists of the epigenetic rules--the hereditary regularities in mental development. Their study is now well under way, at the biological, social science, and humanities levels. Examples of epigenetic rules include the origin of color vocabularies, incest avoidance, optimum arousal in artistic design, and response to the natural environment. The convergence of the great branches of learning is mostly an empirical process, light on formal logic and theory in its initial stages. The value of the consilience program is that at long last we appear to have acquired the means either to establish the intrinsic truth of the fundamental unity of knowledge, or to discard it. I will argue the likelihood of its existence and early establishment. PMID:11411162

  19. Biologically inspired robotic inspectors: the engineering reality and future outlook (Keynote address)

    NASA Astrophysics Data System (ADS)

    Bar-Cohen, Yoseph

    2005-04-01

    Human errors have long been recognized as a major factor in the reliability of nondestructive evaluation results. To minimize such errors, there is an increasing reliance on automatic inspection tools that allow faster and consistent tests. Crawlers and various manipulation devices are commonly used to perform variety of inspection procedures that include C-scan with contour following capability to rapidly inspect complex structures. The emergence of robots has been the result of the need to deal with parts that are too complex to handle by a simple automatic system. Economical factors are continuing to hamper the wide use of robotics for inspection applications however technology advances are increasingly changing this paradigm. Autonomous robots, which may look like human, can potentially address the need to inspect structures with configuration that are not predetermined. The operation of such robots that mimic biology may take place at harsh or hazardous environments that are too dangerous for human presence. Biomimetic technologies such as artificial intelligence, artificial muscles, artificial vision and numerous others are increasingly becoming common engineering tools. Inspired by science fiction, making biomimetic robots is increasingly becoming an engineering reality and in this paper the state-of-the-art will be reviewed and the outlook for the future will be discussed.

  20. Bioethicists Can and Should Contribute to Addressing Racism.

    PubMed

    Danis, Marion; Wilson, Yolonda; White, Amina

    2016-01-01

    The problems of racism and racially motivated violence in predominantly African American communities in the United States are complex, multifactorial, and historically rooted. While these problems are also deeply morally troubling, bioethicists have not contributed substantially to addressing them. Concern for justice has been one of the core commitments of bioethics. For this and other reasons, bioethicists should contribute to addressing these problems. We consider how bioethicists can offer meaningful contributions to the public discourse, research, teaching, training, policy development, and academic scholarship in response to the alarming and persistent patterns of racism and implicit biases associated with it. To make any useful contribution, bioethicists will require preparation and should expect to play a significant role through collaborative action with others. PMID:26982911

  1. Addressing single trapped ions for Rydberg quantum logic

    NASA Astrophysics Data System (ADS)

    Bachor, P.; Feldker, T.; Walz, J.; Schmidt-Kaler, F.

    2016-08-01

    We demonstrate the excitation of ions to the Rydberg state 22F by vacuum ultraviolet radiation at a wavelength of 123 nm combined with the coherent manipulation of the optical qubit transition in {}40{{Ca}}+. With a tightly focused beam at 729 nm wavelength we coherently excite a single ion from a linear string into the metastable 3{D}5/2 state before a VUV pulse excites it to the Rydberg state. In combination with ion shuttling in the trap, we extend this approach to the addressed excitation of multiple ions. The coherent initialization as well as the addressed Rydberg excitation are key prerequisites for more complex applications of Rydberg ions in quantum simulation or quantum information processing.

  2. Evaluating local indirect addressing in SIMD proc essors

    NASA Technical Reports Server (NTRS)

    Middleton, David; Tomboulian, Sherryl

    1989-01-01

    In the design of parallel computers, there exists a tradeoff between the number and power of individual processors. The single instruction stream, multiple data stream (SIMD) model of parallel computers lies at one extreme of the resulting spectrum. The available hardware resources are devoted to creating the largest possible number of processors, and consequently each individual processor must use the fewest possible resources. Disagreement exists as to whether SIMD processors should be able to generate addresses individually into their local data memory, or all processors should access the same address. The tradeoff is examined between the increased capability and the reduced number of processors that occurs in this single instruction stream, multiple, locally addressed, data (SIMLAD) model. Factors are assembled that affect this design choice, and the SIMLAD model is compared with the bare SIMD and the MIMD models.

  3. The Study of Address Tree Coding Based on the Maximum Matching Algorithm in Courier Business

    NASA Astrophysics Data System (ADS)

    Zhou, Shumin; Tang, Bin; Li, Wen

    As an important component of EMS monitoring system, address is different from user name with great uncertainty because there are many ways to represent it. Therefore, address standardization is a difficult task. Address tree coding has been trying to resolve that issue for many years. Zip code, as its most widely used algorithm, can only subdivide the address down to a designated post office, not the recipients' address. This problem needs artificial identification method to be accurately delivered. This paper puts forward a new encoding algorithm of the address tree - the maximum matching algorithm to solve the problem. This algorithm combines the characteristics of the address tree and the best matching theory, and brings in the associated layers of tree nodes to improve the matching efficiency. Taking the variability of address into account, the thesaurus of address tree should be updated timely by increasing new nodes automatically through intelligent tools.

  4. Shared address collectives using counter mechanisms

    SciTech Connect

    Blocksome, Michael; Dozsa, Gabor; Gooding, Thomas M; Heidelberger, Philip; Kumar, Sameer; Mamidala, Amith R; Miller, Douglas

    2014-02-18

    A shared address space on a compute node stores data received from a network and data to transmit to the network. The shared address space includes an application buffer that can be directly operated upon by a plurality of processes, for instance, running on different cores on the compute node. A shared counter is used for one or more of signaling arrival of the data across the plurality of processes running on the compute node, signaling completion of an operation performed by one or more of the plurality of processes, obtaining reservation slots by one or more of the plurality of processes, or combinations thereof.

  5. Initiative Addresses Subsurface Energy and Environment Problems

    NASA Astrophysics Data System (ADS)

    Bodvarsson, Gudmundur S.; Majer, Ernest L.; Wang, Joseph S. Y.; Colwell, Frederick; Redden, George

    2006-01-01

    Members of the geoscience community are cooperating in conceptualizing fundamental, crosscutting research to address major obstacles to solving energy and environmental problems related to the subsurface, through the SECUREarth initiative, which began in 2004. Addressing problems, such as reliable nuclear waste storage and safe carbon dioxide (CO2) sequestration, are critical to maintaining an economical and safe energy supply and clean environment. A recent workshop in Golden, Colo., helped to further the development of the SECUREarth (Scientific Energy/Environmental Crosscutting Underground Research for Urgent Solutions to Secure the Earth's Future) initiative by identifying the key scientific challenges in the geosciences, as well as to target possible approaches for overcoming roadblocks.

  6. Frequency addressable beams for land mobile communications

    NASA Technical Reports Server (NTRS)

    Thompson, J. D.; Dubellay, G. G.

    1988-01-01

    Satellites used for mobile communications need to serve large numbers of small, low cost terminals. The most important parameters affecting the capacity of such systems are the satellite equivalent isotropically radiated power (EIRP) and gain to noise temperature ratio (G/T) and available bandwidth. Satellites using frequency addressed beams provide high EIRP and G/T with high-gain antenna beams that also permit frequency reuse over the composite coverage area. Frequency addressing is easy to implement and compatible with low-cost terminals and offers higher capacity than alternative approaches.

  7. Cheaper Adjoints by Reversing Address Computations

    DOE PAGESBeta

    Hascoët, L.; Utke, J.; Naumann, U.

    2008-01-01

    The reverse mode of automatic differentiation is widely used in science and engineering. A severe bottleneck for the performance of the reverse mode, however, is the necessity to recover certain intermediate values of the program in reverse order. Among these values are computed addresses, which traditionally are recovered through forward recomputation and storage in memory. We propose an alternative approach for recovery that uses inverse computation based on dependency information. Address storage constitutes a significant portion of the overall storage requirements. An example illustrates substantial gains that the proposed approach yields, and we show use cases in practical applications.

  8. New generation of content addressable memories for associative processing

    NASA Astrophysics Data System (ADS)

    Lewis, H. G., Jr.; Giambalov, Paul

    2000-05-01

    Content addressable memories (CAMS) store both key and association data. A key is presented to the CAN when it is searched and all of the addresses are scanned in parallel to find the address referenced by the key. When a match occurs, the corresponding association is returned. With the explosion of telecommunications packet switching protocols, large data base servers, routers and search engines a new generation of dense sub-micron high throughput CAMS has been developed. The introduction of this paper presents a brief history and tutorial on CAMS, their many uses and advantages, and describes the architecture and functionality of several of MUSIC Semiconductors CAM devices. In subsequent sections of the paper we address using Associative Processing to accommodate the continued increase in sensor resolution, number of spectral bands, required coverage, the desire to implement real-time target cueing, and the data flow and image processing required for optimum performance of reconnaissance and surveillance Unmanned Aerial Vehicles (UAVs). To be competitive the system designer must provide the most computational power, per watt, per dollar, per cubic inch, within the boundaries of cost effective UAV environmental control systems. To address these problems we demonstrate leveraging DARPA and DoD funded Commercial Off-the-Shelf technology to integrate CAM based Associative Processing into a real-time heterogenous multiprocessing system for UAVs and other platforms with limited weight, volume and power budgets.

  9. Rottlerin potentiates camptothecin-induced cytotoxicity in human hormone refractory prostate cancers through increased formation and stabilization of topoisomerase I-DNA cleavage complexes in a PKCδ-independent pathway

    PubMed Central

    Hsu, Jui-Ling; Ho, Yunn-Fang; Li, Tsai-Kun; Chen, Ching-Shih; Hsu, Lih-Ching; Guh, Jih-Hwa

    2014-01-01

    Combination therapy, which can optimize killing activity to cancers and minimize drug resistance, is a mainstream therapy against hormone-refractory prostate cancers (HRPCs). Rottlerin, a natural polyphenolic component, synergistically increased PC-3 (a HRPC cell line) apoptosis induced by camptothecin (a topoisomerase I inhibitor). Using siRNA technique to knockdown protein kinase C-δ (PKCδ), the data showed that rottlerin-mediated synergistic effect was PKCδ-independent, although rottlerin has been used as a PKCδ inhibitor. Rottlerin potentiated camptothecin-induced DNA fragmentation at S phase and ATM phosphorylation at Ser1981. The effect was correlated to apoptosis (r2 = 0.9). To detect upstream signals, the data showed that camptothecin acted on and stabilized topoisomerase I-DNA complex, leading to the formation of camptothecin-trapped cleavage complexes (TOP1cc). The effect was potentiated by rottlerin. To determine DNA repair capability, the time-related γH2A.X formation was examined after camptothecin removal. Consequently, rottlerin significantly inhibited camptothecin removal-mediated decline of γH2A.X formation at S phase, indicating the impairment of DNA repair activity in the presence of rottlerin. The combinatory treatment of camptothecin and rottlerin induced conformational change and activation of Bax and formation of truncated Bad, suggesting the contribution of mitochondria stress to apoptosis. In summary, the data suggest that rottlerin-mediated camptothecin sensitization is through the augmented stabilization of TOP1cc, leading to an increase of DNA damage stress and, possibly, an impairment of DNA repair capability. Subsequently, mitochondria-involved apoptosis is triggered through Bax activation and truncated Bad formation. The novel discovery may provide an anticancer approach of combinatory use between rottlerin and camptothecin for the treatment of HRPCs. PMID:22490701

  10. Addressable Inverter Matrix Tests Integrated-Circuit Wafer

    NASA Technical Reports Server (NTRS)

    Buehler, Martin G.

    1988-01-01

    Addressing elements indirectly through shift register reduces number of test probes. With aid of new technique, complex test structure on silicon wafer tested with relatively small number of test probes. Conserves silicon area by reduction of area devoted to pads. Allows thorough evaluation of test structure characteristics and of manufacturing process parameters. Test structure consists of shift register and matrix of inverter/transmission-gate cells connected to two-by-ten array of probe pads. Entire pattern contained in square area having only 1.6-millimeter sides. Shift register is conventional static CMOS device using inverters and transmission gates in master/slave D flip-flop configuration.

  11. Federal Offices That Address Women's Issues.

    ERIC Educational Resources Information Center

    Weber, Patricia A.; And Others

    This directory contains a listing of federal offices that address women's issues. Among the departments and agencies included are: the executive branch and the executive agencies departments of agriculture, commerce, defense (Air Force, Army, Coast Guard, Marine Corps, National Guard and Navy), education, health and human services, housing and…

  12. Preservice Educators' Confidence in Addressing Sexuality Education

    ERIC Educational Resources Information Center

    Wyatt, Tammy Jordan

    2009-01-01

    This study examined 328 preservice educators' level of confidence in addressing four sexuality education domains and 21 sexuality education topics. Significant differences in confidence levels across the four domains were found for gender, academic major, sexuality education philosophy, and sexuality education knowledge. Preservice educators…

  13. 50 CFR 228.8 - Mailing address.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Mailing address. 228.8 Section 228.8 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION... the Presiding Officer, c/o Assistant Administrator, National Marine Fisheries Service, 1315...

  14. Latitude and Longitude. AIR Presidential Address.

    ERIC Educational Resources Information Center

    Chaffee, Ellen Earle

    This speech addresses the problem of higher education's response to the forces of change and argues for a reinventing of higher education rather than repeatedly amending core teaching and research activities to fit new social and economic situations. Three higher education organizational dynamics (recruitment, budgeting, and handling outside…

  15. 40 CFR 80.174 - Addresses.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... FUELS AND FUEL ADDITIVES Detergent Gasoline § 80.174 Addresses. (a) The detergent additive sample..., 2565 Plymouth Road, Ann Arbor, Michigan 48105. (b) Other detergent registration and certification data, and certain other information which may be specified in this subpart, shall be sent to:...

  16. Addressing Gender Differences in Young Adolescents.

    ERIC Educational Resources Information Center

    Butler, Deborah A.; Manning, M. Lee

    The current interest in identifying gender differences in young adolescents suggests a need to focus on how gender differences affect teaching and learning situations and on how middle level school educators can address these differences. This book explains what gender differences are, how gender differences affect learning, how both girls and…

  17. Addressing South Africa's Engineering Skills Gaps

    ERIC Educational Resources Information Center

    Hall, Jonathan; Sandelands, Eric

    2009-01-01

    Purpose: This paper aims to provide a case study of how engineering skills gaps are being addressed by Murray & Roberts in South Africa. Design/methodology/approach: The paper focuses on skills challenges in South Africa from a reflective practitioner perspective, exploring a case example from an industry leader. Findings: The paper explores how…

  18. 76 FR 80903 - Mandatory Declassification Review Addresses

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-27

    ... of the Secretary Mandatory Declassification Review Addresses AGENCY: Department of Defense. ACTION... Declassification Review requests may be sent. This notice benefits the public in advising them where to send such requests for declassification review. FOR FURTHER INFORMATION CONTACT: Mr. Robert Storer, (571)...

  19. Registering Names and Addresses for Information Technology.

    ERIC Educational Resources Information Center

    Knapp, Arthur A.

    The identification of administrative authorities and the development of associated procedures for registering and accessing names and addresses of communications data systems are considered in this paper. It is noted that, for data communications systems using standards based on the Open Systems Interconnection (OSI) Reference Model specified by…

  20. 50 CFR 228.8 - Mailing address.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 11 2013-10-01 2013-10-01 false Mailing address. 228.8 Section 228.8 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION... the Presiding Officer, c/o Assistant Administrator, National Marine Fisheries Service, 1315...

  1. Naming and Address in Afghan Society.

    ERIC Educational Resources Information Center

    Miran, M. Alam

    Forms of address in Afghan society reflect the relationships between the speakers as well as the society's structure. In Afghan Persian, or Dari, first, second, and last names have different semantic dimensions. Boys' first names usually consist of two parts or morphemes, of which one may be part of the father's name. Girls' names usually consist…

  2. Addressing Student Debt in the Classroom

    ERIC Educational Resources Information Center

    Perkins, David; Johnston, Tim; Lytle, Rick

    2016-01-01

    Student debt is a national concern. The authors address debt in the classroom to enhance students' understanding of the consequences of debt and the need for caution when financing their education. However, student feedback indicates this understanding has a delayed effect on borrowing behavior and underscores the importance of making difficult…

  3. Native Women at Risk: Addressing Cancer Prevention.

    ERIC Educational Resources Information Center

    Thiemann, Kay M. B.

    1994-01-01

    Discusses outcomes of a conference that brought together representatives from Indian tribes, state health departments, the Indian Health Service, the Mayo Clinic, and the American Cancer Society, to address the high rate of cervical cancer among American Indian women. Describes barriers to health care and plans to promote cancer screening among…

  4. Autocheck: Addressing the Problem of Rural Transportation.

    ERIC Educational Resources Information Center

    Payne, Guy A.

    This paper describes a project implemented by a social worker from the Glynn County School District in rural Georgia to address transportation problems experienced by students and their families. The project aims to assist families who are unable to keep appointments or attend other important events due to unreliable transportation. A county needs…

  5. Problem Solvers: Solutions--The Inaugural Address

    ERIC Educational Resources Information Center

    Dause, Emily

    2014-01-01

    Fourth graders in Miss Dause's and Mrs. Hicks's mathematics classes at South Mountain Elementary School in Dillsburg, Pennsylvania, worked with the data from the Inauagural Address problem that was previously published published in the February 2013 issue of "Teaching Children Mathematics". This activity allowed students to…

  6. EMAIL -- E-mail address searching

    NASA Astrophysics Data System (ADS)

    Bly, M. J.; Mellor, G. R.

    One of the most common activities on networked computers is the sending and receiving of personal electronic mail (email). Starlink nodes are connected to the worldwide Internet network. This document describes how to find email addresses to communicate with other astronomers and astronomy groups in the UK and the rest of the world.

  7. Address Systems in "The Plum Plum Pickers"

    ERIC Educational Resources Information Center

    Geuder, Patricia A.

    1975-01-01

    The address systems in Raymond Barrio's "The Plum Plum Pickers" imply sociolinguistic differences between the Chicano and the Anglo characters. The kinds of sociolinguistic situations, the number of dyadic patterns, and the quantity of the dyadic patterns strongly suggest the differences. (Author)

  8. Addressing Issues Related to Technology and Engineering

    ERIC Educational Resources Information Center

    Technology Teacher, 2008

    2008-01-01

    This article presents an interview with Michael Hacker and David Burghardt, codirectors of Hoftra University's Center for Technological Literacy. Hacker and Burghardt address issues related to technology and engineering. They argue that teachers need to be aware of the problems kids are facing, and how to present these problems in an engaging…

  9. How Sociology Texts Address Gun Control

    ERIC Educational Resources Information Center

    Tonso, William R.

    2004-01-01

    William R. Tonso has chosen an issue that he knows something about to examine how sociology textbooks address controversy. Appealing for gun control is fashionable, but it is at odds with a fondness that ordinary Americans have for their firearms--one that is supported by a growing body of research on deterrence to crime. There are two sides to…

  10. 40 CFR 374.6 - Addresses.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 28 2011-07-01 2011-07-01 false Addresses. 374.6 Section 374.6 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SUPERFUND, EMERGENCY PLANNING, AND... Administrator, Region VII, U.S. Environmental Protection Agency, 726 Minnesota Avenue, Kansas City, KS...

  11. 40 CFR 374.6 - Addresses.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 27 2010-07-01 2010-07-01 false Addresses. 374.6 Section 374.6 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SUPERFUND, EMERGENCY PLANNING, AND... Administrator, Region VII, U.S. Environmental Protection Agency, 726 Minnesota Avenue, Kansas City, KS...

  12. Opening Address of Chairman Michael Pertschuk.

    ERIC Educational Resources Information Center

    Pertschuk, Michael

    Presented to a symposium sponsored by the Federal Trade Commission (FTC) to consider some of the issues involved in the continuing growth of a few large companies in the field of communication, this address cites statements of concern, made by the Supreme Court and by some periodicals, that excessive concentrations of power threaten First…

  13. 37 CFR 301.2 - Official addresses.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Section 301.2 Patents, Trademarks, and Copyrights COPYRIGHT ROYALTY BOARD, LIBRARY OF CONGRESS GENERAL...., and be addressed as follows: Copyright Royalty Board, Library of Congress, James Madison Memorial... Royalty Board, Library of Congress, James Madison Memorial Building, 101 Independence Avenue,...

  14. 37 CFR 301.2 - Official addresses.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Section 301.2 Patents, Trademarks, and Copyrights COPYRIGHT ROYALTY BOARD, LIBRARY OF CONGRESS GENERAL...., and be addressed as follows: Copyright Royalty Board, Library of Congress, James Madison Memorial... Royalty Board, Library of Congress, James Madison Memorial Building, 101 Independence Avenue,...

  15. 37 CFR 301.2 - Official addresses.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Section 301.2 Patents, Trademarks, and Copyrights COPYRIGHT ROYALTY BOARD, LIBRARY OF CONGRESS GENERAL...., and be addressed as follows: Copyright Royalty Board, Library of Congress, James Madison Memorial... Royalty Board, Library of Congress, James Madison Memorial Building, 101 Independence Avenue,...

  16. 37 CFR 301.2 - Official addresses.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Section 301.2 Patents, Trademarks, and Copyrights COPYRIGHT ROYALTY BOARD, LIBRARY OF CONGRESS GENERAL...., and be addressed as follows: Copyright Royalty Board, Library of Congress, James Madison Memorial... Royalty Board, Library of Congress, James Madison Memorial Building, 101 Independence Avenue,...

  17. The Conversational Frame in Public Address.

    ERIC Educational Resources Information Center

    Branham, Robert James; Pearce, W. Barnett

    1996-01-01

    Explores the diverse forms and motives of the conversational frame in public address. Argues that, by framing their remarks and transactions with their listeners as conversational, orators may attempt to reconstruct or seem to reconstruct speaker-audience relationships and to position themselves and their audiences within networks of reciprocal…

  18. Rational Rhymes for Addressing Common Childhood Issues

    ERIC Educational Resources Information Center

    Warren, Jeffrey M.

    2011-01-01

    Music-based interventions are valuable tools counselors can use when working with children. Specific types of music-based interventions, such as songs or rhymes, can be especially pertinent in addressing the thoughts, feelings, and behaviors of children. Rational-emotive behavior therapy (REBT) provides a therapeutic framework that encourages…

  19. Chemical Address Tags of Fluorescent Bioimaging Probes

    PubMed Central

    Shedden, Kerby; Rosania, Gus R.

    2010-01-01

    Chemical address tags can be defined as specific structural features shared by a set of bioimaging probes having a predictable influence on cell-associated visual signals obtained from these probes. Here, using a large image dataset acquired with a high content screening instrument, machine vision and cheminformatics analysis have been applied to reveal chemical address tags. With a combinatorial library of fluorescent molecules, fluorescence signal intensity, spectral, and spatial features characterizing each one of the probes' visual signals were extracted from images acquired with the three different excitation and emission channels of the imaging instrument. With multivariate regression, the additive contribution from each one of the different building blocks of the bioimaging probes towards each measured, cell-associated image-based feature was calculated. In this manner, variations in the chemical features of the molecules were associated with the resulting staining patterns, facilitating quantitative, objective analysis of chemical address tags. Hierarchical clustering and paired image-cheminformatics analysis revealed key structure-property relationships amongst many building blocks of the fluorescent molecules. The results point to different chemical modifications of the bioimaging probes that can exert similar (or different) effects on the probes' visual signals. Inspection of the clustered structures suggests intramolecular charge migration or partial charge distribution as potential mechanistic determinants of chemical address tag behavior. PMID:20104576

  20. Comprehensive Planning To Address Homelessness. City Initiatives.

    ERIC Educational Resources Information Center

    Zawisza, Kris

    This packet contains documents that provide information about the planning and implementation of a comprehensive plan to address homelessness in cities throughout the U.S. Information on the following components of a comprehensive strategy are included: (1) "Task Forces"; (2) "Assessment Studies"; (3) "Emergency Services"; (4) "Transitional…

  1. 40 CFR 80.174 - Addresses.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... FUELS AND FUEL ADDITIVES Detergent Gasoline § 80.174 Addresses. (a) The detergent additive sample..., 2565 Plymouth Road, Ann Arbor, Michigan 48105. (b) Other detergent registration and certification data, and certain other information which may be specified in this subpart, shall be sent to:...

  2. 40 CFR 98.9 - Addresses.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... submitted to the following address: (a) For U.S. mail. Director, Climate Change Division, 1200 Pennsylvania Ave., NW., Mail Code: 6207J, Washington, DC 20460. (b) For package deliveries. Director, Climate Change Division, 1310 L St, NW., Washington, DC 20005....

  3. 40 CFR 98.9 - Addresses.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... submitted to the following address: (a) For U.S. mail. Director, Climate Change Division, 1200 Pennsylvania Ave., NW., Mail Code: 6207J, Washington, DC 20460. (b) For package deliveries. Director, Climate Change Division, 1310 L St, NW., Washington, DC 20005....

  4. 37 CFR 251.1 - Official addresses.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Copyright Arbitration Royalty Panels (CARPs) must be addressed as follows: (a) If hand delivered by a... Friday between 8:30 a.m. and 5 p.m. (b) If hand delivered by a commercial courier (excluding Federal...) located at Second and D Street, NE., Washington, DC. The CCAS will accept items from couriers with...

  5. Mapping virtual addresses to different physical addresses for value disambiguation for thread memory access requests

    DOEpatents

    Gala, Alan; Ohmacht, Martin

    2014-09-02

    A multiprocessor system includes nodes. Each node includes a data path that includes a core, a TLB, and a first level cache implementing disambiguation. The system also includes at least one second level cache and a main memory. For thread memory access requests, the core uses an address associated with an instruction format of the core. The first level cache uses an address format related to the size of the main memory plus an offset corresponding to hardware thread meta data. The second level cache uses a physical main memory address plus software thread meta data to store the memory access request. The second level cache accesses the main memory using the physical address with neither the offset nor the thread meta data after resolving speculation. In short, this system includes mapping of a virtual address to a different physical addresses for value disambiguation for different threads.

  6. Increased Progesterone Production in Cumulus–Oocyte Complexes of Female Mice Sired by Males With the Y-Chromosome Long Arm Deletion and its Potential Influence on Fertilization Efficiency

    PubMed Central

    Galas, Jerzy; Przybyło, Małgorzata; Bilińska, Barbara; Styrna, Józefa

    2015-01-01

    It was revealed previously that B10.BR(Ydel) females sired by males with the Y-chromosome long arm deletion differ from genetically identical B10.BR females sired by males with the intact Y chromosome. This is interpreted as a result of different epigenetic information which females of both groups inherit from their fathers. In the following study, we show that cumulus–oocyte complexes ovulated by B10.BR(Ydel) females synthesize increased amounts of progesterone, which is important sperm stimulator. Because their extracellular matrix is excessively firm, the increased progesterone secretion belongs presumably to factors that compensate this feature enabling unchanged fertilization ratios. Described compensatory mechanism can act only on sperm of high quality, presenting proper receptors. Indeed, low proportion of sperm of Ydel males that poorly fertilize B10.BR(Ydel) oocytes demonstrates positive staining of membrane progesterone receptors. This proportion is significantly higher for sperm of control males that fertilize B10.BR(Ydel) and B10.BR oocytes with the same efficiency. PMID:24899473

  7. Increased progesterone production in cumulus-oocyte complexes of female mice sired by males with the Y-chromosome long arm deletion and its potential influence on fertilization efficiency.

    PubMed

    Kotarska, Katarzyna; Galas, Jerzy; Przybyło, Małgorzata; Bilińska, Barbara; Styrna, Józefa

    2015-02-01

    It was revealed previously that B10.BR(Y(del)) females sired by males with the Y-chromosome long arm deletion differ from genetically identical B10.BR females sired by males with the intact Y chromosome. This is interpreted as a result of different epigenetic information which females of both groups inherit from their fathers. In the following study, we show that cumulus-oocyte complexes ovulated by B10.BR(Y(del)) females synthesize increased amounts of progesterone, which is important sperm stimulator. Because their extracellular matrix is excessively firm, the increased progesterone secretion belongs presumably to factors that compensate this feature enabling unchanged fertilization ratios. Described compensatory mechanism can act only on sperm of high quality, presenting proper receptors. Indeed, low proportion of sperm of Y(del) males that poorly fertilize B10.BR(Y(del)) oocytes demonstrates positive staining of membrane progesterone receptors. This proportion is significantly higher for sperm of control males that fertilize B10.BR(Y(del)) and B10.BR oocytes with the same efficiency. PMID:24899473

  8. Addressing Emerging Risks: Scientific and Regulatory Challenges Associated with Environmentally Persistent Free Radicals

    PubMed Central

    Dugas, Tammy R.; Lomnicki, Slawomir; Cormier, Stephania A.; Dellinger, Barry; Reams, Margaret

    2016-01-01

    Airborne fine and ultrafine particulate matter (PM) are often generated through widely-used thermal processes such as the combustion of fuels or the thermal decomposition of waste. Residents near Superfund sites are exposed to PM through the inhalation of windblown dust, ingestion of soil and sediments, and inhalation of emissions from the on-site thermal treatment of contaminated soils. Epidemiological evidence supports a link between exposure to airborne PM and an increased risk of cardiovascular and pulmonary diseases. It is well-known that during combustion processes, incomplete combustion can lead to the production of organic pollutants that can adsorb to the surface of PM. Recent studies have demonstrated that their interaction with metal centers can lead to the generation of a surface stabilized metal-radical complex capable of redox cycling to produce ROS. Moreover, these free radicals can persist in the environment, hence their designation as Environmentally Persistent Free Radicals (EPFR). EPFR has been demonstrated in both ambient air PM2.5 (diameter < 2.5 µm) and in PM from a variety of combustion sources. Thus, low-temperature, thermal treatment of soils can potentially increase the concentration of EPFR in areas in and around Superfund sites. In this review, we will outline the evidence to date supporting EPFR formation and its environmental significance. Furthermore, we will address the lack of methodologies for specifically addressing its risk assessment and challenges associated with regulating this new, emerging contaminant. PMID:27338429

  9. Addressing Emerging Risks: Scientific and Regulatory Challenges Associated with Environmentally Persistent Free Radicals.

    PubMed

    Dugas, Tammy R; Lomnicki, Slawomir; Cormier, Stephania A; Dellinger, Barry; Reams, Margaret

    2016-01-01

    Airborne fine and ultrafine particulate matter (PM) are often generated through widely-used thermal processes such as the combustion of fuels or the thermal decomposition of waste. Residents near Superfund sites are exposed to PM through the inhalation of windblown dust, ingestion of soil and sediments, and inhalation of emissions from the on-site thermal treatment of contaminated soils. Epidemiological evidence supports a link between exposure to airborne PM and an increased risk of cardiovascular and pulmonary diseases. It is well-known that during combustion processes, incomplete combustion can lead to the production of organic pollutants that can adsorb to the surface of PM. Recent studies have demonstrated that their interaction with metal centers can lead to the generation of a surface stabilized metal-radical complex capable of redox cycling to produce ROS. Moreover, these free radicals can persist in the environment, hence their designation as Environmentally Persistent Free Radicals (EPFR). EPFR has been demonstrated in both ambient air PM2.5 (diameter < 2.5 µm) and in PM from a variety of combustion sources. Thus, low-temperature, thermal treatment of soils can potentially increase the concentration of EPFR in areas in and around Superfund sites. In this review, we will outline the evidence to date supporting EPFR formation and its environmental significance. Furthermore, we will address the lack of methodologies for specifically addressing its risk assessment and challenges associated with regulating this new, emerging contaminant. PMID:27338429

  10. Emerging Infections Program Efforts to Address Health Equity

    PubMed Central

    Vugia, Duc J.; Bennett, Nancy M.; Moore, Matthew R.

    2015-01-01

    The Emerging Infections Program (EIP), a collaboration between (currently) 10 state health departments, their academic center partners, and the Centers for Disease Control and Prevention, was established in 1995. The EIP performs active, population-based surveillance for important infectious diseases, addresses new problems as they arise, emphasizes projects that lead to prevention, and develops and evaluates public health practices. The EIP has increasingly addressed the health equity challenges posed by Healthy People 2020. These challenges include objectives to increase the proportion of Healthy People–specified conditions for which national data are available by race/ethnicity and socioeconomic status as a step toward first recognizing and subsequently eliminating health inequities. EIP has made substantial progress in moving from an initial focus on monitoring social determinants exclusively through collecting and analyzing data by race/ethnicity to identifying and piloting ways to conduct population-based surveillance by using area-based socioeconomic status measures. PMID:26291875

  11. The Health and Sport Engagement (HASE) Intervention and Evaluation Project: protocol for the design, outcome, process and economic evaluation of a complex community sport intervention to increase levels of physical activity

    PubMed Central

    Mansfield, Louise; Anokye, Nana; Fox-Rushby, Julia; Kay, Tess

    2015-01-01

    Introduction Sport is being promoted to raise population levels of physical activity for health. National sport participation policy focuses on complex community provision tailored to diverse local users. Few quality research studies exist that examine the role of community sport interventions in raising physical activity levels and no research to date has examined the costs and cost-effectiveness of such provision. This study is a protocol for the design, outcome, process and economic evaluation of a complex community sport intervention to increase levels of physical activity, the Health and Sport Engagement (HASE) project part of the national Get Healthy Get Active programme led by Sport England. Methods and analysis The HASE study is a collaborative partnership between local community sport deliverers and sport and public health researchers. It involves designing, delivering and evaluating community sport interventions. The aim is to engage previously inactive people in sustained sporting activity for 1×30 min a week and to examine associated health and well-being outcomes. The study uses mixed methods. Outcomes (physical activity, health, well-being costs to individuals) will be measured by a series of self-report questionnaires and attendance data and evaluated using interrupted time series analysis controlling for a range of sociodemographic factors. Resource use will be identified and measured using diaries, interviews and records and presented alongside effectiveness data as incremental cost-effectiveness ratios and cost-effectiveness acceptability curves. A longitudinal process evaluation (focus groups, structured observations, in-depth interview methods) will examine the efficacy of the project for achieving its aim using the principles of thematic analysis. Ethics and dissemination The results of this study will be disseminated through peer-reviewed publications, academic conference presentations, Sport England and national public health organisation

  12. Addressable parallel cavity-based quantum memory

    NASA Astrophysics Data System (ADS)

    Vetlugin, Anton N.; Sokolov, Ivan V.

    2014-09-01

    We elaborate theoretically a model of addressable parallel cavity-based quantum memory for light able to store multiple transverse spatial modes of the input light signal of finite duration and, at the same time, a time sequence of the signals by side illumination. Having in mind possible applications for, e.g., quantum repeaters, we reveal the addressability of our memory, that is, its handiness for the read-out on demand of a given transverse quantized signal mode and of a given signal from the time sequence. The addressability is achieved by making use of different spatial configurations of pump wave during the write-in and the readout. We also demonstrate that for the signal durations of the order of few cavity decay times, better efficiency is achieved when one excites the cavity with zero light-matter coupling and finally performs fast excitation transfer from the intracavity field to the collective spin. On the other hand, the light-matter coupling control in time, based on dynamical impedance matching, allows to store and retrieve time restricted signals of the on-demand smooth time shape.

  13. Matching Alternative Addresses: a Semantic Web Approach

    NASA Astrophysics Data System (ADS)

    Ariannamazi, S.; Karimipour, F.; Hakimpour, F.

    2015-12-01

    Rapid development of crowd-sourcing or volunteered geographic information (VGI) provides opportunities for authoritatives that deal with geospatial information. Heterogeneity of multiple data sources and inconsistency of data types is a key characteristics of VGI datasets. The expansion of cities resulted in the growing number of POIs in the OpenStreetMap, a well-known VGI source, which causes the datasets to outdate in short periods of time. These changes made to spatial and aspatial attributes of features such as names and addresses might cause confusion or ambiguity in the processes that require feature's literal information like addressing and geocoding. VGI sources neither will conform specific vocabularies nor will remain in a specific schema for a long period of time. As a result, the integration of VGI sources is crucial and inevitable in order to avoid duplication and the waste of resources. Information integration can be used to match features and qualify different annotation alternatives for disambiguation. This study enhances the search capabilities of geospatial tools with applications able to understand user terminology to pursuit an efficient way for finding desired results. Semantic web is a capable tool for developing technologies that deal with lexical and numerical calculations and estimations. There are a vast amount of literal-spatial data representing the capability of linguistic information in knowledge modeling, but these resources need to be harmonized based on Semantic Web standards. The process of making addresses homogenous generates a helpful tool based on spatial data integration and lexical annotation matching and disambiguating.

  14. Global-Address Space Networking (GASNet) Library

    SciTech Connect

    Welcome, Michael L.; Bell, Christian S.

    2011-04-06

    GASNet (Global-Address Space Networking) is a language-independent, low-level networking layer that provides network-independent, high-performance communication primitives tailored for implementing parallel global address space SPMD languages such as UPC and Titanium. The interface is primarily intended as a compilation target and for use by runtime library writers (as opposed to end users), and the primary goals are high performance, interface portability, and expressiveness. GASNet is designed specifically to support high-performance, portable implementations of global address space languages on modern high-end communication networks. The interface provides the flexibility and extensibility required to express a wide variety of communication patterns without sacrificing performance by imposing large computational overheads in the interface. The design of the GASNet interface is partitioned into two layers to maximize porting ease without sacrificing performance: the lower level is a narrow but very general interface called the GASNet core API - the design is basedheavily on Active Messages, and is implemented directly on top of each individual network architecture. The upper level is a wider and more expressive interface called GASNet extended API, which provides high-level operations such as remote memory access and various collective operations. This release implements GASNet over MPI, the Quadrics "elan" API, the Myrinet "GM" API and the "LAPI" interface to the IBM SP switch. A template is provided for adding support for additional network interfaces.

  15. Global-Address Space Networking (GASNet) Library

    2011-04-06

    GASNet (Global-Address Space Networking) is a language-independent, low-level networking layer that provides network-independent, high-performance communication primitives tailored for implementing parallel global address space SPMD languages such as UPC and Titanium. The interface is primarily intended as a compilation target and for use by runtime library writers (as opposed to end users), and the primary goals are high performance, interface portability, and expressiveness. GASNet is designed specifically to support high-performance, portable implementations of global address spacemore » languages on modern high-end communication networks. The interface provides the flexibility and extensibility required to express a wide variety of communication patterns without sacrificing performance by imposing large computational overheads in the interface. The design of the GASNet interface is partitioned into two layers to maximize porting ease without sacrificing performance: the lower level is a narrow but very general interface called the GASNet core API - the design is basedheavily on Active Messages, and is implemented directly on top of each individual network architecture. The upper level is a wider and more expressive interface called GASNet extended API, which provides high-level operations such as remote memory access and various collective operations. This release implements GASNet over MPI, the Quadrics "elan" API, the Myrinet "GM" API and the "LAPI" interface to the IBM SP switch. A template is provided for adding support for additional network interfaces.« less

  16. OUS Diversity Report, 2004: Addressing the Needs of an Increasingly Diverse Society

    ERIC Educational Resources Information Center

    Oregon University System, 2004

    2004-01-01

    The Oregon University System (OUS) annual diversity report provides: (1) a "vision" for diversity with continuing themes regarding the enhancement of representation, inclusion, and engagement; and (2) an overview of the progress made in racial/ethnic diversity within the populations of OUS students, faculty and staff. The purposes of this report…

  17. Addressing The Achievement Gap Between Minority And Nonminority Children By Increasing Access To Gifted Programs

    ERIC Educational Resources Information Center

    Olszewski-Kubilius, Paula; Lee, Seon-Young; Ngoi, Mephie; Ngoi,Daphne

    2004-01-01

    Project EXCITE is a collaborative program of a university-based gifted center and local school districts designed to prepare gifted minority elementary and middle school students for advanced tracks in math and science in high school. This paper describes the characteristics and components of the EXCITE program and gives data regarding the…

  18. Addressing the Needs of an Increasingly Diverse Society. OUS Diversity Report, 2004

    ERIC Educational Resources Information Center

    Oregon University System, 2004

    2004-01-01

    The report includes an overview of the relevance of diverse educational environments and descriptions of the current initiatives within OUS to enhance the representation, inclusion, and engagement of diverse racial/ethnic populations. The issues associated with higher education diversity are multifaceted. Within OUS, the vision for diversity is a…

  19. Vertically integrated sensor array technology for unattended sensor networks (Keynote Address)

    NASA Astrophysics Data System (ADS)

    Balcerak, Raymond; Thurston, John; Breedlove, Jonathan

    2005-05-01

    The increasing need for unattended sensor networks drives individual sensor development, signal processing for network management, and communication technology. The application space is becoming more complex, with requirements for sensor networks in force protection; surveillance of large expanses of rugged terrain; and monitoring complex urban areas. Individual sensors exhibit excellent performance and include a wide variety of sensing modes, such as acoustic, electro-optical imaging, seismic, and radio frequency devices. These sensors continue to shrink with packaging, while applications continue to demand more of the sensor technology. Although single imaging arrays, which are available in spectral bands from the visible through the infrared, can be integrated into packages size as small as a cubic inch, the information from a single sensor is not sufficient to meet requirements for day/night, all-weather operation. This has driven the need for integration of multiple sensors into the compact packages intended for an individual sensor. A major step toward addressing the need for more effective sensor technology for unattended sensor networks is being taken through development of Vertically Integrated Sensor Array (VISA) technology. This technology, currently being developed for imaging sensors, builds multiple layers of signal processing at each pixel in the sensor array. Processing power is dramatically increased, allowing the integration of multiple sensors in small compact packages. This paper reviews the VISA approach to imaging sensors and describes applications for unattended sensors.

  20. Addressing Extremes within the WCRP - GEWEX Framework

    NASA Astrophysics Data System (ADS)

    van Oevelen, P. J.; Stewart, R.; Detemmerman, V.

    2008-12-01

    For large international coordination programs such as the Global Energy and Water Cycle Experiment (GEWEX) as part of the World Climate Research Programme (WCRP) it is difficult to strike a good balance between enabling as much international involvement as is possible and desirable and the achievability of the objectives. WCRP has decided that "Extremes Research" is one of several areas where it would like to see its efforts strengthened and scientific research pushed forward. The foci that are being selected should be phrased such that they are practical and achievable within a time span of 1 to 3 years. Preferably these foci build upon the expertise from cross WCRP activities and are not restricted to single core project activities. In this presentation an overview will be given of the various activities within GEWEX that are related to extremes and which ones would be most ideal to be addressed as WCRP foci from a GEWEX perspective. The rationale and context of extreme research will be presented as well links to other national and international programs. "Extremes Research" as a topic is attractive since it has a high societal relevance and impact. However, numerous definitions of extremes exist and they are being used in widely varying contexts making it not always clear of what exactly is being addressed. This presentation will give an outlook on what can be expected research wise in the near future based upon the outcomes of the Extremes Workshop organised last June in Vancouver in the context of the Coordinated Energy and water cycle Observations Project (CEOP) as part of GEWEX. In particular it will be shown how these activities, which will only address certain types of extremes, can be linked to adaptation and mitigation efforts taking place in other organisations and by national and international bodies.

  1. Addressing Risks to Advance Mental Health Research

    PubMed Central

    Iltis, Ana S.; Misra, Sahana; Dunn, Laura B.; Brown, Gregory K.; Campbell, Amy; Earll, Sarah A.; Glowinski, Anne; Hadley, Whitney B.; Pies, Ronald; DuBois, James M.

    2015-01-01

    Objective Risk communication and management are essential to the ethical conduct of research, yet addressing risks may be time consuming for investigators and institutional review boards (IRBs) may reject study designs that appear too risky. This can discourage needed research, particularly in higher risk protocols or those enrolling potentially vulnerable individuals, such as those with some level of suicidality. Improved mechanisms for addressing research risks may facilitate much needed psychiatric research. This article provides mental health researchers with practical approaches to: 1) identify and define various intrinsic research risks; 2) communicate these risks to others (e.g., potential participants, regulatory bodies, society); 3) manage these risks during the course of a study; and 4) justify the risks. Methods As part of a National Institute of Mental Health (NIMH)-funded scientific meeting series, a public conference and a closed-session expert panel meeting were held on managing and disclosing risks in mental health clinical trials. The expert panel reviewed the literature with a focus on empirical studies and developed recommendations for best practices and further research on managing and disclosing risks in mental health clinical trials. IRB review was not required because there were no human subjects. The NIMH played no role in developing or reviewing the manuscript. Results Challenges, current data, practical strategies, and topics for future research are addressed for each of four key areas pertaining to management and disclosure of risks in clinical trials: identifying and defining risks, communicating risks, managing risks during studies, and justifying research risks. Conclusions Empirical data on risk communication, managing risks, and the benefits of research can support the ethical conduct of mental health research and may help investigators better conceptualize and confront risks and to gain IRB approval. PMID:24173618

  2. Photosensitive biosensor array system using optical addressing without an addressing circuit on array biochips

    NASA Astrophysics Data System (ADS)

    Ahn, Chang-Geun; Ah, Chil Seong; Kim, Tae-Youb; Park, Chan Woo; Yang, Jong-Heon; Kim, Ansoon; Sung, Gun Yong

    2010-09-01

    This paper introduces a photosensitive biosensor array system with a simple photodiode array that detects photocurrent changes caused by reactions between probe and target molecules. Using optical addressing, the addressing circuit on the array chip is removed for low-cost application, and real cell addressing is achieved using an externally located computer-controllable light-emitting diode array module. The fabricated biosensor array chip shows a good dynamic range of 1-100 ng/mL under prostate-specific antigen detection, with an on-chip resolution of roughly 1 ng/mL.

  3. A Task Force to Address Bullying.

    PubMed

    Keller, Ronald; Budin, Wendy C; Allie, Tammy

    2016-02-01

    Bullying in the workplace can create a dysfunctional environment that is associated with serious physical and psychological harm to the person being bullied. Nurses' experience with bullying has gained considerable attention in recent years, and warrants further discussion. Nurse leaders need to develop and implement effective bullying prevention initiatives that will foster the functioning of a professional and productive staff in a healthy work environment. The aim of this article is to review workplace bullying as experienced by nurses, and describe how nurses at a Magnet-designated academic medical center developed and implemented a bullying task force to address the problem. PMID:26817556

  4. Building technology services that address student needs.

    PubMed

    Le Ber, Jeanne M; Lombardo, Nancy T; Wimmer, Erin

    2015-01-01

    A 16-question technology use survey was conducted to assess incoming health sciences students' knowledge of and interest in current technologies, and to identify student device and tool preferences. Survey questions were developed by colleagues at a peer institution and then edited to match this library's student population. Two years of student responses have been compiled, compared, and reviewed as a means for informing library decisions related to technology and resource purchases. Instruction and event programming have been revised to meet student preferences. Based on the number of students using Apple products, librarians are addressing the need to become more proficient with this platform. PMID:25611437

  5. Addressing the water budget with SMOS

    NASA Astrophysics Data System (ADS)

    Kerr, Y. H.; AlBitar, A.; Tomer, S. K.; Merlin, O.; Pellarin, T.

    2012-12-01

    SMOS, a L Band radiometer using aperture synthesis to achieve a good spatial resolution, was successfully launched on November 2, 2009. It was developed and made under the leadership of the European Space Agency (ESA) as an Earth Explorer Opportunity mission. It is a joint program with the Centre National d'Etudes Spatiales (CNES) in France and the Centro para el Desarrollo Teccnologico Industrial (CDTI) in Spain. SMOS carries a single payload, an L band 2D interferometric,radiometer in the 1400-1427 MHz h protected band. This wavelength penetrates well through the vegetation and the atmosphere is almost transparent enabling to infer both soil moisture and vegetation water content. SMOS achieves an unprecedented spatial resolution of 50 km at L-band maximum (43 km on average) with multi angular-dual polarized (or fully polarized) brightness temperatures over the globe and with a revisit time smaller than 3 days. SMOS as been now acquiring data for almost 2 years. The data quality exceeds what was expected, showing very good sensitivity and stability. The data is however very much impaired by man made emission in the protected band, leading to degraded measurements in several areas including parts of Europe and of China. However, many different international teams are now addressing cal val activities in various parts of the world, with notably large field campaigns either on the long time scale or over specific targets to address the specific issues. In parallel different teams are now starting addressing data use in various fields including hydrology. It requires coupling with other models and or disaggregation to address soil moisture distribution over watersheds. Significant new results were obtained for floods and drought events, together with new potential applications in terms of precipitation monitoring This paper thus gives an overview of the science goals of the SMOS mission, a description of its main elements, and a taste of the first results including

  6. Addressing the challenges of emerging infectious disease.

    PubMed

    Pinner, R W

    1996-01-01

    Through the recent examples of diphtheria in the former Soviet Union, plague in India, and trends in pneumonia mortality in the United States, the author, in this article, illustrates issues in emerging infectious diseases. The Centers for Disease Control's plan, Addressing Emerging Infectious Disease Threats: A Prevention Strategy for the United States, is summarized. Initial efforts to implement this plan are described, with particular focus on the development of Emerging Infections Programs, which are conducting epidemiologic and laboratory projects on several infectious diseases, including invasive bacterial diseases, unexplained deaths, foodborne diseases, and ehrlichiosis in four population-based sites in the United States. PMID:8571983

  7. Versions to Address Business Process Flexibility Issue

    NASA Astrophysics Data System (ADS)

    Chaâbane, Mohamed Amine; Andonoff, Eric; Bouaziz, Rafik; Bouzguenda, Lotfi

    This paper contributes to address an important issue in business process management: the Business Process (BP) flexibility issue. First, it defends that versions are an interesting solution to deal with both a priori (when designing BPs) and a posteriori (when executing BPs) flexibility. It also explains why previous contributions about versions of BPs are incomplete, and need to be revisited. Then, the paper presents a meta-model for BP versions, which combines five perspectives -the functional, process, informational, organizational and operation perspectives- for BP modelling, and which allows a comprehensive description of versionalized BPs.

  8. Complex systems thinking and current impasses in health disparities research.

    PubMed

    Diez Roux, Ana V

    2011-09-01

    Complex systems approaches have received increasing attention in public health because reductionist approaches yield limited insights in the context of dynamic systems. Most discussions have been highly abstract. There is a need to consider the application of complex systems approaches to specific research questions. I review the features of population health problems for which complex systems approaches are most likely to yield new insights, and discuss possible applications of complex systems to health disparities research. I provide illustrative examples of how complex systems approaches may help address unanswered and persistent questions regarding genetic factors, life course processes, place effects, and the impact of upstream policies. The concepts and methods of complex systems may help researchers move beyond current impasse points in health disparities research. PMID:21778505

  9. Teaching for Diversity: Addressing Diversity Issues in Responsive ESL Instruction

    ERIC Educational Resources Information Center

    Fu, Jing

    2013-01-01

    Student diversity has become a typical phenomenon in American public schools. The impact of increasing diversity on literacy instruction is unchallenged. Teachers reinforce this message by often citing ESL student diversity as a barrier for literacy teaching. In order to better understand the complexity of diversity issues, I explored two ESL…

  10. Addressing Science Use Cases with HELIO

    NASA Astrophysics Data System (ADS)

    Bentley, R. D.; Aboudarham, J.; Csillaghy, A.; Jacquey, C.; Hapgood, M. A.; Messerotti, M.; Gallagher, P.; Bocchialini, K.; Hurlburt, N. E.; Roberts, D.; Sanchez Duarte, L.

    2009-12-01

    The Heliophysics Integrated Observatory (HELIO) is a new VO project funded under the EC's Seventh Framework Programme (FP7). It includes thirteen partners scattered over six countries and is led by University College London. HELIO is designed to support the heliophysics community and is based on a Service Oriented Architecture. The services developed by and integrated into HELIO can be used to address a wide range of science problems; they can be used individually or as part of a work-flow driven search engine that can use a propagation (or other) model to help locate obervations that describe interesting phenomena. We will describe and discuss how the components of HELIO could be used to address science use cases, particularly how a user can adapt the work flow to their own science interests. Networking is one of the three Activities of the HELIO Integrated Infrastructure Initiatives (I3) project. Within this activity we plan to involve the community in all aspects of the design and testing of the HELIO system, including determining which data and metadata should be included, how the quality and content of metadata can be included, etc. We are investigating ways of making HELIO "domain-aware" so that researchers who are specialists in one of the communities that constitute heliophysics can easily identify, access and use data they need from the other communities. We will discuss how the community can help us develop this capability.

  11. Multi-port, optically addressed RAM

    NASA Technical Reports Server (NTRS)

    Johnston, Alan R. (Inventor); Nixon, Robert H. (Inventor); Bergman, Larry A. (Inventor); Esener, Sadik (Inventor)

    1989-01-01

    A random access memory addressing system utilizing optical links between memory and the read/write logic circuits comprises addressing circuits including a plurality of light signal sources, a plurality of optical gates including optical detectors associated with the memory cells, and a holographic optical element adapted to reflect and direct the light signals to the desired memory cell locations. More particularly, it is a multi-port, binary computer memory for interfacing with a plurality of computers. There are a plurality of storage cells for containing bits of binary information, the storage cells being disposed at the intersections of a plurality of row conductors and a plurality of column conductors. There is interfacing logic for receiving information from the computers directing access to ones of the storage cells. There are first light sources associated with the interfacing logic for transmitting a first light beam with the access information modulated thereon. First light detectors are associated with the storage cells for receiving the first light beam, for generating an electrical signal containing the access information, and for conducting the electrical signal to the one of the storage cells to which it is directed. There are holographic optical elements for reflecting the first light beam from the first light sources to the first light detectors.

  12. Addressing medical errors in hand surgery.

    PubMed

    Johnson, Shepard P; Adkinson, Joshua M; Chung, Kevin C

    2014-09-01

    Influential think tanks such as the Institute of Medicine have raised awareness about the implications of medical errors. In response, organizations, medical societies, and hospitals have initiated programs to decrease the incidence and prevent adverse effects of these errors. Surgeons deal with the direct implications of adverse events involving patients. In addition to managing the physical consequences, they are confronted with ethical and social issues when caring for a harmed patient. Although there is considerable effort to implement system-wide changes, there is little guidance for hand surgeons on how to address medical errors. Admitting an error by a physician is difficult, but a transparent environment where patients are notified of errors and offered consolation and compensation is essential to maintain physician-patient trust. Furthermore, equipping hand surgeons with a guide for addressing medical errors will help identify system failures, provide learning points for safety improvement, decrease litigation against physicians, and demonstrate a commitment to ethical and compassionate medical care. PMID:25154576

  13. Light addressable potentiometric sensor with an array of sensing regions

    NASA Astrophysics Data System (ADS)

    Liang, Weiguo; Han, JingHong; Zhang, Hong; Chen, Deyong

    2001-09-01

    This paper describes the mechanism of light addressable poteniometric sensors (LAPS) from the viewpoints of Semiconductor Physics, and introduces the fabrication of a multi-parameter LAPS chip. The MEMS technology is applied to produce a matrix of sensing regions on the wafer. By doing that, the cross talk among these regions is reduced, and the precision of the LAPS is increased. An IR-LED matrix is used as the light source, and the flow-injection method is used to input samples. The sensor system is compact and highly integrated. The measure and control system is composed of a personal computer, a lock-in amplifier, a potentiostat, a singlechip system, and an addressing circuit. Some experiments have been done with this device. The results show that this device is very promising for practical use.

  14. Addressing Consent Issues in Donation After Circulatory Determination of Death.

    PubMed

    Overby, Kim J; Weinstein, Michael S; Fiester, Autumn

    2015-01-01

    Given the widening gap between the number of individuals on transplant waiting lists and the availability of donated organs, as well as the recent plateau in donations based on neurological criteria (i.e., brain death), there has been a growing interest in expanding donation after circulatory determination of death. While the prevalence of this form of organ donation continues to increase, many thorny ethical issues remain, often creating moral distress in both clinicians and families. In this article, we address one of these issues, namely, the challenges surrounding patient and surrogate informed consent for donation after circulatory determination of death. First we discuss several general concerns regarding consent related to this form of organ donation, and then we address additional issues that are unique to three different patient categories: adult patients with medical decision-making capacity or potential capacity, adult patients who lack capacity, and pediatric patients. PMID:26225503

  15. An Integrated Assessment Approach to Address Artisanal and Small-Scale Gold Mining in Ghana

    PubMed Central

    Basu, Niladri; Renne, Elisha P.; Long, Rachel N.

    2015-01-01

    Artisanal and small-scale gold mining (ASGM) is growing in many regions of the world including Ghana. The problems in these communities are complex and multi-faceted. To help increase understanding of such problems, and to enable consensus-building and effective translation of scientific findings to stakeholders, help inform policies, and ultimately improve decision making, we utilized an Integrated Assessment approach to study artisanal and small-scale gold mining activities in Ghana. Though Integrated Assessments have been used in the fields of environmental science and sustainable development, their use in addressing specific matter in public health, and in particular, environmental and occupational health is quite limited despite their many benefits. The aim of the current paper was to describe specific activities undertaken and how they were organized, and the outputs and outcomes of our activity. In brief, three disciplinary workgroups (Natural Sciences, Human Health, Social Sciences and Economics) were formed, with 26 researchers from a range of Ghanaian institutions plus international experts. The workgroups conducted activities in order to address the following question: What are the causes, consequences and correctives of small-scale gold mining in Ghana? More specifically: What alternatives are available in resource-limited settings in Ghana that allow for gold-mining to occur in a manner that maintains ecological health and human health without hindering near- and long-term economic prosperity? Several response options were identified and evaluated, and are currently being disseminated to various stakeholders within Ghana and internationally. PMID:26393627

  16. An Integrated Assessment Approach to Address Artisanal and Small-Scale Gold Mining in Ghana.

    PubMed

    Basu, Niladri; Renne, Elisha P; Long, Rachel N

    2015-09-01

    Artisanal and small-scale gold mining (ASGM) is growing in many regions of the world including Ghana. The problems in these communities are complex and multi-faceted. To help increase understanding of such problems, and to enable consensus-building and effective translation of scientific findings to stakeholders, help inform policies, and ultimately improve decision making, we utilized an Integrated Assessment approach to study artisanal and small-scale gold mining activities in Ghana. Though Integrated Assessments have been used in the fields of environmental science and sustainable development, their use in addressing specific matter in public health, and in particular, environmental and occupational health is quite limited despite their many benefits. The aim of the current paper was to describe specific activities undertaken and how they were organized, and the outputs and outcomes of our activity. In brief, three disciplinary workgroups (Natural Sciences, Human Health, Social Sciences and Economics) were formed, with 26 researchers from a range of Ghanaian institutions plus international experts. The workgroups conducted activities in order to address the following question: What are the causes, consequences and correctives of small-scale gold mining in Ghana? More specifically: What alternatives are available in resource-limited settings in Ghana that allow for gold-mining to occur in a manner that maintains ecological health and human health without hindering near- and long-term economic prosperity? Several response options were identified and evaluated, and are currently being disseminated to various stakeholders within Ghana and internationally. PMID:26393627

  17. Enabling a Highly-Scalable Global Address Space Model for Petascale Computing

    SciTech Connect

    Apra, Edoardo; Vetter, Jeffrey S; Yu, Weikuan

    2010-01-01

    Over the past decade, the trajectory to the petascale has been built on increased complexity and scale of the underlying parallel architectures. Meanwhile, software de- velopers have struggled to provide tools that maintain the productivity of computational science teams using these new systems. In this regard, Global Address Space (GAS) programming models provide a straightforward and easy to use addressing model, which can lead to improved produc- tivity. However, the scalability of GAS depends directly on the design and implementation of the runtime system on the target petascale distributed-memory architecture. In this paper, we describe the design, implementation, and optimization of the Aggregate Remote Memory Copy Interface (ARMCI) runtime library on the Cray XT5 2.3 PetaFLOPs computer at Oak Ridge National Laboratory. We optimized our implementation with the flow intimation technique that we have introduced in this paper. Our optimized ARMCI implementation improves scalability of both the Global Arrays (GA) programming model and a real-world chemistry application NWChem from small jobs up through 180,000 cores.

  18. Protecting the confidentiality of interim data: addressing current challenges.

    PubMed

    Fleming, Thomas R

    2015-02-01

    There is compelling evidence supporting the importance of maintaining confidentiality of interim data in clinical trials designed to reliably address the benefit-to-risk profile of interventions. While this is widely recognized, creative approaches are needed to achieve this in challenging settings where interim data are released for regulatory review and action, even though the trial would be continued to address its primary hypothesis. An illustration is the recently emerging setting of cardiovascular safety trials in type 2 diabetes mellitus. At the first stage of such trials, if large relative increases in cardiovascular major morbidity/mortality can be ruled out, data can be released solely for the purpose of allowing regulatory decision making about marketing approval. The trial is then continued in the post-marketing setting to address the primary hypothesis regarding whether smaller relative increases can be ruled out. Active rather than passive approaches are needed to protect the integrity of cardiovascular safety trials. Given the importance to trial integrity of maintaining confidentiality of interim data such as the estimated relative effect on cardiovascular risk, a Data Access Plan should be in place in these trials to ensure such data are not revealed to study participants and their caregivers, investigators involved in trial conduct, the sponsor's management team, and the public, until trial completion. A Performance Standards Document also should be developed to pre-specify targeted and minimally acceptable levels for recruitment rate, best real-world achievable adherence, avoidance of cross-ins, and retention rate. This document should specify creative approaches for achieving these targets, oversight procedures during trial conduct to monitor performance levels, and actions to be taken if emerging data indicate minimally acceptable levels are not being reached. In settings where meaningful breaches in confidentiality have occurred, such

  19. Addressing submarine geohazards through scientific drilling

    NASA Astrophysics Data System (ADS)

    Camerlenghi, A.

    2009-04-01

    Natural submarine geohazards (earthquakes, volcanic eruptions, landslides, volcanic island flank collapses) are geological phenomena originating at or below the seafloor leading to a situation of risk for off-shore and on-shore structures and the coastal population. Addressing submarine geohazards means understanding their spatial and temporal variability, the pre-conditioning factors, their triggers, and the physical processes that control their evolution. Such scientific endeavour is nowadays considered by a large sector of the international scientific community as an obligation in order to contribute to the mitigation of the potentially destructive societal effects of submarine geohazards. The study of submarine geohazards requires a multi-disciplinary scientific approach: geohazards must be studied through their geological record; active processes must be monitored; geohazard evolution must be modelled. Ultimately, the information must be used for the assessment of vulnerability, risk analysis, and development of mitigation strategies. In contrast with the terrestrial environment, the oceanic environment is rather hostile to widespread and fast application of high-resolution remote sensing techniques, accessibility for visual inspection, sampling and installation of monitoring stations. Scientific Drilling through the IODP (including the related pre site-survey investigations, sampling, logging and in situ measurements capability, and as a platform for deployment of long term observatories at the surface and down-hole) can be viewed as the centre of gravity of an international, coordinated, multi-disciplinary scientific approach to address submarine geohazards. The IODP Initial Science Plan expiring in 2013 does not address openly geohazards among the program scientific objectives. Hazards are referred to mainly in relation to earthquakes and initiatives towards the understanding of seismogenesis. Notably, the only drilling initiative presently under way is the

  20. Heuristic dynamic complexity coding

    NASA Astrophysics Data System (ADS)

    Škorupa, Jozef; Slowack, Jürgen; Mys, Stefaan; Lambert, Peter; Van de Walle, Rik

    2008-04-01

    Distributed video coding is a new video coding paradigm that shifts the computational intensive motion estimation from encoder to decoder. This results in a lightweight encoder and a complex decoder, as opposed to the predictive video coding scheme (e.g., MPEG-X and H.26X) with a complex encoder and a lightweight decoder. Both schemas, however, do not have the ability to adapt to varying complexity constraints imposed by encoder and decoder, which is an essential ability for applications targeting a wide range of devices with different complexity constraints or applications with temporary variable complexity constraints. Moreover, the effect of complexity adaptation on the overall compression performance is of great importance and has not yet been investigated. To address this need, we have developed a video coding system with the possibility to adapt itself to complexity constraints by dynamically sharing the motion estimation computations between both components. On this system we have studied the effect of the complexity distribution on the compression performance. This paper describes how motion estimation can be shared using heuristic dynamic complexity and how distribution of complexity affects the overall compression performance of the system. The results show that the complexity can indeed be shared between encoder and decoder in an efficient way at acceptable rate-distortion performance.