WorldWideScience

Sample records for complex worksite requiring

  1. The LHC Continuous Cryostat Interconnections The Organization of a Logistically Complex Worksite Requiring Strict Quality Standards and High Output

    CERN Document Server

    Fessia, P; Bozzini, D; Cruikshank, P; Jacquemod, A; Maan, W; Musso, A; Oberli, L; Poncet, A; Russenschuck, Stephan; Savary, F; Struik, M; Tock, J Ph; Tommasini, D; Völlinger, C; Kotarba, A; Olek, S; Sulek, Z; Grimaud, A; Vaudaux, L

    2008-01-01

    The interconnections of the Large Hadron Collider (LHC) continuous cryostat have been completed in fall 2007: 1695 interconnections magnet to magnet and 224 interconnections between the continuous cryostat and the cryogenic distribution line have been executed along the 27 km of the LHC. The very tight schedule, the complexity of the interconnection sequence, the strict quality standards applied have required the creation of an ad hoc organization in order to steer and coordinate the activities on the worksite dispersed along the whole accelerator ring. The concatenation of construction and test phases carried out by CERN staff, CERN collaborating institutes and contractors have led to the necessity of a common approach and of a very effective information flow. In this paper, after having recalled the main technical challenges, we review the organizational choices that have been taken and we briefly analyze the development of the worksite in term of allocated resources and production.

  2. Update on Validity of Required Competencies for Worksite Health Professionals

    Science.gov (United States)

    Becker, Craig; Rager, Robin C.; Wright, Fred Egbert

    2013-01-01

    Background: To improve global health, the workforce capacity of health promotion professionals must be strengthened through the provision of competencies necessary to deliver effective programs. Purpose: This study provides an updated analysis of the validity of the worksite health promotion (WHP) professional competencies developed in 2000 by the…

  3. Moving the worksite health promotion profession forward: is the time right for requiring standards? A review of the literature.

    Science.gov (United States)

    Watkins, Cecilia; English, Gary

    2015-01-01

    Standards in any profession are adopted to assure that the individuals hired are adequately trained and the programs that they oversee are of the highest quality. Worksite health promotion should be no different from any other field. A review of the research conducted by experts in worksite health promotion is examined, along with an assessment of skills needed to ensure that wellness programs are effective and employees, their families, and even their communities are educated on the ways to best prevent chronic diseases and occupational incidences through healthy and safe behaviors. This article is consistent with Health Promotion Practice's mission and focuses on the exploration of the processes used to plan effective worksite health promotion programs, and it suggests initial discussions on whether these processes should become standards for professionals in the worksite health promotion field.

  4. Potentials for health promotion at worksite

    DEFF Research Database (Denmark)

    Nygaard, Rikke; Mikkelsen, Bent Egberg

    2013-01-01

    their worksite foodscapes and we will identify barriers that should be taken into account in the planning of food based innovations at worksites. This study shows that the shaping of eating patterns evolves in a complex matrix of cultural, social, mental and ethnic influences and that worksites can play......Eating has an immense impact on our health, and the contribution of research literature that tries to understand and explain our food habits has grown considerably over the past decades. These studies have showed that in our eating behaviour, we interact not only with the physical environment...... but also with the social and mental environment. Food and eating has increasingly become an object of public governance, especially when we are eating out of home as part of our work or educational life. Interventions aiming at improve our eating patterns have become mainstream in many of our everyday life...

  5. Social shaping of food intervention initiatives at worksites: Canteen takeaway schemes at two Danish hospitals

    DEFF Research Database (Denmark)

    Poulsen, Signe; Jørgensen, Michael Søgaard

    2011-01-01

    AIMS: The aim of this article is to analyse the social shaping of worksite food interventions at two Danish worksites. The overall aims are to contribute first, to the theoretical frameworks for the planning and analysis of food and health interventions at worksites and second, to a foodscape......, to take home or to eat at the worksite during irregular working hours. Data collection was carried out through semi-structured interviews with stakeholders within the two change processes. Two focus group interviews were also carried out at one hospital and results from a user survey carried out by other...... researchers at the other hospital were included. Theoretically, the study was based on the social constitution approach to change processes at worksites and a co-evolution approach to problem–solution complexes as part of change processes. RESULTS: Both interventions were initiated because of the need...

  6. Using organization theory to understand the determinants of effective implementation of worksite health promotion programs.

    Science.gov (United States)

    Weiner, Bryan J; Lewis, Megan A; Linnan, Laura A

    2009-04-01

    The field of worksite health promotion has moved toward the development and testing of comprehensive programs that target health behaviors with interventions operating at multiple levels of influence. Yet, observational and process evaluation studies indicate that such programs are challenging for worksites to implement effectively. Research has identified several organizational factors that promote or inhibit effective implementation of comprehensive worksite health promotion programs. However, no integrated theory of implementation has emerged from this research. This article describes a theory of the organizational determinants of effective implementation of comprehensive worksite health promotion programs. The model is adapted from theory and research on the implementation of complex innovations in manufacturing, education and health care settings. The article uses the Working Well Trial to illustrate the model's theoretical constructs. Although the article focuses on comprehensive worksite health promotion programs, the conceptual model may also apply to other types of complex health promotion programs. An organization-level theory of the determinants of effective implementation of worksite health promotion programs.

  7. Central waste complex interim operational safety requirements

    Energy Technology Data Exchange (ETDEWEB)

    Bendixsen, R.B.; Ames, R.R., Fluor Daniel Hanford

    1997-03-20

    This Interim Operational Safety Requirements document supports the authorization basis for interim operations and identifies restrictions on interim operations for the disposal and storage of solid waste in the Central Waste Complex. The Central Waste Complex Interim Operational Safety Requirements provide the necessary controls on operations in the Central Waste Complex to ensure the radiological and hazardous material exposure will be acceptable from an overall health and safety standpoint to the worker, the onsite personnel, 1327 the public and the environment.

  8. Effectiveness of worksite physical activity counseling

    NARCIS (Netherlands)

    Proper, K.I.

    2003-01-01

    The aim of this thesis was to describe the effectiveness of a particular worksite physical activity intervention involving individual counseling of workers. First, a summary of the existing literature is given as to the effectiveness of worksite physical activity programs. A strong evidence was foun

  9. Minimum Energy Requirements in Complex Distillation Arrangements

    Energy Technology Data Exchange (ETDEWEB)

    Halvorsen, Ivar J.

    2001-07-01

    Distillation is the most widely used industrial separation technology and distillation units are responsible for a significant part of the total heat consumption in the world's process industry. In this work we focus on directly (fully thermally) coupled column arrangements for separation of multicomponent mixtures. These systems are also denoted Petlyuk arrangements, where a particular implementation is the dividing wall column. Energy savings in the range of 20-40% have been reported with ternary feed mixtures. In addition to energy savings, such integrated units have also a potential for reduced capital cost, making them extra attractive. However, the industrial use has been limited, and difficulties in design and control have been reported as the main reasons. Minimum energy results have only been available for ternary feed mixtures and sharp product splits. This motivates further research in this area, and this thesis will hopefully give some contributions to better understanding of complex column systems. In the first part we derive the general analytic solution for minimum energy consumption in directly coupled columns for a multicomponent feed and any number of products. To our knowledge, this is a new contribution in the field. The basic assumptions are constant relative volatility, constant pressure and constant molar flows and the derivation is based on Underwood's classical methods. An important conclusion is that the minimum energy consumption in a complex directly integrated multi-product arrangement is the same as for the most difficult split between any pair of the specified products when we consider the performance of a conventional two-product column. We also present the Vmin-diagram, which is a simple graphical tool for visualisation of minimum energy related to feed distribution. The Vmin-diagram provides a simple mean to assess the detailed flow requirements for all parts of a complex directly coupled arrangement. The main purpose in

  10. Strengthening environmental and educational nutrition programmes in worksite cafeterias and supermarkets in The Netherlands.

    Science.gov (United States)

    Steenhuis, I H; Van Assema, P; Glanz, K

    2001-03-01

    The purpose of this study was to assess conditions for the adoption and continued implementation of different healthy nutrition programmes in worksite cafeterias and supermarkets, i.e. an educational programme and two environmental programmes (a food labelling programme and a food supply programme). Twenty semi-structured interviews were conducted with representatives of worksite cafeterias and supermarkets. Concepts of theories of diffusion were used as a framework for the study. Questions were formulated about the attributes of the innovation, and organizational and personal characteristics that might influence programme adoption and implementation. Results indicated that educational and environmental programmes in both worksite cafeterias and supermarkets should meet specific requirements regarding programme design, methods and materials in order to be adopted and implemented. Besides, some important implementation strategies of the educational and environmental programmes were identified. It is concluded that it seems feasible to conduct educational and environmental intervention programmes in worksite cafeterias and supermarkets, but that certain conditions for adoption and continued implementation have to be met. Based on the implications of this study, the development of an educational programme, a labelling programme and a food supply programme was completed.

  11. Implementing healthier foodservice guidelines in hospital and federal worksite cafeterias: barriers, facilitators and keys to success.

    Science.gov (United States)

    Jilcott Pitts, S B; Graham, J; Mojica, A; Stewart, L; Walter, M; Schille, C; McGinty, J; Pearsall, M; Whitt, O; Mihas, P; Bradley, A; Simon, C

    2016-12-01

    Healthy foodservice guidelines are being implemented in worksites and healthcare facilities to increase access to healthy foods by employees and public populations. However, little is known about the barriers to and facilitators of implementation. The present study aimed to examine barriers to and facilitators of implementation of healthy foodservice guidelines in federal worksite and hospital cafeterias. Using a mixed-methods approach, including a quantitative survey followed by a qualitative, in-depth interview, we examined: (i) barriers to and facilitators of implementation; (ii) behavioural design strategies used to promote healthier foods and beverages; and (iii) how implementation of healthy foodservice guidelines influenced costs and profitability. We used a purposive sample of five hospital and four federal worksite foodservice operators who recently implemented one of two foodservice guidelines: the United States Department of Health and Human Services/General Services Administration Health and Sustainability Guidelines ('Guidelines') in federal worksites or the Partnership for a Healthier America Hospital Healthier Food Initiative ('Initiative') in hospitals. Descriptive statistics were used to analyse quantitative survey data. Qualitative data were analysed using a deductive approach. Implementation facilitators included leadership support, adequate vendor selections and having dietitians assist with implementation. Implementation barriers included inadequate selections from vendors, customer complaints and additional expertise required for menu labelling. Behavioural design strategies used most frequently included icons denoting healthier options, marketing using social media and placement of healthier options in prime locations. Lessons learned can guide subsequent steps for future healthy foodservice guideline implementation in similar settings. © 2016 The British Dietetic Association Ltd.

  12. Can worksite nutritional interventions improve productivity and firm profitability?

    DEFF Research Database (Denmark)

    Jensen, Jørgen Dejgård

    2011-01-01

    ’ nutritional knowledge, food intake and health and on the firm’s profitability, mainly in terms of reduced absenteeism and presenteeism. Conclusions: Well-targeted and efficiently implemented diet-related worksite health promotion interventions may improve labour productivity by 1%–2%. On larger worksites...

  13. Nutrition Programs in the Workplace. WBGH Worksite Wellness Series.

    Science.gov (United States)

    Glanz, Karen

    As is the case with other worksite wellness programs, company-sponsored nutrition programs have been expanding both in numbers and in depth. Besides offering a convenient health-enhancing benefit to employees, worksite nutrition programs benefit business by preventing several costly nutrition-related health problems, enhancing employees' overall…

  14. Worksite interventions to increase stair climbing; reasons for caution.

    Science.gov (United States)

    Eves, Frank F; Webb, Oliver J

    2006-07-01

    Point-of-choice prompts to use the stairs rather than the escalator consistently increase physical activity at public access staircases such as those in shopping malls. More recently, exercise promoters have targeted stair climbing in the worksite. A review of interventions in worksites reveals little hard evidence of successful increases in stair climbing, though the increases in stair usage are encouraging. The contrast between the worksites and public access staircases, however, is not simply one of location. In a worksite, the choice is between the stairs and an elevator rather than an escalator. We reason that the availability of the elevator or the stairwell may be the major immediate determinant of stair climbing in worksites and dilute any possible effects of an intervention.

  15. Eating at worksites in Nordic countries: national experiences and policy initiatives

    DEFF Research Database (Denmark)

    Jørgensen, Michael Søgaard; Arsky, Gunn Helene; Brandhøj, Mia

    2010-01-01

    with healthier worksite eating schemes based on employee participation can change the worksite eating substantially, also at blue-collar worksites. However, the dissemination to other worksites not participating in experiments seems limited. There is need for more research in the embedding of experiments...

  16. A Complexity measure based on Requirement Engineering Document

    CERN Document Server

    Sharma, Ashish

    2010-01-01

    Research shows, that the major issue in development of quality software is precise estimation. Further this estimation depends upon the degree of intricacy inherent in the software i.e. complexity. This paper attempts to empirically demonstrate the proposed complexity which is based on IEEE Requirement Engineering document. It is said that a high quality SRS is pre requisite for high quality software. Requirement Engineering document (SRS) is a specification for a particular software product, program or set of program that performs some certain functions for a specific environment. The various complexity measure given so far are based on Code and Cognitive metrics value of software, which are code based. So these metrics provide no leverage to the developer of the code. Considering the shortcoming of code based approaches, the proposed approach identifies complexity of software immediately after freezing the requirement in SDLC process. The proposed complexity measure compares well with established complexity...

  17. Death at the Worksite: Helping Grieving Family Members

    Science.gov (United States)

    ... Grief at Work Working Through Grief About Us Death at the Worksite: Helping Grieving Family Members By ... fatal heart attacks occur in the workplace. Other deaths — from accidents, for example — can also happen during ...

  18. Using Augmented Reality to Plan Virtual Construction Worksite

    Directory of Open Access Journals (Sweden)

    Xiangyu Wang

    2008-11-01

    Full Text Available Current construction worksite layout planning heavily relies on 2D paper media where the worksite planners sketch the future layout adjacent to their real environment. This traditional approach turns out to be ineffective and prone to error because only experienced and well-trained planners are able to generate the effective layout design with paper sketch. Augmented Reality (AR, as a new user interface technology, introduces a completely new perspective for construction worksite planning. This paper disucsses the related AR work and issues in construction and describes the concept and prototype of an AR-based construction planning tool, AR Planner with virtual elements sets and tangible interface. The focus of the paper is to identify and integrate worksite planning rules into the AR planner with the purpose of intelligently preventing potential planning errors and process inefficiency, thus maximizing the overall productivity. Future work includes refining and verifying AR Planner in realistic projects.

  19. Worksite health and wellness programs in India.

    Science.gov (United States)

    Babu, Abraham Samuel; Madan, Kushal; Veluswamy, Sundar Kumar; Mehra, Rahul; Maiya, Arun G

    2014-01-01

    Worksite health and wellness (WH&W) are gaining popularity in targeting cardiovascular (CV) risk factors among various industries. India is a large country with a larger workforce in the unorganized sector than the organized sector. This imbalance creates numerous challenges and barriers to implementation of WH&W programs in India. Large scale surveys have identified various CV risk factors across various industries. However, there is scarcity of published studies focusing on the effects of WH&W programs in India. This paper will highlight: 1) the current trend of CV risk factors across the industrial community, 2) the existing models of delivery for WH&W in India and their barriers, and 3) a concise evidence based review of various WH&W interventions in India.

  20. Worksite Characteristics and Environmental and Policy Supports for Cardiovascular Disease Prevention in New York State

    Directory of Open Access Journals (Sweden)

    Ian Brissette, PhD

    2008-04-01

    Full Text Available IntroductionWorksite policy and environmental supports that promote physical activity, healthy eating, stress management, and preventive health screenings can contribute to the prevention of cardiovascular disease and lower employer costs. This study examines the availability of these four categories of supports in a statewide survey of New York State worksites.MethodsIn 2002, we recruited a statewide sample of worksites in New York State with 75 or more employees to participate in a mailed survey assessing worksite policy and environmental supports for wellness and health promotion. The overall response rate was 34.8%. The analysis included data from 832 worksites.ResultsWorksite size was an independent predictor of health promotion supports with small (75–99 employees and medium-small (100–199 employees worksites reporting significantly fewer policy and environmental supports in all four categories than worksites with 300 or more employees. Worksites in which most employees were nonwhite reported fewer supports for physical activity, healthy eating, and stress management than worksites in which most employees were white. A wellness committee or wellness coordinator was associated with more health promotion supports, regardless of the size of the worksite or composition of its workforce.ConclusionWorksites with fewer than 200 employees have an increased need for assistance in establishing environmental and policy supports promoting cardiovascular health. Worksites that have a wellness committee or coordinator are better able to establish and sustain supports with the potential to improve the health of their workers.

  1. Application of Strength Requirements to Complex Loading Scenarios

    Science.gov (United States)

    England, Scott; Rajulu, Sudhakar

    2016-01-01

    NASA's endeavors in human spaceflight rely on extensive volumes of human-systems integration requirements to ensure mission success. These requirements protect for space hardware accommodation for the full range of potential crewmembers, but cannot cover every possible action and contingency in detail. This study was undertaken in response to questions from various strength requirement users who were unclear how to apply idealized strength requirements that did not map well to the complex loading scenarios that crewmembers would encounter. Three of the most commonly occurring questions from stakeholders were selected to be investigated with human testing and human modeling. Preliminary findings indicate deviation from nominal postures can affect strength requirement compliance positively or negatively, depending on the nature of the deviation. Human modeling offers some avenues for quickly addressing requirement verification questions, but is limited by the fidelity of the model and environment.

  2. The worksite for the tram-line reaches CERN

    CERN Multimedia

    2009-01-01

    The civil-engineering work for the tram-line outside CERN starts on 16 February. The zones affected by the work. The darkest line represents the part of the road where the work will be carried out between March and July 2009.The worksite for the section of tram-line between Meyrin-Village and CERN is entering a new phase. The contractors are to begin by upgrading the underground pipelines to comply with the installation requirements for the tramline track. The next stage will be to install the track itself, which will entail a complete reconstruction of the roadway. In the coming weeks a roundabout will be created in front of Gate A, which will allow CERN personnel travelling towards Saint-Genis-Pouilly to exit via Gate A rather than having to use the car park where the flags are as a thoroughfare. Once the roundabout is complete, it is planned to prohibit direct access to the Route de Meyrin at Gate B via this car park to all traffic ...

  3. University Worksite Health-Promotion Programs: An Opportunity for Experiential Learning

    Science.gov (United States)

    Leininger, Lisa; Adams, Kent

    2017-01-01

    Worksite health-promotion programs (WHPPs) are prevalent in a variety of worksite settings, including universities, due to their numerous individual health and organizational benefits. Simultaneously, WHPPs provide many employment opportunities for kinesiology graduates. However, few students graduate with applied experience in worksite health…

  4. Selected aspects of worksite health promotion (WHP in the Czech republic

    Directory of Open Access Journals (Sweden)

    Radim Šlachta

    2010-03-01

    Full Text Available The World Health Organisation (WHO and other internationally active Worksite Health Promotion (WHP organizations co-ordinately aim to implement a healthy lifestyle by health programmes. They also specify general principles to prevent the mass occurrence of non-infectious diseases in the world. Recommended programs are in developed countries usually implemented by administrative institutions and authorities and their results are evaluated. This paper aims to evaluate the implementation of recommended programmes in the Czech Republic by specific aspects - cultural, legislative, medical, economic etc. The paper is an introductory study in a complex and comprehensive interdisciplinary field of human health in the context of workplace and sustainable social development.

  5. State analysis requirements database for engineering complex embedded systems

    Science.gov (United States)

    Bennett, Matthew B.; Rasmussen, Robert D.; Ingham, Michel D.

    2004-01-01

    It has become clear that spacecraft system complexity is reaching a threshold where customary methods of control are no longer affordable or sufficiently reliable. At the heart of this problem are the conventional approaches to systems and software engineering based on subsystem-level functional decomposition, which fail to scale in the tangled web of interactions typically encountered in complex spacecraft designs. Furthermore, there is a fundamental gap between the requirements on software specified by systems engineers and the implementation of these requirements by software engineers. Software engineers must perform the translation of requirements into software code, hoping to accurately capture the systems engineer's understanding of the system behavior, which is not always explicitly specified. This gap opens up the possibility for misinterpretation of the systems engineer's intent, potentially leading to software errors. This problem is addressed by a systems engineering tool called the State Analysis Database, which provides a tool for capturing system and software requirements in the form of explicit models. This paper describes how requirements for complex aerospace systems can be developed using the State Analysis Database.

  6. Automated Derivation of Complex System Constraints from User Requirements

    Science.gov (United States)

    Foshee, Mark; Murey, Kim; Marsh, Angela

    2010-01-01

    The Payload Operations Integration Center (POIC) located at the Marshall Space Flight Center has the responsibility of integrating US payload science requirements for the International Space Station (ISS). All payload operations must request ISS system resources so that the resource usage will be included in the ISS on-board execution timelines. The scheduling of resources and building of the timeline is performed using the Consolidated Planning System (CPS). The ISS resources are quite complex due to the large number of components that must be accounted for. The planners at the POIC simplify the process for Payload Developers (PD) by providing the PDs with a application that has the basic functionality PDs need as well as list of simplified resources in the User Requirements Collection (URC) application. The planners maintained a mapping of the URC resources to the CPS resources. The process of manually converting PD's science requirements from a simplified representation to a more complex CPS representation is a time-consuming and tedious process. The goal is to provide a software solution to allow the planners to build a mapping of the complex CPS constraints to the basic URC constraints and automatically convert the PD's requirements into systems requirements during export to CPS.

  7. State analysis requirements database for engineering complex embedded systems

    Science.gov (United States)

    Bennett, Matthew B.; Rasmussen, Robert D.; Ingham, Michel D.

    2004-01-01

    It has become clear that spacecraft system complexity is reaching a threshold where customary methods of control are no longer affordable or sufficiently reliable. At the heart of this problem are the conventional approaches to systems and software engineering based on subsystem-level functional decomposition, which fail to scale in the tangled web of interactions typically encountered in complex spacecraft designs. Furthermore, there is a fundamental gap between the requirements on software specified by systems engineers and the implementation of these requirements by software engineers. Software engineers must perform the translation of requirements into software code, hoping to accurately capture the systems engineer's understanding of the system behavior, which is not always explicitly specified. This gap opens up the possibility for misinterpretation of the systems engineer's intent, potentially leading to software errors. This problem is addressed by a systems engineering tool called the State Analysis Database, which provides a tool for capturing system and software requirements in the form of explicit models. This paper describes how requirements for complex aerospace systems can be developed using the State Analysis Database.

  8. Improving sleep: outcomes from a worksite healthy sleep program.

    Science.gov (United States)

    Steffen, Mark W; Hazelton, Angela C; Moore, Wendy R; Jenkins, Sarah M; Clark, Matthew M; Hagen, Philip T

    2015-01-01

    Unhealthy and inadequate sleep is a common and significant problem impacting absenteeism, presenteeism, health, and productivity. This study aimed at analyzing the effect of a worksite-based healthy sleep program. Retrospective analysis of 53 adult members of a worksite wellness center who participated in an 8-week healthy sleep program and completed pre- and postintervention health behavior questionnaires. Following the intervention participants felt significantly more rested, more confident in their ability to deal with sleep problems, and more knowledgeable about sleep. In addition, they reported a reduction in their stress level, improved quality of life, and increase energy level. These results support the effectiveness of worksite programs designed to promote healthy sleep. Future randomized studies are needed to further investigate the effectiveness and optimal delivery of healthy sleep promotion.

  9. The tramway worksite edges ever closer to CERN

    CERN Multimedia

    DG Unit

    2009-01-01

    You will have probably noticed that worksite machinery has been installed opposite CERN’s Gate A. They are carrying out work in preparation for the major tramway worksite that is due to reach CERN in a few weeks’ time. This preliminary work should cause no disruption to traffic. Full information on the tramway worksite adjacent to CERN’s Meyrin site will be published in forthcoming issues of the Bulletin. The traffic arrangements on the outskirts of Meyrin village will be modified with effect from 2 February. The section of the Route de Meyrin between the Avenue de Vaudagne and the roundabout at the intersection with Avenue J.-D.-Maillard/Chemin de la Planche will be closed off to traffic. Access to the Hôpital de la Tour will remain unchanged. Diversion signs to the centre of the village will be in operation. More information at http://www.way-tram.ch

  10. Can worksite nutritional interventions improve productivity and firm profitability?

    DEFF Research Database (Denmark)

    Jensen, Jørgen Dejgård

    2011-01-01

    Aims: This paper investigates whether and how worksite nutrition policies can improve employee productivity. Methods: The questions are pursued through a literature review, including a systematic search of literature – combined with literature identified from backward references – on randomized...... controlled or quasi-experimental worksite intervention trials and observational cross-sectional studies. Studies were selected on the basis of topic relevance, according to publication title and subsequently according to abstract content. A quality appraisal of the studies was based on study design...... and clarity in definition of interventions, as well as environmental and outcome variables. Results: The search identified 2,358 publications, 30 of which were found suitable for the review. Several of the reviewed studies suggest that diet-related worksite interventions have positive impacts on employees...

  11. GPS and Electronic Fence Data Fusion for Positioning within Railway Worksite Scenarios

    DEFF Research Database (Denmark)

    Figueiras, Joao; Grønbæk, Lars Jesper; Ceccarelli, Andrea

    2012-01-01

    for personalized warning systems for railway workers, where the safety aspects require timely and precise identification whether a worker is located in a dangerous (red) or safe (green) zone within the worksite. The paper proposes and analyzes a data fusion approach based on low-cost GPS receivers integrated...... on mobile devices, combined with electronic fences strategically placed in the adjacent boundaries between safe and unsafe geographic zones. An approach based on the combination of a Kalman Filter for GPS-based trajectory estimation and a Hidden Markov Model for inclusion of mobility constraints and fusion...

  12. Building a sustainable administrative infrastructure for worksite wellness programs.

    Science.gov (United States)

    Chapman, Larry S

    2009-01-01

    As health care reform intensifies increasing references are being made to Worksite Wellness. These references are naturally leading to higher expectations for the effectiveness of Worksite Wellness programs. Yet the ultimate provisions regarding prevention and Wellness are not known. In the absence of legislative outcomes the focus for this edition is on the necessary administrative infrastructure that is needed to produce behavioral change, health risk mitigation and economic return from Wellness programming. Sixteen (16) administrative components are identified as critical to effective Wellness programming. Employee or health plan population size is seen as a significant variable in the design of the Wellness program's administrative infrastructure. Factors in sustainability and programming are also considered.

  13. Best practices in evaluating worksite health promotion programs.

    Science.gov (United States)

    Grossmeier, Jessica; Terry, Paul E; Cipriotti, Aldo; Burtaine, Jeffrey E

    2010-01-01

    Program evaluation is generally recognized as a "best practice" activity for worksite health promotion programs. The importance of "best practice" worksite health promotion programming is increasing with the stakes anticipated by health care reform. Volvo's health promotion activities are used as an example of "best practice" programming with a particular focus on creating a dashboard of evaluation metrics that can meet the accountability needs of senior management. The role of a comprehensive evaluation framework using nine components is explored along with reasonable expectations for program outcomes. Finally, stakeholder utility from the evaluation approach is explored.

  14. Supplemental design requirements document solid waste operations complex

    Energy Technology Data Exchange (ETDEWEB)

    Ocampo, V.P.; Boothe, G.F.; Broz, D.R.; Eaton, H.E.; Greager, T.M.; Huckfeldt, R.A.; Kooiker, S.L.; Lamberd, D.L.; Lang, L.L.; Myers, J.B. [and others

    1994-11-01

    This document provides additional and supplemental information to the WHC-SD-W112-FDC-001, WHC-SD-W113-FDC-001, and WHC-SD-W100-FDC-001. It provides additional requirements for the design and summarizes Westinghouse Hanford Company key design guidance and establishes the technical baseline agreements to be used for definitive design common to the Solid Waste Operations Complex (SWOC) Facilities (Project W-112, Project W-113, and WRAP 2A).

  15. Can weight management programs in worksites reduce the obesity epidemic?

    Science.gov (United States)

    Worksites can potentially be important locations for weight management programs that contribute to curbing the national obesity epidemic. In published studies, weight loss programs targeting overweight and obese employees have been relatively more effective for weight loss than programs for preventi...

  16. Worksite health promotion programs with environmental changes a systematic review

    NARCIS (Netherlands)

    Engbers, L.H.; Poppel, van M.N.M.; Chin A Paw, M.J.M.; Mechelen, van W.

    2005-01-01

    BACKGROUND: It is now widely believed that health promotion strategies should go beyond education or communication to achieve significant behavioral changes among the target population. Environmental modifications are thought to be an important addition to a worksite health promotion program (WHPP).

  17. A nutrition labeling intervention in worksite cafeterias: an implementation evaluation across two large catering companies in the Netherlands.

    Science.gov (United States)

    Vyth, Ellis L; Van Der Meer, Esther W C; Seidell, Jacob C; Steenhuis, Ingrid H M

    2012-06-01

    By both increasing the availability of healthy foods and labeling these products with the Choices logo, caterers may facilitate employees to make a healthier choice in their worksite cafeterias. The aim of this study was to explore which attributes influence the implementation of the Choices logo in worksite cafeterias in the Netherlands. Questionnaires were completed by catering managers of 316 cafeterias of two large caterers in the Netherlands (response rate 49.8%). Attributes from the Diffusion of Innovations Theory were used to investigate whether they could predict implementation. Compatibility (consistency with the beliefs of the catering manager; OR = 1.52), voluntariness (perception of the implementation as voluntary; OR = 0.50), result demonstrability (ability to communicate the implementation; OR = 1.52) and complexity in the sense of time (time needed for implementation; OR = 0.70) were the best predictors for the frequency of offering fresh Choices products (all significant). For the frequency of using Choices promotion material, voluntariness (OR = 0.54), result demonstrability (OR = 1.51) and relative advantage (perceived advantage of the implementation; OR = 1.44) were the best predictors (all significant). In conclusion, this study provides unique insights into which perceived attributes influence the implementation of a nutrition logo in worksite cafeterias. To increase the implementation, the Choices logo should be consistent with catering managers' ideas about healthy food, the workload of implementing the logo should be limited and it could be recommended to incorporate the logo in the health policy of the caterer.

  18. [Worksite physical activity and nutrition programmes: beneficial to our health and wallet?].

    Science.gov (United States)

    van Wier, Marieke F; van Dongen, J M Hanneke; van Tulder, Maurits W

    2013-01-01

    The unhealthy lifestyle of many Dutch employees may negatively influence their health in general as well as their ability to work. Worksite physical activity, nutrition or combination programmes could improve employee health and, as a consequence of this, reduce costs due to illness absenteeism, early retirement, and health care use. In this article, we present current scientific research in terms of health-related effectiveness, cost-effectiveness and the financial return of these programmes. There is moderate evidence that programmes aimed at nutrition, as well as combined nutrition-and-physical activity programmes, do result in modest improvements in weight-related outcomes and the consumption of fruit, vegetables and fat after 6-12 months. There is also moderate evidence that physical fitness programmes improve physical activity and fitness in the short term. The programmes result in financial returns for the employer, but this conclusion is based on non-randomised studies. No firm conclusions can be drawn regarding their cost-effectiveness. Wide implementation of singular worksite physical activity, nutrition or combination programmes is therefore currently discouraged. It would probably be more effective and economical to set up a broad range of interventions and measures. This requires more research, however, as well as more opportunities for offering tailor-made programmes.

  19. GPS and Electronic Fence Data Fusion for Positioning within Railway Worksite Scenarios

    DEFF Research Database (Denmark)

    Figueiras, Joao; Grønbæk, Lars Jesper; Ceccarelli, Andrea

    2012-01-01

    Context-dependent decisions in safety-critical applications require careful consideration of accuracy and timeliness of the underlying context information. Relevant examples include location-dependent actions in mobile distributed systems. This paper considers localization functions for personali......Context-dependent decisions in safety-critical applications require careful consideration of accuracy and timeliness of the underlying context information. Relevant examples include location-dependent actions in mobile distributed systems. This paper considers localization functions...... for personalized warning systems for railway workers, where the safety aspects require timely and precise identification whether a worker is located in a dangerous (red) or safe (green) zone within the worksite. The paper proposes and analyzes a data fusion approach based on low-cost GPS receivers integrated...

  20. Mental health, absenteeism and earnings at a large manufacturing worksite.

    Science.gov (United States)

    French, Michael T.; Zarkin, Gary A.

    1998-12-01

    BACKGROUND: A few recent studies have examined the relationship between mental illness and labor market variables. The findings are inconsistent, however, and leave unanswered many questions concerning both the nature and magnitude of the relationship. AIMS OF THE STUDY: A recently available worksite-based data set is analyzed to explore the relationship between symptoms of emotional and psychological problems and employee absenteeism and earnings among employees at a large US worksite. METHODS: The analysis was based on data collected through a random and anonymous survey of workers at a large US manufacturing worksite. Two measures of absenteeism are combined - days absent during the past 30 days due to sickness or injury and days absent during the past 30 days because the employee did not want to be at work - to create both a dichotomous (i.e., ever absent) and a continuous (i.e., number of days absent) absenteeism variable. Annual earnings were measured as personal earnings from the primary job. Various statistical models were tested to determine the independent and joint (with alcohol and illicit drug use) relationship between symptoms of emotional problems and labor market variables. RESULTS: The analysis consistently finds that workers who report symptoms of emotional/psychological problems have higher absenteeism and lower earnings than otherwise similar coworkers. This finding is robust to model specification and to the inclusion of comorbid conditions such as alcohol and illicit drug use. DISCUSSION: This study contributes new information to the literature in this area by estimating the effects of emotional/psychological symptoms on two important labor market variables: absenteeism and earnings. Several specifications of the absenteeism and earnings equations were estimated to test the independent effect of emotional symptoms and the joint effects of emotional symptoms and other comorbid conditions. The results suggest that employers should consider the

  1. Using nudging and social marketing techniques to create healthy worksite cafeterias in the Netherlands: intervention development and study design

    OpenAIRE

    Velema, Elizabeth; Vyth, Ellis L.; Steenhuis, Ingrid H. M.

    2017-01-01

    Background The worksite cafeteria is a suitable setting for interventions focusing on changing eating behavior, because a lot of employees visit the worksite cafeteria regularly and a variety of interventions could be implemented there. The aim of this paper is to describe the intervention development and design of the evaluation of an intervention to make the purchase behavior of employees in the worksite cafeteria healthier. The developed intervention called “the worksite cafeteria 2.0” con...

  2. Factors related to participatory employee advisory boards in small, blue-collar worksites.

    Science.gov (United States)

    Thompson, Beti; Hannon, Peggy A; Bishop, Sonia K; West, Briana E; Peterson, Amber K; Beresford, Shirley A A

    2005-01-01

    To identify factors related to formation, participation, and characteristics of employee advisory boards (EABs) in blue-collar worksites. This study used a nonexperimental qualitative design to assess EAB formation, activity, and enthusiasm levels and examined those factors relative to employee participation in worksite-wide health promotion activities. Twenty-two blue-collar worksites with a total of 113 EAB members in the greater Seattle area. Individuals who agreed to serve on EABs in the intervention worksites. Participants received training in involving employees in the 5-A-Day project intervention activities. Measures include type of worksite, number of EAB members, method of EAB recruitment, and variables describing EAB functioning, including attendance at meetings, assistance at project activities, and level of enthusiasm. All worksites formed EABs. There was no association between the way the EAB was formed and subsequent EAB attendance at meetings, participation in project activities, representativeness of the EAB, or level of EAB enthusiasm. Enthusiasm of the EAB was associated with employee participation, and EABs with a higher level of enthusiasm showed more participation by employees than worksites with less enthusiastic EABs. It is possible to develop participatory structures in small, blue-collar worksites. More information is needed about factors related to levels of enthusiasm of EABs.

  3. Partially Testing a Process Model for Understanding Victim Responses to an Anticipated Worksite Closure

    Science.gov (United States)

    Blau, Gary

    2007-01-01

    This study partially tested a recent process model for understanding victim responses to worksite/function closure (W/FC) proposed by Blau [Blau, G. (2006). A process model for understanding victim responses to worksite/function closure. "Human Resource Management Review," 16, 12-28], in a pharmaceutical manufacturing site. Central to the model…

  4. Attitudes, practices and beliefs towards worksite smoking among administrators of private and public enterprises in Armenia.

    Science.gov (United States)

    Movsisyan, Narine K; Thompson, Michael E; Petrosyan, Varduhi

    2010-08-01

    In March 2005, Armenia enacted legislation protecting employees from secondhand smoke. This research was the first attempt to understand the attitudes, beliefs and practices of managers of public and private enterprises regarding smoke-free worksite policies. Mixed methods were used. The study team conducted focus group discussions with worksite administrators to explore their beliefs, attitudes and practices related to worksite smoking. These findings guided development of a quantitative instrument to collect more representative data on the same issues. Using stratified random sampling, 243 worksites were interviewed from June-July 2005, representing state/municipal, health, educational, culture and business institutions in three of Armenia's largest cities. Smoking-related practices differed significantly across institutions. More than half of the managers (55.6%) reported having smoking restrictions at worksites, including 37.0% who reported smoke-free workplaces; however, smoking or the presence of ashtrays was observed in 27.8% of workplaces reported to be smoke-free. A substantial proportion of the administrators favored both banning indoor smoking and allowing smoking in special areas. Only 38.0% of managers were aware of employees' existing legal protections from exposure to secondhand smoke. Knowledge of these regulations was not related to adherence to smoke-free worksite policies. The research also revealed widespread confusion between the concepts of worksite smoking restrictions and smoke-free workplaces. Public awareness campaigns that promote promulgation and enforcement of worksite smoking regulations could increase employee demand for smoke-free worksites. As one of the first studies to investigate smoking-related worksite practices, attitudes and beliefs in former Soviet countries, these findings provide insight into law enforcement processes in economies in transition.

  5. An evaluation of the Vermont worksite smoking law.

    OpenAIRE

    Paulozzi, L. J.; Spengler, R F; Gower, M A

    1992-01-01

    In view of the fact that the impact of statewide smoking laws on private worksite policies and the smoking behavior of employees has not been evaluated, two cross-sectional surveys were performed in Vermont to measure compliance with such a law: a random-digit telephone survey of employees and a subsequent mail survey of their employers. Employers were not aware that one of their employees had been surveyed. Roughly half (56 percent) of the employees and 66.5 percent of their employers descri...

  6. Prediction of Software Requirements Stability Based on Complexity Point Measurement Using Multi-Criteria Fuzzy Approach

    Directory of Open Access Journals (Sweden)

    D. Francis Xavier Christopher

    2012-12-01

    Full Text Available Many software projects fail due to instable requirements and lack of managing the requirements changesefficiently. Software Requirements Stability Index Metric (RSI helps to evaluate the overall stability ofrequirements and also keep track of the project status. Higher the stability, less changes tends topropagate. The existing system use Function Point modeling for measuring the Requirements Stability.However, the main drawback of the existing modeling is that the complexity of non-functional requirementshas not been measured for Requirements Stability. The Non-Functional Factors plays a vital role inassessing the Requirements Stability. Numerous Measurement methods have been proposed for measuringthe software complexity. This paper proposes Multi-criteria Fuzzy Based approach for finding out thecomplexity weight based on Requirement Complexity Attributes such as Functional RequirementComplexity, Non-Functional Requirement Complexity, Input Output Complexity, Interface and FileComplexity. Based on the complexity weight, this paper computes the software complexity point. And thenpredict the Software Requirements Stability based on Software Complexity Point changes. The advantageof this model is that it is able to estimate the software complexity early which in turn predicts the SoftwareRequirement Stability during the software development life cycle.

  7. Assembly of a Notch transcriptional activation complex requires multimerization.

    Science.gov (United States)

    Vasquez-Del Carpio, Rodrigo; Kaplan, Fred M; Weaver, Kelly L; VanWye, Jeffrey D; Alves-Guerra, Marie-Clotilde; Robbins, David J; Capobianco, Anthony J

    2011-04-01

    Notch transmembrane receptors direct essential cellular processes, such as proliferation and differentiation, through direct cell-to-cell interactions. Inappropriate release of the intracellular domain of Notch (N(ICD)) from the plasma membrane results in the accumulation of deregulated nuclear N(ICD) that has been linked to human cancers, notably T-cell acute lymphoblastic leukemia (T-ALL). Nuclear N(ICD) forms a transcriptional activation complex by interacting with the coactivator protein Mastermind-like 1 and the DNA binding protein CSL (for CBF-1/Suppressor of Hairless/Lag-1) to regulate target gene expression. Although it is well understood that N(ICD) forms a transcriptional activation complex, little is known about how the complex is assembled. In this study, we demonstrate that N(ICD) multimerizes and that these multimers function as precursors for the stepwise assembly of the Notch activation complex. Importantly, we demonstrate that the assembly is mediated by N(ICD) multimers interacting with Skip and Mastermind. These interactions form a preactivation complex that is then resolved by CSL to form the Notch transcriptional activation complex on DNA.

  8. Minimizing makespan in flowshops with pallet requirements: computational complexity

    NARCIS (Netherlands)

    M. Wang (Michael); S. Sethi (Suresh); C. Sriskandarajah (Chelliah); S.L. van de Velde (Steef)

    1997-01-01

    textabstractStudies the minimization in flowshops with pallet requirements. Importance of pallets in automated or flexible manufacturing environments; Mounting and dismounting of work pieces; Planning problems involved.

  9. Workforce gender, company size and corporate financial support are predictors of availability of healthy meals in Danish worksite canteens

    DEFF Research Database (Denmark)

    Thorsen, Anne Vibeke; Lassen, Anne Dahl; Andersen, Jens Strodl

    2009-01-01

    Objective: Environmental strategies at worksites may help consumers (change dietary behaviour towards a more healthy diet. The present study aimed to evaluate the availability of healthy meal options at Danish worksite canteens and to identify predictors of worksite canteens providing healthy meals....... Design: A self-administered questionnaire was randomly mailed to 1967 worksite canteen managers. Besides information and characteristics about the canteen and the worksite. the canteen managers specified the Menus available Two different health groups (Healthy and Less Healthy) were defined in three...... different meal categories (Sandwiches, [lot meals and Salads) as well as a combined category (Combined) combining all the three meal categories The characteristics of the worksites were compared With regard to the different health groups. Setting Randomly selected Danish worksite canteens. Subjects 553...

  10. Workforce gender, company size and corporate financialsupport are predictors of availability of healthy meals in Danish worksite canteens

    DEFF Research Database (Denmark)

    Thorsen, Anne Vibeke; Lassen, Anne; Andersen, Strodel

    2009-01-01

    Objective: Environmental strategies at worksites may help consumers change dietary behaviour towards a more healthy diet. The present study aimed to evaluate the availability of healthy meal options at Danish worksite canteens and to identify predictors of worksite canteens providing healthy meals....... Design: A self-administered questionnaire was randomly mailed to 1967 worksite canteen managers. Besides information and characteristics about the canteen and the worksite, the canteen managers specified the menus available. Two different health groups (Healthy and Less Healthy) were defined in three...... different meal categories (Sandwiches, Hot meals and Salads) as well as a combined category (Combined) combining all the three meal categories. The characteristics of the worksites were compared with regard to the different health groups. Setting: Randomly selected Danish worksite canteens. Subjects: 553...

  11. The integrator complex is required for integrity of Cajal bodies.

    Science.gov (United States)

    Takata, Hideaki; Nishijima, Hitoshi; Maeshima, Kazuhiro; Shibahara, Kei-ichi

    2012-01-01

    The nucleus in eukaryotic cells is a highly organized and dynamic structure containing numerous subnuclear bodies. The morphological appearance of nuclear bodies seems to be a reflection of ongoing functions, such as DNA replication, transcription, repair, RNA processing and RNA transport. The integrator complex mediates processing of small nuclear RNA (snRNA), so it might play a role in nuclear body formation. Here, we show that the integrator complex is essential for integrity of the Cajal body. Depletion of INTS4, an integrator complex subunit, abrogated 3'-end processing of snRNA. A defect in this activity caused a significant accumulation of the Cajal body marker protein coilin in nucleoli. Some fractions of coilin still formed nucleoplasmic foci; however, they were free of other Cajal body components, such as survival of motor neuron protein (SMN), Sm proteins and snRNAs. SMN and Sm proteins formed striking cytoplasmic granules. These findings demonstrate that the integrator complex is essential for snRNA maturation and Cajal body homeostasis.

  12. Tuberous sclerosis complex neuropathology requires glutamate-cysteine ligase

    NARCIS (Netherlands)

    Malik, A.R.; Liszewska, E.; Skalecka, A.; Urbanska, M.; Iyer, A.M.; Swiech, L.J.; Perycz, M.; Parobczak, K.; Pietruszka, P.; Zarebska, M.M.; Macias, M.; Kotulska, K.; Borkowska, J.; Grajkowska, W.; Tyburczy, M.E.; Jozwiak, S.; Kwiatkowski, D.J.; Aronica, E.; Jaworski, J.

    2015-01-01

    INTRODUCTION: Tuberous sclerosis complex (TSC) is a genetic disease resulting from mutation in TSC1 or TSC2 and subsequent hyperactivation of mammalian Target of Rapamycin (mTOR). Common TSC features include brain lesions, such as cortical tubers and subependymal giant cell astrocytomas (SEGAs). How

  13. Requirements engineering: the key to designing complex medical systems.

    Science.gov (United States)

    Carr, J J; McCullough, C E

    2000-01-01

    A variety of business systems, clinical work systems, instrumentation systems, information systems, infrastructure systems, and management systems interact to make the modern healthcare facility work. The key to designing for such a system is systems engineering, a skill often little appreciated among clinical engineers. At the heart of systems engineering is requirements engineering and management (REAM), which is defined as "the process of discovering, documenting and managing systems requirements." The principal activities of REAM include eliciting, understanding, negotiating, describing, validating, and managing system requirements. When REAM is done improperly, the resulting system will be satisfactory only if chance intervenes. Well-done REAM is likely to bring the project in on time, under budget, and at full performance.

  14. Healthy meals at worksite canteens - Social shaping as a framework for understanding sustainable interventions

    DEFF Research Database (Denmark)

    Thorsen, Anne Vibeke

    towards healthy eating may help consumers change dietary behavior and meet the guidelines for a healthy diet. The sustainability of interventions is found to be a central challenge in public health promotion not only related to the worksite setting, but in health promotion in general. Relatively few...... by the involved local actors' ideas of health and nutrition and also by their concepts of how these ideas interrelate with the worksite’s working conditions and working performance. A combination of a social shaping approach and a worksite policy process approach to the shaping and embedding of healthy worksite...

  15. The GARP complex is required for cellular sphingolipid homeostasis

    Science.gov (United States)

    Fröhlich, Florian; Petit, Constance; Kory, Nora; Christiano, Romain; Hannibal-Bach, Hans-Kristian; Graham, Morven; Liu, Xinran; Ejsing, Christer S; Farese, Robert V; Walther, Tobias C

    2015-01-01

    Sphingolipids are abundant membrane components and important signaling molecules in eukaryotic cells. Their levels and localization are tightly regulated. However, the mechanisms underlying this regulation remain largely unknown. In this study, we identify the Golgi-associated retrograde protein (GARP) complex, which functions in endosome-to-Golgi retrograde vesicular transport, as a critical player in sphingolipid homeostasis. GARP deficiency leads to accumulation of sphingolipid synthesis intermediates, changes in sterol distribution, and lysosomal dysfunction. A GARP complex mutation analogous to a VPS53 allele causing progressive cerebello-cerebral atrophy type 2 (PCCA2) in humans exhibits similar, albeit weaker, phenotypes in yeast, providing mechanistic insights into disease pathogenesis. Inhibition of the first step of de novo sphingolipid synthesis is sufficient to mitigate many of the phenotypes of GARP-deficient yeast or mammalian cells. Together, these data show that GARP is essential for cellular sphingolipid homeostasis and suggest a therapeutic strategy for the treatment of PCCA2. DOI: http://dx.doi.org/10.7554/eLife.08712.001 PMID:26357016

  16. Complex rectal polyps: other treatment modalities required when offering a transanal endoscopic microsurgery service.

    LENUS (Irish Health Repository)

    Joyce, Myles R

    2011-09-01

    Complex rectal polyps may present a clinical challenge. The study aim was to assess different treatment modalities required in the management of patients referred for transanal endoscopic microsurgery.

  17. Working on wellness (WOW: A worksite health promotion intervention programme

    Directory of Open Access Journals (Sweden)

    Kolbe-Alexander Tracy L

    2012-05-01

    Full Text Available Abstract Background Insufficient PA has been shown to cluster with other CVD risk factors including insufficient fruit and vegetable intake, overweight, increased serum cholesterol concentrations and elevated blood pressure. This paper describes the development of Working on Wellness (WOW, a worksite intervention program incorporating motivational interviewing by wellness specialists, targeting employees at risk. In addition, we describe the evaluation the effectiveness of the intervention among employees at increased risk for cardiovascular disease. Methods The intervention mapping (IM protocol was used in the planning and design of WOW. Focus group discussions and interviews with employees and managers identified the importance of addressing risk factors for CVD at the worksite. Based on the employees’ preference for individual counselling, and previous evidence of the effectiveness of this approach in the worksite setting, we decided to use motivational interviewing as part of the intervention strategy. Thus, as a cluster-randomised, controlled control trial, employees at increased risk for CVD (N = 928 will be assigned to a control or an intervention group, based on company random allocation. The sessions will include motivational interviewing techniques, comprised of two face-to-face and four telephonic sessions, with the primary aim to increase habitual levels of PA. Measures will take place at baseline, 6 and 12 months. Secondary outcomes include changes in nutritional habits, serum cholesterol and glucose concentrations, blood pressure and BMI. In addition, healthcare expenditure and absenteeism will be measured for the economic evaluation. Analysis of variance will be performed to determine whether there were significant changes in physical activity habits in the intervention and control groups at 6 and 12 months. Discussion The formative work on which this intervention is based suggests that the strategy of targeting

  18. Healthy meals at worksite canteens - Social shaping as a framework for understanding sustainable interventions

    DEFF Research Database (Denmark)

    Thorsen, Anne Vibeke

    by the involved local actors' ideas of health and nutrition and also by their concepts of how these ideas interrelate with the worksite’s working conditions and working performance. A combination of a social shaping approach and a worksite policy process approach to the shaping and embedding of healthy worksite...... are the point of departure of this research. The long term sustainability of these interventions has up till now only been analyzed to a limited extent. Furthermore health promotions at worksites have only had a limited focus on analyses of the organizational context‟s significance for the efficiency...... the sustainability if this implies frequent changes of worksite employees and new employees question the F&V intensive food supply. The engagement of the canteen manager and the ability to develop strategies for integration of more F&V in the food supply and good cooperation with the F&V suppliers also play...

  19. Ergonomic workforce scheduling under complex worker limitation and task requirements:

    Directory of Open Access Journals (Sweden)

    Tanuchporn Wongwien

    2012-11-01

    Full Text Available The ergonomic workforce scheduling problem (WPS is addressed in this paper. Unlike its previous related works, theproblem considers realistic worker limitation and task requirements that include heterogeneous workforce with limited taskflexibility, varying worker team sizes, and pre-defined task operation schedules. Its main objective is to find a daily rotatingwork schedule solution using a minimum number of workers such that all workers’ ergonomics hazard exposures do notexceed a permissible limit. Initially, the ergonomic WPS is explained. Its mathematical model and approximation procedure toobtain the workforce schedule solution are described. From the results of the computation experiment, it can be concludedthat the approximation procedure is both efficient and effective in solving large-sized ergonomic workforce schedulingproblems.

  20. Use of participant focus groups to identify barriers and facilitators to worksite exercise therapy adherence in randomized controlled trials involving firefighters

    Directory of Open Access Journals (Sweden)

    Mayer JM

    2013-03-01

    Full Text Available John M Mayer,1 James L Nuzzo,1 Simon Dagenais2 1School of Physical Therapy and Rehabilitation Sciences, College of Medicine, University of South Florida, Tampa, FL, 2Palladian Health, West Seneca, NY, USA Background: Firefighters are at increased risk for back injuries, which may be mitigated through exercise therapy to increase trunk muscle endurance. However, long-term adherence to exercise therapy is generally poor, limiting its potential benefits. Focus groups can be used to identify key barriers and facilitators to exercise adherence among study participants. Objective: To explore barriers and facilitators to worksite exercise therapy adherence among firefighters to inform future randomized controlled trials (RCTs. Methods: Participants enrolled in a previous RCT requiring twice-weekly worksite exercise therapy for 24 weeks were asked to take part in moderated focus group discussions centered on eight open-ended questions related to exercise adherence. Responses were analyzed qualitatively using a social ecological framework to identify key intrapersonal, interpersonal, and institutional barriers and potential facilitators to exercise adherence. Results: A total of 27 participants were included in the four focus group discussions, representing 50% of those assigned to a worksite exercise therapy group in the previous RCT, in which only 67% of scheduled exercise therapy sessions were completed. Lack of self-motivation was cited as the key intrapersonal barrier to adherence, while lack of peer support was the key interpersonal barrier reported, and lack of time to exercise during work shifts was the key institutional barrier identified. Conclusion: Focus group discussions identified both key barriers and potential facilitators to increase worksite exercise therapy adherence among firefighters. Future studies should consider educating and reminding participants about the benefits of exercise, providing individual and group incentives based on

  1. Engaging participants in design of a Native Hawaiian worksite wellness program.

    Science.gov (United States)

    Leslie, Jodi Haunani; Hughes, Claire Ku; Braun, Kathryn L

    2010-01-01

    Native Hawaiians today face a disproportionately high rate of obesity. The Designing Healthy Worksites (DHW) project investigated existing administrative policies and supports for healthy eating and physical activity at eight Native Hawaiian-serving organizations in Hawai'i, along with employee preferences for worksite wellness programming. We describe the process by which Native Hawaiian researchers and community members worked together to gather formative data to design future worksite wellness programs. A Native Hawaiian doctoral student (JHL) and a Native Hawaiian activist (CKH) spearheaded the project, mentored by a Caucasian professor (KLB) who has worked in Hawaii communities for 30 years. Advisors from the worksites supported the use of environmental assessments (n = 36), administrative interviews (n = 33), focus groups (n = 9), and an employee survey (n = 437) to collect data. We used an interactive process of data collection, sharing, and interpretation to assure mutual agreement on conclusions and future directions. Worksites were at different stages of readiness for worksite wellness programming, suggesting that a toolkit be developed from which agencies could create a program that fit. Activities preferred by large proportions of employees included support groups, experiential nutrition education (e.g., cooking demonstrations and field trips for smart food shopping), food buying clubs, and administrative policies supporting healthy lifestyles. High participation in data collection and interpretation suggest that our methods fostered enthusiasm for worksite wellness programming and for Native Hawaiians as researchers. The team continues to work together to develop and test interventions to promote worksite wellness. Native-directed research that engages administrators and employees in designing programs heightens program acceptability and applicability.

  2. The relationship of individual characteristics, perceived worksite support and perceived creativity to clinical nurses' innovative outcome.

    Science.gov (United States)

    Tsai, Hsiu-Min; Liou, Shwu-Ru; Hsiao, Ya-Chu; Cheng, Ching-Yu

    2013-09-01

    To understand the relationship of individual characteristics, perceived worksite support and perceived personal creativity to clinical nurses' innovative outcome (receiving the Nursing Innovation Award). Since the idea of applying creativity and innovation to clinical nursing practice and management was first advocated in the Nursing Administration Quarterly in 1982, the topic of nursing innovation has gained worldwide attention. To increase the prevalence of nursing innovation, it is important to identify and understand the related factors that influence nurses' innovative outcome. This study used a cross-sectional descriptive survey design. A self-administered questionnaire was completed by 32 award winners and 506 nonawarded clinical nurses in Taiwan. The level of creativity perceived by all participants was moderate-to-high. Individual characteristics (r = 0·61) and worksite support (r = 0·27) were both correlated with perceived creativity. Individual characteristics and worksite support showed some correlation as well (r = 0·21). Individual characteristics and worksite support could predict perceived creativity after controlling for demographic variables, but only individual characteristics had an effect on innovative outcome. Perceived creativity did not have mediation effects either between individual characteristics and innovative outcome or between worksite support and innovative outcome. Clinical nurses' individual characteristics had a direct relationship to innovative outcome, whereas neither worksite support nor creativity was correlated with innovative outcome. Although worksite support did not show effects on innovative outcome, it was related to both perceived creativity and individual characteristics. As suggested by other scholars, there might be other related factors between creativity and innovative outcome. Although worksite support did not have effect on clinical nurses' innovative outcome, it was related to individual characteristics

  3. Effects of worksite health promotion interventions on employee diets: a systematic review

    Directory of Open Access Journals (Sweden)

    Aston Louise M

    2010-02-01

    Full Text Available Abstract Background Public health strategies place increasing emphasis on opportunities to promote healthy behaviours within the workplace setting. Previous research has suggested worksite health promotion programmes have positive effects on physical activity and weight loss, yet little is known regarding their effects on dietary behaviour. The aim of this review was to assess the effects of worksite interventions on employee diets. Methods Electronic databases (MEDLINE, The Cochrane Library, PsycINFO, EMBASE, LexisNexis were searched for relevant articles published between 1995 and April 2009. Studies were eligible for inclusion if they were peer-reviewed English language publications describing a worksite-based health promotion intervention with minimum study duration of eight weeks. All study designs were eligible. Studies had to report one or more diet-related outcome (energy, fat, fruit, or vegetable intakes. Methodological quality was assessed using a checklist that included randomisation methods, use of a control group, and study attrition rates. Results Sixteen studies were included in the review. Eight programmes focussed on employee education, and the remainder targeted change to the worksite environment, either alone or in combination with education. Study methodological quality was moderate. In general, worksite interventions led to positive changes in fruit, vegetable and total fat intake. However, reliance on self-reported methods of dietary assessment means there is a significant risk of bias. No study measured more robust outcomes such as absenteeism, productivity, or healthcare utilisation. Conclusions The findings of this review suggest that worksite health promotion programmes are associated with moderate improvement in dietary intake. The quality of studies to date has been frequently sub-optimal and further, well designed studies are needed in order to reliably determine effectiveness and cost-effectiveness. Future

  4. Worksite environment physical activity and healthy food choices: measurement of the worksite food and physical activity environment at four metropolitan bus garages

    Directory of Open Access Journals (Sweden)

    Gerlach Anne F

    2007-05-01

    Full Text Available Abstract Background The present research describes a measure of the worksite environment for food, physical activity and weight management. The worksite environment measure (WEM instrument was developed for the Route H Study, a worksite environmental intervention for weight gain prevention in four metro transit bus garages in Minneapolis-St. Paul. Methods Two trained raters visited each of the four bus garages and independently completed the WEM. Food, physical activity and weight management-related items were observed and recorded on a structured form. Inter-rater reliability was computed at the item level using a simple percentage agreement. Results The WEM showed high inter-rater reliability for the number and presence of food-related items. All garages had vending machines, microwaves and refrigerators. Assessment of the physical activity environment yielded similar reliability for the number and presence/absence of fitness items. Each garage had a fitness room (average of 4.3 items of fitness equipment. All garages had at least one stationary bike and treadmill. Three garages had at least one weighing scale available. There were no designated walking areas inside or outside. There were on average Conclusion The WEM is a reliable measure of the worksite nutrition, physical activity, and weight management environment that can be used to assess changes in the work environment.

  5. 77 FR 50726 - Software Requirement Specifications for Digital Computer Software and Complex Electronics Used in...

    Science.gov (United States)

    2012-08-22

    ... COMMISSION Software Requirement Specifications for Digital Computer Software and Complex Electronics Used in... Digital Computer Software and Complex Electronics used in Safety Systems of Nuclear Power Plants.'' The DG... National Standards Institute and Institute of Electrical and Electronics Engineers (ANSI/IEEE) Standard...

  6. Fast Vesicle Fusion in Living Cells Requires at Least Three SNARE Complexes

    DEFF Research Database (Denmark)

    Mohrmann, Ralf; de Wit, Heidi; Verhage, Matthijs

    2010-01-01

    Exocytosis requires formation of SNARE complexes between vesicle- and target-membranes. Recent assessments in reduced model systems have produced divergent estimates of the number of SNARE complexes needed for fusion. Here, we used a titration approach to answer this question in intact, cultured ...

  7. Development and Implementation of Worksite Health and Wellness Programs: A Focus on Non-Communicable Disease.

    Science.gov (United States)

    Cahalin, Lawrence P; Kaminsky, Leonard; Lavie, Carl J; Briggs, Paige; Cahalin, Brendan L; Myers, Jonathan; Forman, Daniel E; Patel, Mahesh J; Pinkstaff, Sherry O; Arena, Ross

    2015-01-01

    The development and implementation of worksite health and wellness programs (WHWPs) in the United States (US) hold promise as a means to improve population health and reverse current trends in non-communicable disease incidence and prevalence. However, WHWPs face organizational, economic, systematic, legal, and logistical challenges which have combined to impact program availability and expansion. Even so, there is a burgeoning body of evidence indicating WHWPs can significantly improve the health profile of participating employees in a cost effective manner. This foundation of scientific knowledge justifies further research inquiry to elucidate optimal WHWP models. It is clear that the development, implementation and operation of WHWPs require a strong commitment from organizational leadership, a pervasive culture of health and availability of necessary resources and infrastructure. Since organizations vary significantly, there is a need to have flexibility in creating a customized, effective health and wellness program. Furthermore, several key legal issues must be addressed to facilitate employer and employee needs and responsibilities; the US Affordable Care Act will play a major role moving forward. The purposes of this review are to: 1) examine currently available health and wellness program models and considerations for the future; 2) highlight key legal issues associated with WHWP development and implementation; and 3) identify challenges and solutions for the development and implementation of as well as adherence to WHWPs.

  8. The Relationship Between the Use of a Worksite Medical Home and ED Visits or Hospitalizations

    Directory of Open Access Journals (Sweden)

    Marissa Stroo BS

    2015-10-01

    Full Text Available Worksite medical homes may be a good model for improving employee health. The aim of this study was to compare the likelihood of being seen in the emergency department (ED or being hospitalized by level of use (no use, occasional use, or primary care of a worksite medical home, overall and by type of user (employee, adult dependent, or pediatric dependent. This was a retrospective analysis of claims data, using covariate-adjusted logistic regression models for ED visits and inpatient hospitalizations. Secondary data for the years 2006 to 2008 from a company that offers an on-site health care center (HCC were used. Analyses were based on a data set that combines health plan claims and human resources demographic data. Overall, people who did not use the HCC were more likely to be seen in the ED (adjusted odds ratio [OR] = 1.20, 95% confidence interval or CI [1.06, 1.37], P = .005 or to be hospitalized (adjusted OR = 1.58; 95% CI [1.34, 1.86]; P < .0001 compared with those who used the HCC for primary care. Both ED visits and hospitalizations for employees and dependents in this study were lower among those who used the worksite medical home for primary care. Worksite medical homes can improve chronic disease management and thus reduce ED visits and hospitalizations. These findings contribute to growing evidence that worksite medical homes are potentially cost-effective.

  9. Civil engineering status report for the ATLAS & CMS worksites

    CERN Document Server

    Rammer, H; CERN. Geneva. ST Division

    2003-01-01

    Construction work on the civil engineering contracts at Point 1 and Point 5 started in 1998. The new surface buildings and underground structures are necessary to accommodate the ATLAS and CMS detectors for the LHC Project. The principal underground works at both points consist of two new shafts, two caverns along with a number of small connection tunnels and galleries. At Point 1, the works are 90% complete. Most of the surface buildings as well as the shafts and one of the two new caverns have been completed, and the construction of the second cavern is well underway. At Point 5, the works are 70% complete. Most of the surface buildings as well as the shafts and the pillar have been completed. With excavation of the two large caverns complete, the concreting of the final linings has started. The aim of this paper is to present the status of the civil engineering on these worksites and in particular the challenges encountered constructing the experimental caverns.

  10. Examining incentive design strategies for worksite wellness program engagement.

    Science.gov (United States)

    Norman, Gregory J; Heltemes, Kevin J; Drew, Joseph

    2014-12-01

    The objective was to examine employee engagement in worksite wellness activities at 2 large US companies that differed in engagement strategy and incentive plan. Inclusion criteria were US employees aged 18 to 65 who were eligible to receive wellness benefits throughout 2012. Company B's incentive was twice the dollar value of Company A's and produced higher engagement rates for the health assessment (HA; 26.1% vs. 24.4%, Pemployees who completed the HA and the biometric screening, 44.6% (N=2,309) at Company A engaged in at least 1 coaching session compared to 8.9% (N=594) at Company B. Fewer employees at Company A with high-risk cholesterol engaged in coaching compared to Company B (44.6% vs. 54.9%, P=.009). However, more Company A employees with high-risk blood pressure engaged in coaching compared to Company B (41.3% vs. 34.8%, P=.053). Company A engaged more obese employees compared to Company B (43.7% vs. 13.9%, Pengagement engaged high-risk employees in coaching, and engaged a high proportion of employees not at high risk, but who can still be at risk for chronic diseases.

  11. Beyond Planning: The Implementation of a Worksite Health Promotional Scheme

    Directory of Open Access Journals (Sweden)

    Thor Christian Bjørnstad

    2012-06-01

    Full Text Available The aim of this article is to provide insight into how the presence of diverging organizational logics influences the outcome of worksite health promotion projects. The study is based on a one-year qualitative single-case study of the implementation of a health promotional physical exercise program in a transnational transport and logistics company based in Norway. While the program that was implemented was based on dominant logics in Norway, i.e., the emphasis on worker participation and influence, the organizational logics of the transport company defined company–worker relationships in other terms. We found that the logic of a highly specialized work organization that combined strict work distribution with a set of narrowly defined work tasks contradicted the logic that underpinned the health promotional program, and that this contradiction is an important reason why the initiative failed. We therefore conclude that in implementing health promotion projects at the workplace, there is a need to observe the relationship between logics related both to the project and to the organization.

  12. Effect of Fresh Fruit Availability at Worksites on the Fruit and Vegetable Consumption of Low-Wage Employees

    Science.gov (United States)

    Backman, Desiree; Gonzaga, Gian; Sugerman, Sharon; Francis, Dona; Cook, Sara

    2011-01-01

    Objective: To examine the impact of fresh fruit availability at worksites on the fruit and vegetable consumption and related psychosocial determinants of low-wage employees. Design: A prospective, randomized block experimental design. Setting: Seven apparel manufacturing and 2 food processing worksites. Participants: A convenience sample of 391…

  13. Using nudging and social marketing techniques to create healthy worksite cafeterias in the Netherlands: intervention development and study design.

    Science.gov (United States)

    Velema, Elizabeth; Vyth, Ellis L; Steenhuis, Ingrid H M

    2017-01-11

    The worksite cafeteria is a suitable setting for interventions focusing on changing eating behavior, because a lot of employees visit the worksite cafeteria regularly and a variety of interventions could be implemented there. The aim of this paper is to describe the intervention development and design of the evaluation of an intervention to make the purchase behavior of employees in the worksite cafeteria healthier. The developed intervention called "the worksite cafeteria 2.0" consists of a set of 19 strategies based on theory of nudging and social marketing (marketing mix). The intervention will be evaluated in a real-life setting, that is Dutch worksite cafeterias of different companies and with a number of contract catering organizations. The study is a randomized controlled trial (RCT), with 34 Dutch worksite cafeterias randomly allocated to the 12-week intervention or to the control group. Primary outcomes are sales data of selected products groups like sandwiches, salads, snacks and bread topping. Secondary outcomes are satisfaction of employees with the cafeteria and vitality. When executed, the described RCT will provide better knowledge in the effect of the intervention "the worksite cafeteria 2.0" on the purchasing behavior of Dutch employees in worksite cafeterias. Dutch Trial register: NTR5372 .

  14. Contemporary Challenges in Requirements Discovery and Validation: Two Case Studies in Complex Environments

    Science.gov (United States)

    Hansen, Sean; Lyytinen, Kalle

    Requirements have remained a key source of difficulty since the dawn of computing. Complicating this fact, recent substantive changes in systems development and associated requirements processes - as reflected in reliance on packaged software components, off-shore development, and software-as-a-service - demand a reappraisal of requirements challenges. Yet, there are few empirical studies focusing on what current requirements challenges are, why they emerge and how they affect requirements engineering (RE) efforts. In the present study, we assess the cognitive, social, and complexity-based impediments to effective requirements discovery through two exploratory case studies of large, multi-party development projects. We develop a rich understanding of the requirements challenges facing these development efforts, how these challenges interact and affect the requirements engineering process and outcomes. The analyses reveal significant consistency in the primary challenges of large RE efforts and the profoundly systemic nature of requirements-related impediments. Several recommendations for research and practice of RE are developed.

  15. Evaluation of a Worksite Diabetes Education Program at a Large Urban Medical Center.

    Science.gov (United States)

    Renda, Susan; Baernholdt, Marianne; Becker, Kathleen

    2016-01-01

    Evidence suggests that diabetes education can be delivered at the worksite to better support employees' diabetes self-management and improve productivity and health care costs. This study was conducted to address the feasibility of a diabetes worksite education program for employees at a large urban academic health care institution. The diabetes education program was delivered in the diabetes center at the institution, a resource that was previously underutilized by employees. Through collaboration with groups in the institution, 20 employees of diverse ethnicity participated in the worksite diabetes education program with positive outcomes: improved glycemic control measured (HbA1c), attainment of self-management goals, and satisfaction with the program. Work absences trended downward, but numbers of hospitalizations and emergency department visits were unchanged in the 3 months following education. Recommendations include replication of the study with more employee participation and program evaluation over a longer period of time to continue assessment of employees' educational needs.

  16. Long-term sustainability of a worksite canteen intervention of serving more fruit and vegetables

    DEFF Research Database (Denmark)

    Thorsen, Anne Vibeke; Lassen, Anne Dahl; Tetens, Inge

    2010-01-01

    Objective: To analyse the 5-year sustainability of a worksite canteen intervention of serving more fruit and vegetables (F&V). Design: Average F&V consumption per customer per meal per day was assessed in five worksite canteens by weighing F&V served and subtracting waste. Data were collected...... by the canteen staff during a 3-week continuous period and compared to data from the same five canteens measured at baseline, at end point and at 1-year follow-up. The intervention used a participatory and empowering approach, self-monitoring and networking among the canteen staff, management and a consultant....... The method focused on providing ideas for increased F&V for lunch, making environmental changes in the canteens by giving access to tasteful and healthy food choices and reducing the availability of unhealthy options. Setting: Five Danish worksites serving from 50 to 500 meals a day: a military base...

  17. Demonstration of an E-mailed Worksite Nutrition Intervention Program

    Directory of Open Access Journals (Sweden)

    Gladys Block

    2004-10-01

    Full Text Available Introduction Dietary fat and low fruit and vegetable intake are linked to many chronic diseases, and U.S. population intake does not meet recommendations. Interventions are needed that incorporate effective behavior-change principles and that can be delivered inexpensively to large segments of the population. Methods Employees at a corporate worksite were invited to participate in a program, delivered entirely by e-mail, to reduce dietary fat and increase fruit and vegetable intake. Behavior-change principles underlying the intervention included tailoring to the participant’s dietary lifestyle, baseline assessment and feedback about dietary intake, family participation, and goal setting. Assessment, tailoring, and delivery was fully automated. The program was delivered weekly to participants’ e-mail inboxes for 12 weeks. Each e-mail included information on nutrition or on the relationship between diet and health, dietary tips tailored to the individual, and small goals to try for the next week. In this nonrandomized pilot study, we assessed technical feasibility, acceptability to employees, improvement in Stage of Change, increase in fruit and vegetable consumption, and decrease in fat intake. Results Approximately one third (n = 84 of employees who were offered the 12-week program signed up for it, and satisfaction was high. There was significant improvement in Stage of Change: 74% of those not already at the top had forward movement (P < .001. In addition, results suggest significant increase in fruit and vegetable consumption (0.73 times/day, P < .001 and significant decrease in intake of fat sources (-0.39 times/day, P < .001. Conclusion This inexpensive program is feasible and appears to be effective. A randomized controlled trial is needed.

  18. Effectiveness of Financial Incentives in a Worksite Diabetes Prevention Program.

    Science.gov (United States)

    Faghri, Pouran D; Li, Rui

    To evaluate the effect of financial incentive in a diabetes prevention weight loss program at worksites. Group-level randomized intervention study. Four long-term care facilities, randomly assigned to "incentive-IG" or "non incentive-NIG" groups. Ninety-nine employees, all overweight or obese (BMI= mean 34.8±7.4 kg/m(2)) and at risk for type 2 diabetes. A 16 week weight loss program (diabetes prevention program) with a 3 month follow up. IG could either choose a "standard incentive" to receive cash award when achieving the projected weight loss or to participate in a "standard plus deposit incentive" to get additional money matched with their deposit for projected weight loss. All of the participants received a one-hour consultation for a healthy weight loss at the beginning. Weight-loss, diabetes risk score (DRS), and cardiovascular risk outcomes. Linear and logistic regressions for completed cases with adjustments for clustering effect at group level. IG lost on average more pounds (p=0.027), reduced BMI (p=0.04), and reduced in DRS (p=0.011) compared to NIG at week 16. At the 12-week follow-up period, those in IG plus deposit subgroup had twice the odds (OR=2.2, p=0.042) and those in the standard IG had three times the odds of achieving weight loss goals than NIG; those in the IG plus deposit group reduced DRS by 0.4 (p=0.045). Monetary incentives appear to be effective in reducing weight and diabetes risk.

  19. [Exposure to mineral oils at worksites and novel solutions for polymer protective materials in selected personal protective equipment].

    Science.gov (United States)

    Krzemińska, Sylwia; Irzmańska, Emilia

    2011-01-01

    Exposure of workers to health hazards due to contact with mineral oils occurs primarily in the chemical, petrochemical, machine-building, metallurgic and car industries. Under worksite conditions, the respiratory system and the skin are the primary routes of entry of mineral oils into the human body. Long-term exposure of the skin to oily substances may lead not only to irritation and allergic lesions. The studies conducted in this area have confirmed a significant increase in the incidence of skin cancers in persons chronically exposed to mineral oils. Protection of workers' health at worksites associated with the risk of contact with mineral oils requires, in addition to collective protective and organizational solutions, personal protective equipment with appropriate protection and utility parameters confirmed by laboratory tests. The essential preventive measures include protection of the human skin by means of appropriate protective clothing and gloves, which provide an effective barrier against a wide spectrum of chemical compounds present in mineral oils. Knowledge of polymer materials is the prerequisite for designing more and more effective and functional protective clothing and gloves. Studies aimed at obtaining higher levels of skin protection against varied toxic substances, including mineral oils, have been conducted, among others, to develop modern glove and clothing materials ensuring resistance to oils. The rapid progress of nanotechnology and the use of nanoadditives in polymer materials has made it possible to undertake works aimed at developing modern polymer nanostructures designed for construction of oil-resistant protective clothing and gloves. In this review paper the authors have presented the current knowledge of polymer materials, from traditional ones to polymer nanostructures, used in personal equipment protecting against mineral oils.

  20. Application of a Modified Universal Design Survey for Evaluation of Ares 1 Ground Crew Worksites

    Science.gov (United States)

    Blume, Jennifer L.

    2010-01-01

    Operability is a driving requirement for NASA's Ares 1 launch vehicle. Launch site ground operations include several operator tasks to prepare the vehicle for launch or to perform maintenance. Ensuring that components requiring operator interaction at the launch site are designed for optimal human use is a high priority for operability. To support design evaluation, the Ares 1 Upper Stage (US) element Human Factors Engineering (HFE) group developed a survey based on the Universal Design approach. Universal Design is a process to create products that can be used effectively by as many people as possible. Universal Design per se is not a priority for Ares 1 because launch vehicle processing is a specialized skill and not akin to a consumer product that should be used by all people of all abilities. However, applying principles of Universal Design will increase the probability of an error free and efficient design which is a priority for Ares 1. The Design Quality Evaluation Survey centers on the following seven principles: (1) Equitable use, (2) Flexibility in use, (3) Simple and intuitive use, (4) Perceptible information, (5) Tolerance for error, (6) Low physical effort, (7) Size and space for approach and use. Each principle is associated with multiple evaluation criteria which were rated with the degree to which the statement is true. All statements are phrased in the utmost positive, or the design goal so that the degree to which judgments tend toward "completely agree" directly reflects the degree to which the design is good. The Design Quality Evaluation Survey was employed for several US analyses. The tool was found to be most useful for comparative judgments as opposed to an assessment of a single design option. It provided a useful piece of additional data when assessing possible operator interfaces or worksites for operability

  1. The impact of educational and environmental interventions in Dutch worksite cafeterias

    NARCIS (Netherlands)

    I.H.M. Steenhuis; P. van Assema (Patricia); G.J.P. van Breukelen (Gerard); K. Glanz; G.J. Kok (Gerjo); H. de Vries (Hein)

    2004-01-01

    textabstractEnvironmental interventions as labeling of healthy foods and an increased availability of healthy foods may help consumers to meet the guidelines for a healthy diet. This article describes a study into the effectiveness of two environmental programs to be used in worksite cafeterias alon

  2. Effectiveness of physical activity programs at worksites with respect to work-related outcomes

    NARCIS (Netherlands)

    Proper, K.I.; Staal, B.J.; Hildebrandt, V.H.; Beek, A.J. van der; Mechelen, W. van

    2002-01-01

    This paper systematically reviews the literature on the effectiveness of physical activity programs at worksites with respect to work-related outcomes. A computerized literature search, a reference search, and a manual search of personal databases were performed using the following inclusion

  3. Effectiveness of physical activity programs at worksites with respect to work-related outcomes

    NARCIS (Netherlands)

    Proper, K.I.; Staal, B.J.; Hildebrandt, V.H.; Beek, A.J. van der; Mechelen, W. van

    2002-01-01

    This paper systematically reviews the literature on the effectiveness of physical activity programs at worksites with respect to work-related outcomes. A computerized literature search, a reference search, and a manual search of personal databases were performed using the following inclusion criteri

  4. The effectiveness of worksite physical activity programs on physical activity, physical fitness, and health

    NARCIS (Netherlands)

    Proper, K.I.; Koning, M.; Beek, A.J. van der; Hildebrandt, V.H.; Bosscher, R.J.; Mechelen, W. van

    2003-01-01

    Objective: To critically review the literature with respect to the effectiveness of worksite physical activity programs on physical activity, physical fitness, and health. Data Sources: A search for relevant English-written papers published between 1980 and 2000 was conducted using MEDLINE, EMBASE,

  5. Costs, benefits and effectiveness of worksite physical activity counseling from the employer's perspective

    NARCIS (Netherlands)

    Proper, K.I.; Bruyne, M.C. de; Hildebrandt, V.H.; Beek, A.J. van der; Meerding, W.J.; Mechelen, W. van

    2004-01-01

    Objectives. This study evaluated the impact of worksite physical activity counseling using cost-benefit and cost-effectiveness analyses. Methods. Civil servants (N=299) were randomly assigned to an intervention (N=131) or control (N=168) group for 9 months. The intervention costs were compared with

  6. Effectiveness of a worksite mindfulness-based multi-component intervention on lifestyle behaviors

    NARCIS (Netherlands)

    Berkel, J. van; Boot, C.R.L.; Proper, K.I.; Bongers, P.M.; Beek, A.J. van der

    2014-01-01

    Introduction: Overweight and obesity are associated with an increased risk of morbidity. Mindfulness training could be an effective strategy to optimize lifestyle behaviors related to body weight gain. The aim of this study was to evaluate the effectiveness of a worksite mindfulness-based multi-comp

  7. An Evaluation of a Worksite Exercise Intervention Using the Social Cognitive Theory: A Pilot Study

    Science.gov (United States)

    Amaya, Megan; Petosa, R. L.

    2012-01-01

    Purpose: To increase exercise adherence among insufficiently active adult employees. Design: A quasi-experimental separate samples pre-test-post-test group design was used to compare treatment and comparison group. Setting: The worksite. Subjects: Employees (n = 127) who did not meet current American College of Sports Medicine (ACSM)…

  8. The Job Worksite: An Additional Resource in Preparing Psychiatric Clients for Job Placement.

    Science.gov (United States)

    Gerber, Norman M.

    1979-01-01

    Describes the job worksite program developed by Altro Workshops, Inc., Bronx, New York, to serve as an intermediate step between the protected vocational training workshop and the unprotected work world. Psychiatric clients of the workshop selected for the program were placed in facility-supervised or company-supervised jobs with generally good…

  9. The impact of educational and environmental interventions in Dutch worksite cafeterias

    NARCIS (Netherlands)

    I.H.M. Steenhuis; P. van Assema (Patricia); G.J.P. van Breukelen (Gerard); K. Glanz; G.J. Kok (Gerjo); H. de Vries (Hein)

    2004-01-01

    textabstractEnvironmental interventions as labeling of healthy foods and an increased availability of healthy foods may help consumers to meet the guidelines for a healthy diet. This article describes a study into the effectiveness of two environmental programs to be used in worksite cafeterias alon

  10. A worksite prevention program for construction workers: Design of a randomized controlled trial

    NARCIS (Netherlands)

    Hengel, K.M.O.; Joling, C.I.; Proper, K.I.; Blatter, B.M.; Bongers, P.M.

    2010-01-01

    Background. A worksite prevention program was developed to promote the work ability of construction workers and thereby prolong a healthy working life. The objective of this paper is to present the design of a randomized controlled trial evaluating the effectiveness of that intervention program comp

  11. FoodSteps : The effects of a worksite environmental intervention on cardiovascular risk indicators

    NARCIS (Netherlands)

    Engbers, L.H.

    2007-01-01

    This dissertation describes the results of the FoodSteps project. The purpose of this project is to evaluate the effects of a relatively modest worksite environmental intervention on physical activity, food habits and biological cardiovascular risk indicators. The effects of FoodSteps study are eva

  12. Strategies to promote healthier eating at worksites -analysis of experiences from a social shaping perspective

    DEFF Research Database (Denmark)

    Thorsen, Anne Vibeke; Jørgensen, Michael Søgaard; Lassen, Anne Dahl

    2005-01-01

    There is a strong need for strategies that can help promote healthy eating. The paper explores the shaping of initiatives aimed at promoting and implementing healthy eating in a worksite catering setting by analysing the sustainability of the intervention of healthier eating in a canteen model...

  13. Participation of Danish and immigrant cleaners in a 1-year worksite intervention preventingphysical deterioration

    DEFF Research Database (Denmark)

    Rasmussen, Charlotte D N; Jørgensen, Marie B; Carneiro, Isabella G;

    2012-01-01

    was equally distributed among Danish and immigrant cleaners. This study indicates that a worksite health promotion intervention among a female-dominated, high-risk occupation such as cleaning can be equally appealing for Danes and immigrants. Statement of Relevance: This study provides insight about...... of the workers, but also to be specifically tailored to the job group....

  14. Work-site musculoskeletal pain risk estimates by trained observers - a prospective cohort study

    NARCIS (Netherlands)

    Coenen, P.; Kingma, I.; Boot, C.R.L.; Douwes, M.; Bongers, P.M.; Dieën, J.H. van

    2012-01-01

    Work-related musculoskeletal pain (MSP) risk assessments by trained observers are often used in ergonomic practice; however, the validity may be questionable. We investigated the predictive value of work-site MSP risk estimates in a prospective cohort study of 1745 workers. Trained observers estimat

  15. Work-site musculoskeletal pain risk estimates by trained observers - a prospective cohort study

    NARCIS (Netherlands)

    Coenen, P.; Kingma, I.; Boot, C.R.L.; Douwes, M.; Bongers, P.M.; Dieën, J.H. van

    2012-01-01

    Work-related musculoskeletal pain (MSP) risk assessments by trained observers are often used in ergonomic practice; however, the validity may be questionable. We investigated the predictive value of work-site MSP risk estimates in a prospective cohort study of 1745 workers. Trained observers

  16. Impact of worksite wellness intervention on cardiac risk factors and one-year health care costs.

    Science.gov (United States)

    Milani, Richard V; Lavie, Carl J

    2009-11-15

    Cardiac rehabilitation and exercise training (CRET) provides health risk intervention in cardiac patients over a relatively short time frame. Worksite health programs offer a unique opportunity for health intervention, but these programs remain underused due to concerns over recouping the costs. We evaluated the clinical efficacy and cost-effectiveness of a 6-month worksite health intervention using staff from CRET. Employees (n = 308) and spouses (n = 31) of a single employer were randomized to active intervention (n = 185) consisting of worksite health education, nutritional counseling, smoking cessation counseling, physical activity promotion, selected physician referral, and other health counseling versus usual care (n = 154). Health risk status was assessed at baseline and after the 6-month intervention program, and total medical claim costs were obtained in all participants during the year before and the year after intervention. Significant improvements were demonstrated in quality-of-life scores (+10%, p = 0.001), behavioral symptoms (depression -33%, anxiety -32%, somatization -33%, and hostility -47%, all p values health habits (-60%, p = 0.0001), and total health risk (-25%, p = 0.0001). Of employees categorized as high risk at baseline, 57% were converted to low-risk status. Average employee annual claim costs decreased 48% (p = 0.002) for the 12 months after the intervention, whereas control employees' costs remained unchanged (-16%, p = NS), thus creating a sixfold return on investment. In conclusion, worksite health intervention using CRET staff decreased total health risk and markedly decreased medical claim costs within 12 months.

  17. The transmembrane nucleoporin NDC1 is required for targeting of ALADIN to nuclear pore complexes

    Energy Technology Data Exchange (ETDEWEB)

    Yamazumi, Yusuke; Kamiya, Atsushi; Nishida, Ayumu; Nishihara, Ayako [Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Bioscience, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Iemura, Shun-ichiro; Natsume, Tohru [Biological Information Research Center (AIST), Japan Biological Information Research Center (JBIC), Aomi 2-41-6, Koutou-ku, Tokyo 135-0064 (Japan); Akiyama, Tetsu, E-mail: akiyama@iam.u-tokyo.ac.jp [Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Bioscience, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan)

    2009-11-06

    NDC1 is a transmembrane nucleoporin that is required for NPC assembly and nucleocytoplasmic transport. We show here that NDC1 directly interacts with the nucleoporin ALADIN, mutations of which are responsible for triple-A syndrome, and that this interaction is required for targeting of ALADIN to nuclear pore complexes (NPCs). Furthermore, we show that NDC1 is required for selective nuclear import. Our findings suggest that NDC1-mediated localization of ALADIN to NPCs is essential for selective nuclear protein import, and that abrogation of the interaction between ALADIN and NDC1 may be important for the development of triple-A syndrome.

  18. Lifestyle intervention reduces body weight and improves cardiometabolic risk factors in worksites.

    Science.gov (United States)

    Salinardi, Taylor C; Batra, Payal; Roberts, Susan B; Urban, Lorien E; Robinson, Lisa M; Pittas, Anastassios G; Lichtenstein, Alice H; Deckersbach, Thilo; Saltzman, Edward; Das, Sai Krupa

    2013-04-01

    Worksites are potentially effective locations for obesity control because they provide opportunities for group intervention and social support. Studies are needed to identify effective interventions in these settings. We examined the effects of a multicomponent lifestyle intervention on weight loss and prevention of regain in 4 worksites (2 intervention and 2 control sites). Overweight and obese employees (n = 133) enrolled in this pilot worksite-randomized controlled trial with a 0-6-mo weight-loss phase and a 6-12-mo structured weight-maintenance phase. The intervention combined recommendations to consume a reduced-energy, low-glycemic load, high-fiber diet with behavioral change education. Outcome measurements included changes in body weight and cardiometabolic risk factors. The mean ± SEM weight loss was substantial in intervention participants, whereas control subjects gained weight (-8.0 ± 0.7 compared with +0.9 ± 0.5 kg, respectively; P weight-loss phase. Intervention effects were not significant at the 0.05 level but would have been at the 0.10 level (P = 0.08) in a mixed model in which the worksite nested within group was a random factor. There were also significant improvements in cardiometabolic risk factors in intervention compared with control subjects regarding fasting total cholesterol, glucose, systolic blood pressure, and diastolic blood pressure (P ≤ 0.02 for each). No significant weight regain was observed in participants who enrolled in the structured weight-maintenance program (0.5 ± 0.7 kg; P = 0.65), and overweight and obese employees in intervention worksites who were not enrolled in the weight-loss program lost weight compared with subjects in control worksites (-1.3 ± 0.5 compared with +0.7 ± 0.2 kg, respectively; P = 0.02). Worksites can be effective for achieving clinically important reductions in body weight and improved cardiometabolic risk factors. This trial was registered at clinicaltrials.gov as NCT01470222.

  19. A worksite prevention program for construction workers: design of a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Proper Karin I

    2010-06-01

    Full Text Available Abstract Background A worksite prevention program was developed to promote the work ability of construction workers and thereby prolong a healthy working life. The objective of this paper is to present the design of a randomized controlled trial evaluating the effectiveness of that intervention program compared with usual care for construction workers. Methods The study is designed as a randomized controlled trial with a follow-up of one year. Employees eligible for this study are construction workers performing actual construction work. The worksite intervention will be compared with usual care. This intervention was developed by using the Intervention Mapping approach and consists of the following components: (1 two individual training sessions of a physical therapist to lower the physical workload, (2 a Rest-Break tool to improve the balance between work and recovery, and (3 two empowerment training sessions to increase the influence of the construction workers at the worksite. Outcome measures are assessed at baseline, 3, 6, and 12 months. The primary outcome measures of this study are work ability and health-related quality of life. Secondary outcome measures include need for recovery, musculoskeletal complaints, work engagement and self efficacy. Cost-effectiveness will be evaluated from the company perspective. Moreover, a process evaluation will be conducted. Discussion The feasibility of the intervention and the study has been enhanced by creating an intervention program that explicitly appeals to construction workers and will not interfere too much with the ongoing construction. The feasibility and effectiveness of this worksite prevention program will be investigated by means of an effect- and a process evaluation. If proven effective, this worksite prevention program can be implemented on a larger scale within the construction industry. Trial Registration NTR1278

  20. Kinetochore biorientation in Saccharomyces cerevisiae requires a tightly folded conformation of the Ndc80 complex.

    Science.gov (United States)

    Tien, Jerry F; Umbreit, Neil T; Zelter, Alex; Riffle, Michael; Hoopmann, Michael R; Johnson, Richard S; Fonslow, Bryan R; Yates, John R; MacCoss, Michael J; Moritz, Robert L; Asbury, Charles L; Davis, Trisha N

    2014-12-01

    Accurate transmission of genetic material relies on the coupling of chromosomes to spindle microtubules by kinetochores. These linkages are regulated by the conserved Aurora B/Ipl1 kinase to ensure that sister chromatids are properly attached to spindle microtubules. Kinetochore-microtubule attachments require the essential Ndc80 complex, which contains two globular ends linked by large coiled-coil domains. In this study, we isolated a novel ndc80 mutant in Saccharomyces cerevisiae that contains mutations in the coiled-coil domain. This ndc80 mutant accumulates erroneous kinetochore-microtubule attachments, resulting in misalignment of kinetochores on the mitotic spindle. Genetic analyses with suppressors of the ndc80 mutant and in vitro cross-linking experiments suggest that the kinetochore misalignment in vivo stems from a defect in the ability of the Ndc80 complex to stably fold at a hinge in the coiled coil. Previous studies proposed that the Ndc80 complex can exist in multiple conformations: elongated during metaphase and bent during anaphase. However, the distinct functions of individual conformations in vivo are unknown. Here, our analysis revealed a tightly folded conformation of the Ndc80 complex that is likely required early in mitosis. This conformation is mediated by a direct, intracomplex interaction and involves a greater degree of folding than the bent form of the complex at anaphase. Furthermore, our results suggest that this conformation is functionally important in vivo for efficient error correction by Aurora B/Ipl1 and, consequently, to ensure proper kinetochore alignment early in mitosis.

  1. Management of Sodium-reduced Meals at Worksite Cafeterias: Perceptions, Practices, Barriers, and Needs among Food Service Personnel

    OpenAIRE

    Lee, Jounghee; Park, Sohyun

    2015-01-01

    Objectives The sodium content of meals provided at worksite cafeterias is greater than the sodium content of restaurant meals and home meals. The objective of this study was to assess the relationships between sodium-reduction practices, barriers, and perceptions among food service personnel. Methods We implemented a cross-sectional study by collecting data on perceptions, practices, barriers, and needs regarding sodium-reduced meals at 17 worksite cafeterias in South Korea. We implemented Ch...

  2. Yeast SREBP cleavage activation requires the Golgi Dsc E3 ligase complex.

    Science.gov (United States)

    Stewart, Emerson V; Nwosu, Christine C; Tong, Zongtian; Roguev, Assen; Cummins, Timothy D; Kim, Dong-Uk; Hayles, Jacqueline; Park, Han-Oh; Hoe, Kwang-Lae; Powell, David W; Krogan, Nevan J; Espenshade, Peter J

    2011-04-22

    Mammalian lipid homeostasis requires proteolytic activation of membrane-bound sterol regulatory element binding protein (SREBP) transcription factors through sequential action of the Golgi Site-1 and Site-2 proteases. Here we report that while SREBP function is conserved in fungi, fission yeast employs a different mechanism for SREBP cleavage. Using genetics and biochemistry, we identified four genes defective for SREBP cleavage, dsc1-4, encoding components of a transmembrane Golgi E3 ligase complex with structural homology to the Hrd1 E3 ligase complex involved in endoplasmic reticulum-associated degradation. The Dsc complex binds SREBP and cleavage requires components of the ubiquitin-proteasome pathway: the E2-conjugating enzyme Ubc4, the Dsc1 RING E3 ligase, and the proteasome. dsc mutants display conserved aggravating genetic interactions with components of the multivesicular body pathway in fission yeast and budding yeast, which lacks SREBP. Together, these data suggest that the Golgi Dsc E3 ligase complex functions in a post-ER pathway for protein degradation.

  3. The Smc5-Smc6 complex is required to remove chromosome junctions in meiosis.

    Directory of Open Access Journals (Sweden)

    Sarah Farmer

    Full Text Available Meiosis, a specialized cell division with a single cycle of DNA replication round and two consecutive rounds of nuclear segregation, allows for the exchange of genetic material between parental chromosomes and the formation of haploid gametes. The structural maintenance of chromosome (SMC proteins aid manipulation of chromosome structures inside cells. Eukaryotic SMC complexes include cohesin, condensin and the Smc5-Smc6 complex. Meiotic roles have been discovered for cohesin and condensin. However, although Smc5-Smc6 is known to be required for successful meiotic divisions, the meiotic functions of the complex are not well understood. Here we show that the Smc5-Smc6 complex localizes to specific chromosome regions during meiotic prophase I. We report that meiotic cells lacking Smc5-Smc6 undergo catastrophic meiotic divisions as a consequence of unresolved linkages between chromosomes. Surprisingly, meiotic segregation defects are not rescued by abrogation of Spo11-induced meiotic recombination, indicating that at least some chromosome linkages in smc5-smc6 mutants originate from other cellular processes. These results demonstrate that, as in mitosis, Smc5-Smc6 is required to ensure proper chromosome segregation during meiosis by preventing aberrant recombination intermediates between homologous chromosomes.

  4. IDN2 and its paralogs form a complex required for RNA-directed DNA methylation.

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    Cui-Jun Zhang

    Full Text Available IDN2/RDM12 has been previously identified as a component of the RNA-directed DNA methylation (RdDM machinery in Arabidopsis thaliana, but how it functions in RdDM remains unknown. By affinity purification of IDN2, we co-purified two IDN2 paralogs IDP1 and IDP2 (IDN2 PARALOG 1 and 2. The coiled-coil domain between the XS and XH domains of IDN2 is essential for IDN2 homodimerization, whereas the IDN2 C-terminal XH domain but not the coiled-coil domain is required for IDN2 interaction with IDP1 and IDP2. By introducing the wild-type IDN2 sequence and its mutated derivatives into the idn2 mutant for complementation testing, we demonstrated that the previously uncharacterized IDN2 XH domain is required for the IDN2-IDP1/IDP2 complex formation as well as for IDN2 function. IDP1 is required for de novo DNA methylation, siRNA accumulation, and transcriptional gene silencing, whereas IDP2 has partially overlapping roles with IDP1. Unlike IDN2, IDP1 and IDP2 are incapable of binding double-stranded RNA, suggesting that the roles of IDP1 and IDP2 are different from those of IDN2 in the IDN2-IDP1/IDP2 complex and that IDP1 and IDP2 are essential for the functioning of the complex in RdDM.

  5. The Mre11-Rad50-Xrs2 complex is required for yeast DNA postreplication repair.

    Science.gov (United States)

    Ball, Lindsay G; Hanna, Michelle D; Lambrecht, Amanda D; Mitchell, Bryan A; Ziola, Barry; Cobb, Jennifer A; Xiao, Wei

    2014-01-01

    Yeast DNA postreplication repair (PRR) bypasses replication-blocking lesions to prevent damage-induced cell death. PRR employs two different mechanisms to bypass damaged DNA, namely translesion synthesis (TLS) and error-free PRR, which are regulated via sequential ubiquitination of proliferating cell nuclear antigen (PCNA). We previously demonstrated that error-free PRR utilizes homologous recombination to facilitate template switching. To our surprise, genes encoding the Mre11-Rad50-Xrs2 (MRX) complex, which are also required for homologous recombination, are epistatic to TLS mutations. Further genetic analyses indicated that two other nucleases involved in double-strand end resection, Sae2 and Exo1, are also variably required for efficient lesion bypass. The involvement of the above genes in TLS and/or error-free PRR could be distinguished by the mutagenesis assay and their differential effects on PCNA ubiquitination. Consistent with the observation that the MRX complex is required for both branches of PRR, the MRX complex was found to physically interact with Rad18 in vivo. In light of the distinct and overlapping activities of the above nucleases in the resection of double-strand breaks, we propose that the interplay between distinct single-strand nucleases dictate the preference between TLS and error-free PRR for lesion bypass.

  6. Structuring requirements as necessary premise for customer-oriented development of complex products: A generic approach

    Directory of Open Access Journals (Sweden)

    Sandra Klute

    2011-10-01

    Full Text Available Purpose: Complex products like for example intra-logistical facilities make high demands on developers and producers and involve high investment and operating costs. When planning and developing and also making buying decisions the facility utilization and the thus ensuing requirements on the facility and its components are inadequately considered to date. Nevertheless, with regard to customer-directed product design, these requirements must all be taken into account – especially as they can contribute to possible savings. In this context, it is necessary to survey and systematically regard requirements from a large number of areas like for example the operator, the facility producer and also requirements of external parties such as the law and to implement into adequate product characteristics to produce customer-oriented products. This is, however, a difficult task because of the diversity of stakeholders involved and their numerous and often divergent requirements. Therefore, it is essential to structure the requirements, so that planners and developers are able to manage the large amount of information. Structure models can be used in this context to cluster requirements. Within the German Collaborative Research Centre 696 a 10-dimensional model has been developed. This model allows structuring of all requirements on intra-logistical facilities or respectively complex products in general. In the context of dealing with hundreds of data records, structuring requirements is mandatory to achieve accuracy, clarity and consequently satisfactory results when transforming requirements into product characteristics which fit customer needs. In the paper an excerpt of this model is presented. Design/methodology/approach: In literature a multitude of methods which deal with the topic of structuring exist. The methods have been analysed regarding their purpose and their level of specification, i.e. the number of differentiated categories, to check if

  7. Functional Requirements for Fab-7 Boundary Activity in the Bithorax Complex.

    Science.gov (United States)

    Wolle, Daniel; Cleard, Fabienne; Aoki, Tsutomu; Deshpande, Girish; Schedl, Paul; Karch, Francois

    2015-11-01

    Chromatin boundaries are architectural elements that determine the three-dimensional folding of the chromatin fiber and organize the chromosome into independent units of genetic activity. The Fab-7 boundary from the Drosophila bithorax complex (BX-C) is required for the parasegment-specific expression of the Abd-B gene. We have used a replacement strategy to identify sequences that are necessary and sufficient for Fab-7 boundary function in the BX-C. Fab-7 boundary activity is known to depend on factors that are stage specific, and we describe a novel ∼700-kDa complex, the late boundary complex (LBC), that binds to Fab-7 sequences that have insulator functions in late embryos and adults. We show that the LBC is enriched in nuclear extracts from late, but not early, embryos and that it contains three insulator proteins, GAF, Mod(mdg4), and E(y)2. Its DNA binding properties are unusual in that it requires a minimal sequence of >65 bp; however, other than a GAGA motif, the three Fab-7 LBC recognition elements display few sequence similarities. Finally, we show that mutations which abrogate LBC binding in vitro inactivate the Fab-7 boundary in the BX-C.

  8. Worksite dining as a collective good or individualization of health - a Danish perspective

    DEFF Research Database (Denmark)

    Jørgensen, Michael Søgaard; Mikkelsen, Bent Egberg; Thorsen, Anne Vibeke

    The paper is based on a survey of Danish literature about worksite eating carried out as a part of the project ‘Food at work around the clock?’ carried by Lunds University and Technical University of Denmark and financed by Øresund Food Network. The focus has especially been on the relations....... The few analyses which have been conducted show that negative and long-term stress, where the employee lack influence and control on own work may cause health problems and changes in body weight, so that slim persons become slimmer and the obese become more obese. A small interview survey shows...... that the type and the organization of work influence how the worksite eating is organized. Especially in the service sector it is difficult for the employees to eat at the same time. The eating schedule is negotiated among the employees according to the needs of the individual employee. An area with Danish...

  9. A follow-up of a media-based, worksite smoking cessation program.

    Science.gov (United States)

    Salina, D; Jason, L A; Hedeker, D; Kaufman, J; Lesondak, L; McMahon, S D; Taylor, S; Kimball, P

    1994-04-01

    Described an examination of data collected 2 years following the onset of a media-based, worksite smoking cessation intervention. Thirty-eight companies in Chicago were randomly assigned to one of two experimental conditions. In the initial 3-week phase, all participants in both conditions received self-help manuals and were instructed to watch a 20-day televised series designed to accompany the manual. In addition, participants in the group (G) condition received six sessions emphasizing quitting techniques and social support. In the second phase, which continued for 12 months, employees in G participated in monthly peer-led support groups and received incentives, while participants in the nongroup (NG) condition received no further treatment. Twenty-four months after pretest, 30% of employees in G were abstinent compared to only 19.5% in NG. This study is one of the few experimentally controlled worksite smoking cessation interventions to demonstrate significant program differences 2 years following the initial intervention.

  10. Implementation of a worksite educational program focused on promoting healthy eating habits

    OpenAIRE

    Dimitra Tanagra; Dimitris Panidis; Yannis Tountas; Elina Remoudaki; Alexopoulos, Evangelos C.

    2014-01-01

    Objective: To estimate the effectiveness of a short-term educational-counseling worksite program focused on lipid intake, by monitoring the possible change on nutrition knowledge and eating habits. Methods: an 8-week educational program based on the Health Belief Model was implemented in a honey packaging and sales company in Greece. 20 out of the 29 employees initially enrolled completed the program. Knowledge level and eating habits were evaluated prior and after the intervention by the “Nu...

  11. Assessing management support for worksite health promotion: psychometric analysis of the leading by example (LBE) instrument.

    Science.gov (United States)

    Della, Lindsay J; DeJoy, David M; Goetzel, Ron Z; Ozminkowski, Ronald J; Wilson, Mark G

    2008-01-01

    Describe the development of the leading by example (LBE) instrument. A total of 135 responses from employees of a private corporation working at 11 different worksites were factor analyzed in 2005. Exploratory factor analysis was used to obtain an initial factor structure. Factor validity was evaluated using confirmatory factor analysis methods. A second sample was collected in 2006 from the same population (N = 178) and was used to confirm the factor structure via confirmatory factor analysis. Cronbach's alpha and item-total correlations provided information on the reliability of the factor subscales. Four subscales were identified: business alignment with health promotion objectives, awareness of the health-productivity link, worksite support for health promotion, and leadership support for health promotion. Factor by group comparisons revealed that the initial factor structure was effective in detecting differences in organizational support for health promotion across different employee groups. Management support for health promotion can be assessed using the LBE, a brief self-report questionnaire. Researchers can use the LBE to diagnose, track, and evaluate worksite health promotion programs.

  12. The role of health and wellness coaching in worksite health promotion.

    Science.gov (United States)

    Chapman, Larry S; Lesch, Nancy; Baun, MaryBeth Pappas

    2007-01-01

    Health and wellness coaching has rapidly become a best practice element of worksite health promotion programs. Coaching as a process is a very old technology, but its use in the field of health promotion is relatively new. Coaching can be provided in different forms or modalities yet currently lacks a rigorous science base or a defined set of standards or common elements. In larger worksite settings several variants or forms of coaching are usually provided to employee populations. The need for more proactive and direct forms of intervention in health promotion is contributing to the rapid growth of coaching programs. There are currently an assortment of coaching strategies or techniques that are in common use in most coaching interventions. A main contention of current coaching practice is that coaching that uses facilitation strategies rather than prescriptive advice is more effective at producing long term behavior change. The congruence and size of wellness incentives with the coaching process are likely to be of significant importance. From a long term perspective, coaching is likely to become a staple of worksite health promotion practice.

  13. Implementation of an Internet Weight Loss Program in a Worksite Setting

    Directory of Open Access Journals (Sweden)

    Kathryn M. Ross

    2016-01-01

    Full Text Available Background. Worksite wellness programs typically produce modest weight losses. We examined whether an efficacious Internet behavioral weight loss program could be successfully implemented in a worksite setting. Methods. Participants were 75 overweight or obese employees/dependents of a large healthcare system who were given access to a 12-week Internet-based, multicomponent behavioral weight loss program. Assessments occurred at baseline, Month 3 (end of intervention, and Month 6 (follow-up. Results. Retention was excellent (93% at Month 3 and 89% at Month 6. Intent-to-treat analyses demonstrated that participants lost an average (±SE of -5.8±.60 kg from baseline to Month 3 and regained 1.1±.31 kg from Month 3 to Month 6; overall, weight loss from baseline to Month 6 was -4.7±.71 kg, p<.001. Men lost more weight than women, p=.022, and individuals who had a college degree or higher lost more weight than those with less education, p=.005. Adherence to viewing lessons (8 of 12 and self-monitoring (83% of days was excellent and significantly associated with weight loss, ps<.05. Conclusions. An Internet-based behavioral weight management intervention can be successfully implemented in a worksite setting and can lead to clinically significant weight losses. Given the low costs of offering this program, it could easily be widely disseminated.

  14. The Par-PrkC polarity complex is required for cilia growth in zebrafish photoreceptors.

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    Bryan L Krock

    Full Text Available Specification and development of the apical membrane in epithelial cells requires the function of polarity proteins, including Pard3 and an atypical protein kinase C (PrkC. Many epithelial cells possess microtubule-based organelles, known as cilia, that project from their apical surface and the membrane surrounding the cilium is contiguous with the apical cell membrane. Although cilia formation in cultured cells required Pard3, the in vivo requirement for Pard3 in cilia development remains unknown. The vertebrate photoreceptor outer segment represents a highly specialized cilia structure in which to identify factors necessary for apical and ciliary membrane formation. Pard3 and PrkC localized to distinct domains within vertebrate photoreceptors. Using partial morpholino knockdown, photo-morpholinos, and pharmacological approaches, the function of Pard3 and PrkC were found to be required for the formation of both the apical and ciliary membrane of vertebrate photoreceptors. Inhibition of Pard3 or PrkC activity significantly reduced the size of photoreceptor outer segments and resulted in mislocalization of rhodopsin. Suppression of Pard3 or PrkC also led to a reduction in cilia size and cilia number in Kupffer's Vesicle, which resulted in left-right asymmetry defects. Thus, the Par-PrkC complex functions in cilia formation in vivo and this likely reflects a general role in specifying non-ciliary and ciliary compartments of the apical domain.

  15. A Protein Complex Required for Polymerase V Transcripts and RNA- Directed DNA Methylation in Arabidopsis

    KAUST Repository

    Law, Julie A.

    2010-05-01

    DNA methylation is an epigenetic modification associated with gene silencing. In Arabidopsis, DNA methylation is established by DOMAINS REARRANGED METHYLTRANSFERASE 2 (DRM2), which is targeted by small interfering RNAs through a pathway termed RNA-directed DNA methylation (RdDM) [1, 2]. Recently, RdDM was shown to require intergenic noncoding (IGN) transcripts that are dependent on the Pol V polymerase. These transcripts are proposed to function as scaffolds for the recruitment of downstream RdDM proteins, including DRM2, to loci that produce both siRNAs and IGN transcripts [3]. However, the mechanism(s) through which Pol V is targeted to specific genomic loci remains largely unknown. Through affinity purification of two known RdDM components, DEFECTIVE IN RNA-DIRECTED DNA METHYLATION 1 (DRD1) [4] and DEFECTIVE IN MERISTEM SILENCING 3 (DMS3) [5, 6], we found that they copurify with each other and with a novel protein, RNA-DIRECTED DNA METHYLATION 1 (RDM1), forming a complex we term DDR. We also found that DRD1 copurified with Pol V subunits and that RDM1, like DRD1 [3] and DMS3 [7], is required for the production of Pol V-dependent transcripts. These results suggest that the DDR complex acts in RdDM at a step upstream of the recruitment or activation of Pol V. © 2010 Elsevier Ltd. All rights reserved.

  16. Education requirements for nurses working with people with complex neurological conditions: nurses' perceptions.

    Science.gov (United States)

    Baker, Mark

    2012-01-01

    Following a service evaluation methodology, this paper reports on registered nurses' (RNs) and healthcare assistants' (HCAs) perceptions about education and training requirements in order to work with people with complex neurological disabilities. A service evaluation was undertaken to meet the study aim using a non-probability, convenience method of sampling 368 nurses (n=110 RNs, n=258 HCAs) employed between October and November 2008 at one specialist hospital in south-west London in the U.K. The main results show that respondents were clear about the need to develop an education and training programme for RNs and HCAs working in this speciality area (91% of RNs and 94% of HCAs). A variety of topics were identified to be included within a work-based education and training programme, such as positively managing challenging behaviour, moving and handling, working with families. Adults with complex neurological needs have diverse needs and thus nurses working with this patient group require diverse education and training in order to deliver quality patient-focused nursing care.

  17. The mammalian INO80 chromatin remodeling complex is required for replication stress recovery

    Science.gov (United States)

    Vassileva, Ivelina; Yanakieva, Iskra; Peycheva, Michaela; Gospodinov, Anastas; Anachkova, Boyka

    2014-01-01

    A number of studies have implicated the yeast INO80 chromatin remodeling complex in DNA replication, but the function of the human INO80 complex during S phase remains poorly understood. Here, we have systematically investigated the involvement of the catalytic subunit of the human INO80 complex during unchallenged replication and under replication stress by following the effects of its depletion on cell survival, S-phase checkpoint activation, the fate of individual replication forks, and the consequences of fork collapse. We report that INO80 was specifically needed for efficient replication elongation, while it was not required for initiation of replication. In the absence of the Ino80 protein, cells became hypersensitive to hydroxyurea and displayed hyperactive ATR-Chk1 signaling. Using bulk and fiber labeling of DNA, we found that cells deficient for Ino80 and Arp8 had impaired replication restart after treatment with replication inhibitors and accumulated double-strand breaks as evidenced by the formation of γ-H2AX and Rad51 foci. These data indicate that under conditions of replication stress mammalian INO80 protects stalled forks from collapsing and allows their subsequent restart. PMID:25016522

  18. Transcriptional repression of the yeast CHA1 gene requires the chromatin-remodeling complex RSC

    DEFF Research Database (Denmark)

    Moreira, José Manuel Alfonso; Holmberg, S

    1999-01-01

    In eukaryotes, DNA is packaged into chromatin, a compact structure that must be disrupted when genes are transcribed by RNA polymerase II. For transcription to take place, chromatin is remodeled via nucleosome disruption or displacement, a fundamental transcriptional regulatory mechanism in eukar......In eukaryotes, DNA is packaged into chromatin, a compact structure that must be disrupted when genes are transcribed by RNA polymerase II. For transcription to take place, chromatin is remodeled via nucleosome disruption or displacement, a fundamental transcriptional regulatory mechanism...... in eukaryotic organisms. Here we show that the yeast chromatin-remodeling complex, RSC (remodels the structure of chromatin), isolated on the basis of homology to the SWI/SNF complex, is required for proper transcriptional regulation and nucleosome positioning in the highly inducible CHA1 promoter...... of the CHA1 promoter is disrupted, an architectural change normally only observed during transcriptional induction. In addition, deletion of the gene-specific activator Cha4p did not affect derepression of CHA1 in cells depleted for Swh3p. Thus, CHA1 constitutes a target for the RSC complex, and we propose...

  19. Complex problems require complex solutions: the utility of social quality theory for addressing the Social Determinants of Health

    Directory of Open Access Journals (Sweden)

    Ward Paul R

    2011-08-01

    Full Text Available Abstract Background In order to improve the health of the most vulnerable groups in society, the WHO Commission on Social Determinants of Health (CSDH called for multi-sectoral action, which requires research and policy on the multiple and inter-linking factors shaping health outcomes. Most conceptual tools available to researchers tend to focus on singular and specific social determinants of health (SDH (e.g. social capital, empowerment, social inclusion. However, a new and innovative conceptual framework, known as social quality theory, facilitates a more complex and complete understanding of the SDH, with its focus on four domains: social cohesion, social inclusion, social empowerment and socioeconomic security, all within the same conceptual framework. This paper provides both an overview of social quality theory in addition to findings from a national survey of social quality in Australia, as a means of demonstrating the operationalisation of the theory. Methods Data were collected using a national random postal survey of 1044 respondents in September, 2009. Multivariate logistic regression analysis was conducted. Results Statistical analysis revealed that people on lower incomes (less than $45000 experience worse social quality across all of the four domains: lower socio-economic security, lower levels of membership of organisations (lower social cohesion, higher levels of discrimination and less political action (lower social inclusion and lower social empowerment. The findings were mixed in terms of age, with people over 65 years experiencing lower socio-economic security, but having higher levels of social cohesion, experiencing lower levels of discrimination (higher social inclusion and engaging in more political action (higher social empowerment. In terms of gender, women had higher social cohesion than men, although also experienced more discrimination (lower social inclusion. Conclusions Applying social quality theory allows

  20. The CA domain of the respiratory complex I is required for normal embryogenesis in Arabidopsis thaliana.

    Science.gov (United States)

    Córdoba, Juan Pablo; Marchetti, Fernanda; Soto, Débora; Martin, María Victoria; Pagnussat, Gabriela Carolina; Zabaleta, Eduardo

    2016-03-01

    The NADH-ubiquinone oxidoreductase [complex I (CI), EC 1.6.5.3] of the mitochondrial respiratory chain is the principal entry point of electrons, and vital in maintaining metabolism and the redox balance. In a variety of eukaryotic organisms, except animal and fungi (Opisthokonta), it contains an extra domain composed of putative gamma carbonic anhydrases subunits, named the CA domain, which was proposed to be essential for complex I assembly. There are two kinds of carbonic anhydrase subunits: CAs (of which there are three) and carbonic anhydrase-like proteins (CALs) (of which there are two). In plants, the CA domain has been linked to photorespiration. In this work, we report that Arabidopsis mutant plants affected in two specific CA subunits show a lethal phenotype. Double homozygous knockouts ca1ca2 embryos show a significant developmental delay compared to the non-homozygous embryos, which show a wild-type (WT) phenotype in the same silique. Mutant embryos show impaired mitochondrial membrane potential and mitochondrial reactive oxygen species (ROS) accumulation. The characteristic embryo greening does not take place and fewer but larger oil bodies are present. Although seeds look dark brown and wrinkled, they are able to germinate 12 d later than WT seeds. However, they die immediately, most likely due to oxidative stress.Since the CA domain is required for complex I biogenesis, it is predicted that in ca1ca2 mutants no complex I could be formed, triggering the lethal phenotype. The in vivo composition of a functional CA domain is proposed.

  1. A Consensus-Based Grouping Algorithm for Multi-agent Cooperative Task Allocation with Complex Requirements.

    Science.gov (United States)

    Hunt, Simon; Meng, Qinggang; Hinde, Chris; Huang, Tingwen

    2014-01-01

    This paper looks at consensus algorithms for agent cooperation with unmanned aerial vehicles. The foundation is the consensus-based bundle algorithm, which is extended to allow multi-agent tasks requiring agents to cooperate in completing individual tasks. Inspiration is taken from the cognitive behaviours of eusocial animals for cooperation and improved assignments. Using the behaviours observed in bees and ants inspires decentralised algorithms for groups of agents to adapt to changing task demand. Further extensions are provided to improve task complexity handling by the agents with added equipment requirements and task dependencies. We address the problems of handling these challenges and improve the efficiency of the algorithm for these requirements, whilst decreasing the communication cost with a new data structure. The proposed algorithm converges to a conflict-free, feasible solution of which previous algorithms are unable to account for. Furthermore, the algorithm takes into account heterogeneous agents, deadlocking and a method to store assignments for a dynamical environment. Simulation results demonstrate reduced data usage and communication time to come to a consensus on multi-agent tasks.

  2. Making Healthy Behaviors the Easy Choice for Employees: A Review of the Literature on Environmental and Policy Changes in Worksite Health Promotion

    Science.gov (United States)

    Kahn-Marshall, Jennifer L.; Gallant, Mary P.

    2012-01-01

    As employers look for ways to reduce rising health care costs, worksite health promotion interventions are increasingly being used to improve employee health behaviors. An alternative approach to traditional worksite health promotion programs is the implementation of environmental and/or policy changes to encourage employees to adopt healthier…

  3. A comprehensive five-step surgical management approach to penetrating liver injuries that require complex repair.

    Science.gov (United States)

    Ordoñez, Carlos Alberto; Parra, Michael W; Salamea, Juan Carlos; Puyana, Juan Carlos; Millán, Mauricio; Badiel, Marisol; Sanjuán, Juán; Pino, Luis F; Scavo, David; Botache, Wilmer; Ferrada, Ricardo

    2013-08-01

    The objective of this study was to describe a comprehensive five-step surgical management approach for patients with penetrating liver trauma based on our collective institutional experience. A prospective consecutive study of all penetrating liver traumas from January 2003 to December 2011 at a regional Level I trauma center in Cali, Colombia, was conducted. A total of 538 patients with penetrating thoracoabdominal trauma were operated on at our institution. Of these, 146 had penetrating liver injuries that satisfied the inclusion criteria for surgical intervention to manage their hepatic and/or associated injuries. Eighty-eight patients (60%) had an American Association for the Surgery of Trauma-Organ Injury Scale (AAST-OIS) of Grade III (54 patients, 37%), Grade IV (24 patients, 16%), and Grade V (10 patients, 7%). This group of patients required advanced "complex" techniques of hemostasis such as the Pringle maneuver (PM), perihepatic liver packing (PHLP), and/or hepatotomy with selective vessel ligation (SVL). The focus of our study was this subgroup of patients, which we further divided into two as follows: those who required only PM + PHLP (55 patients, 63%) to obtain control of their liver hemorrhage and those who required PM + PHLP + SVL (33 patients, 37%). Of the patients who required PM + PHLP + SVL, 10 (27%) required ligation of major intrahepatic branches, which included suprahepatic veins (n = 4), portal vein (n = 4), retrohepatic vena cava (n = 1), and hepatic artery (n = 1). The remaining 23 patients (73%) required direct vessel ligation of smaller intraparenchymal vessels. The overall mortality was 15.9% (14 of 88), with 71.4% (10 of 14) related to coagulopathy. Mortality rates for Grade III was 3.7% (2 of 54), for Grade IV was 20.8% (5 of 24), and for Grade V was 70% (7 of 10). The mortality in the PM + PHLP + SVL group was higher compared with the PM + PHLP group (12 [36.4%] vs. 2 [3.6%], p = 0.001]. For those patients who fail to respond to PM

  4. The AP-3 adaptor complex is required for vacuolar function in Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    Maria Zwiewka; Elena Feraru; Barbara M(o)ller; Inhwan Hwang; Mugurel I Feraru; Jürgen Kleine-Vehn; Dolf Weijers; Ji(n) Friml

    2011-01-01

    Subcellular trafficking is required for a multitude of functions in eukaryotic cells.It involves regulation of cargo sorting,vesicle formation,trafficking and fusion processes at multiple levels.Adaptor protein (AP) complexes are key regulators of cargo sorting into vesicles in yeast and mammals but their existence and function in plants have not been demonstrated.Here we report the identification of the protein-affected trafficking 4 (pat4) mutant defective in the putative δ subunit of the AP-3 complex.pat4 and pat2,a mutant isolated from the same GFP imaging-based forward genetic screen that lacks a functional putative AP-3 β,as well as dominant negative AP-3 μ transgenic lines display undistinguishable phenotypes characterized by largely normal morphology and development,but strong intracellular accumulation of membrane proteins in aberrant vacuolar structures.All mutants are defective in morphology and function of lytic and protein storage vacuoles (PSVs) but show normal sorting of reserve proteins to PSVs.Immunoprecipitation experiments and genetic studies revealed tight functional and physical associations of putative AP-3 β and AP-3 δ subunits.Furthermore,both proteins are closely linked with putative AP-3 μ and σ subunits and several components of the clathrin and dynamin machineries.Taken together,these results demonstrate that AP complexes,similar to those in other eukaryotes,exist in plants,and that AP-3 plays a specific role in the regulation of biogenesis and function of vacuoles in plant cells.

  5. Efficient nuclear export of p65-IkappaBalpha complexes requires 14-3-3 proteins.

    Science.gov (United States)

    Aguilera, Cristina; Fernández-Majada, Vanessa; Inglés-Esteve, Julia; Rodilla, Verónica; Bigas, Anna; Espinosa, Lluís

    2006-09-01

    IkappaB are responsible for maintaining p65 in the cytoplasm under non-stimulating conditions and promoting the active export of p65 from the nucleus following NFkappaB activation to terminate the signal. We now show that 14-3-3 proteins regulate the NFkappaB signaling pathway by physically interacting with p65 and IkappaBalpha proteins. We identify two functional 14-3-3 binding domains in the p65 protein involving residues 38-44 and 278-283, and map the interaction region of IkappaBalpha in residues 60-65. Mutation of these 14-3-3 binding domains in p65 or IkappaBalpha results in a predominantly nuclear distribution of both proteins. TNFalpha treatment promotes recruitment of 14-3-3 and IkappaBalpha to NFkappaB-dependent promoters and enhances the binding of 14-3-3 to p65. Disrupting 14-3-3 activity by transfection with a dominant-negative 14-3-3 leads to the accumulation of nuclear p65-IkappaBalpha complexes and the constitutive association of p65 with the chromatin. In this situation, NFkappaB-dependent genes become unresponsive to TNFalpha stimulation. Together our results indicate that 14-3-3 proteins facilitate the nuclear export of IkappaBalpha-p65 complexes and are required for the appropriate regulation of NFkappaB signaling.

  6. Bax-PGAM5L-Drp1 complex is required for intrinsic apoptosis execution.

    Science.gov (United States)

    Xu, Wenjuan; Jing, Linlin; Wang, Quanshi; Lin, Chung-Chih; Chen, Xiaoting; Diao, Jianxin; Liu, Yuanliang; Sun, Xuegang

    2015-10-06

    Intrinsic apoptosis eliminates cells with damaged DNA and cells with dysregulated expression of oncogene. PGAM5, a member of the phosphoglycerate mutase family, has two splicing variants: PGAM5L (the long form) and PGAM5S (the short form). It has been well established that PGAM5 is at the convergent point of multiple necrosis pathways. However, the role of PGAM5 in intrinsic apoptosis is still controversial. Here we report that the PGAM5L, but not PGAM5S is a prerequisite for the activation of Bax and dephosphorylation of Drp1 in arenobufagin and staurosporine induced intrinsic apoptosis. Knockdown of PGAM5L inhibits the translocation of Bax to the mitochondria and reduces mitochondrial fission. The interaction between PGAM5L and Drp1 was observed in both arenobufagin and staurosporine treated HCT116 cells, but not in HCT116 Bax(-/-) cells. Bax transfection rescues the formation of the triplex in both arenobufagin and staurosporine stimulated HCT116 Bax(-/-) cells. Arenobufagin shows remarkable anti-cancer effects both in orthotropic and heterotropic CRC models and demonstrates less toxic effects as compared with that of cisplatin. Bax-PGAM5L-Drp1 complex is detected in arenobufagin and staurosporine treated CRC cells in vitro and in arenobufagin and cisplatin treated tumor in vivo as well. In summary, our results demonstrate that Bax-PGAM5L-Drp1 complex is required for intrinsic apoptosis execution.

  7. An analysis of the processing requirements of a complex perceptual-motor task

    Science.gov (United States)

    Kramer, A. F.; Wickens, C. D.; Donchin, E.

    1983-01-01

    Current concerns in the assessment of mental workload are discussed, and the event-related brain potential (ERP) is introduced as a promising mental-workload index. Subjects participated in a series of studies in which they were required to perform a target acquisition task while also covertly counting either auditory or visual probes. The effects of several task-difficulty manipulations on the P300 component of the ERP elicited by the counted stimulus probes were investigated. With sufficiently practiced subjects the amplitude of the P300 was found to decrease with increases in task difficulty. The second experiment also provided evidence that the P300 is selectively sensitive to task-relevant attributes. A third experiment demonstrated a convergence in the amplitude of the P300s elicited in the simple and difficult versions of the tracking task. The amplitude of the P300 was also found to covary with the measures of tracking performance. The results of the series of three experiments illustrate the sensitivity of the P300 to the processing requirements of a complex target acquisition task. The findings are discussed in terms of the multidimensional nature of processing resources.

  8. Technique of Substantiating Requirements for the Vision Systems of Industrial Robotic Complexes

    Directory of Open Access Journals (Sweden)

    V. Ya. Kolyuchkin

    2015-01-01

    Full Text Available In references, there is a lack of approaches to describe the justified technical requirements for the vision systems (VS of industrial robotics complexes (IRC. Therefore, an objective of the work is to develop a technique that allows substantiating requirements for the main quality indicators of VS, functioning as a part of the IRC.The proposed technique uses a model representation of VS, which, as a part of the IRC information system, sorts the objects in the work area, as well as measures their linear and angular coordinates. To solve the problem of statement there is a proposal to define the target function of a designed IRC as a dependence of the IRC indicator efficiency on the VS quality indicators. The paper proposes to use, as an indicator of the IRC efficiency, the probability of a lack of fault products when manufacturing. Based on the functions the VS perform as a part of the IRC information system, the accepted indicators of VS quality are as follows: a probability of the proper recognition of objects in the working IRC area, and confidential probabilities of measuring linear and angular orientation coordinates of objects with the specified values of permissible error. Specific values of these errors depend on the orientation errors of working bodies of manipulators that are a part of the IRC. The paper presents mathematical expressions that determine the functional dependence of the probability of a lack of fault products when manufacturing on the VS quality indicators and the probability of failures of IRC technological equipment.The offered technique for substantiating engineering requirements for the VS of IRC has novelty. The results obtained in this work can be useful for professionals involved in IRC VS development, and, in particular, in development of VS algorithms and software.

  9. The impact of educational and environmental interventions in Dutch worksite cafeterias.

    Science.gov (United States)

    Steenhuis, Ingrid; Van Assema, Patricia; Van Breukelen, Gerard; Glanz, Karen; Kok, Gerjo; De Vries, Hein

    2004-09-01

    Environmental interventions such as labeling and an increased availability of healthy foods may help consumers to meet guidelines for a healthy diet. This article describes a study into the effectiveness of two environmental programs to be used in worksite cafeterias along with an educational program. The aim of the interventions was to reduce fat intake, and to increase fruit and vegetable intake. In the labeling program, low-fat products were labeled. The food supply program comprised an increased availability of low-fat products and fruits and vegetables in worksite cafeterias. The educational program consisted of information about healthy nutrition through brochures, table tents, a self-help manual and posters. The design consisted of a pre-test-post-test experimental control group design, with four conditions: the educational program; the food supply program plus educational program; the labeling program plus educational program; and a control group. Seventeen worksites were randomly assigned to one of the four research conditions. Total fat, fruit and vegetable intake was measured with a quantitative, self-administered food frequency questionnaire (35 questions). Intake during lunch was measured by asking respondents to write down which food items they had purchased during their last lunch in the cafeteria. Furthermore, sales data for some targeted product categories were collected (milk, butter, cheese, meat products, desserts). For the whole study population, no significant effects on consumption data were found for any of the programs. The data showed a beneficial and significant treatment effect of the labeling program on total fat intake for respondents who believed they ate a high-fat diet. Sales data revealed a significant effect of the labeling program on desserts, but not for the other products.

  10. Population health management as a strategy for creation of optimal healing environments in worksite and corporate settings.

    Science.gov (United States)

    Chapman, Larry S; Pelletier, Kenneth R

    2004-01-01

    This paper provides an (OHE) overview of a population health management (PHM) approach to the creation of optimal healing environments (OHEs) in worksite and corporate settings. It presents a framework for consideration as the context for potential research projects to examine the health, well-being, and economic effects of a set of newer "virtual" prevention interventions operating in an integrated manner in worksite settings. The main topics discussed are the fundamentals of PHM with basic terminology and core principles, a description of PHM core technology and implications of a PHM approach to creating OHEs.

  11. Improving the diet of employees at blue-collar worksites: results from the "Food at work" intervention study

    DEFF Research Database (Denmark)

    Lassen, Anne Dahl; Thorsen, Anne Vibeke; Sommer, Helle Mølgaard

    2011-01-01

    ) changes in employees' dietary habits derived from 4 d pre-coded food diaries of a group of employees at the worksites (paired-data structure); and (ii) the canteen nutrition environment as identified by aggregating chemical nutritional analysis of individual canteen lunches (different participants......Objective. To examine the impact of a 6-month participatory and empowerment-based intervention study on employees' dietary habits and on changes in the canteen nutrition environment. Design. Worksites were stratified by company type and by the presence or absence of an in-house canteen...

  12. Cardiorespiratory fitness, cardiovascular workload and risk factors among cleaners; a cluster randomized worksite intervention

    Directory of Open Access Journals (Sweden)

    Korshøj Mette

    2012-08-01

    Full Text Available Abstract Background Prevalence of cardiovascular risk factors is unevenly distributed among occupational groups. The working environment, as well as lifestyle and socioeconomic status contribute to the disparity and variation in prevalence of these risk factors. High physical work demands have been shown to increase the risk for cardiovascular disease and mortality, contrary to leisure time physical activity. High physical work demands in combination with a low cardiorespiratory fitness infer a high relative workload and an excessive risk for cardiovascular mortality. Therefore, the aim of this study is to examine whether a worksite aerobic exercise intervention will reduce the relative workload and cardiovascular risk factors by an increased cardiorespiratory fitness. Methods/design A cluster-randomized controlled trial is performed to evaluate the effect of the worksite aerobic exercise intervention on cardiorespiratory fitness and cardiovascular risk factors among cleaners. Cleaners are eligible if they are employed ≥ 20 hours/week, at one of the enrolled companies. In the randomization, strata are formed according to the manager the participant reports to. The clusters will be balanced on the following criteria: Geographical work location, gender, age and seniority. Cleaners are randomized to either I a reference group, receiving lectures concerning healthy living, or II an intervention group, performing worksite aerobic exercise “60 min per week”. Data collection will be conducted at baseline, four months and 12 months after baseline, at the worksite during working hours. The data collection will consist of a questionnaire-based interview, physiological testing of health and capacity-related measures, and objective diurnal measures of heart rate, physical activity and blood pressure. Primary outcome is cardiorespiratory fitness. Discussion Information is lacking about whether an improved cardiorespiratory fitness will affect

  13. Effect of forced ventilation on the dust concentration of partially ventilated mine worksites

    Energy Technology Data Exchange (ETDEWEB)

    Vekeny, H.

    1985-01-01

    The stone drifts and about two-thirds of the roadways in coal seams of the Mecsek Coal Mines, Hungary, are driven by forced ventilation which, in addition to its numerous merits, causes also air velocities significantly higher than optimum resulting in delivering dust particles and rock material produced by breaking of mineral and rock material into the atmosphere of worksites. This also increases the risk of silicosis of miners. A new device called a wind rose was developed and applied to the blow-out end of the ventilation duct leading to a better distribution of the discharged air stream in the drift.

  14. The Arabidopsis thaliana vernalization response requires a polycomb-like protein complex that also includes VERNALIZATION INSENSITIVE 3.

    Science.gov (United States)

    Wood, Craig C; Robertson, Masumi; Tanner, Greg; Peacock, W James; Dennis, Elizabeth S; Helliwell, Chris A

    2006-09-26

    In Arabidopsis thaliana, the promotion of flowering by cold temperatures, vernalization, is regulated via a floral-repressive MADS box transcription factor, FLOWERING LOCUS C (FLC). Vernalization leads to the epigenetic repression of FLC expression, a process that requires the polycomb group (PcG) protein VERNALIZATION 2 (VRN2) and the plant homeodomain protein VERNALIZATION INSENSITIVE 3 (VIN3). We demonstrate that the repression of FLC by vernalization requires homologues of other Polycomb Repressive Complex 2 proteins and VRN2. We show in planta that VRN2 and VIN3 are part of a large protein complex that can include the PcG proteins FERTILIZATION INDEPENDENT ENDOSPERM, CURLY LEAF, and SWINGER. These findings suggest a single protein complex is responsible for histone deacetylation at FLC and histone methylation at FLC in vernalized plants. The abundance of the complex increases during vernalization and declines after plants are returned to higher temperatures, consistent with the complex having a role in establishing FLC repression.

  15. Constitutive turnover of histone H2A.Z at yeast promoters requires the preinitiation complex.

    Science.gov (United States)

    Tramantano, Michael; Sun, Lu; Au, Christy; Labuz, Daniel; Liu, Zhimin; Chou, Mindy; Shen, Chen; Luk, Ed

    2016-07-20

    The assembly of the preinitiation complex (PIC) occurs upstream of the +1 nucleosome which, in yeast, obstructs the transcription start site and is frequently assembled with the histone variant H2A.Z. To understand the contribution of the transcription machinery in the disassembly of the +1 H2A.Z nucleosome, conditional mutants were used to block PIC assembly. A quantitative ChIP-seq approach, which allows detection of global occupancy change, was employed to measure H2A.Z occupancy. Blocking PIC assembly resulted in promoter-specific H2A.Z accumulation, indicating that the PIC is required to evict H2A.Z. By contrast, H2A.Z eviction was unaffected upon depletion of INO80, a remodeler previously reported to displace nucleosomal H2A.Z. Robust PIC-dependent H2A.Z eviction was observed at active and infrequently transcribed genes, indicating that constitutive H2A.Z turnover is a general phenomenon. Finally, sites with strong H2A.Z turnover precisely mark transcript starts, providing a new metric for identifying cryptic and alternative sites of initiation.

  16. The requirement for the Dam1 complex is dependent upon the number of kinetochore proteins and microtubules.

    Science.gov (United States)

    Burrack, Laura S; Applen, Shelly E; Berman, Judith

    2011-05-24

    The Dam1 complex attaches the kinetochore to spindle microtubules and is a processivity factor in vitro. In Saccharomyces cerevisiae, which has point centromeres that attach to a single microtubule, deletion of any Dam1 complex member results in chromosome segregation failures and cell death. In Schizosaccharomyces pombe, which has epigenetically defined regional centromeres that each attach to 3-5 kinetochore microtubules, Dam1 complex homologs are not essential. To determine why the complex is essential in some organisms and not in others, we used Candida albicans, a multimorphic yeast with regional centromeres that attach to a single microtubule. Interestingly, the Dam1 complex was essential in C. albicans, suggesting that the number of microtubules per centromere is critical for its requirement. Importantly, by increasing CENP-A expression levels, more kinetochore proteins and microtubules were recruited to the centromeres, which remained fully functional. Furthermore, Dam1 complex members became less crucial for growth in cells with extra kinetochore proteins and microtubules. Thus, the requirement for the Dam1 complex is not due to the DNA-specific nature of point centromeres. Rather, the Dam1 complex is less critical when chromosomes have multiple kinetochore complexes and microtubules per centromere, implying that it functions as a processivity factor in vivo as well as in vitro.

  17. The integration of studio cycling into a worksite stress management programme.

    Science.gov (United States)

    Clark, Matthew M; Soyring, Jason E; Jenkins, Sarah M; Daniels, Denise C; Berkland, Bridget E; Werneburg, Brooke L; Hagen, Philip T; Lopez-Jimenez, Francisco; Warren, Beth A; Olsen, Kerry D

    2014-04-01

    High stress is a prevalent problem in the worksite. To reduce stress, improve productivity, reduce absenteeism, and lower healthcare costs, many companies offer exercise classes or stress management programmes. Although physical activity is an important component of stress management, few worksites have integrated physical activity into their comprehensive stress reduction programmes. The purpose of this single-arm pilot project was to examine the potential effectiveness of an integrated exercise (studio cycling) and cognitive-behavioural stress management programme. Eighty-four adults, 75% female, mostly aged 40+ years, participated in an integrated 12-week cycling studio and cognitive-behavioural stress management programme. Participants experienced a significant and clinically meaningful reduction on the Perceived Stress Scale (p diet, higher spiritual well-being, improved sleep, receiving more support for maintaining healthy living and improved quality of life at the completion of the 12-week programme and 1-month follow-up. These findings provide further support for an integrated exercise and stress management programme.

  18. Work, Weight, and Wellness: the 3W Program: a worksite obesity prevention and intervention trial.

    Science.gov (United States)

    Williams, Andrew E; Vogt, Thomas M; Stevens, Victor J; Albright, Cheryl A; Nigg, Claudio R; Meenan, Richard T; Finucane, Melissa L

    2007-11-01

    In this paper, we describe the aims, intervention, and design of the Work, Weight, and Wellness program, a group-randomized worksite obesity prevention and intervention trial being conducted at 31 hotels with 11,559 employees on the island of Oahu in Hawaii. We report baseline prevalence of overweight and obesity, and the distribution of BMI (kilograms per meter squared) across sex, race, and job categories. We also describe factors that have influenced intervention adoption and employee participation. The study's primary outcome is change in BMI among hotel employees over a 2-year intervention period. The intervention includes environmental and group components that target diet, physical activity, and weight management. Men, Pacific Islanders, and individuals employed in managerial or facility maintenance roles had higher prevalence of obesity and higher mean BMI than women and individuals from other races or in other occupational categories. These results may be helpful in guiding choices about the adoption or design of future worksite and community interventions addressing at-risk ethnically diverse populations and are especially relevant to the hotel industry and similar industries.

  19. Endoplasmic Reticulum Exit of Golgi-resident Defective for SREBP Cleavage (Dsc) E3 Ligase Complex Requires Its Activity.

    Science.gov (United States)

    Raychaudhuri, Sumana; Espenshade, Peter J

    2015-06-01

    Layers of quality control ensure proper protein folding and complex formation prior to exit from the endoplasmic reticulum. The fission yeast Dsc E3 ligase is a Golgi-localized complex required for sterol regulatory element-binding protein (SREBP) transcription factor activation that shows architectural similarity to endoplasmic reticulum-associated degradation E3 ligases. The Dsc E3 ligase consists of five integral membrane proteins (Dsc1-Dsc5) and functionally interacts with the conserved AAA-ATPase Cdc48. Utilizing an in vitro ubiquitination assay, we demonstrated that Dsc1 has ubiquitin E3 ligase activity that requires the E2 ubiquitin-conjugating enzyme Ubc4. Mutations that specifically block Dsc1-Ubc4 interaction prevent SREBP cleavage, indicating that SREBP activation requires Dsc E3 ligase activity. Surprisingly, Golgi localization of the Dsc E3 ligase complex also requires Dsc1 E3 ligase activity. Analysis of Dsc E3 ligase complex formation, glycosylation, and localization indicated that Dsc1 E3 ligase activity is specifically required for endoplasmic reticulum exit of the complex. These results define enzyme activity-dependent sorting as an autoregulatory mechanism for protein trafficking.

  20. Long-Term Cost-Effectiveness and Return-on-Investment of a Mindfulness-Based Worksite Intervention

    NARCIS (Netherlands)

    Dongen, J.M. van; Berkel, J. van; Boot, C.R.L.; Bosmans, J.E.; Proper, K.I.; Bongers, P.M.; Beek, A.J. van der; Tulder, M.W. van; Wier, M.F. van

    2016-01-01

    Objectives: The aim of this study was to conduct a cost-effectiveness and return-on-investment analysis comparing a mindfulness-based worksite intervention to usual practice. Methods: Two hundred fifty-seven governmental research institute employees were randomized to the intervention or control gro

  1. A systematic review of the cost-effectiveness of worksite physical activity and/or nutrition programs

    NARCIS (Netherlands)

    Dongen, J.M. van; Proper, K.I.; Wier, M.F. van; Beek, A.J. van der; Bongers, P.M.; Mechelen, W. van; Tulder, M.W. van

    2012-01-01

    Objective The aim of this study was to appraise and summarize the evidence on the cost-effectiveness of worksite physical activity and/or nutrition programs. Methods We searched EMBASE, MEDLINE, SportDiscus, PsycInfo, NIOSHTIC-2, NHSEED, HTA, and Econlit for studies published up to 14 January 2011.

  2. Effects of a Worksite Weight-Control Programme in Obese Male Workers: A Randomized Controlled Crossover Trial

    Science.gov (United States)

    Iriyama, Yae; Murayama, Nobuko

    2014-01-01

    Objective: We conducted a randomized controlled crossover trial to evaluate the effects of a new worksite weight-control programme designed for men with or at risk of obesity using a combination of nutrition education and nutrition environmental interventions. Subjects and methods: Male workers with or at risk of obesity were recruited for this…

  3. The influence of worksite and employee variables on employee engagement in telephonic health coaching programs: a retrospective multivariate analysis.

    Science.gov (United States)

    Grossmeier, Jessica

    2013-01-01

    This study assessed 11 determinants of health coaching program participation. A cross-sectional study design used secondary data to assess the role of six employee-level and five worksite-level variables on telephone-based coaching enrollment, active participation, and completion. Data was provided by a national provider of worksite health promotion program services for employers. A random sample of 34,291 employees from 52 companies was selected for inclusion in the study. Survey-based measures included age, gender, job type, health risk status, tobacco risk, social support, financial incentives, comprehensive communications, senior leadership support, cultural support, and comprehensive program design. Gender-stratified multivariate logistic regression models were applied using backwards elimination procedures to yield parsimonious prediction models for each of the dependent variables. Employees were more likely to enroll in coaching programs if they were older, female, and in poorer health, and if they were at worksites with fewer environmental supports for health, clear financial incentives for participation in coaching, more comprehensive communications, and more comprehensive programs. Once employees were enrolled, program completion was greater among those who were older, did not use tobacco, worked at a company with strong communications, and had fewer environmental supports for health. Both worksite-level and employee-level factors have significant influences on health coaching engagement, and there are gender differences in the strength of these predictors.

  4. Multi-hypothesis GPS and electronic fence data fusion for safety-critical positioning in railway worksites

    DEFF Research Database (Denmark)

    Figueiras, Joao; Gronbaek, Jesper; Schwefel, Hans-Peter

    2013-01-01

    . Position accuracy for safety assessment purposes is defined as the precise identification whether the worker is located in a dangerous or safe zone within a certain worksite. This paper extends a previous publication from the same authors to a scenario with multiple workers, while analyzing the combination...... alarm and safety-related missed detection events....

  5. Effectiveness of a worksite lifestyle intervention on vitality, work engagement, productivity, and sick leave: Results of a randomized controlled trial

    NARCIS (Netherlands)

    Strijk, J.E.; Proper, K.I.; Mechelen, W. van; Beek, A.J. van der

    2013-01-01

    Objective A worksite lifestyle intervention aiming to improve lifestyle behaviors could be an effective tool to keep older workers vital, and thereby prolong their labor participation. This study evaluates the effectiveness of such an intervention on vitality, work engagement, productivity and sick

  6. Does Successful Weight Loss in an Internet-Based Worksite Weight Loss Program Improve Employee Presenteeism and Absenteeism?

    Science.gov (United States)

    Harden, Samantha M.; You, Wen; Almeida, Fabio A.; Hill, Jennie L.; Linnan, Laura A.; Allen, Kacie C.; Estabrooks, Paul A.

    2015-01-01

    Certain risk factors associated with overweight and obesity may lead to reduced productivity in the workforce (i.e., increased absenteeism and presenteeism). Participants in a large, Internet-based worksite weight loss intervention, who were present at follow-up (N = 1,030), completed a self-reported productivity measure (World Health…

  7. A worksite vitality intervention to improve older workers' lifestyle and vitality-related outcomes: results of a randomised controlled trial

    NARCIS (Netherlands)

    Strijk, J.E.; Proper, K.I.; Beek, A. van der; Meschelen, W. van

    2012-01-01

    ObjectiveTo evaluate the effectiveness of a worksite vitality intervention on vigorous physical activity (VPA), fruit intake, aerobic capacity, mental health and need for recovery after work among older hospital workers (ie, 45 years and older).MethodsThe 6-month intervention was evaluated using a r

  8. Effectiveness of a worksite lifestyle intervention on vitality, work engagement, productivity, and sick leave: Results of a randomized controlled trial

    NARCIS (Netherlands)

    Strijk, J.E.; Proper, K.I.; Mechelen, W. van; Beek, A.J. van der

    2013-01-01

    Objective A worksite lifestyle intervention aiming to improve lifestyle behaviors could be an effective tool to keep older workers vital, and thereby prolong their labor participation. This study evaluates the effectiveness of such an intervention on vitality, work engagement, productivity and sick

  9. Evaluation of a Worksite Cervical Screening Initiative to Increase Pap Smear Uptake in Malaysia: A Cluster Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Fauziah Abdullah

    2013-01-01

    Full Text Available Background. Despite the significant burden of cervical cancer, Malaysia like many middle-income countries relies on opportunistic cervical screening as opposed to a more organized population-based program. The aim of this study was to ascertain the effectiveness of a worksite screening initiative upon Papanicolaou smear test (Pap test uptake among educated working women in Malaysia. Methods. 403 female teachers who never or infrequently attended for a Pap test from 40 public secondary schools in Kuala Lumpur were recruited into a cluster randomized trial conducted between January and November 2010. The intervention group participated in a worksite cervical screening initiative whilst the control group received usual care from the existing cervical screening program. Multivariate logistic regression was performed to determine the impact of the intervention program on Pap smear uptake after 24 weeks of followup. Results. The proportion of women attending for a Pap test was significantly higher in the intervention than in the control group (18.1% versus 10.1%, P value < 0.05 with the worksite screening initiative doubling the Pap smear uptake, adjusted odds ratio 2.44 (95% CI: 1.29–4.62. Conclusion. Worksite health promotion interventions can effectively increase cervical smear uptake rates among eligible workers in middle-income countries. Policy makers and health care providers in these countries should include such interventions in strategies for reducing cervical cancer burden. This trial is registered with IRCT201103186088N1.

  10. Does Successful Weight Loss in an Internet-Based Worksite Weight Loss Program Improve Employee Presenteeism and Absenteeism?

    Science.gov (United States)

    Harden, Samantha M.; You, Wen; Almeida, Fabio A.; Hill, Jennie L.; Linnan, Laura A.; Allen, Kacie C.; Estabrooks, Paul A.

    2015-01-01

    Certain risk factors associated with overweight and obesity may lead to reduced productivity in the workforce (i.e., increased absenteeism and presenteeism). Participants in a large, Internet-based worksite weight loss intervention, who were present at follow-up (N = 1,030), completed a self-reported productivity measure (World Health…

  11. Comparison of buffet and a la carte serving at worksite canteens on nutrient intake and fruit and vegetable consumption

    DEFF Research Database (Denmark)

    Lassen, Anne Dahl; Hansen, K.S.; Trolle, Ellen

    2007-01-01

    Objective: To evaluate the nutritional composition of worksite canteen lunches and to examine the impact of two meal serving systems on employee intake, i.e. buffet style with a fixed price for a varied number of dishes and A la carte style with a separate price for each item on the menu. Design...

  12. High-level inhibition of mitochondrial complexes III and IV is required to increase glutamate release from the nerve terminal

    LENUS (Irish Health Repository)

    Kilbride, Sean M

    2011-07-26

    Abstract Background The activities of mitochondrial complex III (ubiquinol-cytochrome c reductase, EC 1.10.2.2) and complex IV (cytochrome c oxidase EC 1.9.3.1) are reduced by 30-70% in Huntington\\'s disease and Alzheimer\\'s disease, respectively, and are associated with excitotoxic cell death in these disorders. In this study, we investigated the control that complexes III and complex IV exert on glutamate release from the isolated nerve terminal. Results Inhibition of complex III activity by 60-90% was necessary for a major increase in the rate of Ca2+-independent glutamate release to occur from isolated nerve terminals (synaptosomes) depolarized with 4-aminopyridine or KCl. Similarly, an 85-90% inhibition of complex IV activity was required before a major increase in the rate of Ca2+-independent glutamate release from depolarized synaptosomes was observed. Inhibition of complex III and IV activities by ~ 60% and above was required before rates of glutamate efflux from polarized synaptosomes were increased. Conclusions These results suggest that nerve terminal mitochondria possess high reserves of complex III and IV activity and that high inhibition thresholds must be reached before excess glutamate is released from the nerve terminal. The implications of the results in the context of the relationship between electron transport chain enzyme deficiencies and excitotoxicity in neurodegenerative disorders are discussed.

  13. Rybp, a polycomb complex-associated protein, is required for mouse eye development

    Directory of Open Access Journals (Sweden)

    Schreiber-Agus Nicole

    2007-04-01

    Full Text Available Abstract Background Rybp (Ring1 and YY1 binding protein is a zinc finger protein which interacts with the members of the mammalian polycomb complexes. Previously we have shown that Rybp is critical for early embryogenesis and that haploinsufficiency of Rybp in a subset of embryos causes failure of neural tube closure. Here we investigated the requirement for Rybp in ocular development using four in vivo mouse models which resulted in either the ablation or overexpression of Rybp. Results Our results demonstrate that loss of a single Rybp allele in conventional knockout mice often resulted in retinal coloboma, an incomplete closure of the optic fissure, characterized by perturbed localization of Pax6 but not of Pax2. In addition, about one half of Rybp-/- Rybp+/+ chimeric embryos also developed retinal colobomas and malformed lenses. Tissue-specific transgenic overexpression of Rybp in the lens resulted in abnormal fiber cell differentiation and severe lens opacification with increased levels of AP-2α and Sox2, and reduced levels of βA4-crystallin gene expression. Ubiquitous transgenic overexpression of Rybp in the entire eye caused abnormal retinal folds, corneal neovascularization, and lens opacification. Additional changes included defects in anterior eye development. Conclusion These studies establish Rybp as a novel gene that has been associated with coloboma. Other genes linked to coloboma encode various classes of transcription factors such as BCOR, CBP, Chx10, Pax2, Pax6, Six3, Ski, Vax1 and Vax2. We propose that the multiple functions for Rybp in regulating mouse retinal and lens development are mediated by genetic, epigenetic and physical interactions between these genes and proteins.

  14. Cost of talking parents, healthy teens: a worksite-based intervention to promote parent-adolescent sexual health communication.

    Science.gov (United States)

    Ladapo, Joseph A; Elliott, Marc N; Bogart, Laura M; Kanouse, David E; Vestal, Katherine D; Klein, David J; Ratner, Jessica A; Schuster, Mark A

    2013-11-01

    To examine the cost and cost-effectiveness of implementing Talking Parents, Healthy Teens, a worksite-based parenting program designed to help parents address sexual health with their adolescent children. We enrolled 535 parents with adolescent children at 13 worksites in southern California in a randomized trial. We used time and wage data from employees involved in implementing the program to estimate fixed and variable costs. We determined cost-effectiveness with nonparametric bootstrap analysis. For the intervention, parents participated in eight weekly 1-hour teaching sessions at lunchtime. The program included games, discussions, role plays, and videotaped role plays to help parents learn to communicate with their children about sex-related topics, teach their children assertiveness and decision-making skills, and supervise and interact with their children more effectively. Implementing the program cost $543.03 (standard deviation, $289.98) per worksite in fixed costs, and $28.05 per parent (standard deviation, $4.08) in variable costs. At 9 months, this $28.05 investment per parent yielded improvements in number of sexual health topics discussed, condom teaching, and communication quality and openness. The cost-effectiveness was $7.42 per new topic discussed using parental responses and $9.18 using adolescent responses. Other efficacy outcomes also yielded favorable cost-effectiveness ratios. Talking Parents, Healthy Teens demonstrated the feasibility and cost-effectiveness of a worksite-based parenting program to promote parent-adolescent communication about sexual health. Its cost is reasonable and is unlikely to be a significant barrier to adoption and diffusion for most worksites considering its implementation. Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  15. Analysis of the spacial requirements for RNA-protein interactions within the N antitermination complex of bacteriophage lambda.

    Science.gov (United States)

    Horiya, Satoru; Inaba, Mitsuru; Koh, Chang-Song; Uehara, Hiroaki; Masui, Naomi; Ishibashi, Masaya; Matsufuji, Senya; Harada, Kazuo

    2009-01-01

    In bacteriophage lambda, formation of a transcriptional antitermination complex consisting of the lambda N protein, nut RNA transcript (boxA-boxB), host factors, and RNA polymerase is mediated by the interaction of the boxB RNA with the RNA-binding domain of N. In order to understand the spacial requirements of this boxB/N interaction within the complex, the effects of changes in the length of the nut site linker, the boxB stem, and the peptide spacer connecting the RNA-binding domain and activation domain of N were examined using a bacterial reporter system. As a result, we found that the requirements for the boxB stem length and N peptide linker length were optimized and strict. In contrast, when the boxB/N interaction was replaced by heterologous RNA/peptide interactions, the strict requirement for the length of the peptide linker and the RNA stem was relaxed, presumably due to the absence of the interaction between boxB/N and the host factor NusA in the wild-type complex. It was also shown that the decrease in activity upon stem lengthening could be partially suppressed by simultaneous lengthening of the RNA spacer, suggesting that a further understanding of the organization of the antitermination complex may provide insights into the engineering of functional ribonucleoprotein complexes.

  16. The complex nature of mixed farming systems requires multidimensional actions supported by integrative research and development efforts

    DEFF Research Database (Denmark)

    González-García, E; Gourdine, J L; Alexandre, G

    2012-01-01

    the requirement for a change in research strategies and initiatives through the development of a complex but necessary multi-/inter-/trans-disciplinary teamwork spirit. We stress as essential the collaboration and active participation of local and regional actors, stakeholders and end-users in the identification...

  17. Using Project Complexity Determinations to Establish Required Levels of Project Rigor

    Energy Technology Data Exchange (ETDEWEB)

    Andrews, Thomas D.

    2015-10-01

    This presentation discusses the project complexity determination process that was developed by National Security Technologies, LLC, for the U.S. Department of Energy, National Nuclear Security Administration Nevada Field Office for implementation at the Nevada National Security Site (NNSS). The complexity determination process was developed to address the diversity of NNSS project types, size, and complexity; to fill the need for one procedure but with provision for tailoring the level of rigor to the project type, size, and complexity; and to provide consistent, repeatable, effective application of project management processes across the enterprise; and to achieve higher levels of efficiency in project delivery. These needs are illustrated by the wide diversity of NNSS projects: Defense Experimentation, Global Security, weapons tests, military training areas, sensor development and testing, training in realistic environments, intelligence community support, sensor development, environmental restoration/waste management, and disposal of radioactive waste, among others.

  18. Process evaluation of two environmental nutrition programmes and an educational nutrition programme conducted at supermarkets and worksite cafeterias in the Netherlands

    NARCIS (Netherlands)

    I.H.M. Steenhuis; P. van Assema (Patricia); A. Reubsaet; G.J. Kok (Gerjo)

    2004-01-01

    textabstractThis article describes the process evaluation of two environmental programs and a educational nutrition program, implemented at supermarkets and worksite cafeterias. Studies conducted earlier, indicated that the programs had no effect on consumers’ eating behavior. Consequently, the more

  19. The p25 Subunit of the Dynactin Complex is Required for Dynein-Early Endosome Interaction

    Science.gov (United States)

    2011-01-01

    dynein–early endosome interaction in the filamen- tous fungus Aspergillus nidulans. In filamentous fungi , dynein and its regulators are important for...backbone of the dynactin complex, and its loss leads to a disruption of the whole complex. In Drosoph- ila and in filamentous fungi such as N. crassa...how the motor is targeted to these cargoes is still a topic under investigation. In filamentous fungi and higher eukaryotic cells such as neurons

  20. Implementation of a worksite educational program focused on promoting healthy eating habits.

    Science.gov (United States)

    Tanagra, Dimitra; Panidis, Dimitris; Tountas, Yannis; Remoudaki, Elina; Alexopoulos, Evangelos C

    2013-01-01

    To estimate the effectiveness of a short-term educational-counseling worksite program focused on lipid intake, by monitoring the possible change on nutrition knowledge and eating habits. an 8-week educational program based on the Health Belief Model was implemented in a honey packaging and sales company in Greece. 20 out of the 29 employees initially enrolled completed the program. Knowledge level and eating habits were evaluated prior and after the intervention by the "Nutrition Knowledge Questionnaire" and the "Food Habits Questionnaire". ANOVA, Spearman rho test and paired Wilcoxon test were employed in statistical analysis. Non smokers and those with higher educational level had healthier eating habits. Knowledge following the intervention was significantly improved concerning recommendations and basic food ingredients but as far as eating habits were concerned, scores were not improved significantly, while intake of fried food was increased. Short-term interventions may produce substantial improvement in knowledge but not necessarily modifications in unhealthy eating habits.

  1. New approach in the evaluation of a fitness program at a worksite.

    Science.gov (United States)

    Shirasaya, K; Miyakawa, M; Yoshida, K; Tanaka, C; Shimada, N; Kondo, T

    1999-03-01

    The most common methods for the economic evaluation of a fitness program at a worksite are cost-effectiveness, cost-benefit, and cost-utility analyses. In this study, we applied a basic microeconomic theory, "neoclassical firm's problems," as the new approach for it. The optimal number of physical-exercise classes that constitute the core of the fitness program are determined using the cubic health production function. The optimal number is defined as the number that maximizes the profit of the program. The optimal number corresponding to any willingness-to-pay amount of the participants for the effectiveness of the program is presented using a graph. For example, if the willingness-to-pay is $800, the optimal number of classes is 23. Our method can be applied to the evaluation of any health care program if the health production function can be estimated.

  2. Guidance to employers on integrating e-cigarettes/electronic nicotine delivery systems into tobacco worksite policy.

    Science.gov (United States)

    Whitsel, Laurie P; Benowitz, Neal; Bhatnagar, Aruni; Bullen, Chris; Goldstein, Fred; Matthias-Gray, Lena; Grossmeier, Jessica; Harris, John; Isaac, Fikry; Loeppke, Ron; Manley, Marc; Moseley, Karen; Niemiec, Ted; OʼBrien, Vince; Palma-Davis, LaVaughn; Pronk, Nico; Pshock, Jim; Stave, Gregg M; Terry, Paul

    2015-03-01

    In recent years, new products have entered the marketplace that complicate decisions about tobacco control policies and prevention in the workplace. These products, called electronic cigarettes (e-cigarettes) or electronic nicotine delivery systems, most often deliver nicotine as an aerosol for inhalation, without combustion of tobacco. This new mode of nicotine delivery raises several questions about the safety of the product for the user, the effects of secondhand exposure, how the public use of these products should be handled within tobacco-free and smoke-free air policies, and how their use affects tobacco cessation programs, wellness incentives, and other initiatives to prevent and control tobacco use. In this article, we provide a background on e-cigarettes and then outline key policy recommendations for employers on how the use of these new devices should be managed within worksite tobacco prevention programs and control policies.

  3. Does work-site physical activity improve self-reported psychosocial workplace factors and job satisfaction?

    DEFF Research Database (Denmark)

    Roessler, K K; Rugulies, R; Bilberg, R

    2013-01-01

    , with 199 participants in the training group and 228 in the control group. Influence at work, sense of community, time pressure, and job satisfaction were measured with the Copenhagen Psychosocial Questionnaire at baseline and post-intervention after 20 weeks. RESULTS: There was no statistically significant...... change in any of the four variables in the training group from baseline to follow-up (all p ≥ 0.39). When we used MANOVA to test for between-group effects over time, we did not find any statistically significant result (all p > 0.14). CONCLUSIONS: This study does not provide evidence for an effect......PURPOSE: To investigate whether a work-site strength-training program has a positive effect on self-reported psychosocial workplace factors and job satisfaction. METHODS: We conducted a randomized controlled trial among laboratory technicians implementing neck and shoulder exercises for pain relief...

  4. A Worksite Occupational Health Clinic-Based Diabetes Mellitus Management Program.

    Science.gov (United States)

    Burton, Wayne N; Chen, Chin-Yu; Li, Xingquan; Erickson, Denise; McCluskey, Maureen; Schultz, Alyssa

    2015-12-01

    This study is an analysis of a workplace diabetes management program offered to employees of a Fortune 100 financial services corporation located in the United States. The 12-month worksite-based educational program was for employees who were at risk for diabetes, had prediabetes, or were diagnosed with diabetes. This employed population, with health benefits, generally had acceptable control of their diabetes at the start of the program. They statistically improved most self-efficacy measures, but improvement in biometric tests at 6 and 12 months were not significantly different from baseline. Mean hemoglobin A1c at baseline, 6 months, and 12 months was 7.2%, 7.2%, and 7.3%, respectively. At 12 months, about 40% of preprogram survey participants completed all screenings and the post-program questionnaire. Disease management programs at the workplace can be an important component in helping employees enhance their knowledge of diabetes and maintain and improve their health.

  5. Effects of a worksite physical activity intervention for hospital nurses who are working mothers.

    Science.gov (United States)

    Tucker, Sharon J; Lanningham-Foster, Lorraine M; Murphy, Justyne N; Thompson, Warren G; Weymiller, Audrey J; Lohse, Christine; Levine, James A

    2011-09-01

    Hospital nurses who are working mothers are challenged to maintain their personal health and model healthy behaviors for their children. This study aimed to develop and test an innovative 10-week worksite physical activity intervention integrated into the work flow of hospital-based nurses who were mothers. Three volunteer adult medical-surgical nursing units participated as intervention units. Fifty-eight nurses (30 intervention and 28 control) provided baseline and post-intervention repeated measurements of physical activity (steps) and body composition. Intervention participants provided post-intervention focus group feedback. For both groups, daily steps averaged more than 12,400 at baseline and post-intervention. No significant effects were found for physical activity; significant effects were found for fat mass, fat index, and percent fat (p working mothers. Future research is warranted with a larger sample, longer intervention, and additional measures.

  6. Office workers' objectively assessed total and prolonged sitting time: Individual-level correlates and worksite variations

    Directory of Open Access Journals (Sweden)

    Nyssa T. Hadgraft

    2016-12-01

    Full Text Available Sedentary behavior is highly prevalent in office-based workplaces; however, few studies have assessed the attributes associated with this health risk factor in the workplace setting. This study aimed to identify the correlates of office workers' objectively-assessed total and prolonged (≥30 min bouts workplace sitting time. Participants were 231 Australian office workers recruited from 14 sites of a single government employer in 2012–13. Potential socio-demographic, work-related, health-related and cognitive-social correlates were measured through a self-administered survey and anthropometric measurements. Associations with total and prolonged workplace sitting time (measured with the activPAL3 were tested using linear mixed models. Worksites varied significantly in total workplace sitting time (overall mean [SD]: 79% [10%] of work hours and prolonged workplace sitting time (42% [19%], after adjusting for socio-demographic and work-related characteristics. Organisational tenure of 3–5 years (compared to tenure >5 years was associated with more time spent in total and prolonged workplace sitting time, while having a BMI categorised as obese (compared to a healthy BMI was associated with less time spent in total and prolonged workplace sitting time. Significant variations in sitting time were observed across different worksites of the same employer and the variation remained after adjusting for individual-level factors. Only BMI and organisational tenure were identified as correlates of total and prolonged workplace sitting time. Additional studies are needed to confirm the present findings across diverse organisations and occupations.

  7. From Collective Knowledge to Intelligence : Pre-Requirements Analysis of Large and Complex Systems

    NARCIS (Netherlands)

    Liang, Peng; Avgeriou, Paris; He, Keqing; Xu, Lai

    2010-01-01

    Requirements engineering is essentially a social collaborative activity in which involved stakeholders have to closely work together to communicate, elicit, negotiate, define, confirm, and finally come up with the requirements for the system to be implemented or upgraded. In the development of large

  8. From Collective Knowledge to Intelligence : Pre-Requirements Analysis of Large and Complex Systems

    NARCIS (Netherlands)

    Liang, Peng; Avgeriou, Paris; He, Keqing; Xu, Lai

    2010-01-01

    Requirements engineering is essentially a social collaborative activity in which involved stakeholders have to closely work together to communicate, elicit, negotiate, define, confirm, and finally come up with the requirements for the system to be implemented or upgraded. In the development of large

  9. Multiple Stressors and Ecological Complexity Require A New Approach to Coral Reef Research

    Directory of Open Access Journals (Sweden)

    Linwood Hagan Pendleton

    2016-03-01

    Full Text Available Ocean acidification, climate change, and other environmental stressors threaten coral reef ecosystems and the people who depend upon them. New science reveals that these multiple stressors interact and may affect a multitude of physiological and ecological processes in complex ways. The interaction of multiple stressors and ecological complexity may mean that the negative effects on coral reef ecosystems will happen sooner and be more severe than previously thought. Yet, most research on the effects of global change on coral reefs focus on one or few stressors and pathways or outcomes (e.g. bleaching. Based on a critical review of the literature, we call for a regionally targeted strategy of mesocosm-level research that addresses this complexity and provides more realistic projections about coral reef impacts in the face of global environmental change. We believe similar approaches are needed for other ecosystems that face global environmental change.

  10. Evaluation of environmental management resources (ISO 14001) at civil engineering construction worksites: a case study of the community of Madrid.

    Science.gov (United States)

    Rodríguez, Gracia; Alegre, Francisco Javier; Martínez, Germán

    2011-07-01

    In recent years, significant advances have been made in business organization and management. The growing demands of clients as well as the globalization of world markets are among the many factors that have led to the establishment of systems of quality control and environmental management as a competitive strategy for businesses. When compared to other professional sectors, the construction sector has been slower to respond to environmental problems and to adopt Environmental Management Systems (EMS). In the world today the ISO 14001 standard is currently the main frame of reference used by construction companies to implement this type of management system. This article presents the results of a general study regarding the evaluation of the application of the ISO 14001 standard at civil engineering construction worksites in the Community of Madrid (Spain), specifically pertaining to requirement 4.4.1, Resources, roles, responsibilities, and authority. According to requirement 4.4.1, company executives should appoint people responsible for implementing the EMS and also specify their responsibilities and functions. The personnel designated for supervising environmental work should also have sufficient authority to establish and maintain the EMS. The results obtained were the following: - EMS supervisors did not generally possess adequate training and solid experience in construction work and in the environment. Furthermore, supervisors were usually forced to combine their environmental work with other tasks, which made their job even more difficult. - Generally speaking, supervisors were not given sufficient authority and autonomy because productivity at the construction site had priority over environmental management. This was due to the fact that the company management did not have a respectful attitude toward the environment, nor was the management actively involved in the establishment of the EMS. - Insufficient resources were allocated to the Environmental

  11. Repressive LTR nucleosome positioning by the BAF complex is required for HIV latency

    NARCIS (Netherlands)

    H. Rafati (Haleh); M. Parra (Maribel); S. Hakre (Shweta); Y.M. Moshkin (Yuri); E. Verdin (Eric); T. Mahmoudi (Tokameh)

    2011-01-01

    textabstractPersistence of a reservoir of latently infected memory T cells provides a barrier to HIV eradication in treated patients. Several reports have implicated the involvement of SWI/SNF chromatin remodeling complexes in restricting early steps in HIV infection, in coupling the processes of in

  12. Visual Pattern Memory Requires "Foraging" Function in the Central Complex of "Drosophila"

    Science.gov (United States)

    Wang, Zhipeng; Pan, Yufeng; Li, Weizhe; Jiang, Huoqing; Chatzimanolis, Lazaros; Chang, Jianhong; Gong, Zhefeng; Liu, Li

    2008-01-01

    The role of the "foraging" ("for)" gene, which encodes a cyclic guanosine-3',5'-monophosphate (cGMP)-dependent protein kinase (PKG), in food-search behavior in "Drosophila" has been intensively studied. However, its functions in other complex behaviors have not been well-characterized. Here, we show experimentally in "Drosophila" that the "for"…

  13. Formal Verification of Complex Systems based on SysML Functional Requirements

    Science.gov (United States)

    2014-12-23

    functional, and structural modeling, etc. Those with particu- lar focus on requirements engineering are the Unified Model- ing Language ( UML ) (OMG, 2007) to...requirements through design and implementation. UML is developed by the Object Management Group (OMG) in co- operation with the International Council of...Systems Engi- neering (INCOSE). UML is an Object-oriented modeling lan- guage that allows hierarchical organization of system compo- nent models, which in

  14. Efficient Wnt mediated intestinal hyperproliferation requires the cyclin D2-CDK4/6 complex

    Directory of Open Access Journals (Sweden)

    Sansom Owen

    2011-02-01

    Full Text Available Abstract Inactivation of the gene encoding the adenomatous polyposis coli (APC tumour suppressor protein is recognized as the key early event in the development of colorectal cancers (CRC. Apc loss leads to nuclear localization of beta-catenin and constitutive activity of the beta-catenin-Tcf4 transcription complex. This complex drives the expression of genes involved in cell cycle progression such as c-Myc and cyclin D2. Acute loss of Apc in the small intestine leads to hyperproliferation within the intestinal crypt, increased levels of apoptosis, and perturbed differentiation and migration. It has been demonstrated that c-Myc is a critical mediator of the phenotypic abnormalities that follow Apc loss in the intestine. As it may be difficult to pharmacologically inhibit transcription factors such as c-Myc, investigating more druggable targets of the Wnt-c-Myc pathway within the intestine may reveal potential therapeutic targets for CRC. Recent work in our laboratory has shown that the cyclin D2-cyclin-dependent kinase 4/6 (CDK4/6 complex promotes hyperproliferation in Apc deficient intestinal tissue and ApcMin/+ adenomas. We showed that the hyperproliferative phenotype associated with Apc loss in vivo was partially dependent on the expression of cyclin D2. Most importantly, tumour growth and development in ApcMin/+ mice was strongly perturbed in mice lacking cyclin D2. Furthermore, pharmacological inhibition of CDK4/6 suppressed the proliferation of adenomatous cells. This commentary discusses the significance of this work in providing evidence for the importance of the cyclin D2-CDK4/6 complex in colorectal adenoma formation. It also argues that inhibition of this complex may be an effective chemopreventative strategy in CRC.

  15. Transcriptional repression of frequency by the IEC-1-INO80 complex is required for normal Neurospora circadian clock function.

    Science.gov (United States)

    Gai, Kexin; Cao, Xuemei; Dong, Qing; Ding, Zhaolan; Wei, Yashang; Liu, Yingchun; Liu, Xiao; He, Qun

    2017-04-01

    Rhythmic activation and repression of the frequency (frq) gene are essential for normal function of the Neurospora circadian clock. WHITE COLLAR (WC) complex, the positive element of the Neurospora circadian system, is responsible for stimulation of frq transcription. We report that a C2H2 finger domain-containing protein IEC-1 and its associated chromatin remodeling complex INO80 play important roles in normal Neurospora circadian clock function. In iec-1KO strains, circadian rhythms are abolished, and the frq transcript levels are increased compared to that of the wild-type strain. Similar results are observed in mutant strains of the INO80 subunits. Furthermore, ChIP data show that recruitment of the INO80 complex to the frq promoter is IEC-1-dependent. WC-mediated transcription of frq contributes to the rhythmic binding of the INO80 complex at the frq promoter. As demonstrated by ChIP analysis, the INO80 complex is required for the re-establishment of the dense chromatin environment at the frq promoter. In addition, WC-independent frq transcription is present in ino80 mutants. Altogether, our data indicate that the INO80 complex suppresses frq transcription by re-assembling the suppressive mechanisms at the frq promoter after transcription of frq.

  16. Fission yeast MOZART1/Mzt1 is an essential γ-tubulin complex component required for complex recruitment to the microtubule organizing center, but not its assembly.

    Science.gov (United States)

    Masuda, Hirohisa; Mori, Risa; Yukawa, Masashi; Toda, Takashi

    2013-09-01

    γ-Tubulin plays a universal role in microtubule nucleation from microtubule organizing centers (MTOCs) such as the animal centrosome and fungal spindle pole body (SPB). γ-Tubulin functions as a multiprotein complex called the γ-tubulin complex (γ-TuC), consisting of GCP1-6 (GCP1 is γ-tubulin). In fungi and flies, it has been shown that GCP1-3 are core components, as they are indispensable for γ-TuC complex assembly and cell division, whereas the other three GCPs are not. Recently a novel conserved component, MOZART1, was identified in humans and plants, but its precise functions remain to be determined. In this paper, we characterize the fission yeast homologue Mzt1, showing that it is essential for cell viability. Mzt1 is present in approximately equal stoichiometry with Alp4/GCP2 and localizes to all the MTOCs, including the SPB and interphase and equatorial MTOCs. Temperature-sensitive mzt1 mutants display varying degrees of compromised microtubule organization, exhibiting multiple defects during both interphase and mitosis. Mzt1 is required for γ-TuC recruitment, but not sufficient to localize to the SPB, which depends on γ-TuC integrity. Intriguingly, the core γ-TuC assembles in the absence of Mzt1. Mzt1 therefore plays a unique role within the γ-TuC components in attachment of this complex to the major MTOC site.

  17. Synaptonemal complex components persist at centromeres and are required for homologous centromere pairing in mouse spermatocytes.

    Directory of Open Access Journals (Sweden)

    C Gaston Bisig

    2012-06-01

    Full Text Available Recent studies in simple model organisms have shown that centromere pairing is important for ensuring high-fidelity meiotic chromosome segregation. However, this process and the mechanisms regulating it in higher eukaryotes are unknown. Here we present the first detailed study of meiotic centromere pairing in mouse spermatogenesis and link it with key events of the G2/metaphase I transition. In mouse we observed no evidence of the persistent coupling of centromeres that has been observed in several model organisms. We do however find that telomeres associate in non-homologous pairs or small groups in B type spermatogonia and pre-leptotene spermatocytes, and this association is disrupted by deletion of the synaptonemal complex component SYCP3. Intriguingly, we found that, in mid prophase, chromosome synapsis is not initiated at centromeres, and centromeric regions are the last to pair in the zygotene-pachytene transition. In late prophase, we first identified the proteins that reside at paired centromeres. We found that components of the central and lateral element and transverse filaments of the synaptonemal complex are retained at paired centromeres after disassembly of the synaptonemal complex along diplotene chromosome arms. The absence of SYCP1 prevents centromere pairing in knockout mouse spermatocytes. The localization dynamics of SYCP1 and SYCP3 suggest that they play different roles in promoting homologous centromere pairing. SYCP1 remains only at paired centromeres coincident with the time at which some kinetochore proteins begin loading at centromeres, consistent with a role in assembly of meiosis-specific kinetochores. After removal of SYCP1 from centromeres, SYCP3 then accumulates at paired centromeres where it may promote bi-orientation of homologous centromeres. We propose that, in addition to their roles as synaptonemal complex components, SYCP1 and SYCP3 act at the centromeres to promote the establishment and/or maintenance of

  18. Critical evaluation of the JDO API for the persistence and portability requirements of complex biological databases

    Directory of Open Access Journals (Sweden)

    Schwieger Michael

    2005-01-01

    Full Text Available Abstract Background Complex biological database systems have become key computational tools used daily by scientists and researchers. Many of these systems must be capable of executing on multiple different hardware and software configurations and are also often made available to users via the Internet. We have used the Java Data Object (JDO persistence technology to develop the database layer of such a system known as the SigPath information management system. SigPath is an example of a complex biological database that needs to store various types of information connected by many relationships. Results Using this system as an example, we perform a critical evaluation of current JDO technology; discuss the suitability of the JDO standard to achieve portability, scalability and performance. We show that JDO supports portability of the SigPath system from a relational database backend to an object database backend and achieves acceptable scalability. To answer the performance question, we have created the SigPath JDO application benchmark that we distribute under the Gnu General Public License. This benchmark can be used as an example of using JDO technology to create a complex biological database and makes it possible for vendors and users of the technology to evaluate the performance of other JDO implementations for similar applications. Conclusions The SigPath JDO benchmark and our discussion of JDO technology in the context of biological databases will be useful to bioinformaticians who design new complex biological databases and aim to create systems that can be ported easily to a variety of database backends.

  19. Synaptonemal Complex Components Persist at Centromeres and Are Required for Homologous Centromere Pairing in Mouse Spermatocytes

    Science.gov (United States)

    Kouznetsova, Anna; Scherthan, Harry; Höög, Christer; Dawson, Dean S.; Pezza, Roberto J.

    2012-01-01

    Recent studies in simple model organisms have shown that centromere pairing is important for ensuring high-fidelity meiotic chromosome segregation. However, this process and the mechanisms regulating it in higher eukaryotes are unknown. Here we present the first detailed study of meiotic centromere pairing in mouse spermatogenesis and link it with key events of the G2/metaphase I transition. In mouse we observed no evidence of the persistent coupling of centromeres that has been observed in several model organisms. We do however find that telomeres associate in non-homologous pairs or small groups in B type spermatogonia and pre-leptotene spermatocytes, and this association is disrupted by deletion of the synaptonemal complex component SYCP3. Intriguingly, we found that, in mid prophase, chromosome synapsis is not initiated at centromeres, and centromeric regions are the last to pair in the zygotene-pachytene transition. In late prophase, we first identified the proteins that reside at paired centromeres. We found that components of the central and lateral element and transverse filaments of the synaptonemal complex are retained at paired centromeres after disassembly of the synaptonemal complex along diplotene chromosome arms. The absence of SYCP1 prevents centromere pairing in knockout mouse spermatocytes. The localization dynamics of SYCP1 and SYCP3 suggest that they play different roles in promoting homologous centromere pairing. SYCP1 remains only at paired centromeres coincident with the time at which some kinetochore proteins begin loading at centromeres, consistent with a role in assembly of meiosis-specific kinetochores. After removal of SYCP1 from centromeres, SYCP3 then accumulates at paired centromeres where it may promote bi-orientation of homologous centromeres. We propose that, in addition to their roles as synaptonemal complex components, SYCP1 and SYCP3 act at the centromeres to promote the establishment and/or maintenance of centromere pairing and

  20. Allele-dependent recombination frequency: homology requirement in meiotic recombination at the hot spot in the mouse major histocompatibility complex.

    Science.gov (United States)

    Yoshino, M; Sagai, T; Lindahl, K F; Toyoda, Y; Moriwaki, K; Shiroishi, T

    1995-05-20

    Meiotic recombination break joints in the mouse major histocompatibility complex (MHC) are clustered within short segments known as hot spots. We systematically investigated the requirement for sequence homology between two chromosomes for recombination activity at the hot spot next to the Lmp2 gene. The results indicated that a high rate of recombination required a high degree of similarity of overall genome structure at the hot spot. In particular, the same copy number of repetitive sequences within the hot spot was essential for a high frequency of recombination, suggesting that recombination in mouse meiosis is more sensitive to heterozygous deletion or insertion of DNA than to mismatches of single-base substitutions.

  1. A Comprehensive Worksite Wellness Program in Austin, Texas: Partnership Between Steps to a Healthier Austin and Capital Metropolitan Transportation Authority

    OpenAIRE

    Davis, Lynn; Loyo, Karina; Schwertfeger, Rick; Glowka, Aerie; Danielson, Lisa; Brea, Cecily; Easton, Alyssa; Griffin-Blake, Shannon

    2009-01-01

    Background In 2003, Steps to a Healthier Austin was funded by the Centers for Disease Control and Prevention to implement chronic disease prevention and health promotion activities. We report Steps to a Healthier Austin's partnership with Health & Lifestyles Corporate Wellness, Inc (Health & Lifestyles), to provide a worksite wellness program for Capital Metropolitan Transportation Authority (Capital Metro), Austin's local transit authority. Context Capital Metro employs 1,282 people. In 2003...

  2. Wingless secretion requires endosome-to-Golgi retrieval of Wntless/Evi/Sprinter by the retromer complex.

    Science.gov (United States)

    Franch-Marro, Xavier; Wendler, Franz; Guidato, Sonia; Griffith, Janice; Baena-Lopez, Alberto; Itasaki, Nobue; Maurice, Madelon M; Vincent, Jean-Paul

    2008-02-01

    The glycolipoproteins of the Wnt family raise interesting trafficking issues, especially with respect to spreading within tissues. Recently, the retromer complex has been suggested to participate in packaging Wnts into long-range transport vehicles. Our analysis of a Drosophila mutant in Vps35 show that, instead, the retromer complex is required for efficient progression of Wingless (a Drosophila Wnt) through the secretory pathway. Indeed expression of senseless, a short-range target gene, is lost in Vps35-deficient imaginal discs. In contrast, Vps35 is not required for Hedgehog secretion, suggesting specificity. Overexpression of Wntless, a transmembrane protein known to be specifically required for Wingless secretion overcomes the secretion block of Vps35-mutant cells. Furthermore, biochemical evidence confirms that Wntless engages with the retromer complex. We propose that Wntless accompanies Wingless to the plasma membrane where the two proteins dissociate. Following dissociation from Wingless, Wntless is internalized and returns to the Golgi apparatus in a retromer-dependent manner. Without the retromer-dependent recycling route, Wingless secretion is impaired and, as electron microscopy suggests, Wntless is diverted to a degradative compartment.

  3. Complex Domains Call for Automation but Automation Requires More Knowledge and Learning

    DEFF Research Database (Denmark)

    Madsen, Erik Skov; Mikkelsen, Lars Lindegaard

    This paper discusses productivity in relation to tacit knowledge and domain complexity. The study is based on five very different case studies; three studies are conducted in Denmark, Mexico, and the Czech Republic in relation to knowledge transfer when relocating manufacturing facilities. Two...... studies investigate operation and automation of oil and gas production in the North Sea. Semi-structured interviews, surveys, and observations are the main methods used. The paper provides a novel conceptual framework around which management may generate discussions about productivity and the need...

  4. The Born rule from a consistency requirement on hidden measurements in complex Hilbert space

    CERN Document Server

    Aerts, S

    2002-01-01

    We formalize the hidden measurement approach within the very general notion of an interactive probability model. We narrow down the model by assuming the state space of a physical entity is a complex Hilbert space and introduce the principle of consistent interaction which effectively partitions the space of apparatus states. The normalized measure of the set of apparatus states that interact with a pure state giving rise to a fixed outcome is shown to be in accordance with the probability obtained using the Born rule.

  5. Relationship of cravings with weight loss and hunger. Results from a 6 month worksite weight loss intervention.

    Science.gov (United States)

    Batra, Payal; Das, Sai Krupa; Salinardi, Taylor; Robinson, Lisa; Saltzman, Edward; Scott, Tammy; Pittas, Anastassios G; Roberts, Susan B

    2013-10-01

    We examined the association of food cravings with weight loss and eating behaviors in a lifestyle intervention for weight loss in worksites. This research was part of a randomized controlled trial of a 6-month weight loss intervention versus a wait-listed control in 4 Massachusetts worksites. The intervention emphasized reducing energy intake by adherence to portion-controlled menu suggestions, and assessments were obtained in 95 participants at baseline and 6 months including non-fasting body weight, food cravings (Craving Inventory and Food Craving Questionnaire for state and trait) and the eating behavior constructs restraint, disinhibition and hunger (Eating Inventory). There were statistically significant reductions in all craving variables in the intervention group compared to the controls. Within the intervention group, changes in craving-trait were significantly associated with weight loss after controlling for baseline weight, age, gender and worksite. However, in a multivariate model with craving-trait and eating behaviors (restraint, disinhibition and hunger), hunger was the only significant predictor of weight change. In contrast to some previous reports of increased food cravings with weight loss in lifestyle interventions, this study observed a broad reduction in cravings associated with weight loss. In addition, greater reductions in craving-trait were associated with greater weight change, but craving-trait was not a significant independent correlate of weight change when hunger was included in statistical models. Studies are needed to examine the effectiveness of hunger suppressing versus craving-suppressing strategies in lifestyle interventions for obesity.

  6. The effectiveness of worksite nutrition and physical activity interventions for controlling employee overweight and obesity: a systematic review.

    Science.gov (United States)

    Anderson, Laurie M; Quinn, Toby A; Glanz, Karen; Ramirez, Gilbert; Kahwati, Leila C; Johnson, Donna B; Buchanan, Leigh Ramsey; Archer, W Roodly; Chattopadhyay, Sajal; Kalra, Geetika P; Katz, David L

    2009-10-01

    This report presents the results of a systematic review of the effectiveness of worksite nutrition and physical activity programs to promote healthy weight among employees. These results form the basis for the recommendation by the Task Force on Community Preventive Services on the use of these interventions. Weight-related outcomes, including weight in pounds or kilograms, BMI, and percentage body fat were used to assess effectiveness of these programs. This review found that worksite nutrition and physical activity programs achieve modest improvements in employee weight status at the 6-12-month follow-up. A pooled effect estimate of -2.8 pounds (95% CI=-4.6, -1.0) was found based on nine RCTs, and a decrease in BMI of -0.5 (95% CI=-0.8, -0.2) was found based on six RCTs. The findings appear to be applicable to both male and female employees, across a range of worksite settings. Most of the studies combined informational and behavioral strategies to influence diet and physical activity; fewer studies modified the work environment (e.g., cafeteria, exercise facilities) to promote healthy choices. Information about other effects, barriers to implementation, cost and cost effectiveness of interventions, and research gaps are also presented in this article. The findings of this systematic review can help inform decisions of employers, planners, researchers, and other public health decision makers.

  7. A Worksite Health Education Workshop as Empowerment Intervention for Health Promotion in the National Research Centre of Egypt

    Directory of Open Access Journals (Sweden)

    Nagat Mohamed Amer

    2016-09-01

    Full Text Available AIM: The study aimed to assess worksite health education workshops as a successful tool for health promotion of employees. MATERIAL AND METHODS: A one day workshop was held for individuals engaged in research activities in the National research Centre of Egypt at the worksite. Its main objective was to highlight the nature, causes, symptoms and management of job stress. Participants were asked to fill a personality assessment sheet, a self-reported questionnaire for job satisfaction. Other questionnaires for assessment of falsification of type and some socio-demographic data were filled by the attendants. A concise survey was introduced at the end of the workshop for feedback collection. RESULTS: Attendants of the workshop were 36 subjects mainly females (94.4%. Mean age was 40.5 years with 63.9% of participants at their postdoctoral studies stage. Participants were at midway in the scale of job satisfaction (3.3 and did not suffer from falsification (0.3. The feedback survey score (11.5 showed great acceptance for the intervention. Special interest in the topic of stress was reported by 35.1% of attendants who found it the best item in the workshop and the interactive manipulation came next as declared by 18.9% of the participants. CONCLUSION: Worksite health education workshops seem to be a successful practice for empowerment in the Egyptian workplace.

  8. Homologs of SCAR/WAVE complex components are required for epidermal cell morphogenesis in rice.

    Science.gov (United States)

    Zhou, Wenqi; Wang, Yuchuan; Wu, Zhongliang; Luo, Liang; Liu, Ping; Yan, Longfeng; Hou, Suiwen

    2016-07-01

    Filamentous actins (F-actins) play a vital role in epidermal cell morphogenesis. However, a limited number of studies have examined actin-dependent leaf epidermal cell morphogenesis events in rice. In this study, two recessive mutants were isolated: less pronounced lobe epidermal cell2-1 (lpl2-1) and lpl3-1, whose leaf and stem epidermis developed a smooth surface, with fewer serrated pavement cell (PC) lobes, and decreased papillae. The lpl2-1 also exhibited irregular stomata patterns, reduced plant height, and short panicles and roots. Molecular genetic studies demonstrated that LPL2 and LPL3 encode the PIROGI/Specifically Rac1-associated protein 1 (PIR/SRA1)-like and NCK-associated protein 1 (NAP1)-like proteins, respectively, two components of the suppressor of cAMP receptor/Wiskott-Aldrich syndrome protein-family verprolin-homologous protein (SCAR/WAVE) regulatory complex involved in actin nucleation and function. Epidermal cells exhibited abnormal arrangement of F-actins in both lpl2 and lpl3 expanding leaves. Moreover, the distorted trichomes of Arabidopsis pir could be partially restored by an overexpression of LPL2 A yeast two-hybrid assay revealed that LPL2 can directly interact with LPL3 in vitro Collectively, the results indicate that LPL2 and LPL3 are two functionally conserved homologs of the SCAR/WAVE complex components, and that they play an important role in controlling epidermal cell morphogenesis in rice by organising F-actin.

  9. Human-chromatin-related protein interactions identify a demethylase complex required for chromosome segregation.

    Science.gov (United States)

    Marcon, Edyta; Ni, Zuyao; Pu, Shuye; Turinsky, Andrei L; Trimble, Sandra Smiley; Olsen, Jonathan B; Silverman-Gavrila, Rosalind; Silverman-Gavrila, Lorelei; Phanse, Sadhna; Guo, Hongbo; Zhong, Guoqing; Guo, Xinghua; Young, Peter; Bailey, Swneke; Roudeva, Denitza; Zhao, Dorothy; Hewel, Johannes; Li, Joyce; Gräslund, Susanne; Paduch, Marcin; Kossiakoff, Anthony A; Lupien, Mathieu; Emili, Andrew; Wodak, Shoshana J; Greenblatt, Jack

    2014-07-10

    Chromatin regulation is driven by multicomponent protein complexes, which form functional modules. Deciphering the components of these modules and their interactions is central to understanding the molecular pathways these proteins are regulating, their functions, and their relation to both normal development and disease. We describe the use of affinity purifications of tagged human proteins coupled with mass spectrometry to generate a protein-protein interaction map encompassing known and predicted chromatin-related proteins. On the basis of 1,394 successful purifications of 293 proteins, we report a high-confidence (85% precision) network involving 11,464 protein-protein interactions among 1,738 different human proteins, grouped into 164 often overlapping protein complexes with a particular focus on the family of JmjC-containing lysine demethylases, their partners, and their roles in chromatin remodeling. We show that RCCD1 is a partner of histone H3K36 demethylase KDM8 and demonstrate that both are important for cell-cycle-regulated transcriptional repression in centromeric regions and accurate mitotic division.

  10. QIL1 is a novel mitochondrial protein required for MICOS complex stability and cristae morphology.

    Science.gov (United States)

    Guarani, Virginia; McNeill, Elizabeth M; Paulo, Joao A; Huttlin, Edward L; Fröhlich, Florian; Gygi, Steven P; Van Vactor, David; Harper, J Wade

    2015-05-21

    The mitochondrial contact site and cristae junction (CJ) organizing system (MICOS) dynamically regulate mitochondrial membrane architecture. Through systematic proteomic analysis of human MICOS, we identified QIL1 (C19orf70) as a novel conserved MICOS subunit. QIL1 depletion disrupted CJ structure in cultured human cells and in Drosophila muscle and neuronal cells in vivo. In human cells, mitochondrial disruption correlated with impaired respiration. Moreover, increased mitochondrial fragmentation was observed upon QIL1 depletion in flies. Using quantitative proteomics, we show that loss of QIL1 resulted in MICOS disassembly with the accumulation of a MIC60-MIC19-MIC25 sub-complex and degradation of MIC10, MIC26, and MIC27. Additionally, we demonstrated that in QIL1-depleted cells, overexpressed MIC10 fails to significantly restore its interaction with other MICOS subunits and SAMM50. Collectively, our work uncovers a previously unrecognized subunit of the MICOS complex, necessary for CJ integrity, cristae morphology, and mitochondrial function and provides a resource for further analysis of MICOS architecture.

  11. Human-Chromatin-Related Protein Interactions Identify a Demethylase Complex Required for Chromosome Segregation

    Directory of Open Access Journals (Sweden)

    Edyta Marcon

    2014-07-01

    Full Text Available Chromatin regulation is driven by multicomponent protein complexes, which form functional modules. Deciphering the components of these modules and their interactions is central to understanding the molecular pathways these proteins are regulating, their functions, and their relation to both normal development and disease. We describe the use of affinity purifications of tagged human proteins coupled with mass spectrometry to generate a protein-protein interaction map encompassing known and predicted chromatin-related proteins. On the basis of 1,394 successful purifications of 293 proteins, we report a high-confidence (85% precision network involving 11,464 protein-protein interactions among 1,738 different human proteins, grouped into 164 often overlapping protein complexes with a particular focus on the family of JmjC-containing lysine demethylases, their partners, and their roles in chromatin remodeling. We show that RCCD1 is a partner of histone H3K36 demethylase KDM8 and demonstrate that both are important for cell-cycle-regulated transcriptional repression in centromeric regions and accurate mitotic division.

  12. A two-component enzyme complex is required for dolichol biosynthesis in tomato.

    Science.gov (United States)

    Brasher, Megan I; Surmacz, Liliana; Leong, Bryan; Pitcher, Jocelyn; Swiezewska, Ewa; Pichersky, Eran; Akhtar, Tariq A

    2015-06-01

    Dolichol plays an indispensable role in the N-glycosylation of eukaryotic proteins. As proteins enter the secretory pathway they are decorated by a 'glycan', which is preassembled onto a membrane-anchored dolichol molecule embedded within the endoplasmic reticulum (ER). Genetic and biochemical evidence in yeast and animals indicate that a cis-prenyltransferase (CPT) is required for dolichol synthesis, but also point to other factor(s) that could be involved. In this study, RNAi-mediated suppression of one member of the tomato CPT family (SlCPT3) resulted in a ~60% decrease in dolichol content. We further show that the involvement of SlCPT3 in dolichol biosynthesis requires the participation of a distantly related partner protein, designated as CPT-binding protein (SlCPTBP), which is a close homolog of the human Nogo-B receptor. Yeast two-hybrid and co-immunoprecipitation assays demonstrate that SlCPT3 and its partner protein interact in vivo and that both SlCPT3 and SlCPTBP are required to complement the growth defects and dolichol deficiency of the yeast dolichol mutant, rer2∆. Co-expression of SlCPT3 and SlCPTBP in yeast and in E. coli confirmed that dolichol synthase activity strictly requires both proteins. Finally, organelle isolation and in vivo localization of fluorescent protein fusions showed that both SlCPT3 and SlCPTBP localize to the ER, the site of dolichol accumulation and synthesis in eukaryotes.

  13. Complexity

    CERN Document Server

    Gershenson, Carlos

    2011-01-01

    The term complexity derives etymologically from the Latin plexus, which means interwoven. Intuitively, this implies that something complex is composed by elements that are difficult to separate. This difficulty arises from the relevant interactions that take place between components. This lack of separability is at odds with the classical scientific method - which has been used since the times of Galileo, Newton, Descartes, and Laplace - and has also influenced philosophy and engineering. In recent decades, the scientific study of complexity and complex systems has proposed a paradigm shift in science and philosophy, proposing novel methods that take into account relevant interactions.

  14. Polycomb complex 2 is required for E-cadherin repression by the Snail1 transcription factor

    DEFF Research Database (Denmark)

    Herranz, Nicolás; Pasini, Diego; Díaz, Víctor M

    2008-01-01

    The transcriptional factor Snail1 is a repressor of E-cadherin gene (CDH1) expression essential for triggering epithelial-mesenchymal transition (EMT). Snail1 represses CDH1 directly binding its promoter and inducing the synthesis of Zeb1 repressor. In this article we show that repression of CDH1...... by Snail1, but not by Zeb1, is dependent on the activity of the Polycomb repressive complex 2 (PRC2). ES cells null for Suz12, one of the components of PRC2, show higher levels of Cdh1 mRNA than control ES cells. In tumour cells, interference of PRC2 activity prevents the ability of Snail1 to down......-regulate CDH1 and partially de-represses CDH1. Chromatin immunoprecipitation assays demonstrated that Snail1 increases the binding of Suz12 to CDH1 promoter and the tri-methylation of lysine 27 in the histone 3. Moreover, Snail1 interacts with Suz12 and Ezh2 as shown by coimmunoprecipitation experiments...

  15. On the use of prothrombin complex concentrate in patients with coagulopathy requiring tooth extraction.

    Science.gov (United States)

    Morimoto, Yoshinari; Niwa, Hitoshi; Nakatani, Takeshi

    2010-12-01

    In patients on high-level anticoagulant therapy (prothrombin time-international normalized ratio [PT-INR] ≥ 4.5), surgical procedures can be carried out with bridging therapy using heparin. However, surgical treatment options are severely limited in patients on high-level anticoagulant therapy and who have heparin-induced thrombocytopenia (HIT), as heparin use is contraindicated. We performed tooth extraction using prothrombin complex concentrate (PCC) in 2 HIT patients on high-level anticoagulation therapy (PT-INR ≥ 4.5). Five hundred units of PCC were administered intravenously, and after 15 minutes, it was confirmed that PT-INR was less than 2.0. Tooth extraction was then performed and sufficient local hemostasis was achieved. At 3 hours after tooth extraction, PT-INR was 2.0 or higher and later increased to 4.0 or higher, but postoperative bleeding was mostly absent. When performing tooth extraction in HIT patients on high-level anticoagulant therapy, favorable hemostatic management was achieved through sufficient local hemostasis and transient warfarin reversal using PCC.

  16. N-terminal palmitoylation is required for Toxoplasma gondii HSP20 inner membrane complex localization.

    Science.gov (United States)

    De Napoli, M G; de Miguel, N; Lebrun, M; Moreno, S N J; Angel, S O; Corvi, M M

    2013-06-01

    Toxoplasma gondii is an obligate intracellular parasite and the causative agent of toxoplasmosis. Protein palmitoylation is known to play roles in signal transduction and in enhancing the hydrophobicity of proteins thus contributing to their membrane association. Global inhibition of protein palmitoylation has been shown to affect T. gondii physiology and invasion of the host cell. However, the proteins affected by this modification have been understudied. This paper shows that the small heat shock protein 20 from T. gondii (TgHSP20) is synthesized as a mature protein in the cytosol and is palmitoylated in three cysteine residues. However, its localization at the inner membrane complex (IMC) is dependent only on N-terminal palmitoylation. Absence or incomplete N-terminal palmitoylation causes TgHSP20 to partially accumulate in a membranous structure. Interestingly, TgHSP20 palmitoylation is not responsible for its interaction with the daughter cells IMCs. Together, our data describe the importance of palmitoylation in protein targeting to the IMC in T. gondii.

  17. [Children's medically complex diseases unit. A model required in all our hospitals].

    Science.gov (United States)

    Climent Alcalá, Francisco José; García Fernández de Villalta, Marta; Escosa García, Luis; Rodríguez Alonso, Aroa; Albajara Velasco, Luis Adolfo

    2017-05-09

    The increase in survival of children with severe diseases has led to the rise of children with chronic diseases, sometimes with lifelong disabilities. In 2008, a unit for the specific care of medically complex children (MCC) was created in Hospital La Paz. To describe the work and care activities of this Unit. Patients and methods An analysis was performed on all discharge reports of the Unit between January 2014 and July 2016. The MCC Unit has 6 beds and daily outpatient clinic. A total of 1,027 patients have been treated since the creation of the unit, with 243 from 2014. The median age was 24.2 months (IQ: 10.21-84.25). The large majority (92.59%) have multiple diseases, the most frequent chronic conditions observed were neurological (76.95%), gastrointestinal (63.78%), and respiratory diseases (61.72%). More than two-thirds (69.54%) of MCC are dependent on technology, 53.49% on respiratory support, and 35.80% on nutritional support. Hospital admission rates have increased annually. There have been 403 admissions since 2014, of which 8.93% were re-admissions within 30 days of hospital discharge. The median stay during 2014-2016 was 6 days (IQ: 3-14). The occupancy rate has been above 100% for this period. Currently, 210 patients remain on follow-up (86.42%), and 11 children (4.53%) were discharged to their referral hospitals. The mortality rate is 9.05% (22 deaths). The main condition of these 22 patients was neurological (9 patients). Infectious diseases were the leading cause of death. MCC should be treated in specialized units in tertiary or high-level hospitals. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Complex

    African Journals Online (AJOL)

    CLEMENT O BEWAJI

    Schiff bases and their complex compounds have been studied for their .... establishing coordination of the N–(2 – hydroxybenzyl) - L - α - valine Schiff base ..... (1967); “Spectrophotometric Identification of Organic Compounds”, Willey, New.

  19. A Bacterial Glucanotransferase Can Replace the Complex Maltose Metabolism Required for Starch to Sucrose Conversion in Leaves at Night

    DEFF Research Database (Denmark)

    Ruzanski, Christian; Smirnova, Julia; Rejzek, Martin

    2013-01-01

    Controlled conversion of leaf starch to sucrose at night is essential for the normal growth of Arabidopsis. The conversion involves the cytosolic metabolism of maltose to hexose phosphates via an unusual, multidomain protein with 4-glucanotransferase activity, DPE2, believed to transfer glucosyl...... moieties to a complex heteroglycan prior to their conversion to hexose phosphate via a cytosolic phosphorylase. The significance of this complex pathway is unclear; conversion of maltose to hexose phosphate in bacteria proceeds via a more typical 4-glucanotransferase that does not require a heteroglycan...... approaches suggested that it can potentially generate a glucosyl buffer between maltose and hexose phosphate because, unlike DPE2, it can generate polydisperse malto-oligosaccharides from maltose. Consistent with this suggestion, MalQ is capable of restoring an essentially wild-type phenotype when expressed...

  20. The Visual Orientation Memory of "Drosophila" Requires Foraging (PKG) Upstream of Ignorant (RSK2) in Ring Neurons of the Central Complex

    Science.gov (United States)

    Kuntz, Sara; Poeck, Burkhard; Sokolowski, Marla B.; Strauss, Roland

    2012-01-01

    Orientation and navigation in a complex environment requires path planning and recall to exert goal-driven behavior. Walking "Drosophila" flies possess a visual orientation memory for attractive targets which is localized in the central complex of the adult brain. Here we show that this type of working memory requires the cGMP-dependent protein…

  1. The Visual Orientation Memory of "Drosophila" Requires Foraging (PKG) Upstream of Ignorant (RSK2) in Ring Neurons of the Central Complex

    Science.gov (United States)

    Kuntz, Sara; Poeck, Burkhard; Sokolowski, Marla B.; Strauss, Roland

    2012-01-01

    Orientation and navigation in a complex environment requires path planning and recall to exert goal-driven behavior. Walking "Drosophila" flies possess a visual orientation memory for attractive targets which is localized in the central complex of the adult brain. Here we show that this type of working memory requires the cGMP-dependent protein…

  2. Cross-cultural adaptation of the CDC Worksite Health ScoreCard questionnaire into Portuguese

    Directory of Open Access Journals (Sweden)

    Patrícia Coelho de Soárez

    2016-06-01

    Full Text Available SUMMARY Objective: Despite the progress in the implementation of health promotion programs in the workplace, there are no questionnaires in Brazil to assess the scope of health promotion interventions adopted and their scientific basis. This study aimed to translate into Brazilian Portuguese and culturally adapt the CDC Worksite Health ScoreCard (HSC questionnaire. Method: The HSC has 100 questions grouped into twelve domains. The steps are as follows: translation, reconciliation, back-translation, review by expert panel, pretesting, and final revision. The convenience sample included 27 individuals from health insurance providers and companies of various sizes, types and industries in São Paulo. Data were analyzed using descriptive statistics. Results: The average age of the sample was 38 years, most of the subjects were female (21 of 27, and were responsible for programs to promote health in these workplaces. Most questions were above the minimum value of understanding set at 90%. The participants found the questionnaire very useful to determine the extent of existing health promotion programs and to pinpoint areas that could be developed. Conclusion: The Brazilian Portuguese version of the HSC questionnaire may be a valid measure and useful to assess the degree of implementation of health promotion interventions based on evidence in local health organizations.

  3. Work-site musculoskeletal pain risk estimates by trained observers--a prospective cohort study.

    Science.gov (United States)

    Coenen, Pieter; Kingma, Idsart; Boot, Cécile R L; Douwes, Marjolein; Bongers, Paulien M; van Dieën, Jaap H

    2012-01-01

    Work-related musculoskeletal pain (MSP) risk assessments by trained observers are often used in ergonomic practice; however, the validity may be questionable. We investigated the predictive value of work-site MSP risk estimates in a prospective cohort study of 1745 workers. Trained observers estimated the risk of MSP (neck, shoulder or low-back pain) using a three-point scale (high, moderate and low risk) after observing a video of randomly selected workers representing a task group. Associations of the estimated risk of pain and reported pain during a three-year follow-up were assessed using logistic regression. Estimated risk of neck and shoulder pain did (odds ratio, OR: 1.45 (95% confidence interval, CI: 1.01-2.08); 1.64 (95% CI: 1.05-2.55)), however, estimated risk of low-back pain did not significantly predict pain (OR: 1.27 (95% CI: 0.91-1.79)). The results show that observers were able to estimate the risk of shoulder and neck pain, whereas they found it difficult to estimate the risk of low-back pain. Practitioner Summary: Work-related musculoskeletal pain risk assessments by observers are often used in ergonomic practice. We showed that observers were able to estimate shoulder and neck pain risk, but had difficulties to estimate the risk of low-back pain. Therefore, observers' risk estimates might provide a useful method for musculoskeletal pain risk assessments.

  4. Does a video displaying a stair climbing model increase stair use in a worksite setting?

    Science.gov (United States)

    Van Calster, L; Van Hoecke, A-S; Octaef, A; Boen, F

    2017-08-01

    This study evaluated the effects of improving the visibility of the stairwell and of displaying a video with a stair climbing model on climbing and descending stair use in a worksite setting. Intervention study. Three consecutive one-week intervention phases were implemented: (1) the visibility of the stairs was improved by the attachment of pictograms that indicated the stairwell; (2) a video showing a stair climbing model was sent to the employees by email; and (3) the same video was displayed on a television screen at the point-of-choice (POC) between the stairs and the elevator. The interventions took place in two buildings. The implementation of the interventions varied between these buildings and the sequence was reversed. Improving the visibility of the stairs increased both stair climbing (+6%) and descending stair use (+7%) compared with baseline. Sending the video by email yielded no additional effect on stair use. By contrast, displaying the video at the POC increased stair climbing in both buildings by 12.5% on average. One week after the intervention, the positive effects on stair climbing remained in one of the buildings, but not in the other. These findings suggest that improving the visibility of the stairwell and displaying a stair climbing model on a screen at the POC can result in a short-term increase in both climbing and descending stair use. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  5. [Relationship between organisational structure and worksite health management in the information technology and communications sector].

    Science.gov (United States)

    Ansmann, L; Jung, J; Nitzsche, A; Pfaff, H

    2012-05-01

    Worksite health management (WHM) can positively influence employee health and performance. However, it has not yet been comprehensively implemented in companies. This study aims to identify the role of organisational structures in the implementation of WHM. In this cross-sectional study, data were collected on the companies' WHM and the organisational structure. Out of 522 randomly selected companies within the German information technology and communication (ITC) sector, one managing director for each company was being questioned through telephone interviews. Bivariate and multivariate logistic regression analyses were conducted. The results of the study reveal that the implementation of WHM is positively correlated with a large company size (OR 2.75; 95%-CI 1.10-6.88) and with the existence of an employee representation (OR 2.48; 95%-CI 1.54-3.98). Other structural characteristics, such as the employment of a company physician, the percentage of temporary workers as well as the staff's age and sex distribution do not seem to have a significant impact on the implementation of WHM. The results indicate that the implementation of WHM can only be explained to a certain degree by organisational structures. However, the findings highlight the fact that companies with few structural resources are in particular need of tailored support when implementing WHM. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Production patterns of packaging waste categories generated at typical Mediterranean residential building worksites.

    Science.gov (United States)

    González Pericot, N; Villoria Sáez, P; Del Río Merino, M; Liébana Carrasco, O

    2014-11-01

    The construction sector is responsible for around 28% of the total waste volume generated in Europe, which exceeds the amount of household waste. This has led to an increase of different research studies focusing on construction waste quantification. However, within the research studies made, packaging waste has been analyzed to a limited extent. This article focuses on the packaging waste stream generated in the construction sector. To this purpose current on-site waste packaging management has been assessed by monitoring ten Mediterranean residential building works. The findings of the experimental data collection revealed that the incentive measures implemented by the construction company to improve on-site waste sorting failed to achieve the intended purpose, showing low segregation ratios. Subsequently, through an analytical study the generation patterns for packaging waste are established, leading to the identification of the prevailing kinds of packaging and the products responsible for their generation. Results indicate that plastic waste generation maintains a constant trend throughout the whole construction process, while cardboard becomes predominant towards the end of the construction works with switches and sockets from the electricity stage. Understanding the production patterns of packaging waste will be beneficial for adapting waste management strategies to the identified patterns for the specific nature of packaging waste within the context of construction worksites. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Integrating complex functions: coordination of nuclear pore complex assembly and membrane expansion of the nuclear envelope requires a family of integral membrane proteins.

    Science.gov (United States)

    Schneiter, Roger; Cole, Charles N

    2010-01-01

    The nuclear envelope harbors numerous large proteinaceous channels, the nuclear pore complexes (NPCs), through which macromolecular exchange between the cytosol and the nucleoplasm occurs. This double-membrane nuclear envelope is continuous with the endoplasmic reticulum and thus functionally connected to such diverse processes as vesicular transport, protein maturation and lipid synthesis. Recent results obtained from studies in Saccharomyces cerevisiae indicate that assembly of the nuclear pore complex is functionally dependent upon maintenance of lipid homeostasis of the ER membrane. Previous work from one of our laboratories has revealed that an integral membrane protein Apq12 is important for the assembly of functional nuclear pores. Cells lacking APQ12 are viable but cannot grow at low temperatures, have aberrant NPCs and a defect in mRNA export. Remarkably, these defects in NPC assembly can be overcome by supplementing cells with a membrane fluidizing agent, benzyl alcohol, suggesting that Apq12 impacts the flexibility of the nuclear membrane, possibly by adjusting its lipid composition when cells are shifted to a reduced temperature. Our new study now expands these findings and reveals that an essential membrane protein, Brr6, shares at least partially overlapping functions with Apq12 and is also required for assembly of functional NPCs. A third nuclear envelope membrane protein, Brl1, is related to Brr6, and is also required for NPC assembly. Because maintenance of membrane homeostasis is essential for cellular survival, the fact that these three proteins are conserved in fungi that undergo closed mitoses, but are not found in metazoans or plants, may indicate that their functions are performed by proteins unrelated at the primary sequence level to Brr6, Brl1 and Apq12 in cells that disassemble their nuclear envelopes during mitosis.

  8. Implementation of a complex of measures to fulfill the planetary protection requirements of the ExoMars-2016 mission

    Science.gov (United States)

    Khamidullina, Natalia; Novikova, Nataliya; Deshevaya, Elena; Orlov, Oleg; Guridov, Alexander; Zakharenko, Dmitry; Zaytseva, Olga

    2016-07-01

    The major purpose of the planetary protection program in the ExoMars-2016 mission is to forestall Mars contamination by terrestrial microorganisms. Since Martian descent module is not intended for biological experiments, ExoMars-2016 mission falls under COSPAR category IVa. Within the joint project co-sponsored by ESA and Roscosmos the European side holds full responsibility for ensuring a prescribed level of SC microbiological purity, while the Russian side is charged with compliance of the launch services provided on Baikonur technical complex with the planetary protection requirements that is, specifically, prevention of SC recontamination. To this end, a complex of measures was executed to control microbial contamination of cosmodrome facilities on the prescribed level which included: - regular decontamination of clean rooms using an effective disinfectant and impulse ultraviolet radiation that created favorable conditions for reliable functioning of the ESA clean tent, - replacement of airline filters in the Thermal Conditioning Unit (TCU) air duct for SC conditioning with pure air. The results of microbiological tests performed in the period of 2015 - 2016 lead to the conclusion that the Baikonur clean rooms (ISO class 8), TCU air ducts and Air Thermal Control System (ATCS) at launch site are ready for the launch campaign and that the Russian side fulfilled the planetary protection requirements of the ExoMars-2016 mission.

  9. The apical complex protein Pals1 is required to maintain cerebellar progenitor cells in a proliferative state.

    Science.gov (United States)

    Park, Jun Young; Hughes, Lucinda J; Moon, Uk Yeol; Park, Raehee; Kim, Sang-Bae; Tran, Khoi; Lee, Ju-Seog; Cho, Seo-Hee; Kim, Seonhee

    2016-01-01

    Through their biased localization and function within the cell, polarity complex proteins are necessary to establish the cellular asymmetry required for tissue organization. Well-characterized germinal zones, mitogenic signals and cell types make the cerebellum an excellent model for addressing the crucial function of polarity complex proteins in the generation and organization of neural tissues. Deletion of the apical polarity complex protein Pals1 in the developing cerebellum results in a remarkably undersized cerebellum with disrupted layers in poorly formed folia and strikingly reduced granule cell production. We demonstrate that Pals1 is not only essential for cerebellum organogenesis, but also for preventing premature differentiation and thus maintaining progenitor pools in cerebellar germinal zones, including cerebellar granule neuron precursors in the external granule layer. In the Pals1 mouse mutants, the expression of genes that regulate the cell cycle was diminished, correlating with the loss of the proliferating cell population of germinal zones. Furthermore, enhanced Shh signaling through activated Smo cannot overcome impaired cerebellar cell generation, arguing for an epistatic role of Pals1 in proliferation capacity. Our study identifies Pals1 as a novel intrinsic factor that regulates the generation of cerebellar cells and Pals1 deficiency as a potential inhibitor of overactive mitogenic signaling.

  10. Combinatorial interactions are required for the efficient recruitment of pho repressive complex (PhoRC to polycomb response elements.

    Directory of Open Access Journals (Sweden)

    Tatyana G Kahn

    2014-07-01

    Full Text Available Polycomb Group (PcG proteins are epigenetic repressors that control metazoan development and cell differentiation. In Drosophila, PcG proteins form five distinct complexes targeted to genes by Polycomb Response Elements (PREs. Of all PcG complexes PhoRC is the only one that contains a sequence-specific DNA binding subunit (PHO or PHOL, which led to a model that places PhoRC at the base of the recruitment hierarchy. Here we demonstrate that in vivo PHO is preferred to PHOL as a subunit of PhoRC and that PHO and PHOL associate with PREs and a subset of transcriptionally active promoters. Although the binding to the promoter sites depends on the quality of recognition sequences, the binding to PREs does not. Instead, the efficient recruitment of PhoRC to PREs requires the SFMBT subunit and crosstalk with Polycomb Repressive Complex 1. We find that human YY1 protein, the ortholog of PHO, binds sites at active promoters in the human genome but does not bind most PcG target genes, presumably because the interactions involved in the targeting to Drosophila PREs are lost in the mammalian lineage. We conclude that the recruitment of PhoRC to PREs is based on combinatorial interactions and propose that such a recruitment strategy is important to attenuate the binding of PcG proteins when the target genes are transcriptionally active. Our findings allow the appropriate placement of PhoRC in the PcG recruitment hierarchy and provide a rationale to explain why YY1 is unlikely to serve as a general recruiter of mammalian Polycomb complexes despite its reported ability to participate in PcG repression in flies.

  11. Farm to Work: Development of a Modified Community-Supported Agriculture Model at Worksites, 2007-2012.

    Science.gov (United States)

    Thi, Christina A; Horton, Karissa D; Loyo, Jennifer; Jowers, Esbelle M; Rodgers, Lindsay Faith; Smiley, Andrew W; Leversen, Eric; Hoelscher, Deanna M

    2015-10-22

    The Farm to Work program is a modified community-supported agriculture model at worksites in Texas. The objective of the Farm to Work program is to increase fruit and vegetable intake among employees and their households by decreasing cost, improving convenience, and increasing access while also creating a new market for local farmers at worksites. The objectives of this article were to describe the development, implementation, and outcome of a 5-year participation trend analysis and to describe the community relationships that were formed to enable the successful implementation of the program. The Farm to Work program began in November 2007 as a collaborative effort between the nonprofit Sustainable Food Center, the Texas Department of State Health Services, the Web development company WebChronic Consulting LLC, and Naegelin Farm. The program provides a weekly or biweekly opportunity for employees to order a basket of produce online to be delivered to the worksite by a local farmer. A 5-year participation trend analysis, including seasonal variation and sales trends, was conducted using sales data from November 2007 through December 2012. The total number of baskets delivered from November 2007 through December 2012 was 38,343; of these, 37,466 were sold and 877 were complimentary. The total value of sold and complimentary baskets was $851,035 and $21,925, respectively. Participation in the program increased over time and was highest in 2012. The Farm to Work program increased access to locally grown fruits and vegetables for employees and created a new market for farmers. Increased program participation indicates that Farm to Work can increase employees' fruit and vegetable consumption and thus help prevent chronic diseases in this population.

  12. Farm to Work: Development of a Modified Community-Supported Agriculture Model at Worksites, 2007–2012

    Science.gov (United States)

    Horton, Karissa D.; Loyo, Jennifer; Jowers, Esbelle M.; Rodgers, Lindsay Faith; Smiley, Andrew W.; Leversen, Eric; Hoelscher, Deanna M.

    2015-01-01

    Background The Farm to Work program is a modified community-supported agriculture model at worksites in Texas. Community Context The objective of the Farm to Work program is to increase fruit and vegetable intake among employees and their households by decreasing cost, improving convenience, and increasing access while also creating a new market for local farmers at worksites. The objectives of this article were to describe the development, implementation, and outcome of a 5-year participation trend analysis and to describe the community relationships that were formed to enable the successful implementation of the program. Methods The Farm to Work program began in November 2007 as a collaborative effort between the nonprofit Sustainable Food Center, the Texas Department of State Health Services, the Web development company WebChronic Consulting LLC, and Naegelin Farm. The program provides a weekly or biweekly opportunity for employees to order a basket of produce online to be delivered to the worksite by a local farmer. A 5-year participation trend analysis, including seasonal variation and sales trends, was conducted using sales data from November 2007 through December 2012. Outcome The total number of baskets delivered from November 2007 through December 2012 was 38,343; of these, 37,466 were sold and 877 were complimentary. The total value of sold and complimentary baskets was $851,035 and $21,925, respectively. Participation in the program increased over time and was highest in 2012. Interpretation The Farm to Work program increased access to locally grown fruits and vegetables for employees and created a new market for farmers. Increased program participation indicates that Farm to Work can increase employees’ fruit and vegetable consumption and thus help prevent chronic diseases in this population PMID:26491816

  13. Effects of a worksite supervised adapted physical activity program on trunk muscle endurance, flexibility and pain sensitivity among vineyard workers

    DEFF Research Database (Denmark)

    Balaguier, Romain; Madeleine, Pascal; Rose-Dulcina, Kevin

    2017-01-01

    OBJECTIVES: In viticulture, the prevalence of low back pain is particularly high among vineyard workers exposed to sustained and awkward postures. One promising setting for low back pain prevention resides in the implementation of workplace physical activity. METHODS: This non-randomized pilot...... was assessed using flexibility tests for the trunk, along with trunk muscle flexor and extensor endurance tests. Finally, pain sensitivity was evaluated by assessing pressure pain thresholds over 14 anatomical locations in the low back region. RESULTS: For the intervention group, the endurance of the trunk...... of worksite supervised adapted physical activity and most likely, offer a new promising approach to prevent low back pain among vineyard-workers....

  14. Impact of financial incentives on behavior change program participation and risk reduction in worksite health promotion.

    Science.gov (United States)

    Gingerich, Stefan B; Anderson, David R; Koland, Heidi

    2012-01-01

    To examine the impact of financial incentives on behavior change program registration, completion, and risk improvement rates. Retrospective cohort study conducted to observe the relationship between financial incentives and behavior change program registration, completion, and risk improvement rates. Large public- or private-sector employers. Twenty-four organizations (n = 511,060 eligible employees) that offered comprehensive worksite health promotion (WHP) programs. Financial incentives offered for completion of a behavior change program as part of a WHP program. Behavior change program registration and completion data were obtained from standard reports. Company-level risk change was calculated from the average per-person number of risks on baseline and follow-up health risk assessments. Incentive design was determined from questionnaires completed by WHP program managers. Average registration rates, program completion rates, and risk improvement rates were compared using t-tests for companies that did versus did not offer incentives. Comparisons were also made between companies with incentives of less than $100 and those with incentives of $100 or more. Correlations between incentive value and outcome variables were assessed using Pearson correlations. Companies that offered incentives had significantly higher health coaching completion rates than companies not offering an incentive (82.9% vs. 76.4%, respectively, p = .017) but there was no significant association with registration (p = .384) or risk improvement rates (p = .242). Incentive values were not significantly associated with risk improvement rates (p = .240). Offering incentives for completing behavior change programs may increase completion rates, but increased health improvement does not necessarily follow.

  15. An intervention study targeting energy and nutrient intake in worksite cafeterias.

    Science.gov (United States)

    Lowe, Michael R; Tappe, Karyn A; Butryn, Meghan L; Annunziato, Rachel A; Coletta, Maria C; Ochner, Christopher N; Rolls, Barbara J

    2010-08-01

    Modifying the food environment is a promising strategy for promoting healthier eating behavior. This study aimed to evaluate nutritional and weight changes in a program that used worksite cafeterias to reduce employees' calorie content of purchased foods and improve their macronutrient intake. Participants were randomly assigned to one of two conditions: 1) only environmental change (i.e., the introduction of 10 new low-energy-density (ED) foods and provision of labels for all foods sold at lunch, which listed ED, calories, and macronutrient content) or 2) the environmental change plus pricing incentives for purchasing low-ED foods and education about low-ED eating delivered in four, 1-hour group sessions. Participant lunch choices were monitored electronically at the point of purchase for 3 months before the intervention was instituted (i.e., the baseline period) and for 3 months afterward (i.e., intervention period). Participants were adults (n=96, BMI=29.7+/-6.0 kg/m(2)) who regularly ate lunch at their workplace cafeteria. There was no difference between groups in total energy intake over the study period. Across groups, energy and percent of energy from fat decreased and percent of energy from carbohydrate increased from baseline to the intervention period (all p<.01). Follow-up analyses, conducted by averaging Baseline Months 1 and 2 and comparing them to Intervention Month 3 as a conservative estimate of overall impact of the intervention, indicated that change in energy, carbohydrate, and fat intake remained significant (p<.001). Providing nutrition labels and reducing the ED of selected foods was associated with improved dietary intake.

  16. Production patterns of packaging waste categories generated at typical Mediterranean residential building worksites

    Energy Technology Data Exchange (ETDEWEB)

    González Pericot, N., E-mail: natalia.gpericot@upm.es [Escuela Técnica Superior de Edificación, Universidad Politécnica de Madrid, Calle Juan de Herrera n°6, 28040 Madrid (Spain); Villoria Sáez, P., E-mail: paola.villoria@upm.es [Escuela Técnica Superior de Edificación, Universidad Politécnica de Madrid, Calle Juan de Herrera n°6, 28040 Madrid (Spain); Del Río Merino, M., E-mail: mercedes.delrio@upm.es [Escuela Técnica Superior de Edificación, Universidad Politécnica de Madrid, Calle Juan de Herrera n°6, 28040 Madrid (Spain); Liébana Carrasco, O., E-mail: oscar.liebana@uem.es [Escuela de Arquitectura, Universidad Europea de Madrid, Calle Tajo s/n, 28670 Villaviciosa de Odón (Spain)

    2014-11-15

    Highlights: • On-site segregation level: 1.80%; training and motivation strategies were not effective. • 70% Cardboard waste: from switches and sockets during the building services stage. • 40% Plastic waste: generated during structures and partition works due to palletizing. • >50% Wood packaging waste, basically pallets, generated during the envelope works. - Abstract: The construction sector is responsible for around 28% of the total waste volume generated in Europe, which exceeds the amount of household waste. This has led to an increase of different research studies focusing on construction waste quantification. However, within the research studies made, packaging waste has been analyzed to a limited extent. This article focuses on the packaging waste stream generated in the construction sector. To this purpose current on-site waste packaging management has been assessed by monitoring ten Mediterranean residential building works. The findings of the experimental data collection revealed that the incentive measures implemented by the construction company to improve on-site waste sorting failed to achieve the intended purpose, showing low segregation ratios. Subsequently, through an analytical study the generation patterns for packaging waste are established, leading to the identification of the prevailing kinds of packaging and the products responsible for their generation. Results indicate that plastic waste generation maintains a constant trend throughout the whole construction process, while cardboard becomes predominant towards the end of the construction works with switches and sockets from the electricity stage. Understanding the production patterns of packaging waste will be beneficial for adapting waste management strategies to the identified patterns for the specific nature of packaging waste within the context of construction worksites.

  17. Strategies for Worksite Health Interventions to Employees with Elevated Risk of Chronic Diseases

    Directory of Open Access Journals (Sweden)

    Lu Meng

    2017-06-01

    Full Text Available Chronic disease rates have become more prevalent in the modern American workforce, which has negative implications for workplace productivity and healthcare costs. Offering workplace health interventions is recognized as an effective strategy to reduce chronic disease progression, absenteeism, and healthcare costs as well as improve population health. This review documents intervention and evaluation strategies used for health promotion programs delivered in workplaces. Using predetermined search terms in five online databases, we identified 1,131 published items from 1995 to 2014. Of these items, 27 peer-reviewed articles met the inclusion criteria; reporting data from completed United States-based workplace interventions that recruited at-risk employees based on their disease or disease-related risk factors. A content rubric was developed and used to catalogue these 27 published field studies. Selected workplace interventions targeted obesity (n = 13, cardiovascular diseases (n = 8, and diabetes (n = 6. Intervention strategies included instructional education/counseling (n = 20, workplace environmental change (n = 6, physical activity (n = 10, use of technology (n = 10, and incentives (n = 13. Self-reported data (n = 21, anthropometric measurements (n = 17, and laboratory tests (n = 14 were used most often in studies with outcome evaluation. This is the first literature review to focus on interventions for employees with elevated risk for chronic diseases. The review has the potential to inform future workplace health interventions by presenting strategies related to implementation and evaluation strategies in workplace settings. These strategies can help determine optimal worksite health programs based on the unique characteristics of work settings and the health risk factors of their employee populations.

  18. State and Local Comprehensive Smoke-Free Laws for Worksites, Restaurants, and Bars - United States, 2015.

    Science.gov (United States)

    Tynan, Michael A; Holmes, Carissa Baker; Promoff, Gabbi; Hallett, Cynthia; Hopkins, Maggie; Frick, Bronson

    2016-06-24

    Exposure to secondhand smoke from burning tobacco products causes stroke, lung cancer, and coronary heart disease in adults (1,2). Children who are exposed to secondhand smoke are at increased risk for sudden infant death syndrome, acute respiratory infections, middle ear disease, more severe asthma, respiratory symptoms, and slowed lung growth (1,2). Secondhand smoke exposure contributes to approximately 41,000 deaths among nonsmoking adults and 400 deaths in infants each year (2). This report updates a previous CDC report that evaluated state smoke-free laws in effect from 2000-2010 (3), and estimates the proportion of the population protected by comprehensive smoke-free laws. The number of states, including the District of Columbia (DC), with comprehensive smoke-free laws (statutes that prohibit smoking in indoor areas of worksites, restaurants, and bars) increased from zero in 2000 to 26 in 2010 and 27 in 2015. The percentage of the U.S. population that is protected increased from 2.72% in 2000 to 47.8% in 2010 and 49.6% in 2015. Regional disparities remain in the proportions of state populations covered by state or local comprehensive smoke-free policies, as no state in the southeast has a state comprehensive law. In addition, nine of the 24 states that lack state comprehensive smoke-free laws also lack any local comprehensive smoke-free laws. Opportunities exist to accelerate the adoption of smoke-free laws in states that lack local comprehensive smoke-free laws, including those in the south, to protect nonsmokers from the harmful effects of secondhand smoke exposure.

  19. Prevalence of obesity and factors associated with it in a worksite setting in Malaysia.

    Science.gov (United States)

    Cheong, Siew Man; Kandiah, Mirnalini; Chinna, Karuthan; Chan, Yoke Mun; Saad, Hazizi Abu

    2010-12-01

    Socio-economic status, lifestyle behaviors, and psychosocial factors have been implicated in the development of overweight and obesity. This study aims to observe the prevalence of overweight and obesity in an academic worksite and to examine the possible association between variables such as socio-economic characteristics, work factors, psychosocial factors, and weight control behaviors and obesity. In this study, the target population were full-time academic and non-academic staff. Body mass index (BMI) and waist circumference (WC) were computed to determine obesity. A pretested self-administered questionnaire was used to obtain information on socio-demographic factors, work related factors, psychosocial factors, and weight control behaviors. Data were obtained on 367 adults of whom 39.2% were males and 60.8% females. Overweight was seen in 31.9% of males and 26.5% of females while 16.1% of them were obese, irrespective of gender. Central obesity was noted in about 37% of males and 39% of females. The results showed that socio-demographic factors (age, gender, and education) and psychosocial factors (perceived health status, body weight perception, and weight-control goals) were significantly associated with BMI. Working hours were also significantly associated with BMI. However, weight control practices (diet-control practices and physical activity practices) were not significantly associated with BMI. In conclusion, this study found a higher prevalence of overweight and obesity among employees of a selected public university in comparison to the general population. Socio-demographic, psychosocial factors, and working hours were found to contribute to obesity in this sample of adults.

  20. Localization of the sensory neurons and mechanoreceptors required for stretch-evoked colonic migrating motor complexes in mouse colon

    Directory of Open Access Journals (Sweden)

    Vladimir P Zagorodnyuk

    2011-12-01

    Full Text Available The pacemaker and pattern generator that underlies the cyclical generation of spontaneous colonic migrating motor complexes (CMMCs has recently been identified to lie within the myenteric plexus and/or muscularis externa. Neither the mucosa, nor the release of substances from the mucosa were found to be required for the spontaneous generation of CMMCs. However, it is known that stretch applied to the colonic wall can also evoke CMMCs and since stretch of the gut wall is known to stimulate the mucosa, it is not clear whether release of substances from the mucosa and/or submucosal plexus are required for stretch-evoked CMMCs. Therefore, the aim of this study was to determine whether circumferential stretch-evoked CMMCs require the presence of the mucosa and/or submucosal plexus in isolated mouse colon. Spontaneous CMMCs were recorded from full length sheet preparations of colon in vitro. Graded circumferential stretch (at a rate of 100μm/s applied to a 15mm segment of mid-distal colon reliably evoked a CMMC, which propagated to the oral recording site. Sharp dissection to remove the mucosa and submucosal plexus from the entire colon did not prevent spontaneous CMMCs and circumferential stretch-evoked CMMCs were still reliably evoked by circumferential stretch even at lower thresholds. In contrast, in intact preparations, direct stimulation of the mucosa (without accompanying stretch proved highly inconsistent and rarely evoked a CMMC. These observations lead to the inescapable conclusion that the sensory neurons activated by colonic stretch to initiate CMMCs lie in the myenteric plexus, while the mechanoreceptors activated by stretch, lie in the myenteric ganglia and/or muscularis externa. Stretch activation of these mechanoreceptors does not require release of any substance(s from the mucosa, or neural inputs arising from submucosal ganglia.

  1. The MARVEL domain protein, Singles Bar, is required for progression past the pre-fusion complex stage of myoblast fusion.

    Science.gov (United States)

    Estrada, Beatriz; Maeland, Anne D; Gisselbrecht, Stephen S; Bloor, James W; Brown, Nicholas H; Michelson, Alan M

    2007-07-15

    Multinucleated myotubes develop by the sequential fusion of individual myoblasts. Using a convergence of genomic and classical genetic approaches, we have discovered a novel gene, singles bar (sing), that is essential for myoblast fusion. sing encodes a small multipass transmembrane protein containing a MARVEL domain, which is found in vertebrate proteins involved in processes such as tight junction formation and vesicle trafficking where--as in myoblast fusion--membrane apposition occurs. sing is expressed in both founder cells and fusion competent myoblasts preceding and during myoblast fusion. Examination of embryos injected with double-stranded sing RNA or embryos homozygous for ethane methyl sulfonate-induced sing alleles revealed an identical phenotype: replacement of multinucleated myofibers by groups of single, myosin-expressing myoblasts at a stage when formation of the mature muscle pattern is complete in wild-type embryos. Unfused sing mutant myoblasts form clusters, suggesting that early recognition and adhesion of these cells are unimpaired. To further investigate this phenotype, we undertook electron microscopic ultrastructural studies of fusing myoblasts in both sing and wild-type embryos. These experiments revealed that more sing mutant myoblasts than wild-type contain pre-fusion complexes, which are characterized by electron-dense vesicles paired on either side of the fusing plasma membranes. In contrast, embryos mutant for another muscle fusion gene, blown fuse (blow), have a normal number of such complexes. Together, these results lead to the hypothesis that sing acts at a step distinct from that of blow, and that sing is required on both founder cell and fusion-competent myoblast membranes to allow progression past the pre-fusion complex stage of myoblast fusion, possibly by mediating fusion of the electron-dense vesicles to the plasma membrane.

  2. Quality Control of Biomedicinal Allergen Products - Highly Complex Isoallergen Composition Challenges Standard MS Database Search and Requires Manual Data Analyses.

    Science.gov (United States)

    Spiric, Jelena; Engin, Anna M; Karas, Michael; Reuter, Andreas

    2015-01-01

    Allergy against birch pollen is among the most common causes of spring pollinosis in Europe and is diagnosed and treated using extracts from natural sources. Quality control is crucial for safe and effective diagnosis and treatment. However, current methods are very difficult to standardize and do not address individual allergen or isoallergen composition. MS provides information regarding selected proteins or the entire proteome and could overcome the aforementioned limitations. We studied the proteome of birch pollen, focusing on allergens and isoallergens, to clarify which of the 93 published sequence variants of the major allergen, Bet v 1, are expressed as proteins within one source material in parallel. The unexpectedly complex Bet v 1 isoallergen composition required manual data interpretation and a specific design of databases, as current database search engines fail to unambiguously assign spectra to highly homologous, partially identical proteins. We identified 47 non-allergenic proteins and all 5 known birch pollen allergens, and unambiguously proved the existence of 18 Bet v 1 isoallergens and variants by manual data analysis. This highly complex isoallergen composition raises questions whether isoallergens can be ignored or must be included for the quality control of allergen products, and which data analysis strategies are to be applied.

  3. Quality Control of Biomedicinal Allergen Products - Highly Complex Isoallergen Composition Challenges Standard MS Database Search and Requires Manual Data Analyses.

    Directory of Open Access Journals (Sweden)

    Jelena Spiric

    Full Text Available Allergy against birch pollen is among the most common causes of spring pollinosis in Europe and is diagnosed and treated using extracts from natural sources. Quality control is crucial for safe and effective diagnosis and treatment. However, current methods are very difficult to standardize and do not address individual allergen or isoallergen composition. MS provides information regarding selected proteins or the entire proteome and could overcome the aforementioned limitations. We studied the proteome of birch pollen, focusing on allergens and isoallergens, to clarify which of the 93 published sequence variants of the major allergen, Bet v 1, are expressed as proteins within one source material in parallel. The unexpectedly complex Bet v 1 isoallergen composition required manual data interpretation and a specific design of databases, as current database search engines fail to unambiguously assign spectra to highly homologous, partially identical proteins. We identified 47 non-allergenic proteins and all 5 known birch pollen allergens, and unambiguously proved the existence of 18 Bet v 1 isoallergens and variants by manual data analysis. This highly complex isoallergen composition raises questions whether isoallergens can be ignored or must be included for the quality control of allergen products, and which data analysis strategies are to be applied.

  4. Increased Maternal Genome Dosage Bypasses the Requirement of the FIS Polycomb Repressive Complex 2 in Arabidopsis Seed Development

    Science.gov (United States)

    Kradolfer, David; Hennig, Lars; Köhler, Claudia

    2013-01-01

    Seed development in flowering plants is initiated after a double fertilization event with two sperm cells fertilizing two female gametes, the egg cell and the central cell, leading to the formation of embryo and endosperm, respectively. In most species the endosperm is a polyploid tissue inheriting two maternal genomes and one paternal genome. As a consequence of this particular genomic configuration the endosperm is a dosage sensitive tissue, and changes in the ratio of maternal to paternal contributions strongly impact on endosperm development. The FERTILIZATION INDEPENDENT SEED (FIS) Polycomb Repressive Complex 2 (PRC2) is essential for endosperm development; however, the underlying forces that led to the evolution of the FIS-PRC2 remained unknown. Here, we show that the functional requirement of the FIS-PRC2 can be bypassed by increasing the ratio of maternal to paternal genomes in the endosperm, suggesting that the main functional requirement of the FIS-PRC2 is to balance parental genome contributions and to reduce genetic conflict. We furthermore reveal that the AGAMOUS LIKE (AGL) gene AGL62 acts as a dosage-sensitive seed size regulator and that reduced expression of AGL62 might be responsible for reduced size of seeds with increased maternal genome dosage. PMID:23326241

  5. Genetic and molecular requirements for function of the Pto/Prf effector recognition complex in tomato and Nicotiana benthamiana.

    Science.gov (United States)

    Balmuth, Alexi; Rathjen, John P

    2007-09-01

    The Pto gene of tomato (Solanum lycopersicum) confers specific recognition of the unrelated bacterial effector proteins AvrPto and AvrPtoB. Pto resides in a constitutive molecular complex with the nucleotide binding site-leucine rich repeats protein Prf. Prf is absolutely required for specific recognition of both effectors. Here, using stable transgenic lines, we show that expression of Pto from its genomic promoter in susceptible tomatoes was sufficient to complement recognition of Pseudomonas syringae pv. tomato (Pst) bacteria expressing either avrPto or avrPtoB. Pto kinase activity was absolutely required for specific immunity. Expression of the Pto N-myristoylation mutant, pto(G2A), conferred recognition of Pst (avrPtoB), but not Pst (avrPto), although bacterial growth in these lines was intermediate between resistant and susceptible lines. Overexpression of pto(G2A) complemented recognition of avrPto. Transgenic tomato plants overexpressing wild-type Pto exhibited constitutive growth phenotypes, but these were absent in lines overexpressing pto(G2A). Therefore, Pto myristoylation is a quantitative factor for effector recognition in tomato, but is absolutely required for overexpression phenotypes. Native expression of Pto in the heterologous species Nicotiana benthamiana did not confer resistance to P. syringae pv. tabaci (Pta) expressing avrPto or avrPtoB, but recognition of both effectors was complemented by Prf co-expression. Thus, specific resistance conferred solely by Pto in N. benthamiana is an artefact of overexpression. Finally, pto(G2A) did not confer recognition of either avrPto or avrPtoB in N. benthamiana, regardless of the presence of Prf. Thus, co-expression of Prf in N. benthamiana complements many but not all aspects of normal Pto function.

  6. Comparing tailored and narrative worksite interventions at increasing colonoscopy adherence in adults 50-75: a randomized controlled trial.

    Science.gov (United States)

    Jensen, Jakob D; King, Andy J; Carcioppolo, Nick; Krakow, Melinda; Samadder, N Jewel; Morgan, Susan

    2014-03-01

    Research has identified several communication strategies that could increase adherence to colorectal cancer screening recommendations. Two promising strategies are tailoring and narrative-based approaches. Tailoring is the personalization of information based on individual characteristics. Narrative-based approaches use stories about similar others to counter perceived barriers and cultivate self-efficacy. To compare these two approaches, a randomized controlled trial was carried out at 8 worksites in Indiana. Adults 50-75 (N = 209) received one of four messages about colorectal cancer screening: stock, narrative, tailored, tailored narrative. The primary outcome was whether participants filed a colonoscopy claim in the 18 months following the intervention. Individuals receiving narrative messages were 4 times more likely to screen than those not receiving narrative messages. Tailoring did not increase screening behavior overall. However, individuals with higher cancer information overload were 8 times more likely to screen if they received tailored messages. The results suggest that narrative-based approaches are more effective than tailoring at increasing colorectal cancer screening in worksite interventions. Tailoring may be valuable as a strategy for reaching individuals with high overload, perhaps as a follow-up effort to a larger communication campaign.

  7. Effects of a Worksite Supervised Adapted Physical Activity Program on Trunk Muscle Endurance, Flexibility, and Pain Sensitivity Among Vineyard Workers.

    Science.gov (United States)

    Balaguier, Romain; Madeleine, Pascal; Rose-Dulcina, Kévin; Vuillerme, Nicolas

    2017-01-01

    In viticulture, the prevalence of low back pain is particularly high among vineyard workers exposed to sustained and awkward postures. One promising setting for low back pain prevention resides in the implementation of workplace physical activity. This nonrandomized pilot study aims at evaluating the effects of a worksite supervised adapted physical activity program among 17 vineyard workers volunteered to enter either an intervention group (n = 10) or a control group (n = 7).The intervention group followed a physical activity program for 8 weeks involving (1) 15 minutes of warm-up every working day and (2) two weekly 1-hour adapted physical activity sessions targeting trunk muscle endurance and flexibility. The control group was advised to continue normal physical activity. Evaluations were carried out at weeks 0, 4, 8, and 12. Physical capacity was assessed using flexibility tests for the trunk, along with trunk muscle flexor and extensor endurance tests. Finally, pain sensitivity was evaluated by assessing pressure pain thresholds over 14 anatomical locations in the low back region. For the intervention group, the endurance of the trunk extensor and flexor significantly increased from baseline to week 8 as well as the pressure pain thresholds. No change was observed for the control group over the same period. These encouraging results in combination with the high adherence rate set interesting foundations for the promotion of worksite supervised adapted physical activity and, most likely, offer a new promising approach to prevent low back pain among vineyard workers.

  8. A worksite vegan nutrition program is well-accepted and improves health-related quality of life and work productivity.

    Science.gov (United States)

    Katcher, Heather I; Ferdowsian, Hope R; Hoover, Valerie J; Cohen, Joshua L; Barnard, Neal D

    2010-01-01

    Vegetarian and vegan diets are effective in preventing and treating several chronic diseases. However, their acceptability outside a clinical trial setting has not been extensively studied. The aim of this study was to determine the acceptability of a worksite vegan nutrition program and its effects on health-related quality of life and work productivity. Employees of a major insurance corporation with a body mass index > or =25 kg/m(2) and/or a previous diagnosis of type 2 diabetes received either weekly group instruction on a low-fat vegan diet (n = 68) or received no diet instruction (n = 45) for 22 weeks. The vegan group reported improvements in general health (p = 0.002), physical functioning (p = 0.001), mental health (p = 0.03), vitality (p = 0.004), and overall diet satisfaction (p vegan group also reported a decrease in food costs (p = 0.003), and increased difficulty finding foods when eating out (p = 0.04) compared with the control group. The vegan group reported a 40-46% decrease in health-related productivity impairments at work (p = 0.03) and in regular daily activities (p = 0.004). A worksite vegan nutrition program is well-accepted and can be implemented by employers to improve the health, quality of life, and work productivity of employees.

  9. Effect of improving the knowledge, attitude and practice of reproductive health among female migrant workers: a worksite-based intervention in Guangzhou, China

    NARCIS (Netherlands)

    Gao, X.; Xu, L.; Lu, C.; Wu, J.; Wang, Z.; Decat, P.; Zhang, W.-H.; Chen, Y.; Moyer, E.; Wu, S.; Minkauskiene, M.; van Braeckel, D.; Temmerman, M.

    2014-01-01

    Background: The sexual and reproductive health (SRH) knowledge and attitudes of female migrant workers are far from optimum in China. A worksite-based intervention program on SRH-related knowledge, attitude and practice (SRH KAP) modification may be an effective approach to improve the SRH status am

  10. Systematic review on the financial return of worksite health promotion programmes aimed at improving nutrition and/or increasing physical activity

    NARCIS (Netherlands)

    Dongen, J.M. van; Proper, K.I.; Wier, M.F. van; Beek, A.J. van der; Bongers, P.M.; Mechelen, W. van; Tulder, M.W. van

    2011-01-01

    Summary: This systematic review summarizes the current evidence on the financial return of worksite health promotion programmes aimed at improving nutrition and/or increasing physical activity. Data on study characteristics and results were extracted from 18 studies published up to 14 January 2011.

  11. The (cost-)effectiveness of an individually tailored long-term worksite health promotion programme on physical activity and nutrition: design of a pragmatic cluster randomised controlled trial

    NARCIS (Netherlands)

    S.J.W. Robroek (Suzan); F.J. Bredt (Folef); A. Burdorf (Alex)

    2007-01-01

    textabstractCardiovascular disease is the leading cause of disability and mortality in most Western countries. The prevalence of several risk factors, most notably low physical activity and poor nutrition, is very high. Therefore, lifestyle behaviour changes are of great importance. The worksite off

  12. Effectiveness of an intervention at construction worksites on work engagement, social support, physical workload, and need for recovery: Results from a cluster randomized controlled trial

    NARCIS (Netherlands)

    Oude Hengel, K.M.; Blatter, B.M.; Joling, C.I.; Beek, A.J. van der; Bongers, P.M.

    2012-01-01

    Background: To prolong sustainable healthy working lives of construction workers, a worksite prevention program was developed which aimed to improve the health and work ability of construction workers. The aim of the current study was to investigate the effectiveness of this program on social suppor

  13. Effectiveness of a worksite mindfulness-related multi-component health promotion intervention on work engagement and mental health: Results of a randomized controlled trial

    NARCIS (Netherlands)

    Berkel, J. van; Boot, C.R.L.; Proper, K.I.; Bongers, P.M.; Beek, A.J. van der

    2014-01-01

    Objectives: The aim of the present study was to evaluate the effectiveness of a worksite mindfulness-related multicomponent health promotion intervention on work engagement, mental health, need for recovery and mindfulness. Methods: In a randomized controlled trial design, 257 workers of two researc

  14. The effect of worksite physical activity intervention on physical capacity, health, and productivity: A 1-year randomized controlled trial

    DEFF Research Database (Denmark)

    Pedersen, Mogens T; Blangsted, Anne K.; Andersen, Lars L.

    2009-01-01

    OBJECTIVE: To investigate the effect of two contrasting physical activity worksite interventions versus a reference intervention (REF) on various health outcomes. METHODS: A 1-year randomized controlled trial was conducted with specific resistance training (SRT), all-round physical exercise (APE...... symptoms, in combination with minor increases in physical capacity....

  15. The effectiveness of a construction worksite prevention program on work ability, health, and sick leave: Results from a cluster randomized controlled trial

    NARCIS (Netherlands)

    Oude Hengel, K.M.; Blatter, B.M.; Molen, H.F. van der; Bongers, P.M.; Beek, A.J. van der

    2013-01-01

    Objective This study aimed to investigate the effectiveness of a prevention program on work ability, health, and sick leave targeted at construction worksites. Methods A total of 15 departments (N=297 workers) from 6 construction companies participated in this cluster randomized controlled trial and

  16. Effectiveness of an intervention at construction worksites on work engagement, social support, physical workload, and need for recovery: Results from a cluster randomized controlled trial

    NARCIS (Netherlands)

    Oude Hengel, K.M.; Blatter, B.M.; Joling, C.I.; Beek, A.J. van der; Bongers, P.M.

    2012-01-01

    Background: To prolong sustainable healthy working lives of construction workers, a worksite prevention program was developed which aimed to improve the health and work ability of construction workers. The aim of the current study was to investigate the effectiveness of this program on social

  17. A worksite vitality intervention for older hospital workers to improve vitality work engegement, productivity ans sick leave: results of a randomized controlled trial

    NARCIS (Netherlands)

    Strijk, J.E.; Proper, K.I.; Meschelen, W. van; Beek, A. van der

    2012-01-01

    Objectives A worksite vitality intervention aiming to improve lifestyle behaviors could be an effective tool to keep older workers vital, and thereby prolong their labor participation. Therefore, this study evaluates the effectiveness of such an intervention on vitality, work engagement, productivit

  18. Effectiveness of a worksite social & physical environment intervention on need for recovery, physical activity and relaxation; results of a randomized controlled trial

    NARCIS (Netherlands)

    Coffeng, J.K.; Boot, C.R.L.; Duijts, S.F.A.; Twisk, J.W.R.; Mechelen, W. van; Hendriksen, I.J.M.

    2014-01-01

    OBJECTIVE: To investigate the effectiveness of a worksite social and physical environment intervention on need for recovery (i.e., early symptoms of work-related mental and physical fatigue), physical activity and relaxation. Also, the effectiveness of the separate interventions was investigated.

  19. Flexibility and rigidity, requirements for the function of proteins and protein pigment complexes. Eleventh Keilin memorial lecture.

    Science.gov (United States)

    Huber, R

    1987-12-01

    Proteins may be rigid or flexible to various degrees as required for optimum function. Flexibility at the level of amino acid side-chains occurs universally and is important for binding and catalysis. Flexibility of large parts of a protein which rearrange or move are particularly interesting and will be discussed here. We differentiate between certain categories of large-scale flexibility although the boundaries between them are diffuse: flexibility of peptide segments, domain motions and order-disorder transitions of spatially contigous regions. The domains may be flexibly linked to allow rather unrestricted motion or the motion may be constrained to certain modes. The polypeptide segments linking the domains show characteristic structural features. The various categories of flexibility will be illustrated with the following examples. (a) Small protein proteinase inhibitors which are rather rigid molecules which provide binding surfaces complementary to their cognate proteases, but also show limited segmental flexibility and adaptation. (b) Large plasma inhibitors which exhibit large conformational changes upon interaction with proteases probably for regulatory purposes. (c) Pancreatic serine proteases which employ a disorder-order transition of their activation domain as a means to regulate enzymic activity. (d) Immunoglobulins in which rather unrestricted and also hinged domain motions occur in different parts of the molecule probably to allow binding to antigens in different arrangements. (e) Citrate synthase which adopts open and closed forms by a hinged domain motion to bind substrates and release products and to perform the catalytic condensation reaction, respectively. (f) The bifunctional multienzyme complex riboflavin synthase in which two enzymes (alpha and beta) catalyse two consecutive enzymic reactions. The beta-subunits form a shell, in which the alpha-subunits are enclosed. Diffusional motion of the catalytic intermediates is therefore restricted

  20. Intraflagellar transport is required for polarized recycling of the TCR/CD3 complex to the immune synapse.

    Science.gov (United States)

    Finetti, Francesca; Paccani, Silvia Rossi; Riparbelli, Maria Giovanna; Giacomello, Emiliana; Perinetti, Giuseppe; Pazour, Gregory J; Rosenbaum, Joel L; Baldari, Cosima T

    2009-11-01

    Most eukaryotic cells have a primary cilium which functions as a sensory organelle. Cilia are assembled by intraflagellar transport (IFT), a process mediated by multimeric IFT particles and molecular motors. Here we show that lymphoid and myeloid cells, which lack primary cilia, express IFT proteins. IFT20, an IFT component essential for ciliary assembly, was found to colocalize with both the microtubule organizing centre (MTOC) and Golgi and post-Golgi compartments in T-lymphocytes. In antigen-specific conjugates, IFT20 translocated to the immune synapse. IFT20 knockdown resulted in impaired T-cell receptor/CD3 (TCR/CD3) clustering and signalling at the immune synapse, due to defective polarized recycling. Moreover, IFT20 was required for the inducible assembly of a complex with other IFT components (IFT57 and IFT88) and the TCR. The results identify IFT20 as a new regulator of immune synapse assembly in T cells and provide the first evidence to implicate IFT in membrane trafficking in cells lacking primary cilia, thereby introducing a new perspective on IFT function beyond its role in ciliogenesis.

  1. An Asp–CaM complex is required for centrosome–pole cohesion and centrosome inheritance in neural stem cells

    Science.gov (United States)

    Schoborg, Todd; Zajac, Allison L.; Fagerstrom, Carey J.; Guillen, Rodrigo X.

    2015-01-01

    The interaction between centrosomes and mitotic spindle poles is important for efficient spindle formation, orientation, and cell polarity. However, our understanding of the dynamics of this relationship and implications for tissue homeostasis remains poorly understood. Here we report that Drosophila melanogaster calmodulin (CaM) regulates the ability of the microcephaly-associated protein, abnormal spindle (Asp), to cross-link spindle microtubules. Both proteins colocalize on spindles and move toward spindle poles, suggesting that they form a complex. Our binding and structure–function analysis support this hypothesis. Disruption of the Asp–CaM interaction alone leads to unfocused spindle poles and centrosome detachment. This behavior leads to randomly inherited centrosomes after neuroblast division. We further show that spindle polarity is maintained in neuroblasts despite centrosome detachment, with the poles remaining stably associated with the cell cortex. Finally, we provide evidence that CaM is required for Asp’s spindle function; however, it is completely dispensable for Asp’s role in microcephaly suppression. PMID:26620907

  2. Accessory subunit NUYM (NDUFS4) is required for stability of the electron input module and activity of mitochondrial complex I.

    Science.gov (United States)

    Kahlhöfer, Flora; Kmita, Katarzyna; Wittig, Ilka; Zwicker, Klaus; Zickermann, Volker

    2017-02-01

    Mitochondrial complex I is an intricate 1MDa membrane protein complex with a central role in aerobic energy metabolism. The minimal form of complex I consists of fourteen central subunits that are conserved from bacteria to man. In addition, eukaryotic complex I comprises some 30 accessory subunits of largely unknown function. The gene for the accessory NDUFS4 subunit of human complex I is a hot spot for fatal pathogenic mutations in humans. We have deleted the gene for the orthologous NUYM subunit in the aerobic yeast Yarrowia lipolytica, an established model system to study eukaryotic complex I and complex I linked diseases. We observed assembly of complex I which lacked only subunit NUYM and retained weak interaction with assembly factor N7BML (human NDUFAF2). Absence of NUYM caused distortion of iron sulfur clusters of the electron input domain leading to decreased complex I activity and increased release of reactive oxygen species. We conclude that NUYM has an important stabilizing function for the electron input module of complex I and is essential for proper complex I function.

  3. Translocation of the papillomavirus L2/vDNA complex across the limiting membrane requires the onset of mitosis.

    Science.gov (United States)

    Calton, Christine M; Bronnimann, Matthew P; Manson, Ariana R; Li, Shuaizhi; Chapman, Janice A; Suarez-Berumen, Marcela; Williamson, Tatum R; Molugu, Sudheer K; Bernal, Ricardo A; Campos, Samuel K

    2017-05-01

    The human papillomavirus type 16 (HPV16) L2 protein acts as a chaperone to ensure that the viral genome (vDNA) traffics from endosomes to the trans-Golgi network (TGN) and eventually the nucleus, where HPV replication occurs. En route to the nucleus, the L2/vDNA complex must translocate across limiting intracellular membranes. The details of this critical process remain poorly characterized. We have developed a system based on subcellular compartmentalization of the enzyme BirA and its cognate substrate to detect membrane translocation of L2-BirA from incoming virions. We find that L2 translocation requires transport to the TGN and is strictly dependent on entry into mitosis, coinciding with mitotic entry in synchronized cells. Cell cycle arrest causes retention of L2/vDNA at the TGN; only release and progression past G2/M enables translocation across the limiting membrane and subsequent infection. Microscopy of EdU-labeled vDNA reveals a rapid and dramatic shift in vDNA localization during early mitosis. At late G2/early prophase vDNA egresses from the TGN to a pericentriolar location, accumulating there through prometaphase where it begins to associate with condensed chromosomes. By metaphase and throughout anaphase the vDNA is seen bound to the mitotic chromosomes, ensuring distribution into both daughter nuclei. Mutations in a newly defined chromatin binding region of L2 potently blocked translocation, suggesting that translocation is dependent on chromatin binding during prometaphase. This represents the first time a virus has been shown to functionally couple the penetration of limiting membranes to cellular mitosis, explaining in part the tropism of HPV for mitotic basal keratinocytes.

  4. SUPERKILLER Complex Components Are Required for the RNA Exosome-Mediated Control of Cuticular Wax Biosynthesis in Arabidopsis Inflorescence Stems.

    Science.gov (United States)

    Zhao, Lifang; Kunst, Ljerka

    2016-06-01

    ECERIFERUM7 (CER7)/AtRRP45B core subunit of the exosome, the main cellular 3'-to-5' exoribonuclease, is a positive regulator of cuticular wax biosynthesis in Arabidopsis (Arabidopsis thaliana) inflorescence stems. CER7-dependent exosome activity determines stem wax load by controlling transcript levels of the wax-related gene CER3 Characterization of the second-site suppressors of the cer7 mutant revealed that small interfering RNAs (siRNAs) are direct effectors of CER3 expression. To explore the relationship between the exosome and posttranscriptional gene silencing (PTGS) in regulating CER3 transcript levels, we investigated two additional suppressor mutants, wax restorer1 (war1) and war7. We show that WAR1 and WAR7 encode Arabidopsis SUPERKILLER3 (AtSKI3) and AtSKI2, respectively, components of the SKI complex that associates with the exosome during cytoplasmic 3'-to-5' RNA degradation, and that CER7-dependent regulation of wax biosynthesis also requires participation of AtSKI8. Our study further reveals that it is the impairment of the exosome-mediated 3'-5' decay of CER3 transcript in the cer7 mutant that triggers extensive production of siRNAs and efficient PTGS of CER3. This identifies PTGS as a general mechanism for eliminating highly abundant endogenous transcripts that is activated when 3'-to-5' mRNA turnover by the exosome is disrupted. Diminished efficiency of PTGS in ski mutants compared with cer7, as evidenced by lower accumulation of CER3-related siRNAs, suggests that reduced amounts of CER3 transcript are available for siRNA synthesis, possibly because CER3 mRNA that does not interact with SKI is degraded by 5'-to-3' XRN4 exoribonuclease.

  5. A conceptual model for worksite intelligent physical exercise training - IPET - intervention for decreasing life style health risk indicators among employees

    DEFF Research Database (Denmark)

    Sjøgaard, Gisela; Justesen, Just Bendix; Murray, Mike

    2014-01-01

    with a conceptual model for planning the optimal individually tailored physical exercise training for each worker based on individual health check, existing guidelines and state of the art sports science training recommendations in the broad categories of cardiorespiratory fitness, muscle strength in specific body......BACKGROUND: Health promotion at the work site in terms of physical activity has proven positive effects but optimization of relevant exercise training protocols and implementation for high adherence are still scanty.Methods/design: The aim of this paper is to present a study protocol...... parts, and functional training including balance training. The hypotheses of this research are that individually tailored worksite-based intelligent physical exercise training, IPET, among workers with inactive job categories will: 1) Improve cardiorespiratory fitness and/or individual health risk...

  6. Current trends in reducing cardiovascular risk factors in the United States: focus on worksite health and wellness.

    Science.gov (United States)

    Cahalin, Lawrence P; Myers, Jonathan; Kaminsky, Leonard; Briggs, Paige; Forman, Daniel E; Patel, Mahesh J; Pinkstaff, Sherry O; Arena, Ross

    2014-01-01

    Health care in the United States (US) is changing with a broad provision of health care services to every American due to the Affordable Care Act (ACA) slated to begin in January of 2014. An important aspect of the ACA is that US companies may begin to offer health insurance incentives to employees for participating in health and wellness initiatives. Moreover, since US employers directly absorb many of the financial costs associated with the high degree of cardiovascular (CV) risk factors present in their personnel, employers may be financially vested in improving employee health. However, employers must also consider the costs of developing and maintaining programs to improve employee health and their return on investment (ROI). This review will identify key risk factors to address in a worksite health and wellness program and to examine the performance of such programs in improving CV risk factors and their ROI.

  7. Is sociality required for the evolution of communicative complexity? Evidence weighed against alternative hypotheses in diverse taxonomic groups.

    Science.gov (United States)

    Ord, Terry J; Garcia-Porta, Joan

    2012-07-05

    Complex social communication is expected to evolve whenever animals engage in many and varied social interactions; that is, sociality should promote communicative complexity. Yet, informal comparisons among phylogenetically independent taxonomic groups seem to cast doubt on the putative role of social factors in the evolution of complex communication. Here, we provide a formal test of the sociality hypothesis alongside alternative explanations for the evolution of communicative complexity. We compiled data documenting variations in signal complexity among closely related species for several case study groups--ants, frogs, lizards and birds--and used new phylogenetic methods to investigate the factors underlying communication evolution. Social factors were only implicated in the evolution of complex visual signals in lizards. Ecology, and to some degree allometry, were most likely explanations for complexity in the vocal signals of frogs (ecology) and birds (ecology and allometry). There was some evidence for adaptive evolution in the pheromone complexity of ants, although no compelling selection pressure was identified. For most taxa, phylogenetic null models were consistently ranked above adaptive models and, for some taxa, signal complexity seems to have accumulated in species via incremental or random changes over long periods of evolutionary time. Becoming social presumably leads to the origin of social communication in animals, but its subsequent influence on the trajectory of signal evolution has been neither clear-cut nor general among taxonomic groups.

  8. The (cost-effectiveness of an individually tailored long-term worksite health promotion programme on physical activity and nutrition: design of a pragmatic cluster randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Burdorf Alex

    2007-09-01

    Full Text Available Abstract Background Cardiovascular disease is the leading cause of disability and mortality in most Western countries. The prevalence of several risk factors, most notably low physical activity and poor nutrition, is very high. Therefore, lifestyle behaviour changes are of great importance. The worksite offers an efficient structure to reach large groups and to make use of a natural social network. This study investigates a worksite health promotion programme with individually tailored advice in physical activity and nutrition and individual counselling to increase compliance with lifestyle recommendations and sustainability of a healthy lifestyle. Methods/Design The study is a pragmatic cluster randomised controlled trial with the worksite as the unit of randomisation. All workers will receive a standard worksite health promotion program. Additionally, the intervention group will receive access to an individual Health Portal consisting of four critical features: a computer-tailored advice, a monitoring function, a personal coach, and opportunities to contact professionals at request. Participants are employees working for companies in the Netherlands, being literate enough to read and understand simple Internet-based messages in the Dutch language. A questionnaire to assess primary outcomes (compliance with national recommendations on physical activity and on fruit and vegetable intake will take place at baseline and after 12 and 24 months. This questionnaire also assesses secondary outcomes including fat intake, self-efficacy and self-perceived barriers on physical activity and fruit and vegetable intake. Other secondary outcomes, including a cardiovascular risk profile and physical fitness, will be measured at baseline and after 24 months. Apart from the effect evaluation, a process evaluation will be carried out to gain insight into participation and adherence to the worksite health promotion programme. A cost-effectiveness analysis and

  9. SAG101 forms a ternary complex with EDS1 and PAD4 and is required for resistance signaling against turnip crinkle virus.

    Science.gov (United States)

    Zhu, Shifeng; Jeong, Rae-Dong; Venugopal, Srivathsa C; Lapchyk, Ludmila; Navarre, DuRoy; Kachroo, Aardra; Kachroo, Pradeep

    2011-11-01

    EDS1, PAD4, and SAG101 are common regulators of plant immunity against many pathogens. EDS1 interacts with both PAD4 and SAG101 but direct interaction between PAD4 and SAG101 has not been detected, leading to the suggestion that the EDS1-PAD4 and EDS1-SAG101 complexes are distinct. We show that EDS1, PAD4, and SAG101 are present in a single complex in planta. While this complex is preferentially nuclear localized, it can be redirected to the cytoplasm in the presence of an extranuclear form of EDS1. PAD4 and SAG101 can in turn, regulate the subcellular localization of EDS1. We also show that the Arabidopsis genome encodes two functionally redundant isoforms of EDS1, either of which can form ternary complexes with PAD4 and SAG101. Simultaneous mutations in both EDS1 isoforms are essential to abrogate resistance (R) protein-mediated defense against turnip crinkle virus (TCV) as well as avrRps4 expressing Pseudomonas syringae. Interestingly, unlike its function as a PAD4 substitute in bacterial resistance, SAG101 is required for R-mediated resistance to TCV, thus implicating a role for the ternary complex in this defense response. However, only EDS1 is required for HRT-mediated HR to TCV, while only PAD4 is required for SA-dependent induction of HRT. Together, these results suggest that EDS1, PAD4 and SAG101 also perform independent functions in HRT-mediated resistance.

  10. Molecular features of biguanides required for targeting of mitochondrial respiratory complex I and activation of AMP-kinase

    OpenAIRE

    2016-01-01

    Background The biguanides are a family of drugs with diverse clinical applications. Metformin, a widely used anti-hyperglycemic biguanide, suppresses mitochondrial respiration by inhibiting respiratory complex I. Phenformin, a related anti-hyperglycemic biguanide, also inhibits respiration, but proguanil, which is widely used for the prevention of malaria, does not. The molecular structures of phenformin and proguanil are closely related and both inhibit isolated complex I. Proguanil does not...

  11. Successful strategies to increase the consumption of fruits and vegetables: results from the Danish '6 a day' Work-site Canteen Model Study

    DEFF Research Database (Denmark)

    Lassen, Anne Dahl; Thorsen, Anne Vibeke; Trolle, Ellen

    2004-01-01

    Objective: To investigate changes in the consumption of fruits and vegetables in work-site canteens using the tools of continuous quality improvement, and to gain knowledge of practical strategies being effective in increasing the consumption. Design: Study design included baseline data collection......, an 8 h training session for all canteen staff, goal setting, strategy development and implementation for each canteen, end-point data collection and a follow-up data collection 4 months from the end-point (1 year from baseline). The main outcome measurement was average grams of fruits and vegetables...... consumption, the average increase being 95 g per customer compared with baseline (77, 60, 86, 70 and 183 g, respectively). Conclusions: This study demonstrates a large potential for work-site canteens to increase customers' intake of fruits and vegetables at lunch and suggests a broad spectrum of strategies...

  12. The endosomal sorting complex required for transport (ESCRT) is required for the sensitivity of yeast cells to nickel ions in Saccharomyces cerevisiae.

    Science.gov (United States)

    Luo, Chong; Cao, Chunlei; Jiang, Linghuo

    2016-05-01

    Nickel is one of the toxic environment metal pollutants and is linked to various human diseases. In this study, through a functional genomics approach we have identified 16 nickel-sensitive and 22 nickel-tolerant diploid deletion mutants of budding yeast genes, many of which are novel players in the regulation of nickel homeostasis. The 16 nickel-sensitive mutants are of genes mainly involved in the protein folding, modification and destination and the cellular transport processes, while the 22 nickel-tolerant mutants are of genes encoding components of ESCRT complexes as well as protein factors involved in both the cell wall integrity maintenance and the vacuolar protein sorting process. In consistence with their phenotypes, most of these nickel-sensitive mutants show reduced intracellular nickel contents, while the majority of these nickel-tolerant mutants show elevated intracellular nickel contents, as compared to the wild type in response to nickel stress. Our data provides a basis for our understanding the regulation of nickel homeostasis and molecular mechanisms of nickel-induced human pathogenesis.

  13. The budding yeast amphiphysin complex is required for contractile actin ring (CAR assembly and post-contraction GEF-independent accumulation of Rho1-GTP.

    Directory of Open Access Journals (Sweden)

    Michael John Cundell

    Full Text Available The late events of the budding yeast cell division cycle, cytokinesis and cell separation, require the assembly of a contractile actomyosin ring (CAR, primary and secondary septum formation followed by enzymatic degradation of the primary septum. Here we present evidence that demonstrates a role for the budding yeast amphiphysin complex, a heterodimer comprising Rvs167 and Rvs161, in CAR assembly and cell separation. The iqg1-1 allele is synthetically lethal with both rvs167 and rvs161 null mutations. We show that both Iqg1 and the amphiphysin complex are required for CAR assembly in early anaphase but cells are able to complete assembly in late anaphase when these activities are, respectively, either compromised or absent. Amphiphysin dependent CAR assembly is dependent upon the Rvs167 SH3 domain, but this function is insufficient to explain the observed synthetic lethality. Dosage suppression of the iqg1-1 allele demonstrates that endocytosis is required for the default cell separation pathway in the absence of CAR contraction but is unlikely to be required to maintain viability. The amphiphysin complex is required for normal, post-mitotic, localization of Chs3 and the Rho1 GEF, Rom2, which are responsible for secondary septum deposition and the accumulation of GTP bound Rho1 at the bud neck. It is concluded that a failure of polarity establishment in the absence of CAR contraction and amphiphysin function leads to loss of viability as a result of the consequent cell separation defect.

  14. The Arabidopsis CUL4-DDB1 complex interacts with MSI1 and is required to maintain MEDEA parental imprinting.

    Science.gov (United States)

    Dumbliauskas, Eva; Lechner, Esther; Jaciubek, Miłosława; Berr, Alexandre; Pazhouhandeh, Maghsoud; Alioua, Malek; Cognat, Valerie; Brukhin, Vladimir; Koncz, Csaba; Grossniklaus, Ueli; Molinier, Jean; Genschik, Pascal

    2011-02-16

    Protein ubiquitylation regulates a broad variety of biological processes in all eukaryotes. Recent work identified a novel class of cullin-containing ubiquitin ligases (E3s) composed of CUL4, DDB1, and one WD40 protein, believed to act as a substrate receptor. Strikingly, CUL4-based E3 ligases (CRL4s) have important functions at the chromatin level, including responses to DNA damage in metazoans and plants and, in fission yeast, in heterochromatin silencing. Among putative CRL4 receptors we identified MULTICOPY SUPPRESSOR OF IRA1 (MSI1), which belongs to an evolutionary conserved protein family. MSI1-like proteins contribute to different protein complexes, including the epigenetic regulatory Polycomb repressive complex 2 (PRC2). Here, we provide evidence that Arabidopsis MSI1 physically interacts with DDB1A and is part of a multimeric protein complex including CUL4. CUL4 and DDB1 loss-of-function lead to embryo lethality. Interestingly, as in fis class mutants, cul4 mutants exhibit autonomous endosperm initiation and loss of parental imprinting of MEDEA, a target gene of the Arabidopsis PRC2 complex. In addition, after pollination both MEDEA transcript and protein accumulate in a cul4 mutant background. Overall, our work provides the first evidence of a physical and functional link between a CRL4 E3 ligase and a PRC2 complex, thus indicating a novel role of ubiquitylation in the repression of gene expression.

  15. The Axin/TNKS complex interacts with KIF3A and is required for insulin-stimulated GLUT4 translocation

    Institute of Scientific and Technical Information of China (English)

    Hui-Ling Guo; Zhiyun Ye; Shu-Yong Lin; Sheng-Cai Lin; Cixiong Zhang; Qi Liu; Qinxi Li; Guili Lian; Di Wu; Xuebin Li; Wei Zhang; Yuemao Shen

    2012-01-01

    Insulin-stimulated glucose uptake by the glucose transporter GLUT4 plays a central role in whole-body glucose homeostasis,dysregulation of which leads to type 2 diabetes.However,the molecular components and mechanisms regulating insulin-stimulated glucose uptake remain largely unclear.Here,we demonstrate that Axin interacts with the ADP-ribosylase tankyrase 2 (TNKS2) and the kinesin motor protein KIF3A,forming a ternary complex crucial for GLUT4 translocation in response to insulin.Specific knockdown of the individual components of the complex attenuated insulin-stimulated GLUT4 translocation to the plasma membrane.Importantly,TNKS2-/- mice exhibit reduced insulin sensitivity and higher blood glucose levels when re-fed after fasting.Mechanistically,we demonstrate that in the absence of insulin,Axin,TNKS and KIF3A are co-localized with GLUT4 on the trans-Golgi network.Insulin treatment suppresses the ADP-ribosylase activity of TNKS,leading to a reduction in ADP ribosylation and ubiquitination of both Axin and TNKS,and a concurrent stabilization of the complex.Inhibition of Akt,the major effector kinase of insulin signaling,abrogates the insulin-mediated complex stabilization.We have thus elucidated a new protein complex that is directly associated with the motor protein kinesin in insulin-stimulated GLUT4 translocation.

  16. 'When operating a cafeteria, sales come before nutrition' - finding barriers and facilitators to serving reduced-sodium meals in worksite cafeterias.

    Science.gov (United States)

    Park, Sohyun; Lee, Jounghee

    2016-06-01

    The present study was conducted to examine barriers to and facilitators of serving reduced-sodium meals (RSM) in worksite cafeterias. We conducted in-depth interviews with key stakeholders in food catering companies. Food catering companies at various customer sites in South Korea. A total of nineteen interviews with twenty-five participants from ten catering companies were conducted. Sixteen on-site dietitians and nine managers from the catering companies' headquarters participated in the interviews. Four main themes emerged from the interviews. First, key stakeholders' psychosocial characteristics (perception, intention and knowledge) are important in serving RSM in worksite cafeterias. Second, skills and techniques related to measuring sodium content and preparing RSM were emphasized by the interviewees. Third, the lack of various delicious low-sodium menus is a barrier to serving RSM. Lastly, a number of environmental factors were addressed, which include social support for reduced-sodium diets (a facilitator) and pressure to maintain profit margins (a barrier), that contribute to serving meals with less salt. Based on these factors, various recommendations for future sodium reduction policies and programmes were suggested. It is important to implement population-wide sodium reduction as a means of preventing CVD and stroke. The study provided important facilitators of and barriers to serving RSM in worksite cafeterias, which could be helpful in developing environmental interventions that promote low-sodium diets.

  17. Complexes of Usher proteins preassemble at the endoplasmic reticulum and are required for trafficking and ER homeostasis

    Directory of Open Access Journals (Sweden)

    Bernardo Blanco-Sánchez

    2014-05-01

    Full Text Available Usher syndrome (USH, the leading cause of hereditary combined hearing and vision loss, is characterized by sensorineural deafness and progressive retinal degeneration. Mutations in several different genes produce USH, but the proximal cause of sensory cell death remains mysterious. We adapted a proximity ligation assay to analyze associations among three of the USH proteins, Cdh23, Harmonin and Myo7aa, and the microtubule-based transporter Ift88 in zebrafish inner ear mechanosensory hair cells. We found that the proteins are in close enough proximity to form complexes and that these complexes preassemble at the endoplasmic reticulum (ER. Defects in any one of the three USH proteins disrupt formation and trafficking of the complex and result in diminished levels of the other proteins, generalized trafficking defects and ER stress that triggers apoptosis. ER stress, thus, contributes to sensory hair cell loss and provides a new target to explore for protective therapies for USH.

  18. Atg6/UVRAG/Vps34-Containing Lipid Kinase Complex Is Required for Receptor Downregulation through Endolysosomal Degradation and Epithelial Polarity during Drosophila Wing Development

    Directory of Open Access Journals (Sweden)

    Péter Lőrincz

    2014-01-01

    Full Text Available Atg6 (Beclin 1 in mammals is a core component of the Vps34 PI3K (III complex, which promotes multiple vesicle trafficking pathways. Atg6 and Vps34 form two distinct PI3K (III complexes in yeast and mammalian cells, either with Atg14 or with UVRAG. The functions of these two complexes are not entirely clear, as both Atg14 and UVRAG have been suggested to regulate both endocytosis and autophagy. In this study, we performed a microscopic analysis of UVRAG, Atg14, or Atg6 loss-of-function cells in the developing Drosophila wing. Both autophagy and endocytosis are seriously impaired and defective endolysosomes accumulate upon loss of Atg6. We show that Atg6 is required for the downregulation of Notch and Wingless signaling pathways; thus it is essential for normal wing development. Moreover, the loss of Atg6 impairs cell polarity. Atg14 depletion results in autophagy defects with no effect on endocytosis or cell polarity, while the silencing of UVRAG phenocopies all but the autophagy defect of Atg6 depleted cells. Thus, our results indicate that the UVRAG-containing PI3K (III complex is required for receptor downregulation through endolysosomal degradation and for the establishment of proper cell polarity in the developing wing, while the Atg14-containing complex is involved in autophagosome formation.

  19. Molecular features of biguanides required for targeting of mitochondrial respiratory complex I and activation of AMP-kinase

    OpenAIRE

    2016-01-01

    Abstract Background The biguanides are a family of drugs with diverse clinical applications. Metformin, a widely used anti-hyperglycemic biguanide, suppresses mitochondrial respiration by inhibiting respiratory complex I. Phenformin, a related anti-hyperglycemic biguanide, also inhibits respiration, but proguanil, which is widely used for the prevention of malaria, does not. The molecular structures of phenformin and proguanil are closel...

  20. XRCC3 ATPase activity is required for normal XRCC3-Rad51C complex dynamics and homologous recombination

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, N; Hinz, J; Kopf, V L; Segalle, K; Thompson, L

    2004-02-25

    Homologous recombinational repair is a major DNA repair pathway that preserves chromosomal integrity by removing double-strand breaks, crosslinks, and other DNA damage. In eukaryotic cells, the Rad51 paralogs (XRCC2, XRCC3, Rad51B, Rad51C, and Rad51D) are involved in this process, although their exact functions are largely undetermined. All five paralogs contain ATPase motifs, and XRCC3 appears to exist in a single complex with Rad51C. To begin to examine the function of this Rad51C-XRCC3 complex, we generated mammalian expression vectors that produce human wild-type XRCC3 or mutant XRCC3 with either a non-conservative mutation (K113A) or a conservative mutation (K113R) in the GKT Walker A box of the ATPase motif. The three vectors were independently transfected into Xrcc3-deficient irs1SF CHO cells. Wild-type XRCC3 complemented irs1SF cells, albeit to varying degrees, while ATPase mutants had no complementing activity, even when the mutant protein was expressed at comparable levels to that in wild-type-complemented clones. Because of the mutants' dysfunction, we propose that ATP binding and hydrolyzing activities of XRCC3 are essential. We tested in vitro complex formation by wild-type and mutant XRCC3 with His6-tagged Rad51C upon coexpression in bacteria, nickel affinity purification, and western blotting. Wild-type and K113A mutant XRCC3 formed stable complexes with Rad51C and co-purified with Rad51C, while the K113R mutant did not and was predominantly insoluble. Addition of 5 mM ATP, but not ADP, also abolished complex formation by the wild-type proteins. These results suggest that XRCC3 is likely to regulate the dissociation and formation of Rad51C-XRCC3 complex through ATP binding and hydrolysis, with both processes being essential for the complex's ability to participate in HRR.

  1. Zinc finger domain of Su(Hw) protein is required for the formation of functional Su(Hw)-dependent insulator complex.

    Science.gov (United States)

    Golovnin, A K; Molodina, V V; Georgiev, P G; Melnikova, L S

    2016-07-01

    This study is devoted to clarifying the role of Mod(mdg4)-67.2 and Su(Hw) proteins in the interaction between Su(Hw)-dependent insulator complexes and identifying the specific domains of the Su(Hw) protein required for insulation or mutual neutralization of insulators. Using genetic techniques and experiments in yeast two-hybrid system, we have demonstrated that the zinc finger domain of the Su(Hw) protein is involved in forming a functional insulator complex and cannot be replaced with the DNA-binding domain of the GAL4 protein.

  2. Effect of an office worksite-based yoga program on heart rate variability: A randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Chang Dennis

    2011-07-01

    Full Text Available Abstract Background Chronic work-related stress is a significant and independent risk factor for cardiovascular and metabolic diseases and associated mortality, particularly when compounded by a sedentary work environment. Heart rate variability (HRV provides an estimate of parasympathetic and sympathetic autonomic control, and can serve as a marker of physiological stress. Hatha yoga is a physically demanding practice that can help to reduce stress; however, time constraints incurred by work and family life may limit participation. The purpose of the present study is to determine if a 10-week, worksite-based yoga program delivered during lunch hour can improve resting HRV and related physical and psychological parameters in sedentary office workers. Methods and design This is a parallel-arm RCT that will compare the outcomes of participants assigned to the experimental treatment group (yoga to those assigned to a no-treatment control group. Participants randomized to the experimental condition will engage in a 10-week yoga program delivered at their place of work. The yoga sessions will be group-based, prescribed three times per week during lunch hour, and will be led by an experienced yoga instructor. The program will involve teaching beginner students safely and progressively over 10 weeks a yoga sequence that incorporates asanas (poses and postures, vinyasa (exercises, pranayama (breathing control and meditation. The primary outcome of this study is the high frequency (HF spectral power component of HRV (measured in absolute units; i.e. ms2, a measure of parasympathetic autonomic control. Secondary outcomes include additional frequency and time domains of HRV, and measures of physical functioning and psychological health status. Measures will be collected prior to and following the intervention period, and at 6 months follow-up to determine the effect of intervention withdrawal. Discussion This study will determine the effect of worksite

  3. Why O2 is required by complex life on habitable planets and the concept of planetary "oxygenation time".

    Science.gov (United States)

    Catling, David C; Glein, Christopher R; Zahnle, Kevin J; McKay, Christopher P

    2005-06-01

    Life is constructed from a limited toolkit: the Periodic Table. The reduction of oxygen provides the largest free energy release per electron transfer, except for the reduction of fluorine and chlorine. However, the bonding of O2 ensures that it is sufficiently stable to accumulate in a planetary atmosphere, whereas the more weakly bonded halogen gases are far too reactive ever to achieve significant abundance. Consequently, an atmosphere rich in O2 provides the largest feasible energy source. This universal uniqueness suggests that abundant O2 is necessary for the high-energy demands of complex life anywhere, i.e., for actively mobile organisms of approximately 10(-1)-10(0) m size scale with specialized, differentiated anatomy comparable to advanced metazoans. On Earth, aerobic metabolism provides about an order of magnitude more energy for a given intake of food than anaerobic metabolism. As a result, anaerobes do not grow beyond the complexity of uniseriate filaments of cells because of prohibitively low growth efficiencies in a food chain. The biomass cumulative number density, n, at a particular mass, m, scales as n (> m) proportional to m(-1) for aquatic aerobes, and we show that for anaerobes the predicted scaling is n proportional to m (-1.5), close to a growth-limited threshold. Even with aerobic metabolism, the partial pressure of atmospheric O2 (P(O2)) must exceed approximately 10(3) Pa to allow organisms that rely on O2 diffusion to evolve to a size approximately 10(3) m x P(O2) in the range approximately 10(3)-10(4) Pa is needed to exceed the threshold of approximately 10(2) m size for complex life with circulatory physiology. In terrestrial life, O(2) also facilitates hundreds of metabolic pathways, including those that make specialized structural molecules found only in animals. The time scale to reach P(O(2)) approximately 10(4) Pa, or "oxygenation time," was long on the Earth (approximately 3.9 billion years), within almost a factor of 2 of the Sun

  4. The SUFBC2 D complex is required for the biogenesis of all major classes of plastid Fe-S proteins.

    Science.gov (United States)

    Hu, Xueyun; Kato, Yukako; Sumida, Akihiro; Tanaka, Ayumi; Tanaka, Ryouichi

    2017-04-01

    Iron-sulfur (Fe-S) proteins play crucial roles in plastids, participating in photosynthesis and other metabolic pathways. Fe-S clusters are thought to be assembled on a scaffold complex composed of SUFB, SUFC and SUFD proteins. However, several additional proteins provide putative scaffold functions in plastids, and, therefore, the contribution of SUFB, C and D proteins to overall Fe-S assembly still remains unclear. In order to gain insights regarding Fe-S cluster biosynthesis in plastids, we analyzed the complex composed of SUFB, C and D in Arabidopsis by blue native-polyacrylamide gel electrophoresis. Using this approach, a major complex of 170 kDa containing all subunits was detected, indicating that these proteins constitute a SUFBC2 D complex similar to their well characterized bacterial counterparts. The functional effects of SUFB, SUFC or SUFD depletion were analyzed using an inducible RNAi silencing system to specifically target the aforementioned components; resulting in a decrease of various plastidic Fe-S proteins including the PsaA/B and PsaC subunits of photosystem I, ferredoxin and glutamine oxoglutarate aminotransferase. In contrast, the knockout of potential Fe-S scaffold proteins, NFU2 and HCF101, resulted in a specific decrease in the PsaA/B and PsaC levels. These results indicate that the functions of SUFB, SUFC and SUFD for Fe-S cluster biosynthesis cannot be replaced by other scaffold proteins and that SUFBC2 D, NFU2 and HCF101 are involved in the same pathway for the biogenesis of PSI. Taken together, our results provide in vivo evidence supporting the hypothesis that SUFBC2 D is the major, and possibly sole scaffold in plastids.

  5. Receptor component protein (RCP): a member of a multi-protein complex required for G-protein-coupled signal transduction.

    Science.gov (United States)

    Prado, M A; Evans-Bain, B; Dickerson, I M

    2002-08-01

    The calcitonin-gene-related peptide (CGRP) receptor component protein (RCP) is a 148-amino-acid intracellular protein that is required for G-protein-coupled signal transduction at receptors for the neuropeptide CGRP. RCP works in conjunction with two other proteins to constitute a functional CGRP receptor: calcitonin-receptor-like receptor (CRLR) and receptor-activity-modifying protein 1 (RAMP1). CRLR has the stereotypical seven-transmembrane topology of a G-protein-coupled receptor; it requires RAMP1 for trafficking to the cell surface and for ligand specificity, and requires RCP for coupling to the cellular signal transduction pathway. We have made cell lines that expressed an antisense construct of RCP and determined that CGRP-mediated signal transduction was reduced, while CGRP binding was unaffected. Furthermore, signalling at two other endogenous G-protein-coupled receptors was unaffected, suggesting that RCP was specific for a limited subset of receptors.

  6. The EARP Complex and Its Interactor EIPR-1 Are Required for Cargo Sorting to Dense-Core Vesicles.

    Science.gov (United States)

    Topalidou, Irini; Cattin-Ortolá, Jérôme; Pappas, Andrea L; Cooper, Kirsten; Merrihew, Gennifer E; MacCoss, Michael J; Ailion, Michael

    2016-05-01

    The dense-core vesicle is a secretory organelle that mediates the regulated release of peptide hormones, growth factors, and biogenic amines. Dense-core vesicles originate from the trans-Golgi of neurons and neuroendocrine cells, but it is unclear how this specialized organelle is formed and acquires its specific cargos. To identify proteins that act in dense-core vesicle biogenesis, we performed a forward genetic screen in Caenorhabditis elegans for mutants defective in dense-core vesicle function. We previously reported the identification of two conserved proteins that interact with the small GTPase RAB-2 to control normal dense-core vesicle cargo-sorting. Here we identify several additional conserved factors important for dense-core vesicle cargo sorting: the WD40 domain protein EIPR-1 and the endosome-associated recycling protein (EARP) complex. By assaying behavior and the trafficking of dense-core vesicle cargos, we show that mutants that lack EIPR-1 or EARP have defects in dense-core vesicle cargo-sorting similar to those of mutants in the RAB-2 pathway. Genetic epistasis data indicate that RAB-2, EIPR-1 and EARP function in a common pathway. In addition, using a proteomic approach in rat insulinoma cells, we show that EIPR-1 physically interacts with the EARP complex. Our data suggest that EIPR-1 is a new interactor of the EARP complex and that dense-core vesicle cargo sorting depends on the EARP-dependent trafficking of cargo through an endosomal sorting compartment.

  7. An Epichloë festucae homologue of MOB3, a component of the STRIPAK complex, is required for the establishment of a mutualistic symbiotic interaction with Lolium perenne

    OpenAIRE

    Green, Kimberly A.; Becker, Yvonne; Helen L Fitzsimons; Scott, Barry

    2016-01-01

    Summary In both Sordaria macrospora and Neurospora crassa, components of the conserved STRIPAK (striatin‐interacting phosphatase and kinase) complex regulate cell–cell fusion, hyphal network development and fruiting body formation. Interestingly, a number of Epichloë festucae genes that are required for hyphal cell–cell fusion, such as noxA, noxR, proA, mpkA and mkkA, are also required for the establishment of a mutualistic symbiotic interaction with Lolium perenne. To determine whether MobC,...

  8. Platelet Activation and Thrombus Formation over IgG Immune Complexes Requires Integrin αIIbβ3 and Lyn Kinase.

    Science.gov (United States)

    Zhi, Huiying; Dai, Jing; Liu, Junling; Zhu, Jieqing; Newman, Debra K; Gao, Cunji; Newman, Peter J

    2015-01-01

    IgG immune complexes contribute to the etiology and pathogenesis of numerous autoimmune disorders, including heparin-induced thrombocytopenia, systemic lupus erythematosus, rheumatoid- and collagen-induced arthritis, and chronic glomerulonephritis. Patients suffering from immune complex-related disorders are known to be susceptible to platelet-mediated thrombotic events. Though the role of the Fc receptor, FcγRIIa, in initiating platelet activation is well understood, the role of the major platelet adhesion receptor, integrin αIIbβ3, in amplifying platelet activation and mediating adhesion and aggregation downstream of encountering IgG immune complexes is poorly understood. The goal of this investigation was to gain a better understanding of the relative roles of these two receptor systems in immune complex-mediated thrombotic complications. Human platelets, and mouse platelets genetically engineered to differentially express FcγRIIa and αIIbβ3, were allowed to interact with IgG-coated surfaces under both static and flow conditions, and their ability to spread and form thrombi evaluated in the presence and absence of clinically-used fibrinogen receptor antagonists. Although binding of IgG immune complexes to FcγRIIa was sufficient for platelet adhesion and initial signal transduction events, platelet spreading and thrombus formation over IgG-coated surfaces showed an absolute requirement for αIIbβ3 and its ligands. Tyrosine kinases Lyn and Syk were found to play key roles in IgG-induced platelet activation events. Taken together, our data suggest a complex functional interplay between FcγRIIa, Lyn, and αIIbβ3 in immune complex-induced platelet activation. Future studies may be warranted to determine whether patients suffering from immune complex disorders might benefit from treatment with anti-αIIbβ3-directed therapeutics.

  9. Platelet Activation and Thrombus Formation over IgG Immune Complexes Requires Integrin αIIbβ3 and Lyn Kinase.

    Directory of Open Access Journals (Sweden)

    Huiying Zhi

    Full Text Available IgG immune complexes contribute to the etiology and pathogenesis of numerous autoimmune disorders, including heparin-induced thrombocytopenia, systemic lupus erythematosus, rheumatoid- and collagen-induced arthritis, and chronic glomerulonephritis. Patients suffering from immune complex-related disorders are known to be susceptible to platelet-mediated thrombotic events. Though the role of the Fc receptor, FcγRIIa, in initiating platelet activation is well understood, the role of the major platelet adhesion receptor, integrin αIIbβ3, in amplifying platelet activation and mediating adhesion and aggregation downstream of encountering IgG immune complexes is poorly understood. The goal of this investigation was to gain a better understanding of the relative roles of these two receptor systems in immune complex-mediated thrombotic complications. Human platelets, and mouse platelets genetically engineered to differentially express FcγRIIa and αIIbβ3, were allowed to interact with IgG-coated surfaces under both static and flow conditions, and their ability to spread and form thrombi evaluated in the presence and absence of clinically-used fibrinogen receptor antagonists. Although binding of IgG immune complexes to FcγRIIa was sufficient for platelet adhesion and initial signal transduction events, platelet spreading and thrombus formation over IgG-coated surfaces showed an absolute requirement for αIIbβ3 and its ligands. Tyrosine kinases Lyn and Syk were found to play key roles in IgG-induced platelet activation events. Taken together, our data suggest a complex functional interplay between FcγRIIa, Lyn, and αIIbβ3 in immune complex-induced platelet activation. Future studies may be warranted to determine whether patients suffering from immune complex disorders might benefit from treatment with anti-αIIbβ3-directed therapeutics.

  10. SAG101 forms a ternary complex with EDS1 and PAD4 and is required for resistance signaling against turnip crinkle virus.

    Directory of Open Access Journals (Sweden)

    Shifeng Zhu

    2011-11-01

    Full Text Available EDS1, PAD4, and SAG101 are common regulators of plant immunity against many pathogens. EDS1 interacts with both PAD4 and SAG101 but direct interaction between PAD4 and SAG101 has not been detected, leading to the suggestion that the EDS1-PAD4 and EDS1-SAG101 complexes are distinct. We show that EDS1, PAD4, and SAG101 are present in a single complex in planta. While this complex is preferentially nuclear localized, it can be redirected to the cytoplasm in the presence of an extranuclear form of EDS1. PAD4 and SAG101 can in turn, regulate the subcellular localization of EDS1. We also show that the Arabidopsis genome encodes two functionally redundant isoforms of EDS1, either of which can form ternary complexes with PAD4 and SAG101. Simultaneous mutations in both EDS1 isoforms are essential to abrogate resistance (R protein-mediated defense against turnip crinkle virus (TCV as well as avrRps4 expressing Pseudomonas syringae. Interestingly, unlike its function as a PAD4 substitute in bacterial resistance, SAG101 is required for R-mediated resistance to TCV, thus implicating a role for the ternary complex in this defense response. However, only EDS1 is required for HRT-mediated HR to TCV, while only PAD4 is required for SA-dependent induction of HRT. Together, these results suggest that EDS1, PAD4 and SAG101 also perform independent functions in HRT-mediated resistance.

  11. The Chriz–Z4 complex recruits JIL-1 to polytene chromosomes, a requirement for interband-specific phosphorylation of H3S10

    Indian Academy of Sciences (India)

    Miao Gan; Selina Moebus; Harald Eggert; Harald Saumweber

    2011-08-01

    The conserved band-interband pattern is thought to reflect the looped-domain organization of insect polytene chromosomes. Previously, we have shown that the chromodomain protein Chriz and the zinc-finger protein Z4 are essentially required for the maintenance of polytene chromosome structure. Here we show that both proteins form a complex that recruits the JIL-1 kinase to polytene chromosomes, enabling local H3S10 phosphorylation of interband nucleosomal histones. Interband targeting domains were identified at the N-terminal regions of Chriz and Z4, and our data suggest partial cooperation of the complex with the BEAF boundary element protein in polytene and diploid cells. Reducing the core component Chriz by RNAi results in destabilization of the complex and a strong reduction of interband-specific histone H3S10 phosphorylation.

  12. Dynamic assembly of end-joining complexes requires interaction between Ku70/80 and XRCC4

    NARCIS (Netherlands)

    P.O. Mari (Pierre-Olivier); T.M. Luider (Theo); A.B. Houtsmuller (Adriaan); D.C. van Gent (Dik); B.I. Florea (Bogdan); S.P. Persengiev (Stephan); N.S. Verkaik (Nicole); H.T. Brüggenwirth (Hennie); M. Modesti (Mauro); G. Giglia-Mari (Giuseppina); K. Bezstarosti (Karel); J.A.A. Demmers (Jeroen)

    2006-01-01

    textabstractDNA double-strand break (DSB) repair by nonhomologous end joining (NHEJ) requires the assembly of several proteins on DNA ends. Although biochemical studies have elucidated several aspects of the NHEJ reaction mechanism, much less is known about NHEJ in living cells, mainly because of

  13. Independent regions of adenovirus E1A are required for binding to and dissociation of E2F-protein complexes

    DEFF Research Database (Denmark)

    Fattaey, A R; Harlow, E; Helin, K

    1993-01-01

    overexpression of pRB or p107 in cells lacking a functional pRB leads to the repression of E2F activity. The products of the adenovirus E1A gene can disrupt E2F complexes and result in free and presumably active E2F transcription factor. The regions of E1A required for this function are also essential...

  14. SIMPL enhancement of tumor necrosis factor-α dependent p65-MED1 complex formation is required for mammalian hematopoietic stem and progenitor cell function.

    Directory of Open Access Journals (Sweden)

    Weina Zhao

    Full Text Available Significant insight into the signaling pathways leading to activation of the Rel transcription factor family, collectively termed NF-κB, has been gained. Less well understood is how subsets of NF-κB-dependent genes are regulated in a signal specific manner. The SIMPL protein (signaling molecule that interacts with mouse pelle-like kinase is required for full Tumor Necrosis Factor-α (TNFα induced NF-κB activity. We show that SIMPL is required for steady-state hematopoiesis and the expression of a subset of TNFα induced genes whose products regulate hematopoietic cell activity. To gain insight into the mechanism through which SIMPL modulates gene expression we focused on the Tnf gene, an immune response regulator required for steady-state hematopoiesis. In response to TNFα SIMPL localizes to the Tnf gene promoter where it modulates the initiation of Tnf gene transcription. SIMPL binding partners identified by mass spectrometry include proteins involved in transcription and the interaction between SIMPL and MED1 was characterized in more detail. In response to TNFα, SIMPL is found in p65-MED1 complexes where SIMPL enhances p65/MED1/SIMPL complex formation. Together our results indicate that SIMPL functions as a TNFα-dependent p65 co-activator by facilitating the recruitment of MED1 to p65 containing transcriptional complexes to control the expression of a subset of TNFα-induced genes.

  15. Vipp1 is required for basic thylakoid membrane formation but not for the assembly of thylakoid protein complexes.

    Science.gov (United States)

    Aseeva, Elena; Ossenbühl, Friederich; Sippel, Claudia; Cho, Won K; Stein, Bernhard; Eichacker, Lutz A; Meurer, Jörg; Wanner, Gerhard; Westhoff, Peter; Soll, Jürgen; Vothknecht, Ute C

    2007-02-01

    Vipp1 (vesicle inducing protein in plastids 1) is found in cyanobacteria and chloroplasts where it is essential for thylakoid formation. Arabidopsis thaliana mutant plants with a reduction of Vipp1 to about 20% of wild type content become albinotic at an early stage. We propose that this drastic phenotype results from an inability of the remaining Vipp1 protein to assemble into a homo-oligomeric complex, indicating that oligomerization is a prerequisite for Vipp1 function. A Vipp1-ProteinA fusion protein, expressed in the Deltavipp1 mutant background, is able to reinstate oligomerization and restore photoautotrophic growth. Plants containing Vipp1-ProteinA in amounts comparable to Vipp1 in the wild type exhibit a wild type phenotype. However, plants with a reduced amount of Vipp1-ProteinA protein are growth-retarded and significantly paler than the wild type. This phenotype is caused by a decrease in thylakoid membrane content and a concomitant reduction in photosynthetic activity. To the extent that thylakoid membranes are made in these plants they are properly assembled with protein-pigment complexes and are photosynthetically active. This strongly supports a function of Vipp1 in basic thylakoid membrane formation and not in the functional assembly of thylakoid protein complexes. Intriguingly, electron microscopic analysis shows that chloroplasts in the mutant plants are not equally affected by the Vipp1 shortage. Indeed, a wide range of different stages of thylakoid development ranging from wild-type-like chloroplasts to plastids nearly devoid of thylakoids can be observed in organelles of one and the same cell.

  16. Do intervention fidelity and dose influence outcomes? Results from the move to improve worksite physical activity program.

    Science.gov (United States)

    Wilson, Mark G; Basta, Tania B; Bynum, Bethany H; DeJoy, David M; Vandenberg, Robert J; Dishman, Rod K

    2010-04-01

    The purpose of this paper is to evaluate the implementation of the Move to Improve worksite physical activity program using a four step framework that includes the following: (i) defining the active ingredients, (ii) using good methods to measure implementation, (iii) monitoring implementation and (iv) relating implementation to outcomes. The intervention active ingredients consisted of a goal setting behavior change program, a team competition and environmental supports. Intervention fidelity and dose were measured by surveys administered to site co-ordinators, team captains and employees. Implementation was monitored by the use of biweekly assessments that tracked individual physical activity levels and through weekly reports of the project director and site co-ordinators. Latent growth modeling was conducted to determine whether intervention outcomes were affected by site implementation (i.e. fidelity) and/or participation by employees (i.e. dose). Results showed high levels of intervention fidelity, moderate to high levels of intervention dose delivered and moderate levels of the intervention dose received. Level of implementation affected the degree of change in vigorous physical activity (Mean = 5.4 versus 2.2; chi(2) = 4.9, df = 1), otherwise outcome measures were unaffected by fidelity and dose. These findings suggest that practitioners should focus more energy assuring that the core components are fully implemented and be less concerned about the level of participation.

  17. Nutrition Standards for Food Service Guidelines for Foods Served or Sold in Municipal Government Buildings or Worksites, United States, 2014.

    Science.gov (United States)

    Onufrak, Stephen J; Zaganjor, Hatidza; Moore, Latetia V; Carlson, Susan; Kimmons, Joel; Galuska, Deborah

    2016-12-22

    The Institute of Medicine and Centers for Disease Control and Prevention have recommended that government agencies use nutrition standards for foods and beverages sold and provided at their facilities. In this study, we examine written nutrition standards for foods sold or served in local government buildings or worksites among US municipalities. We used data from a 2014 national survey of 1,945 municipal governments serving populations of 1,000 or more to assess the presence of written nutrition standards, the food groups or nutrients addressed by standards, and the populations served by facilities where standards are applied. The prevalence of standards was estimated by municipality population size, rural-urban status, census region, poverty prevalence, education level, and racial/ethnic composition. Overall, 3.2% of US municipalities reported nutrition standards with greater prevalence observed among large municipalities (12.8% of municipalities with ≥50,000 people vs 2.2% of municipalities with beverages, fruits and vegetables, and free drinking water. Most standards applied to facilities serving government employees (67%) or the general public (66%), with fewer serving institutionalized populations (23%). Few municipal governments reported having written nutrition standards for foods and beverages sold in their facilities in 2014. Implementing nutrition standards for foods sold or served by local governments is a strategy for increasing access to healthier foods and beverages among municipal employees and local residents.

  18. Effectiveness of progressive muscle relaxation therapy as a worksite health promotion program in the automobile assembly line

    Science.gov (United States)

    SUNDRAM, Bala Murali; DAHLUI, Maznah; CHINNA, Karuthan

    2015-01-01

    The aim of this study was to examine the effectiveness of Progressive Muscle Relaxation (PMR) as part of a Worksite Health Promotion Program on self-perceived stress, anxiety and depression among male automotive assembly-line workers through a quasi-experimental trial. Two assembly plants were chosen with one receiving PMR therapy and the other Pamphlets. Intention-to-treat analysis was conducted to test the effectiveness of the relaxation therapy. Stress, Depression and Anxiety levels were measured using the shortened DASS-21 questionnaire. Data were analyzed using Chi-square, Independent sample t test and Repeated-measures analysis of variance to test the significance of the effects of intervention (time * group) for the measures of Stress, Depression and Anxiety. Significant favourable intervention effects on stress were found in the PMR group (Effect size=0.6) as compared to the Pamphlet group (Effect size=0.2). There was a significant group *time interaction effect (p<0.001) on Stress levels. Depression and Anxiety levels were minimal at baseline in both the groups with mild or no reduction in levels. The improvement in stress levels showed the potential of PMR therapy as a coping strategy at the workplace. Further research in this field is necessary to examine the beneficial effects of coping strategies in the workplace. PMID:26726829

  19. A Focus Group Assessment to Determine Motivations, Barriers and Effectiveness of a University-Based Worksite Wellness Program

    Directory of Open Access Journals (Sweden)

    Patricia E. Hill-Mey

    2013-12-01

    Full Text Available Background: This study explores university employee perceptions and under-standing about its Worksite Health Promotion Program (WHPP. The WHPP included a Health Risk Appraisal (HRA, biometric screening, publicity for on-campus health programs and facilities, and health coaching. Methods: A qualitative design was used based on a grounded theory approach. Four 90 minutes focus groups with 6-8 participants in each were con-ducted within a two 2 week period among employees, representing faculty/participants, faculty/nonparticipants, staff/participants, and staff/nonparticipants. Responses to questions about motivations, barriers, and perceived health benefits that impacted participation in the WHPP were digitally recorded, transcribed and coded for themes. Results: Incentives effectively motivated participation. Biometric screening had the largest impact on behavior change, followed by the information learned from the HRA. However, despite two-thirds of the employees participating in the program, lack of a full understanding of WHPP benefits and services lowered participation in follow-up services and supplemental pro-grams. Conclusions: Biometric screening and HRAs effectively motivate program participation. Communication of benefits and services are important when providing WHPPs.

  20. Health Behaviors and Overweight in Nursing Home Employees: Contribution of Workplace Stressors and Implications for Worksite Health Promotion.

    Science.gov (United States)

    Miranda, Helena; Gore, Rebecca J; Boyer, Jon; Nobrega, Suzanne; Punnett, Laura

    2015-01-01

    Many worksite health promotion programs ignore the potential influence of working conditions on unhealthy behaviors. A study of nursing home employees (56% nursing aides) utilized a standardized questionnaire. We analyzed the cross-sectional associations between workplace stressors and obesity, cigarette smoking, and physical inactivity. Of 1506 respondents, 20% reported exposure to three or more workplace stressors (physical or organizational), such as lifting heavy loads, low decision latitude, low coworker support, regular night work, and physical assault. For each outcome, the prevalence ratio was between 1.5 and 2 for respondents with four or five job stressors. Individuals under age 40 had stronger associations between workplace stressors and smoking and obesity. Workplace stressors were strongly associated with smoking, obesity, and physical inactivity, even among the lowest-status workers. Current working conditions affected younger workers more than older workers. Although this study is cross-sectional, it has other strengths, including the broad range of work stressors studied. Strenuous physical work and psychosocial strain are common among low-wage workers such as nursing home aides. Workplace health promotion programs may be more effective if they include measures to reduce stressful work environment features, so that working conditions support rather than interfere with employee health.

  1. Health Behaviors and Overweight in Nursing Home Employees: Contribution of Workplace Stressors and Implications for Worksite Health Promotion

    Directory of Open Access Journals (Sweden)

    Helena Miranda

    2015-01-01

    Full Text Available Background. Many worksite health promotion programs ignore the potential influence of working conditions on unhealthy behaviors. Methods. A study of nursing home employees (56% nursing aides utilized a standardized questionnaire. We analyzed the cross-sectional associations between workplace stressors and obesity, cigarette smoking, and physical inactivity. Results. Of 1506 respondents, 20% reported exposure to three or more workplace stressors (physical or organizational, such as lifting heavy loads, low decision latitude, low coworker support, regular night work, and physical assault. For each outcome, the prevalence ratio was between 1.5 and 2 for respondents with four or five job stressors. Individuals under age 40 had stronger associations between workplace stressors and smoking and obesity. Conclusions. Workplace stressors were strongly associated with smoking, obesity, and physical inactivity, even among the lowest-status workers. Current working conditions affected younger workers more than older workers. Although this study is cross-sectional, it has other strengths, including the broad range of work stressors studied. Strenuous physical work and psychosocial strain are common among low-wage workers such as nursing home aides. Workplace health promotion programs may be more effective if they include measures to reduce stressful work environment features, so that working conditions support rather than interfere with employee health.

  2. A focus group assessment to determine motivations, barriers and effectiveness of a university-based worksite wellness program.

    Science.gov (United States)

    Hill-Mey, Patricia E; Merrill, Ray M; Kumpfer, Karol L; Reel, Justine; Hyatt-Neville, Beverly

    2013-01-01

    This study explores university employee perceptions and under-standing about its Worksite Health Promotion Program (WHPP). The WHPP included a Health Risk Appraisal (HRA), biometric screening, publicity for on-campus health programs and facilities, and health coaching. A qualitative design was used based on a grounded theory ap-proach. Four 90 minutes focus groups with 6-8 participants in each were conducted within a two 2 week period among employees, representing fac-ulty/participants, fac-ulty/nonparticipants, staff/participants, and staff/nonparticipants. Responses to questions about motivations, barriers, and perceived health benefits that impacted participation in the WHPP were digi-tally recorded, transcribed and coded for themes. Incentives effectively motivated participation. Biometric screening had the largest impact on behavior change, followed by the information learned from the HRA. However, despite two-thirds of the employees partici-pating in the pro-gram, lack of a full understanding of WHPP benefits and services lowered partici-pation in follow-up services and supplemental pro-grams. Biometric screening and HRAs effectively motivate program par-ticipation. Communication of benefits and services are important when providing WHPPs.

  3. A comparative approach to using the diabetes prevention program to reduce diabetes risk in a worksite setting.

    Science.gov (United States)

    Dallam, George M; Foust, Carol P

    2013-03-01

    The rapidly increasing rate of non-insulin-dependent diabetes (NIDDM) among both market economy and developing countries is a worldwide health phenomenon. The number of diabetics worldwide has been projected to increase from 135 million in 1995 to 300 million in 2025. The purpose of this study was to examine the relative effectiveness of three different approaches to the implementation of the Diabetes Prevention Program, a standardized diabetes prevention curriculum, in various worksite organizations within a single community. The methods of implementation selected included an intensive one-on-one counseling approach, a support group meeting approach, and a passive transfer of information approach. The intervention was successful in creating significant mean improvements overall in the participants who completed the 26-week program as follows: (a) reduction in overall mean body weight and mean body mass index, (b) reduction in overall average mean arterial blood pressure, (c) reduction in overall mean diabetes risk score, and (d) increase in overall mean physical activity level. Although the largest proportion of these changes occurred in the one-on-one intervention group, significant changes in some factors were found in all groups. This illustrates the utility of an on-site and incentive-driven approach to diabetes risk factor modification in the workplace.

  4. Effectiveness of offering healthy labelled meals in improving the nutritional quality of lunch meals eaten in a worksite canteen.

    Science.gov (United States)

    Lassen, A D; Beck, A; Leedo, E; Andersen, E W; Christensen, T; Mejborn, H; Thorsen, A V; Tetens, I

    2014-04-01

    Healthier meal selections at restaurants and canteens are often limited and not actively promoted. In this Danish study the effectiveness of a healthy labelling certification program in improving dietary intake and influencing edible plate waste was evaluated in a quasi-experimental study design. Employees from an intervention worksite canteen and a matched control canteen were included in the study at baseline (February 2012), after completing the certification process (end-point) and six month from end-point (follow-up) (total n=270). In order to estimate nutrient composition of the consumed lunch meals and plate waste a validated digital photographic method was used combining estimation of food intake with food nutrient composition data. Food satisfaction was rated by participants using a questionnaire. Several significant positive nutritional effects were observed at the intervention canteen including a mean decrease in energy density in the consumed meals from 561kJ/100g at baseline to 368 and 407kJ/100g at end-point and follow-up, respectively (Pcanteen no positive nutritional effects were observed. The results of the study highlight the potential of using healthy labelling certification programs as a possible driver for increasing both the availability and awareness of healthy meal choices, thereby improving dietary intake when eating out.

  5. Recruitment of Mediator Complex by Cell Type and Stage-Specific Factors Required for Tissue-Specific TAF Dependent Gene Activation in an Adult Stem Cell Lineage.

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    Chenggang Lu

    2015-12-01

    Full Text Available Onset of terminal differentiation in adult stem cell lineages is commonly marked by robust activation of new transcriptional programs required to make the appropriate differentiated cell type(s. In the Drosophila male germ line stem cell lineage, the switch from proliferating spermatogonia to spermatocyte is accompanied by one of the most dramatic transcriptional changes in the fly, as over 1000 new transcripts turn on in preparation for meiosis and spermatid differentiation. Here we show that function of the coactivator complex Mediator is required for activation of hundreds of new transcripts in the spermatocyte program. Mediator appears to act in a sequential hierarchy, with the testis activating Complex (tMAC, a cell type specific form of the Mip/dREAM general repressor, required to recruit Mediator subunits to the chromatin, and Mediator function required to recruit the testis TAFs (tTAFs, spermatocyte specific homologs of subunits of TFIID. Mediator, tMAC and the tTAFs co-regulate expression of a major set of spermatid differentiation genes. The Mediator subunit Med22 binds the tMAC component Topi when the two are coexpressed in S2 cells, suggesting direct recruitment. Loss of Med22 function in spermatocytes causes meiosis I maturation arrest male infertility, similar to loss of function of the tMAC subunits or the tTAFs. Our results illuminate how cell type specific versions of the Mip/dREAM complex and the general transcription machinery cooperate to drive selective gene activation during differentiation in stem cell lineages.

  6. A mitochondrial-focused genetic interaction map reveals a scaffold-like complex required for inner membrane organization in mitochondria.

    Science.gov (United States)

    Hoppins, Suzanne; Collins, Sean R; Cassidy-Stone, Ann; Hummel, Eric; Devay, Rachel M; Lackner, Laura L; Westermann, Benedikt; Schuldiner, Maya; Weissman, Jonathan S; Nunnari, Jodi

    2011-10-17

    To broadly explore mitochondrial structure and function as well as the communication of mitochondria with other cellular pathways, we constructed a quantitative, high-density genetic interaction map (the MITO-MAP) in Saccharomyces cerevisiae. The MITO-MAP provides a comprehensive view of mitochondrial function including insights into the activity of uncharacterized mitochondrial proteins and the functional connection between mitochondria and the ER. The MITO-MAP also reveals a large inner membrane-associated complex, which we term MitOS for mitochondrial organizing structure, comprised of Fcj1/Mitofilin, a conserved inner membrane protein, and five additional components. MitOS physically and functionally interacts with both outer and inner membrane components and localizes to extended structures that wrap around the inner membrane. We show that MitOS acts in concert with ATP synthase dimers to organize the inner membrane and promote normal mitochondrial morphology. We propose that MitOS acts as a conserved mitochondrial skeletal structure that differentiates regions of the inner membrane to establish the normal internal architecture of mitochondria.

  7. Replication-Coupled PCNA Unloading by the Elg1 Complex Occurs Genome-wide and Requires Okazaki Fragment Ligation

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    Takashi Kubota

    2015-08-01

    Full Text Available The sliding clamp PCNA is a crucial component of the DNA replication machinery. Timely PCNA loading and unloading are central for genome integrity and must be strictly coordinated with other DNA processing steps during replication. Here, we show that the S. cerevisiae Elg1 replication factor C-like complex (Elg1-RLC unloads PCNA genome-wide following Okazaki fragment ligation. In the absence of Elg1, PCNA is retained on chromosomes in the wake of replication forks, rather than at specific sites. Degradation of the Okazaki fragment ligase Cdc9 leads to PCNA accumulation on chromatin, similar to the accumulation caused by lack of Elg1. We demonstrate that Okazaki fragment ligation is the critical prerequisite for PCNA unloading, since Chlorella virus DNA ligase can substitute for Cdc9 in yeast and simultaneously promotes PCNA unloading. Our results suggest that Elg1-RLC acts as a general PCNA unloader and is dependent upon DNA ligation during chromosome replication.

  8. Cross-linking staphylococcal enterotoxin A bound to major histocompatibility complex class I is required for TNF-alpha secretion

    Science.gov (United States)

    Wright, A. D.; Chapes, S. K.

    1999-01-01

    The mechanism of how superantigens function to activate cells has been linked to their ability to bind and cross-link the major histocompatibility complex class II (MHCII) molecule. Cells that lack the MHCII molecule also respond to superantigens, however, with much less efficiency. Therefore, the purpose of this study was to confirm that staphylococcal enterotoxin A (SEA) could bind the MHCI molecule and to test the hypothesis that cross-linking SEA bound to MHCII-deficient macrophages would induce a more robust cytokine response than without cross-linking. We used a capture enzyme-linked immunosorbent assay and an immunprecipitation assay to directly demonstrate that MHCI molecules bind SEA. Directly cross-linking MHCI using monoclonal antibodies or cross-linking bound SEA with an anti-SEA antibody or biotinylated SEA with avidin increased TNF-alpha and IL-6 secretion by MHCII(-/-) macrophages. The induction of a vigorous macrophage cytokine response by SEA/anti-SEA cross-linking of MHCI offers a mechanism to explain how MHCI could play an important role in superantigen-mediated pathogenesis. Copyright 1999 Academic Press.

  9. The cytoskeletal binding domain of band 3 is required for multiprotein complex formation and retention during erythropoiesis

    Science.gov (United States)

    Satchwell, Timothy J; Hawley, Bethan R; Bell, Amanda J; Ribeiro, M. Leticia; Toye, Ashley M

    2015-01-01

    Band 3 is the most abundant protein in the erythrocyte membrane and forms the core of a major multiprotein complex. The absence of band 3 in human erythrocytes has only been reported once, in the homozygous band 3 Coimbra patient. We used in vitro culture of erythroblasts derived from this patient, and separately short hairpin RNA-mediated depletion of band 3, to investigate the development of a band 3-deficient erythrocyte membrane and to specifically assess the stability and retention of band 3 dependent proteins in the absence of this core protein during terminal erythroid differentiation. Further, using lentiviral transduction of N-terminally green fluorescent protein-tagged band 3, we demonstrated the ability to restore expression of band 3 to normal levels and to rescue secondary deficiencies of key proteins including glycophorin A, protein 4.2, CD47 and Rh proteins arising from the absence of band 3 in this patient. By transducing band 3-deficient erythroblasts from this patient with band 3 mutants with absent or impaired ability to associate with the cytoskeleton we also demonstrated the importance of cytoskeletal connectivity for retention both of band 3 and of its associated dependent proteins within the reticulocyte membrane during the process of erythroblast enucleation. PMID:25344524

  10. Comparative studies between mice molars and incisors are required to draw an overview of enamel structural complexity

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    MICHEL eGOLDBERG

    2014-09-01

    Full Text Available In the field of dentistry, the murine incisor has long been considered as an outstanding model to study amelogenesis. However, it clearly appears that enamel from wild type mouse incisors and molars presents several structural differences. In incisor, exclusively radial enamel is observed. In molars, enamel displays a high level of complexity since the inner part is lamellar whereas the outer enamel shows radial and tangential structures. Recently, the serotonin 2B receptor (5-HT2BR was shown to be involved in ameloblast function and enamel mineralization. The incisors from 5HT2BR knockout (KO mice exhibit mineralization defects mostly in the outer maturation zone and porous matrix network in the inner zone. In the molars, the mutation affects both secretory and maturation stages of amelogenesis since pronounced alterations concern overall enamel structures. Molars from 5HT2BR KO mice display reduction in enamel thickness, alterations of inner enamel architecture including defects in Hunter-Schreger Bands arrangements, and altered maturation of the outer radial enamel. Differences of enamel structure were also observed between incisor and molar from other KO mice depleted for genes encoding enamel extracellular matrix proteins.

  11. Obesity-Associated Autoantibody Production Requires AIM to Retain the Immunoglobulin M Immune Complex on Follicular Dendritic Cells

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    Satoko Arai

    2013-04-01

    Full Text Available Natural immunoglobulin M (IgM is reactive to autoantigens and is believed to be important for autoimmunity. Blood pentameric IgM loaded with antigens forms a large immune complex (IC that contains various elements, including apoptosis inhibitor of macrophage (AIM. Here we demonstrate that this IgM-AIM association contributes to autoantibody production under obese conditions. In mice fed a high-fat diet, natural IgM increased through B cell TLR4 stimulation. AIM associated with IgM and protected AIM from renal excretion, increasing blood AIM levels along with the obesity-induced IgM augmentation. Meanwhile, the AIM association inhibited IgM binding to the Fcα/μ receptor on splenic follicular dendritic cells, thereby protecting the IgM IC from Fcα/μ receptor-mediated internalization. This supported IgM-dependent autoantigen presentation to B cells, stimulating IgG autoantibody production. Accordingly, in obese AIM-deficient (AIM−/− mice, the increase of multiple IgG autoantibodies observed in obese wild-type mice was abrogated. Thus, the AIM-IgM association plays a critical role in the obesity-associated autoimmune process.

  12. 复杂业务需求下的光网络规划问题的研究%Study of optical network planning under complex traffic requirements

    Institute of Scientific and Technical Information of China (English)

    巩强; 曾凌; 徐世中; 王晟; 李乐民

    2011-01-01

    This paper studied optical network planning under complex traffic requirements.Formulated the planning problem into an integer linear programming( ILP), where supported connections or applications with different bandwidth requirements and protection requirements.Due to the very high computation complexity induced in solving the ILP for large networks, introduced Bender decomposition.Results show that using Bender decomposition can find the solution for large optical networks effectively, with much less time and memory consumptions.%研究了复杂业务需求下的光网络规划问题,建立了支持多种业务需求和保护需求的ILP数学模型;针对大型光网络相应的整数线性模型规模过大、难以求解的困难,引入了Bender数学分解方法.计算结果表明,利用Bender分解可以有效地求解复杂业务需求和保护需求下的光网络规划问题,同时降低时间和内存的消耗.

  13. Adaptor Protein Complexes AP-1 and AP-3 Are Required by the HHV-7 Immunoevasin U21 for Rerouting of Class I MHC Molecules to the Lysosomal Compartment

    Science.gov (United States)

    Kimpler, Lisa A.; Glosson, Nicole L.; Downs, Deanna; Gonyo, Patrick; May, Nathan A.; Hudson, Amy W.

    2014-01-01

    The human herpesvirus-7 (HHV-7) U21 gene product binds to class I major histocompatibility complex (MHC) molecules and reroutes them to a lysosomal compartment. Trafficking of integral membrane proteins to lysosomes is mediated through cytoplasmic sorting signals that recruit heterotetrameric clathrin adaptor protein (AP) complexes, which in turn mediate protein sorting in post-Golgi vesicular transport. Since U21 can mediate rerouting of class I molecules to lysosomes even when lacking its cytoplasmic tail, we hypothesize the existence of a cellular protein that contains the lysosomal sorting information required to escort class I molecules to the lysosomal compartment. If such a protein exists, we expect that it might recruit clathrin adaptor protein complexes as a means of lysosomal sorting. Here we describe experiments demonstrating that the μ adaptins from AP-1 and AP-3 are involved in U21-mediated trafficking of class I molecules to lysosomes. These experiments support the idea that a cellular protein(s) is necessary for U21-mediated lysosomal sorting of class I molecules. We also examine the impact of transient versus chronic knockdown of these adaptor protein complexes, and show that the few remaining μ subunits in the cells are eventually able to reroute class I molecules to lysosomes. PMID:24901711

  14. Identification of RFC(Ctf18p, Ctf8p, Dcc1p): an alternative RFC complex required for sister chromatid cohesion in S. cerevisiae.

    Science.gov (United States)

    Mayer, M L; Gygi, S P; Aebersold, R; Hieter, P

    2001-05-01

    We have identified and characterized an alternative RFC complex RFC(Ctf18p, Ctf8p, Dcc1p) that is required for sister chromatid cohesion and faithful chromosome transmission. Ctf18p, Ctf8p, and Dcc1p interact physically in a complex with Rfc2p, Rfc3p, Rfc4p, and Rfc5p but not with Rfc1p or Rad24p. Deletion of CTF18, CTF8, or DCC1 singly or in combination (ctf18Deltactf8Deltadcc1Delta) leads to sensitivity to microtubule depolymerizing drugs and a severe sister chromatid cohesion defect. Furthermore, temperature-sensitive mutations in RFC4 result in precocious sister chromatid separation. Our results highlight a novel function of the RFC proteins and support a model in which sister chromatid cohesion is established at the replication fork via a polymerase switching mechanism and a replication-coupled remodeling of chromatin.

  15. Vinculin and Rab5 complex is required [correction of requited]for uptake of Staphylococcus aureus and interleukin-6 expression.

    Directory of Open Access Journals (Sweden)

    Makoto Hagiwara

    Full Text Available Vinculin, a 116-kDa membrane cytoskeletal protein, is an important molecule for cell adhesion; however, little is known about its other cellular functions. Here, we demonstrated that vinculin binds to Rab5 and is required for Staphylococcus aureus (S. aureus uptake in cells. Viunculin directly bound to Rab5 and enhanced the activation of S. aureus uptake. Over-expression of active vinculin mutants enhanced S. aureus uptake, whereas over-expression of an inactive vinculin mutant decreased S. aureus uptake. Vinculin bound to Rab5 at the N-terminal region (1-258 of vinculin. Vinculin and Rab5 were involved in the S. aureus-induced phosphorylation of MAP kinases (p38, Erk, and JNK and IL-6 expression. Finally, vinculin and Rab5 knockdown reduced infection of S. aureus, phosphorylation of MAPKs and IL-6 expression in murine lungs. Our results suggest that vinculin binds to Rab5 and that these two molecules cooperatively enhance bacterial infection and the inflammatory response.

  16. The design of a real-time formative evaluation of the implementation process of lifestyle interventions at two worksites using a 7-step strategy (BRAVO@Work).

    Science.gov (United States)

    Wierenga, Debbie; Engbers, Luuk H; van Empelen, Pepijn; Hildebrandt, Vincent H; van Mechelen, Willem

    2012-08-07

    Worksite health promotion programs (WHPPs) offer an attractive opportunity to improve the lifestyle of employees. Nevertheless, broad scale and successful implementation of WHPPs in daily practice often fails. In the present study, called BRAVO@Work, a 7-step implementation strategy was used to develop, implement and embed a WHPP in two different worksites with a focus on multiple lifestyle interventions.This article describes the design and framework for the formative evaluation of this 7-step strategy under real-time conditions by an embedded scientist with the purpose to gain insight into whether this this 7-step strategy is a useful and effective implementation strategy. Furthermore, we aim to gain insight into factors that either facilitate or hamper the implementation process, the quality of the implemented lifestyle interventions and the degree of adoption, implementation and continuation of these interventions. This study is a formative evaluation within two different worksites with an embedded scientist on site to continuously monitor the implementation process. Each worksite (i.e. a University of Applied Sciences and an Academic Hospital) will assign a participating faculty or a department, to implement a WHPP focusing on lifestyle interventions using the 7-step strategy. The primary focus will be to describe the natural course of development, implementation and maintenance of a WHPP by studying [a] the use and adherence to the 7-step strategy, [b] barriers and facilitators that influence the natural course of adoption, implementation and maintenance, and [c] the implementation process of the lifestyle interventions. All data will be collected using qualitative (i.e. real-time monitoring and semi-structured interviews) and quantitative methods (i.e. process evaluation questionnaires) applying data triangulation. Except for the real-time monitoring, the data collection will take place at baseline and after 6, 12 and 18 months. This is one of the few

  17. A multi-component stair climbing promotional campaign targeting calorific expenditure for worksites; a quasi-experimental study testing effects on behaviour, attitude and intention

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    Eves Frank F

    2012-06-01

    Full Text Available Abstract Background Accumulation of lifestyle physical activity is a current aim of health promotion, with increased stair climbing one public health target. While the workplace provides an opportunity for regular stair climbing, evidence for effectiveness of point-of-choice interventions is equivocal. This paper reports a new approach to worksite interventions, aimed at changing attitudes and, hence, behaviour. Methods Pre-testing of calorific expenditure messages used structured interviews with members of the public (n = 300. Effects of multi-component campaigns on stair climbing were tested with quasi-experimental, interrupted time-series designs. In one worksite, a main campaign poster outlining the amount of calorific expenditure obtainable from stair climbing and a conventional point-of-choice prompt were used (Poster alone site. In a second worksite, additional messages in the stairwell about calorific expenditure reinforced the main campaign (Poster + Stairwell messages site. The outcome variables were automated observations of stair and lift ascent (28,854 and descent (29,352 at baseline and for three weeks after the intervention was installed. Post-intervention questionnaires for employees at the worksites assessed responses to the campaign (n = 253. Analyses employed Analysis of Variance with follow-up Bonferroni t-tests (message pre-testing, logistic regression of stair ascent and descent (campaign testing, and Bonferroni t-tests and multiple regression (follow-up questionnaire. Results Pre-testing of messages based on calorific expenditure suggested they could motivate stair climbing if believed. The new campaign increased stair climbing, with greater effects at the Poster + Stairwell messages site (OR = 1.52, 95% CI = 1.40-1.66 than Posters alone (OR = 1.24, 95% CI = 1.15-1.34. Follow-up revealed higher agreement with two statements about calorific outcomes of stair climbing in the site where they

  18. A multi-component stair climbing promotional campaign targeting calorific expenditure for worksites; a quasi-experimental study testing effects on behaviour, attitude and intention

    Science.gov (United States)

    2012-01-01

    Background Accumulation of lifestyle physical activity is a current aim of health promotion, with increased stair climbing one public health target. While the workplace provides an opportunity for regular stair climbing, evidence for effectiveness of point-of-choice interventions is equivocal. This paper reports a new approach to worksite interventions, aimed at changing attitudes and, hence, behaviour. Methods Pre-testing of calorific expenditure messages used structured interviews with members of the public (n = 300). Effects of multi-component campaigns on stair climbing were tested with quasi-experimental, interrupted time-series designs. In one worksite, a main campaign poster outlining the amount of calorific expenditure obtainable from stair climbing and a conventional point-of-choice prompt were used (Poster alone site). In a second worksite, additional messages in the stairwell about calorific expenditure reinforced the main campaign (Poster + Stairwell messages site). The outcome variables were automated observations of stair and lift ascent (28,854) and descent (29,352) at baseline and for three weeks after the intervention was installed. Post-intervention questionnaires for employees at the worksites assessed responses to the campaign (n = 253). Analyses employed Analysis of Variance with follow-up Bonferroni t-tests (message pre-testing), logistic regression of stair ascent and descent (campaign testing), and Bonferroni t-tests and multiple regression (follow-up questionnaire). Results Pre-testing of messages based on calorific expenditure suggested they could motivate stair climbing if believed. The new campaign increased stair climbing, with greater effects at the Poster + Stairwell messages site (OR = 1.52, 95% CI = 1.40-1.66) than Posters alone (OR = 1.24, 95% CI = 1.15-1.34). Follow-up revealed higher agreement with two statements about calorific outcomes of stair climbing in the site where they were installed in

  19. Effectiveness of 6 months of tailored text message reminders for obese male participants in a worksite weight loss program: randomized controlled trial.

    Science.gov (United States)

    Kim, Ju-Young; Oh, Sohee; Steinhubl, Steven; Kim, Sohye; Bae, Woo Kyung; Han, Jong Soo; Kim, Jeong-Hyun; Lee, Keehyuck; Kim, Mi Jin

    2015-02-03

    Worksite nutrition and physical activity interventions are important to help overweight and obese employees lose weight, but costs and insufficient sustained motivation prevent the majority of these programs from succeeding. Tailored text messaging in aiding weight management has been effective in several studies, but no studies have evaluated the effect of a tailored text message service on weight loss in a worksite health promotion program. We studied the efficacy of a tailored text-messaging intervention for obese male participants in a worksite weight loss program of 6 months duration. The study was an unblinded, randomized controlled trial. Men with a body mass index greater than 25 kg/m(2) were recruited from the Korea District Heating Corporation, the Korea Expressway Corporation, and the Korea Gas Corporation. The participants were identified by nurse managers. Participants were randomly allocated to 1 of the following 2 groups for 24 weeks: (1) intervention group, which received tailored text message reminders every other day plus 4 offline education sessions and brief counseling with monthly weight check by nurses for weight control over 6 months and (2) control group, which received the 4 offline education sessions and brief counseling with monthly weight check by nurses about weight control over 6 months. The primary outcome was the difference in weight loss at 6 months. A mixed-model repeated-measures analysis was performed to evaluate the effect of the intervention group's weight loss compared with the control group. A total of 205 obese men were randomized into either the intervention (n=104) or the control group (n=101). At the end of 6 months, the intervention group (n=63) had lost 1.71 kg (95% CI -2.53 to -0.88) and the control group (n=59) had lost 1.56 kg (95% CI -2.45 to -0.66); the difference between the 2 groups was not significant (mean difference -0.15, 95% CI -1.36 to 1.07). At the end of the study, 60% (34/57) of the intervention group

  20. The design of a real-time formative evaluation of the implementation process of lifestyle interventions at two worksites using a 7-step strategy (BRAVO@Work

    Directory of Open Access Journals (Sweden)

    Wierenga Debbie

    2012-08-01

    Full Text Available Abstract Background Worksite health promotion programs (WHPPs offer an attractive opportunity to improve the lifestyle of employees. Nevertheless, broad scale and successful implementation of WHPPs in daily practice often fails. In the present study, called BRAVO@Work, a 7-step implementation strategy was used to develop, implement and embed a WHPP in two different worksites with a focus on multiple lifestyle interventions. This article describes the design and framework for the formative evaluation of this 7-step strategy under real-time conditions by an embedded scientist with the purpose to gain insight into whether this this 7-step strategy is a useful and effective implementation strategy. Furthermore, we aim to gain insight into factors that either facilitate or hamper the implementation process, the quality of the implemented lifestyle interventions and the degree of adoption, implementation and continuation of these interventions. Methods and design This study is a formative evaluation within two different worksites with an embedded scientist on site to continuously monitor the implementation process. Each worksite (i.e. a University of Applied Sciences and an Academic Hospital will assign a participating faculty or a department, to implement a WHPP focusing on lifestyle interventions using the 7-step strategy. The primary focus will be to describe the natural course of development, implementation and maintenance of a WHPP by studying [a] the use and adherence to the 7-step strategy, [b] barriers and facilitators that influence the natural course of adoption, implementation and maintenance, and [c] the implementation process of the lifestyle interventions. All data will be collected using qualitative (i.e. real-time monitoring and semi-structured interviews and quantitative methods (i.e. process evaluation questionnaires applying data triangulation. Except for the real-time monitoring, the data collection will take place at baseline and

  1. Healthy Team Healthy U: A Prospective Validation of an Evidence-based Worksite Health Promotion and Wellness Platform

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    Linn eGoldberg

    2015-08-01

    Full Text Available Objective: To evaluate the effects of a research tested, team-based health promotion and wellness program combined with digital technologies and implemented in a diverse worksite setting among hospital, clinic and university employees. Methods: A prospective cohort study of employees completing biometrics and questionnaires before and after the initial 12-session wellness program and its 12-session booster, one year later. Results: After both the initial intervention and booster, blood pressure and weight were reduced, with greater reductions among employees with pre-hypertension and hypertension and those with a BMI > 25. After both the initial intervention and booster, there was a significant increase in, 1 daily intake of fruit and vegetable servings; 2 days per week of > 30 minutes of exercise; 3 days per week of strength training and 4 levels of moderately vigorous and vigorous daily physical activity. Self-reported indices of depression and work related stress were reduced, while participants reported increased happiness after the initial program and booster. Post booster, average sleep quality and sleep duration increased, among higher risk employees reporting < 6 hours of daily sleep. Employees reported receiving encouragement from co-workers to engage in healthful activities, exercising with fellow employees more, and indicated they would recommend the program to co-workers. Longitudinal analysis revealed the durability of the initial intervention outcomes with further beneficial effects after the booster. Conclusion: A research-tested, comprehensive team-based health promotion and wellness program, combined with digital technologies, positively impacted employee health behaviors, mood, sleep, worker cohesion and biometrics among a diverse multi-site workforce. Positive program effects were durable, with enhanced results after the booster.

  2. PriC-mediated DNA replication restart requires PriC complex formation with the single-stranded DNA-binding protein.

    Science.gov (United States)

    Wessel, Sarah R; Marceau, Aimee H; Massoni, Shawn C; Zhou, Ruobo; Ha, Taekjip; Sandler, Steven J; Keck, James L

    2013-06-14

    Frequent collisions between cellular DNA replication complexes (replisomes) and obstacles such as damaged DNA or frozen protein complexes make DNA replication fork progression surprisingly sporadic. These collisions can lead to the ejection of replisomes prior to completion of replication, which, if left unrepaired, results in bacterial cell death. As such, bacteria have evolved DNA replication restart mechanisms that function to reload replisomes onto abandoned DNA replication forks. Here, we define a direct interaction between PriC, a key Escherichia coli DNA replication restart protein, and the single-stranded DNA-binding protein (SSB), a protein that is ubiquitously associated with DNA replication forks. PriC/SSB complex formation requires evolutionarily conserved residues from both proteins, including a pair of Arg residues from PriC and the C terminus of SSB. In vitro, disruption of the PriC/SSB interface by sequence changes in either protein blocks the first step of DNA replication restart, reloading of the replicative DnaB helicase onto an abandoned replication fork. Consistent with the critical role of PriC/SSB complex formation in DNA replication restart, PriC variants that cannot bind SSB are non-functional in vivo. Single-molecule experiments demonstrate that PriC binding to SSB alters SSB/DNA complexes, exposing single-stranded DNA and creating a platform for other proteins to bind. These data lead to a model in which PriC interaction with SSB remodels SSB/DNA structures at abandoned DNA replication forks to create a DNA structure that is competent for DnaB loading.

  3. Distinct mechanisms of recognizing endosomal sorting complex required for transport III (ESCRT-III) protein IST1 by different microtubule interacting and trafficking (MIT) domains.

    Science.gov (United States)

    Guo, Emily Z; Xu, Zhaohui

    2015-03-27

    The endosomal sorting complex required for transport (ESCRT) machinery is responsible for membrane remodeling in a number of biological processes including multivesicular body biogenesis, cytokinesis, and enveloped virus budding. In mammalian cells, efficient abscission during cytokinesis requires proper function of the ESCRT-III protein IST1, which binds to the microtubule interacting and trafficking (MIT) domains of VPS4, LIP5, and Spartin via its C-terminal MIT-interacting motif (MIM). Here, we studied the molecular interactions between IST1 and the three MIT domain-containing proteins to understand the structural basis that governs pairwise MIT-MIM interaction. Crystal structures of the three molecular complexes revealed that IST1 binds to the MIT domains of VPS4, LIP5, and Spartin using two different mechanisms (MIM1 mode versus MIM3 mode). Structural comparison revealed that structural features in both MIT and MIM contribute to determine the specific binding mechanism. Within the IST1 MIM sequence, two phenylalanine residues were shown to be important in discriminating MIM1 versus MIM3 binding. These observations enabled us to deduce a preliminary binding code, which we applied to provide CHMP2A, a protein that normally only binds the MIT domain in the MIM1 mode, the additional ability to bind the MIT domain of Spartin in the MIM3 mode. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Distinct Mechanisms of Recognizing Endosomal Sorting Complex Required for Transport III (ESCRT-III) Protein IST1 by Different Microtubule Interacting and Trafficking (MIT) Domains*

    Science.gov (United States)

    Guo, Emily Z.; Xu, Zhaohui

    2015-01-01

    The endosomal sorting complex required for transport (ESCRT) machinery is responsible for membrane remodeling in a number of biological processes including multivesicular body biogenesis, cytokinesis, and enveloped virus budding. In mammalian cells, efficient abscission during cytokinesis requires proper function of the ESCRT-III protein IST1, which binds to the microtubule interacting and trafficking (MIT) domains of VPS4, LIP5, and Spartin via its C-terminal MIT-interacting motif (MIM). Here, we studied the molecular interactions between IST1 and the three MIT domain-containing proteins to understand the structural basis that governs pairwise MIT-MIM interaction. Crystal structures of the three molecular complexes revealed that IST1 binds to the MIT domains of VPS4, LIP5, and Spartin using two different mechanisms (MIM1 mode versus MIM3 mode). Structural comparison revealed that structural features in both MIT and MIM contribute to determine the specific binding mechanism. Within the IST1 MIM sequence, two phenylalanine residues were shown to be important in discriminating MIM1 versus MIM3 binding. These observations enabled us to deduce a preliminary binding code, which we applied to provide CHMP2A, a protein that normally only binds the MIT domain in the MIM1 mode, the additional ability to bind the MIT domain of Spartin in the MIM3 mode. PMID:25657007

  5. Cross-linking mass spectrometry identifies new interfaces of Augmin required to localise the γ-tubulin ring complex to the mitotic spindle

    Directory of Open Access Journals (Sweden)

    Jack W. C. Chen

    2017-05-01

    Full Text Available The hetero-octameric protein complex, Augmin, recruits γ-Tubulin ring complex (γ-TuRC to pre-existing microtubules (MTs to generate branched MTs during mitosis, facilitating robust spindle assembly. However, despite a recent partial reconstitution of the human Augmin complex in vitro, the molecular basis of this recruitment remains unclear. Here, we used immuno-affinity purification of in vivo Augmin from Drosophila and cross-linking/mass spectrometry to identify distance restraints between residues within the eight Augmin subunits in the absence of any other structural information. The results allowed us to predict potential interfaces between Augmin and γ-TuRC. We tested these predictions biochemically and in the Drosophila embryo, demonstrating that specific regions of the Augmin subunits, Dgt3, Dgt5 and Dgt6 all directly bind the γ-TuRC protein, Dgp71WD, and are required for the accumulation of γ-TuRC, but not Augmin, to the mitotic spindle. This study therefore substantially increases our understanding of the molecular mechanisms underpinning MT-dependent MT nucleation.

  6. Late steps in cytoplasmic maturation of assembly-competent axonemal outer arm dynein in Chlamydomonas require interaction of ODA5 and ODA10 in a complex.

    Science.gov (United States)

    Dean, Anudariya B; Mitchell, David R

    2015-10-15

    Axonemal dyneins are multisubunit enzymes that must be preassembled in the cytoplasm, transported into cilia by intraflagellar transport, and bound to specific sites on doublet microtubules, where their activity facilitates microtubule sliding-based motility. Outer dynein arms (ODAs) require assembly factors to assist their preassembly, transport, and attachment to cargo (specific doublet A-tubule sites). In Chlamydomonas, three assembly factors--ODA5, ODA8, and ODA10--show genetic interactions and have been proposed to interact in a complex, but we recently showed that flagellar ODA8 does not copurify with ODA5 or ODA10. Here we show that ODA5 and ODA10 depend on each other for stability and coexist in a complex in both cytoplasmic and flagellar extracts. Immunofluorescence and immuno-electron microscopy reveal that ODA10 in flagella localizes strictly to a proximal region of doublet number 1, which completely lacks ODAs in Chlamydomonas. Studies of the in vitro binding of ODAs to axonemal doublets reveal a role for the ODA5/ODA10 assembly complex in cytoplasmic maturation of ODAs into a form that can bind to doublet microtubules.

  7. Microtubule-based localization of a synaptic calcium-signaling complex is required for left-right neuronal asymmetry in C. elegans

    Science.gov (United States)

    Chang, Chieh; Hsieh, Yi-Wen; Lesch, Bluma J.; Bargmann, Cornelia I.; Chuang, Chiou-Fen

    2011-01-01

    The axons of C. elegans left and right AWC olfactory neurons communicate at synapses through a calcium-signaling complex to regulate stochastic asymmetric cell identities called AWCON and AWCOFF. However, it is not known how the calcium-signaling complex, which consists of UNC-43/CaMKII, TIR-1/SARM adaptor protein and NSY-1/ASK1 MAPKKK, is localized to postsynaptic sites in the AWC axons for this lateral interaction. Here, we show that microtubule-based localization of the TIR-1 signaling complex to the synapses regulates AWC asymmetry. Similar to unc-43, tir-1 and nsy-1 loss-of-function mutants, specific disruption of microtubules in AWC by nocodazole generates two AWCON neurons. Reduced localization of UNC-43, TIR-1 and NSY-1 proteins in the AWC axons strongly correlates with the 2AWCON phenotype in nocodazole-treated animals. We identified kinesin motor unc-104/kif1a mutants for enhancement of the 2AWCON phenotype of a hypomorphic tir-1 mutant. Mutations in unc-104, like microtubule depolymerization, lead to a reduced level of UNC-43, TIR-1 and NSY-1 proteins in the AWC axons. In addition, dynamic transport of TIR-1 in the AWC axons is dependent on unc-104, the primary motor required for the transport of presynaptic vesicles. Furthermore, unc-104 acts non-cell autonomously in the AWCON neuron to regulate the AWCOFF identity. Together, these results suggest a model in which UNC-104 may transport some unknown presynaptic factor(s) in the future AWCON cell that non-cell autonomously control the trafficking of the TIR-1 signaling complex to postsynaptic regions of the AWC axons to regulate the AWCOFF identity. PMID:21771813

  8. Long Term Effects on Risk Factors for Cardiovascular Disease after 12-Months of Aerobic Exercise Intervention - A Worksite RCT among Cleaners.

    Science.gov (United States)

    Korshøj, Mette; Lidegaard, Mark; Krustrup, Peter; Jørgensen, Marie Birk; Søgaard, Karen; Holtermann, Andreas

    2016-01-01

    Occupational groups exposed to high occupational physical activity have an increased risk for cardiovascular disease (CVD). This may be explained by the high relative aerobic workload. Enhanced cardiorespiratory fitness reduces the relative aerobic workload. Thus, the aim was to evaluate the 12-months effects of worksite aerobic exercise on risk factors for CVD among cleaners. One hundred and sixteen cleaners aged 18-65 years were randomized to a group performing aerobic exercise and a reference group receiving lectures. Outcomes were collected at baseline and after 12-months. A repeated measures 2×2 multi-adjusted mixed-model design was applied to compare the between-group differences using intention-to-treat analysis. Between-group differences (pexercise group: cardiorespiratory fitness 2.15 (SE 1.03) mlO2/min/kg, aerobic workload -2.15 (SE 1.06) %HRR, resting HR -5.31 (SE 1.61) beats/min, high sensitive C-reactive protein -0.65 (SE 0.24) μg/ml. The blood pressure was unaltered. Stratified analyses on relative aerobic workload at baseline revealed that those with relative aerobic workloads ≥30% of HRR seems to impose a notable adverse effect on resting and ambulatory blood pressure. This long-term worksite aerobic exercise intervention among cleaners led to several beneficial effects, but also potential adverse effects among those with high relative aerobic workloads. Controlled-Trials.com ISRCTN86682076.

  9. Effectiveness of a worksite mindfulness-related multi-component health promotion intervention on work engagement and mental health: results of a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Jantien van Berkel

    Full Text Available OBJECTIVES: The aim of the present study was to evaluate the effectiveness of a worksite mindfulness-related multi-component health promotion intervention on work engagement, mental health, need for recovery and mindfulness. METHODS: In a randomized controlled trial design, 257 workers of two research institutes participated. The intervention group (n = 129 received a targeted mindfulness-related training, followed by e-coaching. The total duration of the intervention was 6 months. Data on work engagement, mental health, need for recovery and mindfulness were collected using questionnaires at baseline and after 6 and 12 months follow-up. Effects were analyzed using linear mixed effect models. RESULTS: There were no significant differences in work engagement, mental health, need for recovery and mindfulness between the intervention and control group after either 6- or 12-months follow-up. Additional analyses in mindfulness-related training compliance subgroups (high and low compliance versus the control group as a reference and subgroups based on baseline work engagement scores showed no significant differences either. CONCLUSIONS: This study did not show an effect of this worksite mindfulness-related multi-component health promotion intervention on work engagement, mental health, need for recovery and mindfulness after 6 and 12 months. TRIAL REGISTRATION: Netherlands Trial Register NTR2199.

  10. Are physical activity and nutrition indicators of the checklist of health promotion environments at worksites (CHEW) associated with employee obesity among hotel workers?

    Science.gov (United States)

    Nigg, Claudio R; Albright, Cheryl; Williams, Rebecca; Nichols, Carol; Renda, Gloria; Stevens, Victor J; Vogt, Thomas M

    2010-01-01

    Worksites provide opportunities to reach more than 60% of adults in the United States, including populations diverse in race, ethnicity, gender, age, occupation, income, and health status. Employers that provide worksite weight management interventions have the potential to reduce sick leave, health care costs, and workers compensation costs, and increase employee morale and worker efficiency. Hotels specifically, represent a broad cross-section of job categories, and most hotels are staffed and operated similarly around the world. However, from our literature review, there have been no investigations of the association between the hotel environment and employees' obesity. For this study, we tested the relationship between environmental factors in hotels and employees' body mass index (BMI). Overall no substantial correlations were found on any environmental variable. However, hotel size affected some relationships. Higher BMI was related to greater number of stairs, stair facilitation, and the healthy eating facilitation variables (excluding nutrition signs or posters) in medium sized hotels. Lower BMI was found with greater stair facilitation in small hotels; and with greater number of physical activity (PA) signs, lunch room nutrition signs, and hotel nutrition signs in large hotels. Unionized status affected only two environmental variables. For unionized hotels, BMI was negatively correlated with PA signs and positively correlated with the healthy eating facilitation. No logical pattern of association was found between workplace environmental factors and hotel employee BMI levels. Further research should investigate the interaction of the size and structure of the workplace with the impact of environmental efforts to reduce overweight and obesity.

  11. Are green caterers more likely to serve healthy meals than non-green caterers? Results from a quantitative study in Danish worksite catering.

    Science.gov (United States)

    Mikkelsen, Be; Bruselius-Jensen, M; Andersen, Js; Lassen, A

    2006-10-01

    The present study aimed to investigate whether organic conversion in catering has positive effects on the nutritional quality of menus offered. The methodology was based on a self-administered questionnaire. The self-declared priority given to the use of organic foods was measured as the basis for assigning catering managers to one of two groups: 'green' or 'non-green' caterers. These groups were then compared with regard to the relative nutritional quality of the menu options offered to customers. The study was carried out among randomly selected Danish worksite catering outlets. The subjects participating in the study comprised 526 Danish worksite catering managers. The results showed a strong correlation between caterers' 'green-ness' and the nutritional quality of the menu options offered. Green caters had more healthy options in their menus than non-green caters, which is likely to result in improved nutritional quality of the diets of end consumers. The reason for this may partly be the increased service training efforts that green caterers practise in order to be able to implement organic foods successfully. It may also be associated with the fact that the price premiums and availability of the organic products forces caterers to serve menus with higher amounts of root and non-green leafy vegetables, pulses and seasonal vegetables. The present findings suggest that organic conversion of public canteens may be a good opportunity to promote healthier eating in public catering.

  12. NSF- and SNARE-mediated membrane fusion is required for nuclear envelope formation and completion of nuclear pore complex assembly in Xenopus laevis egg extracts.

    Science.gov (United States)

    Baur, Tina; Ramadan, Kristijan; Schlundt, Andreas; Kartenbeck, Jürgen; Meyer, Hemmo H

    2007-08-15

    Despite the progress in understanding nuclear envelope (NE) reformation after mitosis, it has remained unclear what drives the required membrane fusion and how exactly this is coordinated with nuclear pore complex (NPC) assembly. Here, we show that, like other intracellular fusion reactions, NE fusion in Xenopus laevis egg extracts is mediated by SNARE proteins that require activation by NSF. Antibodies against Xenopus NSF, depletion of NSF or the dominant-negative NSF(E329Q) variant specifically inhibited NE formation. Staging experiments further revealed that NSF was required until sealing of the envelope was completed. Moreover, excess exogenous alpha-SNAP that blocks SNARE function prevented membrane fusion and caused accumulation of non-flattened vesicles on the chromatin surface. Under these conditions, the nucleoporins Nup107 and gp210 were fully recruited, whereas assembly of FxFG-repeat-containing nucleoporins was blocked. Together, we define NSF- and SNARE-mediated membrane fusion events as essential steps during NE formation downstream of Nup107 recruitment, and upstream of membrane flattening and completion of NPC assembly.

  13. VgrG C terminus confers the type VI effector transport specificity and is required for binding with PAAR and adaptor-effector complex.

    Science.gov (United States)

    Bondage, Devanand D; Lin, Jer-Sheng; Ma, Lay-Sun; Kuo, Chih-Horng; Lai, Erh-Min

    2016-07-05

    Type VI secretion system (T6SS) is a macromolecular machine used by many Gram-negative bacteria to inject effectors/toxins into eukaryotic hosts or prokaryotic competitors for survival and fitness. To date, our knowledge of the molecular determinants and mechanisms underlying the transport of these effectors remains limited. Here, we report that two T6SS encoded valine-glycine repeat protein G (VgrG) paralogs in Agrobacterium tumefaciens C58 specifically control the secretion and interbacterial competition activity of the type VI DNase toxins Tde1 and Tde2. Deletion and domain-swapping analysis identified that the C-terminal extension of VgrG1 specifically confers Tde1 secretion and Tde1-dependent interbacterial competition activity in planta, and the C-terminal variable region of VgrG2 governs this specificity for Tde2. Functional studies of VgrG1 and VgrG2 variants with stepwise deletion of the C terminus revealed that the C-terminal 31 aa (C31) of VgrG1 and 8 aa (C8) of VgrG2 are the molecular determinants specifically required for delivery of each cognate Tde toxin. Further in-depth studies on Tde toxin delivery mechanisms revealed that VgrG1 interacts with the adaptor/chaperone-effector complex (Tap-1-Tde1) in the absence of proline-alanine-alanine-arginine (PAAR) and the VgrG1-PAAR complex forms independent of Tap-1 and Tde1. Importantly, we identified the regions involved in these interactions. Although the entire C31 segment is required for binding with the Tap-1-Tde1 complex, only the first 15 aa of this region are necessary for PAAR binding. These results suggest that the VgrG1 C terminus interacts sequentially or simultaneously with the Tap-1-Tde1 complex and PAAR to govern Tde1 translocation across bacterial membranes and delivery into target cells for antibacterial activity.

  14. Worksite Health Promotion in Six Varied US Sites: Beta Testing as a Needed Translational Step

    Directory of Open Access Journals (Sweden)

    Diane L. Elliot

    2011-01-01

    Full Text Available Background. Dissemination of health promotion interventions generally has followed an efficacy, effectiveness to full scale paradigm, and most programs have failed to traverse that sequence. Objective. Report national dissemination of a health promotion program and juxtapose sequential case study observations with the current technology transfer literature. Design. Multiple department-level case studies using contact logs, transcribed interactions, augmented with field notes and validated by respondent review; at least two investigators independently generated site summaries, which were compared to formulate a final report. Results. Adoption was facilitated with national partners and designing branded materials. Critical site influences included departmental features, local champions, and liaison relationships. Achieving distal reach and fidelity required sequential process and program revisions based on new findings at each site. Conclusions. Beta testing to redesign program elements and modify process steps appears to be a needed and often ignored translational step between efficacy and more widespread dissemination.

  15. Regulation of Hxt3 and Hxt7 turnover converges on the Vid30 complex and requires inactivation of the Ras/cAMP/PKA pathway in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Chris Snowdon

    Full Text Available Eukaryotic cells adjust their intracellular protein complement as a mechanism to adapt to changing environmental signals. In Saccharomyces cerevisiae the hexose transporters Hxt3 and Hxt7 are expressed and function on the plasma membrane in high and low glucose abundance, respectively. By contrast, Hxt3 is endocytosed and degraded in the vacuole when cells are starved of glucose and Hxt7 in response to rapamycin treatment or when nitrogen is limiting. Yeast uses several signaling pathways, including the TORC1 and Ras/cAMP/Protein Kinase A (PKA pathways, to adapt to nutrient changes in the environment. The multi-protein Vid30 complex (Vid30c, an E3 ubiquitin ligase required for the degradation of FBPase, assists in this adaptation process in a mechanism that is poorly understood. Here we show the endocytosis and the subsequent degradation of both Hxt3 and Hxt7, in response to different nutrient signals, is dependent on components of the Vid30c. Additionally, we define the signaling events required for the turnover of Hxt3 and Hxt7 by showing that Hxt3 turnover requires Ras2 and PKA inactivation, whereas Hxt7 turnover requires TORC1 and Ras2 inactivation. Further investigation led us to identify Rim15, a kinase that is inhibited by both the TORC1 and Ras/cAMP/PKA pathways, as a key downstream effector in signaling both turnover events. Finally, we show that the turnover of both Hxt3 and Hxt7 is dependent on the essential E3 ubiquitin ligase, Rsp5, indicating that the role of the Vid30c might be indirect of Hxt ubiquitylation.

  16. Old world arenaviruses enter the host cell via the multivesicular body and depend on the endosomal sorting complex required for transport.

    Directory of Open Access Journals (Sweden)

    Giulia Pasqual

    2011-09-01

    Full Text Available The highly pathogenic Old World arenavirus Lassa virus (LASV and the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV use α-dystroglycan as a cellular receptor and enter the host cell by an unusual endocytotic pathway independent of clathrin, caveolin, dynamin, and actin. Upon internalization, the viruses are delivered to acidified endosomes in a Rab5-independent manner bypassing classical routes of incoming vesicular trafficking. Here we sought to identify cellular factors involved in the unusual and largely unknown entry pathway of LASV and LCMV. Cell entry of LASV and LCMV required microtubular transport to late endosomes, consistent with the low fusion pH of the viral envelope glycoproteins. Productive infection with recombinant LCMV expressing LASV envelope glycoprotein (rLCMV-LASVGP and LCMV depended on phosphatidyl inositol 3-kinase (PI3K as well as lysobisphosphatidic acid (LBPA, an unusual phospholipid that is involved in the formation of intraluminal vesicles (ILV of the multivesicular body (MVB of the late endosome. We provide evidence for a role of the endosomal sorting complex required for transport (ESCRT in LASV and LCMV cell entry, in particular the ESCRT components Hrs, Tsg101, Vps22, and Vps24, as well as the ESCRT-associated ATPase Vps4 involved in fission of ILV. Productive infection with rLCMV-LASVGP and LCMV also critically depended on the ESCRT-associated protein Alix, which is implicated in membrane dynamics of the MVB/late endosomes. Our study identifies crucial cellular factors implicated in Old World arenavirus cell entry and indicates that LASV and LCMV invade the host cell passing via the MVB/late endosome. Our data further suggest that the virus-receptor complexes undergo sorting into ILV of the MVB mediated by the ESCRT, possibly using a pathway that may be linked to the cellular trafficking and degradation of the cellular receptor.

  17. Old world arenaviruses enter the host cell via the multivesicular body and depend on the endosomal sorting complex required for transport.

    Science.gov (United States)

    Pasqual, Giulia; Rojek, Jillian M; Masin, Mark; Chatton, Jean-Yves; Kunz, Stefan

    2011-09-01

    The highly pathogenic Old World arenavirus Lassa virus (LASV) and the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) use α-dystroglycan as a cellular receptor and enter the host cell by an unusual endocytotic pathway independent of clathrin, caveolin, dynamin, and actin. Upon internalization, the viruses are delivered to acidified endosomes in a Rab5-independent manner bypassing classical routes of incoming vesicular trafficking. Here we sought to identify cellular factors involved in the unusual and largely unknown entry pathway of LASV and LCMV. Cell entry of LASV and LCMV required microtubular transport to late endosomes, consistent with the low fusion pH of the viral envelope glycoproteins. Productive infection with recombinant LCMV expressing LASV envelope glycoprotein (rLCMV-LASVGP) and LCMV depended on phosphatidyl inositol 3-kinase (PI3K) as well as lysobisphosphatidic acid (LBPA), an unusual phospholipid that is involved in the formation of intraluminal vesicles (ILV) of the multivesicular body (MVB) of the late endosome. We provide evidence for a role of the endosomal sorting complex required for transport (ESCRT) in LASV and LCMV cell entry, in particular the ESCRT components Hrs, Tsg101, Vps22, and Vps24, as well as the ESCRT-associated ATPase Vps4 involved in fission of ILV. Productive infection with rLCMV-LASVGP and LCMV also critically depended on the ESCRT-associated protein Alix, which is implicated in membrane dynamics of the MVB/late endosomes. Our study identifies crucial cellular factors implicated in Old World arenavirus cell entry and indicates that LASV and LCMV invade the host cell passing via the MVB/late endosome. Our data further suggest that the virus-receptor complexes undergo sorting into ILV of the MVB mediated by the ESCRT, possibly using a pathway that may be linked to the cellular trafficking and degradation of the cellular receptor.

  18. Minichromosome Maintenance Complex is Required for Checkpoint Kinase 2 Chromatin Loading and its Phosphorylation to DNA Damage Response in SCC-4 Cells.

    Science.gov (United States)

    Li, Liang; Feng, Yi; Luo, Rui

    2017-01-01

    Checkpoint kinase 2 (Chk2) is a significant mediator of diverse responses to DNA damage. The present study was aimed to identify possible interactive proteins of Chk2 and try to clarify the underlying mechanism regarding Chk2 chromatin loading and its phosphorylation to DNA damage response in oral squamous cell carcinoma (OSCC). Differently tagged Chk2 and minichromosome maintenance (MCM) complex (MCM2, MCM3, MCM5, and MCM6) were overexpressed into SCC-4 cells. After 48 h of transfection cell fractionation was performed to localize proteins. In addition, immunoreactive species were detected by immunoprecipitation (IP) and immunoblot (IB) analysis, and protein-protein interaction between Chk2 and MCM complex was ensured by glutathione S-transferase (GST) pull-down assay. Expression of MCM2 and MCM6 was downregulated by small interfering RNA (siRNA), and the chromatin and non-chromatin fraction were analyzed. The expression of Chk2 phosphorylation (pT68-Chk2) was measured after administration of different dosages of siMCM2 (0.5 μg, 1 μg, and 2.5 μg) and camptothecin (CPT). Our results showed that Chk2 directly interacts with MCM2, MCM3, MCM5, and MCM6 in SCC-4 cells. Downregulation of MCM2 and MCM6 markedly reduced Chk2 chromatin fraction, and downregulation of MCM2 decreased the expression of pT68-Chk2 to DNA damage response in a dose manner. Our results suggest that the interaction between Chk2 and MCM complex is required for Chk2 chromatin loading and its phosphorylation to DNA damage response in SCC-4 cells. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. A Cytosolic Multiprotein Complex Containing p85α Is Required for β-Catenin Activation in Colitis and Colitis-associated Cancer.

    Science.gov (United States)

    Goretsky, Tatiana; Bradford, Emily M; Ryu, Hyunji; Tahir, Maryam; Moyer, Mary Pat; Gao, Tianyan; Li, Linheng; Barrett, Terrence A

    2016-02-19

    Wnt/β-catenin signaling is required for crypt structure maintenance. We previously observed nuclear accumulation of Ser-552 phosphorylated β-catenin (pβ-Cat(Ser-552)) in intestinal epithelial cells (IEC) during colitis and colitis-associated cancer. Data here delineate a novel multiprotein cytosolic complex (MCC) involved in β-catenin signaling in the intestine. The MCC contains p85α, the class IA subunit of PI3K, along with β-catenin, 14-3-3ζ, Akt, and p110α. MCC levels in IEC increase in colitis and colitis-associated cancer patients. IEC-specific p85α-deficient (p85(ΔIEC)) mice develop more severe dextran sodium sulfate colitis due to delayed ulcer healing and reduced epithelial β-catenin activation. In colonic IEC, p85α deficiency did not alter PI3K signaling. In vitro shRNA depletion of individual complex members disrupts the MCC and reduces β-catenin signaling. Despite worse colitis, p85(ΔIEC) mice have reduced tumor burden after azoxymethane/dextran sodium sulfate treatment. Together the data indicate that the β-catenin MCC is needed for mucosal repair and carcinogenesis. This novel MCC may be an attractive therapeutic target in preventing cancer in colitis patients.

  20. Measuring cereblon as a biomarker of response or resistance to lenalidomide and pomalidomide requires use of standardized reagents and understanding of gene complexity.

    Science.gov (United States)

    Gandhi, Anita K; Mendy, Derek; Waldman, Michelle; Chen, Gengxin; Rychak, Emily; Miller, Karen; Gaidarova, Svetlana; Ren, Yan; Wang, Maria; Breider, Michael; Carmel, Gilles; Mahmoudi, Afshin; Jackson, Pilgrim; Abbasian, Mahan; Cathers, Brian E; Schafer, Peter H; Daniel, Tom O; Lopez-Girona, Antonia; Thakurta, Anjan; Chopra, Rajesh

    2014-01-01

    Cereblon, a member of the cullin 4 ring ligase complex (CRL4), is the molecular target of the immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide and is required for the antiproliferative activity of these agents in multiple myeloma (MM) and immunomodulatory activity in T cells. Cereblon's central role as a target of lenalidomide and pomalidomide suggests potential utility as a predictive biomarker of response or resistance to IMiD therapy. Our studies characterized a cereblon monoclonal antibody CRBN65, with high sensitivity and specificity in Western analysis and immunohistochemistry that is superior to commercially available antibodies. We identified multiple cereblon splice variants in both MM cell lines and primary cells, highlighting challenges with conventional gene expression assays given this gene complexity. Using CRBN65 antibody and TaqMan quantitative reverse transcription polymerase chain reaction assays, we showed lack of correlation between cereblon protein and mRNA levels. Furthermore, lack of correlation between cereblon expression in MM cell lines and sensitivity to lenalidomide was shown. In cell lines made resistant to lenalidomide and pomalidomide, cereblon protein is greatly reduced. These studies show limitations to the current approaches of cereblon measurement that rely on commercial reagents and assays. Standardized reagents and validated assays are needed to accurately assess the role of cereblon as a predictive biomarker.

  1. Mechanisms of assembly of the enzyme-ssDNA complexes required for recombination-dependent DNA synthesis and repair in bacteriophage T4

    Energy Technology Data Exchange (ETDEWEB)

    Morrical, S.; Hempstead, K.; Morrical, M. [Univ. of Vermont College of Medicine, Burlington, VT (United States)

    1994-12-31

    During late stages of bacteriophage T4 infection in E. coli, the initiation of phage DNA replication is dependent on the homologous recombination activity of the T4 uvsX protein. In vitro, uvsX protein initiates DNA synthesis on a duplex template by inserting the 3{prime} end of a homologous ssDNA molecule into the duplex. The resulting D-loop structure serves as a primer-template junction for the assembly of the T4 replication fork. Two key steps in this initiation process are (A) the assembly of uvsX-ssDNA complexes necessary for recombination activity and for the priming of lead-strand DNA synthesis, and (B) the assembly of the T4 primosome (gp41 helicase/gp61 primase complex) onto the single-stranded template for lagging-strand synthesis. Our laboratory is focusing on the mechanisms of these two different but related enzyme-ssDNA assembly processes. In this extended abstract, we describe recent efforts in our laboratory to elucidate the mechanism by which the gp41 helicase enzyme is assembled onto gp32-covered ssDNA, a process requiring the activity of a special helicase assembly factor, the T4 gp59 protein.

  2. Quality Control of Biomedicinal Allergen Products – Highly Complex Isoallergen Composition Challenges Standard MS Database Search and Requires Manual Data Analyses

    Science.gov (United States)

    Spiric, Jelena; Engin, Anna M.; Karas, Michael; Reuter, Andreas

    2015-01-01

    Allergy against birch pollen is among the most common causes of spring pollinosis in Europe and is diagnosed and treated using extracts from natural sources. Quality control is crucial for safe and effective diagnosis and treatment. However, current methods are very difficult to standardize and do not address individual allergen or isoallergen composition. MS provides information regarding selected proteins or the entire proteome and could overcome the aforementioned limitations. We studied the proteome of birch pollen, focusing on allergens and isoallergens, to clarify which of the 93 published sequence variants of the major allergen, Bet v 1, are expressed as proteins within one source material in parallel. The unexpectedly complex Bet v 1 isoallergen composition required manual data interpretation and a specific design of databases, as current database search engines fail to unambiguously assign spectra to highly homologous, partially identical proteins. We identified 47 non-allergenic proteins and all 5 known birch pollen allergens, and unambiguously proved the existence of 18 Bet v 1 isoallergens and variants by manual data analysis. This highly complex isoallergen composition raises questions whether isoallergens can be ignored or must be included for the quality control of allergen products, and which data analysis strategies are to be applied. PMID:26561299

  3. Protein complex of Drosophila ATRX/XNP and HP1a is required for the formation of pericentric beta-heterochromatin in vivo.

    Science.gov (United States)

    Emelyanov, Alexander V; Konev, Alexander Y; Vershilova, Elena; Fyodorov, Dmitry V

    2010-05-14

    ATRX belongs to the family of SWI2/SNF2-like ATP-dependent nucleosome remodeling molecular motor proteins. Mutations of the human ATRX gene result in a severe genetic disorder termed X-linked alpha-thalassemia mental retardation (ATR-X) syndrome. Here we perform biochemical and genetic analyses of the Drosophila melanogaster ortholog of ATRX. The loss of function allele of the Drosophila ATRX/XNP gene is semilethal. Drosophila ATRX is expressed throughout development in two isoforms, p185 and p125. ATRX185 and ATRX125 form distinct multisubunit complexes in fly embryo. The ATRX185 complex comprises p185 and heterochromatin protein HP1a. Consistently, ATRX185 but not ATRX125 is highly concentrated in pericentric beta-heterochromatin of the X chromosome in larval cells. HP1a strongly stimulates biochemical activities of ATRX185 in vitro. Conversely, ATRX185 is required for HP1a deposition in pericentric beta-heterochromatin of the X chromosome. The loss of function allele of the ATRX/XNP gene and mutant allele that does not express p185 are strong suppressors of position effect variegation. These results provide evidence for essential biological functions of Drosophila ATRX in vivo and establish ATRX as a major determinant of pericentric beta-heterochromatin identity.

  4. Evidence, Theory and Context: Using intervention mapping to develop a worksite physical activity intervention

    Directory of Open Access Journals (Sweden)

    Conner Mark

    2008-09-01

    Full Text Available Abstract Background The workplace is an ideal setting for health promotion. Helping employees to be more physically active can not only improve their physical and mental health, but can also have economic benefits such as reduced sickness absence. The current paper describes the development of a three month theory-based intervention that aims to increase levels of moderate intensity physical activity amongst employees in sedentary occupations. Methods The intervention was developed using an intervention mapping protocol. The intervention was also informed by previous literature, qualitative focus groups, an expert steering group, and feedback from key contacts within a range of organisations. Results The intervention was designed to target awareness (e.g. provision of information, motivation (e.g. goal setting, social support and environment (e.g. management support and to address behavioural (e.g. increasing moderate physical activity in work and interpersonal outcomes (e.g. encourage colleagues to be more physically active. The intervention can be implemented by local facilitators without the requirement for a large investment of resources. A facilitator manual was developed which listed step by step instructions on how to implement each component along with a suggested timetable. Conclusion Although time consuming, intervention mapping was found to be a useful tool for developing a theory based intervention. The length of this process has implications for the way in which funding bodies allow for the development of interventions as part of their funding policy. The intervention will be evaluated in a cluster randomised trial involving 1350 employees from 5 different organisations, results available September 2009.

  5. Temperature requirements differ for the two stages of seed dormancy break in Aegopodium podagraria (Apiaceae), a species with deep complex morphophysiological dormancy.

    Science.gov (United States)

    Phartyal, Shyam S; Kondo, Tetsuya; Baskin, Jerry M; Baskin, Carol C

    2009-06-01

    Only a few studies have considered the possibility that low temperature requirements may vary among stages of dormancy break in seeds with morphophysiological dormancy (MPD). We show that this lack of consideration in previous studies on seed dormancy and germination of Aegopodium podagraria might explain the low germination percentages and/or the relatively long periods of incubation needed for germination. Under natural temperatures, embryos began to grow in September and were fully elongated by late December; most growth occurred when the average daily mean temperature was about 10°C. Radicles emerged under snow in late winter, and cotyledons emerged after snowmelt in early spring. In laboratory experiments, 100% of the embryos grew to full length at both 0 and 5°C, whereas 0°C was much more effective than 5°C in overcoming the physiological dormancy in seeds after embryos were fully elongated. Following radicle emergence, cotyledons emerged readily in a wide range of temperatures ≥5°C. GA(3) did not substitute for the low temperature requirement for dormancy break. Seed dormancy in A. podagraria fits Nikolaeva's formula for deep complex MPD, i.e., C(3)B-C(3). Better germination of seeds pretreated at 0° than at 5°C has practical implications for cultivating this species.

  6. Hepatitis C Virus Proteins Interact with the Endosomal Sorting Complex Required for Transport (ESCRT Machinery via Ubiquitination To Facilitate Viral Envelopment

    Directory of Open Access Journals (Sweden)

    Rina Barouch-Bentov

    2016-11-01

    Full Text Available Enveloped viruses commonly utilize late-domain motifs, sometimes cooperatively with ubiquitin, to hijack the endosomal sorting complex required for transport (ESCRT machinery for budding at the plasma membrane. However, the mechanisms underlying budding of viruses lacking defined late-domain motifs and budding into intracellular compartments are poorly characterized. Here, we map a network of hepatitis C virus (HCV protein interactions with the ESCRT machinery using a mammalian-cell-based protein interaction screen and reveal nine novel interactions. We identify HRS (hepatocyte growth factor-regulated tyrosine kinase substrate, an ESCRT-0 complex component, as an important entry point for HCV into the ESCRT pathway and validate its interactions with the HCV nonstructural (NS proteins NS2 and NS5A in HCV-infected cells. Infectivity assays indicate that HRS is an important factor for efficient HCV assembly. Specifically, by integrating capsid oligomerization assays, biophysical analysis of intracellular viral particles by continuous gradient centrifugations, proteolytic digestion protection, and RNase digestion protection assays, we show that HCV co-opts HRS to mediate a late assembly step, namely, envelopment. In the absence of defined late-domain motifs, K63-linked polyubiquitinated lysine residues in the HCV NS2 protein bind the HRS ubiquitin-interacting motif to facilitate assembly. Finally, ESCRT-III and VPS/VTA1 components are also recruited by HCV proteins to mediate assembly. These data uncover involvement of ESCRT proteins in intracellular budding of a virus lacking defined late-domain motifs and a novel mechanism by which HCV gains entry into the ESCRT network, with potential implications for other viruses.

  7. Cofactor requirements and reconstitution of microcin B17 synthetase: a multienzyme complex that catalyzes the formation of oxazoles and thiazoles in the antibiotic microcin B17.

    Science.gov (United States)

    Milne, J C; Roy, R S; Eliot, A C; Kelleher, N L; Wokhlu, A; Nickels, B; Walsh, C T

    1999-04-13

    In the maturation of the Escherichia coli antibiotic Microcin B17 (MccB17), the McbA prepro-antibiotic is modified post-translationally by the multimeric microcin synthetase complex (composed of the McbB, -C, and -D proteins), which cyclizes four cysteines and four serines to thiazoles and oxazoles, respectively. Herein, we report the purification of individual subunits of MccB17 synthetase as fusions to maltose binding protein (MBP), and the in vitro reconstitution of heterocyclization activity. Preliminary characterization of each subunit reveals McbB to be a zinc-containing protein that may catalyze the initial cyclodehydration step, and McbC to contain flavin, consistent with an anticipated role for a dehydrogenase. We have previously demonstrated that McbD is a regulated ATPase/GTPase that may function as a conformational switch. Photolabeling experiments with the McbA propeptide now identify McbD as the initial site of substrate recognition. Heterocyclization activity was reconstituted only by combining all three subunits, demonstrating that each protein is required for heterocycle formation. Titration assays indicate that the subunits bind to each other with at least micromolar affinities, although McbD affords activity only after the MBP tag is proteolytically removed. Subunit competition assays with an McbDD147A mutant, which yields a catalytically deficient synthetase in vivo, show it to be defective in complex formation, whereas the McbBC181A/C184A double mutant, which is also inactive, competitively inhibits reconstitution by native McbB. Addition of the HtpG chaperone (originally shown to copurify with MccB17 synthetase), does not stimulate synthetase reconstitution or heterocyclization activity in vitro. A model for synthetase activity is proposed.

  8. Long term effects on risk factors for cardiovascular disease after 12-months of aerobic exercise intervention - A worksite RCT among cleaners

    DEFF Research Database (Denmark)

    Korshøj, Mette; Lidegaard, Mark; Krustrup, Peter

    2016-01-01

    to impose a notable adverse effect on resting and ambulatory blood pressure. CONCLUSION: This long-term worksite aerobic exercise intervention among cleaners led to several beneficial effects, but also potential adverse effects among those with high relative aerobic workloads. TRIAL REGISTRATION: Controlled......OBJECTIVES: Occupational groups exposed to high occupational physical activity have an increased risk for cardiovascular disease (CVD). This may be explained by the high relative aerobic workload. Enhanced cardiorespiratory fitness reduces the relative aerobic workload. Thus, the aim....../kg, aerobic workload -2.15 (SE 1.06) %HRR, resting HR -5.31 (SE 1.61) beats/min, high sensitive C-reactive protein -0.65 (SE 0.24) μg/ml. The blood pressure was unaltered. Stratified analyses on relative aerobic workload at baseline revealed that those with relative aerobic workloads ≥30% of HRR seems...

  9. Demographic, Behavioral, and Psychosocial Correlates of Using the Website Component of a Worksite Physical Activity and Healthy Nutrition Promotion Program: A Longitudinal Study

    Science.gov (United States)

    Robroek, Suzan JW; Brouwer, Wendy; Lindeboom, Dennis; Oenema, Anke

    2010-01-01

    Background Internet-delivered behavior change programs have the potential to reach a large population. However, low participation levels and high levels of attrition are often observed. The worksite could be a setting suitable for reaching and retaining large numbers of people, but little is known about reach and use of Internet-delivered health promotion programs in the worksite setting. Objective This study aimed (1) to gain more insight in the use of the website component of a worksite behavior change intervention and (2) to identify demographic, behavioral, and psychosocial factors associated with website use. Methods The study was an observational study among participants from 5 workplaces in a cluster randomized controlled trial. At baseline, all participants visited a study website to fill out the baseline questionnaire. Then a physical health check was done followed by face-to-face advice. After this contact, all participants received an email to promote visiting the website to view their health check results and the personal advice based on the baseline questionnaire. In the subsequent period, only participants in the intervention group received monthly email messages to promote website visits and were offered additional Web-based tools (self-monitors and a food frequency questionnaire [FFQ] assessing saturated fat intake) to support their behavior change. Website use was monitored by website statistics registering website access. Complete data were available for 726 employees. Logistic regression analyses were conducted to identify characteristics of employees who visited and used the website. Results In total, 43% of the participants visited the website after the email to promote website visits. Participants who were insufficiently physically active were less likely to visit the website (odds ratio [OR] 0.63, 95% confidence interval [CI] 0.45-0.88), whereas individuals with an elevated total cholesterol level visited the website more often (OR 1.44, 95

  10. Are green caterers more likely to serve healthy meals than non-green caterers? Results from a quantitative study in Danish worksite catering

    DEFF Research Database (Denmark)

    Mikkelsen, Bent Egberg; Bruselius-Jensen, Maria Louisa; Andersen, J. S.

    2006-01-01

    with the fact that the price premiums and availability of the organic products forces caterers to serve menus with higher amounts of root and non-green leafy vegetables, pulses and seasonal vegetables. Conclusion: The present findings suggest that organic conversion of public canteens may be a good opportunity......Objective: The present study aimed to investigate whether organic conversion in catering has positive effects on the nutritional quality of menus offered. Design: The methodology was based on a self-administered questionnaire. The self-declared priority given to the use of organic foods...... was measured as the basis for assigning catering managers to one of two groups: 'green' or 'non-green' caterers. These groups were then compared with regard to the relative nutritional quality of the menu options offered to customers. Setting: The study was carried out among randomly selected Danish worksite...

  11. Long Term Effects on Risk Factors for Cardiovascular Disease after 12-Months of Aerobic Exercise Intervention - A Worksite RCT among Cleaners

    Science.gov (United States)

    Korshøj, Mette; Lidegaard, Mark; Krustrup, Peter; Jørgensen, Marie Birk; Søgaard, Karen; Holtermann, Andreas

    2016-01-01

    Objectives Occupational groups exposed to high occupational physical activity have an increased risk for cardiovascular disease (CVD). This may be explained by the high relative aerobic workload. Enhanced cardiorespiratory fitness reduces the relative aerobic workload. Thus, the aim was to evaluate the 12-months effects of worksite aerobic exercise on risk factors for CVD among cleaners. Methods One hundred and sixteen cleaners aged 18–65 years were randomized to a group performing aerobic exercise and a reference group receiving lectures. Outcomes were collected at baseline and after 12-months. A repeated measures 2×2 multi-adjusted mixed-model design was applied to compare the between-group differences using intention-to-treat analysis. Results Between-group differences (p<0.05) were found favouring the aerobic exercise group: cardiorespiratory fitness 2.15 (SE 1.03) mlO2/min/kg, aerobic workload -2.15 (SE 1.06) %HRR, resting HR -5.31 (SE 1.61) beats/min, high sensitive C-reactive protein -0.65 (SE 0.24) μg/ml. The blood pressure was unaltered. Stratified analyses on relative aerobic workload at baseline revealed that those with relative aerobic workloads ≥30% of HRR seems to impose a notable adverse effect on resting and ambulatory blood pressure. Conclusion This long-term worksite aerobic exercise intervention among cleaners led to several beneficial effects, but also potential adverse effects among those with high relative aerobic workloads. Trial Registration Controlled-Trials.com ISRCTN86682076 PMID:27513932

  12. The master regulator for biofilm formation in Bacillus subtilis governs the expression of an operon encoding secreted proteins required for the assembly of complex multicellular communities.

    Energy Technology Data Exchange (ETDEWEB)

    Branda, Steven S. (Harvard Medical School, Cambridge, MA); Losick, Richard (Harvard University, Cambridge, MA); Kolter, Roberto (Harvard Medical School, Cambridge, MA); Kearns, Daniel B. (Harvard University, Cambridge, MA); Chu, Frances (Harvard University, Cambridge, MA)

    2005-08-01

    Wild strains of Bacillus subtilis are capable of forming architecturally complex communities of cells known as biofilms. Critical to biofilm formation is the eps operon, which is believed to be responsible for the biosynthesis of an exopolysaccharide that binds chains of cells together in bundles. We report that transcription of eps is under the negative regulation of SinR, a repressor that was found to bind to multiple sites in the regulatory region of the operon. Mutations in sinR bypassed the requirement in biofilm formation of two genes of unknown function, ylbF and ymcA, and sinI, which is known to encode an antagonist of SinR. We propose that these genes are members of a pathway that is responsible for counteracting SinR-mediated repression. We further propose that SinR is a master regulator that governs the transition between a planktonic state in which the bacteria swim as single cells in liquid or swarm in small groups over surfaces, and a sessile state in which the bacteria adhere to each other to form bundled chains and assemble into multicellular communities.

  13. Detection of the Endosomal Sorting Complex Required for Transport in Entamoeba histolytica and Characterization of the EhVps4 Protein

    Directory of Open Access Journals (Sweden)

    Israel López-Reyes

    2010-01-01

    Full Text Available Eukaryotic endocytosis involves multivesicular bodies formation, which is driven by endosomal sorting complexes required for transport (ESCRT. Here, we showed the presence and expression of homologous ESCRT genes in Entamoeba histolytica. We cloned and expressed the Ehvps4 gene, an ESCRT member, to obtain the recombinant EhVps4 and generate specific antibodies, which immunodetected EhVps4 in cytoplasm of trophozoites. Bioinformatics and biochemical studies evidenced that rEhVps4 is an ATPase, whose activity depends on the conserved E211 residue. Next, we generated trophozoites overexpressing EhVps4 and mutant EhVps4-E211Q FLAG-tagged proteins. The EhVps4-FLAG was located in cytosol and at plasma membrane, whereas the EhVps4-E211Q-FLAG was detected as abundant cytoplasmic dots in trophozoites. Erythrophagocytosis, cytopathic activity, and hepatic damage in hamsters were not improved in trophozoites overexpressing EhVps4-FLAG. In contrast, EhVps4-E211Q-FLAG protein overexpression impaired these properties. The localization of EhVps4-FLAG around ingested erythrocytes, together with our previous results, strengthens the role for EhVps4 in E. histolytica phagocytosis and virulence.

  14. Detection of the Endosomal Sorting Complex Required for Transport in Entamoeba histolytica and Characterization of the EhVps4 Protein

    Science.gov (United States)

    López-Reyes, Israel; García-Rivera, Guillermina; Bañuelos, Cecilia; Herranz, Silvia; Vincent, Olivier; López-Camarillo, César; Marchat, Laurence A.; Orozco, Esther

    2010-01-01

    Eukaryotic endocytosis involves multivesicular bodies formation, which is driven by endosomal sorting complexes required for transport (ESCRT). Here, we showed the presence and expression of homologous ESCRT genes in Entamoeba histolytica. We cloned and expressed the Ehvps4 gene, an ESCRT member, to obtain the recombinant EhVps4 and generate specific antibodies, which immunodetected EhVps4 in cytoplasm of trophozoites. Bioinformatics and biochemical studies evidenced that rEhVps4 is an ATPase, whose activity depends on the conserved E211 residue. Next, we generated trophozoites overexpressing EhVps4 and mutant EhVps4-E211Q FLAG-tagged proteins. The EhVps4-FLAG was located in cytosol and at plasma membrane, whereas the EhVps4-E211Q-FLAG was detected as abundant cytoplasmic dots in trophozoites. Erythrophagocytosis, cytopathic activity, and hepatic damage in hamsters were not improved in trophozoites overexpressing EhVps4-FLAG. In contrast, EhVps4-E211Q-FLAG protein overexpression impaired these properties. The localization of EhVps4-FLAG around ingested erythrocytes, together with our previous results, strengthens the role for EhVps4 in E. histolytica phagocytosis and virulence. PMID:20508821

  15. Accumulation of cyclin B1 requires E2F and cyclin-A-dependent rearrangement of the anaphase-promoting complex

    DEFF Research Database (Denmark)

    Lukas, C; Sørensen, Claus Storgaard; Kramer, E

    1999-01-01

    In mammalian somatic-cell cycles, progression through the G1-phase restriction point and initiation of DNA replication are controlled by the ability of the retinoblastoma tumour-suppressor protein (pRb) family to regulate the E2F/DP transcription factors. Continuing transcription of E2F target ge...... in the timely accumulation of cyclin B1 and the coordination of cell-cycle progression during the post-restriction point period.......In mammalian somatic-cell cycles, progression through the G1-phase restriction point and initiation of DNA replication are controlled by the ability of the retinoblastoma tumour-suppressor protein (pRb) family to regulate the E2F/DP transcription factors. Continuing transcription of E2F target...... genes beyond the G1/S transition is required for coordinating S-phase progression with cell division, a process driven by cyclin-B-dependent kinase and anaphase-promoting complex (APC)-mediated proteolysis. How E2F-dependent events at G1/S transition are orchestrated with cyclin B and APC activity...

  16. Nup2 requires a highly divergent partner, NupA, to fulfill functions at nuclear pore complexes and the mitotic chromatin region.

    Science.gov (United States)

    Markossian, Sarine; Suresh, Subbulakshmi; Osmani, Aysha H; Osmani, Stephen A

    2015-02-15

    Chromatin and nuclear pore complexes (NPCs) undergo dramatic changes during mitosis, which in vertebrates and Aspergillus nidulans involves movement of Nup2 from NPCs to the chromatin region to fulfill unknown functions. This transition is shown to require the Cdk1 mitotic kinase and be promoted prematurely by ectopic expression of the NIMA kinase. Nup2 localizes with a copurifying partner termed NupA, a highly divergent yet essential NPC protein. NupA and Nup2 locate throughout the chromatin region during prophase but during anaphase move to surround segregating DNA. NupA function is shown to involve targeting Nup2 to its interphase and mitotic locations. Deletion of either Nup2 or NupA causes identical mitotic defects that initiate a spindle assembly checkpoint (SAC)-dependent mitotic delay and also cause defects in karyokinesis. These mitotic problems are not caused by overall defects in mitotic NPC disassembly-reassembly or general nuclear import. However, without Nup2 or NupA, although the SAC protein Mad1 locates to its mitotic locations, it fails to locate to NPCs normally in G1 after mitosis. Collectively the study provides new insight into the roles of Nup2 and NupA during mitosis and in a surveillance mechanism that regulates nucleokinesis when mitotic defects occur after SAC fulfillment.

  17. Signaling components of the 1α,25(OH)2D3-dependent Pdia3 receptor complex are required for Wnt5a calcium-dependent signaling.

    Science.gov (United States)

    Doroudi, Maryam; Olivares-Navarrete, Rene; Hyzy, Sharon L; Boyan, Barbara D; Schwartz, Zvi

    2014-11-01

    Wnt5a and 1α,25(OH)2D3 are important regulators of endochondral ossification. In osteoblasts and growth plate chondrocytes, 1α,25(OH)2D3 initiates rapid effects via its membrane-associated receptor protein disulfide isomerase A3 (Pdia3) in caveolae, activating phospholipase A2 (PLA2)-activating protein (PLAA), calcium/calmodulin-dependent protein kinase II (CaMKII), and PLA2, resulting in protein kinase C (PKC) activation. Wnt5a initiates its calcium-dependent effects via intracellular calcium release, activating PKC and CaMKII. We investigated the requirement for components of the Pdia3 receptor complex in Wnt5a calcium-dependent signaling. We determined that Wnt5a signals through a CaMKII/PLA2/PGE2/PKC cascade. Silencing or blocking Pdia3, PLAA, or vitamin D receptor (VDR), and inhibition of calmodulin (CaM), CaMKII, or PLA2 inhibited Wnt5a-induced PKC activity. Wnt5a activated PKC in caveolin-1-silenced cells, but methyl-beta-cyclodextrin reduced its stimulatory effect. 1α,25(OH)2D3 reduced stimulatory effects of Wnt5a on PKC in a dose-dependent manner. In contrast, Wnt5a had a biphasic effect on 1α,25(OH)2D3-stimulated PKC activation; 50ng/ml Wnt5a caused a 2-fold increase in 1α,25(OH)2D3-stimulated PKC but higher Wnt5a concentrations reduced 1α,25(OH)2D3-stimulated PKC activation. Western blots showed that Wnt receptors Frizzled2 (FZD2) and Frizzled5 (FZD5), and receptor tyrosine kinase-like orphan receptor 2 (ROR2) were localized to caveolae. Blocking ROR2, but not FZD2 or FZD5, abolished the stimulatory effects of 1α,25(OH)2D3 on PKC and CaMKII. 1α,25(OH)2D3 membrane receptor complex components (Pdia3, PLAA, caveolin-1, CaM) interacted with Wnt5a receptors/co-receptors (ROR2, FZD2, FZD5) in immunoprecipitation studies, interactions that changed with either 1α,25(OH)2D3 or Wnt5a treatment. This study demonstrates that 1α,25(OH)2D3 and Wnt5a mediate their effects via similar receptor components and suggests that these pathways may interact.

  18. An Epstein-Barr Virus-Encoded Protein Complex Requires an Origin of Lytic Replication In Cis to Mediate Late Gene Transcription.

    Directory of Open Access Journals (Sweden)

    Reza Djavadian

    2016-06-01

    Full Text Available Epstein-Barr virus lytic replication is accomplished by an intricate cascade of gene expression that integrates viral DNA replication and structural protein synthesis. Most genes encoding structural proteins exhibit "true" late kinetics-their expression is strictly dependent on lytic DNA replication. Recently, the EBV BcRF1 gene was reported to encode a TATA box binding protein homolog, which preferentially recognizes the TATT sequence found in true late gene promoters. BcRF1 is one of seven EBV genes with homologs found in other β- and γ-, but not in α-herpesviruses. Using EBV BACmids, we systematically disrupted each of these "βγ" genes. We found that six of them, including BcRF1, exhibited an identical phenotype: intact viral DNA replication with loss of late gene expression. The proteins encoded by these six genes have been found by other investigators to form a viral protein complex that is essential for activation of TATT-containing reporters in EBV-negative 293 cells. Unexpectedly, in EBV infected 293 cells, we found that TATT reporter activation was weak and non-specific unless an EBV origin of lytic replication (OriLyt was present in cis. Using two different replication-defective EBV genomes, we demonstrated that OriLyt-mediated DNA replication is required in cis for TATT reporter activation and for late gene expression from the EBV genome. We further demonstrate by fluorescence in situ hybridization that the late BcLF1 mRNA localizes to EBV DNA replication factories. These findings support a model in which EBV true late genes are only transcribed from newly replicated viral genomes.

  19. The First Development of Human Factors Engineering Requirements for Application to Ground Task Design for a NASA Flight Program

    Science.gov (United States)

    Dischinger, H. Charles, Jr.; Stambolian, Damon B.; Miller, Darcy H.

    2008-01-01

    The National Aeronautics and Space Administration has long applied standards-derived human engineering requirements to the development of hardware and software for use by astronauts while in flight. The most important source of these requirements has been NASA-STD-3000. While there have been several ground systems human engineering requirements documents, none has been applicable to the flight system as handled at NASA's launch facility at Kennedy Space Center. At the time of the development of previous human launch systems, there were other considerations that were deemed more important than developing worksites for ground crews; e.g., hardware development schedule and vehicle performance. However, experience with these systems has shown that failure to design for ground tasks has resulted in launch schedule delays, ground operations that are more costly than they might be, and threats to flight safety. As the Agency begins the development of new systems to return humans to the moon, the new Constellation Program is addressing this issue with a new set of human engineering requirements. Among these requirements is a subset that will apply to the design of the flight components and that is intended to assure ground crew success in vehicle assembly and maintenance tasks. These requirements address worksite design for usability and for ground crew safety.

  20. Human RNase P ribonucleoprotein is required for formation of initiation complexes of RNA polymerase III

    Science.gov (United States)

    Serruya, Raphael; Orlovetskie, Natalie; Reiner, Robert; Dehtiar-Zilber, Yana; Wesolowski, Donna; Altman, Sidney; Jarrous, Nayef

    2015-01-01

    Human RNase P is implicated in transcription of small non-coding RNA genes by RNA polymerase III (Pol III), but the precise role of this ribonucleoprotein therein remains unknown. We here show that targeted destruction of HeLa nuclear RNase P inhibits transcription of 5S rRNA genes in whole cell extracts, if this precedes the stage of initiation complex formation. Biochemical purification analyses further reveal that this ribonucleoprotein is recruited to 5S rRNA genes as a part of proficient initiation complexes and the activity persists at reinitiation. Knockdown of RNase P abolishes the assembly of initiation complexes by preventing the formation of the initiation sub-complex of Pol III. Our results demonstrate that the structural intactness, but not the endoribonucleolytic activity per se, of RNase P is critical for the function of Pol III in cells and in extracts. PMID:25953854

  1. The NDUFB6 subunit of the mitochondrial respiratory chain complex I is required for electron transfer activity: A proof of principle study on stable and controlled RNA interference in human cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Loublier, Sandrine; Bayot, Aurelien; Rak, Malgorzata; El-Khoury, Riyad; Benit, Paule [Inserm U676, Hopital Robert Debre, F-75019 Paris (France); Universite Paris 7, Faculte de medecine Denis Diderot, IFR02 Paris (France); Rustin, Pierre, E-mail: pierre.rustin@inserm.fr [Inserm U676, Hopital Robert Debre, F-75019 Paris (France); Universite Paris 7, Faculte de medecine Denis Diderot, IFR02 Paris (France)

    2011-10-22

    Highlights: {yields} NDUFB6 is required for activity of mitochondrial complex I in human cell lines. {yields} Lentivirus based RNA interference results in frequent off target insertions. {yields} Flp-In recombinase mediated miRNA insertion allows gene-specific extinction. -- Abstract: Molecular bases of inherited deficiencies of mitochondrial respiratory chain complex I are still unknown in a high proportion of patients. Among 45 subunits making up this large complex, more than half has unknown function(s). Understanding the function of these subunits would contribute to our knowledge on mitochondrial physiology but might also reveal that some of these subunits are not required for the catalytic activity of the complex. A direct consequence of this finding would be the reduction of the number of candidate genes to be sequenced in patients with decreased complex I activity. In this study, we tested two different methods to stably extinct complex I subunits in cultured cells. We first found that lentivirus-mediated shRNA expression frequently resulted in the unpredicted extinction of additional gene(s) beside targeted ones. This can be ascribed to uncontrolled genetic material insertions in the genome of the host cell. This approach thus appeared inappropriate to study unknown functions of a gene. Next, we found it possible to specifically extinct a CI subunit gene by direct insertion of a miR targeting CI subunits in a Flp site (HEK293 Flp-In cells). By using this strategy we unambiguously demonstrated that the NDUFB6 subunit is required for complex I activity, and defined conditions suitable to undertake a systematic and stable extinction of the different supernumerary subunits in human cells.

  2. Sgf29 binds histone H3K4me2/3 and is required for SAGA complex recruitment and histone H3 acetylation

    Energy Technology Data Exchange (ETDEWEB)

    Bian, Chuanbing; Xu, Chao; Ruan, Jianbin; Lee, Kenneth K.; Burke, Tara L.; Tempel, Wolfram; Barsyte, Dalia; Li, Jing; Wu, Minhao; Zhou, Bo O.; Fleharty, Brian E.; Paulson, Ariel; Allali-Hassani, Abdellah; Zhou, Jin-Qiu; Mer, Georges; Grant, Patrick A.; Workman, Jerry L.; Zang, Jianye; Min, Jinrong (Toronto); (Stowers); (UST - China); (UV); (Chinese Aca. Sci.); (MCCM)

    2011-09-28

    The SAGA (Spt-Ada-Gcn5 acetyltransferase) complex is an important chromatin modifying complex that can both acetylate and deubiquitinate histones. Sgf29 is a novel component of the SAGA complex. Here, we report the crystal structures of the tandem Tudor domains of Saccharomyces cerevisiae and human Sgf29 and their complexes with H3K4me2 and H3K4me3 peptides, respectively, and show that Sgf29 selectively binds H3K4me2/3 marks. Our crystal structures reveal that Sgf29 harbours unique tandem Tudor domains in its C-terminus. The tandem Tudor domains in Sgf29 tightly pack against each other face-to-face with each Tudor domain harbouring a negatively charged pocket accommodating the first residue alanine and methylated K4 residue of histone H3, respectively. The H3A1 and K4me3 binding pockets and the limited binding cleft length between these two binding pockets are the structural determinants in conferring the ability of Sgf29 to selectively recognize H3K4me2/3. Our in vitro and in vivo functional assays show that Sgf29 recognizes methylated H3K4 to recruit the SAGA complex to its targets sites and mediates histone H3 acetylation, underscoring the importance of Sgf29 in gene regulation.

  3. The Arabidopsis CUL4–DDB1 complex interacts with MSI1 and is required to maintain MEDEA parental imprinting

    Science.gov (United States)

    Dumbliauskas, Eva; Lechner, Esther; Jaciubek, Miłosława; Berr, Alexandre; Pazhouhandeh, Maghsoud; Alioua, Malek; Cognat, Valerie; Brukhin, Vladimir; Koncz, Csaba; Grossniklaus, Ueli; Molinier, Jean; Genschik, Pascal

    2011-01-01

    Protein ubiquitylation regulates a broad variety of biological processes in all eukaryotes. Recent work identified a novel class of cullin-containing ubiquitin ligases (E3s) composed of CUL4, DDB1, and one WD40 protein, believed to act as a substrate receptor. Strikingly, CUL4-based E3 ligases (CRL4s) have important functions at the chromatin level, including responses to DNA damage in metazoans and plants and, in fission yeast, in heterochromatin silencing. Among putative CRL4 receptors we identified MULTICOPY SUPPRESSOR OF IRA1 (MSI1), which belongs to an evolutionary conserved protein family. MSI1-like proteins contribute to different protein complexes, including the epigenetic regulatory Polycomb repressive complex 2 (PRC2). Here, we provide evidence that Arabidopsis MSI1 physically interacts with DDB1A and is part of a multimeric protein complex including CUL4. CUL4 and DDB1 loss-of-function lead to embryo lethality. Interestingly, as in fis class mutants, cul4 mutants exhibit autonomous endosperm initiation and loss of parental imprinting of MEDEA, a target gene of the Arabidopsis PRC2 complex. In addition, after pollination both MEDEA transcript and protein accumulate in a cul4 mutant background. Overall, our work provides the first evidence of a physical and functional link between a CRL4 E3 ligase and a PRC2 complex, thus indicating a novel role of ubiquitylation in the repression of gene expression. PMID:21240189

  4. Implementation of a worksite educational program focused on promoting healthy eating habits [v2; ref status: indexed, http://f1000r.es/32x

    Directory of Open Access Journals (Sweden)

    Dimitra Tanagra

    2014-03-01

    Full Text Available Objective: To estimate the effectiveness of a short-term educational-counseling worksite program focused on lipid intake, by monitoring the possible change on nutrition knowledge and eating habits. Methods: an 8-week educational program based on the Health Belief Model was implemented in a honey packaging and sales company in Greece. 20 out of the 29 employees initially enrolled completed the program. Knowledge level and eating habits were evaluated prior and after the intervention by the “Nutrition Knowledge Questionnaire” and the “Food Habits Questionnaire”. ANOVA, Spearman rho test and paired Wilcoxon test were employed in statistical analysis. Results: Non smokers and those with higher educational level had healthier eating habits. Knowledge following the intervention was significantly improved concerning recommendations and basic food ingredients but as far as eating habits were concerned, scores were not improved significantly, while intake of fried food was increased. Conclusions and Implications: Short-term interventions may produce substantial improvement in knowledge but not necessarily modifications in unhealthy eating habits.

  5. CVD Prevention Through Policy: a Review of Mass Media, Food/Menu Labeling, Taxation/Subsidies, Built Environment, School Procurement, Worksite Wellness, and Marketing Standards to Improve Diet.

    Science.gov (United States)

    Afshin, Ashkan; Penalvo, Jose; Del Gobbo, Liana; Kashaf, Michael; Micha, Renata; Morrish, Kurtis; Pearson-Stuttard, Jonathan; Rehm, Colin; Shangguan, Siyi; Smith, Jessica D; Mozaffarian, Dariush

    2015-11-01

    Poor diet is the leading cause of cardiovascular disease in the USA and globally. Evidence-based policies are crucial to improve diet and population health. We reviewed the effectiveness for a range of policy levers to alter diet and diet-related risk factors. We identified evidence to support benefits of focused mass media campaigns (especially for fruits, vegetables, salt), food pricing strategies (both subsidies and taxation, with stronger effects at lower income levels), school procurement policies (for increasing healthful or reducing unhealthful choices), and worksite wellness programs (especially when comprehensive and multicomponent). Evidence was inconclusive for food and menu labeling (for consumer or industry behavior) and changes in local built environment (e.g., availability or accessibility of supermarkets, fast food outlets). We found little empiric evidence evaluating marketing restrictions, although broad principles and large resources spent on marketing suggest utility. Widespread implementation and evaluation of evidence-based policy strategies, with further research on other strategies with mixed/limited evidence, are essential "population medicine" to reduce health and economic burdens and inequities of diet-related illness worldwide.

  6. Events during eucaryotic rRNA transcription initiation and elongation: Conversion from the closed to the open promoter complex requires nucleotide substrates

    Energy Technology Data Exchange (ETDEWEB)

    Bateman, E.; Paule, M.R.

    1988-05-01

    Chemical footprinting and topological analysis were carried out on the Acanthamoeba castellanii rRNA transcription initiation factor (TIF) and RNA polymerase I complexes with DNA during transcription initiation and elongation. The results show that the binding of TIF and polymerase to the promoter does not alter the supercoiling of the DNA template and the template does not become sensitive to modification by diethylpyro-carbonate, which can identify melted DNA regions. Thus, in contrast to bacterial RNA polymerase, the eucaryotic RNA polymerase I-promoter complex is in a closed configuration preceding addition of nucleotides in vitro. Initiation and 3'-O-methyl CTP-limited translocation by RNA polymerase I results in separation of the polymerase-TIF footprints, leaving the TIF footprint unaltered. In contrast, initiation and translocation result in a significant change in the conformation of the polymerase-DNA complex, culminating in an unwound DNA region of at least 10 base pairs.

  7. The Ndc80 internal loop is required for recruitment of the Ska complex to establish end-on microtubule attachment to kinetochores

    DEFF Research Database (Denmark)

    Zhang, Gang; Kelstrup, Christian D; Hu, Xiao-Wen;

    2012-01-01

    the chromosomes and stable kinetochore fibers are absent. Through quantitative mass spectrometry and immunofluorescence we find that the binding of the Ska complex depends on the loop region explaining why end-on attachment is defective. This underscores the importance of the Ndc80 loop region in coordinating......The Ndc80 complex establishes end-on attachment of kinetochores to microtubules essential for chromosome segregation. The Ndc80 subunit is characterized by an N-terminal region, that binds directly to microtubules, and a long coiled-coil region that interacts with Nuf2. A loop region in Ndc80...

  8. The yeast chromatin remodeler Rsc1-RSC complex is required for transcriptional activation of autophagy-related genes and inhibition of the TORC1 pathway in response to nitrogen starvation.

    Science.gov (United States)

    Yu, Feifei; Imamura, Yuko; Ueno, Masaru; Suzuki, Sho W; Ohsumi, Yoshinori; Yukawa, Masashi; Tsuchiya, Eiko

    2015-09-01

    The yeast RSC, an ATP-dependent chromatin-remodeling complex, is essential for mitotic and meiotic growth. There are two distinct isoforms of this complex defined by the presence of either Rsc1 or Rsc2; however, the functional differences between these complexes are unclear. Here we show that the RSC complex containing Rsc1, but not Rsc2, functions in autophagy induction. Rsc1 was required not only for full expression of ATG8 mRNA but also for maintenance of Atg8 protein stability. Interestingly, decreased autophagic activity and Atg8 protein stability in rsc1Δ cells, but not the defect in ATG8 mRNA expression, were partially suppressed by deletion of TOR1. In addition, we found that rsc1Δ impaired the binding between the Rho GTPase Rho1 and the TORC1-specific component Kog1, which is required for down-regulation of TORC1 activity. These results suggest that the Rsc1-containing RSC complex plays dual roles in the proper induction of autophagy: 1) the transcriptional activation of autophagy-related genes independent of the TORC1 pathway and 2) the inactivation of TORC1, possibly through enhancement of Rho1-Kog1 binding.

  9. BAF250B-associated SWI/SNF chromatin-remodeling complex is required to maintain undifferentiated mouse embryonic stem cells

    Science.gov (United States)

    Yan, Zhijiang; Wang, Zhong; Sharova, Lioudmila; Sharov, Alexei A.; Ling, Chen; Piao, Yulan; Aiba, Kazuhiro; Matoba, Ryo; Wang, Weidong; Ko, Minoru S.H.

    2008-01-01

    Whether SWI/SNF chromatin remodeling complexes play roles in embryonic stem (ES) cells remains unknown. Here we show that SWI/SNF complexes are present in mouse ES cells, and their composition is dynamically regulated upon induction of ES cell differentiation. For example, the SWI/SNF purified from undifferentiated ES cells contains a high level of BAF155 and a low level of BAF170 (both of which are homologs of yeast SWI3 protein), whereas that from differentiated cells contains near equal amounts of both. Moreover, the levels of BAF250A and BAF250B decrease, whereas that of BRM increases, during the differentiation of ES cells. The altered expression of SWI/SNF components hinted that these complexes could play roles in ES cell maintenance or differentiation. We therefore generated ES cells with biallelic inactivation of BAF250B, and found that these cells display a reduced proliferation rate and an abnormal cell cycle. Importantly, these cells are deficient in self-renewal capacity of undifferentiated ES cells, and exhibit certain phenotypes of differentiated cells, including reduced expression of several pluripotency-related genes, and increased expression of some differentiation-related genes. These data suggest that the BAF250B-associated SWI/SNF is essential for mouse ES cells to maintain its normal proliferation and pluripotency. The work presented here underscores the importance of SWI/SNF chromatin remodeling complexes in pluripotent stem cells. PMID:18323406

  10. gamma-Secretase activity requires the presenilin-dependent trafficking of nicastrin through the Golgi apparatus but not its complex glycosylation.

    Science.gov (United States)

    Herreman, An; Van Gassen, Geert; Bentahir, Mustapha; Nyabi, Omar; Craessaerts, Katleen; Mueller, Ulrike; Annaert, Wim; De Strooper, Bart

    2003-03-15

    Nicastrin and presenilin are two major components of the gamma-secretase complex, which executes the intramembrane proteolysis of type I integral membrane proteins such as the amyloid precursor protein (APP) and Notch. Nicastrin is synthesized in fibroblasts and neurons as an endoglycosidase-H-sensitive glycosylated precursor protein (immature nicastrin) and is then modified by complex glycosylation in the Golgi apparatus and by sialylation in the trans-Golgi network (mature nicastrin). These modifications are not observed with exogenously overexpressed nicastrin. Under normal cell culture conditions, only mature nicastrin is expressed at the cell surface and binds to the presenilin heterodimers. Mature nicastrin has a half-life of more than 24 hours. In the absence of presenilin 1 and 2, nicastrin remains entirely endoglycosidase H sensitive, is retained in the endoplasmic reticulum and is slowly degraded. Single presenilin 1 or presenilin 2 deficiency affects glycosylation of nicastrin to a lesser extent than the combined presenilin deficiencies, suggesting a correlation between either the transport of nicastrin out of the endoplasmic reticulum or the concomitant complex glycosylation of nicastrin, and gamma-secretase activity. However, when complex glycosylation of nicastrin was inhibited using mannosidase I inhibitors, gamma-secretase cleavage of APP or Notch was not inhibited and the immature nicastrin still associates with presenilin and appears at the cell surface. Complex glycosylation of nicastrin is therefore not needed for gamma-secretase activity. Because the trafficking of nicastrin to the Golgi apparatus is dependent on presenilins, our data point to a central role of presenilin in nicastrin maturation/localization, which could help to partially resolve the 'spatial paradox'.

  11. Requirement for C-X-C chemokines (macrophage inflammatory protein-2 and cytokine-induced neutrophil chemoattractant) in IgG immune complex-induced lung injury

    DEFF Research Database (Denmark)

    Shanley, T P; Schmal, H; Warner, R L

    1997-01-01

    The C-X-C chemokines of the IL-8 family possess potent chemotactic activity for neutrophils, but their in vivo role in inflammatory responses is not well understood. In the IgG immune complex-induced model of acute lung inflammatory injury in the rat we have evaluated the roles of two rat...... chemokines, macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (CINC). Both mRNA and protein for MIP-2 and CINC appeared in a time-dependent manner after initiation of IgG immune complex deposition in lung. There exists a 69% homology between the amino acid sequences...... by 125I-labeled albumin leakage from the pulmonary vasculature) and reduced neutrophil accumulation in the lung (as determined by myeloperoxidase (MPO content) and neutrophil counts in bronchoalveolar lavage (BAL) fluids); however, no change in TNF-alpha levels in BAL fluids was found. Chemotactic...

  12. Purified monomeric ligand.MD-2 complexes reveal molecular and structural requirements for activation and antagonism of TLR4 by Gram-negative bacterial endotoxins.

    Science.gov (United States)

    Gioannini, Theresa L; Teghanemt, Athmane; Zhang, DeSheng; Esparza, Gregory; Yu, Liping; Weiss, Jerrold

    2014-08-01

    A major focus of work in our laboratory concerns the molecular mechanisms and structural bases of Gram-negative bacterial endotoxin recognition by host (e.g., human) endotoxin-recognition proteins that mediate and/or regulate activation of Toll-like receptor (TLR) 4. Here, we review studies of wild-type and variant monomeric endotoxin.MD-2 complexes first produced and characterized in our laboratories. These purified complexes have provided unique experimental reagents, revealing both quantitative and qualitative determinants of TLR4 activation and antagonism. This review is dedicated to the memory of Dr. Theresa L. Gioannini (1949-2014) who played a central role in many of the studies and discoveries that are reviewed.

  13. CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs

    DEFF Research Database (Denmark)

    Merveille, Anne-Christine; Davis, Erica E; Becker-Heck, Anita

    2011-01-01

    cilia that are responsible for airway clearance, the flagella that propel sperm cells and the nodal monocilia that determine left-right asymmetry. Recessive mutations that cause PCD have been identified in genes encoding components of the outer dynein arms, radial spokes and cytoplasmic pre...... with axonemal disorganization and abnormal ciliary beating. Functional analyses indicated that CCDC39 localizes to ciliary axonemes and is essential for assembly of inner dynein arms and the dynein regulatory complex....

  14. The rice DUF1620-containing and WD40-like repeat protein is required for the assembly of the restoration of fertility complex.

    Science.gov (United States)

    Qin, Xiaojian; Huang, Qi; Xiao, Haijun; Zhang, Qiannan; Ni, Chenzi; Xu, Yanghong; Liu, Gai; Yang, Daichang; Zhu, Yingguo; Hu, Jun

    2016-05-01

    Cytoplasmic male sterility (CMS) and restoration of fertility (Rf) are widely distributed in plant species utilized by humans. RF5 and GRP162 are subunits of the restoration of fertility complex (RFC) in Hong-Lian rice. Despite the fact that the RFC is 400-500 kDa in size, the other proteins or factors in the complex still remain unknown. Here, we identified RFC subunit 3, which encodes a DUF1620-containing and WD40-like repeat protein (RFC3) that is present in all tissues but highly expressed in leaves. We established that RFC3 interacts with both RF5 and GRP162 in vitro and in vivo, and is transported into the mitochondria as a membrane protein. Furthermore, CMS RNA (atp6-orfH79) and CMS cytotoxic protein (ORFH79) accumulate when RFC3 is silenced in restorer lines. We presented the analysis with blue-native polyacrylamide gel electrophoresis, indicating that RFC is disrupted in the RNAi line. We concluded that RCF3 is indispensable as a scaffold protein for the assembly of the RFC complex. We unveil a new molecular player of the RFC in the Rf pathway in rice and propose the model of RFC based on these data.

  15. Identification of a region required for TSC1 stability by functional analysis of TSC1 missense mutations found in individuals with tuberous sclerosis complex

    Directory of Open Access Journals (Sweden)

    den Dunnen Johan T

    2009-09-01

    Full Text Available Abstract Background Tuberous sclerosis complex (TSC is an autosomal dominant disorder characterised by the development of hamartomas in a variety of organs and tissues. The disease is caused by mutations in either the TSC1 gene on chromosome 9q34, or the TSC2 gene on chromosome 16p13.3. The TSC1 and TSC2 gene products, TSC1 and TSC2, form a protein complex that inhibits signal transduction to the downstream effectors of the mammalian target of rapamycin (mTOR. Recently it has been shown that missense mutations to the TSC1 gene can cause TSC. Methods We have used in vitro biochemical assays to investigate the effects on TSC1 function of TSC1 missense variants submitted to the Leiden Open Variation Database. Results We identified specific substitutions between amino acids 50 and 190 in the N-terminal region of TSC1 that result in reduced steady state levels of the protein and lead to increased mTOR signalling. Conclusion Our results suggest that amino acid residues within the N-terminal region of TSC1 are important for TSC1 function and for maintaining the activity of the TSC1-TSC2 complex.

  16. The UBC Domain Is Required for BRUCE to Promote BRIT1/MCPH1 Function in DSB Signaling and Repair Post Formation of BRUCE-USP8-BRIT1 Complex.

    Science.gov (United States)

    Ge, Chunmin; Che, Lixiao; Du, Chunying

    2015-01-01

    BRUCE is implicated in the regulation of DNA double-strand break response to preserve genome stability. It acts as a scaffold to tether USP8 and BRIT1, together they form a nuclear BRUCE-USP8-BRIT1 complex, where BRUCE holds K63-ubiquitinated BRIT1 from access to DSB in unstressed cells. Following DSB induction, BRUCE promotes USP8 mediated deubiquitination of BRIT1, a prerequisite for BRIT1 to be released from the complex and recruited to DSB by binding to γ-H2AX. BRUCE contains UBC and BIR domains, but neither is required for the scaffolding function of BRUCE mentioned above. Therefore, it remains to be determined whether they are required for BRUCE in DSB response. Here we show that the UBC domain, not the BIR domain, is required for BRUCE to promote DNA repair at a step post the formation of BRUCE-USP8-BRIT1 complex. Mutation or deletion of the BRUCE UBC domain did not disrupt the BRUCE-USP8-BRIT1 complex, but impaired deubiquitination and consequent recruitment of BRIT1 to DSB. This leads to impaired chromatin relaxation, decreased accumulation of MDC1, NBS1, pATM and RAD51 at DSB, and compromised homologous recombination repair of DNA DSB. These results demonstrate that in addition to the scaffolding function in complex formation, BRUCE has an E3 ligase function to promote BRIT1 deubiquitination by USP8 leading to accumulation of BRIT1 at DNA double-strand break. These data support a crucial role for BRUCE UBC activity in the early stage of DSB response.

  17. SEPT12/SPAG4/LAMINB1 complexes are required for maintaining the integrity of the nuclear envelope in postmeiotic male germ cells.

    Directory of Open Access Journals (Sweden)

    Chung-Hsin Yeh

    Full Text Available Male infertility affects approximately 50% of all infertile couples. The male-related causes of intracytoplasmic sperm injection failure include the absence of sperm, immotile or immature sperm, and sperm with structural defects such as those caused by premature chromosomal condensation and DNA damage. Our previous studies based on a knockout mice model indicated that SEPT12 proteins are critical for the terminal morphological formation of sperm. SEPT12 mutations in men result in teratozospermia and oligozospermia. In addition, the spermatozoa exhibit morphological defects of the head and tail, premature chromosomal condensation, and nuclear damage. However, the molecular functions of SEPT12 during spermatogenesis remain unclear. To determine the molecular functions of SEPT12, we applied a yeast 2-hybrid system to identify SEPT12 interactors. Seven proteins that interact with SEPT12 were identified: SEPT family proteins (SEPT4 and SEPT6, nuclear or nuclear membrane proteins (protamine 2, sperm-associated antigen 4, and NDC1 transmembrane nucleoproine, and sperm-related structural proteins (pericentriolar material 1 and obscurin-like 1. Sperm-associated antigen 4 (SPAG4; also known as SUN4 belongs to the SUN family of proteins and acts as a linker protein between nucleoskeleton and cytoskeleton proteins and localizes in the nuclear membrane. We determined that SEPT12 interacts with SPAG4 in a male germ cell line through coimmunoprecipitation. During human spermiogenesis, SEPT12 is colocalized with SPAG4 near the nuclear periphery in round spermatids and in the centrosome region in elongating spermatids. Furthermore, we observed that SEPT12/SPAG4/LAMINB1 formed complexes and were coexpressed in the nuclear periphery of round spermatids. In addition, mutated SEPT12, which was screened from an infertile man, affected the integration of these nuclear envelope complexes through coimmunoprecipitation. This was the first study that suggested that SEPT

  18. Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase

    DEFF Research Database (Denmark)

    Hernández-Muñoz, Inmaculada; Lund, Anders H; van der Stoop, Petra

    2005-01-01

    . This recruitment results in an inactive state that is initially labile but is further locked in by epigenetic marks such as DNA methylation, histone hypoacetylation, and MACROH2A deposition. Here, we report that the E3 ubiquitin ligase consisting of SPOP and CULLIN3 is able to ubiquitinate the Polycomb group...... inactivation in somatic cells. We further demonstrate that MACROH2A1 deposition is regulated by the CULLIN3/SPOP ligase complex and is actively involved in stable X inactivation, likely through the formation of an additional layer of epigenetic silencing....

  19. Evaluación de un programa de deshabituación tabáquica en el medio laboral Evaluation of a worksite smoking cessation program

    Directory of Open Access Journals (Sweden)

    Maria Sala

    2005-10-01

    Full Text Available Objetivos: Se evalúa una intervención realizada en el lugar del trabajo para facilitar el abandono del hábito tabáquico y reducir la prevalencia de fumadores entre el personal del Ayuntamiento de Sabadell. Población y métodos: Estudio preintervención y postintervención. Se realizó una encuesta para conocer la prevalencia y las características de los fumadores e invitarles a participar en un programa de deshabituación. El programa constaba de una visita individual con historia clínica, medida de monóxido de carbono en aire espirado y prescripción de terapia con sustitutos de nicotina y 12 sesiones de terapia grupal para reforzar la abstinencia a lo largo de 1 año. A los 6, 12 y 24 meses se realizaron controles para conocer la abstinencia. Con una encuesta postintervención se valoró el impacto del programa. Resultados: Se enviaron 1.203 cuestionarios con una tasa de respuesta del 51%. Un 33% (n = 204 era fumador y 101 personas iniciaron el programa. La abstinencia a los 12 meses fue del 45% y a los 24 meses del 33%, sin que se observaran diferencias según el sexo. La dependencia moderada o baja a la nicotina se asoció con una mayor probabilidad de estar abstinente a los 6 meses (odds ratio [OR] = 6,7; p = 0,01 y a los 12 meses (OR = 5,4; p = 0,05 ajustando por sexo, edad y seguimiento del tratamiento con sustitutos de nicotina. La prevalencia de fumadores en el cuestionario postintervención fue del 19%. Un 26% (n = 10 de los que habían dejado de fumar en el último año sin participar en el programa declaró haberlo dejado gracias a él. Conclusiones: Los resultados indican que este tipo de programa en un entorno laboral puede contribuir de forma notable a reducir el tabaquismo.Aims: To evaluate the effects of a worksite smoking cessation program conducted to reduce the prevalence of smokers among staff of the town council of Sabadell (Spain. Population and methods: A pre-post intervention study was conducted. A survey was

  20. Complex oligomeric structure of a truncated form of DdrA: A protein required for the extreme radio-tolerance of Deinococcus

    Energy Technology Data Exchange (ETDEWEB)

    Gutsche, I. [CNRS-EMBL-Univ Grenoble 1, Unit Virus Host Cell Interact UMR5233, F-38042 Grenoble (France); Vujicic-Zagar, A.; Serre, L. [CEA-CNRS-Univ Grenoble 1, Inst Biol Struct, UMR5075, Lab Prot Membranaires, F-38027 Grenoble 01 (France); Siebert, X. [CEA-CNRS-Univ Grenoble 1, Inst Biol Struct UMR5075, Lab Microscopie Elect et struct, F-38027 Grenoble 01 (France); Servant, P.; Vannier, F.; Sommer, S. [Univ Paris 11, CNRS UMR 8621, CEA LRC42V, Inst Genet et Microbiol, F-91405 Orsay (France); Castaing, B. [CNRS, UMR4301, Ctr Biophys Mol, F-45071 Orleans 02 (France); Gallet, B. [CEA-CNRS-Univ Grenoble 1, Inst Biol Struct UMR 5075, ROBIOMOL, Lab Ingn Macrom, F-38027 Grenoble 01 (France); Heulin, T.; De Groot, A. [CEA, DSV, IBEB, SBVME, Lab Ecol Microbienne Rhizosphere et Environm Extre, UMR 6191, F-13108 St Paul Les Durance (France)

    2008-07-01

    In order to preserve their genome integrity, organisms have developed elaborate tactics for genome protection and repair. The Deinococcus radiodurans bacteria famous for their extraordinary tolerance toward high doses of radiations or long period of desiccation, possess some specific genes with unknown function which are related to their survival in such extreme conditions. Among them, ddrA is an orphan gene specific of Deinococcus genomes. DdrA, the product of this gene was suggested to be a component of the DNA end protection system. Here we provide a three-dimensional reconstruction of the Deinococcus deserti DdrA(1-160) by electron microscopy. Although not functional in vivo, this truncated protein keeps its DNA binding ability at the wild-type level. DdrA(1-160) has a complex three-dimensional structure based on a hepta-meric ring that can self-associate to form a larger molecular weight assembly. We suggest that the complex architecture of DdrA plays a role in the substrate specificity and favors an efficient DNA repair. (authors)

  1. Worksite health screening programs for predicting the development of Metabolic Syndrome in middle-aged employees: a five-year follow-up study

    Directory of Open Access Journals (Sweden)

    Chen Jong-Dar

    2010-12-01

    Full Text Available Abstract Background Metabolic syndrome (MetS management programs conventionally focus on the adults having MetS. However, risk assessment for MetS development is also important for many adults potentially at risk but do not yet fulfill MetS criteria at screening. Therefore, we conducted this follow-up study to explore whether initial screening records can be efficiently applied on the prediction of the MetS occurrence in healthy middle-aged employees. Methods Utilizing health examination data, a five-year follow-up observational study was conducted for 1384 middle-aged Taiwanese employees not fulfilling MetS criteria. Data analyzed included: gender, age, MetS components, uric acid, insulin, liver enzymes, sonographic fatty liver, hepatovirus infections and lifestyle factors. Multivariate logistic regression was used to estimate the adjusted odds ratios (OR and 95% confidence interval (CI of risk for MetS development. The synergistic index (SI values and their confidence intervals of risk factor combinations were calculated; and were used to estimate the interacting effects of coupling MetS components on MetS development. Results Within five years, 13% (175 out of 1384 participants fulfilled MetS criteria. The ORs for MetS development among adults initially having one or two MetS components were 2.8 and 7.3, respectively (both p Conclusion MetS component count and combination can be used in predicting MetS development for participants potentially at risk. Worksite MetS screening programs simultaneously allow for finding out cases and for assessing risk of MetS development.

  2. Effectiveness of a worksite social & physical environment intervention on need for recovery, physical activity and relaxation; results of a randomized controlled trial.

    Science.gov (United States)

    Coffeng, Jennifer K; Boot, Cécile R L; Duijts, Saskia F A; Twisk, Jos W R; van Mechelen, Willem; Hendriksen, Ingrid J M

    2014-01-01

    To investigate the effectiveness of a worksite social and physical environment intervention on need for recovery (i.e., early symptoms of work-related mental and physical fatigue), physical activity and relaxation. Also, the effectiveness of the separate interventions was investigated. In this 2 × 2 factorial design study, 412 office employees from a financial service provider participated. Participants were allocated to the combined social and physical intervention, to the social intervention only, to the physical intervention only or to the control group. The primary outcome measure was need for recovery. Secondary outcomes were work-related stress (i.e., exhaustion, detachment and relaxation), small breaks, physical activity (i.e., stair climbing, active commuting, sport activities, light/moderate/vigorous physical activity) and sedentary behavior. Outcomes were measured by questionnaires at baseline, 6 and 12 months follow-up. Multilevel analyses were performed to investigate the effects of the three interventions. In all intervention groups, a non-significant reduction was found in need for recovery. In the combined intervention (n = 92), exhaustion and vigorous physical activities decreased significantly, and small breaks at work and active commuting increased significantly compared to the control group. The social intervention (n = 118) showed a significant reduction in exhaustion, sedentary behavior at work and a significant increase in small breaks at work and leisure activities. In the physical intervention (n = 96), stair climbing at work and active commuting significantly increased, and sedentary behavior at work decreased significantly compared to the control group. None of the interventions was effective in improving the need for recovery. It is recommended to implement the social and physical intervention among a population with higher baseline values of need for recovery. Furthermore, the intervention itself could be improved by increasing the

  3. Multi-hypothesis GPS and electronic fence data fusion for safety-critical positioning in railway worksites

    DEFF Research Database (Denmark)

    Figueiras, Joao; Gronbaek, Jesper; Schwefel, Hans-Peter

    2013-01-01

    Safety-critical applications often use position information as a mean of assessing the safety level of people. For this reason, such information is required to be precise in terms of accuracy and timeliness. This paper regards position mechanisms for personalized warning systems for railway worke...

  4. Several tetratricopeptide repeat (TPR) motifs of FANCG are required for assembly of the BRCA2/D1-D2-G-X3 complex, FANCD2 monoubiquitylation and phleomycin resistance.

    Science.gov (United States)

    Wilson, James B; Blom, Eric; Cunningham, Ryan; Xiao, Yuxuan; Kupfer, Gary M; Jones, Nigel J

    2010-07-01

    The Fanconi anaemia (FA) FANCG protein is an integral component of the FA nuclear core complex that is required for monoubiquitylation of FANCD2. FANCG is also part of another protein complex termed D1-D2-G-X3 that contains FANCD2 and the homologous recombination repair proteins BRCA2 (FANCD1) and XRCC3. Formation of the D1-D2-G-X3 complex is mediated by serine-7 phosphorylation of FANCG and occurs independently of the FA core complex and FANCD2 monoubiquitylation. FANCG contains seven tetratricopeptide repeat (TPR) motifs that mediate protein-protein interactions and here we show that mutation of several of the TPR motifs at a conserved consensus residue ablates the in vivo binding activity of FANCG. Expression of mutated TPR1, TPR2, TPR5 and TPR6 in Chinese hamster fancg mutant NM3 fails to functionally complement its hypersensitivities to mitomycin C (MMC) and phleomycin and fails to restore FANCD2 monoubiquitylation. Using co-immunoprecipitation analysis, we demonstrate that these TPR-mutated FANCG proteins fail to interact with BRCA2, XRCC3, FANCA or FANCF. The interactions of other proteins in the D1-D2-G-X3 complex are also absent, including the interaction of BRCA2 with both the monoubiquitylated (FANCD2-L) and non-ubiquitylated (FANCD2-S) isoforms of FANCD2. Interestingly, a mutation of TPR7 (R563E), that complements the MMC and phleomycin hypersensitivity of human FA-G EUFA316 cells, fails to complement NM3, despite the mutated FANCG protein co-precipitating with FANCA, BRCA2 and XRCC3. Whilst interaction of TPR7-mutated FANCG with FANCF does appear to be reduced in NM3, FANCD2 is monoubiquitylated suggesting that sub-optimal interactions of FANCG in the core complex and the D1-D2-G-X3 complex are responsible for the observed MMC- and phleomycin-hypersensitivity, rather than a defect in FANCD2 monoubiquitylation. Our data demonstrate that FANCG functions as a mediator of protein-protein interactions and is vital for the assembly of multi-protein complexes

  5. Several tetratricopeptide repeat (TPR) motifs of FANCG are required for assembly of the BRCA2/D1-D2-G-X3 complex, FANCD2 monoubiquitylation and phleomycin resistance

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, James B. [Molecular Oncology and Stem Cell Research Group, School of Biological Sciences, University of Liverpool, Biosciences Building, Crown Street, Liverpool L69 7ZB (United Kingdom); Blom, Eric [Department of Clinical Genetics and Human Genetics, VU University Medical Center, Van der Boechorststraat 7, NL-1081 BT Amsterdam (Netherlands); Cunningham, Ryan; Xiao, Yuxuan [Molecular Oncology and Stem Cell Research Group, School of Biological Sciences, University of Liverpool, Biosciences Building, Crown Street, Liverpool L69 7ZB (United Kingdom); Kupfer, Gary M. [Departments of Pediatrics and Pathology, Yale University School of Medicine, Section of Hematology/Oncology, 333 Cedar Street, New Haven, CT 0652 (United States); Jones, Nigel J., E-mail: njjones@liv.ac.uk [Molecular Oncology and Stem Cell Research Group, School of Biological Sciences, University of Liverpool, Biosciences Building, Crown Street, Liverpool L69 7ZB (United Kingdom)

    2010-07-07

    The Fanconi anaemia (FA) FANCG protein is an integral component of the FA nuclear core complex that is required for monoubiquitylation of FANCD2. FANCG is also part of another protein complex termed D1-D2-G-X3 that contains FANCD2 and the homologous recombination repair proteins BRCA2 (FANCD1) and XRCC3. Formation of the D1-D2-G-X3 complex is mediated by serine-7 phosphorylation of FANCG and occurs independently of the FA core complex and FANCD2 monoubiquitylation. FANCG contains seven tetratricopeptide repeat (TPR) motifs that mediate protein-protein interactions and here we show that mutation of several of the TPR motifs at a conserved consensus residue ablates the in vivo binding activity of FANCG. Expression of mutated TPR1, TPR2, TPR5 and TPR6 in Chinese hamster fancg mutant NM3 fails to functionally complement its hypersensitivities to mitomycin C (MMC) and phleomycin and fails to restore FANCD2 monoubiquitylation. Using co-immunoprecipitation analysis, we demonstrate that these TPR-mutated FANCG proteins fail to interact with BRCA2, XRCC3, FANCA or FANCF. The interactions of other proteins in the D1-D2-G-X3 complex are also absent, including the interaction of BRCA2 with both the monoubiquitylated (FANCD2-L) and non-ubiquitylated (FANCD2-S) isoforms of FANCD2. Interestingly, a mutation of TPR7 (R563E), that complements the MMC and phleomycin hypersensitivity of human FA-G EUFA316 cells, fails to complement NM3, despite the mutated FANCG protein co-precipitating with FANCA, BRCA2 and XRCC3. Whilst interaction of TPR7-mutated FANCG with FANCF does appear to be reduced in NM3, FANCD2 is monoubiquitylated suggesting that sub-optimal interactions of FANCG in the core complex and the D1-D2-G-X3 complex are responsible for the observed MMC- and phleomycin-hypersensitivity, rather than a defect in FANCD2 monoubiquitylation. Our data demonstrate that FANCG functions as a mediator of protein-protein interactions and is vital for the assembly of multi-protein complexes

  6. Development of a 3D Coupled Physical-Biogeochemical Model for the Marseille Coastal Area (NW Mediterranean Sea): What Complexity Is Required in the Coastal Zone?

    Science.gov (United States)

    Fraysse, Marion; Pinazo, Christel; Faure, Vincent Martin; Fuchs, Rosalie; Lazzari, Paolo; Raimbault, Patrick; Pairaud, Ivane

    2013-01-01

    Terrestrial inputs (natural and anthropogenic) from rivers, the atmosphere and physical processes strongly impact the functioning of coastal pelagic ecosystems. The objective of this study was to develop a tool for the examination of these impacts on the Marseille coastal area, which experiences inputs from the Rhone River and high rates of atmospheric deposition. Therefore, a new 3D coupled physical/biogeochemical model was developed. Two versions of the biogeochemical model were tested, one model considering only the carbon (C) and nitrogen (N) cycles and a second model that also considers the phosphorus (P) cycle. Realistic simulations were performed for a period of 5 years (2007–2011). The model accuracy assessment showed that both versions of the model were able of capturing the seasonal changes and spatial characteristics of the ecosystem. The model also reproduced upwelling events and the intrusion of Rhone River water into the Bay of Marseille well. Those processes appeared to greatly impact this coastal oligotrophic area because they induced strong increases in chlorophyll-a concentrations in the surface layer. The model with the C, N and P cycles better reproduced the chlorophyll-a concentrations at the surface than did the model without the P cycle, especially for the Rhone River water. Nevertheless, the chlorophyll-a concentrations at depth were better represented by the model without the P cycle. Therefore, the complexity of the biogeochemical model introduced errors into the model results, but it also improved model results during specific events. Finally, this study suggested that in coastal oligotrophic areas, improvements in the description and quantification of the hydrodynamics and the terrestrial inputs should be preferred over increasing the complexity of the biogeochemical model. PMID:24324589

  7. Structure of the E6/E6AP/p53 complex required for HPV-mediated degradation of p53

    Science.gov (United States)

    Martinez-Zapien, Denise; Ruiz, Francesc Xavier; Poirson, Juline; Mitschler, André; Ramirez-Ramos, Juan; Forster, Anne; Cousido-Siah, Alexandra; Masson, Murielle; Pol, Scott Vande; Podjarny, Alberto; Travé, Gilles; Zanier, Katia

    2015-01-01

    Summary The p53 pro-apoptotic tumor suppressor is mutated or functionally altered in most cancers. In epithelial tumors induced by “high-risk” mucosal Human Papillomaviruses (hrm-HPVs), including human cervical carcinoma and a growing number of head-and-neck cancers 1, p53 is degraded by the viral oncoprotein E6 2. In this process, E6 binds to a short LxxLL consensus sequence within the cellular ubiquitin ligase E6AP 3. Subsequently, the E6/E6AP heterodimer recruits and degrades p53 4. Neither E6 nor E6AP are separately able to recruit p53 3,5, and the precise mode of assembly of E6, E6AP and p53 is unknown. Here, we solved the crystal structure of a ternary complex comprising full-length HPV16 E6, the LxxLL motif of E6AP and the core domain of p53. The LxxLL motif of E6AP renders the conformation of E6 competent for interaction with p53 by structuring a p53-binding cleft on E6. Mutagenesis of critical positions at the E6-p53 interface disrupts p53 degradation. The E6-binding site of p53 is distal from previously described DNA- and protein-binding surfaces of the core domain. This suggests that, in principle, E6 may avoid competition with cellular factors by targeting both free and bound p53 molecules. The E6/E6AP/p53 complex represents a prototype of viral hijacking of both the ubiquitin-mediated protein degradation pathway and the p53 tumor suppressor pathway. The present structure provides a framework for the design of inhibitory therapeutic strategies against HPV-mediated oncogenesis. PMID:26789255

  8. ZTF-8 interacts with the 9-1-1 complex and is required for DNA damage response and double-strand break repair in the C. elegans germline.

    Directory of Open Access Journals (Sweden)

    Hyun-Min Kim

    2014-10-01

    Full Text Available Germline mutations in DNA repair genes are linked to tumor progression. Furthermore, failure in either activating a DNA damage checkpoint or repairing programmed meiotic double-strand breaks (DSBs can impair chromosome segregation. Therefore, understanding the molecular basis for DNA damage response (DDR and DSB repair (DSBR within the germline is highly important. Here we define ZTF-8, a previously uncharacterized protein conserved from worms to humans, as a novel factor involved in the repair of both mitotic and meiotic DSBs as well as in meiotic DNA damage checkpoint activation in the C. elegans germline. ztf-8 mutants exhibit specific sensitivity to γ-irradiation and hydroxyurea, mitotic nuclear arrest at S-phase accompanied by activation of the ATL-1 and CHK-1 DNA damage checkpoint kinases, as well as accumulation of both mitotic and meiotic recombination intermediates, indicating that ZTF-8 functions in DSBR. However, impaired meiotic DSBR progression partially fails to trigger the CEP-1/p53-dependent DNA damage checkpoint in late pachytene, also supporting a role for ZTF-8 in meiotic DDR. ZTF-8 partially co-localizes with the 9-1-1 DDR complex and interacts with MRT-2/Rad1, a component of this complex. The human RHINO protein rescues the phenotypes observed in ztf-8 mutants, suggesting functional conservation across species. We propose that ZTF-8 is involved in promoting repair at stalled replication forks and meiotic DSBs by transducing DNA damage checkpoint signaling via the 9-1-1 pathway. Our findings define a conserved function for ZTF-8/RHINO in promoting genomic stability in the germline.

  9. A comparative analysis of the resources required for test and evaluation on Army-led weapon system programs, based upon program size and acquisition management complexity

    OpenAIRE

    Johnson, Arne A.; Philistine, John J.

    2007-01-01

    Joint Applied Project Test and Evaluation (TandE) is an integral part of every acquisition program, as such, it consumes considerable program resources. The Department of Defense (DoD) TandE program management requirements are written to meet the risk reduction needs of large acquisition programs, but do not provide the details needed to consistently scale TandE management efforts for smaller programs across DoD. This research study investigates ways that the TandE burden to programs d...

  10. A cullin E3 ubiquitin ligase complex associates with Rik1 and the Clr4 histone H3-K9 methyltransferase and is required for RNAi-mediated heterochromatin formation.

    Science.gov (United States)

    Hong, Eun-Jin Erica; Villén, Judit; Gerace, Erica L; Gygi, Steven P; Moazed, Danesh

    2005-01-01

    The assembly of heterochromatin in fission yeast and metazoans requires histone H3-lysine 9 (-K9) methylation by the conserved Clr4/Suv39h methyltransferase. In fission yeast, H3-K9 methylation requires components of the RNAi machinery and is initiated by the RNA-Induced Transcriptional Silencing (RITS) complex. Here we report the purification of a novel complex that associates with the Clr4 methyltransferase, termed the CLRC (CLr4-Rik1-Cul4) complex. By affinity purification of the Clr4-associated protein Rik1, we show that, in addition to Clr4, Rik1 is associated with the fission yeast E3 ubiquitin ligase Cullin4 (Cul4, encoded by cul4(+)), the ubiquitin-like protein, Ned8, and two previously uncharacterized proteins, designated Cmc1 and Cmc2. In addition, the complex contains substochiometric amounts of histones H2B and H4, and the 14-3-3 protein, Rad24. Deletion of cul4(+), cmc1(+), cmc2(+) and rad24(+) results in a complete loss of silencing of a ura4(+) reporter gene inserted within centromeric DNA repeats or the silent mating type locus. Each of the above deletions also results in accumulation of noncoding RNAs transcribed from centromeric repeats and telomeric DNA regions, and a corresponding loss of small RNAs that are homologous to centromeric repeats, suggesting a defect in the processing of noncoding RNA to small RNA. Based on these results, we propose that the components of the Clr4-Rik1-Cul4 complex act concertedly at an early step in heterochromatin formation.

  11. Glucocorticoid-induced tethered transrepression requires SUMOylation of GR and formation of a SUMO-SMRT/NCoR1-HDAC3 repressing complex

    Science.gov (United States)

    Hua, Guoqiang; Ganti, Krishna Priya; Chambon, Pierre

    2016-01-01

    Upon binding of a glucocorticoid (GC), the GC receptor (GR) can exert one of three transcriptional regulatory functions. We recently reported that SUMOylation of the GR at position K293 in humans (K310 in mice) within the N-terminal domain is indispensable for GC-induced evolutionary conserved inverted repeated negative GC response element (IR nGRE)-mediated direct transrepression. We now demonstrate that the integrity of this GR SUMOylation site is mandatory for the formation of a GR-small ubiquitin-related modifiers (SUMOs)-SMRT/NCoR1-HDAC3 repressing complex, which is indispensable for NF-κB/AP1-mediated GC-induced tethered indirect transrepression in vitro. Using GR K310R mutant mice or mice containing the N-terminal truncated GR isoform GRα-D3 lacking the K310 SUMOylation site, revealed a more severe skin inflammation than in WT mice. Importantly, cotreatment with dexamethasone (Dex) could not efficiently suppress a 12-O-tetradecanoylphorbol-13-acetate (TPA)–induced skin inflammation in these mutant mice, whereas it was clearly decreased in WT mice. In addition, in mice selectively ablated in skin keratinocytes for either nuclear receptor corepressor 1 (NCoR1)/silencing mediator for retinoid or thyroid-hormone receptors (SMRT) corepressors or histone deacetylase 3 (HDAC3), Dex-induced tethered transrepression and the formation of a repressing complex on DNA-bound NF-κB/AP1 were impaired. We previously suggested that GR ligands that would lack both (+)GRE-mediated transactivation and IR nGRE-mediated direct transrepression activities of GCs may preferentially exert the therapeutically beneficial GC antiinflammatory properties. Interestingly, we now identified a nonsteroidal antiinflammatory selective GR agonist (SEGRA) that selectively lacks both Dex-induced (+)GRE-mediated transactivation and IR nGRE-mediated direct transrepression functions, while still exerting a tethered indirect transrepression activity and could therefore be clinically lesser

  12. Unusual Development of Iatrogenic Complex, Mixed Biliary and Duodenal Fistulas Complicating Roux-en-Y Antrectomy for Stenotic Peptic Disease of the Supraampullary Duodenum Requiring Whipple Procedure: An Uncommon Clinical Dilemma

    Directory of Open Access Journals (Sweden)

    Francesco A. Polistina

    2010-10-01

    Full Text Available Complex fistulas of the duodenum and biliary tree are severe complications of gastric surgery. The association of duodenal and major biliary fistulas occurs rarely and is a major challenge for treatment. They may occur during virtually any kind of operation, but they are more frequent in cases complicated by the presence of difficult duodenal ulcers or cancer, with a mortality rate of up to 35%. Options for treatment are many and range from simple drainage to extended resections and difficult reconstructions. Conservative treatment is the choice for well-drained fistulas, but some cases require reoperation. Very little is known about reoperation techniques and technical selection of the right patients. We present the case of a complex iatrogenic duodenal and biliary fistula. A 42-year-old Caucasian man with a diagnosis of postoperative peritonitis had been operated on 3 days earlier; an antrectomy with a Roux-en-Y reconstruction for stenotic peptic disease was performed. Conservative treatment was attempted with mixed results. Two more operations were required to achieve a definitive resolution of the fistula and related local complications. The decision was made to perform a pancreatoduodenectomy with subsequent reconstruction on a double jejunal loop. The patient did well and was discharged on postoperative day 17. In our experience pancreaticoduodenectomy may be an effective treatment of refractory and complex iatrogenic fistulas involving both the duodenum and the biliary tree.

  13. Unusual Development of Iatrogenic Complex, Mixed Biliary and Duodenal Fistulas Complicating Roux-en-Y Antrectomy for Stenotic Peptic Disease of the Supraampullary Duodenum Requiring Whipple Procedure: An Uncommon Clinical Dilemma

    Science.gov (United States)

    Polistina, Francesco A.; Costantin, Giorgio; Settin, Alessandro; Lumachi, Franco; Ambrosino, Giovanni

    2010-01-01

    Complex fistulas of the duodenum and biliary tree are severe complications of gastric surgery. The association of duodenal and major biliary fistulas occurs rarely and is a major challenge for treatment. They may occur during virtually any kind of operation, but they are more frequent in cases complicated by the presence of difficult duodenal ulcers or cancer, with a mortality rate of up to 35%. Options for treatment are many and range from simple drainage to extended resections and difficult reconstructions. Conservative treatment is the choice for well-drained fistulas, but some cases require reoperation. Very little is known about reoperation techniques and technical selection of the right patients. We present the case of a complex iatrogenic duodenal and biliary fistula. A 42-year-old Caucasian man with a diagnosis of postoperative peritonitis had been operated on 3 days earlier; an antrectomy with a Roux-en-Y reconstruction for stenotic peptic disease was performed. Conservative treatment was attempted with mixed results. Two more operations were required to achieve a definitive resolution of the fistula and related local complications. The decision was made to perform a pancreatoduodenectomy with subsequent reconstruction on a double jejunal loop. The patient did well and was discharged on postoperative day 17. In our experience pancreaticoduodenectomy may be an effective treatment of refractory and complex iatrogenic fistulas involving both the duodenum and the biliary tree. PMID:21103208

  14. Measurement of Nursing's Complex Health Care Work: Evolution of the Science For Determining the Required Staffing For Safe and Effective Patient Care.

    Science.gov (United States)

    Malloch, Kathy

    2015-01-01

    The availability of technology to monitor and manage data increases our ability to better understand the processes and outcomes needed for patient care. It is important to remember this work requires not only the science of data management, but also the art of integrating the multiple variables involved in the dynamic of safe staffing. Fasoli and Haddock (2010) provided an excellent summary of the literature. Nurse leaders must be open to new additions to this work and the possibility that the essential ingredient of the gold standard for patient classification systems (PCS) might still be missing. The goal of a new approach to determine time for nurse work was to advance the science of PCS from the perspective of the characteristics identified by Fasoli and Haddock.

  15. Biofilm formation by Bacillus subtilis requires an endoribonuclease-containing multisubunit complex that controls mRNA levels for the matrix gene repressor SinR.

    Science.gov (United States)

    DeLoughery, Aaron; Dengler, Vanina; Chai, Yunrong; Losick, Richard

    2016-01-01

    Biofilm formation by Bacillus subtilis is largely governed by a circuit in which the response regulator Spo0A turns on the gene for the anti-repressor SinI. SinI, in turn, binds to and inactivates SinR, a dedicated repressor of genes for matrix production. Mutants of the genes ylbF, ymcA and yaaT are blocked in biofilm formation, but the mechanism by which they act has been mysterious. A recent report attributed their role in biofilm formation to stimulating Spo0A activity. However, we detect no measurable effect on the transcription of sinI. Instead, we find that the block in biofilm formation is caused by an increase in the levels of SinR and of its mRNA. Evidence is presented that YlbF, YmcA and YaaT interact with, and control the activity of, RNase Y, which is known to destabilize sinR mRNA. We also show that the processing of another target of RNase Y, cggR-gapA mRNA, similarly depends on YlbF and YmcA. Our work suggests that sinR mRNA stability is an additional posttranscriptional control mechanism governing the switch to multicellularity and raises the possibility that YlbF, YmcA and YaaT broadly regulate mRNA stability as part of an RNase Y-containing, multi-subunit complex.

  16. Crystal structure of the human LRH-1 DBD-DNA complex reveals Ftz-F1 domain positioning is required for receptor activity.

    Science.gov (United States)

    Solomon, Isaac H; Hager, Janet M; Safi, Rachid; McDonnell, Donald P; Redinbo, Matthew R; Ortlund, Eric A

    2005-12-16

    The DNA-binding and ligand-binding functions of nuclear receptors are localized to independent domains separated by a flexible hinge. The DNA-binding domain (DBD) of the human liver receptor homologue-1 (hLRH-1), which controls genes central to development and metabolic homeostasis, interacts with monomeric DNA response elements and contains an Ftz-F1 motif that is unique to the NR5A nuclear receptor subfamily. Here, we present the 2.2A resolution crystal structure of the hLRH-1 DBD in complex with duplex DNA, and elucidate the sequence-specific DNA contacts essential for the ability of LRH-1 to bind to DNA as a monomer. We show that the unique Ftz-F1 domain folds into a novel helix that packs against the DBD but does not contact DNA. Mutations expected to disrupt the positioning of the Ftz-F1 helix do not eliminate DNA binding but reduce the transcriptional activity of full-length LRH-1 significantly. Moreover, we find that altering the Ftz-F1 helix positioning eliminates the enhancement of LRH-1-mediated transcription by the coactivator GRIP1, an action that is associated primarily with the distantly located ligand-binding domain (LBD). Taken together, these results indicate that subtle structural changes in a nuclear receptor DBD can exert long-range functional effects on the LBD of a receptor, and significantly impact transcriptional regulation.

  17. A yeast two-hybrid screen for SYP-3 interactors identifies SYP-4, a component required for synaptonemal complex assembly and chiasma formation in Caenorhabditis elegans meiosis.

    Directory of Open Access Journals (Sweden)

    Sarit Smolikov

    2009-10-01

    Full Text Available The proper assembly of the synaptonemal complex (SC between homologs is critical to ensure accurate meiotic chromosome segregation. The SC is a meiotic tripartite structure present from yeast to humans, comprised of proteins assembled along the axes of the chromosomes and central region (CR proteins that bridge the two chromosome axes. Here we identify SYP-4 as a novel structural component of the SC in Caenorhabditis elegans. SYP-4 interacts in a yeast two-hybrid assay with SYP-3, one of components of the CR of the SC, and is localized at the interface between homologs during meiosis. SYP-4 is essential for the localization of SYP-1, SYP-2, and SYP-3 CR proteins onto chromosomes, thereby playing a crucial role in the stabilization of pairing interactions between homologous chromosomes. In the absence of SYP-4, the levels of recombination intermediates, as indicated by RAD-51 foci, are elevated in mid-prophase nuclei, and crossover recombination events are significantly reduced. The lack of chiasmata observed in syp-4 mutants supports the elevated levels of chromosome nondisjunction manifested in high embryonic lethality. Altogether our findings place SYP-4 as a central player in SC formation and broaden our understanding of the structure of the SC and its assembly.

  18. CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs

    Science.gov (United States)

    Merveille, Anne-Christine; Davis, Erica E; Becker-Heck, Anita; Legendre, Marie; Amirav, Israel; Bataille, Géraldine; Belmont, John; Beydon, Nicole; Billen, Frédéric; Clément, Annick; Clercx, Cécile; Coste, André; Crosbie, Rachelle; de Blic, Jacques; Deleuze, Stephane; Duquesnoy, Philippe; Escalier, Denise; Escudier, Estelle; Fliegauf, Manfred; Horvath, Judith; Hill, Kent; Jorissen, Mark; Just, Jocelyne; Kispert, Andreas; Lathrop, Mark; Loges, Niki Tomas; Marthin, June K; Momozawa, Yukihide; Montantin, Guy; Nielsen, Kim G; Olbrich, Heike; Papon, Jean-François; Rayet, Isabelle; Roger, Gilles; Schmidts, Miriam; Tenreiro, Henrique; Towbin, Jeffrey A; Zelenika, Diana; Zentgraf, Hanswalter; Georges, Michel; Lequarré, Anne-Sophie; Katsanis, Nicholas; Omran, Heymut; Amselem, Serge

    2012-01-01

    Primary ciliary dyskinesia (PCD) is an inherited disorder characterized by recurrent infections of the upper and lower respiratory tract, reduced fertility in males and situs inversus in about 50% of affected individuals (Kartagener syndrome). It is caused by motility defects in the respiratory cilia that are responsible for airway clearance, the flagella that propel sperm cells and the nodal monocilia that determine left-right asymmetry1. Recessive mutations that cause PCD have been identified in genes encoding components of the outer dynein arms, radial spokes and cytoplasmic pre-assembly factors of axonemal dyneins, but these mutations account for only about 50% of cases of PCD. We exploited the unique properties of dog populations to positionally clone a new PCD gene, CCDC39. We found that loss-of-function mutations in the human ortholog underlie a substantial fraction of PCD cases with axonemal disorganization and abnormal ciliary beating. Functional analyses indicated that CCDC39 localizes to ciliary axonemes and is essential for assembly of inner dynein arms and the dynein regulatory complex. PMID:21131972

  19. CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs.

    Science.gov (United States)

    Merveille, Anne-Christine; Davis, Erica E; Becker-Heck, Anita; Legendre, Marie; Amirav, Israel; Bataille, Géraldine; Belmont, John; Beydon, Nicole; Billen, Frédéric; Clément, Annick; Clercx, Cécile; Coste, André; Crosbie, Rachelle; de Blic, Jacques; Deleuze, Stephane; Duquesnoy, Philippe; Escalier, Denise; Escudier, Estelle; Fliegauf, Manfred; Horvath, Judith; Hill, Kent; Jorissen, Mark; Just, Jocelyne; Kispert, Andreas; Lathrop, Mark; Loges, Niki Tomas; Marthin, June K; Momozawa, Yukihide; Montantin, Guy; Nielsen, Kim G; Olbrich, Heike; Papon, Jean-François; Rayet, Isabelle; Roger, Gilles; Schmidts, Miriam; Tenreiro, Henrique; Towbin, Jeffrey A; Zelenika, Diana; Zentgraf, Hanswalter; Georges, Michel; Lequarré, Anne-Sophie; Katsanis, Nicholas; Omran, Heymut; Amselem, Serge

    2011-01-01

    Primary ciliary dyskinesia (PCD) is an inherited disorder characterized by recurrent infections of the upper and lower respiratory tract, reduced fertility in males and situs inversus in about 50% of affected individuals (Kartagener syndrome). It is caused by motility defects in the respiratory cilia that are responsible for airway clearance, the flagella that propel sperm cells and the nodal monocilia that determine left-right asymmetry. Recessive mutations that cause PCD have been identified in genes encoding components of the outer dynein arms, radial spokes and cytoplasmic pre-assembly factors of axonemal dyneins, but these mutations account for only about 50% of cases of PCD. We exploited the unique properties of dog populations to positionally clone a new PCD gene, CCDC39. We found that loss-of-function mutations in the human ortholog underlie a substantial fraction of PCD cases with axonemal disorganization and abnormal ciliary beating. Functional analyses indicated that CCDC39 localizes to ciliary axonemes and is essential for assembly of inner dynein arms and the dynein regulatory complex.

  20. Emi2 inhibition of the anaphase-promoting complex/cyclosome absolutely requires Emi2 binding via the C-terminal RL tail.

    Science.gov (United States)

    Ohe, Munemichi; Kawamura, Yoshiko; Ueno, Hiroyuki; Inoue, Daigo; Kanemori, Yoshinori; Senoo, Chiharu; Isoda, Michitaka; Nakajo, Nobushige; Sagata, Noriyuki

    2010-03-15

    Emi2 (also called Erp1) inhibits the anaphase-promoting complex/cyclosome (APC/C) and thereby causes metaphase II arrest in unfertilized vertebrate eggs. Both the D-box and the zinc-binding region (ZBR) of Emi2 have been implicated in APC/C inhibition. However, it is not well known how Emi2 interacts with and hence inhibits the APC/C. Here we show that Emi2 binds the APC/C via the C-terminal tail, termed here the RL tail. When expressed in Xenopus oocytes and egg extracts, Emi2 lacking the RL tail fails to interact with and inhibit the APC/C. The RL tail itself can directly bind to the APC/C, and, when added to egg extracts, either an excess of RL tail peptides or anti-RL tail peptide antibody can dissociate endogenous Emi2 from the APC/C, thus allowing APC/C activation. Furthermore, and importantly, the RL tail-mediated binding apparently promotes the inhibitory interactions of the D-box and the ZBR (of Emi2) with the APC/C. Finally, Emi1, a somatic paralog of Emi2, also has a functionally similar RL tail. We propose that the RL tail of Emi1/Emi2 serves as a docking site for the APC/C, thereby promoting the interaction and inhibition of the APC/C by the D-box and the ZBR.

  1. G9a/GLP histone lysine dimethyltransferase complex activity in the hippocampus and the entorhinal cortex is required for gene activation and silencing during memory consolidation.

    Science.gov (United States)

    Gupta-Agarwal, Swati; Franklin, Aimee V; Deramus, Thomas; Wheelock, Muriah; Davis, Robin L; McMahon, Lori L; Lubin, Farah D

    2012-04-18

    Learning triggers alterations in gene transcription in brain regions such as the hippocampus and the entorhinal cortex (EC) that are necessary for long-term memory (LTM) formation. Here, we identify an essential role for the G9a/G9a-like protein (GLP) lysine dimethyltransferase complex and the histone H3 lysine 9 dimethylation (H3K9me2) marks it catalyzes, in the transcriptional regulation of genes in area CA1 of the rat hippocampus and the EC during memory consolidation. Contextual fear learning increased global levels of H3K9me2 in area CA1 and the EC, with observable changes at the Zif268, DNMT3a, BDNF exon IV, and cFOS gene promoters, which occurred in concert with mRNA expression. Inhibition of G9a/GLP in the EC, but not in the hippocampus, enhanced contextual fear conditioning relative to control animals. The inhibition of G9a/GLP in the EC induced several histone modifications that include not only methylation but also acetylation. Surprisingly, we found that downregulation of G9a/GLP activity in the EC enhanced H3K9me2 in area CA1, resulting in transcriptional silencing of the non-memory permissive gene COMT in the hippocampus. In addition, synaptic plasticity studies at two distinct EC-CA1 cellular pathways revealed that G9a/GLP activity is critical for hippocampus-dependent long-term potentiation initiated in the EC via the perforant pathway, but not the temporoammonic pathway. Together, these data demonstrate that G9a/GLP differentially regulates gene transcription in the hippocampus and the EC during memory consolidation. Furthermore, these findings support the possibility of a role for G9a/GLP in the regulation of cellular and molecular cross talk between these two brain regions during LTM formation.

  2. Microprocessor complex subunit DiGeorge syndrome critical region gene 8 (Dgcr8) is required for schwann cell myelination and myelin maintenance.

    Science.gov (United States)

    Lin, Hsin-Pin; Oksuz, Idil; Hurley, Edward; Wrabetz, Lawrence; Awatramani, Rajeshwar

    2015-10-02

    We investigated the role of a key component of the Microprocessor complex, DGCR8, in the regulation of myelin formation and maintenance. We found that conditionally ablating Dgcr8 in Schwann cells (SCs) during development results in an arrest of SC differentiation. Dgcr8 conditional knock-out (cKO) SCs fail to form 1:1 relationships with axons or, having achieved this, fail to form myelin sheaths. The expression of genes normally found in immature SCs, such as sex-determining region Y-box 2 (Sox2), is increased in Dgcr8 cKO SCs, whereas the expression of myelin-related genes, including the master regulatory transcription factor early growth response 2 (Egr2), is decreased. Additionally, expression of a novel gene expression program involving sonic hedgehog (Shh), activated de novo in injured nerves, is elevated in Dgcr8 cKOs but not in Egr2 null mice, a model of SC differentiation arrest, suggesting that the injury-related gene expression program in Dgcr8 cKOs cannot be attributed to differentiation arrest. Inducible ablation of Dgcr8 in adult SCs results in gene expression changes similar to those found in cKOs, including an increase in the expression of Sox2 and Shh. Analyses of these nerves mainly reveal normal myelin thickness and axon size distribution but some dedifferentiated SCs and increased macrophage infiltration. Together our data suggest that Dgcr8 is responsible for modulation of gene expression programs underlying myelin formation and maintenance as well as suppression of an injury-related gene expression program.

  3. Inheritance of an epigenetic mark: the CpG DNA methyltransferase 1 is required for de novo establishment of a complex pattern of non-CpG methylation.

    Directory of Open Access Journals (Sweden)

    Valérie Grandjean

    Full Text Available Site-specific methylation of cytosines is a key epigenetic mark of vertebrate DNA. While a majority of the methylated residues are in the symmetrical (meCpG:Gp(meC configuration, a smaller, but significant fraction is found in the CpA, CpT and CpC asymmetric (non-CpG dinucleotides. CpG methylation is reproducibly maintained by the activity of the DNA methyltransferase 1 (Dnmt1 on the newly replicated hemimethylated substrates (meCpG:GpC. On the other hand, establishment and hereditary maintenance of non-CpG methylation patterns have not been analyzed in detail. We previously reported the occurrence of site- and allele-specific methylation at both CpG and non-CpG sites. Here we characterize a hereditary complex of non-CpG methylation, with the transgenerational maintenance of three distinct profiles in a constant ratio, associated with extensive CpG methylation. These observations raised the question of the signal leading to the maintenance of the pattern of asymmetric methylation. The complete non-CpG pattern was reinstated at each generation in spite of the fact that the majority of the sperm genomes contained either none or only one methylated non-CpG site. This observation led us to the hypothesis that the stable CpG patterns might act as blueprints for the maintenance of non-CpG DNA methylation. As predicted, non-CpG DNA methylation profiles were abrogated in a mutant lacking Dnmt1, the enzymes responsible for CpG methylation, but not in mutants defective for either Dnmt3a or Dnmt2.

  4. Mammalian target of rapamycin complex 1 activation is required for the stimulation of human skeletal muscle protein synthesis by essential amino acids.

    Science.gov (United States)

    Dickinson, Jared M; Fry, Christopher S; Drummond, Micah J; Gundermann, David M; Walker, Dillon K; Glynn, Erin L; Timmerman, Kyle L; Dhanani, Shaheen; Volpi, Elena; Rasmussen, Blake B

    2011-05-01

    The relationship between mammalian target of rapamycin complex 1 (mTORC1) signaling and muscle protein synthesis during instances of amino acid surplus in humans is based solely on correlational data. Therefore, the goal of this study was to use a mechanistic approach specifically designed to determine whether increased mTORC1 activation is requisite for the stimulation of muscle protein synthesis following L-essential amino acid (EAA) ingestion in humans. Examination of muscle protein synthesis and signaling were performed on vastus lateralis muscle biopsies obtained from 8 young (25 ± 2 y) individuals who were studied prior to and following ingestion of 10 g of EAA during 2 separate trials in a randomized, counterbalanced design. The trials were identical except during 1 trial, participants were administered a single oral dose of a potent mTORC1 inhibitor (rapamycin) prior to EAA ingestion. In response to EAA ingestion, an ~60% increase in muscle protein synthesis was observed during the control trial, concomitant with increased phosphorylation of mTOR (Ser(2448)), ribosomal S6 kinase 1 (Thr(389)), and eukaryotic initiation factor 4E binding protein 1 (Thr(37/46)). In contrast, prior administration of rapamycin completely blocked the increase in muscle protein synthesis and blocked or attenuated activation of mTORC1-signaling proteins. The inhibition of muscle protein synthesis and signaling was not due to differences in either extracellular or intracellular amino acid availability, because these variables were similar between trials. These data support a fundamental role for mTORC1 activation as a key regulator of human muscle protein synthesis in response to increased EAA availability. This information will be useful in the development of evidence-based nutritional therapies targeting mTORC1 to counteract muscle wasting associated with numerous clinical conditions.

  5. Monomeric TonB and the Ton box are required for the formation of a high-affinity transporter-TonB complex.

    Science.gov (United States)

    Freed, Daniel M; Lukasik, Stephen M; Sikora, Arthur; Mokdad, Audrey; Cafiso, David S

    2013-04-16

    The energy-dependent uptake of trace nutrients by Gram-negative bacteria involves the coupling of an outer membrane transport protein to the transperiplasmic protein TonB. In this study, a soluble construct of Escherichia coli TonB (residues 33-239) was used to determine the affinity of TonB for outer membrane transporters BtuB, FecA, and FhuA. Using fluorescence anisotropy, TonB(33-239) was found to bind with high affinity (tens of nanomolar) to both BtuB and FhuA; however, no high-affinity binding to FecA was observed. In BtuB, the high-affinity binding of TonB(33-239) was eliminated by mutations in the Ton box, which yield transport-defective protein, or by the addition of a Colicin E3 fragment, which stabilizes the Ton box in a folded state. These results indicate that transport requires a high-affinity transporter-TonB interaction that is mediated by the Ton box. Characterization of TonB(33-239) using double electron-electron resonance (DEER) demonstrates that a significant population of TonB(33-239) exists as a dimer; moreover, interspin distances are in approximate agreement with interlocked dimers observed previously by crystallography for shorter TonB fragments. When the TonB(33-239) dimer is bound to the outer membrane transporter, DEER shows that the TonB(33-239) dimer is converted to a monomeric form, suggesting that a dimer-monomer conversion takes place at the outer membrane during the TonB-dependent transport cycle.

  6. The E3 Ubiquitin Ligase Activity Associated with the Adenoviral E1B-55K–E4orf6 Complex Does Not Require CRM1-Dependent Export ▿

    OpenAIRE

    Schmid, Melanie; Kindsmüller, Kathrin; Wimmer, Peter; Groitl, Peter; Gonzalez, Ramon A.; Dobner, Thomas

    2011-01-01

    The adenovirus type 5 (Ad5) E1B-55K and E4orf6 (E1B-55K/E4orf6) proteins are multifunctional regulators of Ad5 replication, participating in many processes required for virus growth. A complex containing the two proteins mediates the degradation of cellular proteins through assembly of an E3 ubiquitin ligase and induces shutoff of host cell protein synthesis through selective nucleocytoplasmic viral late mRNA export. Both proteins shuttle between the nuclear and cytoplasmic compartments via l...

  7. Complex analysis

    CERN Document Server

    Freitag, Eberhard

    2005-01-01

    The guiding principle of this presentation of ``Classical Complex Analysis'' is to proceed as quickly as possible to the central results while using a small number of notions and concepts from other fields. Thus the prerequisites for understanding this book are minimal; only elementary facts of calculus and algebra are required. The first four chapters cover the essential core of complex analysis: - differentiation in C (including elementary facts about conformal mappings) - integration in C (including complex line integrals, Cauchy's Integral Theorem, and the Integral Formulas) - sequences and series of analytic functions, (isolated) singularities, Laurent series, calculus of residues - construction of analytic functions: the gamma function, Weierstrass' Factorization Theorem, Mittag-Leffler Partial Fraction Decomposition, and -as a particular highlight- the Riemann Mapping Theorem, which characterizes the simply connected domains in C. Further topics included are: - the theory of elliptic functions based on...

  8. The ACTIVATE study: results from a group-randomized controlled trial comparing a traditional worksite health promotion program with an activated consumer program.

    Science.gov (United States)

    Terry, Paul E; Fowles, Jinnet Briggs; Xi, Min; Harvey, Lisa

    2011-01-01

    PURPOSE. This study compares a traditional worksite-based health promotion program with an activated consumer program and a control program DESIGN. Group randomized controlled trial with 18-month intervention. SETTING. Two large Midwestern companies. SUBJECTS. Three hundred and twenty employees (51% response). INTERVENTION. The traditional health promotion intervention offered population-level campaigns on physical activity, nutrition, and stress management. The activated consumer intervention included population-level campaigns for evaluating health information, choosing a health benefits plan, and understanding the risks of not taking medications as prescribed. The personal development intervention (control group) offered information on hobbies. The interventions also offered individual-level coaching for high risk individuals in both active intervention groups. MEASURES. Health risk status, general health status, consumer activation, productivity, and the ability to evaluate health information. ANALYSIS. Multivariate analyses controlled for baseline differences among the study groups. RESULTS. At the population level, compared with baseline performance, the traditional health promotion intervention improved health risk status, consumer activation, and the ability to recognize reliable health websites. Compared with baseline performance, the activated consumer intervention improved consumer activation, productivity, and the ability to recognize reliable health websites. At the population level, however, only the activated consumer intervention improved any outcome more than the control group did; that outcome was consumer activation. At the individual level for high risk individuals, both traditional health coaching and activated consumer coaching positively affected health risk status and consumer activation. In addition, both coaching interventions improved participant ability to recognize a reliable health website. Consumer activation coaching also

  9. Effectiveness of a worksite social & physical environment intervention on need for recovery, physical activity and relaxation; results of a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Jennifer K Coffeng

    Full Text Available OBJECTIVE: To investigate the effectiveness of a worksite social and physical environment intervention on need for recovery (i.e., early symptoms of work-related mental and physical fatigue, physical activity and relaxation. Also, the effectiveness of the separate interventions was investigated. METHODS: In this 2 × 2 factorial design study, 412 office employees from a financial service provider participated. Participants were allocated to the combined social and physical intervention, to the social intervention only, to the physical intervention only or to the control group. The primary outcome measure was need for recovery. Secondary outcomes were work-related stress (i.e., exhaustion, detachment and relaxation, small breaks, physical activity (i.e., stair climbing, active commuting, sport activities, light/moderate/vigorous physical activity and sedentary behavior. Outcomes were measured by questionnaires at baseline, 6 and 12 months follow-up. Multilevel analyses were performed to investigate the effects of the three interventions. RESULTS: In all intervention groups, a non-significant reduction was found in need for recovery. In the combined intervention (n = 92, exhaustion and vigorous physical activities decreased significantly, and small breaks at work and active commuting increased significantly compared to the control group. The social intervention (n = 118 showed a significant reduction in exhaustion, sedentary behavior at work and a significant increase in small breaks at work and leisure activities. In the physical intervention (n = 96, stair climbing at work and active commuting significantly increased, and sedentary behavior at work decreased significantly compared to the control group. CONCLUSION: None of the interventions was effective in improving the need for recovery. It is recommended to implement the social and physical intervention among a population with higher baseline values of need for recovery. Furthermore, the

  10. A systematic review of internet-based worksite wellness approaches for cardiovascular disease risk management: outcomes, challenges & opportunities.

    Directory of Open Access Journals (Sweden)

    Ehimen C Aneni

    Full Text Available CONTEXT: The internet is gaining popularity as a means of delivering employee-based cardiovascular (CV wellness interventions though little is known about the cardiovascular health outcomes of these programs. In this review, we examined the effectiveness of internet-based employee cardiovascular wellness and prevention programs. EVIDENCE ACQUISITION: We conducted a systematic review by searching PubMed, Web of Science and Cochrane library for all published studies on internet-based programs aimed at improving CV health among employees up to November 2012. We grouped the outcomes according to the American Heart Association (AHA indicators of cardiovascular wellbeing--weight, BP, lipids, smoking, physical activity, diet, and blood glucose. EVIDENCE SYNTHESIS: A total of 18 randomized trials and 11 follow-up studies met our inclusion/exclusion criteria. Follow-up duration ranged from 6-24 months. There were significant differences in intervention types and number of components in each intervention. Modest improvements were observed in more than half of the studies with weight related outcomes while no improvement was seen in virtually all the studies with physical activity outcome. In general, internet-based programs were more successful if the interventions also included some physical contact and environmental modification, and if they were targeted at specific disease entities such as hypertension. Only a few of the studies were conducted in persons at-risk for CVD, none in blue-collar workers or low-income earners. CONCLUSION: Internet based programs hold promise for improving the cardiovascular wellness among employees however much work is required to fully understand its utility and long term impact especially in special/at-risk populations.

  11. Mis17 is a regulatory module of the Mis6-Mal2-Sim4 centromere complex that is required for the recruitment of CenH3/CENP-A in fission yeast.

    Directory of Open Access Journals (Sweden)

    Yoshiharu Shiroiwa

    Full Text Available BACKGROUND: The centromere is the chromosome domain on which the mitotic kinetochore forms for proper segregation. Deposition of the centromeric histone H3 (CenH3, CENP-A is vital for the formation of centromere-specific chromatin. The Mis6-Mal2-Sim4 complex of the fission yeast S. pombe is required for the recruitment of CenH3 (Cnp1, but its function remains obscure. METHODOLOGY/PRINCIPAL FINDINGS: Mass spectrometry was performed on the proteins precipitated with Mis6- and Mis17-FLAG. The results together with the previously identified Sim4- and Mal2-TAP precipitated proteins indicated that the complex contains 12 subunits, Mis6, Sim4, Mal2, Mis15, Mis17, Cnl2, Fta1-4, Fta6-7, nine of which have human centromeric protein (CENP counterparts. Domain dissection indicated that the carboxy-half of Mis17 is functional, while its amino-half is regulatory. Overproduction of the amino-half caused strong negative dominance, which led to massive chromosome missegregation and hypersensitivity to the histone deacetylase inhibitor TSA. Mis17 was hyperphosphorylated and overproduction-induced negative dominance was abolished in six kinase-deletion mutants, ssp2 (AMPK, ppk9 (AMPK, ppk15 (Yak1, ppk30 (Ark1, wis4 (Ssk2, and lsk1 (P-TEFb. CONCLUSIONS: Mis17 may be a regulatory module of the Mis6 complex. Negative dominance of the Mis17 fragment is exerted while the complex and CenH3 remain at the centromere, a result that differs from the mislocalization seen in the mis17-362 mutant. The known functions of the kinases suggest an unexpected link between Mis17 and control of the cortex actin, nutrition, and signal/transcription. Possible interpretations are discussed.

  12. Requirements Reasoning for Distributed Requirements Analysis using Semantic Wiki

    NARCIS (Netherlands)

    Liang, Peng; Avgeriou, Paris; Clerc, Viktor

    2009-01-01

    In large-scale collaborative software projects, thousands of requirements with complex interdependencies and different granularity spreading in different levels are elicited, documented, and evolved during the project lifecycle. Non-technical stakeholders involved in requirements engineering activit

  13. The C-terminal Domain (CTD) of Human DNA Glycosylase NEIL1 Is Required for Forming BERosome Repair Complex with DNA Replication Proteins at the Replicating Genome: DOMINANT NEGATIVE FUNCTION OF THE CTD.

    Science.gov (United States)

    Hegde, Pavana M; Dutta, Arijit; Sengupta, Shiladitya; Mitra, Joy; Adhikari, Sanjay; Tomkinson, Alan E; Li, Guo-Min; Boldogh, Istvan; Hazra, Tapas K; Mitra, Sankar; Hegde, Muralidhar L

    2015-08-21

    The human DNA glycosylase NEIL1 was recently demonstrated to initiate prereplicative base excision repair (BER) of oxidized bases in the replicating genome, thus preventing mutagenic replication. A significant fraction of NEIL1 in cells is present in large cellular complexes containing DNA replication and other repair proteins, as shown by gel filtration. However, how the interaction of NEIL1 affects its recruitment to the replication site for prereplicative repair was not investigated. Here, we show that NEIL1 binarily interacts with the proliferating cell nuclear antigen clamp loader replication factor C, DNA polymerase δ, and DNA ligase I in the absence of DNA via its non-conserved C-terminal domain (CTD); replication factor C interaction results in ∼8-fold stimulation of NEIL1 activity. Disruption of NEIL1 interactions within the BERosome complex, as observed for a NEIL1 deletion mutant (N311) lacking the CTD, not only inhibits complete BER in vitro but also prevents its chromatin association and reduced recruitment at replication foci in S phase cells. This suggests that the interaction of NEIL1 with replication and other BER proteins is required for efficient repair of the replicating genome. Consistently, the CTD polypeptide acts as a dominant negative inhibitor during in vitro repair, and its ectopic expression sensitizes human cells to reactive oxygen species. We conclude that multiple interactions among BER proteins lead to large complexes, which are critical for efficient BER in mammalian cells, and the CTD interaction could be targeted for enhancing drug/radiation sensitivity of tumor cells.

  14. Cyclin-Dependent Kinase CRK9, Required for Spliced Leader trans Splicing of Pre-mRNA in Trypanosomes, Functions in a Complex with a New L-Type Cyclin and a Kinetoplastid-Specific Protein.

    Science.gov (United States)

    Badjatia, Nitika; Park, Sung Hee; Ambrósio, Daniela L; Kirkham, Justin K; Günzl, Arthur

    2016-03-01

    In eukaryotes, cyclin-dependent kinases (CDKs) control the cell cycle and critical steps in gene expression. The lethal parasite Trypanosoma brucei, member of the phylogenetic order Kinetoplastida, possesses eleven CDKs which, due to high sequence divergence, were generically termed CDC2-related kinases (CRKs). While several CRKs have been implied in the cell cycle, CRK9 was the first trypanosome CDK shown to control the unusual mode of gene expression found in kinetoplastids. In these organisms, protein-coding genes are arranged in tandem arrays which are transcribed polycistronically. Individual mRNAs are processed from precursor RNA by spliced leader (SL) trans splicing and polyadenylation. CRK9 ablation was lethal in cultured trypanosomes, causing a block of trans splicing before the first transesterification step. Additionally, CRK9 silencing led to dephosphorylation of RNA polymerase II and to hypomethylation of the SL cap structure. Here, we tandem affinity-purified CRK9 and, among potential CRK9 substrates and modifying enzymes, discovered an unusual tripartite complex comprising CRK9, a new L-type cyclin (CYC12) and a protein, termed CRK9-associated protein (CRK9AP), that is only conserved among kinetoplastids. Silencing of either CYC12 or CRK9AP reproduced the effects of depleting CRK9, identifying these proteins as functional partners of CRK9 in vivo. While mammalian cyclin L binds to CDK11, the CRK9 complex deviates substantially from that of CDK11, requiring CRK9AP for efficient CRK9 complex formation and autophosphorylation in vitro. Interference with this unusual CDK rescued mice from lethal trypanosome infections, validating CRK9 as a potential chemotherapeutic target.

  15. Biogenesis of photosynthetic complexes in the chloroplast of Chlamydomonas reinhardtii requires ARSA1, a homolog of prokaryotic arsenite transporter and eukaryotic TRC40 for guided entry of tail-anchored proteins.

    Science.gov (United States)

    Formighieri, Cinzia; Cazzaniga, Stefano; Kuras, Richard; Bassi, Roberto

    2013-03-01

    as1, for antenna size mutant 1, was obtained by insertion mutagenesis of the unicellular green alga Chlamydomonas reinhardtii. This strain has a low chlorophyll content, 8% with respect to the wild type, and displays a general reduction in thylakoid polypeptides. The mutant was found to carry an insertion into a homologous gene, prokaryotic arsenite transporter (ARSA), whose yeast and mammal counterparts were found to be involved in the targeting of tail-anchored (TA) proteins to cytosol-exposed membranes, essential for several cellular functions. Here we present the characterization in a photosynthetic organism of an insertion mutant in an ARSA-homolog gene. The ARSA1 protein was found to be localized in the cytosol, and yet its absence in as1 leads to a small chloroplast and a strongly decreased chlorophyll content per cell. ARSA1 appears to be required for optimal biogenesis of photosynthetic complexes because of its involvement in the accumulation of TOC34, an essential component of the outer chloroplast membrane translocon (TOC) complex, which, in turn, catalyzes the import of nucleus-encoded precursor polypeptides into the chloroplast. Remarkably, the effect of the mutation appears to be restricted to biogenesis of chlorophyll-binding polypeptides and is not compensated by the other ARSA homolog encoded by the C. reinhardtii genome, implying a non-redundant function. © 2012 The Authors The Plant Journal © 2012 Blackwell Publishing Ltd.

  16. Oral health promotion at worksites

    DEFF Research Database (Denmark)

    Schou, L

    1989-01-01

    Many workplace-based health promotion programmes have been reported but only a few include or focus specifically on oral health. Although certain obstacles to oral health promotion in the workplace exist from the management side, from the dental profession and from the employees, these seem...... is at present sparse and there are few guidelines to actual strategies for effective oral health promotion. However, elements of strategies that have been successful in various geographical and economic environments include: active involvement of the work force, the use of dental auxiliaries, voluntary daily...... mouthrinsing, screening activities, use of mass media, oral hygiene instruction and prophylaxis and paraprofessional training. It is recommended that future research concentrates on these elements to build up a meaningful and relevant data base upon which effective oral health promotion programmes can...

  17. Transcriptional activation is a conserved feature of the early embryonic factor Zelda that requires a cluster of four zinc fingers for DNA binding and a low-complexity activation domain.

    Science.gov (United States)

    Hamm, Danielle C; Bondra, Eliana R; Harrison, Melissa M

    2015-02-01

    Delayed transcriptional activation of the zygotic genome is a nearly universal phenomenon in metazoans. Immediately following fertilization, development is controlled by maternally deposited products, and it is not until later stages that widespread activation of the zygotic genome occurs. Although the mechanisms driving this genome activation are currently unknown, the transcriptional activator Zelda (ZLD) has been shown to be instrumental in driving this process in Drosophila melanogaster. Here we define functional domains of ZLD required for both DNA binding and transcriptional activation. We show that the C-terminal cluster of four zinc fingers mediates binding to TAGteam DNA elements in the promoters of early expressed genes. All four zinc fingers are required for this activity, and splice isoforms lacking three of the four zinc fingers fail to activate transcription. These truncated splice isoforms dominantly suppress activation by the full-length, embryonically expressed isoform. We map the transcriptional activation domain of ZLD to a central region characterized by low complexity. Despite relatively little sequence conservation within this domain, ZLD orthologs from Drosophila virilis, Anopheles gambiae, and Nasonia vitripennis activate transcription in D. melanogaster cells. Transcriptional activation by these ZLD orthologs suggests that ZLD functions through conserved interactions with a protein cofactor(s). We have identified distinct DNA-binding and activation domains within the critical transcription factor ZLD that controls the initial activation of the zygotic genome.

  18. Carney Complex

    Science.gov (United States)

    ... Types of Cancer > Carney Complex Request Permissions Carney Complex Approved by the Cancer.Net Editorial Board , 11/2015 What is Carney complex? Carney complex is a hereditary condition associated with: ...

  19. Complex Beauty

    OpenAIRE

    Franceschet, Massimo

    2014-01-01

    Complex systems and their underlying convoluted networks are ubiquitous, all we need is an eye for them. They pose problems of organized complexity which cannot be approached with a reductionist method. Complexity science and its emergent sister network science both come to grips with the inherent complexity of complex systems with an holistic strategy. The relevance of complexity, however, transcends the sciences. Complex systems and networks are the focal point of a philosophical, cultural ...

  20. Software requirements

    CERN Document Server

    Wiegers, Karl E

    2003-01-01

    Without formal, verifiable software requirements-and an effective system for managing them-the programs that developers think they've agreed to build often will not be the same products their customers are expecting. In SOFTWARE REQUIREMENTS, Second Edition, requirements engineering authority Karl Wiegers amplifies the best practices presented in his original award-winning text?now a mainstay for anyone participating in the software development process. In this book, you'll discover effective techniques for managing the requirements engineering process all the way through the development cy

  1. Complex dynamics

    CERN Document Server

    Carleson, Lennart

    1993-01-01

    Complex dynamics is today very much a focus of interest. Though several fine expository articles were available, by P. Blanchard and by M. Yu. Lyubich in particular, until recently there was no single source where students could find the material with proofs. For anyone in our position, gathering and organizing the material required a great deal of work going through preprints and papers and in some cases even finding a proof. We hope that the results of our efforts will be of help to others who plan to learn about complex dynamics and perhaps even lecture. Meanwhile books in the field a. re beginning to appear. The Stony Brook course notes of J. Milnor were particularly welcome and useful. Still we hope that our special emphasis on the analytic side will satisfy a need. This book is a revised and expanded version of notes based on lectures of the first author at UCLA over several \\Vinter Quarters, particularly 1986 and 1990. We owe Chris Bishop a great deal of gratitude for supervising the production of cour...

  2. Complexity explained

    CERN Document Server

    Erdi, Peter

    2008-01-01

    This book explains why complex systems research is important in understanding the structure, function and dynamics of complex natural and social phenomena. Readers will learn the basic concepts and methods of complex system research.

  3. Energy requirements

    NARCIS (Netherlands)

    Hulzebos, Christian V.; Sauer, Pieter J. J.

    2007-01-01

    The determination of the appropriate energy and nutritional requirements of a newborn infant requires a clear goal of the energy and other compounds to be administered, valid methods to measure energy balance and body composition, and knowledge of the neonatal metabolic capacities. Providing an appr

  4. Energy requirements

    NARCIS (Netherlands)

    Hulzebos, Christian V.; Sauer, Pieter J. J.

    The determination of the appropriate energy and nutritional requirements of a newborn infant requires a clear goal of the energy and other compounds to be administered, valid methods to measure energy balance and body composition, and knowledge of the neonatal metabolic capacities. Providing an

  5. Guide to requirements SL-07

    DEFF Research Database (Denmark)

    Lauesen, Søren

    IT developers and consultants often ask for an exemplary requirements specification as a starting point for their specific project. This document is the guide to such a specification, Requirements Template SL-07. The specification itself is a template filled out with a complex example: requirements...

  6. Guide to requirements SL-07

    DEFF Research Database (Denmark)

    Lauesen, Søren

    IT developers and consultants often ask for an exemplary requirements specification as a starting point for their specific project. This document is the guide to such a specification, Requirements Template SL-07. The specification itself is a template filled out with a complex example: requirements...... for an Electronic Health Record system (EHR)....

  7. Requirements dilemma

    OpenAIRE

    2006-01-01

    This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University. Knowing ‘what’ to build is an integral part of an Information System Development, and it is generally understood that this, which is known as Requirements, is achievable through a process of understanding, communication and management. It is currently maintained by the Requirements theorists that successful system design clarifies the interrelations between information and its representations...

  8. Bucolic Complexes

    CERN Document Server

    Brešar, Bostjan; Chepoi, Victor; Gologranc, Tanja; Osajda, Damian

    2012-01-01

    In this article, we introduce and investigate bucolic complexes, a common generalization of systolic complexes and of CAT(0) cubical complexes. This class of complexes is closed under Cartesian products and amalgamations over some convex subcomplexes. We study various approaches to bucolic complexes: from graph-theoretic and topological viewpoints, as well as from the point of view of geometric group theory. Bucolic complexes can be defined as locally-finite simply connected prism complexes satisfying some local combinatorial conditions. We show that bucolic complexes are contractible, and satisfy some nonpositive-curvature-like properties. In particular, we prove a version of the Cartan-Hadamard theorem, the fixed point theorem for finite group actions, and establish some results on groups acting geometrically on such complexes. We also characterize the 1-skeletons (which we call bucolic graphs) and the 2-skeletons of bucolic complexes. In particular, we prove that bucolic graphs are precisely retracts of Ca...

  9. Leading healthcare in complexity.

    Science.gov (United States)

    Cohn, Jeffrey

    2014-12-01

    Healthcare institutions and providers are in complexity. Networks of interconnections from relationships and technology create conditions in which interdependencies and non-linear dynamics lead to surprising, unpredictable outcomes. Previous effective approaches to leadership, focusing on top-down bureaucratic methods, are no longer effective. Leading in complexity requires leaders to accept the complexity, create an adaptive space in which innovation and creativity can flourish and then integrate the successful practices that emerge into the formal organizational structure. Several methods for doing adaptive space work will be discussed. Readers will be able to contrast traditional leadership approaches with leading in complexity. They will learn new behaviours that are required of complexity leaders, along with challenges they will face, often from other leaders within the organization.

  10. Work-related self-efficacy as a moderator of the impact of a worksite stress management training intervention: Intrinsic work motivation as a higher order condition of effect.

    Science.gov (United States)

    Lloyd, Joda; Bond, Frank W; Flaxman, Paul E

    2017-01-01

    Employees with low levels of work-related self-efficacy may stand to benefit more from a worksite stress management training (SMT) intervention. However, this low work-related self-efficacy/enhanced SMT benefits effect may be conditional on employees also having high levels of intrinsic work motivation. In the present study, we examined this proposition by testing three-way, or higher order, interaction effects. One hundred and fifty-three U.K. government employees were randomly assigned to a SMT intervention group (n = 68), or to a waiting list control group (n = 85). The SMT group received three half-day training sessions spread over two and a half months. Findings indicated that there were significant overall reductions in psychological strain, emotional exhaustion and depersonalization in the SMT group, in comparison to the control group. Furthermore, there were significant higher order Group (SMT vs. control) × Time 1 Work-Related Self-Efficacy × Time 1 Intrinsic Work Motivation interactions, such that reductions in emotional exhaustion and depersonalization at certain time points were experienced only by those who had low baseline levels of work-related self-efficacy and high baseline levels of intrinsic work motivation. Implications for work-related self-efficacy theory and research and SMT research and practice are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  11. Dsl1p, Tip20p, and the novel Dsl3(Sec39) protein are required for the stability of the Q/t-SNARE complex at the endoplasmic reticulum in yeast

    DEFF Research Database (Denmark)

    Kraynack, Bryan A; Chan, Angela; Rosenthal, Eva Helga

    2005-01-01

    -ER retrograde transport. Size exclusion chromatography and affinity purification approaches confirmed that Dsl3p is associated with subunits of the "Dsl1p complex." The complex also includes the Q/t-SNARE proteins, Use1p, Sec20p, and Ufe1p, integral membrane proteins that constitute the trimeric acceptor for R...

  12. Interdependence of Pes1, Bop1, and WDR12 controls nucleolar localization and assembly of the PeBoW complex required for maturation of the 60S ribosomal subunit.

    Science.gov (United States)

    Rohrmoser, Michaela; Hölzel, Michael; Grimm, Thomas; Malamoussi, Anastassia; Harasim, Thomas; Orban, Mathias; Pfisterer, Iris; Gruber-Eber, Anita; Kremmer, Elisabeth; Eick, Dirk

    2007-05-01

    The PeBoW complex is essential for cell proliferation and maturation of the large ribosomal subunit in mammalian cells. Here we examined the role of PeBoW-specific proteins Pes1, Bop1, and WDR12 in complex assembly and stability, nucleolar transport, and pre-ribosome association. Recombinant expression of the three subunits is sufficient for complex formation. The stability of all three subunits strongly increases upon incorporation into the complex. Only overexpression of Bop1 inhibits cell proliferation and rRNA processing, and its negative effects could be rescued by coexpression of WDR12, but not Pes1. Elevated levels of Bop1 induce Bop1/WDR12 and Bop1/Pes1 subcomplexes. Knockdown of Bop1 abolishes the copurification of Pes1 with WDR12, demonstrating Bop1 as the integral component of the complex. Overexpressed Bop1 substitutes for endogenous Bop1 in PeBoW complex assembly, leading to the instability of endogenous Bop1. Finally, indirect immunofluorescence, cell fractionation, and sucrose gradient centrifugation experiments indicate that transport of Bop1 from the cytoplasm to the nucleolus is Pes1 dependent, while Pes1 can migrate to the nucleolus and bind to preribosomal particles independently of Bop1. We conclude that the assembly and integrity of the PeBoW complex are highly sensitive to changes in Bop1 protein levels.

  13. Not so Complex: Iteration in the Complex Plane

    Science.gov (United States)

    O'Dell, Robin S.

    2014-01-01

    The simple process of iteration can produce complex and beautiful figures. In this article, Robin O'Dell presents a set of tasks requiring students to use the geometric interpretation of complex number multiplication to construct linear iteration rules. When the outputs are plotted in the complex plane, the graphs trace pleasing designs…

  14. Cosmic Complexity

    Science.gov (United States)

    Mather, John C.

    2012-01-01

    What explains the extraordinary complexity of the observed universe, on all scales from quarks to the accelerating universe? My favorite explanation (which I certainty did not invent) ls that the fundamental laws of physics produce natural instability, energy flows, and chaos. Some call the result the Life Force, some note that the Earth is a living system itself (Gaia, a "tough bitch" according to Margulis), and some conclude that the observed complexity requires a supernatural explanation (of which we have many). But my dad was a statistician (of dairy cows) and he told me about cells and genes and evolution and chance when I was very small. So a scientist must look for me explanation of how nature's laws and statistics brought us into conscious existence. And how is that seemll"!gly Improbable events are actually happening a!1 the time? Well, the physicists have countless examples of natural instability, in which energy is released to power change from simplicity to complexity. One of the most common to see is that cooling water vapor below the freezing point produces snowflakes, no two alike, and all complex and beautiful. We see it often so we are not amazed. But physlc!sts have observed so many kinds of these changes from one structure to another (we call them phase transitions) that the Nobel Prize in 1992 could be awarded for understanding the mathematics of their common features. Now for a few examples of how the laws of nature produce the instabilities that lead to our own existence. First, the Big Bang (what an insufficient name!) apparently came from an instability, in which the "false vacuum" eventually decayed into the ordinary vacuum we have today, plus the most fundamental particles we know, the quarks and leptons. So the universe as a whole started with an instability. Then, a great expansion and cooling happened, and the loose quarks, finding themselves unstable too, bound themselves together into today's less elementary particles like protons and

  15. Cosmic Complexity

    Science.gov (United States)

    Mather, John C.

    2012-01-01

    What explains the extraordinary complexity of the observed universe, on all scales from quarks to the accelerating universe? My favorite explanation (which I certainty did not invent) ls that the fundamental laws of physics produce natural instability, energy flows, and chaos. Some call the result the Life Force, some note that the Earth is a living system itself (Gaia, a "tough bitch" according to Margulis), and some conclude that the observed complexity requires a supernatural explanation (of which we have many). But my dad was a statistician (of dairy cows) and he told me about cells and genes and evolution and chance when I was very small. So a scientist must look for me explanation of how nature's laws and statistics brought us into conscious existence. And how is that seemll"!gly Improbable events are actually happening a!1 the time? Well, the physicists have countless examples of natural instability, in which energy is released to power change from simplicity to complexity. One of the most common to see is that cooling water vapor below the freezing point produces snowflakes, no two alike, and all complex and beautiful. We see it often so we are not amazed. But physlc!sts have observed so many kinds of these changes from one structure to another (we call them phase transitions) that the Nobel Prize in 1992 could be awarded for understanding the mathematics of their common features. Now for a few examples of how the laws of nature produce the instabilities that lead to our own existence. First, the Big Bang (what an insufficient name!) apparently came from an instability, in which the "false vacuum" eventually decayed into the ordinary vacuum we have today, plus the most fundamental particles we know, the quarks and leptons. So the universe as a whole started with an instability. Then, a great expansion and cooling happened, and the loose quarks, finding themselves unstable too, bound themselves together into today's less elementary particles like protons and

  16. Assessing Requirements Quality through Requirements Coverage

    Science.gov (United States)

    Rajan, Ajitha; Heimdahl, Mats; Woodham, Kurt

    2008-01-01

    In model-based development, the development effort is centered around a formal description of the proposed software system the model. This model is derived from some high-level requirements describing the expected behavior of the software. For validation and verification purposes, this model can then be subjected to various types of analysis, for example, completeness and consistency analysis [6], model checking [3], theorem proving [1], and test-case generation [4, 7]. This development paradigm is making rapid inroads in certain industries, e.g., automotive, avionics, space applications, and medical technology. This shift towards model-based development naturally leads to changes in the verification and validation (V&V) process. The model validation problem determining that the model accurately captures the customer's high-level requirements has received little attention and the sufficiency of the validation activities has been largely determined through ad-hoc methods. Since the model serves as the central artifact, its correctness with respect to the users needs is absolutely crucial. In our investigation, we attempt to answer the following two questions with respect to validation (1) Are the requirements sufficiently defined for the system? and (2) How well does the model implement the behaviors specified by the requirements? The second question can be addressed using formal verification. Nevertheless, the size and complexity of many industrial systems make formal verification infeasible even if we have a formal model and formalized requirements. Thus, presently, there is no objective way of answering these two questions. To this end, we propose an approach based on testing that, when given a set of formal requirements, explores the relationship between requirements-based structural test-adequacy coverage and model-based structural test-adequacy coverage. The proposed technique uses requirements coverage metrics defined in [9] on formal high-level software

  17. Requirements in engineering projects

    CERN Document Server

    Fernandes, João M

    2016-01-01

    This book focuses on various topics related to engineering and management of requirements, in particular elicitation, negotiation, prioritisation, and documentation (whether with natural languages or with graphical models). The book provides methods and techniques that help to characterise, in a systematic manner, the requirements of the intended engineering system.  It was written with the goal of being adopted as the main text for courses on requirements engineering, or as a strong reference to the topics of requirements in courses with a broader scope. It can also be used in vocational courses, for professionals interested in the software and information systems domain.   Readers who have finished this book will be able to: - establish and plan a requirements engineering process within the development of complex engineering systems; - define and identify the types of relevant requirements in engineering projects; - choose and apply the most appropriate techniques to elicit the requirements of a giv...

  18. Communication complexity and information complexity

    Science.gov (United States)

    Pankratov, Denis

    Information complexity enables the use of information-theoretic tools in communication complexity theory. Prior to the results presented in this thesis, information complexity was mainly used for proving lower bounds and direct-sum theorems in the setting of communication complexity. We present three results that demonstrate new connections between information complexity and communication complexity. In the first contribution we thoroughly study the information complexity of the smallest nontrivial two-party function: the AND function. While computing the communication complexity of AND is trivial, computing its exact information complexity presents a major technical challenge. In overcoming this challenge, we reveal that information complexity gives rise to rich geometrical structures. Our analysis of information complexity relies on new analytic techniques and new characterizations of communication protocols. We also uncover a connection of information complexity to the theory of elliptic partial differential equations. Once we compute the exact information complexity of AND, we can compute exact communication complexity of several related functions on n-bit inputs with some additional technical work. Previous combinatorial and algebraic techniques could only prove bounds of the form theta( n). Interestingly, this level of precision is typical in the area of information theory, so our result demonstrates that this meta-property of precise bounds carries over to information complexity and in certain cases even to communication complexity. Our result does not only strengthen the lower bound on communication complexity of disjointness by making it more exact, but it also shows that information complexity provides the exact upper bound on communication complexity. In fact, this result is more general and applies to a whole class of communication problems. In the second contribution, we use self-reduction methods to prove strong lower bounds on the information

  19. Analysis of Multi-Stakeholder Requirements Using Requirement Interaction Matrix

    Directory of Open Access Journals (Sweden)

    Rohayanti Hassan

    2017-09-01

    Full Text Available Software requirements engineering is an imperative phase in the software development life cycle in every project regardless of the project size. In a project, different people are involved in the requirements engineering process, including requirement engineers, stakeholders, end users, and system designers. Amongst them, stakeholders play an essential role. Differences in goals and priorities of multiple stakeholders would make requirements management complex and difficult, which is a huge challenge for requirement engineers. From time to time, new requirements emerge and existing requirements need changes to fulfil stakeholders’ goals. Thus, such situation leads to high requirements volatility and low stability which causes overlapping and conflicting of requirements. The correctness and validity of requirements are of paramount importance as they are the key factors toward a successful system. A deep understanding of requirement management technique that conforms to users’ needs is crucial. Such technique of the concept is applied to the Labour Management System. In this study, we have discussed the implementation of analysis of multi-stakeholder requirements using requirement interaction matrix in the f. The study used real requirements to yield a solid and dependable result. We have documented the requirements using a template and assessed their respective volatility level. An algorithm is constructed to   show   that   the   technique has managed to minimize   the time   used   when   checking requirements.

  20. Requirements Reasoning for Distributed Requirements Analysis using Semantic Wiki

    OpenAIRE

    Liang, Peng; Avgeriou, Paris; Clerc, Viktor

    2009-01-01

    In large-scale collaborative software projects, thousands of requirements with complex interdependencies and different granularity spreading in different levels are elicited, documented, and evolved during the project lifecycle. Non-technical stakeholders involved in requirements engineering activities rarely apply formal techniques; therefore it is infeasible to automatically detect problems in requirements. This situation becomes even worse in a distributed context when all sites are respon...

  1. Tandem DNA-bound cAMP-CRP complexes are required for transcriptional repression of the deoP2 promoter by the CytR repressor in Escherichia coli

    DEFF Research Database (Denmark)

    Søgaard-Andersen, Lotte; Møllegaard, N E; Douthwaite, S R

    1990-01-01

    We have studied the deoP2 promoter in Escherichia coli to define features important for its interaction with the CytR repressor. As is characteristic for CytR-regulated promoters, deoP2 encodes tandem binding sites for the activating complex cAMP-CRP. One of these sites, CRP-1, overlaps the -35 r...... in vitro. These observations are not easily explained by current models for the action of prokaryotic repressors; instead we favour a model in which the interaction of CytR with deoP2 depends on the presence of tandem DNA-bound cAMP-CRP complexes....

  2. Supporting complex search tasks

    DEFF Research Database (Denmark)

    Gäde, Maria; Hall, Mark; Huurdeman, Hugo

    2015-01-01

    There is broad consensus in the field of IR that search is complex in many use cases and applications, both on the Web and in domain specific collections, and both professionally and in our daily life. Yet our understanding of complex search tasks, in comparison to simple look up tasks, is fragme......There is broad consensus in the field of IR that search is complex in many use cases and applications, both on the Web and in domain specific collections, and both professionally and in our daily life. Yet our understanding of complex search tasks, in comparison to simple look up tasks......, and recommendations, and supporting exploratory search to sensemaking and analytics, UI and UX design pose an overconstrained challenge. How do we know that our approach is any good? Supporting complex search task requires new collaborations across the whole field of IR, and the proposed workshop will bring together...

  3. Complexity Plots

    KAUST Repository

    Thiyagalingam, Jeyarajan

    2013-06-01

    In this paper, we present a novel visualization technique for assisting the observation and analysis of algorithmic complexity. In comparison with conventional line graphs, this new technique is not sensitive to the units of measurement, allowing multivariate data series of different physical qualities (e.g., time, space and energy) to be juxtaposed together conveniently and consistently. It supports multivariate visualization as well as uncertainty visualization. It enables users to focus on algorithm categorization by complexity classes, while reducing visual impact caused by constants and algorithmic components that are insignificant to complexity analysis. It provides an effective means for observing the algorithmic complexity of programs with a mixture of algorithms and black-box software through visualization. Through two case studies, we demonstrate the effectiveness of complexity plots in complexity analysis in research, education and application. © 2013 The Author(s) Computer Graphics Forum © 2013 The Eurographics Association and Blackwell Publishing Ltd.

  4. Structure-function analysis of the gE-gI complex of feline herpesvirus: mapping of gI domains required for gE-gI interaction, intracellular transport, and cell-to-cell spread

    NARCIS (Netherlands)

    Horzinek, M.C.; Mijnes, J.D.; Lutters, B.C.; Vlot, A.C.; Anken, E. van; Rottier, P.J.M.; Groot, R.J. de

    1997-01-01

    Alphaherpesvirus glycoproteins gE and gI form a noncovalently associated hetero-oligomeric complex, which is involved in cell-to-cell spread. In the absence of gI, feline herpesvirus (FHV) gE is transport incompetent and fully retained in the endoplasmic reticulum. Here, we assess the effect of

  5. Engaging complexity

    Directory of Open Access Journals (Sweden)

    Gys M. Loubser

    2014-01-01

    Full Text Available In this article, I discuss studies in complexity and its epistemological implications for systematic and practical theology. I argue that engagement with complexity does not necessarily assurea non-reductionist approach. However, if complexity is engaged transversally, it becomes possible to transcend reductionist approaches. Moreover, systematic and practical the ologians can draw on complexity in developing new ways of understanding and, therefore, new ways of describing the focus, epistemic scope and heuristic structures of systematic and practical theology. Firstly, Edgar Morin draws a distinction between restricted and general complexity based on the epistemology drawn upon in studies in complexity. Moving away from foundationalist approaches to epistemology, Morin argues for a paradigm of systems. Secondly,I discuss Kees van Kooten Niekerk�s distinction between epistemology, methodology andontology in studies in complexity and offer an example of a theological argument that drawson complexity. Thirdly, I argue for the importance of transversality in engaging complexity by drawing on the work of Wentzel van Huyssteen and Paul Cilliers. In conclusion, I argue that theologians have to be conscious of the epistemic foundations of each study in complexity, and these studies illuminate the heart of Reformed theology.Intradisciplinary and/or interdisciplinary implications: Therefore, this article has both intradisciplinary and interdisciplinary implications. When theologians engage studies incomplexity, the epistemological roots of these studies need to be considered seeing thatresearchers in complexity draw on different epistemologies. Drawing on transversality wouldenhance such considerations. Furthermore, Edgar Morin�s and Paul Cilliers� approach tocomplexity will inform practical and theoretical considerations in church polity and unity.

  6. Computational Complexity

    Directory of Open Access Journals (Sweden)

    J. A. Tenreiro Machado

    2017-02-01

    Full Text Available Complex systems (CS involve many elements that interact at different scales in time and space. The challenges in modeling CS led to the development of novel computational tools with applications in a wide range of scientific areas. The computational problems posed by CS exhibit intrinsic difficulties that are a major concern in Computational Complexity Theory. [...

  7. Complex narratives

    NARCIS (Netherlands)

    Simons, J.

    2008-01-01

    This paper brings together narratology, game theory, and complexity theory to untangle the intricate nature of complex narratives in contemporary cinema. It interrogates the different terms - forking-path narratives, mind-game films, modular narratives, multiple-draft films, database narratives, puz

  8. Complex odontoma.

    Science.gov (United States)

    Preetha, A; Balikai, Bharati S; Sujatha, D; Pai, Anuradha; Ganapathy, K S

    2010-01-01

    Odontomas are hamartomatous lesions or malformations composed of mature enamel, dentin, and pulp. They may be compound or complex, depending on the extent of morphodifferentiation or their resemblance to normal teeth. The etiology of odontoma is unknown, although several theories have been proposed. This article describes a case of a large infected complex odontoma in the residual mandibular ridge, resulting in considerable mandibular expansion.

  9. Simplifying complexity

    NARCIS (Netherlands)

    Leemput, van de I.A.

    2016-01-01

    In this thesis I use mathematical models to explore the properties of complex systems ranging from microbial nitrogen pathways and coral reefs to the human state of mind. All are examples of complex systems, defined as systems composed of a number of interconnected parts, where the systemic behavior

  10. Unusual Development of Iatrogenic Complex, Mixed Biliary and Duodenal Fistulas Complicating Roux-en-Y Antrectomy for Stenotic Peptic Disease of the Supraampullary Duodenum Requiring Whipple Procedure: An Uncommon Clinical Dilemma

    OpenAIRE

    Polistina, Francesco A.; Giorgio Costantin; Alessandro Settin; Franco Lumachi; Giovanni Ambrosino

    2010-01-01

    Complex fistulas of the duodenum and biliary tree are severe complications of gastric surgery. The association of duodenal and major biliary fistulas occurs rarely and is a major challenge for treatment. They may occur during virtually any kind of operation, but they are more frequent in cases complicated by the presence of difficult duodenal ulcers or cancer, with a mortality rate of up to 35%. Options for treatment are many and range from simple drainage to extended resections and difficult...

  11. A complex of Cas proteins 5, 6, and 7 is required for the biogenesis and stability of clustered regularly interspaced short palindromic repeats (crispr)-derived rnas (crrnas) in Haloferax volcanii.

    Science.gov (United States)

    Brendel, Jutta; Stoll, Britta; Lange, Sita J; Sharma, Kundan; Lenz, Christof; Stachler, Aris-Edda; Maier, Lisa-Katharina; Richter, Hagen; Nickel, Lisa; Schmitz, Ruth A; Randau, Lennart; Allers, Thorsten; Urlaub, Henning; Backofen, Rolf; Marchfelder, Anita

    2014-03-07

    The clustered regularly interspaced short palindromic repeats/CRISPR-associated (CRISPR-Cas) system is a prokaryotic defense mechanism against foreign genetic elements. A plethora of CRISPR-Cas versions exist, with more than 40 different Cas protein families and several different molecular approaches to fight the invading DNA. One of the key players in the system is the CRISPR-derived RNA (crRNA), which directs the invader-degrading Cas protein complex to the invader. The CRISPR-Cas types I and III use the Cas6 protein to generate mature crRNAs. Here, we show that the Cas6 protein is necessary for crRNA production but that additional Cas proteins that form a CRISPR-associated complex for antiviral defense (Cascade)-like complex are needed for crRNA stability in the CRISPR-Cas type I-B system in Haloferax volcanii in vivo. Deletion of the cas6 gene results in the loss of mature crRNAs and interference. However, cells that have the complete cas gene cluster (cas1-8b) removed and are transformed with the cas6 gene are not able to produce and stably maintain mature crRNAs. crRNA production and stability is rescued only if cas5, -6, and -7 are present. Mutational analysis of the cas6 gene reveals three amino acids (His-41, Gly-256, and Gly-258) that are essential for pre-crRNA cleavage, whereas the mutation of two amino acids (Ser-115 and Ser-224) leads to an increase of crRNA amounts. This is the first systematic in vivo analysis of Cas6 protein variants. In addition, we show that the H. volcanii I-B system contains a Cascade-like complex with a Cas7, Cas5, and Cas6 core that protects the crRNA.

  12. A Complex of Cas Proteins 5, 6, and 7 Is Required for the Biogenesis and Stability of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-derived RNAs (crRNAs) in Haloferax volcanii*

    Science.gov (United States)

    Brendel, Jutta; Stoll, Britta; Lange, Sita J.; Sharma, Kundan; Lenz, Christof; Stachler, Aris-Edda; Maier, Lisa-Katharina; Richter, Hagen; Nickel, Lisa; Schmitz, Ruth A.; Randau, Lennart; Allers, Thorsten; Urlaub, Henning; Backofen, Rolf; Marchfelder, Anita

    2014-01-01

    The clustered regularly interspaced short palindromic repeats/CRISPR-associated (CRISPR-Cas) system is a prokaryotic defense mechanism against foreign genetic elements. A plethora of CRISPR-Cas versions exist, with more than 40 different Cas protein families and several different molecular approaches to fight the invading DNA. One of the key players in the system is the CRISPR-derived RNA (crRNA), which directs the invader-degrading Cas protein complex to the invader. The CRISPR-Cas types I and III use the Cas6 protein to generate mature crRNAs. Here, we show that the Cas6 protein is necessary for crRNA production but that additional Cas proteins that form a CRISPR-associated complex for antiviral defense (Cascade)-like complex are needed for crRNA stability in the CRISPR-Cas type I-B system in Haloferax volcanii in vivo. Deletion of the cas6 gene results in the loss of mature crRNAs and interference. However, cells that have the complete cas gene cluster (cas1–8b) removed and are transformed with the cas6 gene are not able to produce and stably maintain mature crRNAs. crRNA production and stability is rescued only if cas5, -6, and -7 are present. Mutational analysis of the cas6 gene reveals three amino acids (His-41, Gly-256, and Gly-258) that are essential for pre-crRNA cleavage, whereas the mutation of two amino acids (Ser-115 and Ser-224) leads to an increase of crRNA amounts. This is the first systematic in vivo analysis of Cas6 protein variants. In addition, we show that the H. volcanii I-B system contains a Cascade-like complex with a Cas7, Cas5, and Cas6 core that protects the crRNA. PMID:24459147

  13. Complex variables

    CERN Document Server

    Fisher, Stephen D

    1999-01-01

    The most important topics in the theory and application of complex variables receive a thorough, coherent treatment in this introductory text. Intended for undergraduates or graduate students in science, mathematics, and engineering, this volume features hundreds of solved examples, exercises, and applications designed to foster a complete understanding of complex variables as well as an appreciation of their mathematical beauty and elegance. Prerequisites are minimal; a three-semester course in calculus will suffice to prepare students for discussions of these topics: the complex plane, basic

  14. Managing Complexity

    DEFF Research Database (Denmark)

    Maylath, Bruce; Vandepitte, Sonia; Minacori, Patricia

    2013-01-01

    This article discusses the largest and most complex international learning-by-doing project to date- a project involving translation from Danish and Dutch into English and editing into American English alongside a project involving writing, usability testing, and translation from English into Dut...... and into French. The complexity of the undertaking proved to be a central element in the students' learning, as the collaboration closely resembles the complexity of international documentation workplaces of language service providers. © Association of Teachers of Technical Writing....

  15. Lecithin Complex

    African Journals Online (AJOL)

    yellow power was collected as polydatin-lecithin complex. ... performed on an Agilent 1260 HPLC system. The injection volume .... rabbits. Biomed. Pharmacother 2009; 63: 457-462. 4. Liu B, Du J, Zeng J, Chen C, Niu S. Characterization and.

  16. Mi2β is required for γ-globin gene silencing: temporal assembly of a GATA-1-FOG-1-Mi2 repressor complex in β-YAC transgenic mice.

    Directory of Open Access Journals (Sweden)

    Flávia C Costa

    Full Text Available Activation of γ-globin gene expression in adults is known to be therapeutic for sickle cell disease. Thus, it follows that the converse, alleviation of repression, would be equally effective, since the net result would be the same: an increase in fetal hemoglobin. A GATA-1-FOG-1-Mi2 repressor complex was recently demonstrated to be recruited to the -566 GATA motif of the (Aγ-globin gene. We show that Mi2β is essential for γ-globin gene silencing using Mi2β conditional knockout β-YAC transgenic mice. In addition, increased expression of (Aγ-globin was detected in adult blood from β-YAC transgenic mice containing a T>G HPFH point mutation at the -566 GATA silencer site. ChIP experiments demonstrated that GATA-1 is recruited to this silencer at day E16, followed by recruitment of FOG-1 and Mi2 at day E17 in wild-type β-YAC transgenic mice. Recruitment of the GATA-1-mediated repressor complex was disrupted by the -566 HPFH mutation at developmental stages when it normally binds. Our data suggest that a temporal repression mechanism is operative in the silencing of γ-globin gene expression and that either a trans-acting Mi2β knockout deletion mutation or the cis-acting -566 (Aγ-globin HPFH point mutation disrupts establishment of repression, resulting in continued γ-globin gene transcription during adult definitive erythropoiesis.

  17. Parp2 is required for the differentiation of post-meiotic germ cells: Identification of a spermatid-specific complex containing Parp1, Parp2, TP2 and HSPA2

    Energy Technology Data Exchange (ETDEWEB)

    Quenet, Delphine [IREBS-FRE 3211, Ecole Superieure de Biotechnologie de Strasbourg, F-67412 Illkirch cedex (France); Mark, Manuel [Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), Institut Clinique de la souris (ICS), F-67404 Illkirch cedex (France); Govin, Jerome [INSERM, U823, Grenoble, F-38706 (France); Universite Joseph Fourier, Institut Albert Bonniot, Grenoble, F-38706 (France); Dorsselear, A. van [Laboratoire de Spectrometrie de Masse Bio-organique, UMR7178, Ecole de Chimie, Polymeres et Materiaux, Strasbourg (France); Schreiber, Valerie [IREBS-FRE 3211, Ecole Superieure de Biotechnologie de Strasbourg, F-67412 Illkirch cedex (France); Khochbin, Saadi [INSERM, U823, Grenoble, F-38706 (France); Universite Joseph Fourier, Institut Albert Bonniot, Grenoble, F-38706 (France); Dantzer, Francoise, E-mail: francoise.dantzer@unistra.fr [IREBS-FRE 3211, Ecole Superieure de Biotechnologie de Strasbourg, F-67412 Illkirch cedex (France)

    2009-10-01

    Spermiogenesis is a complex male germ cell post-meiotic differentiation process characterized by dramatic changes in chromatin structure and function, including chromatin condensation, transcriptional inhibition and the sequential replacement of histones by transition proteins and protamines. Recent advances, in mammalian cells, suggest a possible role of poly(ADP-ribosyl)ation catalyzed by Parp1 and/or Parp2 in this process. We have recently reported severely compromised spermiogenesis in Parp2-deficient mice characterized by a marked delay in nuclear elongation whose molecular mechanisms remain however unknown. Here, using in vitro protein-protein interaction assays, we show that Parp2 interacts significantly with both the transition protein TP2 and the transition chaperone HSPA2, whereas Parp1 binds weakly to HSPA2. Parp2-TP2 interaction is partly mediated by poly(ADP-ribosyl)ation. Only Parp1 poly(ADP-ribosyl)ates HSPA2. In addition, a detailed analysis of spermatid maturation in Parp2-deficient mice, combining immunohistochemistry and electron microscopic approaches, reveals a loss of spermatids expressing TP2, a defect in chromatin condensation and abnormal formation of the manchette microtubules that, together, contribute to spermatid-specific cell death. In conclusion, we propose both Parps as new participants of a spermatid-specific protein complex involved in genome reorganization throughout spermiogenesis.

  18. Blood cholesterol level and risk of stroke in community-based or worksite cohort studies: a review of Japanese cohort studies in the past 20 years.

    Science.gov (United States)

    Tanaka, Taichiro; Okamura, Tomonori

    2012-01-01

    Evidence of the causal relationship between hypercholesterolemia and coronary artery disease (CAD) has been established worldwide. However, little attention has been paid to the relationship between hypercholesterolemia and stroke, despite stroke being the most common cardiovascular disease in Japan. We therefore reviewed cohort studies that investigated this relationship in the Japanese population over the past 20 years, and compared their findings with clinical trials and cohort studies in Western countries. Fourteen cohort studies were carried out in Japan during this period. The number of subjects in the studies ranged from 1621 to 91,219 and the mean follow-up period ranged from 7.6 to 32 years. The majority of studies showed no association between hypercholesterolemia and total stroke. However, one report showed a positive association between low-density lipoprotein cholesterol and atherothrombotic cerebral infarction. The relationship between hypercholesterolemia and cerebral infarction may be modified by the proportion of atherothrombotic infarctions in the population surveyed. Randomized controlled trials on statins have shown a substantial reduction in cerebral infarction, and so the discrepancy between cohort studies and clinical trials requires further study. However, some studies have reported that subjects with low blood cholesterol are more susceptible to intracerebral hemorrhage. Two hypotheses have been proposed to explain this association between low cholesterol and intracerebral hemorrhage. First, low blood cholesterol may induce angionecrosis, possibly in combination with hypertension, and second, low blood cholesterol may reflect a poor nutritional status. Either way, further continuous research in various fields of medical science is required to clarify the overall effect of blood cholesterol on stroke in humans.

  19. A Receptor-Like Kinase, Related to Cell Wall Sensor of Higher Plants, is Required for Sexual Reproduction in the Unicellular Charophycean Alga, Closterium peracerosum-strigosum-littorale Complex.

    Science.gov (United States)

    Hirano, Naoko; Marukawa, Yuka; Abe, Jun; Hashiba, Sayuri; Ichikawa, Machiko; Tanabe, Yoichi; Ito, Motomi; Nishii, Ichiro; Tsuchikane, Yuki; Sekimoto, Hiroyuki

    2015-07-01

    Here, we cloned the CpRLK1 gene, which encodes a receptor-like protein kinase expressed during sexual reproduction, from the heterothallic Closterium peracerosum-strigosum-littorale complex, one of the closest unicellular alga to land plants. Mating-type plus (mt(+)) cells with knockdown of CpRLK1 showed reduced competence for sexual reproduction and formed an abnormally enlarged conjugation papilla after pairing with mt(-) cells. The knockdown cells were unable to release a naked gamete, which is indispensable for zygote formation. We suggest that the CpRLK1 protein is an ancient cell wall sensor that now functions to regulate osmotic pressure in the cell to allow proper gamete release.

  20. Making the Tent Function Complex

    Science.gov (United States)

    Sprows, David J.

    2010-01-01

    This note can be used to illustrate to the student such concepts as periodicity in the complex plane. The basic construction makes use of the Tent function which requires only that the student have some working knowledge of binary arithmetic.

  1. Immobile Complex Verbs in Germanic

    DEFF Research Database (Denmark)

    Vikner, Sten

    2005-01-01

    Certain complex verbs in Dutch, German, and Swiss German do not undergo verb movement. The suggestion to be made in this article is that these ‘‘immobile'' verbs have to fulfill both the requirements imposed on complex verbs of the V° type (=verbs with non-separable prefixes) and the requirements...... are immobile, - why such verbs are not found in Germanic VO-languages such as English and Scandinavian.......Certain complex verbs in Dutch, German, and Swiss German do not undergo verb movement. The suggestion to be made in this article is that these ‘‘immobile'' verbs have to fulfill both the requirements imposed on complex verbs of the V° type (=verbs with non-separable prefixes) and the requirements...

  2. Organization structures for dealing with complexity

    NARCIS (Netherlands)

    Meijer, B.R.

    2006-01-01

    "Complexity is in the eye of the beholder" is a well known quote in the research field of complexity. In the world of managers the word complex is often a synonym for difficult, complicated, involving many factors and highly uncertain. A complex business decision requires careful preparation and clo

  3. Organization structures for dealing with complexity

    NARCIS (Netherlands)

    Meijer, B.R.

    2006-01-01

    "Complexity is in the eye of the beholder" is a well known quote in the research field of complexity. In the world of managers the word complex is often a synonym for difficult, complicated, involving many factors and highly uncertain. A complex business decision requires careful preparation and

  4. Improve Reading with Complex Texts

    Science.gov (United States)

    Fisher, Douglas; Frey, Nancy

    2015-01-01

    The Common Core State Standards have cast a renewed light on reading instruction, presenting teachers with the new requirements to teach close reading of complex texts. Teachers and administrators should consider a number of essential features of close reading: They are short, complex texts; rich discussions based on worthy questions; revisiting…

  5. mCSF1, a nucleus-encoded CRM protein required for the processing of many mitochondrial introns, is involved in the biogenesis of respiratory complexes I and IV in Arabidopsis.

    Science.gov (United States)

    Zmudjak, Michal; Colas des Francs-Small, Catherine; Keren, Ido; Shaya, Felix; Belausov, Eduard; Small, Ian; Ostersetzer-Biran, Oren

    2013-07-01

    The coding regions of many mitochondrial genes in plants are interrupted by intervening sequences that are classified as group II introns. Their splicing is essential for the expression of the genes they interrupt and hence for respiratory function, and is facilitated by various protein cofactors. Despite the importance of these cofactors, only a few of them have been characterized. CRS1-YhbY domain (CRM) is a recently recognized RNA-binding domain that is present in several characterized splicing factors in plant chloroplasts. The Arabidopsis genome encodes 16 CRM proteins, but these are largely uncharacterized. Here, we analyzed the intracellular location of one of these hypothetical proteins in Arabidopsis, mitochondrial CAF-like splicing factor 1 (mCSF1; At4 g31010), and analyzed the growth phenotypes and organellar activities associated with mcsf1 mutants in plants. Our data indicated that mCSF1 resides within mitochondria and its functions are essential during embryogenesis. Mutant plants with reduced mCSF1 displayed inhibited germination and retarded growth phenotypes that were tightly associated with reduced complex I and IV activities. Analogously to the functions of plastid-localized CRM proteins, analysis of the RNA profiles in wildtype and mcsf1 plants showed that mCSF1 acts in the splicing of many of the group II intron RNAs in Arabidopsis mitochondria.

  6. Complex Networks

    CERN Document Server

    Evsukoff, Alexandre; González, Marta

    2013-01-01

    In the last decade we have seen the emergence of a new inter-disciplinary field focusing on the understanding of networks which are dynamic, large, open, and have a structure sometimes called random-biased. The field of Complex Networks is helping us better understand many complex phenomena such as the spread of  deseases, protein interactions, social relationships, to name but a few. Studies in Complex Networks are gaining attention due to some major scientific breakthroughs proposed by network scientists helping us understand and model interactions contained in large datasets. In fact, if we could point to one event leading to the widespread use of complex network analysis is the availability of online databases. Theories of Random Graphs from Erdös and Rényi from the late 1950s led us to believe that most networks had random characteristics. The work on large online datasets told us otherwise. Starting with the work of Barabási and Albert as well as Watts and Strogatz in the late 1990s, we now know th...

  7. Complex chemistry with complex compounds

    Directory of Open Access Journals (Sweden)

    Eichler Robert

    2016-01-01

    Full Text Available In recent years gas-phase chemical studies assisted by physical pre-separation allowed for the investigation of fragile single molecular species by gas-phase chromatography. The latest success with the heaviest group 6 transactinide seaborgium is highlighted. The formation of a very volatile hexacarbonyl compound Sg(CO6 was observed similarly to its lighter homologues molybdenum and tungsten. The interactions of these gaseous carbonyl complex compounds with quartz surfaces were investigated by thermochromatography. Second-generation experiments are under way to investigate the intramolecular bond between the central metal atom of the complexes and the ligands addressing the influence of relativistic effects in the heaviest compounds. Our contribution comprises some aspects of the ongoing challenging experiments as well as an outlook towards other interesting compounds related to volatile complex compounds in the gas phase.

  8. The actin-binding protein Canoe/AF-6 forms a complex with Robo and is required for Slit-Robo signaling during axon pathfinding at the CNS midline.

    Science.gov (United States)

    Slováková, Jana; Speicher, Stephan; Sánchez-Soriano, Natalia; Prokop, Andreas; Carmena, Ana

    2012-07-18

    Axon guidance is a key process during nervous system development and regeneration. One of the best established paradigms to study the mechanisms underlying this process is the axon decision of whether or not to cross the midline in the Drosophila CNS. An essential regulator of that decision is the well conserved Slit-Robo signaling pathway. Slit guidance cues act through Robo receptors to repel axons from the midline. Despite good progress in our knowledge about these proteins, the intracellular mechanisms associated with Robo function remain poorly defined. In this work, we found that the scaffolding protein Canoe (Cno), the Drosophila orthologue of AF-6/Afadin, is essential for Slit-Robo signaling. Cno is expressed along longitudinal axonal pioneer tracts, and longitudinal Robo/Fasciclin2-positive axons aberrantly cross the midline in cno mutant embryos. cno mutant primary neurons show a significant reduction of Robo localized in growth cone filopodia and Cno forms a complex with Robo in vivo. Moreover, the commissureless (comm) phenotype (i.e., lack of commissures due to constitutive surface presentation of Robo in all neurons) is suppressed in comm, cno double-mutant embryos. Specific genetic interactions between cno, slit, robo, and genes encoding other components of the Robo pathway, such as Neurexin-IV, Syndecan, and Rac GTPases, further confirm that Cno functionally interacts with the Slit-Robo pathway. Our data argue that Cno is a novel regulator of the Slit-Robo signaling pathway, crucial for regulating the subcellular localization of Robo and for transducing its signaling to the actin cytoskeleton during axon guidance at the midline.

  9. The cellular RNA export receptor TAP/NXF1 is required for ICP27-mediated export of herpes simplex virus 1 RNA, but the TREX complex adaptor protein Aly/REF appears to be dispensable.

    Science.gov (United States)

    Johnson, Lisa A; Li, Ling; Sandri-Goldin, Rozanne M

    2009-07-01

    Herpes simplex virus 1 (HSV-1) protein ICP27 has been shown to shuttle between the nucleus and cytoplasm and to bind viral RNA during infection. ICP27 was found to interact with the cellular RNA export adaptor protein Aly/REF, which is part of the TREX complex, and to relocalize Aly/REF to viral replication sites. ICP27 is exported to the cytoplasm through the export receptor TAP/NXF1, and ICP27 must be able to interact with TAP/NXF1 for efficient export of HSV-1 early and late transcripts. We examined the dynamics of ICP27 movement and its localization with respect to Aly/REF and TAP/NXF1 in living cells during viral infection. Recombinant viruses with a yellow fluorescent protein (YFP) tag on the N or C terminus of ICP27 were constructed. While the N-terminally tagged ICP27 virus behaved like wild-type HSV-1, the C-terminally tagged virus was defective in viral replication and gene expression, and ICP27 was confined to the nucleus, suggesting that the C-terminal YFP tag interfered with ICP27's C-terminal interactions, including the interaction with TAP/NXF1. To assess the role of Aly/REF and TAP/NXF1 in viral RNA export, these factors were knocked down using small interfering RNA. Knockdown of Aly/REF had little effect on the export of ICP27 or poly(A)(+) RNA during infection. In contrast, a decrease in TAP/NXF1 levels severely impaired export of ICP27 and poly(A)(+) RNA. We conclude that TAP/NXF1 is essential for ICP27-mediated export of RNA during HSV-1 infection, whereas Aly/REF may be dispensable.

  10. Introduction to Complex Plasmas

    CERN Document Server

    Bonitz, Michael; Ludwig, Patrick

    2010-01-01

    Complex plasmas differ from traditional plasmas in many ways: these are low-temperature high pressure systems containing nanometer to micrometer size particles which may be highly charged and strongly interacting. The particles may be chemically reacting or be in contact with solid surfaces, and the electrons may show quantum behaviour. These interesting properties have led to many applications of complex plasmas in technology, medicine and science. Yet complex plasmas are extremely complicated, both experimentally and theoretically, and require a variety of new approaches which go beyond standard plasma physics courses. This book fills this gap presenting an introduction to theory, experiment and computer simulation in this field. Based on tutorial lectures at a very successful recent Summer Institute, the presentation is ideally suited for graduate students, plasma physicists and experienced undergraduates.

  11. The complex pendulum

    Science.gov (United States)

    Bender, Carl M.

    1999-07-01

    This talk proposes a generalization of conventional quantum mechanics. In conventional quantum mechanics one imposes the condition H †=H , where † represents complex conjugation and matrix transpose, to ensure that the Hamiltonian has a real spectrum. By replacing this mathematical condition with the weaker and more physical requirement H ‡=H , where ‡= PT represents combined parity reflection and time reversal, one obtains new infinite classes of complex Hamiltonians whose spectra are also real and positive. These PT-symmetric theories may be viewed as analytic continuations of conventional theories from real to complex-phase space. This talk describes the unusual classical and quantum properties of PT-symmetric quantum-mechanical and quantum-field-theoretic models.

  12. Managing Complexity

    Energy Technology Data Exchange (ETDEWEB)

    Chassin, David P.; Posse, Christian; Malard, Joel M.

    2004-08-01

    Physical analogs have shown considerable promise for understanding the behavior of complex adaptive systems, including macroeconomics, biological systems, social networks, and electric power markets. Many of today’s most challenging technical and policy questions can be reduced to a distributed economic control problem. Indeed, economically-based control of large-scale systems is founded on the conjecture that the price-based regulation (e.g., auctions, markets) results in an optimal allocation of resources and emergent optimal system control. This paper explores the state of the art in the use physical analogs for understanding the behavior of some econophysical systems and to deriving stable and robust control strategies for them. In particular we review and discussion applications of some analytic methods based on the thermodynamic metaphor according to which the interplay between system entropy and conservation laws gives rise to intuitive and governing global properties of complex systems that cannot be otherwise understood.

  13. Requirement emergence computation of networked software

    Institute of Scientific and Technical Information of China (English)

    HE Keqing; LIANG Peng; PENG Rong; LI Bing; LIU Jing

    2007-01-01

    Emergence Computation has become a hot topic in the research of complex systems in recent years.With the substantial increase in scale and complexity of network-based information systems,the uncertain user requirements from the Internet and personalized application requirement result in the frequent change for the software requirement.Meanwhile,the software system with non self-possessed,resource become more and more complex.Furthermore,the interaction and cooperation requirement between software units and running environment in service computing increase the complexity of software systems.The software systems with complex system characteristics are developing into the"Networked Software" with characteristics of change-on-demand and change-with-cooperation.The concepts "programming","compiling" and "running"of software in common sense are extended from "desktop" to "network".The core issue of software engineering is moving to the requirement engineering,which becomes the research focus of complex systemsoftware engineering.In this paper,we present the software network view based on complex system theory,and the concept of networked software and networked requirement.We proposethe challenge problem in the research of emergence computation of networked software requirement.A hierarchical & cooperative Unified requirement modeling framework URF (Unified Requirement Framework) and related RGPS (Role,Goal,Process and Service) meta-models are proposed.Five scales and the evolutionary growth mechanismin requirement emergence computation of networked software are given with focus on user-dominant and domain-oriented requirement,and the rules and predictability in requirement emergence computation are analyzed.A case study in the application of networked e-Business with evolutionary growth based on State design pattern is presented in the end.

  14. Complexity: The bigger picture

    CERN Document Server

    Vicsek, Tamás

    2010-01-01

    If a concept is not well defined, there are grounds for its abuse. This is particularly true of complexity, an inherently interdisciplinary concept that has penetrated very different fields of intellectual activity from physics to linguistics, but with no underlying, unified theory. Complexity has become a popular buzzword used in the hope of gaining attention or funding -- institutes and research networks associated with complex systems grow like mushrooms. Why and how did it happen that this vague notion has become a central motif in modern science? Is it only a fashion, a kind of sociological phenomenon, or is it a sign of a changing paradigm of our perception of the laws of nature and of the approaches required to understand them? Because virtually every real system is inherently extremely complicated, to say that a system is complex is almost an empty statement - couldn't an Institute of Complex Systems just as well be called an Institute for Almost Everything? Despite these valid concerns, the world is ...

  15. Complex variables

    CERN Document Server

    Taylor, Joseph L

    2011-01-01

    The text covers a broad spectrum between basic and advanced complex variables on the one hand and between theoretical and applied or computational material on the other hand. With careful selection of the emphasis put on the various sections, examples, and exercises, the book can be used in a one- or two-semester course for undergraduate mathematics majors, a one-semester course for engineering or physics majors, or a one-semester course for first-year mathematics graduate students. It has been tested in all three settings at the University of Utah. The exposition is clear, concise, and lively

  16. Complex variables

    CERN Document Server

    Flanigan, Francis J

    2010-01-01

    A caution to mathematics professors: Complex Variables does not follow conventional outlines of course material. One reviewer noting its originality wrote: ""A standard text is often preferred [to a superior text like this] because the professor knows the order of topics and the problems, and doesn't really have to pay attention to the text. He can go to class without preparation."" Not so here-Dr. Flanigan treats this most important field of contemporary mathematics in a most unusual way. While all the material for an advanced undergraduate or first-year graduate course is covered, discussion

  17. Sunlight Diffusing Tent for Lunar Worksite

    Science.gov (United States)

    Burleson, Blair; Clark, Todd; Deese, Todd; Gentry, Ernest; Samad, Abdul

    1990-01-01

    The purpose is to provide a solution to problems astronauts encounter with sunlight on the lunar surface. Due to the absence of an atmosphere the Moon is subjected to intense sunlight creating problems with color and contrast. This problem can be overcome by providing a way to reduce intensity and diffuse the light in a working environment. The solution to the problem utilizes an umbrella, tent-like structure covered with a diffusing material. The design takes into account structural materials, stresses, fabrics, and deployment.

  18. Worksite Nutrition: A Decision-Maker's Guide.

    Science.gov (United States)

    American Dietetic Association, Chicago, IL.

    This guide is designed specifically to assist decision makers in business and industry, including chief executive officers, benefits managers, human resource directors, wellness coordinators, and owners of small businesses, in understanding how diet and nutrition affect employees and the company. It addresses the concerns of both small and large…

  19. Potentials for health promotion at worksite

    DEFF Research Database (Denmark)

    Nygaard, Rikke; Mikkelsen, Bent Egberg

    2013-01-01

    but also with the social and mental environment. Food and eating has increasingly become an object of public governance, especially when we are eating out of home as part of our work or educational life. Interventions aiming at improve our eating patterns have become mainstream in many of our everyday life...... health perceptions into account. This paper suggests that active involvement of the workforce, respect for diversity in health perceptions and in relation to norms regarding how health and food are valued, are key elements in the creation of new and healthier ‘ethnodishes’ in future health promotion...

  20. Section 4: Requirements Intertwining

    Science.gov (United States)

    Loucopoulos, Pericles

    Business analysts are being asked to develop increasingly complex and varied business systems that need to cater to the changing and dynamic market conditions of the new economy. This is particularly acute in today’s turbulent business environment where powerful forces such as deregulation, globalisation, mergers, advances in information and telecommunications technologies, and increasing education of people provide opportunities for organising work in ways that have never before been possible. Enterprises attempt to create wealth either by getting better at improving their products and services or by harnessing creativity and human-centred management to create innovative solutions. In these business settings, requirements become critical in bridging system solutions to organisational and societal problems. They intertwine organisational, social, cognitive, and implementation considerations and they can provide unique insights to change in systems and their business context. Such design situations often involve multiple stakeholders from different participating organisations, subcontractors, divisions, etc., who may have a diversity of expertise, come from different organisational cultures and often have competing goals. The success or failure of many projects depends, to a large extent, on understanding the contextual setting of requirements and their interaction amongst a diverse population of stakeholders.

  1. Rationale Management Challenges in Requirements Engineering

    NARCIS (Netherlands)

    Liang, Peng; Avgeriou, Paris; He, Keqing

    2010-01-01

    Rationale and rationale management have been playing an increasingly prominent role in software system development mainly due to the knowledge demand during system evaluation, maintenance, and evolution, especially for large and complex systems. The rationale management for requirements engineering,

  2. Rationale Management Challenges in Requirements Engineering

    NARCIS (Netherlands)

    Liang, Peng; Avgeriou, Paris; He, Keqing

    2010-01-01

    Rationale and rationale management have been playing an increasingly prominent role in software system development mainly due to the knowledge demand during system evaluation, maintenance, and evolution, especially for large and complex systems. The rationale management for requirements engineering,

  3. Groupware requirements evolution patterns

    NARCIS (Netherlands)

    Pumareja, Dulce Trinidad

    2013-01-01

    Requirements evolution is a generally known problem in software development. Requirements are known to change all throughout a system's lifecycle. Nevertheless, requirements evolution is a poorly understood phenomenon. Most studies on requirements evolution focus on changes to written specifications

  4. Complex Functions with GeoGebra

    Science.gov (United States)

    Breda, Ana Maria D'azevedo; Dos Santos, José Manuel Dos Santos

    2016-01-01

    Complex functions, generally feature some interesting peculiarities, seen as extensions of real functions. The visualization of complex functions properties usually requires the simultaneous visualization of two-dimensional spaces. The multiple Windows of GeoGebra, combined with its ability of algebraic computation with complex numbers, allow the…

  5. Sampling and Representation Complexity of Revenue Maximization

    OpenAIRE

    Dughmi, Shaddin; Han, Li; Nisan, Noam

    2014-01-01

    We consider (approximate) revenue maximization in auctions where the distribution on input valuations is given via "black box" access to samples from the distribution. We observe that the number of samples required -- the sample complexity -- is tightly related to the representation complexity of an approximately revenue-maximizing auction. Our main results are upper bounds and an exponential lower bound on these complexities.

  6. Complex Functions with GeoGebra

    Science.gov (United States)

    Breda, Ana Maria D'azevedo; Dos Santos, José Manuel Dos Santos

    2016-01-01

    Complex functions, generally feature some interesting peculiarities, seen as extensions of real functions. The visualization of complex functions properties usually requires the simultaneous visualization of two-dimensional spaces. The multiple Windows of GeoGebra, combined with its ability of algebraic computation with complex numbers, allow the…

  7. Teacher Modeling Using Complex Informational Texts

    Science.gov (United States)

    Fisher, Douglas; Frey, Nancy

    2015-01-01

    Modeling in complex texts requires that teachers analyze the text for factors of qualitative complexity and then design lessons that introduce students to that complexity. In addition, teachers can model the disciplinary nature of content area texts as well as word solving and comprehension strategies. Included is a planning guide for think aloud.

  8. COMPLEXITY AND UNIVERSITY

    Directory of Open Access Journals (Sweden)

    Edna Lemes Martins Pereira

    2013-12-01

    Full Text Available Economic globalization affects different countries on the globe, has positive effects mainly related to access to communication, which promotes the exchange of ideas, information, products and quality of life. However, extends numerous negative aspects such as marginalization, economic dependencies, political, cultural, scientific, educational accentuate social inequalities and cultural conflicts and territorial. In this article it is a dialogue with authors (Cunha 2009; BARNETT 2005; MORIN 1999, 2006, among others, who understand these changes in society from the contemporary world as conceived as the "Complexity era" or "supercomplexity". To understand and cope with this reality, they propose a paradigm that is able to overcome the fragmentation and reductionism of knowledge and to relate the multiple approaches and visions to meet the complexity of reality. Although this paper presents proposals to the aforementioned authors point to education and the university found in this tangle of interconnected global transformations, given the need to be subject to act in a complex reality that requires critical and self-critical professionals, able to think about their own ability to think, understand and act within this complex context.

  9. Project X functional requirements specification

    CERN Document Server

    Holmes, S D; Kephart, R; Kerby, J; Kourbanis, I; Lebedev, V; Mishra, S; Nagaitsev, S; Solyak, N; Tschirhart, R

    2012-01-01

    Project X is a multi-megawatt proton facility being developed to support a world-leading program in Intensity Frontier physics at Fermilab. The facility is designed to support programs in elementary particle and nuclear physics, with possible applications to nuclear energy research. A Functional Requirements Specification has been developed in order to establish performance criteria for the Project X complex in support of these multiple missions, and to assure that the facility is designed with sufficient upgrade capability to provide U.S. leadership for many decades to come. This paper will briefly review the previously described Functional Requirements, and then discuss their recent evolution.

  10. Feed tank transfer requirements

    Energy Technology Data Exchange (ETDEWEB)

    Freeman-Pollard, J.R.

    1998-09-16

    This document presents a definition of tank turnover; DOE responsibilities; TWRS DST permitting requirements; TWRS Authorization Basis (AB) requirements; TWRS AP Tank Farm operational requirements; unreviewed safety question (USQ) requirements; records and reporting requirements, and documentation which will require revision in support of transferring a DST in AP Tank Farm to a privatization contractor for use during Phase 1B.

  11. The GARP complex is required for cellular sphingolipid homeostasis

    DEFF Research Database (Denmark)

    Fröhlich, Florian; Petit, Constance; Kory, Nora

    2015-01-01

    Sphingolipids are abundant membrane components and important signaling molecules in eukaryotic cells. Their levels and localization are tightly regulated. However, the mechanisms underlying this regulation remain largely unknown. In this study, we identify the Golgi-associated retrograde protein ...... of the phenotypes of GARP-deficient yeast or mammalian cells. Together, these data show that GARP is essential for cellular sphingolipid homeostasis and suggest a therapeutic strategy for the treatment of PCCA2....

  12. Complex numbers in quantum theory

    Science.gov (United States)

    Maynard, Glenn

    In 1927, Nobel prize winning physicist, E. Schrodinger, in correspondence with Ehrenfest, wrote the following about the new theory: "What is unpleasant here, and indeed directly to be objected to, is the use of complex numbers. Psi is surely fundamentally a real function." This seemingly simple issue remains unexplained almost ninety years later. In this dissertation I elucidate the physical and theoretical origins of the complex requirement. (Abstract shortened by ProQuest.).

  13. Characterizing biomaterial complexity

    Directory of Open Access Journals (Sweden)

    L.A. Clifton

    2009-07-01

    Full Text Available Biomaterials research will always require a range of techniques to examine structure and function on a range of length scales and in a range of settings. Neutron scattering provides a unique way of disentangling the molecular and structural complexity of biomaterials through study of the constituent components. We examine how the technique has been used to study surface immobilized proteins and lipid films, floating lipid bilayers as mimics of in vitro planar membranes, and formation of fibres from solution by insects and spiders.

  14. Equipment Operational Requirements

    Energy Technology Data Exchange (ETDEWEB)

    Greenwalt, B; Henderer, B; Hibbard, W; Mercer, M

    2009-06-11

    The Iraq Department of Border Enforcement is rich in personnel, but poor in equipment. An effective border control system must include detection, discrimination, decision, tracking and interdiction, capture, identification, and disposition. An equipment solution that addresses only a part of this will not succeed, likewise equipment by itself is not the answer without considering the personnel and how they would employ the equipment. The solution should take advantage of the existing in-place system and address all of the critical functions. The solutions are envisioned as being implemented in a phased manner, where Solution 1 is followed by Solution 2 and eventually by Solution 3. This allows adequate time for training and gaining operational experience for successively more complex equipment. Detailed descriptions of the components follow the solution descriptions. Solution 1 - This solution is based on changes to CONOPs, and does not have a technology component. It consists of observers at the forts and annexes, forward patrols along the swamp edge, in depth patrols approximately 10 kilometers inland from the swamp, and checkpoints on major roads. Solution 2 - This solution adds a ground sensor array to the Solution 1 system. Solution 3 - This solution is based around installing a radar/video camera system on each fort. It employs the CONOPS from Solution 1, but uses minimal ground sensors deployed only in areas with poor radar/video camera coverage (such as canals and streams shielded by vegetation), or by roads covered by radar but outside the range of the radar associated cameras. This document provides broad operational requirements for major equipment components along with sufficient operational details to allow the technical community to identify potential hardware candidates. Continuing analysis will develop quantities required and more detailed tactics, techniques, and procedures.

  15. Workers' exposures and potential health risks to air toxics in a petrochemical complex assessed by improved methodology.

    Science.gov (United States)

    Chan, Chang-Chuan; Shie, Ruei-Hao; Chang, Ta-Yuan; Tsai, Dai-Hua

    2006-02-01

    This study was designed to comprehensively evaluate workers' potential health risks of exposure to 39 air toxics in the Ta-sher Petrochemical Complex. Open-Path Fourier Transform Infrared Spectroscopy (OP-FTIR) was used to measure concentrations of air toxics. We used the measured worksite concentrations between 1997 and 1999 at 11 companies in the petrochemical complex, employing 3,100 on-site workers. The 39 measured air toxics included 10 chemicals with acute reference exposure levels (RELa), 19 chemicals with chronic reference exposure levels (RELc), and 3 chemicals classified as Class 1 or 2A human carcinogens by the International Agency for Research on Cancer (IARC). We then used RELa to calculate the hazard index of acute health effects (HI ( A )) for workers in individual plants. We also calculated the hazard index of chronic health effects (HIc) and cancer risks for all workers in the entire petrochemical complex. Workers in five companies had HI ( A ) greater than 1 because of toluene, benzene, methyl ethyl ketone, chloroform and isopropanol exposures. Workers in this petrochemical complex had HIc greater than 1 because of acrylonitrile, 1,3-butadiene, hydrogen cyanide, and n,n-dimethylformamide exposures. Risk of hematopoietic system cancer because of benzene and ethylene oxide exposure, and respiratory system cancer because of 1,3-butadiene exposure was estimated to be 3.1-6.1 x 10(-4) and 5.2-7.1 x 10(-4), respectively. Our findings indicated that workers in the petrochemical complex might have excess cancer and noncancer risks due to acute or chronic exposures to air toxics from multiple emission sources.

  16. Managing System of Systems Requirements with a Requirements Screening Group

    Energy Technology Data Exchange (ETDEWEB)

    Ronald R. Barden

    2012-07-01

    Figuring out an effective and efficient way to manage not only your Requirement’s Baseline, but also the development of all your individual requirements during a Program’s/Project’s Conceptual and Development Life Cycle Stages can be both daunting and difficult. This is especially so when you are dealing with a complex and large System of Systems (SoS) Program with potentially thousands and thousands of Top Level Requirements as well as an equal number of lower level System, Subsystem and Configuration Item requirements that need to be managed. This task is made even more overwhelming when you have to add in integration with multiple requirements’ development teams (e.g., Integrated Product Development Teams (IPTs)) and/or numerous System/Subsystem Design Teams. One solution for tackling this difficult activity on a recent large System of Systems Program was to develop and make use of a Requirements Screening Group (RSG). This group is essentially a Team made up of co-chairs from the various Stakeholders with an interest in the Program of record that are enabled and accountable for Requirements Development on the Program/Project. The RSG co-chairs, often with the help of individual support team, work together as a Program Board to monitor, make decisions on, and provide guidance on all Requirements Development activities during the Conceptual and Development Life Cycle Stages of a Program/Project. In addition, the RSG can establish and maintain the Requirements Baseline, monitor and enforce requirements traceability across the entire Program, and work with other elements of the Program/Project to ensure integration and coordination.

  17. Feed tank transfer requirements

    Energy Technology Data Exchange (ETDEWEB)

    Freeman-Pollard, J.R.

    1998-09-16

    This document presents a definition of tank turnover. Also, DOE and PC responsibilities; TWRS DST permitting requirements; TWRS Authorization Basis (AB) requirements; TWRS AP Tank Farm operational requirements; unreviewed safety question (USQ) requirements are presented for two cases (i.e., tank modifications occurring before tank turnover and tank modification occurring after tank turnover). Finally, records and reporting requirements, and documentation which will require revision in support of transferring a DST in AP Tank Farm to a privatization contractor are presented.

  18. The SEA complex – the beginning

    Directory of Open Access Journals (Sweden)

    Dokudovskaya S. S.

    2012-07-01

    Full Text Available The presence of distinctive internal membrane compartments, dynamically connected via selective transport pathways, is a hallmark of eukaryotic cells. Many of the proteins required for formation and maintenance of these compartments share an evolutionary history. We have recently identified a new conserved protein complex – the SEA complex – that possesses proteins with structural characteristics similar to the membrane coating complexes such as the nuclear pore complex (NPC, the COPII vesicle coating complex and HOPS/CORVET tethering complexes. The SEA complex in yeast is dynamically associated to the vacuole. The data on the function of the SEA complex remain extremely limited. Here we will discuss a possible role of the SEA complex based on the data from genetic assays and a number of functional studies in both yeast and other eukaryotes.

  19. Assessment and Transfer: Unexamined Complexities.

    Science.gov (United States)

    Mittler, Mary L.; Bers, Trudy H.

    1994-01-01

    Examines the complexities, costs, and questions in planning and implementing feasible, reasoned assessment created by the dual phenomena of assessment and student mobility. Highlights institutional responsibility, student competence, timeliness, multiple and redundant assessment requirements, and lack of interinstitutional collaboration as issues…

  20. Management of Complex Anal Fistulas

    Science.gov (United States)

    Bubbers, Emily J.; Cologne, Kyle G.

    2016-01-01

    Complex anal fistulas require careful evaluation. Prior to any attempts at definitive repair, the anatomy must be well defined and the sepsis resolved. Several muscle-sparing approaches to anal fistula are appropriate, and are often catered to the patient based on their presentation and previous repairs. Emerging technologies show promise for fistula repair, but lack long-term data. PMID:26929751

  1. Metric for Early Measurement of Software Complexity

    Directory of Open Access Journals (Sweden)

    Ghazal Keshavarz,

    2011-06-01

    Full Text Available Software quality depends on several factors such as on time delivery; within budget and fulfilling user's needs. Complexity is one of the most important factors that may affect the quality. Therefore, measuring and controlling the complexity result in improving the quality. So far, most of the researches have tried to identify and measure the complexity in design and code phase. However, whenwe have the code or design for software, it is too late to control complexity. In this article, with emphasis on Requirement Engineering process, we analyze the causes of software complexity, particularly in the first phase of software development, and propose a requirement based metric. This metric enables a software engineer to measure the complexity before actual design and implementation and choosestrategies that are appropriate to the software complexity degree, thus saving on cost and human resource wastage and, more importantly, leading to lower maintenance costs.

  2. Discovering system requirements

    Energy Technology Data Exchange (ETDEWEB)

    Bahill, A.T.; Bentz, B. [Univ. of Arizona, Tucson, AZ (United States). Systems and Industrial Engineering; Dean, F.F. [Sandia National Labs., Albuquerque, NM (United States)

    1996-07-01

    Cost and schedule overruns are often caused by poor requirements that are produced by people who do not understand the requirements process. This report provides a high-level overview of the system requirements process, explaining types, sources, and characteristics of good requirements. System requirements, however, are seldom stated by the customer. Therefore, this report shows ways to help you work with your customer to discover the system requirements. It also explains terminology commonly used in the requirements development field, such as verification, validation, technical performance measures, and the various design reviews.

  3. Ontology Requirements Specification

    OpenAIRE

    Suárez-Figueroa, Mari Carmen; Gómez-Pérez, A.

    2012-01-01

    The goal of the ontology requirements specification activity is to state why the ontology is being built, what its intended uses are, who the end users are, and which requirements the ontology should fulfill. This chapter presents detailed methodological guidelines for specifying ontology requirements efficiently. These guidelines will help ontology engineers to capture ontology requirements and produce the ontology requirements specification document (ORSD). The ORSD will play a key role dur...

  4. CMS Requirements for the Grid

    Institute of Scientific and Technical Information of China (English)

    K.Holtman; J.Amundson; 等

    2001-01-01

    CMS physicists need to seamlessly access their experimental data and results,independent of location and storage medium,in order to focus on the exploration for the new physics signals arther than the complexities of worldwide data management .In order to achieve this goal,CMS has adopted a tiered worldwide computing model which will incorporate emerging Grid technology.CMS has started to use Grid tools for data processing,replication and migration,Important Grid components are expected to be delivered by the Data Grid projects.like projects,CMS has created a set of long-term requirements to the Grid projects.These requirements are presented and discussed.

  5. Postmarket Requirements and Commitments

    Data.gov (United States)

    U.S. Department of Health & Human Services — Provides information to the public on postmarket requirements and commitments. The phrase postmarket requirements and commitments refers to studies and clinical...

  6. Requirements for existing buildings

    DEFF Research Database (Denmark)

    Thomsen, Kirsten Engelund; Wittchen, Kim Bjarne

    2012-01-01

    This report collects energy performance requirements for existing buildings in European member states by June 2012.......This report collects energy performance requirements for existing buildings in European member states by June 2012....

  7. Replacing reserve requirements

    OpenAIRE

    Edward J. Stevens

    1993-01-01

    An examination of the fading significance of the Federal Reserve System's reserve requirements and the recent flowering of required clearing balances, a rapidly growing feature of Reserve Bank operations.

  8. Requirements for existing buildings

    DEFF Research Database (Denmark)

    Thomsen, Kirsten Engelund; Wittchen, Kim Bjarne

    2012-01-01

    This report collects energy performance requirements for existing buildings in European member states by June 2012.......This report collects energy performance requirements for existing buildings in European member states by June 2012....

  9. Replacing reserve requirements

    OpenAIRE

    Edward J. Stevens

    1993-01-01

    An examination of the fading significance of the Federal Reserve System's reserve requirements and the recent flowering of required clearing balances, a rapidly growing feature of Reserve Bank operations.

  10. Future Home Network Requirements

    DEFF Research Database (Denmark)

    Charbonnier, Benoit; Wessing, Henrik; Lannoo, Bart;

    This paper presents the requirements for future Home Area Networks (HAN). Firstly, we discuss the applications and services as well as their requirements. Then, usage scenarios are devised to establish a first specification for the HAN. The main requirements are an increased bandwidth (towards 1...

  11. Future Home Network Requirements

    DEFF Research Database (Denmark)

    Charbonnier, Benoit; Wessing, Henrik; Lannoo, Bart

    This paper presents the requirements for future Home Area Networks (HAN). Firstly, we discuss the applications and services as well as their requirements. Then, usage scenarios are devised to establish a first specification for the HAN. The main requirements are an increased bandwidth (towards 1...

  12. PIT Coating Requirements Analysis

    Energy Technology Data Exchange (ETDEWEB)

    MINTEER, D.J.

    2000-10-20

    This study identifies the applicable requirements for procurement and installation of a coating intended for tank farm valve and pump pit interior surfaces. These requirements are intended to be incorporated into project specification documents and design media. This study also evaluates previously recommended coatings and identifies requirement-compliant coating products.

  13. Accuracy assessment with complex sampling designs

    Science.gov (United States)

    Raymond L. Czaplewski

    2010-01-01

    A reliable accuracy assessment of remotely sensed geospatial data requires a sufficiently large probability sample of expensive reference data. Complex sampling designs reduce cost or increase precision, especially with regional, continental and global projects. The General Restriction (GR) Estimator and the Recursive Restriction (RR) Estimator separate a complex...

  14. Chimera multiscale simulation of complex flowing matter

    CERN Document Server

    Succi, Sauro

    2016-01-01

    We discuss a unified mesoscale framework for the simulation of complex states of flowing matter across scales of motion which requires no explicit coupling between different macro-meso-micro levels. The idea is illustrated through selected examples of complex flows at the micro and nanoscale.

  15. Deriving force field parameters for coordination complexes

    DEFF Research Database (Denmark)

    Norrby, Per-Ola; Brandt, Peter

    2001-01-01

    The process of deriving molecular mechanics force fields for coordination complexes is outlined. Force field basics are introduced with an emphasis on special requirements for metal complexes. The review is then focused on how to set up the initial model, define the target, refine the parameters,...

  16. Transportation System Requirements Document

    Energy Technology Data Exchange (ETDEWEB)

    1993-09-01

    This Transportation System Requirements Document (Trans-SRD) describes the functions to be performed by and the technical requirements for the Transportation System to transport spent nuclear fuel (SNF) and high-level radioactive waste (HLW) from Purchaser and Producer sites to a Civilian Radioactive Waste Management System (CRWMS) site, and between CRWMS sites. The purpose of this document is to define the system-level requirements for Transportation consistent with the CRWMS Requirement Document (CRD). These requirements include design and operations requirements to the extent they impact on the development of the physical segments of Transportation. The document also presents an overall description of Transportation, its functions, its segments, and the requirements allocated to the segments and the system-level interfaces with Transportation. The interface identification and description are published in the CRWMS Interface Specification.

  17. Software Requirements Management

    Directory of Open Access Journals (Sweden)

    Ali Altalbe

    2015-04-01

    Full Text Available Requirements are defined as the desired set of characteristics of a product or a service. In the world of software development, it is estimated that more than half of the failures are attributed towards poor requirements management. This means that although the software functions correctly, it is not what the client requested. Modern software requirements management methodologies are available to reduce the occur-rence of such incidents. This paper performs a review on the available literature in the area while tabulating possible methods of managing requirements. It also highlights the benefits of following a proper guideline for the requirements management task. With the introduction of specific software tools for the requirements management task, better software products are now been developed with lesser resources.

  18. Quantum coherence in photosynthetic complexes

    Energy Technology Data Exchange (ETDEWEB)

    Calhoun, Tessa R.; Fleming, Graham R. [Department of Chemistry, University of California, Berkeley, CA 94720 (United States); Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States)

    2011-04-15

    The initial steps of photosynthesis require the absorption and subsequent transfer of energy through an intricate network of pigment-protein complexes. Held within the protein scaffold of these complexes, chromophore molecules are densely packed and fixed in specific geometries relative to one another resulting in Coulombic coupling. Excitation energy transfer through these systems can be accomplished with near unity quantum efficiency [Wraight and Clayton, Biochim. Biophys. Acta 333, 246 (1974)]. While replication of this feat is desirable for artificial photosynthesis, the mechanism by which nature achieves this efficiency is unknown. Recent experiments have revealed the presence of long-lived quantum coherences in photosynthetic pigment-protein complexes spanning bacterial and plant species with a variety of functions and compositions. Its ubiquitous presence and wavelike energy transfer implicate quantum coherence as key to the high efficiency achieved by photosynthesis. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  19. Turning Desirements into Requirements

    Science.gov (United States)

    2015-09-01

    budgets, assessment teams must wonder when to consider the cost of a particular solution. The DoD management systems wisely separate requirements gen...analysis so the The warfighter—the man or woman who goes into harm’s way— has every imperative to expect much of us as requirements managers, program...the man or woman who goes into harm’s way—has every imperative to expect much of us as requirements managers, program managers, and resource

  20. Anthropometric Requirements for Constellation

    Science.gov (United States)

    Raulu, Sudhakar; Margerum, Sarah; Dory, Jonathan; Rochlis, Jennifer

    2009-01-01

    This slide presentation reviews the requirement from an Anthropometric standpoint for the development of the Constellation's programs hardware, specifically the Orion crew exploration vehicle. The NASA JSC Anthropometry and Biomechanics Facility (ABF) provides anthropometry, strength, mobility, and mass properties requirements; gathers, interprets, manages and maintains the flight crew anthropometry database; and participates and provides input during crew selection. This is used to assist in requirements for vehicle and space suit design and for crew selection.