WorldWideScience

Sample records for programme g8gp physical

  1. Implementation of the G8GP program on physical protection - experiences and results

    International Nuclear Information System (INIS)

    Hagemann, A.

    2006-01-01

    At the Kananaskis Summit in June 2002, G8 Leaders launched the Global Partnership against the Spread of Weapons and Materials of Mass Destruction committing to support projects to issues of non-proliferation, disarmament, counter terrorism and nuclear safety in Russia. Since then progress has been made in implementing projects. The German Federal Foreign Office contracted GRS to implement a program for improving the physical protection of nuclear or highly radioactive materials of relevance at facilities in the Russian Federation. This paper reports about this G8GP Program on physical protection, its implementation, gained experiences, current achievements and results. (author)

  2. Future prospects of the international G-8 Global Partnership Programme

    International Nuclear Information System (INIS)

    Grigor'ev, A.V.; Esaulova, A.V.

    2012-01-01

    The Global Partnership Programme Against the Spread of Weapons and Materials of Mass Destruction was adopt at the Group-8 (G-8) summit on the 27-th of June 2002 for 10 years. At the G-8 summit in May 2011, the decision was made to extent the Global Partnership Programme to beyond 2012 and to expand its reach and geographical coverage. New areas for cooperation were named, such as: nuclear, radiological and biological safety, employment of scientists involved with sensitive industries and assistance to third countries in their compliance with the provisions of United Nations Security Council Resolution No 1540. The parties re-affirmed their commitment to completing a series of priority projects in Russia [ru

  3. The Pathogenicity of Anti-β2GP1-IgG Autoantibodies Depends on Fc Glycosylation

    Directory of Open Access Journals (Sweden)

    Christoph Fickentscher

    2015-01-01

    Full Text Available To analyze the glycosylation of anti-β2GP1, we investigated purified IgG from healthy children, patients with APS, and asymptomatic adult carriers of antiphospholipid antibodies. We observed that in the sera of healthy children and of patients with APS, IgG3 and IgG2 were predominant, respectively. The potentially protective anti-β2GP1-IgM was lower in the sera of healthy children. Although anti-β2GP1-associated C1q did not differ between children and patients with antiphospholipid syndrome, the associated C3c was significantly higher in the sera of healthy children. This indicates a more efficient clearance of anti-β2GP1 immune complexes in the healthy children. This clearance is not accompanied by inflammation or coagulatory events. It is likely that the most important pathogenic factor of the anti-β2GP1-IgG is related to the different glycosylation observed in healthy and diseased individuals. We detected a significantly higher sialylation of anti-β2GP1-IgG isolated from the sera of healthy children and asymptomatic adults when compared with that of patients with clinically apparent antiphospholipid syndrome. Low sialylated IgG reportedly ameliorates inflammation and inflammation promotes hyposialylation. Thus, both reactions create a vicious circle that precipitates the pathology of the antiphospholipid syndrome including thrombus-formation. We conclude that the increased sialylation of anti-β2GP1-IgG of sera of healthy individuals limits their pathogenicity.

  4. HIV-gp120 and physical dependence to buprenorphine.

    Science.gov (United States)

    Palma, J; Abood, M E; Benamar, K

    2015-05-01

    Opioids are among the most effective and commonly used analgesics in clinical practice for severe pain. However, the use of opioid medications is clinically limited by several adverse properties including dependence. While opioid dependence is a complex health condition, the treatment of HIV-infected individuals with opioid dependence presents additional challenges. The goal of this study was to examine the physical dependence to buprenorphine in the context of HIV. Young adult male rats (Sprague-Dawley) were pretreated with HIV-1 envelope glycoprotein 120 (gp120) injected into the periaqueductal gray area (PAG) and we examined the impact on physical dependence to opioid. It was found that the physical dependence to methadone occurred earlier than that to buprenorphine, and that gp120 did not enhance or precipitate the buprenorphine withdrawal. The results suggest that buprenorphine could be the better therapeutic option to manage opioid dependence in HIV. Copyright © 2015. Published by Elsevier Ireland Ltd.

  5. G-8 leaders tackle global energy security

    International Nuclear Information System (INIS)

    Quevenco, R.

    2006-01-01

    Leaders of the Group of 8 countries backed the IAEA's work at their annual summit held 15-17 July 2006 in St. Petersburg, Russia. A concluding summary statement endorsed IAEA programmes and initiatives in areas of nuclear safety, security, and safeguards. The G8 nations adopted a St. Petersburg Plan of Action to increase transparency, predictability and stability of the global energy markets, improve the investment climate in the energy sector, promote energy efficiency and energy saving, diversify energy mix, ensure physical safety of critical energy infrastructure, reduce energy poverty and address climate change and sustainable development. In a statement on global energy security, the G8 said countries who have or are considering plans for nuclear energy believe it will contribute to global energy security while reducing air pollution and addressing climate change. The G8 said it acknowledged the efforts made in development by the Generation IV International Forum (GIF) and the IAEA's International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO). GIF and INPRO both bring together countries to develop next generation nuclear energy systems, including small reactors, very high temperature reactors and supercritical water-cooled reactors. The G8 reaffirmed its full commitment to all three pillars of the NPT and called on all States to comply with their NPT obligations, including IAEA safeguards as well as developing effective measures aimed at preventing trafficking in nuclear equipment, technology and materials. The G8 is seeking universal adherence to IAEA comprehensive safeguards agreements and is actively engaged in efforts to make comprehensive safeguards agreements together with an Additional Protocol the universally accepted verification standard. The G8 noted that an expansion of the peaceful use of nuclear energy must be carried forward in a manner consistent with nuclear non-proliferation commitments and standards. It discussed concrete

  6. Incorporating and evaluating an integrated gender-specific medicine curriculum: a survey study in Dutch GP training

    Science.gov (United States)

    Dielissen, Patrick W; Bottema, Ben JAM; Verdonk, Petra; Lagro-Janssen, Toine LM

    2009-01-01

    Background We recently set standards for gender-specific medicine training as an integrated part of the GP training curriculum. This paper describes the programme and evaluation of this training. Methods The programme is designed for GP registrars throughout the 3-year GP training. The modules emphasize interaction, application, and clinically integrated learning and teaching methods in peer groups. In 2005 - 2008, after completion of each tutorial, GP registrars were asked to fill in a questionnaire on a 5-point Likert scale to assess the programme's methods and content. GP registrars were also asked to identify two learning points related to the programme. Results The teaching programme consists of five 3-hour modules that include gender themes related to and frequently seen by GPs such as in doctor-patient communication and cardiovascular disease. GP registrars evaluated the training course positively. The written learning points suggest that GP registrars have increased their awareness of why attention to gender-specific information is relevant. Conclusion In summary, gender-specific medicine training has been successfully integrated into an existing GP training curriculum. The modules and teaching methods are transferable to other training institutes for postgraduate training. The evaluation of the teaching programme shows a positive impact on GP registrars' gender awareness. PMID:19737396

  7. Incorporating and evaluating an integrated gender-specific medicine curriculum: a survey study in Dutch GP training

    Directory of Open Access Journals (Sweden)

    Lagro-Janssen Toine LM

    2009-09-01

    Full Text Available Abstract Background We recently set standards for gender-specific medicine training as an integrated part of the GP training curriculum. This paper describes the programme and evaluation of this training. Methods The programme is designed for GP registrars throughout the 3-year GP training. The modules emphasize interaction, application, and clinically integrated learning and teaching methods in peer groups. In 2005 - 2008, after completion of each tutorial, GP registrars were asked to fill in a questionnaire on a 5-point Likert scale to assess the programme's methods and content. GP registrars were also asked to identify two learning points related to the programme. Results The teaching programme consists of five 3-hour modules that include gender themes related to and frequently seen by GPs such as in doctor-patient communication and cardiovascular disease. GP registrars evaluated the training course positively. The written learning points suggest that GP registrars have increased their awareness of why attention to gender-specific information is relevant. Conclusion In summary, gender-specific medicine training has been successfully integrated into an existing GP training curriculum. The modules and teaching methods are transferable to other training institutes for postgraduate training. The evaluation of the teaching programme shows a positive impact on GP registrars' gender awareness.

  8. Astroparticle physics: the new ASPERA-2 programme

    CERN Multimedia

    2009-01-01

    On 7 July the ASPERA-2 programme funded by the European Commission was officially launched in Hamburg with the goal of creating a sustainable structure for the coordination of astroparticle physics in Europe. CERN, which is a participant in the programme, could play an important role in this respect. Artist’s impression of the CTA (Cherenkov Telescope Array). The CTA is one of the "Magnificent Seven", the seven large astroparticle physics infrastructures planned for the coming years. It is the next-generation facility destined to succeed the H.E.S.S. telescope in Namibia and the MAGIC telescope in the Canary Islands. (Credit ASPERA/G.Toma/A.Saftoiu). Following the success of ASPERA-1, the European network for astroparticle physics (see box), funding agency representatives gathered in Hamburg on 7 July 2009 for the official launch of ASPERA-2, a new three-year programme funded by the European Commission. Today the strategic roles of ...

  9. Effects of two physical education programmes on health- and skill-related physical fitness of Albanian children.

    Science.gov (United States)

    Jarani, J; Grøntved, A; Muca, F; Spahi, A; Qefalia, D; Ushtelenca, K; Kasa, A; Caporossi, D; Gallotta, M C

    2016-01-01

    This study aims to evaluate the effectiveness of two school-based physical education (PE) programmes (exercise-based and games-based) compared with traditional PE, on health- and skill-related physical fitness components in children in Tirana, Albania. Participants were 378 first-grade (6.8 years) and 389 fourth-grade (9.8 years) children attending four randomly selected schools in Tirana. Twenty-four school classes within these schools were randomly selected (stratified by school and school grade) to participate as exercise group (EG), games group (GG) and control group (CG). Both EG and GG intervention programmes were taught by professional PE teachers using station/circuit teaching framework while CG referred to traditional PE school lessons by a general teacher. All programmes ran in parallel and lasted 5 months, having the same frequency (twice weekly) and duration (45 min). Heart rate (HR) monitoring showed that intensity during PE lessons was significantly higher in the intervention groups compared with control (P games programmes significantly improved several health- and skill-related fitness indicators compared with traditional PE lessons (e.g. gross motor skill summary score: 9.4 (95% CI 7.9; 10.9) for exercise vs. control and 6.5 (95% CI 5.1; 8.1) for games vs. control, cardiorespiratory fitness: 2.0 ml O2 · min(-1) · kg(-1) (95% CI 1.5; 2.4) for exercise vs. control and 1.4 ml O2 · min(-1) · kg(-1) (95% CI 1.0; 1.8) for games vs. control). Furthermore, compared to games-based PE, exercise-based PE showed more positive changes in some gross motor coordination skills outcomes, coordination skills outcomes and cardiorespiratory fitness. The results from this study show that exercise- and games-based PE represents a useful strategy for improving health- and skill-related physical fitness in Albanian elementary school children. In addition, the study shows that exercise-based PE was more effective than games-based PE in improving gross motor function

  10. Review of the book: Yurkevich, G.P. Energetic reactor control systems. Editing by N.S. Khlopkin. Moscow, 2001, 344 p

    International Nuclear Information System (INIS)

    Kondrat'ev, V.V.

    2002-01-01

    Review of the book: Yurkevich, G.P. Energetic reactor control systems. Editing by N.S. Khlopkin. Moscow, 2001, is presented. Advantages of the book, specifically, easy of presentation of sophistical physical processes, new, practical and valid theoretical ways of decision of the problems are discussed. New and original decisions proposed by the author of the book are discussed. The book is beneficial for wide round of specialists [ru

  11. Bone age assessment in Hispanic children: digital hand atlas compared with the Greulich and Pyle (G&P) atlas

    Science.gov (United States)

    Fernandez, James Reza; Zhang, Aifeng; Vachon, Linda; Tsao, Sinchai

    2008-03-01

    Bone age assessment is most commonly performed with the use of the Greulich and Pyle (G&P) book atlas, which was developed in the 1950s. The population of theUnited States is not as homogenous as the Caucasian population in the Greulich and Pyle in the 1950s, especially in the Los Angeles, California area. A digital hand atlas (DHA) based on 1,390 hand images of children of different racial backgrounds (Caucasian, African American, Hispanic, and Asian) aged 0-18 years was collected from Children's Hospital Los Angeles. Statistical analysis discovered significant discrepancies exist between Hispanic and the G&P atlas standard. To validate the usage of DHA as a clinical standard, diagnostic radiologists performed reads on Hispanic pediatric hand and wrist computed radiography images using either the G&P pediatric radiographic atlas or the Children's Hospital Los Angeles Digital Hand Atlas (DHA) as reference. The order in which the atlas is used (G&P followed by DHA or vice versa) for each image was prepared before actual reading begins. Statistical analysis of the results was then performed to determine if a discrepancy exists between the two readings.

  12. The Cytoplasmic Tail Domain of Epstein-Barr Virus gH Regulates Membrane Fusion Activity through Altering gH Binding to gp42 and Epithelial Cell Attachment

    Directory of Open Access Journals (Sweden)

    Jia Chen

    2016-11-01

    Full Text Available Epstein-Barr virus (EBV is associated with infectious mononucleosis and a variety of cancers as well as lymphoproliferative disorders in immunocompromised patients. EBV mediates viral entry into epithelial and B cells using fusion machinery composed of four glycoproteins: gB, the gH/gL complex, and gp42. gB and gH/gL are required for both epithelial and B cell fusion. The specific role of gH/gL in fusion has been the most elusive among the required herpesvirus entry glycoproteins. Previous mutational studies have focused on the ectodomain of EBV gH and not on the gH cytoplasmic tail domain (CTD. In this study, we chose to examine the function of the gH CTD by making serial gH truncation mutants as well as amino acid substitution mutants to determine the importance of the gH CTD in epithelial and B cell fusion. Truncation of 8 amino acids (aa 698 to 706 of the gH CTD resulted in diminished fusion activity using a virus-free syncytium formation assay and fusion assay. The importance of the amino acid composition of the gH CTD was also investigated by amino acid substitutions that altered the hydrophobicity or hydrophilicity of the CTD. These mutations also resulted in diminished fusion activity. Interestingly, some of the gH CTD truncation mutants and hydrophilic tail substitution mutants lost the ability to bind to gp42 and epithelial cells. In summary, our studies indicate that the gH CTD is an important functional domain.

  13. Expression and Significance of gp96 and Immune-related Gene CTLA-4, CD8 in Lung Cancer Tissues

    Directory of Open Access Journals (Sweden)

    Haiyan ZHENG

    2010-08-01

    Full Text Available Background and objective It has been proven that gp96 plays an important role in specific cytotoxic immune response which is involved in anti-tumor effect in the body. The aim of this study is to investigate the biological significance of heat shock protein gp96 and immune-related gene CTLA-4, CD8 expressions in lung cancer tissues of different progressive stages. Methods We used Envision immunohistochemistry method to detect the levels of expression of gp96, CTLA-4, CD8 in tissue microarray, which contained 89 primary lung cancer tissues, 12 lymph node metastasis lung cancer tissues, 12 precancerous lesions and 10 normal lung tissues, and analyzed the relationship between their expressions and clinicopathological parameters. Results (1 The positive rate of gp96 in primary lung cancer was remarkably higher than that in precancerous lesion and normal lung tissue (P < 0.05. The positive rate of CTLA-4 in primary lung cancer tissue and precancerous lesion was significantly higher than that in normal lung tissue (P < 0.05. The positive rate of CD8 in primary lung cancer tissue was significantly higher than that in normal lung tissue (P < 0.05. The positive rate of gp96 in CD8-positive lymphocytes in the high expression group was less than that in the low group (P < 0.05. (2 The positive rate of gp96 was closely related to sex, differentiation and clinical stage (P < 0.05, but not to age, gross type, histological type and lymph node metastasis (P > 0.05. The positive rate of CTLA-4 was closely related to age and differentiation (P < 0.05, but not to sex, gross type, histological type, clinical stage and lymph node metastasis (P > 0.05. CD8 expression was related to clinical stage (P < 0.05, but not to sex, age, gross type, histological type, differentiation and lymph node metastasis (P > 0.05. The positive rates of gp96, CTLA-4 were higher than that of CD8 in squamous cell carcinoma and SCLC, respectively. (3 There was positive correlation between gp

  14. VSVΔG/EBOV GP-induced innate protection enhances natural killer cell activity to increase survival in a lethal mouse adapted Ebola virus infection.

    Science.gov (United States)

    Williams, Kinola J N; Qiu, Xiangguo; Fernando, Lisa; Jones, Steven M; Alimonti, Judie B

    2015-02-01

    Members of the species Zaire ebolavirus cause severe hemorrhagic fever with up to a 90% mortality rate in humans. The VSVΔG/EBOV GP vaccine has provided 100% protection in the mouse, guinea pig, and nonhuman primate (NHP) models, and has also been utilized as a post-exposure therapeutic to protect mice, guinea pigs, and NHPs from a lethal challenge of Ebola virus (EBOV). EBOV infection causes rapid mortality in human and animal models, with death occurring as early as 6 days after infection, suggesting a vital role for the innate immune system to control the infection before cells of the adaptive immune system can assume control. Natural killer (NK) cells are the predominant cell of the innate immune response, which has been shown to expand with VSVΔG/EBOV GP treatment. In the current study, an in vivo mouse model of the VSVΔG/EBOV GP post-exposure treatment was used for a mouse adapted (MA)-EBOV infection, to determine the putative VSVΔG/EBOV GP-induced protective mechanism of NK cells. NK depletion studies demonstrated that mice with NK cells survive longer in a MA-EBOV infection, which is further enhanced with VSVΔG/EBOV GP treatment. NK cell mediated cytotoxicity and IFN-γ secretion was significantly higher with VSVΔG/EBOV GP treatment. Cell mediated cytotoxicity assays and perforin knockout mice experiments suggest that there are perforin-dependent and -independent mechanisms involved. Together, these data suggest that NK cells play an important role in VSVΔG/EBOV GP-induced protection of EBOV by increasing NK cytotoxicity, and IFN-γ secretion.

  15. Development and implementation of a lifestyle intervention to promote physical activity and healthy diet in the Dutch general practice setting: the BeweegKuur programme

    Directory of Open Access Journals (Sweden)

    de Vries Nanne K

    2010-05-01

    Full Text Available Abstract Background The number of patients with diabetes is increasing. BeweegKuur (Dutch for 'Exercise Therapy' is a Dutch lifestyle intervention which aims to effectively and feasibly promote physical activity and better dietary behaviour in primary health care to prevent diabetes. Methods The goal of this paper is to present the development process and the contents of the intervention, using a model of systematic health promotion planning. The intervention consists of a 1-year programme for diabetic and prediabetic patients. Patients are referred by their general practitioner (GP to a lifestyle advisor (LSA, usually the practice nurse or a physiotherapist. Based on specific inclusion criteria and in close collaboration with the patient, an individual exercise programme is designed and supervised by the LSA. This programme can be attended at existing local exercise facilities or (temporarily under the supervision of a specialized exercise coach or physiotherapist. All participants are also referred to a dietician and receive diet-related group education. In the first pilot year (2008, the BeweegKuur programme was implemented in 7 regions in the Netherlands (19 GP practices and health centres, while 14 regions (41 GP practices and health centres participated during the second year. The aim is to implement BeweegKuur in all regions of the Netherlands by 2012. Discussion The BeweegKuur programme was systematically developed in an evidence- and practice-based process. Formative monitoring studies and (controlled effectiveness studies are needed to examine the diffusion process and the effectiveness and cost-effectiveness of the intervention.

  16. Effects of physical exercise programme on happiness among older people.

    Science.gov (United States)

    Khazaee-Pool, M; Sadeghi, R; Majlessi, F; Rahimi Foroushani, A

    2015-02-01

    This randomized-controlled trial investigated the effect of physical exercise programme (PEP) on happiness among older adults in Nowshahr, Iran. Results of this study on 120 male and female volunteers showed that an 8-week group physical exercise programme was significantly effective in older adults' happiness. Findings showed that physical exercise programme is so beneficial for increasing older adults' happiness. Physical activity is associated with well-being and happiness. The purpose of this study was to determine the effects of an 8-week long physical exercise programme (PEP) on happiness among older adults in Nowshahr, Iran. This was a randomized control trial study. The participants consisted of a group of 120 male and female volunteers (mean ± SD age: 71 ± 5.86 years) in a convenience sampling among older adults in public parks in Nowshahr, Iran. We randomly allocated them into experimental (n = 60) and control (n = 60) groups. A validated instrument was used to measure well-being and happiness [Oxford Happiness Inventory (OHI)]. Respondents were asked to complete the OHI before and 2 months after implementing PEP. The 8-week PEP was implemented with the intervention group. The statistical analysis of the data was conducted using paired t-test, Fisher's exact test and χ(2). Before the intervention, there was no significant difference in the happiness mean score between the case and control groups; however, after implementing PEP, happiness significantly improved among the experimental group (P = 0.001) and did not improve within the control group (P = 0.79). It can be concluded that PEP had positive effects on happiness among older adults. Planning and implementing of physical activity is so important for older happiness. © 2014 John Wiley & Sons Ltd.

  17. Sudan ebolavirus long recovered survivors produce GP-specific Abs that are of the IgG1 subclass and preferentially bind FcγRI.

    Science.gov (United States)

    Radinsky, Olga; Edri, Avishay; Brusilovsky, Michael; Fedida-Metula, Shlomit; Sobarzo, Ariel; Gershoni-Yahalom, Orly; Lutwama, Julius; Dye, John; Lobel, Leslie; Porgador, Angel

    2017-07-20

    Ebolavirus is a highly lethal pathogen, causing a severe hemorrhagic disease with a high fatality rate. To better understand immune correlates of protection by virus specific IgG, we investigated the evolution of the Fcγ receptors (FcγRs)-activating capabilities of antiviral IgG in serum samples of long recovered survivors. To this end, longitudinal serum samples from survivors of Sudan ebolavirus (SUDV) infection, studied over years, were examined for the presence of Ebola-GP specific IgG subclasses, and for their binding to FcγRs. We developed a cell-based reporter system to quantitate pathogen-specific antibody binding to FcγRIIIA, FcγRIIA, FcγRIIB and FcγRI. With this system, we demonstrate that anti-GP-specific stimulation of the FcγRI reporter by survivors' sera was substantially high one year after acute infection, with a slight reduction in activity over a decade post infection. We further demonstrate that GP-specific IgG1 is by far the seroprevalent subclass that retained and even enhanced its presence in the sera, over ten years post infection; the prevalence of other GP-specific IgG subclasses was considerably reduced over time. In accordance, GP-specific FcγRI reporter response and GP-specific total IgG1 subclass correlated in the studied group of Ebola survivors. These observations are important for further informing Ebola vaccine and therapeutic development.

  18. Are dinucleoside monophosphates relevant models for the study of DNA intrastrand cross-link lesions? The example of g[8-5m]T.

    Science.gov (United States)

    Garrec, Julian; Dumont, Elise

    2014-07-21

    Oxidatively generated tandem lesions such as G[8-5m]T pose a potent threat to genome integrity. Direct experimental studies of the kinetics and thermodynamics of a specific lesion within DNA are very challenging, mostly due to the variety of products that can be formed in oxidative conditions. Dinucleoside monophosphates (DM) involving only the reactive nucleobases in water represent appealing alternative models on which most physical chemistry and structural techniques can be applied. However, it is not yet clear how relevant these models are. Here, we present QM/MM MD simulations of the cyclization step involved in the formation of G[8-5m]T from the guanine-thymine (GpT) DM in water, with the aim of comparing our results to our previous investigation of the same reaction in DNA ( Garrec , J. , Patel , C. , Rothlisberger , U. , and Dumont , E. ( 2012 ) J. Am. Chem. Soc. 134 , 2111 - 2119 ). We show that, despite the different levels of preorganization of the two systems, the corresponding reactions share many energetic and structural characteristics. The main difference lies in the angle between the G and T bases, which is slightly higher in the transition state (TS) and product of the reaction in water than in the reaction in DNA. This effect is due to the Watson-Crick H-bonds, which are absent in the {GpT+water} system and restrain the relative positioning of the reactive nucleobases in DNA. However, since the lesion is accommodated easily in the DNA macromolecule, the induced energetic penalty is relatively small. The high similarity between the two reactions strongly supports the use of GpT in water as a model of the corresponding reaction in DNA.

  19. Effects of two physical education programmes on health- and skill-related physical fitness of Albanian children

    DEFF Research Database (Denmark)

    Jarani, J; Grøntved, Anders; Muca, F

    2016-01-01

    This study aims to evaluate the effectiveness of two school-based physical education (PE) programmes (exercise-based and games-based) compared with traditional PE, on health- and skill-related physical fitness components in children in Tirana, Albania. Participants were 378 first-grade (6.8 years...... intervention programmes were taught by professional PE teachers using station/circuit teaching framework while CG referred to traditional PE school lessons by a general teacher. All programmes ran in parallel and lasted 5 months, having the same frequency (twice weekly) and duration (45 min). Heart rate (HR......) monitoring showed that intensity during PE lessons was significantly higher in the intervention groups compared with control (P

  20. Physics Teachers Programme or how to bring modern physics to school

    CERN Multimedia

    2002-01-01

    A new programme for teachers took place last weekend at CERN. Fifty high school teachers sacrificed their weekend and plunged into CERN physics to find new inspirations for exciting physics lessons.   The fifty participants in the Physics Teachers programme in the Microcosm garden. High school students are often convinced that physics is a boring and useless subject, and physics teachers have a hard time presenting interesting lessons. To help them, CERN has inaugurated the Physics Teachers Programme, whose goal is to present CERN and its activities, so that teachers can get an idea of what kind of physics research is going on at the frontier of science. 'Our philosophy is to show them today what they will read in textbooks of the future', says Antonella Del Rosso, responsible for this course, 'so that they can inspire their pupils'. This programme can be considered the younger brother of the High School Teachers Programme, since it has a similar aim, but instead of being three-weeks long, it las...

  1. Functional homology of gHs and gLs from EBV-related γ-herpesviruses for EBV-induced membrane fusion

    International Nuclear Information System (INIS)

    Omerovic, Jasmina; Longnecker, Richard

    2007-01-01

    Epstein-Barr virus (EBV) is a human γ-herpesvirus that primarily infects B lymphocytes and epithelial cells. Entry of EBV into B cells requires the viral glycoproteins gp42, gH/gL and gB, while gp42 is not necessary for infection of epithelial cells. In EBV, gH and gL form two distinct complexes, a bipartite complex that contains only gH and gL, used for infection of epithelial cells, and a tripartite complex that additionally includes gp42, used for infection of B cells. The gH/gL complex is conserved within the herpesvirus family, but its exact role in entry and mechanism of fusion is not yet known. To understand more about the functionality of EBVgH/gL, we investigated the functional homology of gHs and gLs from human herpesvirus 8 (HHV8) and two primate (rhesus and marmoset) γ-herpesviruses in EBV-mediated virus-free cell fusion assay. Overall, gHs and gLs from the more homologous primate herpesviruses were better at complementing EBV gH and gL in fusion than HHV8 gH and gL. Interestingly, marmoset gH was able to complement fusion with epithelial cells, but not B cells. Further investigation of this led to the discovery that EBVgH is the binding partner of gp42 in the tripartite complex and the absence of fusion with B cells in the presence of marmoset gH/gL is due to its inability to bind gp42

  2. "Not easy at all but I am trying": barriers and facilitators to physical activity in a South African cohort of people living with HIV participating in a home-based pedometer walking programme.

    Science.gov (United States)

    Roos, Ronel; Myezwa, Hellen; van Aswegen, Helena

    2015-01-01

    The promotion of physical activity is encouraged in people living with HIV and AIDS (PLWHA) as a means of promoting wellness and health. Adherence to programmes that promote exercise is often reduced, and home-based programmes are suggested to improve adherence. This study investigated the personal and environmental factors that cause barriers and facilitators of physical activity in a home-based pedometer walking programme as a means of highlighting adherence challenges. An observational study nested in a randomised controlled trial was conducted in a cohort of South African PLWHA on antiretroviral therapy over a six-month period. Descriptive analysis and qualitative content analysis of 42 participants who underwent physical activity modification assisted with data review. The mean age of the sample was 38.7 (±8.9) years, consisted mostly of women (n = 35; 83.3%) who were employed (n = 19; 45.2%) but earning very little (less than R500 per month) and often single or widowed (n = 23; 54.8%). Barriers to physical activity identified included physical complaints, e.g., low-energy levels; psychological complaints, e.g., stress levels; family responsibility, e.g., being primary caregivers; the physical environment, e.g., adverse weather conditions; social environment, e.g., domestic abuse and crime; and workplace, e.g., being in a sedentary job. Facilitators of physical activity included support and encouragement from friends and family, religious practices during worship and community environment, e.g., having access to parks and sport fields. The study is of benefit as it highlights personal and environmental factors that need to be considered when developing or implementing a home-based walking programme in PLWHA.

  3. Determinants of a GP visit and cervical cancer screening examination in Great Britain.

    Directory of Open Access Journals (Sweden)

    Alexander Michael Labeit

    Full Text Available In the UK, women are requested to attend a cervical cancer test every 3 years as part of the NHS Cervical Screening Programme. This analysis compares the determinants of a cervical cancer screening examination with the determinants of a GP visit in the same year and investigates if cervical cancer screening participation is more likely for women who visit their GP.A recursive probit model was used to analyse the determinants of GP visits and cervical cancer screening examinations. GP visits were considered to be endogenous in the cervical cancer screening examination. The analysed sample consisted of 52,551 observations from 8,386 women of the British Household Panel Survey.The analysis showed that a higher education level and a worsening self-perceived health status increased the probability of a GP visit, whereas smoking decreased the probability of a GP visit. GP visits enhanced the uptake of a cervical cancer screening examination in the same period. The only variables which had the same positive effect on both dependent variables were higher education and living with a partner. The probability of a cervical cancer screening examination increased also with previous cervical cancer screening examinations and being in the recommended age groups. All other variables had different results for the uptake of a GP visit or a cervical cancer screening examination.Most of the determinants of visiting a GP and cervical cancer screening examination differ from each other and a GP visit enhances the uptake of a smear test.

  4. Reactor Physics Programme

    Energy Technology Data Exchange (ETDEWEB)

    De Raedt, C

    2000-07-01

    The Reactor Physics and Department of SCK-CEN offers expertise in various areas of reactor physics, in particular in neutronics calculations, reactor dosimetry, reactor operation, reactor safety and control and non-destructive analysis on reactor fuel. This expertise is applied within the Reactor Physics and MYRRHA Research Department's own research projects in the VENUS critical facility, in the BR1 reactor and in the MYRRHA project (this project aims at designing a prototype Accelerator Driven System). Available expertise is also used in programmes external to the Department such as the reactor pressure steel vessel programme, the BR2 reactor dosimetry, and the preparation and interpretation of irradiation experiments. Progress and achievements in 1999 in the following areas are reported on: (1) investigations on the use of military plutonium in commercial power reactors; (2) neutron and gamma calculations performed for BR-2 and for other reactors; (3) the updating of neutron and gamma cross-section libraries; (4) the implementation of reactor codes; (6) the management of the UNIX workstations; and (6) fuel cycle studies.

  5. Reactor Physics Programme

    International Nuclear Information System (INIS)

    De Raedt, C.

    2000-01-01

    The Reactor Physics and Department of SCK-CEN offers expertise in various areas of reactor physics, in particular in neutronics calculations, reactor dosimetry, reactor operation, reactor safety and control and non-destructive analysis on reactor fuel. This expertise is applied within the Reactor Physics and MYRRHA Research Department's own research projects in the VENUS critical facility, in the BR1 reactor and in the MYRRHA project (this project aims at designing a prototype Accelerator Driven System). Available expertise is also used in programmes external to the Department such as the reactor pressure steel vessel programme, the BR2 reactor dosimetry, and the preparation and interpretation of irradiation experiments. Progress and achievements in 1999 in the following areas are reported on: (1) investigations on the use of military plutonium in commercial power reactors; (2) neutron and gamma calculations performed for BR-2 and for other reactors; (3) the updating of neutron and gamma cross-section libraries; (4) the implementation of reactor codes; (6) the management of the UNIX workstations; and (6) fuel cycle studies

  6. cAMP promotes the synthesis in early G1 of gp115, a yeast glycoprotein containing glycosyl-phosphatidylinositol.

    Science.gov (United States)

    Grandori, R; Popolo, L; Vai, M; Alberghina, L

    1990-08-25

    The glycoprotein gp115 (Mr = 115,000, pI 4.8-5) is localized in the plasma membrane of Saccharomyces cerevisiae cells and maximally expressed during G1 phase. To gain insight on the mechanism regulating its synthesis, we have examined various conditions of cell proliferation arrest. We used pulse-labeling experiments with [35S]methionine and two-dimensional gel electrophoresis analysis, which allow the detection of the well characterized 100-kDa precursor of gp115 (p100). In the cAMP-requiring mutant cyr1, p100 synthesis is active during exponential growth, shut off by cAMP removal, and induced when growth is restored by cAMP readdition. The inhibition of p100 synthesis also occurs in TS1 mutant cells (ras1ras2-ts1) shifted from 24 to 37 degrees C. During nitrogen starvation of rca1 cells, a mutant permeable to cAMP, p100 synthesis is also inhibited. cAMP complements the effect of ammonium deprivation, promoting p100 synthesis, even when added to cells which have already entered G0. Experiments with the bcy1 and cyr1bcy1 mutants have indicated the involvement of the cAMP-dependent protein kinases in the control of p100 synthesis. Moreover, the synthesis of p100 was unaffected in A364A cells, terminally arrested at START B by alpha-factor. These results indicate that the switch operating on p100 synthesis is localized in early G1 (START A) and is one of the multiple events controlled by the cAMP pathway.

  7. The effect of gender medicine education in GP training: a prospective cohort study.

    Science.gov (United States)

    Dielissen, Patrick; Verdonk, Petra; Waard, Magreet Wieringa-de; Bottema, Ben; Lagro-Janssen, Toine

    2014-11-01

    The purpose of this study is to compare the change in general practitioner (GP) trainees' gender awareness following a modular gender medicine programme or a mainstream gender medicine programme. In 2007, a prospective study was conducted in three cohorts of in total 207 GP trainees who entered GP training in the Netherlands. The outcome measure was the Nijmegen Gender Awareness in Medicine Scale and a 16-item gender knowledge questionnaire. Two gender medicine teaching methods were compared: a modular approach (n = 75) versus a mainstream approach (n = 72). Both strategies were compared with a control cohort (n = 60). Statistical analysis included analysis of variance and t-tests. The overall response rates for the modular, mainstream and control cohort were 78, 72 and 82 %, respectively. There was a significant difference in change in gender knowledge scores between the modular cohort compared with the mainstream and control cohort (p = 0.049). There were no statistical differences between the cohorts on gender sensitivity and gender role ideology. At entry and end, female GP trainees demonstrated significantly higher gender awareness than male GP trainees. A modular teaching method is not a more favourable educational method to teach gender medicine in GP training. Female GP trainees are more gender aware, but male GP trainees are not unaware of gender-related issues.

  8. Crystal structure of an EAL domain in complex with reaction product 5'-pGpG.

    Directory of Open Access Journals (Sweden)

    Julien Robert-Paganin

    Full Text Available FimX is a large multidomain protein containing an EAL domain and involved in twitching motility in Pseudomonas aeruginosa. We present here two crystallographic structures of the EAL domain of FimX (residues 438-686: one of the apo form and the other of a complex with 5'-pGpG, the reaction product of the hydrolysis of c-di-GMP. In both crystal forms, the EAL domains form a dimer delimiting a large cavity encompassing the catalytic pockets. The ligand is trapped in this cavity by its sugar phosphate moiety. We confirmed by NMR that the guanine bases are not involved in the interaction in solution. We solved here the first structure of an EAL domain bound to the reaction product 5'-pGpG. Though isolated FimX EAL domain has a very low catalytic activity, which would not be significant compared to other catalytic EAL domains, the structure with the product of the reaction can provides some hints in the mechanism of hydrolysis of the c-di-GMP by EAL domains.

  9. Crystal structure of an EAL domain in complex with reaction product 5'-pGpG.

    Science.gov (United States)

    Robert-Paganin, Julien; Nonin-Lecomte, Sylvie; Réty, Stéphane

    2012-01-01

    FimX is a large multidomain protein containing an EAL domain and involved in twitching motility in Pseudomonas aeruginosa. We present here two crystallographic structures of the EAL domain of FimX (residues 438-686): one of the apo form and the other of a complex with 5'-pGpG, the reaction product of the hydrolysis of c-di-GMP. In both crystal forms, the EAL domains form a dimer delimiting a large cavity encompassing the catalytic pockets. The ligand is trapped in this cavity by its sugar phosphate moiety. We confirmed by NMR that the guanine bases are not involved in the interaction in solution. We solved here the first structure of an EAL domain bound to the reaction product 5'-pGpG. Though isolated FimX EAL domain has a very low catalytic activity, which would not be significant compared to other catalytic EAL domains, the structure with the product of the reaction can provides some hints in the mechanism of hydrolysis of the c-di-GMP by EAL domains.

  10. A multi-modal training programme to improve physical activity, physical fitness and perceived physical ability in obese children.

    Science.gov (United States)

    Morano, Milena; Colella, Dario; Rutigliano, Irene; Fiore, Pietro; Pettoello-Mantovani, Massimo; Campanozzi, Angelo

    2014-01-01

    Actual and perceived physical abilities are important correlates of physical activity (PA) and fitness, but little research has explored these relationships over time in obese children. This study was designed: (a) to assess the feasibility of a multi-modal training programme promoting changes in PA, fundamental motor skills and real and perceived physical abilities of obese children; and (b) to explore cross-sectional and longitudinal relationships between real and perceived physical competence in boys and girls. Forty-one participants (9.2 ± 1.2 years) were assessed before and after an 8-month intervention with respect to body composition, physical fitness, self-reported PA and perceived physical ability. After treatment, obese children reported improvements in the body mass index, PA levels, gross motor performance and actual and perceived physical abilities. Real and perceived physical competence was correlated in boys, but not in girls. Results indicate that a multi-modal programme focused on actual and perceived physical competence as associated with the gradual increase in the volume of activity might be an effective strategy to improve adherence of the participants and to increase the lifelong exercise skills of obese children.

  11. Preparation of the Secretory Recombinant ALV-J gp85 Protein Using Pichia pastoris and Its Immunoprotection as Vaccine Antigen Combining with CpG-ODN Adjuvant.

    Science.gov (United States)

    Jing, Weifang; Zhou, Jinrun; Wang, Chunyang; Qiu, Jianhua; Guo, Huijun; Li, Hongmei

    2018-04-26

    This study focuses on preparing the secretory recombinant J subgroup of avian leukosis virus (ALV-J) gp85 protein using Pichia pastoris and evaluating its immunoprotection as vaccine antigen combining with CpG-ODN adjuvant. The secretory recombinant plasmid pPIC9-gp85 containing ALV-J gp85 gene was designed and was transfected into the genome of P. pastoris (GS115) cells. The recombinant plasmid was expressed under the induction of methanol. The expressed products in the medium of the cells were purified and identified with endoglycosidase digestion assay and western blot mediated with monoclonal antibody (MAb) JE9. The purified product combining with CpG-ODN adjuvant was inoculated intramuscularly into 7-day-old chickens and three booster inoculations were performed on 21 days post first inoculation (dpfi), 42, and 56 dpfi. The antibody responses and cellular immune responses were detected, and the protective effects were analyzed after challenge with ALV-J. The results showed that the secretory pPIC9-gp85 plasmid was successfully constructed and could be stably expressed in GS115 cells. The expressed products were N-acetylglucosylated and could specifically combine with MAb (JE9). The secreted gp85 protein combining with CpG-ODN adjuvant could induce higher antibody response and spleen lymphocyte proliferation response and IFN-γ-inducing response, and could protect all the inoculated chickens against the viremia and the immunosuppressive lesions caused by ALV-J challenge. The results of neutralizing test in vitro suggested that the antisera with some ALV-J antibody titers could neutralize ALV-J strain and inhibit the growth of virus in vitro. The result of IFA showed that IgG antibody in the antisera could specifically combine with ALV-J strain in cells. It can be concluded that the secretory recombinant gp85 protein, as a new acetylglucosylated gp85 protein, was successfully prepared and combining with CpG-ODN adjuvant could protect the inoculated chickens

  12. Tomato juice intake suppressed serum concentration of 8-oxodG after extensive physical activity

    Directory of Open Access Journals (Sweden)

    Harms-Ringdahl Mats

    2012-05-01

    Full Text Available Abstract Background DNA is constantly exposed to reactive oxygen species (ROS, spontaneously arising during the normal oxygen metabolism. ROS may result in temporary as well as permanent modifications in various cellular components such as lipids, proteins and DNA, which may have deleterious consequences. Demonstrating that a dietary supplementation of antioxidants can reduce oxidative DNA damage may provide evidence for the value of such supplementation in prevention of cancer and age related diseases. Findings The present study was conducted to address whether tomato juice protects against ROS induced by extensive physical exercise in untrained individuals. As a marker of oxidative stress, serum levels of 8-oxodG were monitored using a modified ELISA. An intervention was performed involving 15 untrained healthy subjects who performed a 20 min physical exercise at 80% of maximum pulse using an ergometer bicycle. Blood samples were taken before and one hour after the exercise. The procedure was repeated after 5 weeks with a daily intake of 150 ml tomato juice and followed by a 5 weeks wash-out period and another 5 weeks with a daily intake of tomato juice. The results indicated that a daily intake of tomato juice, equal to 15 mg lycopene per day, for 5 weeks significantly reduced the serum levels of 8-oxodG after an extensive physical exercise. Conclusion These data strongly suggest that tomato juice has a potential antioxidant effect and may reduce the elevated level of ROS induced by oxidative stress.

  13. Do practice nurse solve future GP capacity problems?

    NARCIS (Netherlands)

    Lamkaddem, M.; Haan, J. de; Bakker, D. de

    2003-01-01

    Background: Task delegation is viewed as an important policy instrument to counter foreseen future shortages in GP capacity in the Netherlands. Therefore, a national programme to introduce practice nurses in general practice was launched in 1998 by the National Association of General Practice. In

  14. Are physical symptoms among survivors of a disaster presented to the general practitioner? A comparison between self-reports and GP data

    Directory of Open Access Journals (Sweden)

    Stellato Rebecca K

    2007-09-01

    Full Text Available Abstract Background Most studies examining medically unexplained symptoms (MUS have been performed in primary or secondary care and have examined symptoms for which patients sought medical attention. Disasters are often described as precipitating factors for MUS. However, health consequences of disasters are typically measured by means of questionnaires, and it is not known whether these self-reported physical symptoms are presented to the GP. It is also not known if the self-reported symptoms are related to a medical disorder or if they remain medically unexplained. In the present study, three research questions were addressed. Firstly, were self-reported symptoms among survivors presented to the GP? Secondly, were the symptoms presented to the GP associated with a high level of functional impairment and distress? Thirdly, what was the GP's clinical judgment of the presented symptoms, i.e. were the symptoms related to a medical diagnosis or could they be labeled MUS? Methods Survivors of a man-made disaster (N = 887 completed a questionnaire 3 weeks (T1 and 18 months (T2 post-disaster. This longitudinal health survey was combined with an ongoing surveillance program of health problems registered by GPs. Results The majority of self-reported symptoms was not presented to the GP and survivors were most likely to present persistent symptoms to the GP. For example, survivors with stomachache at both T1 and T2 were more likely to report stomachache to their GP (28% than survivors with stomachache at only T1 (6% or only T2 (13%. Presentation of individual symptoms to the GP was not consistently associated with functional impairment and distress. 56 – 91% of symptoms were labeled as MUS after clinical examination. Conclusion These results indicate that the majority of self-reported symptoms among survivors of a disaster are not presented to the GP and that the decision to consult with a GP for an individual symptom is not dependent on the level of

  15. A recombinant mimetics of the HIV-1 gp41 prehairpin fusion intermediate fused with human IgG Fc fragment elicits neutralizing antibody response in the vaccinated mice

    International Nuclear Information System (INIS)

    Qi, Zhi; Pan, Chungen; Lu, Hong; Shui, Yuan; Li, Lin; Li, Xiaojuan; Xu, Xueqing; Liu, Shuwen; Jiang, Shibo

    2010-01-01

    Research highlights: → One recombinant mimetics of gp41 prehairpin fusion intermediate (PFI) consisting of gp41 N46 sequence, foldon and IgG Fc, designated N46FdFc, was expressed. → N46FdFc-induced antibodies in mice that neutralized HIV-1 infection, inhibited PIE7 binding to PFI, blocked gp41 six-helix bundle formation, and suppressed HIV-1 mediated cell-cell fusion. → These findings provide an important clue for developing recombinant gp41 PFI mimetics-based HIV vaccines. -- Abstract: HIV-1 gp41 prehairpin fusion intermediate (PFI) composed of three N-terminal heptad repeats (NHR) plays a crucial role in viral fusion and entry and represents an attractive target for anti-HIV therapeutics (e.g., enfuvirtide) and vaccines. In present study, we constructed and expressed two recombinant gp41 PFI mimetics, designated N46Fd and N46FdFc. N46Fd consists of N46 (residues 536-581) in gp41 NHR and foldon (Fd), a trimerization motif. N46FdFc is composed of N46Fd fused with human IgG Fc fragment as an immunoenhancer. We immunized mice with N46 peptide, N46Fd and N46FdFc, respectively, and found that only N46FdFc elicited neutralizing antibody response in mice against infection by HIV-1 strains IIIB (clade B, X4), 92US657 (clade B, R5), and 94UG103 (clade A, X4R5). Anti-N46FdFc antibodies inhibited PIE7 binding to PFI, blocked gp41 six-helix bundle formation, and suppressed HIV-1 mediated cell-cell fusion. These findings provide an important clue for developing recombinant gp41 PFI mimetics-based HIV vaccines.

  16. Commissioning of the iGp Feedback System at DAΦNE

    International Nuclear Information System (INIS)

    Drago, A.; Fox, J.D.; Teytelman, D.; Tobiyama, M.

    2011-01-01

    The iGp (Integrated Gigasample Processor) is an innovative digital bunch-by-bunch feedback system developed by a KEK / SLAC / INFN-LNF joint collaboration. The processing unit can sample at 500 MHz and compute the bunch-by-bunch output signal for up to ∼5000 bunches. The feedback gateware code is implemented inside just one FPGA (Field Programmable Gate Array) chip, a Xilinx Virtex-II. The FPGA implements two banks of 16-tap FIR (Finite Impulse Response) filters. Each filter is realtime programmable through the operator interface. At DAΦNE, the Frascati Φ-Factory, two iGp units have been commissioned in the April 2007. The iGp systems have substituted the previous betatron feedback systems. This insertion has been very fast and has shown no problems involving just a substitution of the old, less flexible, digital systems, letting unchanged the baseband analog frontend and backend. The commissioning has been very simple, due to the complete and powerful EPICS operator interface, working well in local and remote operations. The software includes also tools for analyzing post processor data. A description of the commissioning with the operations done is reported.

  17. Using photography to enhance GP trainees’ reflective practice and professional development.

    OpenAIRE

    Rutherford,; Forde, Emer; Priego-Hernández, J.; Butcher, Aurelia; Wedderburn, Clare

    2018-01-01

    The capacity and the commitment to reflect are integral to the practice of medicine and are core components of most GP training programmes. Teaching through the Humanities is a growing area within medical education, but one which is often considered a voluntary ‘add on’ for the interested doctor. This article describes an evaluation of a highly innovative pedagogical project which used photography as a means to enhance GP trainees’ reflective capacity, self awareness and professional developm...

  18. Analysis of canine herpesvirus gB, gC and gD expressed by a recombinant vaccinia virus.

    Science.gov (United States)

    Xuan, X; Kojima, A; Murata, T; Mikami, T; Otsuka, H

    1997-01-01

    The genes encoding the canine herpesvirus (CHV) glycoprotein B (gB), gC and gD homologues have been reported already. However, products of these genes have not been identified yet. Previously, we have identified three CHV glycoproteins, gp 145/112, gp80 and gp47 using a panel of monoclonal antibodies (MAbs). To determine which CHV glycoprotein corresponds to gB, gC or gD, the putative genes of gB, gC, and gD of CHV were inserted into the thymidine kinase gene of vaccinia virus LC16mO strain under the control of the early-late promoter for the vaccinia virus 7.5-kilodalton polypeptide. We demonstrated here that gp145/112, gp80 and gp47 were the translation products of the CHV gB, gC and gD genes, respectively. The antigenic authenticity of recombinant gB, gC and gD were confirmed by a panel of MAbs specific for each glycoprotein produced in CHV-infected cells. Immunization of mice with these recombinants produced high titers of neutralizing antibodies against CHV. These results suggest that recombinant vaccinia viruses expressing CHV gB, gC and gD may be useful to develop a vaccine to control CHV infection.

  19. Individual factors and GP approach as predictors for the outcome of rehabilitation among long-term sick listed cases

    DEFF Research Database (Denmark)

    Rasmussen, K.; Andersen, JH

    2005-01-01

    care professionals were found important for a positive outcome of the programme. Especially stable relations to a single General Practitioner (GP), who took good care of the patient in the form of giving good information about health and social possibilities, and an empathic attitude toward these hard...... than 1 year. The remainder had been transferred to receiving social benefits after having exceeded the time limit for being sick-listed. A plan of action for active rehabilitation, which was made at the end of the 8-week rehabilitation programme, was only poorly fulfilled after 9 months, 48% were still...

  20. Using photography to enhance GP trainees' reflective practice and professional development.

    Science.gov (United States)

    Rutherford; Forde, Emer; Priego-Hernandez, Jacqueline; Butcher, Aurelia; Wedderburn, Clare

    2018-02-08

    The capacity and the commitment to reflect are integral to the practice of medicine and are core components of most general practitioners (GP) training programmes. Teaching through the humanities is a growing area within medical education, but one which is often considered a voluntary 'add-on' for the interested doctor. This article describes an evaluation of a highly innovative pedagogical project which used photography as a means to enhance GP trainees' reflective capacity, self-awareness and professional development. Photography was used as a tool to develop GP trainees' skills in recognising and articulating the attitudes, feelings and values that might impact on their clinical work and to enhance their confidence in their ability to deal with these concerns/issues. We submit that photography is uniquely well suited for facilitating insight and self-reflection because it provides the ability to record 'at the touch of a button' those scenes and images to which our attention is intuitively drawn without the need for-or the interference of-conscious decisions. This allows us the opportunity to reflect later on the reasons for our intuitive attraction to these scenes. These photography workshops were a compulsory part of the GP training programme and, despite the participants' traditional scientific backgrounds, the results clearly demonstrate the willingness of participants to accept-even embrace-the use of art as a tool for learning. The GP trainees who took part in this project acknowledged it to be beneficial for both their personal and professional development. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  1. A structured physical activity and fitness programme for older adults with intellectual disabilities: results of a cluster-randomised clinical trial.

    Science.gov (United States)

    van Schijndel-Speet, M; Evenhuis, H M; van Wijck, R; van Montfort, K C A G M; Echteld, M A

    2017-01-01

    The physical activity level of older adults with intellectual disabilities (ID) is extremely low, and their fitness levels are far beneath accepted norms for older people with normal intelligence and comparable with frail older people. A physical activity programme, including an education programme, was developed for older adults with ID using behaviour change techniques. The programme aimed at improving or maintaining adequate levels of physical activity (primary outcome measure) and motor fitness, cardio respiratory fitness, morphologic and metabolic fitness, activities of daily living, cognitive functioning and depressive symptoms (secondary outcome measures). The programme's efficacy was evaluated in a cluster-randomised clinical trial among people aged 43 years and over with mild-moderate levels of ID. Five day-activity centres were randomised to the participation group. In these centres, 81 older adults participated in groups of 8 to 10 in the programme, three times a week during 8 months. The programme was executed by physical activity instructors and staff of day-activity centres. Five other day-activity centres were randomised to the control group; 70 older adults in these centres received care as usual. The generalised linear model with mixed effects was used to test the programme's effectiveness. Significant effects were found on physical activity, muscle strength, systolic and diastolic blood pressure, serum cholesterol level and cognitive functioning, in favour of the programme's participants. No significant improvements were found on balance, serum glucose, weight, waist circumference, walking speed, mobility, depression or instrumental activities of daily living. The physical activity and fitness programme has established small but significant effects in this sample, but generalising the findings to other settings is difficult due to significant participant dropout. Implementation of evidence-based physical activity programmes among older adults

  2. Alphavirus Replicon DNA Vectors Expressing Ebola GP and VP40 Antigens Induce Humoral and Cellular Immune Responses in Mice

    Directory of Open Access Journals (Sweden)

    Shoufeng Ren

    2018-01-01

    Full Text Available Ebola virus (EBOV causes severe hemorrhagic fevers in humans, and no approved therapeutics or vaccine is currently available. Glycoprotein (GP is the major protective antigen of EBOV, and can generate virus-like particles (VLPs by co-expression with matrix protein (VP40. In this study, we constructed a recombinant Alphavirus Semliki Forest virus (SFV replicon vector DREP to express EBOV GP and matrix viral protein (VP40. EBOV VLPs were successfully generated and achieved budding from 293 cells after co-transfection with DREP-based GP and VP40 vectors (DREP-GP+DREP-VP40. Vaccination of BALB/c mice with DREP-GP, DREP-VP40, or DREP-GP+DREP-VP40 vectors, followed by immediate electroporation resulted in a mixed IgG subclass production, which recognized EBOV GP and/or VP40 proteins. This vaccination regimen also led to the generation of both Th1 and Th2 cellular immune responses in mice. Notably, vaccination with DREP-GP and DREP-VP40, which produces both GP and VP40 antigens, induced a significantly higher level of anti-GP IgG2a antibody and increased IFN-γ secreting CD8+ T-cell responses relative to vaccination with DREP-GP or DREP-VP40 vector alone. Our study indicates that co-expression of GP and VP40 antigens based on the SFV replicon vector generates EBOV VLPs in vitro, and vaccination with recombinant DREP vectors containing GP and VP40 antigens induces Ebola antigen-specific humoral and cellular immune responses in mice. This novel approach provides a simple and efficient vaccine platform for Ebola disease prevention.

  3. Structures of Ebola virus GP and sGP in complex with therapeutic antibodies.

    Science.gov (United States)

    Pallesen, Jesper; Murin, Charles D; de Val, Natalia; Cottrell, Christopher A; Hastie, Kathryn M; Turner, Hannah L; Fusco, Marnie L; Flyak, Andrew I; Zeitlin, Larry; Crowe, James E; Andersen, Kristian G; Saphire, Erica Ollmann; Ward, Andrew B

    2016-08-08

    The Ebola virus (EBOV) GP gene encodes two glycoproteins. The major product is a soluble, dimeric glycoprotein (sGP) that is secreted abundantly. Despite the abundance of sGP during infection, little is known regarding its structure or functional role. A minor product, resulting from transcriptional editing, is the transmembrane-anchored, trimeric viral surface glycoprotein (GP). GP mediates attachment to and entry into host cells, and is the intended target of antibody therapeutics. Because large portions of sequence are shared between GP and sGP, it has been hypothesized that sGP may potentially subvert the immune response or may contribute to pathogenicity. In this study, we present cryo-electron microscopy structures of GP and sGP in complex with GP-specific and GP/sGP cross-reactive antibodies undergoing human clinical trials. The structure of the sGP dimer presented here, in complex with both an sGP-specific antibody and a GP/sGP cross-reactive antibody, permits us to unambiguously assign the oligomeric arrangement of sGP and compare its structure and epitope presentation to those of GP. We also provide biophysical evaluation of naturally occurring GP/sGP mutations that fall within the footprints identified by our high-resolution structures. Taken together, our data provide a detailed and more complete picture of the accessible Ebolavirus glycoprotein landscape and a structural basis to evaluate patient and vaccine antibody responses towards differently structured products of the GP gene.

  4. Cyber-Physical Architecture Assisted by Programmable Networking

    OpenAIRE

    Rubio-Hernan, Jose; Sahay, Rishikesh; De Cicco, Luca; Garcia-Alfaro, Joaquin

    2018-01-01

    Cyber-physical technologies are prone to attacks, in addition to faults and failures. The issue of protecting cyber-physical systems should be tackled by jointly addressing security at both cyber and physical domains, in order to promptly detect and mitigate cyber-physical threats. Towards this end, this letter proposes a new architecture combining control-theoretic solutions together with programmable networking techniques to jointly handle crucial threats to cyber-physical systems. The arch...

  5. Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs.

    Science.gov (United States)

    Jiang, Xiaohong; Dalebout, Tim J; Bredenbeek, Peter J; Carrion, Ricardo; Brasky, Kathleen; Patterson, Jean; Goicochea, Marco; Bryant, Joseph; Salvato, Maria S; Lukashevich, Igor S

    2011-02-01

    Yellow Fever (YF) and Lassa Fever (LF) are two prevalent hemorrhagic fevers co-circulating in West Africa and responsible for thousands of deaths annually. The YF vaccine 17D has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) or their subunits, GP1 (attachment glycoprotein) and GP2 (fusion glycoprotein). Cloning shorter inserts, LASV-GP1 and -GP2, between YF17D E and NS1 genes enhanced genetic stability of recombinant viruses, YF17D/LASV-GP1 and -GP2, in comparison with YF17D/LASV-GPC recombinant. The recombinant viruses were replication competent and properly processed YF proteins and LASV GP antigens in infected cells. YF17D/LASV-GP1 and -GP2 induced specific CD8+ T cell responses in mice and protected strain 13 guinea pigs against fatal LF. Unlike immunization with live attenuated reassortant vaccine ML29, immunization with YF17D/LASV-GP1 and -GP2 did not provide sterilizing immunity. This study demonstrates the feasibility of YF17D-based vaccine to control LF in West Africa. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs

    Science.gov (United States)

    Jiang, Xiaohong; Dalebout, Tim J.; Bredenbeek, Peter J.; Carrion, Ricardo; Brasky, Kathleen; Patterson, Jean; Goicochea, Marco; Bryant, Joseph; Salvato, Maria S.; Lukashevich, Igor S.

    2010-01-01

    Yellow Fever (YF) and Lassa Fever (LF) are two prevalent hemorrhagic fevers co-circulating in West Africa and responsible for thousands of deaths annually. The YF vaccine 17D has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) or their subunits, GP1 (attachment glycoprotein) and GP2 (fusion glycoprotein). Cloning shorter inserts, LASV GP1 and GP2, between YF17D E and NS1 genes enhanced genetic stability of recombinant viruses, YF17D/LASV-GP1 and –GP2, in comparison with YF17D/LASV-GPC recombinant. The recombinant viruses were replication competent and properly processed YF and LASV GP proteins in infected cells. YF17D/LASV-GP1&GP2 induced specific CD8+ T cell responses in mice and protected strain 13 guinea pigs against fatal LF. Unlike immunization with live attenuated reassortant vaccine ML29, immunization with YF17D/LASV-GP1&GP2 did not provide sterilizing immunity. This study demonstrates the feasibility of YF17D-based vaccine to control LF in West Africa. PMID:21145373

  7. Postgraduate Medical Physics Academic Programmes. Endorsed by the International Organization for Medical Physics (IOMP)

    International Nuclear Information System (INIS)

    2013-01-01

    The safe and effective implementation of technology in radiation medicine requires expert medical physics support. In order to fulfil their duties, medical physicists working as health professionals should demonstrate competency in their area of specialization by obtaining the appropriate educational qualification and clinical competency training in one or more aspects of medical physics. At the international level, there are very few established, accredited academic education programmes for medical physics students, and no international guidelines exist which provide the recommended requirements, outline and structure of such a programme. An increasing number of Member States with a 'critical mass' of medical physicists are seeking support to initiate their own national postgraduate education programmes. This publication, therefore, seeks to provide guidelines for the establishment of a postgraduate academic education programme in medical physics, which could also be used to achieve harmonized standards of competence worldwide. This publication was developed in support of the internationally harmonized guidelines given in IAEA Human Health Series No. 25 on the requirements for academic education and clinical training of clinically qualified medical physicists. In addition to academic education, medical physicists should obtain specialized clinical training. The IAEA has published three Training Course Series publications with accompanying handbooks, which provide guidelines and references to training material for clinical training programmes for medical physicists specializing in radiation oncology (TCS-37), diagnostic radiology (TCS-47) and nuclear medicine (TCS-50)

  8. Modification on ursodeoxycholic acid (UDCA) scaffold. discovery of bile acid derivatives as selective agonists of cell-surface G-protein coupled bile acid receptor 1 (GP-BAR1).

    Science.gov (United States)

    Sepe, Valentina; Renga, Barbara; Festa, Carmen; D'Amore, Claudio; Masullo, Dario; Cipriani, Sabrina; Di Leva, Francesco Saverio; Monti, Maria Chiara; Novellino, Ettore; Limongelli, Vittorio; Zampella, Angela; Fiorucci, Stefano

    2014-09-25

    Bile acids are signaling molecules interacting with the nuclear receptor FXR and the G-protein coupled receptor 1 (GP-BAR1/TGR5). GP-BAR1 is a promising pharmacological target for the treatment of steatohepatitis, type 2 diabetes, and obesity. Endogenous bile acids and currently available semisynthetic bile acids are poorly selective toward GP-BAR1 and FXR. Thus, in the present study we have investigated around the structure of UDCA, a clinically used bile acid devoid of FXR agonist activity, to develop a large family of side chain modified 3α,7β-dihydroxyl cholanoids that selectively activate GP-BAR1. In vivo and in vitro pharmacological evaluation demonstrated that administration of compound 16 selectively increases the expression of pro-glucagon 1, a GP-BAR1 target, in the small intestine, while it had no effect on FXR target genes in the liver. Further, compound 16 results in a significant reshaping of bile acid pool in a rodent model of cholestasis. These data demonstrate that UDCA is a useful scaffold to generate novel and selective steroidal ligands for GP-BAR1.

  9. Individual and group-based parenting programmes for the treatment of physical child abuse and neglect.

    Science.gov (United States)

    Barlow, J; Johnston, I; Kendrick, D; Polnay, L; Stewart-Brown, S

    2006-07-19

    Child physical abuse and neglect are important public health problems and recent estimates of their prevalence suggest that they are considerably more common than had hitherto been realised. Many of the risk factors for child abuse and neglect are not amenable to change in the short term. Intervening to change parenting practices may, however, be important in its treatment. Parenting programmes are focused, short-term interventions aimed at improving parenting practices in addition to other outcomes (many of which are risk factors for child abuse e.g. parental psychopathology, and parenting attitudes and practices), and may therefore be useful in the treatment of physically abusive or neglectful parents. To assess the efficacy of group-based or one-to-one parenting programmes in addressing child physical abuse or neglect. A range of biomedical and social science databases were searched including MEDLINE, EMBASE, CINAHL, PsychINFO, Sociofile, Social Science Citation Index, ASSIA, the Cochrane Library, Campbell Library (including SPECTR and CENTRAL), National Research Register (NRR) and ERIC, from inception to May 2005. Only randomised controlled trials or randomised studies that compared two treatments were included. Studies had to include at least one standardised instrument measuring some aspect of abusive or neglectful parenting. In the absence of studies using objective assessments of child abuse, studies reporting proxy measures of abusive parenting were included. Only studies evaluating the effectiveness of standardised group-based or one-to-one parenting programmes aimed at the treatment of physical child abuse or neglect were included. Studies were also only eligible for inclusion if they had targeted parents of children aged 0-19 years who had been investigated for physical abuse or neglect. The treatment effect for each outcome in each study was standardised by dividing the mean difference in post-intervention scores for the intervention and treatment

  10. Specific assay measuring binding of /sup 125/I-Gp 120 from HIV to T4/sup +//CD4/sup +/ cells

    Energy Technology Data Exchange (ETDEWEB)

    Lundin, K.; Nygren, A.; Ramstedt, U.; Gidlund, M.; Wigzell, H.; Arthur, L.O.; Robey, W.G.; Morein, B.

    1987-02-26

    The HIV (HTLV-III) envelope glycoprotein, Gp120, was isolated from virus-infected tissue culture cells using affinity chromatography. A radioimmunoassay was developed to determine the degree of iodinated Gp120 to target CD4/sup +/ (T4/sup +/) cells. /sup 125/I-Gp120 could be shown to selectively bind to CD4/sup +/ cells only. The Gp120 remained bound to these cells after repeated washes. Monoclonal anti-CD4 antibodies block the binding of Gp120 to CD4/sup +/ cells. Monoclonal antibodies to other cell surface components do not interfere with /sup 125/I-Gp120 binding. All IgG antibodies from HIV seropositive donors tested block /sup 125/I-GP120 binding, though with variable titers. The authors believe that this assay provides further proof for the use of CD4 (T4) as a component of the receptor for HIV. It represents a safe, objective and sensitive method for the analysis of Gp120-CD4 interactions, as well as the potential of antibodies to interfere with this binding. (Auth.). 24 refs.; 2 figs.; 8 tabs.

  11. Changes in physical health among participants in a multidisciplinary health programme for long-term unemployed persons.

    Science.gov (United States)

    Schutgens, Christine A E; Schuring, Merel; Voorham, Toon A J; Burdorf, Alex

    2009-06-19

    The relationship between poor health and unemployment is well established. Health promotion among unemployed persons may improve their health. The aims of this study were to investigate characteristics of non-participants and drop-outs in a multidisciplinary health promotion programme for long-term unemployed persons with health complaints, to evaluate changes in physical health among participants, and to investigate determinants of improvement in physical health. A longitudinal, non-controlled design was used. The programme consisted of two weekly exercise sessions and one weekly cognitive session during 12 weeks. The main outcome measures were body mass index, blood pressure, cardiorespiratory fitness, abdominal muscle strength, and low back and hamstring flexibility. Potential determinants of change in physical health were demographic variables, psychological variables (self-esteem, mastery, and kinesiophobia), and self-perceived health. The initial response was 73% and 252 persons had complete data collection at baseline. In total, 36 subjects were lost during follow-up. Participants were predominantly low educated, long-term unemployed, and in poor health. Participation in the programme was not influenced by demographic and psychological factors or by self-reported health. Drop-outs were younger and had a lower body mass index at baseline than subjects who completed the programme. At post-test, participants' cardiorespiratory fitness, abdominal muscle strength, and flexibility had increased by 6.8%-51.0%, whereas diastolic and systolic blood pressures had decreased by 2.2%-2.5%. The effect sizes ranges from 0.17-0.68. Participants with the poorest physical health benefited most from the programme and gender differences in improvement were observed. Physical health of unemployed persons with health complaints improved after participation in this health promotion programme, but not sufficiently, considering their poor physical health at baseline.

  12. Changes in physical health among participants in a multidisciplinary health programme for long-term unemployed persons

    Directory of Open Access Journals (Sweden)

    Schuring Merel

    2009-06-01

    Full Text Available Abstract Background The relationship between poor health and unemployment is well established. Health promotion among unemployed persons may improve their health. The aims of this study were to investigate characteristics of non-participants and drop-outs in a multidisciplinary health promotion programme for long-term unemployed persons with health complaints, to evaluate changes in physical health among participants, and to investigate determinants of improvement in physical health. Methods A longitudinal, non-controlled design was used. The programme consisted of two weekly exercise sessions and one weekly cognitive session during 12 weeks. The main outcome measures were body mass index, blood pressure, cardiorespiratory fitness, abdominal muscle strength, and low back and hamstring flexibility. Potential determinants of change in physical health were demographic variables, psychological variables (self-esteem, mastery, and kinesiophobia, and self-perceived health. Results The initial response was 73% and 252 persons had complete data collection at baseline. In total, 36 subjects were lost during follow-up. Participants were predominantly low educated, long-term unemployed, and in poor health. Participation in the programme was not influenced by demographic and psychological factors or by self-reported health. Drop-outs were younger and had a lower body mass index at baseline than subjects who completed the programme. At post-test, participants' cardiorespiratory fitness, abdominal muscle strength, and flexibility had increased by 6.8%–51.0%, whereas diastolic and systolic blood pressures had decreased by 2.2%–2.5%. The effect sizes ranges from 0.17–0.68. Conclusion Participants with the poorest physical health benefited most from the programme and gender differences in improvement were observed. Physical health of unemployed persons with health complaints improved after participation in this health promotion programme, but not

  13. Effect of two kinds of porcelain crown on AST, ALP, TNF-α, IL-8, GP-x and MDA levels in gingival crevicular fluid

    Directory of Open Access Journals (Sweden)

    Ya-Ling Wang

    2016-09-01

    Full Text Available Objective: To investigate the effect of two kinds of porcelain crown on AST, ALP, TNF-α, IL-8, GP-x and MDA levels in gingival crevicular fluid. Methods: A total of 80 patients with dental porcelain crowns at front teeth during February 2013 to February 2016 were randomly divided into cobalt-chromium alloy PFM group (n=40 and gold alloy PFM group (n=40. After 6 months, the amount of gingival crevicular fluid, GI, PD, AST, ALP, TNF-α, IL-8, GP-x and MDA levels in gingival crevicular fluid were recorded and analyzed. Results: There were no differences in amount of gingival crevicular fluid, GI and PD before treatment of the two groups (P>0.05. After treatment, the amount of gingival crevicular fluid, GI and PD of the two groups were significantly higher than before treatment (P0.05. After treatment, the AST, ALP, TNF-α, IL-8 and MDA levels in gingival crevicular fluid of the two groups were significantly higher than before treatment (P<0.05, but that of the gold alloy PFM group were significantly lower than cobalt-chromium alloy PFM group (P<0.05. After treatment, the GP-x level in gingival crevicular fluid of the two groups were significantly lower than before treatment (P<0.05, but that of the gold alloy PFM group were significantly higher than cobalt-chromium alloy PFM group (P<0.05. Conclusions: Gold alloy PFM can significantly reduce the AST, ALP, TNF-α, IL-8 and MDA levels in gingival crevicular fluid, improve the GP-x level in gingival crevicular fluid, shows better biocompatibility and clinical outcomes than cobalt-chromium alloy PFM.

  14. Effectiveness of a physical activity programme based on the Pilates method in pregnancy and labour.

    Science.gov (United States)

    Rodríguez-Díaz, Luciano; Ruiz-Frutos, Carlos; Vázquez-Lara, Juana María; Ramírez-Rodrigo, Jesús; Villaverde-Gutiérrez, Carmen; Torres-Luque, Gema

    To assess the effectiveness and safety of a physical activity programme based on use of the Pilates method, over eight weeks in pregnant women, on functional parameters, such as weight, blood pressure, strength, flexibility and spinal curvature, and on labour parameters, such as, type of delivery, episiotomy, analgesia and newborn weight. A randomized clinical trial was carried out on pregnant women, applying a programme of physical activity using the Pilates method, designed specifically for this population. A sample consisting of a total of 105 pregnant women was divided into two groups: intervention group (n=50) (32.87±4.46 years old) and control group (n=55) (31.52±4.95 years old). The intervention group followed a physical activity programme based on the Pilates method, for 2 weekly sessions, whereas the control group did not follow the program. Significant improvements (p<0.05) in blood pressure, hand grip strength, hamstring flexibility and spinal curvature, in addition to improvements during labour, decreasing the number of Caesareans and obstructed labour, episiotomies, analgesia and the weight of the newborns were found at the end of the intervention. A physical activity programme of 8 weeks based on the Pilates method improves functional parameters in pregnant women and benefits delivery. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  15. HIV-1 specific IgA detected in vaginal secretions of HIV uninfected women participating in a microbicide trial in Southern Africa are primarily directed toward gp120 and gp140 specificities.

    Directory of Open Access Journals (Sweden)

    Kelly E Seaton

    Full Text Available Many participants in microbicide trials remain uninfected despite ongoing exposure to HIV-1. Determining the emergence and nature of mucosal HIV-specific immune responses in such women is important, since these responses may contribute to protection and could provide insight for the rational design of HIV-1 vaccines.We first conducted a pilot study to compare three sampling devices (Dacron swabs, flocked nylon swabs and Merocel sponges for detection of HIV-1-specific IgG and IgA antibodies in vaginal secretions. IgG antibodies from HIV-1-positive women reacted broadly across the full panel of eight HIV-1 envelope (Env antigens tested, whereas IgA antibodies only reacted to the gp41 subunit. No Env-reactive antibodies were detected in the HIV-negative women. The three sampling devices yielded equal HIV-1-specific antibody titers, as well as total IgG and IgA concentrations. We then tested vaginal Dacron swabs archived from 57 HIV seronegative women who participated in a microbicide efficacy trial in Southern Africa (HPTN 035. We detected vaginal IgA antibodies directed at HIV-1 Env gp120/gp140 in six of these women, and at gp41 in another three women, but did not detect Env-specific IgG antibodies in any women.Vaginal secretions of HIV-1 infected women contained IgG reactivity to a broad range of Env antigens and IgA reactivity to gp41. In contrast, Env-binding antibodies in the vaginal secretions of HIV-1 uninfected women participating in the microbicide trial were restricted to the IgA subtype and were mostly directed at HIV-1 gp120/gp140.

  16. Structure and Recognition of a Novel HIV-1 gp120-gp41 Interface Antibody that Caused MPER Exposure through Viral Escape

    Energy Technology Data Exchange (ETDEWEB)

    Wibmer, Constantinos Kurt; Gorman, Jason; Ozorowski, Gabriel; Bhiman, Jinal N.; Sheward, Daniel J.; Elliott, Debra H.; Rouelle, Julie; Smira, Ashley; Joyce, M. Gordon; Ndabambi, Nonkululeko; Druz, Aliaksandr; Asokan, Mangai; Burton, Dennis R.; Connors, Mark; Abdool Karim, Salim S.; Mascola, John R.; Robinson, James E.; Ward, Andrew B.; Williamson, Carolyn; Kwong, Peter D.; Morris, Lynn; Moore, Penny L.; Desrosiers, Ronald C.

    2017-01-11

    A comprehensive understanding of the regions on HIV-1 envelope trimers targeted by broadly neutralizing antibodies may contribute to rational design of an HIV-1 vaccine. We previously identified a participant in the CAPRISA cohort, CAP248, who developed trimer-specific antibodies capable of neutralizing 60% of heterologous viruses at three years post-infection. Here, we report the isolation by B cell culture of monoclonal antibody CAP248-2B, which targets a novel membrane proximal epitope including elements of gp120 and gp41. Despite low maximum inhibition plateaus, often below 50% inhibitory concentrations, the breadth of CAP248-2B significantly correlated with donor plasma. Site-directed mutagenesis, X-ray crystallography, and negative-stain electron microscopy 3D reconstructions revealed how CAP248-2B recognizes a cleavage-dependent epitope that includes the gp120 C terminus. While this epitope is distinct, it overlapped in parts of gp41 with the epitopes of broadly neutralizing antibodies PGT151, VRC34, 35O22, 3BC315, and 10E8. CAP248-2B has a conformationally variable paratope with an unusually long 19 amino acid light chain third complementarity determining region. Two phenylalanines at the loop apex were predicted by docking and mutagenesis data to interact with the viral membrane. Neutralization by CAP248-2B is not dependent on any single glycan proximal to its epitope, and low neutralization plateaus could not be completely explained by N- or O-linked glycosylation pathway inhibitors, furin co-transfection, or pre-incubation with soluble CD4. Viral escape from CAP248-2B involved a cluster of rare mutations in the gp120-gp41 cleavage sites. Simultaneous introduction of these mutations into heterologous viruses abrogated neutralization by CAP248-2B, but enhanced neutralization sensitivity to 35O22, 4E10, and 10E8 by 10-100-fold. Altogether, this study expands the region of the HIV-1 gp120-gp41 quaternary interface that is a target for broadly neutralizing

  17. Investigation of the function of the putative self-association site of Epstein-Barr virus (EBV) glycoprotein 42 (gp42)

    International Nuclear Information System (INIS)

    Rowe, Cynthia L.; Matsuura, Hisae; Jardetzky, Theodore S.; Longnecker, Richard

    2011-01-01

    The Epstein-Barr virus (EBV) glycoprotein 42 (gp42) is a type II membrane protein essential for entry into B cells but inhibits entry into epithelial cells. X-ray crystallography suggests that gp42 may form dimers when bound to human leukocyte antigen (HLA) class II receptor (Mullen et al., 2002) or multimerize when not bound to HLA class II (Kirschner et al., 2009). We investigated this self-association of gp42 using several different approaches. We generated soluble mutants of gp42 containing mutations within the self-association site and found that these mutants have a defect in fusion. The gp42 mutants bound to gH/gL and HLA class II, but were unable to bind wild-type gp42 or a cleavage mutant of gp42. Using purified gp42, gH/gL, and HLA, we found these proteins associate 1:1:1 by gel filtration suggesting that gp42 dimerization or multimerization does not occur or is a transient event undetectable by our methods.

  18. Evaluation of the theory-based Quality Improvement in Physical Therapy (QUIP) programme: a one-group, pre-test post-test pilot study.

    Science.gov (United States)

    Rutten, Geert M; Harting, Janneke; Bartholomew, L Kay; Schlief, Angelique; Oostendorp, Rob A B; de Vries, Nanne K

    2013-05-25

    Guideline adherence in physical therapy is far from optimal, which has consequences for the effectiveness and efficiency of physical therapy care. Programmes to enhance guideline adherence have, so far, been relatively ineffective. We systematically developed a theory-based Quality Improvement in Physical Therapy (QUIP) programme aimed at the individual performance level (practicing physiotherapists; PTs) and the practice organization level (practice quality manager; PQM). The aim of the study was to pilot test the multilevel QUIP programme's effectiveness and the fidelity, acceptability and feasibility of its implementation. A one-group, pre-test, post-test pilot study (N = 8 practices; N = 32 PTs, 8 of whom were also PQMs) done between September and December 2009. Guideline adherence was measured using clinical vignettes that addressed 12 quality indicators reflecting the guidelines' main recommendations. Determinants of adherence were measured using quantitative methods (questionnaires). Delivery of the programme and management changes were assessed using qualitative methods (observations, group interviews, and document analyses). Changes in adherence and determinants were tested in the paired samples T-tests and expressed in effect sizes (Cohen's d). Overall adherence did not change (3.1%; p = .138). Adherence to three quality indicators improved (8%, 24%, 43%; .000 ≤ p ≤ .023). Adherence to one quality indicator decreased (-15.7%; p = .004). Scores on various determinants of individual performance improved and favourable changes at practice organizational level were observed. Improvements were associated with the programme's multilevel approach, collective goal setting, and the application of self-regulation; unfavourable findings with programme deficits. The one-group pre-test post-test design limits the internal validity of the study, the self-selected sample its external validity. The QUIP programme has the potential to change physical

  19. Prolonged effect of a new O-glycoPEGylated FVIII (N8-GP) in a murine saphenous vein bleeding model

    DEFF Research Database (Denmark)

    Pastoft, Anne Engedahl; Ezban, M.; Tranholm, M.

    2013-01-01

    . The objective of this study was to evaluate the acute and prolonged effects of a new glycoPEGylated recombinant factor VIII (rFVIII) (N8-GP) in a venous bleeding model in haemophilia A mice and to compare the efficacy and potency to turoctocog alfa (rFVIII). Following intravenous administration of turoctocog...

  20. Brazilian programme for plasma physics and controlled thermonuclear fusion

    International Nuclear Information System (INIS)

    Chian, A.C.L.; Reusch, M.F.; Nascimento, I.C.; Pantuso-Sudano, J.

    1992-01-01

    A proposal for a National Programme of Plasma Physics and Controlled Thermonuclear Fusion in Brazil is presented, aimimg the dissemination of the researchers thought in plasma physics for the national authorities and the scientific community. (E.O.)

  1. Re-Audit of the Contents of GP Referral letters to General Adult Community Psychiatrists.

    Science.gov (United States)

    Odelola, Catherine; Jabbar, Farid

    2017-09-01

    The quality of information provided by referring general practitioners to secondary care mental health services are crucial elements in the effective management of patients. In order to establish effective communication, both primary and secondary care health professionals should contribute to planning and organising this process taking into account their different opinions and views. Anonymous questionnaire was designed to collect information on items that GPs and psychiatrist rated as most important items in GP referral letters to psychiatrists. The questionnaires were sent out electronically. Each item was scored using a rating scale where 0 was least important and 10 was most important. Items that scored 8 and above were agreed by all as the most important items. 76 GP letters were audited using a devised checklist of the identified most important items. Data was collected and analysed using a devised data collection tool. A re-audit was done 6months later. A response rate of 70% was obtained for both psychiatrists and GPs. Reasons for referral were described in almost all GP referral letters (95%). Only 24% referral letters had details about current physical health which improved to 59%. Concerns about risk were described in only 47% of letters and treatment provided by GP in 50% of letters. These improved in 79% and 71% of letters respectively in the re-audit. The involvement of professionals in devising a standardised approach for referral letters has improved communication in this re-audit between GPs and Psychiatrists. This is evident in the improvement in key aspects of the referral letters: past medical history, past psychiatric history, current physical health, treatment provided by GP. Efficient communication between GPs and psychiatrists improves the quality of health care for patients.

  2. Objectives for an HTR R and D physics programme

    Energy Technology Data Exchange (ETDEWEB)

    Johnstone, I; Scott, J A

    1973-10-15

    The paper reviews important objectives for an HTR R and D programme and the importance of particular characteristics for safety and reactor performance is discussed. Uncertainties in the physics characteristics influence reactor design through the inclusion of design margins and contingency allowances and may even eliminate certain design variants. The paper discusses quantitatively the relationship between some important uncertainties and reactor design and operating costs and derives targets for the precision with which it should be possible to compute the corresponding physics characteristics. To extrapolate to power reactor conditions, the need for a comprehensive computational scheme validated by an adequate experimental programme is emphasised. The reduction in uncertainty as the theoretical and experimental reactor physics development proceeds in order to meet the desired target uncertainty is illustrated with respect to the UK's programme in support of the low enriched HTR concept. The current situation for this concept is discussed and compared briefly with that for the Th cycle HTR for which somewhat less zero energy experimental data are available. (auth)

  3. Current programmes of Metallurgy Division (1991)

    International Nuclear Information System (INIS)

    1991-01-01

    Current research and development programmes of the Metallurgy Division are listed under the headings: 1)Thrust Areas, 2)High Temperature Materials Section, 3)Chemical Metallurgy Section, 4)Metallurgical Thermochemistry Section, 5)Physical Metallurgy Section, 6)Mechanical Metallurgy Section, 7)Corrosion Metallurgy Section, 8)Electrochemical Science and Technology Section, 9)Ceramics Section, and 10)Fabrication and Maintenance Group. A list of equipment in the Division and a list of sciientific personnel of the Division are also given. (M.G.B.)

  4. Psychosocial factors in GP work: the effects of taking a GP position or leaving GP work.

    Science.gov (United States)

    Heponiemi, Tarja; Kouvonen, Anne; Aalto, Anna-Mari; Elovainio, Marko

    2013-06-01

    We examined the effects of leaving public sector general practitioner (GP) work and of taking a GP position on changes in work-related psychosocial factors, such as time pressure, patient-related stress, distress and work interference with family. In addition, we examined whether changes in time pressure and patient-related stress mediated the association of employment change with changes of distress and work interference with family. Participants were 1705 Finnish physicians (60% women) who responded to surveys in 2006 and 2010. Analyses of covariance were conducted to examine the effect of employment change to outcome changes adjusted for gender, age and response format. Mediational effects were tested following the procedures outlined by Baron and Kenny. Employment change was significantly associated with all the outcomes. Leaving public sector GP work was associated with substantially decreased time pressure, patient-related stress, distress and work interference with family. In contrast, taking a position as a public sector GP was associated with an increase in these factors. Mediation tests suggested that the associations of employment change with distress change and work interference with family change were partially explained by the changes in time pressure and patient-related stress. Our results showed that leaving public sector GP work is associated with favourable outcomes, whereas taking a GP position in the public sector is associated with adverse effects. Primary health-care organizations should pay more attention to the working conditions of their GPs, in particular, to time pressure and patient-related stress.

  5. Antigenicity and Immunogenicity of RV144 Vaccine AIDSVAX Clade E Envelope Immunogen Is Enhanced by a gp120 N-Terminal Deletion

    Science.gov (United States)

    Liao, Hua-Xin; Tomaras, Georgia D.; Bonsignori, Mattia; Tsao, Chun-Yen; Hwang, Kwan-Ki; Chen, Haiyan; Lloyd, Krissey E.; Bowman, Cindy; Sutherland, Laura; Jeffries, Thomas L.; Kozink, Daniel M.; Stewart, Shelley; Anasti, Kara; Jaeger, Frederick H.; Parks, Robert; Yates, Nicole L.; Overman, R. Glenn; Sinangil, Faruk; Berman, Phillip W.; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Karasavva, Nicos; Rerks-Ngarm, Supachai; Kim, Jerome H.; Michael, Nelson L.; Zolla-Pazner, Susan; Santra, Sampa; Letvin, Norman L.; Harrison, Stephen C.

    2013-01-01

    An immune correlates analysis of the RV144 HIV-1 vaccine trial revealed that antibody responses to the gp120 V1/V2 region correlated inversely with infection risk. The RV144 protein immunogens (A244-rp120 and MN-rgp120) were modified by an N-terminal 11-amino-acid deletion (Δ11) and addition of a herpes simplex virus (HSV) gD protein-derived tag (gD). We investigated the effects of these modifications on gp120 expression, antigenicity, and immunogenicity by comparing unmodified A244 gp120 with both Δ11 deletion and gD tag and with Δ11 only. Analysis of A244 gp120, with or without Δ11 or gD, demonstrated that the Δ11 deletion, without the addition of gD, was sufficient for enhanced antigenicity to gp120 C1 region, conformational V2, and V1/V2 gp120 conformational epitopes. RV144 vaccinee serum IgGs bound more avidly to A244 gp120 Δ11 than to the unmodified gp120, and their binding was blocked by C1, V2, and V1/V2 antibodies. Rhesus macaques immunized with the three different forms of A244 gp120 proteins gave similar levels of gp120 antibody titers, although higher antibody titers developed earlier in A244 Δ11 gp120-immunized animals. Conformational V1/V2 monoclonal antibodies (MAbs) gave significantly higher levels of blocking of plasma IgG from A244 Δ11 gp120-immunized animals than IgG from animals immunized with unmodified A244 gp120, thus indicating a qualitative difference in the V1/V2 antibodies induced by A244 Δ11 gp120. These results demonstrate that deletion of N-terminal residues in the RV144 A244 gp120 immunogen improves both envelope antigenicity and immunogenicity. PMID:23175357

  6. Conceptualising GP teachers' knowledge: a pedagogical content knowledge perspective.

    Science.gov (United States)

    Cantillon, Peter; de Grave, Willem

    2012-05-01

    Most teacher development initiatives focus on enhancing knowledge of teaching (pedagogy), whilst largely ignoring other important features of teacher knowledge such as subject matter knowledge and awareness of the learning context. Furthermore, teachers' ability to learn from faculty development interventions is limited by their existing (often implicit) pedagogical knowledge and beliefs. Pedagogical content knowledge (PCK) represents a model of teacher knowledge incorporating what they know about subject matter, pedagogy and context. PCK can be used to explore teachers' prior knowledge and to structure faculty development programmes so that they take account of a broader range of teachers' knowledge. We set out to examine the application of a PCK model in a general practice education setting. This study is part of a larger study that employed a mixed method approach (concept mapping, phenomenological interviews and video-stimulated recall) to explore features of GP teachers' subject matter knowledge, pedagogical knowledge and knowledge of the learning environment in the context of a general practice tutorial. This paper presents data on GP teachers' pedagogical and context knowledge. There was considerable overlap between different GP teachers' knowledge and beliefs about learners and the clinical learning environment (i.e. knowledge of context). The teachers' beliefs about learners were largely based on assumptions derived from their own student experiences. There were stark differences, however, between teachers in terms of pedagogical knowledge, particularly in terms of their teaching orientations (i.e. transmission or facilitation orientation) and this was manifest in their teaching behaviours. PCK represents a useful model for conceptualising clinical teacher prior knowledge in three domains, namely subject matter, learning context and pedagogy. It can and should be used as a simple guiding framework by faculty developers to inform the design and delivery of

  7. Greek Teachers Programme 2015

    CERN Multimedia

    Hoch, Michael

    2015-01-01

    The 3rd edition of this year's Greek Teachers Programme was co-organized by CERN Education Group and the Hellenic Physical Society and took place from 8 to 12 November 2015. The programme targets physics high-school teachers from all over Greece. It aims to help teachers inspire the next generation of scientists and engineers by motivating their students to understand and appreciate how science works at the world's largest physics laboratory, whereby increasing their interest in pursuing studies in STEM fields in secondary and post-secondary education. 33 teachers took part in this programme which comprised lectures by Greek members of the CERN scientific community, with visits to experimental facilities, hands-on activities and dedicated sessions on effective and creative ways through which participants may bring physics, particle physics and CERN closer to their school classroom. In 2015, more than 100 teachers took part in the three editions of the Greek Teachers Programme.

  8. Berkeley Nuclear Laboratories Reactor Physics Mk. III Experimental Programme. Description of facility and programme for 1971

    Energy Technology Data Exchange (ETDEWEB)

    Nunn, R M; Waterson, R H; Young, J D

    1971-01-15

    Reactor physics experiments have been carried out at Berkeley Nuclear Laboratories during the past few years in support of the Civil Advanced Gas-Cooled Reactors (Mk. II) the Generating Board is building. These experiments are part of an overall programme whose objective is to assess the accuracy of the calculational methods used in the design and operation of these reactors. This report provides a description of the facility for the Mk. III experimental programme and the planned programme for 1971.

  9. Proteomics computational analyses suggest that baculovirus GP64 superfamily proteins are class III penetrenes

    Directory of Open Access Journals (Sweden)

    Garry Robert F

    2008-02-01

    Full Text Available Abstract Background Members of the Baculoviridae encode two types of proteins that mediate virus:cell membrane fusion and penetration into the host cell. Alignments of primary amino acid sequences indicate that baculovirus fusion proteins of group I nucleopolyhedroviruses (NPV form the GP64 superfamily. The structure of these viral penetrenes has not been determined. The GP64 superfamily includes the glycoprotein (GP encoded by members of the Thogotovirus genus of the Orthomyxoviridae. The entry proteins of other baculoviruses, group II NPV and granuloviruses, are class I penetrenes. Results Class III penetrenes encoded by members of the Rhabdoviridae and Herpesviridae have an internal fusion domain comprised of beta sheets, other beta sheet domains, an extended alpha helical domain, a membrane proximal stem domain and a carboxyl terminal anchor. Similar sequences and structural/functional motifs that characterize class III penetrenes are located collinearly in GP64 of group I baculoviruses and related glycoproteins encoded by thogotoviruses. Structural models based on a prototypic class III penetrene, vesicular stomatitis virus glycoprotein (VSV G, were established for Thogoto virus (THOV GP and Autographa california multiple NPV (AcMNPV GP64 demonstrating feasible cysteine linkages. Glycosylation sites in THOV GP and AcMNPV GP64 appear in similar model locations to the two glycosylation sites of VSV G. Conclusion These results suggest that proteins in the GP64 superfamily are class III penetrenes.

  10. Reactor physics in support of the naval nuclear propulsion programme

    International Nuclear Information System (INIS)

    Lisley, P.G.; Beeley, P.A.

    1994-01-01

    Reactor physics is a core component of all courses but in particular two postgraduate courses taught at the department in support of the naval nuclear propulsion programme. All of the courses include the following elements: lectures and problem solving exercises, laboratory work, experiments on the Jason zero power Argonaut reactor, demonstration of PWR behavior on a digital computer simulator and project work. This paper will highlight the emphasis on reactor physics in all elements of the education and training programme. (authors). 9 refs

  11. Immunoglobulin G1 Allotype Influences Antibody Subclass Distribution in Response to HIV gp140 Vaccination

    Directory of Open Access Journals (Sweden)

    Sven Kratochvil

    2017-12-01

    Full Text Available Antibody subclasses exhibit extensive polymorphisms (allotypes that could potentially impact the quality of HIV-vaccine induced B cell responses. Allotypes of immunoglobulin (Ig G1, the most abundant serum antibody, have been shown to display altered functional properties in regard to serum half-life, Fc-receptor binding and FcRn-mediated mucosal transcytosis. To investigate the potential link between allotypic IgG1-variants and vaccine-generated humoral responses in a cohort of 14 HIV vaccine recipients, we developed a novel protocol for rapid IgG1-allotyping. We combined PCR and ELISA assays in a dual approach to determine the IgG1 allotype identity (G1m3 and/or G1m1 of trial participants, using human plasma and RNA isolated from PBMC. The IgG1-allotype distribution of our participants mirrored previously reported results for caucasoid populations. We observed elevated levels of HIV gp140-specific IgG1 and decreased IgG2 levels associated with the G1m1-allele, in contrast to G1m3 carriers. These data suggest that vaccinees homozygous for G1m1 are predisposed to develop elevated Ag-specific IgG1:IgG2 ratios compared to G1m3-carriers. This elevated IgG1:IgG2 ratio was further associated with higher FcγR-dimer engagement, a surrogate for potential antibody-dependent cellular cytotoxicity (ADCC and antibody-dependent cellular phagocytosis (ADCP function. Although preliminary, these results suggest that IgG1 allotype may have a significant impact on IgG subclass distribution in response to vaccination and associated Fc-mediated effector functions. These results have important implications for ongoing HIV vaccine efficacy studies predicated on engagement of FcγR-mediated cellular functions including ADCC and ADCP, and warrant further investigation. Our novel allotyping protocol provides new tools to determine the potential impact of IgG1 allotypes on vaccine efficacy.

  12. Going global in physical therapist education: International Service-Learning in US-based programmes.

    Science.gov (United States)

    Pechak, Celia; Thompson, Mary

    2011-12-01

     Internationalization is expanding its presence in higher education in the United States. Reflecting this trend that includes incorporating global perspectives in the curricula, physical therapist education programmes increasingly offer international opportunities such as International Service-Learning (ISL) to their students. Service-learning, a teaching strategy that integrates community service with structured learning activities, has gained broad acceptance in health professions education including physical therapy, and is therefore the focus of this paper. The specific purposes of this paper were to identify and analyse the commonalities that existed among established ISL programmes within physical therapist education programmes in terms of structures and processes, and to consider its broader implications for physical therapist education.   A descriptive, exploratory study was performed using grounded theory. Snowball and purposive, theoretical sampling yielded 14 faculty members with experience in international service, international learning or ISL in physical therapist education programmes. Faculty were interviewed by phone. Interview transcriptions and course documents were analysed applying grounded theory methodology. Data from eight programmes which met the operational definition of established ISL were used to address the purposes of this paper.   Five phases of establishing an ISL programme were identified: development, design, implementation, evaluation, and enhancement. Although no single model exists for ISL in physical therapist education; commonalities in structures and processes were identified in each phase. However, attention to service objectives and outcomes is lacking.   While analysis revealed that each programme shared commonalities and demonstrated differences in structures and processes compared with the other programmes, the study demonstrated a general lack of focus on formal community outcomes which raises ethical

  13. A framework for evaluating community-based physical activity promotion programmes in Latin America.

    Science.gov (United States)

    Schmid, Thomas L; Librett, John; Neiman, Andrea; Pratt, Michael; Salmon, Art

    2006-01-01

    A growing interest in promoting physical activity through multi-sectoral community-based programmes has highlighted the need for effective programme evaluation. Meeting in Rio de Janeiro, an international workgroup of behavioural, medical, public health and other scientists and practitioners endorsed the principle of careful evaluation of all programmes and in a consensus process developed the Rio de Janeiro Recommendations for Evaluation of Physical Activity Interventions". Among these recommendations and principles were that when possible, evaluation should 'built into' the programme from the beginning. The workgroup also called for adequate funding for evaluation, setting a goal of about 10% of programme resources for evaluation. The group also determined that evaluations should be developed in conjunction with and the results shared with all appropriate stakeholders in the programme; evaluations should be guided by ethical standards such as those proposed by the American Evaluation Association and should assess programme processes as well as outcomes; evaluation outcomes should be used to revise and refine ongoing programmes and guide decisions about programme continuation or expansion. It was also recognised that additional training in programme evaluation is needed and the Centers for Disease Control and Prevention's Physical Activity Evaluation Handbook could be easily adapted for use in culturally diverse communities, especially in Latin America. This paper describes a 6-step evaluation process and provides the full set of recommendations from the Rio de Janeiro Workgroup. The handbook has been translated and additional case studies from Colombia and Brazil have been added. Spanish and Portuguese language editions of the Evaluation Handbook are available from the Centers for Disease Control and Prevention, Physical Activity and Health Branch.

  14. The UK MK III GCR experimental physics programme at AEE Winfrith

    Energy Technology Data Exchange (ETDEWEB)

    Johnstone, I

    1972-06-15

    The UK programme of reactor physics experiments in support of the Mk III GCR project started in 1968/69 and has now reached its third main phase. The overall programme is broadly summarised in this report.

  15. Enhancing field GP engagement in hospital-based studies. Rationale, design, main results and participation in the diagest 3-GP motivation study

    Directory of Open Access Journals (Sweden)

    Berkhout Christophe

    2012-06-01

    Full Text Available Abstract Background Diagest 3 was a study aimed at lowering the risk of developing type 2 diabetes within 3 years after childbirth. Women with gestational diabetes were enrolled in the study. After childbirth, the subjects showed little interest in the structured education programme and did not attend workshops. Their general practitioners (GPs were approached to help motivate the subjects to participate in Diagest 3, but the GPs were reluctant. The present study aimed to understand field GPs’ attitudes towards hospital-based studies, and to develop strategies to enhance their involvement and reduce subject drop-out rates. Methods We used a three-step process: step one used a phenomenological approach exploring the beliefs, attitudes, motivations and environmental factors contributing to the GPs’ level of interest in the study. Data were collected in face-to-face interviews and coded by hand and with hermeneutic software to develop distinct GP profiles. Step two was a cross-sectional survey by questionnaire to determine the distribution of the profiles in the GP study population and whether completion of an attached case report form (CRF was associated with a particular GP profile. In step three, we assessed the impact of the motivation study on participation rates in the main study. Results Fifteen interviews were conducted to achieve data saturation. Theorisation led to the definition of 4 distinct GP profiles. The response rate to the questionnaire was 73%, but dropped to 52% when a CRF was attached. The link between GP profiles and the rate of CRF completion remains to be verified. The GPs provided data on the CRF that was of comparable quality to those collected in the main trial. Our analysis showed that the motivation study increased overall participation in the main study by 23%, accounting for 16% (24/152 of all final visits for 536 patients who were initially enrolled in the Diagest 3 study. Conclusions When a hospital-led study

  16. Enhancing field GP engagement in hospital-based studies. Rationale, design, main results and participation in the Diagest 3-GP motivation study.

    Science.gov (United States)

    Berkhout, Christophe; Vandaele-Bétancourt, Marie; Robert, Stéphane; Lespinasse, Solène; Mitha, Gamil; Bradier, Quentin; Vambergue, Anne; Fontaine, Pierre

    2012-06-21

    Diagest 3 was a study aimed at lowering the risk of developing type 2 diabetes within 3 years after childbirth. Women with gestational diabetes were enrolled in the study. After childbirth, the subjects showed little interest in the structured education programme and did not attend workshops. Their general practitioners (GPs) were approached to help motivate the subjects to participate in Diagest 3, but the GPs were reluctant. The present study aimed to understand field GPs' attitudes towards hospital-based studies, and to develop strategies to enhance their involvement and reduce subject drop-out rates. We used a three-step process: step one used a phenomenological approach exploring the beliefs, attitudes, motivations and environmental factors contributing to the GPs' level of interest in the study. Data were collected in face-to-face interviews and coded by hand and with hermeneutic software to develop distinct GP profiles. Step two was a cross-sectional survey by questionnaire to determine the distribution of the profiles in the GP study population and whether completion of an attached case report form (CRF) was associated with a particular GP profile. In step three, we assessed the impact of the motivation study on participation rates in the main study. Fifteen interviews were conducted to achieve data saturation. Theorisation led to the definition of 4 distinct GP profiles. The response rate to the questionnaire was 73%, but dropped to 52% when a CRF was attached. The link between GP profiles and the rate of CRF completion remains to be verified. The GPs provided data on the CRF that was of comparable quality to those collected in the main trial. Our analysis showed that the motivation study increased overall participation in the main study by 23%, accounting for 16% (24/152) of all final visits for 536 patients who were initially enrolled in the Diagest 3 study. When a hospital-led study explores issues in primary care, its design must anticipate GP

  17. CXCL10 Decreases GP73 Expression in Hepatoma Cells at the Early Stage of Hepatitis C Virus (HCV Infection

    Directory of Open Access Journals (Sweden)

    Yuan Liu

    2013-12-01

    Full Text Available Golgi protein 73 (GP73, which is up-regulated in hepatocellular carcinoma (HCC, has recently been identified as a novel serum marker for HCC diagnosis. Several reports also noted the increased levels of GP73 expression in chronic liver disease in patients with acute hepatitis of various etiologies, chronic Hepatitis C virus (HCV infection and alcoholic liver disease. The molecular mechanisms of GP73 expression in HCV related liver disease still need to be determined. In this study, we aimed to evaluate the effect of HCV infection on GP73 expression. GP73 was highly expressed in Huh7, Hep3B, 293T and HUVEC cells, and was low-expressed in HepG2 cells. HCV infection led to down-regulation of GP73 in Huh7 and HepG2/CD81 cells at the early stage of infection. CXCL10 decreased GP73 expression in Huh7 and HepG2 cells. Up-regulation of GP73 was noted in hepatocytes with cytopathic effect at advanced stage of HCV infection, and further research is needed to determine the unknown factors affecting GP73 expression. In conclusion, our study provided additional evidence for the roles of GP73 in liver disease.

  18. 8th International Workshop on Top Quark Physics

    CERN Document Server

    2015-01-01

    This workshop, at its 8th edition, will bring together the community of experimental and theoretical physicists working on top quark physics, 20 years after its first discovery, and at the beginning of the exploration of the new energy regime at the Large Hadron Collider. The workshop will provide a comprehensive overview of the latest results from the LHC and Tevatron experiments as well as the most recent theoretical developments and an outlook on top-quark physics at future colliders. The programme will consist of plenary presentations, a poster session and 'question and answers' sessions, targeted for young researchers. A significant fraction of the workshop time will be devoted to discussions. The goal of the workshop is to provide a comprehensive picture of top-quark physics and a forum where experimentalists and theorists can discuss the interpretation of top quark results and plan future measurements. The venue will take place in the Hotel Continental Terme, Ischia, the largest island in the bay of Na...

  19. Comment on ‘Positron scattering in helium: Virtual-positronium resonances’ by G.P. Karwasz, D. Pliszka, A. Zecca, R.S. Brusa [Nucl. Instr. and Meth. B 240 (2005) 666

    Science.gov (United States)

    Zecca, Antonio

    2006-10-01

    A recent paper [G.P. Karwasz, D. Pliszka, A. Zecca, R.S. Brusa, Nucl. Instr. and Meth. B 240 (2005) 666] claims the observation of scattering resonances in the total cross section for positron scattering from helium. In this comment we question the reality of such resonances. Our discussion will be based on the detailed knowledge of the general capabilities of the Trento spectrometer and will be invigorated by new checks we have made on the measurement procedure employed in [G.P. Karwasz, D. Pliszka, A. Zecca, R.S. Brusa, Nucl. Instr. and Meth. B 240 (2005) 666]. We conclude that the observed structures are most likely an experimental artefact rather than being due to the positron-helium interaction.

  20. Current programmes on physical metallurgy and related areas in BARC

    International Nuclear Information System (INIS)

    1994-01-01

    Current research and development programmes on physical metallurgy and related areas from the following Divisions of Bhabha Atomic Research Centre are included in this report : Atomic Fuels Division, High Pressure Physics Division, Metallurgy Division, Radio Metallurgy Division, Solid State Physics Division. Important publications corresponding to each activity have also been listed. (author)

  1. The G8 global partnership - a survey of the German activities and their legal framework

    International Nuclear Information System (INIS)

    Fillbrandt, M.

    2006-01-01

    At the G8 summit in Kananaskis, Canada, in 2002, the G8 partners established the 'Global Partnership against the Proliferation of Weapons and Materials of Mass Destruction'. The Federal Republic of Germany and the Russian Federation at present cooperate in three areas within the framework of the G8 Global Partnership: (1) Destruction of chemical weapons. (2) Construction of a long-term interim store for the safe storage of irradiated reactor segments of decommissioned nuclear submarines. (3) Modernization of the physical protection of Russian nuclear material. The article mainly covers the 'Modernization of the Physical Protection of Russian Nuclear Material' project. The key part contains an explanation of the legal basis of the project. The main contents and functions of applicable bilateral and multilateral agreements are explained on the basis of the principles and guidelines adopted in connection with the declaration of the G8 Heads of State and Government about global partnership. It is shown that a complex set of rules and contracts are necessary to meet the requirements posed by projects of G8 Global Partnership. (orig.)

  2. Identification by Mass Spectrometry and Immune Response Analysis of Guinea Pig Cytomegalovirus (GPCMV Pentameric Complex Proteins GP129, 131 and 133

    Directory of Open Access Journals (Sweden)

    Josephine S. Gnanandarajah

    2014-02-01

    Full Text Available Development of a vaccine against congenital infection with human cytomegalovirus (HCMV is a major public health priority. A potential vaccine target receiving considerable recent attention is the pentameric complex (PC of HCMV proteins consisting of gL, gH, UL128, UL130, and UL131, since some antibodies against these target proteins are capable of potently neutralizing virus at epithelial and endothelial cell surfaces. Recently, homologous proteins have been described for guinea pig cytomegalovirus (GPCMV, consisting of gH, gL, and the GPCMV proteins GP129, GP131, and GP133. To investigate these proteins as potential vaccine targets, expression of GP129-GP133 transcripts was confirmed by reverse-transcriptase PCR. Mass spectrometry combined with western blot assays demonstrated the presence of GP129, GP131, and GP133 proteins in virus particles. Recombinant proteins corresponding to these PC proteins were generated in baculovirus, and as GST fusion proteins. Recombinant proteins were noted to be immunoreactive with convalescent sera from infected animals, suggesting that these proteins are recognized in the humoral immune response to GPCMV infection. These analyses support the study of PC-based recombinant vaccines in the GPCMV congenital infection model.

  3. Microsoft Dynamics GP 2013 implementation

    CERN Document Server

    Yudin, Victoria

    2013-01-01

    A step-by-step guide for planning and carrying out your Microsoft Dynamics GP 2013 implementation. Detailed descriptions and illustrations of setup screens and practical examples and advice are included for the Dynamics GP system and core modules.If you are a new or existing Microsoft Dynamics GP consultant or an end user who wants to implement, install, and set up core modules of Dynamics GP 2013, then this book is for you. A basic understanding of business management systems and either Dynamics GP or a similar application is recommended.

  4. Cost analysis of bluetongue virus serotype 8 surveillance and vaccination programmes in Austria from 2005 to 2013.

    Science.gov (United States)

    Pinior, Beate; Lebl, Karin; Firth, Clair; Rubel, Franz; Fuchs, Reinhard; Stockreiter, Simon; Loitsch, Angelika; Köfer, Josef

    2015-11-01

    This study was designed to evaluate the costs between 2005 and 2013 of the national bluetongue virus (BTV) surveillance and vaccination programmes before, during and after the BTV serotype 8 (BTV-8) outbreak in Austria commencing in 2008. In addition to an assessment of the temporal development of costs, a spatial cost analysis was performed. Within the context of this study, the term 'costs' refers to actual financial expenditure and imputed monetary costs for contributions in-kind. Costs were financed directly by the private-public sectors, by the European Commission (EC), and (in-kind) by responsible national institutions and individuals (e.g. blood sampling by veterinarians). The total net cost of the BTV-8 surveillance and vaccination programmes arising from the outbreak amounted to €22.8 million (0.86% of the national agricultural Gross Value Added), of which 32% was allocated to surveillance and 68% to the vaccination programme. Of the total programme costs, the EC supplied €4.9 million, while the remaining costs (€18 million) were directly financed from national resources. Of the latter, €14.5 million was classed as public costs, including €2 million contributions in-kind, and €3.4 million as private costs. The assessment of the costs revealed heterogeneous temporal and spatial distributions. The methodology of this analysis might assist decision makers in calculating costs for other surveillance and intervention programmes. The assessment of contributions in-kind is of importance to public authorities as it increases visibility of the available resources and shows how they have been employed. This study also demonstrates the importance of tracking changing costs per payer over time. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. G5..., G6..., G7..., G8..., G?

    OpenAIRE

    Monteiro, António

    2001-01-01

    O G8 tem as suas raízes no primitivo embrião do G5 quando, em 1973, o então Secretário de Estado do Tesouro americano, George Schultz, convocou os Ministros das Finanças da França, Japão, Reino Unido e República Federal da Alemanha para uma reunião. O objectivo era analisar como fazer face à primeira crise do petróleo da OPEC e subsequente recessão económica nos países mais industrializados, ao colapso do sistema monetário das taxas de câmbio de paridades fixas de Bretton-Woods e ao alargamen...

  6. Technology-Enhanced Physics Programme for Community-Based Science Learning: Innovative Design and Programme Evaluation in a Theme Park

    Science.gov (United States)

    Tho, Siew Wei; Chan, Ka Wing; Yeung, Yau Yuen

    2015-01-01

    In this study, a new physics education programme is specifically developed for a famous theme park in Hong Kong to provide community-based science learning to her visitors, involving her three newly constructed rides. We make innovative use of digital technologies in this programme and incorporate a rigorous evaluation of the learning…

  7. Long-term effectiveness of a back education programme in elementary schoolchildren: an 8-year follow-up study.

    Science.gov (United States)

    Dolphens, Mieke; Cagnie, Barbara; Danneels, Lieven; De Clercq, Dirk; De Bourdeaudhuij, Ilse; Cardon, Greet

    2011-12-01

    The purpose of this study was to investigate the long-term effectiveness of a spine care education programme conducted in 9- to 11-year-old schoolchildren. The study sample included 96 intervention subjects and 98 controls (9- to 11-year-olds at baseline). Intervention consisted of a 6-week school-based back education programme (predominantly biomechanically oriented) and was implemented by a physical therapist. Self-reported outcomes on back care knowledge, spinal care behaviour, self-efficacy towards favourable back care behaviour, prevalence of back and neck pain during the week and fear-avoidance beliefs were evaluated by the use of questionnaires. Post-tests were performed within 1 week after programme completion, after 1 year and after 8 years. Whereas the educational back care programme resulted in increased back care knowledge up to adulthood (P cognitive aspect of back care up to adulthood, yet not in changing actual behaviour or self-efficacy. The current study does not provide evidence that educational back care programmes have any impact on spinal pain in adulthood. The true long-term impact of school-based spinal health interventions on clinically relevant outcome measures merits further attention.

  8. Gp96 Peptide Antagonist gp96-II Confers Therapeutic Effects in Murine Intestinal Inflammation

    Directory of Open Access Journals (Sweden)

    Claudia A. Nold-Petry

    2017-12-01

    Full Text Available BackgroundThe expression of heat shock protein gp96 is strongly correlated with the degree of tissue inflammation in ulcerative colitis and Crohn’s disease, thereby leading us to the hypothesis that inhibition of expression via gp96-II peptide prevents intestinal inflammation.MethodsWe employed daily injections of gp96-II peptide in two murine models of intestinal inflammation, the first resulting from five daily injections of IL-12/IL-18, the second via a single intrarectal application of TNBS (2,4,6-trinitrobenzenesulfonic acid. We also assessed the effectiveness of gp96-II peptide in murine and human primary cell culture.ResultsIn the IL-12/IL-18 model, all gp96-II peptide-treated animals survived until day 5, whereas 80% of placebo-injected animals died. gp96-II peptide reduced IL-12/IL-18-induced plasma IFNγ by 89%, IL-1β by 63%, IL-6 by 43% and tumor necrosis factor (TNF by 70% compared to controls. The clinical assessment Disease Activity Index of intestinal inflammation severity was found to be significantly lower in the gp96-II-treated animals when compared to vehicle-injected mice. gp96-II peptide treatment in the TNBS model limited weight loss to 5% on day 7 compared with prednisolone treatment, whereas placebo-treated animals suffered a 20% weight loss. Histological disease severity was reduced equally by prednisolone (by 40% and gp96-II peptide (35%. Mice treated with either gp96-II peptide or prednisolone exhibited improved endoscopic scores compared with vehicle-treated control mice: vascularity, fibrin, granularity, and translucency scores were reduced by up to 49% by prednisolone and by up to 30% by gp96-II peptide. In vitro, gp96-II peptide reduced TLR2-, TLR4- and IL-12/IL-18-induced cytokine expression in murine splenocytes, with declines in constitutive IL-6 (54%, lipopolysaccharide-induced TNF (48%, IL-6 (81% and in Staphylococcus epidermidis-induced TNF (67% and IL-6 (81%, as well as IL-12/IL-18-induced IFNγ (75%. gp

  9. The solid state physics programme at ISOLDE: recent developments and perspectives

    Science.gov (United States)

    Johnston, Karl; Schell, Juliana; Correia, J. G.; Deicher, M.; Gunnlaugsson, H. P.; Fenta, A. S.; David-Bosne, E.; Costa, A. R. G.; Lupascu, Doru C.

    2017-10-01

    Solid state physics (SSP) research at ISOLDE has been running since the mid-1970s and accounts for about 10%-15% of the overall physics programme. ISOLDE is the world flagship for the on-line production of exotic radioactive isotopes, with high yields, high elemental selectivity and isotopic purity. Consequently, it hosts a panoply of state-of-the-art nuclear techniques which apply nuclear methods to research on life sciences, material science and bio-chemical physics. The ease of detecting radioactivity—scientists and specialists in nuclear solid state techniques. This article describes the current status of this programme along with recent illustrative results, predicting a bright future for these unique research methods and collaborations.

  10. Applying the trigger review method after a brief educational intervention: potential for teaching and improving safety in GP specialty training?

    OpenAIRE

    McKay, John; de Wet, Carl; Kelly, Moya; Bowie, Paul

    2013-01-01

    Background:\\ud The Trigger Review Method (TRM) is a structured approach to screening clinical records for undetected patient safety incidents (PSIs) and identifying learning and improvement opportunities. In Scotland, TRM participation can inform GP appraisal and has been included as a core component of the national primary care patient safety programme that was launched in March 2013. However, the clinical workforce needs up-skilled and the potential of TRM in GP training has yet to be teste...

  11. Effectiveness of an exercise programme on physical function in patients discharged from hospital following critical illness: a randomised controlled trial (the REVIVE trial).

    Science.gov (United States)

    McDowell, Kathryn; O'Neill, Brenda; Blackwood, Bronagh; Clarke, Chris; Gardner, Evie; Johnston, Paul; Kelly, Michaeline; McCaffrey, John; Mullan, Brian; Murphy, Sally; Trinder, T John; Lavery, Gavin; McAuley, Daniel F; Bradley, Judy M

    2017-07-01

    To investigate the effectiveness of a 6-week exercise programme in patients discharged home following critical illness compared with standard care. Multicentre prospective phase II randomised controlled trial, with blinded outcome assessment after hospital discharge, following the 6-week intervention and at 6 months. 60 patients (30 per group) aged ≥18 years, mechanically ventilated >96 hours, and not in other rehabilitation, that is, cardiac or pulmonary rehabilitation programmes. Participants in the intervention group completed an individually tailored (personalised) exercise programme. Primary outcome measure was SF-36 physical functioning following the intervention. Secondary outcomes included a range of performance-based and patient-reported measures. Improvements in the primary outcome did not differ significantly between groups (mean difference (95% CI) 3.0 (-2.2 to 8.2), p=0.26). The intervention group showed significant improvement compared with the control group (mean difference (95% CI)) in SF-36 role physical (6.6 (0.73 to 12.5), p=0.03); incremental shuttle walk test (83.1 m (8.3 to 157.9), p=0.03); functional limitations profile (-4.8 (-8.7 to -0.9), p=0.02); self-efficacy to exercise (2.2 (0.8 to 3.7), p=0.01) and readiness to exercise (1.3 (0.8 to 1.9), p<0.001). These improvements were not sustained at 6 months except readiness to exercise. Improvements in all other secondary outcome measures were not significant. There was no statistically significant difference in the primary outcome measure of self-reported physical function following this 6-week exercise programme. Secondary outcome results will help inform future studies. NCT01463579. (results), https://clinicaltrials.gov/. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  12. Recent G8, G20 Inclusive Multilevel Food Governance

    Directory of Open Access Journals (Sweden)

    John Kirton

    2014-11-01

    Full Text Available Innovative, integrative, local, and business-inclusive governance for food, agriculture, nutrition, health and wealth can be strengthened through informal global institutions led by the Group of Eight (G8 and the Group of Twenty (G20. Their regular summits include the most important countries’ leaders and have a comprehensive, synergistic agenda, and impulse, as well as the flexibility and authority to link issues, factors, and actors in new ways. The G8 has increasingly addressed food, agriculture, nutrition, health, and the link among them, involved business, civil society, and low-income countries, and made decisions intended to affect the lives of the poor in many locales. The G20 has contributed to some degree in such ways too. Of particular promise is the G8’s New Alliance on Food Security and Nutrition, launched in May 2012, and the G20’s AgResults program built on commitments made in June 2010. Yet there remains much that both institutions can and should do to meet the combined, complex, food-health-wealth challenge now confronting the global community, before the next food crisis comes.

  13. Assessment of nutrition and physical activity education programmes in children.

    Science.gov (United States)

    Burke, V; Beilin, L J; Milligan, R; Thompson, C

    1995-03-01

    1. Studies in children relating blood lipids to the extent of atherosclerosis at post-mortem suggest a link between risk factors for cardiovascular disease in childhood and adult life. Tracking of blood pressure (BP) and cholesterol from childhood also supports this association. However, prospective studies have not yet established the outcome in children with increased levels of risk factors. 2. In a controlled trial in Perth, Western Australia, involving over 1000 10-12 year old children, fitness was improved by physical activity programmes which were associated with a greater fall in diastolic BP and triceps skinfolds in girls compared with controls. Sugar intake decreased in boys and fat intake fell in girls, mainly affecting participants in home nutrition programmes. 3. In higher risk children, identified by cluster analysis, major benefits were associated with the fitness and home nutrition programmes. Physical activity combined with involvement of the family in nutrition education is likely to be the most successful approach to modifying lifestyle in children, including those with higher levels of risk. 4. Undernutrition by too rigid restriction of fat intake must be avoided in young children who need calorie-dense foods. Undernutrition, in itself, may predispose to cardiovascular disease in later life. Programmes should aim to establish a prudent diet appropriate to the age of the child combined with physical activity. As regular activity and a healthy diet in adult life will reduce risks of cardiovascular disease it is likely that childhood education will establish lifestyle habits of potential long-term benefit.

  14. Polymerization by DNA polymerase eta is blocked by cis-diamminedichloroplatinum(II) 1,3-d(GpTpG) cross-link: implications for cytotoxic effects in nucleotide excision repair-negative tumor cells.

    Science.gov (United States)

    Chijiwa, Shotaro; Masutani, Chikahide; Hanaoka, Fumio; Iwai, Shigenori; Kuraoka, Isao

    2010-03-01

    cis-Diamminedichloroplatinum(II) (cisplatin) forms DNA adducts that interfere with replication and transcription. The most common adducts formed in vivo are 1,2-intrastrand d(GpG) cross-links (Pt-GG) and d(ApG) cross-links (Pt-AG), with minor amounts of 1,3-d(GpNpG) cross-links (Pt-GNG), interstrand cross-links and monoadducts. Although the relative contribution of these different adducts to toxicity is not known, literature implicates that Pt-GG and Pt-AG adducts block replication. Thus, nucleotide excision repair (NER), by which platinum adducts are excised, and translesion DNA synthesis (TLS), which permits adduct bypass, are thought to be associated with cisplatin resistance. Recent studies have reported that the clinical benefit from platinum-based chemotherapy is high if tumor cells express low levels of NER factors. To investigate the role of platinum-DNA adducts in mediating tumor cell survival by TLS, we examined whether 1,3-intrastrand d(GpTpG) platinum cross-links (Pt-GTG), which probably exist in NER-negative tumor cells but not in NER-positive tumor cells, are bypassed by the translesion DNA polymerase eta (pol eta), which is known to bypass Pt-GG. We show that pol eta can incorporate the correct deoxycytidine triphosphate opposite the first 3'-cross-linked G of Pt-GTG but cannot insert any nucleotides opposite the second intact T or the third 5'-cross-linked G of the adducts, thereby suggesting that TLS does not facilitate replication past Pt-GTG adducts. Thus, our findings implicate Pt-GNG adducts as mediating the cytotoxicity of platinum-DNA adducts in NER-negative tumors in vivo.

  15. Fusion technology programme

    International Nuclear Information System (INIS)

    Finken, D.

    1985-10-01

    KfK is involved in the European Fusion Programme predominantly in the NET and Fusion Technology part. The following fields of activity are covered: Studies for NET, alternative confinement concepts, and needs and issues of integral testing. Research on structural materials. Development of superconducting magnets. Gyrotron development (part of the Physics Programme). Nuclear technology (breeding materials, blanket design, tritium technology, safety and environmental aspects of fusion, remote maintenance). Reported here are status and results of work under contracts with the CEC within the NET and Technology Programme. The aim of the major part of this R and D work is the support of NET, some areas (e.g. materials, safety and environmental impact, blanket design) have a wider scope and address problems of a demonstration reactor. In the current working period, several new proposals have been elaborated to be implemented into the 85/89 Euratom Fusion Programme. New KfK contributions relate to materials research (dual beam and fast reactor irradiations, ferritic steels), to blanket engineering (MHD-effects) and to safety studies (e.g. magnet safety). (orig./GG)

  16. Effects of a pain programme on nurses' psychosocial, physical and relaxation interventions.

    NARCIS (Netherlands)

    Francke, A.L.; Luiken, J.B.; Garssen, B.; Huijer-Abu Saad, H.; Grypdonck, M.

    1996-01-01

    The effectiveness of a continuing education programme on pain assessment and management was investigated in 106 surgical cancer nurses. It was found that the programme led to a more positive attitude towards physical and relaxation interventions (such as the use of relaxation, distraction and

  17. Selected Thermophysical Properties of 2,2 Dimethylcyclopentyl Methylphosphonofluoridate (GP) and 2,2 Dimethylcyclopentanol (DMCP)

    Science.gov (United States)

    2016-09-01

    chromatography using a thermal conductivity detector (GC-TCD). Table 1. Sample Information for GP and DMCP Chemical Name Mole Fraction Purity...Proving Ground, MD, 1983; UNCLASSIFIED Report (ADC033491). 23. Weast, R.C. CRC Handbook of Chemistry and Physics, 53rd ed.; CRC Press: Boca Raton, FL...gas chromatography GD pinacolyl methylphosphonofluoridate GF cyclohexyl methylphosphonofluoridate GP 2,2-dimethylcyclopentyl

  18. Nuclear Enterprises portable dose rate meter type PDR4 and external probes types BP1/1, BP8 and GP9

    International Nuclear Information System (INIS)

    Burgess, P.H.; Iles, W.J.

    1979-08-01

    The performance characteristics of Nuclear Enterprises Portable Dose Rate Meter Type PDR4 are evaluated under the headings: general description, facilities and controls, radiation characteristics, electrical characteristics, environmental characteristics, mechanical characteristics, the manual, summary of performance, and conclusions. Results of an investigation of the radiation characteristics of the external probes Type BP1/1, Type BP8, and Type GP9 are also detailed. (U.K.)

  19. The effect of a cognitive and a physical stress-reducing programme on psychological complaints

    NARCIS (Netherlands)

    Rhenen, W. van; Blonk, R.W.B.; Klink, J.J. van der; Dijk, F.J. van; Schaufeli, W.B.

    2005-01-01

    Objectives: To investigate the short-term and long-term effectiveness of two, brief, preventive, work stress management programmes. One programme was a cognition-focused programme, the other was a newly developed intervention in which physical exercise and relaxation were combined. It was

  20. Do children's health resources differ according to preschool physical activity programmes and parental behaviour? A mixed methods study.

    Science.gov (United States)

    Sterdt, Elena; Pape, Natalie; Kramer, Silke; Liersch, Sebastian; Urban, Michael; Werning, Rolf; Walter, Ulla

    2014-02-26

    Preschool can have positive effects on the development of a healthy lifestyle. The present study analysed to what extent different conditions, structures and behavioural models in preschool and family-children's central social microsystems-can lead to differences in children's health resources. Using a cross-sectional mixed methods approach, contrast analyses of "preschools with systematic physical activity programmes" versus "preschools without physical activity programmes" were conducted to assess the extent to which children's physical activity, quality of life and social behaviour differ between preschools with systematic and preschools without physical activity programmes. Differences in children's physical activity according to parental behaviour were likewise assessed. Data on child-related outcomes and parent-related factors were collected via parent questionnaires and child interviews. A qualitative focused ethnographic study was performed to obtain deeper insight into the quantitative survey data. Two hundred and twenty seven (227) children were interviewed at 21 preschools with systematic physical activity programmes, and 190 at 25 preschools without physical activity programmes. There was no significant difference in children's physical activity levels between the two preschool types (p = 0.709). However, the qualitative data showed differences in the design and quality of programmes to promote children's physical activity. Data triangulation revealed a strong influence of parental behaviour. The triangulation of methods provided comprehensive insight into the nature and extent of physical activity programmes in preschools and made it possible to capture the associations between systematic physical activity promotion and children's health resources in a differential manner.

  1. A comparative immunogenicity study in rabbits of disulfide-stabilized, proteolytically cleaved, soluble trimeric human immunodeficiency virus type 1 gp140, trimeric cleavage-defective gp140 and monomeric gp120

    International Nuclear Information System (INIS)

    Beddows, Simon; Franti, Michael; Dey, Antu K.; Kirschner, Marc; Iyer, Sai Prasad N.; Fisch, Danielle C.; Ketas, Thomas; Yuste, Eloisa; Desrosiers, Ronald C.; Klasse, Per Johan; Maddon, Paul J.; Olson, William C.; Moore, John P.

    2007-01-01

    The human immunodeficiency virus type 1 (HIV-1) surface envelope glycoprotein (Env) complex, a homotrimer containing gp120 surface glycoprotein and gp41 transmembrane glycoprotein subunits, mediates the binding and fusion of the virus with susceptible target cells. The Env complex is the target for neutralizing antibodies (NAbs) and is the basis for vaccines intended to induce NAbs. Early generation vaccines based on monomeric gp120 subunits did not confer protection from infection; one alternative approach is therefore to make and evaluate soluble forms of the trimeric Env complex. We have directly compared the immunogenicity in rabbits of two forms of soluble trimeric Env and monomeric gp120 based on the sequence of HIV-1 JR-FL . Both protein-only and DNA-prime, protein-boost immunization formats were evaluated, DNA-priming having little or no influence on the outcome. One form of trimeric Env was made by disrupting the gp120-gp41 cleavage site by mutagenesis (gp140 UNC ), the other contains an intramolecular disulfide bond to stabilize the cleaved gp120 and gp41 moieties (SOSIP.R6 gp140). Among the three immunogens, SOSIP.R6 gp140 most frequently elicited neutralizing antibodies against the homologous, neutralization-resistant strain, HIV-1 JR-FL . All three proteins induced NAbs against more sensitive strains, but the breadth of activity against heterologous primary isolates was limited. When antibodies able to neutralize HIV-1 JR-FL were detected, antigen depletion studies showed they were not directed at the V3 region but were targeted at other, undefined gp120 and also non-gp120 epitopes

  2. Educational CPD: how UK GP trainers develop themselves as teachers.

    Science.gov (United States)

    Waters, Mark; Wall, David

    2007-09-01

    There is little in the literature giving the perspective of UK General Practice (GP) trainers on their development as teachers. What motivates GP trainers develop themselves as teachers? What obstacles to their professional development do GP trainers perceive? A questionnaire to all GP trainers in the West Midlands Deanery in 2004. 360/444 (81%) questionnaires were returned. 56.6% of GP trainers had another educational role in addition to training GP Registrars in the practice. 15.8% of trainers possessed an educational qualification. 13 had completed a Certificate in Medical Education and 28 were engaged in study towards that qualification. Trainers wanted more time to spend on their development as teachers than they presently have, and would then be interested in a wider variety of learning methods. However, 56.6% of trainers would still not choose to undertake a university-accredited course. Female GP trainers perceived more difficulty in obtaining protected time for their development as teachers (Educational CPD) (p = 0.021), were significantly less sure of their partners' support for this development (p = 0.033), and were more likely to agree with trainers undertaking a Certificate in Medical Education (p = 0.003). Having an additional educational role did not affect trainers' ability to take protected time, but significantly increased the amount of time aspired to (p = 0.005). Nothing made more difference to trainers' perception of their ability to undertake Educational CPD than did the perceived attitude of their partners. Educational CPD was very important to GP trainers, but getting protected time was difficult. Consideration of the needs and opinions of partners was a very strong barrier to trainers taking sufficient protected time. Given more available time, GP trainers would be more likely to consider gaining academic qualifications in education. However, this was not be something that all trainers wanted.

  3. Characterization of HIV-1 gp120 antibody specificities induced in anogenital secretions of RV144 vaccine recipients after late boost immunizations.

    Directory of Open Access Journals (Sweden)

    Siriwat Akapirat

    Full Text Available Sexual transmission is the principal driver of the human immunodeficiency virus (HIV pandemic. Understanding HIV vaccine-induced immune responses at mucosal surfaces can generate hypotheses regarding mechanisms of protection, and may influence vaccine development. The RV144 (ClinicalTrials.gov NCT00223080 efficacy trial showed protection against HIV infections but mucosal samples were not collected, therefore, the contribution of mucosal antibodies to preventing HIV-1 acquisition is unknown. Here, we report the generation, magnitude and persistence of antibody responses to recombinant gp120 envelope and antigens including variable one and two loop scaffold antigens (gp70V1V2 previously shown to correlate with risk in RV144. We evaluated antibody responses to gp120 A244gD and gp70V1V2 92TH023 (both CRF01_AE and Case A2 (subtype B in cervico-vaginal mucus (CVM, seminal plasma (SP and rectal secretions (RS from HIV-uninfected RV144 vaccine recipients, who were randomized to receive two late boosts of ALVAC-HIV/AIDSVAX®B/E, AIDSVAX®B/E, or ALVAC-HIV alone at 0 and 6 months. Late vaccine boosting increased IgG geometric mean titers (GMT to gp120 A244gD in AIDSVAX®B/E and ALVAC-HIV/AIDSVAX®B/E CVM (28 and 17 fold, respectively, followed by SP and RS. IgG to gp70V1V2 92TH023 increased in AIDSVAX®B/E and ALVAC-HIV/AIDSVAX®B/E CVM (11-17 fold and SP (2 fold two weeks post first boost. IgG to Case A2 was only detected in AIDSVAX®B/E and ALVAC-HIV/AIDSVAX®B/E CVM. Mucosal IgG to gp120 A244gD (CVM, SP, RS, gp70V1V2 92TH023 (CVM, SP, and Case A2 (CVM correlated with plasma IgG levels (p<0.001. Although the magnitude of IgG responses declined after boosting, anti-gp120 A244gD IgG responses in CVM persisted for 12 months post final vaccination. Further studies in localization, persistence and magnitude of envelope specific antibodies (IgG and dimeric IgA in anogenital secretions will help determine their role in preventing mucosal HIV acquisition.

  4. GP's consult and health behaviour change project. Developing a programme to train GPs in communication skills to achieve lifestyle improvements.

    Science.gov (United States)

    Thijs, G A

    2007-08-01

    The European definition of General Practice states that GPs should use their core competence, amongst others, in their communication with patients. Their communication skills are particularly challenged in the field of lifestyle improvements. Most GPs feel they lack efficacy in achieving lifestyle changes. In November 2002 the Prevention Department of the Scientific Society of Flemish GPs (now Domus Medica) decided to start a project "consulting & behaviour change". Under this project, every Flemish GP should by the year 2007, have (amongst others things) a basic knowledge of the principles of lifestyle improvements and should be able to give a short advice to high risk patients. A literature search was conducted to make an inventory of models that could be used to train GPs. Experts at specific methods and topics were consulted to get acquainted with their specific approaches. Experts in the field of CME were gathered to discuss barriers and solutions to these barriers. During steering group meetings, several possible solutions were discussed. The Trans Theoretical Model (TTM-as theoretical framework) and brief motivational interviews (MI-as communication skill) were evaluated as offering the best opportunities for adapting the work situation of the GP. We promoted this approach to the GPs as an ABC concept (Anamnesis/Ask; Be the guide/Decision tree ("Beslissingsboom" in Dutch); Continuity) applied on different topics (smoke stop, alcohol, healthy food, physical activity). In our guidelines we pay more attention to brief motivational interviews for health behaviour changes. Recently we started developing an e-learning website as part of a larger learning project, this in cooperaion with different Flemish partners and disciplines. The Trans Theoretical Model and the brief motivational interviewing approach seem to be accepted by health care, educational and scientific organisations. The process of integrating this approach in the GP's daily practice has to be

  5. High intensity interval and moderate continuous cycle training in a physical education programme improves health-related fitness in young females.

    Science.gov (United States)

    Mazurek, K; Zmijewski, P; Krawczyk, K; Czajkowska, A; Kęska, A; Kapuściński, P; Mazurek, T

    2016-06-01

    The aim of the study was to investigate the effects of eight weeks of regular physical education classes supplemented with high intensity interval cycle exercise (HIIE) or continuous cycle exercises of moderate intensity (CME). Forty-eight collegiate females exercising in two regular physical education classes per week were randomly assigned to two programmes (HIIE; n = 24 or CME; n = 24) of additional (one session of 63 minutes per week) physical activity for 8 weeks. Participants performed HIIE comprising 2 series of 6x10 s sprinting with maximal pedalling cadence and active recovery pedalling with intensity 65%-75% HRmax or performed CME corresponding to 65%-75% HRmax. Before and after the 8-week programmes, anthropometric data and aero- and anaerobic capacity were measured. Two-way ANOVA revealed a significant time main effect for VO2max (p body mass not changing significantly (p = 0.59; +0.4% in HIIE and -0.1% in CME). A significant main time effect was found for relative fat mass (FM) and fat-free mass (FFM) (p body composition than physical education classes supplemented with HIIE sessions. In contrast to earlier, smaller trials, similar improvements in aerobic capacity were observed following physical activity with additional HIIE or CME sessions.

  6. Health programmes for school employees: improving quality of life, health and productivity.

    Science.gov (United States)

    Kolbe, Lloyd J; Tirozzi, Gerald N; Marx, Eva; Bobbitt-Cooke, Mary; Riedel, Sara; Jones, Jack; Schmoyer, Michael

    2005-01-01

    School health programmes in the 21st century could include eight components: 1) health services; 2) health education; 3) healthy physical and psychosocial environments; 4) psychological, counselling, and social services; 5) physical education and other physical activities; 6) healthy food services; and 7) integrated efforts of schools, families, and communities to improve the health of school students and employees. The eighth component of modern school health programmes, health programmes for school employees, is the focus of this article. Health programmes for school employees could be designed to increase the recruitment, retention, and productivity of school employees by partially focusing each of the preceding seven components of the school health programme on improving the health and quality of life of school employees as well as students. Thus, efforts to improve the quality of life, health, and productivity of school employees may be distinct from, but integrated with, efforts to improve the quality of life, health, and education of students. School employee health programmes can improve employee: 1) recruitment; 2) morale; 3) retention; and 4) productivity. They can reduce employee: 5) risk behaviours (e.g., physical inactivity); 6) risk factors (e.g., stress, obesity, high blood pressure); (7) illnesses; 8) work-related injuries; 9) absentee days; 10) worker compensation and disability claims; and 11) health care and health insurance costs. Further, if we hope to improve our schools' performance and raise student achievement levels, developing effective school employee health programmes can increase the likelihood that employees will: 12) serve as healthy role models for students; 13) implement effective school health programmes for students; and 14) present a positive image of the school to the community. If we are to improve the quality of life, health, and productivity of school employees in the 21st century: school administrators, employees, and

  7. Membrane insertion and assembly of epitope-tagged gp9 at the tip of the M13 phage

    Directory of Open Access Journals (Sweden)

    Kuhn Andreas

    2011-09-01

    Full Text Available Abstract Background Filamentous M13 phage extrude from infected Escherichia coli with a tip structure composed of gp7 and gp9. This tip structure is extended by the assembly of the filament composed of the major coat protein gp8. Finally, gp3 and gp6 terminate the phage structure at the proximal end. Up to now, gp3 has been the primary tool for phage display technology. However, gp7, gp8 and gp9 could also be used for phage display and these phage particles should bind to two different or more surfaces when the modified coat proteins are combined. Therefore, we tested here if the amino-terminal end of gp9 can be modified and whether the modified portion is exposed and detectable on the M13 phage particles. Results The amino-terminal region of gp9 was modified by inserting short sequences that encode antigenic epitopes. We show here that the modified gp9 proteins correctly integrate into the membrane using the membrane insertase YidC exposing the modified epitope into the periplasm. The proteins are then efficiently assembled onto the phage particles. Also extensions up to 36 amino acid residues at the amino-terminal end of gp9 did not interfere with membrane integration and phage assembly. The exposure of the antigenic tags on the phage was visualised with immunogold labelling by electron microscopy and verified by dot blotting with antibodies to the tags. Conclusions Our results suggest that gp9 at the phage tip is suitable for the phage display technology. The modified gp9 can be supplied in trans from a plasmid and fully complements M13 phage with an amber mutation in gene 9. The modified phage tip is very well accessible to antibodies.

  8. Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41

    International Nuclear Information System (INIS)

    Anastassopoulou, Cleo G.; Ketas, Thomas J.; Depetris, Rafael S.; Thomas, Antonia M.; Klasse, Per Johan; Moore, John P.

    2011-01-01

    Here, we describe the genetic pathways taken by a human immunodeficiency virus type 1 (HIV-1) isolate, D101.12, to become resistant to the small molecule CCR5 inhibitor, vicriviroc (VCV), in vitro. Resistant D101.12 variants contained at least one substitution in the gp120 V3 region (H308P), plus one of two patterns of gp41 sequence changes involving the fusion peptide (FP) and a downstream residue: G514V+V535M or M518V+F519L+V535M. Studies of Env-chimeric and point-substituted viruses in peripheral blood mononuclear cells (PBMC) and TZM-bl cells showed that resistance can arise from the cooperative action of gp120 and gp41 changes, while retaining CCR5 usage. Modeling the VCV inhibition data from the two cell types suggests that D101.12 discriminates between high- and low-VCV affinity forms of CCR5 less than D1/85.16, a resistant virus with three FP substitutions.

  9. Programme Costing of a Physical Activity Programme in Primary Prevention: Should the Costs of Health Asset Assessment and Participatory Programme Development Count?

    Directory of Open Access Journals (Sweden)

    Silke B. Wolfenstetter

    2012-01-01

    Full Text Available This analysis aims to discuss the implications of the “health asset concept”, introduced by the WHO, and the “investment for health model” requiring a “participatory approach” of cooperative programme development applied on a physical activity programme for socially disadvantaged women and to demonstrate the related costing issues as well as the relevant decision context. The costs of programme implementation amounted to €48,700. Adding the costs for developing the programme design of €48,800 results in total costs of €97,500; adding on top of that the costs of asset assessment running to €35,600 would total €133,100. These four different cost figures match four different types of potentially relevant decisions contexts. Depending on the decision context the total costs, and hence the incremental cost-effectiveness ratio of a health promotion intervention, could differ considerably. Therefore, a detailed cost assessment and the identification of the decision context are of crucial importance.

  10. Safety and immunogenicity of rVSVΔG-ZEBOV-GP Ebola vaccine in adults and children in Lambaréné, Gabon: A phase I randomised trial

    NARCIS (Netherlands)

    Agnandji, Selidji T.; Fernandes, José F.; Bache, Emmanuel B.; Obiang Mba, Régis M.; Brosnahan, Jessica S.; Kabwende, Lumeka; Pitzinger, Paul; Staarink, Pieter; Massinga-Loembe, Marguerite; Krähling, Verena; Biedenkopf, Nadine; Fehling, Sarah Katharina; Strecker, Thomas; Clark, David J.; Staines, Henry M.; Hooper, Jay W.; Silvera, Peter; Moorthy, Vasee; Kieny, Marie-Paule; Adegnika, Akim A.; Grobusch, Martin P.; Becker, Stephan; Ramharter, Michael; Mordmüller, Benjamin; Lell, Bertrand; Krishna, Sanjeev; Kremsner, Peter G.

    2017-01-01

    The rVSVΔG-ZEBOV-GP vaccine prevented Ebola virus disease when used at 2 × 107 plaque-forming units (PFU) in a trial in Guinea. This study provides further safety and immunogenicity data. A randomised, open-label phase I trial in Lambaréné, Gabon, studied 5 single intramuscular vaccine doses of 3 ×

  11. An altered gp100 peptide ligand with decreased binding by TCR and CD8alpha dissects T cell cytotoxicity from production of cytokines and activation of NFAT

    Directory of Open Access Journals (Sweden)

    Niels eSchaft

    2013-09-01

    Full Text Available Altered peptide ligands (APLs provide useful tools to study T cell activation and potentially direct immune responses to improve treatment of cancer patients. To better understand and exploit APLs, we studied the relationship between APLs and T cell function in more detail. Here, we tested a broad panel of gp100(280-288 APLs with respect to T cell cytotoxicity, production of cytokines and activation of Nuclear Factor of Activated T cells (NFAT by human T cells gene-engineered with a gp100-HLA-A2-specific TCRalpha/beta. We demonstrated that gp100-specific cytotoxicity, production of cytokines, and activation of NFAT were not affected by APLs with single amino acid substitutions, except for an APL with an amino acid substitution at position 3 (APL A3, which did not elicit any T cell response. A gp100 peptide with a double amino acid mutation (APL S4S6 elicited T cell cytotoxicity and production of IFNgamma, and to a lesser extent TNFalpha, IL-4, and IL-5, but not production of IL-2 and IL-10, or activation of NFAT. Notably, TCR-mediated functions showed decreases in sensitivities for S4S6 versus gp100 wt peptide, which were minor for cytotoxicity but at least a 1000-fold more prominent for the production of cytokines. TCR-engineered T cells did not bind A3-HLA-A2, but did bind S4S6-HLA-A2 although to a lowered extent compared to wt peptide-HLA-A2. Moreover, S4S6-induced T cell function demonstrated an enhanced dependency on CD8alpha. Taken together, most gp100 APLs functioned as agonists, but A3 and S4S6 peptides acted as a null ligand and partial agonist, respectively. Our results further suggest that TCR-mediated cytotoxicity can be dissected from production of cytokines and activation of NFAT, and that the agonist potential of peptide mutants relates to the extent of binding by TCR and CD8alpha. These findings may facilitate the design of APLs to advance the study of T cell activation and their use for therapeutic applications.

  12. Association between patients' recommendation of their GP and their evaluation of the GP.

    Science.gov (United States)

    Vedsted, Peter; Heje, Hanne N

    2008-01-01

    Patient priorities and patient evaluations indicate that accessibility should receive more attention to increase quality in general practice. The definition of family medicine emphasizes the patient-centred approach, communication skills, continuity, and clinical skills. We aimed to explore the associations between the 23 items in the Europep questionnaire measuring patient evaluation of general practice and the patients' recommendation of their general practitioner (GP) to friends and to study the relationship of these items with the core competences of family medicine. Cross-sectional study where patients aged 18 years and over attending the practice were included. Patients completed the Danish version of the 23 item Europep questionnaire and an additional item about the degree to which they could recommend their GP to friends. Danish general practice (the DanPEP study). A total of 50 191 patients and 690 GPs were included in the analyses. For each item, associations were calculated between a positive answer and the degree to which the patient could recommend the GP. Analyses were made at patient and GP levels. We found 12 items that covered the 10 most strongly associated items from both analyses: four of six items from the "doctor-patient relationship", two of five items from "medical care", and all items from "information and support" and "organization of services". No items from "accessibility" were among the 12 items. Recommending the GP to others was most strongly associated with the "emphatic", "patient-oriented", "informative and coordinating", and "competent/skilled" GP and to a lesser degree with accessibility to general practice.

  13. Analysis of Select Herpes Simplex Virus 1 (HSV-1) Proteins for Restriction of Human Immunodeficiency Virus Type 1 (HIV-1): HSV-1 gM Protein Potently Restricts HIV-1 by Preventing Intracellular Transport and Processing of Env gp160.

    Science.gov (United States)

    Polpitiya Arachchige, Sachith; Henke, Wyatt; Pramanik, Ankita; Kalamvoki, Maria; Stephens, Edward B

    2018-01-15

    Virus-encoded proteins that impair or shut down specific host cell functions during replication can be used as probes to identify potential proteins/pathways used in the replication of viruses from other families. We screened nine proteins from herpes simplex virus 1 (HSV-1) for the ability to enhance or restrict human immunodeficiency virus type 1 (HIV-1) replication. We show that several HSV-1 proteins (glycoprotein M [gM], US3, and UL24) potently restricted the replication of HIV-1. Unlike UL24 and US3, which reduced viral protein synthesis, we observed that gM restriction of HIV-1 occurred through interference with the processing and transport of gp160, resulting in a significantly reduced level of mature gp120/gp41 released from cells. Finally, we show that an HSV-1 gM mutant lacking the majority of the C-terminal domain (HA-gM[Δ345-473]) restricted neither gp160 processing nor the release of infectious virus. These studies identify proteins from heterologous viruses that can restrict viruses through novel pathways. IMPORTANCE HIV-1 infection of humans results in AIDS, characterized by the loss of CD4 + T cells and increased susceptibility to opportunistic infections. Both HIV-1 and HSV-1 can infect astrocytes and microglia of the central nervous system (CNS). Thus, the identification of HSV-1 proteins that directly restrict HIV-1 or interfere with pathways required for HIV-1 replication could lead to novel antiretroviral strategies. The results of this study show that select viral proteins from HSV-1 can potently restrict HIV-1. Further, our results indicate that the gM protein of HSV-1 restricts HIV-1 through a novel pathway by interfering with the processing of gp160 and its incorporation into virus maturing from the cell. Copyright © 2018 American Society for Microbiology.

  14. The Nuclear Physics Programme at CERN (1/3)

    CERN Multimedia

    CERN. Geneva

    2013-01-01

    This lecture series will focus on the two major facilities at CERN for nuclear physics: ISOLDE and nToF. ISOLDE is one of the world's leading radioactive beam facilities which can produce intense beams of unstable nuclei. Some of these beams can also be re-acclerated to energies around the Coulomb barrier and undergo nuclear reactions in turn. ISOLDE can address a wide range of Physics from nuclear structure to nuclear astrophysics (the origin of the chemical elements) and fundamental physics. The second major facility is nToF which is a neutron time-of-flight facility. Intense neutron beams are used to study nuclear reactions important both for nuclear astrophysics and for present and future reactor cycles. An overview will be given of these two facilities including highlights of their Physics programmes and the perspectives for the future.

  15. Structure of HIV-1 gp120 with gp41-interactive region reveals layered envelope architecture and basis of conformational mobility.

    Science.gov (United States)

    Pancera, Marie; Majeed, Shahzad; Ban, Yih-En Andrew; Chen, Lei; Huang, Chih-chin; Kong, Leopold; Kwon, Young Do; Stuckey, Jonathan; Zhou, Tongqing; Robinson, James E; Schief, William R; Sodroski, Joseph; Wyatt, Richard; Kwong, Peter D

    2010-01-19

    The viral spike of HIV-1 is composed of three gp120 envelope glycoproteins attached noncovalently to three gp41 transmembrane molecules. Viral entry is initiated by binding to the CD4 receptor on the cell surface, which induces large conformational changes in gp120. These changes not only provide a model for receptor-triggered entry, but affect spike sensitivity to drug- and antibody-mediated neutralization. Although some of the details of the CD4-induced conformational change have been visualized by crystal structures and cryoelectron tomograms, the critical gp41-interactive region of gp120 was missing from previous atomic-level characterizations. Here we determine the crystal structure of an HIV-1 gp120 core with intact gp41-interactive region in its CD4-bound state, compare this structure to unliganded and antibody-bound forms to identify structurally invariant and plastic components, and use ligand-oriented cryoelectron tomograms to define component mobility in the viral spike context. Newly defined gp120 elements proximal to the gp41 interface complete a 7-stranded beta-sandwich, which appeared invariant in conformation. Loop excursions emanating from the sandwich form three topologically separate--and structurally plastic--layers, topped off by the highly glycosylated gp120 outer domain. Crystal structures, cryoelectron tomograms, and interlayer chemistry were consistent with a mechanism in which the layers act as a shape-changing spacer, facilitating movement between outer domain and gp41-associated beta-sandwich and providing for conformational diversity used in immune evasion. A "layered" gp120 architecture thus allows movement among alternative glycoprotein conformations required for virus entry and immune evasion, whereas a beta-sandwich clamp maintains gp120-gp41 interaction and regulates gp41 transitions.

  16. Microsoft Dynamics GP 2013 financial management

    CERN Document Server

    Grieve, Ian

    2013-01-01

    A standard tutorial-based approach covering Microsoft Dynamics GP 2013 and its six financial modules. The book is intended to allow users to improve their system use and workflow by introducing new modules to assist in financial management.This book is for you if you're a Dynamics GP partner, or Dynamics GP user, primarily focused on delivering application optimizations. This book assumes that you have a working knowledge of Microsoft Dynamics GP and have an understanding of the requirements of financial management.

  17. Serological responses in chimpanzees inoculated with human immunodeficiency virus glycoprotein (gp120) subunit vaccine

    International Nuclear Information System (INIS)

    Arthur, L.O.; Pyle, S.W.; Nara, P.L.

    1987-01-01

    The major envelope glycoprotein of a human immunodeficiency virus (HIV) has been purified and was utilized as a prototype vaccine in chimpanzees. The 120,000-dalton glycoprotein (gp120) was purified from membranes of human T-lymphotropic virus (HTLV)-IIIB-infected cells and the final preparation contained low levels to no detectable HTLV-IIIB core antigen (p24) and low levels of endotoxin. Chimpanzees inoculated with gp120 responded by developing antibodies that precipitated radiolabeled gp120 and neutralized in vitro infection of HTLV-IIIB. Antibodies to HTLV-IIIB p24 were not detected in the gp120-immunized chimpanzees. Peripheral blood leukocytes from the vaccinated animals were examined for T4 + and T8 + cells, and no decrease in the T4/T8 ratio was found, indicating that immunization with a ligand (gp120) that binds to T4 has not detectable adverse effect on the population of T4 + cells. The only current animal model that can be reproducibly infected with HIV is the chimpanzee. Immunization of chimpanzees with HIV proteins will provide an experimental system for testing the effectiveness of prototype vaccines for preventing HIV infection in vivo

  18. Safety and immunogenicity of the rVSV∆G-ZEBOV-GP Ebola virus vaccine candidate in healthy adults: a phase 1b randomised, multicentre, double-blind, placebo-controlled, dose-response study.

    Science.gov (United States)

    Heppner, D Gray; Kemp, Tracy L; Martin, Brian K; Ramsey, William J; Nichols, Richard; Dasen, Emily J; Link, Charles J; Das, Rituparna; Xu, Zhi Jin; Sheldon, Eric A; Nowak, Teresa A; Monath, Thomas P

    2017-08-01

    The 2014 Zaire Ebola virus outbreak highlighted the need for a safe, effective vaccine with a rapid onset of protection. We report the safety and immunogenicity of the recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSV∆G-ZEBOV-GP) across a 6 log 10 dose range in two sequential cohorts. In this phase 1b double-blind, placebo-controlled, dose-response study we enrolled and randomly assigned healthy adults (aged 18-61 years) at eight study sites in the USA to receive a single injection of vaccine or placebo, administered by intramuscular injection. In cohort 1, participants were assigned to receive 3 × 10 3 , 3 × 10 4 , 3 × 10 5 , or 3 × 10 6 PFU doses of rVSV∆G-ZEBOV-GP or placebo. In cohort 2, participants were assigned to receive 3 × 10 6 , 9 × 10 6 , 2 × 10 7 , or 1 × 10 8 PFU doses of rVSV∆G-ZEBOV-GP or placebo. Participants were centrally allocated by the study statistician to vaccine groups or placebo through computer-generated randomisation lists. The primary safety outcome was incidence of adverse events within 14 days in the modified intention-to-treat population (all randomly assigned participants who received vaccine or placebo), and the primary outcome for immunogenicity was IgG ELISA antibody titres at day 28 in the per-protocol population. Surveillance was enhanced for arthritis and dermatitis through to day 56. This study is registered with ClinicalTrials.gov, number NCT02314923. Between Dec 26, 2014, and June 8, 2015, 513 participants were enrolled and randomly assigned; one was not immunised because of unsuccessful phlebotomy. In cohort 1, 256 participants received vaccine (3 × 10 3 [n=64], 3 × 10 4 [n=64], 3 × 10 5 [n=64], or 3 × 10 6 PFU [n=64]) and 74 received placebo. In cohort 2, 162 participants received vaccine (3 × 10 6 [n=20], 9 × 10 6 [n=47], 2 × 10 7 [n=47], or 1 × 10 8 PFU [n=48]) and 20 received placebo. Most

  19. On πgp-continuous functions in topological spaces

    International Nuclear Information System (INIS)

    Park, Jin Han; Park, Jin Keun

    2004-01-01

    The concept of πgp-closed sets was introduced by Park [On πgp-closed sets in topological spaces, Indian J. Pure Appl. Math., in press]. The aim of this paper is to consider and characterize πgp-irresolute and πgp-continuous functions via the concept of πgp-closed sets and to relate these concepts to the classes of πGPO-compact spaces and πGP-connected spaces

  20. An evaluation of Lincolnshire Sports’ ‘Workplace Challenge’ physical activity programme

    OpenAIRE

    Carter, Alice; Bishop, Daniel; Middleton, Geoff; Evans, Adam

    2014-01-01

    This report presents an evaluation of the Workplace Challenge, a County Sport Partnership led physical activity programme which utilises a website designed to engage people from workplaces in physical activity. The Workplace Challenge operated within the geographical boundary of Lincolnshire and thus targeted workplaces within this region. The overarching aim of the Workplace Challenge was to enact culture change within organisations in terms of employees’ physical activity habits. Metho...

  1. Innate immunity glycoprotein gp-340 variants may modulate human susceptibility to dental caries

    Directory of Open Access Journals (Sweden)

    Johansson Ingegerd

    2007-06-01

    Full Text Available Abstract Background Bacterial adhesion is an important determinant of colonization and infection, including dental caries. The salivary scavenger receptor cysteine-rich glycoprotein gp-340, which mediates adhesion of Streptococcus mutans (implicated in caries, harbours three major size variants, designated gp-340 I to III, each specific to an individual saliva. Here we have examined the association of the gp-340 I to III polymorphisms with caries experience and adhesion of S. mutans. Methods A case-referent study was performed in 12-year-old Swedish children with high (n = 19 or low (n = 19 caries experiences. We measured the gp-340 I to III saliva phenotypes and correlated those with multiple outcome measures for caries experience and saliva adhesion of S. mutans using the partial least squares (PLS multivariate projection technique. In addition, we used traditional statistics and 2-year caries increment to verify the established PLS associations, and bacterial adhesion to purified gp-340 I to III proteins to support possible mechanisms. Results All except one subject were typed as gp-340 I to III (10, 23 and 4, respectively. The gp-340 I phenotype correlated positively with caries experience (VIP = 1.37 and saliva adhesion of S. mutans Ingbritt (VIP = 1.47. The gp-340 II and III phenotypes tended to behave in the opposite way. Moreover, the gp-340 I phenotype tended to show an increased 2-year caries increment compared to phenotypes II/III. Purified gp-340 I protein mediated markedly higher adhesion of S. mutans strains Ingbritt and NG8 and Lactococcus lactis expressing AgI/II adhesins (SpaP or PAc compared to gp-340 II and III proteins. In addition, the gp-340 I protein appeared over represented in subjects positive for Db, an allelic acidic PRP variant associated with caries, and subjects positive for both gp-340 I and Db tended to experience more caries than those negative for both proteins. Conclusion Gp-340 I behaves as a caries

  2. Improved cognitive performance in preadolescent Danish children after the school-based physical activity programme "FIFA 11 for Health" for Europe - A cluster-randomised controlled trial.

    Science.gov (United States)

    Lind, Rune Rasmussen; Geertsen, Svend Sparre; Ørntoft, Christina; Madsen, Mads; Larsen, Malte Nejst; Dvorak, Jiri; Ritz, Christian; Krustrup, Peter

    2018-02-01

    Recent studies have shown promising effects of physical activity on cognitive function, but there is a need to investigate this link in real-life settings such as schools. Hence, the objective of the present pilot study was to investigate whether the school-based physical activity programme "FIFA 11 for Health" for Europe could improve cognitive performance in preadolescent Danish children. The pilot study used an 11-week cluster-randomised intervention study design. School classes were randomly assigned to either a control group (CG) (n = 93 children, age = 11.8, s = 0.2 years), which performed the obligatory daily school-based physical activity (5 × 45 minutes per week); or an intervention group (IG) (n = 838 children, age = 11.9, s = 0.4 years), which substituted 2 × 45 minutes per week of the daily school physical activity with the "FIFA 11 for Health" for Europe programme. The programme combines small-sided football games, drills and health education. Cognitive performance was evaluated at baseline and follow-up. The IG improved their cognitive performance compared to the CG for psychomotor function (56, s x -  = 22 ms, p school-based physical activity programme "FIFA 11 for Health" for Europe can improve cognitive performance in preadolescent Danish schoolchildren. Future studies should attempt to disentangle the effects of "FIFA 11 for Health" for Europe on cognitive performance by investigating the characteristics of the programme's physical activity.

  3. The heavy-ion physics programme with the ATLAS detector

    International Nuclear Information System (INIS)

    Pozdnyakov, V.N.; Vertogradova, Yu.L.

    2008-01-01

    The CERN LHC collider will operate with lead ions at √s of 5.5 TeV/nucleon. The ATLAS detector, designed to study high-p T physics in pp mode of the LHC, has potential to study ultrarelativistic heavy-ion collisions in a full range of observables characterizing the extremely dense matter and the formation of a quark-gluon plasma. The ATLAS physics programme includes global event measurements (particle multiplicities, transverse momentum), suppression of heavy-quarkonia production, jet quenching and study of ultraperipheral collisions

  4. CpG methylation controls reactivation of HIV from latency

    Czech Academy of Sciences Publication Activity Database

    Blažková, Jana; Trejbalová, Kateřina; Gondois-Rey, F.; Halfon, P.; Philibert, P.; Guiguen, A.; Verdin, E.; Olive, D.; Van Lint, C.; Hejnar, Jiří; Hirsch, I.

    2009-01-01

    Roč. 5, č. 8 (2009), e1000554-e1000554 E-ISSN 1553-7374 R&D Projects: GA ČR GA204/05/0939; GA ČR GP204/08/P616 Institutional research plan: CEZ:AV0Z50520514 Keywords : HIV-1 * proviral latency * CpG methylation * histone modifications * HAART * epigenetics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.978, year: 2009

  5. Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Jinghe; Kang, Byong H.; Pancera, Marie; Lee, Jeong Hyun; Tong, Tommy; Feng, Yu; Imamichi, Hiromi; Georgiev, Ivelin S.; Chuang, Gwo-Yu; Druz, Aliaksandr; Doria-Rose, Nicole A.; Laub, Leo; Sliepen, Kwinten; van Gils, Marit J.; de la Peña, Alba Torrents; Derking, Ronald; Klasse, Per-Johan; Migueles, Stephen A.; Bailer, Robert T.; Alam, Munir; Pugach, Pavel; Haynes, Barton F.; Wyatt, Richard T.; Sanders, Rogier W.; Binley, James M.; Ward, Andrew B.; Mascola, John R.; Kwong, Peter D.; Connors, Mark [NIH

    2015-10-15

    The isolation of human monoclonal antibodies is providing important insights into the specificities that underlie broad neutralization of HIV-1 (reviewed in ref. 1). Here we report a broad and extremely potent HIV-specific monoclonal antibody, termed 35O22, which binds a novel HIV-1 envelope glycoprotein (Env) epitope. 35O22 neutralized 62% of 181 pseudoviruses with a half-maximum inhibitory concentration (IC50) <50 μg ml-1. The median IC50 of neutralized viruses was 0.033 μg ml-1, among the most potent thus far described. 35O22 did not bind monomeric forms of Env tested, but did bind the trimeric BG505 SOSIP.664. Mutagenesis and a reconstruction by negative-stain electron microscopy of the Fab in complex with trimer revealed that it bound to a conserved epitope, which stretched across gp120 and gp41. The specificity of 35O22 represents a novel site of vulnerability on HIV Env, which serum analysis indicates to be commonly elicited by natural infection. Binding to this new site of vulnerability may thus be an important complement to current monoclonal-antibody-based approaches to immunotherapies, prophylaxis and vaccine design.

  6. Qualitative evaluation of a physical activity health promotion programme for people with intellectual disabilities in a group home setting.

    Science.gov (United States)

    Dixon-Ibarra, A; Driver, S; Nery-Hurwit, M; VanVolkenburg, H

    2018-01-01

    There is a lack of health promotion programming designed to change the physical activity environment of the group home setting. The Menu-Choice programme assists staff in creating physical activity goals alongside residents with intellectual disabilities and provides strategies to incorporate activity into the group home schedule. The purpose of this study was to complete a process evaluation of Menu-Choice utilizing qualitative methods. Twelve participants, who completed a 10-week pilot intervention (n = 7 staff, mean age 42; n = 5 residents, mean age 52), participated in face-to-face interviews. Participants represented five group home sites involved in the intervention. Meta-themes included: (i) Programme training, (ii) Programme implementation, (iii) Programme physical activity, (iv) Programme barriers, (v) Programme facilitators and (vi) Programme feedback. Changes in programme training and simplified programme materials are needed to accommodate identified barriers for implementation. The importance of obtaining increased agency support and policy change is highlighted. © 2017 John Wiley & Sons Ltd.

  7. Anti-coagulation effect of Fc fragment against anti-β2-GP1 antibodies in mouse models with APS.

    Science.gov (United States)

    Xie, Weidong; Zhang, Yaou; Bu, Cunya; Sun, Shijing; Hu, Shaoliang; Cai, Guoping

    2011-01-01

    Anti-beta (2)-glycoprotein I (anti-β2-GP1) is one of the important pathogenesis factors responsible for thrombosis formation in patients with antiphospholipid syndrome (APS). Administration of intravenous immunoglobulin (IVIg) is a common method used to inhibit the abnormal antibody levels and decrease the mortality of APS in emergency situations. We hypothesize that the Fc fragment of IgG is the molecular structure responsible for these effects. The present study investigates the beneficial effects of both recombinant and natural human Fc fragments of heterogeneous IgG against human anti-β2-GP1 antibodies in mouse models with APS. Results showed that both recombinant and natural human Fc fragments moderately but significantly decreased the levels of serum anti-β2-GP1 antibodies and had anti-coagulation effects in human β2-GP1-immunized mice. Furthermore, both recombinant and natural human Fc fragments inhibited thrombosis formation and decreased mortality in mouse models infused intravenously with human anti-β2GP1 antibodies from patients with APS. Findings suggest that the Fc fragment might be one of the active structural units of heterogeneous IgG. Thus, recombinant human Fc fragment administration may be a useful treatment for individuals with APS. Copyright © 2010 Elsevier B.V. All rights reserved.

  8. Investigation of U3O8 immobilization in the GP-91 borosilicate glass by induction melter with a cold crucible (CCIM)

    International Nuclear Information System (INIS)

    Matyunin, Y.I.; Demin, A.V.; Smelova, T.V.; Yudintsev, S.V.; Lapina, M.I.

    1997-01-01

    One of the most promising and intensively developed methods for the solidification of high-level wastes is their vitrification with the use of a cold crucible induction melter (CCIM), which offers a number of advantages over ceramic melter. This work is concerned with comparison studies on the behavior of uranium in vitreous borosilicate materials synthesized by the traditional technique (melting in muffle furnaces) and CCIM method. The incorporation of uranium oxide U 3 O 8 into the GP-91 borosilicate glass with the use of CCIM technology is investigated. The limiting solubility of uranium in the GP-91 borosilicate glass is evaluated. The phase composition of precipitated dispersed particles based on uranium is determined. Some physicochemical properties of synthesized materials are explored. Investigations into the behavior of uranium in borosilicate glass prepared in the CCIM show a feasibility to synthesize the X-ray amorphous homogeneous borosilicate glasses incorporating as much as 25 - 28 wt% uranium, which is 4 - 5 times larger than that in glasses obtained by the traditional method. (author)

  9. [Physical activity programmes to reduce overweight and obesity in children and adolescents; a systematic review].

    Science.gov (United States)

    Aguilar Cordero, M J; Ortegón Piñero, A; Mur Vilar, N; Sánchez García, J C; García Verazaluce, J J; García García, I; Sánchez López, A M

    2014-10-01

    Obesity treatment has been the subject of much controversy; various authors have recommended the application of a comprehensive treatment programme, and in the light of this previous research, we consider the question of what is the most effective programme of physical activity to reduce overweight and obesity in children and adolescents. To analyse major studies on the effectiveness of physical activity in reducing overweight and obesity in children and adolescents. Systematic review of the results of physical activity programmes, published in scientific articles, to reduce overweight and obesity. Using an automated database search in PubMed and Google Scholar, conducted from October 2013 to March 2014, we identified 85 valid items. In selecting the items, the criteria applied included the usefulness and relevance of the subject matter and the credibility or experience of the research study authors. The internal and external validity of each of the articles reviewed was taken into account. This review confirmed the effectiveness of physical activity in reducing overweight and obesity in children and adolescents. The most effective programmes were those combining aerobic and anaerobic exercises. It is generally accepted that at least 180 minutes per week should be dedicated to exercise, in the form of three 60-minute sessions of moderate intensity. Such programmes could be sufficient for persons with overweight or obesity. Researchers in this field agree that when a diet based on an appropriate distribution of meals is combined with regular physical activity, they reinforce each other, and thus optimum results are obtained. Weight reduction programmes that take account of family involvement are more effective than nutrition education itself or other routine interventions that fail to consider family involvement. The role of pa rents and of the persons around the child or adolescent is essential to reinforce positive behaviour toward lifestyle change. Copyright AULA

  10. Long-term influence of multiple heat extraction bore-holes; programme 3-D FRACTure and comparison with a g-function calculated with the SBM programme

    Energy Technology Data Exchange (ETDEWEB)

    Brenni, R.; Kohl, Th. [Eidgenoessische Technische Hochschule (ETH), Institut fuer Geophysik, Hoenggerberg (Switzerland); Pahud, D. [Scuola universitaria professionale della Svizzera italiana (SUPSI), Dipartimento delle costruzioni e del territorio (DCT), Laboratorio di energia, ecologia ed economia LEEE, Canobbio (Switzerland)

    2001-07-01

    For typical bore-hole heat exchangers (length of about 100 m), the long-term influence of neighbouring bore-hole heat exchangers normally appears after several years of operation, and approaches asymptotically a stationary state. Depending on the number of bore-holes involved, it may take from several tens up to several hundred of years before the magnitude of the influence stabilises. Under these conditions it is difficult to collect measurements of thermally interacting bore-hole heat exchangers. However, there is a need to be able to answer the question of the long-term influence of neighbouring borehole heat exchangers, as this situation is supposed to occur more often in the future, as the number of ground-coupled heat pump systems (GCHP system) steadily increases with time. This topic needs also to be studied if themes such as 'neighbour rights' or sustainability related to GCHP system are discussed. This report is focused on the first phase of the project, whose objective is to check the g-function calculation with a more detailed programme. Three bore-holes on an equilateral triangle is the borehole configuration chosen for the comparison between the two computer programmes FRACTure and SBM. SBM is used in the g-function mode, in order to test the concept of g-function against the more detailed programme FRACTure. The agreement between the results obtained with the two programmes indicates that for typical 100 m deep bore-holes the g-function analysis provides fast and sufficiently accurate results. (author)

  11. Pomeron physics

    International Nuclear Information System (INIS)

    Fujisaki, H.

    1986-01-01

    Our discussion is primarily confined to the asymptopia. From the phenomenological point of view, diffraction at presently available high energies can be reasonably well described in terms of the bare simplepole pomeron with the intercept at t=O slightly above unity. From the theoretical point of view, however, the self-consistent explanation of diffraction at the asymptopia inevitably necessitates the clothed physical pomeron with the unit intercept at t=O. The bare pomeron is built up from the normal reggeon through dual topological unitarization. Comparitively, the clothed physical pomeron is generated by multidiffractive unitarization of the bare pomeron. The clothed pomeron is often referred to as the geometrical pomeron (GP). The GP is universal in the sense that the asymptotic behaviour of the clothed pomeron is independent of the fine details of dynamics building up and unitarizing the bare pomeron. All unusual features of the physical pomeron are commonly inherent in universality of the GP which plays the role of the most typical guiding principle in pomeron physics. If the GP parmeterization is continued in t to beyond the lowest threshold, however, t-channel unitarity is seriously violated because of the hard branching nature. It is then of importance to investigate whether or not the GP universality is self-consistently guaranteed not only from the s-channel point of view but also from the t-channel point of view, and how the universal GP dynamically affects normal reggeons through the repeated pomeron exchange. Solutions to these key questions are summarized after geometrodynamical parts of a series of our works on pomeron physics is discussed

  12. The development of an evidence-based physical self-management rehabilitation programme for cancer survivors

    NARCIS (Netherlands)

    van Weert, Ellen; Hoekstra-Weebers, Josette E H M; May, Anne M; Korstjens, Irene; Ros, Wynand J G; van der Schans, Cees

    2008-01-01

    OBJECTIVE: This paper describes the development of a physical training programme for cancer patients. Four related but conceptually and empirically distinct physical problems are described: decreased aerobic capacity, decreased muscle strength, fatigue and impaired role physical functioning. The

  13. The development of an evidence-based physical self-management rehabilitation programme for cancer survivors

    NARCIS (Netherlands)

    van Weert, Ellen; Hoekstra-Weebers, Josette E. H. M.; May, Anne M.; Korstjens, Irene; Ros, Wynand J. G.; van der Schans, Cees P.

    Objective: This paper describes the development of a physical training programme for cancer patients. Four related but conceptually and empirically distinct physical problems are described: decreased aerobic capacity, decreased muscle strength, fatigue and impaired role physical functioning. The

  14. Patient satisfaction with out-of-hours GP cooperatives: a longitudinal study.

    Science.gov (United States)

    Smits, Marleen; Huibers, Linda; Oude Bos, Anita; Giesen, Paul

    2012-12-01

    For over a decade, out-of-hours primary care in the Netherlands has been provided by general practitioner (GP) cooperatives. In the past years, quality improvements have been made and patients have become acquainted with the service. This may have increased patient satisfaction. The objective of this study was to examine changes in patient satisfaction with GP cooperatives over time. Longitudinal observational study. A validated patient satisfaction questionnaire was distributed in 2003-2004 (T1) and 2007-2008 (T2). Items were rated on a scale from 0 to 10 (1 = very bad; 10 = excellent). Eight GP cooperatives in the Netherlands. Stratified sample of 9600 patients. Response was 55% at T1 (n = 2634) and 51% at T2 (n = 2462). Expectations met; satisfaction with triage nurses, GPs, and organization. For most patients the care received at the GP cooperative met their expectations (T1: 86.1% and T2: 88.4%). Patients were satisfied with the triage nurses (overall grade T1: 7.73 and T2: 7.99), GPs (T1: 8.04 and T2: 8.25), and organization (overall grade T1: 7.60 and T2: 7.78). Satisfaction with triage nurses showed the largest increase over time. The quality and effectiveness of advice or treatment were given relatively low grades. Of all organizational aspects, the lowest grades were given for waiting times and information about the cooperative. In general, patients were initially satisfied with GP cooperatives and satisfaction had even increased four years later. However, there is room for improvement in the content of the advice, waiting times, and information supply. More research is needed into satisfaction of specific patient groups.

  15. Optional part-time and longer GP training modules in GP practices associated with more trainees becoming GPs - a cohort study in Switzerland.

    Science.gov (United States)

    Studerus, Lara; Ahrens, Regina; Häuptle, Christian; Goeldlin, Adrian; Streit, Sven

    2018-01-05

    Switzerland, like many other countries, has a shortage of General Practitioners (GPs). Optional GP training modules in GP practices were offered during the at least 5-year GP training program to increase student and trainee interest in becoming a GP. The training modules had not yet been evaluated. We determined how many Swiss GP trainees became practicing GPs after they completed optional training modules, and if longer modules were associated with higher rates of GP specialization. In this population-based cohort study, we included GP trainees who chose an optional GP training module in GP practice, provided by the Foundation to Promote Training in General Practice (WHM) between 2006 and 2015. GP trainees were invited to complete an online survey to assess the primary outcome (becoming a practicing GP by 2016). Data on non-responders was collected via an internet search. We calculated univariate time-to-event curves to become a practicing GP, stratified by trainee's gender, length, part-time training, and number of years after graduation until training modules were completed. We used a multivariate model to adjust for characteristics of participants, training, and satisfaction with training modules. We assessed primary outcome for 351 (92.1%) of 381 former GP trainees who participated in a WHM program between 2006 and 2015. Of these 218 (57%) were practicing GPs by 2016. When focusing on the trainees who had completed training between 2006 and 2010, the rate of practicing GPs was even 73%. Longer (p = 0.018) and part-time training modules (p = 0.003) were associated with higher rates of being a practicing GP. Most (81%) practicing GPs thought their optional GP training module was (very) important in their choice of specialty. GP trainees who spent more time training in a GP practice, or who trained part-time were more likely to become practicing GPs. Most (80%) rated their training module as (very) important in their choice of career, highlighting that

  16. Value of combined detection of serum AFP and GP73 in early diagnosis of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    GAO Haifeng

    2014-07-01

    Full Text Available ObjectiveTo investigate the value of combined detection of serum alpha-fetoprotein (AFP and Golgi protein-73 (GP73 in the diagnosis of hepatocellular carcinoma (HCC and to provide a basis for early diagnosis and differential diagnosis of HCC. MethodsA total of 408 patients hospitalized in Baoji Central Hospital from June 2012 to May 2013, as well as healthy persons who had normal test results in physical examination, were included in the study, and their specimens were collected. These patients were classified into HCC group (n=142, chronic hepatitis group (n=156, and liver cirrhosis group (n=110. Serum levels of AFP and GP73 in the three groups were measured by electrochemiluminescence immunoassay and double-antibody sandwich enzyme-linked immunosorbent assay, respectively. Comparison of test results between groups was made by analysis of variance, and comparison of rates was made by chi-square test. The sensitivity and specificity of the two indicators for the diagnosis of HCC were calculated using MedCalc statistical software. ResultsThe HCC group had significantly higher serum AFP and GP73 levels than the liver cirrhosis group and chronic hepatitis group (P<0.05; the liver cirrhosis group had significantly higher serum AFP and GP73 levels than the chronic hepatitis group (P<0.05. The sensitivity and specificity of the two indicators for the diagnosis of HCC were 95.8% and 98.6%, respectively, showing significant differences compared with those of each indicator alone (P<0.05. ConclusionCombined detection of serum AFP and GP73 has high diagnostic value and clinical significance for HCC, and they can be used as indicators for early diagnosis and differential diagnosis of HCC.

  17. stableGP

    Data.gov (United States)

    National Aeronautics and Space Administration — The code in the stableGP package implements Gaussian process calculations using efficient and numerically stable algorithms. Description of the algorithms is in the...

  18. Soluble rhesus lymphocryptovirus gp350 protects against infection and reduces viral loads in animals that become infected with virus after challenge.

    Directory of Open Access Journals (Sweden)

    Junji Sashihara

    2011-10-01

    Full Text Available Epstein-Barr virus (EBV is a human lymphocryptovirus that is associated with several malignancies. Elevated EBV DNA in the blood is observed in transplant recipients prior to, and at the time of post-transplant lymphoproliferative disease; thus, a vaccine that either prevents EBV infection or lowers the viral load might reduce certain EBV malignancies. Two major approaches have been suggested for an EBV vaccine- immunization with either EBV glycoprotein 350 (gp350 or EBV latency proteins (e.g. EBV nuclear antigens [EBNAs]. No comparative trials, however, have been performed. Rhesus lymphocryptovirus (LCV encodes a homolog for each gene in EBV and infection of monkeys reproduces the clinical, immunologic, and virologic features of both acute and latent EBV infection. We vaccinated rhesus monkeys at 0, 4 and 12 weeks with (a soluble rhesus LCV gp350, (b virus-like replicon particles (VRPs expressing rhesus LCV gp350, (c VRPs expressing rhesus LCV gp350, EBNA-3A, and EBNA-3B, or (d PBS. Animals vaccinated with soluble gp350 produced higher levels of antibody to the glycoprotein than those vaccinated with VRPs expressing gp350. Animals vaccinated with VRPs expressing EBNA-3A and EBNA-3B developed LCV-specific CD4 and CD8 T cell immunity to these proteins, while VRPs expressing gp350 did not induce detectable T cell immunity to gp350. After challenge with rhesus LCV, animals vaccinated with soluble rhesus LCV gp350 had the best level of protection against infection based on seroconversion, viral DNA, and viral RNA in the blood after challenge. Surprisingly, animals vaccinated with gp350 that became infected had the lowest LCV DNA loads in the blood at 23 months after challenge. These studies indicate that gp350 is critical for both protection against infection with rhesus LCV and for reducing the viral load in animals that become infected after challenge. Our results suggest that additional trials with soluble EBV gp350 alone, or in combination with

  19. Carnauba wax nanoparticles enhance strong systemic and mucosal cellular and humoral immune responses to HIV-gp140 antigen.

    Science.gov (United States)

    Arias, Mauricio A; Loxley, Andrew; Eatmon, Christy; Van Roey, Griet; Fairhurst, David; Mitchnick, Mark; Dash, Philip; Cole, Tom; Wegmann, Frank; Sattentau, Quentin; Shattock, Robin

    2011-02-01

    Induction of humoral responses to HIV at mucosal compartments without inflammation is important for vaccine design. We developed charged wax nanoparticles that efficiently adsorb protein antigens and are internalized by DC in the absence of inflammation. HIV-gp140-adsorbed nanoparticles induced stronger in vitro T-cell proliferation responses than antigen alone. Such responses were greatly enhanced when antigen was co-adsorbed with TLR ligands. Immunogenicity studies in mice showed that intradermal vaccination with HIV-gp140 antigen-adsorbed nanoparticles induced high levels of specific IgG. Importantly, intranasal immunization with HIV-gp140-adsorbed nanoparticles greatly enhanced serum and vaginal IgG and IgA responses. Our results show that HIV-gp140-carrying wax nanoparticles can induce strong cellular/humoral immune responses without inflammation and may be of potential use as effective mucosal adjuvants for HIV vaccine candidates. Copyright © 2010 Elsevier Ltd. All rights reserved.

  20. Stated Uptake of Physical Activity Rewards Programmes Among Active and Insufficiently Active Full-Time Employees.

    Science.gov (United States)

    Ozdemir, Semra; Bilger, Marcel; Finkelstein, Eric A

    2017-10-01

    Employers are increasingly relying on rewards programmes in an effort to promote greater levels of activity among employees; however, if enrolment in these programmes is dominated by active employees, then they are unlikely to be a good use of resources. This study uses a stated-preference survey to better understand who participates in rewards-based physical activity programmes, and to quantify stated uptake by active and insufficiently active employees. The survey was fielded to a national sample of 950 full-time employees in Singapore between 2012 and 2013. Participants were asked to choose between hypothetical rewards programmes that varied along key dimensions and whether or not they would join their preferred programme if given the opportunity. A mixed logit model was used to analyse the data and estimate predicted uptake for specific programmes. We then simulated employer payments based on predictions for the percentage of each type of employee likely to meet the activity goal. Stated uptake ranged from 31 to 67% of employees, depending on programme features. For each programme, approximately two-thirds of those likely to enrol were insufficiently active. Results showed that insufficiently active employees, who represent the majority, are attracted to rewards-based physical activity programmes, and at approximately the same rate as active employees, even when enrolment fees are required. This suggests that a programme with generous rewards and a modest enrolment fee may have strong employee support and be within the range of what employers may be willing to spend.

  1. The legacy of the experimental hadron physics programme at COSY

    Energy Technology Data Exchange (ETDEWEB)

    Wilkin, C. [UCL, Physics and Astronomy Department, London (United Kingdom)

    2017-06-15

    The experimental hadronic physics programme at the COoler SYnchrotron of the Forschungszentrum Juelich terminated at the end of 2014. After describing the accelerator and the associated facilities, a review is presented of the major achievements in the field realized over the twenty years of intense research activity. (orig.)

  2. Effect of a multi-dimensional intervention programme on the motivation of physical education students.

    Science.gov (United States)

    Amado, Diana; Del Villar, Fernando; Leo, Francisco Miguel; Sánchez-Oliva, David; Sánchez-Miguel, Pedro Antonio; García-Calvo, Tomás

    2014-01-01

    This research study purports to verify the effect produced on the motivation of physical education students of a multi-dimensional programme in dance teaching sessions. This programme incorporates the application of teaching skills directed towards supporting the needs of autonomy, competence and relatedness. A quasi-experimental design was carried out with two natural groups of 4(th) year Secondary Education students--control and experimental -, delivering 12 dance teaching sessions. A prior training programme was carried out with the teacher in the experimental group to support these needs. An initial and final measurement was taken in both groups and the results revealed that the students from the experimental group showed an increase of the perception of autonomy and, in general, of the level of self-determination towards the curricular content of corporal expression focused on dance in physical education. To this end, we highlight the programme's usefulness in increasing the students' motivation towards this content, which is so complicated for teachers of this area to develop.

  3. Effect of a Multi-Dimensional Intervention Programme on the Motivation of Physical Education Students

    Science.gov (United States)

    Amado, Diana; Del Villar, Fernando; Leo, Francisco Miguel; Sánchez-Oliva, David; Sánchez-Miguel, Pedro Antonio; García-Calvo, Tomás

    2014-01-01

    This research study purports to verify the effect produced on the motivation of physical education students of a multi-dimensional programme in dance teaching sessions. This programme incorporates the application of teaching skills directed towards supporting the needs of autonomy, competence and relatedness. A quasi-experimental design was carried out with two natural groups of 4th year Secondary Education students - control and experimental -, delivering 12 dance teaching sessions. A prior training programme was carried out with the teacher in the experimental group to support these needs. An initial and final measurement was taken in both groups and the results revealed that the students from the experimental group showed an increase of the perception of autonomy and, in general, of the level of self-determination towards the curricular content of corporal expression focused on dance in physical education. To this end, we highlight the programme's usefulness in increasing the students' motivation towards this content, which is so complicated for teachers of this area to develop. PMID:24454831

  4. The impact of leadership development on GP mental health commissioning.

    Science.gov (United States)

    Dickerson, Emma; Fenge, Lee-Ann; Rosenorn-Lanng, Emily

    2017-07-03

    Purpose This paper aims to explore the learning needs of general practitioners (GPs) involved in commissioning mental health provision in England, and offer an evaluation of a leadership and commissioning skills development programme for Mental Health Commissioners. Design/methodology/approach Retrospective mixed method, including online mixed method survey, rating participants' knowledge, skills, abilities, semi-structured telephone interviews and third-party questionnaires were used. Results were analysed for significant differences using the Wilcoxon Signed Ranks test. Open-ended responses and interview transcripts were analysed thematically. Findings Indicative results showed that participants perceived significant impacts in ability across eight key question groups evaluated. Differences were found between the perceived and observed impact in relation to technical areas covered within the programme which were perceived as the highest scoring impacts by participants. Research limitations/implications The indicative results show a positive impact on practice has been both perceived and observed. Findings illustrate the value of this development programme on both the personal development of GP Mental Health Commissioners and commissioning practice. Although the findings of this evaluation increase understanding in relation to an important and topical area, larger scale, prospective evaluations are required. Impact evaluations could be embedded within future programmes to encourage higher participant and third-party engagement. Future evaluations would benefit from collection and analysis of attendance data. Further research could involve patient, service user and carer perspectives on mental health commissioning. Originality value Results of this evaluation could inform the development of future learning programmes for mental health commissioners as part of a national approach to improve mental health provision.

  5. Echinococcus canadensis (Cestoda: Taeniidae) is a valid species consisting of the mitochondrial genotypes G6, G7, G8 and G10

    Science.gov (United States)

    The species status of Echinococcus canadensis has long been controversial, mainly because it consists of the mitochondrial genotypes G6, G7, G8 and G10 with different host affinity: G6 (camel strain) and G7 (pig strain) with domestic cycles and G8 (cervid strain) and G10 (Fennoscandian cervid strain...

  6. Finnish Fusion Research Programme Yearbook 1993-1994

    International Nuclear Information System (INIS)

    Karttunen, S.; Paettikangas, T.

    1995-05-01

    Finnish Fusion Research Programme (FFUSION) is one of the national energy research programmes funded by the Ministry of Trade and Industry and from 1995 by TEKES. National organization for fusion research is necessary for efficient and successful participation in international fusion programmes. FFUSION programme serves well for this purpose and it made possible to establish relations and the dialogue with the European Fusion Programme. The process led to the Finnish Association Euratom-TEKES in early 1995. The first period of the FFUSION programme (1993-1994) was preparation for the association to the Community Programme. The strategy was to emphasize fusion technology parallel with the basic fusion and plasma physics and to activate the related Finnish industry to collaborate and participate in the FFUSION programme and later in the European Fusion Programme. The key element in the strategy is the focusing our fairly small R and D effort to a few topics, which increases possibilities to be competitive in Europe. The physics programme in FFUSION deals mainly with theoretical and computational studies of radio-frequency heating in tokamak plasmas. Technology programme started with prestudies in 1993 and it concentrates into two areas: fusion reactor materials and remote handling systems. (8 figs., 3 tabs.)

  7. IEA policies-G8 recommendations and an afterwards

    International Nuclear Information System (INIS)

    Onoda, Takao

    2009-01-01

    In response to threats posed to the future supply of energy and to the environment, the G8 leaders, in Gleneagles, UK in 2005, agreed to an initiative called the Gleneagles Plan of Action (GPOA) which addresses climate change, clean energy and sustainable development. In the GPOA, G8 leaders pledged to encourage the development of cleaner, more efficient and lower-emitting vehicles, and to promote their deployment by, among other means, asking the IEA to review existing standards and codes for vehicle efficiency and to identify best practices. In order to properly response to the above-mentioned requests from G8 leaders, the IEA has launched, among other activities, study on policies for 'transforming the way we use energy' focusing on end-use efficiency including the one in transport sector and made a comprehensive response to the GPOA at the 2008 G8 Summit Meeting in Japan with 25 recommendations on energy efficiency. Regarding these recommendations, the G8 leaders have proclaimed, in the G8 Hokkaido Toyako Summit Leaders Declaration, that they would maximize implementation of the IEA's 25 recommendations. This paper summarizes the IEA activities in transport sector regarding the GPOA and their findings and recommendations.

  8. Proceedings of the Workshop on relativistic heavy ion physics at present and future accelerators

    International Nuclear Information System (INIS)

    Csoergoe, T.; Hegyi, S.; Lukacs, B.; Zimanyi, J.

    1991-09-01

    This volume contains the Proceedings of the Budapest Workshop on relativistic heavy ion physics at present and future accelerators. The topics includes experimental heavy ion physics, particle phenomenology, Bose-Einstein correlations, relativistic transport theory, quark-gluon plasma rehadronization, astronuclear physics, leptonpair production and intermittency. All contributions were indexed separately for the INIS database. (G.P.)

  9. Suitability of FIFA's "The 11" Training Programme for Young Football Players - Impact on Physical Performance.

    Science.gov (United States)

    Kilding, Andrew E; Tunstall, Helen; Kuzmic, Dejan

    2008-01-01

    There is a paucity of evidence regarding the use of injury prevention programmes for preadolescents participating in sport. "The 11 "injury prevention programme was developed by FIFA's medical research centre (F-MARC) to help reduce the risk of injury in football players aged 14 years and over. The aim of this study was to determine the suitability and effectiveness of "The 11 "for younger football players. Twenty-four [12 experimental (EXP), 12 control (CON)] young football players (age 10.4 ± 1.4 yr) participated. The EXP group followed "The 11 "training programme 5 days per week, for 6 weeks, completing all but one of the 10 exercises. Prior to, and after the intervention, both EXP and CON groups performed a battery of football-specific physical tests. Changes in performance scores within each group were compared using independent t-tests (p ≤ 0.05). Feedback was also gathered on the young players' perceptions of "The 11". No injuries occurred during the study in either group. Compliance to the intervention was 72%. Measures of leg power (3 step jump and counter-movement jump) increased significantly (3.4 and 6.0% respectively, p football players, for both physical development and potential injury prevention purposes, as well as to promote fair play. To further engage young football players in such a programme, some modification to "The 11 "should be considered. Key pointsChildren who participate in recreational and competitive sports, especially football, are susceptible to injury.There is a need for the design and assessment of injury prevention programmes for children.The 11 "improves essential physical performance characteristics and has the potential to reduce the risk of injury.It may be prudent to implement a 'child-friendly' version of "The 11", to enhance long-term programme adherence and to ensure progressive physical development of players.

  10. G8 SUMMIT MEETING AT EVIAN

    CERN Multimedia

    2003-01-01

    The Swiss and French authorities have informed CERN that plans are in hand for the safety and traffic arrangements associated with the G8 Summit Meeting, which will be held in Evian between 1 and 3 June 2003. Detailed information will be communicated in the coming weeks. However, changes to traffic arrangements on certain sections of the road network in the Canton of Geneva (particularly the left bank) and the neighbouring parts of France (specially Haute-Savoie) from 22 May 2003 can already be predicted. All pertinent information and any recommendations by the authorities concerned will be brought to the attention of the personnel as soon as possible. In the mean time, those concerned can consult the various Web sites devoted to this event, especially: - http://www.g8.fr/evian/english/home.html (French site); - http://www.g8info.ch/accueil.htm (Swiss site). Relations with the Host States Service http://www.cern.ch/relations/ Tel. 72848

  11. Malta’s specialist training programme in family medicine : a pre-implementation evaluation

    OpenAIRE

    Sammut, Mario R.

    2009-01-01

    Introduction: As a result of Malta’s EU accession in 2004, family medicine was accepted as a speciality and the Malta College of Family Doctors prepared a Specialist Training Programme in Family Medicine. To facilitate its launch, potential GP trainers and trainees participated in its preimplementation evaluation. Method: Participants’ views were gathered quantitatively through a questionnaire using scales to rate closed statements regarding the programme and its sections. Qualitative openend...

  12. Changes in disability, physical/mental health states and quality of life during an 8-week multimodal physiotherapy programme in patients with chronic non-specific neck pain: a prospective cohort study.

    Directory of Open Access Journals (Sweden)

    Antonio Ignacio Cuesta-Vargas

    Full Text Available The aim of this study was to analyse the effect of an 8-week multimodal physiotherapy programme (MPP, integrating physical land-based therapeutic exercise (TE, adapted swimming and health education, as a treatment for patients with chronic non-specific neck pain (CNSNP, on disability, general health/mental states and quality of life.175 CNSNP patients from a community-based centre were recruited to participate in this prospective study.60-minute session (30 minutes of land-based exercise dedicated to improving mobility, motor control, resistance and strengthening of the neck muscles, and 30 minutes of adapted swimming with aerobic exercise keeping a neutral neck position using a snorkel. Health education was provided using a decalogue on CNSNP and constant repetition of brief advice by the physiotherapist during the supervision of the exercises in each session.primary: disability (Neck Disability Index; secondary: physical and mental health states and quality of life of patients (SF-12 and EuroQoL-5D respectively. Differences between baseline data and that at the 8-week follow-up were calculated for all outcome variables.Disability showed a significant improvement of 24.6% from a mean (SD of 28.2 (13.08 at baseline to 16.88 (11.62 at the end of the 8-week intervention. All secondary outcome variables were observed to show significant, clinically relevant improvements with increase ranges between 13.0% and 16.3% from a mean of 0.70 (0.2 at baseline to 0.83 (0.2, for EuroQoL-5D, and from a mean of 40.6 (12.7 at baseline to 56.9 (9.5, for mental health state, at the end of the 8-week intervention.After 8 weeks of a MPP that integrated land-based physical TE, health education and adapted swimming, clinically-relevant and statistically-significant improvements were observed for disability, physical and mental health states and quality of life in patients who suffer CNSNP. The clinical efficacy requires verification using a randomised controlled study

  13. G8 Regional Security Governance through Sanctions and Force

    Directory of Open Access Journals (Sweden)

    John Kirton

    2014-11-01

    Full Text Available Why do the Group of Eight (G8 members approve its members’ use of material sanctions in some regional conflicts but military force in others?2 As an informal security institution composed of major democratic powers from North America, Europe and Asia, the G8 has often chosen sanctions, notably on Iran in 1980, Afghanistan in 1980, Sudan in 2004, North Korea in 2006, and Syria in 2011. It has increasingly chosen military force, notably in Iraq in 1990, Kosovo in 1999, the USSR over Afghanistan in 2001, Libya in 2011, and Mali in 2013. Yet the G8’s choice, initiation, commitment, compliance, implementation and effectiveness of both sanctions and force has varied. Force was chosen and used effectively only in the post cold war period, primarily where the target was close to southern Europe. A high relative-capability predominance of G8 members over the target country strongly produces the G8’s choice of force, but a high, direct, deadly threat from the target state to G8 countries does not. Geographic proximity and the connectivity coming from the former colonial relationship between G8 members and the target country only weakly cause the G8 to choose force. Support from the most relevant regional organization – the North Atlantic Treaty Organization – and support from the United Nations in the form of an authorizing UN Security Council or General Assembly resolution have a strong, positive effect on the G8’s choice of force. Accompanying accountability mechanisms from the G8 itself have a variable impact, as leaders’ iteration of the issue at subsequent summits does not increase compliance with G8 commitments on force-related cases, but their foreign ministers’ follow up does to a substantial degree.

  14. Autographa californica multiple nucleopolyhedrovirus GP64 protein: Analysis of domain I and V amino acid interactions and membrane fusion activity

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Qianlong [State Key Laboratory of Crop Stress Biology for Arid Areas, Key Laboratory of Northwest Loess Plateau Crop Pest Management of Ministry of Agriculture, College of Plant Protection, Northwest A& F University, Yangling, Shaanxi 712100 (China); Blissard, Gary W. [Boyce Thompson Institute, Cornell University, Ithaca, NY 14853, United State (United States); Liu, Tong-Xian [State Key Laboratory of Crop Stress Biology for Arid Areas, Key Laboratory of Northwest Loess Plateau Crop Pest Management of Ministry of Agriculture, College of Plant Protection, Northwest A& F University, Yangling, Shaanxi 712100 (China); Li, Zhaofei, E-mail: zhaofeili73@outlook.com [State Key Laboratory of Crop Stress Biology for Arid Areas, Key Laboratory of Northwest Loess Plateau Crop Pest Management of Ministry of Agriculture, College of Plant Protection, Northwest A& F University, Yangling, Shaanxi 712100 (China)

    2016-01-15

    The Autographa californica multiple nucleopolyhedrovirus GP64 is a class III viral fusion protein. Although the post-fusion structure of GP64 has been solved, its pre-fusion structure and the detailed mechanism of conformational change are unknown. In GP64, domain V is predicted to interact with two domain I segments that flank fusion loop 2. To evaluate the significance of the amino acids involved in these interactions, we examined 24 amino acid positions that represent interacting and conserved residues within domains I and V. In several cases, substitution of a single amino acid involved in a predicted interaction disrupted membrane fusion activity, but no single amino acid pair appears to be absolutely required. We identified 4 critical residues in domain V (G438, W439, T452, and T456) that are important for membrane fusion, and two residues (G438 and W439) that appear to be important for formation or stability of the pre-fusion conformation of GP64. - Highlights: • The baculovirus envelope glycoprotein GP64 is a class III viral fusion protein. • The detailed mechanism of conformational change of GP64 is unknown. • We analyzed 24 positions that might stabilize the post-fusion structure of GP64. • We identified 4 residues in domain V that were critical for membrane fusion. • Two residues are critical for formation of the pre-fusion conformation of GP64.

  15. Effects of a physical activity programme in the school setting on physical fitness in preschool children.

    Science.gov (United States)

    Latorre-Román, P A; Mora-López, D; García-Pinillos, F

    2018-05-01

    The purpose of this study was to examine the effects of a 10-week aerobic games programme on physical fitness. One hundred eleven children, aged 3 to 6 years, participated in this study; 60 children were male (age: 4.28 ± 0.61 years old), and 51 were female (age 4.59 ± 0.49 years old). Participants were randomly assigned to an experimental group (EG; n = 56) and a control group (CG; n = 55). A fitness test battery previously validated for preschoolers was used. The children in the EG performed 3 weekly training sessions of physical activity in a classroom during a 10-week period. Every EG session lasted about 30 min. There were no significant differences in any variable in the pretest between groups. In the posttest, the EG achieved better results in horizontal jump and sprint. In relation to posttest-pretest differences, the EG showed a greater increase in horizontal jump, sprint, and endurance. An aerobic games programme in the school setting improved physical fitness in preschool children. © 2018 John Wiley & Sons Ltd.

  16. G8 global partnership. 2004-2005-2006 activity report; Partenariat mondial du G8. Rapport d'activite 2004-2005-2006

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-07-01

    The Global Partnership Against the Spread of Weapons and Materials of Mass Destruction was launched by the heads of state and government of the G8 at the G8 summit in Kananaskis in June 2002. Fourteen other countries have since joined this G8 initiative. The aim of this partnership is to 'prevent terrorists, or those who harbor them, from acquiring or developing nuclear, chemical radiological and biological weapons, missiles, and related materials, equipment and technology'. Within the framework of the Partnership, the participants have agreed to support cooperation projects, starting with Russia, to promote non-proliferation, disarmament, the fight against terrorism and nuclear safety. The destruction of chemical weapons, the dismantling of decommissioned nuclear submarines, the disposal of fissile materials and the employment of former weapons scientists are among the priority concerns expressed. Ukraine has also been a beneficiary of this partnership since 2004. The participants in this initiative have agreed to contribute up to 20 billion dollars (up to 750 million euros from France) to support these projects over a period of ten years from 2002. A group of experts from the G8 on the Global Partnership (the GPWG = Global Partnership Working Group) meets regularly and gives an account of the progress made with this initiative in its annual report to the G8. These annual reports are published at the G8 summits. This document is the 2004 to 2006 activity report of the G8 global partnership.

  17. Do Children’s Health Resources Differ According to Preschool Physical Activity Programmes and Parental Behaviour? A Mixed Methods Study

    Directory of Open Access Journals (Sweden)

    Elena Sterdt

    2014-02-01

    Full Text Available Preschool can have positive effects on the development of a healthy lifestyle. The present study analysed to what extent different conditions, structures and behavioural models in preschool and family—children’s central social microsystems—can lead to differences in children’s health resources. Using a cross-sectional mixed methods approach, contrast analyses of “preschools with systematic physical activity programmes” versus “preschools without physical activity programmes” were conducted to assess the extent to which children’s physical activity, quality of life and social behaviour differ between preschools with systematic and preschools without physical activity programmes. Differences in children’s physical activity according to parental behaviour were likewise assessed. Data on child-related outcomes and parent-related factors were collected via parent questionnaires and child interviews. A qualitative focused ethnographic study was performed to obtain deeper insight into the quantitative survey data. Two hundred and twenty seven (227 children were interviewed at 21 preschools with systematic physical activity programmes, and 190 at 25 preschools without physical activity programmes. There was no significant difference in children’s physical activity levels between the two preschool types (p = 0.709. However, the qualitative data showed differences in the design and quality of programmes to promote children’s physical activity. Data triangulation revealed a strong influence of parental behaviour. The triangulation of methods provided comprehensive insight into the nature and extent of physical activity programmes in preschools and made it possible to capture the associations between systematic physical activity promotion and children’s health resources in a differential manner.

  18. Induction of regulatory T cells by high-dose gp96 suppresses murine liver immune hyperactivation.

    Directory of Open Access Journals (Sweden)

    Xinghui Li

    Full Text Available Immunization with high-dose heat shock protein gp96, an endoplasmic reticulum counterpart of the Hsp90 family, significantly enhances regulatory T cell (Treg frequency and suppressive function. Here, we examined the potential role and mechanism of gp96 in regulating immune-mediated hepatic injury in mice. High-dose gp96 immunization elicited rapid and long-lasting protection of mice against concanavalin A (Con A-and anti-CD137-induced liver injury, as evidenced by decreased alanine aminotransaminase (ALT levels, hepatic necrosis, serum pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-6, and number of IFN-γ (+ CD4(+ and IFN-γ (+ CD8(+ T cells in the spleen and liver. In contrast, CD4(+CD25(+Foxp3(+ Treg frequency and suppressive function were both increased, and the protective effect of gp96 could be generated by adoptive transfer of Treg cells from gp96-immunized mice. In vitro co-culture experiments demonstrated that gp96 stimulation enhanced Treg proliferation and suppressive function, and up-regulation of Foxp3, IL-10, and TGF-β1 induced by gp96 was dependent on TLR2- and TLR4-mediated NF-κB activation. Our work shows that activation of Tregs by high-dose gp96 immunization protects against Con A- and anti-CD137-induced T cell-hepatitis and provides therapeutic potential for the development of a gp96-based anti-immune hyperactivation vaccine against immune-mediated liver destruction.

  19. Comparative Glycoprofiling of HIV gp120 Immunogens by Capillary Electrophoresis and MALDI Mass Spectrometry

    Science.gov (United States)

    Guttman, Miklós; Váradi, Csaba; Lee, Kelly K.; Guttman, András

    2015-01-01

    The Human Immunodeficiency Virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. Vaccine trials with the gp120 subunit of Env are ongoing with the recent RV144 trial showing moderate efficacy. gp120 is densely covered with N-linked glycans that are thought to help evade the host's humoral immune response. To assess how the global glycosylation patterns vary between gp120 constructs, the glycan profiles of several gp120s were examined by capillary electrophoresis with laser induced fluorescence detection and MALDI-MS. The glycosylation profiles were found to be similar for chronic vs. transmitter/founder isolates and only varied moderately between gp120s from different clades. This study revealed that the addition of specific tags, such as the gD tag used in the RV144 trial, had significant effects on the overall glycosylation patterns. Such effects are likely to influence the immunogenicity of various Env immunogens and should be considered for future vaccine strategies, emphasizing the importance of the glycosylation analysis approach described in this paper. PMID:25809283

  20. Chemical and biological studies of the major DNA adduct of cis-diamminedichloroplatinum(II), cis-[Pt(NH3)2/d(GpG)/], built into a specific site in a viral genome

    International Nuclear Information System (INIS)

    Naser, L.J.; Pinto, A.L.; Lippard, S.J.; Essigmann, J.M.

    1988-01-01

    A duplex Escherichia coli bacteriophage M13 genome was constructed containing a single cis-[Pt(NH 3 ) 2 /d(GpG)/] intrastrand cross-link, the major DNA adduct of the anticancer drug cis-diamminedichloroplatinum(II). The duplex dodecamer d(AGAAGGCCTAGA) x d(TCTAGGCCTTCT) was ligated into the HincII site of M13mp18 to produce an insertion mutant containing a unique StuI restriction enzyme cleavage site. A genome with a 12-base gap in the minus strand was created by hybridizing HincII-linearized M13mp18 duplex DNA with the single-stranded circular DNA of the 12-base insertion mutant. Characterization by pH-dependent 1 H NMR spectroscopy established that platinum binds to the N7 positions of the adjacent guanosines. The platinated oligonucleotide was phosphorylated in the presence of [γ- 32 P]ATP with bacteriophage T4 polynucleotide kinase and incorporated into the 12-base gap of the heteroduplex, thus situating the adduct specifically within the StuI site in the minus strand of the genome. The site of incorporation of the dodecamer was mapped to the expected 36-base region delimited by the recognition sites of XbaI and HindIII. Gradient denaturing gel electrophoresis of a 289-base-pair fragment encompassing the site of adduction revealed that the presence of the cis-[Pt(NH 3 ) 2 /d)GpG)/] cross-link induces localized weakening of the DNA double helix. Comparative studies revealed no difference in survival between platinated and unmodified double-stranded genomes. In contrast, survival of the single-stranded platinated genome was only 10-12% that of the corresponding unmodified single-stranded genome, indicating that the solitary cis-[Pt(NH 3 ) 2 /d(GpG)/] cross-link is lethal to the single-stranded bacteriophage

  1. The Influence of 8 Weeks of Whey-Protein and Leucine Supplementation on Physical and Cognitive Performance

    Science.gov (United States)

    2010-01-01

    Influence of 8 Weeks of Whey Protein and Leucine Supplementation on Physical and Cognitive Performance 5a. GONTRAGT NUMBER FA8650-04-D-6472 5b. GRANT NUMBER...investigate the ability of whey -protein and leucine supplementation to enhance physical and cognitive performance and body composition. Thirty moderately fit...composition before and after supplementing their daily diet for 8 wk with either 19.7 g of whey protein and 6.2 g leucine (WPL) or a calorie-equivalent placebo

  2. Inhibition of EBV-mediated membrane fusion by anti-gHgL antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Sathiyamoorthy, Karthik; Jiang, Jiansen; Möhl, Britta S.; Chen, Jia; Zhou, Z. Hong; Longnecker, Richard; Jardetzky, Theodore S. (UCLA); (Stanford-MED); (NWU)

    2017-09-22

    Herpesvirus entry into cells requires the coordinated action of multiple virus envelope glycoproteins, including gH, gL, and gB. For EBV, the gp42 protein assembles into complexes with gHgL heterodimers and binds HLA class II to activate gB-mediated membrane fusion with B cells. EBV tropism is dictated by gp42 levels in the virion, as it inhibits entry into epithelial cells while promoting entry into B cells. The gHgL and gB proteins are targets of neutralizing antibodies and potential candidates for subunit vaccine development, but our understanding of their neutralizing epitopes and the mechanisms of inhibition remain relatively unexplored. Here we studied the structures and mechanisms of two anti-gHgL antibodies, CL40 and CL59, that block membrane fusion with both B cells and epithelial cells. We determined the structures of the CL40 and CL59 complexes with gHgL using X-ray crystallography and EM to identify their epitope locations. CL59 binds to the C-terminal domain IV of gH, while CL40 binds to a site occupied by the gp42 receptor binding domain. CL40 binding to gHgL/gp42 complexes is not blocked by gp42 and does not interfere with gp42 binding to HLA class II, indicating that its ability to block membrane fusion with B cells represents a defect in gB activation. These data indicate that anti-gHgL neutralizing antibodies can block gHgL-mediated activation of gB through different surface epitopes and mechanisms.

  3. Lecture at the Globe | "From the Higgs boson to the search for new physics: the prospects for the LHC programme at CERN"

    CERN Multimedia

    2013-01-01

    Christmas lecture (in French, with simultaneous interpreting into English): "From the Higgs boson to the search for new physics: the prospects for the LHC programme at CERN", by Philippe Bloch.   Globe of Science and Innovation Route de Meyrin, 1211 Genève Monday 16 December 2013 at 8:30 p.m. The discovery of the Higgs boson, which was the subject of this year's Nobel prize for physics, has brought us the missing piece of the Standard Model of particle physics. However, many observations (such as the predominance of matter over antimatter in the Universe, the existence of dark matter observed by cosmologists and even the fact that the Higgs boson has a relatively small mass) underline that our knowledge of the structure of matter and its interactions is incomplete.   A wide-ranging programme of research spanning several decades to come thus awaits us at the LHC. Philippe Bloch will begin his lecture by giving us the latest news on the Higg...

  4. Factors that Influence Students in Choosing Physics Programmes at University Level: the Case of Greece

    Science.gov (United States)

    Meli, Kalliopi; Lavidas, Konstantinos; Koliopoulos, Dimitrios

    2018-04-01

    Low enrolment in undergraduate level physics programmes has drawn the attention of the relevant disciplines, education policy-makers, and researchers worldwide. Many reports released during the previous decades attempt to identify the factors that attract young people to study science, but only few of them focus explicitly on physics. In Greece, in contrast to many other countries, physics departments are overflowing with young students. However, there are two categories of students: those for whom physics was the optimal choice of a programme ("choosers") and those for whom physics was an alternative choice that they had to settle for. We suggest that the latter category be called "nearly-choosers," in order to be differentiated from choosers as well as from "non-choosers," namely those candidates that did not apply to a physics programme at all. We are interested in the factors that attract high school students to study physics and the differences (if any) between choosers and nearly-choosers. A newly formed questionnaire was distributed within a Greek physics department (University of Patras), and the students' responses (n = 105) were analysed with exploratory factor analysis and specifically principal component analysis so as to extract broad factors. Three broad factors have arisen: school-based, career, and informal learning. The first two factors proved to be motivating for pursuing a degree in physics, while the third factor appeared to have a rather indifferent association. t tests and Pearson correlations indicated mild differentiations between choosers and nearly-choosers that pertain to school-based influences and informal learning.

  5. Positive messages enhance older adults' motivation and recognition memory for physical activity programmes.

    Science.gov (United States)

    Notthoff, Nanna; Klomp, Peter; Doerwald, Friederike; Scheibe, Susanne

    2016-09-01

    Although physical activity is an effective way to cope with ageing-related impairments, few older people are motivated to turn their sedentary lifestyle into an active one. Recent evidence suggests that walking can be more effectively promoted in older adults with positive messages about the benefits of walking than with negative messages about the risks of inactivity. This study examined motivation and memory as the supposed mechanisms underlying the greater effectiveness of positively framed compared to negatively framed messages for promoting activity. Older adults ( N  = 53, age 60-87 years) were introduced to six physical activity programmes that were randomly paired with either positively framed or negatively framed messages. Participants indicated how motivated they were to participate in each programme by providing ratings on attractiveness, suitability, capability and intention. They also completed surprise free recall and recognition tests. Respondents felt more motivated to participate in physical activity programmes paired with positively framed messages than in those with negatively framed ones. They also had better recognition memory for positively framed than negatively framed messages, and misremembered negatively framed messages to be positively framed. Findings support the notion that socioemotional selectivity theory-a theory of age-related changes in motivation-is a useful basis for health intervention design.

  6. Repeated Vaccination of Cows with HIV Env gp140 during Subsequent Pregnancies Elicits and Sustains an Enduring Strong Env-Binding and Neutralising Antibody Response.

    Directory of Open Access Journals (Sweden)

    Behnaz Heydarchi

    Full Text Available An important feature of a potential vaccine against HIV is the production of broadly neutralising antibodies (BrNAbs capable of potentially blocking infectivity of a diverse array of HIV strains. BrNAbs naturally arise in some HIV infected individuals after several years of infection and their serum IgG can neutralise various HIV strains across different subtypes. We previously showed that vaccination of cows with HIV gp140 AD8 trimers resulted in a high titre of serum IgG against HIV envelope (Env that had strong BrNAb activity. These polyclonal BrNAbs concentrated into the colostrum during the late stage of pregnancy and can be harvested in vast quantities immediately after calving. In this study, we investigated the effect of prolonged HIV gp140 vaccination on bovine colostrum IgG HIV Env-binding and BrNAb activity over subsequent pregnancies. Repeated immunisation led to a maintained high titre of HIV Env specific IgG in the colostrum batches, but this did not increase through repeated cycles. Colostrum IgG from all batches also strongly competed with sCD4 binding to gp140 Env trimer and with human-derived monoclonal VRC01 and b12 BrNAbs that bind the CD4 binding site (CD4bs. Furthermore, competition neutralisation assays using RSC3 Env gp120 protein core and a derivative CD4bs mutant, RSC3 Δ371I/P363N, showed that CD4bs neutralising antibodies contribute to the neutralising activity of all batches of purified bovine colostrum IgG. This result indicates that the high IgG titre/avidity of anti-CD4bs antibodies with BrNAb activity was achieved during the first year of vaccination and was sustained throughout the years of repeated vaccinations in the cow tested. Although IgG of subsequent colostrum batches may have a higher avidity towards the CD4bs, the overall breadth in neutralisation was not enhanced. This implies that the boosting vaccinations over 4 years elicited a polyclonal antibody response that maintained the proportion of both

  7. Evaluation of XD/A Plus and ST8G films for cephalometric radiography with Grenex G8 and BH-III screens.

    Science.gov (United States)

    Wakoh, M; Farman, A G; Scarfe, W C; Shibuya, H; Nishikawa, K; Kuroyanagi, K

    1997-02-01

    Sensitometric properties, clinical image quality, and patient dose requirements are important considerations when selecting film for cephalometrics. Two recently released films, XD/A Plus and ST 8G green sensitive films, were studied. The films were each combined with Grenex G8 (Fuji Medical) green-fluorescing matched and BH-III (Kasei Optonix) blue-fluorescing mismatched intensifying screens. The density response and resolution for each screen-film combination were evaluated by use of the characteristic curve and modulation transfer function. The kilovoltage settings providing clinically acceptable images were assessed individually by 12 observers. Clinically acceptable images for each combination were also compared, and the skin entrance doses in the temporomandibular joint region were determined. The average contrast at the most effective density range was found to be slightly higher for the BH-III group than for the G8 group. The modulation transfer function for the BH-III group was inferior to that for the G8 screens. There were no significant differences in diagnostically acceptable image quality among the four combinations; nevertheless the BH-III screen group required two to three times more exposure than the G8 screen group. XD/A Plus and ST8G films provide acceptable image detail for cephalometrics. To minimize the patient dose they should be used with green-emitting screens.

  8. A Combined Cognitive Stimulation and Physical Exercise Programme (MINDVital) in Early Dementia: Differential Effects on Single- and Dual-Task Gait Performance.

    Science.gov (United States)

    Tay, Laura; Lim, Wee Shiong; Chan, Mark; Ali, Noorhazlina; Chong, Mei Sian

    2016-01-01

    Gait disorders are common in early dementia, with particularly pronounced dual-task deficits, contributing to the increased fall risk and mobility decline associated with cognitive impairment. This study examines the effects of a combined cognitive stimulation and physical exercise programme (MINDVital) on gait performance under single- and dual-task conditions in older adults with mild dementia. Thirty-nine patients with early dementia participated in a multi-disciplinary rehabilitation programme comprising both physical exercise and cognitive stimulation. The programme was conducted in 8-week cycles with participants attending once weekly, and all participants completed 2 successive cycles. Cognitive, functional performance and behavioural symptoms were assessed at baseline and at the end of each 8-week cycle. Gait speed was examined under both single- (Timed Up and Go and 6-metre walk tests) and dual-task (animal category and serial counting) conditions. A random effects model was performed for the independent effect of MINDVital on the primary outcome variable of gait speed under dual-task conditions. The mean age of patients enroled in the rehabilitation programme was 79 ± 6.2 years; 25 (64.1%) had a diagnosis of Alzheimer's dementia, and 26 (66.7%) were receiving a cognitive enhancer therapy. There was a significant improvement in cognitive performance [random effects coefficient (standard error) = 0.90 (0.31), p = 0.003] and gait speed under both dual-task situations [animal category: random effects coefficient = 0.04 (0.02), p = 0.039; serial counting: random effects coefficient = 0.05 (0.02), p = 0.013], with reduced dual-task cost for gait speed [serial counting: random effects coefficient = -4.05 (2.35), p = 0.086] following successive MINDVital cycles. No significant improvement in single-task gait speed was observed. Improved cognitive performance over time was a significant determinant of changes in dual-task gait speed [random effects coefficients

  9. Design and implementation of a radiotherapy programme: Clinical, medical physics, radiation protection and safety aspects

    International Nuclear Information System (INIS)

    1998-09-01

    It is widely acknowledged that the clinical aspects (diagnosis, decision, indication for treatment, follow-up) as well as the procedures related to the physical and technical aspects of patient treatment must be subjected to careful control and planning in order to ensure safe, high quality radiotherapy. Whilst it has long been recognized that the physical aspects of quality assurance in radiotherapy are vital to achieve and effective and safe treatment, it has been increasingly acknowledged only recently that a systematic approach is absolutely necessary to all steps within clinical and technical aspects of a radiotherapy programme as well. The need to establish general guidelines at the IAEA, taking into account clinical medical physics, radiation protection and safety considerations, for designing and implementing radiotherapy programmes in Member States has been identified through the Member States' increased interest in the efficient and safe application of radiation in health care. Several consultants and advisory group meetings were convened to prepare a report providing a basis for establishing a programme in radiotherapy. The present TECDOC is addressed to all professionals and administrators involved in the development, implementation and management of a radiotherapy programme in order to establish a common and consistent framework where all steps and procedures in radiotherapy are taken into account

  10. Clinical and Molecular Characteristics of Human Rotavirus G8P[8] Outbreak Strain, Japan, 2014.

    Science.gov (United States)

    Kondo, Kenji; Tsugawa, Takeshi; Ono, Mayumi; Ohara, Toshio; Fujibayashi, Shinsuke; Tahara, Yasuo; Kubo, Noriaki; Nakata, Shuji; Higashidate, Yoshihito; Fujii, Yoshiki; Katayama, Kazuhiko; Yoto, Yuko; Tsutsumi, Hiroyuki

    2017-06-01

    During March-July 2014, rotavirus G8P[8] emerged as the predominant cause of rotavirus gastroenteritis among children in Hokkaido Prefecture, Japan. Clinical characteristics were similar for infections caused by G8 and non-G8 strains. Sequence and phylogenetic analyses suggest the strains were generated by multiple reassortment events between DS-1-like P[8] strains and bovine strains from Asia.

  11. Applying the Trigger Review Method after a brief educational intervention: potential for teaching and improving safety in GP specialty training?

    Science.gov (United States)

    McKay, John; de Wet, Carl; Kelly, Moya; Bowie, Paul

    2013-08-30

    The Trigger Review Method (TRM) is a structured approach to screening clinical records for undetected patient safety incidents (PSIs) and identifying learning and improvement opportunities. In Scotland, TRM participation can inform GP appraisal and has been included as a core component of the national primary care patient safety programme that was launched in March 2013. However, the clinical workforce needs up-skilled and the potential of TRM in GP training has yet to be tested. Current TRM training utilizes a workplace face-to-face session by a GP expert, which is not feasible. A less costly, more sustainable educational intervention is necessary to build capability at scale. We aimed to determine the feasibility and impact of TRM and a related training intervention in GP training. We recruited 25 west of Scotland GP trainees to attend a 2-hour TRM workshop. Trainees then applied TRM to 25 clinical records and returned findings within 4-weeks. A follow-up feedback workshop was held. 21/25 trainees (84%) completed the task. 520 records yielded 80 undetected PSIs (15.4%). 36/80 were judged potentially preventable (45%) with 35/80 classified as causing moderate to severe harm (44%). Trainees described a range of potential learning and improvement plans. Training was positively received and appeared to be successful given these findings. TRM was valued as a safety improvement tool by most participants. This small study provides further evidence of TRM utility and how to teach it pragmatically. TRM is of potential value in GP patient safety curriculum delivery and preparing trainees for future safety improvement expectations.

  12. [Effect of a physical activity programme in patients with fibromyalgia: a systematic review].

    Science.gov (United States)

    Cadenas-Sánchez, Cristina; Ruiz-Ruiz, Jonatan

    2014-12-23

    The aim of this review was to determine what type of physical activity programmes have been developed in patients with fibromyalgia and what are its effects and benefits on the degree of pain and quality of life. The search was performed in MEDLINE, Web of Science and SPORTDiscus databases. The word "fibromyalgia" was always used as a criterion for combined search (using "AND" connector) with physical activity, exercise, physical therapy and training (MeSH terms). Of the 2,531 initial results, 33 papers were selected for review. The studies reviewed focus primarily on dance activities, water activities, multidisciplinary, mind-body work, fitness and stretching. After applying the intervention program, the pain level was reduced between 10 and 44.2%, and the impact of the disease between 5.3 and 17.9%, improving the symptoms of these patients. In conclusion, a multidisciplinary programme (in which physical activity is included) may have positive effects on the quality of life of people with fibromyalgia. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  13. Corporate sponsorship of physical activity promotion programmes: part of the solution or part of the problem?

    OpenAIRE

    Jane, Ben; Gibson, Kass

    2017-01-01

    Background\\ud Parklives is a programme intended to raise levels of physical activity across the UK, funded by Coca-Cola GB and delivered in association with Local Authorities and other organizations. Such public-private partnerships have been advocated by many however critics suggest that the conflict between stakeholder motives is too great.\\ud Methods\\ud This study conducted a content analysis of twitter content related to the ParkLives physical activity programme. Images and text were anal...

  14. The mutation frequency of 8-oxo-7,8 dihydroguanine (8-oxoG) situated in a multiply damaged site: comparison of a single and two closely opposed 8-oxodG in Escherichia coli

    International Nuclear Information System (INIS)

    Malyarchuk, S.G.; Youngblood, R.C.; Landry, A.M.; Quillin, E.; Harrison, L.

    2003-01-01

    Full text: A multiply damaged site (MDS) is defined as >= two lesions within a distance of 10-15 base pairs (bp). MDS generated by ionizing radiation contains oxidative base damage, and in vitro studies have indicated that if the base damage is less than 3 bp apart, repair of one lesion is inhibited until repair of the lesion in the opposite strand is completed. Inhibition of repair could result in an increase in the mutation frequency of the base damage. We have designed an assay to determine whether a closely opposed lesion causes an increase in adenine insertion opposite an 8-oxodG in bacteria. The double-stranded oligonucleotides (with no damage, each single 8-oxodG or the MDS) were ligated into the firefly luciferase coding region of a reporter vector and transformed into wild type or MutY-deficient bacteria. The MDS contained an 8-oxodG in the transcribed strand (T) and a second 8-oxodG immediately 5' to this lesion in the non-transcribed strand (NT). During two rounds of replication, insertion of adenine opposite the 8-oxodG in the T or NT strand results in a translation termination codon at position 444 or 445, respectively. In wild-type bacteria, we detected a translation stop at a frequency of 0.15% (codon 444) and 0.09% (codon 445) with a single 8-oxodG in the T or NT strand, respectively. This was enhanced ∼3 fold when single lesions were replicated in MutY-deficient bacteria. Positioning an 8-oxodG in the T strand within the MDS enhanced the mutation frequency by ∼2 fold in wild-type bacteria and 8 fold in Mut Y-deficient bacteria, while the mutation frequency of the 8-oxodG in the NT strand increased by 6 fold in Mut Y-deficient bacteria. This enhancement of mutation frequency supports the in vitro MDS studies, which demonstrated the inability of base excision repair to completely repair closely opposed lesions

  15. Meeting the physics design challenges of modern LWRs being inducted into the Indian nuclear power programme

    International Nuclear Information System (INIS)

    Jagannathan, V.; Pal, Usha; Karthikeyan, R.; Raj, Devesh; Srivastava, Argala; Khan, Suhail Ahmad

    2007-01-01

    Indian nuclear power programme started with the two Boiling Water Reactors (BWR) of 210 MWe capacity at Tarapur. Two VVER-1000 MWe reactors which are Pressurized Water Reactors (PWR) of Russian design are being constructed at Kudankulam, Tamilnadu and are expected to be commissioned by end 2008. There may be also a possibility of inducting some western PWRs in future. These reactors belong to the category of light water reactors (LWR). The LWRs are compact and have complex physical characteristics distinctly different from those of the Pressurized Heavy Water Reactors (PHWR) which, currently form the mainstay of our indigenous nuclear power programme. The physics design and analysis capability for the modern LWRs (BWR, PWR and VVER) has been developed at Light Water Reactors Physics Section, BARC. This paper presents the current state of art in this key technology area to meet the physics design and operation challenges when LWRs would be inducted in a major way into the Indian nuclear power programme and commence operating in the coming decades. (author)

  16. Induction of a protein-targeted catalytic response in autoimmune prone mice: antibody-mediated cleavage of HIV-1 glycoprotein GP120.

    Science.gov (United States)

    Ponomarenko, Natalia A; Vorobiev, Ivan I; Alexandrova, Elena S; Reshetnyak, Andrew V; Telegin, Georgy B; Khaidukov, Sergey V; Avalle, Bérangère; Karavanov, Alexander; Morse, Herbert C; Thomas, Daniel; Friboulet, Alain; Gabibov, Alexander G

    2006-01-10

    We have induced a polyclonal IgG that degrades the HIV-1 surface antigen, glycoprotein gp120, by taking advantage of the susceptibility of SJL mice to a peptide-induced autoimmune disorder, experimental autoimmune encephalomyelitis (EAE). Specific pathogen-free SJL mice were immunized with structural fragments of gp120, fused in-frame with encephalitogenic peptide MBP(85-101). It has resulted in a pronounced disease-associated immune response against antigens. A dramatic increase of gp120 degradation level by purified polyclonal IgG from immunized versus nonimmunized mice has been demonstrated by a newly developed fluorescence-based assay. This activity was inhibited by anti-mouse immunoglobulin antibodies as well as by Ser- and His-reactive covalent inhibitors. A dominant proteolysis site in recombinant gp120 incubated with purified polyclonal IgG from immunized mice was shown by SDS-PAGE. The SELDI-based mass spectrometry revealed that these antibodies exhibited significant specificity toward the Pro484-Leu485 peptide bond. The sequence surrounding this site is present in nearly half of the HIV-I variants. This novel strategy can be generalized for creating a catalytic vaccine against viral pathogens.

  17. G8 Global Partnership: Germany's contribution to strengthening international security

    International Nuclear Information System (INIS)

    Pfaffernoschke, A.

    2013-01-01

    This series of slides presents the German contribution to the G8 Global partnership whose aim is to support specific cooperation projects to address non-proliferation, disarmament, counter-terrorism and nuclear safety issues. 4 priorities have been identified: -) destruction of chemical weapons, -) dismantlement of decommissioned nuclear submarines, -) disposition of fissile materials, and -) employment of former weapon scientists. Today there are 23 donor countries and 2 official recipient countries (Russian Federation and Ukraine). Since the beginning Germany's activities in the G8 Global partnership have focused on chemical weapon destruction (340 million euros), dismantlement of nuclear submarines (600 million euros) and physical protection of nuclear materials (170 million euros). In the Gorny project (1995-2005) German provided the incinerator for the thermal treatment of liquid and solid residues and the equipment for destruction by hydrolysis. Germany's contribution to the following projects: -) the Kambarka project (2003-2007) for the destruction of lewisite, -) the Pochep project (2007-2010) for the destruction of munition containing nerve agents, and -) the Sajda-Bay project for the construction of a long-term storage site for reactor sections of decommissioned submarines, are detailed

  18. CGP lil-gp 2.1;1.02 User's Manual

    Science.gov (United States)

    Janikow, Cezary Z.; DeWeese, Scott W.

    1997-01-01

    This document describes extensions provided to lil-gp facilitating dealing with constraints. This document deals specifically with lil-gp 1.02, and the resulting extension is referred to as CGP lil-gp 2.1; 1.02 (the first version is for the extension, the second for the utilized lil-gp version). Unless explicitly needed to avoid confusion, version numbers are omitted.

  19. Conformational alterations in the CD4 binding cavity of HIV-1 gp120 influencing gp120-CD4 interactions and fusogenicity of HIV-1 envelopes derived from brain and other tissues

    Directory of Open Access Journals (Sweden)

    Ramsland Paul A

    2011-06-01

    Full Text Available Abstract Background CD4-binding site (CD4bs alterations in gp120 contribute to HIV-1 envelope (Env mediated fusogenicity and the ability of gp120 to utilize low levels of cell-surface CD4. In a recent study, we constructed three-dimensional models of gp120 to illustrate CD4bs conformations associated with enhanced fusogenicity and enhanced CD4-usage of a modestly-sized panel of blood-derived HIV-1 Envs (n = 16. These conformations were characterized by a wider aperture of the CD4bs cavity, as constrained by the inner-most atoms at the gp120 V1V2 stem and the V5 loop. Here, we sought to provide further validation of the utility of these models for understanding mechanisms that influence Env function, by characterizing the structure-function relationships of a larger panel of Envs derived from brain and other tissues (n = 81. Findings Three-dimensional models of gp120 were generated by our recently validated homology modelling protocol. Analysis of predicted CD4bs structures showed correlations between the aperture width of the CD4bs cavity and ability of the Envs to mediate cell-cell fusion, scavenge low-levels of cell-surface CD4, bind directly to soluble CD4, and bind to the Env mAb IgG1b12 whose epitope overlaps the gp120 CD4bs. These structural alterations in the CD4bs cavity were associated with repositioning of the V5 loop. Conclusions Using a large, independent panel of Envs, we can confirm the utility of three-dimensional gp120 structural models for illustrating CD4bs alterations that can affect Env function. Furthermore, we now provide new evidence that these CD4bs alterations augment the ability of gp120 to interact with CD4 by increasing the exposure of the CD4bs.

  20. Ilves : mida põrgut teeb Venemaa G8-s?

    Index Scriptorium Estoniae

    2007-01-01

    President Toomas Hendrik Ilves viibis Prahas 4. ja 5. juunil 2007 toimunud konverentsil "Demokraatia ja julgeolek", kus ta seadis kahtluse alla selle, kas Euroopat rakettidega ähvardava Venemaa koht on ikka G8-s ja Euroopa Nõukogus. Ilmunud ka: Eesti Elu 8. juuni 2007, lk. 1,4, pealk.: Mida teeb Venemaa G8-s?, ingl. k. lk. 9, pealk.: Ilves: what is Russia doing in the G8? Vabariigi President töövisiidil Prahasse 4.-6.06.2007

  1. Comb-like amphiphilic polypeptide-based copolymer nanomicelles for co-delivery of doxorubicin and P-gp siRNA into MCF-7 cells

    Energy Technology Data Exchange (ETDEWEB)

    Suo, Aili, E-mail: ailisuo@mail.xjtu.edu.cn [Department of Oncology, The First Affiliated Hospital of Xi' an Jiaotong University, Xi' an 710061 (China); Qian, Junmin, E-mail: jmqian@mail.xjtu.edu.cn [State Key Laboratory for Mechanical Behavior of Materials, Xi' an Jiaotong University, Xi' an 710049 (China); Zhang, Yaping; Liu, Rongrong; Xu, Weijun [State Key Laboratory for Mechanical Behavior of Materials, Xi' an Jiaotong University, Xi' an 710049 (China); Wang, Hejing [Department of Oncology, The First Affiliated Hospital of Xi' an Jiaotong University, Xi' an 710061 (China)

    2016-05-01

    A comb-like amphiphilic copolymer methoxypolyethylene glycol-graft-poly(L-lysine)-block-poly(L-phenylalanine) (mPEG-g-PLL-b-Phe) was successfully synthesized. To synthesize mPEG-g-PLL-b-Phe, diblock copolymer PLL-b-Phe was first synthesized by successive ring-opening polymerization of α-amino acid N-carboxyanhydrides followed by the removal of benzyloxycarbonyl protecting groups, and then mPEG was grafted onto PLL-b-Phe by reductive amination via Schiff's base formation. The chemical structures of the copolymers were identified by {sup 1}H NMR. mPEG-g-PLL-b-Phe copolymer had a critical micelle concentration of 6.0 mg/L and could self-assemble in an aqueous solution into multicompartment nanomicelles with a mean diameter of approximately 78 nm. The nanomicelles could encapsulate doxorubicin (DOX) through hydrophobic and π–π stacking interactions between DOX molecules and Phe blocks and simultaneously complex P-gp siRNA with cationic PLL blocks via electrostatic interactions. The DOX/P-gp siRNA-loaded nanomicelles showed spherical morphology, possessed narrow particle size distribution and had a mean particle size of 120 nm. The DOX/P-gp siRNA-loaded nanomicelles exhibited pH-responsive release behaviors and displayed accelerated release under acidic conditions. The DOX/P-gp siRNA-loaded nanomicelles were efficiently internalized into MCF-7 cells, and DOX released could successfully reach nuclei. In vitro cytotoxicity assay demonstrated that the DOX/P-gp siRNA-loaded nanomicelles showed a much higher cytotoxicity in MCF-7 cells than DOX-loaded nanomicelles due to their synergistic killing effect and that the blank nanomicelles had good biocompatibility. Thus, the novel comb-like mPEG-g-PLL-b-Phe nanomicelles could be a promising vehicle for co-delivery of chemotherapeutic drug and genetic material. - Highlights: • Comb-like amphiphilic copolymer mPEG-g-PLL-b-Phe was successfully synthesized. • Polypeptide-based copolymer could self-assemble into

  2. Nurse- and peer-led self-management programme for patients with an implantable cardioverter defibrillator; a feasibility study

    Directory of Open Access Journals (Sweden)

    van Eijk Jacques

    2007-09-01

    Full Text Available Abstract Background The prevalence of cardiovascular disease is increasing. Improved treatment options increase survival after an acute myocardial infarction or sudden cardiac arrest, although patients often have difficulty adjusting and regaining control in daily life. In particular, patients who received an implantable cardioverter defibrillator (ICD experience physical and psychological problems. Interventions to enhance perceived control and acceptance of the device are therefore necessary. This paper describes a small-scale study to explore the feasibility and the possible benefits of a structured nurse- and peer-led self-management programme ('Chronic Disease Self-Management Program' – CDSMP among ICD patients. Methods Ten male ICD patients (mean age = 65.5 years participated in a group programme, consisting of six sessions, led by a team consisting of a nurse specialist and a patient with cardiovascular disease. Programme feasibility was evaluated among patients and leaders by measuring performance of the intervention according to protocol, attendance and adherence of the participating ICD patients, and patients' and leaders' opinions about the programme. In addition, before and directly after attending the intervention, programme benefits (e.g. perceived control, symptoms of anxiety and depression, and quality of life were assessed. Results The programme was conducted largely according to protocol. Eight patients attended at least four sessions, and adherence ranged from good to very good. On average, the patients reported to have benefited very much from the programme, which they gave an overall report mark of 8.4. The leaders considered the programme feasible as well. Furthermore, improvements were identified for general self-efficacy expectancies, symptoms of anxiety, physical functioning, social functioning, role limitations due to physical problems, and pain. Conclusion This study suggests that a self-management programme led by a

  3. G 126.1-0.8-14: A molecular shell related to Sh2-187

    Science.gov (United States)

    Cichowolski, S.; Pineault, S.; Gamen, R.; Ortega, M. E.; Arnal, E. M.; Suad, L. A.

    2014-10-01

    We present a multi-wavelength study of a region where a well defined molecular shell, named G 126.1-0.8-14, is observed. The distance of G 126.1-0.8-14 is about 1 kpc. Based on HI and CO data we analyze the atomic and molecular gas related to the structure and estimate its main physical properties. From the radio continuum and infrared data we analyze whether the emission associated with G 126.1-0.8-14 has a thermal origin. To disentangle the possible origin of the shell, and given the lack of catalogued O-type stars in the area, we observed with GEMINI the spectra of four OB stars located in projection inside the shell, to get their accurate spectral types and distances. The young HII region Sh2-187 is located onto the densest part of this molecular shell. A search for young stellar object candidates (cYSOs) was made using infrared point source catalogs. Several cYSOs are found spread out onto the shell. Based on all the available data, we discuss the possible origin of G 126.1-0.8-14 as well as its role in the formation of a new generation of stars.

  4. Blended learning in CME: the perception of GP trainers.

    Science.gov (United States)

    Te Pas, E; Meinema, J G; Visser, M R M; van Dijk, N

    2016-05-01

    Blended learning (the combination of electronic methods with traditional teaching methods) has the potential to combine the best of traditional education with the best of computer-mediated training. We chose to develop such an intervention for GP trainers who were undertaking a Continuing Medical Education (CME) course in evidence-based medicine (EBM). This study reports on our experience and investigated the factors influencing the perception on usefulness and logistics of blended learning for learners in CME. In total, 170 GP trainers participated in the intervention. We used questionnaires, observations during the four face-to-face meetings and evaluations in the e-course over one year. Additionally we organised focus groups to gain insight in some of the outcomes of the questionnaires and interpretations of the observations. The GP trainers found the design and the educational method (e-course in combination with meetings) attractive, instructive and complementary. Factors influencing their learning were (1) educational design, (2) educational method, (3) topic of the intervention, (4) time (planning), (5) time (intervention), (6) learning style, (7) technical issues, (8) preconditions and (9) level of difficulty. A close link between daily practice and the educational intervention was considered an important precondition for the success of the intervention in this group of learners. GP trainers were positive about blended learning: they found e-learning a useful way to gain knowledge and the meetings a pleasant way of transferring the knowledge into practice. Although some preconditions should be taken into consideration during its development and implementation, they would participate in similarly designed learning in the future.

  5. A soluble form of Epstein-Barr virus gH/gL inhibits EBV-induced membrane fusion and does not function in fusion

    Energy Technology Data Exchange (ETDEWEB)

    Rowe, Cynthia L. [Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611 (United States); Connolly, Sarah A. [Department of Health Sciences, DePaul University, Chicago, IL 60614 (United States); Chen, Jia [Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611 (United States); Jardetzky, Theodore S. [Department of Structural Biology, Stanford University School of Medicine, 371 Serra Mall, Stanford, CA 94305 (United States); Longnecker, Richard, E-mail: r-longnecker@northwestern.edu [Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611 (United States)

    2013-02-05

    We investigated whether soluble EBV gH/gL (sgH/gL) functions in fusion and made a series of truncations of gH/gL domains based on the gH/gL crystal structure. We found sgH/gL failed to mediate cell-cell fusion both when co-expressed with the other entry glycoproteins and when added exogenously to fusion assays. Interestingly, sgH/gL inhibited cell-cell fusion in a dose dependent manner when co-expressed. sgH/gL from HSV was unable to inhibit EBV fusion, suggesting the inhibition was specific to EBV gH/gL. sgH/gL stably binds gp42, but not gB nor gH/gL. The domain mutants, DI/gL, DI-II/gL and DI-II-III/gL were unable to bind gp42. Instead, DI-II/gL, DI-II-III/gL and sgH/gL but not DI/gL decreased the expression of gp42, resulting in decreased overall fusion. Overall, our results suggest that domain IV may be required for proper folding and the transmembrane domain and cytoplasmic tail of EBV gH/gL are required for the most efficient fusion.

  6. A comparison of the provision of the My Choice Weight Management Programme via general practitioner practices and community pharmacies in the United Kingdom.

    Science.gov (United States)

    Bush, J; Langley, C; Mills, S; Hindle, L

    2014-04-01

    This study aimed to assess the effectiveness of a novel, community-based weight management programme delivered through general practitioner (GP) practices and community pharmacies in one city in the United Kingdom. This study used a non-randomized, retrospective, observational comparison of clinical data collected by participating GP practices and community pharmacies. Subjects were 451 overweight or obese men and women resident in areas of high socioeconomic deprivation (82% from black and minority ethnic groups, 86% women, mean age: 41.1 years, mean body mass index [BMI]: 34.5 kg m(-2)). Weight, waist circumference and BMI at baseline, after 12 weeks and after 9 months were measured. Costs of delivery were also analysed. Sixty-four per cent of participants lost weight after the first 12 weeks of the My Choice Weight Management Programme. There was considerable dropout. Mean percentage weight loss (last observation carried forward) was 1.9% at 12 weeks and 1.9% at final follow-up (9 months). There was no significant difference in weight loss between participants attending GP practices and those attending pharmacies at both 12 weeks and at final follow-up. Costs per participant were higher via community pharmacy which was attributable to better attendance at sessions among community pharmacy participants than among GP participants. The My Choice Weight Management Programme produced modest reductions in weight at 12 weeks and 9 months. Such programmes may not be sufficient to tackle the obesity epidemic. © 2014 The Authors. Clinical Obesity © 2014 International Association for the Study of Obesity.

  7. G8 global partnership. 2004-2005-2006 activity report

    International Nuclear Information System (INIS)

    2007-01-01

    The Global Partnership Against the Spread of Weapons and Materials of Mass Destruction was launched by the heads of state and government of the G8 at the G8 summit in Kananaskis in June 2002. Fourteen other countries have since joined this G8 initiative. The aim of this partnership is to 'prevent terrorists, or those who harbor them, from acquiring or developing nuclear, chemical radiological and biological weapons, missiles, and related materials, equipment and technology'. Within the framework of the Partnership, the participants have agreed to support cooperation projects, starting with Russia, to promote non-proliferation, disarmament, the fight against terrorism and nuclear safety. The destruction of chemical weapons, the dismantling of decommissioned nuclear submarines, the disposal of fissile materials and the employment of former weapons scientists are among the priority concerns expressed. Ukraine has also been a beneficiary of this partnership since 2004. The participants in this initiative have agreed to contribute up to 20 billion dollars (up to 750 million euros from France) to support these projects over a period of ten years from 2002. A group of experts from the G8 on the Global Partnership (the GPWG = Global Partnership Working Group) meets regularly and gives an account of the progress made with this initiative in its annual report to the G8. These annual reports are published at the G8 summits. This document is the 2004 to 2006 activity report of the G8 global partnership

  8. G-theory: The generator of M-theory and supersymmetry

    Science.gov (United States)

    Sepehri, Alireza; Pincak, Richard

    2018-04-01

    In string theory with ten dimensions, all Dp-branes are constructed from D0-branes whose action has two-dimensional brackets of Lie 2-algebra. Also, in M-theory, with 11 dimensions, all Mp-branes are built from M0-branes whose action contains three-dimensional brackets of Lie 3-algebra. In these theories, the reason for difference between bosons and fermions is unclear and especially in M-theory there is not any stable object like stable M3-branes on which our universe would be formed on it and for this reason it cannot help us to explain cosmological events. For this reason, we construct G-theory with M dimensions whose branes are formed from G0-branes with N-dimensional brackets. In this theory, we assume that at the beginning there is nothing. Then, two energies, which differ in their signs only, emerge and produce 2M degrees of freedom. Each two degrees of freedom create a new dimension and then M dimensions emerge. M-N of these degrees of freedom are removed by symmetrically compacting half of M-N dimensions to produce Lie-N-algebra. In fact, each dimension produces a degree of freedom. Consequently, by compacting M-N dimensions from M dimensions, N dimensions and N degrees of freedom is emerged. These N degrees of freedoms produce Lie-N-algebra. During this compactification, some dimensions take extra i and are different from other dimensions, which are known as time coordinates. By this compactification, two types of branes, Gp and anti-Gp-branes, are produced and rank of tensor fields which live on them changes from zero to dimension of brane. The number of time coordinates, which are produced by negative energy in anti-Gp-branes, is more sensible to number of times in Gp-branes. These branes are compactified anti-symmetrically and then fermionic superpartners of bosonic fields emerge and supersymmetry is born. Some of gauge fields play the role of graviton and gravitino and produce the supergravity. The question may arise that what is the physical reason

  9. Development of the gas puff charge exchange recombination spectroscopy (GP-CXRS) technique for ion measurements in the plasma edge

    International Nuclear Information System (INIS)

    Churchill, R. M.; Theiler, C.; Lipschultz, B.; Dux, R.; Pütterich, T.; Viezzer, E.

    2013-01-01

    A novel charge-exchange recombination spectroscopy (CXRS) diagnostic method is presented, which uses a simple thermal gas puff for its donor neutral source, instead of the typical high-energy neutral beam. This diagnostic, named gas puff CXRS (GP-CXRS), is used to measure ion density, velocity, and temperature in the tokamak edge/pedestal region with excellent signal-background ratios, and has a number of advantages to conventional beam-based CXRS systems. Here we develop the physics basis for GP-CXRS, including the neutral transport, the charge-exchange process at low energies, and effects of energy-dependent rate coefficients on the measurements. The GP-CXRS hardware setup is described on two separate tokamaks, Alcator C-Mod and ASDEX Upgrade. Measured spectra and profiles are also presented. Profile comparisons of GP-CXRS and a beam based CXRS system show good agreement. Emphasis is given throughout to describing guiding principles for users interested in applying the GP-CXRS diagnostic technique

  10. Development of the gas puff charge exchange recombination spectroscopy (GP-CXRS) technique for ion measurements in the plasma edge

    Energy Technology Data Exchange (ETDEWEB)

    Churchill, R. M.; Theiler, C.; Lipschultz, B. [MIT Plasma Science and Fusion Center, Cambridge, Massachusetts 02139 (United States); Dux, R.; Pütterich, T.; Viezzer, E. [Max-Planck-Institut für Plasmaphysik, EURATOM Association, Boltzmannstrasse 2, D-85748 Garching (Germany); Collaboration: Alcator C-Mod Team; ASDEX Upgrade Team

    2013-09-15

    A novel charge-exchange recombination spectroscopy (CXRS) diagnostic method is presented, which uses a simple thermal gas puff for its donor neutral source, instead of the typical high-energy neutral beam. This diagnostic, named gas puff CXRS (GP-CXRS), is used to measure ion density, velocity, and temperature in the tokamak edge/pedestal region with excellent signal-background ratios, and has a number of advantages to conventional beam-based CXRS systems. Here we develop the physics basis for GP-CXRS, including the neutral transport, the charge-exchange process at low energies, and effects of energy-dependent rate coefficients on the measurements. The GP-CXRS hardware setup is described on two separate tokamaks, Alcator C-Mod and ASDEX Upgrade. Measured spectra and profiles are also presented. Profile comparisons of GP-CXRS and a beam based CXRS system show good agreement. Emphasis is given throughout to describing guiding principles for users interested in applying the GP-CXRS diagnostic technique.

  11. Spécialiste de programmes principal (h/f) | CRDI - Centre de ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... le Gestionnaire de programme (GP) si applicable, et le Directeur de domaine de ... jouer le rôle de premier plan, dans le contexte d'un portefeuille de projets de ... définition et à l'évaluation de tendances clés et de priorités émergentes dans ...

  12. Effects of a physical activity programme on body perception and composition in overweight adolescents

    Directory of Open Access Journals (Sweden)

    Onofre Ricardo Contreras-Jordán

    2017-03-01

    Full Text Available Background The purpose of this study was to examine the effectiveness of a six months' physical activity programme for overweight and obese adolescents, in order to improve the perception of their own body image and composition between two groups of adolescents, and to check possible gender differences. Aims The aim is to improve the body perception and composition in overweight adolescents with a physical activity programme. Methods It was a quasi-experimental design, with a control group and intervention group. Measures of pre-test and post-test were taken. A total of 38 adolescents that belong to the first cycle of Compulsory Secondary aged 12–15, with a body mass index (BMI higher than the 85th percentile according to the WHO (World Health Organization, participated in the intervention. The anthropometric variables, height, weight, BMI, body fat percentage, and the circumference of the waist, hip, arm and medial calf, were measured pre- and post-treatment. The body image perception was measured using the Gardner test. The experimental group participated in the physical activity programme for a six months period. The physical activity intervention consisted of three sessions of 90 minutes each week in a sports centre. The structure of the sessions consisted of a warm-up (5–10 minutes, a main activity (60–70 minutes, combineding strength and cardiovascular training and a cool-down (7–10 minutes. Results After physical activity intervention the results showed significant improvements in the experimental group compared to the control group in the circumference of the waist, the hip, the arm, the medial calf (p<0.01 and as well as the fat percentage, the percentage of muscle mass (p<0.05. The results showed how the body image distortion presented a significant and negative correlation with the circumference of the waist (p<0.001, of the hips (p<0.01, and of the arm (p<0.001, differences were observed between gender. Conclusion Our study

  13. Human immunodeficiency virus envelope protein Gp120 induces proliferation but not apoptosis in osteoblasts at physiologic concentrations.

    Directory of Open Access Journals (Sweden)

    Nathan W Cummins

    Full Text Available Patients with HIV infection have decreased numbers of osteoblasts, decreased bone mineral density and increased risk of fracture compared to uninfected patients; however, the molecular mechanisms behind these associations remain unclear. We questioned whether Gp120, a component of the envelope protein of HIV capable of inducing apoptosis in many cell types, is able to induce cell death in bone-forming osteoblasts. We show that treatment of immortalized osteoblast-like cells and primary human osteoblasts with exogenous Gp120 in vitro at physiologic concentrations does not result in apoptosis. Instead, in the osteoblast-like U2OS cell line, cells expressing CXCR4, a receptor for Gp120, had increased proliferation when treated with Gp120 compared to control (P<0.05, which was inhibited by pretreatment with a CXCR4 inhibitor and a G-protein inhibitor. This suggests that Gp120 is not an inducer of apoptosis in human osteoblasts and likely does not directly contribute to osteoporosis in infected patients by this mechanism.

  14. Synergy of BESIII and LHCb physics programmes

    CERN Document Server

    Malde, Sneha Sirirshkumar

    2016-01-01

    There is potential for BESIII open-charm measurements to have a significant impact on the LHCb physics programme. Despite the general purpose design of the LHCb detector there are certain inputs that can be better determined in other environments or in production mechanisms not accessible at the LHC. With the unprecedented amount of LHCb data that will become available over the one-to-two decades it is necessary to consider where additional inputs are essential, to avoid the situation where the uncertainty on a measurement is dominated by the lack of knowledge of an external input. This document considers the capabilities of the BESIII experiment to provide vital inputs into key LHCb measurements. A number of different potential measurements that could be pursued are discussed.

  15. With a Little Help from my Friends : the role of peer groups in a physics engineering programme

    OpenAIRE

    Salminen-Karlsson, Minna

    2017-01-01

    The paper reports on the importance of informal study groups for the academic achievement and social and emotional wellbeing of physics engineering students at one university in Sweden. It is based on interviews with 26 physics engineering students in different phases of their education and 9 staff members - teachers and study advisors. While the programme structure and pedagogy assumes individual study, many students in fact cope with the demanding programme by using peer learning and peer s...

  16. Clinicopathological correlations of podoplanin (gp38 expression in rheumatoid synovium and its potential contribution to fibroblast platelet crosstalk.

    Directory of Open Access Journals (Sweden)

    Manuel J Del Rey

    Full Text Available Synovial fibroblasts (SF undergo phenotypic changes in rheumatoid arthritis (RA that contribute to inflammatory joint destruction. This study was undertaken to evaluate the clinical and functional significance of ectopic podoplanin (gp38 expression by RA SF.Expression of gp38 and its CLEC2 receptor was analyzed by immunohistochemistry in synovial arthroscopic biopsies from RA patients and normal and osteoarthritic controls. Correlation between gp38 expression and RA clinicopathological variables was analyzed. In patients rebiopsied after anti-TNF-α therapy, changes in gp38 expression were determined. Platelet-SF coculture and gp38 silencing in SF were used to analyze the functional contribution of gp38 to SF migratory and invasive properties, and to SF platelet crosstalk.gp38 was abundantly but variably expressed in RA, and it was undetectable in normal synovial tissues. Among clinicopathologigal RA variables, significantly increased gp38 expression was only found in patients with lymphoid neogenesis (LN, and RF or ACPA autoantibodies. Cultured synovial but not dermal fibroblasts showed strong constitutive gp38 expression that was further induced by TNF-α. In RA patients, anti-TNF-α therapy significantly reduced synovial gp38 expression. In RA synovium, CLEC2 receptor expression was only observed in platelets. gp38 silencing in cultured SF did not modify their migratory and invasive properties but reduced the expression of IL-6 and IL-8 genes induced by SF-platelet interaction.In RA, synovial expression of gp38 is strongly associated to LN and it is reduced after anti-TNF-α therapy. Interaction between gp38 and CLEC2 platelet receptor is feasible in RA synovium in vivo and can specifically contribute to gene expression by SF.

  17. Immunodiagnosis of paracoccidioidomycosis due to Paracoccidioides brasiliensis using a latex test: detection of specific antibody anti-gp43 and specific antigen gp43.

    Directory of Open Access Journals (Sweden)

    Priscila Oliveira Dos Santos

    2015-02-01

    Full Text Available Paracoccidioidomycosis (PCM is a life-threatening systemic disease and is a neglected public health problem in many endemic regions of Latin America. Though several diagnostic methods are available, almost all of them present with some limitations.A latex immunoassay using sensitized latex particles (SLPs with gp43 antigen, the immunodominant antigen of Paracoccidioides brasiliensis, or the monoclonal antibody mAb17c (anti-gp43 was evaluated for antibody or antigen detection in sera, cerebrospinal fluid (CSF, and bronchoalveolar lavage (BAL from patients with PCM due to P. brasiliensis. The gp43-SLPs performed optimally to detect specific antibodies with high levels of sensitivity (98.46%, 95% CI 91.7-100.0, specificity (93.94%, 95% CI 87.3-97.7, and positive (91.4% and negative (98.9% predictive values. In addition, we propose the use of mAb17c-SLPs to detect circulating gp43, which would be particularly important in patients with immune deficiencies who fail to produce normal levels of immunoglobulins, achieving good levels of sensitivity (96.92%, 95% CI 89.3-99.6, specificity (88.89%, 95% CI 81.0-94.3, and positive (85.1% and negative (97.8% predictive values. Very good agreement between latex tests and double immune diffusion was observed for gp43-SLPs (k = 0.924 and mAb17c-SLPs (k = 0.850, which reinforces the usefulness of our tests for the rapid diagnosis of PCM in less than 10 minutes. Minor cross-reactivity occurred with sera from patients with other fungal infections. We successfully detected antigens and antibodies from CSF and BAL samples. In addition, the latex test was useful for monitoring PCM patients receiving therapy.The high diagnostic accuracy, low cost, reduced assay time, and simplicity of this new latex test offer the potential to be commercialized and makes it an attractive diagnostic assay for use not only in clinics and medical mycology laboratories, but mainly in remote locations with limited laboratory infrastructure

  18. Internalization and Axonal Transport of the HIV Glycoprotein gp120

    Science.gov (United States)

    Berth, Sarah; Caicedo, Hector Hugo; Sarma, Tulika; Morfini, Gerardo

    2015-01-01

    The HIV glycoprotein gp120, a neurotoxic HIV glycoprotein that is overproduced and shed by HIV-infected macrophages, is associated with neurological complications of HIV such as distal sensory polyneuropathy, but interactions of gp120 in the peripheral nervous system remain to be characterized. Here, we demonstrate internalization of extracellular gp120 in a manner partially independent of binding to its coreceptor CXCR4 by F11 neuroblastoma cells and cultured dorsal root ganglion neurons. Immunocytochemical and pharmacological experiments indicate that gp120 does not undergo trafficking through the endolysosomal pathway. Instead, gp120 is mainly internalized through lipid rafts in a cholesterol-dependent manner, with a minor fraction being internalized by fluid phase pinocytosis. Experiments using compartmentalized microfluidic chambers further indicate that, after internalization, endocytosed gp120 selectively undergoes retrograde but not anterograde axonal transport from axons to neuronal cell bodies. Collectively, these studies illuminate mechanisms of gp120 internalization and axonal transport in peripheral nervous system neurons, providing a novel framework for mechanisms for gp120 neurotoxicity. PMID:25636314

  19. CERN openlab Summer Student Programme

    CERN Multimedia

    2012-01-01

    CERN openlab is currently taking applications for its summer student programme. The closing date for applications is 30 March 2012.   The openlab Summer Student Programme is open for applications from bachelor, master and PhD students in computer science and physics. Successful applicants will spend 8 weeks at CERN, during the period June to September 2012, to work with some of the latest hardware and software technologies. The programme is more than just a summer at CERN: it can lead to follow-on projects at the home institute and may even inspire the students to become entrepreneurs in cutting-edge computing technologies. A series of lectures will be given by experts in various domains of CERN related high-throughput computing. Study tours to external companies and universities as well as to CERN facilities are also part of the programme. Please visit www.cern.ch/openlab-students for more information.

  20. Structural Basis for Species Selectivity in the HIV-1 gp120-CD4 Interaction: Restoring Affinity to gp120 in Murine CD4 Mimetic Peptides

    Directory of Open Access Journals (Sweden)

    Kristin Kassler

    2011-01-01

    Full Text Available The first step of HIV-1 infection involves interaction between the viral glycoprotein gp120 and the human cellular receptor CD4. Inhibition of the gp120-CD4 interaction represents an attractive strategy to block HIV-1 infection. In an attempt to explore the known lack of affinity of murine CD4 to gp120, we have investigated peptides presenting the putative gp120-binding site of murine CD4 (mCD4. Molecular modeling indicates that mCD4 protein cannot bind gp120 due to steric clashes, while the larger conformational flexibility of mCD4 peptides allows an interaction. This finding is confirmed by experimental binding assays, which also evidenced specificity of the peptide-gp120 interaction. Molecular dynamics simulations indicate that the mCD4-peptide stably interacts with gp120 via an intermolecular β-sheet, while an important salt-bridge formed by a C-terminal lysine is lost. Fixation of the C-terminus by introducing a disulfide bridge between the N- and C-termini of the peptide significantly enhanced the affinity to gp120.

  1. Facilitators and barriers for GP-patient communication in palliative care: a qualitative study among GPs, patients, and end-of-life consultants.

    Science.gov (United States)

    Slort, Willemjan; Blankenstein, Annette H; Deliens, Luc; van der Horst, Henriëtte E

    2011-04-01

    Effective communication is considered to be essential for the delivery of high-quality care. Communication in palliative care may be particularly difficult, and there is still no accepted set of communication skills for GPs in providing palliative care. To obtain detailed information on facilitators and barriers for GP-patient communication in palliative care, with the aim to develop training programmes that enable GPs to improve their palliative care communication skills. Qualitative study with focus groups, interviews, and questionnaires. GPs with patients receiving palliative care at home, and end-of-life consultants in the Netherlands. GP (n = 20) focus groups discussing facilitators and barriers, palliative care patient (n = 6) interviews regarding facilitators, and end-of-life consultant (n = 22) questionnaires concerning barriers. Facilitators reported by both GPs and patients were accessibility, taking time, commitment, and listening carefully. GPs emphasise respect, while patients want GPs to behave in a friendly way, and to take the initiative to discuss end-of-life issues. Barriers reported by both GPs and end-of-life consultants were: difficulty in dealing with former doctors' delay and strong demands from patients' relatives. GPs report difficulty in dealing with strong emotions and troublesome doctor-patient relationships, while consultants report insufficient clarification of patients' problems, promises that could not be kept, helplessness, too close involvement, and insufficient anticipation of various scenarios. The study findings suggest that the quality of GP-patient communication in palliative care in the Netherlands can be improved. It is recommended that specific communication training programmes for GPs should be developed and evaluated.

  2. Determinants of Dutch general practitioners’ nutrition and physical activity guidance practices

    NARCIS (Netherlands)

    Hiddink, G.J.; Woerkum, van C.M.J.; Dillen, van S.M.E.

    2013-01-01

    Objective General practitioners (GP) are uniquely placed to guide their patients on nutrition and physical activity. The aims of the present study were to assess: (i) the extent to which GP guide on nutrition and physical activity; (ii) the determinants that cause GP to give guidance on nutrition

  3. Gravitational Physics Research

    Science.gov (United States)

    Wu, S. T.

    2000-01-01

    Gravitational physics research at ISPAE is connected with NASA's Relativity Mission (Gravity Probe B (GP-B)) which will perform a test of Einstein's General Relativity Theory. GP-B will measure the geodetic and motional effect predicted by General Relativity Theory with extremely stable and sensitive gyroscopes in an earth orbiting satellite. Both effects cause a very small precession of the gyroscope spin axis. The goal of the GP-B experiment is the measurement of the gyroscope precession with very high precision. GP-B is being developed by a team at Stanford University and is scheduled for launch in the year 2001. The related UAH research is a collaboration with Stanford University and MSFC. This research is focussed primarily on the error analysis and data reduction methods of the experiment but includes other topics concerned with experiment systems and their performance affecting the science measurements. The hydrogen maser is the most accurate and stable clock available. It will be used in future gravitational physics missions to measure relativistic effects such as the second order Doppler effect. The HMC experiment, currently under development at the Smithsonian Astrophysical Observatory (SAO), will test the performance and capability of the hydrogen maser clock for gravitational physics measurements. UAH in collaboration with the SAO science team will study methods to evaluate the behavior and performance of the HMC. The GP-B data analysis developed by the Stanford group involves complicated mathematical operations. This situation led to the idea to investigate alternate and possibly simpler mathematical procedures to extract the GP-B measurements form the data stream. Comparison of different methods would increase the confidence in the selected scheme.

  4. Construction and Characterization of a Humanized Anti-Epstein-Barr Virus gp350 Antibody with Neutralizing Activity in Cell Culture

    Directory of Open Access Journals (Sweden)

    Jerome E. Tanner

    2018-04-01

    Full Text Available Acute Epstein-Barr virus (EBV infection in immunosuppressed transplant patients can give rise to a malignant B-cell proliferation known as post-transplant lymphoproliferative disease (PTLD. The EBV major virion surface glycoprotein (gp350 is a principal target of naturally occurring neutralizing antibodies and is viewed as the best target to prevent acute infection and PTLD in at-risk transplant recipients. We have constructed a humanized (hu version of the murine anti-gp350 neutralizing monoclonal antibody 72a1. The hu72a1 IgG1 antibody displayed no significant anti-mouse activity, recognized both gp350 and its splice variant gp220 as well as a gp350 peptide that was shown to constitute the principal EBV gp350 neutralizing epitope when tested in immunoassays. Hu72a1 antibody blocked in vitro EBV infection of B cells at a level which equaled that of a mouse-human chimeric 72a1 antibody construct. This work provides a further structural and immunological understanding of the 72a1 antibody interaction with EBV gp350, and constitutes a launch point for future anti-EBV therapeutic antibodies designed to block EBV infection and prevent PTLD while eliminating the deleterious antigenic murine features of the original 72a1 antibody.

  5. A glycoconjugate antigen based on the recognition motif of a broadly neutralizing human immunodeficiency virus antibody, 2G12, is immunogenic but elicits antibodies unable to bind to the self glycans of gp120

    DEFF Research Database (Denmark)

    Astronomo, Rena D; Lee, Hing-Ken; Scanlan, Christopher N

    2008-01-01

    The glycan shield of human immunodeficiency virus type 1 (HIV-1) gp120 contributes to viral evasion from humoral immune responses. However, the shield is recognized by the HIV-1 broadly neutralizing antibody (Ab), 2G12, at a relatively conserved cluster of oligomannose glycans. The discovery of 2G......12 raises the possibility that a carbohydrate immunogen may be developed that could elicit 2G12-like neutralizing Abs and contribute to an AIDS vaccine. We have previously dissected the fine specificity of 2G12 and reported that the synthetic tetramannoside (Man(4)) that corresponds to the D1 arm...

  6. Antibody to gp41 MPER alters functional properties of HIV-1 Env without complete neutralization.

    Directory of Open Access Journals (Sweden)

    Arthur S Kim

    2014-07-01

    Full Text Available Human antibody 10E8 targets the conserved membrane proximal external region (MPER of envelope glycoprotein (Env subunit gp41 and neutralizes HIV-1 with exceptional potency. Remarkably, HIV-1 containing mutations that reportedly knockout 10E8 binding to linear MPER peptides are partially neutralized by 10E8, producing a local plateau in the dose response curve. Here, we found that virus partially neutralized by 10E8 becomes significantly less neutralization sensitive to various MPER antibodies and to soluble CD4 while becoming significantly more sensitive to antibodies and fusion inhibitors against the heptad repeats of gp41. Thus, 10E8 modulates sensitivity of Env to ligands both pre- and post-receptor engagement without complete neutralization. Partial neutralization by 10E8 was influenced at least in part by perturbing Env glycosylation. With unliganded Env, 10E8 bound with lower apparent affinity and lower subunit occupancy to MPER mutant compared to wild type trimers. However, 10E8 decreased functional stability of wild type Env while it had an opposite, stabilizing effect on MPER mutant Envs. Clade C isolates with natural MPER polymorphisms also showed partial neutralization by 10E8 with altered sensitivity to various gp41-targeted ligands. Our findings suggest a novel mechanism of virus neutralization by demonstrating how antibody binding to the base of a trimeric spike cross talks with adjacent subunits to modulate Env structure and function. The ability of an antibody to stabilize, destabilize, partially neutralize as well as alter neutralization sensitivity of a virion spike pre- and post-receptor engagement may have implications for immunotherapy and vaccine design.

  7. Russkije idut, no eto skoreje G7, a ne G8 / Brian Love

    Index Scriptorium Estoniae

    Love, Brian

    2005-01-01

    Venemaa ületab takistuse maailma suurriigina tunnustamises 2006. a. jaanuaris, kui ta aastaks saab G8 eesistujaameti. Vaatamata toimunud muutustele on Venemaa endiselt külaline, kui kohtuvad G7 rahandusministrid ja keskpankade juhid

  8. 12 CFR 563g.8 - Use of the offering circular.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Use of the offering circular. 563g.8 Section 563g.8 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY SECURITIES OFFERINGS § 563g.8 Use of the offering circular. (a) An offering circular or amendment declared effective by the...

  9. Summer Student Programme

    CERN Multimedia

    2006-01-01

    Date Time Title Speaker 17/07/2006 09:15 - 11:00 Fundamental concepts in Particle Physics (1-2/6) G. ROSS 11:15 - 12:00 Astroparticle Physics (1/3) N. PALANQUE-DELABROUILLE 12:00 Discussion Session 18/07/2006 09:15 - 10:00 Fundamental concepts in Particle Physics (3/6) G. ROSS 10:15 - 12:00 Astroparticle Physics (2-3/3) N. PALANQUE-DELABROUILLE 12:00 Discussion Session 19/07/2006 09:15 - 10:00 Fundamental concepts in Particle Physics (4/6) G. ROSS 10:15 - 11:00 Neutrino Physics (1/4) J-J. GOMEZ-CADENAS 11:15 - 12:00 Seminar on LHC upgrade A. DE ROECK 12:00 Discussion Session 20/07/2006 09:15 - 10:00 Fundamental concepts in Particle Physics (5/6) G. ROSS 10:15 - 12:00 Neutrino Physics (2-3/4) J-J. GOMEZ-CADENAS 12:00 Discussion Session 21/07/2006 09:15 - 10:00 Fundamental concepts in Particle Physics (6/6) G. ROSS 10:15 - 11:00 The Standard Model (1/8) A. PICH 11:15 - 12:00 Neutrino Physics (4/4) J-J. GOMEZ-CADENAS 12:00 Discussion Session Date T...

  10. High intensity interval and moderate continuous cycle training in a physical education programme improves health-related fitness in young females

    Directory of Open Access Journals (Sweden)

    K Mazurek

    2016-04-01

    Full Text Available The aim of the study was to investigate the effects of eight weeks of regular physical education classes supplemented with high intensity interval cycle exercise (HIIE or continuous cycle exercises of moderate intensity (CME. Forty-eight collegiate females exercising in two regular physical education classes per week were randomly assigned to two programmes (HIIE; n=24 or CME; n=24 of additional (one session of 63 minutes per week physical activity for 8 weeks. Participants performed HIIE comprising 2 series of 6x10 s sprinting with maximal pedalling cadence and active recovery pedalling with intensity 65%–75% HRmax or performed CME corresponding to 65%-75% HRmax. Before and after the 8-week programmes, anthropometric data and aero- and anaerobic capacity were measured. Two-way ANOVA revealed a significant time main effect for VO2max (p<0.001, similar improvements being found in both groups (+12% in HIIE and +11% in CME, despite body mass not changing significantly (p=0.59; +0.4% in HIIE and -0.1% in CME. A significant main time effect was found for relative fat mass (FM and fat-free mass (FFM (p<0.001 and p<0.001, respectively. A group x time interaction effect was found for relative FM and FFM (p=0.018 and p=0.018; a greater reduction in FM and greater increase in FFM were noted in the CME than the HIIE group. Improvements in anaerobic power were observed in both groups (p<0.001, but it was greater in the HIIE group (interaction effect, p=0.022. Weight loss is not mandatory for exercise-induced effects on improving aerobic and anaerobic capacity in collegiate females. Eight weeks of regular physical education classes supplemented with CME sessions are more effective in improving body composition than physical education classes supplemented with HIIE sessions. In contrast to earlier, smaller trials, similar improvements in aerobic capacity were observed following physical activity with additional HIIE or CME sessions.

  11. In vitro and in vivo evaluation of the effects of piperine on P-gp function and expression

    International Nuclear Information System (INIS)

    Han Yi; Chin Tan, Theresa May; Lim, Lee-Yong

    2008-01-01

    Piperine, a major component of black pepper, is used as spice and nutrient enhancer. The purpose of the present study was to evaluate the effects of acute and prolonged piperine exposure on cellular P-gp expression and function in vitro and in vivo. Piperine at concentrations ranging from 10 to 100 μM, determined by MTT assay to be non-cytotoxic, was observed to inhibit P-gp mediated efflux transport of [ 3 H]-digoxin across L-MDR1 and Caco-2 cell monolayers. The acute inhibitory effect was dependent on piperine concentration, with abolishment of [ 3 H]-digoxin polarized transport attained at 50 μM of piperine. In contrast, prolonged (48 and 72 h) co-incubation of Caco-2 cell monolayers with piperine (50 and 100 μM) increased P-gp activity through an up-regulation of cellular P-gp protein and MDR1 mRNA levels. The up-regulated protein was functionally active, as demonstrated by a higher degree of [ 3 H]-digoxin efflux across the cell monolayers, but the induction was readily reversed by the removal of the spice from the culture medium. Peroral administration of piperine at the dose of 112 μg/kg body weight/day to male Wistar rats for 14 consecutive days also led to increased intestinal P-gp levels. However, there was a concomitant reduction in the rodent liver P-gp although the kidney P-gp level was unaffected. Our data suggest that caution should be exercised when piperine is to be co-administered with drugs that are P-gp substrates, particularly for patients whose diet relies heavily on pepper

  12. Cannabidiol changes P-gp and BCRP expression in trophoblast cell lines

    Directory of Open Access Journals (Sweden)

    Valeria Feinshtein

    2013-09-01

    Full Text Available Objectives. Marijuana is the most commonly used illicit drug during pregnancy. Due to high lipophilicity, cannabinoids can easily penetrate physiological barriers like the human placenta and jeopardize the developing fetus. We evaluated the impact of cannabidiol (CBD, a major non-psychoactive cannabinoid, on P-glycoprotein (P-gp and Breast Cancer Resistance Protein (BCRP expression, and P-gp function in a placental model, BeWo and Jar choriocarcinoma cell lines (using P-gp induced MCF7 cells (MCF7/P-gp for comparison. Study design. Following the establishment of the basal expression of these transporters in the membrane fraction of all three cell lines, P-gp and BCRP protein and mRNA levels were determined following chronic (24–72 h exposure to CBD, by Western Blot and qPCR. CBD impact on P-gp efflux function was examined by uptake of specific P-gp fluorescent substrates (calcein-AM, DiOC2(3 and rhodamine123(rh123. Cyclosporine A (CsA served as a positive control. Results. Chronic exposure to CBD resulted in significant changes in the protein and mRNA levels of both transporters. While P-gp was down-regulated, BCRP levels were up-regulated in the choriocarcinoma cell lines. CBD had a remarkably different influence on P-gp and BCRP expression in MCF7/P-gp cells, demonstrating that these are cell type specific effects. P-gp dependent efflux (of calcein, DiOC2(3 and rh123 was inhibited upon short-term exposure to CBD. Conclusions. Our study shows that CBD might alter P-gp and BCRP expression in the human placenta, and inhibit P-gp efflux function. We conclude that marijuana use during pregnancy may reduce placental protective functions and change its morphological and physiological characteristics.

  13. Effect of a physical activity programme in the aquatic environment on haemodynamic constants in pregnant women.

    Science.gov (United States)

    Vázquez-Lara, Juana María; Ruiz-Frutos, Carlos; Rodríguez-Díaz, Luciano; Ramírez-Rodrigo, Jesús; Villaverde-Gutiérrez, Carmen; Torres-Luque, Gema

    2017-09-20

    To evaluate the effect of a physical activity programme in the aquatic environment with immersion up to the neck, of six weeks duration, on haemodynamic constants in pregnant women. A six-week physical activity programme in the aquatic environment was carried out with a total of 46 pregnant women, who were distributed into an experimental group (n = 18), which participated in the programme, and a control group (n = 28), which followed routine care. In both groups different haemodynamic measurements were evaluated before and after the program. At the beginning of the programme the mean systolic blood pressure was similar between groups, but diastolic blood pressure was slightly higher in the experimental group. When the measurements at the last session were compared, arterial pressures (systolic, diastolic and mean) were significantly higher in the control group (p <.050). Similarly, the initial plasma volume values did not differ between groups, but after the intervention, the control group women showed a higher mean (p <.010). The fraction of sodium excretion (FENa) increased significantly in the experimental group, after the programme, with a mean three times higher (p <.050). Aldosterone plasma levels did not show significant differences between the groups in the different measurements. A programme of swimming and immersion exercises in pregnant women contributes to hydrosaline balance, preventing an excessive increase in usual plasma volume during pregnancy and in the activity of the renin-aldosterone axis. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  14. Evaluation of the theory-based Quality Improvement in Physical Therapy (QUIP) programme: a one-group, pre-test post-test pilot study

    OpenAIRE

    Rutten, Geert M; Harting, Janneke; Bartholomew, L Kay; Schlief, Angelique; Oostendorp, Rob AB; de Vries, Nanne K

    2013-01-01

    BACKGROUND: Guideline adherence in physical therapy is far from optimal, which has consequences for the effectiveness and efficiency of physical therapy care. Programmes to enhance guideline adherence have, so far, been relatively ineffective. We systematically developed a theory-based Quality Improvement in Physical Therapy (QUIP) programme aimed at the individual performance level (practicing physiotherapists; PTs) and the practice organization level (practice quality manager; PQM). The aim...

  15. Structural delineation of a quaternary, cleavage-dependent epitope at the gp41-gp120 interface on intact HIV-1 Env trimers.

    Science.gov (United States)

    Blattner, Claudia; Lee, Jeong Hyun; Sliepen, Kwinten; Derking, Ronald; Falkowska, Emilia; de la Peña, Alba Torrents; Cupo, Albert; Julien, Jean-Philippe; van Gils, Marit; Lee, Peter S; Peng, Wenjie; Paulson, James C; Poignard, Pascal; Burton, Dennis R; Moore, John P; Sanders, Rogier W; Wilson, Ian A; Ward, Andrew B

    2014-05-15

    All previously characterized broadly neutralizing antibodies to the HIV-1 envelope glycoprotein (Env) target one of four major sites of vulnerability. Here, we define and structurally characterize a unique epitope on Env that is recognized by a recently discovered family of human monoclonal antibodies (PGT151-PGT158). The PGT151 epitope is comprised of residues and glycans at the interface of gp41 and gp120 within a single protomer and glycans from both subunits of a second protomer and represents a neutralizing epitope that is dependent on both gp120 and gp41. Because PGT151 binds only to properly formed, cleaved trimers, this distinctive property, and its ability to stabilize Env trimers, has enabled the successful purification of mature, cleaved Env trimers from the cell surface as a complex with PGT151. Here we compare the structural and functional properties of membrane-extracted Env trimers from several clades with those of the soluble, cleaved SOSIP gp140 trimer. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. The radiation exposure control programme - its effect on design

    International Nuclear Information System (INIS)

    Simmons, R.B.V.

    1975-01-01

    The paper discusses how the Power Projects design organization has responded to the problem of operational exposure. This response took the form of an organized formal Programme developed during the Bruce G.S. design phase. This Radiation Exposure Control Programme considered: radiation conditions, number of items requiring attention, number of occasions item requires attention and manhours involved on each occasion. Analysis of these factors and comparison with target values enabled worthwhile reductions to be made in estimated operating exposure. Activity transport studies, reliability and design detail improvements have all received an impetus from the Programme. The Programme which has value both from the economic and the health physics points of view is now a continuing feature of the CANDU plant design process. (author)

  17. Impact of a community-based exercise programme on physical fitness in middle-aged and older patients with type 2 diabetes.

    Science.gov (United States)

    Mendes, Romeu; Sousa, Nelson; Themudo-Barata, José; Reis, Victor

    2016-01-01

    Physical fitness is related to all-cause mortality, quality of life and risk of falls in patients with type 2 diabetes. This study aimed to analyse the impact of a long-term community-based combined exercise program (aerobic+resistance+agility/balance+flexibility) developed with minimum and low-cost material resources on physical fitness in middle-aged and older patients with type 2 diabetes. This was a non-experimental pre-post evaluation study. Participants (N=43; 62.92±5.92 years old) were engaged in a community-based supervised exercise programme (consisting of combined aerobic, resistance, agility/balance and flexibility exercises; three sessions per week; 70min per session) of 9 months' duration. Aerobic fitness (6-Minute Walk Test), muscle strength (30-Second Chair Stand Test), agility/balance (Timed Up and Go Test) and flexibility (Chair Sit and Reach Test) were assessed before (baseline) and after the exercise intervention. Significant improvements in the performance of the 6-Minute Walk Test (Δ=8.20%, p<0.001), 30-Second Chair Stand Test (Δ=28.84%, p<0.001), Timed Up and Go Test (Δ=14.31%, p<0.001), and Chair Sit and Reach Test (Δ=102.90%, p<0.001) were identified between baseline and end-exercise intervention time points. A long-term community-based combined exercise programme, developed with low-cost exercise strategies, produced significant benefits in physical fitness in middle-aged and older patients with type 2 diabetes. This supervised group exercise programme significantly improved aerobic fitness, muscle strength, agility/balance and flexibility, assessed with field tests in community settings. Copyright © 2016 SESPAS. Published by Elsevier Espana. All rights reserved.

  18. Outsourcing Physical Education in Primary Schools: Evaluating the Impact of Externally Provided Programmes on Generalist Teachers

    Science.gov (United States)

    Whipp, Peter R.; Hutton, Heidi; Grove, J. Robert; Jackson, Ben

    2011-01-01

    In place of generalist delivery, externally provided physical activity programmes (EPPAPs) are potentially an effective method for offering primary school students specialist physical education (PE) instruction, as well as providing training for generalist classroom teachers. In the present study, a group of generalist teachers were interviewed…

  19. Effects of 6-month soccer and traditional physical activity programmes on body composition, cardiometabolic risk factors, inflammatory, oxidative stress markers and cardiorespiratory fitness in obese boys.

    Science.gov (United States)

    Seabra, André; Katzmarzyk, Peter; Carvalho, Maria José; Seabra, Ana; Coelho-E-Silva, Manuel; Abreu, Sandra; Vale, Susana; Póvoas, Susana; Nascimento, Henrique; Belo, Luís; Torres, Sandra; Oliveira, José; Mota, Jorge; Santos-Silva, Alice; Rêgo, Carla; Malina, Robert M

    2016-10-01

    Physical activity is important in obesity prevention, but the effectiveness of different physical activity modalities remains to be determined among children. The main purpose of this study was to compare the effects of a 6-month soccer programme and a traditional physical activity programme on changes in body composition, cardiometabolic risk factors, inflammatory and oxidative markers, cardiorespiratory fitness and perceived psychological status in obese boys. Eighty-eight boys (8-12 years; BMI > +2 standard deviations of WHO reference values) participated in one of three groups: soccer, traditional activity and control. Soccer and traditional activity programmes involved 3 sessions per week for 60-90 min at an average intensity of 70-80% of maximal heart rate. Control group participated in activities of normal daily living. All boys participated in school physical education, two sessions per week of 45-90-min. Measurements were taken at baseline and after 6 months, and included body size and composition, cardiometabolic risk factors, inflammatory and oxidative markers, cardiorespiratory fitness and perceived psychological status. Physical activity and dietary intake were assessed before and immediately following the intervention. The three groups had similar characteristics at baseline. After 6 months, both intervention groups had significantly lower relative fatness (% fat), waist circumference and total cholesterol, and higher cardiorespiratory fitness, self-esteem, perceived physical competence and attraction to physical activity compared with control group. In conclusion, physical activity interventions over 6 months positively influenced several indicators of health status among obese boys. The results also suggested that soccer has the potential as an effective tool for the prevention and reduction of childhood obesity and associated consequences.

  20. [Eukaryotic Expression and Immunogenic Research of Recombination Ebola Virus Membrane Protein Gp-Fc].

    Science.gov (United States)

    Zhang, Xiaoguang; Yang, Ren; Wang, Jiao; Wang, Xuan; Hou, Mieling; An, Lina; Zhu, Ying; Cao, Yuxi; Zeng, Yi

    2016-01-01

    We used 293 cells to express the recombinant membrane protein of the Ebola virus. Then, the immunogenicity of the recombinant protein was studied by immunized BALB/c mice. According to the codon use frequency of humans, the gene encoding the extracellular domain of the Ebola virus membrane protein was optimized, synthesized, and inserted into the eukaryotic expression plasmid pXG-Fc to construct the human IgG Fc and Ebola GP fusion protein expression plasmid pXG-modGP-Fc. To achieve expression, the fusion protein expression vector was transfected into high-density 293 cells using transient transfection technology. The recombinant protein was purified by protein A affinity chromatography. BALB/c mice were immunized with the purified fusion protein, and serum antibody titers evaluated by an indirect enzyme-linked immunosorbent assay (ELISA). Purification and analyses of the protein revealed that the eukaryotic expression vector could express the recombinant protein GP-Fc effectively, and that the recombinant protein in the supernatant of the cell culture was present as a dimer. After immunization with the purified recombinant protein, a high titer of antigen-specific IgG could be detected in the serum of immunized mice by indirect ELISA, showing that the recombinant protein had good immunogenicity. These data suggest that we obtained a recombinant protein with good immunogenicity. Our study is the basis for development of a vaccine against the Ebola virus and for screening of monoclonal antibodies.

  1. Intrinsic acid-base properties of a hexa-2'-deoxynucleoside pentaphosphate, d(ApGpGpCpCpT): neighboring effects and isomeric equilibria.

    Science.gov (United States)

    Domínguez-Martín, Alicia; Johannsen, Silke; Sigel, Astrid; Operschall, Bert P; Song, Bin; Sigel, Helmut; Okruszek, Andrzej; González-Pérez, Josefa María; Niclós-Gutiérrez, Juan; Sigel, Roland K O

    2013-06-17

    The intrinsic acid-base properties of the hexa-2'-deoxynucleoside pentaphosphate, d(ApGpGpCpCpT) [=(A1∙G2∙G3∙C4∙C5∙T6)=(HNPP)⁵⁻] have been determined by ¹H NMR shift experiments. The pKa values of the individual sites of the adenosine (A), guanosine (G), cytidine (C), and thymidine (T) residues were measured in water under single-strand conditions (i.e., 10% D₂O, 47 °C, I=0.1 M, NaClO₄). These results quantify the release of H⁺ from the two (N7)H⁺ (G∙G), the two (N3)H⁺ (C∙C), and the (N1)H⁺ (A) units, as well as from the two (N1)H (G∙G) and the (N3)H (T) sites. Based on measurements with 2'-deoxynucleosides at 25 °C and 47 °C, they were transferred to pKa values valid in water at 25 °C and I=0.1 M. Intramolecular stacks between the nucleobases A1 and G2 as well as most likely also between G2 and G3 are formed. For HNPP three pKa clusters occur, that is those encompassing the pKa values of 2.44, 2.97, and 3.71 of G2(N7)H⁺, G3(N7)H⁺, and A1(N1)H⁺, respectively, with overlapping buffer regions. The tautomer populations were estimated, giving for the release of a single proton from five-fold protonated H₅(HNPP)(±) , the tautomers (G2)N7, (G3)N7, and (A1)N1 with formation degrees of about 74, 22, and 4%, respectively. Tautomer distributions reveal pathways for proton-donating as well as for proton-accepting reactions both being expected to be fast and to occur practically at no "cost". The eight pKa values for H₅(HNPP)(±) are compared with data for nucleosides and nucleotides, revealing that the nucleoside residues are in part affected very differently by their neighbors. In addition, the intrinsic acidity constants for the RNA derivative r(A1∙G2∙G3∙C4∙C5∙U6), where U=uridine, were calculated. Finally, the effect of metal ions on the pKa values of nucleobase sites is briefly discussed because in this way deprotonation reactions can easily be shifted to the physiological pH range. Copyright © 2013 WILEY

  2. Anti-HIV double variable domain immunoglobulins binding both gp41 and gp120 for targeted delivery of immunoconjugates.

    Directory of Open Access Journals (Sweden)

    Ryan B Craig

    Full Text Available BACKGROUND: Anti-HIV immunoconjugates targeted to the HIV envelope protein may be used to eradicate the latent reservoir of HIV infection using activate-and-purge protocols. Previous studies have identified the two target epitopes most effective for the delivery of cytotoxic immunoconjugates the CD4-binding site of gp120, and the hairpin loop of gp41. Here we construct and test tetravalent double variable domain immunoglobulin molecules (DVD-Igs that bind to both epitopes. METHODS: Synthetic genes that encode DVD-Igs utilizing V-domains derived from human anti-gp120 and anti-gp41 Abs were designed and expressed in 293F cells. A series of constructs tested different inter-V-linker domains and orientations of the two V domains. Antibodies were tested for binding to recombinant Ag and native Env expressed on infected cells, for neutralization of infectious HIV, and for their ability to deliver cytotoxic immunoconjugates to infected cells. FINDINGS: The outer V-domain was the major determinant of binding and functional activity of the DVD-Ig. Function of the inner V-domain and bifunctional binding required at least 15 AA in the inter-V-domain linker. A molecular model showing the spatial orientation of the two epitopes is consistent with this observation. Linkers that incorporated helical domains (A[EAAAK](nA resulted in more effective DVD-Igs than those based solely on flexible domains ([GGGGS](n. In general, the DVD-Igs outperformed the less effective parental antibody and equaled the activity of the more effective. The ability of the DVD-Igs to deliver cytotoxic immunoconjugates in the absence of soluble CD4 was improved over that of either parent. CONCLUSIONS: DVD-Igs can be designed that bind to both gp120 and gp41 on the HIV envelope. DVD-Igs are effective in delivering cytotoxic immunoconjugates. The optimal design of these DVD-Igs, in which both domains are fully functional, has not yet been achieved.

  3. The development of an interdepartmental audit as part of a physics quality assurance programme for external beam therapy

    International Nuclear Information System (INIS)

    Bonnett, D.E.; Jaukett, R.J.; Mills, J.A.; Martin-Smith, P.

    1994-01-01

    A cost-effective audit system has been developed that will both detect systematic error in data and procedures, and evaluate the quality assurance programme provided by a physics department for radiotherapy. The audit has been developed for external beam radiotherapy and assesses one modality and one treatment machine per year. The method of assessing the quality assurance programme and the schedule of measurements are described. The process is illustrated using the results of trial audits between the medical physics department at Coventry and Leicester. (author)

  4. The Low Energy Antiproton Ring (LEAR) some months before the start of its particle physics programme

    CERN Multimedia

    1983-01-01

    LEAR*)and its enclosure in the PS South Hall in Jan, 1983, 4 months before the start of its particle physics programme. Visible (in red) are the 90 degree bending magnets consisting of 6 blocks each. Separated from the magnets by short straight sections are the quadrupole doublets (blue with read end-plates). The 4 long straight sections house large equipment like septa for injection/ejection, RF-cavities and later (since 1986) electron cooling and an internal target and its associated detector (JETSET experiment). Two small copper tubes spanning across the ring are coaxial lines transmitting the stochastic cooling signals from pickup to kicker. (see also photos 8205747X, 8207133, 8207541X, 8309026) *)see e.g.: H.Koziol and D. Möhl, Phys. Rep. 403-404 (2004), p.271 and references therein

  5. Immunization With Fc-Based Recombinant Epstein–Barr Virus gp350 Elicits Potent Neutralizing Humoral Immune Response in a BALB/c Mice Model

    Directory of Open Access Journals (Sweden)

    Bingchun Zhao

    2018-05-01

    Full Text Available Epstein–Barr virus (EBV was the first human virus proved to be closely associated with tumor development, such as lymphoma, nasopharyngeal carcinoma, and EBV-associated gastric carcinoma. Despite many efforts to develop prophylactic vaccines against EBV infection and diseases, no candidates have succeeded in effectively blocking EBV infection in clinical trials. Previous investigations showed that EBV gp350 plays a pivotal role in the infection of B-lymphocytes. Nevertheless, using monomeric gp350 proteins as antigens has not been effective in preventing infection. Multimeric forms of the antigen are more potently immunogenic than monomers; however, the multimerization elements used in previous constructs are not approved for human clinical trials. To prepare a much-needed EBV prophylactic vaccine that is potent, safe, and applicable, we constructed an Fc-based form of gp350 to serve as a dimeric antigen. Here, we show that the Fc-based gp350 antigen exhibits dramatically enhanced immunogenicity compared with wild-type gp350 protein. The complete or partial gp350 ectodomain was fused with the mouse IgG2a Fc domain. Fusion with the Fc domain did not impair gp350 folding, binding to a conformation-dependent neutralizing antibody (nAb and binding to its receptor by enzyme-linked immunosorbent assay and surface plasmon resonance. Specific antibody titers against gp350 were notably enhanced by immunization with gp350-Fc dimers compared with gp350 monomers. Furthermore, immunization with gp350-Fc fusion proteins elicited potent nAbs against EBV. Our data strongly suggest that an EBV gp350 vaccine based on Fc fusion proteins may be an efficient candidate to prevent EBV infection in clinical applications.

  6. [Expression and significance of P-gp/mdr1 mRNA, MRP and LRP in non-Hodgkin's lymphoma].

    Science.gov (United States)

    Li, Le; Su, Li-ping; Ma, Li; Zhao, Jin; Zhu, Lei; Zhou, Yong-an

    2009-03-01

    To explore the expression and clinical significance of P-glycoprotein (P-gp)/mdr1mRNA, multidrug resistance-associated protein (MRP) and lung resistance protein (LRP) in newly diagnosed non-Hodgkin's lymphoma. mdr1 mRNA of in 41 patients with non-Hodgkin's lymphoma was assayed by semi-quantitative RT-PCR. The expressions of P-gp, MRP and LRP proteins in lymph node viable blasts were identified by flow cytometry. The results were compared with those obtained from control cases, and the correlation of the changes with clinical outcomes was analyzed. (1) Among the 41 cases, the positive expression of P-gp protein was detected in 8 cases, MRP in 7 cases, LRP in 15 cases, and mdr 1 mRNA in 11 cases. (2) The P-gp and LRP levels in NHL were significantly higher than those in control group, but MRP wasn't. The P-gp over-expression was significantly associated with mdr1mRNA (r = 0.396, P = 0.01). No correlation was showed among the expressions of P-gp, MRP and LRP. (3) Patients with P-gp expression had a poorer outcome of chemotherapy than those with P-gp-negative (P = 0.005). P-gp expression was significantly associated with higher clinical stage (P = 0.046) and elevated serum lactate dehydrogenase level (P = 0.032), but not associated with malignant degree (P = 0.298). MRP had no impact on the outcome of chemotherapy (P = 0.212), and wasn't significantly associated with higher clinical stage (P = 0.369), elevated LDH (P = 0.762) and higher malignant degree (P = 0.451). Patients with LRP expression had a poorer outcome of chemotherapy than those LRP-negative (P = 0.012). LRP expression was significantly associated with higher clinical stage (P = 0.0019), elevated LDH (P = 0.02) and higher malignant degree (P = 0.01). The data of this study indicate that P-gp and LRP expressions but not MRP expression are important in the mechanism of drug resistance associated with a poor clinical outcome in previously untreated NHL.

  7. Marburg Virus Glycoprotein GP2: pH-Dependent Stability of the Ectodomain α-Helical Bundle†

    Science.gov (United States)

    Harrison, Joseph S.; Koellhoffer, Jayne F.; Chandran, Kartik; Lai, Jonathan R.

    2012-01-01

    Marburg virus (MARV) and Ebola virus (EBOV) constitute the family Filoviridae of enveloped viruses (filoviruses) that cause severe hemorrhagic fever. Infection by MARV is required for fusion between the host cell and viral membranes, a process that is mediated by the two subunits of the envelope glycoprotein GP1 (surface subunit) and GP2 (transmembrane subunit). Upon viral attachment and uptake, it is believed that the MARV viral fusion machinery is triggered by host factors and environmental conditions found in the endosome. Next, conformational rearrangements in the GP2 ectodomain result in the formation of a highly stable six-helix bundle; this refolding event provides the energetic driving force for membrane fusion. Both GP1 and GP2 from EBOV have been extensively studied, but there is little information available for the MARV glycoproteins. Here we have expressed two variants of the MARV GP2 ectodomain in Escherichia coli and analyzed their biophysical properties. Circular dichroism indicates that the MARV GP2 ectodomain adopts an α-helical conformation, and one variant sediments as a trimer by equilibrium analytical ultracentrifugation. Denaturation studies indicate the α-helical structure is highly stable at pH 5.3 (unfolding energy, ΔGunf H2O, of 33.4 ± 2.5 kcal/mol and melting temperature, Tm, of 75.3 ± 2.1 °C for one variant). Furthermore, we found the α-helical stability to be strongly dependent on pH with higher stability under lower pH conditions (Tm values ranging from ~92 °C at pH 4.0 to ~38 °C at pH 8.0). Mutational analysis suggests two glutamic acid residues (E579 and E580) are partially responsible for this pH-dependent behavior. Based on these results, we hypothesize that pH-dependent folding stability of the MARV GP2 ectodomain provides a mechanism to control conformational preferences such that the six-helix bundle ‘post-fusion’ state is preferred under conditions of appropriately matured endosomes. PMID:22369502

  8. Antiviral Activity of HIV gp120 Targeting Bispecific T Cell Engager (BiTE®) Antibody Constructs.

    Science.gov (United States)

    Brozy, Johannes; Schlaepfer, Erika; Mueller, Christina K S; Rochat, Mary-Aude; Rampini, Silvana K; Myburgh, Renier; Raum, Tobias; Kufer, Peter; Baeuerle, Patrick A; Muenz, Markus; Speck, Roberto F

    2018-05-02

    Today's gold standard in HIV therapy is the combined antiretroviral therapy (cART). It requires strict adherence by patients and life-long medication, which can lower the viral load below detection limits and prevent HIV-associated immunodeficiency, but cannot cure patients. The bispecific T cell engaging (BiTE®) antibody technology has demonstrated long-term relapse-free outcomes in patients with relapsed and refractory acute lymphocytic leukemia. We here generated BiTE® antibody constructs that target the HIV-1 envelope protein gp120 (HIV gp120) using either the scFv B12 or VRC01, the first two extracellular domains (1+2) of human CD4 alone or joined to the single chain variable fragment (scFv) of the antibody 17b fused to an anti-human CD3ϵ scFv. These engineered human BiTE® antibody constructs showed engagement of T cells for redirected lysis of HIV gp120-transfected CHO cells. Furthermore, they substantially inhibited HIV-1 replication in PBMCs as well as in macrophages co-cultured with autologous CD8+ T-cells, the most potent being the human CD4(1+2) BiTE® antibody construct and the CD4(1+2)L17b BiTE® antibody construct. The CD4(1+2) h BiTE® antibody construct promoted HIV infection of human CD4-/CD8+ T cells. In contrast, the neutralizing B12 and the VRC01 BiTE® antibody constructs as well as the CD4(1+2)L17b BiTE® antibody construct did not. Thus, BiTE® antibody constructs targeting HIV gp120 are very promising for constraining HIV and warrant further development as novel antiviral therapy with curative potential. Importance HIV is a chronic infection well controlled with the current cART. However, we lack cure of HIV, and the HIV pandemic goes on. Here we showed in vitro and ex vivo t hat a bispecific T-cell engaging (BiTE®) antibody construct targeting HIV gp120 resulted in substantially reduced HIV replication. In addition, these BiTE® antibody constructs display efficient killing of gp120 expressing cells and inhibited replication in ex vivo

  9. Epidemiology and resistance patterns in urinary pathogens from long-term care facilities and GP populations.

    LENUS (Irish Health Repository)

    Brabazon, E D

    2012-06-01

    Urinary tract infections (UTIs) are a major source of antimicrobial prescribing in the clinical setting and a potential reservoir for the emergence of resistant organisms. Although studies have been published on resistance rates for urinary pathogens from both hospital and general practitioner (GP) settings, there is little information from Long-Term Care Facilities (LTCFs) in Ireland. This study aimed to document the epidemiology and resistance rates in urinary isolates, in the LTCF and GP setting, from samples submitted to a typical microbiology laboratory. In 2010, there were 963 urinary isolates from LTCFs and 1,169 urinary isolates from GPs, identified from patients 65 years and over, with cytology suggestive of infection. E. coil was the most common causative organism identified. There were significantly higher levels of resistance to ampicillin, co-amoxiclav, ciprofloxacin, nitrofurantoin, trimethoprim, and piperacillin\\/tazobactam in the LTCF population compared to the GP population (e.g. for E. coli, 86%-v-69%; 30%-v- 21%; 58%-v-26%, 10%-v-3%, 68%-v-48%, 10%-v- 4% respectively). Isolates with resistance mechanisms to beta-lactams, were identified in both populations. Results presented in this paper demonstrate significant differences between resistance rates in LTCF and GP populations which suggest that there are implications for empiric antimicrobial prescribing for UTIs in the LTCF setting.

  10. Values of serum AFP, GGTⅡ and GP73 in diagnosis of primary hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    ZHU Chen

    2014-10-01

    Full Text Available ObjectiveTo explore the early diagnostic values of serum alpha-fetoprotein (AFP, gamma-glutamyltransferase Ⅱ (GGTⅡ, and Golgi protein 73 (GP73 in patients with primary hepatocellular carcinoma (PHC. MethodsThe serum specimens of 100 patients with liver diseases (50 cases of hepatitis and liver cirrhosis and 50 cases of PHC and 50 healthy people were collected in our hospital from February 2013 to February 2014. Electrochemical luminescence technique, specific immuno-membrane adsorption assay, and enzyme-linked immunosorbent assay were used to measure the serum levels of AFP, GGTⅡ, and GP73. Comparison of continuous data between multiple groups was made by analysis of variance, and comparison between two groups was made by q test. The receiver operating characteristic (ROC curves of single or combined test results were made, and the areas under the ROC curves (AUCs were calculated. The sensitivity, specificity, and AUCs of AFP, GGTⅡ, GP73, and the combined test were analyzed and compared. ResultsThe level of serum GGTⅡ in the PHC group was significantly different compared with those in the other two groups (F=16.224, P<0.05, but there was no significant difference between the normal group and the hepatitis and liver cirrhosis group (P>0.05. Significant differences in serum levels of AFP and GP73 were observed by paired comparison between the PHC group, hepatitis and liver cirrhosis group, and normal group (F=193.128, F=20.231, P<0.05 for both. When assayed alone, the specificities of GP73, GGTⅡ, and AFP were 69%, 64% and 51%, respectively, and the sensitivities were 92%, 84%, and 76%, respectively. In combined test, the specificity was 94.6% and the sensitivity was 98.8%. ConclusionThe GP73 test is the best performer in the single assays. Combined test of serum AFP, GGTⅡ, and GP73 shows a good diagnostic value for PHC with greatly improved specificity and sensitivity.

  11. Corporate sponsorship of physical activity promotion programmes: part of the solution or part of the problem?

    Science.gov (United States)

    Jane, B; Gibson, K

    2017-06-07

    Parklives is a programme intended to raise levels of physical activity across the UK, funded by Coca-Cola GB and delivered in association with Local Authorities and other organizations. Such public-private partnerships have been advocated by many however critics suggest that the conflict between stakeholder motives is too great. This study conducted a content analysis of twitter content related to the ParkLives physical activity programme. Images and text were analysed from two separate weeks, one from the school vacation period and one during school term time. Three hundred and eighteen tweets were analysed. Content analysis revealed 79% of images contained children and 45% of these images contained prominent Coca-Cola branding, a level of exposure that suggests ParkLives simultaneously provides opportunities for children's physical activity and for targeted marketing. Content analysis also demonstrated that the programme allowed increased access to policy-makers. The sponsorship of a physical activity promotion campaign can allow a corporation to target its marketing at children and gain access to health-related policy development networks. This study reinforces the need for independent evaluation of all potential impacts of such a partnership and calls on those responsible for community health to fully consider the ethical implications of such relationships. © The Author 2017. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  12. Increased Circulating Level of the Survival Factor GP88 (Progranulin in the Serum of Breast Cancer Patients When Compared to Healthy Subjects

    Directory of Open Access Journals (Sweden)

    Katherine Rak Tkaczuk

    2011-01-01

    Full Text Available Introduction GP88 (PC-Cell Derived Growth Factor, progranulin is a glycoprotein overexpressed in breast tumors and involved in their proliferation and survival. Since GP88 is secreted, an exploratory study was established to compare serum GP88 level between breast cancer patients (BC and healthy volunteers (HV. Methods An IRB approved prospective study enrolled 189 stage 1–4 BC patients and 18 HV. GP88 serum concentration was determined by immunoassay. Results Serum GP88 level was 28.7+ 5.8 ng/ml in HV and increased to 40.7+ 16.0 ng/ml ( P = 0.007 for stage 1-3 and 45.3 +23.3 ng/ml ( P = 0.0007 for stage 4 BC patients. There was no correlation between the GP88 level and BC characteristics such as age, race, tumor grade, ER, PR and HER-2 expression. Conclusion These data suggest that serial testing of serum GP88 levels may have value as a circulating biomarker for detection, monitoring and follow up of BC.

  13. Fermi Large Area Telescope Observations of the Supernova Remnant G8.7-0.1

    Energy Technology Data Exchange (ETDEWEB)

    Ajello, M.; Allafort, A.; /Stanford U., HEPL /KIPAC, Menlo Park /SLAC; Baldini, L.; /INFN, Pisa; Ballet, J.; /AIM, Saclay; Barbiellini, G.; /INFN, Trieste /Trieste U.; Bastieri, D.; /INFN, Padua /Padua U.; Bechtol, K.; /Stanford U., HEPL /KIPAC, Menlo Park /SLAC; Bellazzini, R.; /INFN, Pisa; Berenji, B.; Blandford, R.D.; Bloom, E.D.; /Stanford U., HEPL /KIPAC, Menlo Park /SLAC; Bonamente, E.; /INFN, Perugia /Perugia U.; Borgland, A.W.; /Stanford U., HEPL /KIPAC, Menlo Park /SLAC; Bregeon, J.; /INFN, Pisa; Brigida, M.; /Bari Polytechnic /INFN, Bari; Bruel, P.; /Ecole Polytechnique; Buehler, R.; /Stanford U., HEPL /KIPAC, Menlo Park /SLAC; Buson, S.; /INFN, Padua /Padua U.; Caliandro, G.A.; /CSIC, Catalunya; Cameron, R.A.; /Stanford U., HEPL /KIPAC, Menlo Park /SLAC; Caraveo, P.A.; /IASF, Milan /AIM, Saclay /INFN, Perugia /Perugia U. /Stanford U., HEPL /KIPAC, Menlo Park /SLAC /Unlisted, US /Naval Research Lab, Wash., D.C. /Perugia U. /ASDC, Frascati /Stanford U., HEPL /KIPAC, Menlo Park /SLAC /Montpellier U. /ASDC, Frascati /Udine U. /INFN, Trieste /Bari Polytechnic /INFN, Bari /Naval Research Lab, Wash., D.C. /Stanford U., HEPL /KIPAC, Menlo Park /SLAC /Bari Polytechnic /INFN, Bari /Ecole Polytechnique /NASA, Goddard /Stanford U., HEPL /KIPAC, Menlo Park /SLAC /Udine U. /INFN, Trieste /Trieste Observ. /Hiroshima U. /Nagoya U. /Bari Polytechnic /INFN, Bari /INFN, Bari /ASDC, Frascati /INFN, Perugia /Perugia U. /Bari Polytechnic /INFN, Bari /ASDC, Frascati /Bari Polytechnic /INFN, Bari /Bologna Observ. /Stanford U., HEPL /KIPAC, Menlo Park /SLAC /Naval Research Lab, Wash., D.C. /Alabama U., Huntsville /CSIC, Catalunya /Hiroshima U. /NASA, Goddard /Hiroshima U.; /more authors..

    2012-09-14

    We present a detailed analysis of the GeV gamma-ray emission toward the supernova remnant (SNR) G8.7-0.1 with the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope. An investigation of the relationship between G8.7-0.1 and the TeV unidentified source HESS J1804-216 provides us with an important clue on diffusion process of cosmic rays if particle acceleration operates in the SNR. The GeV gamma-ray emission is extended with most of the emission in positional coincidence with the SNR G8.7-0.1 and a lesser part located outside the western boundary of G8.7-0.1. The region of the gamma-ray emission overlaps spatially connected molecular clouds, implying a physical connection for the gamma-ray structure. The total gamma-ray spectrum measured with LAT from 200 MeV-100 GeV can be described by a broken power-law function with a break of 2.4 {+-} 0.6 (stat) {+-} 1.2 (sys) GeV, and photon indices of 2.10 {+-} 0.06 (stat) {+-} 0.10 (sys) below the break and 2.70 {+-} 0.12 (stat) {+-} 0.14 (sys) above the break. Given the spatial association among the gamma rays, the radio emission of G8.7-0.1, and the molecular clouds, the decay of p0s produced by particles accelerated in the SNR and hitting the molecular clouds naturally explains the GeV gamma-ray spectrum. We also find that the GeV morphology is not well represented by the TeV emission from HESS J1804-216 and that the spectrum in the GeV band is not consistent with the extrapolation of the TeV gamma-ray spectrum. The spectral index of the TeV emission is consistent with the particle spectral index predicted by a theory that assumes energy-dependent diffusion of particles accelerated in an SNR. We discuss the possibility that the TeV spectrum originates from the interaction of particles accelerated in G8.7-0.1 with molecular clouds, and we constrain the diffusion coefficient of the particles.

  14. Fermi Large Area Telescope Observations of the Supernova Remnant G8.7-0.1

    International Nuclear Information System (INIS)

    2012-01-01

    We present a detailed analysis of the GeV gamma-ray emission toward the supernova remnant (SNR) G8.7-0.1 with the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope. An investigation of the relationship between G8.7-0.1 and the TeV unidentified source HESS J1804-216 provides us with an important clue on diffusion process of cosmic rays if particle acceleration operates in the SNR. The GeV gamma-ray emission is extended with most of the emission in positional coincidence with the SNR G8.7-0.1 and a lesser part located outside the western boundary of G8.7-0.1. The region of the gamma-ray emission overlaps spatially connected molecular clouds, implying a physical connection for the gamma-ray structure. The total gamma-ray spectrum measured with LAT from 200 MeV-100 GeV can be described by a broken power-law function with a break of 2.4 ± 0.6 (stat) ± 1.2 (sys) GeV, and photon indices of 2.10 ± 0.06 (stat) ± 0.10 (sys) below the break and 2.70 ± 0.12 (stat) ± 0.14 (sys) above the break. Given the spatial association among the gamma rays, the radio emission of G8.7-0.1, and the molecular clouds, the decay of p0s produced by particles accelerated in the SNR and hitting the molecular clouds naturally explains the GeV gamma-ray spectrum. We also find that the GeV morphology is not well represented by the TeV emission from HESS J1804-216 and that the spectrum in the GeV band is not consistent with the extrapolation of the TeV gamma-ray spectrum. The spectral index of the TeV emission is consistent with the particle spectral index predicted by a theory that assumes energy-dependent diffusion of particles accelerated in an SNR. We discuss the possibility that the TeV spectrum originates from the interaction of particles accelerated in G8.7-0.1 with molecular clouds, and we constrain the diffusion coefficient of the particles.

  15. Training-induced changes in physical performance can be achieved without body mass reduction after eight week of strength and injury prevention oriented programme in volleyball female players

    Directory of Open Access Journals (Sweden)

    M Lehnert

    2017-04-01

    Full Text Available The purpose of the study was to analyse the changes in muscle strength, power, and somatic parameters in elite volleyball players after a specific pre-season training programme aimed at improving jumping and strength performance and injury prevention. Twelve junior female volleyball players participated in an 8-week training programme. Anthropometric characteristics, isokinetic peak torque (PT single-joint knee flexion (H and extension (Q at 60º/s and 180º/s, counter movement jump (CMJ, squat jump (SJ, and reactive strength index (RSI were measured before and after intervention. Significant moderate effects were found in flexor concentric PT at 60º/s and at 180 º/s in the dominant leg (DL (18.3±15.1%, likely; 17.8±11.2%, very likely and in extensor concentric PT at 180º/s (7.4%±7.8%, very likely in the DL. In the non-dominant leg (NL significant moderate effects were found in flexor concentric PT at 60º/s and at 180º/s (13.7±11.3%, likely; 13.4±8.0%, very likely and in extensor concentric PT at 180º/s (10.7±11.5%, very likely. Small to moderate changes were observed for H/QCONV in the DL at 60º/s and 180º/s (15.9±14.1%; 9.6±10.4%, both likely and in the NL at 60º/s (moderate change, 9.6±11.8%, likely, and small to moderate decreases were detected for H/QFUNC at 180º/s, in both the DL and NL (-7.0±8.3%, likely; -9.5±10.0%, likely. Training-induced changes in jumping performance were trivial (for RSI to small (for CMJ and SJ. The applied pre-season training programme induced a number of positive changes in physical performance and risk of injury, despite a lack of changes in body mass and composition. CITATION: Lehnert M, Sigmund M, Lipinska P et al. Training-induced changes in physical performance can be achieved without body mass reduction after eight week of strength and injury prevention oriented programme in volleyball female players. Biol Sport. 2017;34(2:205-213.

  16. Prediction of the Secondary Structure of HIV-1 gp120

    DEFF Research Database (Denmark)

    Hansen, Jan; Lund, Ole; Nielsen, Jens O.

    1996-01-01

    Fourier transform infrared spectroscopy. The predicted secondary structure of gp120 compared well with data from NMR analysis of synthetic peptides from the V3 loop and the C4 region. As a first step towards modeling the tertiary structure of gp120, the predicted secondary structure may guide the design......The secondary structure of HIV-1 gp120 was predicted using multiple alignment and a combination of two independent methods based on neural network and nearest-neighbor algorithms. The methods agreed on the secondary structure for 80% of the residues in BH10 gp120. Six helices were predicted in HIV...

  17. GP-initiated preconception counselling in a randomised controlled trial does not induce anxiety

    Directory of Open Access Journals (Sweden)

    Neven A Knuistingh

    2006-11-01

    Full Text Available Abstract Background Preconception counselling (PCC can reduce adverse pregnancy outcome by addressing risk factors prior to pregnancy. This study explores whether anxiety is induced in women either by the offer of PCC or by participation with GP-initiated PCC. Methods Randomised trial of usual care versus GP-initiated PCC for women aged 18–40, in 54 GP practices in the Netherlands. Women completed the six-item Spielberger State Trait Anxiety Inventory (STAI before PCC (STAI-1 and after (STAI-2. After pregnancy women completed a STAI focusing on the first trimester of pregnancy (STAI-3. Results The mean STAI-1-score (n = 466 was 36.4 (95% CI 35.4 – 37.3. Following PCC there was an average decrease of 3.6 points in anxiety-levels (95% CI, 2.4 – 4.8. Mean scores of the STAI-3 were 38.5 (95% CI 37.7 – 39.3 in the control group (n = 1090 and 38.7 (95% CI 37.9 – 39.5 in the intervention group (n = 1186. Conclusion PCC from one's own GP reduced anxiety after participation, without leading to an increase in anxiety among the intervention group during pregnancy. We therefore conclude that GPs can offer PCC to the general population without fear of causing anxiety. Trial Registration: ISRCTN53942912

  18. Variação intraspecífica do lenho de Pseudopiptadenia contorta (DC. G.P. Lewis & M.P. Lima (Leguminosae - Mimosoideae de populações ocorrentes em dois remanescentes de Floresta Atlântica Intraspecific variation in wood anatomy of Pseudopiptadenia contorta (DC G.P. Lewis & M.P. Lima (Leguminosae -Mimosoidae in two Atlantic rain forest remnants

    Directory of Open Access Journals (Sweden)

    Maria Luiza R. da Costa Ribeiro

    2006-12-01

    Full Text Available O presente trabalho compara populações distintas de Pseudopiptadenia contorta (DC. G.P. Lewis & M.P. Lima ocorrentes em dois remanescentes de Floresta Atlântica no Estado do Rio de Janeiro. Foram amostradas árvores de diâmetro semelhante retas e sem defeitos aparentes. Os resultados obtidos comprovam estatisticamente a ocorrência de variação intraspecífica na estrutura anatômica da madeira. Os caracteres qualitativos mantiveram-se constantes, enquanto os quantitativos variaram, sendo os significativos, de acordo com o teste t de Student, a freqüencia, comprimento e diâmetro dos elementos vasos, o comprimento e espessura da parede das fibras, a freqüência e largura dos raios. A análise dos componentes principais, utilizando características anatômicas quantitativas ordenou as duas populações separadamente. O eixo I responde por 33% da variância total principalmente pela relação positiva do diâmetro do elemento de vaso, enquanto o eixo II responde por 20% da variância total, principalmente pelo comprimento das fibras.This study compares distinct populations of Pseudopiptadenia contorta (DC G.P. Lewis & M.P. Lima occurring in two remnants of Atlantic rain forest in Rio de Janeiro state. Trees with similar diameters and with no apparent defects were selected. The results confirm intraspecific variation in wood anatomy. Qualitative features do not change, while according to the Student t test quantitative features showed significant differences in vessel-element frequency, width, and length, fiber length and wall thickness, and ray frequency and width. Principal component analysis showed two separate populations. Factor 1 explains 33% of the total variance, mainly due to the positive relationship of vessel-element tangential diameter; factor 2 explains 20% of the total variance, mainly due to fiber length.

  19. The Agency's Technical Co-operation programme with Costa Rica, 1982-1992. Country programme summaries

    International Nuclear Information System (INIS)

    1992-01-01

    The country programme summary reported here is one in the series of such studies being undertaken of the Agency's TC programme with Member States. With over $2.8 million of Agency support received, Costa Rica ranks 49th among all recipients of technical assistance in the period 1958-1991. Over half of the assistance during the past ten years has been provided in the form of equipment (52%), followed by expert services (37%) and training (11%). Sixty-two per cent of the resources were made available through the Technical Assistance and Co-operation Fund, while 37% of the resources were provided by UNDP. The rest was made available through extrabudgetary contributions (5%) and through in-kind assistance (1%). With regard to project disbursement by sector, the largest areas have been nuclear raw materials (36%), nuclear physics and chemistry (24%) and agriculture (20%). Smaller shares have gone to hydrology (11%) and nuclear medicine (8%)

  20. Randomized Phase I: Safety, Immunogenicity and Mucosal Antiviral Activity in Young Healthy Women Vaccinated with HIV-1 Gp41 P1 Peptide on Virosomes.

    Directory of Open Access Journals (Sweden)

    Geert Leroux-Roels

    Full Text Available Mucosal antibodies harboring various antiviral activities may best protect mucosal surfaces against early HIV-1 entry at mucosal sites and they should be ideally induced by prophylactic HIV-1 vaccines for optimal prevention of sexually transmitted HIV-1. A phase I, double-blind, randomized, placebo-controlled trial was conducted in twenty-four healthy HIV-uninfected young women. The study objectives were to assess the safety, tolerability and immunogenicity of virosomes harboring surface HIV-1 gp41-derived P1 lipidated peptides (MYM-V101. Participants received placebo or MYM-V101 vaccine at 10 μg/dose or 50 μg/dose intramuscularly at week 0 and 8, and intranasally at week 16 and 24. MYM-V101 was safe and well-tolerated at both doses administered by the intramuscular and intranasal routes, with the majority of subjects remaining free of local and general symptoms. P1-specific serum IgGs and IgAs were induced in all high dose recipients after the first injection. After the last vaccination, vaginal and rectal P1-specific IgGs could be detected in all high dose recipients. Approximately 63% and 43% of the low and high dose recipients were respectively tested positive for vaginal P1-IgAs, while 29% of the subjects from the high dose group tested positive for rectal IgAs. Serum samples had total specific IgG and IgA antibody concentrations ≥ 0.4 μg/mL, while mucosal samples were usually below 0.01 μg/mL. Vaginal secretions from MYM-V101 vaccinated subjects were inhibiting HIV-1 transcytosis but had no detectable neutralizing activity. P1-specific Th1 responses could not be detected on PBMC. This study demonstrates the excellent safety and tolerability of MYM-V101, eliciting systemic and mucosal antibodies in the majority of subjects. Vaccine-induced mucosal anti-gp41 antibodies toward conserved gp41 motifs were harboring HIV-1 transcytosis inhibition activity and may contribute to reduce sexually-transmitted HIV-1.ClinicalTrials.gov NCT01084343.

  1. Exploring resilience in rural GP registrars--implications for training.

    Science.gov (United States)

    Walters, Lucie; Laurence, Caroline O; Dollard, Joanne; Elliott, Taryn; Eley, Diann S

    2015-07-02

    Resilience can be defined as the ability to rebound from adversity and overcome difficult circumstances. General Practice (GP) registrars face many challenges in transitioning into general practice, and additional stressors and pressures apply for those choosing a career in rural practice. At this time of international rural generalist medical workforce shortages, it is important to focus on the needs of rural GP registrars and how to support them to become resilient health care providers. This study sought to explore GP registrars' perceptions of their resilience and strategies they used to maintain resilience in rural general practice. In this qualitative interpretive research, semi-structured interviews were recorded, transcribed and analysed using an inductive approach. Initial coding resulted in a coding framework which was refined using constant comparison and negative case analysis. Authors developed consensus around the final conceptual model. Eighteen GP registrars from: Australian College of Rural and Remote Medicine Independent Pathway, and three GP regional training programs with rural training posts. Six main themes emerged from the data. Firstly, rural GP registrars described four dichotomous tensions they faced: clinical caution versus clinical courage; flexibility versus persistence; reflective practice versus task-focused practice; and personal connections versus professional commitment. Further themes included: personal skills for balance which facilitated resilience including optimistic attitude, self-reflection and metacognition; and finally GP registrars recognised the role of their supervisors in supporting and stretching them to enhance their clinical resilience. Resilience is maintained as on a wobble board by balancing professional tensions within acceptable limits. These limits are unique to each individual, and may be expanded through personal growth and professional development as part of rural general practice training.

  2. The teaching of physical assessment skills in pre-registration nursing programmes in Australia: issues for nursing education.

    Science.gov (United States)

    Birks, Melanie; James, Ainsley; Chung, Catherine; Cant, Robyn; Davis, Jenny

    2014-01-01

    Health assessment is a fundamental aspect of the professional nursing role. The teaching of skills in physical assessment is therefore a large component of pre-registration nursing programmes. As the nursing curriculum becomes more crowded with what is deemed to be essential content, there is a need to rationalise what is taught in preparatory nursing programmes to ensure readiness for practice. The study outlined in this paper, as part of a larger project, explored the teaching of physical assessment skills in pre-registration nursing programmes across Australia. Fifty-three academics completed the 121 item online survey, indicating whether each skill was taught with practice, taught with no practice or not taught at all. The results suggest that only half the skills were being taught by more than 80% of the academics and 23 skills (19%) were taught by more than 90%. Of the 121 skills commonly taught--69 skills (57%) were taught with student practice and 29 (24%) were taught with no student practice. The results of this study raise questions about the teaching of physical assessment in pre-registration nursing programmes. The suggestion is not that skills that are used regularly or infrequently should be removed from the curriculum, rather, the authors propose that consideration be given to whether the teaching of skills that are never likely to be used is occurring at the expense of comprehensive mastery of core skills.

  3. A multi-system approach assessing the interaction of anticonvulsants with P-gp.

    Directory of Open Access Journals (Sweden)

    David Dickens

    Full Text Available 30% of epilepsy patients receiving antiepileptic drugs (AEDs are not fully controlled by therapy. The drug transporter hypothesis for refractory epilepsy proposes that P-gp is over expressed at the epileptic focus with a role of P-gp in extruding AEDs from the brain. However, there is controversy regarding whether all AEDs are substrates for this transporter. Our aim was to investigate transport of phenytoin, lamotrigine and carbamazepine by using seven in-vitro transport models. Uptake assays in CEM/VBL cell lines, oocytes expressing human P-gp and an immortalised human brain endothelial cell line (hCMEC/D3 were carried out. Concentration equilibrium transport assays were performed in Caco-2, MDCKII ±P-gp and LLC-PK1±P-gp in the absence or presence of tariquidar, an inhibitor of P-gp. Finally, primary porcine brain endothelial cells were used to determine the apparent permeability (Papp of the three AEDs in the absence or presence of P-gp inhibitors. We detected weak transport of phenytoin in two of the transport systems (MDCK and LLC-PK1 cells transfected with human P-gp but not in the remaining five. No P-gp interaction was observed for lamotrigine or carbamazepine in any of the seven validated in-vitro transport models. Neither lamotrigine nor carbamazepine was a substrate for P-gp in any of the model systems tested. Our data suggest that P-gp is unlikely to contribute to the pathogenesis of refractory epilepsy through transport of carbamazepine or lamotrigine.

  4. [Analysis of a Family-centred Care Programme with Follow-up Home-visits in Neonatology - In Times of the Directive from G-BA].

    Science.gov (United States)

    Hüning, B M; Reimann, M; Sahlmen, S; Leibold, S; Nabring, J C; Felderhoff-Müser, U

    2016-07-01

    Marked progress in neonatology changed care of very preterm infants (VLBW) over the last decades - but also the attitude towards family-centred care (FCC). With the directive of the German Federal Joined Committee (G-BA), politicians recognize the necessity of neonatal FCC. To evaluate time and personnel costs necessary at a centre of established FCC. Elternberatung "Frühstart" is a FCC programme for VLBW and seriously ill neonates from preganancy at risk to follow-up home-visits delivered by one interdisciplinary team. Analysis (2011-2014): 1.) Number of cases /participation in programme, 2.) resources of time, 3) and personnel, 4.) funding, 5) economic impact. 1.1.2011-31.12.2014: 441 cases (total cases: 2 212) participated in the programme. Participation of VLBW: mean 92% (86.4-97,2%). Costs of time are highest in neonates with congenital malformations: median 13.8 h, VLBW: median 11,2 h. Transition to home is most time intensive: median 7,3 (0-42.5) h. In average of 3.1 full-time nurses (part-time workers) are able to counsel 48 families/quarter. In severe cases funding is partly provided by health care insurances for social medical aftercare: positive applications: mean 92.7% (79.6-97.7%). Participation in the FCC programme in neonatology is high and costs of time are manageable. © Georg Thieme Verlag KG Stuttgart · New York.

  5. Progress with Implementing Energy Efficiency Policies in the G8

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-07-01

    At the 2008 G8 Summit in Hokkaido, leaders reaffirmed the critical role improved energy efficiency can play in addressing energy security, environmental and economic objectives. They went even farther than in previous Summits and committed to maximising implementation of the 25 IEA energy efficiency recommendations prepared for the G8. The imperative to enhance energy efficiency remains a priority for all countries. To support governments with their implementation of energy efficiency, the IEA recommended the adoption of a broad range of specific energy efficiency policy measures to the G8 Summits in 2006, 2007 and 2008. The consolidated set of recommendations from these Summits covers 25 fields of action across seven priority areas: cross-sectoral activity, buildings, appliances, lighting, transport, industry and power utilities. If governments want to significantly improve energy efficiency, the IEA considers that no single policy implemented in isolation will be effective at achieving this aim. The IEA Secretariat recommends that governments implement a full set of appropriate measures. The IEA estimates that if implemented globally without delay, the proposed actions could save around 8.2 GtCO2/yr by 2030 -- equivalent to twice the EU's yearly emissions. This report evaluates the progress of the G8 countries in implementing energy efficiency policy, including the 25 G8/IEA recommendations. Information in this report is current up to 31 March 2009.

  6. Development of a novel, guinea pig-specific IFN-γ ELISPOT assay and characterization of guinea pig cytomegalovirus GP83-specific cellular immune responses following immunization with a modified vaccinia virus Ankara (MVA)-vectored GP83 vaccine.

    Science.gov (United States)

    Gillis, Peter A; Hernandez-Alvarado, Nelmary; Gnanandarajah, Josephine S; Wussow, Felix; Diamond, Don J; Schleiss, Mark R

    2014-06-30

    The guinea pig (Cavia porcellus) provides a useful animal model for studying the pathogenesis of many infectious diseases, and for preclinical evaluation of vaccines. However, guinea pig models are limited by the lack of immunological reagents required for characterization and quantification of antigen-specific T cell responses. To address this deficiency, an enzyme-linked immunospot (ELISPOT) assay for guinea pig interferon (IFN)-γ was developed to measure antigen/epitope-specific T cell responses to guinea pig cytomegalovirus (GPCMV) vaccines. Using splenocytes harvested from animals vaccinated with a modified vaccinia virus Ankara (MVA) vector encoding the GPCMV GP83 (homolog of human CMV pp65 [gpUL83]) protein, we were able to enumerate and map antigen-specific responses, both in vaccinated as well as GPCMV-infected animals, using a panel of GP83-specific peptides. Several potential immunodominant GP83-specific peptides were identified, including one epitope, LGIVHFFDN, that was noted in all guinea pigs that had a detectable CD8+ response to GP83. Development of a guinea pig IFN-γ ELISPOT should be useful in characterization of additional T cell-specific responses to GPCMV, as well as other pathogens. This information in turn can help focus future experimental evaluation of immunization strategies, both for GPCMV as well as for other vaccine-preventable illnesses studied in the guinea pig model. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Fusion technology programme

    International Nuclear Information System (INIS)

    Finken, D.

    1984-04-01

    KfK participates to the Fusion Technology Programme of the European Community. Most of the work in progress addresses the Next European Torus (NET) and the long term technology aspects as defined in the 82/86 programme. A minor part serves to preparation of future contributions and to design studies on fusion concepts in a wider perspective. The Fusion Technology Programme of Euratom covers mainly aspects of nuclear engineering. Plasma engineering, heating, refueling and vacuum technology are at present part of the Physics Programme. In view of NET, integration of the different areas of work will be mandatory. KfK is therefore prepared to address technical aspects beyond the actual scope of the physics experiments. The technology tasks are reported project wise under title and code of the Euratom programme. Most of the projects described here are shared with other European fusion laboratories as indicated in the table annexed to this report. (orig./GG)

  8. The Nuclotron-based Ion Collider Facility Project. The Physics Programme for the Multi-Purpose Detector

    Science.gov (United States)

    Geraksiev, N. S.; MPD Collaboration

    2018-05-01

    The Nuclotron-based Ion Collider fAcility (NICA) is a new accelerator complex being constructed at the Joint Institute for Nuclear Research (JINR). The general objective of the project is to provide beams for the experimental study of hot and dense strongly interacting QCD matter. The heavy ion programme includes two planned detectors: BM@N (Baryonic Matter at Nuclotron) a fixed target experiment with extracted Nuclotron beams; and MPD (MultiPurpose Detector) a collider mode experiment at NICA. The accelerated particles can range from protons and light nuclei to gold ions. Beam energies will span\\sqrt{s}=12-27 GeV with luminosity L ≥ 1 × 1030 cm‑2s‑1 and \\sqrt{{s}NN}=4-11 GeV and average luminosity L = 1 × 1027cm‑2 s ‑1(for 197Au79+), respectively. A third experiment for spin physics is planned with the SPD (Spin Physics Detector) at the NICA collider in polarized beams mode. A brief overview of the MPD is presented along with several observables in the MPD physics programme.

  9. Screening and Identification of ssDNA Aptamer for Human GP73

    Directory of Open Access Journals (Sweden)

    Jingchun Du

    2015-01-01

    Full Text Available As one tumor marker of HCC, Golgi Protein 73 (GP73 is given more promise in the early diagnosis of HCC, and aptamers have been developed to compete with antibodies as biorecognition probes in different detection system. In this study, we utilized GP73 to screen specific ssDNA aptamers by SELEX technique. First, GP73 proteins were expressed and purified by prokaryotic expression system and Nickle ion affinity chromatography, respectively. At the same time, the immunogenicity of purified GP73 was confirmed by Western blotting. The enriched ssDNA library with high binding capacity for GP73 was obtained after ten rounds of SELEX. Then, thirty ssDNA aptamers were sequenced, in which two ssDNA aptamers with identical DNA sequence were confirmed, based on the alignment results, and designated as A10-2. Furthermore, the specific antibody could block the binding of A10-2 to GP73, and the specific binding of A10-2 to GP73 was also supported by the observation that several tumor cell lines exhibited variable expression level of GP73. Significantly, the identified aptamer A10-2 could distinguish normal and cancerous liver tissues. So, our results indicate that the aptamer A10-2 might be developed into one molecular probe to detect HCC from normal liver specimens.

  10. The Low Energy Antiproton Ring (LEAR) some months before the start of its particle physics programme

    CERN Multimedia

    1983-01-01

    LEAR [see e.g.: H.Koziol and D. Möhl, Phys. Rep. 403-404 (2004), p.271 and references therein] and its enclosure in the PS South Hall in Jan, 1983, 4 months before the start of its particle physics programme. Visible (in red) are the 90 degree bending magnets consisting of 6 blocks each. Separated from the magnets by short straight sections are the quadrupole doublets (blue with read end-plates). The 4 long straight sections house large equipment like septa for injection/ejection, RF-cavities and later (since 1986) electron cooling and an internal target and its associated detector (JETSET experiment). Two small copper tubes spanning across the ring are coaxial lines transmitting the stochastic cooling signals from pick up to kicker. (see also photos 8205747X, 8207133, 8207541X, 8301550X,8309026X)

  11. Phytosterol Feeding Causes Toxicity in ABCG5/G8 Knockout Mice

    Science.gov (United States)

    McDaniel, Allison L.; Alger, Heather M.; Sawyer, Janet K.; Kelley, Kathryn L.; Kock, Nancy D.; Brown, J. Mark; Temel, Ryan E.; Rudel, Lawrence L.

    2014-01-01

    Plant sterols, or phytosterols, are very similar in structure to cholesterol and are abundant in typical diets. The reason for poor absorption of plant sterols by the body is still unknown. Mutations in the ABC transporters G5 and G8 are known to cause an accumulation of plant sterols in blood and tissues (sitosterolemia). To determine the significance of phytosterol exclusion from the body, we fed wild-type and ABCG5/G8 knockout mice a diet enriched with plant sterols. The high-phytosterol diet was extremely toxic to the ABCG5/G8 knockout mice but had no adverse effects on wild-type mice. ABCG5/G8 knockout mice died prematurely and developed a phenotype that included high levels of plant sterols in many tissues, liver abnormalities, and severe cardiac lesions. This study is the first to report such toxic effects of phytosterol accumulation in ABCG5/G8 knockout mice. We believe these new data support the conclusion that plant sterols are excluded from the body because they are toxic when present at high levels. PMID:23380580

  12. The I.A.G. / A.I.G. SEDIBUD (Sediment Budgets in Cold Environments) Programme: Current and future activities

    Science.gov (United States)

    Beylich, Achim A.; Lamoureux, Scott; Decaulne, Armelle

    2013-04-01

    Projected climate change in cold regions is expected to alter melt season duration and intensity, along with the number of extreme rainfall events, total annual precipitation and the balance between snowfall and rainfall. Similarly, changes to the thermal balance are expected to reduce the extent of permafrost and seasonal ground frost and increase active layer depths. These effects will undoubtedly change surface environments in cold regions and alter the fluxes of sediments, nutrients and solutes, but the absence of quantitative data and coordinated geomorphic process monitoring and analysis to understand the sensitivity of the Earth surface environment is acute in cold climate environments. The International Association of Geomorphologists (I.A.G. / A.I.G. ) SEDIBUD (Sediment Budgets in Cold Environments) Programme was formed in 2005 to address this existing key knowledge gap. SEDIBUD currently has about 400 members worldwide and the Steering Committee of this international programme is composed of ten scientists from eight different countries: Achim A. Beylich (Chair) (Norway), Armelle Decaulne (Secretary) (France), John C. Dixon (USA), Scott F. Lamoureux (Vice-Chair) (Canada), John F. Orwin (Canada), Jan-Christoph Otto (Austria), Irina Overeem (USA), Thorsteinn Sæmundsson (Iceland), Jeff Warburton (UK) and Zbigniew Zwolinski (Poland). The central research question of this global group of scientists is to: Assess and model the contemporary sedimentary fluxes in cold climates, with emphasis on both particulate and dissolved components. Initially formed as European Science Foundation (ESF) Network SEDIFLUX (Sedimentary Source-to-Sink Fluxes in Cold Environments) (2004 - ), SEDIBUD has further expanded to a global group of researchers with field research sites located in polar and alpine regions in the northern and southern hemisphere. Research carried out at each of the close to 50 defined SEDIBUD key test sites varies by programme, logistics and available

  13. Selection of GP. Mur antigen-negative RBC for blood recipients with anti-'Mia ' records decreases transfusion reaction rates in Taiwan.

    Science.gov (United States)

    Yang, C-A; Lin, J-A; Chang, C-W; Wu, K-H; Yeh, S-P; Ho, C-M; Chang, J-G

    2016-10-01

    To evaluate the clinical significance of GP. Mur antigen-negative blood selection for transfusion in patients with anti-'Mi a ' records. The GP. Mur RBC phenotype is prevalent (7·3%) in Taiwan. Antibodies against GP. Mur (anti-'Mi a ') are identified in 1·24% of our population, and anti-'Mi a ' screening using GP. Mur RBC has been routine for Taiwan's blood banks. However, due to the lack of commercial antibodies, only cross-matching was used to prevent transfusion of GP. Mur-positive blood to patients with anti-'Mi a ' in most hospitals. There is still a risk of GP. Mur-positive RBC exposure and subsequent anti-'Mi a '-related transfusion reactions. Since February 2014, GP. Mur antigen-negative RBCs identified by reaction with anti-'Mi a '-positive serum were selected for blood recipients with anti-'Mi a ' records. The transfusion reactions between January 2013 and January 2014 were compared with those that occurred between February 2014 and July 2015. The transfusion reaction rate was significantly higher in anti-'Mi a '-positive blood recipients compared to total subjects receiving an RBC transfusion before GP. Mur-negative donor RBC selection. After antigen-negative RBC selection, the transfusion reaction frequency in subjects with anti-'Mi a ' became similar to total blood recipients. IgG form anti-'Mi a ' antibodies were present in all cases of probable anti-'Mi a '-related transfusion reactions. The time required for anti-'Mi a ' boosting after transfusion was around 4-21 days. Selection of GP. Mur-negative RBC for transfusion to patients with anti-'Mi a ' records could decrease the rate of transfusion reaction and antibody boosting. This procedure should be incorporated into blood bank routines in areas where anti-'Mi a ' is prevalent. © 2016 British Blood Transfusion Society.

  14. 16 CFR Appendix G8 to Part 305 - Boilers-Electric

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Boilers-Electric G8 Appendix G8 to Part 305 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS RULE CONCERNING... Part 305—Boilers—Electric Manufacturer's rated heating capacities (Btu's/hr.) Range of annual fuel...

  15. Extending an Afrikaans pronunciation dictionary using Dutch resources and P2P/GP2P

    CSIR Research Space (South Africa)

    Loots, L

    2010-11-01

    Full Text Available . This is compared to the more common approach of extending the Afrikaans dictionary by means of graphemeto-phoneme (G2P) conversion. The results indicate that the Afrikaans pronunciations obtained by P2P and GP2P from the Dutch dictionary are more accurate than...

  16. Suitability of FIFA’s “The 11” Training Programme for Young Football Players – Impact on Physical Performance

    Science.gov (United States)

    Kilding, Andrew E; Tunstall, Helen; Kuzmic, Dejan

    2008-01-01

    There is a paucity of evidence regarding the use of injury prevention programmes for preadolescents participating in sport. “The 11 ”injury prevention programme was developed by FIFA’s medical research centre (F-MARC) to help reduce the risk of injury in football players aged 14 years and over. The aim of this study was to determine the suitability and effectiveness of “The 11 ”for younger football players. Twenty-four [12 experimental (EXP), 12 control (CON)] young football players (age 10.4 ± 1.4 yr) participated. The EXP group followed “The 11 ”training programme 5 days per week, for 6 weeks, completing all but one of the 10 exercises. Prior to, and after the intervention, both EXP and CON groups performed a battery of football-specific physical tests. Changes in performance scores within each group were compared using independent t-tests (p ≤ 0.05). Feedback was also gathered on the young players’ perceptions of “The 11”. No injuries occurred during the study in either group. Compliance to the intervention was 72%. Measures of leg power (3 step jump and counter-movement jump) increased significantly (3.4 and 6.0% respectively, p football players, for both physical development and potential injury prevention purposes, as well as to promote fair play. To further engage young football players in such a programme, some modification to “The 11 ”should be considered. Key pointsChildren who participate in recreational and competitive sports, especially football, are susceptible to injury.There is a need for the design and assessment of injury prevention programmes for children.The 11 ”improves essential physical performance characteristics and has the potential to reduce the risk of injury.It may be prudent to implement a ‘child-friendly’ version of “The 11”, to enhance long-term programme adherence and to ensure progressive physical development of players. PMID:24149898

  17. Does outpatient physical therapy with the aim of improving health-related physical fitness influence the level of physical activity in patients with long-term musculoskeletal conditions?

    Science.gov (United States)

    Holm, I; Tveter, A T; Moseng, T; Dagfinrud, H

    2015-09-01

    To evaluate any change in self-reported level of physical activity in patients receiving a general physical exercise programme in addition to disease-specific physiotherapy treatment. Pre-post-intervention study. Outpatient physiotherapy clinics. One hundred and ninety patients with long-term musculoskeletal conditions attending outpatient physiotherapy were recruited from seven physiotherapy clinics. Physiotherapy including disease-specific modalities and a general individually tailored exercise programme. Patients were evaluated at baseline and at the end of the programme. International Physical Activity Questionnaire short form (IPAQ-sf) and COOP WONCA functional assessment charts. Forty-two patients were excluded from the analysis because they did not complete the IPAQ-sf correctly or dropped out during the treatment period. There was a significant increase in the number of metabolic equivalent task (MET)-min/week for vigorous and moderate-intensity activities, walking and total physical activity. The number of exercise sessions per week increased from 1.8 [standard deviation (SD) 0.9] to 2.2 (SD 1.2) (P=0.001). The proportion of patients with a low level of physical activity decreased by 12%, and the proportion of the participants who did not/could not exercise decreased from 26% to 8%. The COOP WONCA charts showed significant improvements in the physical fitness, feelings, daily activities and social activities items. A significant increase was found in the number of MET-min/week for all activity levels. Therefore, a general physical exercise programme initiated by a physiotherapist led to a positive change in level of physical activity. Copyright © 2014 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

  18. Teaching Personal and Social Responsibility Model-Based Programmes in Physical Education: A Systematic Review

    Science.gov (United States)

    Pozo, Pablo; Grao-Cruces, Alberto; Pérez-Ordás, Raquel

    2018-01-01

    The purpose of this study was to conduct a review of research on the Teaching Personal and Social Responsibility model-based programme within physical education. Papers selected for analysis were found through searches of Web of Science, SportDiscus (EBSCO), SCOPUS, and ERIC (ProQuest) databases. The keywords "responsibility model" and…

  19. A complete solution for GP-B's gyroscopic precession by retarded gravitational theory

    Science.gov (United States)

    Tang, Keyun

    Mainstream physicists generally believe that Mercury’s Perihelion precession and GP-B’ gyroscopic precession are two of the strongest evidences supporting Einstein’ curved spacetime and general relativity. However, most classical literatures and textbooks (e.g. Ohanain: Gravitation and Spacetime) paint an incorrect picture of Mercury’s orbit anomaly, namely Mercury’s perihelion precessed 43 arc-seconds per century; a correct picture should be that Mercury rotated 43 arc-seconds per century more than along Newtonian theoretical orbit. The essence of Le Verrier’s and Newcomb’s observation and analysis is that the angular speed of Mercury is slightly faster than the Newtonian theoretical value. The complete explanation to Mercury’s orbit anomaly should include two factors, perihelion precession is one of two factors, in addition, the change of orbital radius will also cause a change of angular speed, which is another component of Mercury's orbital anomaly. If Schwarzschild metric is correct, then the solution of the Schwarzschild orbit equation must contain three non-ignorable items. The first corresponds to Newtonian ellipse; the second is a nonlinear perturbation with increasing amplitude, which causes the precession of orbit perihelion; this is just one part of the angular speed anomaly of Mercury; the third part is a linear perturbation, corresponding to a similar figure of the Newton's ellipse, but with a minimal radius; this makes no contribution to the perihelion precession of the Schwarzschild orbit, but makes the Schwarzschild orbital radius slightly smaller, leading to a slight increase in Mercury’s angular speed. All classical literatures of general relativity ignored this last factor, which is a gross oversight. If you correctly take all three factors into consideration, the final result is that the difference between the angles rotated along Schwarzschild’s orbit and the angle rotated along Newton’s orbit for one hundred years should

  20. Extracellular biosynthesis of silver nanoparticles using Bacillus sp. GP-23 and evaluation of their antifungal activity towards Fusarium oxysporum

    Science.gov (United States)

    Gopinath, V.; Velusamy, P.

    2013-04-01

    In last few decades nanoparticles have attracted and emerged as a field in biomedical research due to their incredible applications. The current research was focused on extracellular synthesis of silver nanoparticles (AgNPs) using cell free culture supernatant of strain GP-23. It was found that the strain GP-23 belonged to Bacillus species by 16S rRNA sequence analysis. Biosynthesis of AgNPs was achieved by addition of culture supernatant with aqueous silver nitrate solution, after 24 h it turned to brown color solution with a peak at 420 nm corresponding to the Plasmon absorbance of AgNPs by UV-Vis Spectroscopy. The nanoparticles were characterized by FTIR, XRD, HRTEM, EDX and AFM. The synthesized nanoparticles were found to be spherical in shape with size in the range of 7-21 nm. It was stable in aqueous solution for five months period of storage at room temperature under dark condition. The biosynthesized AgNPs exhibited strong antifungal activity against plant pathogenic fungus, Fusarium oxysporum at the concentration of 8 μg ml-1. The results suggest that the synthesized AgNPs act as an effective antifungal agent/fungicide.

  1. The major surface glycoprotein (gp63) from Leishmania major and Leishmania donovani cleaves CD4 molecules on human T cells

    DEFF Research Database (Denmark)

    Hey, A S; Theander, T G; Hviid, L

    1994-01-01

    The effect of Leishmania major and L. donovani surface protease gp63 on surface markers on human T cells was studied using fluorescence-activated flow cytometry. Purified gp63 (63,000 m.w. glycoprotein) at concentrations above 10 micrograms/ml completely inhibited binding of six different anti-CD4......-expression of CD4, reaching 50% of the initial level after 72 h of incubation in medium. Preincubation of cells with live promastigotes showed an inhibitory effect on CD4 comparable to that seen with purified gp63. The binding of Abs directed against other surface markers present on human T-cells--CD2, CD3, CD5......, CD8, CD11A, CD25, CD45RO, CD45RA, CD58, TCR-alpha, TCR-gamma, and HLA DQ--was not inhibited by gp63. These data suggest that gp63, both in its purified form and in the form anchored to the parasite membrane, cleaves CD4 on human T cells. The cleavage of CD4 by the protease might play a role...

  2. A study of the National Physical Laboratory microdosimetry research programme in collaboration with the University of Leeds

    International Nuclear Information System (INIS)

    Menzel, H.G.

    1987-11-01

    A study of the present programme of work carried out by the National Physical Laboratory and the University of Leeds, has been carried out. The study is based on the use of the tissue-equivalent proportional counter in microdosimetic techniques in radiation protection for monoenergetic neutrons or reference radionuclide neutron sources. This report comments on the programme as a whole and provides recommendations for future research work, taking into account the research programmes carried out at other institutions. It also attempts to summarise the present state of knowledge and experience associated with the application of this technique to radiation fields met in routine radiation protection. (author)

  3. FERMI LARGE AREA TELESCOPE OBSERVATIONS OF THE SUPERNOVA REMNANT G8.7–0.1

    International Nuclear Information System (INIS)

    Ajello, M.; Allafort, A.; Bechtol, K.; Berenji, B.; Blandford, R. D.; Bloom, E. D.; Borgland, A. W.; Buehler, R.; Cameron, R. A.; Baldini, L.; Bellazzini, R.; Bregeon, J.; Ballet, J.; Barbiellini, G.; Bastieri, D.; Buson, S.; Bonamente, E.; Brigida, M.; Bruel, P.; Caliandro, G. A.

    2012-01-01

    We present a detailed analysis of the GeV gamma-ray emission toward the supernova remnant (SNR) G8.7–0.1 with the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope. An investigation of the relationship between G8.7–0.1 and the TeV unidentified source HESS J1804–216 provides us with an important clue on diffusion process of cosmic rays if particle acceleration operates in the SNR. The GeV gamma-ray emission is extended with most of the emission in positional coincidence with the SNR G8.7–0.1 and a lesser part located outside the western boundary of G8.7–0.1. The region of the gamma-ray emission overlaps spatially connected molecular clouds, implying a physical connection for the gamma-ray structure. The total gamma-ray spectrum measured with LAT from 200 MeV-100 GeV can be described by a broken power-law function with a break of 2.4 ± 0.6 (stat) ± 1.2 (sys) GeV, and photon indices of 2.10 ± 0.06 (stat) ± 0.10 (sys) below the break and 2.70 ± 0.12 (stat) ± 0.14 (sys) above the break. Given the spatial association among the gamma rays, the radio emission of G8.7–0.1, and the molecular clouds, the decay of π 0 s produced by particles accelerated in the SNR and hitting the molecular clouds naturally explains the GeV gamma-ray spectrum. We also find that the GeV morphology is not well represented by the TeV emission from HESS J1804–216 and that the spectrum in the GeV band is not consistent with the extrapolation of the TeV gamma-ray spectrum. The spectral index of the TeV emission is consistent with the particle spectral index predicted by a theory that assumes energy-dependent diffusion of particles accelerated in an SNR. We discuss the possibility that the TeV spectrum originates from the interaction of particles accelerated in G8.7–0.1 with molecular clouds, and we constrain the diffusion coefficient of the particles.

  4. Adherence to COPD guidelines in general practice: impact of an educational programme delivered on location in Danish general practices.

    Science.gov (United States)

    Ulrik, Charlotte Suppli; Sørensen, Tina Brandt; Højmark, Torben Brunse; Olsen, Kim Rose; Vedsted, Peter

    2013-03-01

    The general practitioner (GP) is often the first healthcare contact for patients with chronic obstructive pulmonary disease (COPD). To determine whether participating in a standardised educational programme delivered in the GP's own practice is associated with adherence to COPD guidelines. A nationwide register-based observational before and after study was undertaken with a control group of propensity-matched practices (follow-up period 6 months). COPD was defined as age 40+ years and at least two prescriptions for inhaled medication. The educational programme consisted of a 3-hr teaching lesson with a respiratory specialist and five visits by a representative from the sponsoring pharmaceutical company focusing on assessment and management of patients including written algorithms. A one-to-one propensity-matched control group of practices was selected. Register data were used to compare the rate of spirometry testing, preventive consultations, and influenza vaccinations provided to COPD patients and the rate of spirometry testing in non-COPD individuals, assumed to reflect diagnostic activity. Data for 102 participating GP practices were analysed. Participating clinics had a significant increase in preventive consultations and influenza vaccinations (peducation of GPs and their staff delivered in the GPs' own practices may improve adherence to COPD guidelines, not least for clinics with a high potential for improvement.

  5. Adapted yoga to improve physical function and health-related quality of life in physically-inactive older adults: a randomised controlled pilot trial.

    Science.gov (United States)

    Tew, Garry A; Howsam, Jenny; Hardy, Matthew; Bissell, Laura

    2017-06-23

    Yoga is a holistic therapy of expanding popularity, which has the potential to produce a range of physical, mental and social benefits. This trial evaluated the feasibility and effects of an adapted yoga programme on physical function and health-related quality of life in physically-inactive older adults. In this randomised controlled pilot trial, 52 older adults (90% female; mean age 74.8 years, SD 7.2) were randomised 1:1 to a yoga programme or wait-list control. The yoga group (n = 25) received a physical activity education booklet and were invited to attend ten yoga sessions during a 12-week period. The control group (n = 27) received the education booklet only. Measures of physical function (e.g., Short Physical Performance Battery; SPPB), health status (EQ-5D) and mental well-being (Warwick-Edinburgh Mental Well-being Scale; WEMWBS) were assessed at baseline and 3 months. Feasibility was assessed using course attendance and adverse event data, and participant interviews. Forty-seven participants completed follow-up assessments. Median class attendance was 8 (range 3 to 10). At the 3-month follow-up, the yoga group had a higher SPPB total score compared with the control group (mean difference 0.9, 95% confidence interval [CI] -0.3 to 2.0), a faster time to rise from a chair five times (mean difference - 1.73 s, 95% CI -4.08 to 0.62), and better performance on the chair sit-and-reach lower-limb flexibility test (mean difference 5 cm, 95% CI 0 to 10). The yoga group also had superior health status and mental well-being (vs. control) at 3 months, with mean differences in EQ-5D and WEMWBS scores of 0.12 (95% CI, 0.03 to 0.21) and 6 (95% CI, 1 to 11), respectively. The interviews indicated that participants valued attending the yoga programme, and that they experienced a range of benefits. The adapted yoga programme appeared to be feasible and potentially beneficial in terms of improving mental and social well-being and aspects of physical function in

  6. Administration of sulfosuccinimidyl-4-[N-maleimidomethyl] cyclohexane-1-carboxylate conjugated GP10025–33 peptide-coupled spleen cells effectively mounts antigen-specific immune response against mouse melanoma

    International Nuclear Information System (INIS)

    Chang, Xiaoli; Xia, Chang-Qing

    2015-01-01

    It remains a top research priority to develop immunotherapeutic approaches to induce potent antigen-specific immune responses against tumors. However, in spite of some promising results, most strategies are ineffective because they generate low numbers of tumor-reactive cytotoxic T lymphocytes (CTLs). Here we designed a strategy to enhance antigen-specific immune response via administering sulfosuccinimidyl-4-[N-maleimidomethyl] cyclohexane-1-carboxylate (sulfo-SMCC)-conjugated melanoma tumor antigen GP100 25–33 peptide-coupled syngeneic spleen cells in a mouse model of melanoma. We found that infusion of GP100 25–33 peptide-coupled spleen cells significantly attenuated the growth of melanoma in prophylactic and therapeutic immunizations. Consistent with these findings, the adoptive transfer of spleen cells from immunized mice to naïve syngeneic mice was able to transfer anti-tumor effect, suggesting that GP100 25–33 peptide-specific immune response was induced. Further studies showed that, CD8+ T cell proliferation and the frequency of interferon (IFN)-γ-producing CD8+ T cells upon ex vivo stimulation by GP100 25–33 were significantly increased compared to control groups. Tumor antigen, GP100 25–23 specific immune response was also confirmed by ELISpot and GP100-tetramer assays. This approach is simple, easy-handled, and efficiently delivering antigens to lymphoid tissues. Our study offers an opportunity for clinically translating this approach into tumor immunotherapy. - Highlights: • Infusion of GP100 25–33 -coupled spleen cells leads to potent anti-melanoma immunity. • GP100 25–33 -coupled spleen cell treatment induces antigen-specific IFN-γ-producing CD8 T cells. • This approach takes advantage of homing nature of immune cells.

  7. Comprehensive functional analysis of N-linked glycans on Ebola virus GP1.

    Science.gov (United States)

    Lennemann, Nicholas J; Rhein, Bethany A; Ndungo, Esther; Chandran, Kartik; Qiu, Xiangguo; Maury, Wendy

    2014-01-28

    Ebola virus (EBOV) entry requires the virion surface-associated glycoprotein (GP) that is composed of a trimer of heterodimers (GP1/GP2). The GP1 subunit contains two heavily glycosylated domains, the glycan cap and the mucin-like domain (MLD). The glycan cap contains only N-linked glycans, whereas the MLD contains both N- and O-linked glycans. Site-directed mutagenesis was performed on EBOV GP1 to systematically disrupt N-linked glycan sites to gain an understanding of their role in GP structure and function. All 15 N-glycosylation sites of EBOV GP1 could be removed without compromising the expression of GP. The loss of these 15 glycosylation sites significantly enhanced pseudovirion transduction in Vero cells, which correlated with an increase in protease sensitivity. Interestingly, exposing the receptor-binding domain (RBD) by removing the glycan shield did not allow interaction with the endosomal receptor, NPC1, indicating that the glycan cap/MLD domains mask RBD residues required for binding. The effects of the loss of GP1 N-linked glycans on Ca(2+)-dependent (C-type) lectin (CLEC)-dependent transduction were complex, and the effect was unique for each of the CLECs tested. Surprisingly, EBOV entry into murine peritoneal macrophages was independent of GP1 N-glycans, suggesting that CLEC-GP1 N-glycan interactions are not required for entry into this important primary cell. Finally, the removal of all GP1 N-glycans outside the MLD enhanced antiserum and antibody sensitivity. In total, our results provide evidence that the conserved N-linked glycans on the EBOV GP1 core protect GP from antibody neutralization despite the negative impact the glycans have on viral entry efficiency. Filovirus outbreaks occur sporadically throughout central Africa, causing high fatality rates among the general public and health care workers. These unpredictable hemorrhagic fever outbreaks are caused by multiple species of Ebola viruses, as well as Marburg virus. While filovirus

  8. Selection for Dutch postgraduate GP training; time for improvement

    NARCIS (Netherlands)

    Vermeulen, M.I.; Kuyvenhoven, M.M.; Zuithoff, N.P.; Tromp, F.; Graaf, Y. van der; Pieters, R.H.

    2012-01-01

    Background: In the Netherlands we select candidates for the postgraduate GP training by assessing personal qualities in interviews. Because of differences in the ratio of number of candidates and number of vacancies between the eight departments of GP training we questioned whether the risk of being

  9. Variation in ruminal in situ degradation of crude protein and starch from maize grains compared to in vitro gas production kinetics and physical and chemical characteristics.

    Science.gov (United States)

    Seifried, Natascha; Steingaß, Herbert; Schipprack, Wolfgang; Rodehutscord, Markus

    2016-10-01

    The objectives of this study were (1) to evaluate in situ ruminal dry matter (DM), crude protein (CP) and starch degradation characteristics and in vitro gas production (GP) kinetics using a set of 20 different maize grain genotypes and (2) to predict the effective degradation (ED) of CP and starch from chemical and physical characteristics alone or in combination with in vitro GP measurements. Maize grains were characterised by different chemical and physical characteristics. Ruminal in situ degradation was measured in three lactating Jersey cows. Ground grains (sieve size: 2 mm) were incubated in bags for 1, 2, 4, 8, 16, 24, 48 and 72 h. Bag residues were analysed for CP and starch content. Degradation kinetics was determined and the ED of DM, CP and starch calculated using a ruminal passage rate of 5%/h and 8%/h. The GP of the grains (sieve size: 1 mm) was recorded after 2, 4, 6, 8, 12, 24, 48 and 72 h incubation in buffered rumen fluid and fitted to an exponential equation to determine GP kinetics. Correlations and stepwise multiple linear regressions were evaluated for the prediction of ED calculated for a passage rate of 5%/h (ED5) for CP (EDCP5) and starch (EDST5). The in situ parameters and ED5 varied widely between genotypes with average values (±SD) of 64% ± 4.2, 62% ± 4.1 and 65% ± 5.2 for ED5 of DM, EDCP5 and EDST5 and were on average 10 percentage points lower for a passage rate of 8%/h. Degradation rates varied between 4.8%/h and 7.4%/h, 4.1%/h and 6.5%/h and 5.3%/h and 8.9%/h for DM, CP and starch, respectively. These rates were in the same range as GP rates (6.0-8.3%/h). The EDCP5 and EDST5 were related to CP concentration and could be evaluated in detail using CP fractions and specific amino acids. In vitro GP measurements and GP rates correlated well with EDCP5 and EDST5 and predicted EDCP5 and EDST5 in combination with the chemical characteristics of the samples. Equations can be used to obtain quick and cost effective information

  10. The Agency's Technical Co-operation programme with Cameroon, 1982-1992. Country programme summaries

    International Nuclear Information System (INIS)

    1992-01-01

    The country programme summary reported here is one in the series of such studies being undertaken of the Agency's TC programme with Member States. With $1.3 million of Agency support received, Cameroon ranks 68th among all recipients of technical assistance in the period 1958 through 1991. More than half of the assistance received during the past ten years has been provided in the form of equipment (61%), followed by expert services (24%) and training (15%). The best part of the resources were provided by the Technical Assistance and Co-operation Fund (90%); the remaining ten per cent were made available through extrabudgetary contributions (8%) and assistance in kind (2%). With regard to project disbursements by sector, the four major areas have been nuclear physics and chemistry (38%), agriculture (23%), nuclear medicine (14%) and hydrology (13%)

  11. Characterization of Human Colorectal Cancer MDR1/P-gp Fab Antibody

    Directory of Open Access Journals (Sweden)

    Xuemei Zhang

    2013-01-01

    Full Text Available In this study, the peptide sized 21 kDa covering P-gp transmembrane region was first prepared for generating a novel mouse monoclonal antibody Fab fragment with biological activity against multiple drug resistance protein P-gp21 by phage display technology. Phage-displayed antibody library prepared from mice spleen tissues was selected against the recombinant protein P-gp21 with five rounds of panning. A number of clones expressing Fab bound to P-gp21, showing neutralized activity in vitro, were isolated and screened by enzyme-linked immunosorbent assay based on its recognition properties to P-gp21 and human colorectal cancer tissue homogenate, resulting in identification of an optimal recombinant Fab clone (Number 29. Further characterization by recloning number 29 into an expression vector showed significant induction of the Fab antibody in the clone number 29 by Isopropyl β-D-1-thiogalactopyranoside (IPTG. After purified by HiTrap Protein L, the specificity of the Fab antibody to P-gp21 was also confirmed. Not only was the targeted region of this monoclonal Fab antibody identified as a 16-peptide epitope (ALKDKKELEGSGKIAT comprising residues 883–898 within the transmembrane (TM domain of human P-gp, but also the binding ability with it was verified. The clinical implication of our results for development of personalized therapy of colorectal cancer will be further studied.

  12. Preparation of physics commissioning of Mochovce units 3 and 4

    International Nuclear Information System (INIS)

    Sedlacek, M.; Chrapciak, V.

    2010-01-01

    The Project 'Mochovce Units 3 and 4 Completion' started in 2009 and it will be finished in 2013. VUJE, Inc. is one of the five main Project contractors for the Nuclear Island and it is responsible, inter alia, for Mochovce Units 3 and 4 commissioning. The commissioning of Units 3 and 4 includes the stages of Physics Commissioning and Power Commissioning. This paper deals with the preparation of Mochovce Units 3 and 4 Physics Commissioning. In the paper there is presented a preparation of some commissioning documents, e.g. 'Quality Assurance Programme', 'Commissioning Programme', 'Stage Programme for Physics Commissioning', 'Test working programmes', 'Neutron-physics characteristics for Physics and Power Commissioning', etc. The scope of Physics Commissioning is presented by list of tests. For assessment of tests results so-called three-level acceptance criteria will be applied: realization, design and safety criteria. In the paper there are also presented computer codes, which will be used for neutron-physics characteristics calculation and the fuel loading scheme for the reactor core of Mochovce Unit 3. (Authors)

  13. The National Programme of Stellar Physics. Assessment 2011-2014. Prospective 2015-2018

    International Nuclear Information System (INIS)

    Bontemps, Sylvain; Bouchy, Francois; Charbonnel, Corinne; Chieze, Jean-Pierre; Dessart, Luc; Dintrans, Boris; Dougados, Catherine; Josselin, Eric; Kervella, Pierre; Martins, Fabrice; Michel, Eric; Moraux, Estelle; Recio-Blanco, Alejandra; Ristorcelli, Isabelle; Reyle, Celine; Alecian, Evelyne; Bouchy, Francois; Ciardi, Andrea; Dintrans, Boris; Herpin, Fabrice; Jouve, Laurene; Lebreton, Yveline; Motte, Frederique; Nardetto, Nicolas; Robin, Annie; Royer, Frederic; Samadi, Reza

    2015-04-01

    After an introduction which outlines the role of stellar physics as a keystone of research in astrophysics, this report proposes a presentation of the operation of the French national programme of stellar physics (PNPS): status and general operation, annual operation, statistics of budget and calls for bids, scientific animation, education, communication, community census, assessment of projects and thesis. It presents an overview of priority research theses between 2011 and 2014, according to their theme: stellar formation and protoplanetary disks, stellar structure and evolutions, origin and impact of magnetism, and atmospheres, winds and mass loss. Transverse theses are also presented the same way for the same period, with the following themes: basic physics, numeric simulations. The last part presents prospectives in terms of events (colloquium), bodies (new scientific council), themes to be studied, operation (interdisciplinarity and interfaces), means, general recommendations, and strengths and weaknesses of the national community

  14. Transport inhibition of digoxin using several common P-gp expressing cell lines is not necessarily reporting only on inhibitor binding to P-gp.

    Directory of Open Access Journals (Sweden)

    Annie Albin Lumen

    Full Text Available We have reported that the P-gp substrate digoxin required basolateral and apical uptake transport in excess of that allowed by digoxin passive permeability (as measured in the presence of GF120918 to achieve the observed efflux kinetics across MDCK-MDR1-NKI (The Netherlands Cancer Institute confluent cell monolayers. That is, GF120918 inhibitable uptake transport was kinetically required. Therefore, IC50 measurements using digoxin as a probe substrate in this cell line could be due to inhibition of P-gp, of digoxin uptake transport, or both. This kinetic analysis is now extended to include three additional cell lines: MDCK-MDR1-NIH (National Institute of Health, Caco-2 and CPT-B2 (Caco-2 cells with BCRP knockdown. These cells similarly exhibit GF120918 inhibitable uptake transport of digoxin. We demonstrate that inhibition of digoxin transport across these cell lines by GF120918, cyclosporine, ketoconazole and verapamil is greater than can be explained by inhibition of P-gp alone. We examined three hypotheses for this non-P-gp inhibition. The inhibitors can: (1 bind to a basolateral digoxin uptake transporter, thereby inhibiting digoxin's cellular uptake; (2 partition into the basolateral membrane and directly reduce membrane permeability; (3 aggregate with digoxin in the donor chamber, thereby reducing the free concentration of digoxin, with concomitant reduction in digoxin uptake. Data and simulations show that hypothesis 1 was found to be uniformly acceptable. Hypothesis 2 was found to be uniformly unlikely. Hypothesis 3 was unlikely for GF120918 and cyclosporine, but further studies are needed to completely adjudicate whether hetero-dimerization contributes to the non-P-gp inhibition for ketoconazole and verapamil. We also find that P-gp substrates with relatively low passive permeability such as digoxin, loperamide and vinblastine kinetically require basolateral uptake transport over that allowed by +GF120918 passive permeability, while

  15. Effects of 8Ps of Services Marketing on Student Selection of Self-Financing Sub-Degree Programmes in Hong Kong

    Science.gov (United States)

    Lau, Melissa May Yee

    2016-01-01

    Purpose: The purpose of this paper is to investigate how the effects of 8Ps of services marketing affect students' selection of self-financing sub-degree programmes in Hong Kong. The factors that affect students' selection of self-financing sub-degree programmes have not been studied in higher education market of Hong Kong. This research is to…

  16. Identifying current training provision and future training needs in allergy available for UK general practice trainees: national cross-sectional survey of General Practitioner Specialist Training programme directors.

    Science.gov (United States)

    Ellis, Jayne; Rafi, Imran; Smith, Helen; Sheikh, Aziz

    2013-03-01

    There are ongoing concerns about the quality of care provision for allergy in primary care. To identify current training provision in allergy to GP trainees and to understand how this could be enhanced. A cross-sectional survey of GP Speciality Training (GPST) programme directors was undertaken. Programme directors of the 174 GPST schemes were sent an online questionnaire which was informed by the content of the Royal College of General Practitioners curriculum. Quantitative data were descriptively analysed and a thematic analysis was undertaken of free text responses. We obtained responses from 146 directors representing 106 training programmes. Responses indicated that two-thirds (62%, 95% CI 53.1 to 71.5) of programmes were providing at least some allergy training, with the remaining third stating that they either provided no training or were unsure. Overall, one-third (33%, 95% CI 22.7 to 42.2) of programme directors believed that all the relevant allergy-related curriculum requirements were being met. Where provided, this training was believed to be best for organ-specific allergic disorders but was thought to be poorer for systemic allergic disorders, particularly food allergy where 67% (95% CI 57.5 to 76.5) of respondents indicated that training was poor. There was considerable interest in increasing the allergy training provided, preferably through eLearning modules and problem-based learning materials supported by those with relevant specialist knowledge. This UK-wide survey has identified important gaps in the training of GP trainees in relation to allergy care. Addressing these gaps, particularly in the management of systemic allergic disorders, should help to improve delivery of primary care-based allergy care.

  17. Differences in serum IgA responses to HIV-1 gp41 in elite controllers compared to viral suppressors on highly active antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Rafiq Nabi

    Full Text Available Mechanisms responsible for natural control of human immunodeficiency type 1 (HIV replication in elite controllers (EC remain incompletely defined. To determine if EC generate high quality HIV-specific IgA responses, we used Western blotting to compare the specificities and frequencies of IgA to HIV antigens in serum of gender-, age- and race-matched EC and aviremic controllers (HC and viremic noncontrollers (HN on highly active antiretroviral therapy (HAART. Concentrations and avidity of IgA to HIV antigens were measured using ELISA or multiplex assays. Measurements for IgG were performed in parallel. EC were found to have stronger p24- and V1V2-specific IgG responses than HN, but there were no IgG differences for EC and HC. In contrast, IgA in EC serum bound more frequently to gp160 and gag proteins than IgA in HC or HN. The avidity of anti-gp41 IgA was also greater in EC, and these subjects had stronger IgA responses to the gp41 heptad repeat region 1 (HR1, a reported target of anti-bacterial RNA polymerase antibodies that cross react with gp41. However, EC did not demonstrate greater IgA responses to E. coli RNA polymerase or to peptides containing the shared LRAI sequence, suggesting that most of their HR1-specific IgA antibodies were not induced by intestinal microbiota. In both EC and HAART recipients, the concentrations of HIV-specific IgG were greater than HIV-specific IgA, but their avidities were comparable, implying that they could compete for antigen. Exceptions were C1 peptides and V1V2 loops. IgG and IgA responses to these antigens were discordant, with IgG reacting to V1V2, and IgA reacting to C1, especially in EC. Interestingly, EC with IgG hypergammaglobulinemia had greater HIV-specific IgA and IgG responses than EC with normal total IgG levels. Heterogeneity in EC antibody responses may therefore be due to a more focused HIV-specific B cell response in some of these individuals. Overall, these data suggest that development of

  18. Study and preparation of 99Tcm-GP kit for lung ventilation imaging

    International Nuclear Information System (INIS)

    Zhu Lin; Meng Fanmin; Zhang Jihong; Hong Tao; Liu Yunzhong; Liu Xiujie

    1997-01-01

    The preparation of the lyophilizing reagent, D-glucose-l-phosphate (GP) kit and the method of using this kit to label 99 Tc m to form 99 Tc m -GP for lung ventilation imaging at room temperature in a simple, rapid procedure are described. The stability of the lyophilizing reagent kit under various stock conditions is examined. The results show that all of the 99 Tc m -GP yields by the lyophilizing reagent kit are above 95% at 4 degree C (cold), 20-25 degree C (room temperature) and 40 degree C (oven) for 180, 90 and 3 days, respectively. The clinical practice indicates that in comparison with 99 Tc m -DTPA, 99 Tc m -GP has remarkable difference (P 99 Tc m -GP is an ideal radioaerosol for SPECT studies of lung ventilation. It has high alveolar deposition rate but low adhesion in the major airways compared to those of 99 Tc m -DTPA. 99 Tc m -GP also features prolonged pulmonary clearance time

  19. Biochemical characteristics of mutant lines of currant tomato

    International Nuclear Information System (INIS)

    Gorbatenko, I.Yu.; Khrustaleva, V.V.; Shcherbakov, V.K.

    1988-01-01

    The currant tomato is used in breeding for fruit quality. It contains up to 50 mg% ascorbic acid, a large quantity of sugar and 8-10% of dry matter. The weight of the fruit, however, does not exceed 1.2-1.5 g. The plants have long, spreading and very branchy stems. Gamma ray induced mutants of currant tomato were used, as initial material in breeding for fruit quality in varieties suitable for mechanized harvesting. The research was carried out mainly at the Department of Vegetable Growing Ukrainian Scientific Research Institute of Irrigation Farming. The regional variety Lebyazhinskij (suitable for mechanized harvesting) was adopted as the standard. Its fruits contain: 5.6% dry matter, 2.7% sugars, 0.543% titrated acidity, 26.6 mg/100 g ascorbic acid, 0.425 mg% carotene and 0.35% cellulose. The biochemical characteristics of the tomato mutants are shown. In terms of fruit dry matter, all mutants surpassed the standard. The acidity and the ascorbic acid content varied considerably. Most noteworthy in terms of carotene were the lines GP-5, GP-9 and GP-12. An important factor in the production of tomato paste is the fruit cellulose content. The lowest cellulose content is found in mutant GP-3. As shown, all of the mutants were early ripening. The mutants surpassed the standard in simultaneous fruit ripening. Mutant lines GP-3, GP-6, GP-9 and GP-12 will be used in the breeding programme for improving fruit quality of varieties suitable for mechanized harvesting

  20. GP registrar well-being: a cross-sectional survey

    OpenAIRE

    Schattner, Peter; Mazalin, Dennis; Pier, Ciaran; Wainer, Jo; Ling, Mee Yoke

    2010-01-01

    Abstract Objectives To investigate the major stressors affecting GP registrars, how those at risk can be best identified and the most useful methods of managing or reducing their stress. Design, setting and participants Cross-sectional postal questionnaire of all GP registrars in one large regional training provider's catchment area. Main outcome measures The Depression, Anxiety and Stress Scale (DASS), a specifically developed Registrar Stressor Scale consisting of five subscales of potentia...

  1. Attitudes towards obesity treatment in GP training practices: a focus group study

    NARCIS (Netherlands)

    Jochemsen-van der Leeuw, H. G. A.; van Dijk, N.; Wieringa-de Waard, M.

    2011-01-01

    Both patients and government expect the GP to treat obesity. Previous studies reported a negative attitude of GPs towards this task. Little is known about the attitude of GP trainees. To assess the attitude and other factors that influence the willingness and ability of GP trainees to provide

  2. Reduction of cerebral glucose utilization by the HIV envelope glycoprotein Gp-120

    Energy Technology Data Exchange (ETDEWEB)

    Kimes, A.S.; London, E.D.; Szabo, G.; Raymon, L.; Tabakoff, B. (Neuropharmacology Laboratory, National Institute on Drug Abuse, Baltimore, MD (USA))

    1991-05-01

    Gp-120 is a glycoprotein constituent of the human immunodeficiency virus (HIV) envelope. The effects of gp-120 on cerebral glucose utilization in rats were studied by the quantitative 2-deoxy-D-(1-14C) glucose method. Intracerebroventricular injection of gp-120 significantly reduced glucose utilization in the lateral habenula and the suprachiasmatic nucleus and decreased the global cerebral metabolic rate for glucose. The findings suggest that gp-120 and closely related peptides can alter neuronal function, thereby contributing to the sequelae of HIV infection.

  3. Reduction of cerebral glucose utilization by the HIV envelope glycoprotein Gp-120

    International Nuclear Information System (INIS)

    Kimes, A.S.; London, E.D.; Szabo, G.; Raymon, L.; Tabakoff, B.

    1991-01-01

    Gp-120 is a glycoprotein constituent of the human immunodeficiency virus (HIV) envelope. The effects of gp-120 on cerebral glucose utilization in rats were studied by the quantitative 2-deoxy-D-[1-14C] glucose method. Intracerebroventricular injection of gp-120 significantly reduced glucose utilization in the lateral habenula and the suprachiasmatic nucleus and decreased the global cerebral metabolic rate for glucose. The findings suggest that gp-120 and closely related peptides can alter neuronal function, thereby contributing to the sequelae of HIV infection

  4. Federal support for health physics education in the USA

    International Nuclear Information System (INIS)

    Williamson, R.C.

    1990-01-01

    In the USA there is a critical shortage of highly trained and educated health physicists. The university programmes in health physics have had difficulties in keeping up with this high employment demand. In order to solve this problem the US Department of Energy has instituted two graduate fellowship programmes to encourage talented students to enter education and eventually accept a career in health physics. (author). 8 refs

  5. Diagnostic value of Joint Detection of GP73 and AFP-L3 in Primary Hepatic Carcinoma with Low Concentration of AFP

    Directory of Open Access Journals (Sweden)

    Lei CAI

    2015-03-01

    Full Text Available Objective: To explore the applicative value of serum Golgi protein (GP73 and alpha-proteinvariant (AFP-L3 in the diagnosis of patients with primary hepatic carcinoma (PHC. Methods:Totally 110 patients were enrolled, including 60 PHC patients with low concentration of AFP ((1.1-108.0 μg/L and 50 patients with non-PHC digestive system diseases (20 cases of patients with chronic hepatitis, 15 patients with liver cirrhosis, 4 patients with bile duct cancer, 4 patients with gastric cancer, 4 patients with rectal cancer and 3 patients with colon cancer. In addition, 42 healthy people were selected as control group. GP73 was detected by enzyme-linked immunosorbent assay (ELISA trace centrifugal column method was adopted for separation of AFP-L3. Luo's chemiluminescence method was used to determine the total content of AFP and AFP-L3 in eluent for calculating the ratio of AFP-L3/ AFP. Results: The levels of serum GP73 and AFP-L3(% in PHC group were significantly higher than the other 2 groups (P<0.01 and the level of serum GP73 and AFP-L3 (% in Non-PHC group were higher than those in healthy group (P<0.01. ROC analysis showed that the area under ROC curve of single GP73 and AFP-L3(% in diagnosis of PHC and non-PHC were 0.887 and 0.860, respectively. Additionally, the ROC analysis also showed that critical value of GP73 and AFP-L3 for the diagnosis of HPC were 83.78 μg/L and 13.87%, respectively. The sensitivity of joint detection of serum GP73 or AFP-L3 was higher than detection of them alone (90.0 vs. 71.7 and 60.0, P<0.05 but the specificity was similar between single detection and joint detection (P>0.05. The positive predictive value and negative predictive value of joint detection of them was higher than single detections of them and there was significant differences in negative predictive value (P<0.05 but no difference in positive predictive value (P>0.05. The overall response rate of joint detection of GP73 and AFP-L3 was higher

  6. NMR structural studies of the ionizing radiation adduct 7-hydro-8-oxodeoxyguanosine (8-oxo-7H-dG) opposite deoxyadenosine in a DNA duplex. 8-oxo-7H-dG(syn)·dA(anti) alignment at lesion site

    International Nuclear Information System (INIS)

    Kouchakdjian, M.; Patel, D.J.; Bodepudi, V.; Shibutani, S.; Eisenberg, M.; Johnson, F.; Grollman, A.P.

    1991-01-01

    Proton NMR studies are reported on the complementary d(C1-C2-A3-C4-T5-A6-oxo-G7-T8-C9-A10-C11-C12)·d(G13-G14-T15-G16-A17-A18-T19-A20-G21-T22-G23-G24) dodecanucleotide duplex (designated 8-oxo-7H-dG·dA 12-mer), which contains a centrally located 7-hydro-8-oxodeoxyguanosine (8-oxo-7H-dG) residue, a group commonly found in DNA that has been exposed to ionizing radiation or oxidizing free radicals. From the NMR spectra it can be deduced that this moiety exists as two tautomers, or gives rise to two DNA conformations, that are in equilibrium and that exchange slowly. The present study focuses on the major component of the equilibrium that originates in the 6,8-dioxo tautomer of 8-oxo-7H-dG. The authors have assigned the exchangeable NH1, NH7, and NH 2 -2 base protons located on the Watson-Crick and Hoogsteen edges of 8-oxo-7H-dG7 in the 8-oxo-7H-dG·dA 12-mer duplex, using an analysis of one- and two-dimensional nuclear Overhauser enhancement (NOE) data in H 2 O solution. They were able to detect a set of intra- and interstrand NOEs between protons (exchangeable and nonexchangeable) on adjacent residues in the d(A6-oxo-G7-T8)·d(A17-A18-T19) trinucleotide segment centered about the lesion site that establishes stacking of the oxo-dG7(syn)·dA(anti) pair between stable Watson-Crick dA6·dT19 and dT8·A17 base pairs with minimal perturbation of the helix. The structural studies demonstrate that 8-oxo-7H-dG(syn)·dA(anti) forms a stable pair in the interior of the helix, providing a basis for the observed incorporation of dA opposite 8-oxo-7H-dG when readthrough occurs past this oxidized nucleoside base

  7. GP registrar well-being: a cross-sectional survey.

    Science.gov (United States)

    Schattner, Peter; Mazalin, Dennis; Pier, Ciaran; Wainer, Jo; Ling, Mee Yoke

    2010-02-09

    To investigate the major stressors affecting GP registrars, how those at risk can be best identified and the most useful methods of managing or reducing their stress. Cross-sectional postal questionnaire of all GP registrars in one large regional training provider's catchment area. The Depression, Anxiety and Stress Scale (DASS), a specifically developed Registrar Stressor Scale consisting of five subscales of potential stressors, plus closed questions on how to identify and manage stress in GP registrars. Survey response rate of 51% (102/199). Rural difficulties followed by achieving a work/life balance were the principal stressors. Ten percent of registrars were mildly or moderately depressed or anxious (DASS) and 7% mild to moderately anxious (DASS). Registrars preferred informal means of identifying those under stress (a buddy system and talks with their supervisors); similarly, they preferred to manage stress by discussions with family and friends, debriefing with peers and colleagues, or undertaking sport and leisure activities. This study supports research which confirms that poor psychological well-being is an important issue for a significant minority of GP trainees. Regional training providers should ensure that they facilitate formal and informal strategies to identify those at risk and assist them to cope with their stress.

  8. Triosephosphate isomerase gene promoter variation: -5G/A and -8G/A polymorphisms in clinical malaria groups in two African populations.

    Science.gov (United States)

    Guerra, Mónica; Machado, Patrícia; Manco, Licínio; Fernandes, Natércia; Miranda, Juliana; Arez, Ana Paula

    2015-06-01

    TPI1 promoter polymorphisms occur in high prevalence in individuals from African origin. Malaria-patients from Angola and Mozambique were screened for the TPI1 gene promoter variants rs1800200A>G, (-5G>A), rs1800201G>A, (-8G>A), rs1800202T>G, (-24T>G), and for the intron 5 polymorphism rs2071069G>A, (2262G>A). -5G>A and -8G>A variants occur in 47% and 53% in Angola and Mozambique, respectively while -24T>G was monomorphic for the wild-type T allele. Six haplotypes were identified and -8A occurred in 45% of the individuals, especially associated with the GAG haplotype and more frequent in non-severe malaria groups, although not significantly. The arising and dispersion of -5G>A and -8G>A polymorphisms is controversial. Their age was estimated by analyses of two microsatellite loci, CD4 and ATN1, adjacent to TPI1 gene. The -5G>A is older than -8G>A, with an average estimate of approximately 35,000 years. The -8A variant arose in two different backgrounds, suggesting independent mutational events. The first, on the -5G background, may have occurred in East Africa around 20,800 years ago; the second, on the -5A background, may have occurred in West Africa some 7500 years ago. These estimates are within the period of spread of agriculture and the malaria mosquito vector in Africa, which could has been a possible reason for the selection of -8A polymorphism in malaria endemic countries. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. In silico analysis of HIV-1 Env-gp120 reveals structural bases for viral adaptation in growth-restrictive cells

    Directory of Open Access Journals (Sweden)

    Masaru eYokoyama

    2016-02-01

    Full Text Available Variable V1/V2 and V3 loops on human immunodeficiency virus type 1 (HIV-1 envelope-gp120 core play key roles in modulating viral competence to recognize two infection receptors, CD4 and chemokine-receptors. However, molecular bases for the modulation largely remain unclear. To address these issues, we constructed structural models for a full-length gp120 in CD4-free and -bound states. The models showed topologies of gp120 surface loop that agree with those in reported structural data. Molecular dynamics simulation showed that in the unliganded state, V1/V2 loop settled into a thermodynamically stable arrangement near V3 loop for conformational masking of V3 tip, a potent neutralization epitope. In the CD4-bound state, however, V1/V2 loop was rearranged near the bound CD4 to support CD4 binding. In parallel, cell-based adaptation in the absence of anti-viral antibody pressures led to the identification of amino acid substitutions that individually enhance viral entry and growth efficiencies in association with reduced sensitivity to CCR5 antagonist TAK-779. Notably, all these substitutions were positioned on the receptors binding surfaces in V1/V2 or V3 loop. In silico structural studies predicted some physical changes of gp120 by substitutions with alterations in viral replication phenotypes. These data suggest that V1/V2 loop is critical for creating a gp120 structure that masks co-receptor binding site compatible with maintenance of viral infectivity, and for tuning a functional balance of gp120 between immune escape ability and infectivity to optimize HIV-1 replication fitness.

  10. HIV-1 gp41 Fusion Intermediate: A Target for HIV Therapeutics

    Directory of Open Access Journals (Sweden)

    Chungen Pan

    2010-02-01

    Full Text Available Human immunodeficiency virus (HIV-1 infection is initiated by the binding of gp120 envelope glyco-protein to its cell receptor (CD4 and a coreceptor (CXCR4 or CCR5, followed by a series of conformational changes in the gp41 transmembrane subunit. These changes include insertion of fusion peptide into the target cell membrane and association of C-heptad repeat (CHR peptide with the N-heptad repeat (NHR trimer, a pre-hairpin fusion intermediate. A stable six-helix bundle core is then formed, bringing the viral envelope and target cell membrane into close proximity for fusion. Peptides derived from the CHR region, such as T20 and C34, inhibit HIV-1 fusion by interacting with the gp41 fusion intermediate. A number of anti-HIV-1 peptides and small molecule compounds targeting the gp41 NHR-trimer have been identified. By combining HIV fusion/entry inhibitors targeting different sites in the gp41 fusion intermediate, a potent synergistic effect takes place, resulting in a potential new therapeutic strategy for the HIV infection/AIDS. Here, we present an overview of the current development of anti-HIV drugs, particularly those targeting the gp41 fusion intermediate.

  11. The Agency's Technical Co-operation programme with Guatemala, 1982-1992. Country programme summaries

    International Nuclear Information System (INIS)

    1992-01-01

    The country programme summary reported here is one in the series of such studies being undertaken of the Agency's TC programme with Member States. With over $3 million of Agency support received, Guatemala ranks 46th among all recipients of technical assistance in the period 1958 - 1991. Almost three quarters of the assistance during the past ten years has been provided in the form of equipment (72%), followed by training (15%) and expert services (13%). Seventy-eight per cent of the resources were provided by the Technical Assistance and Co-operation Fund, the rest was made available through extrabudgetary contributions (21%) and assistance in kind (1%). With regard to project disbursement by sector, the largest areas have been nuclear physics and chemistry (37%), agriculture (28%), nuclear medicine (16%) and hydrology (8%). The remaining 11% were shared by general atomic energy development, nuclear raw materials, nuclear engineering and technology, and nuclear safety

  12. Summer Student Lecture Programme

    CERN Multimedia

    2004-01-01

    Main Auditorium, bldg. 500 More Information DATE TIME LECTURER TITLE Wednesday 7 July 09:15 - 10:00 L. Fayard, O. Ullaland, D. Heagerty (CERN) Programme Presentation Workshops presentation Information on Computing Rules 10:15 - 11:00 R. Aymar (CERN) Introduction to CERN (1/2) 11:15 - 12:00 J. Engelen (CERN) Introduction to CERN (2/2) 15:00 - 16:30 H. Menzel (CERN) An Introduction to Radiation Protection DATE TIME LECTURER TITLE Thursday 8 july 09:15 - 10:00 L. Di Lella (CERN) Introduction to Particle Physics (1/4) 10:15 - 11:00 L. Di Lella (CERN) Introduction to Particle Physics (2/4) 11:15 - 12:00 P. Chomaz (GANIL / CERN) Fundamental questions in modern nuclear physics: The challenge of exotic nuclei (1/2) DATE TIME LECTURER TITLE Friday 9 July 09:15 - 10:00 L. Di Lella (CERN) Introduction to Particle Physics (3/4) 10:15 - 11:00 P. Chomaz (GANIL / CERN) Fundamental questions in modern nuclear physics: The challenge of exotic nuclei (2/2) 11:15 - 12:00 P....

  13. Modulating immunogenic properties of HIV-1 gp41 membrane-proximal external region by destabilizing six-helix bundle structure

    Energy Technology Data Exchange (ETDEWEB)

    Banerjee, Saikat; Shi, Heliang; Habte, Habtom H.; Qin, Yali; Cho, Michael W., E-mail: mcho@iastate.edu

    2016-03-15

    The C-terminal alpha-helix of gp41 membrane-proximal external region (MPER; {sup 671}NWFDITNWLWYIK{sup 683}) encompassing 4E10/10E8 epitopes is an attractive target for HIV-1 vaccine development. We previously reported that gp41-HR1-54Q, a trimeric protein comprised of the MPER in the context of a stable six-helix bundle (6HB), induced strong immune responses against the helix, but antibodies were directed primarily against the non-neutralizing face of the helix. To better target 4E10/10E8 epitopes, we generated four putative fusion intermediates by introducing double point mutations or deletions in the heptad repeat region 1 (HR1) that destabilize 6HB in varying degrees. One variant, HR1-∆10-54K, elicited antibodies in rabbits that targeted W672, I675 and L679, which are critical for 4E10/10E8 recognition. Overall, the results demonstrated that altering structural parameters of 6HB can influence immunogenic properties of the MPER and antibody targeting. Further exploration of this strategy could allow development of immunogens that could lead to induction of 4E10/10E8-like antibodies. - Highlights: • Four gp41 MPER-based immunogens that resemble fusion intermediates were generated. • C-terminal region of MPER that contains 4E10/10E8 epitopes was highly immunogenic. • Altering 6HB structure can influence immunogenic properties of the MPER. • Induced antibodies targeted multiple residues critical for 4E10/10E8 binding. • Development of immunogens based on fusion intermediates is a promising strategy.

  14. Administration of sulfosuccinimidyl-4-[N-maleimidomethyl] cyclohexane-1-carboxylate conjugated GP100{sub 25–33} peptide-coupled spleen cells effectively mounts antigen-specific immune response against mouse melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Xiaoli [Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing (China); Xia, Chang-Qing, E-mail: cqx65@yahoo.com [Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing (China); Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL32610 (United States)

    2015-12-04

    It remains a top research priority to develop immunotherapeutic approaches to induce potent antigen-specific immune responses against tumors. However, in spite of some promising results, most strategies are ineffective because they generate low numbers of tumor-reactive cytotoxic T lymphocytes (CTLs). Here we designed a strategy to enhance antigen-specific immune response via administering sulfosuccinimidyl-4-[N-maleimidomethyl] cyclohexane-1-carboxylate (sulfo-SMCC)-conjugated melanoma tumor antigen GP100{sub 25–33} peptide-coupled syngeneic spleen cells in a mouse model of melanoma. We found that infusion of GP100{sub 25–33} peptide-coupled spleen cells significantly attenuated the growth of melanoma in prophylactic and therapeutic immunizations. Consistent with these findings, the adoptive transfer of spleen cells from immunized mice to naïve syngeneic mice was able to transfer anti-tumor effect, suggesting that GP100{sub 25–33} peptide-specific immune response was induced. Further studies showed that, CD8+ T cell proliferation and the frequency of interferon (IFN)-γ-producing CD8+ T cells upon ex vivo stimulation by GP100{sub 25–33} were significantly increased compared to control groups. Tumor antigen, GP100{sub 25–23} specific immune response was also confirmed by ELISpot and GP100-tetramer assays. This approach is simple, easy-handled, and efficiently delivering antigens to lymphoid tissues. Our study offers an opportunity for clinically translating this approach into tumor immunotherapy. - Highlights: • Infusion of GP100{sub 25–33}-coupled spleen cells leads to potent anti-melanoma immunity. • GP100{sub 25–33}-coupled spleen cell treatment induces antigen-specific IFN-γ-producing CD8 T cells. • This approach takes advantage of homing nature of immune cells.

  15. South African southern ocean research programme

    CSIR Research Space (South Africa)

    SASCAR

    1987-01-01

    Full Text Available This document describes the South African National Antarctic Research Programme's (SANARP) physical, chemical and biological Southern Ocean research programme. The programme has three main components: ecological studies of the Prince Edward Islands...

  16. Evaluation of the Undergraduate Physics Programme at Indira Gandhi National Open University: A Case Study

    Directory of Open Access Journals (Sweden)

    Arundhati Mishra

    2009-12-01

    Full Text Available The undergraduate science programme was launched at the Indira Gandhi National Open University (IGNOU in 1991-92 with an enrolment of 1,210 students. The programme was well received, and enrolments increased over the years. However, the success rates have not kept pace with enrolment.In this paper, the authors report the results of an evaluation of the undergraduate Physics programme at IGNOU. The evaluation, the first of its type for this programme, adapted the major tenets of the CIPP model. The findings are based on the responses from a randomly chosen sample of 509 learners across India. The methods employed for the study include records, document, and database analysis, surveys, and case studies.Although the University has enhanced access to higher science education, the attrition rate is high (73%, and the success rate is low. The authors recommend that the University review and reorient its strategies for providing good quality, learner-centred higher education in science subjects. The programme should address the concerns of the learners about the effectiveness of the student support systems, the difficulty level, and the learner-friendliness of study materials with the goal of achieving long-term sustainability while maintaining parity with the conventional system. The need for improving the presentation of the courses and simplifying the mathematical details is emphasised.

  17. Inverting the G-Tetrad Polarity of a G-Quadruplex by Using Xanthine and 8-Oxoguanine.

    Science.gov (United States)

    Cheong, Vee Vee; Lech, Christopher Jacques; Heddi, Brahim; Phan, Anh Tuân

    2016-01-04

    G-quadruplexes are four-stranded nucleic acid structures that are built from consecutively stacked guanine tetrad (G-tetrad) assemblies. The simultaneous incorporation of two guanine base lesions, xanthine (X) and 8-oxoguanine (O), within a single G-tetrad of a G-quadruplex was recently shown to lead to the formation of a stable G⋅G⋅X⋅O tetrad. Herein, a judicious introduction of X and O into a human telomeric G-quadruplex-forming sequence is shown to reverse the hydrogen-bond polarity of the modified G-tetrad while preserving the original folding topology. The control exerted over G-tetrad polarity by joint X⋅O modification will be valuable for the design and programming of G-quadruplex structures and their properties. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. John Adams Lecture | Accelerator-Based Neutrino Physics: Past, Present and Future by Kenneth Long | 8 December

    CERN Multimedia

    2014-01-01

    John Adams Lecture: Accelerator-Based Neutrino Physics: Past, Present and Future by Dr. Kenneth Long (Imperial College London & STFC).   Monday, 8 December 2014 from 2 p.m. to 4 p.m. at CERN ( 503-1-001 - Council Chamber ) Abstract: The study of the neutrino is the study of physics beyond the Standard Model. We now know that the neutrinos have mass and that neutrino mixing occurs causing neutrino flavour to oscillate as neutrinos propagate through space and time. Further, some measurements can be interpreted as hints for new particles known as sterile neutrinos. The measured values of the mixing parameters make it possible that the matter-antimatter (CP) symmetry may be violated through the mixing process. The consequences of observing CP-invariance violation in neutrinos would be profound. To discover CP-invariance violation will require measurements of exquisite precision. Accelerator-based neutrino sources are central to the future programme and advances in technique are required ...

  19. A Precise Measurement of the Spin Structure Functions G**P(2) G**D(2) from SLAC Experiment E155X

    Energy Technology Data Exchange (ETDEWEB)

    McNulty, D

    2003-12-18

    A precision measurement of the deep inelastic polarized structure functions g{sub 2}{sup p} (x, Q{sup 2}) and g{sub 2}{sup d} (x, Q{sup 2}) and the virtual photon asymmetries A{sub 2}{sup p}(x, Q{sup 2}) and A{sub 2}{sup d}(x, Q{sup 2}) has been made by the E155x collaboration in the ranges 0.02 < x < 0.8 and 0.7 (GeV/c){sup 2} < Q{sup 2} < 20 (GeV/c){sup 2}. The transverse asymmetry (A{sub {perpendicular}}) was measured at SLAC using 29.1 and 32.3 GeV longitudinally polarized electrons incident on transversely polarized target protons and deuterons; the scattered electrons were detected by three fixed angle spectrometers at 2.75{sup o}, 5.5{sup o}, and 10.5{sup o} from the beam line. g{sub 2} was extracted using the measured A{sub {perpendicular}}, an E155 phenomenological fit to g{sub 1}/F{sub 1}, and the SLAC fit to R(x, Q{sup 2}); the function F{sub 1} was obtained from the most recent NMC fit to F{sub 2}(x, Q{sup 2}). The errors on g{sub 2} for both proton and deuteron are more than three times smaller than those of the previously existing world data set, thus enabling the data to resolve clearly between g{sub 2}{sup ww} and zero as well as make distinctions between various models. In addition, the Burkhardt-Cottingham and Efremov-Leader-Teryaev sum rules were evaluated over the measured kinematic region, as well as the d{sub 2} twist-3 matrix element for the proton and neutron.

  20. Qualitative Evaluation of a Physical Activity Health Promotion Programme for People with Intellectual Disabilities in a Group Home Setting

    Science.gov (United States)

    Dixon-Ibarra, A.; Driver, S.; Nery-Hurwit, M.; VanVolkenburg, H.

    2018-01-01

    Background: There is a lack of health promotion programming designed to change the physical activity environment of the group home setting. The Menu-Choice programme assists staff in creating physical activity goals alongside residents with intellectual disabilities and provides strategies to incorporate activity into the group home schedule. The…

  1. GP and pharmacist inter-professional learning - a grounded theory study.

    Science.gov (United States)

    Cunningham, David E; Ferguson, Julie; Wakeling, Judy; Zlotos, Leon; Power, Ailsa

    2016-05-01

    Practice Based Small Group Learning (PBSGL) is an established learning resource for primary care clinicians in Scotland and is used by one-third of general practitioners (GPs). Scottish Government and UK professional bodies have called for GPs and pharmacists to work more closely together to improve care. To gain GPs' and pharmacists' perceptions and experiences of learning together in an inter-professional PBSGL pilot. Qualitative research methods involving established GP PBSGL groups in NHS Scotland recruiting one or two pharmacists to join them. A grounded theory method was used. GPs were interviewed in focus groups by a fellow GP, and pharmacists were interviewed individually by two researchers, neither being a GP or a pharmacist. Interviews were audio-recorded, transcribed and analysed using grounded theory methods. Data saturation was achieved and confirmed. Three themes were identified: GPs' and pharmacists' perceptions and experiences of inter-professional learning; Inter-professional relationships and team-working; Group identity and purpose of existing GP groups. Pharmacists were welcomed into GP groups and both professions valued inter-professional PBSGL learning. Participants learned from each other and both professions gained a wider perspective of the NHS and of each others' roles in the organisation. Inter-professional relationships, communication and team-working were strengthened and professionals regarded each other as peers and friends.

  2. Lifetime cost effectiveness of a through-school nutrition and physical programme: Project Energize.

    Science.gov (United States)

    Rush, Elaine; Obolonkin, Victor; McLennan, Stephanie; Graham, David; Harris, James D; Mernagh, Paul; Weston, Adéle R

    2014-01-01

    Project Energize, a multicomponent through-school physical activity and nutrition programme, is delivered to all primary school children in the Waikato region. The programme aim is to improve the overall health and reduce the rate of weight gain of all Waikato primary school children. An existing economic model was used to extrapolate the programme effects, initial costs, lifetime health treatment cost structures, quality-adjusted-life-years gained and increased life expectancy to the general and Māori child population of New Zealand. In March 2011, a sample of 2474 younger (7.58 ± 0.57 years, mean ± SD) and 2330 older (10.30 ± 0.51 years) children (36% Māori) attending Energize schools had body mass index measured and compared using mixed effect modelling with unEnergized comparison children from 2004 and 2006 from the same region. In 2011 the median body mass index reduction compared with the comparison younger children was -0.504 (90% CI -0.435 to -0.663) kg/m(2) and in the older children -0.551 (-0.456 to -0.789) kg/m(2). In 2010 there were 42,067 children attending Energize schools and in the same year NZ$1,891,175 was spent to deliver the programme; a cost of $44.96/child/year. Compared to the comparison children the increment in cost/quality-adjusted-life-year gained was $30,438 for the younger and $24,690 for the older children, and lower for Māori (younger $28,241, older $22,151) and for the middle socioeconomic status schools ($23,211, $17,891). Project Energize would improve quality and length of life and when compared with other obesity prevention programmes previously assessed with this model, it would be relatively cost-effective from the health treatment payer's perspective.

  3. Programmēšanas valodas Java 8 iespējas

    OpenAIRE

    Vaivars, Arnis

    2014-01-01

    Java ir viena no pasaulē populārākajām objektorientētajām programmēšanas valodām. Šī platforma ir nepārtraukti attīstīta un pilnveidota, ar katru versiju sniedzot programmatūras izstrādātājiem jaunas iespējas. 2014.gada martā tika izplatīta uz darba izstrādes brīdi jaunākā platformas versija – Java 8. Pateicoties lambda izteiksmēm, Nashorn Javascript dzinējam, jaunajām datuma, laika un straumju lietojumprogrammu saskarnēm un citām iespējām, šis laidiens iespējams ir pati gaidītākā Java versij...

  4. Immunization with Hexon modified adenoviral vectors integrated with gp83 epitope provides protection against Trypanosoma cruzi infection.

    Directory of Open Access Journals (Sweden)

    Anitra L Farrow

    2014-08-01

    Full Text Available Trypanosoma cruzi is the causative agent of Chagas disease. Chagas disease is an endemic infection that affects over 8 million people throughout Latin America and now has become a global challenge. The current pharmacological treatment of patients is unsuccessful in most cases, highly toxic, and no vaccines are available. The results of inadequate treatment could lead to heart failure resulting in death. Therefore, a vaccine that elicits neutralizing antibodies mediated by cell-mediated immune responses and protection against Chagas disease is necessary.The "antigen capsid-incorporation" strategy is based upon the display of the T. cruzi epitope as an integral component of the adenovirus' capsid rather than an encoded transgene. This strategy is predicted to induce a robust humoral immune response to the presented antigen, similar to the response provoked by native Ad capsid proteins. The antigen chosen was T. cruzi gp83, a ligand that is used by T. cruzi to attach to host cells to initiate infection. The gp83 epitope, recognized by the neutralizing MAb 4A4, along with His6 were incorporated into the Ad serotype 5 (Ad5 vector to generate the vector Ad5-HVR1-gp83-18 (Ad5-gp83. This vector was evaluated by molecular and immunological analyses. Vectors were injected to elicit immune responses against gp83 in mouse models. Our findings indicate that mice immunized with the vector Ad5-gp83 and challenged with a lethal dose of T. cruzi trypomastigotes confer strong immunoprotection with significant reduction in parasitemia levels, increased survival rate and induction of neutralizing antibodies.This data demonstrates that immunization with adenovirus containing capsid-incorporated T. cruzi antigen elicits a significant anti-gp83-specific response in two different mouse models, and protection against T. cruzi infection by eliciting neutralizing antibodies mediated by cell-mediated immune responses, as evidenced by the production of several Ig isotypes

  5. Access to and utilisation of GP services among Burmese migrants in London: a cross-sectional descriptive study.

    Science.gov (United States)

    Aung, Nyein Chan; Rechel, Bernd; Odermatt, Peter

    2010-10-12

    An estimated 10,000 Burmese migrants are currently living in London. No studies have been conducted on their access to health services. Furthermore, most studies on migrants in the United Kingdom (UK) have been conducted at the point of service provision, carrying the risk of selection bias. Our cross-sectional study explored access to and utilisation of General Practice (GP) services by Burmese migrants residing in London. We used a mixed-method approach: a quantitative survey using self-administered questionnaires was complemented by qualitative in-depth interviews for developing the questionnaire and triangulating the findings of the survey. Overall, 137 questionnaires were received (a response rate of 57%) and 11 in-depth interviews conducted. The main outcome variables of the study included GP registration, barriers towards registration, GP consultations, barriers towards consultations, and knowledge on entitlements to health care. Quantitative data were analysed using descriptive statistics, association tests, and a multivariate analysis using logistic regression. The qualitative information was analysed using content analysis. The respondents were young, of roughly equal gender (51.5% female), well educated, and had a fair level of knowledge on health services in the UK. Although the GP registration rate was relatively high (80%, 109 out of 136), GP service utilisation during the last episode of illness, at 56.8% (54 out of 95), was low. The statistical analysis showed that age being younger than 35 years, lacking prior overseas experience, having an unstable immigration status, having a shorter duration of stay, and resorting to self-medication were the main barriers hindering Burmese migrants from accessing primary health care services. These findings were corroborated by the in-depth interviews. Our study found that having formal access to primary health care was not sufficient to ensure GP registration and health care utilisation. Some respondents faced

  6. Access to and utilisation of GP services among Burmese migrants in London: a cross-sectional descriptive study

    Directory of Open Access Journals (Sweden)

    Rechel Bernd

    2010-10-01

    Full Text Available Abstract Background An estimated 10,000 Burmese migrants are currently living in London. No studies have been conducted on their access to health services. Furthermore, most studies on migrants in the United Kingdom (UK have been conducted at the point of service provision, carrying the risk of selection bias. Our cross-sectional study explored access to and utilisation of General Practice (GP services by Burmese migrants residing in London. Methods We used a mixed-method approach: a quantitative survey using self-administered questionnaires was complemented by qualitative in-depth interviews for developing the questionnaire and triangulating the findings of the survey. Overall, 137 questionnaires were received (a response rate of 57% and 11 in-depth interviews conducted. The main outcome variables of the study included GP registration, barriers towards registration, GP consultations, barriers towards consultations, and knowledge on entitlements to health care. Quantitative data were analysed using descriptive statistics, association tests, and a multivariate analysis using logistic regression. The qualitative information was analysed using content analysis. Results The respondents were young, of roughly equal gender (51.5% female, well educated, and had a fair level of knowledge on health services in the UK. Although the GP registration rate was relatively high (80%, 109 out of 136, GP service utilisation during the last episode of illness, at 56.8% (54 out of 95, was low. The statistical analysis showed that age being younger than 35 years, lacking prior overseas experience, having an unstable immigration status, having a shorter duration of stay, and resorting to self-medication were the main barriers hindering Burmese migrants from accessing primary health care services. These findings were corroborated by the in-depth interviews. Conclusions Our study found that having formal access to primary health care was not sufficient to ensure GP

  7. Are there practical opportunities for developing leadership skills during GP training and beyond? A survey of GP trainees and trainers in South East Scotland.

    Science.gov (United States)

    Curry, Nicola; Denney, MeiLing

    2016-01-01

    There is currently a lack of formal training in leadership skills, particularly during GP training. This study aimed to explore the current training and practical opportunities which exist, specifically exploring the views of GP trainees and trainers. An electronic questionnaire was sent to 266 GP trainees and trainers in south-east Scotland. Questions focused on respondents' experience of leadership-specific training and opportunities to engage with leadership roles. There were a total of 76 respondents (28.6% response rate). Response rate was 19.0% in trainees and 34.6% in trainers. A majority of respondents (80.0%) were established GPs. Of those who had received training in leadership, most (72.1%) underwent this after qualifying as a GP. Respondents identified a range of leadership roles within and outside the practice covering clinical and non-clinical areas. Most were interested in future leadership roles (46.7% moderately interested; 28% very interested). More time, training opportunities and the presence of GP role models were motivating factors in terms of participants' readiness to take on future leadership roles. Signposting trainees, trainers and general practitioners to leadership opportunities and training would be relatively easy but addressing a lack of motivating factors at a local level is essential. The effectiveness of such training and opportunities for experiential learning in leadership roles requires further research.

  8. Glycolytic pathway (GP), kreb's cycle (KC), and hexose monophosphate shunt (HMS) activity in myocardial subcellular fractions exposed to cannabinoids

    International Nuclear Information System (INIS)

    Watson, A.T.; Manno, B.R.; King, J.W.; Fowler, M.R.; Dempsey, C.A.; Manno, J.E.

    1986-01-01

    Delta-9-tetrahydrocannabinol (Δ 9 -THC), the primary psychoactive component of marihuana, and its active metabolite 11-hydroxy-Δ 9 -tetrahydrocannabinol (11-OH-Δ 9 -THC) have been reported to produce a direct cardiac depressant effect. Studies in isolated perfused rat hearts have indicated a decreased force of contraction (inotropic response) when Δ 9 -THC or 11-OH-Δ 9 -THC was administered in microgram amounts. The mechanism and site of action have not been explained or correlated with associated metabolic pathways. The purpose of this study was to investigate the effects of cannabinoids on major myocardial energy producing pathways, GP and KC, and a non-energy producing pathway, HMS. Cardiac ventricular tissue from male Sprague-Dawley rats (250-300 g) was excised and homogenized for subcellular fractionation. KC, GP and HMS activity was assayed in the appropriate fractions by measuring 14 CO 2 generation from 14 C-2-pyruvate, 14 C-6-glucose and 14 C-1-glucose respectively. Duplicate assays (n=8) were performed on tissue exposed to saline (control), empty liposomes (vehicle) and four doses each of Δ 9 -THC and 11-OH-Δ 9 -THC. Changes in metabolic activity and decreases in cardiac contractile performance may be associated

  9. GP registrar well-being: a cross-sectional survey

    Directory of Open Access Journals (Sweden)

    Schattner Peter

    2010-02-01

    Full Text Available Abstract Objectives To investigate the major stressors affecting GP registrars, how those at risk can be best identified and the most useful methods of managing or reducing their stress. Design, setting and participants Cross-sectional postal questionnaire of all GP registrars in one large regional training provider's catchment area. Main outcome measures The Depression, Anxiety and Stress Scale (DASS, a specifically developed Registrar Stressor Scale consisting of five subscales of potential stressors, plus closed questions on how to identify and manage stress in GP registrars. Results Survey response rate of 51% (102/199. Rural difficulties followed by achieving a work/life balance were the principal stressors. Ten percent of registrars were mildly or moderately depressed or anxious (DASS and 7% mild to moderately anxious (DASS. Registrars preferred informal means of identifying those under stress (a buddy system and talks with their supervisors; similarly, they preferred to manage stress by discussions with family and friends, debriefing with peers and colleagues, or undertaking sport and leisure activities. Conclusions This study supports research which confirms that poor psychological well-being is an important issue for a significant minority of GP trainees. Regional training providers should ensure that they facilitate formal and informal strategies to identify those at risk and assist them to cope with their stress.

  10. The B-Physics Programme of ATLAS in LHC Run-II and in HL-LHC

    CERN Document Server

    Reznicek, P; The ATLAS collaboration

    2014-01-01

    Slides for the talk to be given at Beauty 2014 conference in Edinburgh, 14-18 July 2014. The talk describes the ATLAS B-physics programme planned to future LHC runs: Run 2, 3 and HL-LHC. The relevant ATLAS detector upgrades are dicussed and a results of pilot sensitivity study of $B_{s} \\to J/\\psi \\phi$ measurement in the future runs are shown.

  11. ADS National Programmes: China

    International Nuclear Information System (INIS)

    2015-01-01

    In China the conceptual study of an ADS concept which lasted for about five years ended in 1999. As one project of the National Basic Research Programme of China (973 Programme) in energy domain, which is sponsored by the China Ministry of Science and Technology (MOST), a five year programme of fundamental research of ADS physics and related technology was launched in 2000 and passed national review at the end of 2005. From 2007, another five year 973 Programme Key Technology Research of Accelerator Driven Subcritical System for Nuclear waste Transmutation started. The research activities were focused on HPPA physics and technology, reactor physics of external source driven subcritical assembly, nuclear data base and material study. For HPPA, a high current injector consisting of an ECR ion source, LEBT and an RFQ accelerating structure of 3.5 MeV has been built and were being improved. In reactor physics study, a series of neutron multiplication experimental study has been carrying out. The VENUS I facility has been constructed as the basic experimental platform for neutronics study in ADS blanket. VENUS I a zero power subcritical neutron multiplying assembly driven by external neutron produced by a pulsed neutron generator or 252Cf neutron source. The theoretical, experimental and simulation studies on nuclear data, material properties and nuclear fuel circulation related to ADS are carried out in order to provide the database for ADS system analysis. China Institute of Atomic Energy (CIAE), Institute of High Energy Physics (IHEP) and other Chinese institutes carried out the MOST project together. Besides CIAE, China Academy of Science (CAS) pays more and more attention to Advanced Nuclear Fuel Cycles (ANFC). A large programme of ANFC, including ADS and Th based nuclear fuel cycle, has been launched by CAS

  12. In vivo evaluation of an oral delivery system for P-gp substrates based on thiolated chitosan.

    Science.gov (United States)

    Föger, Florian; Schmitz, Thierry; Bernkop-Schnürch, Andreas

    2006-08-01

    Recently, thiolated polymers, so called thiomers, have been reported to modulate drug absorption by inhibition of intestinal P-glycoprotein (P-gp). The aim of the present study was to provide a proof-of-principle for a delivery system based on thiolated chitosan in vivo in rats, using rhodamine-123 (Rho-123) as representative P-gp substrate. In vitro, the permeation enhancing effect of unmodified chitosan, chitosan-4 thiobutylamidine (Ch-TBA) and the combination of Ch-TBA with reduced glutathione (GSH) was evaluated by using freshly excised rat intestinal mucosa mounted in Ussing-type chambers. In comparison to buffer only, Rho-123 transport in presence of 0.5% (w/v) chitosan, 0.5% (w/v) Ch-TBA and the combination of 0.5% (w/v) Ch-TBA/0.5% (w/v) GSH, was 1.8-fold, 2.6-fold, 3.8-fold improved, respectively. Furthermore, enteric-coated tablets based on unmodified chitosan or Ch-TBA/GSH, were investigated in vivo. In rats, the Ch-TBA/GSH tablets increased the area under the plasma concentration time curve (AUC0-12) of Rho-123 by 217% in comparison to buffer control and by 58% in comparison to unmodified chitosan. This in vivo study showed that a delivery system based on thiolated chitosan significantly increased the oral bioavailability of P-gp substrate Rho-123.

  13. Active Play in After-school Programmes: development of an intervention and description of a matched-pair cluster-randomised trial assessing physical activity play in after-school programmes.

    Science.gov (United States)

    Riiser, Kirsti; Helseth, Sølvi; Ellingsen, Hanna; Fallang, Bjørg; Løndal, Knut

    2017-08-04

    Interventions delivered in after-school programmes (ASPs) have the potential to become a means of ensuring adequate physical activity among schoolchildren. This requires a motivational climate, allowing for self-determined play. If trained, ASP staff may represent a valuable resource for supporting such play. Increasing knowledge and supportive skills among ASP staff may also potentially increase their motivation for work. The purpose of this article is to describe the development of the 'Active Play in ASP' intervention, which aims to promote physical activity among first graders attending ASP, and to present a protocol for a matched-pair cluster-randomised trial to evaluate the intervention. Informed by experiences from practice, evidence-based knowledge and theory, the intervention was developed in a stepwise process including focus group meetings and a small-scale pilot test. The intervention contains a course programme for ASP staff to increase their skills in how to support physical activity through play. In a cluster randomised controlled trial, the ASPs will be matched and randomly allocated to receive the 7-month intervention or to a control group. Outcomes will be assessed at baseline, after 7 and 19 months. First graders attending the ASPs included are eligible. The primary outcome will be accelerometer-determined minutes in moderate to vigorous physical activity in the ASP. The study uses a mixed methods approach including observations and interviews to provide rich descriptions of the concept of children's physical activity in ASP. Moreover, the trial will assess whether the ASP staff benefits from participation in the intervention in terms of increased work motivation. Lastly, process evaluations of programme fidelity, satisfaction and suggestions on improvement will be performed. The study is approved by the Data Protection Official for Research (reference no 46008). Results will be presented in conferences and peer-reviewed journals. Clinical Trials

  14. A structured physical activity and fitness programme for older adults with intellectual disabilities : Results of a cluster-randomised clinical trial

    NARCIS (Netherlands)

    van Schijndel-Speet, M.; Evenhuis, Heleen M.; van Wijck, R.; van Montfort, K. C. A. G. M.; Echteld, M. A.

    BackgroundThe physical activity level of older adults with intellectual disabilities (ID) is extremely low, and their fitness levels are far beneath accepted norms for older people with normal intelligence and comparable with frail older people. A physical activity programme, including an education

  15. Crystallogenesis of bacteriophage P22 tail accessory factor gp26 at acidic and neutral pH

    Energy Technology Data Exchange (ETDEWEB)

    Cingolani, Gino, E-mail: cingolag@upstate.edu; Andrews, Dewan [Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210 (United States); Casjens, Sherwood [Department of Pathology, Division of Cell Biology and Immunology, University of Utah Medical School, Salt Lake City, UT 84112 (United States); Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210 (United States)

    2006-05-01

    The crystallogenesis of bacteriophage P22 tail-fiber gp26 is described. To study possible pH-induced conformational changes in gp26 structure, native trimeric gp26 has been crystallized at acidic pH (4.6) and a chimera of gp26 fused to maltose-binding protein (MBP-gp26) has been crystallized at neutral and alkaline pH (7-10). Gp26 is one of three phage P22-encoded tail accessory factors essential for stabilization of viral DNA within the mature capsid. In solution, gp26 exists as an extended triple-stranded coiled-coil protein which shares profound structural similarities with class I viral membrane-fusion protein. In the cryo-EM reconstruction of P22 tail extracted from mature virions, gp26 forms an ∼220 Å extended needle structure emanating from the neck of the tail, which is likely to be brought into contact with the cell’s outer membrane when the viral DNA-injection process is initiated. To shed light on the potential role of gp26 in cell-wall penetration and DNA injection, gp26 has been crystallized at acidic, neutral and alkaline pH. Crystals of native gp26 grown at pH 4.6 diffract X-rays to 2.0 Å resolution and belong to space group P2{sub 1}, with a dimer of trimeric gp26 molecules in the asymmetric unit. To study potential pH-induced conformational changes in the gp26 structure, a chimera of gp26 fused to maltose-binding protein (MBP-gp26) was generated. Hexagonal crystals of MBP-gp26 were obtained at neutral and alkaline pH using the high-throughput crystallization robot at the Hauptman–Woodward Medical Research Institute, Buffalo, NY, USA. These crystals diffract X-rays to beyond 2.0 Å resolution. Structural analysis of gp26 crystallized at acidic, neutral and alkaline pH is in progress.

  16. Point mutations in EBV gH that abrogate or differentially affect B cell and epithelial cell fusion

    International Nuclear Information System (INIS)

    Wu Liguo; Hutt-Fletcher, Lindsey M.

    2007-01-01

    Cell fusion mediated by Epstein-Barr virus requires three conserved glycoproteins, gB and gHgL, but activation is cell type specific. B cell fusion requires interaction between MHC class II and a fourth virus glycoprotein, gp42, which complexes non-covalently with gHgL. Epithelial cell fusion requires interaction between gHgL and a novel epithelial cell coreceptor and is blocked by excess gp42. We show here that gp42 interacts directly with gH and that point mutations in the region of gH recognized by an antibody that differentially inhibits epithelial and B cell fusion significantly impact both the core fusion machinery and cell-specific events. Substitution of alanine for glycine at residue 594 completely abrogates fusion with either B cells or epithelial cells. Substitution of alanine for glutamic acid at residue 595 reduces fusion with epithelial cells, greatly enhances fusion with B cells and allows low levels of B cell fusion even in the absence of gL

  17. Dual-phase 99mTc-MIBI imaging and the expressions of P-gp, GST-π, and MRP1 in hyperparathyroidism.

    Science.gov (United States)

    Xue, Jianjun; Liu, Yan; Yang, Danrong; Yu, Yan; Geng, Qianqian; Ji, Ting; Yang, Lulu; Wang, Qi; Wang, Yuanbo; Lu, Xueni; Yang, Aimin

    2017-10-01

    The aim of this study was to further elucidate the mechanisms of dual-phase technetium-99m methoxyisobutylisonitrile (Tc-MIBI) parathyroid imaging by exploring the association between early uptake results (EUR), delayed uptake results (DUR), and the retention index (RI) in dual-phase Tc-MIBI parathyroid imaging and P glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1), and glutathione S-transferase-π (GST-π) expression in hyperparathyroidism (HPT). Preoperative dual-phase (early and delayed) Tc-MIBI imaging was performed on 74 patients undergoing parathyroidectomy for HPT. EUR, DUR, and RI were calculated. P-gp, MRP1, and GST-π expressions were assessed using immunohistochemistry in resected tissue from HPT and control patients. The association between P-gp, MRP1, and GST-π expressions and EUR, DUR, and RI in HPT was evaluated. The positive rate of dual-phase T c-MIBI imaging was 91.89% (68/74) and the false-negative rate was 8.11% (6/74). P-gp and GST-π expressions were higher in tissues resected from control compared with HPT patients (47.37 and 81.5%, P<0.05); there was no difference in MRP1. EUR were associated with P-gp and GST-π expressions, and DUR were associated with MRP1 expression. There was a significant difference in MRP1 expression between RI greater than or equal to 0 and RI less than 0. There was no relationship between the sensitivity of dual-phase Tc-MIBI imaging and P-gp, MRP1, and GST-π expressions in resected parathyroid tissue. The six false-negative HPT cases consisted of three P-gp (-)/MRP1 (-) tissues, three P-gp (-)/GST-π (-) tissues, and four MRP1 (-)/GST-π (-) tissues. As P-gp and GST-π expressions were higher in tissues resected from control compared with HPT patients, Tc-MIBI may wash out faster from normal parathyroid tissue surrounding the lesion compared with the lesion itself, facilitating detection.

  18. The pancreatic zymogen granule membrane protein, GP2, binds Escherichia coli type 1 Fimbriae

    Directory of Open Access Journals (Sweden)

    Lowe Anson W

    2009-07-01

    Full Text Available Abstract Background GP2 is the major membrane protein present in the pancreatic zymogen granule, and is cleaved and released into the pancreatic duct along with exocrine secretions. The function of GP2 is unknown. GP2's amino acid sequence is most similar to that of uromodulin, which is secreted by the kidney. Recent studies have demonstrated uromodulin binding to bacterial Type 1 fimbria. The fimbriae serve as adhesins to host receptors. The present study examines whether GP2 also shares similar binding properties to bacteria with Type 1 fimbria. Commensal and pathogenic bacteria, including E. coli and Salmonella, express type 1 fimbria. Methods An in vitro binding assay was used to assay the binding of recombinant GP2 to defined strains of E. coli that differ in their expression of Type 1 fimbria or its subunit protein, FimH. Studies were also performed to determine whether GP2 binding is dependent on the presence of mannose residues, which is a known determinant for FimH binding. Results GP2 binds E. coli that express Type 1 fimbria. Binding is dependent on GP2 glycosylation, and specifically the presence of mannose residues. Conclusion GP2 binds to Type 1 fimbria, a bacterial adhesin that is commonly expressed by members of the Enterobacteriacae family.

  19. The ProActive trial protocol – a randomised controlled trial of the efficacy of a family-based, domiciliary intervention programme to increase physical activity among individuals at high risk of diabetes [ISRCTN61323766

    Directory of Open Access Journals (Sweden)

    Ekelund Ulf

    2004-10-01

    Full Text Available Abstract Background Increasing prevalence of obesity and disorders associated with sedentary living constitute a major global public health problem. While previous evaluations of interventions to increase physical activity have involved communities or individuals with established disease, less attention has been given to interventions for individuals at risk of disease. Methods/design ProActive aims to evaluate the efficacy of a theoretical, evidence- and family-based intervention programme to increase physical activity in a sedentary population, defined as being at-risk through having a parental family history of diabetes. Primary care diabetes or family history registers were used to recruit 365 individuals aged 30–50 years, screened for activity level. Participants were assigned by central randomisation to three intervention programmes: brief written advice (comparison group, or a psychologically based behavioural change programme, delivered either by telephone (distance group or face-to-face in the family home over one year. The protocol-driven intervention programme is delivered by trained facilitators, and aims to support increases in physical activity through the introduction and facilitation of a range of self-regulatory skills (e.g. goal setting. The primary outcome is daytime energy expenditure and its ratio to resting energy expenditure, measured at baseline and one year using individually calibrated heart rate monitoring. Secondary measures include self-report of individual and family activity, psychological mediators of behaviour change, physiological and biochemical correlates, acceptability, and costs, measured at baseline, six months and one year. The primary intention to treat analysis will compare groups at one-year post randomisation. Estimation of the impact on diabetes incidence will be modelled using data from a parallel ten-year cohort study using similar measures. Discussion ProActive is the first efficacy trial of an

  20. General practitioner advice on physical activity: Analyses in a cohort of older primary health care patients (getABI

    Directory of Open Access Journals (Sweden)

    Thiem Ulrich

    2011-05-01

    Full Text Available Abstract Background Although the benefits of physical activity for health and functioning are recognized to extend throughout life, the physical activity level of most older people is insufficient with respect to current guidelines. The primary health care setting may offer an opportunity to influence and to support older people to become physically active on a regular basis. Currently, there is a lack of data concerning general practitioner (GP advice on physical activity in Germany. Therefore, the aim of this study was to evaluate the rate and characteristics of older patients receiving advice on physical activity from their GP. Methods This is a cross-sectional study using data collected at 7 years of follow-up of a prospective cohort study (German epidemiological trial on ankle brachial index, getABI. 6,880 unselected patients aged 65 years and above in the primary health care setting in Germany were followed up since October 2001. During the 7-year follow-up telephone interview, 1,937 patients were asked whether their GP had advised them to get regular physical activity within the preceding 12 months. The interview also included questions on socio-demographic and lifestyle variables, medical conditions, and physical activity. Logistic regression analysis (unadjusted and adjusted for all covariables was used to examine factors associated with receiving advice. Analyses comprised only complete cases with regard to the analysed variables. Results are expressed as odds ratios (ORs with 95% confidence intervals (95% CI. Results Of the 1,627 analysed patients (median age 77; range 72-93 years; 52.5% women, 534 (32.8% stated that they had been advised to get regular physical activity. In the adjusted model, those more likely to receive GP advice on physical activity were men (OR [95% CI] 1.34 [1.06-1.70], patients suffering from pain (1.43 [1.13-1.81], coronary heart disease and/or myocardial infarction (1.56 [1.21-2.01], diabetes mellitus (1

  1. Simulating next-generation Cyber-physical computing platforms

    OpenAIRE

    Burgio, Paolo; Álvarez Martínez, Carlos; Ayguadé Parra, Eduard; Filgueras Izquierdo, Antonio; Jiménez González, Daniel; Martorell Bofill, Xavier; Navarro, Nacho; Giorgi, Roberto

    2015-01-01

    In specific domains, such as cyber-physical systems, platforms are quickly evolving to include multiple (many-) cores and programmable logic in a single system-on-chip, while includ- ing interfaces to commodity sensors/actuators. Programmable Logic (e.g., FPGA) allows for greater flexibility and dependability. However, the task of extracting the performance/watt potentia l of heterogeneous many-cores is often demanded at the application level, and this h...

  2. The Agency's Technical Co-operation programme with Nigeria, 1982-1992. Country programme summaries

    International Nuclear Information System (INIS)

    1992-01-01

    The country programme summary reported here is one in the series of such studies being undertaken of the Agency's TC programme with Member States. With over $9.3 million of Agency support received, Nigeria ranks 14th among all recipients of technical assistance in the period 1958 through 1991. During the past ten years, 44% of this assistance has been provided in the form of equipment, followed by training (27%), expert services (26%) and sub-contracts (3%). With 45% and 44%, respectively, the Technical Assistance and Co-operation Fund and extrabudgetary contributions hold almost equal shares in the total resources made available, while in-kind assistance accounts for 9% and UNDP for 2% of the resources. With regard to project disbursement during the past ten years, by sector, by far the largest area has been agriculture (70%), with significantly smaller shares going to nuclear physics and chemistry (11%), nuclear medicine (8%) and nuclear safety (7%)

  3. 77 FR 73635 - Northwest Storage GP, LLC; Notice of Application

    Science.gov (United States)

    2012-12-11

    ...) 1254 to a proposed 346-megawatt (MW) power plant located within the north industrial area of the Port...] Northwest Storage GP, LLC; Notice of Application Take notice that on November 21, 2012, Northwest Storage GP, LLC. (Northwest) filed with the Federal Energy Regulatory Commission an application under section 7 of...

  4. Tamoxifen reduces P-gp-mediated multidrug resistance via inhibiting the PI3K/Akt signaling pathway in ER-negative human gastric cancer cells.

    Science.gov (United States)

    Mao, Zonglei; Zhou, Jin; Luan, Junwei; Sheng, Weihua; Shen, Xiaochun; Dong, Xiaoqiang

    2014-03-01

    Multidrug resistance (MDR), mediated by overexpression of drug efflux transporters such as P-glycoprotein (P-gp), is a major problem limiting successful chemotherapy of gastric cancer. Tamoxifen (TAM), a triphenylethylene nonsteroidal antiestrogen agent, shows broad-spectrum antitumor properties. Emerging studies demonstrated that TAM could significantly reduce the MDR in a variety of human cancers. Here we investigated the effects and possible underlying mechanisms of action of TAM on the reversion of MDR in ER-negative human gastric cancer cells. Our results demonstrated that in MDR phenotype SGC7901/CDDP gastric cancer cells TAM dramatically lowered the IC50 of CDDP, 5-FU and ADM, increased the intracellular Rhodamine123 accumulation and induced G0/G1 phase arrest, while G2/M phase decreased accordingly. Furthermore, at the molecular level, TAM substantially decreased the expression of P-gp, p-Akt and the Akt-regulated downstream effectors such as p-GSK-3β, p-BAD, Bcl-XL and cyclinD1 proteins without affecting the expression of t-Akt, t-GSK-3β, t-BAD proteins in SGC7901/CDDP cells. Thus, our findings demonstrate that TAM reverses P-gp-mediated gastric cancer cell MDR via inhibiting the PI3K/Akt signaling pathway. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  5. Evaluation of physical activity programmes for elderly people - a descriptive study using the EFQM' criteria

    Directory of Open Access Journals (Sweden)

    Santos Rute

    2011-02-01

    Full Text Available Abstract Background In the past years, there has been a growing concern in designing physical activity (PA programmes for elderly people, because evidence suggests that such health promotion interventions may reduce the deleterious effects of the ageing process. Quality is an important issue when designing a PA programme for older people. Some studies support the Excellence Model of the European Foundation for Quality Management (EFQM as an operational framework for evaluating the quality of an organization. Within this context, the aim of this study was to characterize the quality management models of the PA programmes developed by Portuguese Local Administration to enhance quality of life for elderly people, according to the criteria of the EFQM Excellence Model. Methods A methodological triangulation was conducted in 26 PA programmes using questionnaire surveys, semi-structured interviews and document analysis. We used standard approaches to the statistical analysis of data including frequencies and percentages for the categorical data. Results Results showed that Processes (65,38%, Leadership (61,03%, Customer results (58,46 and People (51,28% had high percentage occurrences of quality practices. In contrast, Partnerships and resources (45,77%, People results (41,03%, Policy and strategy (37,91%, Key performance results (19,23% and Society results (19,23% had lower percentage occurrences. Conclusions Our findings suggest that although there are some good practices in PA programmes, there are still relevant areas that require improvement.

  6. Global physical activity levels

    DEFF Research Database (Denmark)

    Hallal, Pedro C; Andersen, Lars Bo; Bull, Fiona C

    2012-01-01

    To implement effective non-communicable disease prevention programmes, policy makers need data for physical activity levels and trends. In this report, we describe physical activity levels worldwide with data for adults (15 years or older) from 122 countries and for adolescents (13-15-years......-income countries. The proportion of 13-15-year-olds doing fewer than 60 min of physical activity of moderate to vigorous intensity per day is 80·3% (80·1-80·5); boys are more active than are girls. Continued improvement in monitoring of physical activity would help to guide development of policies and programmes......-old) from 105 countries. Worldwide, 31·1% (95% CI 30·9-31·2) of adults are physically inactive, with proportions ranging from 17·0% (16·8-17·2) in southeast Asia to about 43% in the Americas and the eastern Mediterranean. Inactivity rises with age, is higher in women than in men, and is increased in high...

  7. Community-based osteoporosis prevention: Physical activity in relation to bone density, fall prevention, and the effect of training programmes : The Vadstena Osteoporosis Prevention Project

    OpenAIRE

    Grahn Kronhed, Ann-Charlotte

    2003-01-01

    This thesis is based on studies of the ten-year community-based intervention programme entitled, the Vadstena Osteoporosis Prevention Project (VOPP). The specific aims of the research were to describe the effects of physical activity and training programmes on bone mass and balance performance in adults, to determine whether a fall risk prevention programme could motivate personal actions among the elderly, to ascertain whether the intervention programme could reduce the incidence of forearm ...

  8. Functionalization of SU-8 photoresist surfaces with IgG proteins

    International Nuclear Information System (INIS)

    Blagoi, Gabriela; Keller, Stephan; Johansson, Alicia; Boisen, Anja; Dufva, Martin

    2008-01-01

    The negative epoxy-based photoresist SU-8 has a variety of applications within microelectromechanical systems (MEMS) and lab-on-a-chip systems. Here, several methods to functionalize SU-8 surfaces with IgG proteins were investigated. Fluorescent labeled proteins and fluorescent sandwich immunoassays were employed to characterize the binding efficiency of model proteins to bare SU-8 surface, SU-8 treated with cerium ammonium nitrate (CAN) etchant and CAN treated surfaces modified by aminosilanization. The highest binding capacity of antibodies was observed on bare SU-8. This explains why bare SU-8 in a functional fluorescent sandwich immunoassay detecting C-reactive protein (CRP) gave twice as high signal as compared with the other two surfaces. Immunoassays performed on bare SU-8 and CAN treated SU-8 resulted in detection limits of CRP of 30 and 80 ng/ml respectively which is sufficient for detecting CRP in clinical samples, where concentrations of 3-10 μg/ml are normal for healthy individuals. In conclusion, bare SU-8 and etched SU-8 can be modified with antibodies by a simple adsorption procedure which simplifies building lab-on-a-chip systems in SU-8. Additionally, we report the fabrication process and use of microwells created in a SU-8 layer with the same dimensions as a standard microscope glass slide that could fit into fluorescent scanners. The SU-8 microwells minimize the reagent consumption and are straightforward to handle compared to SU-8 coated microscope slides

  9. Positive evolution of the glycoprotein (GP) gene is related to transmission of the Ebola virus.

    Science.gov (United States)

    Jing, Y X; Wang, L N; Wu, X M; Song, C X

    2016-03-28

    Ebola hemorrhagic fever is a fatal disease caused by the negative-strand RNA of the Ebola virus. A high-intensity outbreak of this fever was reported in West Africa last year; however, there is currently no definitive treatment strategy available for this disease. In this study, we analyzed the molecular evolutionary history and attempted to determine the positive selection sites in the Ebola genes using multiple-genomic sequences of the various Ebola virus subtypes, in order to gain greater clarity into the evolution of the virus and its various subtypes. Only the glycoprotein (GP) gene was positively selected among the 8 Ebola genes, with the other genes remaining in the purification stage. The positive selection sites in the GP gene were identified by a random-site model; these sites were found to be located in the mucin-like region, which is associated with transmembrane protein binding. Additionally, different branches of the phylogenetic tree displayed different positive sites, which in turn was responsible for differences in the cell adhesion ability of the virus. In conclusion, the pattern of positive sites in the GP gene is associated with the epidemiology and prevalence of Ebola in different areas.

  10. Introducing a GP copayment in Australia: Who would carry the cost burden?

    Science.gov (United States)

    Elkins, Rosemary Kate; Schurer, Stefanie

    2017-05-01

    Recent policy changes designed to contain unsustainable health expenditure growth imply that many more Australians may soon be charged a copayment to consult a GP. We explore the distributional consequences associated with a range of hypothetical GP copayment scenarios using nationally-representative Australian survey data. For each scenario, we estimate the cost burden that individuals and households across the income distribution would need to absorb to maintain their current GP service utilisation. Even when concessional patients are charged a third or a quarter of the non-concessional copayment rate, the average estimated cost burden in the lowest income quartile is typically between three and six times that of the highest, and the average cost burden for women is significantly higher than for men within every income quartile. These disparities are intensified for those with a chronic illness. We conclude that the widespread implementation of GP copayments would disproportionately burden lower-income families, who experience higher rates of chronic illness, higher demand for GP services, and lower capacity to absorb price increases. The regressive nature of GP copayments is reduced when concessional and child patients are exempted entirely, highlighting the importance of supporting GPs-particularly in disadvantaged areas-to maintain bulk-billing arrangements for vulnerable patient groups. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Evaluation of the theory-based Quality Improvement in Physical Therapy (QUIP) programme: a one-group, pre-test post-test pilot study

    NARCIS (Netherlands)

    Rutten, Geert M.; Harting, Janneke; Bartholomew, L. Kay; Schlief, Angelique; Oostendorp, Rob Ab; de Vries, Nanne K.

    2013-01-01

    Guideline adherence in physical therapy is far from optimal, which has consequences for the effectiveness and efficiency of physical therapy care. Programmes to enhance guideline adherence have, so far, been relatively ineffective. We systematically developed a theory-based Quality Improvement in

  12. Evaluation of the theory-based Quality Improvement in Physical Therapy (QUIP) programme: a one-group, pre-test post-test pilot study

    NARCIS (Netherlands)

    Rutten, G.M.J.; Harting, J.; Bartholomew, L.K.; Schlief, A.; Oostendorp, R.A.B.; Vries, N.K. de

    2013-01-01

    BACKGROUND: Guideline adherence in physical therapy is far from optimal, which has consequences for the effectiveness and efficiency of physical therapy care. Programmes to enhance guideline adherence have, so far, been relatively ineffective. We systematically developed a theory-based Quality

  13. The Effects of IGF-1 on Trk Expressing DRG Neurons with HIV-gp120- Induced Neurotoxicity.

    Science.gov (United States)

    Li, Hao; Liu, Zhen; Chi, Heng; Bi, Yanwen; Song, Lijun; Liu, Huaxiang

    2016-01-01

    HIV envelope glycoprotein gp120 is the main protein that causes HIVassociated sensory neuropathy. However, the underlying mechanisms of gp120-induced neurotoxicity are still unclear. There are lack effective treatments for relieving HIV-related neuropathic symptoms caused by gp120-induced neurotoxicity. In the present study, tyrosine kinase receptor (Trk)A, TrkB, and TrkC expression in primary cultured dorsal root ganglion (DRG) neurons with gp120-induced neurotoxicity was investigated. The effects of IGF-1 on distinct Trk-positive DRG neurons with gp120-induced neurotoxicity were also determined. The results showed that gp120 not only dose-dependently induced DRG neuronal apoptosis and inhibited neuronal survival and neurite outgrowth, but also decreased distinct Trk expression levels. IGF-1 rescued DRG neurons from apoptosis and improved neuronal survival of gp120 neurotoxic DRG neurons in vitro. IGF-1 also improved TrkA and TrkB, but not TrkC, expression in gp120 neurotoxic conditions. The effects of IGF-1 could be blocked by preincubation with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. These results suggested that gp120 may have a wide range of neurotoxicity on different subpopulations of DRG neurons, while IGF-1 might only relieve some subpopulations of DRG neurons with gp120-induced neurotoxicity. These data provide novel information of mechanisms of gp120 neurotoxicity on primary sensory neurons and the potential therapeutic effects of IGF-1 on gp120-induced neurotoxicity.

  14. High Epstein-Barr Virus Load and Genomic Diversity Are Associated with Generation of gp350-Specific Neutralizing Antibodies following Acute Infectious Mononucleosis.

    Science.gov (United States)

    Weiss, Eric R; Alter, Galit; Ogembo, Javier Gordon; Henderson, Jennifer L; Tabak, Barbara; Bakiş, Yasin; Somasundaran, Mohan; Garber, Manuel; Selin, Liisa; Luzuriaga, Katherine

    2017-01-01

    The Epstein-Barr virus (EBV) gp350 glycoprotein interacts with the cellular receptor to mediate viral entry and is thought to be the major target for neutralizing antibodies. To better understand the role of EBV-specific antibodies in the control of viral replication and the evolution of sequence diversity, we measured EBV gp350-specific antibody responses and sequenced the gp350 gene in samples obtained from individuals experiencing primary EBV infection (acute infectious mononucleosis [AIM]) and again 6 months later (during convalescence [CONV]). EBV gp350-specific IgG was detected in the sera of 17 (71%) of 24 individuals at the time of AIM and all 24 (100%) individuals during CONV; binding antibody titers increased from AIM through CONV, reaching levels equivalent to those in age-matched, chronically infected individuals. Antibody-dependent cell-mediated phagocytosis (ADCP) was rarely detected during AIM (4 of 24 individuals; 17%) but was commonly detected during CONV (19 of 24 individuals; 79%). The majority (83%) of samples taken during AIM neutralized infection of primary B cells; all samples obtained at 6 months postdiagnosis neutralized EBV infection of cultured and primary target cells. Deep sequencing revealed interpatient gp350 sequence variation but conservation of the CR2-binding site. The levels of gp350-specific neutralizing activity directly correlated with higher peripheral blood EBV DNA levels during AIM and a greater evolution of diversity in gp350 nucleotide sequences from AIM to CONV. In summary, we conclude that the viral load and EBV gp350 diversity during early infection are associated with the development of neutralizing antibody responses following AIM. Antibodies against viral surface proteins can blunt the spread of viral infection by coating viral particles, mediating uptake by immune cells, or blocking interaction with host cell receptors, making them a desirable component of a sterilizing vaccine. The EBV surface protein gp350 is a

  15. 2002 Conference Programme and Book of Abstracts

    International Nuclear Information System (INIS)

    2002-01-01

    The 25th Annual (Silver Jubilee) Conference 2002 Conference Programme and Book of Abstracts gives a brief on the Nigerian Institute of Physics, the Sheda Science and Technology Complex. It carries the Conference programme and carries the abstracts of all the papers presented. The abstracts cover a wide range of subjects including topics in atmospheric physics, education, policy and planning, geophysics, instrumentation, mathematical sciences, theoretical physics, nuclear and health physics, solid state, electronic and health physics. We are grateful to the Nigerian Institute of Physics for this volume

  16. Safety and immunogenicity of rVSVΔG-ZEBOV-GP Ebola vaccine in adults and children in Lambaréné, Gabon: A phase I randomised trial.

    Science.gov (United States)

    Agnandji, Selidji T; Fernandes, José F; Bache, Emmanuel B; Obiang Mba, Régis M; Brosnahan, Jessica S; Kabwende, Lumeka; Pitzinger, Paul; Staarink, Pieter; Massinga-Loembe, Marguerite; Krähling, Verena; Biedenkopf, Nadine; Fehling, Sarah Katharina; Strecker, Thomas; Clark, David J; Staines, Henry M; Hooper, Jay W; Silvera, Peter; Moorthy, Vasee; Kieny, Marie-Paule; Adegnika, Akim A; Grobusch, Martin P; Becker, Stephan; Ramharter, Michael; Mordmüller, Benjamin; Lell, Bertrand; Krishna, Sanjeev; Kremsner, Peter G

    2017-10-01

    The rVSVΔG-ZEBOV-GP vaccine prevented Ebola virus disease when used at 2 × 107 plaque-forming units (PFU) in a trial in Guinea. This study provides further safety and immunogenicity data. A randomised, open-label phase I trial in Lambaréné, Gabon, studied 5 single intramuscular vaccine doses of 3 × 103, 3 × 104, 3 × 105, 3 × 106, or 2 × 107 PFU in 115 adults and a dose of 2 × 107 PFU in 20 adolescents and 20 children. The primary objective was safety and tolerability 28 days post-injection. Immunogenicity, viraemia, and shedding post-vaccination were evaluated as secondary objectives. In adults, mild-to-moderate adverse events were frequent, but there were no serious or severe adverse events related to vaccination. Before vaccination, Zaire Ebola virus (ZEBOV)-glycoprotein (GP)-specific and ZEBOV antibodies were detected in 11% and 27% of adults, respectively. In adults, 74%-100% of individuals who received a dose 3 × 104, 3 × 105, 3 × 106, or 2 × 107 PFU had a ≥4.0-fold increase in geometric mean titres (GMTs) of ZEBOV-GP-specific antibodies at day 28, reaching GMTs of 489 (95% CI: 264-908), 556 (95% CI: 280-1,101), 1,245 (95% CI: 899-1,724), and 1,503 (95% CI: 931-2,426), respectively. Twenty-two percent of adults had a ≥4-fold increase of ZEBOV antibodies, with GMTs at day 28 of 1,015 (647-1,591), 1,887 (1,154-3,085), 1,445 (1,013-2,062), and 3,958 (2,249-6,967) for the same doses, respectively. These antibodies persisted up to day 180 for doses ≥3 × 105 PFU. Adults with antibodies before vaccination had higher GMTs throughout. Neutralising antibodies were detected in more than 50% of participants at doses ≥3 × 105 PFU. As in adults, no serious or severe adverse events related to vaccine occurred in adolescents or children. At day 2, vaccine RNA titres were higher for adolescents and children than adults. At day 7, 78% of adolescents and 35% of children had recombinant vesicular stomatitis virus RNA detectable in saliva. The vaccine

  17. Safety and immunogenicity of rVSVΔG-ZEBOV-GP Ebola vaccine in adults and children in Lambaréné, Gabon: A phase I randomised trial.

    Directory of Open Access Journals (Sweden)

    Selidji T Agnandji

    2017-10-01

    Full Text Available The rVSVΔG-ZEBOV-GP vaccine prevented Ebola virus disease when used at 2 × 107 plaque-forming units (PFU in a trial in Guinea. This study provides further safety and immunogenicity data.A randomised, open-label phase I trial in Lambaréné, Gabon, studied 5 single intramuscular vaccine doses of 3 × 103, 3 × 104, 3 × 105, 3 × 106, or 2 × 107 PFU in 115 adults and a dose of 2 × 107 PFU in 20 adolescents and 20 children. The primary objective was safety and tolerability 28 days post-injection. Immunogenicity, viraemia, and shedding post-vaccination were evaluated as secondary objectives. In adults, mild-to-moderate adverse events were frequent, but there were no serious or severe adverse events related to vaccination. Before vaccination, Zaire Ebola virus (ZEBOV-glycoprotein (GP-specific and ZEBOV antibodies were detected in 11% and 27% of adults, respectively. In adults, 74%-100% of individuals who received a dose 3 × 104, 3 × 105, 3 × 106, or 2 × 107 PFU had a ≥4.0-fold increase in geometric mean titres (GMTs of ZEBOV-GP-specific antibodies at day 28, reaching GMTs of 489 (95% CI: 264-908, 556 (95% CI: 280-1,101, 1,245 (95% CI: 899-1,724, and 1,503 (95% CI: 931-2,426, respectively. Twenty-two percent of adults had a ≥4-fold increase of ZEBOV antibodies, with GMTs at day 28 of 1,015 (647-1,591, 1,887 (1,154-3,085, 1,445 (1,013-2,062, and 3,958 (2,249-6,967 for the same doses, respectively. These antibodies persisted up to day 180 for doses ≥3 × 105 PFU. Adults with antibodies before vaccination had higher GMTs throughout. Neutralising antibodies were detected in more than 50% of participants at doses ≥3 × 105 PFU. As in adults, no serious or severe adverse events related to vaccine occurred in adolescents or children. At day 2, vaccine RNA titres were higher for adolescents and children than adults. At day 7, 78% of adolescents and 35% of children had recombinant vesicular stomatitis virus RNA detectable in saliva. The

  18. Sickness certification for common mental disorders and GP return-to-work advice.

    Science.gov (United States)

    Gabbay, Mark; Shiels, Chris; Hillage, Jim

    2016-09-01

    Aim To report the types and duration of sickness certification for different common mental disorders (CMDs) and the prevalence of GP advice aimed at returning the patient to work. In the United Kingdom, common mental health problems, such and depression and stress, have become the main reasons for patients requesting a sickness certificate to abstain from usual employment. Increasing attention is being paid to mental health and its impact on employability and work capacity in all parts of the welfare system. However, relatively little is known about the extent to which different mental health diagnoses impact upon sickness certification outcomes, and how the GP has used the new fit note (introduced in 2010) to support a return to work for patients with mental health diagnoses. Sickness certification data was collected from 68 UK-based general practices for a period of 12 months. Findings The study found a large part of all sickness absence certified by GPs was due to CMDs (29% of all sickness absence episodes). Females, younger patients and those living in deprived areas were more likely to receive a fit note for a CMD (compared with one for a physical health problem). The highest proportion of CMD fit notes were issued for 'stress'. However, sickness certification for depression contributed nearly half of all weeks certified for mental health problems. Only 7% of CMD fit notes included any 'may be fit' advice from the GP, with type of advice varying by mental health diagnostic category. Patients living in the most socially deprived neighbourhoods were less likely to receive 'may be fit' advice on their CMD fit notes.

  19. Proteomic plasma membrane profiling reveals an essential role for gp96 in the cell surface expression of LDLR family members, including the LDL receptor and LRP6.

    Science.gov (United States)

    Weekes, Michael P; Antrobus, Robin; Talbot, Suzanne; Hör, Simon; Simecek, Nikol; Smith, Duncan L; Bloor, Stuart; Randow, Felix; Lehner, Paul J

    2012-03-02

    The endoplasmic reticulum chaperone gp96 is required for the cell surface expression of a narrow range of proteins, including toll-like receptors (TLRs) and integrins. To identify a more comprehensive repertoire of proteins whose cell surface expression is dependent on gp96, we developed plasma membrane profiling (PMP), a technique that combines SILAC labeling with selective cell surface aminooxy-biotinylation. This approach allowed us to compare the relative abundance of plasma membrane (PM) proteins on gp96-deficient versus gp96-reconstituted murine pre-B cells. Analysis of unfractionated tryptic peptides initially identified 113 PM proteins, which extended to 706 PM proteins using peptide prefractionation. We confirmed a requirement for gp96 in the cell surface expression of certain TLRs and integrins and found a marked decrease in cell surface expression of four members of the extended LDL receptor family (LDLR, LRP6, Sorl1 and LRP8) in the absence of gp96. Other novel gp96 client proteins included CD180/Ly86, important in the B-cell response to lipopolysaccharide. We highlight common structural motifs in these client proteins that may be recognized by gp96, including the beta-propeller and leucine-rich repeat. This study therefore identifies the extended LDL receptor family as an important new family of proteins whose cell surface expression is regulated by gp96.

  20. A 4-week, lifestyle-integrated, home-based exercise training programme elicits improvements in physical function and lean mass in older men and women: a pilot study.

    Science.gov (United States)

    Cegielski, Jessica; Brook, Matthew S; Quinlan, Jonathan I; Wilkinson, Daniel J; Smith, Kenneth; Atherton, Philip J; Phillips, Bethan E

    2017-01-01

    Developing alternative exercise programmes that can alleviate certain barriers to exercise such as psychological, environmental or socio-economical barriers, but provide similar physiological benefits e.g. increases in muscle mass and strength, is of grave importance. This pilot study aimed to assess the efficacy of an unsupervised, 4-week, whole-body home-based exercise training (HBET) programme, incorporated into daily living activities, on skeletal muscle mass, power and strength. Twelve healthy older volunteers (63±3 years, 7 men: 5 women, BMI: 29±1 kg/m²) carried out the 4-week "lifestyle-integrated" HBET of 8 exercises, 3x12 repetitions each, every day. Before and after HBET, a number of physical function tests were carried out: unilateral leg extension 1-RM (one- repetition maximum), MVC (maximal voluntary contraction) leg extension, lower leg muscle power (via Nottingham Power Rig), handgrip strength and SPPBT (short physical performance battery test). A D 3 -Creatine method was used for assessment of whole-body skeletal muscle mass, and ultrasound was used to measure the quadriceps cross-sectional area (CSA) and vastus lateralis muscle thickness. Four weeks HBET elicited significant (p<0.05) improvements in leg muscle power (276.7±38.5 vs. 323.4±43.4 W), maximal voluntary contraction (60°: 154.2±18.4 vs. 168.8±15.2 Nm, 90°: 152.1±10.5 vs. 159.1±11.4 Nm) and quadriceps CSA (57.5±5.4 vs. 59.0±5.3 cm 2 ), with a trend for an increase in leg strength (1-RM: 45.7±5.9 vs. 49.6±6.0 kg, P=0.08). This was despite there being no significant differences in whole-body skeletal muscle mass, as assessed via D 3 -Creatine. This study demonstrates that increases in multiple aspects of muscle function can be achieved in older adults with just 4-weeks of "lifestyle-integrated" HBET, with a cost-effective means. This training mode may prove to be a beneficial alternative for maintaining and/or improving muscle mass and function in older adults.

  1. Improved cognitive performance in preadolescent Danish children after the school-based physical activity programme "FIFA 11 for Health" for Europe

    DEFF Research Database (Denmark)

    Lind, Rune Rasmussen; Geertsen, Svend Sparre; Ørntoft, Christina Øyangen

    2018-01-01

    , p = .012) and working memory (79, sx– = 35 ms, p = .020). Conclusion: This pilot study provides evidence that the school-based physical activity programme “FIFA 11 for Health” for Europe can improve cognitive performance in preadolescent Danish schoolchildren. Future studies should attempt...... programme. The programme combines small-sided football games, drills and health education. Cognitive performance was evaluated at baseline and follow-up. Results: The IG improved their cognitive performance compared to the CG for psychomotor function (56, sx– = 22 ms, p attention (39, sx– = 17 ms...

  2. Preliminary Analysis of the Social and Scientific Impact of the UAEM-ININ M.Sc. and D.Sc. Graduate Programme in Medical Physics

    Science.gov (United States)

    Mitsoura, Eleni; Isaac-Olive, Keila; Torres-Garcia, Eugenio; Camacho-Lopez, Miguel Angel; Hardy-Perez, Alberto

    2010-12-01

    Sponsored by the International Atomic Energy Agency (IAEA) in 1994, the Instituto Nacional de Investigaciones Nucleares (ININ) started in Mexico a teaching and training programme (Diplomado) in Radiotherapy Medical Physics. Based on this experience, the Universidad Autónoma del Estado de México (UAEM) and the Instituto Nacional de Investigaciones Nucleares (ININ) launched two years later, the first Graduate Programme in Science (M.Sc. and D.Sc.), specialised in Medical Physics in Mexico. A preliminary analysis of the social and scientific impact of the UAEM-ININ Programme is presented in this work based on the achievements attained, regarding the number of graduated Medical Physicists, their geographic and academic origin, their current professional activities and the number of scientific publications produced as a result of the thesis, as well as their citations.

  3. Subtype C gp140 Vaccine Boosts Immune Responses Primed by the South African AIDS Vaccine Initiative DNA-C2 and MVA-C HIV Vaccines after More than a 2-Year Gap.

    Science.gov (United States)

    Gray, Glenda E; Mayer, Kenneth H; Elizaga, Marnie L; Bekker, Linda-Gail; Allen, Mary; Morris, Lynn; Montefiori, David; De Rosa, Stephen C; Sato, Alicia; Gu, Niya; Tomaras, Georgia D; Tucker, Timothy; Barnett, Susan W; Mkhize, Nonhlanhla N; Shen, Xiaoying; Downing, Katrina; Williamson, Carolyn; Pensiero, Michael; Corey, Lawrence; Williamson, Anna-Lise

    2016-06-01

    A phase I safety and immunogenicity study investigated South African AIDS Vaccine Initiative (SAAVI) HIV-1 subtype C (HIV-1C) DNA vaccine encoding Gag-RT-Tat-Nef and gp150, boosted with modified vaccinia Ankara (MVA) expressing matched antigens. Following the finding of partial protective efficacy in the RV144 HIV vaccine efficacy trial, a protein boost with HIV-1 subtype C V2-deleted gp140 with MF59 was added to the regimen. A total of 48 participants (12 U.S. participants and 36 Republic of South Africa [RSA] participants) were randomized to receive 3 intramuscular (i.m.) doses of SAAVI DNA-C2 of 4 mg (months 0, 1, and 2) and 2 i.m. doses of SAAVI MVA-C of 1.45 × 10(9) PFU (months 4 and 5) (n = 40) or of a placebo (n = 8). Approximately 2 years after vaccination, 27 participants were rerandomized to receive gp140/MF59 at 100 μg or placebo, as 2 i.m. injections, 3 months apart. The vaccine regimen was safe and well tolerated. After the DNA-MVA regimen, CD4(+) T-cell and CD8(+) T-cell responses occurred in 74% and 32% of the participants, respectively. The protein boost increased CD4(+) T-cell responses to 87% of the subjects. All participants developed tier 1 HIV-1C neutralizing antibody responses as well as durable Env binding antibodies that recognized linear V3 and C5 peptides. The HIV-1 subtype C DNA-MVA vaccine regimen showed promising cellular immunogenicity. Boosting with gp140/MF59 enhanced levels of binding and neutralizing antibodies as well as CD4(+) T-cell responses to HIV-1 envelope. (This study has been registered at ClinicalTrials.gov under registration no. NCT00574600 and NCT01423825.). Copyright © 2016 Gray et al.

  4. Exploring resilience in rural GP registrars ? implications for training

    OpenAIRE

    Walters, Lucie; Laurence, Caroline O.; Dollard, Joanne; Elliott, Taryn; Eley, Diann S.

    2015-01-01

    Background Resilience can be defined as the ability to rebound from adversity and overcome difficult circumstances. General Practice (GP) registrars face many challenges in transitioning into general practice, and additional stressors and pressures apply for those choosing a career in rural practice. At this time of international rural generalist medical workforce shortages, it is important to focus on the needs of rural GP registrars and how to support them to become resilient health care pr...

  5. G4beamline Simulations for H8

    CERN Document Server

    Thoresen, Freja

    2015-01-01

    Detailed simulations of the H8 beam line at the North Area, using the G4beamline software were performed in the framework of this study. The conventions used by the program are analysed. Having modelled precisely the beam line, several studies examining the beam transmission and composition were performed. The results were compared with measurements, where a satisfactory agreement was found. The muon production and transport is studied in details throughout the beam line.

  6. Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance

    International Nuclear Information System (INIS)

    Anastassopoulou, Cleo G.; Ketas, Thomas J.; Sanders, Rogier W.; Johan Klasse, Per; Moore, John P.

    2012-01-01

    A rare pathway of HIV-1 resistance to small molecule CCR5 inhibitors such as Vicriviroc (VCV) involves changes solely in the gp41 fusion peptide (FP). Here, we show that the G516V change is critical to VCV resistance in PBMC and TZM-bl cells, although it must be accompanied by either M518V or F519I to have a substantial impact. Modeling VCV inhibition data from the two cell types indicated that G516V allows both double mutants to use VCV-CCR5 complexes for entry. The model further identified F519I as an independent determinant of preference for the unoccupied, high-VCV affinity form of CCR5. From inhibitor-free reversion cultures, we also identified a substitution in the inner domain of gp120, T244A, which appears to counter the resistance phenotype created by the FP substitutions. Examining the interplay of these changes will enhance our understanding of Env complex interactions that influence both HIV-1 entry and resistance to CCR5 inhibitors.

  7. Reasons for elderly patients GP visits: results of a cross-sectional study

    OpenAIRE

    Frese, Thomas; Mahlmeister, Jarmila; Deutsch, Tobias; Sandholzer, Hagen

    2016-01-01

    Thomas Frese, Jarmila Mahlmeister, Tobias Deutsch, Hagen Sandholzer Department of General Practice, Medical Faculty, University of Leipzig, Leipzig, Germany Objective: The aim of this study is to describe the frequency of reasons for elderly patients visits to a general practice (GP) setting. Subjects and methods: Cross-sectional data from 8,877 randomly selected patients were assessed during a 1-year period by 209 GPs in the German federal state of Saxony. The reasons for visits, performed...

  8. Brief report: Exploring the benefits of a peer-tutored physical education programme among high school students with intellectual disability.

    Science.gov (United States)

    Gobbi, Erica; Greguol, Márcia; Carraro, Attilio

    2018-01-29

    The purpose of this study was to explore possible benefits of a peer-tutored physical education programme (PTPE) in comparison with school physical education (SPE) in high school students with intellectual disability. Nineteen students with intellectual disabilities (15 boys, mean age 17.4 ± 1.7 years) were monitored during three PTPE and three SPE classes. A factorial RM-ANOVA was used to test differences on objective measured physical activity (PA), enjoyment and exertion during the two conditions, considering participants' weight condition as independent factor. During PTPE, participants reported higher light intensity PA, enjoyment and exertion than during SPE. Participants with overweight showed less inactive time and higher light intensity PA during PTPE than during SPE. The peer-tutored programme was beneficial for adolescents with intellectual disability, particularly for those in overweight condition. The higher enjoyment found during PTPE may encourage exercise participation of students with intellectual disability. © 2018 John Wiley & Sons Ltd.

  9. Parallelism at Cern: real-time and off-line applications in the GP-MIMD2 project

    International Nuclear Information System (INIS)

    Calafiura, P.

    1997-01-01

    A wide range of general purpose high-energy physics applications, ranging from Monte Carlo simulation to data acquisition, from interactive data analysis to on-line filtering, have been ported, or developed, and run in parallel on IBM SP-2 and Meiko CS-2 CERN large multi-processor machines. The ESPRIT project GP-MIMD2 has been a catalyst for the interest in parallel computing at CERN. The project provided the 128 processor Meiko CS-2 system that is now succesfully integrated in the CERN computing environment. The CERN experiment NA48 was involved in the GP-MIMD2 project since the beginning. NA48 physicists run, as part of their day-to-day work, simulation and analysis programs parallelized using the message passing interface MPI. The CS-2 is also a vital component of the experiment data acquisition system and will be used to calibrate in real-time the 13000 channels liquid krypton calorimeter. (orig.)

  10. Planetary physics research programme at the Facility for Antiprotons and Ion Research at Darmstadt

    International Nuclear Information System (INIS)

    Tahir, N.A.; Neumayer, P.; Bagnoud, V.; Lomonosov, I.V.; Borm, B.; Piriz, A.R.; Piriz, S.A.; Shutov, A.

    2017-01-01

    Planetary physics research is an important part of the high energy density (HED) physics programme at the Facility for Antiprotons and Ion Research (FAIR) at Darmstadt. In this paper, we report numerical simulations of a proposed experiment named LAboratory PLAnetary Sciences (LAPLAS). These simulations show that in such experiments, an Fe sample can be imploded to extreme physical conditions that are expected to exist in the interior of the Earth and in the interior of more massive rocky planets named, super-Earths. The LAPLAS experiments will thus provide very valuable information on the equation-of-state (EOS) and transport properties of HED Fe, which will help the scientists to understand the structure and evolution of the planets in our solar system and of the extrasolar system planets. (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  11. Planetary physics research programme at the Facility for Antiprotons and Ion Research at Darmstadt

    Energy Technology Data Exchange (ETDEWEB)

    Tahir, N.A.; Neumayer, P.; Bagnoud, V. [Department of Plasma Physics, GSI Helmholtzzentrum fuer Schwerionenforschung, Darmstadt (Germany); Lomonosov, I.V. [Institute of Problems of Chemical Physics, Russian Academy of Sciences, Chernogolovka (Russian Federation); Tomsk University, Tomsk (Russian Federation); Lomonosov Moscow State University, Moscow (Russian Federation); Moscow Institute of Physics and Technology, Dolgoprudny (Russian Federation); Borm, B. [Department of Physics, Goethe-Universitaet Frankfurt, Frankfurt (Germany); Piriz, A.R.; Piriz, S.A. [E.T.S.I. Industrials, University of Castilla-La Mancha, Ciudad Real (Spain); Shutov, A. [Institute of Problems of Chemical Physics, Russian Academy of Sciences, Chernogolovka (Russian Federation)

    2017-11-15

    Planetary physics research is an important part of the high energy density (HED) physics programme at the Facility for Antiprotons and Ion Research (FAIR) at Darmstadt. In this paper, we report numerical simulations of a proposed experiment named LAboratory PLAnetary Sciences (LAPLAS). These simulations show that in such experiments, an Fe sample can be imploded to extreme physical conditions that are expected to exist in the interior of the Earth and in the interior of more massive rocky planets named, super-Earths. The LAPLAS experiments will thus provide very valuable information on the equation-of-state (EOS) and transport properties of HED Fe, which will help the scientists to understand the structure and evolution of the planets in our solar system and of the extrasolar system planets. (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  12. Use of the "Moodle" Platform to Promote an Ongoing Learning When Lecturing General Physics in the Physics, Mathematics and Electronic Engineering Programmes at the University of the Basque Country UPV/EHU

    Science.gov (United States)

    López, Gabriel A.; Sáenz, Jon; Leonardo, Aritz; Gurtubay, Idoia G.

    2016-01-01

    The "Moodle" platform has been used to put into practice an ongoing evaluation of the students' Physics learning process. The evaluation has been done on the frame of the course General Physics, which is lectured during the first year of the Physics, Mathematics and Electronic Engineering Programmes at the Faculty of Science and…

  13. Scotland's GP paediatric scholarship: an evaluation.

    Science.gov (United States)

    MacVicar, Ronald; Borland, Lyndsey; McHale, Sharon; Goh, Dayeel; Potter, Alex

    2018-05-01

    In a previous publication we described the implementation and early evaluation of general practice paediatric scholarships in Scotland. We suggested that it was too early to be able to determine whether this significant investment will produce a return for Scotland in terms of enhanced roles in providing, leading or developing children's services in primary care or at the primary care/secondary care interface. This paper presents the results of a survey of the impact of the scholarship for the first six cohorts of the scholarship (119 General Practitioners). The response rate was 76%. Of the 90 respondents, almost half (44) have developed roles or areas of special paediatric interest either within or out with the practice, or in three cases both within and out with the practice. A total of 37 (43%) of those that continue to work within general practice reported that they have developed areas of special interest of benefit to the practice. Qualitative analysis of free text questions suggested that scholars had benefited from their experience in terms of increased confidence in dealing with child health problems, developing links with secondary care colleagues, and personal gain with respect to role development. What is already known in this area: Changes in GP Training have been suggested in order to provide a workforce that can meet the needs of infants, children and young people. Studies have shown a positive impact of paediatric trainees and GP trainees learning together. Little attention has however been given to the potential to support trained GPs to develop their expertise in child health. What this work adds: Early evaluation of the Scottish Paediatric Scholarship suggested a high degree of satisfaction. This more robust evaluation suggests that almost half (44/90 respondents) have developed roles or areas of special paediatric interest either within or out with the practice, or in three cases both within and out with the practice. Suggestions for future

  14. Comparison between Synchronous and Asynchronous Instructional Delivery Method of Training Programme on In-Service Physical Educators' Knowledge

    Science.gov (United States)

    Emmanouilidou, Kyriaki; Derri, Vassiliki; Antoniou, Panagiotis; Kyrgiridis, Pavlos

    2012-01-01

    The purpose of the study was to compare the influences of a training programme's instructional delivery method (synchronous and asynchronous) on Greek in-service physical educators' cognitive understanding on student assessment. Forty nine participants were randomly divided into synchronous, asynchronous, and control group. The experimental groups…

  15. Health Physics Division annual report for the period ending December 31, 1972 Part I : Research and development

    International Nuclear Information System (INIS)

    1973-01-01

    The Health Physics Division of the Bhabha Atomic Research Centre, Bombay (India) is responsible for: (i) assessment and control of radiation and industrial hazards in various research establishments and industrial installations of the Department of Atomic Energy and (ii) prescribing limits and conditions in respect of waste releases to the environment from the above establishments and installations. For effective discharge of these responsibilities, the Division is engaged in various research programmes in the following areas: (1) radiation dosimetry (2) instrumentation (3) pollution (4) environmental radioactivity, both natural and artificial (5) radioactive contamination and nuclear safety (6) industrial hygiene and safety (7) radioecology (8) micrometeorology. These programmes are described in brief. (M.G.B.)

  16. Validating glycoprotein non-metastatic melanoma B (gpNMB, osteoactivin), a new biomarker of Gaucher disease.

    Science.gov (United States)

    Murugesan, Vagishwari; Liu, Jun; Yang, Ruhua; Lin, Haiquin; Lischuk, Andrew; Pastores, Gregory; Zhang, Xiaokui; Chuang, Wei-Lien; Mistry, Pramod K

    2018-02-01

    In the spleens of Gaucher disease mice and patients, there is a striking elevation of expression of glycoprotein non-Metastatic Melanoma B (gpNMB). We conducted a study in a large cohort of patients with Gaucher disease to assess the utility of serum levels of soluble fragment of gpNMB as a biomarker of disease activity. There was >15-fold elevation of gpNMB in sera of untreated patients with Gaucher disease. gpNMB levels correlated with overall disease severity as well as the severity of individual organ compartments: liver, spleen, bone and hematological disease. Imiglucerase enzyme replacement therapy resulted in significant reduction of gpNMB. Serum levels of gpNMB were highly correlated with accumulation of bioactive lipid substrate of Gaucher disease, glucosylsphingosine as well as established biomarkers, chitotriosidase and chemokine, CCL18. Our results suggest utility of gpNMB as a biomarker of Gaucher disease to monitor individual patients and cohorts of patients for disease progression or response to therapy. Investigation of gpNMB in Gaucher disease pathophysiology is likely to illuminate our understanding disease mechanisms. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. A neuromuscular exercise programme versus standard care for patients with traumatic anterior shoulder instability

    DEFF Research Database (Denmark)

    Eshoj, Henrik; Rasmussen, Sten; Frich, Lars Henrik

    2017-01-01

    BACKGROUND: Anterior shoulder dislocation is a common injury and may have considerable impact on shoulder-related quality of life (QoL). If not warranted for initial stabilising surgery, patients are mostly left with little to no post-traumatic rehabilitation. This may be due to lack of evidence......-based exercise programmes. In similar, high-impact injuries (e.g. anterior cruciate ligament tears in the knee) neuromuscular exercise has shown large success in improving physical function and QoL. Thus, the objective of this trial is to compare a nonoperative neuromuscular exercise shoulder programme...... dislocations due to at least one traumatic event will be randomised to 12 weeks of either a standardised, individualised or physiotherapist-supervised neuromuscular shoulder exercise programme or standard care (self-managed shoulder exercise programme). Patients will be stratified according to injury status...

  18. Physical Fault Injection and Monitoring Methods for Programmable Devices

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00510096; Ferencei, Jozef

    A method of detecting faults for evaluating the fault cross section of any field programmable gate array (FPGA) was developed and is described in the thesis. The incidence of single event effects in FPGAs was studied for different probe particles (proton, neutron, gamma) using this method. The existing accelerator infrastructure of the Nuclear Physics Institute in Rez was supplemented by more sensitive beam monitoring system to ensure that the tests are done under well defined beam conditions. The bit cross section of single event effects was measured for different types of configuration memories, clock signal phase and beam energies and intensities. The extended infrastructure served also for radiation testing of components which are planned to be used in the new Inner Tracking System (ITS) detector of the ALICE experiment and for selecting optimal fault mitigation techniques used for securing the design of the FPGA-based ITS readout unit against faults induced by ionizing radiation.

  19. Barriers to participation in a phase II cardiac rehabilitation programme.

    Science.gov (United States)

    Mak, Y M W; Chan, W K; Yue, C S S

    2005-12-01

    To identify barriers to participation in a phase II cardiac rehabilitation programme and measures that may enhance participation. Prospective study. Regional hospital, Hong Kong. Cardiac patients recruited for a phase I cardiac rehabilitation programme from July 2002 to January 2003. Reasons for not participating in a phase II cardiac rehabilitation programme. Of the 193 patients recruited for a phase I cardiac rehabilitation programme, 152 (79%) patients, with a mean age of 70.3 years (standard deviation, 11.9 years), did not proceed to phase II programme. Eleven (7%) deaths occurred before commencement of phase II and 74 (49%) patients were considered physically unfit. Reasons for the latter included fractures, pain, or degenerative changes in the lower limbs (24%), and co-morbidities such as cerebrovascular accident (19%), chronic renal failure (11%), congestive heart failure (9%), and unstable angina (8%). Phase II rehabilitation was postponed until after completion of scheduled cardiac interventions in 13% of patients. Failure of physicians to arrange the pre-phase II exercise stress test as per protocol was reported in 7% of patients. Other reasons were reported: work or time conflicts (16%), non-compliance with cardiac treatment (5%), financial constraints (4%), self-exercise (3%), fear after exercise stress testing (3%), and patients returning to their original cardiologists for treatment (3%). A significant (79%) proportion of patients did not proceed to a phase II cardiac rehabilitation programme for a variety of reasons. These included physical unfitness, work or time conflicts, and need to attend scheduled cardiac interventions. Further studies are required to determine how to overcome obstacles to cardiac rehabilitation.

  20. Effects on Physical Health of a Multicomponent Programme for Overweight and Obesity for Adults with Intellectual Disabilities

    Science.gov (United States)

    Martínez-Zaragoza, Fermín; Campillo-Martínez, José M.; Ato-García, Manuel

    2016-01-01

    Background: Overweight and obesity are major health risk factors in people with intellectual disabilities. The aim of this study was to test the effectiveness of a multicomponent programme (physical activity, diet and motivation) for overweight and obesity in adults with intellectual disabilities. Material and Methods: A quasi-experimental design…

  1. Engineering and exploitation of a fluorescent HIV-1 gp120 for live cell CD4 binding assays

    Energy Technology Data Exchange (ETDEWEB)

    Costantini, Lindsey M. [Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Irvin, Susan C. [Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Kennedy, Steven C. [Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Guo, Feng [Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Goldstein, Harris; Herold, Betsy C. [Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Snapp, Erik L., E-mail: erik-lee.snapp@einstein.yu.edu [Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States)

    2015-02-15

    The HIV-1 envelope glycoprotein, gp120, binds the host cell receptor, CD4, in the initial step of HIV viral entry and infection. This process is an appealing target for the development of inhibitory drugs and neutralizing antibodies. To study gp120 binding and intracellular trafficking, we engineered a fluorescent fusion of the humanized gp120 JRFL HIV-1 variant and GFP. Gp120-sfGFP is glycosylated with human sugars, robustly expressed, and secreted from cultured human cells. Protein dynamics, quality control, and trafficking can be visualized in live cells. The fusion protein can be readily modified with different gp120 variants or fluorescent proteins. Finally, secreted gp120-sfGFP enables a sensitive and easy binding assay that can quantitatively screen potential inhibitors of gp120-CD4 binding on live cells via fluorescence imaging or laser scanning cytometry. This adaptable research tool should aid in studies of gp120 cell biology and the development of novel anti-HIV drugs. - Highlights: • Development of fluorescent protein labeled HIV-1 envelope gp120. • Imaging of gp120 dynamics and trafficking in live cells. • Quantitative visual assay of antibody-mediated inhibition of gp120 binding to CD4 on live cells.

  2. Engineering and exploitation of a fluorescent HIV-1 gp120 for live cell CD4 binding assays

    International Nuclear Information System (INIS)

    Costantini, Lindsey M.; Irvin, Susan C.; Kennedy, Steven C.; Guo, Feng; Goldstein, Harris; Herold, Betsy C.; Snapp, Erik L.

    2015-01-01

    The HIV-1 envelope glycoprotein, gp120, binds the host cell receptor, CD4, in the initial step of HIV viral entry and infection. This process is an appealing target for the development of inhibitory drugs and neutralizing antibodies. To study gp120 binding and intracellular trafficking, we engineered a fluorescent fusion of the humanized gp120 JRFL HIV-1 variant and GFP. Gp120-sfGFP is glycosylated with human sugars, robustly expressed, and secreted from cultured human cells. Protein dynamics, quality control, and trafficking can be visualized in live cells. The fusion protein can be readily modified with different gp120 variants or fluorescent proteins. Finally, secreted gp120-sfGFP enables a sensitive and easy binding assay that can quantitatively screen potential inhibitors of gp120-CD4 binding on live cells via fluorescence imaging or laser scanning cytometry. This adaptable research tool should aid in studies of gp120 cell biology and the development of novel anti-HIV drugs. - Highlights: • Development of fluorescent protein labeled HIV-1 envelope gp120. • Imaging of gp120 dynamics and trafficking in live cells. • Quantitative visual assay of antibody-mediated inhibition of gp120 binding to CD4 on live cells

  3. Novel Epstein-Barr virus-like particles incorporating gH/gL-EBNA1 or gB-LMP2 induce high neutralizing antibody titers and EBV-specific T-cell responses in immunized mice.

    Science.gov (United States)

    Perez, Elizabeth M; Foley, Joslyn; Tison, Timelia; Silva, Rute; Ogembo, Javier Gordon

    2017-03-21

    Previous Epstein-Barr virus (EBV) prophylactic vaccines based on the major surface glycoprotein gp350/220 as an immunogen have failed to block viral infection in humans, suggesting a need to target other viral envelope glycoproteins. In this study, we reasoned that incorporating gH/gL or gB, critical glycoproteins for viral fusion and entry, on the surface of a virus-like particle (VLP) would be more immunogenic than gp350/220 for generating effective neutralizing antibodies to prevent viral infection of both epithelial and B cell lines. To boost the humoral response and trigger cell-mediated immunity, EBV nuclear antigen 1 (EBNA1) and latent membrane protein 2 (LMP2), intracellular latency proteins expressed in all EBV-infected cells, were also included as critical components of the polyvalent EBV VLP. gH/gL-EBNA1 and gB-LMP2 VLPs were efficiently produced in Chinese hamster ovary cells, an FDA-approved vehicle for mass-production of biologics. Immunization with gH/gL-EBNA1 and gB-LMP2 VLPs without adjuvant generated both high neutralizing antibody titers in vitro and EBV-specific T-cell responses in BALB/c mice. These data demonstrate that will be invaluable not only in preventing EBV infection, but importantly, in preventing and treating the 200,000 cases of EBV-associated cancers that occur globally every year.

  4. Glycolytic pathway (GP), kreb's cycle (KC), and hexose monophosphate shunt (HMS) activity in myocardial subcellular fractions exposed to cannabinoids

    Energy Technology Data Exchange (ETDEWEB)

    Watson, A.T.; Manno, B.R.; King, J.W.; Fowler, M.R.; Dempsey, C.A.; Manno, J.E.

    1986-03-05

    Delta-9-tetrahydrocannabinol (..delta../sup 9/-THC), the primary psychoactive component of marihuana, and its active metabolite 11-hydroxy-..delta../sup 9/-tetrahydrocannabinol (11-OH-..delta../sup 9/-THC) have been reported to produce a direct cardiac depressant effect. Studies in isolated perfused rat hearts have indicated a decreased force of contraction (inotropic response) when ..delta../sup 9/-THC or 11-OH-..delta../sup 9/-THC was administered in microgram amounts. The mechanism and site of action have not been explained or correlated with associated metabolic pathways. The purpose of this study was to investigate the effects of cannabinoids on major myocardial energy producing pathways, GP and KC, and a non-energy producing pathway, HMS. Cardiac ventricular tissue from male Sprague-Dawley rats (250-300 g) was excised and homogenized for subcellular fractionation. KC, GP and HMS activity was assayed in the appropriate fractions by measuring /sup 14/CO/sub 2/ generation from /sup 14/C-2-pyruvate, /sup 14/C-6-glucose and /sup 14/C-1-glucose respectively. Duplicate assays (n=8) were performed on tissue exposed to saline (control), empty liposomes (vehicle) and four doses each of ..delta../sup 9/-THC and 11-OH-..delta../sup 9/-THC. Changes in metabolic activity and decreases in cardiac contractile performance may be associated.

  5. G8 decision on fusion would herald nuclear future

    CERN Multimedia

    Starck, Peter

    2005-01-01

    Nuclear fusion as a future abundant energy source would receive a boost if G8 leaders agree next month on the site for the world's first fusion test reactor, two nuclear scientists said on Wednesday (1 page)

  6. G8+5 collaboration on energy efficiency and IPEEC: Shortcut to a sustainable future?

    International Nuclear Information System (INIS)

    Lesage, Dries; Van de Graaf, Thijs; Westphal, Kirsten

    2010-01-01

    In recent years, the G8+5 system has proven to be a major focal point of international cooperation in the field of energy efficiency. The G8 has set up multiple dialogues and collaborative frameworks with five emerging economies (China, India, Brazil, Mexico and South Africa) on energy and energy efficiency. The most prominent initiative so far is the creation of the International Partnership for Energy Efficiency Cooperation (IPEEC) in 2009. This article critically evaluates these joint efforts between the G8 and the 'Plus Five' on energy efficiency. More specifically, the purpose of this article is (1) to frame and explain the emergence of this kind of great-power cooperation; (2) to map G8+5 collaboration on energy efficiency; and (3) to provide a critical assessment of the relevance, impact and results of G8+5 initiated energy efficiency initiatives. The main conclusion is that the G8+5 system has performed better on the external dimension (steering global governance) than on the internal dimension (coordination of domestic policies) of global energy efficiency governance.

  7. Physical activity as a treatment for depression: the TREAD randomised trial protocol.

    Science.gov (United States)

    Baxter, Helen; Winder, Rachel; Chalder, Melanie; Wright, Christine; Sherlock, Sofie; Haase, Anne; Wiles, Nicola J; Montgomery, Alan A; Taylor, Adrian H; Fox, Ken R; Lawlor, Debbie A; Peters, Tim J; Sharp, Deborah J; Campbell, John; Lewis, Glyn

    2010-11-12

    Depression is one of the most common reasons for consulting a General Practitioner (GP) within the UK. Whilst antidepressants have been shown to be clinically effective, many patients and healthcare professionals would like to access other forms of treatment as an alternative or adjunct to drug therapy for depression. A recent systematic review presented some evidence that physical activity could offer one such option, although further investigation is needed to test its effectiveness within the context of the National Health Service.The aim of this paper is to describe the protocol for a randomised, controlled trial (RCT) designed to evaluate an intervention developed to increase physical activity as a treatment for depression within primary care. The TREAD study is a pragmatic, multi-centre, two-arm RCT which targets patients presenting with a new episode of depression. Patients were approached if they were aged 18-69, had recently consulted their GP for depression and, where appropriate, had been taking antidepressants for less than one month. Only those patients with a confirmed diagnosis of a depressive episode as assessed by the Clinical Interview Schedule-Revised (CIS-R), a Beck Depression Inventory (BDI) score of at least 14 and informed written consent were included in the study. Eligible patients were individually randomised to one of two treatment groups; usual GP care or usual GP care plus facilitated physical activity. The primary outcome of the trial is clinical symptoms of depression assessed using the BDI four months after randomisation. A number of secondary outcomes are also measured at the 4-, 8- and 12-month follow-up points including quality of life, attitude to and involvement in physical activity and antidepressant use/adherence. Outcomes will be analysed on an intention-to-treat (ITT) basis and will use linear and logistic regression models to compare treatments. The results of the trial will provide information about the effectiveness of

  8. Physical activity as a treatment for depression: the TREAD randomised trial protocol

    Directory of Open Access Journals (Sweden)

    Lawlor Debbie A

    2010-11-01

    Full Text Available Abstract Background Depression is one of the most common reasons for consulting a General Practitioner (GP within the UK. Whilst antidepressants have been shown to be clinically effective, many patients and healthcare professionals would like to access other forms of treatment as an alternative or adjunct to drug therapy for depression. A recent systematic review presented some evidence that physical activity could offer one such option, although further investigation is needed to test its effectiveness within the context of the National Health Service. The aim of this paper is to describe the protocol for a randomised, controlled trial (RCT designed to evaluate an intervention developed to increase physical activity as a treatment for depression within primary care. Methods/design The TREAD study is a pragmatic, multi-centre, two-arm RCT which targets patients presenting with a new episode of depression. Patients were approached if they were aged 18-69, had recently consulted their GP for depression and, where appropriate, had been taking antidepressants for less than one month. Only those patients with a confirmed diagnosis of a depressive episode as assessed by the Clinical Interview Schedule-Revised (CIS-R, a Beck Depression Inventory (BDI score of at least 14 and informed written consent were included in the study. Eligible patients were individually randomised to one of two treatment groups; usual GP care or usual GP care plus facilitated physical activity. The primary outcome of the trial is clinical symptoms of depression assessed using the BDI four months after randomisation. A number of secondary outcomes are also measured at the 4-, 8- and 12-month follow-up points including quality of life, attitude to and involvement in physical activity and antidepressant use/adherence. Outcomes will be analysed on an intention-to-treat (ITT basis and will use linear and logistic regression models to compare treatments. Discussion The results of

  9. Insight derived from molecular dynamics simulations into molecular motions, thermodynamics and kinetics of HIV-1 gp120.

    Directory of Open Access Journals (Sweden)

    Peng Sang

    Full Text Available Although the crystal structures of the HIV-1 gp120 core bound and pre-bound by CD4 are known, the details of dynamics involved in conformational equilibrium and transition in relation to gp120 function have remained elusive. The homology models of gp120 comprising the N- and C-termini and loops V3 and V4 in the CD4-bound and CD4-unbound states were built and subjected to molecular dynamics (MD simulations to investigate the differences in dynamic properties and molecular motions between them. The results indicate that the CD4-bound gp120 adopted a more compact and stable conformation than the unbound form during simulations. For both the unbound and bound gp120, the large concerted motions derived from essential dynamics (ED analyses can influence the size/shape of the ligand-binding channel/cavity of gp120 and, therefore, were related to its functional properties. The differences in motion direction between certain structural components of these two forms of gp120 were related to the conformational interconversion between them. The free energy calculations based on the metadynamics simulations reveal a more rugged and complex free energy landscape (FEL for the unbound than for the bound gp120, implying that gp120 has a richer conformational diversity in the unbound form. The estimated free energy difference of ∼-6.0 kJ/mol between the global minimum free energy states of the unbound and bound gp120 indicates that gp120 can transform spontaneously from the unbound to bound states, revealing that the bound state represents a high-probability "ground state" for gp120 and explaining why the unbound state resists crystallization. Our results provide insight into the dynamics-and-function relationship of gp120, and facilitate understandings of the thermodynamics, kinetics and conformational control mechanism of HIV-1 gp120.

  10. Why are some patients in treatment for advanced cancer reluctant to consult their GP?

    DEFF Research Database (Denmark)

    Åbom, Birgit; Pfeiffer, Per

    2009-01-01

    and therefore consulted the doctor or the staff at the cancer treatment centre before seeking advice from their GP. Some patients found that the GP was not familiar enough with the treatments given; others that they did not want to inconvenience the busy GP with what they perceived to be minor non...

  11. The general practitioner's role in promoting physical activity to older adults: a review based on program theory.

    Science.gov (United States)

    Hinrichs, Timo; Brach, Michael

    2012-02-01

    Positive influences of physical activity both on many chronic diseases and on preservation of mobility are well documented. But chronically ill or mobility restricted elderly living in their own homes are difficult to reach for interventions. The general practitioner's (GP) surgery offers one of the few opportunities to give advice for physical activity to those people. We used program theory to sound out knowledge on GP-centered physical activity counseling. The "conceptual theory" (evidence for training effects in old age) and the "implementation theory" (unique position of the GP) were reviewed narratively. The "action theory" (effects of GP counseling) was reviewed systematically. According to program theory, appropriate MeSH (Medical subject headings) concepts were Aged OR Aged, 80 and over (Target group), Physicians, Family OR Primary Health Care (Implementation/Setting), Counseling OR Patient Education as Topic OR Disease Management OR Health promotion (Intervention), Exercise OR Motor Activity OR Physical Fitness OR Sports (Determinants). The resulting six review papers (Pubmed, 2000-2009) were presented using the STARLITE mnemonic. Authors agree, that the GP plays a central role in the promotion of physical activity to elderly people, but there is conflicting evidence concerning counseling effectiveness. Utilizing behavioral change strategies and the collaboration between GPs and specialised professions are recommended and currently under research.

  12. A Programmable, Scalable-Throughput Interleaver

    Directory of Open Access Journals (Sweden)

    E. J. C. Rijshouwer

    2010-01-01

    Full Text Available The interleaver stages of digital communication standards show a surprisingly large variation in throughput, state sizes, and permutation functions. Furthermore, data rates for 4G standards such as LTE-Advanced will exceed typical baseband clock frequencies of handheld devices. Multistream operation for Software Defined Radio and iterative decoding algorithms will call for ever higher interleave data rates. Our interleave machine is built around 8 single-port SRAM banks and can be programmed to generate up to 8 addresses every clock cycle. The scalable architecture combines SIMD and VLIW concepts with an efficient resolution of bank conflicts. A wide range of cellular, connectivity, and broadcast interleavers have been mapped on this machine, with throughputs up to more than 0.5 Gsymbol/second. Although it was designed for channel interleaving, the application domain of the interleaver extends also to Turbo interleaving. The presented configuration of the architecture is designed as a part of a programmable outer receiver on a prototype board. It offers (near universal programmability to enable the implementation of new interleavers. The interleaver measures 2.09 mm2 in 65 nm CMOS (including memories and proves functional on silicon.

  13. A Programmable, Scalable-Throughput Interleaver

    Directory of Open Access Journals (Sweden)

    Rijshouwer EJC

    2010-01-01

    Full Text Available The interleaver stages of digital communication standards show a surprisingly large variation in throughput, state sizes, and permutation functions. Furthermore, data rates for 4G standards such as LTE-Advanced will exceed typical baseband clock frequencies of handheld devices. Multistream operation for Software Defined Radio and iterative decoding algorithms will call for ever higher interleave data rates. Our interleave machine is built around 8 single-port SRAM banks and can be programmed to generate up to 8 addresses every clock cycle. The scalable architecture combines SIMD and VLIW concepts with an efficient resolution of bank conflicts. A wide range of cellular, connectivity, and broadcast interleavers have been mapped on this machine, with throughputs up to more than 0.5 Gsymbol/second. Although it was designed for channel interleaving, the application domain of the interleaver extends also to Turbo interleaving. The presented configuration of the architecture is designed as a part of a programmable outer receiver on a prototype board. It offers (near universal programmability to enable the implementation of new interleavers. The interleaver measures 2.09 m in 65 nm CMOS (including memories and proves functional on silicon.

  14. Impact of Leishmania metalloprotease GP63 on macrophage signaling

    Science.gov (United States)

    Isnard, Amandine; Shio, Marina T.; Olivier, Martin

    2012-01-01

    The intramacrophage protozoan parasites of Leishmania genus have developed sophisticated ways to subvert the innate immune response permitting their infection and propagation within the macrophages of the mammalian host. Several Leishmania virulence factors have been identified and found to be of importance for the development of leishmaniasis. However, recent findings are now further reinforcing the critical role played by the zinc-metalloprotease GP63 as a virulence factor that greatly influence host cell signaling mechanisms and related functions. GP63 has been found to be involved not only in the cleavage and degradation of various kinases and transcription factors, but also to be the major molecule modulating host negative regulatory mechanisms involving for instance protein tyrosine phosphatases (PTPs). Those latter being well recognized for their pivotal role in the regulation of a great number of signaling pathways. In this review article, we are providing a complete overview about the role of Leishmania GP63 in the mechanisms underlying the subversion of macrophage signaling and functions. PMID:22919663

  15. Conjugated nanoliposome with the HER2/neu-derived peptide GP2 as an effective vaccine against breast cancer in mice xenograft model.

    Directory of Open Access Journals (Sweden)

    Atefeh Razazan

    Full Text Available One of the challenging issues in vaccine development is peptide and adjuvant delivery into target cells. In this study, we developed a vaccine and therapeutic delivery system to increase cytotoxic T lymphocyte (CTL response against a breast cancer model overexpressing HER2/neu. Gp2, a HER2/neu-derived peptide, was conjugated to Maleimide-mPEG2000-DSPE micelles and post inserted into liposomes composed of DMPC, DMPG phospholipids, and fusogenic lipid dioleoylphosphatidylethanolamine (DOPE containing monophosphoryl lipid A (MPL adjuvant (DMPC-DMPG-DOPE-MPL-Gp2. BALB/c mice were immunized with different formulations and the immune response was evaluated in vitro and in vivo. ELISpot and intracellular cytokine analysis by flow cytometry showed that the mice vaccinated with Lip-DOPE-MPL-GP2 incited the highest number of IFN-γ+ in CD8+ cells and CTL response. The immunization led to lower tumor sizes and longer survival time compared to the other groups of mice immunized and treated with the Lip-DOPE-MPL-GP2 formulation in both prophylactic and therapeutic experiments. These results showed that co-formulation of DOPE and MPL conjugated with GP2 peptide not only induces high antitumor immunity but also enhances therapeutic efficacy in TUBO mice model. Lip-DOPE-MPL-GP2 formulation could be a promising vaccine and a therapeutic delivery system against HER2 positive cancers and merits further investigation.

  16. Motivation for career choice and job satisfaction of GP trainees and newly qualified GPs across Europe: a seven countries cross-sectional survey.

    Science.gov (United States)

    Roos, Marco; Watson, Jessica; Wensing, Michel; Peters-Klimm, Frank

    2014-07-01

    Recruitment to general practice is a major concern in many countries. Cross-national exploration of motivation for career choice and career satisfaction could help inform workforce planning. Our aim was to explore motivation for career choice and job satisfaction of GP trainees and newly qualified GPs (NQGP) across seven European countries. We surveyed GP trainees and recently qualified GPs in the Czech Republic, Denmark, Germany, Italy, Norway, Portugal and the United Kingdom using a web-based questionnaire. The number of individuals who responded was 3722 (2533 GP trainees; 1189 NQGP). The most frequently cited reasons for choosing GP were 'compatibility with family life' (59.5%), 'challenging medically broad discipline' (58.9%), 'individual approach to people' (40.1%), 'holistic approach' (37.8%) and 'autonomy and independence' (30.4%). Despite differences in workload, work-life balance and earnings, overall job satisfaction was high, with over 80% saying that they would choose to be a doctor again; of these 78.4% would choose to be a GP again. In our sample reasons for choosing general practice as a career were strongly positive, with compatibility with family life the most frequently cited reason overall. This has implications for workforce planning. Further qualitative studies are needed to explore issues raised in more detail.

  17. Characteristics and career intentions of Scottish rural and urban GP registrars: cause for concern?

    Science.gov (United States)

    Ross, S; Gillies, J C

    1999-01-01

    To investigate the differences between the characteristics and career intentions of GP registrars in urban and rural areas, and to make recommendations to reduce a potential work force crisis in rural practice. Postal survey. All general practices in Scotland. In February 1996, 40/196 (20%) of urban and 45/150 (30%) of rural GP registrar places available in Scotland, were vacant (chi 2 = 4.22, df = 1, p = 0.02). Postal questionnaires were sent to all 261 GP registrars in post. Of 235 respondents (90%), the majority wished to remain in general practice (63% of urban and 53% of rural registrars), but only 22% of urban and 18% of rural registrars intended to apply for principal posts immediately after training. Fewer urban (8%) than rural registrars (21%) stated an intention to go abroad to work after training. Rural registrars tended to want to work in rural areas, and vice versa. Part-time and job-sharing were attractive employment options for both groups, and more flexible career structures were favoured by over 80%. Though much more attention has been paid to recruitment in inner cities, the findings from this study suggest that in Scotland difficulties in finding principals may occur first in rural areas. As general practitioners have an extended role in rural areas, including that of emergency care, shortages could have a serious impact on patient care.

  18. The design of a community lifestyle programme to improve the physical and psychological well-being of pregnant women with a BMI of 30 kg/m2 or more

    Directory of Open Access Journals (Sweden)

    Chmiel Catherine

    2010-05-01

    Full Text Available Abstract Background Obesity is a global public health issue. Having a BMI of 30 kg/m2 or more (classifying a person as obese at the start of pregnancy is a significant risk factor for maternal and fetal morbidity. There is a dearth of evidence to inform suitable inteventions to support pregnant women with a BMI of 30 kg/m2 or more. Here we describe a study protocol to test the feasibility of a variety of potential healthy lifestyle interventions for pregnant women with a BMI of 30 kg/m2 or more in a community based programme. Methods/Design Four hundred women will be approached to attend a 10-week community lifestyle programme. The programme will be provided as a supplement to standard antenatal care. The programme is multi-faceted, aimed at equipping participants with the skills and knowledge needed to adopt healthy behaviours. The social (cognitive learning theory will be used as a tool to encourage behaviour change, the behaviour change techniques are underpinned by five theoretical components; self-efficacy, outcome expectancies, goal setting, feedback and positive reinforcement. The main outcomes are pregnancy weight gain and caesarean section rate. Other important outcomes include clinical outcomes (e.g., birth weight and psychological outcomes (e.g., well-being. Secondary outcomes include women's experience of pregnancy and health care services, amount of physical activity, food intake and the suitability of the intervention components. A prospective study using quantitative and qualitative methods will inform the feasibility of implementing the community lifestyle programme with pregnant women with a BMI of 30 kg/m2 or more. Mixed methods of data collection will be used, including diaries, focus groups/interviews, pedometers, validated and specifically designed questionnaires, a programme register, weight gain during pregnancy and perinatal outcome data. Discussion Findings from this current feasibility study will inform future

  19. Radiation physics as a new science discipline

    International Nuclear Information System (INIS)

    Sri Ram, K.

    1987-01-01

    After tracing the evolution of radiation physics teaching at the university level in U.S.A., the current status of teaching of radiation physics in Indian Universities is reviewed. It is noted that parts of radiation physics are taught in some Indian academic institutions. Only Madras University offers an M.Sc. programme in radiation physics. Its curriculum is critically examined and it is noted that more emphasis is required on practical and applied aspects of radiation physics. Closer interaction between academic and R and D institutions is required. (M.G.B.)

  20. Increasing the general level of academic capacity in general practice: introducing mandatory research training for general practitioner trainees through a participatory research process

    DEFF Research Database (Denmark)

    Tulinius, Anne-Charlotte; Nielsen, Anni Brit Sternhagen; Hansen, Lars Jørgen

    2012-01-01

    skills, and through the development and implementation of the mandatory programme to gradually empower the GP community to achieve academic capacity by creating a link between the GP researchers and the GP training community. This was done by developing a faculty, giving teaching skills to GP academics...... of the planning phase. RESULTS: From 2006 to 2009, we built a teaching faculty of 25 teachers among clinical GPs and GP academics; developed the training programme; and delivered the programme to 95 GP trainees. Some of the GP trainees later showed an interest in more substantial research projects, and GP...... and teaching. There is, however, a generic barrier in the regulation of academia itself....

  1. Study protocol: using the Q-STEPS to assess and improve the quality of physical activity programmes for the elderly.

    Science.gov (United States)

    Marques, Ana I; Rosa, Maria J; Amorim, Marlene; Soares, Pedro; Oliveira-Tavares, António; Santos, Rute; Mota, Jorge; Carvalho, Joana

    2012-07-09

    Aging is one of the most important and obvious phenomenon observed in our society. In the past years, there has been a growing concern in designing physical activity (PA) programmes for elderly people, because evidence suggests that such health promotion interventions may reduce the deleterious effects of the ageing process. Accordingly, a growing body of literature points to the importance of a sound approach to planning and evaluation in order to improve the quality of PA programmes. However, while numerous PA programmes have been designed for the elderly in recent years, their evaluation has been scarce. Quality management processes and tools provide a practical way for organisations to assess, identify and shed light on the areas requiring improvement. The Quality Self-assessment Tool for Exercise Programmes for Seniors (Q-STEPS) seems to provide a framework tailored to evaluate PA programmes for the elderly. The primary purpose of this study is 1) to determine feasibility, acceptability and usability of the Q-STEPS. Secondary purposes of the study are: 2) to examine the quality of the PA programmes for elderly people developed by the Portuguese Local Administration over a three-year period of self-assessments in terms of: a) Enabler domains (Leadership, Policy and Strategy, People, Partnership and Resources, Processes); b) Result domains (Customer Results, People Results, Society Results and Key Performance Results); 3) to estimate the association between the use of Q-STEPS and some indicators relating to the elderly participants, during the three self-assessments, such as: attendance rates, physical fitness, health-related quality of life and the elderly's perceived quality of the programme. The study will be conducted in PA programmes for elderly adults from mainland Portuguese municipalities over a three-year period. The project will adopt a participative quality improvement approach that features annual learning cycles of: 1) self-assessment with the Q

  2. The Agency's Technical Co-operation programme with Cuba, 1982-1992. Country programme summaries

    International Nuclear Information System (INIS)

    1992-01-01

    The country programme summary reported here is one in the series of such studies being undertaken of the Agency's TC programme with Member States. With almost $8.2 million of Agency support received, Cuba ranks 19th among all recipients of technical assistance in the period 1958 - 1991, whereby it ranked as high as 3rd in 1982 and 4th in 1984. Over three quarters of the assistance during the past ten years has been provided in the form of equipment (81%), followed by expert services (10%) and training (9%). Seventy-one per cent of the resources were made available through the Technical Assistance and Co-operation Fund, while 28% of the resources were provided by UNDP. The remaining 1% was made available through extrabudgetary and in-kind contributions. With regard to project disbursements by sector, the largest areas have been general atomic energy development (36%), agriculture (20%), nuclear physics and chemistry (10%) and nuclear safety (10%). Industry and hydrology, nuclear engineering and technology, and nuclear medicine have each received less than ten per cent of the assistance provided

  3. 65 nm LP/GP mix low cost platform for multi-media wireless and consumer applications

    Science.gov (United States)

    Tavel, B.; Duriez, B.; Gwoziecki, R.; Basso, M. T.; Julien, C.; Ortolland, C.; Laplanche, Y.; Fox, R.; Sabouret, E.; Detcheverry, C.; Boeuf, F.; Morin, P.; Barge, D.; Bidaud, M.; Biénacel, J.; Garnier, P.; Cooper, K.; Chapon, J. D.; Trouiller, Y.; Belledent, J.; Broekaart, M.; Gouraud, P.; Denais, M.; Huard, V.; Rochereau, K.; Difrenza, R.; Planes, N.; Marin, M.; Boret, S.; Gloria, D.; Vanbergue, S.; Abramowitz, P.; Vishnubhotla, L.; Reber, D.; Stolk, P.; Woo, M.; Arnaud, F.

    2006-04-01

    A complete 65 nm CMOS platform, called LP/GP Mix, has been developed employing thick oxide transistor (IO), Low Power (LP) and General Purpose (GP) devices on the same chip. Dedicated to wireless multi-media and consumer applications, this new triple gate oxide platform is low cost (+1mask only) and saves over 35% of dynamic power with the use of the low operating voltage GP. The LP/GP mix shows competitive digital performance with a ring oscillator (FO = 1) speed equal to 7 ps per stage (GP) and 6T-SRAM static power lower than 10 pA/cell (LP). Compatible with mixed-signal design requirements, transistors show high voltage gain, low mismatch factor and low flicker noise. Moreover, to address mobile phone demands, excellent RF performance has been achieved with FT = 160 GHz for LP and 280 GHz for GP nMOS transistors.

  4. THE EFFECT OF COMMUNICATION SKILLS TRAINING PROGRAMME ON THE ATTITUDE AND PERCEPTIONS OF THE RESIDENTS OF PHYSICAL MEDICINE AND REHABILITATION

    Directory of Open Access Journals (Sweden)

    Reeba Mary Mani

    2016-12-01

    Full Text Available BACKGROUND Communication skills are essential for all practicing doctors, which can be taught and assessed by a structured programme. Hence, a specialty-based communication skills training programme was conducted among the residents of the Physical Medicine and Rehabilitation (PMR Department. The aim of the study is to assess the change in attitude and perception among the residents of PMR by a communication skills training programme. MATERIALS AND METHODS It comprised of a data collection procedure. Here, a semi-structured questionnaire was administered to the subjects. It was given as a pre-intervention, post-intervention and as a second phase post-intervention questionnaire. The communication skills training programme (n=16 was conducted after a pre-test evaluation using the validated questionnaire tool. A half-day training programme using composite Teaching-Learning methods (lectures/role play/videos/check list were included. The post-test-1 (n=16 was conducted after the training programme and the post-test-2 (n=16 was conducted after 6 weeks. All the tests used the same validated questionnaire tool with scores allocated to each item. Settings- Physical Medicine and Rehabilitation (PMR Department among the residents. Study Design- Educational Intervention- A communication skills training programme using composite teaching learning methods. Statistical Analysis- Analysed using SPSS-16 package software. RESULTS The median pre-test score of the sixteen PMR residents was noted to be 33. The median post-test-1 score of the group was noted to be 37. A significant difference was noted between the pre- and post-test-1 score, which was statistically significant Wilcoxon Signed Rank Test z=-3.249 and p value <0.0001. The post-test-2, which was done after 6 weeks of the programme yielded a score of 36, a similar value of post-test-1. The comparison of pre-test score with post-test-1 and post-test-2 scores showed a highly significant improvement in the

  5. Mixed methods evaluation of an interdisciplinary sexuality education programme for staff working with people who have an acquired physical disability.

    Science.gov (United States)

    Higgins, Agnes; Sharek, Danika; Nolan, Maeve; Sheerin, Barbara; Flanagan, Paul; Slaicuinaite, Sniguole; Mc Donnell, Sinead; Walsh, Heather

    2012-11-01

    .  To report a study evaluating the effectiveness of a 1-day interdisciplinary sexuality education programme for staff working with people with acquired physical disability.   Changes associated with an acquired physical disability can diminish a person's self-esteem, sense of attractiveness, relationships, and sexual functioning. Research suggests that people are dissatisfied with the quality of information and support around sexuality during their rehabilitation.   A mixed methods design was used, involving pretest and posttest questionnaires and interviews. Questionnaire data were analysed using descriptive statistics and paired samples t-tests to evaluate the effects of the programme on knowledge, skills, and comfort. Interview data were analyzed thematically, with particular emphasis on participants' opinions about the application of the course within practice. Participants were working in the area of acquired disability and rehabilitation, and were drawn from a number of disciplines. Data were collected between 2008-2009.   Comparison of the pre- and postmeasures, based on paired samples t-tests, showed that the programme statistically significantly increased participants' knowledge, skills, and comfort. Participants felt positive and enthusiastic about the programme and reported numerous incidents where they were more willing to raise issues for discussion and create a supportive listening space for patients to talk about their concerns around sexuality.   Providing healthcare practitioners with a 1-day programme leads to positive changes in knowledge, skills, and comfort towards sexuality. Sexuality education may be an ideal topic for bringing practitioners together within an interdisciplinary education context. © 2012 Blackwell Publishing Ltd.

  6. Peripheral bone mineral density and different intensities of physical activity in children 6-8 years old: the Copenhagen School Child Intervention study

    DEFF Research Database (Denmark)

    Hasselstrøm, H; Karlsson, K M; Hansen, S E

    2007-01-01

    -stimulating physical activity, we evaluated different definitions of vigorous physical activity. The boys had 3.2% higher distal forearm bone mineral content (BMC, P girls. They also carried out 9.7% more daily physical activity and spent 14.6-19.0% more...... time in vigorous physical activity (all P girls. In contrast, the girls had 3.8% higher calcaneal BMC (P boys. Both calcaneal and forearm BMD were significantly related to total time of daily physical activity as well......This study aimed to evaluate the association between objectively measured habitual physical activity and calcaneal and forearm bone mineral density (BMD, g/cm(2)), one mechanically more loaded and one less loaded skeletal region, in children aged 6-8 years. BMD was measured in 297 boys and 265...

  7. Esters of the Marine-Derived Triterpene Sipholenol A Reverse P-GP-Mediated Drug Resistance

    Directory of Open Access Journals (Sweden)

    Yongchao Zhang

    2015-04-01

    Full Text Available Our previous studies showed that several sipholane triterpenes, sipholenol A, sipholenone E, sipholenol L and siphonellinol D, have potent reversal effect for multidrug resistance (MDR in cancer cells that overexpressed P-glycoprotein (P-gp/ABCB1. Through comparison of cytotoxicity towards sensitive and multi-drug resistant cell lines, we identified that the semisynthetic esters sipholenol A-4-O-acetate and sipholenol A-4-O-isonicotinate potently reversed P-gp-mediated MDR but had no effect on MRP1/ABCC1 and BCRP/ABCG2-mediated MDR. The results from [3H]-paclitaxel accumulation and efflux studies suggested that these two triterpenoids were able to increase the intracellular accumulation of paclitaxel by inhibiting its active efflux. In addition, western blot analysis revealed that these two compounds did not alter the expression levels of P-gp when treated up to 72 h. These sipholenol derivatives also stimulated the ATPase activity of P-gp membranes, which suggested that they might be substrates of P-gp. Moreover, in silico molecular docking studies revealed the virtual binding modes of these two compounds into human homology model of P-gp. In conclusion, sipholenol A-4-O-acetate and sipholenol A-4-O-isonicotinate efficiently inhibit the P-gp and may represent potential reversal agents for the treatment of multidrug resistant cancers.

  8. Correlation of serum GP73, SOD and GPC3 contents with cell proliferation and angiogenesis in liver cancer lesion

    Directory of Open Access Journals (Sweden)

    Hua Xin

    2017-11-01

    Full Text Available Objective: To study the correlation of serum GP73, SOD and GPC3 contents with cell proliferation and angiogenesis in liver cancer lesion. Methods: Patients who were diagnosed with primary liver cancer in Jianghan Oilfield General Hospital between June 2014 and February 2017 were selected as liver cancer group, and healthy subjects who received physical examination in Jianghan Oilfield General Hospital during the same period were selected as control group. Serum was collected from two groups of subjects to determine the contents of GP73, SOD and GPC3; liver cancer lesion and adjacent lesion were collected from liver cancer group to determine the expression of cell proliferation molecules and angiogenesis molecules. Results: Serum GP73 and GPC3 levels of liver cancer group were obviously higher than those of control group while SOD content was obviously lower than that of control group; DNMT3B, STC2, SIRT6, LETM1, EphB4, SULT2B1, HIF-1α, VEGF, Ang-2, HGF and TGF-β1 protein expression levels in liver cancer lesion of liver cancer group were significantly higher than those in adjacent lesion; DNMT3B, STC2, SIRT6, LETM1, EphB4, SULT2B1, HIF-1α, VEGF, Ang-2, HGF and TGF-β1 protein expression levels in liver cancer lesion of liver cancer group were positively correlated with serum GP73 and GPC3 levels, and negatively correlated with serum SOD level. Conclusion: The changes of GP73, SOD and GPC3 levels in the serum of patients with liver cancer are closely related to the cell proliferation and angiogenesis in liver cancer lesion.

  9. The Astringency of the GP Algorithm for Forecasting Software Failure Data Series

    Directory of Open Access Journals (Sweden)

    Yong-qiang Zhang

    2007-05-01

    Full Text Available The forecasting of software failure data series by Genetic Programming (GP can be realized without any assumptions before modeling. This discovery has transformed traditional statistical modeling methods as well as improved consistency for model applicability. The individuals' different characteristics during the evolution of generations, which are randomly changeable, are treated as Markov random processes. This paper also proposes that a GP algorithm with "optimal individuals reserved strategy" is the best solution to this problem, and therefore the adaptive individuals finally will be evolved. This will allow practical applications in software reliability modeling analysis and forecasting for failure behaviors. Moreover it can verify the feasibility and availability of the GP algorithm, which is applied to software failure data series forecasting on a theoretical basis. The results show that the GP algorithm is the best solution for software failure behaviors in a variety of disciplines.

  10. Computer programmes for nuclear physics

    International Nuclear Information System (INIS)

    Wilmore, D.

    1981-02-01

    Two programmes for use in the calculation of problems involving the scattering of neutrons, protons or heavier composite particles from nuclei are described. The first, an optical model for the calculation of the elastic, total and absorption cross-sections from an optical potential, includes facilities for automatically finding the appropriate optical potential to describe any given set of experimental data. The second a statistical model for the calculation of inelastic and other compound nucleus scattering processes, according to three different theories, includes level width fluctuation calculations. (U.K.)

  11. The GP Patient Survey for use in primary care in the National Health Service in the UK--development and psychometric characteristics.

    Science.gov (United States)

    Campbell, John; Smith, Patten; Nissen, Sonja; Bower, Peter; Elliott, Marc; Roland, Martin

    2009-08-22

    The UK National GP Patient Survey is one of the largest ever survey programmes of patients registered to receive primary health care, inviting five million respondents to report their experience of NHS primary healthcare. The third such annual survey (2008/9) involved the development of a new survey instrument. We describe the process of that development, and the findings of an extensive pilot survey in UK primary healthcare. The survey was developed following recognised guidelines and involved expert and stakeholder advice, cognitive testing of early versions of the survey instrument, and piloting of the questionnaire in a cross sectional pilot survey of 1,500 randomly selected individuals from the UK electoral register with two reminders to non-respondents. The questionnaire comprises 66 items addressing a range of aspects of UK primary healthcare. A response rate of 590/1500 (39.3%) was obtained. Non response to individual items ranged from 0.8% to 15.3% (median 5.2%). Participants did not always follow internal branching instructions in the questionnaire although electronic controls allow for correction of this problem in analysis. There was marked skew in the distribution of responses to a number of items indicating an overall favourable impression of care. Principal components analysis of 23 items offering evaluation of various aspects of primary care identified three components (relating to doctor or nurse care, or addressing access to care) accounting for 68.3% of the variance in the sample. The GP Patient Survey has been carefully developed and pilot-tested. Survey findings, aggregated at practice level, will be used to inform the distribution of pound sterling 65 million ($107 million) of UK NHS resource in 2008/9 and this offers the opportunity for NHS service planners and providers to take account of users' experiences of health care in planning and delivering primary healthcare in the UK.

  12. Programmable assembly of pressure sensors using pattern-forming bacteria.

    Science.gov (United States)

    Cao, Yangxiaolu; Feng, Yaying; Ryser, Marc D; Zhu, Kui; Herschlag, Gregory; Cao, Changyong; Marusak, Katherine; Zauscher, Stefan; You, Lingchong

    2017-11-01

    Biological systems can generate microstructured materials that combine organic and inorganic components and possess diverse physical and chemical properties. However, these natural processes in materials fabrication are not readily programmable. Here, we use a synthetic-biology approach to assemble patterned materials. We demonstrate programmable fabrication of three-dimensional (3D) materials by printing engineered self-patterning bacteria on permeable membranes that serve as a structural scaffold. Application of gold nanoparticles to the colonies creates hybrid organic-inorganic dome structures. The dynamics of the dome structures' response to pressure is determined by their geometry (colony size, dome height, and pattern), which is easily modified by varying the properties of the membrane (e.g., pore size and hydrophobicity). We generate resettable pressure sensors that process signals in response to varying pressure intensity and duration.

  13. The southern molecular environment of SNR G18.8+0.3

    OpenAIRE

    Paron, S.; Peña, M. Celis; Ortega, M. E.; Petriela, A.; Dubner, G.; Giacina, E.; Rubio, M.

    2015-01-01

    In a previous paper we have investigated the molecular environment towardsthe eastern border of the SNR G18.8+0.3. Continuing with the study of thesurroundings of this SNR, in this work we focus on its southern border, whichin the radio continuum emission shows a very peculiar morphology with acorrugated corner and a very flattened southern flank. We observed two regionstowards the south of SNR G18.8+0.3 using the Atacama Submillimeter TelescopeExperiment (ASTE) in the 12CO J=3-2. One of thes...

  14. Referral from primary care to a physical activity programme: establishing long-term adherence? A randomized controlled trial. Rationale and study design

    Directory of Open Access Journals (Sweden)

    Puig-Ribera Anna

    2009-01-01

    Full Text Available Abstract Background Declining physical activity is associated with a rising burden of global disease. There is little evidence about effective ways to increase adherence to physical activity. Therefore, interventions are needed that produce sustained increases in adherence to physical activity and are cost-effective. The purpose is to assess the effectiveness of a primary care physical activity intervention in increasing adherence to physical activity in the general population seen in primary care. Method and design Randomized controlled trial with systematic random sampling. A total of 424 subjects of both sexes will participate; all will be over the age of 18 with a low level of physical activity (according to the International Physical Activity Questionnaire, IPAQ, self-employed and from 9 Primary Healthcare Centres (PHC. They will volunteer to participate in a physical activity programme during 3 months (24 sessions; 2 sessions a week, 60 minutes per session. Participants from each PHC will be randomly allocated to an intervention (IG and control group (CG. The following parameters will be assessed pre and post intervention in both groups: (1 health-related quality of life (SF-12, (2 physical activity stage of change (Prochaska's stages of change, (3 level of physical activity (IPAQ-short version, (4 change in perception of health (vignettes from the Cooperative World Organization of National Colleges, Academies, and Academic Associations of Family Physicians, COOP/WONCA, (5 level of social support for the physical activity practice (Social Support for Physical Activity Scale, SSPAS, and (6 control based on analysis (HDL, LDL and glycated haemoglobin. Participants' frequency of visits to the PHC will be registered over the six months before and after the programme. There will be a follow up in a face to face interview three, six and twelve months after the programme, with the reduced version of IPAQ, SF-12, SSPAS, and Prochaska's stages

  15. Family effects on the rurality of GP's work location: a longitudinal panel study.

    Science.gov (United States)

    McGrail, Matthew R; Russell, Deborah J; O'Sullivan, Belinda G

    2017-10-19

    Reduced opportunities for children's schooling and spouse's/partner's employment are identified internationally as key barriers to general practitioners (GPs) working rurally. This paper aims to measure longitudinal associations between the rurality of GP work location and having (i) school-aged children and (ii) a spouse/partner in the workforce. Participants included 4377 GPs responding to at least two consecutive annual surveys of the Medicine in Australia: Balancing Employment and Life (MABEL) national longitudinal study between 2008 and 2014. The main outcome, GP work location, was categorised by remoteness and population size. Five sequential binary school-age groupings were defined according to whether a GP had no children, only preschool children (aged 0-4 years), at least one primary-school child (aged 5-11 years), at least one child in secondary school (aged 12-18 years), and all children older than secondary school (aged ≥ 19). Partner in the workforce was defined by whether a GP had a partner who was either currently working or looking for work, or not. Separate generalised estimating equation models, which aggregated consecutive annual observations per GP, tested associations between work location and (i) educational stages and (ii) partner employment, after adjusting for key covariates. Male GPs with children in secondary school were significantly less likely to work rurally (inclusive of > 50 000 regional centres through to the smallest rural towns of locations were not significantly associated with the educational stage of their children. Having a partner in the workforce was not associated with work location for male GPs, whereas female GPs with a partner in the workforce were significantly less likely to work in smaller rural/remote communities (location is related to key family needs which differ according to GP gender and educational stages of children. Such non-professional factors are likely to be dynamic across the GP's lifespan and

  16. Effect of an aerobic-based physical activity programme on physical ...

    African Journals Online (AJOL)

    The purpose of this study was to determine whether a 10 week aerobic-based exercise programme performed twice a week, with a 30 minutes duration and an intensity level of 55 – 70% heart rate max would improve aerobic endurance, muscular strength, muscular endurance, flexibility and body composition of 10 – 15 ...

  17. Protective Effect of Vitamin D3 and Gp63 Conjugated with Tetanus Toxoid on Outcome of Cutaneous Leishmaniasis Lesions in Balb/C Mice

    Directory of Open Access Journals (Sweden)

    S Soudi

    2006-01-01

    Full Text Available Introduction: GP63 is a major surface protease of Leishmania promastigotes that plays an important role in its virulance. As GP63 on its own can not develop an effective protection against leishmaniasis, the goal of this study was to evaluate the protective effect of GP63 conjugated with tetanus toxoid (TT and Vitamin D3 in susceptible BALB/c mice against cutaneous leishmaniasis. Methods: This study was a basic-applied experimental study performed in Tarbiat Modarres University from September 2002 to April 2005. Cloned virulant Leishmania (L. major [MRHO / IR / 75 / ER] strain was cultured and 5109 cells were harvested. GP63 Molecule was purified and conjugated with TT and conjugated molecule was used for immunization of 8 groups of female BALB/c mice. Results: Results showed that the group of mice receiving conjugated molecule with Vitamin D3 had significant differences from other groups regarding lesion progression (P0.05. The culture of spleen cells showed that the disease did not become systemic in this group. Conclusion: Conjugation of GP63 with TT strengthens cell immunity and its use along with vitamin D3 provokes macrophages activity. This basis can be used for production of an appropriate preparation for protection against Leishmaniasis.

  18. The HERA physics programme

    International Nuclear Information System (INIS)

    Saxon, D.H.

    1991-09-01

    The construction of the HERA accelerator and its detectors H1 and ZEUS opens up new physic regimes to explore at high-Q 2 and low-x. The physics interest and methods of exploration are described, starting from the environment provided by the accelerator and the reaction kinematics. (orig.)

  19. Zeolite-derived hybrid materials with adjustable organic pillars

    Czech Academy of Sciences Publication Activity Database

    Opanasenko, Maksym; Shamzhy, Mariya; Yu, F.; Zhou, W.; Morris, R. E.; Čejka, Jiří

    2016-01-01

    Roč. 7, č. 6 (2016), s. 3589-3601 ISSN 2041-6520 R&D Projects: GA ČR GP13-17593P; GA ČR GBP106/12/G015 Institutional support: RVO:61388955 Keywords : zeolites * inorganic aluminosilicate * nanoporous materials Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 8.668, year: 2016

  20. Theoretical physics 8 statistical physics

    CERN Document Server

    Nolting, Wolfgang

    2018-01-01

    This textbook offers a clear and comprehensive introduction to statistical physics, one of the core components of advanced undergraduate physics courses. It follows on naturally from the previous volumes in this series, using methods of probability theory and statistics to solve physical problems. The first part of the book gives a detailed overview on classical statistical physics and introduces all mathematical tools needed. The second part of the book covers topics related to quantized states, gives a thorough introduction to quantum statistics, followed by a concise treatment of quantum gases. Ideally suited to undergraduate students with some grounding in quantum mechanics, the book is enhanced throughout with learning features such as boxed inserts and chapter summaries, with key mathematical derivations highlighted to aid understanding. The text is supported by numerous worked examples and end of chapter problem sets. About the Theoretical Physics series Translated from the renowned and highly successf...

  1. Impact of a Six-Month Empowerment-Based Exercise Intervention Programme in Non-Physically Active Adolescent Swedish Girls

    Science.gov (United States)

    Lindgren, Eva-Carin; Baigi, Amir; Apitzsch, Erwin; Bergh, Hakan

    2011-01-01

    Objective: This study evaluated changes in self-efficacy in non-physically active adolescent girls (13-19 years old) who participated in a six-month, empowerment-based exercise intervention programme (EIP). Design: The study used a pre- and post-test randomized group design and included one pre- and one post-test (at six months) and non-physically…

  2. Which positive factors determine the GP satisfaction in clinical practice? A systematic literature review.

    Science.gov (United States)

    Le Floch, B; Bastiaens, H; Le Reste, J Y; Lingner, H; Hoffman, R D; Czachowski, S; Assenova, R; Koskela, T H; Klemenc-Ketis, Z; Nabbe, P; Sowinska, A; Montier, T; Peremans, L

    2016-09-13

    Looking at what makes General Practitioners (GPs) happy in their profession, may be important in increasing the GP workforce in the future. The European General Practice Research Network (EGPRN) created a research team (eight national groups) in order to clarify the factors involved in GP job satisfaction throughout Europe. The first step of this study was a literature review to explore how the satisfaction of GPs had been studied before. The research question was "Which factors are related to GP satisfaction in Clinical Practice?" Systematic literature review according to the PRISMA statement. The databases searched were Pubmed, Embase and Cochrane. All articles were identified, screened and included by two separate research teams, according to inclusion or exclusion criteria. Then, a qualitative appraisal was undertaken. Next, a thematic analysis process was undertaken to capture any issue relevant to the research question. The number of records screened was 458. One hundred four were eligible. Finally, 17 articles were included. The data revealed 13 subthemes, which were grouped into three major themes for GP satisfaction. First there were general profession-related themes, applicable to many professions. A second group of issues related specifically to a GP setting. Finally, a third group was related to professional life and personal issues. A number of factors leading to GP job satisfaction, exist in literature They should be used by policy makers within Europe to increase the GP workforce. The research team needs to undertake qualitative studies to confirm or enhance those results.

  3. 'Just a GP': a mixed method study of undermining of general practice as a career choice in the UK.

    Science.gov (United States)

    Alberti, Hugh; Banner, Kimberley; Collingwood, Helen; Merritt, Kymberlee

    2017-11-03

    Failure to recruit sufficient applicants to general practice (GP) training has been a problem both nationally and internationally for many years and undermining of GP is one possible contributing factor. The aim of our study was to ascertain what comments, both negative and positive, are being made in UK clinical settings to GP trainees about GP and to further explore these comments and their influence on career choice. We conducted a mixed methods study. We surveyed all foundation doctors and GP trainees within one region of Health Education England regarding any comments they experienced relating to a career in GP. We also conducted six focus groups with early GP trainees to discuss any comments that they experienced and whether these comments had any influence on their or others career choice. Positive comments reported by trainees centred around the concept that choosing GP is a positive, family-focused choice which facilities a good work-life balance. Workload was the most common negative comment, alongside the notion of being 'just a GP'; the belief that GP is boring, a waste of training and a second-class career choice. The reasons for and origin of the comments are multifactorial in nature. Thematic analysis of the focus groups identified key factors such as previous exposure to and experience of GP, family members who were GPs, GP role models, demographics of the clinician and referral behaviour. Trainees perceived that negative comments may be discouraging others from choosing GP as a career. Our study demonstrates that negative comments towards GP as a career do exist within clinical settings and are having a potential impact on poor recruitment rates to GP training. We have identified areas in which further negative comments could be prevented by changing perceptions of GP as a career. Additional time spent in GP as undergraduates and postgraduates, and positive GP role models, could particularly benefit recruitment. We recommend that undermining of GP

  4. Burden of paediatric Rotavirus Gastroenteritis (RVGE and potential benefits of a universal Rotavirus vaccination programme with a pentavalent vaccine in Spain

    Directory of Open Access Journals (Sweden)

    Diez-Domingo Javier

    2010-08-01

    Full Text Available Abstract Background Rotavirus is the most common cause of gastroenteritis in young children worldwide. The aim of the study was to assess the health outcomes and the economic impact of a universal rotavirus vaccination programme with RotaTeq, the pentavalent rotavirus vaccine, versus no vaccination programme in Spain. Methods A birth cohort was followed up to the age of 5 using a cohort model. Epidemiological parameters were taken from the REVEAL study (a prospective epidemiological study conducted in Spain, 2004-2005 and from the literature. Direct and indirect costs were assessed from the national healthcare payer and societal perspectives by combining health care resource utilisation collected in REVEAL study and unit costs from official sources. RotaTeq per protocol efficacy data was taken from a large worldwide rotavirus clinical trial (70,000 children. Health outcomes included home care cases, General Practioner (GP/Paediatrician, emergency department visits, hospitalisations and nosocomial infections. Results The model estimates that the introduction of a universal rotavirus vaccination programme with RotaTeq (90% coverage rate would reduce the rotavirus gastroenteritis (RVGE burden by 75% in Spain; 53,692 home care cases, 35,187 GP/Paediatrician visits, 34,287 emergency department visits, 10,987 hospitalisations and 2,053 nosocomial infections would be avoided. The introduction of RotaTeq would avoid about 76% of RVGE-related costs from both perspectives: €22 million from the national health system perspective and €38 million from the societal perspective. Conclusions A rotavirus vaccination programme with RotaTeq would reduce significantly the important medical and economic burden of RVGE in Spain.

  5. Triage of febrile children at a GP cooperative : determinants of a consultation

    NARCIS (Netherlands)

    Monteny, Miriam; Berger, Marjolein Y.; van der Wouden, Johannes C.; Broekman, Berth J.; Koes, Bart W.

    Background Most febrile children contacting a GP cooperative are seen by a GP, although the incidence of serious illness is low. The guidelines for triage might not be suitable in primary care. Aim To investigate the determinants related to the outcome of triage in febrile children. Design of study

  6. Phylogenetic analysis of G1P[8] and G12P[8] rotavirus A samples obtained in the pre- and post-vaccine periods, and molecular modeling of VP4 and VP7 proteins.

    Science.gov (United States)

    Almeida, Tâmera Nunes Vieira; de Sousa, Teresinha Teixeira; da Silva, Roosevelt Alves; Fiaccadori, Fabíola Souza; Souza, Menira; Badr, Kareem Rady; de Paula Cardoso, Divina das Dôres

    2017-09-01

    Reduction in morbimortality rates for acute gastroenteritis (AGE) by Rotavirus A (RVA) has been observed after the introduction of vaccines, however the agent continues to circulate. The present study described the genomic characterization of the 11 dsRNA segments of two RVA samples G1P[8] obtained in the pre- and post-vaccination periods and one of G12P[8] sample (post-vaccine), compared to Rotarix™ vaccine. Analysis by molecular sequencing of the samples showed that the three samples belonged to genogroup I. In addition, the analysis of VP7 gene revealed that the samples G1 (pre-vaccine), G1 (post-vaccine) and G12 were characterized as lineages II, I and III, respectively. Regarding to VP4 and NSP4 gene it was observed that all samples belonged to lineage III, whereas for VP6 gene, the sample of the pre- and post-vaccine belonged to the lineage IV and I, respectively. Considering the VP7 gene, it was observed high nucleotide and amino acid identity for the two G1 samples when compared to Rotarix™ vaccine and lesser identity for the G12 sample. In relation to antigenic epitope of VP7 greater modifications were observed for the G12 sample in the 7-2 epitope that was confirmed by molecular modeling. On the other hand, for VP4, some changes in the 8-1 and 8-3 antigenic epitopes was observed for the three samples. This data could be interpreted as a low selective pressure exerted by vaccination in relation to G1P[8] samples and lesser protection in relation to G12P[8]. Thus, the continuous monitoring of RVA circulating samples remains important. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Binding of the mannose-specific lectin, griffithsin, to HIV-1 gp120 exposes the CD4-binding site

    CSIR Research Space (South Africa)

    Alexandre, Kabamba B

    2011-09-01

    Full Text Available of the lectin griffithsin (GRFT) with HIV-1 gp120 and its effects on exposure of the CD4-binding site (CD4bs). We found that GRFT enhanced the binding of HIV-1 onto plates coated with anti-CD4bs antibodies b12, b6 or the CD4 receptor mimetic, CD4-IgG2...

  8. Influences on GP coping and resilience: a qualitative study in primary care.

    Science.gov (United States)

    Cheshire, Anna; Ridge, Damien; Hughes, John; Peters, David; Panagioti, Maria; Simon, Chantal; Lewith, George

    2017-06-01

    'Neoliberal' work policies, austerity, NHS restructuring, and increased GP consultation rates provide the backdrop against increasing reports of GP burnout and an impending shortage of GPs. To explore GPs' experiences of workplace challenges and stresses, and their coping strategies, particularly focusing on understanding the impact of recent NHS workplace change. Study design was qualitative, with data collected from two focus groups and seven one-to-one telephone interviews. Focus groups and one-to-one telephone interviews explored the experiences of GPs currently practising in England, recruited through convenience sampling. Data were collected using a semi-structured interview approach and analysed using thematic analysis. There were 22 GP participants recruited: focus groups ( n = 15) and interviews ( n = 7). Interviewees understood GPs to be under intense and historically unprecedented pressures, which were tied to the contexts in which they work, with important moral implications for 'good' doctoring. Many reported that being a full-time GP was too stressful: work-related stress led to mood changes, sleep disruption, increases in anxiety, and tensions with loved ones. Some had subsequently sought ways to downsize their clinical workload. Workplace change resulted in little time for the things that helped GP resilience: a good work-life balance and better contact with colleagues. Although some GPs were coping better than others, GPs acknowledged that there was only so much an individual GP could do to manage their stress, given the external work issues they faced. GPs experience their emotional lives and stresses as being meaningfully shaped by NHS factors. To support GPs to provide effective care, resilience building should move beyond the individual to include systemic work issues. © British Journal of General Practice 2017.

  9. Molecular characterization of Cryptosporidium parvum and Cryptosporidium hominis GP60 subtypes worldwide

    Directory of Open Access Journals (Sweden)

    Catalina Avendaño V

    2017-09-01

    Full Text Available Cryptosporidium is a zoonotic parasite very important in animal health as well as in public health. It is because this is one of the main causes of diarrhea in children, calves, lambs and other variety of youth mammalians in a lot of countries. The globalization has enabled the exchange of biological material in different regions worldwide, encouraging the spread of diseases and exposure to these biological agents to different environmental conditions, inducing adaptation through genetic changes. Based in the polymorphism of the gene for GP60, this review intended to present the distribution of Cryptosporidium parvum and Cryptosporidium hominis in humans and calves worldwide. The subtype that affects cattle more frequently corresponds to IIaA15G2R; while the subtype most frequently isolated from human samples is IaA19G2.

  10. Unreliable alcohol testing in a shipping safety programme.

    Science.gov (United States)

    Helander, Anders; Hagelberg, Charlotte Asker; Beck, Olof; Petrini, Björn

    2009-08-10

    Within a maritime alcohol and drug testing programme, a case showing an unphysiological urine ethanol concentration (235 mmol/L, 10.8 g/L) was found. The sample contained low levels of the ethanol metabolites ethyl glucuronide (EtG) and ethyl sulphate (EtS) which confirmed prior drinking, but also tested positive for the fermenting yeast Candida albicans which suggested post-sampling ethanol formation. This and other questionable cases prompted investigation of the suitability of urine alcohol testing for the intended application. Besides the routine measurements of ethanol, illicit drugs and creatinine, randomly selected ethanol-positive and ethanol-negative urines collected within the maritime programme were checked for the presence of EtG and EtS and for fungal and bacterial growth. Data on sample handling and storage was also gathered. Ten of 15 (67%) ethanol-positive and 4 of 9 (44%) ethanol-negative urines contained yeast and/or bacteria. Among the ethanol-positive cases, 4 (27%) were obviously false positives because EtG and EtS were not detected. Microbial action as the reason for false-high ethanol concentrations was indicated in other cases. When 17 bacteria-infected but fungi-negative urines were supplemented with glucose and stored for 1 week at 21 degrees C, ethanol was formed in 2 specimens containing Escherichia coli and E. coli plus P. aeruginosa. In these samples, EtG was also formed on storage while EtS was not. The routines employed for urine collection and handling within this substance abuse programme caused many false-positive identifications of alcohol use with unintended medico-legal consequences. Unpreserved urines stored without cooling should not be used for alcohol testing, given the high risk for microbial interference.

  11. H-2g, a glucose analog of blood group H antigen, mediates monocyte recruitment in vitro and in vivo via IL-8/CXCL8

    Directory of Open Access Journals (Sweden)

    Rabquer BJ

    2012-09-01

    Full Text Available Bradley J Rabquer,1,2 Yong Hou,1 Jeffrey H Ruth,1 Wei Luo,1 Daniel T Eitzman,1 Alisa E Koch,3,1 Mohammad A Amin11University of Michigan Medical School, Department of Internal Medicine, Ann Arbor, MI, USA; 2Albion College, Biology Department, Albion, MI, USA; 3VA Medical Service, Department of Veterans Affairs, Ann Arbor, MI, USAObjective: Monocyte (MN recruitment is an essential inflammatory component of many autoimmune diseases, including rheumatoid arthritis (RA. In this study we investigated the ability of 2-fucosyllactose (H-2g, a glucose analog of blood group H antigen to induce MN migration in vivo and determined if H-2g-induced interleukin-8 (IL-8/CXCL8 plays a role in MN ingress in RA.Methods: Sponge granuloma and intravital microscopy assays were performed to examine H-2g-induced in vivo MN migration and rolling, respectively. MNs were stimulated with H-2g, and the production of IL-8/CXCL8 was assessed by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction. Lastly, in vitro MN migration assays and an in vivo RA synovial tissue severe combined immunodeficiency mouse model were used to determine the role of IL-8/CXCL8 in H-2g-induced MN migration.Results: In vivo, H-2g induced significantly greater MN migration compared to phosphate buffered saline. Intravital microscopy revealed that H-2g mediates MN migration in vivo by inducing MN rolling. In addition, H-2g induced MN production of IL-8/CXCL8, a process that was dependent on Src kinase. Moreover, we found that H-2g mediated MN migration in vitro, and in vivo migration was inhibited by a neutralizing anti-IL-8/CXCL8 antibody.Conclusion: These findings suggest that H-2g mediates MN recruitment in vitro and in vivo (in part via IL-8/CXCL8.Keywords: inflammation, rheumatoid arthritis, chemokine, migration

  12. The G8 global partnership against proliferation

    International Nuclear Information System (INIS)

    Devaux, O.

    2003-01-01

    Launched in 2002, the G8 global partnership against the proliferation of massive destruction weapons will contribute up to 20 billion dollars to the dismantling of the nuclear and chemical weapons of the former USSR (20000 nuclear warheads stored in 123 sites, 1350 tons of weapon grade plutonium and enriched uranium, 40000 tons of chemical agents, 190 decommissioned nuclear submarines etc..). This partnership, which has entered its realization phase, inaugurates a new cooperation with the Russian Federation. I could be used tomorrow in other regions of the world and become an instrument of the international community for the fight against proliferation. (J.S.)

  13. G8 global partnership. France's contribution

    International Nuclear Information System (INIS)

    2005-09-01

    During the G8 summit at Kananaskis (Canada) in June 2002, G8 Leaders decided to launch the Global Partnership against the Spread of Weapons and Materials of Mass Destruction. Under this initiative, partners support specific cooperation projects to address non-proliferation, disarmament, counter-terrorism and nuclear safety issues. Since then, thirteen other donor countries have joined the initiative from which the Ukraine may also now benefit. France intends to make an effective contribution, up to 750 million euros, to the implementation of this initiative, giving priority to a genuine partnership between France and Russia covering projects in the nuclear, chemical and biological fields. France intends to be involved in the various fields identified at Kananaskis: in the nuclear field, it is participating in nuclear submarine dismantling actions and contributes to the improvement of nuclear safety and security. It also supports the program for the disposition of Russian weapons-grade plutonium designated as no longer required for defence purposes. France is also involved in the destruction of chemical weapons and intends to develop responses to bio-terrorist threats, while promoting reemployment of scientists. To optimise its action, France has committed itself to both multilateral and bilateral programs. In the multilateral framework, France contributes to: - the NDEP fund (Northern Dimension Environment Partnership) which will finance projects related to the dismantling of nuclear submarines and remediation of the sites concerned; - the MPDG (Multilateral Plutonium Disposition Group), whose objective is to enable the disposition of Russian weapons-grade plutonium designated as no longer required for defence purposes; - the construction of the new Chernobyl shelter in the Ukraine. France is also developing bilateral cooperation, primarily with Russia: - in the nuclear field, the implementing agreement negotiated in the framework of the Multilateral Environmental

  14. Applying the Innov8 approach for reviewing national health programmes to leave no one behind: lessons learnt from Indonesia

    Science.gov (United States)

    Saint, Victoria; Floranita, Rustini; Koemara Sakti, Gita Maya; Pambudi, Imran; Hermawan, Lukas; Villar, Eugenio; Magar, Veronica

    2018-01-01

    ABSTRACT The World Health Organization’s Innov8 Approach for Reviewing National Health Programmes to Leave No One Behind is an eight-step process that supports the operationalization of the Sustainable Development Goals’ commitment to ‘leave no one behind’. In 2014–2015, Innov8 was adapted and applied in Indonesia to review how the national neonatal and maternal health action plans could become more equity-oriented, rights-based and gender-responsive, and better address critical social determinants of health. The process was led by the Indonesian Ministry of Health, with the support of WHO. It involved a wide range of actors and aligned with/fed into the drafting of the maternal newborn health action plan and the implementation planning of the newborn action plan. Key activities included a sensitization meeting, diagnostic checklist, review workshop and in-country work by the review teams. This ‘methods forum’ article describes this adaptation and application process, the outcomes and lessons learnt. In conjunction with other sources, Innov8 findings and recommendations informed national and sub-national maternal and neonatal action plans and programming to strengthen a ‘leave no one behind’ approach. As follow-up during 2015–2017, components of the Innov8 methodology were integrated into district-level planning processes for maternal and newborn health, and Innov8 helped generate demand for health inequality monitoring and its use in planning. In Indonesia, Innov8 enhanced national capacity for equity-oriented, rights-based and gender-responsive approaches and addressing critical social determinants of health. Adaptation for the national planning context (e.g. decentralized structure) and linking with health inequality monitoring capacity building were important lessons learnt. The pilot of Innov8 in Indonesia suggests that this approach can help operationalize the SDGs’ commitment to leave no one behind, in particular in relation to

  15. How can educators support general practice (GP) trainees to develop resilience to prevent burnout?

    Science.gov (United States)

    Sales, Bryony; Macdonald, Alexandra; Scallan, Samantha; Crane, Sue

    2016-11-01

    Burnout impacts adversely on professional and personal life, and holds implications for patient care. Current research on burnout mainly focuses on established general practitioners but it is unclear how early the signs of burnout really start. This work seeks to identify whether specific GP trainee groups are particularly at risk of burnout and the aspects of training they find stressful. A longitudinal cohort study, collecting qualitative and quantitative data through a single mode of data collection (questionnaire) took place with trainees from all GP training years (ST1-3), across a vocational training scheme (n = 48). Data gathered included the Oldenburg Burnout Inventory (OLBI). Higher than anticipated levels of burnout were displayed by all trainees. A sub-group self reporting higher levels of burnout comprised all-female, UK-trained-at-undergraduate GP trainees, with a partner but no children. Top reported stressors included knowledge/uncertainty, workload/time pressures and ePortfolio. Less than 50% of trainees perceived their burnout levels to be as high as their OLBI showing potential lack of insight. This research demonstrates that high levels of burnout are experienced in GP trainees as early as the first year of training. Early identification of burnout amongst trainees is essential by GP educators to help protect the future GP workforce.

  16. 8-Hydroxy-2'-deoxyguanosine (8-OH-dG): A biomarker of oxidative damage in yellow bullheads chronically exposed to low-level radiation

    International Nuclear Information System (INIS)

    McCreedy, C.D.; Glickman, L.T.

    1995-01-01

    8-hydroxy-2'-deoxyguanosine (8-OH-dG), an oxidation product of the nucleotide deoxyguanosine (dG) was used as a biomarker to assess oxidative damage in brain and gill tissues of yellow bullhead catfish (Ameiurus natalis; n = 18) inhabiting an abandoned reactor reservoir contaminated with low levels of d137 Cs (Pond B, Savannah River Site, SC). DNA was isolated by chloroform-isoamyl extraction, enzymatically digested with Nuclease P1/Calf Intestinal Phosphatase, and analyzed by HPLC with electrochemical detection.Length, weight, age, condition and muscle 137 Cs activity of each fish were also determined. Concentrations of 8-OH-dG were greater in brain than in gill tissues. 8-OH-dG in gill tissues decreased as condition of fish increased, but as age increased, the effect of condition declined. Brain 8-OH-dG concentration was not related to age or condition of fish, but was greater in females and the interaction between gender and 137 Cs was significant. Brain 8-OH-dG was positively associated with muscle 137 Cs concentration among females, but was unrelated to 137 Cs concentration in males. At lower 137 Cs concentrations, females tended to have fewer oxidative DNA adducts in brian than did males. Deposition of somatic lipids into eggs may provide females some anti-oxidant benefit by diminishing the contribution of lipid peroxidation to DNA damage. 8-OH-dG is a sensitive biomarker of low-level radiation exposure, however, its application in fish requires consideration of factors such as gender, age, body-condition, and the tissue type sampled

  17. Expression of HIV gp120 protein increases sensitivity to the rewarding properties of methamphetamine in mice

    Science.gov (United States)

    Kesby, James P.; Hubbard, David T.; Markou, Athina; Semenova, Svetlana

    2012-01-01

    Methamphetamine abuse and human immunodeficiency virus (HIV) infection induce neuropathological changes in corticolimbic brain areas involved in reward and cognitive function. Little is known about the combined effects of methamphetamine and HIV infection on cognitive and reward processes. The HIV/gp120 protein induces neurodegeneration in mice, similar to HIV-induced pathology in humans. We investigated the effects of gp120 expression on associative learning, preference for methamphetamine and non-drug reinforcers, and sensitivity to the conditioned rewarding properties of methamphetamine in transgenic (tg) mice expressing HIV/gp120 protein (gp120-tg). gp120-tg mice learned the operant response for food at the same rate as non-tg mice. In the two-bottle choice procedure with restricted access to drugs, gp120-tg mice exhibited greater preference for methamphetamine and saccharin than non-tg mice, whereas preference for quinine was similar between genotypes. Under conditions of unrestricted access to methamphetamine, the mice exhibited a decreased preference for increasing methamphetamine concentrations. However, male gp120-tg mice showed a decreased preference for methamphetamine at lower concentrations than non-tg male mice. gp120-tg mice developed methamphetamine-induced conditioned place preference at lower methamphetamine doses compared with non-tg mice. No differences in methamphetamine pharmacokinetics were found between genotypes. These results indicate that gp120-tg mice exhibit no deficits in associative learning or reward/motivational function for a natural reinforcer. Interestingly, gp120 expression resulted in increased preference for methamphetamine and a highly palatable non-drug reinforcer (saccharin) and increased sensitivity to methamphetamine-induced conditioned reward. These data suggest that HIV-positive individuals may have increased sensitivity to methamphetamine, leading to high methamphetamine abuse potential in this population. PMID

  18. Fast reactors fuel cycle core physics results from the CAPRA-CADRA programme

    Energy Technology Data Exchange (ETDEWEB)

    Vasile, A.; Rimpault, G.; Tommasi, J.; Saint Jean, C. de; Delpech, M. [CEA Cadarache, 13 - Saint Paul lez Durance (France); Hesketh, K. [BNFL, Inc., Denver, CO (United States); Beaumont, H.M.; Sunderland, R.E. [NNC Ltd. (United Kingdom); Newton, T.; Smith, P. [AEA Technology (United Kingdom); Raedt, Ch. de [SCK.CEN, Mol (Belgium); Vambenepe, G. [Electricite de France (EDF), 75 - Paris (France); Lefevre, J.C. [FRAMATOME, 92 - Paris-La-Defence (France); Maschek, W.; Haas, D

    2001-07-01

    This paper presents an overview of fast reactor core physics results obtained in the context of the CAPRA-CADRA European collaborative programme, whose aim is to investigate a broad range of possible options for plutonium and radioactive waste management. Different types of fast reactors have been studied to evaluate their potential capabilities with respect to the long term management of plutonium, minor actinides (MAs) and long- lived fission products (LLFPs). Among the several options aiming at reducing waste and consequently radio toxicity are: homogeneous recycling of Minor Actinides, heterogeneous recycling of Minor Actinides either without or with moderation, dedicated critical cores (fuelled mainly with Minor Actinides) and Accelerator Driven System (ADS) variants. In order to achieve a detailed understanding of the potential of the various options, advanced core physics methods have been implemented and tested and applied, for example, to improving control rod modeling and to studying safety aspects. There has also been code development and experimental work carried out to improve the understanding of fuel performance behaviors. (author)

  19. Fast reactors fuel cycle core physics results from the CAPRA-CADRA programme

    International Nuclear Information System (INIS)

    Vasile, A.; Rimpault, G.; Tommasi, J.; Saint Jean, C. de; Delpech, M.; Hesketh, K.; Beaumont, H.M.; Sunderland, R.E.; Newton, T.; Smith, P.; Raedt, Ch. de; Vambenepe, G.; Lefevre, J.C.; Maschek, W.; Haas, D

    2001-01-01

    This paper presents an overview of fast reactor core physics results obtained in the context of the CAPRA-CADRA European collaborative programme, whose aim is to investigate a broad range of possible options for plutonium and radioactive waste management. Different types of fast reactors have been studied to evaluate their potential capabilities with respect to the long term management of plutonium, minor actinides (MAs) and long- lived fission products (LLFPs). Among the several options aiming at reducing waste and consequently radio toxicity are: homogeneous recycling of Minor Actinides, heterogeneous recycling of Minor Actinides either without or with moderation, dedicated critical cores (fuelled mainly with Minor Actinides) and Accelerator Driven System (ADS) variants. In order to achieve a detailed understanding of the potential of the various options, advanced core physics methods have been implemented and tested and applied, for example, to improving control rod modeling and to studying safety aspects. There has also been code development and experimental work carried out to improve the understanding of fuel performance behaviors. (author)

  20. Programme evaluation: Maintaining quality in higher education ...

    African Journals Online (AJOL)

    The evaluation of educational or social programmes is paramount for establishing success or impact in higher education. Evaluation questions about programme goals (e.g. better performance of first-year students) or about the quality of programme strategies (design and implementation) and effectiveness of delivery ...

  1. Structural and functional characterization of EIAV gp45 fusion peptide proximal region and asparagine-rich layer

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Liangwei; Du, Jiansen [State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China); Wang, Xuefeng; Zhou, Jianhua; Wang, Xiaojun [State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001 (China); Liu, Xinqi, E-mail: liu2008@nankai.edu.cn [State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China)

    2016-04-15

    Equine infectious anaemia virus (EIAV) and human immunodeficiency virus (HIV) are members of the lentiviral genus. Similar to HIV gp41, EIAV gp45 is a fusogenic protein that mediates fusion between the viral particle and the host cell membrane. The crystal structure of gp45 reported reveals a different conformation in the here that includes the fusion peptide proximal region (FPPR) and neighboring asparagine-rich layer compared with previous HIV-1 gp41 structures. A complicated hydrogen-bond network containing a cluster of solvent molecules appears to be critical for the stability of the gp45 helical bundle. Interestingly, viral replication was relatively unaffected by site-directed mutagenesis of EIAV, in striking contrast to that of HIV-1. Based on these observations, we speculate that EIAV is more adaptable to emergent mutations, which might be important for the evolution of EIAV as a quasi-species, and could potentially contribute to the success of the EIAV vaccine. - Highlights: • The crystal structure of EIAV gp45 was determined. • The fusion peptide proximal region adopts a novel conformation different to HIV-1. • The asparagine-rich layer includes an extensive hydrogen-bond network. • These regions of EIAV are highly tolerant to mutations. • The results provide insight into the mechanism of gp41/gp45-mediated membrane fusion.

  2. Patients' perceptions of GP non-verbal communication: a qualitative study.

    Science.gov (United States)

    Marcinowicz, Ludmila; Konstantynowicz, Jerzy; Godlewski, Cezary

    2010-02-01

    During doctor-patient interactions, many messages are transmitted without words, through non-verbal communication. To elucidate the types of non-verbal behaviours perceived by patients interacting with family GPs and to determine which cues are perceived most frequently. In-depth interviews with patients of family GPs. Nine family practices in different regions of Poland. At each practice site, interviews were performed with four patients who were scheduled consecutively to see their family doctor. Twenty-four of 36 studied patients spontaneously perceived non-verbal behaviours of the family GP during patient-doctor encounters. They reported a total of 48 non-verbal cues. The most frequent features were tone of voice, eye contact, and facial expressions. Less frequent were examination room characteristics, touch, interpersonal distance, GP clothing, gestures, and posture. Non-verbal communication is an important factor by which patients spontaneously describe and evaluate their interactions with a GP. Family GPs should be trained to better understand and monitor their own non-verbal behaviours towards patients.

  3. Leaf-GP: an open and automated software application for measuring growth phenotypes for arabidopsis and wheat.

    Science.gov (United States)

    Zhou, Ji; Applegate, Christopher; Alonso, Albor Dobon; Reynolds, Daniel; Orford, Simon; Mackiewicz, Michal; Griffiths, Simon; Penfield, Steven; Pullen, Nick

    2017-01-01

    Plants demonstrate dynamic growth phenotypes that are determined by genetic and environmental factors. Phenotypic analysis of growth features over time is a key approach to understand how plants interact with environmental change as well as respond to different treatments. Although the importance of measuring dynamic growth traits is widely recognised, available open software tools are limited in terms of batch image processing, multiple traits analyses, software usability and cross-referencing results between experiments, making automated phenotypic analysis problematic. Here, we present Leaf-GP (Growth Phenotypes), an easy-to-use and open software application that can be executed on different computing platforms. To facilitate diverse scientific communities, we provide three software versions, including a graphic user interface (GUI) for personal computer (PC) users, a command-line interface for high-performance computer (HPC) users, and a well-commented interactive Jupyter Notebook (also known as the iPython Notebook) for computational biologists and computer scientists. The software is capable of extracting multiple growth traits automatically from large image datasets. We have utilised it in Arabidopsis thaliana and wheat ( Triticum aestivum ) growth studies at the Norwich Research Park (NRP, UK). By quantifying a number of growth phenotypes over time, we have identified diverse plant growth patterns between different genotypes under several experimental conditions. As Leaf-GP has been evaluated with noisy image series acquired by different imaging devices (e.g. smartphones and digital cameras) and still produced reliable biological outputs, we therefore believe that our automated analysis workflow and customised computer vision based feature extraction software implementation can facilitate a broader plant research community for their growth and development studies. Furthermore, because we implemented Leaf-GP based on open Python-based computer vision, image

  4. Functionalization of SU-8 Photoresist Surfaces with IgG Proteins

    DEFF Research Database (Denmark)

    Blagoi, Gabriela; Keller, Stephan Urs; Johansson, Alicia

    2008-01-01

    immunoassays were employed to characterize the binding efficiency of model proteins to bare SU-8 surface, SU-8 treated with cerium ammonium nitrate (CAN) etchant and CAN treated surfaces modified by aminosilanization. The highest binding capacity of antibodies was observed on bare SU-8. This explains why bare...... SU-8 in a functional fluorescent sandwich immunoassay detecting C-reactive protein (CRP) gave twice as high signal as compared with the other two surfaces. Immunoassays performed on bare SU-8 and CAN treated SU-8 resulted in detection limits of CRP of 30 and 80 ng/ml respectively which is sufficient...... for detecting CRP in clinical samples, where concentrations of 3–10 μg/ml are normal for healthy individuals. In conclusion, bare SU-8 and etched SU-8 can be modified with antibodies by a simple adsorption procedure which simplifies building lab-on-a-chip systems in SU-8. Additionally, we report the fabrication...

  5. The effect of an active implementation of a disease management programme for chronic obstructive pulmonary disease on healthcare utilization--a cluster-randomised controlled trial.

    Science.gov (United States)

    Smidth, Margrethe; Christensen, Morten Bondo; Fenger-Grøn, Morten; Olesen, Frede; Vedsted, Peter

    2013-10-03

    The growing population living with chronic conditions calls for efficient healthcare-planning and effective care. Implementing disease-management-programmes is one option for responding to this demand. Knowledge is scarce about the effect of implementation processes and their effect on patients; only few studies have reported the effectiveness of disease-management-programmes targeting patients with chronic obstructive pulmonary disease (COPD). The objective of this paper was to determine the effect on healthcare-utilization of an active implementation model for a disease-management-programme for patients with one of the major multimorbidity diseases, COPD. The standard implementation of a new disease-management-programme for COPD was ongoing during the study-period from November 2008 to November 2010 in the Central Denmark Region. We wanted to test a strategy using Breakthrough Series, academic detailing and lists of patients with COPD. It targeted GPs and three hospitals serving approx. 60,000 inhabitants aged 35 or older and included interventions directed at professionals, organisations and patients. The study was a non-blinded block- and cluster-randomised controlled trial with GP-practices as the unit of randomisation. In Ringkoebing-Skjern Municipality, Denmark, 16 GP-practices involving 38 GPs were randomised to either the intervention-group or the control-group. A comparable neighbouring municipality acted as an external-control-group which included nine GP-practices with 25 GPs. An algorithm based on health-registry-data on lung-related contacts to the healthcare-system identified 2,736 patients who were alive at the end of the study-period. The population included in this study counted 1,372 (69.2%) patients who responded to the baseline questionnaire and confirmed their COPD diagnosis; 458 (33.4%) patients were from the intervention-group, 376 (27.4%) from the control-group and 538(39.2%) from the external-control-group. The primary outcome was

  6. 48 CFR 1019.202-70-8 - Protégé firms.

    Science.gov (United States)

    2010-10-01

    ... multiple mentors unless approved, in writing, by the Director, Office of Small Business Development (OSBD... SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Policies 1019.202-70-8 Protégé firms. (a) For selection as a protégé, a firm must be: (1) A small business, women-owned small business, small disadvantaged business...

  7. Neutronic Analysis of the RSG-GAS Compact Core without CIP Silicide 3.55 g U/cc and 4.8 g U/cc

    International Nuclear Information System (INIS)

    Jati S; Lily S; Tukiran S

    2004-01-01

    Fuel conversion from U 3 O 8 -Al to U 3 Si 2 -Al 2.96 g U/cc density in the RSG-GAS core had done successfully step by step since 36 th core until 44 th core. So that, since the 45 th core until now (48 th core) had been using full of silicide 2.96 g U/cc. Even though utilization program of silicide fuel with high density (3.55 g U/cc and 4.8 g U/cc) and optimize operation of RSG-GAS core under research. Optimalitation of core with increasing operation cycle have been analyzing about compact core. The mean of compact core is the RSG-GAS core with decrease number of IP or CIP position irradiation. In this research, the neutronic calculation to cover RSG-GAS core and RSG-GAS core without CIP that are using U 3 Si 2 -Al 2.96 g U/cc, 3.55 g U/cc and 4.8 g U/cc had done. Two core calculation done at 15 MW power using SRAC-ASMBURN code. The calculation result show that fuel conversion from 2.96 g U/cc density to 3.55 g U/cc and 4.8 g U/cc will increasing cycle length for both RSG-GAS core and RSG-GAS compact core without CIP. However, increasing of excess reactivity exceeded from nominal value of first design that 9.2%. Change of power peaking factor is not show significant value and still less than 1.4. Core fuelled with U 3 Si 2 -Al 4.8 g U/cc density have maximum discharge burn-up which exceeded from licensing value (70%). RSG-GAS compact core without CIP fuelled U 3 Si 2 -Al 2.96 g U/cc have longer cycle operation then RSG-GAS core and fulfil limitation neutronic parameter at the first design value. (author)

  8. Programme Evaluation: Maintaining Quality in Higher Education

    Science.gov (United States)

    Loots, A.

    2008-01-01

    The evaluation of educational or social programmes is paramount for establishing success or impact in higher education. Evaluation questions about programme goals (e.g. better performance of first-year students) or about the quality of programme strategies (design and implementation) and effectiveness of delivery (coordinator inputs and…

  9. FFUSION research programme 1993-1998. Final report of the Finnish fusion research programme

    Energy Technology Data Exchange (ETDEWEB)

    Karttunen, S.; Heikkinen, J.; Korhonen, R. [VTT Energy, Espoo (Finland)] [and others

    1998-12-31

    This report summarizes the results of the Fusion Energy Research Programme, FFUSION, during the period 1993-1998. After the planning phase the programme started in 1994, and later in March 1995 the FFUSION Programme was integrated into the EU Fusion Programme and the Association Euratom-Tekes was established. Research areas in the FFUSION Programme are (1) fusion physics and plasma engineering, (2) fusion reactor materials and (3) remote handling systems. In all research areas industry is involved. Recently, a project on environmental aspects of fusion and other future energy systems started as a part of the socio-economic research (SERF) in the Euratom Fusion Programme. A crucial component of the FFUSION programme is the close collaboration between VTT Research Institutes, universities and Finnish industry. This collaboration has guaranteed dynamic and versatile research teams, which are large enough to tackle challenging research and development projects. Regarding industrial fusion R and D activities, the major step was the membership of Imatran Voima Oy in the EFET Consortium (European Fusion Engineering and Technology), which further strengthened the position of industry in the engineering design activities of ITER. The number of FFUSION research projects was 66. In addition, there were 32 industrial R and D projects. The total cost of the FFUSION Programme in 1993-1998 amounted to FIM 54 million in research at VTT and universities and an additional FIM 21 million for R and D in Finnish industry. The main part of the funding was provided by Tekes, 36%. Since 1995, yearly Euratom funding has exceeded 25%. The FFUSION research teams have played an active role in the European Programme, receiving excellent recognition from the European partners. Theoretical and computational fusion physics has been at a high scientific level and the group collaborates with the leading experimental laboratories in Europe. Fusion technology is focused on reactor materials, joining

  10. FFUSION research programme 1993-1998. Final report of the Finnish fusion research programme

    International Nuclear Information System (INIS)

    Karttunen, S.; Heikkinen, J.; Korhonen, R.

    1998-01-01

    This report summarizes the results of the Fusion Energy Research Programme, FFUSION, during the period 1993-1998. After the planning phase the programme started in 1994, and later in March 1995 the FFUSION Programme was integrated into the EU Fusion Programme and the Association Euratom-Tekes was established. Research areas in the FFUSION Programme are (1) fusion physics and plasma engineering, (2) fusion reactor materials and (3) remote handling systems. In all research areas industry is involved. Recently, a project on environmental aspects of fusion and other future energy systems started as a part of the socio-economic research (SERF) in the Euratom Fusion Programme. A crucial component of the FFUSION programme is the close collaboration between VTT Research Institutes, universities and Finnish industry. This collaboration has guaranteed dynamic and versatile research teams, which are large enough to tackle challenging research and development projects. Regarding industrial fusion R and D activities, the major step was the membership of Imatran Voima Oy in the EFET Consortium (European Fusion Engineering and Technology), which further strengthened the position of industry in the engineering design activities of ITER. The number of FFUSION research projects was 66. In addition, there were 32 industrial R and D projects. The total cost of the FFUSION Programme in 1993-1998 amounted to FIM 54 million in research at VTT and universities and an additional FIM 21 million for R and D in Finnish industry. The main part of the funding was provided by Tekes, 36%. Since 1995, yearly Euratom funding has exceeded 25%. The FFUSION research teams have played an active role in the European Programme, receiving excellent recognition from the European partners. Theoretical and computational fusion physics has been at a high scientific level and the group collaborates with the leading experimental laboratories in Europe. Fusion technology is focused on reactor materials, joining

  11. Vertically Aligned Co9 S8 Nanotube Arrays onto Graphene Papers as High-Performance Flexible Electrodes for Supercapacitors.

    Science.gov (United States)

    Xiong, Dongbin; Li, Xifei; Bai, Zhimin; Li, Jianwei; Han, Yan; Li, Dejun

    2018-02-16

    Paper-like electrodes are emerging as a new category of advanced electrodes for flexible supercapacitors (SCs). Graphene, a promising two-dimensional material with high conductivity, can be easily processed into papers. Here, we report a rational design of flexible architecture with Co 9 S 8 nanotube arrays (NAs) grown onto graphene paper (GP) via a facile two-step hydrothermal method. When employed as flexible free-standing electrode for SCs, the proposed architectured Co 9 S 8 /GPs exhibits superior electrochemical performance with ultrahigh capacitance and outstanding rate capability (469 F g -1 at 10 A g -1 ). These results demonstrate that the new nanostructured Co 9 S 8 /GPs can be potentially applied in high performance flexible supercapacitors. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Fangchinoline inhibits human immunodeficiency virus type 1 replication by interfering with gp160 proteolytic processing.

    Directory of Open Access Journals (Sweden)

    Zhitao Wan

    Full Text Available The introduction of highly active antiretroviral therapy has led to a significant reduction in the morbidity and mortality of acquired immunodeficiency syndrome patients. However, the emergence of drug resistance has resulted in the failure of treatments in large numbers of patients and thus necessitates the development of new classes of anti-HIV drugs. In this study, more than 200 plant-derived small-molecule compounds were evaluated in a cell-based HIV-1 antiviral screen, resulting in the identification of a novel HIV-1 inhibitor (fangchinoline. Fangchinoline, a bisbenzylisoquinoline alkaloid isolated from Radix Stephaniae tetrandrae, exhibited antiviral activity against HIV-1 laboratory strains NL4-3, LAI and BaL in MT-4 and PM1 cells with a 50% effective concentration ranging from 0.8 to 1.7 µM. Mechanism-of-action studies showed that fangchinoline did not exhibit measurable antiviral activity in TZM-b1 cells but did inhibit the production of infectious virions in HIV-1 cDNA transfected 293T cells, which suggests that the compound targets a late event in infection cycle. Furthermore, the antiviral effect of fangchinoline seems to be HIV-1 envelope-dependent, as the production of infectious HIV-1 particles packaged with a heterologous envelope, the vesicular stomatitis virus G glycoprotein, was unaffected by fangchinoline. Western blot analysis of HIV envelope proteins expressed in transfected 293T cells and in isolated virions showed that fangchinoline inhibited HIV-1 gp160 processing, resulting in reduced envelope glycoprotein incorporation into nascent virions. Collectively, our results demonstrate that fangchinoline inhibits HIV-1 replication by interfering with gp160 proteolytic processing. Fangchinoline may serve as a starting point for developing a new HIV-1 therapeutic approach.

  13. Cognitive deficits associated with combined HIV gp120 expression and chronic methamphetamine exposure in mice

    Science.gov (United States)

    Kesby, James P.; Markou, Athina; Semenova, Svetlana

    2014-01-01

    Methamphetamine abuse is common among individuals infected by human immunodeficiency virus (HIV). Neurocognitive outcomes tend to be worse in methamphetamine users with HIV. However, it is unclear whether discrete cognitive domains are susceptible to impairment after combined HIV infection and methamphetamine abuse. The expression of HIV/gp120 protein induces neuropathology in mice similar to HIV-induced pathology in humans. We investigated the separate and combined effects of methamphetamine exposure and gp120 expression on cognitive function in transgenic (gp120-tg) and control mice. The mice underwent an escalating methamphetamine binge regimen and were tested in novel object/location recognition, object-in-place recognition, and Barnes maze tests. gp120 expression disrupted performance in the object-in-place test (i.e., similar time spent with all objects, regardless of location), indicating deficits in associative recognition memory. gp120 expression also altered reversal learning in the Barnes maze, suggesting impairments in executive function. Methamphetamine exposure impaired spatial strategy in the Barnes maze, indicating deficits in spatial learning. Methamphetamine-exposed gp120-tg mice had the lowest spatial strategy scores in the final acquisition trials in the Barnes maze, suggesting greater deficits in spatial learning than all of the other groups. Although HIV infection involves interactions between multiple proteins and processes, in addition to gp120, our findings in gp120-tg mice suggest that humans with the dual insult of HIV infection and methamphetamine abuse may exhibit a broader spectrum of cognitive deficits than those with either factor alone. Depending on the cognitive domain, the combination of both insults may exacerbate deficits in cognitive performance compared with each individual insult. PMID:25476577

  14. The third international workshop on the physics and modern applications of lasers 8-20 August, 1994

    International Nuclear Information System (INIS)

    1994-08-01

    The document contains 31 abstracts and 7 papers on lasers and optical fibers presented at the 3. international workshop on the physics and modern applications of lasers. The main topics covered include: basics in lasers, geometrical, physical and quantum optics; optical techniques for research, education and development in Africa; application of lasers in optical fibre communication, environmental studies, bio medicine, chemistry, agriculture, engineering and industry. A list of lecturers, participants and programme of activities are also given. (EAA)

  15. In vitro culture and structural differences in the major immunoreactive protein gp36 of geographically distant Ehrlichia canis isolates

    Czech Academy of Sciences Publication Activity Database

    Zweygarth, E.; Cabezas Cruz, Alejandro; Josemans, A.I.; Oosthuizen, M.C.; Matjila, P.T.; Lis, K.; Broniszewska, M.; Schöl, H.; Ferrolho, J.; Grubhoffer, Libor; Passos, L.M.F.

    2014-01-01

    Roč. 5, č. 4 (2014), s. 423-431 ISSN 1877-959X Institutional support: RVO:60077344 Keywords : Ehrlichia canis * In vitro culture * IDE8 tick cells * DH82 * 16S rRNA * gp36 Subject RIV: FN - Epidemiology, Contagious Diseases ; Clinical Immunology Impact factor: 2.718, year: 2014

  16. 2007 2008 ACADEMIC TRAINING PROGRAMME

    CERN Multimedia

    2008-01-01

    LECTURE SERIES 6 & 8 May 2008 11:00 -12:00 – Main Auditorium, bldg. 500-1 Energy isn’t Everything: CERN’s Fixed Target Niche Prof. John DAINTON / Cockcroft Institute & Liverpool University, UK Fixed target physics at CERN remains an essential part of the Laboratory’s scientific programme and horizon. In recent years fixed target and decay physics using CERN’s unique accelerator and beam facilities has continued to enable unique experiments to be undertaken. An overview is presented of the status of this physics and, wherever appropriate, of its future. LECTURE SERIES 7 May 2008 11:00 -12:00 – TH Auditorium – Bldg. 4-3-006 A rich revenue from the use of radioactive beams and radioactive targets: recent highlights from the nTOF and ISOLDE facilities 9 May 2008 11:00 -12:00 – Main Auditorium, bldg. 500-1 The fifth decade of ISOLDE: HIE-ISOLDE Professor Mark HUYSE, Leuven University, BE The On-Line Isotope Mass Separator ISOLDE is a facility dedicated to the production of a...

  17. A review of a GP registrar-run mobile health clinic for homeless people.

    Science.gov (United States)

    O'Carroll, A; Irving, N; O'Neill, J; Flanagan, E

    2017-08-01

    Homeless people have excessively high morbidity and mortality rates, yet they face barriers accessing primary care. A mobile health clinic, staffed by GP registrars, was developed to provide services to homeless people, particularly rough sleepers and sex workers. The aims were to improve access to primary care and to challenge the stereotypes and prejudices of GP registrars through direct contact with homeless people. This was a qualitative study; questionnaires were completed on the mobile health clinic and two focus groups were conducted. All service users were asked to complete a questionnaire over a 3 month period. Two focus groups were conducted with 6 and 14 GP registrars who had worked on the bus. There was an 80% response rate (116 of 145). Fifty-two percent had no Medical Card meaning that they had no way to access the free primary care to which they are entitled. Had the clinic not been available, over half would not have sought further treatment and 16% would have gone to an Emergency Department. Ninety-one percent of users rated the service 10/10. The focus groups found that GP registrars who worked on the mobile health clinic had decreased negative stereotypes, increased empathy, and more knowledge of homeless issues. Furthermore, they intended to ensure that homeless people will not face discrimination in their future practice. A GP Registrar-run Mobile Health Clinic achieved its aims of improving access to primary care for rough sleepers and sex workers, and challenging stereotypes of GP Registrars.

  18. Social relationships and GP use of middle-aged and older adults in Europe: a moderator analysis.

    Science.gov (United States)

    Bremer, Daniel; Lüdecke, Daniel; Vonneilich, Nico; von dem Knesebeck, Olaf

    2018-04-07

    This paper investigates (1) how social relationships (SRs) relate to the frequency of general practitioner (GP) visits among middle-aged and older adults in Europe, (2) if SRs moderate the association between self-rated health and GP visits, and (3) how the associations vary regarding employment status. Data stem from the Survey of Health, Ageing and Retirement in Europe project (wave 4, 56 989 respondents, 50 years or older). GP use was assessed by frequency of contacts with GPs in the last 12 months. Predictors were self-rated health and structural (Social Integration Index (SII), social contact frequency) and functional (emotional closeness) aspects of SR. Regressions were used to measure the associations between GP use and those predictors. Sociodemographic and socioeconomic factors were used as covariates. Additional models were computed with interactions. Analyses did not reveal significant associations of functional and structural aspects of SR with frequency of GP visits (SII: incidence rate ratio (IRR)=0.99, 95% CI 0.97 to 1.01, social contact frequency: IRR=1.04, 95% CI 1.00 to 1.07, emotional closeness: IRR=1.02, 95% CI 1.00 to 1.04). Moderator analyses showed that 'high social contact frequency people' with better health had more statistically significant GP visits than 'low social contact frequency people' with better health. Furthermore, people with poor health and an emotionally close network showed a significantly higher number of GP visits compared with people with same health, but less close networks. Three-way interaction analyses indicated employment status specific behavioural patterns with regard to SR and GP use, but coefficients were mostly not significant. All in all, the not employed groups showed a higher number of GP visits. Different indicators of SR showed statistically insignificantly associations with GP visits. Consequently, the relevance of SR may be rated rather low in quantitative terms for investigating GP use behaviour

  19. Characterization of incompletely typed rotavirus strains from Guinea-Bissau: identification of G8 and G9 types and a high frequency of mixed infections

    International Nuclear Information System (INIS)

    Fischer, T.K.; Page, N.A.; Griffin, D.D.; Eugen-Olsen, J.; Pedersen, A.G.; Valentiner-Branth, P.; Moelbak, K.; Sommerfelt, H.; Nielsen, N. Munk

    2003-01-01

    Among 167 rotavirus specimens collected from young children in a suburban area of Bissau, Guinea-Bissau, from 1996 to 1998, most identifiable strains belonged to the uncommon P[6], G2 type and approximately 50% remained incompletely typed. In the present study, 76 such strains were further characterized. Due to interprimer interaction during the standard multiplex PCR approach, modifications of this procedure were implemented. The modified analyses revealed a high frequency of G2, G8, and G9 genotypes, often combined with P[4] and/or P[6]. The Guinean G8 and G9 strains were 97 and 98%, respectively, identical to other African G8 and G9 strains. Multiple G and/or P types were identified at a high frequency (59%), including two previously undescribed mixed infections, P[4]P[6], G2G8 and P[4]P[6], G2G9. These mixed infections most likely represent naturally occurring reassortance of rotavirus strains. Detection of such strains among the previously incompletely typed strains indicates a potential underestimation of mixed infections, if only a standard multiplex PCR procedure is followed. Furthermore cross-priming of the G3 primer with the G8 primer binding site and silent mutations at the P[4] and P[6] primer binding sites were detected. These findings highlight the need for regular evaluation of the multiplex primer PCR method and typing primers. The high frequency of uncommon as well as reassortant rotavirus strains in countries where rotavirus is an important cause of child mortality underscores the need for extensive strain surveillance as a basis to develop appropriate rotavirus vaccine candidates

  20. 1981 research programme and budget of Hahn-Meitner-Institut fuer Kernforschung Berlin

    International Nuclear Information System (INIS)

    Anon.

    1981-01-01

    Hahn-Meitner-Institut fuer Kernforschung Berlin (HMI) is one of the twelve large research centers of the Federal Republic of Germany; like the other centers, it has to present a combined research programme and budget (programme budget) every year. In these programme budgets, as in the medium-term financial planning in the federal budget, planning for the current year is combined with a medium-term plan for the three next years. For the year 1981, the budget of HMI includes a total expenditure of about DM 85 million, DM 71.2 million of which are direct R + D expenditures. This R + D programme is carried by 396 of the total staff of 705. Research is done in the following fields (approximate figures): Heavy ion physics DM 23.0 million. Radiation- and photochemistry DM 11.4 million. Solid state research DM 20.9 million. Nuclear chemistry DM 8.9 million. Data processing/electronics DM 7.0 million. (orig./UA) [de

  1. A produção acadêmica publicada na revista Gestão & Produção de 1999 a 2010: tendências e direções para pesquisas futuras Academic research published in the Management & Production Journal (G&P, 1999-2010: trends and future research directions

    Directory of Open Access Journals (Sweden)

    Lucas Nogueira Bortollossi

    2012-01-01

    Full Text Available Esta pesquisa analisou as publicações da revista Gestão & Produção (G&P nos últimos doze anos. O objetivo foi identificar as tendências de pesquisa na área "Gestão da Produção e Operações" (POM: sua diversidade em termos de quantidade, tópico de interesse, fonte de dados, contribuição da pesquisa e redes sociais. Os artigos da revista G&P foram classificados quanto ao tipo de contribuição primária (conceitual, aplicação da teoria e construção de teoria, abordagem de coleta de dados (questionário, estudo de caso, pesquisa qualitativa, pesquisa de arquivo, pesquisa de laboratório, técnica de análise de dados (estatística básica, técnicas de análise multivariada e modelagem matemática e tópico de interesse (estratégia de operações, qualidade, gestão da cadeia de suprimento, entre outros. Com o levantamento realizado, observa-se que a pesquisa em gestão de operações cresceu consideravelmente na última década. O foco dos artigos amadureceu, passou de uma ênfase de artigos descritivos para uma vertente mais voltada à aplicação de teoria. A principal das fontes foram casos. Sugestões de direções para pesquisas futuras foram propostas.This study is a review and evaluation of studies published in a Brazilian journal of management & production (G&P from 1999 to 2010 in order to investigate the diversity of articles in terms of the purposes of research, data collection approaches, and data analysis techniques. The research articles were classified based on their primary purpose (theory building, application, and concepts, data collection approach (case study, qualitative research, archival research, survey-based research, laboratory research, and field research, data analysis technique (descriptive statistics, various multivariate statistical techniques, and mathematical modeling, and operations topics (strategy, quality, and supply chain management. The numbers of articles published increased substantially

  2. Patient influences on satisfaction and loyalty for GP services.

    Science.gov (United States)

    Rundle-Thiele, Sharyn; Russell-Bennett, Rebekah

    2010-04-01

    Little is known about the influence that patients themselves have on their loyalty to a general practitioner (GP). Consequently, a theoretical framework that draws on diverse literature is proposed to suggest that along with satisfaction, patient loyalty is an important outcome for GPs. Comprising 174 Australian patients, this study identified that knowledgeable patients reported lower levels of loyalty while older patients and patients visiting a GP more frequently reported higher levels of loyalty. The results suggest that extending patient-centered care practices to encompass all patients may be warranted in order to improve patient satisfaction and loyalty. Further, future research opportunities abound, with intervention and dyadic research methodologies recommended.

  3. Cloning of gp-340, a putative opsonin receptor for lung surfactant protein D

    DEFF Research Database (Denmark)

    Holmskov, U; Mollenhauer, J; Madsen, J

    1999-01-01

    in a soluble form and in association with the membranes of alveolar macrophages. The primary structure of gp-340 has been established by molecular cloning, which yielded a 7,686-bp cDNA sequence encoding a polypeptide chain of 2, 413 amino acids. The domain organization features 13 scavenger receptor cysteine...... in a way that suggested capping, whereas other macrophages showed strong intracellular staining within the phagosome/phagolysosome compartments. In some macrophages, SP-D and gp-340 were located in the same cellular compartment. Immunoreactive gp-340 was also found in epithelial cells of the small...

  4. Mass rearing and radiation sterilization of tsetse flies. Part of a coordinated programme on control and eradication of tsetse flies by the sterile insect technique

    International Nuclear Information System (INIS)

    Offori, E.

    1980-12-01

    Studies were conducted with the tsetse flies Glossina palpalis palpalis, G.p. gambiensis and G. tachinoides to evaluate the practicality in Ghana of various laboratory and field procedures used to conduct a sterile insect release programme. Investigations revealed that in colony rearing rabbits, guinea pigs and goats could be used as host animals and that alternation of hosts had little effect on colony performance. Over 90% sterility in 10-day-old males irradiated at 12 kR was obtained with little or no effect on survival. At 15 kR, 98% sterility was obtained but with some loss in viability observed. In mating experiments, G. p. palpalis and G. p. gambiensis mated readily with each other and indicated that sterile males of one sub-species could be released with advantage into an area predominantly occupied by the other sub-species. In field tests, the moving vehicle traps proved most efficient of the various sampling techniques evaluated. It was noted that in spite of the rapid expansion of the city of Accra, tsetse flies were still present within a distance of 4 km of the city

  5. Modeling relationships of achievement motivation and physical fitness with academic performance in Japanese schoolchildren: Moderation by gender.

    Science.gov (United States)

    Ishihara, Toru; Morita, Noriteru; Nakajima, Toshihiro; Okita, Koichi; Sagawa, Masato; Yamatsu, Koji

    2018-04-25

    The aim of this study was to determine, using structural equation modeling, the comprehensive relationships of achievement motivation (self-fulfillment achievement motivation [SFAM] and competitive achievement motivation [CAM]), daily behaviors (exercise habits, screen time, and learning duration), body mass index [BMI], and cardiorespiratory fitness [CRF]) with academic performance among schoolchildren. Three hundred twenty-five schoolchildren (172 males and 153 females; 12-13 years old) were recruited. Academic performance was assessed using the total grade points in 8 academic subjects (GP8); CRF using the 20-m shuttle run; and achievement motivation, daily behaviors, and socioeconomic status using questionnaires. Socioeconomic status was included as a control variable. In males, two cascade associations of achievement motivation to GP8 were detected: (1) SFAM → screen time/learning duration → GP8, and (2) CAM → exercise habit → CRF → GP8 (χ 2  = 8.72, p = .19, AGFI = .92). In females, two cascade associations were also detected: (1) SFAM → screen time/learning habit → GP8, and (2) exercise habit → BMI 2  → GP8 (χ 2  = 6.17, p = .41, AGFI = .93). Our results suggest that greater achievement motivation is associated with academic success via various physiological/behavioral factors, and that these associations differ by gender. Copyright © 2018. Published by Elsevier Inc.

  6. Crystal Structure of the Carboxy-Terminal Region of the Bacteriophage T4 Proximal Long Tail Fiber Protein Gp34

    Directory of Open Access Journals (Sweden)

    Meritxell Granell

    2017-06-01

    Full Text Available Long tail fibers of bacteriophage T4 are formed by proteins gp34, gp35, gp36, and gp37, with gp34 located at the phage-proximal end and gp37 at the phage-distal, receptor-binding end. We have solved the structure of the carboxy-terminal region of gp34, consisting of amino acids 894–1289, by single-wavelength anomalous diffraction and extended the structure to amino acids 744–1289 using data collected from crystals containing longer gp34-fragments. The structure reveals three repeats of a mixed α-β fibrous domain in residues 744 to 877. A triple-helical neck connects to an extended triple β-helix domain (amino acids 900–1127 punctuated by two β-prism domains. Next, a β-prism domain decorated with short helices and extended β-helices is present (residues 1146–1238, while the C-terminal end is capped with another short β-helical region and three β-hairpins. The structure provides insight into the stability of the fibrous gp34 protein.

  7. P-gp Expression and Rh 123 Efflux Assay Have no Impact on Survival in Egyptian Pediatric Acute Lymphoblastic Leukemia Patients

    International Nuclear Information System (INIS)

    Kamel, A.M.; El-Sharkawy, N.; Yassin, D.; Shaaban, Kh.; Hussein, H.; Sidhom, I; Abo El-Naga, S.; Ameen, M.; El-Hattab, O.; Aly El-Din, N.H.

    2005-01-01

    In a previous work we have studied MDR status in terms of P-glycoprotein (P-gp) expression and Rhodamine 123 efflux assay in Egyptian acute leukemia patients. We have reported results comparable to the literature as regards ANLL both in pediatric and adult cases. However, higher figures were encountered for the functional assay in ALL. As our ALL cases especially in pediatric age group show worse prognosis compared to literature, we hypothesized that the higher percentage of cases with positive Rh 123 efflux assay might be a contributing factor. Material and Methods: A total of 108 cases were studied including 80 ALL and 28 ANLL. ALL cases included 48 male and 32 female with an age range of 6m to 18 yrs and a median of 7 yrs. ANLL cases included 18 male and 10 female with an age range of 6m to 18 yrs and a median of 8 yrs. P-gp expression was evaluated using 4E3 and DIC2 mAb, analyzed by Coulter XL flow cytometer and expressed as a ratio at a cut off of ≤1.1 and/or ≤5% positive cells. For the evaluation of MDR function Rh 123 efflux assay using cyclosporine as a blocker and expressed as a ratio at a cutoff of ≤1. 1 and/or ≤ 10% positive cells was performed. MDR expression and function were correlated to age, Hb, TLC, CD34 expression, immuno phenotype and DNA index in ALL, FAB subtypes in ANLL as well as to CR, DFS and EFS in ALL. In ALL, P-gp expression was encountered in 26.4% of cases. Positive Rh efflux was reported in 61.5%. No correlation was encountered between neither expression nor functional assay with age, Hb, TLC, CD34 expression or immuno phenotype. CR was achieved in 89.8%; neither P-gp expression nor Rh123 efflux had an impact on CR except for Rh 123 efflux in T-ALL where a cutoff of 1.25 could predict CR at a total accuracy of 70.6%. DFS was 92.3% while EFS was 72.2% for the whole group. No significant difference was encountered neither between cases expressing or lacking P-gp nor between cases with negative or positive Rh 123 efflux assay

  8. Deletion and aberrant CpG island methylation of Caspase 8 gene in medulloblastoma.

    Science.gov (United States)

    Gonzalez-Gomez, Pilar; Bello, M Josefa; Inda, M Mar; Alonso, M Eva; Arjona, Dolores; Amiñoso, Cinthia; Lopez-Marin, Isabel; de Campos, Jose M; Sarasa, Jose L; Castresana, Javier S; Rey, Juan A

    2004-09-01

    Aberrant methylation of promoter CpG islands in human genes is an alternative genetic inactivation mechanism that contributes to the development of human tumors. Nevertheless, few studies have analyzed methylation in medulloblastomas. We determined the frequency of aberrant CpG island methylation for Caspase 8 (CASP8) in a group of 24 medulloblastomas arising in 8 adult and 16 pediatric patients. Complete methylation of CASP8 was found in 15 tumors (62%) and one case displayed hemimethylation. Three samples amplified neither of the two primer sets for methylated or unmethylated alleles, suggesting that genomic deletion occurred in the 5' flanking region of CASP8. Our findings suggest that methylation commonly contributes to CASP8 silencing in medulloblastomas and that homozygous deletion or severe sequence changes involving the promoter region may be another mechanism leading to CASP8 inactivation in this neoplasm.

  9. A Critical View on In Vitro Analysis of P-glycoprotein (P-gp) Transport Kinetics.

    Science.gov (United States)

    Saaby, Lasse; Brodin, Birger

    2017-09-01

    Transport proteins expressed in the different barriers of the human body can have great implications on absorption, distribution, and excretion of drug compounds. Inhibition or saturation of a transporter can potentially alter these absorbtion, distribution, metabolism and elimination properties and thereby also the pharmacokinetic profile and bioavailability of drug compounds. P-glycoprotein (P-gp, ABCB1) is an efflux transporter which is present in most of the barriers of the body, including the small intestine, the blood-brain barrier, the liver, and the kidney. In all these tissues, P-gp may mediate efflux of drug compounds and may also be a potential site for drug-drug interactions. Consequently, there is a need to be able to predict the saturation and inhibition of P-gp and other transporters in vivo. For this purpose, Michaelis-Menten steady-state analysis has been applied to estimate kinetic parameters, such as K m and V max , for carrier-mediated transport, whereas half-maximal inhibitor concentration (IC 50 ) and the disassociation constant for an inhibitor/P-gp complex (K i ) have been determined to estimate P-gp inhibition. This review addresses in vitro methods commonly used to study P-gp transport kinetics and aims at providing a critical evaluation of the application of steady-state Michaelis-Menten analysis of kinetic parameters for substrate/P-gp interactions. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  10. Curcumin improves synaptic plasticity impairment induced by HIV-1gp120 V3 loop

    Directory of Open Access Journals (Sweden)

    Ling-ling Shen

    2015-01-01

    Full Text Available Curcumin has been shown to significantly improve spatial memory impairment induced by HIV-1 gp120 V3 in rats, but the electrophysiological mechanism remains unknown. Using extracellular microelectrode recording techniques, this study confirmed that the gp120 V3 loop could suppress long-term potentiation in the rat hippocampal CA1 region and synaptic plasticity, and that curcumin could antagonize these inhibitory effects. Using a Fura-2/AM calcium ion probe, we found that curcumin resisted the effects of the gp120 V3 loop on hippocampal synaptosomes and decreased Ca 2+ concentration in synaptosomes. This effect of curcumin was identical to nimodipine, suggesting that curcumin improved the inhibitory effects of gp120 on synaptic plasticity, ameliorated damage caused to the central nervous system, and might be a potential neuroprotective drug.

  11. 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.

  12. Conserved region at the COOH terminus of human immunodeficiency virus gp120 envelope protein contains an immunodominant epitope

    International Nuclear Information System (INIS)

    Palker, T.J.; Matthews, T.J.; Clark, M.E.

    1987-01-01

    A highly immunogenic epitope from a conserved COOH-terminal region of the human immunodeficiency virus (HIV) gp120 envelope protein has been identified with antisera from HIV-seropositive subjects and a synthetic peptide (SP-22) containing 15 amino acids from this region (Ala-Pro-Thr-Lys-Ala-Lys-Arg-Arg-Val-Val-Gln-Arg-Glu-Lys-Arg). Peptide SP-22 absorbed up to 100% of anti-gp120 antibody reactivity from select HIV + patient sera in immunoblot assays and up to 79% of serum anti-gp120 antibody reactivity in competition RIA. In RIA, 45% of HIV-seropositive subjects had antibodies that bound to peptide SP-22. Human anti-SP-22 antibodies that bound to and were eluted from an SP-22 affinity column reacted with gp120 in RIA and immunoblot assays but did not neutralize HIV or inhibit HIV-induced syncytium formation in vitro, even though these antibodies comprised 70% of all anti-gp120 antibodies in the test serum. In contrast, the remaining 30% of SP-22 nonreactive anti-gp120 antibodies did not react with gp120 in immunoblot assays but did react in RIA and neutralized HIV in vitro. Thus, ≅ 50% of HIV-seropositive patients make high titers of nonneutralizing antibodies to an immunodominant antigen on gp120 defined by SP-22. Moreover, the COOH terminus of gp120 contains the major antigen or antigens identified by human anti-gp120 antibodies in immunoblot assays

  13. Gp120 stability on HIV-1 virions and Gag-Env pseudovirions is enhanced by an uncleaved Gag core

    International Nuclear Information System (INIS)

    Hammonds, Jason; Chen Xuemin; Ding Lingmei; Fouts, Timothy; De Vico, Anthony; Megede, Jan zur; Barnett, Susan; Spearman, Paul

    2003-01-01

    Human immunodeficiency virus type-1 (HIV-1) particles incorporate a trimeric envelope complex (Env) made of gp120 (SU) and gp41 (TM) heterodimers. It has been previously established that soluble CD4 (sCD4) interaction leads to shedding of gp120 from viral particles, and that gp120 may also be easily lost from virions during incubation or particle purification procedures. In the design of HIV particle or pseudovirion-based HIV vaccines, it may be important to develop strategies to maximize the gp120 content of particles. We analyzed the gp120 retention of HIV-1 laboratory-adapted isolates and primary isolates following incubation with sCD4 and variations in temperature. NL4-3 shed gp120 readily in a temperature- and sCD4-dependent manner. Surprisingly, inactivation of the viral protease led to markedly reduced shedding of gp120. Gp120 shedding was shown to vary markedly between HIV-1 strains, and was not strictly determined by whether the isolate was adapted to growth on immortalized T cell lines or was a primary isolate. Pseudovirions produced by expression of codon-optimized gag and env genes also demonstrated enhanced gp120 retention when an immature core structure was maintained. Pseudovirions of optimal stability were produced through a combination of an immature Gag protein core and a primary isolate Env. These results support the feasibility of utilizing pseudovirion particles as immunogens for the induction of humoral responses directed against native envelope structures

  14. Binding kinetics of aptamers to gp120 derived from HIV-1 subtype C

    CSIR Research Space (South Africa)

    Millroy, L

    2011-02-01

    Full Text Available aptamers with specific and strong affinity to the HIV-1 envelope glycoprotein gp120 and act as novel HIV-1 entry inhibitor drugs or as targeted drug delivery systems to HIV-1 infected cells. Prior to any downstream applications, novel gp120 aptamers need...

  15. P-gp expression in brown trout erythrocytes: evidence of a detoxification mechanism in fish erythrocytes.

    Science.gov (United States)

    Valton, Emeline; Amblard, Christian; Wawrzyniak, Ivan; Penault-Llorca, Frederique; Bamdad, Mahchid

    2013-12-05

    Blood is a site of physiological transport for a great variety of molecules, including xenobiotics. Blood cells in aquatic vertebrates, such as fish, are directly exposed to aquatic pollution. P-gp are ubiquitous "membrane detoxification proteins" implicated in the cellular efflux of various xenobiotics, such as polycyclic aromatic hydrocarbons (PAHs), which may be pollutants. The existence of this P-gp detoxification system inducible by benzo [a] pyrene (BaP), a highly cytotoxic PAH, was investigated in the nucleated erythrocytes of brown trout. Western blot analysis showed the expression of a 140-kDa P-gp in trout erythrocytes. Primary cultures of erythrocytes exposed to increasing concentrations of BaP showed no evidence of cell toxicity. Yet, in the same BaP-treated erythrocytes, P-gp expression increased significantly in a dose-dependent manner. Brown trout P-gp erythrocytes act as membrane defence mechanism against the pollutant, a property that can be exploited for future biomarker development to monitor water quality.

  16. CERN launches high-school internship programme

    Science.gov (United States)

    Johnston, Hamish

    2017-07-01

    The CERN particle-physics lab has hosted 22 high-school students from Hungary in a pilot programme designed to show teenagers how science, technology, engineering and mathematics is used at the particle-physics lab.

  17. N-terminal substitutions in HIV-1 gp41 reduce the expression of non-trimeric envelope glycoproteins on the virus

    International Nuclear Information System (INIS)

    Dey, Antu K.; David, Kathryn B.; Ray, Neelanjana; Ketas, Thomas J.; Klasse, Per J.; Doms, Robert W.; Moore, John P.

    2008-01-01

    The native, functional HIV-1 envelope glycoprotein (Env) complex is a trimer of two non-covalently associated subunits: the gp120 surface glycoprotein and the gp41 transmembrane glycoprotein. However, various non-functional forms of Env are present on virus particles and HIV-1-infected cells, some of which probably arise as the native complex decays. The aberrant forms include gp120-gp41 monomers and oligomers, as well as gp41 subunits from which gp120 has dissociated. The presence of non-functional Env creates binding sites for antibodies that do not recognize native Env complexes and that are, therefore, non-neutralizing. Non-native Env forms (monomers, dimers, tetramers and aggregates) can also arise when soluble gp140 proteins, lacking the cytoplasmic and transmembrane domains of gp41, are expressed for vaccine studies. We recently identified five amino acids in the gp41 N-terminal region (I535, Q543, S553, K567 and R588) that promote gp140 trimerization. We have now studied their influence on the function and antigenic properties of JR-FL Env expressed on the surfaces of pseudoviruses and Env-transfected cells. The 5 substitutions in gp41 reduce the expression of non-trimeric gp160s, without affecting trimer levels. Pseudovirions bearing the mutant Env are fully infectious with similar kinetics of Env-mediated fusion. Various non-neutralizing antibodies bind less strongly to the Env mutant, but neutralizing antibody binding is unaffected. Hence the gp41 substitutions do not adversely affect Env structure, supporting their use for making new Env-based vaccines. The mutant Env might also help in studies intended to correlate antibody binding to virus neutralization. Of note is that the 5 residues are much more frequent, individually or collectively, in viruses from subtypes other than B

  18. Role for the disulfide-bonded region of human immunodeficiency virus type 1 gp41 in receptor-triggered activation of membrane fusion function

    International Nuclear Information System (INIS)

    Bellamy-McIntyre, Anna K.; Baer, Severine; Ludlow, Louise; Drummer, Heidi E.; Poumbourios, Pantelis

    2010-01-01

    The conserved disulfide-bonded region (DSR) of the human immunodeficiency virus type 1 (HIV-1) fusion glycoprotein, gp41, mediates association with the receptor-binding glycoprotein, gp120. Interactions between gp120, CD4 and chemokine receptors activate the fusion activity of gp41. The introduction of W596L and W610F mutations to the DSR of HIV-1 QH1549.13 blocked viral entry and hemifusion without affecting gp120-gp41 association. The fusion defect correlated with inhibition of CD4-triggered gp41 pre-hairpin formation, consistent with the DSR mutations having decoupled receptor-induced conformational changes in gp120 from gp41 activation. Our data implicate the DSR in sensing conformational changes in the gp120-gp41 complex that lead to fusion activation.

  19. Missed opportunities in the evaluation of public health interventions: a case study of physical activity programmes

    Directory of Open Access Journals (Sweden)

    Sarah Hanson

    2017-08-01

    Full Text Available Abstract Background Evidence-based approaches are requisite in evaluating public health programmes. Nowhere are they more necessary than physical activity interventions where evidence of effectiveness is often poor, especially within hard to reach groups. Our study reports on the quality of the evaluation of a government funded walking programme in five ‘Walking Cities’ in England. Cities were required to undertake a simple but robust evaluation using the Standard Evaluation Framework (SEF for physical activity interventions to enable high quality, consistent evaluation. Our aim was not to evaluate the outcomes of this programme but to evaluate whether the evaluation process had been effective in generating new and reliable evidence on intervention design and what had worked in ‘real world’ circumstances. Methods Funding applications and final reports produced by the funder and the five walking cities were obtained. These totalled 16 documents which were systematically analysed against the 52 criteria in the SEF. Data were cross checked between the documents at the bid and reporting stage with reference to the SEF guidance notes. Results Generally, the SEF reporting requirements were not followed well. The rationale for the interventions was badly described, the target population was not precisely specified, and neither was the method of recruitment. Demographics of individual participants, including socio-economic status were reported poorly, despite being a key criterion for funding. Conclusions Our study of the evaluations demonstrated a missed opportunity to confidently establish what worked and what did not work in walking programmes with particular populations. This limited the potential for evidence synthesis and to highlight innovative practice warranting further investigation. Our findings suggest a mandate for evaluability assessment. Used at the planning stage this may have ensured the development of realistic objectives and

  20. GP50 as a promising early diagnostic antigen for Taenia multiceps infection in goats by indirect ELISA.

    Science.gov (United States)

    Huang, Xing; Xu, Jing; Wang, Yu; Guo, Cheng; Chen, Lin; Gu, Xiaobin; Lai, Weimin; Peng, Xuerong; Yang, Guangyou

    2016-12-01

    Coenurosis is caused by coenurus, the metacestode of Taenia multiceps, which mainly parasitizes the brain and spinal cord of cattle, sheep and goats. To date, no widely-approved methods are available to identify early coenurus infection. In this study, we identified a full-length cDNA that encodes GP50 (TmGP50) from the transcriptome of T. multiceps, and then cloned and expressed in E. coli. The native proteins in adult stage and coenurus were located via immunofluorescence assays, while the potential of recombinant TmGP50 protein (rTmGP50) for indirect ELISA-based serodiagnostics was assessed using native goat sera. In addition, we orally infected 20 goats with mature T. multiceps eggs. Praziquantel (10%) was given to 10 of the goats 45 days post-infection (p.i.). Blood samples were collected for 17 weeks p.i. from the 20 goats and anti-rTmGP50 antibodies were evaluated using the indirect ELISA established here. The TmGP50 contains an 897 bp open reading frame, in which signal sequence resides in 1 ~ 48 sites and mature polypeptide consists of 282 amino acid residues. Immunofluorescence staining showed that native TmGP50 was localized to the microthrix and parenchymatous zone of the adult parasite and coenurus, and the coenurus cystic wall. The indirect ELISA based on rTmGP50 exhibited a sensitivity of 95.0% and a specificity of 92.6% when detecting GP50 antibodies in sera of naturally infected goats and sheep. In goats experimentally infected with T. multiceps, anti-TmGP50 antibody was detectable from 2 to 17 weeks p.i. in the control group, while the antibody fell below the cut-off value about 3 weeks after praziquantel treatment. Our results indicate that recombinant TmGP50 is a suitable early diagnostic antigen for coenurus infection in goats.

  1. Impact of the Leading an Empowered Organisation programme.

    Science.gov (United States)

    Hancock, Helen; Campbell, Steve

    To evaluate the impact of the Leading an Empowered Organisation (LEO) programme on the role of grade G nurses and their multidisciplinary colleagues in one NHS trust. The LEO programme encourages and promotes leadership skills among NHS staff. A purposive sample of four grade G nurses, one from each of the hospital's four clinical divisions, was included. Each grade G nurse, and his or her matron, nominated eight colleagues for interview. The final sample comprised four grade G nurses and 32 of their colleagues. Data were analysed using the principles of thematic analysis described by Attride-Stirling (2001). The LEO programme improved the grade G nurses' approach to their work in relation to competence, communication strategies, problem solving, risk taking, leadership and management style. Factors that affected the grade G nurses' implementation of the LEO principles included: relationships, personality, experience, work context, staffing levels, autonomy and authority. This study provided insight into how the grade G nurses applied the principles of the LEO programme in their daily work. Their ability to apply the LEO principles was both restricted and assisted by the culture in which they worked. A partnership between theory and practice is needed. This finding has implications for the LEO programme and the need for it to be implicit in the local working philosophy, that is, the context in which its principles are to be used. This is so that the working context and people within it are intimately engaged with the individual undertaking the course.

  2. Leishmania major surface protease Gp63 interferes with the function of human monocytes and neutrophils in vitro

    DEFF Research Database (Denmark)

    Sørensen, A L; Hey, A S; Kharazmi, A

    1994-01-01

    In the present study the effect of Leishmania major surface protease Gp63 on the chemotaxis and oxidative burst response of human peripheral blood monocytes and neutrophils was investigated. It was shown that prior incubation of cells with Gp63 inhibited chemotaxis of neutrophils but not monocytes...... towards the chemotactic peptide f-met-leu-phe. On the other hand, chemotaxis of both neutrophils and monocytes towards zymosan-activated serum containing C5a was inhibited by Gp63. Monocyte and neutrophil chemiluminescence response to opsonized zymosan was reduced by preincubation of the cells with Gp63...... in a concentration-dependent manner. Notably, monocytes were inhibited to a much greater degree than neutrophils by a given concentration of Gp63, and they were also inhibited at much lower concentrations of the protease. The inhibitory effect of Gp63 on chemotaxis and chemiluminescence was completely abolished...

  3. 21 CFR 870.3700 - Pacemaker programmers.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Pacemaker programmers. 870.3700 Section 870.3700...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3700 Pacemaker programmers. (a) Identification. A pacemaker programmer is a device used to change noninvasively one or more of...

  4. Inhibition of a NEDD8 Cascade Restores Restriction of HIV by APOBEC3G.

    Directory of Open Access Journals (Sweden)

    David J Stanley

    2012-12-01

    Full Text Available Cellular restriction factors help to defend humans against human immunodeficiency virus (HIV. HIV accessory proteins hijack at least three different Cullin-RING ubiquitin ligases, which must be activated by the small ubiquitin-like protein NEDD8, in order to counteract host cellular restriction factors. We found that conjugation of NEDD8 to Cullin-5 by the NEDD8-conjugating enzyme UBE2F is required for HIV Vif-mediated degradation of the host restriction factor APOBEC3G (A3G. Pharmacological inhibition of the NEDD8 E1 by MLN4924 or knockdown of either UBE2F or its RING-protein binding partner RBX2 bypasses the effect of Vif, restoring the restriction of HIV by A3G. NMR mapping and mutational analyses define specificity determinants of the UBE2F NEDD8 cascade. These studies demonstrate that disrupting host NEDD8 cascades presents a novel antiretroviral therapeutic approach enhancing the ability of the immune system to combat HIV.

  5. A competency based selection procedure for Dutch postgraduate GP training: a pilot study on validity and reliability.

    Science.gov (United States)

    Vermeulen, Margit I; Tromp, Fred; Zuithoff, Nicolaas P A; Pieters, Ron H M; Damoiseaux, Roger A M J; Kuyvenhoven, Marijke M

    2014-12-01

    Abstract Background: Historically, semi-structured interviews (SSI) have been the core of the Dutch selection for postgraduate general practice (GP) training. This paper describes a pilot study on a newly designed competency-based selection procedure that assesses whether candidates have the competencies that are required to complete GP training. The objective was to explore reliability and validity aspects of the instruments developed. The new selection procedure comprising the National GP Knowledge Test (LHK), a situational judgement tests (SJT), a patterned behaviour descriptive interview (PBDI) and a simulated encounter (SIM) was piloted alongside the current procedure. Forty-seven candidates volunteered in both procedures. Admission decision was based on the results of the current procedure. Study participants did hardly differ from the other candidates. The mean scores of the candidates on the LHK and SJT were 21.9 % (SD 8.7) and 83.8% (SD 3.1), respectively. The mean self-reported competency scores (PBDI) were higher than the observed competencies (SIM): 3.7(SD 0.5) and 2.9(SD 0.6), respectively. Content-related competencies showed low correlations with one another when measured with different instruments, whereas more diverse competencies measured by a single instrument showed strong to moderate correlations. Moreover, a moderate correlation between LHK and SJT was found. The internal consistencies (intraclass correlation, ICC) of LHK and SJT were poor while the ICC of PBDI and SIM showed acceptable levels of reliability. Findings on content validity and reliability of these new instruments are promising to realize a competency based procedure. Further development of the instruments and research on predictive validity should be pursued.

  6. Characterisation of different forms of the accessory gp3 canine coronavirus type I protein identified in cats.

    Science.gov (United States)

    d'Orengiani, Anne-Laure Pham-Hung d'Alexandry; Duarte, Lidia; Pavio, Nicole; Le Poder, Sophie

    2015-04-16

    ORF3 is a supplemental open reading frame coding for an accessory glycoprotein gp3 of unknown function, only present in genotype I canine strain (CCoV-I) and some atypical feline FCoV strains. In these latter hosts, the ORF3 gene systematically displays one or two identical deletions leading to the synthesis of truncated proteins gp3-Δ1 and gp3-Δ2. As deletions in CoV accessory proteins have already been involved in tissue or host switch, studies of these different gp3 proteins were conducted in canine and feline cell. All proteins oligomerise through covalent bonds, are N-glycosylated and are maintained in the ER in non-infected but also in CCoV-II infected cells, without any specific retention signal. However, deletions influence their level of expression. In canine cells, all proteins are expressed with similar level whereas in feline cells, the expression of gp3-Δ1 is higher than the two other forms of gp3. None of the gp3 proteins modulate the viral replication cycle of heterologous genotype II CCoV in canine cell line, leading to the conclusion that the gp3 proteins are probably advantageous only for CCoV-I and atypical FCoV strains. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Association between general practice characteristics and use of out-of-hours GP cooperatives.

    Science.gov (United States)

    Smits, Marleen; Peters, Yvonne; Broers, Sanne; Keizer, Ellen; Wensing, Michel; Giesen, Paul

    2015-05-01

    The use of out-of-hours healthcare services for non-urgent health problems is believed to be related to the organisation of daytime primary care but insight into underlying mechanisms is limited. Our objective was to examine the association between daytime general practice characteristics and the use of out-of-hours care GP cooperatives. A cross-sectional observational study in 100 general practices in the Netherlands, connected to five GP cooperatives. In each GP cooperative, we took a purposeful sample of the 10 general practices with the highest use of out-of-hours care and the 10 practices with the lowest use. Practice and population characteristics were obtained by questionnaires, interviews, data extraction from patient registration systems and telephone accessibility measurements. To examine which aspects of practice organisation were associated with patients' use of out-of-hours care, we performed logistic regression analyses (low versus high out-of-hours care use), correcting for population characteristics. The mean out-of-hours care use in the high use group of general practices was 1.8 times higher than in the low use group. Day time primary care practices with more young children and foreigners in their patient populations and with a shorter distance to the GP cooperative had higher out-of-hours primary care use. In addition, longer telephone waiting times and lower personal availability for palliative patients in daily practice were associated with higher use of out-of-hours care. Moreover, out-of-hours care use was higher when practices performed more diagnostic tests and therapeutic procedures and had more assistant employment hours per 1000 patients. Several other aspects of practice management showed some non-significant trends: high utilising general practices tended to have longer waiting times for non-urgent appointments, lower availability of a telephone consulting hour, lower availability for consultations after 5 p.m., and less frequent

  8. HIV-1 gp120 and drugs of abuse: interactions in the central nervous system.

    Science.gov (United States)

    Silverstein, Peter S; Shah, Ankit; Weemhoff, James; Kumar, Santosh; Singh, D P; Kumar, Anil

    2012-07-01

    HIV-1 infection is a global public health problem with more than 34 million people living with HIV infection. Although great strides have been made in treating this epidemic with therapeutic agents, the increase in patient life span has been coincident with an increase in the prevalence of HIV-associated neurocognitive disorders (HAND). HAND is thought to result from the neurotoxic effects of viral proteins that are shed from HIV-infected microglial cells. One of the primary neurotoxins responsible for this effect is the HIV-1 glycoprotein gp120. Exposure of neurons to gp120 has been demonstrated to cause apoptosis in neurons, as well as numerous indirect effects such as an increase in inflammatory cytokines, an increase in oxidative stress, and an increase in permeability of the blood-brain barrier. In many patients, the use of drugs of abuse (DOA) exacerbates the neurotoxic effects of gp120. Cocaine, methamphetamine and morphine are three DOAs that are commonly used by those infected with HIV-1. All three of these DOAs have been demonstrated to increase oxidative stress in the CNS as well as to increase permeability of the blood-brain barrier. Numerous model systems have demonstrated that these DOAs have the capability of exacerbating the neurotoxic effects of gp120. This review will summarize the neurotoxic effects of gp120, the deleterious effects of cocaine, methamphetamine and morphine on the CNS, and the combined effects of gp120 in the context of these drugs.

  9. OSBP-related protein 8 (ORP8) interacts with Homo sapiens sperm associated antigen 5 (SPAG5) and mediates oxysterol interference of HepG2 cell cycle

    International Nuclear Information System (INIS)

    Zhong, Wenbin; Zhou, You; Li, Jiwei; Mysore, Raghavendra; Luo, Wei; Li, Shiqian; Chang, Mau-Sun; Olkkonen, Vesa M.; Yan, Daoguang

    2014-01-01

    We earlier identified OSBP-related protein 8 (ORP8) as an endoplasmic reticulum/nuclear envelope oxysterol-binding protein implicated in cellular lipid homeostasis, migration, and organization of the microtubule cytoskeleton. Here, a yeast two-hybrid screen identified Homo sapiens sperm associated antigen 5 (SPAG5)/Astrin as interaction partner of ORP8. The putative interaction was further confirmed by pull-down and co-immunoprecipitation assays. ORP8 did not colocalize with kinetochore-associated SPAG5 in mitotic HepG2 or HuH7 cells, but overexpressed ORP8 was capable of recruiting SPAG5 onto endoplasmic reticulum membranes in interphase cells. In our experiments, 25-hydroxycholesterol (25OHC) retarded the HepG2 cell cycle, causing accumulation in G2/M phase; ORP8 overexpression resulted in the same phenotype. Importantly, ORP8 knock-down dramatically inhibited the oxysterol effect on HepG2 cell cycle, suggesting a mediating role of ORP8. Furthermore, knock-down of SPAG5 significantly reduced the effects of both ORP8 overexpression and 25OHC on the cell cycle, placing SPAG5 downstream of the two cell-cycle interfering factors. Taken together, the present results suggest that ORP8 may via SPAG5 mediate oxysterol interference of the HepG2 cell cycle. - Highlights: • The oxysterol-binding protein ORP8 was found to interact with the mitotic regulator SPAG5/Astrin. • Treatment of HepG2 cells with 25-hydroxycholesterol caused cell cycle retardation in G2/M. • ORP8 overexpression caused a similar G2/M accumulation, and ORP8 knock-down reversed the 25-hydroxycholesterol effect. • Reduction of cellular of SPAG5/Astrin reversed the cell cycle effects of both 25-hydroxycholesterol and ORP8 overexpression. • Our results suggest that ORP8 mediates via SPAG5/Astrin the oxysterol interference of HepG2 cell cycle

  10. OSBP-related protein 8 (ORP8) interacts with Homo sapiens sperm associated antigen 5 (SPAG5) and mediates oxysterol interference of HepG2 cell cycle

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, Wenbin [Department of Biotechnology, Jinan University, Guangzhou 510632 (China); Zhou, You [Minerva Foundation Institute for Medical Research, Helsinki (Finland); Li, Jiwei [Department of Biotechnology, Jinan University, Guangzhou 510632 (China); Mysore, Raghavendra [Minerva Foundation Institute for Medical Research, Helsinki (Finland); Luo, Wei; Li, Shiqian [Department of Biotechnology, Jinan University, Guangzhou 510632 (China); Chang, Mau-Sun [Institute of Biochemical Sciences, National Taiwan University, No. 1, Taipei, Taiwan (China); Olkkonen, Vesa M. [Minerva Foundation Institute for Medical Research, Helsinki (Finland); Yan, Daoguang, E-mail: tydg@jnu.edu.cn [Department of Biotechnology, Jinan University, Guangzhou 510632 (China)

    2014-04-01

    We earlier identified OSBP-related protein 8 (ORP8) as an endoplasmic reticulum/nuclear envelope oxysterol-binding protein implicated in cellular lipid homeostasis, migration, and organization of the microtubule cytoskeleton. Here, a yeast two-hybrid screen identified Homo sapiens sperm associated antigen 5 (SPAG5)/Astrin as interaction partner of ORP8. The putative interaction was further confirmed by pull-down and co-immunoprecipitation assays. ORP8 did not colocalize with kinetochore-associated SPAG5 in mitotic HepG2 or HuH7 cells, but overexpressed ORP8 was capable of recruiting SPAG5 onto endoplasmic reticulum membranes in interphase cells. In our experiments, 25-hydroxycholesterol (25OHC) retarded the HepG2 cell cycle, causing accumulation in G2/M phase; ORP8 overexpression resulted in the same phenotype. Importantly, ORP8 knock-down dramatically inhibited the oxysterol effect on HepG2 cell cycle, suggesting a mediating role of ORP8. Furthermore, knock-down of SPAG5 significantly reduced the effects of both ORP8 overexpression and 25OHC on the cell cycle, placing SPAG5 downstream of the two cell-cycle interfering factors. Taken together, the present results suggest that ORP8 may via SPAG5 mediate oxysterol interference of the HepG2 cell cycle. - Highlights: • The oxysterol-binding protein ORP8 was found to interact with the mitotic regulator SPAG5/Astrin. • Treatment of HepG2 cells with 25-hydroxycholesterol caused cell cycle retardation in G2/M. • ORP8 overexpression caused a similar G2/M accumulation, and ORP8 knock-down reversed the 25-hydroxycholesterol effect. • Reduction of cellular of SPAG5/Astrin reversed the cell cycle effects of both 25-hydroxycholesterol and ORP8 overexpression. • Our results suggest that ORP8 mediates via SPAG5/Astrin the oxysterol interference of HepG2 cell cycle.

  11. Membrane binding properties of EBV gp110 C-terminal domain; evidences for structural transition in the membrane environment

    International Nuclear Information System (INIS)

    Park, Sung Jean; Seo, Min-Duk; Lee, Suk Kyeong; Lee, Bong Jin

    2008-01-01

    Gp110 of Epstein-Barr virus (EBV) mainly localizes on nuclear/ER membranes and plays a role in the assembly of EBV nucleocapsid. The C-terminal tail domain (gp110 CTD) is essential for the function of gp110 and the nuclear/ER membranes localization of gp110 is ruled by its C-terminal unique nuclear localization signal (NLS), consecutive four arginines. In the present study, the structural properties of gp110 CTD in membrane mimics were investigated using CD, size-exclusion chromatography, and NMR, to elucidate the effect of membrane environment on the structural transition and to compare the structural feature of the protein in the solution state with that of the membrane-bound form. CD and NMR analysis showed that gp110 CTD in a buffer solution appears to adopt a stable folding intermediate which lacks compactness, and a highly helical structure is formed only in membrane environments. The helical content of gp110 CTD was significantly affected by the negative charge as well as the size of membrane mimics. Based on the elution profiles of the size-exclusion chromatography, we found that gp110 CTD intrinsically forms a trimer, revealing that a trimerization region may exist in the C-terminal domain of gp110 like the ectodomain of gp110. The mutation of NLS (RRRR) to RTTR does not affect the overall structure of gp110 CTD in membrane mimics, while the helical propensity in a buffer solution was slightly different between the wild-type and the mutant proteins. This result suggests that not only the helicity induced in membrane environment but also the local structure around NLS may be related to trafficking to the nuclear membrane. More detailed structural difference between the wild-type and the mutant in membrane environment was examined using synthetic two peptides including the wild-type NLS and the mutant NLS

  12. Glycoprotein 5 of porcine reproductive and respiratory syndrome virus strain SD16 inhibits viral replication and causes G2/M cell cycle arrest, but does not induce cellular apoptosis in Marc-145 cells

    International Nuclear Information System (INIS)

    Mu, Yang; Li, Liangliang; Zhang, Beibei; Huang, Baicheng; Gao, Jiming

    2015-01-01

    Cell apoptosis is common after infection with porcine reproductive and respiratory syndrome virus (PRRSV). PRRSV GP5 has been reported to induce cell apoptosis. To further understand the role of GP5 in PRRSV induced cell apoptosis, we established Marc-145 cell lines stably expressing full-length GP5, GP5 Δ84-96 (aa 84-96 deletion), and GP5 Δ97-119 (aa 97-119 deletion). Cell proliferation, cell cycle progression, cell apoptosis and virus replication in these cell lines were evaluated. Neither truncated nor full-length GP5 induced cell apoptosis in Marc-145 cells. However, GP5 Δ97-119 , but not full-length or GP5 Δ84-96 , induced a cell cycle arrest at the G2/M phase resulting in a reduction in the growth of Marc-145 cells. Additionally, GP5 Δ84-96 inhibited the replication of PRRSV in Marc-145 cells through induction of IFN-β. These findings suggest that PRRSV GP5 is not responsible for inducing cell apoptosis in Marc-145 cells under these experimental conditions; however it has other important roles in virus/host cell biology. - Highlights: • Marc-145 cell lines stable expression PRRSV GP5 or truncated GP5 were constructed. • GP5 Δ97-119 expression in Marc-145 cell induced cell cycle arrest at G2/M phase. • Expression of GP5 and truncated GP5 could not induce Marc-145 cells apoptosis. • PRRSV replication in Marc-145-GP5 Δ84-96 was significantly inhibited

  13. Cloning and Characterization of the Genes Encoding the Murine Homologues of the Human Melanoma Antigens MART1 and gp100

    Science.gov (United States)

    Zhai, Yifan; Yang, James C.; Spiess, Paul; Nishimura, Michael I.; Overwijk, Willem W.; Roberts, Bruce; Restifo, Nicholas P.; Rosenberg, Steven A.

    2008-01-01

    The recent identification of genes encoding melanoma-associated antigens has opened new possibilities for the development of cancer vaccines designed to cause the rejection of established tumors. To develop a syngeneic animal model for evaluating antigen-specific vaccines in cancer therapy, the murine homologues of the human melanoma antigens MART1 and gp 100, which were specifically recognized by tumor-infiltrating lymphocytes from patients with melanoma, were cloned and sequenced from a murine B16 melanoma cDNA library. The open reading frames of murine MART1 and gp 100 encode proteins of 113- and 626-amino acids with 68.8 and 77% identity to the respective human proteins. Comparison of the DNA sequences of the murine MART1 genes, derived from normal melanocytes, the immortalized nontumorgenic melanocyte line Melan-a and the B16 melanoma, showed all to be identical. Northern and Western blot analyses confirmed that both genes encoded products that were melanocyte lineage proteins. Mice immunized with murine MART1 or gp 100 using recombinant vaccinia virus failed to produce any detectable T-cell responses or protective immunity against B16 melanoma. In contrast, immunization of mice with human gp 100 using recombinant adenoviruses elicited T cells specific for hgp100, but these T cells also cross reacted with B16 tumor in vitro and induced significant but weak protection against B16 challenge. Immunization with human and mouse gp100 together [adenovirus type 2 (Ad2)-hep100 plus recombinant vaccinia virus (rVV)-mgp100], or immunization with human gp100 (Ad2-hgp100) and boosting with heterologous vector (rVV-hgp100 or rVV-mgp100) or homologous vector (Ad2-hgp100), did not significantly enhance the protective response against B16 melanoma. These results may suggest that immunization with heterologous tumor antigen, rather than self, may be more effective as an immunotherapeutic reagent in designing antigen-specific cancer vaccines. PMID:9101410

  14. Genome profiling (GP method based classification of insects: congruence with that of classical phenotype-based one.

    Directory of Open Access Journals (Sweden)

    Shamim Ahmed

    Full Text Available Ribosomal RNAs have been widely used for identification and classification of species, and have produced data giving new insights into phylogenetic relationships. Recently, multilocus genotyping and even whole genome sequencing-based technologies have been adopted in ambitious comparative biology studies. However, such technologies are still far from routine-use in species classification studies due to their high costs in terms of labor, equipment and consumables.Here, we describe a simple and powerful approach for species classification called genome profiling (GP. The GP method composed of random PCR, temperature gradient gel electrophoresis (TGGE and computer-aided gel image processing is highly informative and less laborious. For demonstration, we classified 26 species of insects using GP and 18S rDNA-sequencing approaches. The GP method was found to give a better correspondence to the classical phenotype-based approach than did 18S rDNA sequencing employing a congruence value. To our surprise, use of a single probe in GP was sufficient to identify the relationships between the insect species, making this approach more straightforward.The data gathered here, together with those of previous studies show that GP is a simple and powerful method that can be applied for actually universally identifying and classifying species. The current success supported our previous proposal that GP-based web database can be constructible and effective for the global identification/classification of species.

  15. Correlation between the GP78 Gene Polymorphism and Coronary Atherosclerotic Heart Disease

    Directory of Open Access Journals (Sweden)

    Long Wang

    2018-01-01

    Full Text Available Objective: To study the correlation between the GP78 gene polymorphism and blood fat, blood glucose, blood pressure and coronary atherosclerotic heart disease. Methods: A total of 72 patients with coronary atherosclerotic heart disease were selected as the observation group, and 68 healthy participants were selected as the control group. The gp78 gene polymorphism of both groups was studied via polymerase chain reaction-restriction fragment length polymorphism (RFLP. At the same time, the multiple expression quantities of the GP78 gene in the tissues of both groups were tested via fluorogenic quantitative PCR, enzyme-linked immunosorbent assay (ELISA and Western-blotting assay. Furthermore, the blood fat, blood glucose and blood pressure of subjects in both groups were tested. Results: The percentages of the gp78 gene polymorphisms of Arg/Arg, Arg/Gly and Gly/Gly at the 145 locus of the study subjects in the observation group were 12.3%, 43.2% and 44.5%, respectively, while those in the control group were 74.3%, 11.2% and 14.5%, respectively, and there were significant differences between both groups. Based on the test results of the blood fat, blood glucose and blood pressure of the objects in the observation group and control group, significant differences were found between the two groups (P<0.05. Conclusion: There was a significant correlation between the 145 locus of the gp89 gene and coronary atherosclerotic heart disease, indexes of blood fat, blood glucose and blood pressure. Keywords: blood fat, blood glucose, blood pressure, coronary sclerosis, heart disease

  16. A 4-week, lifestyle-integrated, home-based exercise training programme elicits improvements in physical function and lean mass in older men and women: a pilot study [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Jessica Cegielski

    2017-09-01

    Full Text Available Background: Developing alternative exercise programmes that can alleviate certain barriers to exercise such as psychological, environmental or socio-economical barriers, but provide similar physiological benefits e.g. increases in muscle mass and strength, is of grave importance. This pilot study aimed to assess the efficacy of an unsupervised, 4-week, whole-body home-based exercise training (HBET programme, incorporated into daily living activities, on skeletal muscle mass, power and strength. Methods: Twelve healthy older volunteers (63±3 years, 7 men: 5 women, BMI: 29±1 kg/m² carried out the 4-week “lifestyle-integrated” HBET of 8 exercises, 3x12 repetitions each, every day. Before and after HBET, a number of physical function tests were carried out: unilateral leg extension 1-RM (one- repetition maximum, MVC (maximal voluntary contraction leg extension, lower leg muscle power (via Nottingham Power Rig, handgrip strength and SPPBT (short physical performance battery test. A D3-Creatine method was used for assessment of whole-body skeletal muscle mass, and ultrasound was used to measure the quadriceps cross-sectional area (CSA and vastus lateralis muscle thickness. Results: Four weeks HBET elicited significant (p<0.05 improvements in leg muscle power (276.7±38.5 vs. 323.4±43.4 W, maximal voluntary contraction (60°: 154.2±18.4 vs. 168.8±15.2 Nm, 90°: 152.1±10.5 vs. 159.1±11.4 Nm and quadriceps CSA (57.5±5.4 vs. 59.0±5.3 cm2, with a trend for an increase in leg strength (1-RM: 45.7±5.9 vs. 49.6±6.0 kg, P=0.08. This was despite there being no significant differences in whole-body skeletal muscle mass, as assessed via D3-Creatine. Conclusions: This study demonstrates that increases in multiple aspects of muscle function can be achieved in older adults with just 4-weeks of “lifestyle-integrated” HBET, with a cost-effective means. This training mode may prove to be a beneficial alternative for maintaining and/or improving

  17. Debriefing Note Secondary Education Support Programme

    DEFF Research Database (Denmark)

    Webster, Neil; Vagnby, Bo Hellisen; Thomsen, Thomas J.

    Debriefing note regarding joint programming for the Secondary Education Support Programme (2003- 2007). The note specifies preparation of SIP Physical Guidelines; Training needs assessment for Physical School Status and Rapid Technical Assessments; SIP/DEP preparation; Selection criteria...

  18. [IgG4-related lung disease: analysis of 8 cases and literature review].

    Science.gov (United States)

    Han, G J; Hu, H; Mao, D; Bai, X; She, D Y; Zhao, S F; Wen, Z L; Gao, J

    2017-03-12

    Objective: To improve the understanding and treatment of IgG4-related lung disease (IgG4-RLD). Methods: The clinical characteristics, serum IgG4 levels, pathological features, chest CT, therapy and prognosis of 8 patients with IgG4-RLD were retrospectively analyzed. These patients were admitted to the People's Liberation Army General Hospital and the pathological diagnosis was made between December 2005 and March 2016. Relevant literatures were reviewed. Results: The 8 patients with IgG4-RLD included 4 men and 4 women, with an average age of (59±4) years (range, 37-74). The respiratory symptoms included shortness of breath, cough, and expectoration. Extra-pulmonary symptoms included abdominal pain, facial edema, and fever. Extrapulmonary organs were involved in 7 cases. Serum IgG4 levels were elevated in 8 cases, with an average concentration of(17±6)g/L. Chest CT showed solid lung nodules in 6, alveolar-interstitial infiltration in 5, bronchovascular lesions in 3 and ground glass shadows in 2 cases. PET/CT was performed in 2 cases and it showed multiple organ involvement with higher radioactivity uptake(SUVmax2.9-4.2). The pathological examination found lymphocyte and plasma cell infiltration in 7, fibrous tissue hyperplasia in 5, and occlusive vasculitis in 2 cases. On immunohistochemical staining, the ratio of IgG4-positive plasma cells to IgG-positive plasma cells was higher than 40%in 3 cases. The number of IgG4-positive plasma cells was 10-50/HP in 8 cases. The misdiagnosis rate was 100% before the final diagnosis was made. Three cases received glucocorticoids with immunosuppressant therapy, 2 received surgery combined with glucocorticoid therapy, 2 received glucocorticoid therapy alone, and 1 only received surgery. The follow-up time was 4-132 months, with remission in 7 cases, and disease progression in 1 case, but no death. A total of 195 cases of IgG4-RLD were reviewed from the literature, among whom 111 cases were admitted with respiratory symptoms

  19. The learner’s perspective in GP teaching practices with multi-level learners: a qualitative study

    Science.gov (United States)

    2014-01-01

    Background Medical students, junior hospital doctors on rotation and general practice (GP) registrars are undertaking their training in clinical general practices in increasing numbers in Australia. Some practices have four levels of learner. This study aimed to explore how multi-level teaching (also called vertical integration of GP education and training) is occurring in clinical general practice and the impact of such teaching on the learner. Methods A qualitative research methodology was used with face-to-face, semi-structured interviews of medical students, junior hospital doctors, GP registrars and GP teachers in eight training practices in the region that taught all levels of learners. Interviews were audio-recorded and transcribed. Qualitative analysis was conducted using thematic analysis techniques aided by the use of the software package N-Vivo 9. Primary themes were identified and categorised by the co-investigators. Results 52 interviews were completed and analysed. Themes were identified relating to both the practice learning environment and teaching methods used. A practice environment where there is a strong teaching culture, enjoyment of learning, and flexible learning methods, as well as learning spaces and organised teaching arrangements, all contribute to positive learning from a learners’ perspective. Learners identified a number of innovative teaching methods and viewed them as positive. These included multi-level learner group tutorials in the practice, being taught by a team of teachers, including GP registrars and other health professionals, and access to a supernumerary GP supervisor (also termed “GP consultant teacher”). Other teaching methods that were viewed positively were parallel consulting, informal learning and rural hospital context integrated learning. Conclusions Vertical integration of GP education and training generally impacted positively on all levels of learner. This research has provided further evidence about the

  20. The effect of smoking on the urinary excretion of 8-oxodG and 8-oxoGuo in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Sørensen, Anne-Sofie; Kjær, Laura Kofoed; Petersen, Kasper Meidahl

    2017-01-01

    as urinary 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8-oxodG) excretion in smokers compared with non-smokers in a healthy population. We aimed to investigate if an increased urinary excretion of 8-oxodG in smokers versus never smokers and former smokers could be verified in a population with type 2 diabetes......Over the past decades, attention has been paid to understanding the impact of oxidative stress and related modifications of DNA and RNA on various human health risks. A recent meta-analysis comprising 1915 smokers and 3462 non-smokers found a significantly higher level of DNA oxidation measured...... to examine the relationship between daily smokers (n = 462) versus former (n = 1341) and never smokers (n = 918) regarding the RNA and DNA oxidation, respectively. We did not find any significant effect of smoking on urinary excretion of 8-oxodG or 8-oxoGuo in our study. Due to a sparse study area...

  1. Lessons learned from an Internet GP information system.

    Science.gov (United States)

    Briggs, J S; Bradley, M P

    1998-01-01

    We describe the prototype of an application that in actual use would allow GPs to find out more information about consultants at hospitals. This would aid the GP in making the decision about which consultant a patient should be referred to. The requirements of the application from the GP's perspective are described, together with some of the issues that have to be resolved before hospitals can provide the necessary information in a standard format. The application is implemented as a client--server system using standard Internet technologies such as Java and HTML. This architecture has a number of advantages but also revealed some issues concerning security and the format of data, among other things. The project showed that there is a desire for such a system and that that desire can be fulfilled at a relatively low cost.

  2. Gaharu Leaf Extract Water Reduce MDA and 8-OHdG Levels and Increase Activities SOD and Catalase in Wistar Rats Provided Maximum Physical Activity

    Directory of Open Access Journals (Sweden)

    I Made Oka Adi Parwata

    2016-09-01

    Full Text Available Background: Oxidative stress occurs due to an imbalance of the number of free radicals by the number of endogenous antioxidant produced by the body i.e. Superoxide Dismutase (SOD, Gluthathione Peroxidase (GPx, and Catalase. The imbalance between the number of free radicals and antioxidants can be overcome with the endogenous antioxidant intake that exogenous oxidative stress can be reduced. One of exogenous antioxidants is natural Gaharu leaf water extract. Objective: This research focus on the effect of Gaharu leaf water extract in reducing MDA and 8-OHdG and increase the activity of SOD and Catalase. Methods: This study was an experimental with post only controls group design. Experiment was divided  into 5 groups of wistar rats, each consisting of 5 animals, i.e. negative control group without extract [K (-], treatment 1 treated 50 mg/kg BW/day of the extract (T1, treatment 2 treated 100 mg/kg BW/day of the extract (T2, treatment 3 treated 200 mg/ kg BW/day of the extract (T3, and positive control group [K (+] treated with vitamin Cat a dose 50 mg/kg BW/day. All groups treated for 10 weeks. Every day, before treatment, each group was given a maximum swimming activity for 1.5 hours for 10 weeks. ELISA was used to measure MDA, 8-OHdG, SOD, and Catalase activities. Result: The research results showed that treatment of extract of  leaves of Gaharu with an higher dose from 50 mg/kg BW up to 200 mg/ kg BW significantly decline (p <0.05 levels of MDA with the average ranging from 6.37±0.23, 5,56±0.27 and 4.32±0.27, 8-OHdG with a mean of 1.64±0.11, 1.26±0.46, and 1.09±0.17. On the other hand the treatment also increase SOD activity with less ranging from 12.15±1.04, 15.70±2.02, and 18.84±1.51, and Catalase ranging from 6,68±0.63, 8.20±1.14 and 9.29±0,79 in the blood of Wistar rats were given a maximum activity compared to the negative control group. This is probably higher phenol compounds (bioflavonoids quantity content of the extract

  3. Oncostatin M induces heat hypersensitivity by gp130-dependent sensitization of TRPV1 in sensory neurons

    Directory of Open Access Journals (Sweden)

    Langeslag Michiel

    2011-12-01

    Full Text Available Abstract Oncostatin M (OSM is a member of the interleukin-6 cytokine family and regulates eg. gene activation, cell survival, proliferation and differentiation. OSM binds to a receptor complex consisting of the ubiquitously expressed signal transducer gp130 and the ligand binding OSM receptor subunit, which is expressed on a specific subset of primary afferent neurons. In the present study, the effect of OSM on heat nociception was investigated in nociceptor-specific gp130 knock-out (SNS-gp130-/- and gp130 floxed (gp130fl/fl mice. Subcutaneous injection of pathophysiologically relevant concentrations of OSM into the hind-paw of C57BL6J wild type mice significantly reduced paw withdrawal latencies to heat stimulation. In contrast to gp130fl/fl mice, OSM did not induce heat hypersensitivity in vivo in SNS-gp130-/- mice. OSM applied at the receptive fields of sensory neurons in in vitro skin-nerve preparations showed that OSM significantly increased the discharge rate during a standard ramp-shaped heat stimulus. The capsaicin- and heat-sensitive ion channel TRPV1, expressed on a subpopulation of nociceptive neurons, has been shown to play an important role in inflammation-induced heat hypersensitivity. Stimulation of cultured dorsal root ganglion neurons with OSM resulted in potentiation of capsaicin induced ionic currents. In line with these recordings, mice with a null mutation of the TRPV1 gene did not show any signs of OSM-induced heat hypersensitivity in vivo. The present data suggest that OSM induces thermal hypersensitivity by directly sensitizing nociceptors via OSMR-gp130 receptor mediated potentiation of TRPV1.

  4. Graduate nuclear engineering programmes motivate educational and research activities

    International Nuclear Information System (INIS)

    Mavko, B.

    2000-01-01

    Some fifteen years ago the University of Ljubljana, Faculty for Mathematics and Physics together with the national research organisation the J. Stefan jointly established a Graduate programme of Nuclear Engineering. From the onset, the programme focused on nuclear technology, nuclear safety, and reactor physics and environment protection. Over the years this graduate programme has became the focal point of nuclear related, research and educational activities in Slovenia. It has grown into a meeting ground for recognised national and distinguished foreign educators and experienced professionals from the industry. In conjunction with an important national project, supported by the Slovenian government, entitled 'Jung Researcher' it also enhances the knowledge transfer to the next generation. Since the programme was introduced, the interest for this programme has been steadily growing. Accordingly, a number of PhD and MS degrees in NE have been awarded. The graduates of this programme have encountered very good job opportunities in nuclear as well as in non-nuclear sector. (author)

  5. Admission and poor performance of trainees in the postgraduate GP training in the Netherlands

    NARCIS (Netherlands)

    Vermeulen, M.I.

    2014-01-01

    Until 2014 the selection for the Dutch postgraduate GP training was conducted locally, on the eight GP departments. The procedure consisted of a letter of application and a semi-structured interview. We investigated to what extend department of choice, candidates’ characteristics and qualities

  6. [Analysis of fourteen French national programmes on physical activity and sports as determinants of health from 2001 to 2006].

    Science.gov (United States)

    Bréchat, Pierre-Henri; Vogel, Thomas; Berthel, Marc; Kaltenbach, Georges; Le Divenah, Aude; Segouin, Christophe; Rymer, Roland; Lonsdorfer, Jean

    2009-01-01

    Physical activity and sports are considered as one of the determinants of health. The aim of this study is to review the rationale for the formulation of this public health issue and its integration in national action plans. The study shows that fourteen national programmes were drafted and implemented between 2001 and 2006 by seven institutions. The research methodology was based on crossing data obtained from semi-directed interviews and documents regarding the design, implementation and follow-up of these programmes. For the conditions of the success, the fourteen actions scored an average of 175.0 +/- 66.9 out of 300%. Public health actors and professionals must be given more opportunities to involve themselves and engage in developing stronger relationships and linkages, in particular with the institutional and community settings. In general, the most invested parts of a programme are the structural and operational aspects of activities. Six significant points surfaced from the study: consideration of drug use as an addictive behaviour; recognition of the psychological stress of professional athletes; acknowledgment of youth as being at high risk for doping behaviour; integration of the concept that physical activity and sports must take the benefit/risk perspective into account; and the necessity to promote health. Through the exchange of numerous local and regional experiences, an optimisation of their synergistic connections was made possible on a continuum extending from "health promotion through physical activity and sports" to "prevention of drug-use and doping behaviours". Professionals have been able to develop actions in the above-mentioned domains across this continuum that have, to date, remained isolated. Proposals are made to strengthen these dynamics. Other health determinants and public health priorities could be investigated with the same methodology.

  7. Computational Fluid Dynamics (CFD) Technology Programme 1995- 1999

    Energy Technology Data Exchange (ETDEWEB)

    Haekkinen, R.J.; Hirsch, C.; Krause, E.; Kytoemaa, H.K. [eds.

    1997-12-31

    The report is a mid-term evaluation of the Computational Fluid Dynamics (CFD) Technology Programme started by Technology Development Centre Finland (TEKES) in 1995 as a five-year initiative to be concluded in 1999. The main goal of the programme is to increase the know-how and application of CFD in Finnish industry, to coordinate and thus provide a better basis for co-operation between national CFD activities and encouraging research laboratories and industry to establish co-operation with the international CFD community. The projects of the programme focus on the following areas: (1) studies of modeling the physics and dynamics of the behaviour of fluid material, (2) expressing the physical models in a numerical mode and developing a computer codes, (3) evaluating and testing current physical models and developing new ones, (4) developing new numerical algorithms, solvers, and pre- and post-processing software, and (5) applying the new computational tools to problems relevant to their ultimate industrial use. The report consists of two sections. The first considers issues concerning the whole programme and the second reviews each project

  8. Cigotica programme: pediatric experiences

    Directory of Open Access Journals (Sweden)

    Lešović Snežana

    2011-01-01

    BMI (p< 0.05 was reduced by -2.12 ± 0.31 in all examinees, in boys by -2.33 ± 48 and in girls by -2.04 ± 0.41 kg/m2. The BMI z-score was considerably lower in all examinees upon release and it was (p<0.05-0.26 ±0.08, in girls 0.28 ±0.06 and in boys 0.31 ± 0.08. % of fat was considerably lower (p< 0.05 in all examinees -1.65 ± 0.23, in girls 1.72 ± 0.32 and in boys 1.50% ± 0.20. The waist circumference was reduced by -7.85 ±3.01 in all examinees, in girls -8.20 ± 4.3 and in boys -7.25 ± 2.6. Hypertension was observed in 28% of adolescents. Two factors of metabolic syndrome were present in 27.6%, and metabolic syndrome was present in 18.3% of the examinees. The disorder in sugar transport was observed in 8.9% of the examinees. Conclusion The effects of the 'Cigotica' Programme are very encouraging and they show that the multidisciplinary approach directed towards the reduction in energetic intake, education, change of lifestyle and habits related to nutrition and physical activity, leads to a considerable reduction in body mass, improvement in blood pressure, laboratory analyses, aerobic capacities and self-confidence in obese adolescents. There are obe­sity complications in a large number of adolescents, which indicates that the obesity problem has not been duly detected by parents or medical workers and that more efficient prevention programmes are needed. A great interest of children, parents, doctors and their participation in the 'Cigotica' Programme are going to contribute to raising awareness of obesity risks and the importance of health prevention in ado­lescents in our region.

  9. Targeted Delivery of GP5 Antigen of PRRSV to M Cells Enhances the Antigen-Specific Systemic and Mucosal Immune Responses

    Directory of Open Access Journals (Sweden)

    Luping Du

    2018-01-01

    Full Text Available Efficient delivery of antigens through oral immunization is a first and critical step for successful induction of mucosal immunity, which can provide protection against pathogens invading the mucosa. Membranous/microfold cells (M cells within the mucosa can transcytose internalized antigen without degradation and thus play an important role in initiating antigen-specific mucosal immune responses through inducing secretory IgA production. In this research, we modified poly (D, L-lactide-co-glycolide (PLGA nanoparticles (NPs with Ulex europaeus agglutinin 1 (UEA-1 and successfully prepared an oral vaccine delivery system, UEA-1/PLGA NPs. PLGA NPs were prepared using a standard double emulsion solvent evaporation technique, which can protect the entrapped PRRSV DNA vaccine [pcDNA3.1-SynORF5 (synthetic ORF5] or subunit vaccine ORF5-encoded glycoprotein (GP5 from exposure to the gastrointestinal (GI tract and release the plasmids in a controlled manner. With UEA-1 modification, the UEA-1/PLGA NPs can be effectively transported by M-cells. We investigated immune response induced by UEA-1/PLGA-SynORF5 or UEA-1/PLGA-GP5 following inoculation in mice and piglets. Compared with PLGA-SynORF5 or PLGA-GP5 NPs, UEA-1/PLGA-SynORF5, or UEA-1/PLGA-GP5 NPs stimulated significantly increased serum IgG levels and augmented intestinal IgA levels in mice and piglets (P < 0.05. Our findings indicate UEA-1/PLGA NPs can be applied as a promising and universally robust oral vaccine delivery system.

  10. Targeted Delivery of GP5 Antigen of PRRSV to M Cells Enhances the Antigen-Specific Systemic and Mucosal Immune Responses

    Science.gov (United States)

    Du, Luping; Yu, Zhengyu; Pang, Fengjiao; Xu, Xiangwei; Mao, Aihua; Yuan, Wanzhe; He, Kongwang; Li, Bin

    2018-01-01

    Efficient delivery of antigens through oral immunization is a first and critical step for successful induction of mucosal immunity, which can provide protection against pathogens invading the mucosa. Membranous/microfold cells (M cells) within the mucosa can transcytose internalized antigen without degradation and thus play an important role in initiating antigen-specific mucosal immune responses through inducing secretory IgA production. In this research, we modified poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) with Ulex europaeus agglutinin 1 (UEA-1) and successfully prepared an oral vaccine delivery system, UEA-1/PLGA NPs. PLGA NPs were prepared using a standard double emulsion solvent evaporation technique, which can protect the entrapped PRRSV DNA vaccine [pcDNA3.1-SynORF5 (synthetic ORF5)] or subunit vaccine ORF5-encoded glycoprotein (GP5) from exposure to the gastrointestinal (GI) tract and release the plasmids in a controlled manner. With UEA-1 modification, the UEA-1/PLGA NPs can be effectively transported by M-cells. We investigated immune response induced by UEA-1/PLGA-SynORF5 or UEA-1/PLGA-GP5 following inoculation in mice and piglets. Compared with PLGA-SynORF5 or PLGA-GP5 NPs, UEA-1/PLGA-SynORF5, or UEA-1/PLGA-GP5 NPs stimulated significantly increased serum IgG levels and augmented intestinal IgA levels in mice and piglets (P < 0.05). Our findings indicate UEA-1/PLGA NPs can be applied as a promising and universally robust oral vaccine delivery system. PMID:29423381

  11. Fatal Indifference: The G8, Africa, and Global Health | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Book cover Fatal Indifference: The G8, Africa, and Global Health ... It is also the most powerful political force behind the multilateral institutions that are shaping global economic practice ... IDRC joins more than 800 international delegates at the Resilient Cities ... Asian outlook: New growth dependent on new productivity.

  12. Modernizing the G8 Summit Process | CRDI - Centre de recherches ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Modernizing the G8 Summit Process. This project is based on the premise that emerging countries must be full participants in key agenda-setting bodies if international governance mechanisms are to be realistic and relevant. The project brings together leaders, senior advisors, experts, researchers and opinion leaders to ...

  13. 'I need her to be a doctor': patients' experiences of presenting health information from the internet in GP consultations.

    Science.gov (United States)

    Bowes, Parvathy; Stevenson, Fiona; Ahluwalia, Sanjiv; Murray, Elizabeth

    2012-11-01

    Patients are increasingly using the internet for health-related information and may bring this to a GP consultation. There is scant information about why patients do this and what they expect from their GP. The aim was to explore patients' motivation in presenting information, their perception of the GP's response and what they wanted from their doctor. Qualitative study based in North London involving patients with experience of bringing health information from the internet to their GP. Semi-structured face-to-face and telephone interviews using a critical incident technique, recorded, transcribed verbatim, and subjected to thematic analysis by a multidisciplinary team of researchers. Twenty-six interviews were completed. Participants reported using the internet to become better informed about their health and hence make best use of the limited time available with the GP and to enable the GP to take their problem more seriously. Patients expected their GP to acknowledge the information; discuss, explain, or contextualise it; and offer a professional opinion. Patients tended to prioritise the GP opinion over the internet information. However, if the GP appeared disinterested, dismissive or patronising patients reported damage to the doctor-patient relationship, occasionally to the extent of seeking a second opinion or changing their doctor. This is the first in-depth qualitative study to explore why patients present internet information to their GP within the consultation and what they want when they do this. This information should help GPs respond appropriately in such circumstances.

  14. GPs' experiences with out-of-hours GP cooperatives: a survey study from the Netherlands.

    Science.gov (United States)

    Smits, Marleen; Keizer, Ellen; Huibers, Linda; Giesen, Paul

    2014-09-01

    Out-of-hours primary care has been provided by general practitioner (GP) cooperatives since the year 2000 in the Netherlands. Early studies in countries with similar organizational structures showed positive GP experiences. However, nowadays it is said that GPs experience a high workload at the cooperative and that they outsource a considerable part of their shifts. To examine positive and negative experiences of GPs providing out-of-hours primary care, and the frequency and reasons for outsourcing shifts. A cross-sectional observational survey among 688 GPs connected to six GP cooperatives in the Netherlands, using a web-based questionnaire. The response was 55% (n = 378). The main reasons for working in GP cooperatives were to retain registration as GP (79%) and remain experienced in acute care (74%). GPs considered the peak hours (81%) and the high number of patients (73%) as the most negative aspects. Most GPs chose to provide the out-of-hours shifts themselves: 85% outsourced maximally 25% of their shifts. The percentage of outsourced shifts increased with age. Main reasons for outsourcing were the desire to have more private time (76%); the high workload in daytime practice (71%); and less the workload during out-of-hours (46%). GPs are motivated to work in out-of-hours GP cooperatives, and they outsource few shifts. GPs consider the peak load and the large number of (non-urgent) help requests as the most negative aspects. To motivate and involve GPs for 7 × 24-h primary care, it is important to set limits on their workload.

  15. Mutations in gp41 are correlated with coreceptor tropism but do not improve prediction methods substantially.

    Science.gov (United States)

    Thielen, Alexander; Lengauer, Thomas; Swenson, Luke C; Dong, Winnie W Y; McGovern, Rachel A; Lewis, Marilyn; James, Ian; Heera, Jayvant; Valdez, Hernan; Harrigan, P Richard

    2011-01-01

    The main determinants of HIV-1 coreceptor usage are located in the V3-loop of gp120, although mutations in V2 and gp41 are also known. Incorporation of V2 is known to improve prediction algorithms; however, this has not been confirmed for gp41 mutations. Samples with V3 and gp41 genotypes and Trofile assay (Monogram Biosciences, South San Francisco, CA, USA) results were taken from the HOMER cohort (n=444) and from patients screened for the MOTIVATE studies (n=1,916; 859 with maraviroc outcome data). Correlations of mutations with tropism were assessed using Fisher's exact test and prediction models trained using support vector machines. Models were validated by cross-validation, by testing models from one dataset on the other, and by analysing virological outcome. Several mutations within gp41 were highly significant for CXCR4 usage; most strikingly an insertion occurring in 7.7% of HOMER-R5 and 46.3% of HOMER-X4 samples (MOTIVATE 5.7% and 25.2%, respectively). Models trained on gp41 sequence alone achieved relatively high areas under the receiver-operating characteristic curve (AUCs; HOMER 0.713 and MOTIVATE 0.736) that were almost as good as V3 models (0.773 and 0.884, respectively). However, combining the two regions improved predictions only marginally (0.813 and 0.902, respectively). Similar results were found when models were trained on HOMER and validated on MOTIVATE or vice versa. The difference in median log viral load decrease at week 24 between patients with R5 and X4 virus was 1.65 (HOMER 2.45 and MOTIVATE 0.79) for V3 models, 1.59 for gp41-models (2.42 and 0.83, respectively) and 1.58 for the combined predictor (2.44 and 0.86, respectively). Several mutations within gp41 showed strong correlation with tropism in two independent datasets. However, incorporating gp41 mutations into prediction models is not mandatory because they do not improve substantially on models trained on V3 sequences alone.

  16. M Theory, G2-manifolds and four dimensional physics

    International Nuclear Information System (INIS)

    Acharya, B.S.

    2003-01-01

    M theory on a manifold of G 2 -holonomy is a natural framework for obtaining vacua with four large spacetime dimensions and N = 1 supersymmetry. In order to obtain, within this framework, the standard features of particle physics, namely non-Abelian gauge groups and chiral fermions, we consider G 2 -manifolds with certain kinds of singularities at which these features reside. The aim of these lectures is to describe in detail how the above picture emerges. Along the way we will see how interesting aspects of strongly coupled gauge theories, such as confinement, receive relatively simple explanations within the context of M theory. (author)

  17. Host-Primed Ebola Virus GP Exposes a Hydrophobic NPC1 Receptor-Binding Pocket, Revealing a Target for Broadly Neutralizing Antibodies.

    Science.gov (United States)

    Bornholdt, Zachary A; Ndungo, Esther; Fusco, Marnie L; Bale, Shridhar; Flyak, Andrew I; Crowe, James E; Chandran, Kartik; Saphire, Erica Ollmann

    2016-02-23

    The filovirus surface glycoprotein (GP) mediates viral entry into host cells. Following viral internalization into endosomes, GP is cleaved by host cysteine proteases to expose a receptor-binding site (RBS) that is otherwise hidden from immune surveillance. Here, we present the crystal structure of proteolytically cleaved Ebola virus GP to a resolution of 3.3 Å. We use this structure in conjunction with functional analysis of a large panel of pseudotyped viruses bearing mutant GP proteins to map the Ebola virus GP endosomal RBS at molecular resolution. Our studies indicate that binding of GP to its endosomal receptor Niemann-Pick C1 occurs in two distinct stages: the initial electrostatic interactions are followed by specific interactions with a hydrophobic trough that is exposed on the endosomally cleaved GP1 subunit. Finally, we demonstrate that monoclonal antibodies targeting the filovirus RBS neutralize all known filovirus GPs, making this conserved pocket a promising target for the development of panfilovirus therapeutics. Ebola virus uses its glycoprotein (GP) to enter new host cells. During entry, GP must be cleaved by human enzymes in order for receptor binding to occur. Here, we provide the crystal structure of the cleaved form of Ebola virus GP. We demonstrate that cleavage exposes a site at the top of GP and that this site binds the critical domain C of the receptor, termed Niemann-Pick C1 (NPC1). We perform mutagenesis to find parts of the site essential for binding NPC1 and map distinct roles for an upper, charged crest and lower, hydrophobic trough in cleaved GP. We find that this 3-dimensional site is conserved across the filovirus family and that antibody directed against this site is able to bind cleaved GP from every filovirus tested and neutralize viruses bearing those GPs. Copyright © 2016 Bornholdt et al.

  18. N-acetylcysteine prevents HIV gp 120-related damage of human cultured astrocytes: correlation with glutamine synthase dysfunction

    Directory of Open Access Journals (Sweden)

    Costa Nicola

    2007-12-01

    Full Text Available Abstract Background HIV envelope gp 120 glycoprotein is released during active HIV infection of brain macrophages thereby generating inflammation and oxidative stress which contribute to the development of the AIDS-Dementia Complex (ADC. Gp120 has also been found capable to generate excitotoxic effect on brain tissue via enhancement of glutamatergic neurotransmission, leading to neuronal and astroglial damage, though the mechanism is still to be better understood. Here we investigated on the effect of N-acetylcysteine (NAC, on gp120-induced damage in human cultured astroglial cells and the possible contribution of gp120-related reacting oxygen species (ROS in the imbalanced activity of glutamine synthase (GS, the enzyme that metabolizes glutamate into glutamine within astroglial cells playing a neuroprotective role in brain disorders. Results Incubation of Lipari human cultured astroglial cells with gp 120 (0.1–10 nM produced a significant reduction of astroglial cell viability and apoptosis as evaluated by TUNEL reaction and flow cytometric analysis (FACS. This effect was accompanied by lipid peroxidation as detected by means of malondialdehyde assay (MDA. In addition, gp 120 reduced both glutamine concentration in astroglial cell supernatants and GS expression as detected by immunocytochemistry and western blotting analysis. Pre-treatment of cells with NAC (0.5–5 mM, dose-dependently antagonised astroglial apoptotic cell death induced by gp 120, an effect accompanied by significant attenuation of MDA accumulation. Furthermore, both effects were closely associated with a significant recovery of glutamine levels in cell supernatants and by GS expression, thus suggesting that overproduction of free radicals might contribute in gp 120-related dysfunction of GS in astroglial cells. Conclusion In conclusion, the present experiments demonstrate that gp 120 is toxic to astroglial cells, an effect accompanied by lipid peroxidation and by altered

  19. Effects of an exercise programme with people living with HIV ...

    African Journals Online (AJOL)

    Effects of an exercise programme with people living with HIV: research in a disadvantaged setting. Clemens Ley, Lloyd Leach, María Rato Barrio, Susan Bassett. Abstract. This study aimed to analyse the physical health effects of a community based 10-week physical activity programme with people living with HIV.

  20. Nuclear pore complex assembly and maintenance in POM121- and gp210-deficient cells

    DEFF Research Database (Denmark)

    Stavru, Fabrizia; Nautrup-Pedersen, Gitte; Cordes, Volker C

    2006-01-01

    So far, POM121 and gp210 are the only known anchoring sites of vertebrate nuclear pore complexes (NPCs) within the lipid bilayer of the nuclear envelope (NE) and, thus, are excellent candidates for initiating the NPC assembly process. Indeed, we demonstrate that POM121 can recruit several...... as depletion of POM121 from human fibroblasts, which do not express gp210, further suggest that NPCs can assemble or at least persist in a POM121- and gp210-free form. This points to extensive redundancies in protein-protein interactions within NPCs and suggests that vertebrate NPCs contain additional membrane...