Sample records for marburg germany 26-29

  1. Forty-five years of Marburg virus research.

    PubMed

    Brauburger, Kristina; Hume, Adam J; Mühlberger, Elke; Olejnik, Judith

    2012-10-01

    In 1967, the first reported filovirus hemorrhagic fever outbreak took place in Germany and the former Yugoslavia. The causative agent that was identified during this outbreak, Marburg virus, is one of the most deadly human pathogens. This article provides a comprehensive overview of our current knowledge about Marburg virus disease ranging from ecology to pathogenesis and molecular biology.

  2. Forty-Five Years of Marburg Virus Research

    PubMed Central

    Brauburger, Kristina; Hume, Adam J.; Mühlberger, Elke; Olejnik, Judith

    2012-01-01

    In 1967, the first reported filovirus hemorrhagic fever outbreak took place in Germany and the former Yugoslavia. The causative agent that was identified during this outbreak, Marburg virus, is one of the most deadly human pathogens. This article provides a comprehensive overview of our current knowledge about Marburg virus disease ranging from ecology to pathogenesis and molecular biology. PMID:23202446

  3. Calculation of incubation period and serial interval from multiple outbreaks of Marburg virus disease.

    PubMed

    Pavlin, Boris I

    2014-12-13

    Marburg viruses have been responsible for a number of outbreaks throughout sub-Saharan Africa, as well as a number of laboratory infections. Despite many years of experience with the viruses, little is known about several important epidemiologic parameters relating to the development of Marburg virus disease. The analysis uses pooled data from all Marburg cases between 1967 and 2008 to develop estimates for the incubation period and the clinical onset serial interval (COSI). Data were obtained from original outbreak investigation forms (n=406) and from published data (n=45). Incubation periods were calculated for person-to-person exposure, for laboratory-acquired infections, and for presumed zoonotic exposures. Similar analysis was conducted for COSI, using only cases with unambiguous person-to-person transmission where both the primary and the secondary case patients had well-defined illness onsets. Seventy-six cases were retained for the incubation period analysis. Incubation periods ranged from a minimum of 2 days in the case of two laboratory workers to a maximum of at least 26 days for a person-to-person household transmission. Thirty-eight cases were retained for COSI analysis. The median COSI was 11 days, with an interquartile range of 8 to 15. This study extends the maximum known incubation period of Marburg virus disease to 26 days. The analysis was severely hampered by a lack of completeness in epidemiologic data. It is necessary to prioritize obtaining more accurate epidemiologic data in future outbreaks; greater use of COSI may facilitate an improved understanding of outbreak dynamics in Marburg and other diseases.

  4. 10 CFR 26.29 - Training.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Training. 26.29 Section 26.29 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Program Elements § 26.29 Training. (a) Training content. Licensees and other entities shall ensure that the individuals who are subject to this subpart have the following KAs...

  5. 10 CFR 26.29 - Training.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Training. 26.29 Section 26.29 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Program Elements § 26.29 Training. (a) Training content. Licensees and other entities shall ensure that the individuals who are subject to this subpart have the following KAs...

  6. 10 CFR 26.29 - Training.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Training. 26.29 Section 26.29 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Program Elements § 26.29 Training. (a) Training content. Licensees and other entities shall ensure that the individuals who are subject to this subpart have the following KAs...

  7. 10 CFR 26.29 - Training.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Training. 26.29 Section 26.29 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Program Elements § 26.29 Training. (a) Training content. Licensees and other entities shall ensure that the individuals who are subject to this subpart have the following KAs...

  8. 10 CFR 26.29 - Training.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Training. 26.29 Section 26.29 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Program Elements § 26.29 Training. (a) Training content. Licensees and other entities shall ensure that the individuals who are subject to this subpart have the following KAs...

  9. Lessons learned during active epidemiological surveillance of Ebola and Marburg viral hemorrhagic fever epidemics in Africa.

    PubMed

    Allaranga, Yokouide; Kone, Mamadou Lamine; Formenty, Pierre; Libama, Francois; Boumandouki, Paul; Woodfill, Celia J I; Sow, Idrissa; Duale, Sambe; Alemu, Wondimagegnehu; Yada, Adamou

    2010-03-01

    To review epidemiological surveillance approaches used during Ebola and Marburg hemorrhagic fever epidemics in Africa in the past fifteen years. Overall, 26 hemorrhagic epidemic outbreaks have been registered in 12 countries; 18 caused by the Ebola virus and eight by the Marburg virus. About 2551 cases have been reported, among which 268 were health workers (9,3%). Based on articles and epidemic management reports, this review analyses surveillance approaches, route of introduction of the virus into the population (urban and rural), the collaboration between the human health sector and the wildlife sector and factors that have affected epidemic management. Several factors affecting the epidemiological surveillance during Ebola and Marburg viruses hemorrhagic epidemics have been observed. During epidemics in rural settings, outbreak investigations have shown multiple introductions of the virus into the human population through wildlife. In contrast, during epidemics in urban settings a single introduction of the virus in the community was responsible for the epidemic. Active surveillance is key to containing outbreaks of Ebola and Marburg viruses Collaboration with those in charge of the conservation of wildlife is essential for the early detection of viral hemorrhagic fever epidemics. Hemorrhagic fever epidemics caused by Ebola and Marburg viruses are occurring more and more frequently in Sub-Saharan Africa and only an adapted epidemiological surveillance system will allow for early detection and effective response.

  10. Quinoxaline-based inhibitors of Ebola and Marburg VP40 egress.

    PubMed

    Loughran, H Marie; Han, Ziying; Wrobel, Jay E; Decker, Sarah E; Ruthel, Gordon; Freedman, Bruce D; Harty, Ronald N; Reitz, Allen B

    2016-08-01

    We prepared a series of quinoxalin-2-mercapto-acetyl-urea analogs and evaluated them for their ability to inhibit viral egress in our Marburg and Ebola VP40 VLP budding assays in HEK293T cells. We also evaluated selected compounds in our bimolecular complementation assay (BiMC) to detect and visualize a Marburg mVP40-Nedd4 interaction in live mammalian cells. Antiviral activity was assessed for selected compounds using a live recombinant vesicular stomatitis virus (VSV) (M40 virus) that expresses the EBOV VP40 PPxY L-domain. Finally selected compounds were evaluated in several ADME assays to have an early assessment of their drug properties. Our compounds had low nM potency in these assays (e.g., compounds 21, 24, 26, 39), and had good human liver microsome stability, as well as little or no inhibition of P450 3A4. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. [Marburg and Ebola hemorrhagic fevers--pathogens, epidemiology and therapy].

    PubMed

    Stock, Ingo

    2014-09-01

    Marburg and Ebola hemorrhagic fevers are severe, systemic viral diseases affecting humans and non-human primates. They are characterized by multiple symptoms such as hemorrhages, fever, headache, muscle and abdominal pain, chills, sore throat, nausea, vomiting and diarrhea. Elevated liver-associated enzyme levels and coagulopathy are also associated with these diseases. Marburg and Ebola hemorrhagic fevers are caused by (Lake victoria) Marburg virus and different species of Ebola viruses, respectively. They are enveloped, single-stranded RNA viruses and belong to the family of filoviridae. Case fatality rates of filovirus disease outbreaks are among the highest reported for any human pathogen, ranging from 25 to 90% or more. Outbreaks of Marburg and Ebola hemorrhagic fever occur in certain regions of equatorial Africa at irregular intervals. Since 2000, the number of outbreaks has increased. In 2014, the biggest outbreak of a filovirus-induced hemorrhagic fever that has been documented so far occurred from March to July 2014 in Guinea, Sierra Leone, Liberia and Nigeria. The outbreak was caused by a new variant of Zaire Ebola-Virus, affected more than 2600 people (stated 20 August) and was associated with case-fatality rates of up to 67% (Guinea). Treatment of Marburg and Ebola hemorrhagic fevers is symptomatic and supportive, licensed antiviral agents are currently not available. Recently, BCX4430, a promising synthetic adenosine analogue with high in vitro and in vivo activity against filoviruses and other RNA viruses, has been described. BCX4430 inhibits viral RNA polymerase activity and protects cynomolgus macaques from Marburg virus infection when administered as late as 48 hours after infection. Nucleic acid-based products, recombinant vaccines and antibodies appear to be less suitable for the treatment of Marburg and Ebola hemorrhagic fevers.

  12. Ebola and marburg hemorrhagic fever.

    PubMed

    Hartman, Amy L; Towner, Jonathan S; Nichol, Stuart T

    2010-03-01

    Ebola and Marburg viruses cause a severe viral hemorrhagic fever disease mainly in Sub-Saharan Africa. Although outbreaks are sporadic, there is the potential for filoviruses to spread to other continents unintentionally because of air travel or intentionally because of bioterrorism. This article discusses the natural history, epidemiology, and clinical presentation of patients infected with Ebola and Marburg viruses. Clinicians in the United States should be aware of the symptoms of these viral infections in humans and know the appropriate procedures for contacting local, state, and national reference laboratories in the event of a suspected case of filoviral hemorrhagic fever. 2010 Elsevier Inc. All rights reserved.

  13. A hamster model for Marburg virus infection accurately recapitulates Marburg hemorrhagic fever

    PubMed Central

    Marzi, Andrea; Banadyga, Logan; Haddock, Elaine; Thomas, Tina; Shen, Kui; Horne, Eva J.; Scott, Dana P.; Feldmann, Heinz; Ebihara, Hideki

    2016-01-01

    Marburg virus (MARV), a close relative of Ebola virus, is the causative agent of a severe human disease known as Marburg hemorrhagic fever (MHF). No licensed vaccine or therapeutic exists to treat MHF, and MARV is therefore classified as a Tier 1 select agent and a category A bioterrorism agent. In order to develop countermeasures against this severe disease, animal models that accurately recapitulate human disease are required. Here we describe the development of a novel, uniformly lethal Syrian golden hamster model of MHF using a hamster-adapted MARV variant Angola. Remarkably, this model displayed almost all of the clinical features of MHF seen in humans and non-human primates, including coagulation abnormalities, hemorrhagic manifestations, petechial rash, and a severely dysregulated immune response. This MHF hamster model represents a powerful tool for further dissecting MARV pathogenesis and accelerating the development of effective medical countermeasures against human MHF. PMID:27976688

  14. A hamster model for Marburg virus infection accurately recapitulates Marburg hemorrhagic fever.

    PubMed

    Marzi, Andrea; Banadyga, Logan; Haddock, Elaine; Thomas, Tina; Shen, Kui; Horne, Eva J; Scott, Dana P; Feldmann, Heinz; Ebihara, Hideki

    2016-12-15

    Marburg virus (MARV), a close relative of Ebola virus, is the causative agent of a severe human disease known as Marburg hemorrhagic fever (MHF). No licensed vaccine or therapeutic exists to treat MHF, and MARV is therefore classified as a Tier 1 select agent and a category A bioterrorism agent. In order to develop countermeasures against this severe disease, animal models that accurately recapitulate human disease are required. Here we describe the development of a novel, uniformly lethal Syrian golden hamster model of MHF using a hamster-adapted MARV variant Angola. Remarkably, this model displayed almost all of the clinical features of MHF seen in humans and non-human primates, including coagulation abnormalities, hemorrhagic manifestations, petechial rash, and a severely dysregulated immune response. This MHF hamster model represents a powerful tool for further dissecting MARV pathogenesis and accelerating the development of effective medical countermeasures against human MHF.

  15. 29 CFR 1905.26 - Hearings.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 5 2014-07-01 2014-07-01 false Hearings. 1905.26 Section 1905.26 Labor Regulations... OCCUPATIONAL SAFETY AND HEALTH ACT OF 1970 Hearings § 1905.26 Hearings. (a) Order of proceeding. Except as may be ordered otherwise by the presiding hearing examiner, the party applicant for relief shall proceed...

  16. 29 CFR 1905.26 - Hearings.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 5 2010-07-01 2010-07-01 false Hearings. 1905.26 Section 1905.26 Labor Regulations... OCCUPATIONAL SAFETY AND HEALTH ACT OF 1970 Hearings § 1905.26 Hearings. (a) Order of proceeding. Except as may be ordered otherwise by the presiding hearing examiner, the party applicant for relief shall proceed...

  17. Characteristics of Filoviridae: Marburg and Ebola Viruses

    NASA Astrophysics Data System (ADS)

    Beer, Brigitte; Kurth, Reinhard; Bukreyev, Alexander

    Filoviruses are enveloped, nonsegmented negative-stranded RNA viruses. The two species, Marburg and Ebola virus, are serologically, biochemically, and genetically distinct. Marburg virus was first isolated during an outbreak in Europe in 1967, and Ebola virus emerged in 1976 as the causative agent of two simultaneous outbreaks in southern Sudan and northern Zaire. Although the main route of infection is known to be person-to-person transmission by intimate contact, the natural reservoir for filoviruses still remains a mystery.

  18. Isolated Case of Marburg Virus Disease, Kampala, Uganda, 2014.

    PubMed

    Nyakarahuka, Luke; Ojwang, Joseph; Tumusiime, Alex; Balinandi, Stephen; Whitmer, Shannon; Kyazze, Simon; Kasozi, Sam; Wetaka, Milton; Makumbi, Issa; Dahlke, Melissa; Borchert, Jeff; Lutwama, Julius; Ströher, Ute; Rollin, Pierre E; Nichol, Stuart T; Shoemaker, Trevor R

    2017-06-01

    In September 2014, a single fatal case of Marburg virus was identified in a healthcare worker in Kampala, Uganda. The source of infection was not identified, and no secondary cases were identified. We describe the rapid identification, laboratory diagnosis, and case investigation of the third Marburg virus outbreak in Uganda.

  19. 29 CFR 32.26 - Discrimination prohibited.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 1 2014-07-01 2013-07-01 true Discrimination prohibited. 32.26 Section 32.26 Labor Office... RECEIVING FEDERAL FINANCIAL ASSISTANCE Accessibility § 32.26 Discrimination prohibited. No qualified... discrimination under any program or activity to which this part applies. ...

  20. 29 CFR 32.26 - Discrimination prohibited.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 1 2011-07-01 2011-07-01 false Discrimination prohibited. 32.26 Section 32.26 Labor Office... RECEIVING FEDERAL FINANCIAL ASSISTANCE Accessibility § 32.26 Discrimination prohibited. No qualified... discrimination under any program or activity to which this part applies. ...

  1. 29 CFR 32.26 - Discrimination prohibited.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 1 2013-07-01 2013-07-01 false Discrimination prohibited. 32.26 Section 32.26 Labor Office... RECEIVING FEDERAL FINANCIAL ASSISTANCE Accessibility § 32.26 Discrimination prohibited. No qualified... discrimination under any program or activity to which this part applies. ...

  2. 29 CFR 32.26 - Discrimination prohibited.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 1 2012-07-01 2012-07-01 false Discrimination prohibited. 32.26 Section 32.26 Labor Office... RECEIVING FEDERAL FINANCIAL ASSISTANCE Accessibility § 32.26 Discrimination prohibited. No qualified... discrimination under any program or activity to which this part applies. ...

  3. 29 CFR 32.26 - Discrimination prohibited.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Discrimination prohibited. 32.26 Section 32.26 Labor Office... RECEIVING FEDERAL FINANCIAL ASSISTANCE Accessibility § 32.26 Discrimination prohibited. No qualified... discrimination under any program or activity to which this part applies. ...

  4. 32 CFR 720.26-720.29 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 5 2010-07-01 2010-07-01 false [Reserved] 720.26-720.29 Section 720.26-720.29 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY PERSONNEL DELIVERY OF PERSONNEL; SERVICE OF PROCESS AND SUBPOENAS; PRODUCTION OF OFFICIAL RECORDS Service of Process and Subpoenas Upon...

  5. [Ebola and Marburg viruses: the humans strike back].

    PubMed

    Alazard-Dany, Nathalie; Ottmann Terrangle, Michèle; Volchkov, Viktor

    2006-04-01

    Ebola and Marburg viruses are the causative agents of rapidly progressive hemorrhagic fevers with high mortality rates. Pre- or post-exposure treatments against the diseases are currently not available for human use. In the field, establishment of strict quarantine measures preventing further virus transmission are still the only way to fight the infections. However, our knowledge of Ebola and Marburg viruses has markedly increased as a result of two recent discoveries discussed in this review. Chandran et al. have elucidated the mechanism by which Ebola GP is converted to a fusion-active form. Infectivity of Ebola virus was shown to be dependent on the cleavage of GP by cellular endosomal proteases, cathepsin B and L, thus opening new therapeutic approaches options. As for Jones SM et al., they have successfully vaccinated monkeys with recombinant vesicular stomatitis virus expressing Ebola or Marburg virus surface glycoprotein GP, a promising vaccine approach.

  6. 29 CFR 70.26 - Business information.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 1 2011-07-01 2011-07-01 false Business information. 70.26 Section 70.26 Labor Office of... of Records Under the Freedom of Information Act § 70.26 Business information. (a) In general. Confidential business information will be disclosed under the FOIA only in accordance with this section. (b...

  7. 29 CFR 70.26 - Business information.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 1 2014-07-01 2013-07-01 true Business information. 70.26 Section 70.26 Labor Office of... of Records Under the Freedom of Information Act § 70.26 Business information. (a) In general. Confidential business information will be disclosed under the FOIA only in accordance with this section. (b...

  8. 29 CFR 70.26 - Business information.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 1 2013-07-01 2013-07-01 false Business information. 70.26 Section 70.26 Labor Office of... of Records Under the Freedom of Information Act § 70.26 Business information. (a) In general. Confidential business information will be disclosed under the FOIA only in accordance with this section. (b...

  9. 29 CFR 70.26 - Business information.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 1 2012-07-01 2012-07-01 false Business information. 70.26 Section 70.26 Labor Office of... of Records Under the Freedom of Information Act § 70.26 Business information. (a) In general. Confidential business information will be disclosed under the FOIA only in accordance with this section. (b...

  10. 29 CFR 70.26 - Business information.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Business information. 70.26 Section 70.26 Labor Office of... of Records Under the Freedom of Information Act § 70.26 Business information. (a) In general. Confidential business information will be disclosed under the FOIA only in accordance with this section. (b...

  11. Studies of Reservoir Hosts for Marburg Virus

    PubMed Central

    Smit, Sheilagh B.; Rollin, Pierre E.; Formenty, Pierre; Leman, Patricia A.; Kemp, Alan; Burt, Felicity J.; Grobbelaar, Antoinette A.; Croft, Janice; Bausch, Daniel G.; Zeller, Hervé; Leirs, Herwig; Braack, L.E.O.; Libande, Modeste L.; Zaki, Sherif; Nichol, Stuart T.; Ksiazek, Thomas G.; Paweska, Janusz T.

    2007-01-01

    To determine reservoir hosts for Marburg virus (MARV), we examined the fauna of a mine in northeastern Democratic Republic of the Congo. The mine was associated with a protracted outbreak of Marburg hemorrhagic fever during 1998–2000. We found MARV nucleic acid in 12 bats, comprising 3.0%–3.6% of 2 species of insectivorous bat and 1 species of fruit bat. We found antibody to the virus in the serum of 9.7% of 1 of the insectivorous species and in 20.5% of the fruit bat species, but attempts to isolate virus were unsuccessful. PMID:18258034

  12. [A Japanese in Marburg : Excerpts from the Memories - Jiden - of the Japanese Bacteriologist Taichi Kitashima (1870-1956)].

    PubMed

    Enke, Ulrike; Ishihara, Aeka

    2017-06-01

    The heart of this article is the transmission of selected chapters from the Japanese bacteriologist Taichi Kitashima's (1870-1956) autobiographical memoirs (in Japanese, Jiden) published in 1955, in which Kitashima reports on his stay in Marburg in a very personal and subjective way. Like other Japanese physicians of his generation, Kitashima spent several years in Germany in order to work with the serum researcher Emil von Behring and continued his education there. The contact came through Kitashima's teacher Shibasaburô Kitasato, who had worked with Behring in Berlin on questions of immunology. The memoir gives insight into Behring's laboratory work and his relation to his "subordinates". The editors investigate to what extent Kitashima's assessment, made from a distance of fifty years, of his stay in Germany as "wasted time" was accurate, given the advantages that arose from having been part of a vibrant European scientific community, including encounters in the Pasteur Institute in Paris, and why he cultivated his contacts with Germany and the Behring family during National Socialism.

  13. Distribution of Marburg virus in Africa: An evolutionary approach.

    PubMed

    Zehender, Gianguglielmo; Sorrentino, Chiara; Veo, Carla; Fiaschi, Lisa; Gioffrè, Sonia; Ebranati, Erika; Tanzi, Elisabetta; Ciccozzi, Massimo; Lai, Alessia; Galli, Massimo

    2016-10-01

    The aim of this study was to investigate the origin and geographical dispersion of Marburg virus, the first member of the Filoviridae family to be discovered. Seventy-three complete genome sequences of Marburg virus isolated from animals and humans were retrieved from public databases and analysed using a Bayesian phylogeographical framework. The phylogenetic tree of the Marburg virus data set showed two significant evolutionary lineages: Ravn virus (RAVV) and Marburg virus (MARV). MARV divided into two main clades; clade A included isolates from Uganda (five from the European epidemic in 1967), Kenya (1980) and Angola (from the epidemic of 2004-2005); clade B included most of the isolates obtained during the 1999-2000 epidemic in the Democratic Republic of the Congo (DRC) and a group of Ugandan isolates obtained in 2007-2009. The estimated mean evolutionary rate of the whole genome was 3.3×10(-4) substitutions/site/year (credibility interval 2.0-4.8). The MARV strain had a mean root time of the most recent common ancestor of 177.9years ago (YA) (95% highest posterior density 87-284), thus indicating that it probably originated in the mid-XIX century, whereas the RAVV strain had a later origin dating back to a mean 33.8 YA. The most probable location of the MARV ancestor was Uganda (state posterior probability, spp=0.41), whereas that of the RAVV ancestor was Kenya (spp=0.71). There were significant migration rates from Uganda to the DRC (Bayes Factor, BF=42.0) and in the opposite direction (BF=5.7). Our data suggest that Uganda may have been the cradle of Marburg virus in Africa. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. [Multiplex real-time PCR method for rapid detection of Marburg virus and Ebola virus].

    PubMed

    Yang, Yu; Bai, Lin; Hu, Kong-Xin; Yang, Zhi-Hong; Hu, Jian-Ping; Wang, Jing

    2012-08-01

    Marburg virus and Ebola virus are acute infections with high case fatality rates. A rapid, sensitive detection method was established to detect Marburg virus and Ebola virus by multiplex real-time fluorescence quantitative PCR. Designing primers and Taqman probes from highly conserved sequences of Marburg virus and Ebola virus through whole genome sequences alignment, Taqman probes labeled by FAM and Texas Red, the sensitivity of the multiplex real-time quantitative PCR assay was optimized by evaluating the different concentrations of primers and Probes. We have developed a real-time PCR method with the sensitivity of 30.5 copies/microl for Marburg virus positive plasmid and 28.6 copies/microl for Ebola virus positive plasmids, Japanese encephalitis virus, Yellow fever virus, Dengue virus were using to examine the specificity. The Multiplex real-time PCR assays provide a sensitive, reliable and efficient method to detect Marburg virus and Ebola virus simultaneously.

  15. Isolation of genetically diverse Marburg viruses from Egyptian fruit bats.

    PubMed

    Towner, Jonathan S; Amman, Brian R; Sealy, Tara K; Carroll, Serena A Reeder; Comer, James A; Kemp, Alan; Swanepoel, Robert; Paddock, Christopher D; Balinandi, Stephen; Khristova, Marina L; Formenty, Pierre B H; Albarino, Cesar G; Miller, David M; Reed, Zachary D; Kayiwa, John T; Mills, James N; Cannon, Deborah L; Greer, Patricia W; Byaruhanga, Emmanuel; Farnon, Eileen C; Atimnedi, Patrick; Okware, Samuel; Katongole-Mbidde, Edward; Downing, Robert; Tappero, Jordan W; Zaki, Sherif R; Ksiazek, Thomas G; Nichol, Stuart T; Rollin, Pierre E

    2009-07-01

    In July and September 2007, miners working in Kitaka Cave, Uganda, were diagnosed with Marburg hemorrhagic fever. The likely source of infection in the cave was Egyptian fruit bats (Rousettus aegyptiacus) based on detection of Marburg virus RNA in 31/611 (5.1%) bats, virus-specific antibody in bat sera, and isolation of genetically diverse virus from bat tissues. The virus isolates were collected nine months apart, demonstrating long-term virus circulation. The bat colony was estimated to be over 100,000 animals using mark and re-capture methods, predicting the presence of over 5,000 virus-infected bats. The genetically diverse virus genome sequences from bats and miners closely matched. These data indicate common Egyptian fruit bats can represent a major natural reservoir and source of Marburg virus with potential for spillover into humans.

  16. Transcriptional Profiling of the Immune Response to Marburg Virus Infection.

    PubMed

    Connor, John H; Yen, Judy; Caballero, Ignacio S; Garamszegi, Sara; Malhotra, Shikha; Lin, Kenny; Hensley, Lisa; Goff, Arthur J

    2015-10-01

    Marburg virus is a genetically simple RNA virus that causes a severe hemorrhagic fever in humans and nonhuman primates. The mechanism of pathogenesis of the infection is not well understood, but it is well accepted that pathogenesis is appreciably driven by a hyperactive immune response. To better understand the overall response to Marburg virus challenge, we undertook a transcriptomic analysis of immune cells circulating in the blood following aerosol exposure of rhesus macaques to a lethal dose of Marburg virus. Using two-color microarrays, we analyzed the transcriptomes of peripheral blood mononuclear cells that were collected throughout the course of infection from 1 to 9 days postexposure, representing the full course of the infection. The response followed a 3-stage induction (early infection, 1 to 3 days postexposure; midinfection, 5 days postexposure; late infection, 7 to 9 days postexposure) that was led by a robust innate immune response. The host response to aerosolized Marburg virus was evident at 1 day postexposure. Analysis of cytokine transcripts that were overexpressed during infection indicated that previously unanalyzed cytokines are likely induced in response to exposure to Marburg virus and further suggested that the early immune response is skewed toward a Th2 response that would hamper the development of an effective antiviral immune response early in disease. Late infection events included the upregulation of coagulation-associated factors. These findings demonstrate very early host responses to Marburg virus infection and provide a rich data set for identification of factors expressed throughout the course of infection that can be investigated as markers of infection and targets for therapy. Marburg virus causes a severe infection that is associated with high mortality and hemorrhage. The disease is associated with an immune response that contributes to the lethality of the disease. In this study, we investigated how the immune cells

  17. Multidistrict Outbreak of Marburg Virus Disease-Uganda, 2012.

    PubMed

    Knust, Barbara; Schafer, Ilana J; Wamala, Joseph; Nyakarahuka, Luke; Okot, Charles; Shoemaker, Trevor; Dodd, Kimberly; Gibbons, Aridth; Balinandi, Stephen; Tumusiime, Alex; Campbell, Shelley; Newman, Edmund; Lasry, Estrella; DeClerck, Hilde; Boum, Yap; Makumbi, Issa; Bosa, Henry Kyobe; Mbonye, Anthony; Aceng, Jane Ruth; Nichol, Stuart T; Ströher, Ute; Rollin, Pierre E

    2015-10-01

    In October 2012, a cluster of illnesses and deaths was reported in Uganda and was confirmed to be an outbreak of Marburg virus disease (MVD). Patients meeting the case criteria were interviewed using a standard investigation form, and blood specimens were tested for evidence of acute or recent Marburg virus infection by reverse transcription-polymerase chain reaction (RT-PCR) and antibody enzyme-linked immunosorbent assay. The total count of confirmed and probable MVD cases was 26, of which 15 (58%) were fatal. Four of 15 laboratory-confirmed cases (27%) were fatal. Case patients were located in 4 different districts in Uganda, although all chains of transmission originated in Ibanda District, and the earliest case detected had an onset in July 2012. No zoonotic exposures were identified. Symptoms significantly associated with being a MVD case included hiccups, anorexia, fatigue, vomiting, sore throat, and difficulty swallowing. Contact with a case patient and attending a funeral were also significantly associated with being a case. Average RT-PCR cycle threshold values for fatal cases during the acute phase of illness were significantly lower than those for nonfatal cases. Following the institution of contact tracing, active case surveillance, care of patients with isolation precautions, community mobilization, and rapid diagnostic testing, the outbreak was successfully contained 14 days after its initial detection. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  18. Isolation of Genetically Diverse Marburg Viruses from Egyptian Fruit Bats

    PubMed Central

    Towner, Jonathan S.; Amman, Brian R.; Sealy, Tara K.; Carroll, Serena A. Reeder; Comer, James A.; Kemp, Alan; Swanepoel, Robert; Paddock, Christopher D.; Balinandi, Stephen; Khristova, Marina L.; Formenty, Pierre B. H.; Albarino, Cesar G.; Miller, David M.; Reed, Zachary D.; Kayiwa, John T.; Mills, James N.; Cannon, Deborah L.; Greer, Patricia W.; Byaruhanga, Emmanuel; Farnon, Eileen C.; Atimnedi, Patrick; Okware, Samuel; Katongole-Mbidde, Edward; Downing, Robert; Tappero, Jordan W.; Zaki, Sherif R.; Ksiazek, Thomas G.; Nichol, Stuart T.; Rollin, Pierre E.

    2009-01-01

    In July and September 2007, miners working in Kitaka Cave, Uganda, were diagnosed with Marburg hemorrhagic fever. The likely source of infection in the cave was Egyptian fruit bats (Rousettus aegyptiacus) based on detection of Marburg virus RNA in 31/611 (5.1%) bats, virus-specific antibody in bat sera, and isolation of genetically diverse virus from bat tissues. The virus isolates were collected nine months apart, demonstrating long-term virus circulation. The bat colony was estimated to be over 100,000 animals using mark and re-capture methods, predicting the presence of over 5,000 virus-infected bats. The genetically diverse virus genome sequences from bats and miners closely matched. These data indicate common Egyptian fruit bats can represent a major natural reservoir and source of Marburg virus with potential for spillover into humans. PMID:19649327

  19. 29 CFR 15.26 - Claims procedures.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... forth in § 15.21(d) will be accepted and considered a claim under the Act if it constitutes a demand for compensation from the Department. A demand is not required to be for a specific sum of money. (c) Notification... 29 Labor 1 2010-07-01 2010-07-01 true Claims procedures. 15.26 Section 15.26 Labor Office of the...

  20. 29 CFR 1601.26 - Confidentiality of endeavors.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Confidentiality of endeavors. 1601.26 Section 1601.26 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION PROCEDURAL REGULATIONS Procedure for the Prevention of Unlawful Employment Practices Procedure to Rectify Unlawful Employment...

  1. 29 CFR 1601.26 - Confidentiality of endeavors.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 4 2011-07-01 2011-07-01 false Confidentiality of endeavors. 1601.26 Section 1601.26 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION PROCEDURAL REGULATIONS Procedure for the Prevention of Unlawful Employment Practices Procedure to Rectify Unlawful Employment...

  2. Development and Characterization of a Mouse Model for Marburg Hemorrhagic Fever

    DTIC Science & Technology

    2009-07-01

    Microbiology. All Rights Reserved. Development and Characterization of a Mouse Model for Marburg Hemorrhagic Fever Kelly L. Warfield,* Steven B...mouse model has hampered an understanding of the pathogenesis and immunity of Marburg hemorrhagic fever (MHF), the disease caused by marburgvirus (MARV...cause severe hemorrhagic fevers in humans and non- human primates (27). The incubation time is estimated to be 3 to 21 days, with human case fatality

  3. Knowledge and attitude towards Ebola and Marburg virus diseases in Uganda using quantitative and participatory epidemiology techniques

    PubMed Central

    Skjerve, Eystein; Nabadda, Daisy; Sitali, Doreen Chilolo; Mumba, Chisoni; Mwiine, Frank N.; Lutwama, Julius J.; Balinandi, Stephen; Shoemaker, Trevor; Kankya, Clovice

    2017-01-01

    Background Uganda has reported five (5) Ebola virus disease outbreaks and three (3) Marburg virus disease outbreaks from 2000 to 2016. Peoples’ knowledge and attitude towards Ebola and Marburg virus disease impact on control and prevention measures especially during outbreaks. We describe knowledge and attitude towards Ebola and Marburg virus outbreaks in two affected communities in Uganda to inform future outbreak responses and help in the design of health education and communication messages. Methods The study was a community survey done in Luweero, Ibanda and Kamwenge districts that have experienced outbreaks of Ebola and Marburg virus diseases. Quantitative data were collected using a structured questionnaire and triangulated with qualitative participatory epidemiology techniques to gain a communities’ knowledge and attitude towards Ebola and Marburg virus disease. Results Out of 740 respondents, 48.5% (359/740) were categorized as being knowledgeable about Ebola and Marburg virus diseases, whereas 60.5% (448/740) were having a positive attitude towards control and prevention of Ebola and Marburg virus diseases. The mean knowledge and attitude percentage scores were 54.3 (SD = 23.5, 95%CI = 52.6–56.0) and 69.9 (SD = 16.9, 95%CI = 68.9–71.1) respectively. People educated beyond primary school were more likely to be knowledgeable about Ebola and Marburg virus disease than those who did not attain any formal education (OR = 3.6, 95%CI = 2.1–6.1). Qualitative data revealed that communities describe Ebola and Marburg virus diseases as very severe diseases with no cure and they believe the diseases spread so fast. Respondents reported fear and stigma suffered by survivors, their families and the broader community due to these diseases. Conclusion Communities in Uganda affected by filovirus outbreaks have moderate knowledge about these diseases and have a positive attitude towards practices to prevent and control Ebola and Marburg viral diseases. The public

  4. Knowledge and attitude towards Ebola and Marburg virus diseases in Uganda using quantitative and participatory epidemiology techniques.

    PubMed

    Nyakarahuka, Luke; Skjerve, Eystein; Nabadda, Daisy; Sitali, Doreen Chilolo; Mumba, Chisoni; Mwiine, Frank N; Lutwama, Julius J; Balinandi, Stephen; Shoemaker, Trevor; Kankya, Clovice

    2017-09-01

    Uganda has reported five (5) Ebola virus disease outbreaks and three (3) Marburg virus disease outbreaks from 2000 to 2016. Peoples' knowledge and attitude towards Ebola and Marburg virus disease impact on control and prevention measures especially during outbreaks. We describe knowledge and attitude towards Ebola and Marburg virus outbreaks in two affected communities in Uganda to inform future outbreak responses and help in the design of health education and communication messages. The study was a community survey done in Luweero, Ibanda and Kamwenge districts that have experienced outbreaks of Ebola and Marburg virus diseases. Quantitative data were collected using a structured questionnaire and triangulated with qualitative participatory epidemiology techniques to gain a communities' knowledge and attitude towards Ebola and Marburg virus disease. Out of 740 respondents, 48.5% (359/740) were categorized as being knowledgeable about Ebola and Marburg virus diseases, whereas 60.5% (448/740) were having a positive attitude towards control and prevention of Ebola and Marburg virus diseases. The mean knowledge and attitude percentage scores were 54.3 (SD = 23.5, 95%CI = 52.6-56.0) and 69.9 (SD = 16.9, 95%CI = 68.9-71.1) respectively. People educated beyond primary school were more likely to be knowledgeable about Ebola and Marburg virus disease than those who did not attain any formal education (OR = 3.6, 95%CI = 2.1-6.1). Qualitative data revealed that communities describe Ebola and Marburg virus diseases as very severe diseases with no cure and they believe the diseases spread so fast. Respondents reported fear and stigma suffered by survivors, their families and the broader community due to these diseases. Communities in Uganda affected by filovirus outbreaks have moderate knowledge about these diseases and have a positive attitude towards practices to prevent and control Ebola and Marburg viral diseases. The public health sector should enhance this community

  5. How severe and prevalent are Ebola and Marburg viruses? A systematic review and meta-analysis of the case fatality rates and seroprevalence.

    PubMed

    Nyakarahuka, Luke; Kankya, Clovice; Krontveit, Randi; Mayer, Benjamin; Mwiine, Frank N; Lutwama, Julius; Skjerve, Eystein

    2016-11-25

    Ebola and Marburg virus diseases are said to occur at a low prevalence, but are very severe diseases with high lethalities. The fatality rates reported in different outbreaks ranged from 24-100%. In addition, sero-surveys conducted have shown different seropositivity for both Ebola and Marburg viruses. We aimed to use a meta-analysis approach to estimate the case fatality and seroprevalence rates of these filoviruses, providing vital information for epidemic response and preparedness in countries affected by these diseases. Published literature was retrieved through a search of databases. Articles were included if they reported number of deaths, cases, and seropositivity. We further cross-referenced with ministries of health, WHO and CDC databases. The effect size was proportion represented by case fatality rate (CFR) and seroprevalence. Analysis was done using the metaprop command in STATA. The weighted average CFR of Ebola virus disease was estimated to be 65.0% [95% CI (54.0-76.0%), I 2  = 97.98%] whereas that of Marburg virus disease was 53.8% (26.5-80.0%, I 2  = 88.6%). The overall seroprevalence of Ebola virus was 8.0% (5.0%-11.0%, I 2  = 98.7%), whereas that for Marburg virus was 1.2% (0.5-2.0%, I 2  = 94.8%). The most severe species of ebolavirus was Zaire ebolavirus while Bundibugyo Ebolavirus was the least severe. The pooled CFR and seroprevalence for Ebola and Marburg viruses were found to be lower than usually reported, with species differences despite high heterogeneity between studies. Countries with an improved health surveillance and epidemic response have lower CFR, thereby indicating need for improving early detection and epidemic response in filovirus outbreaks.

  6. 29 CFR 531.26 - Relation to other laws.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 3 2012-07-01 2012-07-01 false Relation to other laws. 531.26 Section 531.26 Labor... PAYMENTS UNDER THE FAIR LABOR STANDARDS ACT OF 1938 Interpretations § 531.26 Relation to other laws... Administrator should be taken to override or nullify the provisions of these laws. How Payments May Be Made ...

  7. 29 CFR 531.26 - Relation to other laws.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 3 2013-07-01 2013-07-01 false Relation to other laws. 531.26 Section 531.26 Labor... PAYMENTS UNDER THE FAIR LABOR STANDARDS ACT OF 1938 Interpretations § 531.26 Relation to other laws... Administrator should be taken to override or nullify the provisions of these laws. How Payments May Be Made ...

  8. 9 CFR 78.26-78.29 - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AGRICULTURE INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS BRUCELLOSIS Restrictions on Interstate Movement of Bison Because of Brucellosis §§ 78.26-78.29 [Reserved] ...

  9. 9 CFR 78.26-78.29 - [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AGRICULTURE INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS BRUCELLOSIS Restrictions on Interstate Movement of Bison Because of Brucellosis §§ 78.26-78.29 [Reserved] ...

  10. 9 CFR 78.26-78.29 - [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AGRICULTURE INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS BRUCELLOSIS Restrictions on Interstate Movement of Bison Because of Brucellosis §§ 78.26-78.29 [Reserved] ...

  11. 9 CFR 78.26-78.29 - [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AGRICULTURE INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS BRUCELLOSIS Restrictions on Interstate Movement of Bison Because of Brucellosis §§ 78.26-78.29 [Reserved] ...

  12. 9 CFR 78.26-78.29 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AGRICULTURE INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS BRUCELLOSIS Restrictions on Interstate Movement of Bison Because of Brucellosis §§ 78.26-78.29 [Reserved] ...

  13. Recombinant vesicular stomatitis virus-based vaccines against Ebola and Marburg virus infections.

    PubMed

    Geisbert, Thomas W; Feldmann, Heinz

    2011-11-01

    The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with a high mortality rate in humans and nonhuman primates. Among the most-promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Importantly, a single injection of blended rVSV-based filovirus vaccines was shown to completely protect nonhuman primates against Marburg virus and 3 different species of Ebola virus. These rVSV-based vaccines have also shown utility when administered as a postexposure treatment against filovirus infections, and a rVSV-based Ebola virus vaccine was recently used to treat a potential laboratory exposure. Here, we review the history of rVSV-based vaccines and pivotal animal studies showing their utility in combating Ebola and Marburg virus infections.

  14. Recombinant Vesicular Stomatitis Virus–Based Vaccines Against Ebola and Marburg Virus Infections

    PubMed Central

    Feldmann, Heinz

    2011-01-01

    The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with a high mortality rate in humans and nonhuman primates. Among the most-promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Importantly, a single injection of blended rVSV-based filovirus vaccines was shown to completely protect nonhuman primates against Marburg virus and 3 different species of Ebola virus. These rVSV-based vaccines have also shown utility when administered as a postexposure treatment against filovirus infections, and a rVSV-based Ebola virus vaccine was recently used to treat a potential laboratory exposure. Here, we review the history of rVSV-based vaccines and pivotal animal studies showing their utility in combating Ebola and Marburg virus infections. PMID:21987744

  15. The Disappearing Fourth Wall: John Marburger, Science Policy, and the SSC

    NASA Astrophysics Data System (ADS)

    Crease, Robert

    2015-04-01

    John H. Marburger (1941-2011) was a skilled science administrator who had a fresh and unique approach to science policy and science leadership. His posthumously published book Science Policy up Close contains recollections of key science policy episodes in which he participated or observed closely. One was the administration of the Superconducting Supercollider (SSC); Marburger was Chairman of the Universities Research Association, the group charged with managing the SSC, from 1988-1994. Many accounts of the SSC saga attribute its demise to a combination of transitory factors: poor management, rising cost estimates, the collapse of the Soviet Union and thus of the Cold War threat, complaints by ``small science'' that the SSC's ``big science'' was consuming their budget, Congress's desire to cut spending, unwarranted contract regulations imposed by the Department of Energy (DOE) in response to environmental lapses at nuclear weapons laboratories, and so forth. Marburger tells a subtler story whose implications for science policy are more significant and far-reaching. The story involves changes in the attitude of the government towards large scientific projects that reach back to management reforms introduced by the administration of Presidents Johnson, Nixon, and Carter in the 1960s and 1970s. This experience impressed Marburger with the inevitability of public oversight of large scientific projects, and with the need for planners of such projects to establish and make public a cost and schedule tracking system that would model the project's progress and expenditures.

  16. 25 CFR 26.29 - What is the scope of the Job Training Program?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false What is the scope of the Job Training Program? 26.29 Section 26.29 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR HUMAN SERVICES JOB PLACEMENT AND TRAINING PROGRAM Training Services § 26.29 What is the scope of the Job Training Program? A...

  17. 25 CFR 26.29 - What is the scope of the Job Training Program?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true What is the scope of the Job Training Program? 26.29 Section 26.29 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR HUMAN SERVICES JOB PLACEMENT AND TRAINING PROGRAM Training Services § 26.29 What is the scope of the Job Training Program? A...

  18. 25 CFR 26.29 - What is the scope of the Job Training Program?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false What is the scope of the Job Training Program? 26.29 Section 26.29 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR HUMAN SERVICES JOB PLACEMENT AND TRAINING PROGRAM Training Services § 26.29 What is the scope of the Job Training Program? A...

  19. 25 CFR 26.29 - What is the scope of the Job Training Program?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false What is the scope of the Job Training Program? 26.29 Section 26.29 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR HUMAN SERVICES JOB PLACEMENT AND TRAINING PROGRAM Training Services § 26.29 What is the scope of the Job Training Program? A...

  20. 25 CFR 26.29 - What is the scope of the Job Training Program?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false What is the scope of the Job Training Program? 26.29 Section 26.29 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR HUMAN SERVICES JOB PLACEMENT AND TRAINING PROGRAM Training Services § 26.29 What is the scope of the Job Training Program? A...

  1. 29 CFR 35.26 - Recipient assessment of age distinctions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 1 2012-07-01 2012-07-01 false Recipient assessment of age distinctions. 35.26 Section 35.26 Labor Office of the Secretary of Labor NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR....26 Recipient assessment of age distinctions. (a) In order to assess a recipient's compliance with the...

  2. 29 CFR 35.26 - Recipient assessment of age distinctions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 1 2011-07-01 2011-07-01 false Recipient assessment of age distinctions. 35.26 Section 35.26 Labor Office of the Secretary of Labor NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR....26 Recipient assessment of age distinctions. (a) In order to assess a recipient's compliance with the...

  3. 29 CFR 35.26 - Recipient assessment of age distinctions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 1 2013-07-01 2013-07-01 false Recipient assessment of age distinctions. 35.26 Section 35.26 Labor Office of the Secretary of Labor NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR....26 Recipient assessment of age distinctions. (a) In order to assess a recipient's compliance with the...

  4. 29 CFR 35.26 - Recipient assessment of age distinctions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Recipient assessment of age distinctions. 35.26 Section 35.26 Labor Office of the Secretary of Labor NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR....26 Recipient assessment of age distinctions. (a) In order to assess a recipient's compliance with the...

  5. 29 CFR 35.26 - Recipient assessment of age distinctions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 1 2014-07-01 2013-07-01 true Recipient assessment of age distinctions. 35.26 Section 35.26 Labor Office of the Secretary of Labor NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR....26 Recipient assessment of age distinctions. (a) In order to assess a recipient's compliance with the...

  6. Experimental respiratory Marburg virus haemorrhagic fever infection in the common marmoset (Callithrix jacchus)

    PubMed Central

    Smither, Sophie J; Nelson, Michelle; Eastaugh, Lin; Laws, Thomas R; Taylor, Christopher; Smith, Simon A; Salguero, Francisco J; Lever, Mark S

    2013-01-01

    Marburg virus causes a highly infectious and lethal haemorrhagic fever in primates and may be exploited as a potential biothreat pathogen. To combat the infection and threat of Marburg haemorrhagic fever, there is a need to develop and license appropriate medical countermeasures. To determine whether the common marmoset (Callithrix jacchus) would be an appropriate model to assess therapies against Marburg haemorrhagic fever, initial susceptibility, lethality and pathogenesis studies were performed. Low doses of virus, between 4 and 28 TCID50, were sufficient to cause a lethal, reproducible infection. Animals became febrile between days 5 and 6, maintaining a high fever before succumbing to disease between 8 and 11 days postchallenge. Typical signs of Marburg virus infection were observed including haemorrhaging and a transient rash. In pathogenesis studies, virus was isolated from the animals’ lungs from day 3 postchallenge and from the liver, spleen and blood from day 5 postchallenge. Early signs of histopathology were apparent in the kidney and liver from day 3. The most striking features were observed in animals exhibiting severe clinical signs, which included high viral titres in all organs, with the highest levels in the blood, increased levels in liver function enzymes and blood clotting times, decreased levels in platelets, multifocal moderate-to-severe hepatitis and perivascular oedema. PMID:23441639

  7. 7 CFR 29.1132 - Rule 26.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... INSPECTION Standards Rules § 29.1132 Rule 26. Tobacco that contains a moderate amount of dirt or sand, but which otherwise meets the specifications of any Primings grade, including the first quality Nondescript from the Primings group, shall be designated by placing the special factor, “dirt” or “sand” after the...

  8. Phylogenetic assessment of filoviruses: how many lineages of Marburg virus?

    PubMed Central

    Peterson, A Townsend; Holder, Mark T

    2012-01-01

    Filoviruses have to date been considered as consisting of one diverse genus (Ebola viruses) and one undifferentiated genus (Marburg virus). We reconsider this idea by means of detailed phylogenetic analyses of sequence data available for the Filoviridae: using coalescent simulations, we ascertain that two Marburg isolates (termed the “RAVN” strain) represent a quite-distinct lineage that should be considered in studies of biogeography and host associations, and may merit recognition at the level of species. In contrast, filovirus isolates recently obtained from bat tissues are not distinct from previously known strains, and should be considered as drawn from the same population. Implications for understanding the transmission geography and host associations of these viruses are discussed. PMID:22957185

  9. Oral shedding of Marburg virus in experimentally infected Egyptian fruit bats (Rousettus aegyptiacus).

    PubMed

    Amman, Brian R; Jones, Megan E B; Sealy, Tara K; Uebelhoer, Luke S; Schuh, Amy J; Bird, Brian H; Coleman-McCray, JoAnn D; Martin, Brock E; Nichol, Stuart T; Towner, Jonathan S

    2015-01-01

    Marburg virus (Marburg marburgvirus; MARV) causes sporadic outbreaks of Marburg hemorrhagic fever (MHF) in Africa. The Egyptian fruit bat (Rousettus aegyptiacus) has been identified as a natural reservoir based most-recently on the repeated isolation of MARV directly from bats caught at two locations in southwestern Uganda where miners and tourists separately contracted MHF from 2007-08. Despite learning much about the ecology of MARV through extensive field investigations, there remained unanswered questions such as determining the primary routes of virus shedding and the severity of disease, if any, caused by MARV in infected bats. To answer these questions and others, we experimentally infected captive-bred R. aegyptiacus with MARV under high (biosafety level 4) containment. These experiments have shown infection profiles consistent with R. aegyptiacus being a bona fide natural reservoir host for MARV and demonstrated routes of viral shedding capable of infecting humans and other animals.

  10. Marburg Virus Reverse Genetics Systems.

    PubMed

    Schmidt, Kristina Maria; Mühlberger, Elke

    2016-06-22

    The highly pathogenic Marburg virus (MARV) is a member of the Filoviridae family and belongs to the group of nonsegmented negative-strand RNA viruses. Reverse genetics systems established for MARV have been used to study various aspects of the viral replication cycle, analyze host responses, image viral infection, and screen for antivirals. This article provides an overview of the currently established MARV reverse genetic systems based on minigenomes, infectious virus-like particles and full-length clones, and the research that has been conducted using these systems.

  11. Experimental respiratory Marburg virus haemorrhagic fever infection in the common marmoset (Callithrix jacchus).

    PubMed

    Smither, Sophie J; Nelson, Michelle; Eastaugh, Lin; Laws, Thomas R; Taylor, Christopher; Smith, Simon A; Salguero, Francisco J; Lever, Mark S

    2013-04-01

    Marburg virus causes a highly infectious and lethal haemorrhagic fever in primates and may be exploited as a potential biothreat pathogen. To combat the infection and threat of Marburg haemorrhagic fever, there is a need to develop and license appropriate medical countermeasures. To determine whether the common marmoset (Callithrix jacchus) would be an appropriate model to assess therapies against Marburg haemorrhagic fever, initial susceptibility, lethality and pathogenesis studies were performed. Low doses of virus, between 4 and 28 TCID50 , were sufficient to cause a lethal, reproducible infection. Animals became febrile between days 5 and 6, maintaining a high fever before succumbing to disease between 8 and 11 days postchallenge. Typical signs of Marburg virus infection were observed including haemorrhaging and a transient rash. In pathogenesis studies, virus was isolated from the animals' lungs from day 3 postchallenge and from the liver, spleen and blood from day 5 postchallenge. Early signs of histopathology were apparent in the kidney and liver from day 3. The most striking features were observed in animals exhibiting severe clinical signs, which included high viral titres in all organs, with the highest levels in the blood, increased levels in liver function enzymes and blood clotting times, decreased levels in platelets, multifocal moderate-to-severe hepatitis and perivascular oedema. © 2013 Crown copyright. International Journal of Experimental Pathology © 2013 International Journal of Experimental Pathology.

  12. [Ebola and Marburg hemorrhagic fever viruses: update on filoviruses].

    PubMed

    Leroy, E; Baize, S; Gonzalez, J P

    2011-04-01

    The Ebola and Marburg viruses are the sole members of the Filoviridae family of viruses. They are characterized by a long filamentous form that is unique in the viral world. Filoviruses are among the most virulent pathogens currently known to infect humans. They cause fulminating disease characterized by acute fever followed by generalized hemorrhagic syndrome that is associated with 90% mortality in the most severe forms. Epidemic outbreaks of Marburg and Ebola viruses have taken a heavy toll on human life in Central Africa and devastated large ape populations in Gabon and Republic of Congo. Since their discovery in 1967 (Marburg) and 1976 (Ebola), more than 2,300 cases and 1,670 deaths have been reported. These numbers pale in comparison with the burden caused by malnutrition or other infectious disease scourges in Africa such as malaria, cholera, AIDS, dengue or tuberculosis. However, due to their extremely high lethality, association with multifocal hemorrhaging and specificity to the African continent, these hemorrhagic fever viruses have given rise to great interest on the part not only of the international scientific community but also of the general public because of their perceived potential as biological weapons. Much research has been performed on these viruses and major progress has been made in knowledge of their ecology, epidemiology and physiopathology and in development of vaccine candidates and therapeutic schemes. The purpose of this review is to present the main developments in these particular fields in the last decade.

  13. Marburg Virus Reverse Genetics Systems

    PubMed Central

    Schmidt, Kristina Maria; Mühlberger, Elke

    2016-01-01

    The highly pathogenic Marburg virus (MARV) is a member of the Filoviridae family and belongs to the group of nonsegmented negative-strand RNA viruses. Reverse genetics systems established for MARV have been used to study various aspects of the viral replication cycle, analyze host responses, image viral infection, and screen for antivirals. This article provides an overview of the currently established MARV reverse genetic systems based on minigenomes, infectious virus-like particles and full-length clones, and the research that has been conducted using these systems. PMID:27338448

  14. Protective mAbs and Cross-Reactive mAbs Raised by Immunization with Engineered Marburg Virus GPs.

    PubMed

    Fusco, Marnie L; Hashiguchi, Takao; Cassan, Robyn; Biggins, Julia E; Murin, Charles D; Warfield, Kelly L; Li, Sheng; Holtsberg, Frederick W; Shulenin, Sergey; Vu, Hong; Olinger, Gene G; Kim, Do H; Whaley, Kevin J; Zeitlin, Larry; Ward, Andrew B; Nykiforuk, Cory; Aman, M Javad; Berry, Jody D; Berry, Jody; Saphire, Erica Ollmann

    2015-06-01

    The filoviruses, which include the marburg- and ebolaviruses, have caused multiple outbreaks among humans this decade. Antibodies against the filovirus surface glycoprotein (GP) have been shown to provide life-saving therapy in nonhuman primates, but such antibodies are generally virus-specific. Many monoclonal antibodies (mAbs) have been described against Ebola virus. In contrast, relatively few have been described against Marburg virus. Here we present ten mAbs elicited by immunization of mice using recombinant mucin-deleted GPs from different Marburg virus (MARV) strains. Surprisingly, two of the mAbs raised against MARV GP also cross-react with the mucin-deleted GP cores of all tested ebolaviruses (Ebola, Sudan, Bundibugyo, Reston), but these epitopes are masked differently by the mucin-like domains themselves. The most efficacious mAbs in this panel were found to recognize a novel "wing" feature on the GP2 subunit that is unique to Marburg and does not exist in Ebola. Two of these anti-wing antibodies confer 90 and 100% protection, respectively, one hour post-exposure in mice challenged with MARV.

  15. Vaccine to Confer to Nonhuman Primates Complete Protection Against Multistrain Ebola and Marburg Virus Infections

    DTIC Science & Technology

    2008-01-01

    current filovirus threats in the event of natural hemorrhagic fever outbreak or biological attack. Ebola virus (EBOV) and Marburg virus (MARV) are mem...lethal, causing severe hemorrhagic fever disease in humans and apes with high mortality rates (up to 90%). The recent description of massive gorilla...threats in the event of natural hemorrhagic fever outbreak or biological attack. 15. SUBJECT TERMS filovirus, Ebola, Marburg, adenovirus-based vaccine

  16. 29 CFR 452.26 - Elections in local labor organizations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 2 2011-07-01 2011-07-01 false Elections in local labor organizations. 452.26 Section 452... REPORTING AND DISCLOSURE ACT OF 1959 Frequency and Kinds of Elections § 452.26 Elections in local labor organizations. Local labor organizations must conduct their regular elections of officers by secret ballot among...

  17. 29 CFR 1917.26 - First aid and lifesaving facilities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false First aid and lifesaving facilities. 1917.26 Section 1917..., DEPARTMENT OF LABOR (CONTINUED) MARINE TERMINALS Marine Terminal Operations § 1917.26 First aid and..., to the employer. (b) A first aid kit shall be available at the terminal, and at least one person...

  18. Infection and Activation of Monocytes by Marburg and Ebola Viruses

    PubMed Central

    Ströher, Ute; West, Elmar; Bugany, Harald; Klenk, Hans-Dieter; Schnittler, Hans-Joachim; Feldmann, Heinz

    2001-01-01

    In this study we investigated the effects of Marburg virus and Ebola virus (species Zaire and Reston) infections on freshly isolated suspended monocytes in comparison to adherent macrophages under culture conditions. Our data showed that monocytes are permissive for both filoviruses. As is the case in macrophages, infection resulted in the activation of monocytes which was largely independent of virus replication. The activation was triggered similarly by Marburg and Ebola viruses, species Zaire and Reston, as indicated by the release of the proinflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor α, and IL-6 as well as the chemokines IL-8 and gro-α. Our data suggest that infected monocytes may play an important role in the spread of filoviruses and in the pathogenesis of filoviral hemorrhagic disease. PMID:11602743

  19. Natural History of Aerosol Exposure with Marburg Virus in Rhesus Macaques

    PubMed Central

    Ewers, Evan C.; Pratt, William D.; Twenhafel, Nancy A.; Shamblin, Joshua; Donnelly, Ginger; Esham, Heather; Wlazlowski, Carly; Johnson, Joshua C.; Botto, Miriam; Hensley, Lisa E.; Goff, Arthur J.

    2016-01-01

    Marburg virus causes severe and often lethal viral disease in humans, and there are currently no Food and Drug Administration (FDA) approved medical countermeasures. The sporadic occurrence of Marburg outbreaks does not allow for evaluation of countermeasures in humans, so therapeutic and vaccine candidates can only be approved through the FDA animal rule—a mechanism requiring well-characterized animal models in which efficacy would be evaluated. Here, we describe a natural history study where rhesus macaques were surgically implanted with telemetry devices and central venous catheters prior to aerosol exposure with Marburg-Angola virus, enabling continuous physiologic monitoring and blood sampling without anesthesia. After a three to four day incubation period, all animals developed fever, viremia, and lymphopenia before developing tachycardia, tachypnea, elevated liver enzymes, decreased liver function, azotemia, elevated D-dimer levels and elevated pro-inflammatory cytokines suggesting a systemic inflammatory response with organ failure. The final, terminal period began with the onset of sustained hypotension, dehydration progressed with signs of major organ hypoperfusion (hyperlactatemia, acute kidney injury, hypothermia), and ended with euthanasia or death. The most significant pathologic findings were marked infection of the respiratory lymphoid tissue with destruction of the tracheobronchial and mediastinal lymph nodes, and severe diffuse infection in the liver, and splenitis. PMID:27043611

  20. Natural History of Aerosol Exposure with Marburg Virus in Rhesus Macaques.

    PubMed

    Ewers, Evan C; Pratt, William D; Twenhafel, Nancy A; Shamblin, Joshua; Donnelly, Ginger; Esham, Heather; Wlazlowski, Carly; Johnson, Joshua C; Botto, Miriam; Hensley, Lisa E; Goff, Arthur J

    2016-03-30

    Marburg virus causes severe and often lethal viral disease in humans, and there are currently no Food and Drug Administration (FDA) approved medical countermeasures. The sporadic occurrence of Marburg outbreaks does not allow for evaluation of countermeasures in humans, so therapeutic and vaccine candidates can only be approved through the FDA animal rule-a mechanism requiring well-characterized animal models in which efficacy would be evaluated. Here, we describe a natural history study where rhesus macaques were surgically implanted with telemetry devices and central venous catheters prior to aerosol exposure with Marburg-Angola virus, enabling continuous physiologic monitoring and blood sampling without anesthesia. After a three to four day incubation period, all animals developed fever, viremia, and lymphopenia before developing tachycardia, tachypnea, elevated liver enzymes, decreased liver function, azotemia, elevated D-dimer levels and elevated pro-inflammatory cytokines suggesting a systemic inflammatory response with organ failure. The final, terminal period began with the onset of sustained hypotension, dehydration progressed with signs of major organ hypoperfusion (hyperlactatemia, acute kidney injury, hypothermia), and ended with euthanasia or death. The most significant pathologic findings were marked infection of the respiratory lymphoid tissue with destruction of the tracheobronchial and mediastinal lymph nodes, and severe diffuse infection in the liver, and splenitis.

  1. Prospects for immunisation against Marburg and Ebola viruses.

    PubMed

    Geisbert, Thomas W; Bausch, Daniel G; Feldmann, Heinz

    2010-11-01

    For more than 30 years the filoviruses, Marburg virus and Ebola virus, have been associated with periodic outbreaks of hemorrhagic fever that produce severe and often fatal disease. The filoviruses are endemic primarily in resource-poor regions in Central Africa and are also potential agents of bioterrorism. Although no vaccines or antiviral drugs for Marburg or Ebola are currently available, remarkable progress has been made over the last decade in developing candidate preventive vaccines against filoviruses in nonhuman primate models. Due to the generally remote locations of filovirus outbreaks, a single-injection vaccine is desirable. Among the prospective vaccines that have shown efficacy in nonhuman primate models of filoviral hemorrhagic fever, two candidates, one based on a replication-defective adenovirus serotype 5 and the other on a recombinant VSV (rVSV), were shown to provide complete protection to nonhuman primates when administered as a single injection. The rVSV-based vaccine has also shown utility when administered for postexposure prophylaxis against filovirus infections. A VSV-based Ebola vaccine was recently used to manage a potential laboratory exposure. 2010 John Wiley & Sons, Ltd.

  2. Sequencing ebola and marburg viruses genomes using microarrays.

    PubMed

    Hardick, Justin; Woelfel, Roman; Gardner, Warren; Ibrahim, Sofi

    2016-08-01

    Periodic outbreaks of Ebola and Marburg hemorrhagic fevers have occurred in Africa over the past four decades with case fatality rates reaching as high as 90%. The latest Ebola outbreak in West Africa in 2014 raised concerns that these infections can spread across continents and pose serious health risks. Early and accurate identification of the causative agents is necessary to contain outbreaks. In this report, we describe sequencing-by-hybridization (SBH) technique using high density microarrays to identify Ebola and Marburg viruses. The microarrays were designed to interrogate the sequences of entire viral genomes, and were evaluated with three species of Ebolavirus (Reston, Sudan, and Zaire), and three strains of Marburgvirus (Angola, Musoke, and Ravn). The results showed that the consensus sequences generated with four or more hybridizations had 92.1-98.9% accuracy over 95-99% of the genomes. Additionally, with SBH microarrays it was possible to distinguish between different strains of the Lake Victoria Marburgvirus. J. Med. Virol. 88:1303-1308, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. Ad35 and Ad26 Vaccine Vectors Induce Potent and Cross-Reactive Antibody and T-Cell Responses to Multiple Filovirus Species

    PubMed Central

    Zahn, Roland; Gillisen, Gert; Roos, Anna; Koning, Marina; van der Helm, Esmeralda; Spek, Dirk; Weijtens, Mo; Grazia Pau, Maria; Radošević, Katarina; Weverling, Gerrit Jan; Custers, Jerome; Vellinga, Jort; Schuitemaker, Hanneke; Goudsmit, Jaap; Rodríguez, Ariane

    2012-01-01

    Filoviruses cause sporadic but highly lethal outbreaks of hemorrhagic fever in Africa in the human population. Currently, no drug or vaccine is available for treatment or prevention. A previous study with a vaccine candidate based on the low seroprevalent adenoviruses 26 and 35 (Ad26 and Ad35) was shown to provide protection against homologous Ebola Zaire challenge in non human primates (NHP) if applied in a prime-boost regimen. Here we have aimed to expand this principle to construct and evaluate Ad26 and Ad35 vectors for development of a vaccine to provide universal filovirus protection against all highly lethal strains that have caused major outbreaks in the past. We have therefore performed a phylogenetic analysis of filovirus glycoproteins to select the glycoproteins from two Ebola species (Ebola Zaire and Ebola Sudan/Gulu,), two Marburg strains (Marburg Angola and Marburg Ravn) and added the more distant non-lethal Ebola Ivory Coast species for broadest coverage. Ad26 and Ad35 vectors expressing these five filovirus glycoproteins were evaluated to induce a potent cellular and humoral immune response in mice. All adenoviral vectors induced a humoral immune response after single vaccination in a dose dependent manner that was cross-reactive within the Ebola and Marburg lineages. In addition, both strain-specific as well as cross-reactive T cell responses could be detected. A heterologous Ad26–Ad35 prime-boost regime enhanced mainly the humoral and to a lower extend the cellular immune response against the transgene. Combination of the five selected filovirus glycoproteins in one multivalent vaccine potentially elicits protective immunity in man against all major filovirus strains that have caused lethal outbreaks in the last 20 years. PMID:23236343

  4. Successful treatment of Marburg virus with orally administrated T-705 (Favipiravir) in a mouse model.

    PubMed

    Zhu, Wenjun; Zhang, Zirui; He, Shihua; Wong, Gary; Banadyga, Logan; Qiu, Xiangguo

    2018-03-01

    Filoviruses, such as Marburg and Ebola viruses, cause severe disease in humans with high case fatality rates and are therefore considered biological threat agents. To date, no licensed vaccine or therapeutic exists for their treatment. T-705 (favipiravir) is a pyrazinecarboxamide derivative that has shown broad antiviral activity against a number of viruses and is clinically licenced in Japan to treat influenza. Here we report the efficacy of T-705 against Marburg virus infection in vitro and in vivo. Notably, oral administration of T-705 beginning one or two days post-infection and continuing for eight days resulted in complete survival of mice that had been intraperitoneally infected with mouse-adapted Marburg virus (variant Angola). Moreover, lower doses of T-705 and higher doses administered later during infection (day 3 or 4 post-infection) showed partial efficacy, with at least half the infected mice surviving. Accordingly, we observed reductions in infectious virus particles and virus RNA levels following drug treatment that appeared to correlate with survival. Our findings suggest that T-705 may be an effective therapeutic against Marburg virus and might be especially promising for use in the event of an outbreak, where it could be orally administered quickly and safely even after exposure. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  5. 29 CFR 503.26 - Civil money penalties-payment and collection.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 3 2012-07-01 2012-07-01 false Civil money penalties-payment and collection. 503.26... SECTION 214(c)(1) OF THE IMMIGRATION AND NATIONALITY ACT Enforcement § 503.26 Civil money penalties—payment and collection. Where a civil money penalty is assessed in a final order by the Administrator, WHD...

  6. 29 CFR 503.26 - Civil money penalties-payment and collection.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 3 2014-07-01 2014-07-01 false Civil money penalties-payment and collection. 503.26... SECTION 214(c)(1) OF THE IMMIGRATION AND NATIONALITY ACT Enforcement § 503.26 Civil money penalties—payment and collection. Where a civil money penalty is assessed in a final order by the Administrator, WHD...

  7. 29 CFR 503.26 - Civil money penalties-payment and collection.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 3 2013-07-01 2013-07-01 false Civil money penalties-payment and collection. 503.26... SECTION 214(c)(1) OF THE IMMIGRATION AND NATIONALITY ACT Enforcement § 503.26 Civil money penalties—payment and collection. Where a civil money penalty is assessed in a final order by the Administrator, WHD...

  8. Sorting of Marburg Virus Surface Protein and Virus Release Take Place at Opposite Surfaces of Infected Polarized Epithelial Cells

    PubMed Central

    Sänger, Christian; Mühlberger, Elke; Ryabchikova, Elena; Kolesnikova, Larissa; Klenk, Hans-Dieter; Becker, Stephan

    2001-01-01

    Marburg virus, a filovirus, causes severe hemorrhagic fever with hitherto poorly understood molecular pathogenesis. We have investigated here the vectorial transport of the surface protein GP of Marburg virus in polarized epithelial cells. To this end, we established an MDCKII cell line that was able to express GP permanently (MDCK-GP). The functional integrity of GP expressed in these cells was analyzed using vesicular stomatitis virus pseudotypes. Further experiments revealed that GP is transported in MDCK-GP cells mainly to the apical membrane and is released exclusively into the culture medium facing the apical membrane. When MDCKII cells were infected with Marburg virus, the majority of GP was also transported to the apical membrane, suggesting that the protein contains an autonomous apical transport signal. Release of infectious progeny virions, however, took place exclusively at the basolateral membrane of the cells. Thus, vectorial budding of Marburg virus is presumably determined by factors other than the surface protein. PMID:11152500

  9. Prevalence of weather sensitivity in Germany and Canada

    NASA Astrophysics Data System (ADS)

    Mackensen, Sylvia; Hoeppe, Peter; Maarouf, Abdel; Tourigny, Pierre; Nowak, Dennis

    2005-01-01

    Several studies have shown that atmospheric conditions can affect well-being or disease, and that some individuals seem to be more sensitive to weather than others. Since epidemiological data on the prevalence of weather-related health effects are lacking, two representative weather sensitivity (WS) surveys were conducted independently in Germany and Canada. The objectives of this paper are: (1) to identify the prevalence of WS in Germany and Canada, (2) to describe weather-related symptoms and the corresponding weather conditions, and (3) to compare the findings in the two countries. In Germany 1,064 citizens (age >16 years) were interviewed in January 2001, and in Canada 1,506 persons (age >18 years) were interviewed in January 1994. The results showed that 19.2% of the German population thought that weather affected their health “to a strong degree,” 35.3% that weather had “some influence on their health” (sum of both = 54.5% weather sensitive), whereas the remaining 45.5% did not consider that weather had an effect on their health status. In Canada 61% of the respondents considered themselves to be sensitive to the weather. The highest prevalence of WS (high + some influence) in Germans was found in the age group older than 60 years (68%), which was almost identical in the Canadian population (69%). The highest frequencies of weather-related symptoms were reported in Germany for stormy weather (30%) and when it became colder (29%). In Canada mainly cold weather (46%), dampness (21%) and rain (20%) were considered to affect health more than other weather types. The most frequent symptoms reported in Germany were headache/migraine (61%), lethargy (47%), sleep disturbances (46%), fatigue (42%), joint pain (40%), irritation (31%), depression (27%), vertigo (26%), concentration problems (26%) and scar pain (23%). Canadian weather-sensitive persons reported colds (29%), psychological effects (28%) and painful joints, muscles or arthritis (10%). In Germany 32

  10. 26. SECOND FLOOR BLDG. 29 LOOKING NORTH. Fafnir Bearing ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    26. SECOND FLOOR BLDG. 29 LOOKING NORTH. - Fafnir Bearing Plant, Bounded on North side by Myrtle Street, on South side by Orange Street, on East side by Booth Street & on West side by Grove Street, New Britain, Hartford County, CT

  11. Therapeutic treatment of Marburg and Ravn virus infection in nonhuman primates with a human monoclonal antibody.

    PubMed

    Mire, Chad E; Geisbert, Joan B; Borisevich, Viktoriya; Fenton, Karla A; Agans, Krystle N; Flyak, Andrew I; Deer, Daniel J; Steinkellner, Herta; Bohorov, Ognian; Bohorova, Natasha; Goodman, Charles; Hiatt, Andrew; Kim, Do H; Pauly, Michael H; Velasco, Jesus; Whaley, Kevin J; Crowe, James E; Zeitlin, Larry; Geisbert, Thomas W

    2017-04-05

    As observed during the 2013-2016 Ebola virus disease epidemic, containment of filovirus outbreaks is challenging and made more difficult by the lack of approved vaccine or therapeutic options. Marburg and Ravn viruses are highly virulent and cause severe and frequently lethal disease in humans. Monoclonal antibodies (mAbs) are a platform technology in wide use for autoimmune and oncology indications. Previously, we described human mAbs that can protect mice from lethal challenge with Marburg virus. We demonstrate that one of these mAbs, MR191-N, can confer a survival benefit of up to 100% to Marburg or Ravn virus-infected rhesus macaques when treatment is initiated up to 5 days post-inoculation. These findings extend the small but growing body of evidence that mAbs can impart therapeutic benefit during advanced stages of disease with highly virulent viruses and could be useful in epidemic settings. Copyright © 2017, American Association for the Advancement of Science.

  12. Case definition for Ebola and Marburg haemorrhagic fevers: a complex challenge for epidemiologists and clinicians.

    PubMed

    Pittalis, Silvia; Fusco, Francesco Maria; Lanini, Simone; Nisii, Carla; Puro, Vincenzo; Lauria, Francesco Nicola; Ippolito, Giuseppe

    2009-10-01

    Viral haemorrhagic fevers (VHFs) represent a challenge for public health because of their epidemic potential, and their possible use as bioterrorism agents poses particular concern. In 1999 the World Health Organization (WHO) proposed a case definition for VHFs, subsequently adopted by other international institutions with the aim of early detection of initial cases/outbreaks in western countries. We applied this case definition to reports of Ebola and Marburg virus infections to estimate its sensitivity to detect cases of the disease. We analyzed clinical descriptions of 795 reported cases of Ebola haemorrhagic fever: only 58.5% of patients met the proposed case definition. A similar figure was obtained reviewing 169 cases of Marburg diseases, of which only 64.5% were in accordance with the case definition. In conclusion, the WHO case definition for hemorrhagic fevers is too specific and has poor sensitivity both for case finding during Ebola or Marburg outbreaks, and for early detection of suspected cases in western countries. It can lead to a hazardous number of false negatives and its use should be discouraged for early detection of cases.

  13. Evaluation of the Protective Efficacy of Recombinant Vesicular Stomatitis Virus Vectors Against Marburg Hemorrhagic Fever in Nonhuman Primate Models

    DTIC Science & Technology

    2007-01-19

    fever in Nonhuman Primate Models" Date d?JO )oi Date )&*7 Date Dissertation and Abstract Approved: Robert Friedm ,M.D. Department of Pathology Committee...thesis manuscript entitled: "Evaluation of the Protective Efficacy of Recombinant Vesicular Stomatitis Virus Vectors Against Marburg Hemorrhagic fever ...stomatitis virus vectors against Marburg hemorrhagic fever in nonhuman primate models By Kathleen Daddario-DiCaprio Dissertation

  14. Crystal Structure of the Marburg Virus VP35 Oligomerization Domain.

    PubMed

    Bruhn, Jessica F; Kirchdoerfer, Robert N; Urata, Sarah M; Li, Sheng; Tickle, Ian J; Bricogne, Gérard; Saphire, Erica Ollmann

    2017-01-15

    Marburg virus (MARV) is a highly pathogenic filovirus that is classified in a genus distinct from that of Ebola virus (EBOV) (genera Marburgvirus and Ebolavirus, respectively). Both viruses produce a multifunctional protein termed VP35, which acts as a polymerase cofactor, a viral protein chaperone, and an antagonist of the innate immune response. VP35 contains a central oligomerization domain with a predicted coiled-coil motif. This domain has been shown to be essential for RNA polymerase function. Here we present crystal structures of the MARV VP35 oligomerization domain. These structures and accompanying biophysical characterization suggest that MARV VP35 is a trimer. In contrast, EBOV VP35 is likely a tetramer in solution. Differences in the oligomeric state of this protein may explain mechanistic differences in replication and immune evasion observed for MARV and EBOV. Marburg virus can cause severe disease, with up to 90% human lethality. Its genome is concise, only producing seven proteins. One of the proteins, VP35, is essential for replication of the viral genome and for evasion of host immune responses. VP35 oligomerizes (self-assembles) in order to function, yet the structure by which it assembles has not been visualized. Here we present two crystal structures of this oligomerization domain. In both structures, three copies of VP35 twist about each other to form a coiled coil. This trimeric assembly is in contrast to tetrameric predictions for VP35 of Ebola virus and to known structures of homologous proteins in the measles, mumps, and Nipah viruses. Distinct oligomeric states of the Marburg and Ebola virus VP35 proteins may explain differences between them in polymerase function and immune evasion. These findings may provide a more accurate understanding of the mechanisms governing VP35's functions and inform the design of therapeutics. Copyright © 2017 American Society for Microbiology.

  15. Inactivation of Lassa, Marburg, and Ebola viruses by gamma irradiation

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

    Elliott, L.H.; McCormick, J.B.; Johnson, K.M.

    1982-10-01

    Because of the cumbersome conditions experienced in a maximum containment laboratory, methods for inactivating highly pathogenic viruses were investigated. The infectivity of Lassa, Marburg, and Ebola viruses was inactivated without altering the immunological activity after radiation with /sup 60/Co gamma rays. At 4 degrees C, Lassa virus was the most difficult to inactivate with a rate of 5.3 X 10(-6) log 50% tissue culture infective dose per rad of /sup 60/Co radiation, as compared with 6.8 X 10(-6) log 50% tissue culture infective dose per rad for Ebola virus and 8.4 X 10(-6) log 50% tissue culture infective dose permore » rad for Marburg virus. Experimental inactivation curves, as well as curves giving the total radiation needed to inactivate a given concentration of any of the three viruses, are presented. We found this method of inactivation to be superior to UV light or beta-propiolactone inactivation and now routinely use it for preparation of material for protein-chemistry studies or for preparation of immunological reagents.« less

  16. Inactivation of Lassa, Marburg, and Ebola viruses by gamma irradiation

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

    Elliott, L.H.; McCormick, J.B.; Johnson, K.M.

    1982-10-01

    Because of the cumbersome conditions experienced in a maximum containment laboratory, methods for inactivating highly pathogenic viruses were investigated. The infectivity of Lassa, Marburg, and Ebola viruses was inactivated without altering the immunological activity after radiation with /sup 60/CO gamma rays. At 4 degrees C, Lassa virus was the most difficult to inactivate with a rate of 5.3 X 10(-6) log 50% tissue culture infective dose per rad of /sup 60/CO radiation, as compared with 6.8 X 10(-6) log 50% tissue culture infective dose per rad for Ebola virus and 8.4 X 10(-6) log 50% tissue culture infective dose permore » rad for Marburg virus. Experimental inactivation curves, as well as curves giving the total radiation needed to inactivate a given concentration of any of the three viruses, are presented. The authors found this method of inactivation to be superior to UV light or beta-propiolactone inactivation and now routinely use it for preparation of material for protein-chemistry studies or for preparation of immunological reagents.« less

  17. Plasma membrane association facilitates conformational changes in the Marburg virus protein VP40 dimer.

    PubMed

    Bhattarai, Nisha; Gc, Jeevan B; Gerstman, Bernard S; Stahelin, Robert V; Chapagain, Prem P

    2017-04-26

    Filovirus infections cause hemorrhagic fever in humans and non-human primates that often results in high fatality rates. The Marburg virus is a lipid-enveloped virus from the Filoviridae family and is closely related to the Ebola virus. The viral matrix layer underneath the lipid envelope is formed by the matrix protein VP40 (VP40), which is also involved in other functions during the viral life-cycle. As in the Ebola virus VP40 (eVP40), the recently determined X-ray crystal structure of the Marburg virus VP40 (mVP40) features loops containing cationic residues that form a lipid binding basic patch. However, the mVP40 basic patch is significantly flatter with a more extended surface than in eVP40, suggesting the possibility of differences in the plasma membrane interactions and phospholipid specificity between the VP40 dimers. In this paper, we report on molecular dynamics simulations that investigate the roles of various residues and lipid types in PM association as well as the conformational changes of the mVP40 dimer facilitated by membrane association. We compared the structural changes of the mVP40 dimer with the mVP40 dimer in both lipid free and membrane associated conditions. Despite the significant structural differences in the crystal structure, the Marburg VP40 dimer is found to adopt a configuration very similar to the Ebola VP40 dimer after associating with the membrane. This conformational rearrangement upon lipid binding allows Marburg VP40 to localize and stabilize at the membrane surface in a manner similar to the Ebola VP40 dimer. Consideration of the structural information in its lipid-interacting condition may be important in targeting mVP40 for novel drugs to inhibit viral budding from the plasma membrane.

  18. Genetic transformation system in the archaebacterium Methanobacterium thermoautotrophicum Marburg.

    PubMed Central

    Worrell, V E; Nagle, D P; McCarthy, D; Eisenbraun, A

    1988-01-01

    A wild-type strain of Methanobacterium thermoautotrophicum Marburg was transformed by DNA from strains resistant to 5-fluorouracil. Recipient cells were grown without selection on gellan gum (GELRITE) plates with DNA. Drug-resistant cells were recovered by replica plating the resulting colonies onto drug plates. Transformation required high-molecular-weight DNA with appropriate markers and was not observed on agar or in liquid media under a variety of conditions. PMID:3422229

  19. Establishment and characterization of a lethal mouse model for the Angola strain of Marburg virus.

    PubMed

    Qiu, Xiangguo; Wong, Gary; Audet, Jonathan; Cutts, Todd; Niu, Yulian; Booth, Stephanie; Kobinger, Gary P

    2014-11-01

    Infections with Marburg virus (MARV) and Ebola virus (EBOV) cause severe hemorrhagic fever in humans and nonhuman primates (NHPs) with fatality rates up to 90%. A number of experimental vaccine and treatment platforms have previously been shown to be protective against EBOV infection. However, the rate of development for prophylactics and therapeutics against MARV has been lower in comparison, possibly because a small-animal model is not widely available. Here we report the development of a mouse model for studying the pathogenesis of MARV Angola (MARV/Ang), the most virulent strain of MARV. Infection with the wild-type virus does not cause disease in mice, but the adapted virus (MARV/Ang-MA) recovered from liver homogenates after 24 serial passages in severe combined immunodeficient (SCID) mice caused severe disease when administered intranasally (i.n.) or intraperitoneally (i.p.). The median lethal dose (LD50) was determined to be 0.015 50% TCID50 (tissue culture infective dose) of MARV/Ang-MA in SCID mice, and i.p. infection at a dose of 1,000× LD50 resulted in death between 6 and 8 days postinfection in SCID mice. Similar results were obtained with immunocompetent BALB/c and C57BL/6 mice challenged i.p. with 2,000× LD50 of MARV/Ang-MA. Virological and pathological analyses of MARV/Ang-MA-infected BALB/c mice revealed that the associated pathology was reminiscent of observations made in NHPs with MARV/Ang. MARV/Ang-MA-infected mice showed most of the clinical hallmarks observed with Marburg hemorrhagic fever, including lymphopenia, thrombocytopenia, marked liver damage, and uncontrolled viremia. Virus titers reached 10(8) TCID50/ml in the blood and between 10(6) and 10(10) TCID50/g tissue in the intestines, kidney, lungs, brain, spleen, and liver. This model provides an important tool to screen candidate vaccines and therapeutics against MARV infections. The Angola strain of Marburg virus (MARV/Ang) was responsible for the largest outbreak ever documented for

  20. Seasonal pulses of Marburg virus circulation in juvenile Rousettus aegyptiacus bats coincide with periods of increased risk of human infection.

    PubMed

    Amman, Brian R; Carroll, Serena A; Reed, Zachary D; Sealy, Tara K; Balinandi, Stephen; Swanepoel, Robert; Kemp, Alan; Erickson, Bobbie Rae; Comer, James A; Campbell, Shelley; Cannon, Deborah L; Khristova, Marina L; Atimnedi, Patrick; Paddock, Christopher D; Crockett, Rebekah J Kent; Flietstra, Timothy D; Warfield, Kelly L; Unfer, Robert; Katongole-Mbidde, Edward; Downing, Robert; Tappero, Jordan W; Zaki, Sherif R; Rollin, Pierre E; Ksiazek, Thomas G; Nichol, Stuart T; Towner, Jonathan S

    2012-01-01

    Marburg virus (family Filoviridae) causes sporadic outbreaks of severe hemorrhagic disease in sub-Saharan Africa. Bats have been implicated as likely natural reservoir hosts based most recently on an investigation of cases among miners infected in 2007 at the Kitaka mine, Uganda, which contained a large population of Marburg virus-infected Rousettus aegyptiacus fruit bats. Described here is an ecologic investigation of Python Cave, Uganda, where an American and a Dutch tourist acquired Marburg virus infection in December 2007 and July 2008. More than 40,000 R. aegyptiacus were found in the cave and were the sole bat species present. Between August 2008 and November 2009, 1,622 bats were captured and tested for Marburg virus. Q-RT-PCR analysis of bat liver/spleen tissues indicated ~2.5% of the bats were actively infected, seven of which yielded Marburg virus isolates. Moreover, Q-RT-PCR-positive lung, kidney, colon and reproductive tissues were found, consistent with potential for oral, urine, fecal or sexual transmission. The combined data for R. aegyptiacus tested from Python Cave and Kitaka mine indicate low level horizontal transmission throughout the year. However, Q-RT-PCR data show distinct pulses of virus infection in older juvenile bats (~six months of age) that temporarily coincide with the peak twice-yearly birthing seasons. Retrospective analysis of historical human infections suspected to have been the result of discrete spillover events directly from nature found 83% (54/65) events occurred during these seasonal pulses in virus circulation, perhaps demonstrating periods of increased risk of human infection. The discovery of two tags at Python Cave from bats marked at Kitaka mine, together with the close genetic linkages evident between viruses detected in geographically distant locations, are consistent with R. aegyptiacus bats existing as a large meta-population with associated virus circulation over broad geographic ranges. These findings provide a

  1. Seasonal Pulses of Marburg Virus Circulation in Juvenile Rousettus aegyptiacus Bats Coincide with Periods of Increased Risk of Human Infection

    PubMed Central

    Amman, Brian R.; Carroll, Serena A.; Reed, Zachary D.; Sealy, Tara K.; Balinandi, Stephen; Swanepoel, Robert; Kemp, Alan; Erickson, Bobbie Rae; Comer, James A.; Campbell, Shelley; Cannon, Deborah L.; Khristova, Marina L.; Atimnedi, Patrick; Paddock, Christopher D.; Kent Crockett, Rebekah J.; Flietstra, Timothy D.; Warfield, Kelly L.; Unfer, Robert; Katongole-Mbidde, Edward; Downing, Robert; Tappero, Jordan W.; Zaki, Sherif R.; Rollin, Pierre E.; Ksiazek, Thomas G.; Nichol, Stuart T.; Towner, Jonathan S.

    2012-01-01

    Marburg virus (family Filoviridae) causes sporadic outbreaks of severe hemorrhagic disease in sub-Saharan Africa. Bats have been implicated as likely natural reservoir hosts based most recently on an investigation of cases among miners infected in 2007 at the Kitaka mine, Uganda, which contained a large population of Marburg virus-infected Rousettus aegyptiacus fruit bats. Described here is an ecologic investigation of Python Cave, Uganda, where an American and a Dutch tourist acquired Marburg virus infection in December 2007 and July 2008. More than 40,000 R. aegyptiacus were found in the cave and were the sole bat species present. Between August 2008 and November 2009, 1,622 bats were captured and tested for Marburg virus. Q-RT-PCR analysis of bat liver/spleen tissues indicated ∼2.5% of the bats were actively infected, seven of which yielded Marburg virus isolates. Moreover, Q-RT-PCR-positive lung, kidney, colon and reproductive tissues were found, consistent with potential for oral, urine, fecal or sexual transmission. The combined data for R. aegyptiacus tested from Python Cave and Kitaka mine indicate low level horizontal transmission throughout the year. However, Q-RT-PCR data show distinct pulses of virus infection in older juvenile bats (∼six months of age) that temporarily coincide with the peak twice-yearly birthing seasons. Retrospective analysis of historical human infections suspected to have been the result of discrete spillover events directly from nature found 83% (54/65) events occurred during these seasonal pulses in virus circulation, perhaps demonstrating periods of increased risk of human infection. The discovery of two tags at Python Cave from bats marked at Kitaka mine, together with the close genetic linkages evident between viruses detected in geographically distant locations, are consistent with R. aegyptiacus bats existing as a large meta-population with associated virus circulation over broad geographic ranges. These findings provide

  2. Performance differences when using 26- and 29-inch-wheel bikes in Swiss National Team cross-country mountain bikers.

    PubMed

    Steiner, Thomas; Müller, Beat; Maier, Thomas; Wehrlin, Jon Peter

    2016-08-01

    The purpose of this study was to analyse the effect of bike type - the 26-inch-wheel bike (26" bike) and the 29-inch-wheel bike (29" bike) - on performance in elite mountain bikers. Ten Swiss National Team athletes (seven males, three females) completed six trials with individual start on a simulated cross-country course with 35 min of active recovery between trials (three trials on a 26" bike and three trials on a 29" bike, alternate order, randomised start-bike). The course consisted of two separate sections expected to favour either the 29" bike (section A) or the 26" bike (section B). For each trial performance, power output, cadence and heart rate were recorded and athletes' experiences were documented. Mean overall performance (time: 304 ± 27 s vs. 311 ± 29 s; P < 0.01) and performance in sections A (P < 0.001) and B (P < 0.05) were better when using the 29" bike. No significant differences were observed for power output, cadence or heart rate. Athletes rated the 29" bike as better for performance in general, passing obstacles and traction. The 29" bike supports superior performance for elite mountain bikers, even on sections supposed to favour the 26" bike.

  3. Generation and characterization of protective antibodies to Marburg virus.

    PubMed

    Froude, Jeffrey W; Pelat, Thibaut; Miethe, Sebastian; Zak, Samantha E; Wec, Anna Z; Chandran, Kartik; Brannan, Jennifer Mary; Bakken, Russell R; Hust, Michael; Thullier, Philippe; Dye, John M

    Marburg virus (MARV) and Ebola virus (EBOV) have been a source of epidemics and outbreaks for several decades. We present here the generation and characterization of the first protective antibodies specific for wild-type MARV. Non-human primates (NHP), cynomolgus macaques, were immunized with viral-replicon particles expressing the glycoproteins (GP) of MARV (Ci67 isolate). An antibody fragment (single-chain variable fragment, scFv) phage display library was built after four immunogen injections, and screened against the GP 1-649 of MARV. Sequencing of 192 selected clones identified 18 clones with distinct V H and V L sequences. Four of these recombinant antibodies (R4A1, R4B11, R4G2, and R3F6) were produced in the scFv-Fc format for in vivo studies. Mice that were challenged with wild-type Marburg virus (Ci67 isolate) receiving 100 µg of scFv-Fc on days -1, 1 and 3 demonstrated protective efficacies ranging from 75-100%. The amino-acid sequences of the scFv-Fcs are similar to those of their human germline counterparts, sharing an identity ranging between 68 and 100% to human germline immunoglobulin. These results demonstrate for the first time that recombinant antibodies offer protection against wild-type MARV, and suggest they may be promising candidates for further therapeutic development especially due to their human homology.

  4. Crystal Structure of Marburg Virus VP40 Reveals a Broad, Basic Patch for Matrix Assembly and a Requirement of the N-Terminal Domain for Immunosuppression.

    PubMed

    Oda, Shun-Ichiro; Noda, Takeshi; Wijesinghe, Kaveesha J; Halfmann, Peter; Bornholdt, Zachary A; Abelson, Dafna M; Armbrust, Tammy; Stahelin, Robert V; Kawaoka, Yoshihiro; Saphire, Erica Ollmann

    2016-02-15

    Marburg virus (MARV), a member of the filovirus family, causes severe hemorrhagic fever with up to 90% lethality. MARV matrix protein VP40 is essential for assembly and release of newly copied viruses and also suppresses immune signaling in the infected cell. Here we report the crystal structure of MARV VP40. We found that MARV VP40 forms a dimer in solution, mediated by N-terminal domains, and that formation of this dimer is essential for budding of virus-like particles. We also found the N-terminal domain to be necessary and sufficient for immune antagonism. The C-terminal domains of MARV VP40 are dispensable for immunosuppression but are required for virus assembly. The C-terminal domains are only 16% identical to those of Ebola virus, differ in structure from those of Ebola virus, and form a distinct broad and flat cationic surface that likely interacts with the cell membrane during virus assembly. Marburg virus, a cousin of Ebola virus, causes severe hemorrhagic fever, with up to 90% lethality seen in recent outbreaks. Molecular structures and visual images of the proteins of Marburg virus are essential for the development of antiviral drugs. One key protein in the Marburg virus life cycle is VP40, which both assembles the virus and suppresses the immune system. Here we provide the molecular structure of Marburg virus VP40, illustrate differences from VP40 of Ebola virus, and reveal surfaces by which Marburg VP40 assembles progeny and suppresses immune function. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  5. Structural Basis for Marburg Virus Neutralization by a Cross-Reactive Human Antibody

    DOE PAGES

    Hashiguchi, Takao; Fusco, Marnie L.; Bornholdt, Zachary A.; ...

    2015-02-26

    The filoviruses, including Marburg and Ebola, express a single glycoprotein on their surface, termed GP, which is responsible for attachment and entry of target cells. Filovirus GPs differ by up to 70% in protein sequence, and no antibodies are yet described that cross-react among them. Here, we present the 3.6 Å crystal structure of Marburg virus GP in complex with a cross-reactive antibody from a human survivor, and a lower resolution structure of the antibody bound to Ebola virus GP. The antibody, MR78, recognizes a GP1 epitope conserved across the filovirus family, which likely represents the binding site of theirmore » NPC1 receptor. Indeed, MR78 blocks binding of the essential NPC1 domain C. We find that these structures and additional small-angle X-ray scattering of mucin-containing MARV and EBOV GPs suggest why such antibodies were not previously elicited in studies of Ebola virus, and provide critical templates for development of immunotherapeutics and inhibitors of entry.« less

  6. Structural basis for Marburg virus neutralization by a cross-reactive human antibody.

    PubMed

    Hashiguchi, Takao; Fusco, Marnie L; Bornholdt, Zachary A; Lee, Jeffrey E; Flyak, Andrew I; Matsuoka, Rei; Kohda, Daisuke; Yanagi, Yusuke; Hammel, Michal; Crowe, James E; Saphire, Erica Ollmann

    2015-02-26

    The filoviruses, including Marburg and Ebola, express a single glycoprotein on their surface, termed GP, which is responsible for attachment and entry of target cells. Filovirus GPs differ by up to 70% in protein sequence, and no antibodies are yet described that cross-react among them. Here, we present the 3.6 Å crystal structure of Marburg virus GP in complex with a cross-reactive antibody from a human survivor, and a lower resolution structure of the antibody bound to Ebola virus GP. The antibody, MR78, recognizes a GP1 epitope conserved across the filovirus family, which likely represents the binding site of their NPC1 receptor. Indeed, MR78 blocks binding of the essential NPC1 domain C. These structures and additional small-angle X-ray scattering of mucin-containing MARV and EBOV GPs suggest why such antibodies were not previously elicited in studies of Ebola virus, and provide critical templates for development of immunotherapeutics and inhibitors of entry. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. How Ebola and Marburg viruses battle the immune system.

    PubMed

    Mohamadzadeh, Mansour; Chen, Lieping; Schmaljohn, Alan L

    2007-07-01

    The filoviruses Ebola and Marburg have emerged in the past decade from relative obscurity to serve now as archetypes for some of the more intriguing and daunting challenges posed by such agents. Public imagination is captured by deadly outbreaks of these viruses and reinforced by the specter of bioterrorism. As research on these agents has accelerated, it has been found increasingly that filoviruses use a combination of familiar and apparently new ways to baffle and battle the immune system. Filoviruses have provided thereby a new lens through which to examine the immune system itself.

  8. Formate auxotroph of Methanobacterium thermoautotrophicum Marburg.

    PubMed Central

    Tanner, R S; McInerney, M J; Nagle, D P

    1989-01-01

    A formate-requiring auxotroph of Methanobacterium thermoautotrophicum Marburg was isolated after hydroxylamine mutagenesis and bacitracin selection. The requirement for formate is unique and specific; combined pools of other volatile fatty acids, amino acids, vitamins, and nitrogen bases did not substitute for formate. Compared with those of the wild type, cell extracts of the formate auxotroph were deficient in formate dehydrogenase activity, but cells of all of the strains examined catalyzed a formate-carbon dioxide exchange activity. All of the strains examined took up a small amount (200 to 260 mumol/liter) of formate (3 mM) added to medium. The results of the study of this novel auxotroph indicate a role for formate in biosynthetic reactions in this methanogen. Moreover, because methanogenesis from H2-CO2 is not impaired in the mutant, free formate is not an intermediate in the reduction of CO2 to CH4. PMID:2687241

  9. Human Survivors of Disease Outbreaks Caused by Ebola or Marburg Virus Exhibit Cross-Reactive and Long-Lived Antibody Responses.

    PubMed

    Natesan, Mohan; Jensen, Stig M; Keasey, Sarah L; Kamata, Teddy; Kuehne, Ana I; Stonier, Spencer W; Lutwama, Julius Julian; Lobel, Leslie; Dye, John M; Ulrich, Robert G

    2016-08-01

    A detailed understanding of serological immune responses to Ebola and Marburg virus infections will facilitate the development of effective diagnostic methods, therapeutics, and vaccines. We examined antibodies from Ebola or Marburg survivors 1 to 14 years after recovery from disease, by using a microarray that displayed recombinant nucleoprotein (NP), viral protein 40 (VP40), envelope glycoprotein (GP), and inactivated whole virions from six species of filoviruses. All three outbreak cohorts exhibited significant antibody responses to antigens from the original infecting species and a pattern of additional filoviruses that varied by outbreak. NP was the most cross-reactive antigen, while GP was the most specific. Antibodies from survivors of infections by Marburg marburgvirus (MARV) species were least cross-reactive, while those from survivors of infections by Sudan virus (SUDV) species exhibited the highest cross-reactivity. Based on results revealed by the protein microarray, persistent levels of antibodies to GP, NP, and VP40 were maintained for up to 14 years after infection, and survival of infection caused by one species imparted cross-reactive antibody responses to other filoviruses. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  10. USSR Space Life Sciences Digest. Index to issues 26-29

    NASA Technical Reports Server (NTRS)

    Stone, Lydia Razran (Editor)

    1991-01-01

    This bibliography provides an index to issues 26 through 29 of the USSR Space Life Sciences Digest. There are two sections. The first section lists bibliographic citations of abstracts in these issues, grouped by topic area categories. The second section provides a key word index for the same abstracts. The topic categories include exobiology, space medicine and psychology, human performance and man-machine systems, various life/body systems, human behavior and adaptation, biospherics, and others.

  11. [A report on clinical PET activities in Germany].

    PubMed

    Tashiro, M; Kubota, K; Itoh, M; Sasaki, H; Moser, E

    1999-09-01

    Clinical diagnostic procedure using positron emission tomography (PET) requires high costs. To promote clinical use of PET, sociomedical evaluation is necessary. In this paper, sociomedical situations concerning clinical use of PET in Germany is reported. Some comparisons are made between Japan and this country putting emphases on several points such as 1) number of cyclotron and PET facilities, 2) social restriction to transportation of radioisotopes, 3) activities of satellite PET facilities, and 4) clinical indications for PET studies. Number of cyclotron was larger in Japan (29) than in Germany (17), but number of PET facilities was larger in Germany (47) than in Japan (29). The reason seems that in Germany transportation and buying of radioisotopes is less restricted. Hence, more than half of PET facilities in Germany are "satellite facilities" which do not have their own cyclotrons. Radioisotope distribution seems to serve as a backbone of "satellite concept." Additionally in Germany, list of clinical indications for PET study is almost completed and now is widely in applied to most cases. To promote clinical use of PET in Japan, the German system might serve as an important socioeconomic model in Europe instead of the United States.

  12. Ebola virus disease and Marburg disease in pregnancy: a review and management considerations for filovirus infection.

    PubMed

    Bebell, Lisa M; Riley, Laura E

    2015-06-01

    The largest-ever recorded outbreak of viral hemorrhagic fever is ongoing. As a result of the epidemic and rural nature of outbreaks, little is published about the Filovirus infections Ebola virus disease and Marburg disease in pregnancy. This review of viral hemorrhagic fever focusing on Marburg and Ebola uses knowledge of disease in nonpregnant individuals and pregnancy-specific data to inform management for pregnant women. Filovirus infection presentation is similar between pregnant and nonpregnant patients, although infections may be more severe in pregnancy. Although labeled as hemorrhagic fevers, Marburg and Ebola do not commonly cause gross bleeding and should be conceptualized as diseases of high gastrointestinal losses. Early, aggressive supportive care is the mainstay of Filovirus infection management with massive fluid resuscitation as the key management principle. Patients often require 5-10 L or more per day of intravenous or oral fluid to maintain circulating blood volume in the setting of ongoing gastrointestinal loss. Fluid shifts warrant aggressive monitoring and correction of potassium levels and acid-base disturbances to prevent life-threatening arrhythmias and metabolic complications. Regardless of maternal survival, fetal loss rates are nearly 100% in Filovirus infection, likely resulting from unchecked transplacental and hematogenous viral spread. High fetal loss rates support the placenta as a difficult-to-eradicate Filovirus infection reservoir. In conclusion, the management of Filovirus infection in pregnancy should focus on stabilizing the mother with intensive monitoring and aggressive fluid and electrolyte repletion as well as maintaining strict infection control to minimize transmission to others.

  13. Live-cell imaging of Marburg virus-infected cells uncovers actin-dependent transport of nucleocapsids over long distances

    PubMed Central

    Schudt, Gordian; Kolesnikova, Larissa; Dolnik, Olga; Sodeik, Beate; Becker, Stephan

    2013-01-01

    Transport of large viral nucleocapsids from replication centers to assembly sites requires contributions from the host cytoskeleton via cellular adaptor and motor proteins. For the Marburg and Ebola viruses, related viruses that cause severe hemorrhagic fevers, the mechanism of nucleocapsid transport remains poorly understood. Here we developed and used live-cell imaging of fluorescently labeled viral and host proteins to characterize the dynamics and molecular requirements of nucleocapsid transport in Marburg virus-infected cells under biosafety level 4 conditions. The study showed a complex actin-based transport of nucleocapsids over long distances from the viral replication centers to the budding sites. Only after the nucleocapsids had associated with the matrix viral protein VP40 at the plasma membrane were they recruited into filopodia and cotransported with host motor myosin 10 toward the budding sites at the tip or side of the long cellular protrusions. Three different transport modes and velocities were identified: (i) Along actin filaments in the cytosol, nucleocapsids were transported at ∼200 nm/s; (ii) nucleocapsids migrated from one actin filament to another at ∼400 nm/s; and (iii) VP40-associated nucleocapsids moved inside filopodia at 100 nm/s. Unique insights into the spatiotemporal dynamics of nucleocapsids and their interaction with the cytoskeleton and motor proteins can lead to novel classes of antivirals that interfere with the trafficking and subsequent release of the Marburg virus from infected cells. PMID:23940347

  14. Live-cell imaging of Marburg virus-infected cells uncovers actin-dependent transport of nucleocapsids over long distances.

    PubMed

    Schudt, Gordian; Kolesnikova, Larissa; Dolnik, Olga; Sodeik, Beate; Becker, Stephan

    2013-08-27

    Transport of large viral nucleocapsids from replication centers to assembly sites requires contributions from the host cytoskeleton via cellular adaptor and motor proteins. For the Marburg and Ebola viruses, related viruses that cause severe hemorrhagic fevers, the mechanism of nucleocapsid transport remains poorly understood. Here we developed and used live-cell imaging of fluorescently labeled viral and host proteins to characterize the dynamics and molecular requirements of nucleocapsid transport in Marburg virus-infected cells under biosafety level 4 conditions. The study showed a complex actin-based transport of nucleocapsids over long distances from the viral replication centers to the budding sites. Only after the nucleocapsids had associated with the matrix viral protein VP40 at the plasma membrane were they recruited into filopodia and cotransported with host motor myosin 10 toward the budding sites at the tip or side of the long cellular protrusions. Three different transport modes and velocities were identified: (i) Along actin filaments in the cytosol, nucleocapsids were transported at ∼200 nm/s; (ii) nucleocapsids migrated from one actin filament to another at ∼400 nm/s; and (iii) VP40-associated nucleocapsids moved inside filopodia at 100 nm/s. Unique insights into the spatiotemporal dynamics of nucleocapsids and their interaction with the cytoskeleton and motor proteins can lead to novel classes of antivirals that interfere with the trafficking and subsequent release of the Marburg virus from infected cells.

  15. PREFACE: Selected invited contributions from the International Conference on Magnetism (Karlsruhe, Germany, 26-31 July 2009) Selected invited contributions from the International Conference on Magnetism (Karlsruhe, Germany, 26-31 July 2009)

    NASA Astrophysics Data System (ADS)

    Goll, Gernot; Löhneysen, Hilbert v.; Loidl, Alois; Pruschke, Thomas; Richter, Manuel; Schultz, Ludwig; Sürgers, Christoph; Wosnitza, Jochen

    2010-04-01

    The International Conference on Magnetism 2009 (ICM 2009) was held in Karlsruhe, Germany, from 26 to 31 July 2009. Previous conferences in this series were organized in Edinburgh, UK (1991), Warsaw, Poland (1994), Cairns, Australia (1997), Recife, Brazil (2000), Rome, Italy (2003), and Kyoto, Japan (2006). As with previous ICM conferences, the annual Conference on Strongly Correlated Electron Systems (SCES) was integrated into ICM 2009. The topics presented at ICM 2009 were strongly correlated electron systems, quantum and classical spin systems, magnetic structures and interactions, magnetization dynamics and micromagnetics, spin-dependent transport, spin electronics, magnetic thin films, particles and nanostructures, soft and hard magnetic materials and their applications, novel materials and device applications, magnetic recording and memories, measuring techniques and instrumentation, as well as interdisciplinary topics. We are grateful to the International Advisory Committee for their help in coordinating an attractive program encompassing practically all aspects of magnetism, both experimentally and theoretically. The Program Committee comprised A Loidl, Germany (Chair), M A Continentino, Brazil, D E Dahlberg, USA, D Givord, France, G Güntherodt, Germany, H Mikeska, Germany, D Kaczorowski, Poland, Ching-Ray Chang, South Korea, I Mertig, Germany, D Vollhardt, Germany, and E F Wassermann, Germany. E F Wassermann was also head of the National Organizing Committee. His help is gratefully acknowledged. The scientific program started on Monday 27 July 2009 with opening addresses by the Conference Chairman, the Deputy Mayor of Karlsruhe, Ms M Mergen and the Chairman of the Executive Board of Forschungszentrum Karlsruhe, E Umbach. ICM 2009 was attended by the Nobel Laureates P W Anderson, A Fert and P Grünberg who gave plenary talks. A special highlight was the presentation of the Magnetism Award and Néel Medal to S S P Parkin who also presented his newest results

  16. Ebola and Marburg virus vaccines.

    PubMed

    Reynolds, Pierce; Marzi, Andrea

    2017-08-01

    The filoviruses, Ebola virus (EBOV), and Marburg virus (MARV), are among the most pathogenic viruses known to man and the causative agents of viral hemorrhagic fever outbreaks in Africa with case fatality rates of up to 90%. Nearly 30,000 infections were observed in the latest EBOV epidemic in West Africa; previous outbreaks were much smaller, typically only affecting less than a few hundred people. Compared to other diseases such as AIDS or Malaria with millions of cases annually, filovirus hemorrhagic fever (FHF) is one of the neglected infectious diseases. There are no licensed vaccines or therapeutics available to treat EBOV and MARV infections; therefore, these pathogens can only be handled in maximum containment laboratories and are classified as select agents. Under these limitations, a very few laboratories worldwide conducted basic research and countermeasure development for EBOV and MARV since their respective discoveries in 1967 (MARV) and 1976 (EBOV). In this review, we discuss several vaccine platforms against EBOV and MARV, which have been assessed for their protective efficacy in animal models of FHF. The focus is on the most promising approaches, which were accelerated in clinical development (phase I-III trials) during the EBOV epidemic in West Africa.

  17. 29 CFR 783.26 - The section 6(b)(2) minimum wage requirement.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false The section 6(b)(2) minimum wage requirement. 783.26... The section 6(b)(2) minimum wage requirement. Section 6(b), with paragraph (2) thereof, requires the... prescribed by” paragraph (1) of the subsection is the minimum wage rate applicable according to the schedule...

  18. 29 CFR 5.26 - “* * * contribution irrevocably made * * * to a trustee or to a third person”.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true â* * * contribution irrevocably made * * * to a trustee or to a third personâ. 5.26 Section 5.26 Labor Office of the Secretary of Labor LABOR STANDARDS PROVISIONS APPLICABLE TO CONTRACTS COVERING FEDERALLY FINANCED AND ASSISTED CONSTRUCTION (ALSO LABOR...

  19. Lassa and Marburg viruses elicit distinct host transcriptional responses early after infection.

    PubMed

    Caballero, Ignacio S; Yen, Judy Y; Hensley, Lisa E; Honko, Anna N; Goff, Arthur J; Connor, John H

    2014-11-06

    Lassa virus and Marburg virus are two causative agents of viral hemorrhagic fever. Their diagnosis is difficult because patients infected with either pathogen present similar nonspecific symptoms early after infection. Current diagnostic tests are based on detecting viral proteins or nucleic acids in the blood, but these cannot be found during the early stages of disease, before the virus starts replicating in the blood. Using the transcriptional response of the host during infection can lead to earlier diagnoses compared to those of traditional methods. In this study, we use RNA sequencing to obtain a high-resolution view of the in vivo transcriptional dynamics of peripheral blood mononuclear cells (PBMCs) throughout both types of infection. We report a subset of host mRNAs, including heat-shock proteins like HSPA1B, immunoglobulins like IGJ, and cell adhesion molecules like SIGLEC1, whose differences in expression are strong enough to distinguish Lassa infection from Marburg infection in non-human primates. We have validated these infection-specific expression differences by using microarrays on a larger set of samples, and by quantifying the expression of individual genes using RT-PCR. These results suggest that host transcriptional signatures are correlated with specific viral infections, and that they can be used to identify highly pathogenic viruses during the early stages of disease, before standard detection methods become effective.

  20. Ebola and Marburg Hemorrhagic Fevers: Neglected Tropical Diseases?

    PubMed Central

    MacNeil, Adam; Rollin, Pierre E.

    2012-01-01

    Ebola hemorrhagic fever (EHF) and Marburg hemorrhagic fever (MHF) are rare viral diseases, endemic to central Africa. The overall burden of EHF and MHF is small in comparison to the more common protozoan, helminth, and bacterial diseases typically referred to as neglected tropical diseases (NTDs). However, EHF and MHF outbreaks typically occur in resource-limited settings, and many aspects of these outbreaks are a direct consequence of impoverished conditions. We will discuss aspects of EHF and MHF disease, in comparison to the “classic” NTDs, and examine potential ways forward in the prevention and control of EHF and MHF in sub-Saharan Africa, as well as examine the potential for application of novel vaccines or antiviral drugs for prevention or control of EHF and MHF among populations at highest risk for disease. PMID:22761967

  1. Mannose-binding lectin binds to Ebola and Marburg envelope glycoproteins, resulting in blocking of virus interaction with DC-SIGN and complement-mediated virus neutralization.

    PubMed

    Ji, Xin; Olinger, Gene G; Aris, Sheena; Chen, Ying; Gewurz, Henry; Spear, Gregory T

    2005-09-01

    Mannose-binding lectin (MBL), a serum lectin that mediates innate immune functions including activation of the lectin complement pathway, binds to carbohydrates expressed on some viral glycoproteins. In this study, the ability of MBL to bind to virus particles pseudotyped with Ebola and Marburg envelope glycoproteins was evaluated. Virus particles bearing either Ebola (Zaire strain) or Marburg (Musoke strain) envelope glycoproteins bound at significantly higher levels to immobilized MBL compared with virus particles pseudotyped with vesicular stomatitis virus glycoprotein or with no virus glycoprotein. As observed in previous studies, Ebola-pseudotyped virus bound to cells expressing the lectin DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin). However, pre-incubation of virus with MBL blocked DC-SIGN-mediated binding to cells, suggesting that the two lectins bind at the same or overlapping sites on the Ebola glycoprotein. Neutralization experiments showed that virus pseudotyped with Ebola or Marburg (Musoke) glycoprotein was neutralized by complement, while the Marburg (Ravn strain) glycoprotein-pseudotyped virus was less sensitive to neutralization. Neutralization was partially mediated through the lectin complement pathway, since a complement source deficient in MBL was significantly less effective at neutralizing viruses pseudotyped with filovirus glycoproteins and addition of purified MBL to the MBL-deficient complement increased neutralization. These experiments demonstrated that MBL binds to filovirus envelope glycoproteins resulting in important biological effects and suggest that MBL can interact with filoviruses during infection in humans.

  2. INSTRUCTIONAL TELEVISION IN GERMANY.

    ERIC Educational Resources Information Center

    International Central Inst. for Youth and Educational Television, Munich (West Germany).

    DISCUSSIONS HELD AT THE BERLIN CONGRESS ON INSTRUCTIONAL AND EDUCATIONAL TELEVISION (SEPTEMBER 27-29, 1966) ARE BRIEFLY SUMMARIZED. THIS DOCUMENT ALSO LISTS RESEARCH PROJECTS IN INSTRUCTIONAL TELEVISION IN GERMANY, DESCRIBES THE BAVARIAN RADIO INSTRUCTIONAL TELEVISION PROGRAM, SUMMARIZES THE OPINIONS OF THE GERMAN PRESS ON INSTRUCTIONAL…

  3. One-Step Reverse Transcription-Polymerase Chain Reaction for Ebola and Marburg Viruses.

    PubMed

    Park, Sun-Whan; Lee, Ye-Ji; Lee, Won-Ja; Jee, Youngmee; Choi, WooYoung

    2016-06-01

    Ebola and Marburg viruses (EBOVs and MARVs, respectively) are causative agents of severe hemorrhagic fever with high mortality rates in humans and nonhuman primates. In 2014, there was a major Ebola outbreak in various countries in West Africa, including Guinea, Liberia, Republic of Sierra Leone, and Nigeria. EBOV and MARV are clinically difficult to diagnose and distinguish from other African epidemic diseases. Therefore, in this study, we aimed to develop a method for rapid identification of the virus to prevent the spread of infection. We established a conventional one-step reverse transcription-polymerase chain reaction (RT-PCR) assay for these pathogens based on the Superscript Reverse Transcriptase-Platinum Taq polymerase enzyme mixture. All assays were thoroughly optimized using in vitro-transcribed RNA. We designed seven primer sets of nucleocapsid protein (NP) genes based on sequences from seven filoviruses, including five EBOVs and two MARVs. To evaluate the sensitivity of the RT-PCR assay for each filovirus, 10-fold serial dilutions of synthetic viral RNA transcripts of EBOV or MARV NP genes were used to assess detection limits of viral RNA copies. The potential for these primers to cross react with other filoviruses was also examined. The results showed that the primers were specific for individual genotype detection in the examined filoviruses. The assay established in this study may facilitate rapid, reliable laboratory diagnosis in suspected cases of Ebola and Marburg hemorrhagic fevers.

  4. Comparison of the Pathogenesis of the Angola and Ravn Strains of Marburg Virus in the Outbred Guinea Pig Model.

    PubMed

    Cross, Robert W; Fenton, Karla A; Geisbert, Joan B; Ebihara, Hideki; Mire, Chad E; Geisbert, Thomas W

    2015-10-01

    Phylogenetic comparisons of known Marburg virus (MARV) strains reveal 2 distinct genetic lineages: Ravn and the Lake Victoria Marburg complex (eg, Musoke, Popp, and Angola strains). Nucleotide variances of >20% between Ravn and other MARV genomes suggest that differing virulence between lineages may accompany this genetic divergence. To date, there exists limited systematic experimental evidence of pathogenic differences between MARV strains. Uniformly lethal outbred guinea pig models of MARV-Angola (MARV-Ang) and MARV-Ravn (MARV-Rav) were developed by serial adaptation. Changes in genomic sequence, weight, temperature, histopathologic findings, immunohistochemical findings, hematologic profiles, circulating biochemical enzyme levels, coagulation parameters, viremia levels, cytokine levels, eicanosoid levels, and nitric oxide production were compared between strains. MARV-Rav infection resulted in delayed increases in circulating inflammatory and prothrombotic elements, notably lower viremia levels, less severe histologic alterations, and a delay in mean time to death, compared with MARV-Ang infection. Both strains produced more marked coagulation abnormalities than previously seen in MARV-infected mice or inbred guinea pigs. Although both strains exhibit great similarity to pathogenic markers of human and nonhuman primate MARV infection, these data highlight several key differences in pathogenicity that may serve to guide the choice of strain and model used for development of vaccines or therapeutics for Marburg hemorrhagic fever. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  5. Crystal Structure of the Marburg Virus VP35 Oligomerization Domain

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

    Bruhn, Jessica F.; Kirchdoerfer, Robert N.; Urata, Sarah M.

    ABSTRACT Marburg virus (MARV) is a highly pathogenic filovirus that is classified in a genus distinct from that of Ebola virus (EBOV) (generaMarburgvirusandEbolavirus, respectively). Both viruses produce a multifunctional protein termed VP35, which acts as a polymerase cofactor, a viral protein chaperone, and an antagonist of the innate immune response. VP35 contains a central oligomerization domain with a predicted coiled-coil motif. This domain has been shown to be essential for RNA polymerase function. Here we present crystal structures of the MARV VP35 oligomerization domain. These structures and accompanying biophysical characterization suggest that MARV VP35 is a trimer. In contrast, EBOVmore » VP35 is likely a tetramer in solution. Differences in the oligomeric state of this protein may explain mechanistic differences in replication and immune evasion observed for MARV and EBOV. IMPORTANCEMarburg virus can cause severe disease, with up to 90% human lethality. Its genome is concise, only producing seven proteins. One of the proteins, VP35, is essential for replication of the viral genome and for evasion of host immune responses. VP35 oligomerizes (self-assembles) in order to function, yet the structure by which it assembles has not been visualized. Here we present two crystal structures of this oligomerization domain. In both structures, three copies of VP35 twist about each other to form a coiled coil. This trimeric assembly is in contrast to tetrameric predictions for VP35 of Ebola virus and to known structures of homologous proteins in the measles, mumps, and Nipah viruses. Distinct oligomeric states of the Marburg and Ebola virus VP35 proteins may explain differences between them in polymerase function and immune evasion. These findings may provide a more accurate understanding of the mechanisms governing VP35's functions and inform the design of therapeutics.« less

  6. Differential transcriptional responses to Ebola and Marburg virus infection in bat and human cells.

    PubMed

    Hölzer, Martin; Krähling, Verena; Amman, Fabian; Barth, Emanuel; Bernhart, Stephan H; Carmelo, Victor A O; Collatz, Maximilian; Doose, Gero; Eggenhofer, Florian; Ewald, Jan; Fallmann, Jörg; Feldhahn, Lasse M; Fricke, Markus; Gebauer, Juliane; Gruber, Andreas J; Hufsky, Franziska; Indrischek, Henrike; Kanton, Sabina; Linde, Jörg; Mostajo, Nelly; Ochsenreiter, Roman; Riege, Konstantin; Rivarola-Duarte, Lorena; Sahyoun, Abdullah H; Saunders, Sita J; Seemann, Stefan E; Tanzer, Andrea; Vogel, Bertram; Wehner, Stefanie; Wolfinger, Michael T; Backofen, Rolf; Gorodkin, Jan; Grosse, Ivo; Hofacker, Ivo; Hoffmann, Steve; Kaleta, Christoph; Stadler, Peter F; Becker, Stephan; Marz, Manja

    2016-10-07

    The unprecedented outbreak of Ebola in West Africa resulted in over 28,000 cases and 11,000 deaths, underlining the need for a better understanding of the biology of this highly pathogenic virus to develop specific counter strategies. Two filoviruses, the Ebola and Marburg viruses, result in a severe and often fatal infection in humans. However, bats are natural hosts and survive filovirus infections without obvious symptoms. The molecular basis of this striking difference in the response to filovirus infections is not well understood. We report a systematic overview of differentially expressed genes, activity motifs and pathways in human and bat cells infected with the Ebola and Marburg viruses, and we demonstrate that the replication of filoviruses is more rapid in human cells than in bat cells. We also found that the most strongly regulated genes upon filovirus infection are chemokine ligands and transcription factors. We observed a strong induction of the JAK/STAT pathway, of several genes encoding inhibitors of MAP kinases (DUSP genes) and of PPP1R15A, which is involved in ER stress-induced cell death. We used comparative transcriptomics to provide a data resource that can be used to identify cellular responses that might allow bats to survive filovirus infections.

  7. Evasion of interferon responses by Ebola and Marburg viruses.

    PubMed

    Basler, Christopher F; Amarasinghe, Gaya K

    2009-09-01

    The filoviruses, Ebola virus (EBOV) and Marburg virus (MARV), cause frequently lethal viral hemorrhagic fever. These infections induce potent cytokine production, yet these host responses fail to prevent systemic virus replication. Consistent with this, filoviruses have been found to encode proteins VP35 and VP24 that block host interferon (IFN)-alpha/beta production and inhibit signaling downstream of the IFN-alpha/beta and the IFN-gamma receptors, respectively. VP35, which is a component of the viral nucleocapsid complex and plays an essential role in viral RNA synthesis, acts as a pseudosubstrate for the cellular kinases IKK-epsilon and TBK-1, which phosphorylate and activate interferon regulatory factor 3 (IRF-3) and interferon regulatory factor 7 (IRF-7). VP35 also promotes SUMOylation of IRF-7, repressing IFN gene transcription. In addition, VP35 is a dsRNA-binding protein, and mutations that disrupt dsRNA binding impair VP35 IFN-antagonist activity while leaving its RNA replication functions intact. The phenotypes of recombinant EBOV bearing mutant VP35s unable to inhibit IFN-alpha/beta demonstrate that VP35 IFN-antagonist activity is critical for full virulence of these lethal pathogens. The structure of the VP35 dsRNA-binding domain, which has recently become available, is expected to provide insight into how VP35 IFN-antagonist and dsRNA-binding functions are related. The EBOV VP24 protein inhibits IFN signaling through an interaction with select host cell karyopherin-alpha proteins, preventing the nuclear import of otherwise activated STAT1. It remains to be determined to what extent VP24 may also modulate the nuclear import of other host cell factors and to what extent this may influence the outcome of infection. Notably, the Marburg virus VP24 protein does not detectably block STAT1 nuclear import, and, unlike EBOV, MARV infection inhibits STAT1 and STAT2 phosphorylation. Thus, despite their similarities, there are fundamental differences by which

  8. Post-exposure treatments for Ebola and Marburg virus infections.

    PubMed

    Cross, Robert W; Mire, Chad E; Feldmann, Heinz; Geisbert, Thomas W

    2018-06-01

    The filoviruses - Ebola virus and Marburg virus - cause lethal haemorrhagic fever in humans and non-human primates (NHPs). Filoviruses present a global health threat both as naturally acquired diseases and as potential agents of bioterrorism. In the recent 2013-2016 outbreak of Ebola virus, the most promising therapies for post-exposure use with demonstrated efficacy in the gold-standard NHP models of filovirus disease were unable to show statistically significant protection in patients infected with Ebola virus. This Review briefly discusses these failures and what has been learned from these experiences, and summarizes the current status of post-exposure medical countermeasures in development, including antibodies, small interfering RNA and small molecules. We outline how our current knowledge could be applied to the identification of novel interventions and ways to use interventions more effectively.

  9. Determination of Specific Antibody Responses to the Six Species of Ebola and Marburg Viruses by Multiplexed Protein Microarrays

    PubMed Central

    Kamata, Teddy; Natesan, Mohan; Warfield, Kelly; Aman, M. Javad

    2014-01-01

    Infectious hemorrhagic fevers caused by the Marburg and Ebola filoviruses result in human mortality rates of up to 90%, and there are no effective vaccines or therapeutics available for clinical use. The highly infectious and lethal nature of these viruses highlights the need for reliable and sensitive diagnostic methods. We assembled a protein microarray displaying nucleoprotein (NP), virion protein 40 (VP40), and glycoprotein (GP) antigens from isolates representing the six species of filoviruses for use as a surveillance and diagnostic platform. Using the microarrays, we examined serum antibody responses of rhesus macaques vaccinated with trivalent (GP, NP, and VP40) virus-like particles (VLP) prior to infection with the Marburg virus (MARV) (i.e., Marburg marburgvirus) or the Zaire virus (ZEBOV) (i.e., Zaire ebolavirus). The microarray-based assay detected a significant increase in antigen-specific IgG resulting from immunization, while a greater level of antibody responses resulted from challenge of the vaccinated animals with ZEBOV or MARV. Further, while antibody cross-reactivities were observed among NPs and VP40s of Ebola viruses, antibody recognition of GPs was very specific. The performance of mucin-like domain fragments of GP (GP mucin) expressed in Escherichia coli was compared to that of GP ectodomains produced in eukaryotic cells. Based on results with ZEBOV and MARV proteins, antibody recognition of GP mucins that were deficient in posttranslational modifications was comparable to that of the eukaryotic cell-expressed GP ectodomains in assay performance. We conclude that the described protein microarray may translate into a sensitive assay for diagnosis and serological surveillance of infections caused by multiple species of filoviruses. PMID:25230936

  10. Determination of specific antibody responses to the six species of ebola and Marburg viruses by multiplexed protein microarrays.

    PubMed

    Kamata, Teddy; Natesan, Mohan; Warfield, Kelly; Aman, M Javad; Ulrich, Robert G

    2014-12-01

    Infectious hemorrhagic fevers caused by the Marburg and Ebola filoviruses result in human mortality rates of up to 90%, and there are no effective vaccines or therapeutics available for clinical use. The highly infectious and lethal nature of these viruses highlights the need for reliable and sensitive diagnostic methods. We assembled a protein microarray displaying nucleoprotein (NP), virion protein 40 (VP40), and glycoprotein (GP) antigens from isolates representing the six species of filoviruses for use as a surveillance and diagnostic platform. Using the microarrays, we examined serum antibody responses of rhesus macaques vaccinated with trivalent (GP, NP, and VP40) virus-like particles (VLP) prior to infection with the Marburg virus (MARV) (i.e., Marburg marburgvirus) or the Zaire virus (ZEBOV) (i.e., Zaire ebolavirus). The microarray-based assay detected a significant increase in antigen-specific IgG resulting from immunization, while a greater level of antibody responses resulted from challenge of the vaccinated animals with ZEBOV or MARV. Further, while antibody cross-reactivities were observed among NPs and VP40s of Ebola viruses, antibody recognition of GPs was very specific. The performance of mucin-like domain fragments of GP (GP mucin) expressed in Escherichia coli was compared to that of GP ectodomains produced in eukaryotic cells. Based on results with ZEBOV and MARV proteins, antibody recognition of GP mucins that were deficient in posttranslational modifications was comparable to that of the eukaryotic cell-expressed GP ectodomains in assay performance. We conclude that the described protein microarray may translate into a sensitive assay for diagnosis and serological surveillance of infections caused by multiple species of filoviruses. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  11. The VP35 and VP40 proteins of filoviruses. Homology between Marburg and Ebola viruses.

    PubMed

    Bukreyev, A A; Volchkov, V E; Blinov, V M; Netesov, S V

    1993-05-03

    The fragments of genomic RNA sequences of Marburg (MBG) and Ebola (EBO) viruses are reported. These fragments were found to encode the VP35 and VP40 proteins. The canonic sequences were revealed before and after each open reading frame. It is suggested that these sequences are mRNA extremities and at the same time the regulatory elements for mRNA transcription. Homology between the MBG and EBO proteins was discovered.

  12. Filovirus pathogenesis and immune evasion: insights from Ebola virus and Marburg virus.

    PubMed

    Messaoudi, Ilhem; Amarasinghe, Gaya K; Basler, Christopher F

    2015-11-01

    Ebola viruses and Marburg viruses, members of the filovirus family, are zoonotic pathogens that cause severe disease in people, as highlighted by the latest Ebola virus epidemic in West Africa. Filovirus disease is characterized by uncontrolled virus replication and the activation of host responses that contribute to pathogenesis. Underlying these phenomena is the potent suppression of host innate antiviral responses, particularly the type I interferon response, by viral proteins, which allows high levels of viral replication. In this Review, we describe the mechanisms used by filoviruses to block host innate immunity and discuss the links between immune evasion and filovirus pathogenesis.

  13. IEA Wind Task 26. Wind Technology, Cost, and Performance Trends in Denmark, Germany, Ireland, Norway, the European Union, and the United States: 2007–2012

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

    Vitina, Aisma; Lüers, Silke; Wallasch, Anna-Kathrin

    The International Energy Agency Implementing Agreement for cooperation in Research, Development, and Deployment of Wind Energy Systems (IEA Wind) Task 26—The Cost of Wind Energy represents an international collaboration dedicated to exploring past, present and future cost of wind energy. This report provides an overview of recent trends in wind plant technology, cost, and performance in those countries that are currently represented by participating organizations in IEA Wind Task 26: Denmark, Germany, Ireland, Norway, and the United States as well as the European Union.

  14. Mechanism of human antibody-mediated neutralization of Marburg virus.

    PubMed

    Flyak, Andrew I; Ilinykh, Philipp A; Murin, Charles D; Garron, Tania; Shen, Xiaoli; Fusco, Marnie L; Hashiguchi, Takao; Bornholdt, Zachary A; Slaughter, James C; Sapparapu, Gopal; Klages, Curtis; Ksiazek, Thomas G; Ward, Andrew B; Saphire, Erica Ollmann; Bukreyev, Alexander; Crowe, James E

    2015-02-26

    The mechanisms by which neutralizing antibodies inhibit Marburg virus (MARV) are not known. We isolated a panel of neutralizing antibodies from a human MARV survivor that bind to MARV glycoprotein (GP) and compete for binding to a single major antigenic site. Remarkably, several of the antibodies also bind to Ebola virus (EBOV) GP. Single-particle EM structures of antibody-GP complexes reveal that all of the neutralizing antibodies bind to MARV GP at or near the predicted region of the receptor-binding site. The presence of the glycan cap or mucin-like domain blocks binding of neutralizing antibodies to EBOV GP, but not to MARV GP. The data suggest that MARV-neutralizing antibodies inhibit virus by binding to infectious virions at the exposed MARV receptor-binding site, revealing a mechanism of filovirus inhibition. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Safety and immunogenicity of Ebola virus and Marburg virus glycoprotein DNA vaccines assessed separately and concomitantly in healthy Ugandan adults: a phase 1b, randomised, double-blind, placebo-controlled clinical trial.

    PubMed

    Kibuuka, Hannah; Berkowitz, Nina M; Millard, Monica; Enama, Mary E; Tindikahwa, Allan; Sekiziyivu, Arthur B; Costner, Pamela; Sitar, Sandra; Glover, Deline; Hu, Zonghui; Joshi, Gyan; Stanley, Daphne; Kunchai, Meghan; Eller, Leigh Anne; Bailer, Robert T; Koup, Richard A; Nabel, Gary J; Mascola, John R; Sullivan, Nancy J; Graham, Barney S; Roederer, Mario; Michael, Nelson L; Robb, Merlin L; Ledgerwood, Julie E

    2015-04-18

    the EBO vaccine group had an antibody response to the Ebola Zaire glycoprotein, as did 14 of 30 (47%, 28-66) in the group that received both vaccines. 15 of 30 (50%, 31-69) participants in the EBO vaccine group had an antibody response to the Ebola Sudan glycoprotein, as did 15 of 30 (50%, 31-69) in the group that received both vaccines. Nine of 29 (31%, 15-51) participants in the MAR vaccine groups had an antibody response to the Marburg glycoprotein, as did seven of 30 (23%, 10-42) in the group that received both vaccines. 19 of 30 (63%, 44-80) participants in the EBO vaccine group had a T-cell response to the Ebola Zaire glycoprotein, as did 10 of 30 (33%, 17-53) in the group that received both vaccines. 13 of 30 (43%, 25-63) participants in the EBO vaccine group had a T-cell response to the Ebola Sudan glycoprotein, as did 10 of 30 (33%, 17-53) in the group that received both vaccines. 15 of 29 (52%, 33-71) participants in the MAR vaccine group had a T-cell response to the Marburg glycoprotein, as did 13 of 30 (43%, 25-63) in the group that received both vaccines. This study is the first Ebola or Marburg vaccine trial done in Africa, and the results show that, given separately or together, both vaccines were well tolerated and elicited antigen-specific humoral and cellular immune responses. These findings have contributed to the accelerated development of more potent Ebola virus vaccines that encode the same wild-type glycoprotein antigens as the EBO vaccine, which are being assessed during the 2014 Ebola virus disease outbreak in west Africa. US Department of Defense Infectious Disease Clinical Research Program and US National Institutes of Health Intramural Research Program. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. [A paradigm change in German academic medicine. Merger and privatization as exemplified with the university hospitals in Marburg and Giessen].

    PubMed

    Maisch, Bernhard

    2005-03-01

    1. The intended fusion of the university hospitals Marburg and Giessen in the state of Hessia is "a marriage under pressure with uncalculated risk" (Spiegel 2005). In the present political and financial situation it hardly appears to be avoidable. From the point of the view of the faculty of medicine in Marburg it is difficult to understand, that the profits of this well guided university hospital with a positive yearly budget should go to the neighboring university hospital which still had a fair amount of deficit spending in the last years.2. Both medical faculties suffer from a very low budget from the state of Hessia for research and teaching. Giessen much more than Marburg, have a substantial need for investments in buildings and infrastructure. Both institutions have a similar need for investments in costly medical apparatuses. This is a problem, which many university hospitals face nowadays.3. The intended privatisation of one or both university hospitals will need sound answers to several fundamental questions and problems:a) A privatisation potentially endangers the freedom of research and teaching garanteed by the German constitution. A private company will undoubtedly influence by active or missing additional support the direction of research in the respective academic institution. An example is the priorisation of clinical in contrast to basic research.b) With the privatisation practical absurdities in the separation of research and teaching on one side and hospital care on the other will become obvious with respect to the status of the academic employees, the obligatory taxation (16%) when a transfer of labor from one institution to the other is taken into account. The use of rooms for seminars, lectures and bedside with a double function for both teaching, research and hospital care has to be clarified with a convincing solution in everyday practice.c) The potential additional acquisition of patients, which has been advocated by the Hessian state

  17. Filovirus pathogenesis and immune evasion: insights from Ebola virus and Marburg virus

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

    Messaoudi, Ilhem; Amarasinghe, Gaya K.; Basler, Christopher F.

    Ebola viruses and Marburg viruses, members of the filovirus family, are zoonotic pathogens that cause severe disease in people, as highlighted by the latest Ebola virus epidemic in West Africa. Filovirus disease is characterized by uncontrolled virus replication and the activation of host responses that contribute to pathogenesis. Underlying these phenomena is the potent suppression of host innate antiviral responses, particularly the type I interferon response, by viral proteins, which allows high levels of viral replication. In this Review, we describe the mechanisms used by filoviruses to block host innate immunity and discuss the links between immune evasion and filovirusmore » pathogenesis.« less

  18. Filovirus pathogenesis and immune evasion: insights from Ebola virus and Marburg virus

    PubMed Central

    Messaoudi, Ilhem; Amarasinghe, Gaya K.; Basler, Christopher F.

    2016-01-01

    Ebola viruses and Marburg viruses, members of the filovirus family, are zoonotic pathogens that cause severe disease in people. The Ebola virus epidemic in West Africa, which was first recognized in early 2014, highlights the threat posed by these deadly viruses. Filovirus disease is characterized by uncontrolled virus replication and the activation of damaging host pathways. Underlying these phenomena is the potent suppression of host innate antiviral responses, particularly the type I interferon (IFN) response, which allows high levels of replication. Here we review the mechanisms deployed by filoviruses to block host innate immunity and discuss aspects of virus replication that promote disease. PMID:26439085

  19. Temporal Characterization of Marburg Virus Angola Infection following Aerosol Challenge in Rhesus Macaques.

    PubMed

    Lin, Kenny L; Twenhafel, Nancy A; Connor, John H; Cashman, Kathleen A; Shamblin, Joshua D; Donnelly, Ginger C; Esham, Heather L; Wlazlowski, Carly B; Johnson, Joshua C; Honko, Anna N; Botto, Miriam A; Yen, Judy; Hensley, Lisa E; Goff, Arthur J

    2015-10-01

    Marburg virus (MARV) infection is a lethal hemorrhagic fever for which no licensed vaccines or therapeutics are available. Development of appropriate medical countermeasures requires a thorough understanding of the interaction between the host and the pathogen and the resulting disease course. In this study, 15 rhesus macaques were sequentially sacrificed following aerosol exposure to the MARV variant Angola, with longitudinal changes in physiology, immunology, and histopathology used to assess disease progression. Immunohistochemical evidence of infection and resulting histopathological changes were identified as early as day 3 postexposure (p.e.). The appearance of fever in infected animals coincided with the detection of serum viremia and plasma viral genomes on day 4 p.e. High (>10(7) PFU/ml) viral loads were detected in all major organs (lung, liver, spleen, kidney, brain, etc.) beginning day 6 p.e. Clinical pathology findings included coagulopathy, leukocytosis, and profound liver destruction as indicated by elevated liver transaminases, azotemia, and hypoalbuminemia. Altered cytokine expression in response to infection included early increases in Th2 cytokines such as interleukin 10 (IL-10) and IL-5 and late-stage increases in Th1 cytokines such as IL-2, IL-15, and granulocyte-macrophage colony-stimulating factor (GM-CSF). This study provides a longitudinal examination of clinical disease of aerosol MARV Angola infection in the rhesus macaque model. In this study, we carefully analyzed the timeline of Marburg virus infection in nonhuman primates in order to provide a well-characterized model of disease progression following aerosol exposure. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  20. Vesicular stomatitis virus-based vaccines protect nonhuman primates against aerosol challenge with Ebola and Marburg viruses.

    PubMed

    Geisbert, Thomas W; Daddario-Dicaprio, Kathleen M; Geisbert, Joan B; Reed, Douglas S; Feldmann, Friederike; Grolla, Allen; Ströher, Ute; Fritz, Elizabeth A; Hensley, Lisa E; Jones, Steven M; Feldmann, Heinz

    2008-12-09

    Considerable progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against Ebola and Marburg viruses. A vaccine based on recombinant vesicular stomatitis virus (VSV) seems to be particularly robust as it can also confer protection when administered as a postexposure treatment. While filoviruses are not thought to be transmitted by aerosol in nature the inhalation route is among the most likely portals of entry in the setting of a bioterrorist event. At present, all candidate filoviral vaccines have been evaluated against parenteral challenges but none have been tested against an aerosol exposure. Here, we evaluated our recombinant VSV-based Zaire ebolavirus (ZEBOV) and Marburg virus (MARV) vaccines against aerosol challenge in cynomolgus macaques. All monkeys vaccinated with a VSV vector expressing the glycoprotein of ZEBOV were completely protected against an aerosol exposure of ZEBOV. Likewise, all monkeys vaccinated with a VSV vector expressing the glycoprotein of MARV were completely protected against an aerosol exposure of MARV. All control animals challenged by the aerosol route with either ZEBOV or MARV succumbed. Interestingly, disease in control animals appeared to progress slower than previously seen in macaques exposed to comparable doses by intramuscular injection.

  1. Dimerization Controls Marburg Virus VP24-dependent Modulation of Host Antioxidative Stress Responses.

    PubMed

    Johnson, Britney; Li, Jing; Adhikari, Jagat; Edwards, Megan R; Zhang, Hao; Schwarz, Toni; Leung, Daisy W; Basler, Christopher F; Gross, Michael L; Amarasinghe, Gaya K

    2016-08-28

    Marburg virus (MARV), a member of the Filoviridae family that also includes Ebola virus (EBOV), causes lethal hemorrhagic fever with case fatality rates that have exceeded 50% in some outbreaks. Within an infected cell, there are numerous host-viral interactions that contribute to the outcome of infection. Recent studies identified MARV protein 24 (mVP24) as a modulator of the host antioxidative responses, but the molecular mechanism remains unclear. Using a combination of biochemical and mass spectrometry studies, we show that mVP24 is a dimer in solution that directly binds to the Kelch domain of Kelch-like ECH-associated protein 1 (Keap1) to regulate nuclear factor (erythroid-derived 2)-like 2 (Nrf2). This interaction between Keap1 and mVP24 occurs through the Kelch interaction loop (K-Loop) of mVP24 leading to upregulation of antioxidant response element transcription, which is distinct from other Kelch binders that regulate Nrf2 activity. N-terminal truncations disrupt mVP24 dimerization, allowing monomeric mVP24 to bind Kelch with higher affinity and stimulate higher antioxidative stress response element (ARE) reporter activity. Mass spectrometry-based mapping of the interface revealed overlapping binding sites on Kelch for mVP24 and the Nrf2 proteins. Substitution of conserved cysteines, C209 and C210, to alanine in the mVP24 K-Loop abrogates Kelch binding and ARE activation. Our studies identify a shift in the monomer-dimer equilibrium of MARV VP24, driven by its interaction with Keap1 Kelch domain, as a critical determinant that modulates host responses to pathogenic Marburg viral infections. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Dimerization Controls Marburg Virus VP24-dependent Modulation of Host Antioxidative Stress Responses

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

    Johnson, Britney; Li, Jing; Adhikari, Jagat

    Marburg virus (MARV), a member of the Filoviridae family that also includes Ebola virus (EBOV), causes lethal hemorrhagic fever with case fatality rates that have exceeded 50% in some outbreaks. Within an infected cell, there are numerous host-viral interactions that contribute to the outcome of infection. Recent studies identified MARV protein 24 (mVP24) as a modulator of the host antioxidative responses, but the molecular mechanism remains unclear. Using a combination of biochemical and mass spectrometry studies, we show that mVP24 is a dimer in solution that directly binds to the Kelch domain of Kelch-like ECH-associated protein 1 (Keap1) to regulatemore » nuclear factor (erythroid-derived 2)-like 2 (Nrf2). This interaction between Keap1 and mVP24 occurs through the Kelch interaction loop (K-Loop) of mVP24 leading to upregulation of antioxidant response element transcription, which is distinct from other Kelch binders that regulate Nrf2 activity. N-terminal truncations disrupt mVP24 dimerization, allowing monomeric mVP24 to bind Kelch with higher affinity and stimulate higher antioxidative stress response element (ARE) reporter activity. Mass spectrometry-based mapping of the interface revealed overlapping binding sites on Kelch for mVP24 and the Nrf2 proteins. Substitution of conserved cysteines, C209 and C210, to alanine in the mVP24 K-Loop abrogates Kelch binding and ARE activation. Our studies identify a shift in the monomer-dimer equilibrium of MARV VP24, driven by its interaction with Keap1 Kelch domain, as a critical determinant that modulates host responses to pathogenic Marburg viral infections.« less

  3. Discovery and early development of AVI-7537 and AVI-7288 for the treatment of Ebola virus and Marburg virus infections.

    PubMed

    Iversen, Patrick L; Warren, Travis K; Wells, Jay B; Garza, Nicole L; Mourich, Dan V; Welch, Lisa S; Panchal, Rekha G; Bavari, Sina

    2012-11-06

    There are no currently approved treatments for filovirus infections. In this study we report the discovery process which led to the development of antisense Phosphorodiamidate Morpholino Oligomers (PMOs) AVI-6002 (composed of AVI-7357 and AVI-7539) and AVI-6003 (composed of AVI-7287 and AVI-7288) targeting Ebola virus and Marburg virus respectively. The discovery process involved identification of optimal transcript binding sites for PMO based RNA-therapeutics followed by screening for effective viral gene target in mouse and guinea pig models utilizing adapted viral isolates. An evolution of chemical modifications were tested, beginning with simple Phosphorodiamidate Morpholino Oligomers (PMO) transitioning to cell penetrating peptide conjugated PMOs (PPMO) and ending with PMOplus containing a limited number of positively charged linkages in the PMO structure. The initial lead compounds were combinations of two agents targeting separate genes. In the final analysis, a single agent for treatment of each virus was selected, AVI-7537 targeting the VP24 gene of Ebola virus and AVI-7288 targeting NP of Marburg virus, and are now progressing into late stage clinical development as the optimal therapeutic candidates.

  4. 77 FR 32507 - Brass Sheet and Strip From Germany: Notice of Rescission of Antidumping Duty Administrative Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-01

    ... Germany: Notice of Rescission of Antidumping Duty Administrative Review AGENCY: Import Administration... and strip from Germany for the period of review (``POR''), March 1, 2011, through February 29, 2012.\\1... brass sheet and strip from Germany: Aurubis Stolberg GmbH & Co. KG (``Aurubis''), Carl Schreiber GmbH...

  5. Neurosurgical Resident Training in Germany.

    PubMed

    Stienen, Martin N; Gempt, Jens; Gautschi, Oliver P; Demetriades, Andreas K; Netuka, David; Kuhlen, Dominique E; Schaller, Karl; Ringel, Florian

    2017-07-01

    Introduction  Efficient neurosurgical training is of paramount importance to provide continuing high-quality medical care to patients. In this era of law-enforced working hour restrictions, however, maintaining high-quality training can be a challenge and requires some restructuring. We evaluated the current status of resident training in Germany. Methods  An electronic survey was sent to European neurosurgical trainees between June 2014 and March 2015. The responses of German trainees were compared with those of trainees from other European countries. Logistic regression analysis was performed to assess the effect size of the relationship between a trainee being from Germany and the outcome (e.g., satisfaction, working time). Results  Of 532 responses, 95 were from German trainees (17.8%). In a multivariate analysis corrected for baseline group differences, German trainees were 29% as likely as non-German trainees to be satisfied with clinical lectures given at their teaching facility (odds ratio [OR]: 0.29; 95% confidence interval [CI]: 0.18-0.49; p  < 0.0001). The satisfaction rate with hands-on operating room exposure was 73.9% and equal to the rate in Europe (OR: 0.94; 95% CI, 0.56-1.59; p  = 0.834). German trainees were 2.3 times as likely to perform a lumbar spine intervention as the primary surgeon within the first year of training (OR: 2.27; 95% CI, 1.42-3.64; p  = 0.001). However, they were less likely to perform a cervical spine procedure within 24 months of training (OR: 0.38; 95% CI, 0.17-0.82; p  = 0.014) and less likely to perform a craniotomy within 36 months of training (OR: 0.49; 95% CI, 0.31-0.79; p  = 0.003). Only 25.6% of German trainees currently adhere to the weekly limit of 48 hours as requested from the European Working Time Directive 2003/88/EC, and in an international comparison, German trainees were twice as likely to work > 50 hours per week (OR: 2.13; 95% CI, 1.25-3.61; p  = 0.005). This working time

  6. A Comparison of the Pathogenesis of Marburg Virus Disease in Humans and Nonhuman Primates and Evaluation of the Suitability of These Animal Models for Predicting Clinical Efficacy under the 'Animal Rule'.

    PubMed

    Glaze, Elizabeth R; Roy, Michael J; Dalrymple, Lonnie W; Lanning, Lynda L

    2015-06-01

    Marburg virus outbreaks are sporadic, infrequent, brief, and relatively small in terms of numbers of subjects affected. In addition, outbreaks most likely will occur in remote regions where clinical trials are not feasible; therefore, definitive, well-controlled human efficacy studies to test the effectiveness of a drug or biologic product are not feasible. Healthy human volunteers cannot ethically be deliberately exposed to a lethal agent such as Marburg virus in order to test the efficacy of a therapy or preventive prior to licensure. When human efficacy studies are neither ethical nor feasible, the US Food and Drug Administration may grant marketing approval of a drug or biologic product under the 'Animal Rule,' through which demonstration of the efficacy of a product can be 'based on adequate and well-controlled animal efficacy studies when the results of those studies establish that the drug is reasonably likely to produce clinical benefit in humans.' This process requires that the pathogenic determinants of the disease in the animal model are similar to those that have been identified in humans. After reviewing primarily English-language, peer-reviewed journal articles, we here summarize the clinical manifestations of Marburg virus disease and the results of studies in NHP showing the characteristics and progression of the disease. We also include a detailed comparison of the characteristics of the human disease relative to those for NHP. This review reveals that the disease characteristics of Marburg virus disease are generally similar for humans and 3 NHP species: cynomolgus macaques (Macaca fascicularis), rhesus macaques (Macaca mulatta), and African green monkeys (Chlorocebus aethiops).

  7. Considerations in the Use of Nonhuman Primate Models of Ebola Virus and Marburg Virus Infection.

    PubMed

    Geisbert, Thomas W; Strong, James E; Feldmann, Heinz

    2015-10-01

    The filoviruses, Ebola virus and Marburg virus, are zoonotic pathogens that cause severe hemorrhagic fever in humans and nonhuman primates (NHPs), with case-fatality rates ranging from 23% to 90%. The current outbreak of Ebola virus infection in West Africa, with >26 000 cases, demonstrates the long-underestimated public health danger that filoviruses pose as natural human pathogens. Currently, there are no vaccines or treatments licensed for human use. Licensure of any medical countermeasure may require demonstration of efficacy in the gold standard cynomolgus or rhesus macaque models of filovirus infection. Substantial progress has been made over the last decade in characterizing the filovirus NHP models. However, there is considerable debate over a variety of experimental conditions, including differences among filovirus isolates used, routes and doses of exposure, and euthanasia criteria, all of which may contribute to variability of results among different laboratories. As an example of the importance of understanding these differences, recent data with Ebola virus shows that an addition of a single uridine residue in the glycoprotein gene at the editing site attenuates the virus. Here, we draw on decades of experience working with filovirus-infected NHPs to provide a perspective on the importance of various experimental conditions. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  8. 78 FR 52759 - Brass Sheet and Strip from Germany: Rescission of Antidumping Duty Administrative Review; 2012-2013

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-26

    ... Germany: Rescission of Antidumping Duty Administrative Review; 2012-2013 AGENCY: Import Administration... from Germany for the period March 1, 2012, through February 28, 2013. DATES: Effective Date: August 26... 1, 2013, the Department initiated an administrative review of brass sheet and strip from Germany...

  9. Ebola Virus Disease Candidate Vaccines Under Evaluation in Clinical Trials

    DTIC Science & Technology

    2016-06-02

    studies in HPIV-3-immune guinea pigs with EBOV GP1,2-expressing HPIV-3 have suggested that while pre-existing immunity to the vector suppressed... guinea pigs and nonhuman primates against infection with multiple Marburg viruses. Expert Rev Vaccines, 7(4), 417-429 (2008). 98. Warfield KL...Swenson DL, Negley DL et al. Marburg virus-like particles protect guinea pigs from lethal Marburg virus infection. Vaccine, 22(25-26), 3495-3502 (2004

  10. The VP40 protein of Marburg virus exhibits impaired budding and increased sensitivity to human tetherin following mouse adaptation.

    PubMed

    Feagins, Alicia R; Basler, Christopher F

    2014-12-01

    The Marburg virus VP40 protein is a viral matrix protein that spontaneously buds from cells. It also functions as an interferon (IFN) signaling antagonist by targeting Janus kinase 1 (JAK1). A previous study demonstrated that the VP40 protein of the Ravn strain of Marburg virus (Ravn virus [RAVV]) failed to block IFN signaling in mouse cells, whereas the mouse-adapted RAVV (maRAVV) VP40 acquired the ability to inhibit IFN responses in mouse cells. The increased IFN antagonist function of maRAVV VP40 mapped to residues 57 and 165, which were mutated during the mouse adaptation process. In the present study, we demonstrate that maRAVV VP40 lost the capacity to efficiently bud from human cell lines, despite the fact that both parental and maRAVV VP40s bud efficiently from mouse cell lines. The impaired budding in human cells corresponds with the appearance of protrusions on the surface of maRAVV VP40-expressing Huh7 cells and with an increased sensitivity of maRAVV VP40 to restriction by human tetherin but not mouse tetherin. However, transfer of the human tetherin cytoplasmic tail to mouse tetherin restored restriction of maRAVV VP40. Residues 57 and 165 were demonstrated to contribute to the failure of maRAVV VP40 to bud from human cells, and residue 57 was demonstrated to alter VP40 oligomerization, as assessed by coprecipitation assay, and to determine sensitivity to human tetherin. This suggests that RAVV VP40 acquired, during adaptation to mice, changes in its oligomerization potential that enhanced IFN antagonist function. However, this new capacity impaired RAVV VP40 budding from human cells. Filoviruses, which include Marburg viruses and Ebola viruses, are zoonotic pathogens that cause severe disease in humans and nonhuman primates but do not cause similar disease in wild-type laboratory strains of mice unless first adapted to these animals. Although mouse adaptation has been used as a method to develop small animal models of pathogenesis, the molecular

  11. Critical CALL: Proceedings of the 2015 EUROCALL Conference (22nd, Padova, Italy, August 26-29, 2015)

    ERIC Educational Resources Information Center

    Helm, Francesca, Ed.; Bradley, Linda, Ed.; Guarda, Marta, Ed.; Thouësny, Sylvie, Ed.

    2015-01-01

    The 22nd EUROCALL conference was held at the University of Padova from the 26th to the 29th of August 2015, the first time that EUROCALL has been held in Italy. The event was organized in collaboration with the University Language Centre and the support of the Department of Political Science, Law and International Studies. Over 300 delegates…

  12. Public health impacts of excess NOx emissions from Volkswagen diesel passenger vehicles in Germany

    NASA Astrophysics Data System (ADS)

    Chossière, Guillaume P.; Malina, Robert; Ashok, Akshay; Dedoussi, Irene C.; Eastham, Sebastian D.; Speth, Raymond L.; Barrett, Steven R. H.

    2017-03-01

    In September 2015, the Volkswagen Group (VW) admitted the use of ‘defeat devices’ designed to lower emissions measured during VW vehicle testing for regulatory purposes. Globally, 11 million cars sold between 2008 and 2015 are affected, including about 2.6 million in Germany. On-road emissions tests have yielded mean on-road NOx emissions for these cars of 0.85 g km-1, over four times the applicable European limit of 0.18 g km-1. This study estimates the human health impacts and costs associated with excess emissions from VW cars driven in Germany. A distribution of on-road emissions factors is derived from existing measurements and combined with sales data and a vehicle fleet model to estimate total excess NOx emissions. These emissions are distributed on a 25 by 28 km grid covering Europe, using the German Federal Environmental Protection Agency’s (UBA) estimate of the spatial distribution of NOx emissions from passenger cars in Germany. We use the GEOS-Chem chemistry-transport model to predict the corresponding increase in population exposure to fine particulate matter and ozone in the European Union, Switzerland, and Norway, and a set of concentration-response functions to estimate mortality outcomes in terms of early deaths and of life-years lost. Integrated over the sales period (2008-2015), we estimate median mortality impacts from VW excess emissions in Germany to be 1200 premature deaths in Europe, corresponding to 13 000 life-years lost and 1.9 billion EUR in costs associated with life-years lost. Approximately 60% of mortality costs occur outside Germany. For the current fleet, we estimate that if on-road emissions for all affected VW vehicles in Germany are reduced to the applicable European emission standard by the end of 2017, this would avert 29 000 life-years lost and 4.1 billion 2015 EUR in health costs (median estimates) relative to a counterfactual case with no recall.

  13. Education in the Soviet Zone of Germany. Bulletin, 1959, No. 26

    ERIC Educational Resources Information Center

    Bodenman, Paul S.

    1959-01-01

    The Office of Education frequently receives requests for information regarding the educational developments in the Soviet Zone of Germany. This bulletin is issued by the Office of Education as another in its longstanding series of international education publications. Unlike most bulletins in this series that are based on firsthand interviews and…

  14. Discovery and Early Development of AVI-7537 and AVI-7288 for the Treatment of Ebola Virus and Marburg Virus Infections

    PubMed Central

    Iversen, Patrick L.; Warren, Travis K.; Wells, Jay B.; Garza, Nicole L.; Mourich, Dan V.; Welch, Lisa S.; Panchal, Rekha G.; Bavari, Sina

    2012-01-01

    There are no currently approved treatments for filovirus infections. In this study we report the discovery process which led to the development of antisense Phosphorodiamidate Morpholino Oligomers (PMOs) AVI-6002 (composed of AVI-7357 and AVI-7539) and AVI-6003 (composed of AVI-7287 and AVI-7288) targeting Ebola virus and Marburg virus respectively. The discovery process involved identification of optimal transcript binding sites for PMO based RNA-therapeutics followed by screening for effective viral gene target in mouse and guinea pig models utilizing adapted viral isolates. An evolution of chemical modifications were tested, beginning with simple Phosphorodiamidate Morpholino Oligomers (PMO) transitioning to cell penetrating peptide conjugated PMOs (PPMO) and ending with PMOplus containing a limited number of positively charged linkages in the PMO structure. The initial lead compounds were combinations of two agents targeting separate genes. In the final analysis, a single agent for treatment of each virus was selected, AVI-7537 targeting the VP24 gene of Ebola virus and AVI-7288 targeting NP of Marburg virus, and are now progressing into late stage clinical development as the optimal therapeutic candidates. PMID:23202506

  15. Breaking bad news-what patients want and what they get: evaluating the SPIKES protocol in Germany.

    PubMed

    Seifart, C; Hofmann, M; Bär, T; Riera Knorrenschild, J; Seifart, U; Rief, W

    2014-03-01

    Evaluation of the SPIKES protocol, a recommended guideline for breaking bad news, is sparse, and information about patients' preferences for bad-news delivery in Germany is lacking. Being the first actual-theoretical comparison of a 'breaking bad news' guideline, the present study evaluates the recommended steps of the SPIKES protocol. Moreover, emotional consequences and quality of bad-news delivery are investigated. A total of 350 cancer patients answered the MABBAN (Marburg Breaking Bad News Scale), a questionnaire representing the six SPIKES subscales, asking for the procedure, perception and satisfaction of the first cancer disclosure and patient's assign to these items. Only 46.2% of the asked cancer patients are completely satisfied with how bad news had been broken to them. The overall quality is significantly related to the emotional state after receiving bad news (r = -0.261, P < 0.001). Patients' preferences differ highly significantly from the way bad news were delivered, and the resulting rang list of patients' preferences indicates that the SPIKES protocol do not fully meet the priorities of cancer patients in Germany. It could be postulated that the low satisfaction of patients observed in this study reflects the highly significant difference between patients' preferences and bad-news delivery. Therefore, some adjunctions to the SPIKES protocol should be considered, including a frequent reassurance of listeners' understanding, the perpetual possibility to ask question, respect for prearrangement needs and the conception of bad-news delivery in a two-step procedure.

  16. Digital sensing and sizing of vesicular stomatitis virus pseudotypes in complex media: a model for Ebola and Marburg detection.

    PubMed

    Daaboul, George G; Lopez, Carlos A; Chinnala, Jyothsna; Goldberg, Bennett B; Connor, John H; Ünlü, M Selim

    2014-06-24

    Rapid, sensitive, and direct label-free capture and characterization of nanoparticles from complex media such as blood or serum will broadly impact medicine and the life sciences. We demonstrate identification of virus particles in complex samples for replication-competent wild-type vesicular stomatitis virus (VSV), defective VSV, and Ebola- and Marburg-pseudotyped VSV with high sensitivity and specificity. Size discrimination of the imaged nanoparticles (virions) allows differentiation between modified viruses having different genome lengths and facilitates a reduction in the counting of nonspecifically bound particles to achieve a limit-of-detection (LOD) of 5 × 10(3) pfu/mL for the Ebola and Marburg VSV pseudotypes. We demonstrate the simultaneous detection of multiple viruses in a single sample (composed of serum or whole blood) for screening applications and uncompromised detection capabilities in samples contaminated with high levels of bacteria. By employing affinity-based capture, size discrimination, and a "digital" detection scheme to count single virus particles, we show that a robust and sensitive virus/nanoparticle sensing assay can be established for targets in complex samples. The nanoparticle microscopy system is termed the Single Particle Interferometric Reflectance Imaging Sensor (SP-IRIS) and is capable of high-throughput and rapid sizing of large numbers of biological nanoparticles on an antibody microarray for research and diagnostic applications.

  17. A Comparison of the Pathogenesis of Marburg Virus Disease in Humans and Nonhuman Primates and Evaluation of the Suitability of These Animal Models for Predicting Clinical Efficacy under the ‘Animal Rule’

    PubMed Central

    Glaze, Elizabeth R; Roy, Michael J; Dalrymple, Lonnie W; Lanning, Lynda L

    2015-01-01

    Marburg virus outbreaks are sporadic, infrequent, brief, and relatively small in terms of numbers of subjects affected. In addition, outbreaks most likely will occur in remote regions where clinical trials are not feasible; therefore, definitive, well-controlled human efficacy studies to test the effectiveness of a drug or biologic product are not feasible. Healthy human volunteers cannot ethically be deliberately exposed to a lethal agent such as Marburg virus in order to test the efficacy of a therapy or preventive prior to licensure. When human efficacy studies are neither ethical nor feasible, the US Food and Drug Administration may grant marketing approval of a drug or biologic product under the ‘Animal Rule,’ through which demonstration of the efficacy of a product can be ‘based on adequate and well-controlled animal efficacy studies when the results of those studies establish that the drug is reasonably likely to produce clinical benefit in humans.’ This process requires that the pathogenic determinants of the disease in the animal model are similar to those that have been identified in humans. After reviewing primarily English-language, peer-reviewed journal articles, we here summarize the clinical manifestations of Marburg virus disease and the results of studies in NHP showing the characteristics and progression of the disease. We also include a detailed comparison of the characteristics of the human disease relative to those for NHP. This review reveals that the disease characteristics of Marburg virus disease are generally similar for humans and 3 NHP species: cynomolgus macaques (Macaca fascicularis), rhesus macaques (Macaca mulatta), and African green monkeys (Chlorocebus aethiops). PMID:26141449

  18. Risk Factors Associated with Ebola and Marburg Viruses Seroprevalence in Blood Donors in the Republic of Congo.

    PubMed

    Moyen, Nanikaly; Thirion, Laurence; Emmerich, Petra; Dzia-Lepfoundzou, Amelia; Richet, Hervé; Boehmann, Yannik; Dimi, Yannick; Gallian, Pierre; Gould, Ernest A; Günther, Stephan; de Lamballerie, Xavier

    2015-01-01

    Ebola and Marburg viruses (family Filoviridae, genera Ebolavirus and Marburgvirus) cause haemorrhagic fevers in humans, often associated with high mortality rates. The presence of antibodies to Ebola virus (EBOV) and Marburg virus (MARV) has been reported in some African countries in individuals without a history of haemorrhagic fever. In this study, we present a MARV and EBOV seroprevalence study conducted amongst blood donors in the Republic of Congo and the analysis of risk factors for contact with EBOV. In 2011, we conducted a MARV and EBOV seroprevalence study amongst 809 blood donors recruited in rural (75; 9.3%) and urban (734; 90.7%) areas of the Republic of Congo. Serum titres of IgG antibodies to MARV and EBOV were assessed by indirect double-immunofluorescence microscopy. MARV seroprevalence was 0.5% (4 in 809) without any identified risk factors. Prevalence of IgG to EBOV was 2.5%, peaking at 4% in rural areas and in Pointe Noire. Independent risk factors identified by multivariate analysis were contact with bats and exposure to birds. This MARV and EBOV serological survey performed in the Republic of Congo identifies a probable role for environmental determinants of exposure to EBOV. It highlights the requirement for extending our understanding of the ecological and epidemiological risk of bats (previously identified as a potential ecological reservoir) and birds as vectors of EBOV to humans, and characterising the protection potentially afforded by EBOV-specific antibodies as detected in blood donors.

  19. Inhibition of Ebola and Marburg Virus Entry by G Protein-Coupled Receptor Antagonists.

    PubMed

    Cheng, Han; Lear-Rooney, Calli M; Johansen, Lisa; Varhegyi, Elizabeth; Chen, Zheng W; Olinger, Gene G; Rong, Lijun

    2015-10-01

    Filoviruses, consisting of Ebola virus (EBOV) and Marburg virus (MARV), are among the most lethal infectious threats to mankind. Infections by these viruses can cause severe hemorrhagic fevers in humans and nonhuman primates with high mortality rates. Since there is currently no vaccine or antiviral therapy approved for humans, there is an urgent need to develop prophylactic and therapeutic options for use during filoviral outbreaks and bioterrorist attacks. One of the ideal targets against filoviral infection and diseases is at the entry step, which is mediated by the filoviral glycoprotein (GP). In this report, we screened a chemical library of small molecules and identified numerous inhibitors, which are known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs, including histamine receptors, 5-HT (serotonin) receptors, muscarinic acetylcholine receptor, and adrenergic receptor. These inhibitors can effectively block replication of both infectious EBOV and MARV, indicating a broad antiviral activity of the GPCR antagonists. The time-of-addition experiment and microscopic studies suggest that GPCR antagonists block filoviral entry at a step following the initial attachment but prior to viral/cell membrane fusion. These results strongly suggest that GPCRs play a critical role in filoviral entry and GPCR antagonists can be developed as an effective anti-EBOV/MARV therapy. Infection of Ebola virus and Marburg virus can cause severe illness in humans with a high mortality rate, and currently there is no FDA-approved vaccine or therapeutic treatment available. The 2013-2015 epidemic in West Africa underscores a lack of our understanding in the infection and pathogenesis of these viruses and the urgency of drug discovery and development. In this study, we have identified numerous inhibitors that are known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs. These inhibitors can effectively block replication of both infectious

  20. Inhibition of Ebola and Marburg Virus Entry by G Protein-Coupled Receptor Antagonists

    PubMed Central

    Cheng, Han; Lear-Rooney, Calli M.; Johansen, Lisa; Varhegyi, Elizabeth; Chen, Zheng W.; Olinger, Gene G.

    2015-01-01

    ABSTRACT Filoviruses, consisting of Ebola virus (EBOV) and Marburg virus (MARV), are among the most lethal infectious threats to mankind. Infections by these viruses can cause severe hemorrhagic fevers in humans and nonhuman primates with high mortality rates. Since there is currently no vaccine or antiviral therapy approved for humans, there is an urgent need to develop prophylactic and therapeutic options for use during filoviral outbreaks and bioterrorist attacks. One of the ideal targets against filoviral infection and diseases is at the entry step, which is mediated by the filoviral glycoprotein (GP). In this report, we screened a chemical library of small molecules and identified numerous inhibitors, which are known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs, including histamine receptors, 5-HT (serotonin) receptors, muscarinic acetylcholine receptor, and adrenergic receptor. These inhibitors can effectively block replication of both infectious EBOV and MARV, indicating a broad antiviral activity of the GPCR antagonists. The time-of-addition experiment and microscopic studies suggest that GPCR antagonists block filoviral entry at a step following the initial attachment but prior to viral/cell membrane fusion. These results strongly suggest that GPCRs play a critical role in filoviral entry and GPCR antagonists can be developed as an effective anti-EBOV/MARV therapy. IMPORTANCE Infection of Ebola virus and Marburg virus can cause severe illness in humans with a high mortality rate, and currently there is no FDA-approved vaccine or therapeutic treatment available. The 2013-2015 epidemic in West Africa underscores a lack of our understanding in the infection and pathogenesis of these viruses and the urgency of drug discovery and development. In this study, we have identified numerous inhibitors that are known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs. These inhibitors can effectively block replication of

  1. Crystal Structure of the Marburg Virus Nucleoprotein Core Domain Chaperoned by a VP35 Peptide Reveals a Conserved Drug Target for Filovirus.

    PubMed

    Zhu, Tengfei; Song, Hao; Peng, Ruchao; Shi, Yi; Qi, Jianxun; Gao, George F

    2017-09-15

    Filovirus nucleoprotein (NP), viral protein 35 (VP35), and polymerase L are essential for viral replication and nucleocapsid formation. Here, we identify a 28-residue peptide (NP binding peptide [NPBP]) from Marburg virus (MARV) VP35 through sequence alignment with previously identified Ebola virus (EBOV) NPBP, which bound to the core region (residues 18 to 344) of the N-terminal portion of MARV NP with high affinity. The crystal structure of the MARV NP core/NPBP complex at a resolution of 2.6 Å revealed that NPBP binds to the C-terminal region of the NP core via electrostatic and nonpolar interactions. Further structural analysis revealed that the MARV and EBOV NP cores hold a conserved binding pocket for NPBP, and this pocket could serve as a promising target for the design of universal drugs against filovirus infection. In addition, cross-binding assays confirmed that the NP core of MARV or EBOV can bind the NPBP from the other virus, although with moderately reduced binding affinities that result from termini that are distinct between the MARV and EBOV NPBPs. IMPORTANCE Historically, Marburg virus (MARV) has caused severe disease with up to 90% lethality. Among the viral proteins produced by MARV, NP and VP35 are both multifunctional proteins that are essential for viral replication. In its relative, Ebola virus (EBOV), an N-terminal peptide from VP35 binds to the NP N-terminal region with high affinity. Whether this is a common mechanism among filoviruses is an unsolved question. Here, we present the crystal structure of a complex that consists of the core domain of MARV NP and the NPBP peptide from VP35. As we compared MARV NPBP with EBOV NPBP, several different features at the termini were identified. Although these differences reduce the affinity of the NP core for NPBPs across genera, a conserved pocket in the C-terminal region of the NP core makes cross-species binding possible. Our results expand our knowledge of filovirus NP-VP35 interactions and

  2. Proceedings of the International Conference on Educational Data Mining (EDM) (8th, Madrid, Spain, June 26-29, 2015)

    ERIC Educational Resources Information Center

    Santos, Olga Cristina, Ed.; Boticario, Jesus Gonzalez, Ed.; Romero, Cristobal, Ed.; Pechenizkiy, Mykola, Ed.; Merceron, Agathe, Ed.; Mitros, Piotr, Ed.; Luna, Jose Maria, Ed.; Mihaescu, Cristian, Ed.; Moreno, Pablo, Ed.; Hershkovitz, Arnon, Ed.; Ventura, Sebastian, Ed.; Desmarais, Michel, Ed.

    2015-01-01

    The 8th International Conference on Educational Data Mining (EDM 2015) is held under auspices of the International Educational Data Mining Society at UNED, the National University for Distance Education in Spain. The conference held in Madrid, Spain, July 26-29, 2015, follows the seven previous editions (London 2014, Memphis 2013, Chania 2012,…

  3. Anaplasma phagocytophilum Infection in Ixodes ricinus, Bavaria, Germany

    PubMed Central

    Gilles, Jérémie; Höhle, Michael; Fingerle, Volker; Just, Frank Thomas; Pfister, Kurt

    2008-01-01

    Anaplasma phagocytophilum DNA was detected by real-time PCR, which targeted the msp2 gene, in 2.9% of questing Ixodes ricinus ticks (adults and nymphs; n = 2,862), collected systematically from selected locations in Bavaria, Germany, in 2006. Prevalence was significantly higher in urban public parks in Munich than in natural forests. PMID:18507918

  4. Lifetime and 12-month prevalence estimates for mental disorders in northeastern Germany: findings from the Study of Health in Pomerania.

    PubMed

    Asselmann, E; Beesdo-Baum, K; Hamm, A; Schmidt, C O; Hertel, J; Grabe, H J; Pané-Farré, C A

    2018-06-15

    Few epidemiological studies presented 12-month and lifetime prevalence estimates for DSM-IV mental disorders in the adult general population by sex and age up to very old age. From 2007 to 2010, DSM-IV mental disorders were assessed with the DIA-X/M-CIDI among N = 2400 participants (aged 29-89 years) from the Study of Health in Pomerania, an epidemiological study based on a two-stage stratified cluster sample randomly drawn from the adult general population in northeastern Germany. 36.3% of the sample was affected by any 12-month and 54.8% by any lifetime mental disorder. The most frequent diagnostic groups were anxiety (12-month: 14.8%, lifetime: 23.4%), substance use (12-month: 14.5%, lifetime: 25.0%), somatoform (12-month: 12.9%, lifetime: 20.4%) and depressive (12-month: 7.3%, lifetime: 18.6%) disorders. Except for substance use (higher prevalence in men) and bipolar disorders (comparable prevalence in men and women), higher 12-month and lifetime prevalence estimates were found in women vs. men. Moreover, lower 12-month and lifetime prevalence estimates were found in older (aged 60-74 or 75-89 years) vs. younger (aged 29-44 or 45-59 years) age groups. 22.6% (men: 21.1%, women: 23.9%) of those affected by any 12-month disorder met criteria for two and 13.6% (men: 9.6%, women: 16.9%) for three or more 12-month diagnoses. Similarly, 26.4% (men: 25.7%, women: 26.9%) of those affected by any lifetime disorder met criteria for two and 22.7% (men: 19.6%, women: 25.2%) for three or more lifetime diagnoses. Our findings demonstrate the frequency of mental disorders in northeastern Germany and emphasize the need for continued prevention and intervention efforts.

  5. Breaking bad news–what patients want and what they get: evaluating the SPIKES protocol in Germany

    PubMed Central

    Seifart, C.; Hofmann, M.; Bär, T.; Riera Knorrenschild, J.; Seifart, U.; Rief, W.

    2014-01-01

    Background Evaluation of the SPIKES protocol, a recommended guideline for breaking bad news, is sparse, and information about patients' preferences for bad-news delivery in Germany is lacking. Being the first actual–theoretical comparison of a ‘breaking bad news’ guideline, the present study evaluates the recommended steps of the SPIKES protocol. Moreover, emotional consequences and quality of bad-news delivery are investigated. Patients and methods A total of 350 cancer patients answered the MABBAN (Marburg Breaking Bad News Scale), a questionnaire representing the six SPIKES subscales, asking for the procedure, perception and satisfaction of the first cancer disclosure and patient’s assign to these items. Results Only 46.2% of the asked cancer patients are completely satisfied with how bad news had been broken to them. The overall quality is significantly related to the emotional state after receiving bad news (r = −0.261, P < 0.001). Patients’ preferences differ highly significantly from the way bad news were delivered, and the resulting rang list of patients’ preferences indicates that the SPIKES protocol do not fully meet the priorities of cancer patients in Germany. Conclusions It could be postulated that the low satisfaction of patients observed in this study reflects the highly significant difference between patients’ preferences and bad-news delivery. Therefore, some adjunctions to the SPIKES protocol should be considered, including a frequent reassurance of listeners’ understanding, the perpetual possibility to ask question, respect for prearrangement needs and the conception of bad-news delivery in a two-step procedure. PMID:24504443

  6. STS-26 MS Nelson during Crew escape system (CES) testing in JSC WETF Bldg 29

    NASA Image and Video Library

    1988-07-08

    S88-42409 (20 July 1988) --- STS-26 Discovery, Orbiter Vehicle (OV) 103, Mission Specialist (MS) George D. Nelson participates in crew escape system (CES) testing in JSC Weightless Environment Training Facility (WETF) Bldg 29. Nelson, wearing the newly designed (navy blue) launch and entry suit (LES), floats in WETF pool with the aid of an underarm flotation device (modern version of Mas West floats). He awaits the assistance of SCUBA-equipped divers during a simulation of escape and rescue operations utilizing a new CES pole for emergency exit from the Space Shuttle.

  7. Risk Factors Associated with Ebola and Marburg Viruses Seroprevalence in Blood Donors in the Republic of Congo

    PubMed Central

    Moyen, Nanikaly; Thirion, Laurence; Emmerich, Petra; Dzia-Lepfoundzou, Amelia; Richet, Hervé; Boehmann, Yannik; Dimi, Yannick; Gallian, Pierre; Gould, Ernest A.; Günther, Stephan; de Lamballerie, Xavier

    2015-01-01

    Background Ebola and Marburg viruses (family Filoviridae, genera Ebolavirus and Marburgvirus) cause haemorrhagic fevers in humans, often associated with high mortality rates. The presence of antibodies to Ebola virus (EBOV) and Marburg virus (MARV) has been reported in some African countries in individuals without a history of haemorrhagic fever. In this study, we present a MARV and EBOV seroprevalence study conducted amongst blood donors in the Republic of Congo and the analysis of risk factors for contact with EBOV. Methodology and Findings In 2011, we conducted a MARV and EBOV seroprevalence study amongst 809 blood donors recruited in rural (75; 9.3%) and urban (734; 90.7%) areas of the Republic of Congo. Serum titres of IgG antibodies to MARV and EBOV were assessed by indirect double-immunofluorescence microscopy. MARV seroprevalence was 0.5% (4 in 809) without any identified risk factors. Prevalence of IgG to EBOV was 2.5%, peaking at 4% in rural areas and in Pointe Noire. Independent risk factors identified by multivariate analysis were contact with bats and exposure to birds. Conclusions/Significance This MARV and EBOV serological survey performed in the Republic of Congo identifies a probable role for environmental determinants of exposure to EBOV. It highlights the requirement for extending our understanding of the ecological and epidemiological risk of bats (previously identified as a potential ecological reservoir) and birds as vectors of EBOV to humans, and characterising the protection potentially afforded by EBOV-specific antibodies as detected in blood donors. PMID:26047124

  8. A bioluminescent imaging mouse model for Marburg virus based on a pseudovirus system.

    PubMed

    Zhang, Li; Li, Qianqian; Liu, Qiang; Huang, Weijin; Nie, Jianhui; Wang, Youchun

    2017-08-03

    Marburg virus (MARV) can cause lethal hemorrhagic fever in humans. Handling of MARV is restricted to high-containment biosafety level 4 (BSL-4) facilities, which greatly impedes research into this virus. In this study, a high titer of MARV pseudovirus was generated through optimization of the HIV backbone vectors, the ratio of backbone vector to MARV glycoprotein expression vector, and the transfection reagents. An in vitro neutralization assay and an in vivo bioluminescent imaging mouse model for MARV were developed based on the pseudovirus. Protective serum against MARV was successfully induced in guinea pigs, which showed high neutralization activity in vitro and could also protect Balb/c mice from MARV pseudovirus infection in vivo. This system could be a convenient tool to enable the evaluation of vaccines and therapeutic drugs against MARV in non-BSL-4 laboratories.

  9. Investigation of the Lipid Binding Properties of the Marburg Virus Matrix Protein VP40.

    PubMed

    Wijesinghe, Kaveesha J; Stahelin, Robert V

    2015-12-30

    Marburg virus (MARV), which belongs to the virus family Filoviridae, causes hemorrhagic fever in humans and nonhuman primates that is often fatal. MARV is a lipid-enveloped virus that during the replication process extracts its lipid coat from the plasma membrane of the host cell it infects. MARV carries seven genes, one of which encodes its matrix protein VP40 (mVP40), which regulates the assembly and budding of the virions. Currently, little information is available on mVP40 lipid binding properties. Here, we have investigated the in vitro and cellular mechanisms by which mVP40 associates with lipid membranes. mVP40 associates with anionic membranes in a nonspecific manner that is dependent upon the anionic charge density of the membrane. These results are consistent with recent structural determination of mVP40, which elucidated an mVP40 dimer with a flat and extensive cationic lipid binding interface. Marburg virus (MARV) is a lipid-enveloped filamentous virus from the family Filoviridae. MARV was discovered in 1967, and yet little is known about how its seven genes are used to assemble and form a new viral particle in the host cell it infects. The MARV matrix protein VP40 (mVP40) underlies the inner leaflet of the virus and regulates budding from the host cell plasma membrane. In vitro and cellular assays in this study investigated the mechanism by which mVP40 associates with lipids. The results demonstrate that mVP40 interactions with lipid vesicles or the inner leaflet of the plasma membrane are electrostatic but nonspecific in nature and are dependent on the anionic charge density of the membrane surface. Small molecules that can disrupt lipid trafficking or reduce the anionic charge of the plasma membrane interface may be useful in inhibiting assembly and budding of MARV. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  10. In Vitro Effect of Activated Recombinant Factor VII (rFVIIa) on Coagulation Properties of Human Blood at Hypothermic Temperatures

    DTIC Science & Technology

    2007-11-01

    purified soy phosphatides in ellagic acid (Actin FS Activated PTT Reagent, Dade Behring, Marburg, Germany) was added to plasma samples in a 1:1 volume...acetylsali- cylic acid or any other nonsteroidal anti-inflammatory drugs for the 7 days before blood sampling. A smooth cubital venipuncture was

  11. Geographic potential of disease caused by Ebola and Marburg viruses in Africa.

    PubMed

    Peterson, A Townsend; Samy, Abdallah M

    2016-10-01

    Filoviruses represent a significant public health threat worldwide. West Africa recently experienced the largest-scale and most complex filovirus outbreak yet known, which underlines the need for a predictive understanding of the geographic distribution and potential for transmission to humans of these viruses. Here, we used ecological niche modeling techniques to understand the relationship between known filovirus occurrences and environmental characteristics. Our study derived a picture of the potential transmission geography of Ebola virus species and Marburg, paired with views of the spatial uncertainty associated with model-to-model variation in our predictions. We found that filovirus species have diverged ecologically, but only three species are sufficiently well known that models could be developed with significant predictive power. We quantified uncertainty in predictions, assessed potential for outbreaks outside of known transmission areas, and highlighted the Ethiopian Highlands and scattered areas across East Africa as additional potentially unrecognized transmission areas. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Analysis of Signals from an Unique Ground-Truth Infrasound Source Observed at IMS Station IS26 in Southern Germany

    NASA Astrophysics Data System (ADS)

    Koch, Karl

    2010-05-01

    Quantitative modeling of infrasound signals and development and verification of the corresponding atmospheric propagation models requires the use of well-calibrated sources. Numerous sources have been detected by the currently installed network of about 40 of the final 60 IMS infrasound stations. Besides non-nuclear explosions such as mining and quarry blasts and atmospheric phenomena like auroras, these sources include meteorites, volcanic eruptions and supersonic aircraft including re-entering spacecraft and rocket launches. All these sources of infrasound have one feature in common, in that their source parameters are not precisely known and the quantitative interpretation of the corresponding signals is therefore somewhat ambiguous. A source considered well-calibrated has been identified producing repeated infrasound signals at the IMS infrasound station IS26 in the Bavarian forest. The source results from propulsion tests of the ARIANE-5 rocket's main engine at a testing facility near Heilbronn, southern Germany. The test facility is at a range of 320 km and a backazimuth of ~280° from IS26. Ground-truth information was obtained for nearly 100 tests conducted in a 5-year period. Review of the available data for IS26 revealed that at least 28 of these tests show signals above the background noise level. These signals are verified based on the consistency of various signal parameters, e.g., arrival times, durations, and estimates of propagation characteristics (backazimuth, apparent velocity). Signal levels observed are a factor of 2-8 above the noise and reach values of up to 250 mPa for peak amplitudes, and a factor of 2-3 less for RMS measurements. Furthermore, only tests conducted during the months from October to April produce observable signals, indicating a significant change in infrasound propagation conditions between summer and winter months.

  13. Expert Meeting and Membership Meetings, Standing Committee Meeting. Section of Libraries for the Blind. International Federation of Library Associations. Summary.

    ERIC Educational Resources Information Center

    Cylke, Frank Kurt

    Two meetings of the International Federation of Library Associations Section of Libraries for the Blind (BLISTA) are summarized. The first was an expert meeting which was held in Marburg/Lahn, Federal Republic of Germany, in August 1983. Participants included 51 librarians and technical experts serving blind and physically disabled individuals in…

  14. 40 CFR 467.26 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    .... 467.26 Section 467.26 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS ALUMINUM FORMING POINT SOURCE CATEGORY Rolling With Emulsions Subcategory § 467.26... parameter) 13.29 13.29 Subpart B Solution Heat Treatment Contact Cooling Water Pollutant or pollutant...

  15. Immune Response to Marburg Virus Angola Infection in Nonhuman Primates.

    PubMed

    Fernando, Lisa; Qiu, Xiangguo; Melito, P Leno; Williams, Kinola J N; Feldmann, Friederike; Feldmann, Heinz; Jones, Steven M; Alimonti, Judie B

    2015-10-01

    The 2005 outbreak of Marburg virus (MARV) infection in Angola was the most lethal MARV infection outbreak in history, with a case-fatality rate (90%) similar to that for Zaire ebolavirus (EBOV) infection. However, very little is known about the pathogenicity of MARV Angola, as few studies have been conducted to date. Therefore, the immune response was examined in MARV Angola-infected nonhuman primates. Cynomolgus macaques were infected with MARV Angola and monitored for survival. The effect of MARV Angola on the immune system was examined by immunophenotyping whole-blood and by analyzing cytokine and chemokine levels in plasma and spleen specimens, using flow cytometry. The prominent clinical findings were rapid onset of disease and death (mean time after infection, 6.7 days), fever, depression, anorexia, petechial rash, and lymphopenia. Specifically, T, B, and natural killer cells were severely depleted in the blood by day 6. The typical cytokine storm was present, with levels of interferon γ, tumor necrosis factor, interleukin 6, and CCL2 rising in the blood early during infection. MARV Angola displayed the same virulence and disease pathology as EBOV. MARV Angola appears to cause a more rapid onset and severe outcome of infection than other MARV strains. © Crown copyright 2015.

  16. Differential Regulation of Interferon Responses by Ebola and Marburg Virus VP35 Proteins

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

    Edwards, Megan R.; Liu, Gai; Mire, Chad E.

    2016-02-11

    Suppression of innate immune responses during filoviral infection contributes to disease severity. Ebola (EBOV) and Marburg (MARV) viruses each encode a VP35 protein that suppresses RIG-I-like receptor signaling and interferon-α/β (IFN-α/β) production by several mechanisms, including direct binding to double stranded RNA (dsRNA). Here, we demonstrate that in cell culture, MARV infection results in a greater upregulation of IFN responses as compared to EBOV infection. This correlates with differences in the efficiencies by which EBOV and MARV VP35s antagonize RIG-I signaling. Furthermore, structural and biochemical studies suggest that differential recognition of RNA elements by the respective VP35 C-terminal IFN inhibitorymore » domain (IID) rather than affinity for RNA by the respective VP35s is critical for this observation. Our studies reveal functional differences in EBOV versus MARV VP35 RNA binding that result in unexpected differences in the host response to deadly viral pathogens.« less

  17. Ebola Virus and Marburg Virus in Human Milk Are Inactivated by Holder Pasteurization.

    PubMed

    Hamilton Spence, Erin; Huff, Monica; Shattuck, Karen; Vickers, Amy; Yun, Nadezda; Paessler, Slobodan

    2017-05-01

    Potential donors of human milk are screened for Ebola virus (EBOV) using standard questions, but testing for EBOV and Marburg virus (MARV) is not part of routine serological testing performed by milk banks. Research aim: This study tested the hypothesis that EBOV would be inactivated in donor human milk (DHM) by standard pasteurization techniques (Holder) used in all North American nonprofit milk banks. Milk samples were obtained from a nonprofit milk bank. They were inoculated with EBOV (Zaire strain) and MARV (Angola strain) and processed by standard Holder pasteurization technique. Plaque assays for EBOV and MARV were performed to detect the presence of virus after pasteurization. Neither EBOV nor MARV was detectable by viral plaque assay in DHM or culture media samples, which were pasteurized by the Holder process. EBOV and MARV are safely inactivated in human milk by standard Holder pasteurization technique. Screening for EBOV or MARV beyond questionnaire and self-deferral is not needed to ensure safety of DHM for high-risk infants.

  18. Ecological Niche Modeling for Filoviruses: A Risk Map for Ebola and Marburg Virus Disease Outbreaks in Uganda.

    PubMed

    Nyakarahuka, Luke; Ayebare, Samuel; Mosomtai, Gladys; Kankya, Clovice; Lutwama, Julius; Mwiine, Frank Norbert; Skjerve, Eystein

    2017-09-05

    Uganda has reported eight outbreaks caused by filoviruses between 2000 to 2016, more than any other country in the world. We used species distribution modeling to predict where filovirus outbreaks are likely to occur in Uganda to help in epidemic preparedness and surveillance. The MaxEnt software, a machine learning modeling approach that uses presence-only data was used to establish filovirus - environmental relationships. Presence-only data for filovirus outbreaks were collected from the field and online sources. Environmental covariates from Africlim that have been downscaled to a nominal resolution of 1km x 1km were used. The final model gave the relative probability of the presence of filoviruses in the study area obtained from an average of 100 bootstrap runs. Model evaluation was carried out using Receiver Operating Characteristic (ROC) plots. Maps were created using ArcGIS 10.3 mapping software. We showed that bats as potential reservoirs of filoviruses are distributed all over Uganda. Potential outbreak areas for Ebola and Marburg virus disease were predicted in West, Southwest and Central parts of Uganda, which corresponds to bat distribution and previous filovirus outbreaks areas. Additionally, the models predicted the Eastern Uganda region and other areas that have not reported outbreaks before to be potential outbreak hotspots. Rainfall variables were the most important in influencing model prediction compared to temperature variables. Despite the limitations in the prediction model due to lack of adequate sample records for outbreaks, especially for the Marburg cases, the models provided risk maps to the Uganda surveillance system on filovirus outbreaks. The risk maps will aid in identifying areas to focus the filovirus surveillance for early detection and responses hence curtailing a pandemic. The results from this study also confirm previous findings that suggest that filoviruses are mainly limited by the amount of rainfall received in an area.

  19. Ecological Niche Modeling for Filoviruses: A Risk Map for Ebola and Marburg Virus Disease Outbreaks in Uganda

    PubMed Central

    Nyakarahuka, Luke; Ayebare, Samuel; Mosomtai, Gladys; Kankya, Clovice; Lutwama, Julius; Mwiine, Frank Norbert; Skjerve, Eystein

    2017-01-01

    Introduction: Uganda has reported eight outbreaks caused by filoviruses between 2000 to 2016, more than any other country in the world. We used species distribution modeling to predict where filovirus outbreaks are likely to occur in Uganda to help in epidemic preparedness and surveillance. Methods: The MaxEnt software, a machine learning modeling approach that uses presence-only data was used to establish filovirus – environmental relationships. Presence-only data for filovirus outbreaks were collected from the field and online sources. Environmental covariates from Africlim that have been downscaled to a nominal resolution of 1km x 1km were used. The final model gave the relative probability of the presence of filoviruses in the study area obtained from an average of 100 bootstrap runs. Model evaluation was carried out using Receiver Operating Characteristic (ROC) plots. Maps were created using ArcGIS 10.3 mapping software. Results: We showed that bats as potential reservoirs of filoviruses are distributed all over Uganda. Potential outbreak areas for Ebola and Marburg virus disease were predicted in West, Southwest and Central parts of Uganda, which corresponds to bat distribution and previous filovirus outbreaks areas. Additionally, the models predicted the Eastern Uganda region and other areas that have not reported outbreaks before to be potential outbreak hotspots. Rainfall variables were the most important in influencing model prediction compared to temperature variables. Conclusions: Despite the limitations in the prediction model due to lack of adequate sample records for outbreaks, especially for the Marburg cases, the models provided risk maps to the Uganda surveillance system on filovirus outbreaks. The risk maps will aid in identifying areas to focus the filovirus surveillance for early detection and responses hence curtailing a pandemic. The results from this study also confirm previous findings that suggest that filoviruses are mainly limited by

  20. Physicochemical inactivation of Lassa, Ebola, and Marburg viruses and effect on clinical laboratory analyses

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

    Mitchell, S.W.; McCormick, J.B.

    1984-09-01

    Clinical specimens from patients infected with Lassa, Ebola, or Marburg virus may present a serious biohazard to laboratory workers. The authors have examined the effects of heat, alteration of pH, and gamma radiation on these viruses in human blood and on the electrolytes, enzymes, and coagulation factors measured in laboratory tests that are important in the care of an infected patient. Heating serum at 60 degrees C for 1 h reduced high titers of these viruses to noninfectious levels without altering the serum levels of glucose, blood urea nitrogen, and electrolytes. Dilution of blood in 3% acetic acid, diluent formore » a leukocyte count, inactivated all of these viruses. All of the methods tested for viral inactivation markedly altered certain serum proteins, making these methods unsuitable for samples that are to be tested for certain enzyme levels and coagulation factors.« less

  1. 29 CFR 102.26 - Motions, rulings, and orders part of the record; rulings not to be appealed directly to the Board...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... regional director or by the administrative law judge on motions and/or by the administrative law judge on... 29 Labor 2 2010-07-01 2010-07-01 false Motions, rulings, and orders part of the record; rulings... Unfair Labor Practices 1 Motions § 102.26 Motions, rulings, and orders part of the record; rulings not to...

  2. Work Hours and Self rated Health of Hospital Doctors in Norway and Germany. A comparative study on national samples

    PubMed Central

    2011-01-01

    Background The relationship between extended work hours and health is well documented among hospital doctors, but the effect of national differences in work hours on health is unexplored. The study examines the relationship between work hours and self rated health in two national samples of hospital doctors. Methods The study population consisted of representative samples of 1,260 German and 562 Norwegian hospital doctors aged 25-65 years (N = 1,822) who received postal questionnaires in 2006 (Germany) and 2008 (Norway). The questionnaires contained items on demography, work hours (number of hours per workday and on-call per month) and self rated subjective health on a five point scale - dichotomized into "good" (above average) and "average or below". Results Compared to Norway, a significantly higher proportion of German doctors exceeded a 9 hour work day (58.8% vs. 26.7%) and 60 hours on-call per month (63.4% vs. 18.3%). Every third (32.2%) hospital doctor in Germany worked more than this, while this pattern was rare in Norway (2.9%). In a logistic regression model, working in Norway (OR 4.17; 95% CI 3.02-5.73), age 25-44 years (OR 1.66; 95% CI 1.29-2.14) and not exceeding 9 hour work day and 60 hours on-call per month (OR 1.35; 95% CI 1.03-1.77) were all independent significant predictors of good self reported health. Conclusion A lower percentage of German hospital doctors reported self rated health as "good", which is partly explained by the differences in work time pattern. Initiatives to increase doctors' control over their work time are recommended. PMID:21338494

  3. 29 CFR 1910.26 - Portable metal ladders.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR OCCUPATIONAL SAFETY AND HEALTH STANDARDS Walking-Working Surfaces § 1910.26 Portable metal ladders. (a... material for the safety of the user. (viii) A metal spreader or locking device of sufficient size and...

  4. 46 CFR 54.20-5 - Welding qualification tests and production testing (modifies UW-26, UW-28, UW-29, UW-47, and UW-48).

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Welding qualification tests and production testing... OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Fabrication by Welding § 54.20-5 Welding qualification tests and production testing (modifies UW-26, UW-28, UW-29, UW-47, and UW-48). (a...

  5. 46 CFR 54.20-5 - Welding qualification tests and production testing (modifies UW-26, UW-28, UW-29, UW-47, and UW-48).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Welding qualification tests and production testing... OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Fabrication by Welding § 54.20-5 Welding qualification tests and production testing (modifies UW-26, UW-28, UW-29, UW-47, and UW-48). (a...

  6. 46 CFR 54.20-5 - Welding qualification tests and production testing (modifies UW-26, UW-28, UW-29, UW-47, and UW-48).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Welding qualification tests and production testing... OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Fabrication by Welding § 54.20-5 Welding qualification tests and production testing (modifies UW-26, UW-28, UW-29, UW-47, and UW-48). (a...

  7. 46 CFR 54.20-5 - Welding qualification tests and production testing (modifies UW-26, UW-28, UW-29, UW-47, and UW-48).

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Welding qualification tests and production testing... OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Fabrication by Welding § 54.20-5 Welding qualification tests and production testing (modifies UW-26, UW-28, UW-29, UW-47, and UW-48). (a...

  8. 46 CFR 54.20-5 - Welding qualification tests and production testing (modifies UW-26, UW-28, UW-29, UW-47, and UW-48).

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Welding qualification tests and production testing... OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Fabrication by Welding § 54.20-5 Welding qualification tests and production testing (modifies UW-26, UW-28, UW-29, UW-47, and UW-48). (a...

  9. Economic burden of advanced melanoma in France, Germany and the UK: a retrospective observational study (Melanoma Burden-of-Illness Study).

    PubMed

    Grange, Florent; Mohr, Peter; Harries, Mark; Ehness, Rainer; Benjamin, Laure; Siakpere, Obukohwo; Barth, Janina; Stapelkamp, Ceilidh; Pfersch, Sylvie; McLeod, Lori D; Kaye, James A; Wolowacz, Sorrel; Kontoudis, Ilias

    2017-12-01

    The aim of this study was to estimate the cost-of-illness associated with completely resected stage IIIB/IIIC melanoma with macroscopic lymph node involvement, overall and by disease phase, in France, Germany and the UK. This retrospective observational study included patients aged older than or equal to 18 years first diagnosed with stage IIIB/IIIC cutaneous melanoma between 1 January 2009 and 31 December 2011. Data were obtained from medical records and a patient survey. Direct costs, indirect costs and patient out-of-pocket expenses were estimated in euros (€) (and British pounds, £) by collecting resource use and multiplying by country-specific unit costs. National annual costs were estimated using national disease prevalence from the European cancer registry and other published data. Forty-nine centres provided data on 558 patients (58.2% aged <65 years, 53.6% stage IIIB disease at diagnosis). The mean follow-up duration was 27 months (France), 26 months (Germany) and 22 months (UK). The mean total direct cost per patient during follow-up was €23 582 in France, €32 058 in Germany and €37 970 (£31 123) in the UK. The largest cost drivers were melanoma drugs [mean €14 004, €21 269, €29 750 (£24 385), respectively] and hospitalization/emergency treatment [mean: €6634, €6950, €3449 (£2827), respectively]. The total mean indirect costs per patient were €129 (France), €4,441 (Germany) and €1712 (£1427) (UK). Estimates for annual national direct cost were €13.1 million (France), €30.2 million (Germany) and €27.8 (£22.8) million (UK). The economic burden of stage IIIB/IIIC melanoma with macroscopic lymph node involvement was substantial in all three countries. Total direct costs were the highest during the period with distant metastasis/terminal illness.

  10. 29 CFR 553.26 - Cash overtime payments.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...)-Compensatory Time and Compensatory Time Off § 553.26 Cash overtime payments. (a) Overtime compensation due under section 7 may be paid in cash at the employer's option, in lieu of providing compensatory time off... from freely substituting cash, in whole or part, for compensatory time off; and overtime payment in...

  11. 29 CFR 553.26 - Cash overtime payments.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...)-Compensatory Time and Compensatory Time Off § 553.26 Cash overtime payments. (a) Overtime compensation due under section 7 may be paid in cash at the employer's option, in lieu of providing compensatory time off... from freely substituting cash, in whole or part, for compensatory time off; and overtime payment in...

  12. Animal models for Ebola and Marburg virus infections

    PubMed Central

    Nakayama, Eri; Saijo, Masayuki

    2013-01-01

    Ebola and Marburg hemorrhagic fevers (EHF and MHF) are caused by the Filoviridae family, Ebolavirus and Marburgvirus (ebolavirus and marburgvirus), respectively. These severe diseases have high mortality rates in humans. Although EHF and MHF are endemic to sub-Saharan Africa. A novel filovirus, Lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in Spain where filoviral hemorrhagic fever had never been reported. The virulence of this virus has not been determined. Ebolavirus and marburgvirus are classified as biosafety level-4 (BSL-4) pathogens and Category A agents, for which the US government requires preparedness in case of bioterrorism. Therefore, preventive measures against these viral hemorrhagic fevers should be prepared, not only in disease-endemic regions, but also in disease-free countries. Diagnostics, vaccines, and therapeutics need to be developed, and therefore the establishment of animal models for EHF and MHF is invaluable. Several animal models have been developed for EHF and MHF using non-human primates (NHPs) and rodents, which are crucial to understand pathophysiology and to develop diagnostics, vaccines, and therapeutics. Rhesus and cynomolgus macaques are representative models of filovirus infection as they exhibit remarkably similar symptoms to those observed in humans. However, the NHP models have practical and ethical problems that limit their experimental use. Furthermore, there are no inbred and genetically manipulated strains of NHP. Rodent models such as mouse, guinea pig, and hamster, have also been developed. However, these rodent models require adaptation of the virus to produce lethal disease and do not mirror all symptoms of human filovirus infection. This review article provides an outline of the clinical features of EHF and MHF in animals, including humans, and discusses how the animal models have been developed to study pathophysiology, vaccines, and therapeutics. PMID:24046765

  13. Animal models for Ebola and Marburg virus infections.

    PubMed

    Nakayama, Eri; Saijo, Masayuki

    2013-09-05

    Ebola and Marburg hemorrhagic fevers (EHF and MHF) are caused by the Filoviridae family, Ebolavirus and Marburgvirus (ebolavirus and marburgvirus), respectively. These severe diseases have high mortality rates in humans. Although EHF and MHF are endemic to sub-Saharan Africa. A novel filovirus, Lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in Spain where filoviral hemorrhagic fever had never been reported. The virulence of this virus has not been determined. Ebolavirus and marburgvirus are classified as biosafety level-4 (BSL-4) pathogens and Category A agents, for which the US government requires preparedness in case of bioterrorism. Therefore, preventive measures against these viral hemorrhagic fevers should be prepared, not only in disease-endemic regions, but also in disease-free countries. Diagnostics, vaccines, and therapeutics need to be developed, and therefore the establishment of animal models for EHF and MHF is invaluable. Several animal models have been developed for EHF and MHF using non-human primates (NHPs) and rodents, which are crucial to understand pathophysiology and to develop diagnostics, vaccines, and therapeutics. Rhesus and cynomolgus macaques are representative models of filovirus infection as they exhibit remarkably similar symptoms to those observed in humans. However, the NHP models have practical and ethical problems that limit their experimental use. Furthermore, there are no inbred and genetically manipulated strains of NHP. Rodent models such as mouse, guinea pig, and hamster, have also been developed. However, these rodent models require adaptation of the virus to produce lethal disease and do not mirror all symptoms of human filovirus infection. This review article provides an outline of the clinical features of EHF and MHF in animals, including humans, and discusses how the animal models have been developed to study pathophysiology, vaccines, and therapeutics.

  14. Patterns of Enterprise Flexibility: IAB Establishment Panel Results, Western Germany, 1993-95.

    ERIC Educational Resources Information Center

    Bellmann, Lutz; Dull, Herbert; Kuhl, Jurgen; Lahner, Manfred; Lehmann, Udo

    1997-01-01

    Data on flexibility in German companies were compiled through interviews and followed up annually. Employment trends in western Germany indicated a historic peak of 29.5 million employed in 1992 followed by a steady decline of about 1 million to 28.5 million in 1995. Employment losses continued in 1996; 1997 showed some signs of stability.…

  15. Epidemiology of trichinellosis in Germany, 1996-2006.

    PubMed

    Jansen, Andreas; Schöneberg, Irene; Stark, Klaus; Nöckler, Karsten

    2008-04-01

    The epidemiology of trichinellosis in Germany was investigated by analyzing national surveillance data from 1996-2006. During this period, 95 laboratory-confirmed infections and 12 outbreaks were reported. The highest mean annual incidence was found in immigrants from southeast European countries (0.3 cases/100,000 vs. 0.01 cases/100,000 in the German population) with an incidence rate ratio of 26.0 (95% confidence interval 11.6-51.8). The predominant clinical symptom was muscle pain in 79 patients (83%). Mean diagnostic delay was 49 days. Among patients with reported source of infection (85%; n = 81), the consumption of pork (mostly originating from endemic countries) represented the most frequent exposure (93%; n = 75). In addition, trichinellosis cases were associated with both indigenous (n = 1) and imported (n = 5) wild boar meat. Although domestic pigs in Germany are practically free from Trichinella spp., the parasite was found in German wild animals such as wild boars, foxes, and racoon dogs. We conclude that trichinellosis still remains a public health issue in Germany, especially among individuals with a migrational background. Immigrants from endemic countries need to be educated about the risks of consuming raw or inadequately cooked pork and wild boar products from their homeland. In addition, German healthcare providers need to be aware of trichinellosis, especially in areas with a large immigrant population.

  16. A multiagent filovirus DNA vaccine delivered by intramuscular electroporation completely protects mice from ebola and Marburg virus challenge.

    PubMed

    Grant-Klein, Rebecca J; Van Deusen, Nicole M; Badger, Catherine V; Hannaman, Drew; Dupuy, Lesley C; Schmaljohn, Connie S

    2012-11-01

    We evaluated the immunogenicity and protective efficacy of DNA vaccines expressing the codon-optimized envelope glycoprotein genes of Zaire ebolavirus, Sudan ebolavirus, and Marburg marburgvirus (Musoke and Ravn). Intramuscular or intradermal delivery of the vaccines in BALB/c mice was performed using the TriGrid™ electroporation device. Mice that received DNA vaccines against the individual viruses developed robust glycoprotein-specific antibody titers as determined by ELISA and survived lethal viral challenge with no display of clinical signs of infection. Survival curve analysis revealed there was a statistically significant increase in survival compared to the control groups for both the Ebola and Ravn virus challenges. These data suggest that further analysis of the immune responses generated in the mice and additional protection studies in nonhuman primates are warranted.

  17. 40 CFR 268.21-268.29 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false [Reserved] 268.21-268.29 Section 268.21-268.29 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) LAND DISPOSAL RESTRICTIONS Prohibitions on Land Disposal §§ 268.21-268.29 [Reserved] ...

  18. Interferon-β therapy prolongs survival in rhesus macaque models of Ebola and Marburg hemorrhagic fever.

    PubMed

    Smith, Lauren M; Hensley, Lisa E; Geisbert, Thomas W; Johnson, Joshua; Stossel, Andrea; Honko, Anna; Yen, Judy Y; Geisbert, Joan; Paragas, Jason; Fritz, Elizabeth; Olinger, Gene; Young, Howard A; Rubins, Kathleen H; Karp, Christopher L

    2013-07-15

    There is a clear need for novel, effective therapeutic approaches to hemorrhagic fever due to filoviruses. Ebola virus hemorrhagic fever is associated with robust interferon (IFN)-α production, with plasma concentrations of IFN-α that greatly (60- to 100-fold) exceed those seen in other viral infections, but little IFN-β production. While all of the type I IFNs signal through the same receptor complex, both quantitative and qualitative differences in biological activity are observed after stimulation of the receptor complex with different type I IFNs. Taken together, this suggested potential for IFN-β therapy in filovirus infection. Here we show that early postexposure treatment with IFN-β significantly increased survival time of rhesus macaques infected with a lethal dose of Ebola virus, although it failed to alter mortality. Early treatment with IFN-β also significantly increased survival time after Marburg virus infection. IFN-β may have promise as an adjunctive postexposure therapy in filovirus infection.

  19. The Use of a Mobile Laboratory Unit in Support of Patient Management and Epidemiological Surveillance during the 2005 Marburg Outbreak in Angola

    PubMed Central

    Grolla, Allen; Jones, Steven M.; Fernando, Lisa; Strong, James E.; Ströher, Ute; Möller, Peggy; Paweska, Janusz T.; Burt, Felicity; Pablo Palma, Pedro; Sprecher, Armand; Formenty, Pierre; Roth, Cathy; Feldmann, Heinz

    2011-01-01

    Background Marburg virus (MARV), a zoonotic pathogen causing severe hemorrhagic fever in man, has emerged in Angola resulting in the largest outbreak of Marburg hemorrhagic fever (MHF) with the highest case fatality rate to date. Methodology/Principal Findings A mobile laboratory unit (MLU) was deployed as part of the World Health Organization outbreak response. Utilizing quantitative real-time PCR assays, this laboratory provided specific MARV diagnostics in Uige, the epicentre of the outbreak. The MLU operated over a period of 88 days and tested 620 specimens from 388 individuals. Specimens included mainly oral swabs and EDTA blood. Following establishing on site, the MLU operation allowed a diagnostic response in <4 hours from sample receiving. Most cases were found among females in the child-bearing age and in children less than five years of age. The outbreak had a high number of paediatric cases and breastfeeding may have been a factor in MARV transmission as indicated by the epidemiology and MARV positive breast milk specimens. Oral swabs were a useful alternative specimen source to whole blood/serum allowing testing of patients in circumstances of resistance to invasive procedures but limited diagnostic testing to molecular approaches. There was a high concordance in test results between the MLU and the reference laboratory in Luanda operated by the US Centers for Disease Control and Prevention. Conclusions/Significance The MLU was an important outbreak response asset providing support in patient management and epidemiological surveillance. Field laboratory capacity should be expanded and made an essential part of any future outbreak investigation. PMID:21629730

  20. Development and characterization of a guinea pig model for Marburg virus.

    PubMed

    Wong, Gary; Cao, Wen-Guang; He, Shi-Hua; Zhang, Zi-Rui; Zhu, Wen-Jun; Moffat, Estella; Ebihara, Hideki; Embury-Hyatt, Carissa; Qiu, Xiang-Guo

    2018-01-18

    The Angolan strain of Marburg virus (MARV/Ang) can cause lethal disease in humans with a case fatality rate of up to 90%, but infection of immunocompetent rodents do not result in any observable symptoms. Our previous work includes the development and characterization of a MARV/Ang variant that can cause lethal disease in mice (MARV/Ang-MA), with the aim of using this tool to screen for promising prophylactic and therapeutic candidates. An intermediate animal model is needed to confirm any findings from mice studies before testing in the gold-standard non-human primate (NHP) model. In this study, we serially passaged the clinical isolate of MARV/Ang in the livers and spleens of guinea pigs until a variant emerged that causes 100% lethality in guinea pigs (MARV/Ang-GA). Animals infected with MARV/Ang-GA showed signs of filovirus infection including lymphocytopenia, thrombocytopenia, and high viremia leading to spread to major organs, including the liver, spleen, lungs, and kidneys. The MARV/Ang-GA guinea pigs died between 7-9 days after infection, and the LD 50 was calculated to be 1.1×10 -1 TCID 50 (median tissue culture infective dose). Mutations in MARV/Ang-GA were identified and compared to sequences of known rodent-adapted MARV/Ang variants, which may benefit future studies characterizing important host adaptation sites in the MARV/Ang viral genome.

  1. Complex adenovirus-vectored vaccine protects guinea pigs from three strains of Marburg virus challenges.

    PubMed

    Wang, Danher; Hevey, Michael; Juompan, Laure Y; Trubey, Charles M; Raja, Nicholas U; Deitz, Stephen B; Woraratanadharm, Jan; Luo, Min; Yu, Hong; Swain, Benjamin M; Moore, Kevin M; Dong, John Y

    2006-09-30

    The Marburg virus (MARV), an African filovirus closely related to the Ebola virus, causes a deadly hemorrhagic fever in humans, with up to 90% mortality. Currently, treatment of disease is only supportive, and no vaccines are available to prevent spread of MARV infections. In order to address this need, we have developed and characterized a novel recombinant vaccine that utilizes a single complex adenovirus-vectored vaccine (cAdVax) to overexpress a MARV glycoprotein (GP) fusion protein derived from the Musoke and Ci67 strains of MARV. Vaccination with the cAdVaxM(fus) vaccine led to efficient production of MARV-specific antibodies in both mice and guinea pigs. Significantly, guinea pigs vaccinated with at least 5 x 10(7) pfu of cAdVaxM(fus) vaccine were 100% protected against lethal challenges by the Musoke, Ci67 and Ravn strains of MARV, making it a vaccine with trivalent protective efficacy. Therefore, the cAdVaxM(fus) vaccine serves as a promising vaccine candidate to prevent and contain multi-strain infections by MARV.

  2. Marburg virus survivor immune responses are Th1 skewed with limited neutralizing antibody responses.

    PubMed

    Stonier, Spencer W; Herbert, Andrew S; Kuehne, Ana I; Sobarzo, Ariel; Habibulin, Polina; Dahan, Chen V Abramovitch; James, Rebekah M; Egesa, Moses; Cose, Stephen; Lutwama, Julius Julian; Lobel, Leslie; Dye, John M

    2017-09-04

    Until recently, immune responses in filovirus survivors remained poorly understood. Early studies revealed IgM and IgG responses to infection with various filoviruses, but recent outbreaks have greatly expanded our understanding of filovirus immune responses. Immune responses in survivors of Ebola virus (EBOV) and Sudan virus (SUDV) infections have provided the most insight, with T cell responses as well as detailed antibody responses having been characterized. Immune responses to Marburg virus (MARV), however, remain almost entirely uncharacterized. We report that immune responses in MARV survivors share characteristics with EBOV and SUDV infections but have some distinct differences. MARV survivors developed multivariate CD4 + T cell responses but limited CD8 + T cell responses, more in keeping with SUDV survivors than EBOV survivors. In stark contrast to SUDV survivors, rare neutralizing antibody responses in MARV survivors diminished rapidly after the outbreak. These results warrant serious consideration for any vaccine or therapeutic that seeks to be broadly protective, as different filoviruses may require different immune responses to achieve immunity. © 2017 Stonier et al.

  3. Complex adenovirus-vectored vaccine protects guinea pigs from three strains of Marburg virus challenges

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

    Wang Danher; Hevey, Michael; Juompan, Laure Y.

    2006-09-30

    The Marburg virus (MARV), an African filovirus closely related to the Ebola virus, causes a deadly hemorrhagic fever in humans, with up to 90% mortality. Currently, treatment of disease is only supportive, and no vaccines are available to prevent spread of MARV infections. In order to address this need, we have developed and characterized a novel recombinant vaccine that utilizes a single complex adenovirus-vectored vaccine (cAdVax) to overexpress a MARV glycoprotein (GP) fusion protein derived from the Musoke and Ci67 strains of MARV. Vaccination with the cAdVaxM(fus) vaccine led to efficient production of MARV-specific antibodies in both mice and guineamore » pigs. Significantly, guinea pigs vaccinated with at least 5 x 10{sup 7} pfu of cAdVaxM(fus) vaccine were 100% protected against lethal challenges by the Musoke, Ci67 and Ravn strains of MARV, making it a vaccine with trivalent protective efficacy. Therefore, the cAdVaxM(fus) vaccine serves as a promising vaccine candidate to prevent and contain multi-strain infections by MARV.« less

  4. 40 CFR 305.26 - Prehearing conference.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 29 2012-07-01 2012-07-01 false Prehearing conference. 305.26 Section 305.26 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SUPERFUND, EMERGENCY... LIABILITY ACT (CERCLA) ADMINISTRATIVE HEARING PROCEDURES FOR CLAIMS AGAINST THE SUPERFUND Prehearing...

  5. 40 CFR 305.26 - Prehearing conference.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 29 2013-07-01 2013-07-01 false Prehearing conference. 305.26 Section 305.26 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SUPERFUND, EMERGENCY... LIABILITY ACT (CERCLA) ADMINISTRATIVE HEARING PROCEDURES FOR CLAIMS AGAINST THE SUPERFUND Prehearing...

  6. Tissue and cellular tropism, pathology and pathogenesis of Ebola and Marburg viruses.

    PubMed

    Martines, Roosecelis Brasil; Ng, Dianna L; Greer, Patricia W; Rollin, Pierre E; Zaki, Sherif R

    2015-01-01

    Ebola viruses and Marburg viruses include some of the most virulent and fatal pathogens known to humans. These viruses cause severe haemorrhagic fevers, with case fatality rates in the range 25-90%. The diagnosis of filovirus using formalin-fixed tissues from fatal cases poses a significant challenge. The most characteristic histopathological findings are seen in the liver; however, the findings overlap with many other viral and non-viral haemorrhagic diseases. The need to distinguish filovirus infections from other haemorrhagic fevers, particularly in areas with multiple endemic viral haemorrhagic agents, is of paramount importance. In this review we discuss the current state of knowledge of filovirus infections and their pathogenesis, including histopathological findings, epidemiology, modes of transmission and filovirus entry and spread within host organisms. The pathogenesis of filovirus infections is complex and involves activation of the mononuclear phagocytic system, with release of pro-inflammatory cytokines, chemokines and growth factors, endothelial dysfunction, alterations of the innate and adaptive immune systems, direct organ and endothelial damage from unrestricted viral replication late in infection, and coagulopathy. Although our understanding of the pathogenesis of filovirus infections has rapidly increased in the past few years, many questions remain unanswered. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  7. Biophysical characterization and conformational stability of Ebola and Marburg virus-like particles.

    PubMed

    Hu, Lei; Trefethen, Jared M; Zeng, Yuhong; Yee, Luisa; Ohtake, Satoshi; Lechuga-Ballesteros, David; Warfield, Kelly L; Aman, M Javad; Shulenin, Sergey; Unfer, Robert; Enterlein, Sven G; Truong-Le, Vu; Volkin, David B; Joshi, Sangeeta B; Middaugh, C Russell

    2011-12-01

    The filoviruses, Ebola virus and Marburg virus, cause severe hemorrhagic fever with up to 90% human mortality. Virus-like particles of EBOV (eVLPs) and MARV (mVLPs) are attractive vaccine candidates. For the development of stable vaccines, the conformational stability of these two enveloped VLPs produced in insect cells was characterized by various spectroscopic techniques over a wide pH and temperature range. Temperature-induced aggregation of the VLPs at various pH values was monitored by light scattering. Temperature/pH empirical phase diagrams (EPDs) of the two VLPs were constructed to summarize the large volume of data generated. The EPDs show that both VLPs lose their conformational integrity above about 50°C-60°C, depending on solution pH. The VLPs were maximally thermal stable in solution at pH 7-8, with a significant reduction in stability at pH 5 and 6. They were much less stable in solution at pH 3-4 due to increased susceptibility of the VLPs to aggregation. The characterization data and conformational stability profiles from these studies provide a basis for selection of optimized solution conditions for further vaccine formulation and long-term stability studies of eVLPs and mVLPs. Copyright © 2011 Wiley-Liss, Inc.

  8. The glycoproteins of Marburg and Ebola virus and their potential roles in pathogenesis.

    PubMed

    Feldmann, H; Volchkov, V E; Volchkova, V A; Klenk, H D

    1999-01-01

    Filoviruses cause systemic infections that can lead to severe hemorrhagic fever in human and non-human primates. The primary target of the virus appears to be the mononuclear phagocytic system. As the virus spreads through the organism, the spectrum of target cells increases to include endothelial cells, fibroblasts, hepatocytes, and many other cells. There is evidence that the filovirus glycoprotein plays an important role in cell tropism, spread of infection, and pathogenicity. Biosynthesis of the glycoprotein forming the spikes on the virion surface involves cleavage by the host cell protease furin into two disulfide linked subunits GP1 and GP2. GP1 is also shed in soluble form from infected cells. Different strains of Ebola virus show variations in the cleavability of the glycoprotein, that may account for differences in pathogenicity, as has been observed with influenza viruses and paramyxoviruses. Expression of the spike glycoprotein of Ebola virus, but not of Marburg virus, requires transcriptional editing. Unedited GP mRNA yields the nonstructural glycoprotein sGP, which is secreted extensively from infected cells. Whether the soluble glycoproteins GP1 and sGP interfere with the humoral immune response and other defense mechanisms remains to be determined.

  9. Structural Insight into Nucleoprotein Conformation Change Chaperoned by VP35 Peptide in Marburg Virus.

    PubMed

    Liu, Baocheng; Dong, Shishang; Li, Guobang; Wang, Wenming; Liu, Xiang; Wang, Yantong; Yang, Cheng; Rao, Zihe; Guo, Yu

    2017-08-15

    Marburg virus (MARV) encodes a nucleoprotein (NP) to encapsidate its genome by oligomerization and form a ribonucleoprotein complex (RNP). According to previous investigation on nonsegmented negative-sense RNA viruses (nsNSV), the newly synthesized NPs must be prevented from indiscriminately binding to noncognate RNAs. During the viral RNA synthesis process, the RNPs undergo a transition from an RNA-bound form to a template-free form, to open access for the interaction between the viral polymerase and the RNA template. In filoviruses, this transition is regulated by VP35 peptide and other viral components. To further understand the dynamic process of filovirus RNP formation, we report here the structure of MARV NP core , both in the apo form and in the VP35 peptide-chaperoned form. These structures reveal a typical bilobed structure, with a positive-charged RNA binding groove between two lobes. In the apo form, the MARV NP exists in an interesting hexameric state formed by the hydrophobic interaction within the long helix of the NP core C-terminal region, which shows high structural flexibility among filoviruses and may imply critical function during RNP formation. Moreover, the VP35 peptide-chaperoned NP core remains in a monomeric state and completely loses its affinity for single-stranded RNA (ssRNA). The structural comparison reveals that the RNA binding groove undergoes a transition from closed state to open state, chaperoned by VP35 peptide, thus preventing the interaction for viral RNA. Our investigation provides considerable structural insight into the filovirus RNP working mechanism and may support the development of antiviral therapies targeting the RNP formation of filovirus. IMPORTANCE Marburg virus is one of the most dangerous viruses, with high morbidity and mortality. A recent outbreak in Angola in 2005 caused the deaths of 272 persons. NP is one of the most essential proteins, as it encapsidates and protects the whole virus genome simultaneously

  10. Egyptian rousette bats maintain long-term protective immunity against Marburg virus infection despite diminished antibody levels.

    PubMed

    Schuh, Amy J; Amman, Brian R; Sealy, Tara K; Spengler, Jessica R; Nichol, Stuart T; Towner, Jonathan S

    2017-08-18

    Although bats are natural reservoir hosts for numerous zoonotic viruses, little is known about the long-term dynamics of the host immune response following infection and how these viruses are maintained in nature. The Egyptian rousette bat (ERB) is a known reservoir host for Marburg virus (MARV). Following infection of ERBs with MARV, virus-specific IgG antibodies are induced but rapidly wane and by 3 months post-infection the bats are seronegative. To determine whether reinfection of ERBs plays a role in MARV maintenance, we challenge groups of ERBs that were "naturally" or experimentally infected with MARV 17-24 months prior. No bats in either group exhibit evidence of MARV replication or shedding and all bats develop virus-specific secondary immune responses. This study demonstrates that infection of ERBs with MARV induces long-term protective immunity against reinfection and indicates that other factors, such as host population dynamics, drive MARV maintenance in nature.

  11. 40 CFR 463.26 - Pretreatment for new sources.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Pretreatment for new sources. 463.26 Section 463.26 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS PLASTICS MOLDING AND FORMING POINT SOURCE CATEGORY Cleaning Water Subcategory § 463.26...

  12. Establishment of a voluntary electronic Chlamydia trachomatis laboratory surveillance system in Germany, 2008 to 2014

    PubMed Central

    Dudareva-Vizule, Sandra; Haar, Karin; Sailer, Andrea; Jansen, Klaus; Hamouda, Osamah; Wisplinghoff, Hilmar; Tiemann, Carsten; Pape, Eberhard; Bremer, Viviane

    2017-01-01

    Chlamydia trachomatis (CT) infections are not reportable in Germany and limited data on prevalence are available. CT screening has been offered free of charge to pregnant women since 1995 and to all women under 25 years since 2008. For symptomatic women and men, diagnostic testing is covered by statutory health insurance. We describe the establishment of a nationwide, laboratory-based, voluntary sentinel that electronically collects information on all performed CT tests with test results, test reason and patient information. The sentinel represents one third of all performed CT tests in Germany. In the period from 2008 to 2014, 3,877,588 CT tests were reported, 93% in women. Women aged 20–24 years and men aged 25–29 years were the most frequently tested age groups. The overall proportion of positive tests (PPT) among women was 3.9% and among men 11.0%. The highest PPT among women was in the age groups 15–19 (6.8%) and 20–24 years (5.9%), and among men in the age groups 20–24 (19.2%), 15–19 (15.4%) and 25–29 years (14.8%). The PPT for CT was high among women and men younger than 25 years. Prevention is urgently needed. Monitoring of CT infection in Germany should be continued. PMID:28205505

  13. Establishment of a voluntary electronic Chlamydia trachomatis laboratory surveillance system in Germany, 2008 to 2014.

    PubMed

    Dudareva-Vizule, Sandra; Haar, Karin; Sailer, Andrea; Jansen, Klaus; Hamouda, Osamah; Wisplinghoff, Hilmar; Tiemann, Carsten; Pape, Eberhard; Bremer, Viviane

    2017-02-09

    Chlamydia trachomatis (CT) infections are not reportable in Germany and limited data on prevalence are available. CT screening has been offered free of charge to pregnant women since 1995 and to all women under 25 years since 2008. For symptomatic women and men, diagnostic testing is covered by statutory health insurance. We describe the establishment of a nationwide, laboratory-based, voluntary sentinel that electronically collects information on all performed CT tests with test results, test reason and patient information. The sentinel represents one third of all performed CT tests in Germany. In the period from 2008 to 2014, 3,877,588 CT tests were reported, 93% in women. Women aged 20-24 years and men aged 25-29 years were the most frequently tested age groups. The overall proportion of positive tests (PPT) among women was 3.9% and among men 11.0%. The highest PPT among women was in the age groups 15-19 (6.8%) and 20-24 years (5.9%), and among men in the age groups 20-24 (19.2%), 15-19 (15.4%) and 25-29 years (14.8%). The PPT for CT was high among women and men younger than 25 years. Prevention is urgently needed. Monitoring of CT infection in Germany should be continued. This article is copyright of The Authors, 2017.

  14. The Mother Centers in Germany--Empowerment Strategies for Community Women in Germany.

    ERIC Educational Resources Information Center

    Jaeckel, Monika

    Mother Centers are a grassroots self-help movement in Germany that help stay-at-home mothers break through the isolation they experience in German society when they have children and are not available for full-time employment. There are about 300 mother center projects currently in Germany, including 40 in the former East Germany. The programs…

  15. Lack of Marburg Virus Transmission From Experimentally Infected to Susceptible In-Contact Egyptian Fruit Bats.

    PubMed

    Paweska, Janusz T; Jansen van Vuren, Petrus; Fenton, Karla A; Graves, Kerry; Grobbelaar, Antoinette A; Moolla, Naazneen; Leman, Patricia; Weyer, Jacqueline; Storm, Nadia; McCulloch, Stewart D; Scott, Terence P; Markotter, Wanda; Odendaal, Lieza; Clift, Sarah J; Geisbert, Thomas W; Hale, Martin J; Kemp, Alan

    2015-10-01

    Egyptian fruit bats (Rousettus aegyptiacus) were inoculated subcutaneously (n = 22) with Marburg virus (MARV). No deaths, overt signs of morbidity, or gross lesions was identified, but microscopic pathological changes were seen in the liver of infected bats. The virus was detected in 15 different tissues and plasma but only sporadically in mucosal swab samples, urine, and fecal samples. Neither seroconversion nor viremia could be demonstrated in any of the in-contact susceptible bats (n = 14) up to 42 days after exposure to infected bats. In bats rechallenged (n = 4) on day 48 after infection, there was no viremia, and the virus could not be isolated from any of the tissues tested. This study confirmed that infection profiles are consistent with MARV replication in a reservoir host but failed to demonstrate MARV transmission through direct physical contact or indirectly via air. Bats develop strong protective immunity after infection with MARV. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. An active site mutation increases the polymerase activity of the guinea pig-lethal Marburg virus.

    PubMed

    Koehler, Alexander; Kolesnikova, Larissa; Becker, Stephan

    2016-10-01

    Marburg virus (MARV) causes severe, often fatal, disease in humans and transient illness in rodents. Sequential passaging of MARV in guinea pigs resulted in selection of a lethal virus containing 4 aa changes. A D184N mutation in VP40 (VP40D184N), which leads to a species-specific gain of viral fitness, and three mutations in the active site of viral RNA-dependent RNA polymerase L, which were investigated in the present study for functional significance in human and guinea pig cells. The transcription/replication activity of L mutants was strongly enhanced by a substitution at position 741 (S741C), and inhibited by other substitutions (D758A and A759D) in both species. The polymerase activity of L carrying the S741C substitution was eightfold higher in guinea pig cells than in human cells upon co-expression with VP40D184N, suggesting that the additive effect of the two mutations provides MARV a replicative advantage in the new host.

  17. Genetic and physiological characterization of the purine salvage pathway in the archaebacterium Methanobacterium thermoautotrophicum Marburg.

    PubMed Central

    Worrell, V E; Nagle, D P

    1990-01-01

    The enzymes involved in the purine interconversion pathway of wild-type and purine analog-resistant strains of Methanobacterium thermoautotrophicum Marburg were assayed by radiometric and spectrophotometric methods. Wild-type cells incorporated labeled adenine, guanine, and hypoxanthine, whereas mutant strains varied in their ability to incorporate these bases. Adenine, guanine, hypoxanthine, and xanthine were activated by phosphoribosyltransferase activities present in wild-type cell extracts. Some mutant strains simultaneously lost the ability to convert both guanine and hypoxanthine to the respective nucleotide, suggesting that the same enzyme activates both bases. Adenosine, guanosine, and inosine phosphorylase activities were detected for the conversion of base to nucleoside. Adenine deaminase activity was detected at low levels. Guanine deaminase activity was not detected. Nucleoside kinase activities for the conversion of adenosine, guanosine, and inosine to the respective nucleotides were detected by a new assay. The nucleotide-interconverting enzymes AMP deaminase, succinyl-AMP synthetase, succinyl-AMP lyase, IMP dehydrogenase, and GMP synthetase were present in extracts; GMP reductase was not detected. The results indicate that this autotrophic methanogen has a complex system for the utilization of exogenous purines. PMID:2345148

  18. Three of the Four Nucleocapsid Proteins of Marburg Virus, NP, VP35, and L, Are Sufficient To Mediate Replication and Transcription of Marburg Virus-Specific Monocistronic Minigenomes

    PubMed Central

    Mühlberger, Elke; Lötfering, Beate; Klenk, Hans-Dieter; Becker, Stephan

    1998-01-01

    This paper describes the first reconstituted replication system established for a member of the Filoviridae, Marburg virus (MBGV). MBGV minigenomes containing the leader and trailer regions of the MBGV genome and the chloramphenicol acetyltransferase (CAT) gene were constructed. In MBGV-infected cells, these minigenomes were replicated and encapsidated and could be passaged. Unlike most other members of the order Mononegavirales, filoviruses possess four proteins presumed to be components of the nucleocapsid (NP, VP35, VP30, and L). To determine the protein requirements for replication and transcription, a reverse genetic system was established for MBGV based on the vaccinia virus T7 expression system. Northern blot analysis of viral RNA revealed that three nucleocapsid proteins (NP, VP35, and L) were essential and sufficient for transcription as well as replication and encapsidation. These data indicate that VP35, rather than VP30, is the functional homologue of rhabdo- and paramyxovirus P proteins. The reconstituted replication system was profoundly affected by the NP-to-VP35 expression ratio. To investigate whether CAT gene expression was achieved entirely by mRNA or in part by full-length plus-strand minigenomes, a copy-back minireplicon containing the CAT gene but lacking MBGV-specific transcriptional start sites was employed in the artificial replication system. This construct was replicated without accompanying CAT activity. It was concluded that the CAT activity reflected MBGV-specific transcription and not replication. PMID:9765419

  19. Earth observation taken by the Expedition 29 crew

    NASA Image and Video Library

    2011-10-02

    ISS029-E-021997 (2 Oct. 2011) --- This is one of a series of night time images photographed by one of the Expedition 29 crew members from the International Space Station. It features Central and Eastern Europe. The view includes the northeast portion of Italy, Germany, Poland, and Hungary. The station was over Corsica at 44.19 degrees north latitude and 12.13 degrees east longitude.

  20. Revised Uniform Summary of Surface Weather Observations (RUSSWO) Nurnberg Germany/Furth

    DTIC Science & Technology

    1972-10-25

    snow when reported from non-W&IN sources.) u and or sand - Included are blowing dust, blowing sand, and dust. A-I L 7ɟ_ &~i~-’.~Thi:ltc ~ ~ td , 1 nt...6.67 1 4 4 A ____4 8.1 4 4 ,6log_ 1 2! __ o9. 11 31 a 61 49.6!7/ 5, tD -3TA 14-1501- I _ _&61 * 44 1 DATA PROCESSING CIVISIC% USAF ETAC WEATHER...22,2 23.6 24.4’ 26,1ൢ,5 27,- 27;0 27’ ś.0 27,1 27A., 2Ŗ >-100 -23,2 1 29,9 3 , 360" 3Uv .13 p0 39,’ 39.0 39. 3 9~2 I___ Alt 6 23.1 26.1 g 29. 29

  1. Long-term follow-up of HBsAg-positive patients in Germany.

    PubMed

    Niederau, Claus; Amani, Asef; Thiel, Andreas

    2016-01-01

    Little is known about the prognosis and complications of chronic hepatitis B in countries with low disease prevalence including Germany. This retrospective/prospective study analyzes the course of 608 HBsAg-positive patients between 2002 and 2012 in Germany. The follow-up duration was 5.2±2.9 years (mean±SD) and the age of the patients was 40.4±13.8 years. Of the total cohort, 59.9% were men; 34.9% had been born in Germany, 30.4% in Turkey, and 34.7% in other countries. In 78.3% of women, diagnosis was made during pregnancy screening, which is the only reinforced screening procedure in Germany. During follow-up, 21 patients died, five had a LTX, and 20 developed a hepatocellular carcinoma. Of the total cohort, 15% developed at least one severe liver-associated complication. By multivariate analysis, prognosis was associated with high age and cirrhosis, but not with sex, HBV-DNA, alanine aminotransferase, and ethnic origin. Of the 608 patients, 211 (34.7%) had at least one antiviral therapy. Of the 178 patients who were treated with nucleot(s)ides at the last visit 88.8% had an HBV-DNA less than 20 IU/ml. Today, in Germany, hepatitis B is a disease of migrants. The present data show that mandatory screening is effective and needs to include more high-risk groups. Mortality and complications including hepatocellular carcinoma are associated primarily with cirrhosis and age, but not with HBeAg status or viral load probably because modern therapies considerably reduce viral replication in almost all patients. The prognosis is exclusively determined by the risk for hepatocellular carcinoma.

  2. Large-Scale Screening and Identification of Novel Ebola Virus and Marburg Virus Entry Inhibitors.

    PubMed

    Anantpadma, Manu; Kouznetsova, Jennifer; Wang, Hang; Huang, Ruili; Kolokoltsov, Andrey; Guha, Rajarshi; Lindstrom, Aaron R; Shtanko, Olena; Simeonov, Anton; Maloney, David J; Maury, Wendy; LaCount, Douglas J; Jadhav, Ajit; Davey, Robert A

    2016-08-01

    Filoviruses are highly infectious, and no FDA-approved drug therapy for filovirus infection is available. Most work to find a treatment has involved only a few strains of Ebola virus and testing of relatively small drug libraries or compounds that have shown efficacy against other virus types. Here we report the findings of a high-throughput screening of 319,855 small molecules from the Molecular Libraries Small Molecule Repository library for their activities against Marburg virus and Ebola virus. Nine of the most potent, novel compounds that blocked infection by both viruses were analyzed in detail for their mechanisms of action. The compounds inhibited known key steps in the Ebola virus infection mechanism by blocking either cell surface attachment, macropinocytosis-mediated uptake, or endosomal trafficking. To date, very few specific inhibitors of macropinocytosis have been reported. The 2 novel macropinocytosis inhibitors are more potent inhibitors of Ebola virus infection and less toxic than ethylisopropylamiloride, one commonly accepted macropinocytosis inhibitor. Each compound blocked infection of primary human macrophages, indicating their potential to be developed as new antifiloviral therapies. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  3. Durability of a vesicular stomatitis virus-based marburg virus vaccine in nonhuman primates.

    PubMed

    Mire, Chad E; Geisbert, Joan B; Agans, Krystle N; Satterfield, Benjamin A; Versteeg, Krista M; Fritz, Elizabeth A; Feldmann, Heinz; Hensley, Lisa E; Geisbert, Thomas W

    2014-01-01

    The filoviruses, Marburg virus (MARV) and Ebola virus, causes severe hemorrhagic fever with high mortality in humans and nonhuman primates. A promising filovirus vaccine under development is based on a recombinant vesicular stomatitis virus (rVSV) that expresses individual filovirus glycoproteins (GPs) in place of the VSV glycoprotein (G). These vaccines have shown 100% efficacy against filovirus infection in nonhuman primates when challenge occurs 28-35 days after a single injection immunization. Here, we examined the ability of a rVSV MARV-GP vaccine to provide protection when challenge occurs more than a year after vaccination. Cynomolgus macaques were immunized with rVSV-MARV-GP and challenged with MARV approximately 14 months after vaccination. Immunization resulted in the vaccine cohort of six animals having anti-MARV GP IgG throughout the pre-challenge period. Following MARV challenge none of the vaccinated animals showed any signs of clinical disease or viremia and all were completely protected from MARV infection. Two unvaccinated control animals exhibited signs consistent with MARV infection and both succumbed. Importantly, these data are the first to show 100% protective efficacy against any high dose filovirus challenge beyond 8 weeks after final vaccination. These findings demonstrate the durability of VSV-based filovirus vaccines.

  4. Protection against lethal Marburg virus infection mediated by lipid encapsulated small interfering RNA.

    PubMed

    Ursic-Bedoya, Raul; Mire, Chad E; Robbins, Marjorie; Geisbert, Joan B; Judge, Adam; MacLachlan, Ian; Geisbert, Thomas W

    2014-02-15

    Marburg virus (MARV) infection causes severe morbidity and mortality in humans and nonhuman primates. Currently, there are no licensed therapeutics available for treating MARV infection. Here, we present the in vitro development and in vivo evaluation of lipid-encapsulated small interfering RNA (siRNA) as a potential therapeutic for the treatment of MARV infection. The activity of anti-MARV siRNAs was assessed using dual luciferase reporter assays followed by in vitro testing against live virus. Lead candidates were tested in lethal guinea pig models of 3 different MARV strains (Angola, Ci67, Ravn). Treatment resulted in 60%-100% survival of guinea pigs infected with MARV. Although treatment with siRNA targeting other MARV messenger RNA (mRNA) had a beneficial effect, targeting the MARV NP mRNA resulted in the highest survival rates. NP-718m siRNA in lipid nanoparticles provided 100% protection against MARV strains Angola and Ci67, and 60% against Ravn. A cocktail containing NP-718m and NP-143m provided 100% protection against MARV Ravn. These data show protective efficacy against the most pathogenic Angola strain of MARV. Further development of the lipid nanoparticle technology has the potential to yield effective treatments for MARV infection.

  5. Protection Against Lethal Marburg Virus Infection Mediated by Lipid Encapsulated Small Interfering RNA

    PubMed Central

    Ursic-Bedoya, Raul; Mire, Chad E.; Robbins, Marjorie; Geisbert, Joan B.; Judge, Adam; MacLachlan, Ian; Geisbert, Thomas W.

    2014-01-01

    Background. Marburg virus (MARV) infection causes severe morbidity and mortality in humans and nonhuman primates. Currently, there are no licensed therapeutics available for treating MARV infection. Here, we present the in vitro development and in vivo evaluation of lipid-encapsulated small interfering RNA (siRNA) as a potential therapeutic for the treatment of MARV infection. Methods. The activity of anti-MARV siRNAs was assessed using dual luciferase reporter assays followed by in vitro testing against live virus. Lead candidates were tested in lethal guinea pig models of 3 different MARV strains (Angola, Ci67, Ravn). Results. Treatment resulted in 60%–100% survival of guinea pigs infected with MARV. Although treatment with siRNA targeting other MARV messenger RNA (mRNA) had a beneficial effect, targeting the MARV NP mRNA resulted in the highest survival rates. NP-718m siRNA in lipid nanoparticles provided 100% protection against MARV strains Angola and Ci67, and 60% against Ravn. A cocktail containing NP-718m and NP-143m provided 100% protection against MARV Ravn. Conclusions. These data show protective efficacy against the most pathogenic Angola strain of MARV. Further development of the lipid nanoparticle technology has the potential to yield effective treatments for MARV infection. PMID:23990568

  6. IEA Wind Task 26. Wind Technology, Cost and Performance Trends in Denmark, Germany, Ireland, Norway, the European Union, and the United States. 2007 - 2012

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

    Vitina, Aisma; Luers, Silke; Wallasch, Anna-Kathrin

    This report builds from a similar previous analysis (Schwabe et al., 2011) exploring the differences in cost of wind energy in 2008 among countries participating in IEA Wind Task 26 at that time. The levelized cost of energy (LCOE) is a widely recognized metric for understanding how technology, capital investment, operations, and financing impact the life-cycle cost of building and operating a wind plant. Schwabe et al. (2011) apply a spreadsheet-based cash flow model developed by the Energy Research Centre of the Netherlands (ECN) to estimate LCOE. This model is a detailed, discounted cash flow model used to represent themore » various cost structures in each of the participating countries from the perspective of a financial investor in a domestic wind energy project. This model is used for the present analysis as well, and comparisons are made for those countries who contributed to both reports, Denmark, Germany, and the United States.« less

  7. 40 CFR 411.26 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 29 2014-07-01 2012-07-01 true Pretreatment standards for new sources. 411.26 Section 411.26 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS CEMENT MANUFACTURING POINT SOURCE CATEGORY Leaching Subcategory § 411.26...

  8. Status and Challenges of Filovirus Vaccines

    DTIC Science & Technology

    2007-03-01

    comprise the family Filoviridae cause ome of the most lethal viral hemorrhagic fevers known. n 1967, an outbreak in Marburg, Germany occurred among...been reported in some but not all cases. ithin 6–8 days of fever , hemorrhagic complications can evelop, and patients develop increasingly severe...with ZEBOV infection cynomolgus acaques and rhesus macaques are more likely to develop petechial rash and coagulation defects while baboons are ore

  9. Anticipating the Species Jump: Surveillance for Emerging Viral Threats

    DTIC Science & Technology

    2010-12-01

    views expressed herein are those of the author and do not necessarily reflect the official policy or position of the Defense Threat Reduction Agency...Germany** [10, 11] Hantavirus (Sin Nombre virus) Deer mouse (Peromyscus maniculatus) 1993 Four Corners area, US [12] Monkeypox (Monkeypox virus...genetically diverse Marburg viruses from Egyptian fruit bats." PLoS Pathog 5(7): e1000536. 12. "Update: Outbreak of Hantavirus Infection — Southwestern

  10. Interaction of Tsg101 with Marburg Virus VP40 Depends on the PPPY Motif, but Not the PT/SAP Motif as in the Case of Ebola Virus, and Tsg101 Plays a Critical Role in the Budding of Marburg Virus-Like Particles Induced by VP40, NP, and GP▿

    PubMed Central

    Urata, Shuzo; Noda, Takeshi; Kawaoka, Yoshihiro; Morikawa, Shigeru; Yokosawa, Hideyoshi; Yasuda, Jiro

    2007-01-01

    Marburg virus (MARV) VP40 is a matrix protein that can be released from mammalian cells in the form of virus-like particles (VLPs) and contains the PPPY sequence, which is an L-domain motif. Here, we demonstrate that the PPPY motif is important for VP40-induced VLP budding and that VLP production is significantly enhanced by coexpression of NP and GP. We show that Tsg101 interacts with VP40 depending on the presence of the PPPY motif, but not the PT/SAP motif as in the case of Ebola virus, and plays an important role in VLP budding. These findings provide new insights into the mechanism of MARV budding. PMID:17301151

  11. 40 CFR 406.26 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 29 2011-07-01 2009-07-01 true Pretreatment standards for new sources. 406.26 Section 406.26 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GRAIN MILLS POINT SOURCE CATEGORY Corn Dry Milling Subcategory § 406.26 Pretreatment...

  12. Passive surveillance of Leptospira infection in swine in Germany.

    PubMed

    Strutzberg-Minder, Katrin; Tschentscher, Astrid; Beyerbach, Martin; Homuth, Matthias; Kreienbrock, Lothar

    2018-01-01

    As no current data are available on the prevalence of leptospiral infection in swine in Germany, we analysed laboratory data from diagnostic examinations carried out on samples from swine all over Germany from January 2011 to September 2016. A total of 29,829 swine sera were tested by microscopic agglutination test (MAT) for antibodies against strains of eleven Leptospira serovars. Overall, 20.2% (6025) of the total sample collection tested positive for leptospiral infection. Seropositivity ranged between 16.3% (964) in 2011 and 30.9% (941) in 2016 (January to September only). Of all samples, 11.6% (57.3% of the positives) reacted with only one Leptospira serovar, and only 8.6% (42.7% of the positives) reacted simultaneously with two or more serovars. The most frequently detected serovar was Bratislava, which was found in 11.6% (3448) of all samples, followed by the serovars Australis in 7.3% (2185), Icterohaemorrhagiae in 4.0% (1191), Copenhageni in 4.0% (1182), Autumnalis in 3.7% (1054), Canicola in 2.0% (585), and Pomona in 1.2% (368). Modelling shows that both the year and the reason for testing at the laboratory had statistically strong effects on the test results; however, no interactions were determined between those factors. The results support the suggestion that the seropositivities found may be considered to indicate the state of leptospiral infections in the German swine population. Although data from passive surveillance are prone to selection bias, stratified analysis by initial reason for examination and analyses by model approaches may correct for biases. A prevalence of about 20% for a leptospiral infection is most probable for sows with reproductive problems in Germany, with an increasing trend. Swine in Germany are probably a reservoir host for serovar Bratislava, but in contrast to other studies not for Pomona and Tarassovi.

  13. Multiagent vaccines vectored by Venezuelan equine encephalitis virus replicon elicits immune responses to Marburg virus and protection against anthrax and botulinum neurotoxin in mice.

    PubMed

    Lee, John S; Groebner, Jennifer L; Hadjipanayis, Angela G; Negley, Diane L; Schmaljohn, Alan L; Welkos, Susan L; Smith, Leonard A; Smith, Jonathan F

    2006-11-17

    The development of multiagent vaccines offers the advantage of eliciting protection against multiple diseases with minimal inoculations over a shorter time span. We report here the results of using formulations of individual Venezuelan equine encephalitis (VEE) virus replicon-vectored vaccines against a bacterial disease, anthrax; a viral disease, Marburg fever; and against a toxin-mediated disease, botulism. The individual VEE replicon particles (VRP) expressed mature 83-kDa protective antigen (MAT-PA) from Bacillus anthracis, the glycoprotein (GP) from Marburg virus (MBGV), or the H(C) fragment from botulinum neurotoxin (BoNT H(C)). CBA/J mice inoculated with a mixture of VRP expressing BoNT H(C) serotype C (BoNT/C H(C)) and MAT-PA were 80% protected from a B. anthracis (Sterne strain) challenge and then 100% protected from a sequential BoNT/C challenge. Swiss mice inoculated with individual VRP or with mixtures of VRP vaccines expressing BoNT H(C) serotype A (BoNT/A H(C)), MAT-PA, and MBGV-GP produced antibody responses specific to the corresponding replicon-expressed protein. Combination of the different VRP vaccines did not diminish the antibody responses measured for Swiss mice inoculated with formulations of two or three VRP vaccines as compared to mice that received only one VRP vaccine. Swiss mice inoculated with VRP expressing BoNT/A H(C) alone or in combination with VRP expressing MAT-PA and MBGV GP, were completely protected from a BoNT/A challenge. These studies demonstrate the utility of combining individual VRP vaccines into multiagent formulations for eliciting protective immune responses to various types of diseases.

  14. Structural and Functional Studies on the Marburg Virus GP2 Fusion Loop.

    PubMed

    Liu, Nina; Tao, Yisong; Brenowitz, Michael D; Girvin, Mark E; Lai, Jonathan R

    2015-10-01

    Marburg virus (MARV) and the ebolaviruses belong to the family Filoviridae (the members of which are filoviruses) that cause severe hemorrhagic fever. Infection requires fusion of the host and viral membranes, a process that occurs in the host cell endosomal compartment and is facilitated by the envelope glycoprotein fusion subunit, GP2. The N-terminal fusion loop (FL) of GP2 is a hydrophobic disulfide-bonded loop that is postulated to insert and disrupt the host endosomal membrane during fusion. Here, we describe the first structural and functional studies of a protein corresponding to the MARV GP2 FL. We found that this protein undergoes a pH-dependent conformational change, as monitored by circular dichroism and nuclear magnetic resonance. Furthermore, we report that, under low pH conditions, the MARV GP2 FL can induce content leakage from liposomes. The general aspects of this pH-dependent structure and lipid-perturbing behavior are consistent with previous reports on Ebola virus GP2 FL. However, nuclear magnetic resonance studies in lipid bicelles and mutational analysis indicate differences in structure exist between MARV and Ebola virus GP2 FL. These results provide new insight into the mechanism of MARV GP2-mediated cell entry. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. 40 CFR 503.26 - Frequency of monitoring.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Frequency of monitoring. 503.26... STANDARDS FOR THE USE OR DISPOSAL OF SEWAGE SLUDGE Surface Disposal § 503.26 Frequency of monitoring. (a) Sewage sludge (other than domestic septage). (1) The frequency of monitoring for the pollutants in Tables...

  16. The administrative stabilization of vaccines: Regulating the diphtheria antitoxin in France and Germany, 1894-1900.

    PubMed

    Hess, Volker

    2008-06-01

    It is well known that the development of a diphtheria anti-toxin serum evolved in a competitive race between two groups of researchers, one affiliated with Emil Behring in Berlin and Marburg, and another affiliated with Emile Roux in Paris. Proceeding on the basis of different theoretical assumptions and experimental practices, the two groups developed a therapeutic serum almost simultaneously. But the standardized substance they developed took on very different forms in the two countries. In Germany the new serum was marketed in the private sphere and subjected to state regulations, becoming a kind ofprototype of industrial medications. In France, however, the same substance was marketed as a gift of science to humanity and distributed through the communal health care system. This article demonstrates how a new medication emerged from the efforts to produce, market, regulate, distribute, and apply it in the two respective countries. It attributes the difference to the negotiations between the respective actors (scientists, industrialists, politicians, officers, and the public) and institutions (firms, academies, private and public institutes, legislative bodies, professional corporations). I develop this argument on three different levels: First, I stress the importance of the institutional foundations of serum production; second, I illustrate the decisive role played by existing "ways of regulating" in the rapid development of new legal statutes; and third, I describe the consequences that flowed from the respective administrative organization of marketing and dissemination. In sum, I explore how an experimental object was transformed into an object of the public health system and stabilized by administrative means.

  17. The prevalence rates of refractive errors among children, adolescents, and adults in Germany.

    PubMed

    Jobke, Sandra; Kasten, Erich; Vorwerk, Christian

    2008-09-01

    The prevalence rates of myopia vary between 5% in Australian Aborigines to 84% in Hong Kong and Taiwan, 30% in Norwegian adults, and 49.5% in Swedish schoolchildren. The aim of this study was to determine the prevalence of refractive errors in German children, adolescents, and adults. The parents (aged 24-65 years) and their children (516 subjects aged 2-35 years) were asked to fill out a questionnaire about their refractive error and spectacle use. Emmetropia was defined as refractive status between +0.25D and -0.25D. Myopia was characterized as /=+0.5D. All information concerning refractive error were controlled by asking their opticians. The prevalence rates of myopia differed significantly between all investigated age groups: it was 0% in children aged 2-6 years, 5.5% in children aged 7-11 years, 21.0% in adolescents (aged 12-17 years) and 41.3% in adults aged 18-35 years (Pearson's Chi-square, p = 0.000). Furthermore, 9.8% of children aged 2-6 years were hyperopic, 6.4% of children aged 7-11 years, 3.7% of adolescents, and 2.9% of adults (p = 0.380). The prevalence of myopia in females (23.6%) was significantly higher than in males (14.6%, p = 0.018). The difference between the self-reported and the refractive error reported by their opticians was very small and was not significant (p = 0.850). In Germany, the prevalence of myopia seems to be somewhat lower than in Asia and Europe. There are few comparable studies concerning the prevalence rates of hyperopia.

  18. Lectin Affinity Plasmapheresis for Middle East Respiratory Syndrome-Coronavirus and Marburg Virus Glycoprotein Elimination.

    PubMed

    Koch, Benjamin; Schult-Dietrich, Patricia; Büttner, Stefan; Dilmaghani, Bijan; Lohmann, Dario; Baer, Patrick C; Dietrich, Ursula; Geiger, Helmut

    2018-04-26

    Middle East respiratory syndrome coronavirus (MERS-CoV) and Marburg virus (MARV) are among the World Health Organization's top 8 emerging pathogens. Both zoonoses share nonspecific early symptoms, a high lethality rate, and a reduced number of specific treatment options. Therefore, we evaluated extracorporeal virus and glycoprotein (GP) elimination by lectin affinity plasmapheresis (LAP). For both MERS-CoV (pseudovirus) as well as MARV (GPs), 4 LAP devices (Mini Hemopurifiers, Aethlon Medical, San Diego, CA, USA) and 4 negative controls were tested. Samples were collected every 30 min and analyzed for reduction in virus infectivity by a flow cytometry-based infectivity assay (MERS-CoV) and in soluble GP content (MARV) by an immunoassay. The experiments show a time-dependent clearance of MERS-CoV of up to 80% within 3 h (pseudovirus). Up to 70% of MARV-soluble GPs were eliminated at the same time. Substantial saturation of the binding resins was detected within the first treatment hour. MERS-CoV (pseudovirus) and MARV soluble GPs are eliminated by LAP in vitro. Considering the high lethality and missing established treatment options, LAP should be evaluated in vivo. Especially early initiation, continuous therapy, and timed cartridge exchanges could be of importance. The Author(s). Published by S. Karger AG, Basel.

  19. 40 CFR 414.26 - Pretreatment standards for new sources (PSNS).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 29 2011-07-01 2009-07-01 true Pretreatment standards for new sources (PSNS). 414.26 Section 414.26 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS ORGANIC CHEMICALS, PLASTICS, AND SYNTHETIC FIBERS Rayon Fibers § 414.26...

  20. 40 CFR 414.26 - Pretreatment standards for new sources (PSNS).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 29 2014-07-01 2012-07-01 true Pretreatment standards for new sources (PSNS). 414.26 Section 414.26 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS ORGANIC CHEMICALS, PLASTICS, AND SYNTHETIC FIBERS Rayon Fibers § 414.26...

  1. Monitoring the prevalence of thyroid disorders in the adult population of Northeast Germany.

    PubMed

    Khattak, Rehman Mehmood; Ittermann, Till; Nauck, Matthias; Below, Harald; Völzke, Henry

    2016-01-01

    Only a few studies like ours have investigated the effect of long-term stable iodine supply on thyroid disorders in a historically iodine-deficient population, but not with a long follow-up time of 10 years. Data were derived from two independent population-based cohorts of the Study of Health in Pomerania (SHIP-0 [1997-2001] and SHIP-TREND [2008-2012]) comprising 4308 and 4420 subjects, respectively. Diagnosed thyroid disorders were assessed. Thyroid gland dimensions were examined by ultrasound. Levels of serum thyrotropin (TSH) and autoantibodies to thyroperoxidase (anti-TPO Abs) were measured from blood samples. Median urinary iodine excretion levels decreased from 123.0 μg/l to 112.0 μg/l ( p  = <0.001) between 2000 and 2010. The prevalence of known thyroid disorders increased from 7.6 % [CI 6.9-8.5] to 18.9 % [CI 17.6-20.1] and of thyroid medication use from 6.2 to 11.1 %. The prevalence of goiter decreased from 35.1 to 29.4 % ( p  = <0.001), while the prevalence of positive anti-TPO Abs decreased from 3.9 to 2.9 % ( p  = 0.022). Median serum TSH levels increased from 0.69 mIU/L to 1.19 mIU/L ( p  = <0.001). Consequently, prevalence of high TSH (mIU/L) increased from 2.6 to 2.9 % ( p  = 0.452), and low TSH (mIU/L) decreased from 6.6 to 6.4 % ( p  = 0.737). The decreased prevalence of iodine-deficient disorders and a stable prevalence of markers of autoimmune thyroid disorders argue for an improved iodine supply of the adult population in Northeast Germany. In contrast, the prevalence of diagnosed thyroid disorders and the intake of thyroid medication increased, although this might be related to inappropriate therapeutic decisions.

  2. Who gets dipyrone (metamizole) in Germany? Prescribing by age, sex and region.

    PubMed

    Hoffmann, F; Meinecke, P; Freitag, M H; Glaeske, G; Schulze, J; Schmiemann, G

    2015-06-01

    Metamizole (dipyrone) is an analgesic that has been the focus of considerable controversy regarding its safety. Because of potentially life-threatening blood disorders such as agranulocytosis, it has been withdrawn in many countries but not in Germany, where prescribing even increased over recent years. We aimed to evaluate prescribing of metamizole in Germany with respect to age, sex and regional variations. Using data of a statutory health insurance, we analysed a cohort of 1·7 million persons who were insured at least 1 day in each quarter of 2009. Outcome of interest was the outpatient prescription prevalence, for example the proportion of persons receiving at least one prescription of metamizole. A total of 6·8% received metamizole with a higher prescribing prevalence in females (7·8% vs. 6·0%). The prevalence increased with age up to 26·7% in persons ≥85 years (men: 21·1%; and women: 30·4%). We found large regional variations with higher prevalences in the northern part of Germany. Most of the prescriptions were issued by general practitioners (78·9%). 58·3% were liquid oral formulations with considerable regional variations ranging between 32·3% in Mecklenburg-West Pomerania and 67·3% in North Rhine-Westphalia. Overall, liquid oral forms are much more often prescribed in the western than in the eastern part of Germany. Metamizole - a drug with a relatively narrow indication - is often prescribed in Germany with relevant differences by age, sex and region. Qualitative studies should clarify reasons for this. Further quantitative research should investigate small-area variations, indications and treatment durations. © 2015 John Wiley & Sons Ltd.

  3. Ebola and Marburg haemorrhagic fever viruses: major scientific advances, but a relatively minor public health threat for Africa.

    PubMed

    Leroy, E M; Gonzalez, J-P; Baize, S

    2011-07-01

    Ebola and Marburg viruses are the only members of the Filoviridae family (order Mononegavirales), a group of viruses characterized by a linear, non-segmented, single-strand negative RNA genome. They are among the most virulent pathogens for humans and great apes, causing acute haemorrhagic fever and death within a matter of days. Since their discovery 50 years ago, filoviruses have caused only a few outbreaks, with 2317 clinical cases and 1671 confirmed deaths, which is negligible compared with the devastation caused by malnutrition and other infectious diseases prevalent in Africa (malaria, cholera, AIDS, dengue, tuberculosis …). Yet considerable human and financial resourses have been devoted to research on these viruses during the past two decades, partly because of their potential use as bioweapons. As a result, our understanding of the ecology, host interactions, and control of these viruses has improved considerably. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

  4. Recombinant Marburg viruses containing mutations in the IID region of VP35 prevent inhibition of Host immune responses.

    PubMed

    Albariño, César G; Wiggleton Guerrero, Lisa; Spengler, Jessica R; Uebelhoer, Luke S; Chakrabarti, Ayan K; Nichol, Stuart T; Towner, Jonathan S

    2015-02-01

    Previous in vitro studies have demonstrated that Ebola and Marburg virus (EBOV and MARV) VP35 antagonize the host cell immune response. Moreover, specific mutations in the IFN inhibitory domain (IID) of EBOV and MARV VP35 that abrogate their interaction with virus-derived dsRNA, lack the ability to inhibit the host immune response. To investigate the role of MARV VP35 in the context of infectious virus, we used our reverse genetics system to generate two recombinant MARVs carrying specific mutations in the IID region of VP35. Our data show that wild-type and mutant viruses grow to similar titers in interferon deficient cells, but exhibit attenuated growth in interferon-competent cells. Furthermore, in contrast to wild-type virus, both MARV mutants were unable to inhibit expression of various antiviral genes. The MARV VP35 mutants exhibit similar phenotypes to those previously described for EBOV, suggesting the existence of a shared immune-modulatory strategy between filoviruses. Published by Elsevier Inc.

  5. Update on Germany: Now Eastern Germany Gets a Free Press. Special Report SO 8, 1991.

    ERIC Educational Resources Information Center

    Meyn, Hermann

    Since the former East German Communist State--the German Democratic Republic (GDR)--was incorporated into the Federal Republic of Germany, the federal constitution has been valid throughout the whole of Germany, guaranteeing press freedom and ending press censorship in eastern Germany. In October 1989, the GDR had 39 daily newspapers (many…

  6. Germany: The Search for Unity.

    ERIC Educational Resources Information Center

    Blankenship, Glen, Ed.

    The 12 lessons in this collection are designed so that they may be used individually, integrated into the curriculum at appropriate places, or used as a complete unit. The lessons are entitled: (1) Impressions of Germany and Germans; (2) The Location and Population of Germany; (3) Pollution in Germany: A Complex Problems; (4) German Political…

  7. Drugs in East Germany.

    PubMed

    Dressler, J; Müller, E

    1997-09-01

    Germany was divided into two parts after World War II. The closed border and a nonconvertible currency in the Eastern part were the factors that did not allow a drug market to develop. Alcohol and medicaments were used as substitute drugs. Since Germany was reunified 5 years ago, there are now the same conditions prevailing for the procurement and sale of drugs in East Germany as there are in the Western German states. This report describes the current state of drug traffic, especially in Saxony, under the new social conditions.

  8. A parallel genome-wide RNAi screening strategy to identify host proteins important for entry of Marburg virus and H5N1 influenza virus.

    PubMed

    Cheng, Han; Koning, Katie; O'Hearn, Aileen; Wang, Minxiu; Rumschlag-Booms, Emily; Varhegyi, Elizabeth; Rong, Lijun

    2015-11-24

    Genome-wide RNAi screening has been widely used to identify host proteins involved in replication and infection of different viruses, and numerous host factors are implicated in the replication cycles of these viruses, demonstrating the power of this approach. However, discrepancies on target identification of the same viruses by different groups suggest that high throughput RNAi screening strategies need to be carefully designed, developed and optimized prior to the large scale screening. Two genome-wide RNAi screens were performed in parallel against the entry of pseudotyped Marburg viruses and avian influenza virus H5N1 utilizing an HIV-1 based surrogate system, to identify host factors which are important for virus entry. A comparative analysis approach was employed in data analysis, which alleviated systematic positional effects and reduced the false positive number of virus-specific hits. The parallel nature of the strategy allows us to easily identify the host factors for a specific virus with a greatly reduced number of false positives in the initial screen, which is one of the major problems with high throughput screening. The power of this strategy is illustrated by a genome-wide RNAi screen for identifying the host factors important for Marburg virus and/or avian influenza virus H5N1 as described in this study. This strategy is particularly useful for highly pathogenic viruses since pseudotyping allows us to perform high throughput screens in the biosafety level 2 (BSL-2) containment instead of the BSL-3 or BSL-4 for the infectious viruses, with alleviated safety concerns. The screening strategy together with the unique comparative analysis approach makes the data more suitable for hit selection and enables us to identify virus-specific hits with a much lower false positive rate.

  9. 40 CFR 409.26 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 29 2014-07-01 2012-07-01 true Pretreatment standards for new sources. 409.26 Section 409.26 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SUGAR PROCESSING POINT SOURCE CATEGORY Crystalline Cane Sugar Refining Subcategory...

  10. 40 CFR 426.26 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Pretreatment standards for new sources. 426.26 Section 426.26 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GLASS MANUFACTURING POINT SOURCE CATEGORY Sheet Glass Manufacturing Subcategory...

  11. 40 CFR 409.26 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 29 2011-07-01 2009-07-01 true Pretreatment standards for new sources. 409.26 Section 409.26 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SUGAR PROCESSING POINT SOURCE CATEGORY Crystalline Cane Sugar Refining Subcategory...

  12. Reform of health care in Germany

    PubMed Central

    Hurst, Jeremy W.

    1991-01-01

    For the past 45 years Germany has had two health care systems: one in the former Federal Republic of Germany and one in the former German Democratic Republic. The system in the Federal Republic was undergoing some important reforms when German reunification took place in October 1990. Now the system in eastern Germany is undergoing a major transformation to bring it more into line with that in western Germany. PMID:10110879

  13. 40 CFR 419.26 - Standards of performance for new sources (NSPS).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 29 2011-07-01 2009-07-01 true Standards of performance for new sources (NSPS). 419.26 Section 419.26 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS PETROLEUM REFINING POINT SOURCE CATEGORY Cracking Subcategory § 419.26...

  14. Impact of disease management programs on women with breast cancer in Germany.

    PubMed

    Jacob, Louis; Hadji, Peyman; Albert, Ute-Susann; Kalder, Matthias; Kostev, Karel

    2015-09-01

    The aim of the study was to analyze the impact of disease management programs (DMPs) on adherence in women with breast cancer (BC) in Germany. Data on 4915 BC patients [1874 DMP and 3041 standard care (SC)] who started hormone therapy between 2008 and 2013 in 234 gynecological practices in Germany were analyzed retrospectively. The primary outcome measure was the rate of discontinuation of hormone therapy within 3 years of the start of treatment. Discontinuation of therapy was defined as a period of at least 90 days without treatment. A multivariate Cox regression model was created to determine the effect of DMPs on the risk of discontinuation. Region (western vs. eastern Germany), patient age, and concomitant diagnoses (depression, osteoporosis, thrombosis, and diabetes) were included as covariates. There was a significant difference between DMPs and SC in terms of age (63 ± 12 years vs. 64 ± 12 years, p value = 0.0012) and region (79.2% of patients living in western Germany vs. 88.6%, p value < 0.0001), but not initial therapy (51.8% vs. 52%, p value = 0.8696). Depression was also more common in patients in DMPs than those in SC (26.8% vs. 17.3%, p value < 0.0001). Within 3 years of therapy initiation, 32.7% of DMP patients and 39.6% of SC patients had discontinued their treatment (p < 0.001). Women with BC who were enrolled in a DMP had a lower risk of discontinuing therapy (HR = 0.91, 95% CI: 0.85-0.98, p value = 0.0092). This risk was also slightly higher in western Germany (HR = 1.13, 95% CI: 1.02-1.24, p value = 0.0143). Involvement in DMPs has a positive impact on the adherence of BC patients.

  15. History of modern genetics in Germany.

    PubMed

    Hammar, Friederike

    2002-01-01

    The history of modern genetics in Germany during the 20th century is a story of missed chances. In the USA the genetic revolution opened a fascinating new field for ambitious scientists and created a rapidly growing new industry. Meanwhile Germany stood aside, combating with political and social restrictions. Promising young scientists who wanted to work in the field left Germany for the US, and big companies moved their facilities out of the country. Up until the middle of the 1990s molecular biology in Germany remained a "sleeping beauty" even though many brilliant scientists did their jobs very well. Then a somewhat funny idea changed everything: the German minister for education and science proclaimed the BioRegio contest in order to award the most powerful biotechnology region in Germany concerning academia and especially industry. Since then Germany's biotechnology industry has grown constantly and rapidly due to the foundation of a number of small biotech companies; big companies have returned their interests and their investments to Germany, paralleled by an improvement in academic research because of more funding and better support especially for younger scientists. In respect to biotechnology and molecular biology, Germany is still a developing country, but it has started to move and to take its chances in an exciting global competition.

  16. 40 CFR 408.26 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 29 2011-07-01 2009-07-01 true Pretreatment standards for new sources. 408.26 Section 408.26 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS CANNED AND PRESERVED SEAFOOD PROCESSING POINT SOURCE CATEGORY Conventional Blue Crab...

  17. 40 CFR 408.26 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 29 2014-07-01 2012-07-01 true Pretreatment standards for new sources. 408.26 Section 408.26 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS CANNED AND PRESERVED SEAFOOD PROCESSING POINT SOURCE CATEGORY Conventional Blue Crab...

  18. 40 CFR 427.26 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Pretreatment standards for new sources. 427.26 Section 427.26 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS ASBESTOS MANUFACTURING POINT SOURCE CATEGORY Asbestos-Cement Sheet Subcategory § 427...

  19. 40 CFR 407.26 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 29 2014-07-01 2012-07-01 true Pretreatment standards for new sources. 407.26 Section 407.26 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS CANNED AND PRESERVED FRUITS AND VEGETABLES PROCESSING POINT SOURCE CATEGORY Apple...

  20. 40 CFR 407.26 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 29 2011-07-01 2009-07-01 true Pretreatment standards for new sources. 407.26 Section 407.26 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS CANNED AND PRESERVED FRUITS AND VEGETABLES PROCESSING POINT SOURCE CATEGORY Apple...

  1. 40 CFR 417.26 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 29 2011-07-01 2009-07-01 true Pretreatment standards for new sources. 417.26 Section 417.26 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Fatty Acid Manufacturing by...

  2. 40 CFR 417.26 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 29 2014-07-01 2012-07-01 true Pretreatment standards for new sources. 417.26 Section 417.26 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Fatty Acid Manufacturing by...

  3. Variability of Seasonal CO2 Ice Caps on Mars for Mars Years 26 through 29

    NASA Astrophysics Data System (ADS)

    Feldman, W. C.; Maurice, S.; Prettyman, T. H.

    2011-12-01

    We have developed an improved thermal, epithermal, and fast neutron counting-rate time series data of the Mars Odyssey Neutron Spectrometer (MONS), optimized to greatly reduce both statistical and systematic uncertainties. This new data set was applied to study temporal and spatial distributions of the growth, decay, and maximum amount of precipitated CO2 ice during Martian years (MY) 26, 27, 28, and 29. For this study, we concentrate on the epithermal counting rate detected using the down-looking prism (P1) of MONS, and a combination of the epithermal and thermal counting rate detected by the forward-looking sensor (P2) of MONS. Although the energy range of neutrons detected by P2 covers both the thermal and epithermal range, it is heavily weighted to the thermal range. We find that the variance of the maximum epithermal counting rate is remarkably small over both north and south seasonal caps, varying by less than 3% over the four-year period. In contrast, although the maximum P2 counting rate over both poles is sensibly the same within error bars (about 2%) during the first three years, it drops by 18% over the north pole and 8% over the south pole during MY 29. The most-likely explanation of this drop is that abundances of the non-condensable gases N2 and Ar, are unusually enhanced during MY 29. Movies were also made of maps of the growth and decay of P2 counting rates summed over the first three years of these data. Careful inspection shows that both the growth and decay in the north were cylindrically symmetric, centered near the geographic north pole. In contrast, both the growth and decay of CO2 buildup in the south were skewed off the geographic pole to the center of the CO2 residual cap, and contained a small, but definitely distinct ring-like annular enhancement centered at a latitude of about 83.5° S spread over a longitude range that extends between about -35° and +35° E. This arc runs parallel to, and overlays, the very steep drop in altitude from

  4. Field Feeding: Behavioral Sciences Studies

    DTIC Science & Technology

    1975-01-01

    C Rations, ham and eggs was the item most frequently identified for removal (Table 4) with more than 24 subjects in each field exercise expressing...Field C Ration ŕ REMOVE GERMANY 29 PALMS LEJEUNE Ham and Eggs 29 26 25 Cakes 9 31 26 Spiced Beef 6 Crackers 5 10 11 Ham and Limas 8 Peanut...Milk 7 Powdered Eggs 5 ADDS Steak 9 7 Hamburger 6 4 Hot Dogs 4 Pork Chops 5 Ham 4 Fruit 16 Fresh Milk 5 Fish 5 ’All other response

  5. Codon-optimized filovirus DNA vaccines delivered by intramuscular electroporation protect cynomolgus macaques from lethal Ebola and Marburg virus challenges.

    PubMed

    Grant-Klein, Rebecca J; Altamura, Louis A; Badger, Catherine V; Bounds, Callie E; Van Deusen, Nicole M; Kwilas, Steven A; Vu, Hong A; Warfield, Kelly L; Hooper, Jay W; Hannaman, Drew; Dupuy, Lesley C; Schmaljohn, Connie S

    2015-01-01

    Cynomolgus macaques were vaccinated by intramuscular electroporation with DNA plasmids expressing codon-optimized glycoprotein (GP) genes of Ebola virus (EBOV) or Marburg virus (MARV) or a combination of codon-optimized GP DNA vaccines for EBOV, MARV, Sudan virus and Ravn virus. When measured by ELISA, the individual vaccines elicited slightly higher IgG responses to EBOV or MARV than did the combination vaccines. No significant differences in immune responses of macaques given the individual or combination vaccines were measured by pseudovirion neutralization or IFN-γ ELISpot assays. Both the MARV and mixed vaccines were able to protect macaques from lethal MARV challenge (5/6 vs. 6/6). In contrast, a greater proportion of macaques vaccinated with the EBOV vaccine survived lethal EBOV challenge in comparison to those that received the mixed vaccine (5/6 vs. 1/6). EBOV challenge survivors had significantly higher pre-challenge neutralizing antibody titers than those that succumbed.

  6. High-throughput, luciferase-based reverse genetics systems for identifying inhibitors of Marburg and Ebola viruses.

    PubMed

    Uebelhoer, Luke S; Albariño, César G; McMullan, Laura K; Chakrabarti, Ayan K; Vincent, Joel P; Nichol, Stuart T; Towner, Jonathan S

    2014-06-01

    Marburg virus (MARV) and Ebola virus (EBOV), members of the family Filoviridae, represent a significant challenge to global public health. Currently, no licensed therapies exist to treat filovirus infections, which cause up to 90% mortality in human cases. To facilitate development of antivirals against these viruses, we established two distinct screening platforms based on MARV and EBOV reverse genetics systems that express secreted Gaussia luciferase (gLuc). The first platform is a mini-genome replicon to screen viral replication inhibitors using gLuc quantification in a BSL-2 setting. The second platform is complementary to the first and expresses gLuc as a reporter gene product encoded in recombinant infectious MARV and EBOV, thereby allowing for rapid quantification of viral growth during treatment with antiviral compounds. We characterized these viruses by comparing luciferase activity to virus production, and validated luciferase activity as an authentic real-time measure of viral growth. As proof of concept, we adapt both mini-genome and infectious virus platforms to high-throughput formats, and demonstrate efficacy of several antiviral compounds. We anticipate that both approaches will prove highly useful in the development of anti-filovirus therapies, as well as in basic research on the filovirus life cycle. Published by Elsevier B.V.

  7. Efficacy of favipiravir (T-705) in nonhuman primates infected with Ebola virus or Marburg virus.

    PubMed

    Bixler, Sandra L; Bocan, Thomas M; Wells, Jay; Wetzel, Kelly S; Van Tongeren, Sean A; Dong, Lian; Garza, Nicole L; Donnelly, Ginger; Cazares, Lisa H; Nuss, Jonathan; Soloveva, Veronica; Koistinen, Keith A; Welch, Lisa; Epstein, Carol; Liang, Li-Fang; Giesing, Dennis; Lenk, Robert; Bavari, Sina; Warren, Travis K

    2018-03-01

    Favipiravir is a broad-spectrum antiviral agent that has demonstrated efficacy against Ebola virus (EBOV) in rodents. However, there are no published reports of favipiravir efficacy for filovirus infection of nonhuman primates (NHPs). Here we evaluated the pharmacokinetic profile of favipiravir in NHPs, as well as in vivo efficacy against two filoviruses, EBOV and Marburg virus (MARV). While no survival benefit was observed in two studies employing once- or twice-daily oral dosing of favipiravir during EBOV infection of NHPs, an antiviral effect was observed in terms of extended time-to-death and reduced levels of viral RNA. However, oral dosing in biosafety level-4 (BSL-4) presents logistical and technical challenges, and repeated anesthesia events may potentially worsen survival outcome in animals. For the third study of treatment of MARV infection, we therefore made use of catheters, jackets, and tethers for intravenous (IV) dosing and blood collection, which minimized the requirement for repeated anesthesia events. When MARV infection was treated with IV favipiravir, five of six animals (83%) survived infection, while all untreated NHPs succumbed. An accompanying report presents the results of favipiravir treatment of EBOV infection in mice. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  8. 29 CFR 1918.26 - Access to barges and river towboats.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....26 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR LONGSHORING Gangways and Other Means of... made fast to the vessel, wharf, or dolphins. ...

  9. Marburg virus-like particles produced in insect cells induce neutralizing antibodies in rhesus macaques.

    PubMed

    Weiwei, Gai; Xuexing, Zheng; Chong, Wang; Yongkun, Zhao; Qi, Wang; Hualei, Wang; Gary, Wong; Ying, Xie; Haijun, Wang; Zengguo, Cao; Na, Feng; Hang, Chi; Tiecheng, Wang; Yuwei, Gao; Junjie, Shan; Songtao, Yang; Xianzhu, Xia

    2017-12-01

    Marburg virus (MARV), which is one of the most virulent agents in the world, causes lethal haemorrhagic fever in humans and nonhuman primates (NHPs) with a mortality rate of up to 90%. Currently, there is no effective treatment or approved vaccine for MARV for human use to control disease outbreak and spread. Virus-like particles (VLPs), which are morphologically identical to the native infectious virus particle, are efficacious as vaccines against many viruses, including human papilloma virus (HPV), porcine circovirus (PCV) type 2 and hepatitis B virus (HBV). In this study, we generated MARV virus-like particles (VLPs) by co-expressing a glycoprotein (GP) and matrix protein (VP40) using the baculovirus expression system. Rhesus macaques vaccinated with MARV VLPs mixed with adjuvant Poria cocos polysaccharides (PCP-II) produced a GP-specific IgG titer of up to 1:1280 and virus-neutralizing antibody titers that reached 1:320. MARV VLPs also elicited interferon-γ (IFN-γ) and interleukin-4 (IL-4) secretion associated with T-helper 1 cell (Th1)- and T-helper 2 cell (Th2)-mediated immunity, as detected using enzyme-linked immunospot (ELISpot) assays. These data indicate that MARV VLPs mixed with adjuvant PCP-II have excellent immunogenicity in rhesus macaques and may be a promising candidate vaccine against MARV. © 2017 Wiley Periodicals, Inc.

  10. Hypertension in Germany.

    PubMed

    Neuhauser, Hannelore; Diederichs, Claudia; Boeing, Heiner; Felix, Stephan B; Jünger, Claus; Lorbeer, Roberto; Meisinger, Christine; Peters, Annette; Völzke, Henry; Weikert, Cornelia; Wild, Philipp; Dörr, Marcus

    2016-12-02

    Hypertension is a key risk factor. However, population data based on blood pressure measurements in Germany are scarce. Standardized blood pressure (BP) measurements and medication data from seven population-based studies conducted in Germany between 1994 and 2012 (66 845 participants, 25-74 years) were analyzed: the EPICPotsdam study (1994-1998, EPIC), the KORA-S4 Study (1999-2001) in Augsburg, and the Gutenberg Health Study (2007-2012, GHS) in Mainz/Mainz-Bingen provided data for descriptive comparisons. Time trends were analyzed based on identical study regions for the German National Health Interview and Examination Survey 1998 (BGS98) and the German Health Examination Survey for Adults (2008-11, DEGS1) as well as the Study of Health in Pomerania (SHIP) in Northeast Germany (1997-2001) and the SHIP-TREND study (2008-2012). BP data were adjusted for study-specific measurement devices based on calibration studies. After adjustment for study-specific measurement devices, mean systolic and diastolic BP values were lower and treatment proportions higher in recent (2007-2012) compared to older (1994-2001) studies. Mean BP decrease was most pronounced (systolic ≥ 10 mmHg) in the elderly (55-74 years). The regional SHIP-TREND data for Northeast Germany showed a decrease in mean systolic BP in young men aged 25 to 34 years; on a national level according to the DEGS1 data, however, no such decrease was observed for this group. New data add evidence for lower BP in Germany. However, the prevention potential remains high. Future research based on population-based data should place a special focus on blood pressure data in young men.

  11. Dental tourism from Switzerland to Germany.

    PubMed

    Gheorghe, Raluca; Zürcher, Andrea; Filippi, Andreas

    In recent years the topic of dental tourism has increasingly come into focus of dentists and patients. In the present study an attempt was made to find out, why patients from a restricted region travel to Germany for dental care. In five German dental clinics located in the border area between Switzerland and Germany, 272 women and 236 men ranging in age from 5 to 94 years, who had undergone at least one dental treatment in Germany, were questioned concerning the reasons for their visits. The interviews took place within a period of 6 months and relied on a questionnaire to collect data regarding sociodemographic features and patient behavior. In comparison to residents of Germany, patients residing in Switzerland took on considerably longer travel distances for the dental visit, in some cases more than 50km (9.7%). For patients residing in Switzerland the technical equipment of the practice was more important (p<0.001), whereas for residents of Germany the cost-effective treatment was decisive (p<0.05). Almost all patients residing in Switzerland (95.6%) confirmed that dental treatments in Germany were cheaper and that additional family members also came to Germany for dental care (65.0%).

  12. [Integration and utilization of physiotherapy in hospice and palliative care : A survey on clinical practice in Germany].

    PubMed

    Woitha, K; Schneider, N; Wünsch, A; Wiese, B; Fimm, S; Müller-Mundt, G

    2017-02-01

    Palliative care is an approach that improves the quality of life of patients with incurable and progressive illnesses; therefore, in these situations physiotherapy can play an important role. This study was carried out to examine the integration and utilization of physiotherapy in palliative and hospice care services in Germany. A cross-sectional survey including all palliative care units, specialized outpatient palliative care teams and hospices in Germany (n = 680) in 2013 was carried out. The response rate was 43.5 % (n = 296). Physiotherapy is predominantly applied in palliative care units (79 %) but rarely in hospices (38 %) and outpatient palliative care teams (30 %). A structured physiotherapeutic assessment is rarely carried out even on palliative care units (26 %). Positive effects of physiotherapy are especially described for symptoms, such as edema, pain, constipation and dyspnea. Despite its significant potential to relieve symptoms, physiotherapy is not systematically integrated into palliative care practice in Germany.

  13. 40 CFR 439.26 - Pretreatment standards for existing sources (PSES).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Pretreatment standards for existing sources (PSES). 439.26 Section 439.26 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS PHARMACEUTICAL MANUFACTURING POINT SOURCE CATEGORY Extraction Products...

  14. 2. West portal of Tunnel 26, contextual view to northeast ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. West portal of Tunnel 26, contextual view to northeast from track level, 135mm lens. Tunnel 27 (HAER CA-203) is visible in the distance. - Central Pacific Transcontinental Railroad, Tunnel No. 26, Milepost 133.29, Applegate, Placer County, CA

  15. Earth observation taken by the Expedition 29 crew

    NASA Image and Video Library

    2011-10-02

    ISS029-E-021987 (2 Oct. 2011) --- This is one of a series of night time images photographed by one of the Expedition 29 crew members from the International Space Station. It features Central and Eastern Europe, extending from the Netherlands to Hungary and Italy to northern Poland. Overall, the view includes the Netherlands, Italy, Germany, Poland, and Hungary. When the photo was taken on Oct 2, 2011, the station was over Corsica at 43.18 degrees north latitude and 9.95 degrees east longitude.

  16. 40 CFR 415.26 - Pretreatment standards for new sources (PSNS).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 29 2014-07-01 2012-07-01 true Pretreatment standards for new sources (PSNS). 415.26 Section 415.26 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS INORGANIC CHEMICALS MANUFACTURING POINT SOURCE CATEGORY Aluminum Sulfate...

  17. 40 CFR 412.26 - Pretreatment standards for new sources (PSNS).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 29 2011-07-01 2009-07-01 true Pretreatment standards for new sources (PSNS). 412.26 Section 412.26 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS CONCENTRATED ANIMAL FEEDING OPERATIONS (CAFO) POINT SOURCE CATEGORY Ducks...

  18. 40 CFR 412.26 - Pretreatment standards for new sources (PSNS).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 29 2014-07-01 2012-07-01 true Pretreatment standards for new sources (PSNS). 412.26 Section 412.26 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS CONCENTRATED ANIMAL FEEDING OPERATIONS (CAFO) POINT SOURCE CATEGORY Ducks...

  19. 5. East portal of Tunnel 26, view to southwest, 135mm ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. East portal of Tunnel 26, view to southwest, 135mm lens. Tunnel 25 (HAER CA-201) is visible in the distance. - Central Pacific Transcontinental Railroad, Tunnel No. 26, Milepost 133.29, Applegate, Placer County, CA

  20. 1. West portal of Tunnel 26, contextual view to northeast ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. West portal of Tunnel 26, contextual view to northeast from atop Tunnel 25 (HAER CA-201), with Tunnel 27 (HAER CA-203) visible in distance, 210mm lens. View is along new line, with original Central Pacific Transcontinental line crossing over the top above Tunnel 26. - Central Pacific Transcontinental Railroad, Tunnel No. 26, Milepost 133.29, Applegate, Placer County, CA

  1. Wind Technology, Cost, and Performance Trends in Denmark, Germany, Ireland, Norway, the European Union, and the United States: 2007 - 2012; NREL (National Renewable Energy Laboratory)

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

    Hand, Maureen

    This presentation provides a summary of IEA Wind Task 26 report on Wind Technology, Cost, and Performance Trends in Denmark, Germany, Ireland, Norway, the European Union, and the United States: 2007-2012

  2. 29 CFR 4041.26 - PBGC review of standard termination notice.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 4041.26 Labor Regulations Relating to Labor (Continued) PENSION BENEFIT GUARANTY CORPORATION PLAN... on termination proceeding. A request for additional information will suspend the running of the PBGC's 60-day review period. The review period will begin running again on the day the required...

  3. 40 CFR 425.26 - Pretreatment standards for new sources (PSNS)

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Pretreatment standards for new sources (PSNS) 425.26 Section 425.26 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS LEATHER TANNING AND FINISHING POINT SOURCE CATEGORY Hair Save, Chrome Tan...

  4. Music Training in Germany.

    ERIC Educational Resources Information Center

    Tapia, Ivan, Ed.

    1994-01-01

    This special-issue volume examines music education in the two Germanies and how music has had a great influence in the culture of the nations. The presentation is a professional and objective portrayal of music training and cultivation in Germany in the last decade of the present century. The articles attempt to outline the problems and tasks that…

  5. Prevalence of pain medication prescriptions in France, Germany, and the UK - a cross-sectional study including 4,270,142 patients.

    PubMed

    Jacob, Louis; Kostev, Karel

    2018-01-01

    The goal of the present study was to analyze the prevalence of pain medication prescriptions in general practices in France, Germany, and the UK. This study included all patients aged ≥18 years followed in 2016 in general practitioner practices in France, Germany and the UK. The primary outcome was the prevalence of patients receiving prescriptions for pain medications in France, Germany, and the UK in 2016. The following drugs were included in the analysis: anti-inflammatory and antirheumatic products, non-steroids and analgesics including opioids, antimigraine preparations, and other analgesics and antipyretics. Demographic variables included age and gender. This study included 4,270,142 patients. The prevalences of pain medication prescriptions were 57.3% in France, 29.6% in Germany, and 21.7% in the UK. Although this prevalence generally remained consistent between age groups in France (54.3%-60.3%), it increased with age in Germany (18-30 years: 23.8%; >70 years: 35.8%) and in the UK (18-30 years: 9.3%; >70 years: 43.8%). Finally, the prevalence of pain medication prescriptions was higher in women than in men in all three countries. Paracetamol was prescribed to 82.3% and 60.1% of patients receiving pain medication in France and the UK, respectively, whereas ibuprofen was prescribed to 46.5% of individuals in Germany. The prevalence of pain medication prescriptions was higher in France than in Germany and the UK. Further research is needed to gain a better understanding of the differences in the prescription patterns between these three European countries.

  6. [Microsporum canis: Current data on the prevalence of the zoophilic dermatophyte in central Germany].

    PubMed

    Uhrlaß, S; Krüger, C; Nenoff, P

    2015-11-01

    Microsporum (M.) canis, whose source of infection is mostly cats, is still considered as the most frequently occurring zoophilic dermatophyte in Germany and Europe. In distinct areas of Germany, the zoophilic dermatophyte Trichophyton (T.) anamorph of Arthroderma (A.) benhamiae also presents a frequent and emerging causative agent of dermatophytoses. Over a period of 3 years, from March 2010 to March 2013, skin samples from scalp, face, trunk, and limbs were investigated using mycological cultivation and by polymerase chain reaction (PCR) for dermatophytes. Materials originated in particular from the German Free States Saxony and Thuringia, and from the Federal State Saxony-Anhalt, but also included samples submitted from around Germany. The cultural detection of dermatophytes was performed on Sabouraud's 4% glucose agar with and without cycloheximide. For dermatophyte DNA detection, a uniplex PCR-ELISA was used. In all, 8464 samples from a total of 7680 patients were investigated. In 114 (1.5%) of 7680 patients, M. canis could be detected both by culture and/or PCR. M. canis was detected culturally in 100 samples, in 107 samples by PCR, in 91 samples both culturally and by PCR. For 12 patients, only cultural detection was done (without PCR). Also detected was tinea corporis due to M. canis in 59 patients, tinea capitis 8, tinea faciei 5, and tinea manus 2 patients. Of the patients, 45% were younger than 20 years, 42% were 20-49 years old, and 13% were 50 years or older. In comparison, T. anamorph of A. benhamiae was detectable by culture and/or PCR in 231 of 7680 patients (2.9%). M. canis was the second most common zoophilic dermatophyte. M. canis is still a frequent zoophilic dermatophyte in Germany. Since a few years ago, a rise of infections due to T. anamorph of A. benhamiae has been observed in Germany and other European countries. At least in distinct regions of Germany, this zoophilic dermatophyte, which is transferred from guinea pigs to human beings

  7. Activation of triggering receptor expressed on myeloid cells-1 on human neutrophils by marburg and ebola viruses.

    PubMed

    Mohamadzadeh, Mansour; Coberley, Sadie S; Olinger, Gene G; Kalina, Warren V; Ruthel, Gordon; Fuller, Claudette L; Swenson, Dana L; Pratt, William D; Kuhns, Douglas B; Schmaljohn, Alan L

    2006-07-01

    Marburg virus (MARV) and Ebola virus (EBOV), members of the viral family Filoviridae, cause fatal hemorrhagic fevers in humans and nonhuman primates. High viral burden is coincident with inadequate adaptive immune responses and robust inflammatory responses, and virus-mediated dysregulation of early host defenses has been proposed. Recently, a novel class of innate receptors called the triggering receptors expressed in myeloid cells (TREM) has been discovered and shown to play an important role in innate inflammatory responses and sepsis. Here, we report that MARV and EBOV activate TREM-1 on human neutrophils, resulting in DAP12 phosphorylation, TREM-1 shedding, mobilization of intracellular calcium, secretion of proinflammatory cytokines, and phenotypic changes. A peptide specific to TREM-1 diminished the release of tumor necrosis factor alpha by filovirus-activated human neutrophils in vitro, and a soluble recombinant TREM-1 competitively inhibited the loss of cell surface TREM-1 that otherwise occurred on neutrophils exposed to filoviruses. These data imply direct activation of TREM-1 by filoviruses and also indicate that neutrophils may play a prominent role in the immune and inflammatory responses to filovirus infections.

  8. Membrane insertion of fusion peptides from Ebola and Marburg viruses studied by replica-exchange molecular dynamics simulations.

    PubMed

    Olson, Mark A; Lee, Michael S; Yeh, In-Chul

    2017-06-15

    This work presents replica-exchange molecular dynamics simulations of inserting a 16-residue Ebola virus fusion peptide into a membrane bilayer. A computational approach is applied for modeling the peptide at the explicit all-atom level and the membrane-aqueous bilayer by a generalized Born continuum model with a smoothed switching function (GBSW). We provide an assessment of the model calculations in terms of three metrics: (1) the ability to reproduce the NMR structure of the peptide determined in the presence of SDS micelles and comparable structural data on other fusion peptides; (2) determination of the effects of the mutation Trp-8 to Ala and sequence discrimination of the homologous Marburg virus; and (3) calculation of potentials of mean force for estimating the partitioning free energy and their comparison to predictions from the Wimley-White interfacial hydrophobicity scale. We found the GBSW implicit membrane model to produce results of limited accuracy in conformational properties of the peptide when compared to the NMR structure, yet the model resolution is sufficient to determine the effect of sequence differentiation on peptide-membrane integration. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. [Acculturation, bicultural identity and psychiatric morbidity in young Turkish patients in Germany].

    PubMed

    Gül, Vahdet; Kolb, Semra

    2009-01-01

    This study was designed to examine, with the use of Berry's acculturation concept (2003), personal self-esteem and collective esteem in the acculturation of young Turks in Germany. Further, it was aimed to examine whether ethnic identity is linked to better mental health. Consecutive psychiatric primary care patients with Turkish background were screened with the 5-item Acculturation Questionnaire, adopted from the Latin American Validated Acculturation Scale. The interviewed patients were also assessed for psychiatric disorders according to ICD-10. By using the acculturation questionnaire among 220 patients included to this study, 154 (70%) patients, (88 male- 57,14%, mean age:22,1 sd. +/- 3,26 and 66 female- 42,85%, mean age: 21,73 sd. +/- 1,19) were found to be relatively good adjusted (group 1), and of 66 (30%) patients (44 male- 66,6%, mean age:26,3 sd. +/-3,39 and 22 female- 33,3%, mean age:25,88 sd. +/- 3,41) were found to be relatively poor adjusted (group 2) to the host community. The psychiatric co-morbidity showed in these two groups two distinct patterns (p< 0.001). Endogenous depression and the depression caused by the conflicts in the family-milieu are significantly more common in the group I. Unlike, the depression triggered by the psycho-social maladjustment is clearly more prevalent in the group II. The predictors of good adaptation were shown to be: bilingualism, bicultural identity and Germany as country of birth, whereas poor adaptation was related to: dominance of ethnic culture and language, and being born outside of Germany. The research presented provides firm evidence for a bicultural identity through assessments of several domains of acculturation: language spoken most of the time, language thought, ethnic identity, birthplace and the degree of adjustment to the host community. Cultural identity is one of the key determinants of mental health in evaluating adaptation to the host culture among immigrants. It is vital for the mental health

  10. Marburg virus infection in nonhuman primates: Therapeutic treatment by lipid-encapsulated siRNA.

    PubMed

    Thi, Emily P; Mire, Chad E; Ursic-Bedoya, Raul; Geisbert, Joan B; Lee, Amy C H; Agans, Krystle N; Robbins, Marjorie; Deer, Daniel J; Fenton, Karla A; MacLachlan, Ian; Geisbert, Thomas W

    2014-08-20

    Marburg virus (MARV) and the closely related filovirus Ebola virus cause severe and often fatal hemorrhagic fever (HF) in humans and nonhuman primates with mortality rates up to 90%. There are no vaccines or drugs approved for human use, and no postexposure treatment has completely protected nonhuman primates against MARV-Angola, the strain associated with the highest rate of mortality in naturally occurring human outbreaks. Studies performed with other MARV strains assessed candidate treatments at times shortly after virus exposure, before signs of disease are detectable. We assessed the efficacy of lipid nanoparticle (LNP) delivery of anti-MARV nucleoprotein (NP)-targeting small interfering RNA (siRNA) at several time points after virus exposure, including after the onset of detectable disease in a uniformly lethal nonhuman primate model of MARV-Angola HF. Twenty-one rhesus monkeys were challenged with a lethal dose of MARV-Angola. Sixteen of these animals were treated with LNP containing anti-MARV NP siRNA beginning at 30 to 45 min, 1 day, 2 days, or 3 days after virus challenge. All 16 macaques that received LNP-encapsulated anti-MARV NP siRNA survived infection, whereas the untreated or mock-treated control subjects succumbed to disease between days 7 and 9 after infection. These results represent the successful demonstration of therapeutic anti-MARV-Angola efficacy in nonhuman primates and highlight the substantial impact of an LNP-delivered siRNA therapeutic as a countermeasure against this highly lethal human disease. Copyright © 2014, American Association for the Advancement of Science.

  11. [Fostering of health economics in Germany].

    PubMed

    Ulrich, V

    2012-05-01

    Health economics is now well established in Germany with the aim to apply economic tools to answer problems in health and health care. After a short review of the international development of health economics and the development in Germany in particular, the article looks at selected recent topics of health economic analysis in Germany (economic evaluation, industrial economics, health and education).

  12. 14 CFR 29.473 - Ground loading conditions and assumptions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... through the center of gravity throughout the landing impact. This lift may not exceed two-thirds of the... rotorcraft must be designed for a limit load factor of not less than the limit inertia load factor... factor of safety prescribed in § 29.303 need not be used. [Amdt. 29-3, 33 FR 966, Jan. 26, 1968] ...

  13. 14 CFR 29.473 - Ground loading conditions and assumptions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... through the center of gravity throughout the landing impact. This lift may not exceed two-thirds of the... rotorcraft must be designed for a limit load factor of not less than the limit inertia load factor... factor of safety prescribed in § 29.303 need not be used. [Amdt. 29-3, 33 FR 966, Jan. 26, 1968] ...

  14. 14 CFR 29.473 - Ground loading conditions and assumptions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... through the center of gravity throughout the landing impact. This lift may not exceed two-thirds of the... rotorcraft must be designed for a limit load factor of not less than the limit inertia load factor... factor of safety prescribed in § 29.303 need not be used. [Amdt. 29-3, 33 FR 966, Jan. 26, 1968] ...

  15. 29 CFR 4043.26 - Inability to pay benefits when due.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... REPORTABLE EVENTS AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.26 Inability to pay benefits when due. (a) Reportable event. A reportable event occurs when a plan is...) Waivers. Notice is waived unless the reportable event occurs during a plan year for which the plan is...

  16. 29 CFR 4043.26 - Inability to pay benefits when due.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... REPORTABLE EVENTS AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.26 Inability to pay benefits when due. (a) Reportable event. A reportable event occurs when a plan is...) Waivers. Notice is waived unless the reportable event occurs during a plan year for which the plan is...

  17. 29 CFR 4043.26 - Inability to pay benefits when due.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... REPORTABLE EVENTS AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.26 Inability to pay benefits when due. (a) Reportable event. A reportable event occurs when a plan is...) Waivers. Notice is waived unless the reportable event occurs during a plan year for which the plan is...

  18. 29 CFR 4043.26 - Inability to pay benefits when due.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... REPORTABLE EVENTS AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.26 Inability to pay benefits when due. (a) Reportable event. A reportable event occurs when a plan is...) Waivers. Notice is waived unless the reportable event occurs during a plan year for which the plan is...

  19. 29 CFR 4043.26 - Inability to pay benefits when due.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... REPORTABLE EVENTS AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.26 Inability to pay benefits when due. (a) Reportable event. A reportable event occurs when a plan is...) Waivers. Notice is waived unless the reportable event occurs during a plan year for which the plan is...

  20. 3. West portal of Tunnel 26, view to northeast, 135mm ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. West portal of Tunnel 26, view to northeast, 135mm lens. Note use of granite voussoirs and coping on this otherwise all-reinforced concrete structure. - Central Pacific Transcontinental Railroad, Tunnel No. 26, Milepost 133.29, Applegate, Placer County, CA

  1. [The Marburg surgical curriculum - improving the attraction of medical education by teaching central surgical competence].

    PubMed

    Schwarting, T; Ruchholtz, S; Josephs, D; Oberkircher, L; Bartsch, D K; Fendrich, V

    2012-04-01

    The quality of medical education is an ongoing challenge due to the continuing changes of the health-care politics and general social conditions. At many German university hospitals the dominating picture is overfilled courses, lack of hands-on practice, reduced patient contact and the dull provision of theoretical, abstract knowledge. The reformed surgical curriculum at the University of Marburg university hospital is used to demonstrate that, in spite of large student numbers, a practice-oriented, small-group training at a high didactic level is possible. The surgical training courses are organized in detail and coordinated. Course contents and structure are media available in print and online versions for both students and teachers and thus fulfill not only transparency needs but also contemporary requirements. The strategy of a practice- and patient-oriented, small-group training is followed strictly in the surgical curriculum. In addition, accompanying tutorial possibilities for individual study in an up-to-date learning center are offered. Here the students have the opportunity to intensify knowledge acquired in previous or future courses with numerous attractive education means. Continuous evaluation of the individual training courses at the end of each semester not only document motivation of the students but also serve to continuously improve the training concepts. © Georg Thieme Verlag KG Stuttgart · New York.

  2. Shana Dale Swearing-in Ceremony

    NASA Image and Video Library

    2005-11-29

    Shana Dale, center, is sworn in as NASA's deputy administrator by Dr. John H. Marburger, left, Director, Office of Science and Technology Policy (OSTP), Executive Office of the President, Tuesday, Nov. 29, 2005, at NASA Headquarters in Washington. With Ms. Dale is Mr. Mike Fagan. Photo Credit: (NASA/Bill Ingalls)

  3. [Assisted suicide in Germany: medical diagnoses and personal reasons of 117 decedents].

    PubMed

    Bruns, F; Blumenthal, S; Hohendorf, G

    2016-02-01

    In Germany both scientific and public debates on physician assisted suicide often focus on patients with unbearable suffering in terminal condition. Proponents of physician assisted suicide bring forward the argument that there are end-of-life situations where only assisted suicide can bring relief from intolerable pain, dyspnea or other symptoms. But does focusing on unbearable symptoms in terminal condition reflect the reality of assisted suicide? Our data from 117 assisted suicides in Germany indicates that the reasons for assisted suicide are more complex than the current debate in Germany suggests. We analyzed diagnoses and reasons that prompted patients to suicide with the help of the German right-to-die organization "Sterbehilfe Deutschland" (StHD) between 2010 and 2013. 118 case reports of assisted suicide published by StHD were evaluated retrospectively. Between 2010 and 2013 StHD provided assistance in 118 suicides. 71 % of the deceased were women. 67 % were aged 70 years or older. 25,6 % suffered from metastasized cancer, 20,5 % had a severe neurological disease. 23 % suffered from age-associated diseases or disability. 14,5 % of the decedents had a predominant psychiatric diagnose, 7,7 % were physically and mentally healthy. The main reasons for suicide were loss of life perspective in the face of a severe disease (29 %), fear of care dependency (23,9 %), weariness of life without any severe disease (20,5 %). Only 12,8 % named non-treatable symptoms as a reason. Loss of life perspective in the face of a severe disease, fear of long-term care and weariness of life without any severe disease rather than unbearable suffering of non-treatable symptoms seem to be the most common reasons for members of StHD to commit suicide. These empirical findings should be mentioned in future debates on assisted suicide in Germany. © Georg Thieme Verlag KG Stuttgart · New York.

  4. GEOSAT Follow-On (GFO) Altimeter Document Series, Volume 8: GFO Altimeter Engineering Assessment Report Update:The First 109 Cycles Since Acceptance November 29, 2000 to December 26, 2005. Version 1, Volume 8

    NASA Technical Reports Server (NTRS)

    Conger, A. M.; Hancock, D. W., III; Hayne, G. S.; Brooks, R. L.

    2006-01-01

    The purpose of this document is to present and document GFO performance analyses and results. This is the fifth Assessment Report since the initial report. This report extends the performance assessment since acceptance to 26 December 2005. The initial GFO Altimeter Engineering Assessment Report, March 2001 (NASA/TM-2001-209984/Ver.1/Vol.1) covered the GFO performance from Launch to Acceptance (10 February 1998 to 29 November 2000). The second of the series covered the performance from Acceptance to the end of Cycle 20 (29 November 2000 to 21 November 2001). The third of the series covered the performance from Acceptance to the end of Cycle 42 (29 November 2000 to 30 November 2002). The fourth of the series covered the performance from Acceptance to the end of Cycle 64 (29 November 2000 to 17 December 2003). The fifth of the series covered performance from Acceptance to the end of Cycle 86 (29 November 2000 to 17 December 2004). Since launch, we have performed a variety of GFO performance studies; an accumulative index of those studies is provided in Appendix A.

  5. Comparison of the Transcription and Replication Strategies of Marburg Virus and Ebola Virus by Using Artificial Replication Systems

    PubMed Central

    Mühlberger, Elke; Weik, Michael; Volchkov, Viktor E.; Klenk, Hans-Dieter; Becker, Stephan

    1999-01-01

    The members of the family Filoviridae, Marburg virus (MBGV) and Ebola virus (EBOV), are very similar in terms of morphology, genome organization, and protein composition. To compare the replication and transcription strategies of both viruses, an artificial replication system based on the vaccinia virus T7 expression system was established for EBOV. Specific transcription and replication of an artificial monocistronic minireplicon was demonstrated by reporter gene expression and detection of the transcribed and replicated RNA species. As it was shown previously for MBGV, three of the four EBOV nucleocapsid proteins, NP, VP35, and L, were essential and sufficient for replication. In contrast to MBGV, EBOV-specific transcription was dependent on the presence of the fourth nucleocapsid protein, VP30. When EBOV VP30 was replaced by MBGV VP30, EBOV-specific transcription was observed but with lower efficiency. Exchange of NP, VP35, and L between the two replication systems did not lead to detectable reporter gene expression. It was further observed that neither MBGV nor EBOV were able to replicate the heterologous minigenomes. A chimeric minigenome, however, containing the EBOV leader and the MBGV trailer was encapsidated, replicated, transcribed, and packaged by both viruses. PMID:9971816

  6. Cryo-Electron Tomography of Marburg Virus Particles and Their Morphogenesis within Infected Cells

    PubMed Central

    Kolesnikova, Larissa; Welsch, Sonja; Krähling, Verena; Davey, Norman; Parsy, Marie-Laure; Becker, Stephan; Briggs, John A. G.

    2011-01-01

    Several major human pathogens, including the filoviruses, paramyxoviruses, and rhabdoviruses, package their single-stranded RNA genomes within helical nucleocapsids, which bud through the plasma membrane of the infected cell to release enveloped virions. The virions are often heterogeneous in shape, which makes it difficult to study their structure and assembly mechanisms. We have applied cryo-electron tomography and sub-tomogram averaging methods to derive structures of Marburg virus, a highly pathogenic filovirus, both after release and during assembly within infected cells. The data demonstrate the potential of cryo-electron tomography methods to derive detailed structural information for intermediate steps in biological pathways within intact cells. We describe the location and arrangement of the viral proteins within the virion. We show that the N-terminal domain of the nucleoprotein contains the minimal assembly determinants for a helical nucleocapsid with variable number of proteins per turn. Lobes protruding from alternate interfaces between each nucleoprotein are formed by the C-terminal domain of the nucleoprotein, together with viral proteins VP24 and VP35. Each nucleoprotein packages six RNA bases. The nucleocapsid interacts in an unusual, flexible “Velcro-like” manner with the viral matrix protein VP40. Determination of the structures of assembly intermediates showed that the nucleocapsid has a defined orientation during transport and budding. Together the data show striking architectural homology between the nucleocapsid helix of rhabdoviruses and filoviruses, but unexpected, fundamental differences in the mechanisms by which the nucleocapsids are then assembled together with matrix proteins and initiate membrane envelopment to release infectious virions, suggesting that the viruses have evolved different solutions to these conserved assembly steps. PMID:22110401

  7. Black soils and/or sediments at the western border of the Nördlinger Ries (South Germany)

    NASA Astrophysics Data System (ADS)

    Mailänder, S.; Eberle, J.; Blümel, W. D.

    2009-04-01

    In the framework of a geoarchaeological research project by the Institute of Geography, University of Stuttgart, in the year 2006 the construction of a kerosene pipeline trench was monitored at the western border of the impact crater "Nördlinger Ries" in South Germany (MAILÄNDER ET AL. 2008). Thereby black horizons were recognized at several places. They occured predominantly in depressions and were covered by holocene colluvial sediments, but rested on different bedrocks which include mud- and sandstones as well as lime. The most of these horizons seemed to be rich in humic material and clay. By means of various studies, which involve sedimentological, pedological, archaeobotanical and -zoological analysis as well as 14C-(AMS)-datings, the periods and circumstances of the development of these black horizons are explored. The poster presents the itemised research methods and their first results. Particularly micromorphological analysis and mollusc classifications turned out to be very valuable to reconstruct the palaeoenvironmental conditions during their formation and subsequent modifications. First datings of bulk samples and charcoal pieces refer to the Atlantic period, but the measured ages distribute to a long time space from about cal BC 5200 to cal BC 4000. The outcomes of this investigation should facilitate a comparison with similar horizons which are recovered in several Central European sediment profiles, for example in the Amöneburger Becken near Marburg in Hessen (RITTWEGER 2000). Also their composition will be contrasted with samples from archaeological findings in the surrounding and the possibility of an anthropogenic influence on their development will be checked. References MAILÄNDER, S., W. D. BLÜMEL & J. EBERLE (2008): Paläoumweltbedingungen und anthropogene Landoberflächenveränderungen im Umfeld des frühkeltischen Fürstensitzes auf dem Ipf am Westrand des Nördlinger Rieses: Erste Geländebefunde und Auswertungen 2005/2006.- In

  8. Update: Federal Republic of Germany.

    ERIC Educational Resources Information Center

    Loewenthal, Nessa P.

    The Federal Republic of Germany is widely respected for its highly developed economy, rich cultural life, and significant contributions to science, mathematics, and the arts. Designed for families or individuals planning to move to or live in Germany for extended periods of time, this book provides guidance in such practical matters as entry…

  9. Epidemiology of subacute sclerosing panencephalitis (SSPE) in Germany from 2003 to 2009: a risk estimation.

    PubMed

    Schönberger, Katharina; Ludwig, Maria-Sabine; Wildner, Manfred; Weissbrich, Benedikt

    2013-01-01

    Subacute sclerosing panencephalitis (SSPE) is a fatal long-term complication of measles infection. We performed an estimation of the total number of SSPE cases in Germany for the period 2003 to 2009 and calculated the risk of SSPE after an acute measles infection. SSPE cases were collected from the Surveillance Unit for Rare Paediatric Diseases in Germany and the Institute of Virology and Immunobiology at the University of Würzburg. The total number of SSPE cases was estimated by capture-recapture analysis. For the period 2003 to 2009, 31 children with SSPE who were treated at German hospitals were identified. The capture-recapture estimate was 39 cases (95% confidence interval: 29.2-48.0). The risk of developing SSPE for children contracting measles infection below 5 years of age was calculated as 1∶1700 to 1∶3300. This risk is in the same order of magnitude as the risk of a fatal acute measles infection.

  10. Epidemiology of Subacute Sclerosing Panencephalitis (SSPE) in Germany from 2003 to 2009: A Risk Estimation

    PubMed Central

    Schönberger, Katharina; Ludwig, Maria-Sabine; Wildner, Manfred; Weissbrich, Benedikt

    2013-01-01

    Subacute sclerosing panencephalitis (SSPE) is a fatal long-term complication of measles infection. We performed an estimation of the total number of SSPE cases in Germany for the period 2003 to 2009 and calculated the risk of SSPE after an acute measles infection. SSPE cases were collected from the Surveillance Unit for Rare Paediatric Diseases in Germany and the Institute of Virology and Immunobiology at the University of Würzburg. The total number of SSPE cases was estimated by capture-recapture analysis. For the period 2003 to 2009, 31 children with SSPE who were treated at German hospitals were identified. The capture-recapture estimate was 39 cases (95% confidence interval: 29.2–48.0). The risk of developing SSPE for children contracting measles infection below 5 years of age was calculated as 1∶1700 to 1∶3300. This risk is in the same order of magnitude as the risk of a fatal acute measles infection. PMID:23874807

  11. Youth exposure to alcohol advertising on television in the UK, the Netherlands and Germany.

    PubMed

    Patil, Sunil; Winpenny, Eleanor M; Elliott, Marc N; Rohr, Charlene; Nolte, Ellen

    2014-08-01

    Exposure of young people to alcohol advertising is a risk factor for underage drinking. This study assessed youth exposure to television alcohol advertising in the UK, the Netherlands and Germany, from December 2010 to May 2011. A negative binomial regression model predicted number of alcohol advertisements from the proportion of the television viewership in each age group. This allowed comparison of alcohol advertisement incidence for each youth age category relative to an adult reference category. In the UK, those aged 10-15 years were significantly more exposed to alcohol advertisements per viewing hour than adults aged ≥ 25 years [incidence rate ratio (IRR) = 1.11; 95% confidence interval (95% CI): 1.06, 1.18; P < 0.01]; in the Netherlands, those aged 13-19 years were more exposed per viewing hour than adults aged ≥ 20 years (IRR = 1.29; 95% CI: 1.19, 1.39; P < 0.01). Conversely, in Germany, those aged 10-15 years were less exposed to alcohol advertisements than adults aged ≥ 25 years (IRR = 0.79; 95% CI: 0.73, 0.85; P < 0.01). In each country, young children (aged 4-9 years in the UK and Germany, 6-12 years in the Netherlands) were less exposed than adults. Adolescents in the UK and the Netherlands, but not Germany, had higher exposure to television alcohol advertising relative to adults than would be expected from their television viewing. Further work across a wider range of countries is needed to understand the relationship between national policies and youth exposure to alcohol advertising on television. © The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

  12. Adherence to antiepileptic drugs in children and adolescents: A retrospective study in primary care settings in Germany.

    PubMed

    Jacob, Louis; Hamer, Hajo M; Kostev, Karel

    2017-10-01

    The goal of this study was to analyze adherence to antiepileptic drugs (AED) in children and adolescents treated in pediatric practices in Germany. The present study included patients aged between 2 and 17years who were diagnosed with epilepsy (ICD-10: G40) and had received at least two prescriptions of AED between January 2006 and December 2015 in 243 pediatric practices in Germany. The medication possession ratio (MPR) was used to estimate adherence, and patients with a MPR greater than 80% were considered adherent. The impact of patient and drug characteristics on adherence was analyzed using a multivariate logistic regression model. A total of 5214 patients were included. Mean age was 10.9years (SD=4.9years). The overall MPR was 88.8% (SD=34.1%), and 68.9% of patients were considered adherent. Children aged 5years or younger were more adherent to AED than those aged between 14 and 17years (OR=1.22, 95% CI: 1.07-1.39). Individuals living in western Germany were also found to be more adherent than those living in eastern Germany (OR=1.71, 95% CI: 1.55-1.88). Asthma as a comorbidity (OR=1.59, 95% CI: 1.29-1.96) was positively and attention-deficit hyperactivity disorder (OR=0.81, 95% CI: 0.71-0.93) negatively associated with treatment adherence. Finally, no significant association was found between adherence and the type of AED. Two-thirds of children and adolescents suffering from epilepsy in Germany were adherent to AED. Age, place of residence, and comorbidities were significantly associated with adherence. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Germany Country Analysis Brief

    EIA Publications

    2016-01-01

    Germany was the largest energy consumer in Europe and the seventh-largest energy consumer in the world in 2015, according to BP Statistical Review of World Energy. It was also the fourth-largest economy in the world by nominal gross domestic product (GDP) after the United States, China, and Japan in 2015. Its size and location give it considerable influence over the European Union’s energy sector. However, Germany must rely on imports to meet the majority of its energy demand.

  14. Decline of Neurologic Varicella Complications in Children During the First Seven Years After Introduction of Universal Varicella Vaccination in Germany, 2005-2011.

    PubMed

    Streng, Andrea; Grote, Veit; Rack-Hoch, Anita; Liese, Johannes G

    2017-01-01

    Universal varicella vaccination for 1-year-old children was introduced in Germany in 2004. We investigated changes in the incidence and type of varicella-associated neurologic complications in children during the first 7 years after universal vaccination recommendation. A surveillance study was conducted based on patients <17 years of age with an International Classification of Diseases (10th Revision) discharge diagnosis of varicella, annually reported by 22-29 pediatric hospitals in Bavaria, Germany, 2005 to 2011. Annual incidences were estimated and linear trend across years was assessed by Poisson regression models. Of a total of 1263 varicella-associated pediatric hospitalizations, 228 children (18.1%) had neurologic complications (median age 4 years, interquartile range 2-7; 56% male). The most frequent neurologic complications were febrile convulsion (32.0% of 228 children, median age 3.0 years), varicella encephalitis or meningitis (28.9%; median age 4.5 years), syncope (13.2%; median age 7.0 years) and cerebral convulsion (11.0%; median age 4.0 years). Other complications included ataxia (3.1%), facial nerve palsy (2.6%) and cerebral vasculitis/infarction (1.8%). Neurologic complications showed a continuous decrease between 2005 and 2011, from an incidence of 2.8 (95% confidence interval: 2.1-3.6) per 100,000 children <17 years of age to 1.2 (95% confidence interval: 0.7-2.1; P < 0.001). In particular, a marked decline was observed among children up to 7 years of age, mainly because of a decrease in the number of febrile convulsions and encephalitis or meningitis. The incidence of varicella-associated neurologic complications in children decreased approximately by 60% during the first 7 years following the recommendation for universal vaccination.

  15. Chronicle of Higher Education. Volume 50, Number 29, March 26, 2004

    ERIC Educational Resources Information Center

    Chronicle of Higher Education, 2004

    2004-01-01

    "Chronicle of Higher Education" presents an abundant source of news and information for college and university faculty members and administrators. This March 26, 2004 issue of "Chronicle of Higher Education" includes the following articles: (1) "Going Over the Falls" (Brady, John N.); (2) "Lessons in Departmental…

  16. 26Al-26Mg systematics in chondrules from Kaba and Yamato 980145 CV3 carbonaceous chondrites

    NASA Astrophysics Data System (ADS)

    Nagashima, Kazuhide; Krot, Alexander N.; Komatsu, Mutsumi

    2017-03-01

    We report the mineralogy, petrography, and in situ measured 26Al-26Mg systematics in chondrules from the least metamorphosed CV3 (Vigarano-type) chondrites, Kaba and Yamato (Y) 980145. Two Y 980145 chondrules measured show no resolvable excesses in 26Mg (26Mg∗), a decay product of a short-lived (t1/2 ∼0.7 Ma) radionuclide 26Al. Plagioclase in one of the chondrules is replaced by nepheline, indicative of thermal metamorphism. The lack of 26Mg∗ in the Y 980145 chondrules is most likely due to disturbance of their 26Al-26Mg systematics during the metamorphism. Although Kaba experienced extensive metasomatic alteration (<300 °C), it largely avoided subsequent thermal metamorphism, and the 26Al-26Mg systematics of its chondrules appear to be undisturbed. All eight Kaba chondrules measured show 26Mg∗, corresponding to the initial 26Al/27Al ratios [(26Al/27Al)0] ranging from (2.9 ± 1.7) × 10-6 to (6.3 ± 2.7) × 10-6. If CV parent asteroid accreted rapidly after chondrule formation, the inferred (26Al/27Al)0 ratios in Kaba chondrules provide an upper limit on 26Al available in this asteroid at the time of its accretion. The estimated initial abundance of 26Al in the CV asteroid is too low to melt it and contradicts the existence of a molten core in this body suggested from the paleomagnetic records of Allende [Carporzen et al. (2011) Magnetic evidence for a partially differentiated carbonaceous chondrite parent body. Proc. Natl. Acad. Sci. USA108, 6386-6389] and Kaba [Gattacceca et al. (2013) More evidence for a partially differentiated CV parent body from the meteorite Kaba. Lunar Planet. Sci.44, abstract#1721].

  17. 48 CFR 252.229-7002 - Customs exemptions (Germany).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... (Germany). 252.229-7002 Section 252.229-7002 Federal Acquisition Regulations System DEFENSE ACQUISITION... of Provisions And Clauses 252.229-7002 Customs exemptions (Germany). As prescribed in 229.402-70(b), use the following clause: Customs Exemptions (Germany) (JUN 1997) Imported products required for the...

  18. 48 CFR 252.229-7002 - Customs exemptions (Germany).

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... (Germany). 252.229-7002 Section 252.229-7002 Federal Acquisition Regulations System DEFENSE ACQUISITION... of Provisions And Clauses 252.229-7002 Customs exemptions (Germany). As prescribed in 229.402-70(b), use the following clause: Customs Exemptions (Germany) (JUN 1997) Imported products required for the...

  19. 48 CFR 252.229-7002 - Customs exemptions (Germany).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... (Germany). 252.229-7002 Section 252.229-7002 Federal Acquisition Regulations System DEFENSE ACQUISITION... of Provisions And Clauses 252.229-7002 Customs exemptions (Germany). As prescribed in 229.402-70(b), use the following clause: Customs Exemptions (Germany) (JUN 1997) Imported products required for the...

  20. 48 CFR 252.229-7002 - Customs exemptions (Germany).

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... (Germany). 252.229-7002 Section 252.229-7002 Federal Acquisition Regulations System DEFENSE ACQUISITION... of Provisions And Clauses 252.229-7002 Customs exemptions (Germany). As prescribed in 229.402-70(b), use the following clause: Customs Exemptions (Germany) (JUN 1997) Imported products required for the...

  1. 48 CFR 252.229-7002 - Customs exemptions (Germany).

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... (Germany). 252.229-7002 Section 252.229-7002 Federal Acquisition Regulations System DEFENSE ACQUISITION... of Provisions And Clauses 252.229-7002 Customs exemptions (Germany). As prescribed in 229.402-70(b), use the following clause: Customs Exemptions (Germany) (JUN 1997) Imported products required for the...

  2. Sport in Germany. Basis-Info: Social Policy. In-Press.

    ERIC Educational Resources Information Center

    Beitz, Steffen

    This report describes sports in Germany, explaining that sport is part of Germany's culture. Popular sports are enjoyed by both the public and private sector. Germany has a well-developed club and association sector. One in three Germans belongs to a sports organization. A major feature of sport in Germany is its autonomy. Popular sports begin in…

  3. Novel Chemical Ligands to Ebola Virus and Marburg Virus Nucleoproteins Identified by Combining Affinity Mass Spectrometry and Metabolomics Approaches

    PubMed Central

    Fu, Xu; Wang, Zhihua; Li, Lixin; Dong, Shishang; Li, Zhucui; Jiang, Zhenzuo; Wang, Yuefei; Shui, Wenqing

    2016-01-01

    The nucleoprotein (NP) of Ebola virus (EBOV) and Marburg virus (MARV) is an essential component of the viral ribonucleoprotein complex and significantly impacts replication and transcription of the viral RNA genome. Although NP is regarded as a promising antiviral druggable target, no chemical ligands have been reported to interact with EBOV NP or MARV NP. We identified two compounds from a traditional Chinese medicine Gancao (licorice root) that can bind both NPs by combining affinity mass spectrometry and metabolomics approaches. These two ligands, 18β-glycyrrhetinic acid and licochalcone A, were verified by defined compound mixture screens and further characterized with individual ligand binding assays. Accompanying biophysical analyses demonstrate that binding of 18β-glycyrrhetinic acid to EBOV NP significantly reduces protein thermal stability, induces formation of large NP oligomers, and disrupts the critical association of viral ssRNA with NP complexes whereas the compound showed no such activity on MARV NP. Our study has revealed the substantial potential of new analytical techniques in ligand discovery from natural herb resources. In addition, identification of a chemical ligand that influences the oligomeric state and RNA-binding function of EBOV NP sheds new light on antiviral drug development. PMID:27403722

  4. Prevalence, Duration and Severity of Parkinson's Disease in Germany: A Combined Meta-Analysis from Literature Data and Outpatient Samples.

    PubMed

    Enders, Dirk; Balzer-Geldsetzer, Monika; Riedel, Oliver; Dodel, Richard; Wittchen, Hans-Ulrich; Sensken, Sven-Christian; Wolff, Björn; Reese, Jens-Peter

    2017-01-01

    Epidemiological data on the prevalence of Parkinson's disease (PD) in Germany are limited. The aims of this study were to estimate the age- and gender-specific prevalence of PD in Germany as well as the severity and illness duration. A systematic literature search was performed in 5 different databases. European studies were included if they reported age- and gender-specific numbers of prevalence rates of PD. Meta-analytic approaches were applied to derive age- and gender-specific pooled prevalence estimates. Data of 4 German outpatient samples were incorporated to calculate the proportion of patients with PD in Germany grouped by Hoehn and Yahr (HY) stages and disease duration. In the German population, 178,169 cases of PD were estimated (prevalence: 217.22/100,000). The estimated relative illness duration was 40% with less than 5 years, 31% with 5-9 years, and 29% with more than 9 years. The proportions for different HY stages were estimated at 13% (I), 30% (II), 35% (III), 17% (IV), and 4% (V), respectively. Key Message: We provide an up-to-date estimation of age- and gender-specific as well as severity-based prevalence figures for PD in Germany. Further community studies are needed to estimate population-based severity distributions and distributions of non-motor symptoms in PD. © 2017 S. Karger AG, Basel.

  5. Groundwater nitrate pollution: High-resolution approach of calculating the nitrogen balance surplus for Germany

    NASA Astrophysics Data System (ADS)

    Klement, Laura; Bach, Martin; Breuer, Lutz; Häußermann, Uwe

    2017-04-01

    The latest inventory of the EU Water Framework Directive determined that 26.3% of Germany's groundwater bodies are in a poor chemical state regarding nitrate. As of late October 2016, the European Commission has filed a lawsuit against Germany for not taking appropriate measures against high nitrate levels in water bodies and thus failing to comply with the EU Nitrate Directive. Due to over-fertilization and high-density animal production, Agriculture was identified as the main source of nitrate pollution. One way to characterize the potential impact of reactive nitrogen on water bodies is the soil surface nitrogen balance where all agricultural nitrogen inputs within an area are contrasted with the output, i.e. the harvest. The surplus nitrogen (given in kg N per ha arable land and year) can potentially leach into the groundwater and thus can be used as a risk indicator. In order to develop and advocate appropriate measures to mitigate the agricultural nitrogen surplus with spatial precision, high-resolution data for the nitrogen surplus is needed. In Germany, not all nitrogen input data is available with the required spatial resolution, especially the use of mineral fertilizers is only given statewide. Therefore, some elements of the nitrogen balance need to be estimated based on agricultural statistics. Hitherto, statistics from the Federal Statistical Office and the statistical offices of the 16 federal states of Germany were used to calculate the soil surface balance annually for the spatial resolution of the 402 districts of Germany (mean size 890 km2). In contrast, this study presents an approach to estimate the nitrogen surplus at a much higher spatial resolution by using the comprehensive Agricultural census data collected in 2010 providing data for 326000 agricultural holdings. This resulted in a nitrogen surplus map with a 5 km x 5 km grid which was subsequently used to calculate the nitrogen concentration of percolation water. This provides a

  6. Evaluation of the level of depression among medical students from Poland, Portugal and Germany.

    PubMed

    Seweryn, Mariusz; Tyrała, Kinga; Kolarczyk-Haczyk, Aleksandra; Bonk, Magdalena; Bulska, Weronika; Krysta, Krzysztof

    2015-09-01

    Depression is a serious illness affecting health, family and professional life of many people of all sectors of society. It also concerns students, regardless of their geographical location. The Beck Depression Inventory (BDI) is a proper tool to brief check of the level of depression because it has high correlation with depression. The aim of this study was to assess and compare the level of depression among medical students from Poland, Portugal and Germany. Students from different countries were asked to fill in an electronic form containing the BDI. The form was created separately for each country, using official translation of the BDI, approved by the competent psychiatric association. Google Drive software was used for the electronic form, and Stat soft Statistica v10 software for statistical analysis. There were statistically significant differences (p<0.05) in terms of average score of the BDI and of the proportion of the scores more than 10 points of medical and technology students among kinds of studies and countries. The average score of the BDI of medical students: Poland: 13.76±9.99 points; Germany: 8.49±7.64 points; Portugal: 7.37±7.67 points. The average score of the BDI of technology students: Poland: 12.42±9.66 points; Germany: 10.51±8.49 points; Portugal: 9.25±8.97 points. The proportion of the scores more than 10 points of medical students: Poland 56.32% (285/506) Germany 34.92% (154/441) Portugal 26.03% (82/315). The proportion of the scores more than 10 points of technology students: Poland 55.01% (368/669) Germany 43.82% (156/356) Portugal 37.57% (136/362). The highest depression score among medical and technology students according the BDI was found in Poland. A proper monitoring of depression is required, as well as rapid and appropriate help for those who suffer from it.

  7. Explaining differences in stakeholder take up of disease management programmes: A comparative analysis of policy implementation in Austria and Germany.

    PubMed

    Schang, Laura; Thomson, Sarah; Czypionka, Thomas

    2016-03-01

    Understanding why policies to improve care for people with chronic conditions fail to be implemented is a pressing issue in health system reform. We explore reasons for the relatively high uptake of disease management programmes (DMPs) in Germany, in contrast to low uptake in Austria. We focus on the motivation, information and power of key stakeholder groups (payers, physician associations, individual physicians and patients). We conducted a comparative stakeholder analysis using qualitative data from interviews (n=15 in Austria and n=26 in Germany), legal documents and media reports. Stakeholders in Germany appeared to have systematically stronger motivation, exposure to more positive information about DMPs and better ability to implement DMPs than their counterparts in Austria. Policy in Austria focused on financial incentives to physicians only. In Germany, limited evidence about the quality improvement and cost savings potential of DMPs was mitigated by strong financial incentives to sickness funds but proved a fundamental obstacle in Austria. Efforts to promote DMPs should seek to ensure the cooperation of payers and patients, not just physicians, using a mix of financial and non-financial instruments suited to the context. A singular focus on financially incentivising providers is unlikely to stimulate uptake of DMPs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Evaluating Frequency, Diagnostic Quality, and Cost of Lyme Borreliosis Testing in Germany: A Retrospective Model Analysis

    PubMed Central

    Müller, I.; Freitag, M. H.; Poggensee, G.; Scharnetzky, E.; Straube, E.; Schoerner, Ch.; Hlobil, H.; Hagedorn, H.-J.; Stanek, G.; Schubert-Unkmeir, A.; Norris, D. E.; Gensichen, J.; Hunfeld, K.-P.

    2012-01-01

    Background. Data on the economic impact of Lyme borreliosis (LB) on European health care systems is scarce. This project focused on the epidemiology and costs for laboratory testing in LB patients in Germany. Materials and Methods. We performed a sentinel analysis of epidemiological and medicoeconomic data for 2007 and 2008. Data was provided by a German statutory health insurance (DAK) company covering approx. 6.04 million members. In addition, the quality of diagnostic testing for LB in Germany was studied. Results. In 2007 and 2008, the incident diagnosis LB was coded on average for 15,742 out of 6.04 million insured members (0.26%). 20,986 EIAs and 12,558 immunoblots were ordered annually for these patients. For all insured members in the outpatient sector, a total of 174,820 EIAs and 52,280 immunoblots were reimbursed annually to health care providers (cost: 2,600,850€). For Germany, the overall expected cost is estimated at 51,215,105€. However, proficiency testing data questioned test quality and standardization of diagnostic assays used. Conclusion. Findings from this study suggest ongoing issues related to care for LB and may help to improve future LB disease management. PMID:22242037

  9. [Tularemia in Germany].

    PubMed

    Kohlmann, R; Geis, G; Gatermann, S G

    2014-07-01

    The bacterium Francisella tularensis is known for more than 100 years by now as the etiological agent of the disease tularemia, a zoonotic infection with a worldwide distribution in the Northern Hemisphere. The prevalence of tularemia shows a wide geographic variation, being comparably infrequent in Germany. Tularemia can present itself with multiple clinical manifestations including ulceroglandular, glandular, oropharyngeal, oculoglandular, respiratory and typhoidal forms. Due to the low prevalence and the unspecific symptomatology, a rapid diagnosis and early start of an effective therapy are rarely obtained. Thus, in this article we summarize important aspects concerning etiology, ecology and routes of transmission, recent epidemiologic situation, clinical picture, diagnostics and treatment of tularemia, focusing on the situation in Germany. © Georg Thieme Verlag KG Stuttgart · New York.

  10. Recombinant Marburg Virus Expressing EGFP Allows Rapid Screening of Virus Growth and Real-time Visualization of Virus Spread

    PubMed Central

    Schmidt, Kristina Maria; Schümann, Michael; Olejnik, Judith; Krähling, Verena

    2011-01-01

    The generation of recombinant enhanced green fluorescent protein (EGFP)--expressing viruses has significantly improved the study of their life cycle and opened up the possibility for the rapid screening of antiviral drugs. Here we report rescue of a recombinant Marburg virus (MARV) expressing EGFP from an additional transcription unit (ATU). The ATU was inserted between the second and third genes, encoding VP35 and VP40, respectively. Live-cell imaging was used to follow virus spread in real time. EGFP expression was detected at 32 hours postinfection (hpi), and infection of neighboring cells was monitored at 55 hpi. Compared to the parental virus, production of progeny rMARV-EGFP was reduced 4-fold and lower protein levels of VP40, but not nucleoprotein, were observed, indicating a decrease in downstream protein expression due to the insertion of an ATU. Interestingly, EGFP concentrated in viral inclusions in infected cells. This was reproduced by transient expression of both EGFP and other fluorescent proteins along with filovirus nucleocapsid proteins, and may suggest that a general increase in protein synthesis occurs at viral inclusion sites. In conclusion, the EGFP-expressing MARV will be a useful tool not only to monitor virus spread and screen for antiviral compounds, but also to investigate the biology of inclusion body formation. PMID:21987762

  11. [Evaluation of the Marburg Spelling Training (MRT) in 2nd- and 3rd-grade students with spelling difficulties].

    PubMed

    Barkmann, Claus; Kuhlmann, Ester; Rosenboom, Lea; Wessolowski, Nino; Schulte-Markwort, Michael

    2012-05-01

    Children with severe dyslexia are substantially impaired because reading and writing are key competencies necessary for a successful academic and occupational career. In this evaluation study, a cohort of 2nd- and 3rd-grade students from a variety of Hamburg primary schools was trained with the Marburger Rechtschreibtraining (MRT) by supervised university graduates. The research questions focused on the feasibility of the MRT as a within-school training, the improvement of spelling and reading skills of the participants, subjective assessments of success, as well as potential predictors. Besides established performance tests, we also considered the subjective appraisals of parents, teachers, and coaches. The results demonstrate that standardized spelling training methods like the MRT can be consistently used during morning hours at schools. Within a year of starting MRT exercises, mean effect sizes in writing and reading were observed in performance tests using test norms. However, parent, teacher, and coach reports failed to replicate these improvements. Changes in writing performance were mainly associated with school class level; improvements in reading ability were dependent on initial writing performance. The results provide starting points for optimizing current training practices in elementary schools and for posing questions regarding the effectiveness of the MRT, as well as for training programs in general.

  12. Intracellular transport and processing of the Marburg virus surface protein in vertebrate and insect cells.

    PubMed

    Becker, S; Klenk, H D; Mühlberger, E

    1996-11-01

    The surface protein (GP) of Marburg virus (MBG) is synthesized as a 90-kDa precursor protein which is cotranslationally modified by the addition of high-mannose sugars (140 kDa). This step is followed by the conversion of the N-linked sugars to endoglycosidase H (endo H)-resistant species and the addition of O-linked oliosaccharides leading to a mature protein of 170-200 kDa approximately 30 min after pulse labelling. The mature form of GP is efficiently transported to the plasma membrane. GP synthesized using the T7 polymerase-driven vaccinia virus expression system was transported with essentially the same kinetics as the authentic GP. However, the protein that is shown to appear 30 min after pulse labeling at the plasma membrane was slighly smaller (160 kDa) than GP incorporated into the virions (170 kDa). Using a recombinant baculovirus, GP was expressed at high levels in insect cells. Three different species could be identified: a 90-kDa unglycosylated GP localized in the cytoplasm and two 140-kDa glycosylated proteins. Characterization of the glycosylated GPs revealed that processing of the oligosaccharides of GP was less efficient in insect cells than in mammalian cells. The majority of GP remained endo H sensitive containing high-mannose type N-linked glycans, whereas only a small fraction became endo H resistant carrying processed N-glycans and O-glycans. Tunicamycin treatment of the GP-expressing cells demonstrated that N-glycosylation is essential for the transport of the MBG surface protein.

  13. Temporal development of extreme precipitation in Germany projected by EURO-CORDEX simulations

    NASA Astrophysics Data System (ADS)

    Brendel, Christoph; Deutschländer, Thomas

    2017-04-01

    A sustainable operation of transport infrastructure requires an enhanced resilience to the increasing impacts of climate change and related extreme meteorological events. To meet this challenge, the German Federal Ministry of Transport and Digital Infrastructure (BMVI) commenced a comprehensive national research program on safe and sustainable transport in Germany. A network of departmental research institutes addresses the "Adaptation of the German transport infrastructure towards climate change and extreme events". Various studies already have identified an increase in the average global precipitation for the 20th century. There is some indication that these increases are most visible in a rising frequency of precipitation extremes. However, the changes are highly variable between regions and seasons. With a further increase of atmospheric greenhouse gas concentrations in the 21st century, the likelihood of occurrence of such extreme events will continue to rise. A kernel estimator has been used in order to obtain a robust estimate of the temporal development of extreme precipitation events projected by an ensemble of EURO-CORDEX simulations. The kernel estimator measures the intensity of the poisson point process indicating temporal changes in the frequency of extreme events. Extreme precipitation events were selected using the peaks over threshold (POT) method with the 90th, 95th and 99th quantile of daily precipitation sums as thresholds. Application of this non-parametric approach with relative thresholds renders the use of a bias correction non-mandatory. In addition, in comparison to fitting an extreme value theory (EVT) distribution, the method is completely unsusceptible to outliers. First results show an overall increase of extreme precipitation events for Germany until the end of the 21st century. However, major differences between seasons, quantiles and the three different Representative Concentration Pathways (RCP 2.6, 4.5, and 8.5) have been

  14. Lung Cancer Screening Using Low Dose CT Scanning in Germany. Extrapolation of results from the National Lung Screening Trial.

    PubMed

    Stang, Andreas; Schuler, Martin; Kowall, Bernd; Darwiche, Kaid; Kühl, Hilmar; Jöckel, Karl-Heinz

    2015-09-18

    It is now debated whether the screening of heavy smokers for lung cancer with low dose computed tomography (low dose CT) might lower their mortality due to lung cancer. We use data from the National Lung Screening Trial (NLST) in the USA to predict the likely effects of such screening in Germany. The number of heavy smokers aged 55-74 in Germany was extrapolated from survey data obtained by the Robert Koch Institute. Published data from the NLST were then used to estimate the likely effects of low dose CT screening of heavy smokers in Germany. If low dose CT screening were performed on 50% of the heavy smokers in Germany aged 55-74, an estimated 1 329 506 persons would undergo such screening. If the screening were repeated annually, then, over three years, 916 918 screening CTs would reveal suspect lesions, and the diagnosis of lung cancer would be confirmed thereafter in 32 826 persons. At least one positive test result in three years would be obtained in 39.1% of the participants (519 837 persons). 4155 deaths from lung cancer would be prevented over 6.5 years, and the number of persons aged 55-74 who die of lung cancer in Germany would fall by 2.6%. 12 449 persons would have at least one complication, and 1074 persons would die in the 60 days following screening. The screening of heavy smokers for lung cancer can lower their risk of dying of lung cancer by 20% in relative terms, corresponding to an absolute risk reduction of 0.3 percentage points. These figures can provide the background for a critical discussion of the putative utility of this type of screening in Germany.

  15. [Future supply of tuberculin in Germany].

    PubMed

    Sagebiel, D; Hauer, B; Haas, W; Magdorf, K; Priwitzer, M; Loddenkemper, R

    2005-04-01

    The manufacturers of the only tuberculin available up to now in Germany for intradermal TB tests according to Mantoux, Chiron Vaccines Behring, in 2004 unexpectedly stopped the production of the tuberculin Behring GT (GT="gereinigtes Tuberkulin"-purified protein derivative tuberculin). Only residual stocks were sold during the preceding months. The stocks of GT 10 were already depleted at the beginning of 2005, while there are small supplies left of GT 100 and GT 1000. As a temporary solution, Chiron Vaccines Behring is offering to import the Italian tuberculin Biocine PPD 5 IE lyophil produced by Chiron S.r.l. in Siena. As this is not licensed for sale in Germany, it is necessary to obtain an exceptional prescription (Einzelverordnung) according to section sign 73 (3) of the Federal Law Relating to the Manufacture and Distribution of Medicine (Arzneimittelgesetz, AMG). In the long term, Chiron Vaccines Behring plan to secure the supply of tuberculin in Germany by importing, starting in the summer of 2006, the tuberculin produced by Chiron Vaccines Evans in the UK (PPD Evans). However, these plans involve changing over to a different type of tuberculin twice within a very short period of time. Another problem is the unresolved issue of bioequivalence. Besides the above-mentioned tuberculins produced by Chiron Vaccines, a further possibility would be the import of the tuberculin PPD RT23 SSI of the Statens Serums Institute (Copenhagen/Denmark), which is recommended by the World Health Organization (WHO) as the standard tuberculin and which has already been introduced in several European countries, or of other tuberculins such as Tubersol (PPD CT68), which is used in the US. Together with the Robert Koch Institute (RKI) and the Paul Ehrlich Institute (PEI), the German Central Committee against Tuberculosis (DZK) is striving to find a solution, in view of the urgent need for an uninterrupted supply of tuberculin in Germany for diagnostic purposes and contact tracing

  16. Antibody Responses to Marburg Virus in Egyptian Rousette Bats and Their Role in Protection against Infection.

    PubMed

    Storm, Nadia; Jansen Van Vuren, Petrus; Markotter, Wanda; Paweska, Janusz T

    2018-02-10

    Egyptian rousette bats (ERBs) are reservoir hosts for the Marburg virus (MARV). The immune dynamics and responses to MARV infection in ERBs are poorly understood, and limited information exists on the role of antibodies in protection of ERBs against MARV infection. Here, we determine the duration of maternal immunity to MARV in juvenile ERBs, and evaluate the duration of the antibody response to MARV in bats naturally or experimentally infected with the virus. We further explore whether antibodies in previously naturally exposed bats is fully protective against experimental reinfection with MARV. Maternal immunity was lost in juvenile ERBs by 5 months of age. Antibodies to MARV remained detectable in 67% of experimentally infected bats approximately 4 months post inoculation (p.i.), while antibodies to MARV remained present in 84% of naturally exposed bats at least 11 months after capture. Reinfection of seropositive ERBs with MARV produced an anamnestic response from day 5 p.i. Although PCR-defined viremia was present in 73.3% of reinfected ERBs, replicating virus was recovered from the serum of only one bat on day 3 p.i. The negative PCR results in the salivary glands, intestines, bladders and reproductive tracts of reinfected bats, and the apparent absence of MARV in the majority of swabs collected from these bats suggest that reinfection may only play a minor role in the transmission and maintenance of MARV amongst ERBs in nature.

  17. The Corporate University Landscape in Germany

    ERIC Educational Resources Information Center

    Andresen, Maike; Lichtenberger, Bianka

    2007-01-01

    Purpose: The paper seeks first to present an overview of the corporate university landscape in Germany contrasting it with the US-American corporate university market and, second, to outline the development in Germany during the last 15 years and to have a look at future trends such as learning alliances. Design/methodology/approach: The…

  18. Projections of Trends in Overweight in the Elderly Population in Germany until 2030 and International Comparison

    PubMed Central

    Westphal, Christina; Doblhammer, Gabriele

    2014-01-01

    Background/Aims To project the numbers of pre-obese (BMI 25-29.99 kg/m²) and obese (BMI > 30 kg/m²) men and women aged 50+ in Germany until 2030 and to compare our estimates with actual figures from four European countries and the USA. Estimates are based on six scenarios encompassing improvements as well as worsenings of current trends. Methods We used pooled data from 1999 to 2009 of the German Microcensus (n = 1,472,547). Using multinomial logistic regression models we estimated age-specific probabilities of pre-obesity and obesity and applied them to the 12th population projection of the Federal Statistical Office. Results We project overall increases in absolute numbers of pre-obesity ranging between 14.2 and 18.2 million. However, the prevalence of pre-obesity is likely to decrease slightly. In contrast, absolute and relative numbers of obesity are projected to increase, ranging between 7.2 and 15.8 million. The international comparison revealed that pre-obesity prevalences will remain among the highest in Germany, while obesity is projected to fall below current levels of the UK or the USA. Conclusion Pre-obesity and, particularly, obesity are likely to become a more prominent health issue in Germany in the near future which could have large repercussions for the public health system. PMID:24525549

  19. 26. UPSTREAM VIEW OF DISCHARGE END OF OUTLET STRUCTURE.... Volume ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    26. UPSTREAM VIEW OF DISCHARGE END OF OUTLET STRUCTURE.... Volume XVI, No. 17, September 29, 1939. - Prado Dam, Outlet Works, Santa Ana River near junction of State Highways 71 & 91, Corona, Riverside County, CA

  20. Declining male births in Germany before and after reunification.

    PubMed

    Grech, Victor

    2013-01-01

    Male births occur 3% in excess of female births in mammals in a ratio (M/F) of 0.515. Many factors have been shown to influence this, including socioeconomic deprivation. This paper reviews live birth data for Germany over the period 1946-2009, and identifies secular trends in M/F pre- and post-reunification. The null hypothesis is that there were no differences between East and West Germany, geographically or temporally, before and after reunification. Annual data on male and female live births were obtained from the Human Mortality Database and analyzed with contingency tables. These data were available separately for East and West Germany (1950-1989). There was a significant decline in M/F in both German Republics overall and before reunification (p<0.0001). No decline was present after. Pre-reunification, West Germany had a lower overall M/F than East Germany (p=0.001). In conclusion, a declining M/F has been shown in many countries over the past decades. The two German Republics' M/F fell prior to reunification and the economic collapse of East Germany. Contracting societies that offer poor socioeconomic conditions (such as the communist former East Germany) may result in a decrease in M/F, but this is not reflected in the data, which show that M/F in West Germany prior to reunification was lower than in East Germany. This is not explicable with the contracting economies hypothesis; other and as yet unknown influences may have modified M/F trends anticipated by known variables.

  1. A new focus of Aedes japonicus japonicus (Theobald, 1901) (Diptera, Culicidae) distribution in Western Germany: rapid spread or a further introduction event?

    PubMed Central

    2012-01-01

    Background The Asian bush mosquito, Aedes japonicus japonicus, a potential vector of several viruses, was first detected in Germany in 2008 on the Swiss-German border. In the following years, this invasive species apparently succeeded in establishing populations in southern Germany and in spreading northwards. In 2011, its distribution area already covered large areas of the federal state of Baden-Wurttemberg, and its northernmost German collection point was reported to be close to Stuttgart. Several independent submissions to our laboratories of Ae. j. japonicus specimens in July 2012, originating from the same area in the federal state of North Rhine-Westphalia, western Germany, prompted us to carry out an immediate surveillance in this region in the expectation of finding a further distribution focus of Ae. j. japonicus in Germany. Methods After inspecting the places of residence of the collectors of the submitted mosquito specimens, all kinds of water containers in 123 cemeteries in surrounding towns and villages were checked for mosquito developmental stages. These were collected and kept to produce adults for morphological species identification. One specimen per collection site was identified genetically by COI sequence analysis. Results Aedes j. japonicus adults and immature stages were found in 36 towns/villages that were checked (29%) over an area of approximately 2,000 km2 in southern North Rhine-Westphalia and northern Rhineland Palatinate. The species could not be demonstrated further south when monitoring towards the northernmost previous collection sites in southern Germany. It therefore remains to be elucidated whether the species has entered western Germany from the south, from Belgium in the west where it has been demonstrated to occur locally since 2002, or through a new introduction. Conclusions Aedes j. japonicus is obviously much more widely distributed in Germany than previously thought. It appears to be well adapted, to have a strong

  2. The costs and consequences of obesity in Germany: a new approach from a prevalence and life-cycle perspective.

    PubMed

    Effertz, Tobias; Engel, Susanne; Verheyen, Frank; Linder, Roland

    2016-12-01

    With the steadily growing health burden of obesity in Germany, the measuring and quantification of its costs and relevant economic consequences have become increasingly important. The usual quantifications via previous cost-of-illness approaches mostly have several weaknesses, e.g., applying "indirect methods" by using "population-attributable fractions" to identify parts of costs that can be accrued to obesity, second using highly aggregated data and third often only displaying part of the costs. This article presents a new approach and a new estimation of the cost and consequences of obesity in Germany using claims data from a German health insurance company. A sample of 146,000 individuals was analyzed with both a prevalence and a life-cycle focus on the cost and consequences of obesity. With additional data sets, we calculate the deaths per year due to obesity, the excess costs per year and several intangible consequences usually referred to as "pain and suffering". Our results show that the cost estimations of obesity in Germany so far have been largely underestimated. The annual direct costs of obesity in Germany amount to approximately €29.39 billion and the indirect costs to an additional €33.65 billion. A total of 102,000 subjects die prematurely each year because of obesity, and there is a significant excess of unemployment, long-term nursing care, and pain and suffering due to obesity. From a lifetime perspective, every obese man is equal to an additional burden of €166,911 and each woman of €206,526 for the social security system in Germany. Obesity due to unhealthy eating is thus about to replace tobacco consumption in terms of costs and consequences as the main hazardous lifestyle factor and thus should be more intensively focussed by public health policy.

  3. 48 CFR 252.246-7002 - Warranty of construction (Germany).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... (Germany). 252.246-7002 Section 252.246-7002 Federal Acquisition Regulations System DEFENSE ACQUISITION... of Provisions And Clauses 252.246-7002 Warranty of construction (Germany). As prescribed in 246.710(4), use the following clause: Warranty of Construction (Germany) (JUN 1997) (a) In addition to any other...

  4. 48 CFR 252.246-7002 - Warranty of construction (Germany).

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... (Germany). 252.246-7002 Section 252.246-7002 Federal Acquisition Regulations System DEFENSE ACQUISITION... of Provisions And Clauses 252.246-7002 Warranty of construction (Germany). As prescribed in 246.710(4), use the following clause: Warranty of Construction (Germany) (JUN 1997) (a) In addition to any other...

  5. 48 CFR 252.246-7002 - Warranty of construction (Germany).

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... (Germany). 252.246-7002 Section 252.246-7002 Federal Acquisition Regulations System DEFENSE ACQUISITION... of Provisions And Clauses 252.246-7002 Warranty of construction (Germany). As prescribed in 246.710(4), use the following clause: Warranty of Construction (Germany) (JUN 1997) (a) In addition to any other...

  6. 48 CFR 252.246-7002 - Warranty of construction (Germany).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... (Germany). 252.246-7002 Section 252.246-7002 Federal Acquisition Regulations System DEFENSE ACQUISITION... of Provisions And Clauses 252.246-7002 Warranty of construction (Germany). As prescribed in 246.710(2), use the following clause: Warranty of Construction (Germany) (JUN 1997) (a) In addition to any other...

  7. 48 CFR 252.246-7002 - Warranty of construction (Germany).

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... (Germany). 252.246-7002 Section 252.246-7002 Federal Acquisition Regulations System DEFENSE ACQUISITION... of Provisions And Clauses 252.246-7002 Warranty of construction (Germany). As prescribed in 246.710(4), use the following clause: Warranty of Construction (Germany) (JUN 1997) (a) In addition to any other...

  8. 29. INTERIOR VIEW TO THE NORTHEAST OF CONTROL PANEL AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    29. INTERIOR VIEW TO THE NORTHEAST OF CONTROL PANEL AND VIEWING WINDOW IN ROOM 105, THE CONTROL ROOM. - Nevada Test Site, Pluto Facility, Disassembly Building, Area 26, Wahmonie Flats, Cane Spring Road, Mercury, Nye County, NV

  9. The Definition of Vocational Diplomas in Germany and France.

    ERIC Educational Resources Information Center

    Mobus, Martine; Verdier, Eric

    1997-01-01

    In both France and Germany, the government, employers' organizations, and unions all participate in defining vocational diplomas based on a national framework of procedures of elaborating and standardizing titles. Important differences between the diploma definition processes in France and Germany may be identified. In Germany, the issue is…

  10. Warm-season severe wind events in Germany

    NASA Astrophysics Data System (ADS)

    Gatzen, Christoph

    2013-04-01

    A 15-year data set of wind measurements was analyzed with regard to warm season severe wind gusts in Germany. For April to September of the years 1997 to 2011, 1035 wind measurements of 26 m/s or greater were found. These wind reports were associated with 268 wind events. In total, 252 convective wind events contributed to 837 (81%) of the wind reports, 16 non-convective synoptic-scale wind events contributed to 198 reports (19%). Severe wind events were found with synoptic situations characterized by rather strong mid-level flow and advancing mid-level troughs. Severe convective wind events were analyzed using radar images and classified with respect to the observed radar structure. The most important convective mode was squall lines that were associated with one third of all severe wind gusts, followed by groups, bow echo complexes, and bow echoes. Supercells and cells were not associated with many wind reports. The low contribution of isolated cells indicates that rather large-scale forcing by synoptic-scale features like fronts is important for German severe wind events. Bow echoes were found to be present for 58% of all wind reports. The movement speed of bow echoes indicated a large variation with a maximum speed of 33 m/s. Extreme wind events as well as events with more than 15 wind reports were found to be related to higher movement speeds. Concentrating on the most intense events, derechos seem to be very important to the warm season wind threat in Germany. Convective events with a path length of more than 400 km contributed to 36% of all warm-season wind gusts in this data set. Furthermore, eight of nine extreme gusts exceeding 40 m/s were recorded with derecho events.

  11. Privacy Laws and Biobanking in Germany.

    PubMed

    Hoppe, Nils

    2016-03-01

    While the possibility of enacting a sui generis Biobank Act has been debated in Germany at great length, as of yet the country has not implemented any biobankspecific legislation. Instead, oversight is available via a network of research and privacy laws, including those of the European Union. The Nationale Kohorte, Germany's large-scale, population-based epidemiological research biobank, is funded by the Federal Ministry of Education and Research, and there are currently 108 registered bio-banks throughout Germany. The current system, including the structure and study design of the Nationale Kohorte, privileges the protection of personal information even at the cost of socially desirable research; it remains to be seen if forthcoming legislation will shift this balance. © 2016 American Society of Law, Medicine & Ethics.

  12. ANTIFERROMAGNETIC SPIN RESONANCE OF COBR2.6H20,

    DTIC Science & Technology

    Electron spin resonance experiments were carried out on single crystals of CoBr2.6H20 at temperatures from 1.2 to 4.2K, using a microwave transmission spectrometer over a range of frequencies from 29 to 59 kMc .

  13. Delayed Time-to-Treatment of an Antisense Morpholino Oligomer Is Effective against Lethal Marburg Virus Infection in Cynomolgus Macaques.

    PubMed

    Warren, Travis K; Whitehouse, Chris A; Wells, Jay; Welch, Lisa; Charleston, Jay S; Heald, Alison; Nichols, Donald K; Mattix, Marc E; Palacios, Gustavo; Kugleman, Jeffrey R; Iversen, Patrick L; Bavari, Sina

    2016-02-01

    Marburg virus (MARV) is an Ebola-like virus in the family Filovirdae that causes sporadic outbreaks of severe hemorrhagic fever with a case fatality rate as high as 90%. AVI-7288, a positively charged antisense phosphorodiamidate morpholino oligomer (PMOplus) targeting the viral nucleoprotein gene, was evaluated as a potential therapeutic intervention for MARV infection following delayed treatment of 1, 24, 48, and 96 h post-infection (PI) in a nonhuman primate lethal challenge model. A total of 30 cynomolgus macaques were divided into 5 groups of 6 and infected with 1,830 plaque forming units of MARV subcutaneously. AVI-7288 was administered by bolus infusion daily for 14 days at 15 mg/kg body weight. Survival was the primary endpoint of the study. While none (0 of 6) of the saline group survived, 83-100% of infected monkeys survived when treatment was initiated 1, 24, 48, or 96 h post-infection (PI). The antisense treatment also reduced serum viremia and inflammatory cytokines in all treatment groups compared to vehicle controls. The antibody immune response to virus was preserved and tissue viral antigen was cleared in AVI-7288 treated animals. These data show that AVI-7288 protects NHPs against an otherwise lethal MARV infection when treatment is initiated up to 96 h PI.

  14. Education in Germany: A Bibliography of English Language Publications.

    ERIC Educational Resources Information Center

    Max-Planck-Institut fuer Bildungsforschung, Berlin (West Germany).

    This bibliography cites bibliographies, journals, books, essays, journal articles, and monographs on education in Germany. All publications cited are in English. The three major sections of the bibliography are education in Germany up to 1945, education in the Federal Republic of Germany, and education in the German Democratic Republic. Topics…

  15. Eradication of bovine viral diarrhea virus in Germany-Diversity of subtypes and detection of live-vaccine viruses.

    PubMed

    Wernike, Kerstin; Schirrmeier, Horst; Strebelow, Heinz-Günter; Beer, Martin

    2017-09-01

    Bovine viral diarrhea (BVD) causes high economic losses in the cattle population worldwide. In Germany, an obligatory control program with detection and removal of persistently infected animals is in force since 2011. For molecular tracing of virus transmission, a comprehensive sequence data base of the currently circulating BVD viruses was established. Partial sequences of 1007 samples collected between 2008 and 2016 were generated. As dominant viruses, subtypes 1b (47.0%) and 1d (26.5%) could be identified with no marked geographic or sampling year effect, a much higher amount of BVDV-2c was detected in 2013 compared to other years, predominantly in Western Germany. In addition, subtypes 1a, 1e, 1f, 1h, 1g, 1k, and 2a were found. Interestingly, besides field-viruses, two different live-vaccine viruses were detected in tissue samples of newborn calves (n=37) whose mothers were immunized during pregnancy. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Is Germany a model for managers?

    PubMed

    Wever, K S; Allen, C S

    1992-01-01

    Most American managers have a hard time making sense of Germany. The country has a fraction of the resources and less than one-third the population of the United States. Labor costs are substantially higher, paid vacations are at least three times as long, and strong unions are deeply involved at all levels of business, from the local plant to the corporate boardroom. Yet German companies manage to produce internationally competitive products in key manufacturing sectors, making Germany the greatest competitive threat to the United States after Japan. The seemingly paradoxical nature of the German economy typically evokes one of two diametrically opposed responses. The first is to celebrate the German economy as a "model" worth emulating--indeed, as the answer to declining U.S. competitiveness. The alternative, more skeptical response is to question Germany's staying power in a new, more competitive global economy. According to Kirsten Wever and Christopher Allen, the problem with both points of view is that they miss the forest for the trees. Observers are so preoccupied with praising--or blaming--individual components of the German economy that they fail to see the dynamic logic that ties these components together into a coherent system. In their review of recent research on the German business system, Wever and Allen argue that managers can learn an important lesson from Germany. In the global economy, competition isn't just between companies but between entire socioeconomic systems. Germany's ability to design a cohesive economic and social system that adapts continuously to changing requirements goes a long way toward explaining that country's competitive success.

  17. [Hepatitis A immunity in refugees in Germany during the current exodus].

    PubMed

    Jablonka, A; Solbach, P; Happle, C; Hampel, A; Schmidt, R E; Behrens, G M N

    2017-05-01

    Germany is facing a huge humanitarian challenge with rapidly rising numbers of refugees entering the country. Data on hepatitis A seroprevalence and infection in refugees and asylum seekers in Europe during the current refugee exodus is scarce. To assess hepatitis A (HAV) seroprevalence and immunity in refugees arriving in northern Germany in 2015. A cross-sectional study of 235 refugees seeking shelter in reception centers in Northern Germany in August 2015 was performed, as acute Hepatitis A had been detected in one refugee in this camp. In order to analyze acute HAV infection and overall immunity, serological screening for HAV antibodies (combined IgG and IgM) was performed. The immunity threshold was defined as <20 IU/l. In all positive screening results, separate IgM testing was performed to detect acute infections. Males accounted for 84.3 % of HAV screened refugees and the mean age of refugees was 29.1 ± 11.2 years. Children and adolescents below the age of 18 years made up 8.8 % of the migrants. Overall HAV immunity within the cohort was 90 %, and a mild age-dependent increase in HAV immunity was observed, with 81.1 % immunity in children <18 years and a 100 % seropositivity in subjects >50 years. One 20-year-old female refugee had positive IgM results with high HAV antibodies, most likely due to subacute HAV infection. This comparably high rate of HAV protected refugees in our cohort supports the notion that the probability of large HAV outbreaks in current German refugee centers is low. However, depending on their current living situation, HAV vaccination should be considered for each refugee child, and healthcare providers and personnel working in refugee centers should be vaccinated against HAV.

  18. Antibiotic prescribing behavior among general practitioners - a questionnaire-based study in Germany.

    PubMed

    Salm, Florian; Schneider, Sandra; Schmücker, Katja; Petruschke, Inga; Kramer, Tobias S; Hanke, Regina; Schröder, Christin; Heintze, Christoph; Schwantes, Ulrich; Gastmeier, Petra; Gensichen, Jochen

    2018-05-04

    This study investigates the barriers and facilitators of the use of antibiotics in acute respiratory tract infections by general practitioners (GPs) in Germany. A multidisciplinary team designed and pre-tested a written questionnaire addressing the topics awareness of antimicrobial resistance (7 items), use of antibiotics (9 items), guidelines/sources of information (9 items) and sociodemographic factors (7 items), using a five-point-Likert-scale ("never" to "very often"). The questionnaire was mailed by postally to 987 GPs with registered practices in eastern Germany in May 2015. 34% (340/987) of the GPs responded to this survey. Most of the participants assumed a multifactorial origin for the rise of multidrug resistant organisms. In addition, 70.2% (239/340) believed that their own prescribing behavior influenced the drug-resistance situation in their area. GPs with longer work experience (> 25 years) assumed less individual influence on drug resistance than their colleagues with less than 7 years experience as practicing physicians (Odds Ratio [OR] 0.32, 95% Confidence Interval [CI] 0.17-0.62; P < 0.001). 99.1% (337/340) of participants were familiar with the "delayed prescription" strategy to reduce antibiotic prescriptions. However, only 29.4% (74/340) answered that they apply it "often" or "very often". GPs working in rural areas were less likely than those working in urban areas to apply delayed prescription. The knowledge on factors causing antimicrobial resistance in bacteria is good among GPs in eastern Germany. However measures to improve rational prescription are not widely implemented yet. Further efforts have to be made in order to improve rational prescription of antibiotic among GPs. Nevertheless, there is a strong awareness of antimicrobial resistance among the participating GPs.

  19. Poverty, health, and nutrition in Germany.

    PubMed

    Helmert, U; Mielck, A; Shea, S

    1997-01-01

    To investigate the relation between poverty and several variables describing health and nutrition behavior in East Germany and West Germany. Data are from the third National Health Survey in West Germany and the first Health Survey for the new federal states of Germany (1991/92). Both health surveys included a self-administered questionnaire ascertaining sociodemographic variables, smoking history, nutritional behavior (using a food-frequency list), physical activity, and a medical examination comprising measurements of height, weight, blood pressure, and blood sampling for serum cholesterol determination. Participants included 4958 subjects in the West Survey and 2186 subjects in the East Survey aged 25-69 years, with a respective net response rate of 69.0% and 70.2%. Poverty was defined as a household equivalence income of 62.5% or less of the median income of the general population. The lowest income group (poverty or near poverty) comprised 11.6% of East German versus 15.9% of West German males and 14.8% of East German versus 19.3% of West German females. For most but not all health and nutrition parameters, less favorable results were obtained for subjects with an equivalence income below or near poverty. The most striking poverty-related differences regarding cardiovascular disease risk factors were found for lack of regular exercise for both genders and obesity in females. No poverty-related differences were found for the prevalence of hypercholesterolemia, despite a much higher prevalence of obesity in persons with an income below the poverty line. Current nutritional behavior and changes in nutritional behavior during the last three years was strongly related to income status, with a more unhealthy status for low-income population groups in both East and West Germany. In Germany, poverty has strong effects on individual health status and nutritional behavior. Because of rising unemployment rates and reductions in social security payments for low

  20. Chaperone-Mediated Autophagy Protein BAG3 Negatively Regulates Ebola and Marburg VP40-Mediated Egress

    PubMed Central

    Liang, Jingjing; Sagum, Cari A.; Bedford, Mark T.; Sudol, Marius; Han, Ziying

    2017-01-01

    Ebola (EBOV) and Marburg (MARV) viruses are members of the Filoviridae family which cause outbreaks of hemorrhagic fever. The filovirus VP40 matrix protein is essential for virus assembly and budding, and its PPxY L-domain motif interacts with WW-domains of specific host proteins, such as Nedd4 and ITCH, to facilitate the late stage of virus-cell separation. To identify additional WW-domain-bearing host proteins that interact with VP40, we used an EBOV PPxY-containing peptide to screen an array of 115 mammalian WW-domain-bearing proteins. Using this unbiased approach, we identified BCL2 Associated Athanogene 3 (BAG3), a member of the BAG family of molecular chaperone proteins, as a specific VP40 PPxY interactor. Here, we demonstrate that the WW-domain of BAG3 interacts with the PPxY motif of both EBOV and MARV VP40 and, unexpectedly, inhibits budding of both eVP40 and mVP40 virus-like particles (VLPs), as well as infectious VSV-EBOV recombinants. BAG3 is a stress induced protein that regulates cellular protein homeostasis and cell survival through chaperone-mediated autophagy (CMA). Interestingly, our results show that BAG3 alters the intracellular localization of VP40 by sequestering VP40 away from the plasma membrane. As BAG3 is the first WW-domain interactor identified that negatively regulates budding of VP40 VLPs and infectious virus, we propose that the chaperone-mediated autophagy function of BAG3 represents a specific host defense strategy to counteract the function of VP40 in promoting efficient egress and spread of virus particles. PMID:28076420

  1. Chaperone-Mediated Autophagy Protein BAG3 Negatively Regulates Ebola and Marburg VP40-Mediated Egress.

    PubMed

    Liang, Jingjing; Sagum, Cari A; Bedford, Mark T; Sidhu, Sachdev S; Sudol, Marius; Han, Ziying; Harty, Ronald N

    2017-01-01

    Ebola (EBOV) and Marburg (MARV) viruses are members of the Filoviridae family which cause outbreaks of hemorrhagic fever. The filovirus VP40 matrix protein is essential for virus assembly and budding, and its PPxY L-domain motif interacts with WW-domains of specific host proteins, such as Nedd4 and ITCH, to facilitate the late stage of virus-cell separation. To identify additional WW-domain-bearing host proteins that interact with VP40, we used an EBOV PPxY-containing peptide to screen an array of 115 mammalian WW-domain-bearing proteins. Using this unbiased approach, we identified BCL2 Associated Athanogene 3 (BAG3), a member of the BAG family of molecular chaperone proteins, as a specific VP40 PPxY interactor. Here, we demonstrate that the WW-domain of BAG3 interacts with the PPxY motif of both EBOV and MARV VP40 and, unexpectedly, inhibits budding of both eVP40 and mVP40 virus-like particles (VLPs), as well as infectious VSV-EBOV recombinants. BAG3 is a stress induced protein that regulates cellular protein homeostasis and cell survival through chaperone-mediated autophagy (CMA). Interestingly, our results show that BAG3 alters the intracellular localization of VP40 by sequestering VP40 away from the plasma membrane. As BAG3 is the first WW-domain interactor identified that negatively regulates budding of VP40 VLPs and infectious virus, we propose that the chaperone-mediated autophagy function of BAG3 represents a specific host defense strategy to counteract the function of VP40 in promoting efficient egress and spread of virus particles.

  2. Costs and cost-driving factors for acute treatment of adults with status epilepticus: A multicenter cohort study from Germany.

    PubMed

    Kortland, Lena-Marie; Alfter, Anne; Bähr, Oliver; Carl, Barbara; Dodel, Richard; Freiman, Thomas M; Hubert, Kristina; Jahnke, Kolja; Knake, Susanne; von Podewils, Felix; Reese, Jens-Peter; Runge, Uwe; Senft, Christian; Steinmetz, Helmuth; Rosenow, Felix; Strzelczyk, Adam

    2016-12-01

    To provide first data on inpatient costs and cost-driving factors due to nonrefractory status epilepticus (NSE), refractory status epilepticus (RSE), and super-refractory status epilepticus (SRSE). In 2013 and 2014, all adult patients treated due to status epilepticus (SE) at the university hospitals in Frankfurt, Greifswald, and Marburg were analyzed for healthcare utilization. We evaluated 341 admissions in 316 patients (65.7 ± [standard deviation]18.2 years; 135 male) treated for SE. Mean costs of hospital treatment were €14,946 (median €5,278, range €776-€152,911, €787 per treatment day) per patient per admission, with a mean length of stay (LOS) of 19.0 days (median 14.0, range 1-118). Course of SE had a significant impact on mean costs, with €8,314 in NSE (n = 137, median €4,597, €687 per treatment day, 22.3% of total inpatient costs due to SE), €13,399 in RSE (n = 171, median €7,203, €638/day, 45.0% of total costs, p < 0.001), and €50,488 in SRSE (n = 33, median €46,223, €1,365/day, 32.7% of total costs, p < 0.001). Independent cost-driving factors were SRSE, ventilation, and LOS of >14 days. Overall mortality at discharge was 14.4% and significantly higher in RSE/SRSE (20.1%) than in NSE (5.8%). Acute treatment of SE, and particularly SRSE and ventilation, are associated with high hospital costs and prolonged LOS. Extrapolation to the whole of Germany indicates that SE causes hospital costs of >€200 million per year. Along with the demographic change, incidence of SE will increase and costs for hospital treatment and sequelae of SE will rise. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

  3. 29 CFR 776.26 - Relationship of the construction work to the covered facility.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... OF 1938 Construction Industry Individual Employee Coverage in the Construction Industry § 776.26... commerce or the engagement in commerce. For this reason the erection, maintenance or repair of dwellings...

  4. 29 CFR 776.26 - Relationship of the construction work to the covered facility.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... OF 1938 Construction Industry Individual Employee Coverage in the Construction Industry § 776.26... commerce or the engagement in commerce. For this reason the erection, maintenance or repair of dwellings...

  5. Science Across Borders: 5th Annual Natural Health Product Research Conference—March 2629, 2008, Toronto, Canada

    PubMed Central

    2010-01-01

    Canada is experiencing a growing interest in the use of alternative therapies and products particularly natural health products (NHP). In 1997, Canadians spent around C$ 2 billion on NHP. In an attempt to catch with this popularity of NHP use, Canadian researchers and administrators from academia, industry and government jointly established the Natural Health Product Research Society of Canada (NHPRS). Since its formation, NHPRS has been organizing an annual meeting which brings together world renowned researchers and experts in the area of NHP research. For 2008, the annual NHPRS meeting took place in Toronto from the 26th to 29th of March with a focus on ‘Science Across Borders: Global Natural Health Products Research’. The scientific program was spread into three days of plenary lectures and oral presentations. The different sessions containing these talks were on: ethnobotany around the world; chemical analysis of NHP; product standards and quality control; ethnomedicine; novel analytical approaches; systemic research, nutrisciences and molecular medicine; and drug development from NHP. The meeting proved to be a great success in terms of the speakers that were invited and based on the data that was presented which highlighted recent research taking place in the field of NHP not only in Canada but from many parts of the world. PMID:18955362

  6. Amino Acid Residue at Position 79 of Marburg Virus VP40 Confers Interferon Antagonism in Mouse Cells.

    PubMed

    Feagins, Alicia R; Basler, Christopher F

    2015-10-01

    Marburg viruses (MARVs) cause highly lethal infections in humans and nonhuman primates. Mice are not generally susceptible to MARV infection; however, if the strain is first adapted to mice through serial passaging, it becomes able to cause disease in this animal. A previous study correlated changes accrued during mouse adaptation in the VP40 gene of a MARV strain known as Ravn virus (RAVV) with an increased capacity to inhibit interferon (IFN) signaling in mouse cell lines. The MARV strain Ci67, which belongs to a different phylogenetic clade than RAVV, has also been adapted to mice and in the process the Ci67 VP40 acquired a different collection of genetic changes than did RAVV VP40. Here, we demonstrate that the mouse-adapted Ci67 VP40 more potently antagonizes IFN-α/β-induced STAT1 and STAT2 tyrosine phosphorylation, gene expression, and antiviral activity in both mouse and human cell lines, compared with the parental Ci67 VP40. Ci67 VP40 is also demonstrated to target the activation of kinase Jak1. A single change at VP40 residue 79 was found to be sufficient for the increased VP40 IFN antagonism. These data argue that VP40 IFN-antagonist activity plays a key role in MARV pathogenesis in mice. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Silencing the Singer. Antibioethics in Germany.

    PubMed

    Schöne-Seifert, B; Rippe, K P

    1991-01-01

    "Die Gedanken sind frei," in the words of the old song. But in Germany, thoughts are no longer free. Peter Singer, the "death ethicist," has become a special target for activists attempting to silence bioethical debate in Germany. In the context of the trauma inflicted by National Socialism, a profound unease over issues at the end of life is accompanied by an insistence that these issues are not to be discussed.

  8. Forensic hydro-meteorological analysis of an extreme flash flood: The 2016-05-29 event in Braunsbach, SW Germany.

    PubMed

    Bronstert, Axel; Agarwal, Ankit; Boessenkool, Berry; Crisologo, Irene; Fischer, Madlen; Heistermann, Maik; Köhn-Reich, Lisei; López-Tarazón, José Andrés; Moran, Thomas; Ozturk, Ugur; Reinhardt-Imjela, Christian; Wendi, Dadiyorto

    2018-07-15

    The flash-flood in Braunsbach in the north-eastern part of Baden-Wuerttemberg/Germany was a particularly strong and concise event which took place during the floods in southern Germany at the end of May/early June 2016. This article presents a detailed analysis of the hydro-meteorological forcing and the hydrological consequences of this event. A specific approach, the "forensic hydrological analysis" was followed in order to include and combine retrospectively a variety of data from different disciplines. Such an approach investigates the origins, mechanisms and course of such natural events if possible in a "near real time" mode, in order to follow the most recent traces of the event. The results show that it was a very rare rainfall event with extreme intensities which, in combination with catchment properties, led to extreme runoff plus severe geomorphological hazards, i.e. great debris flows, which together resulted in immense damage in this small rural town Braunsbach. It was definitely a record-breaking event and greatly exceeded existing design guidelines for extreme flood discharge for this region, i.e. by a factor of about 10. Being such a rare or even unique event, it is not reliably feasible to put it into a crisp probabilistic context. However, one can conclude that a return period clearly above 100years can be assigned for all event components: rainfall, peak discharge and sediment transport. Due to the complex and interacting processes, no single flood cause or reason for the very high damage can be identified, since only the interplay and the cascading characteristics of those led to such an event. The roles of different human activities on the origin and/or intensification of such an extreme event are finally discussed. Copyright © 2018. Published by Elsevier B.V.

  9. [Private medical education in Germany].

    PubMed

    Schwörer, Beatrix; Wissing, Frank

    2018-02-01

    Through the years, a range of privately funded medical training opportunities has been established in Germany. Only a few of them operate along the German Medical Licensure Act and thus underlie quality assurance regulations in Germany. Most of the courses are a result of German hospitals cooperating with universities from other EU countries. The content of the courses and the examinations underlie the regulations of the university's home country. This article aims to give an overview of the private medical training opportunities offered in Germany and to show differences compared to state funded German medical schools. The authors discuss the opportunities of private medical training as well as its challenges and risks. Basic principles concerning finances and quality assurance of national and international private medical training are provided. Regardless of their mode of financing, the superior goal of the training, according to the German Medical Licensure Act, should always be to enable young doctors to pursue further professional training, so that they can maintain the best possible quality in patient care, research, and medical education.

  10. Germany since 1945: A Focus on Berlin.

    ERIC Educational Resources Information Center

    Blankenship, Glen; Smith, Lindsey

    This lesson accompanies a videotape which examines some of the forces, personalities and events which shaped Berlin and the rest of Germany between 1945 and 1994. The lesson is introduced by using the videotape and uses references from the videotape for further classroom work. Worksheets for student use include "Events in Germany,…

  11. Taxing sugar-sweetened beverages: impact on overweight and obesity in Germany.

    PubMed

    Schwendicke, Falk; Stolpe, Michael

    2017-01-17

    Consumption of sugar-sweetened beverages (SSBs) increases the risk of overweight and obesity. Taxing SSBs could decrease daily energy consumption and body weight. This model-based study evaluated the impact of a 20% SSB-sales tax on overweight and obesity in the context of Germany. The population aged 15-79 years was modelled. Taxation was assumed to affect energy consumption via demand elasticities, which affected weight and BMI. Model-based analysis was performed to estimate the tax impact on BMI in different age, gender and income groups. Implementing a 20% SSB tax reduced energy consumption mainly in younger age groups, males, and those with low income. Taxation decreased the mean BMI in younger groups, with the largest decrease in those aged 20-29 years, while effects in groups 60 years or above were minimal. In absolute terms, taxation was estimated to avoid 1,028,000 (-3% relative reduction) overweight individuals and 479,000 obese individuals (-4%). Overweight decreased the most in males aged 20-29 years (408,000 fewer cases /-22%), the same applied for obesity (204,000/-22%). An SSB tax could have significant impact on overweight and obesity, which could translate into substantial reductions of morbidity and mortality.

  12. Federal Republic of Germany.

    PubMed

    1987-05-01

    The population of the Federal Republic of Germany (FRG) was an estimated 61 million (including West Berlin) in 1986 and is in the process of declining gradually as a result of low birth rates. The infant mortality rate is 11/1000, while life expectancy is 73.4 years for women and 67.2 years for men. Of the work force of 27.6 million, 5.4% are engaged in agriculture, 41.6% work in industry and commerce, 10% are employed by the government, and 42.7% are in the service sector. The gross national product was US$898.8 billion in 1986, with an annual growth rate of 2.6% and a per capita income of $10,680. The government is parliamentary and based on a democratic constitution emphasizing protection of individual liberty and divided power in a federal structure. Political life since the establishment of the FRG in 1949 has been characterized by remarkable stability and orderly succession. The FRG ranks among the most important economic powers in the world. The economy is largely export oriented, with 25-30% of the gross national product shipped abroad each year. Competition and free enterprise are fostered, but the state participates in the ownership and management of major sections of the economy, including public services. A major concern at present is the country's ability to adapt to new markets and to develop sophisticated technologies.

  13. Regional measurements of infrasound signals from ARIANE-5 engine tests in Southern Germany

    NASA Astrophysics Data System (ADS)

    Koch, K.

    2012-04-01

    A well-controlled source of repetitive infrasound emissions was previously identified and has been related to development and acceptance tests of the European Space Agencies ARIANE-5 main engine. The propulsion testing facility of the German Aerospace Agency (DLR) near Heilbronn, Southern Germany, is a distance of about 320 km away from the International Monitoring System (IMS) station IS26 in east-southeasterly direction. In the past, signals associated with these propulsion tests could normally be detected at IS26 during winter months, but not during summer months, reflecting the changes in atmospheric conditions between winter and summer. Over the last year, DLR has prepared to conduct a series of seven propulsion tests which started in November 2011; with interim times between tests of 3-4 weeks it will last until late March or early April 2012. With mobile infrasound recording equipment available at BGR we planned to record the infrasonic wavefield along the path to IS26 at regular distances starting as close as 20 km from the source. Our aim is to study sound propagation from direct paths mainly involving the tropospheric layer through the "zone of silence" to distances close to IS26, where paths through stratospheric layers are followed. Preliminary results show that during the relevant winter season direct path propagation can be observed to some 40 km from the propulsion test source, even at seismographic stations where the acoustic wave couples into the ground. The tests are also observed at IS26, and waveform duration and f-k-analysis confirm the signals to be associated with the GT-type propulsion tests.

  14. Socioeconomic deprivation and cancer survival in Germany: an ecological analysis in 200 districts in Germany.

    PubMed

    Jansen, Lina; Eberle, Andrea; Emrich, Katharina; Gondos, Adam; Holleczek, Bernd; Kajüter, Hiltraud; Maier, Werner; Nennecke, Alice; Pritzkuleit, Ron; Brenner, Hermann

    2014-06-15

    Although socioeconomic inequalities in cancer survival have been demonstrated both within and between countries, evidence on the variation of the inequalities over time past diagnosis is sparse. Furthermore, no comprehensive analysis of socioeconomic differences in cancer survival in Germany has been conducted. Therefore, we analyzed variations in cancer survival for patients diagnosed with one of the 25 most common cancer sites in 1997-2006 in ten population-based cancer registries in Germany (covering 32 million inhabitants). Patients were assigned a socioeconomic status according to the district of residence at diagnosis. Period analysis was used to derive 3-month, 5-year and conditional 1-year and 5-year age-standardized relative survival for 2002-2006 for each deprivation quintile in Germany. Relative survival of patients living in the most deprived district was compared to survival of patients living in all other districts by model-based period analysis. For 21 of 25 cancer sites, 5-year relative survival was lower in the most deprived districts than in all other districts combined. The median relative excess risk of death over the 25 cancer sites decreased from 1.24 in the first 3 months to 1.16 in the following 9 months to 1.08 in the following 4 years. Inequalities persisted after adjustment for stage. These major regional socioeconomic inequalities indicate a potential for improving cancer care and survival in Germany. Studies on individual-level patient data with access to treatment information should be conducted to examine the reasons for these socioeconomic inequalities in cancer survival in more detail. © 2013 UICC.

  15. ANALYTICAL CHEMISTRY IN NUCLEAR REACTOR TECHNOLOGY. Analysis of Reactor Fuels, Fission-Product Mixtures and Related Materials: Analytical Chemistry of Plutonium and the Transplutonic Elements. Third Conference, Gatlinburg, Tennessee, October 26-29, 1959

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

    None

    1960-01-01

    Thirty-one papers and 10 summaries of papers presented at the Third Conference on Analytical Chemistry in Nuclear Reactor Technology held at Gatlinburg, Tennessee, October 26 to 29, 1959, are given. The papers are grouped into four sections: general, analytical chemistry of fuels, analytical chemistry of plutonium and the transplutonic elements, and the analysis of fission-product mixtures. Twenty-seven of the papers are covered by separate abstracts. Four were previously abstracted for NSA. (M.C.G.)

  16. 26 CFR 1.410(a)-7 - Elapsed time.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 5 2014-04-01 2014-04-01 false Elapsed time. 1.410(a)-7 Section 1.410(a)-7...) INCOME TAXES (CONTINUED) Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.410(a)-7 Elapsed time. (a) In general—(1) Introduction to elapsed time method of crediting service. (i) 29 CFR 2530.200b-2 sets...

  17. 26 CFR 1.410(a)-7 - Elapsed time.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 5 2013-04-01 2013-04-01 false Elapsed time. 1.410(a)-7 Section 1.410(a)-7...) INCOME TAXES (CONTINUED) Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.410(a)-7 Elapsed time. (a) In general—(1) Introduction to elapsed time method of crediting service. (i) 29 CFR 2530.200b-2 sets...

  18. Transmission risk of Borrelia burgdorferi sensu lato from Ixodes ricinus ticks to humans in southwest Germany.

    PubMed Central

    Maiwald, M.; Oehme, R.; March, O.; Petney, T. N.; Kimmig, P.; Naser, K.; Zappe, H. A.; Hassler, D.; von Knebel Doeberitz, M.

    1998-01-01

    The risk of Borrelia burgdorferi infection and the value of antibiotic prophylaxis after tick bite are controversial. In this study, performed in two areas of southwestern Germany, ticks were collected from 730 patients and examined by the polymerase chain reaction (PCR) for B. burgdorferi. To assess whether transmission of B. burgdorferi occurred, the patients were clinically and serologically examined after tick removal and during follow-up examinations. Data from all tick bites gave a total transmission rate of 2.6% (19 patients). Eighty-four ticks (11.3%) were PCR positive. Transmission occurred to 16 (26.7%) of 60 patients who were initially seronegative and could be followed up after the bite of an infected tick. These results indicate that the transmission rate from infected ticks in Europe is higher than previously assumed. Examination of ticks and antibiotic prophylaxis in the case of positivity appears to be indicated. PMID:9747761

  19. 40 CFR 455.26 - Pretreatment standards for existing sources (PSES).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Pretreatment standards for existing...) EFFLUENT GUIDELINES AND STANDARDS PESTICIDE CHEMICALS Organic Pesticide Chemicals Manufacturing Subcategory § 455.26 Pretreatment standards for existing sources (PSES). Except as provided in 40 CFR 403.7, any...

  20. [Prescribing valproate to girls and women of childbearing age in Germany : Analysis of trends based on claims data].

    PubMed

    Wentzell, Nadine; Haug, Ulrike; Schink, Tania; Engel, Susanne; Liebentraut, Judith; Linder, Roland; Onken, Marlies; Schaefer, Christof; Dathe, Katarina

    2018-06-19

    Measures to raise awareness of the teratogenic potential of valproate and restrict its use in girls/women of childbearing age have been intensified. For Germany, the impact of these measures on valproate prescription rates remains unknown. Trends in prescribing valproate, the underlying treatment indication, and the specialty of the prescribing physician are analyzed. With claims data from several statutory health insurance providers from 2004 to 2016 (approximately 3.5 million insured persons per year) considering treatment indication and medical specialties of prescribing physicians, we assessed the rate of girls/women (12 to 50 years) with at least one valproate dispensation per year. The age-standardized rate of girls/women with at least one valproate dispensation declined by 28% between 2004 and 2016 (2.91/1000 vs. 2.09/1000). For 2015, the indications were epilepsy (66.9%), bipolar disorder (13.6%), migraine/headache (5.6%), schizoaffective disorder (4.3%), and other mental disorders (8.9%). Among epilepsy patients, the proportion treated with valproate declined from 26.2 to 16.8%, but changed little in patients with bipolar disorder (9.3% vs. 8.0%). A total of 46.3% of valproate dispensations were issued by neurologists or psychiatrists and 29.6% by general practitioners, internal medicine specialists, or family doctors. Based on German claims data, a decline of valproate dispensations was shown for epilepsy patients of childbearing age, while the proportion in other indications has hardly changed since 2004.

  1. Adverse events in vaccinations for travelers - a 1-year prospective survey in a travel clinic in Germany.

    PubMed

    Slesak, Günther; Fleck, Ralf; Scherbaum, Helmut; Blumenstock, Gunnar; Schäfer, Johannes

    2018-01-01

    The study goal was to assess and compare adverse events (AE) of current vaccinations for travelers under 'real-life conditions'. A prospective observational online questionnaire study was performed from May 2015 till April 2016 in a travel clinic in Germany. Online questionnaire links were sent 1 week after the first vaccination date. Severity was rated on a scale from 1 to 5 (minor to very severe AE). Of 1357 vaccinees 781 (57.6%) responded to the questionnaire, corresponding to 1415 vaccinations (1-7 simultaneous vaccinations). Responders were more often female (f:m = 1.29:1). Main age groups were 20-29 years old (36.1%). Most frequent vaccinations were against rabies (277; chick embryo cell vaccine (CEC): 97, human diploid cell vaccine (HDC): 180), yellow fever (250), typhoid fever (198), meningococcal meningitis (126) and Japanese encephalitis (104). A total of 217 vaccinees (27.8%) reported AE; 82 (10.5%) rated AE as more severe (grade 3: 61, grade 4: 18, grade 5: 3). No life-threatening AE was reported. Of 157 systemic AE the most frequent were: fatigue (75), headaches (46) and pyrexia (31). Of 94 local AE most frequently reported were pain (66), myalgia (25) and swelling (12). AE after single vaccinations were more often associated with rabies vaccine (OR 2.2; 1.2-4.2). AE increased with the number of simultaneous vaccinations (single vaccination: 24.1%, 88/365; 2 vaccinations: 26.6%, 73/274, ≥3 vaccinations: 39.4%, 56/142, χ2 = 12.24, P = 0.002, CCorr = 0.18), but more severe AE showed no association with the number of vaccinations (χ2 = 5.55, P = 0.06, CCorr = 0.12). Single and simultaneous vaccinations were overall well tolerated. AE were reported more frequently with rabies vaccinations in single vaccinations. Increased numbers of simultaneous vaccinations led to some incremental AE but not to more severe AE. Simultaneous vaccinations should be encouraged to reduce missed opportunities for immunizations.

  2. Germany's Persistent Balance-of-Payments Disequilibrium Revisited. German Studies Notes.

    ERIC Educational Resources Information Center

    Kindleberger, Charles P.

    This essay compares Germany's persistent financial disequilibrium with the balance of payments situation in the United States. Delivered at a Symposium on German Economic Growth and Stability, the author concentrates on Germany's balance of payments surplus and presents U.S. figures mainly as a point of comparison. The material on Germany has been…

  3. 78 FR 20091 - Foreign-Trade Zone 26-Atlanta, Georgia, Authorization of Production Activity, Perkins Shibaura...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-03

    ... DEPARTMENT OF COMMERCE Foreign-Trade Zones Board [B-90-2012] Foreign-Trade Zone 26--Atlanta, Georgia, Authorization of Production Activity, Perkins Shibaura Engines, LLC (Diesel Engines), Griffin, Georgia On November 29, 2012, Georgia Foreign-Trade Zone, Inc., grantee of FTZ 26, submitted a notification of proposed production activity to the...

  4. Undergraduate medical education in Germany

    PubMed Central

    Chenot, Jean-François

    2009-01-01

    The purpose of this article is to give international readers an overview of the organisation, structure and curriculum, together with important advances and problems, of undergraduate medical education in Germany. Interest in medical education in Germany has been relatively low but has gained momentum with the new "Regulation of the Licensing of Doctors" which came into effect in 2003. Medical education had required substantial reform, particularly with respect to improving the links between theoretical and clinical teaching and the extension of interdisciplinary and topic-related instruction. It takes six years and three months to complete the curriculum and training is divided into three sections: basic science (2 years), clinical science (3 years) and final clinical year. While the reorganisation of graduate medical education required by the new "Regulation of the Licensing of Doctors" has stimulated multiple excellent teaching projects, there is evidence that some of the stipulated changes have not been implemented. Indeed, whether the medical schools have complied with this regulation and its overall success remains to be assessed systematically. Mandatory external accreditation and periodic reaccreditation of medical faculties need to be established in Germany. PMID:19675742

  5. [Home treatment: systematic review and implementation in Germany].

    PubMed

    Gühne, Uta; Weinmann, Stefan; Arnold, Katrin; Atav, Esra-Sultan; Becker, Thomas; Riedel-Heller, Steffi

    2011-04-01

    To report about existing evidence of effectiveness of home treatment for severely mentally ill adults and implementation in Germany. Systematic electronic and manual literature search. Compared to standard care, home treatment was equally or more efficacious with respect to general state of health and mental health. Home treatment was superior with regard to other outcomes. So far, implementation in Germany is limited. Home treatment can be seen as an effective addition to existing approaches of psychiatric care. It may be cost-effective also in Germany. Reasons for limited implementation in routine care are discussed. © Georg Thieme Verlag KG Stuttgart · New York.

  6. The Geography of Germany: Lessons for Teaching the Five Themes of Geography.

    ERIC Educational Resources Information Center

    Blankenship, Glen; Tinkler, D. William

    This activity guide contains five lessons. Lesson 1 deals with "Location of Germany on the Earth's Surface" with two activities: (1) "Germany's Location in the World"; and (2) "Germany's Location in Europe." Lesson 2 is on the "Physical and Human Characteristics of Germany" with four activities on: (1)…

  7. Stuttgart, Germany. Revised Uniform Summary of Surface Weather Observations (RUSSWO)

    DTIC Science & Technology

    1988-07-01

    4rREVISED UNIFORM SUMMARY OF SURFACE WEATHER OBSERVATIONS STUTTGART GERMANY MSC # 107380 N 48 41 K 009 13 ELEV 1300 FT EDOC PARTS A - F HOURS SUMMARIZED 0000...1 .. L. b I.E 725O0 14.2 24.A 26.4 32.3 32.1 33.6 34.2 36.7 37.7 9.2 39.c 39.5 39.7 𔄃.e 40. 1 I. . GE 6’ UC 1 14.4 25.3 27.0 30.6 32.8 34. 2 34*. 37.4...28.9 30.1 33.8 35.8 36.7 37.3 39.1 39.6 40.0 40.2 60.5 60.6 60.7 41.1 1.9 6E 8- uC l7.9 3L. b 31 .9 35.838 V.. 39. 139 . 7- 6’.6 - 42. 1-62. 7 42.9 4

  8. Successful overwintering of Aedes albopictus in Germany.

    PubMed

    Pluskota, Björn; Jöst, Artur; Augsten, Xenia; Stelzner, Lilith; Ferstl, Ina; Becker, Norbert

    2016-08-01

    The Asian tiger mosquito (Aedes albopictus) is of great concern to public health authorities due to its vector competence and rapid spread across the globe. In 2015, two large local breeding populations of Ae. albopictus were discovered in southwest Germany. In spring 2016, we were able to demonstrate the first evidence of a successful overwintering in Germany of this originally tropical mosquito species in different research projects. Particularly noteworthy is the successful hatching of diapause eggs of an Italian strain (Calabria), which overwintered successfully in the field in St. Georgen im Schwarzwald (Baden-Wuerttemberg) at 820 m above sea level. Furthermore, within the scope of a larvae monitoring, the first larvae that hatched in the field were detected on the April 09, 2016 in a rain barrel within the Heidelberg population. Our first results show that self-extinction due to an unsuccessful overwintering cannot be assumed for populations of the Asian tiger mosquito which settled in Germany in previous years. The evidence of a successful overwintering of a large number of diapause eggs and the hatching of the first larvae in field conditions opens the control year against Ae. albopictus in southwest Germany.

  9. The Role of Western Germany in West European Defense

    DTIC Science & Technology

    1966-04-08

    Ralph. Modern German History. New York: E. P. Dutton & Co., Inc., 1964. (DD175 F5) 34. German Research Association. Germany: Franz Steiner Verlag Gmb...and Rudolf , Walter. This Germany. New York: New York Graphic Society Publishers, Ltd., 1954. (DD257 L42) 39. Heidenheimer, Arnold J. The Government...202-07, 243. 47. Lauder, K. H. A Brief Review of Science and Technoloc in Western Germany. London: HIISO, 1955. (Q18 G4G7) 48. Leonhardt, Rudolf Walter

  10. Cathepsins B and L activate Ebola but not Marburg virus glycoproteins for efficient entry into cell lines and macrophages independent of TMPRSS2 expression.

    PubMed

    Gnirss, Kerstin; Kühl, Annika; Karsten, Christina; Glowacka, Ilona; Bertram, Stephanie; Kaup, Franziska; Hofmann, Heike; Pöhlmann, Stefan

    2012-03-01

    Ebola (EBOV) and Marburg virus (MARV) cause severe hemorrhagic fever. The host cell proteases cathepsin B and L activate the Zaire ebolavirus glycoprotein (GP) for cellular entry and constitute potential targets for antiviral intervention. However, it is unclear if different EBOV species and MARV equally depend on cathepsin B/L activity for infection of cell lines and macrophages, important viral target cells. Here, we show that cathepsin B/L inhibitors markedly reduce 293T cell infection driven by the GPs of all EBOV species, independent of the type II transmembrane serine protease TMPRSS2, which cleaved but failed to activate EBOV-GPs. Similarly, a cathepsin B/L inhibitor blocked macrophage infection mediated by different EBOV-GPs. In contrast, MARV-GP-driven entry exhibited little dependence on cathepsin B/L activity. Still, MARV-GP-mediated entry was efficiently blocked by leupeptin. These results suggest that cathepsins B/L promote entry of EBOV while MARV might employ so far unidentified proteases for GP activation. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. 26 CFR 1.410(a)-7 - Elapsed time.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Elapsed time. 1.410(a)-7 Section 1.410(a)-7...) INCOME TAXES Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.410(a)-7 Elapsed time. (a) In general—(1) Introduction to elapsed time method of crediting service. (i) 29 CFR 2530.200b-2 sets forth the...

  12. 29 CFR 785.26 - Section 3(o) of the Fair Labor Standards Act.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Section 785.26 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR STATEMENTS OF GENERAL POLICY OR INTERPRETATION NOT DIRECTLY RELATED TO REGULATIONS HOURS WORKED Application... bargaining agreements. This section provides for the exclusion from hours worked of time spent by an employee...

  13. Gambling experiences, problems, research and policy: gambling in Germany.

    PubMed

    Ludwig, Monika; Kräplin, Anja; Braun, Barbara; Kraus, Ludwig

    2013-09-01

    The objective of this paper is to present an overview of gambling in Germany, including historical development, legislative and economic changes as well as treatment options and their effectiveness. The available scientific literature and research reports on gambling in Germany were reviewed to obtain relevant information on history, commercialization, legislation, treatment and research agenda. Gambling in Germany is characterized by compromises between protective and economic efforts. At present, gambling is illegal in Germany, and provision is subject to the state monopoly. Mere gaming machines (specific slot machines) are not classified as gambling activity, permitting commercial providers. In recent years, implementing regulations for state gambling and gaming machines have been changed. Concerning the treatment of pathological gambling, various options exist; treatment costs have been covered by health and pension insurance since 2001. Information on the effectiveness of treatment in Germany is limited. Similarly, the number of peer-reviewed publications on gambling is small. German gambling legislation was subject to major changes in the past years. Based on the available body of research (longitudinal), studies on risk and protective factors and the aetiology of pathological gambling are needed. The effectiveness of pathological gambling treatment in Germany and the impact of gambling regulations on gambling behaviour also need to be investigated. © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.

  14. Ongoing outbreak of invasive listeriosis, Germany, 2012 to 2015.

    PubMed

    Ruppitsch, Werner; Prager, Rita; Halbedel, Sven; Hyden, Patrick; Pietzka, Ariane; Huhulescu, Steliana; Lohr, Dorothee; Schönberger, Katharina; Aichinger, Elisabeth; Hauri, Anja; Stark, Klaus; Vygen, Sabine; Tietze, Erhard; Allerberger, Franz; Wilking, Hendrik

    2015-01-01

    Listeriosis patient isolates in Germany have shown a new identical pulsed-field gel electrophoresis (PFGE) pattern since 2012 (n = 66). Almost all isolates (Listeria monocytogenes serotype 1/2a) belonged to cases living in southern Germany, indicating an outbreak with a so far unknown source. Case numbers in 2015 are high (n = 28). No outbreak cases outside Germany have been reported. Next generation sequencing revealed the unique cluster type CT1248 and confirmed the outbreak. Investigations into the source are ongoing.

  15. An Active Old Age--Senior Citizens in Germany.

    ERIC Educational Resources Information Center

    Metzler, Birgit

    1998-01-01

    Life expectancies are rising all over the world, leading to higher proportions of older adults in the population. This is especially true in Japan and Germany. In Germany today, "old" no longer means necessarily "poor and frail." Through volunteer work, lifelong learning, study tours, and participation in sports, older Germans…

  16. Germany's Emerging Multiethnic Society: Old Problems and New.

    ERIC Educational Resources Information Center

    Gedmin, Jeffrey

    1994-01-01

    Opinion polls do not indicate a growing neo-Nazism in Germany, but they do reveal substantial hostile attitudes toward Jews and significant bias against other ethnic minorities. Demographic trends suggest that Germany will have an increasingly multiracial society as well as a greater need for foreign labor in the future. (SLD)

  17. 7 CFR 29.29 - Regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Regulations. 29.29 Section 29.29 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE COMMODITY STANDARDS AND STANDARD CONTAINER REGULATIONS TOBACCO...

  18. 7 CFR 29.29 - Regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Regulations. 29.29 Section 29.29 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE COMMODITY STANDARDS AND STANDARD CONTAINER REGULATIONS TOBACCO...

  19. Pushing the limit: forensic nursing in Germany.

    PubMed

    Lambe, Andrea; Gage-Lindner, Nancy

    2007-01-01

    Violence remains a public health challenge and the nursing profession accepts this challenge by expanding its field. Although countries such as the United States, Great Britain, and Canada have employed forensic nurses for decades in different capacities, Germany has yet to follow their lead. This report discusses the German health care and legal systems and challenges Germany to develop an innovative, cost-efficient, and competent profession of forensic nursing.

  20. [Mosquitoes as vectors for exotic pathogens in Germany].

    PubMed

    Becker, N; Krüger, A; Kuhn, C; Plenge-Bönig, A; Thomas, S M; Schmidt-Chanasit, J; Tannich, E

    2014-05-01

    As a result of intensified globalization of international trade and of substantial travel activities, mosquito-borne exotic pathogens are becoming an increasing threat for Europe. In Germany some 50 different mosquito species are known, several of which have vector competence for pathogens. During the last few years a number of zoonotic arboviruses that are pathogenic for humans have been isolated from mosquitoes in Germany including Usutu, Sindbis and Batai viruses. In addition, filarial worms, such as Dirofilaria repens have been repeatedly detected in mosquitoes from the federal state of Brandenburg. Other pathogens, in particular West Nile virus, are expected to emerge sooner or later in Germany as the virus is already circulating in neighboring countries, e.g. France, Austria and the Czech Republic. In upcoming years the risk for arbovirus transmission might increase in Germany due to increased occurrence of new so-called "invasive" mosquito species, such as the Asian bush mosquito Ochlerotatus japonicus or the Asian tiger mosquito Aedes albopictus. These invasive species are characterized by high vector competence for a broad range of pathogens and a preference for human blood meals. For risk assessment, a number of mosquito and pathogen surveillance projects have been initiated in Germany during the last few years; however, mosquito control strategies and plans of action have to be developed and put into place to allow early and efficient action against possible vector-borne epidemics.

  1. Cytomegalovirus (CMV) seroprevalence in pregnant women, bone marrow donors and adolescents in Germany, 1996-2010.

    PubMed

    Enders, Gisela; Daiminger, Anja; Lindemann, Lisa; Knotek, Frank; Bäder, Ursula; Exler, Simone; Enders, Martin

    2012-08-01

    In Germany, studies on the IgG seroprevalence in pregnancy and in women of childbearing age are rare. Therefore, we retrospectively evaluated the CMV IgG seropositive rate in 40,324 pregnant women as well as in 31,093 female and male bone marrow donors over 15 consecutive years (1996-2010). Furthermore, the result of a study conducted in 1999 investigating 1,305 healthy adolescents with known ethnicity was included. The overall CMV IgG seroprevalence in pregnant women (15-50 years) was 42.3%. Age-dependent analysis revealed a significantly higher seropositive rate (55.6%) in young women (15-25 years) than in those aged 26-40 years (37-42%) and in women older than 40 years (48.3%). Over the study period of 15 years, the rate of seroprevalence in pregnant women declined significantly (χ(2) test < 0.01) from 44.3% in the first interval period (1996-2000), to 42.8% (2001-2005) and to 40.9% (2006-2010). The most influencing factor on CMV seropositivity appeared to be the socioeconomic status (SES), which we characterized by type of health insurance: Seroprevalence in women with low, middle and upper SES was 91.8, 46.9 and 33.7%, respectively. Female bone marrow donors of childbearing age (15-45 years) showed a significantly higher seropositive rate of 36.5% than age-matched male donors (28.6%). In adolescents aged 13-16 years, no gender-specific differences were recognized. Concerning ethnicity, youngsters with German descent had a significantly lower seroprevalence (29.9%) than those with non-German descent (67.4%).

  2. Self-Employment in the United Kingdom and Germany.

    ERIC Educational Resources Information Center

    Meager, Nigel; And Others

    In a comparison of self-employment patterns in Germany and the United Kingdom, data from the Labour Force Survey (United Kingdom) and Mikrozensus (Germany) were analyzed to identify the personal characteristics of self-employed individuals in the two countries, the characteristics of their self-employed activity, and movement in and out of…

  3. Special Education in East Germany under Communist Domination.

    ERIC Educational Resources Information Center

    Sengstock, Wayne L.; Ruttgardt, Sieglind Ellger

    1995-01-01

    This article describes the development of special education in East Germany from the close of World War II through the cold war period, and examines the problems and challenges currently facing special education in a reunified Germany. These include a lack of infrastructure, economic needs, staffing problems, and needed curriculum changes. (DB)

  4. 29 CFR 1952.312 - Completion of developmental steps and certification.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Completion of developmental steps and certification. 1952... § 1952.312 Completion of developmental steps and certification. (a) In accordance with § 1952.313(i... 26, 1978 as having completed all developmental steps specified in the plan as approved on December 28...

  5. Physical Activity during Work, Transport and Leisure in Germany - Prevalence and Socio-Demographic Correlates

    PubMed Central

    Wallmann-Sperlich, Birgit; Froboese, Ingo

    2014-01-01

    Background This study aimed 1) to provide data estimates concerning overall moderate- and vigorous-intensity physical activity (MVPA) as well as MVPA during work, transport and leisure in Germany and 2) to investigate MVPA and possible associations with socio-demographic correlates. Methods A cross-sectional telephone survey interviewed 2248 representative participants in the age of 18–65 years (1077 men; 42.4±13.4 years; body mass index: 25.3±4.5kg•m−2) regarding their self-reported physical activity across Germany. The Global Physical Activity Questionnaire was applied to investigate MVPA during work, transport and leisure and questions were answered concerning their demographics. MVPA was stratified by gender, age, body mass index, residential setting, educational and income level. To identify socio-demographic correlates of overall MVPA as well as in the domains, we used a series of linear regressions. Results 52.8% of the sample achieved physical activity recommendations (53.7% men/52.1% women). Overall MVPA was highest in the age group 18–29 years (p<.05), in participants with 10 years of education (p<.05) and in participants with lowest income levels <1.500€ (p<.05). Regression analyses revealed that age, education and income were negatively associated with overall and work MVPA. Residential setting and education was positively correlated with transport MVPA, whereas income level was negatively associated with transport MVPA. Education was the only correlate for leisure MVPA with a positive association. Conclusions The present data underlines the importance of a comprehensive view on physical activity engagement according to the different physical activity domains and discloses a need for future physical activity interventions that consider socio-demographic variables, residential setting as well as the physical activity domain in Germany. PMID:25390071

  6. Physical activity during work, transport and leisure in Germany--prevalence and socio-demographic correlates.

    PubMed

    Wallmann-Sperlich, Birgit; Froboese, Ingo

    2014-01-01

    This study aimed 1) to provide data estimates concerning overall moderate- and vigorous-intensity physical activity (MVPA) as well as MVPA during work, transport and leisure in Germany and 2) to investigate MVPA and possible associations with socio-demographic correlates. A cross-sectional telephone survey interviewed 2248 representative participants in the age of 18-65 years (1077 men; 42.4 ± 13.4 years; body mass index: 25.3 ± 4.5 kg • m(-2)) regarding their self-reported physical activity across Germany. The Global Physical Activity Questionnaire was applied to investigate MVPA during work, transport and leisure and questions were answered concerning their demographics. MVPA was stratified by gender, age, body mass index, residential setting, educational and income level. To identify socio-demographic correlates of overall MVPA as well as in the domains, we used a series of linear regressions. 52.8% of the sample achieved physical activity recommendations (53.7% men/52.1% women). Overall MVPA was highest in the age group 18-29 years (p < .05), in participants with 10 years of education (p < .05) and in participants with lowest income levels < 1.500 € (p < .05). Regression analyses revealed that age, education and income were negatively associated with overall and work MVPA. Residential setting and education was positively correlated with transport MVPA, whereas income level was negatively associated with transport MVPA. Education was the only correlate for leisure MVPA with a positive association. The present data underlines the importance of a comprehensive view on physical activity engagement according to the different physical activity domains and discloses a need for future physical activity interventions that consider socio-demographic variables, residential setting as well as the physical activity domain in Germany.

  7. [Pharmacovigilance in Germany : It is about time].

    PubMed

    Douros, A; Schaefer, C; Kreutz, R; Garbe, E

    2016-06-01

    Pharmacovigilance is defined as the activities relating to the detection, assessment, and prevention of adverse drug reactions (ADRs). Although its beginnings in Germany date back more than 50 years, a stagnation in this field has been observed lately. Different tools of pharmacovigilance will be illustrated and the reasons for its stagnation in Germany will be elucidated. Spontaneous reporting systems are an important tool in pharmacovigilance and are based on reports of ADRs from treating physicians, other healthcare professionals, or patients. Due to several weaknesses of spontaneous reporting systems such as underreporting, media bias, confounding by comorbidity or comedication, and due to the limited quality of the reports, the development of electronic healthcare databases was publicly funded in recent years so that they can be used for pharmacovigilance research. In the US different electronic healthcare databases were merged in a project sponsored by public means resulting in more than 193 million individuals. In Germany the establishment of large longitudinal databases was never conceived as a public duty and has not been implemented so far. Further attempts to use administrative healthcare data for pharmacovigilance purposes are severely restricted by the Code of Social Law (Section 75, Book 10). This situation has led to a stagnation in pharmacovigilance research in Germany. Without publicly funded large longitudinal healthcare databases and an amendment of Section 75, Book 10, of the Code of Social Law, the use of healthcare data in pharmacovigilance research in Germany will remain a rarity. This could have negative effects on the medical care of the general population.

  8. [Performance of in vitro fertilization in Germany].

    PubMed

    van der Ven, Hans; Montag, Markus; van der Ven, Katrin

    2002-07-01

    In Germany the application of assisted reproductive techniques (ART) is regulated by federal legislation. Compared with the international situation the "German Embryo Protection Law" is very "restrictive" and various methods of ART are prohibited, e.g. oocyte/embryo donation, embryo cryopreservation and Preimplantation Genetic Diagnosis (PGD). Furthermore, in Germany only 1 to 3 fertilized oocytes may be cultured to embryo. All these embryos then have to be transferred into the uterus of a particular patient. Additional fertilized oocytes can only be cryopreserved in a pronuclear state. The success rate of ART has increased significantly over the past few years owing to the introduction of blastocyst cultures and the selection of 1 to 2 good quality blastocysts for embryo transfer. Furthermore, the transfer of only 1 to 2 blastocysts effectively reduces the risk of high rank multiple pregnancies. In Germany, however, the selection of only a few good quality blastocysts for transfer is prohibited by law. New laboratory techniques, e.g. pronuclear scoring and polar body biopsy screening for aneuploidy are in accordance with German law. The application of these methods provides a selection of "good quality oocytes" and seems to increase the overall success rate. Further studies are required, however. The success rate, quality and cost effectiveness of ART in Germany appears compromised when compared with many other countries. What is more, in contrast to the international situation research and development in ART in Germany has been decreasing constantly over the past few years, due to the inappropriate regulations of the German health care system and the insufficient support given to university-based centers.

  9. Germany's expanding role in global health.

    PubMed

    Kickbusch, Ilona; Franz, Christian; Holzscheiter, Anna; Hunger, Iris; Jahn, Albrecht; Köhler, Carsten; Razum, Oliver; Schmidt, Jean-Olivier

    2017-08-26

    Germany has become a visible actor in global health in the past 10 years. In this Series paper, we describe how this development complements a broad change in perspective in German foreign policy. Catalysts for this shift have been strong governmental leadership, opportunities through G7 and G20 presidencies, and Germany's involvement in managing the Ebola virus disease outbreak. German global health engagement has four main characteristics that are congruent with the health agenda of the Sustainable Development Goals; it is rooted in human rights, multilateralism, the Bismarck model of social protection, and a link between development and investment on the basis of its own development trajectory after World War 2. The combination of momentum and specific characteristics makes Germany well equipped to become a leader in global health, yet the country needs to accept additional financial responsibility for global health, expand its domestic global health competencies, reduce fragmentation of global health policy making, and solve major incoherencies in its policies both nationally and internationally. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. 29 CFR 2520.104-26 - Limited exemption for certain unfunded dues financed welfare plans maintained by employee...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... welfare plans maintained by employee organizations. 2520.104-26 Section 2520.104-26 Labor Regulations Relating to Labor (Continued) EMPLOYEE BENEFITS SECURITY ADMINISTRATION, DEPARTMENT OF LABOR REPORTING AND... exemption for certain unfunded dues financed welfare plans maintained by employee organizations. (a) Scope...

  11. 75 FR 20828 - Availability for Non-Exclusive, Exclusive, or Partially Exclusive Licensing of U.S. Patent...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-21

    ... Partially Exclusive Licensing of U.S. Patent Application Concerning a Chimeric Ebola and Marburg Virus Glycoproteins Virus Like Particle Vaccine To Protect Against Diverse Ebola and Marburg Viruses AGENCY... Ebola and Marburg Virus Glycoproteins Virus Like Particle Vaccine To Protect Against Diverse Ebola and...

  12. Disparities in nuclear power plant performance in the United States and the Federal Republic of Germany

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

    Hansen, K.F.; Winje, D.K.

    This report presents data comparing the performance of light water reactors in the United States and the Federal Republic of Germany (FRG). The comparisons are made for the years 1980 to 1983 and include 21 Westinghouse Pressurized Water Reactors (PWRs), 22 General Electric Boiling Water Reactors (BWRs) in the US; and 6 Kraftwerk Union (KWU) PWRs and 4 KWU BWRs in the FRG. Data on capacity losses are presented in a disaggregated form for scheduled outages, forced outages, and regulatory imposed outages. Further, within the scheduled and forced outages, the data are subdivided into losses associated with the nuclear island,more » the balance of plant, or other causes. The report also surveys a number of observations relating to the causes of discrepancies between the US and West Germany. These observations were obtained from interviews with executives and engineers in both nations, including people from vendors, utilities, regulators, and architect/engineers. These discussions are distilled into observations relating to national differences in the broad areas of economics and economic regulation, safety regulations, and technical and managerial differences. 9 refs., 2 figs., 26 tabs.« less

  13. Rainfall and human activity impacts on soil losses and rill erosion in vineyards (Ruwer Valley, Germany)

    NASA Astrophysics Data System (ADS)

    Rodrigo Comino, J.; Brings, C.; Lassu, T.; Iserloh, T.; Senciales, J. M.; Martínez Murillo, J. F.; Ruiz Sinoga, J. D.; Seeger, M.; Ries, J. B.

    2015-07-01

    Vineyards are one of the eco-geomorphological systems most conditioned by human activity in Germany. The vineyards of the Ruwer Valley (Germany) are characterized by high soil erosion rates and rill problems on steep slopes (between 23 and 26°) caused by the increasingly frequent heavy rainfall events as well as deterioration due to incorrect land use managements. The objective of this paper is to determine and to quantify the hydrological and erosive phenomena in one vineyard in Germany during different seasons and under different management conditions (before, during and after vintage). For this purpose, a combined methodology was applied. Climatic (rainfall depth distributions and return periods), pedological (soil analysis and classification), geomorphological (sediment movements and rills evolution) and biological (botanic marks on the vines) variables were used on the two experimental plots in the village of Waldrach (Trier, region of Rhineland-Palatinate). The results showed high infiltration rates (near 100 %) and subsurface flow which were detected by rainfall simulations performed at different times of the year (between September and December). The highest variations of the monitored rills (lateral and frontal movements) were noted before and during vintage, when footsteps occurred concentrated during a short period of time (between September and October). Finally, two maps of soil loss were generated, indicated by botanic marks on the graft union of the vines. 62.5 t ha-1 yr-1 soil loss was registered in the experimental plots of the new vineyards (2 years), while 3.4 t ha-1 yr-1 was recorded in the old one (35 years).

  14. How safe are HEMS-programmes in Germany? A retrospective analysis.

    PubMed

    Thies, Karl-Christian; Sep, Daan; Derksen, Remon

    2006-03-01

    Recent accidents with helicopter emergency medical service (HEMS) aircraft raise the question how safe HEMS in Germany is and how accidents could be prevented. We surveyed all German HEMS-programmes and reviewed the data of the German Aviation Authority regarding accidents with HEMS. An average German HEMS-programme encounters one accident leading to at least severe damage or loss of the helicopter in 26 operating years, one accident resulting in casualties in 65 operating years and one fatal accident in 111 operating years. The major causes of accidents were obstacle strikes during landing at the scene. Flying in bad weather conditions and lack of discipline were other factors contributing to HEMS-accidents. HEMS-safety could be improved by special training programmes for pilots and HEMS-crewmembers to address the factors listed above. Safety training for doctors is recommended but we did not find support for the notion of changing the doctor's legal position of a passenger to a HEMS-crewmember.

  15. Intelligent Adversary Risk Analysis: A Bioterrorism Risk Management Model (PREPRINT)

    DTIC Science & Technology

    2009-02-20

    Dengue • Listeria monocytogenes • Filoviruses coronavirus ( SARS -CoV) • Campylobacter jejuni • Ebola • Yersinia enterocolitica) • Marburg...OF: 17. LIMITATION OF ABSTRACT Same as Report ( SAR ) 18. NUMBER OF PAGES 29 19a. NAME OF RESPONSIBLE PERSON a. REPORT unclassified b. ABSTRACT...which may be to maximize the consequences they can inflict (Golany et al., Figure 2: Decision Tree Example  7    Submitted to Risk Analysis

  16. The Great Drama: Germany and the French Revolution.

    ERIC Educational Resources Information Center

    Kurz, Gerhard

    Revolution did not spread to Germany from France at the end of the 18th century, yet the German and other European states were forced to come to terms with the principles of the French Revolution such as political and legal freedoms and national unity. Germany was affected by the French Revolution particularly by the reactions of German…

  17. 29 CFR 1952.152 - Completion of developmental steps and certification.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Completion of developmental steps and certification. 1952... Carolina § 1952.152 Completion of developmental steps and certification. (a) In accordance with § 1952.153... March 31, 1976 all development steps specified in the plan as approved on January 26, 1973. [40 FR 18429...

  18. Health-related quality of life and sense of coherence among Polish immigrants in Germany and indigenous Poles.

    PubMed

    Morawa, Eva; Erim, Yesim

    2015-06-01

    Immigrants are faced with several impediments in the host country that may affect their quality of life (QoL), but little is known about the impact of these stressors as well as about the protective role of sense of coherence (SoC) in the context of Polish immigration to Germany. Health Related QoL (Short Form Health Survey SF-36) and SoC (Sense of Coherence Scale SOC-29) were assessed in a total sample consisting of 511 participants aged between 18 and 84 years (260 Polish immigrants in Germany and 251 indigenous Poles). Polish immigrants reported a significantly lower mental and physical health-related QoL than the German norm population, but they were comparable to native Poles. This result remained the same when the model was adjusted for age but physical health status was better for immigrants compared with indigenous Poles. Both groups scored significantly lower for SoC than Germans, but did not differ from each other. The main differences concerning the examined variables were with respect to the German norm population and are putatively shaped by culture. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  19. Marburg Hemorrhagic Fever (Marburg HF)

    MedlinePlus

    ... infected had been exposed to imported African green monkeys or their tissues while conducting research. One additional ... OIG 1600 Clifton Road Atlanta , GA 30329-4027 USA 800-CDC-INFO (800-232-4636) , TTY: 888- ...

  20. STS-26 crewmembers walk across parking apron to T-38s at Ellington Field

    NASA Technical Reports Server (NTRS)

    1988-01-01

    STS-26 Discovery, Orbiter Vehicle (OV) 103, crewmembers walk toward the flight line of T-38s at Ellington Field prior to their departure for Kennedy Space Center (KSC). STS-26 crewmembers are scheduled for a September 29 launch. Left to right are Mission Specialist (MS) David C. Hilmers, Pilot Richard O. Covey, Commander Frederick H. Hauck, MS George D. Nelson, and MS John M. Lounge.

  1. Thermal-neutron capture for A=26-35

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

    Chunmei, Z.; Firestone, R.B.

    2001-06-01

    The prompt gamma-ray data of thermal- neutron captures fornuclear mass number A=26-35 had been evaluated and published in "ATOMICDATA AND NUCLEAR DATA TABLES, 26, 511 (1981)". Since that time themanyexperimental data of the thermal-neutron captures have been measuredand published. The update of the evaluated prompt gamma-ray data is verynecessary for use in PGAA of high-resolution analytical prompt gamma-rayspectroscopy. Besides, the evaluation is also very needed in theEvaluated Nuclear Structure Data File, ENSDF, because there are no promptgamma-ray data in ENSDF. The levels, prompt gamma-rays and decay schemesof thermal-neutron captures for nuclides (26Mg, 27Al, 28Si, 29Si, 30Si,31P, 32S, 33S, 34S, andmore » 35Cl) with nuclear mass number A=26-35 have beenevaluated on the basis of all experimental data. The normalizationfactors, from which absolute prompt gamma-ray intensity can be obtained,and necessary comments are given in the text. The ENSDF format has beenadopted in this evaluation. The physical check (intensity balance andenergy balance) of evaluated thermal-neutron capture data has been done.The evaluated data have been put into Evaluated Nuclear Structure DataFile, ENSDF. This evaluation may be considered as an update of the promptgamma-ray from thermal-neutron capture data tables as published in"ATOMIC DATA AND NUCLEAR DATA TABLES, 26, 511 (1981)".« less

  2. GENERAL VIEW OF THE PRODUCTION LINE BEING CONVERTED FROM B26 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GENERAL VIEW OF THE PRODUCTION LINE BEING CONVERTED FROM B-26 TO B-29 PRODUCTION SHOWING THE LINK-BELT CONVEYOR SYSTEM AND ENGINE NACELLES READY FOR ASSEMBLY. WHO, 1944 - Offutt Air Force Base, Glenn L. Martin-Nebraska Bomber Plant, Building D, Peacekeeper Drive, Bellevue, Sarpy County, NE

  3. Characteristics of emerging human-pathogenic Escherichia coli O26:H11 strains isolated in France between 2010 and 2013 and carrying the stx2d gene only.

    PubMed

    Delannoy, Sabine; Mariani-Kurkdjian, Patricia; Bonacorsi, Stephane; Liguori, Sandrine; Fach, Patrick

    2015-02-01

    Strains of Escherichia coli O26:H11 that were positive for stx2 alone (n = 23), which were not epidemiologically related or part of an outbreak, were isolated from pediatric patients in France between 2010 and 2013. We were interested in comparing these strains with the new highly virulent stx2a-positive E. coli O26 clone sequence type 29 (ST29) that has emerged recently in Europe, and we tested them by multilocus sequence typing (MLST), stx2 subtyping, clustered regularly interspaced short palindromic repeat (CRISPR) sequencing, and plasmid (ehxA, katP, espP, and etpD) and chromosomal (Z2098, espK, and espV) virulence gene profiling. We showed that 16 of the 23 strains appeared to correspond to this new clone, but the characteristics of 12 strains differed significantly from the previously described characteristics, with negative results for both plasmid and chromosomal genetic markers. These 12 strains exhibited a ST29 genotype and related CRISPR arrays (CRISPR2a alleles 67 or 71), suggesting that they evolved in a common environment. This finding was corroborated by the presence of stx2d in 7 of the 12 ST29 strains. This is the first time that E. coli O26:H11 carrying stx2d has been isolated from humans. This is additional evidence of the continuing evolution of virulent Shiga toxin-producing E. coli (STEC) O26 strains. A new O26:H11 CRISPR PCR assay, SP_O26_E, has been developed for detection of these 12 particular ST29 strains of E. coli O26:H11. This test is useful to better characterize the stx2-positive O26:H11 clinical isolates, which are associated with severe clinical outcomes such as bloody diarrhea and hemolytic uremic syndrome. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  4. Quality of life of Turkish type 2 diabetics in Germany and Turkey--a comparison between Hamburg and Istanbul.

    PubMed

    Kofahl, Christopher; Doğan, Mustafa; Doğan, Gülsün; Mnich, Eva; von dem Knesebeck, Olaf

    2014-01-01

    The analyses address the following research questions: (1) Do Turkish diabetics in Germany and Turkey differ in terms of quality of life? (2) If yes, can these differences (in part) be explained by social factors (age, gender, education, household size), functional limitations and availability of support? (3) Are social factors, functional limitations and availability of support differently associated with quality of life among Turkish diabetics in Germany and Turkey? For this comparative cross-sectional study, 111 patients with type 2 diabetes were personally interviewed in Istanbul (Turkey) and 294 Turkish patients in Hamburg (Germany). For quality of life measurement we have used the Turkish version of the WHOQOL-Bref-26. Sociodemographics included age, sex, education and household-size. Health related functional limitations were assessed on the basis of an index of (instrumental) activities of daily living including the availability of help. Statistical analyses were conducted on group comparisons with Chi-square- and T-tests as well as linear regressions. There are no significant differences between Turkish diabetics in Germany and Turkey in the physical and the psychological dimensions of the WHOQOL-Bref. However, in the WHOQOL-domains 'social QoL' and 'environmental QoL' Turkish diabetics living in Hamburg have a significantly better quality of life than their counterparts in Istanbul. These differences cannot be explained by individual sociodemographic factors, functional limitations and availability of support. Furthermore, we found much stronger positive associations between education and quality of life in Istanbul than in Hamburg. Beyond strong similarities between the two samples in sociodemographics, physical and mental health the social and environmental quality of life was significantly assessed better by the Turkish diabetics living in Hamburg. This is most likely an effect of public investment in social security, infrastructure and health care

  5. HIV-Prevalence in Tuberculosis Patients in Germany, 2002–2009: An Estimation Based on HIV and Tuberculosis Surveillance Data

    PubMed Central

    Fiebig, Lena; Kollan, Christian; Hauer, Barbara; Gunsenheimer-Bartmeyer, Barbara; an der Heiden, Matthias; Hamouda, Osamah; Haas, Walter

    2012-01-01

    Tuberculosis (TB) and HIV comorbidity is a major challenge in TB prevention and control but difficult to assess in Germany as in other countries, where data confidentiality precludes notifying the HIV status of TB patients. We aimed to estimate the HIV-prevalence in TB patients in Germany, 2002–2009, and to characterize the HIV/TB patients demographically. Data from the long-term observational open multicentre cohort ClinSurv HIV were used to identify incident TB in HIV-positive individuals. We assessed the cohort’s coverage for the nationwide HIV-positive population by contrasting ClinSurv HIV patients under antiretroviral therapy (ART) with national HIV patient numbers derived from ART prescriptions (data by Insight Health; available for 2006–2009). The HIV-prevalence in TB patients was calculated as the number of HIV/TB cases projected for Germany over all culture-positive TB notifications. From 2002 to 2009, 298 of 15,531 HIV-positive patients enrolled in the ClinSurv HIV cohort were diagnosed with TB. A 21% cohort coverage was determined. The annual estimates of the HIV-prevalence in TB patients were on average 4.5% and ranged from 3.5% (95%CI 2.3–5.1%) in 2007 to 6.6% (95%CI 5.0–8.5%) in 2005. The most recent estimate for 2009 was 4.0% (95%CI 2.6–5.9%). The 298 HIV/TB patients were characterized by a male-to-female ratio of 2.1, by a median age of 38 years at TB diagnosis, and by 59% of the patients having a foreign origin, mainly from Subsahara Africa. We provide, to our knowledge, the first estimate of the HIV-prevalence in TB patients for Germany by joint evaluation of anonymous HIV and TB surveillance data sources. The identified level of HIV in TB patients approximates available surveillance data from neighbouring countries and indicates a non-negligible HIV/TB burden in Germany. Our estimation approach is valuable for epidemiological monitoring of HIV/TB within the current legal frameworks. PMID:23145087

  6. Estimating trends in atmospheric water vapor and temperature time series over Germany

    NASA Astrophysics Data System (ADS)

    Alshawaf, Fadwa; Balidakis, Kyriakos; Dick, Galina; Heise, Stefan; Wickert, Jens

    2017-08-01

    Ground-based GNSS (Global Navigation Satellite System) has efficiently been used since the 1990s as a meteorological observing system. Recently scientists have used GNSS time series of precipitable water vapor (PWV) for climate research. In this work, we compare the temporal trends estimated from GNSS time series with those estimated from European Center for Medium-Range Weather Forecasts (ECMWF) reanalysis (ERA-Interim) data and meteorological measurements. We aim to evaluate climate evolution in Germany by monitoring different atmospheric variables such as temperature and PWV. PWV time series were obtained by three methods: (1) estimated from ground-based GNSS observations using the method of precise point positioning, (2) inferred from ERA-Interim reanalysis data, and (3) determined based on daily in situ measurements of temperature and relative humidity. The other relevant atmospheric parameters are available from surface measurements of meteorological stations or derived from ERA-Interim. The trends are estimated using two methods: the first applies least squares to deseasonalized time series and the second uses the Theil-Sen estimator. The trends estimated at 113 GNSS sites, with 10 to 19 years temporal coverage, vary between -1.5 and 2.3 mm decade-1 with standard deviations below 0.25 mm decade-1. These results were validated by estimating the trends from ERA-Interim data over the same time windows, which show similar values. These values of the trend depend on the length and the variations of the time series. Therefore, to give a mean value of the PWV trend over Germany, we estimated the trends using ERA-Interim spanning from 1991 to 2016 (26 years) at 227 synoptic stations over Germany. The ERA-Interim data show positive PWV trends of 0.33 ± 0.06 mm decade-1 with standard errors below 0.03 mm decade-1. The increment in PWV varies between 4.5 and 6.5 % per degree Celsius rise in temperature, which is comparable to the theoretical rate of the Clausius

  7. Germany knows mining

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

    NONE

    Whether it is the nuance of precision or robust rock breaking strength, German suppliers have the expertise. Germany has about 120 companies in the mining equipment industry, employing some 16,000 people. The article describes some recent developments of the following companies: DBT, Liebherr, Atlas Copco, BASF, Boart Longyear, Eickhoff, IBS, Maschinenfabrik Glueckauf, Komatsu, TAKRA, Terex O & R, Thyssen Krupp Foerdertechnik and Wirtgen. 7 photos.

  8. Concentrating Solar Power Projects in Germany | Concentrating Solar Power |

    Science.gov Websites

    ;alphabetical by project name. You can browse a project profile by clicking on the project name. Jülich Solar NREL Germany Concentrating solar power (CSP) projects in Germany are listed belowâ€"

  9. Educational Systems and Rising Inequality: Eastern Germany after Unification

    ERIC Educational Resources Information Center

    von Below, Susanne; Powell, Justin J. W.; Roberts, Lance W.

    2013-01-01

    Educational systems considerably influence educational opportunities and the resulting social inequalities. Contrasting institutional regulations of both structures and contents, the authors present a typology of educational system types in Germany to analyze their effects on social inequality in eastern Germany after unification. After 1990, the…

  10. Monovalent virus-like particle vaccine protects guinea pigs and nonhuman primates against infection with multiple Marburg viruses.

    PubMed

    Swenson, Dana L; Warfield, Kelly L; Larsen, Tom; Alves, D Anthony; Coberley, Sadie S; Bavari, Sina

    2008-05-01

    Virus-like particle (VLP)-based vaccines have the advantage of being morphologically and antigenically similar to the live virus from which they are derived. Expression of the glycoprotein and VP40 matrix protein from Lake Victoria marburgvirus (MARV) results in spontaneous production of VLPs in mammalian cells. Guinea pigs vaccinated with Marburg virus VLPs (mVLPs) or inactivated MARV (iMARV) develop homologous humoral and T-cell responses and are completely protected from a lethal homologous MARV challenge. To determine whether mVLPs based on the Musoke (aka Lake Victoria) isolate of MARV could broadly protect against diverse isolates of MARV, guinea pigs were vaccinated with mVLPs or iMARV-Musoke and challenged with MARV-Musoke, -Ravn or -Ci67. Prior to challenge, the mVLP- and iMARV-vaccinated guinea pigs had high levels of homologous MARV-Musoke and heterologous MARV-Ravn and -Ci67 antibodies. The Musoke-based mVLPs and iMARV vaccines provided complete protection in guinea pigs against viremia, viral replication and pathological changes in tissues, and lethal disease following challenge with MARV-Musoke, -Ravn or -Ci67. Guinea pigs vaccinated with RIBI adjuvant alone and infected with guinea pig-adapted MARV-Musoke, -Ravn or -Ci67 had histopathologic findings similar to those seen in the nonhuman primate model for MARV infection. Based on the strong protection observed in guinea pigs, we next vaccinated cynomolgus macaques with Musoke-based mVLPs and showed the VLP-vaccinated monkeys were broadly protected against three isolates of MARV (Musoke, Ravn and Ci67). Musoke mVLPs are effective at inducing broad heterologous immunity and protection against multiple MARV isolates.

  11. Marburg virus inclusions: A virus-induced microcompartment and interface to multivesicular bodies and the late endosomal compartment.

    PubMed

    Dolnik, Olga; Stevermann, Lea; Kolesnikova, Larissa; Becker, Stephan

    2015-01-01

    Filovirus infection of target cells leads to the formation of virally induced cytoplasmic inclusions that contain viral nucleocapsids at different stages of maturation. While the role of the inclusions has been unclear since the identification of Marburg and Ebola viruses, it recently became clear that the inclusions are the sites of viral replication, nucleocapsid formation and maturation. Live cell imaging analyses revealed that mature nucleocapsids are transported from inclusions to the filopodia, which represent the major budding sites. Moreover, inclusions recruit cellular proteins that have been shown to support the transport of nucleocapsids. For example, the tumor susceptibility gene 101 protein (Tsg101) interacts with a late domain motif in the nucleocapsid protein NP and recruits the actin-nucleation factor IQGAP1. Complexes of nucleocapsids together with Tsg101 and IQGAP1 are then co-transported along actin filaments. We detected additional proteins (Alix, Nedd4 and the AAA-type ATPase VPS4) of the endosomal sorting complex required for transport (ESCRT) that are recruited into inclusions. Together, the results suggest that nucleocapsids recruit the machinery that enhances viral budding at the plasma membrane. Furthermore, we identified Lamp1 as a marker of the late endosomal compartment in inclusions, while ER, Golgi, TGN and early endosomal markers were absent. In addition, we observed that LC3, a marker of autophagosomal membranes, was present in inclusions. The 3D structures of inclusions show an intricate structure that seems to accommodate an intimate cooperation between cellular and viral components with the intention to support viral transport and budding. Copyright © 2015 Elsevier GmbH. All rights reserved.

  12. 29 CFR 785.8 - Effect of custom, contract, or agreement.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Effect of custom, contract, or agreement. 785.8 Section 785... for Determination of Hours Worked § 785.8 Effect of custom, contract, or agreement. The principles are... special statutory exceptions discussed in §§ 785.9 and 785.26. [35 FR 15289, Oct. 1, 1970] ...

  13. Parasitism of Trombidium brevimanum larvae on agrobiont linyphiid spiders from Germany.

    PubMed

    Tomić, Vladimir; Mąkol, Joanna; Stamenković, Srdjan; Büchs, Wolfgang; Prescher, Sabine; Sivčev, Ivan; Graora, Draga; Sivčev, Lazar; Gotlin-Čuljak, Tatjana; Dudić, Boris

    2015-08-01

    An experiment on three differently-managed agricultural fields in Ahlum, Germany, which aimed at establishing the impact of different management systems on the biodiversity of predators and decomposers, yielded a significant number of spiders parasitized by larvae of Trombidium brevimanum (Actinotrichida, Parasitengona, Trombidiidae). Spider data from the whole sampling period (September 2010-July 2012), indicated that ectoparasitic larvae were recorded only on spiders in pitfall traps in the period of June-July 2011. In this period, only eight species of Linyphiidae--out of 42 species assigned to nine spider families recorded from the study area--were parasitized by mites; considerable levels of parasitism were recorded on Erigone atra, E. dentipalpis, and Oedothorax apicatus. The highest prevalence of parasitism was recorded on the organic field for E. atra (29%), while on the integrated and conventional fields significantly fewer parasitized spiders were observed. The preferred attachment sites on the spider host were regions with softer cuticle, especially regions on the carapace and on the abdomen, adjacent to the pedicel.

  14. Proceedings of the 26th Project Integration Meeting

    NASA Technical Reports Server (NTRS)

    1986-01-01

    Progress made by the Flat-plate Solar Array (FSA) Project is described for the period July 1985 to April 1986. Included are reports on silicon sheet growth and characterization, silicon material, process development, high-efficienty cells, environmental isolation, engineering sciences, and reliability physics. Also included are technical and plenary presentations made at the 26th Project Integration Meeting (PIM) held on April 29 to 30 and May 1, 1986.

  15. [Continuing Medical Education in Germany - mandatory and voluntary obligations].

    PubMed

    Böthin, Elke

    2013-01-01

    After 1945 the common medical training infrastructure was broken up into two different political systems. While in the Federal Republic of Germany the structure was based on physicians' self-governance, in the German Democratic Republic medical professional structures were organised by the government. After the unification of the two German states, which took place on October 3, 1990, the centralistic structure was replaced by the system of physician self-governance. Before January 1, 2004, continuing medical education (CME) in West Germany relied on a system of voluntary obligations. In East Germany, though, professional CMEs were compulsory; they were called "obligatorische periphere Fortbildung." Based on 15 expert interviews on the topic of "CME in Germany", the different circumstances and conditions were analysed taking account of the historical background. Only selected professionals with experience in both German states (one with a federal, the other with a centralistic system), were chosen for the survey. Copyright © 2013. Published by Elsevier GmbH.

  16. Transferring climate research results to stakeholder needs in Northern Germany

    NASA Astrophysics Data System (ADS)

    Meinke, Insa

    2013-04-01

    The North German Climate Office was established in 2006 at the Institute for Coastal Research at the Helmholtz-Zentrum Geesthacht, Germany as consequence of an increased public information need regarding coastal climate change and its impacts in Northern Germany. The service is characterized by an intensive dialogue between regional climate research and stakeholders in Northern Germany. About once a week scientists of the North German climate office are invited to contribute to public dialogue events. Also, numerous direct inquiries are answered and expert interviews are conducted. From this dialogue process specific stakeholder information needs are localized and analysed to develop tailored information products. To provide easy and user specific access to research results interactive web tools are developed. One example is the North German climate atlas, an interactive web tool on possible future climate change in Northern Germany. Another interactive web tool is informing on present and future coastal protection needs in Northern Germany. Another aim of our information products is to assess and summarize the existing scientific knowledge on climate, climate change and impacts in Northern Germany. A mini IPCC-like regional assessment report has been published in 2010, which is summarizing, discussing and assessing the scientific knowledge on regional climate, climate change and impacts as well as possible adaptation strategies in the metropolitan region of Hamburg.

  17. Incidence of malignant mesothelioma in Germany 2009-2013.

    PubMed

    Lehnert, Martin; Kraywinkel, Klaus; Heinze, Evelyn; Wiethege, Thorsten; Johnen, Georg; Fiebig, Julia; Brüning, Thomas; Taeger, Dirk

    2017-02-01

    The malignant mesothelioma is a rare malignancy and mainly caused by occupational exposure to asbestos. German cancer registries are providing a national database to investigate temporal and regional patterns of mesothelioma incidence. These may be of interest for healthcare planning and for surveillance programs aiming at the formerly exposed workforce. We analyzed population-based incidence data of malignant mesothelioma by site, type, sex, age, as well as district and state of patient's residence. Age-standardized incidence rates (AIRs40+) were calculated according to the European standard population truncated to the age of 40 years and older. We present rates at national, state, and district level and trends of incidence of northern states of Germany. In total, 7,547 malignant mesotheliomas were reported to German cancer registries diagnosed between 2009 and 2013-90% located to the pleura. On average, 1,198 men and 312 women were affected each year. We estimated AIR40+ of 4.77 in 100,000 German men and 0.98 in 100,000 German women. Regional clusters were predominantly located to the seaports of West Germany. The highest regional AIR40+ was 20 per 100,000 men. Corresponding rates in northeast Germany were between 2 and 4 per 100,000 men. Regional clusters of high incidence indicate districts with former shipyards and steel industry, but predominantly in the western part of Germany. The West-to-East difference corresponds to patterns of mortality. Twenty years after banning asbestos in Germany, Bremen and Hamburg are presenting the highest mesothelioma incidence but show steadily decreasing trends.

  18. 29 CFR 779.262 - Excise taxes at the retail level.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 3 2011-07-01 2011-07-01 false Excise taxes at the retail level. 779.262 Section 779.262... Coverage Excise Taxes § 779.262 Excise taxes at the retail level. (a) Federal excise taxes are imposed at the retail level on highway vehicle fuels other than gasoline under the provisions of 26 U.S.C. 4041...

  19. 29 CFR 779.262 - Excise taxes at the retail level.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 3 2013-07-01 2013-07-01 false Excise taxes at the retail level. 779.262 Section 779.262... Coverage Excise Taxes § 779.262 Excise taxes at the retail level. (a) Federal excise taxes are imposed at the retail level on highway vehicle fuels other than gasoline under the provisions of 26 U.S.C. 4041...

  20. 29 CFR 779.262 - Excise taxes at the retail level.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 3 2012-07-01 2012-07-01 false Excise taxes at the retail level. 779.262 Section 779.262... Coverage Excise Taxes § 779.262 Excise taxes at the retail level. (a) Federal excise taxes are imposed at the retail level on highway vehicle fuels other than gasoline under the provisions of 26 U.S.C. 4041...

  1. 29 CFR 779.262 - Excise taxes at the retail level.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 3 2014-07-01 2014-07-01 false Excise taxes at the retail level. 779.262 Section 779.262... Coverage Excise Taxes § 779.262 Excise taxes at the retail level. (a) Federal excise taxes are imposed at the retail level on highway vehicle fuels other than gasoline under the provisions of 26 U.S.C. 4041...

  2. Career Development in Germany.

    ERIC Educational Resources Information Center

    Hass, Hubert

    In Germany, after elementary school, the school system splits into three branches, with students either preparing for an apprenticeship or continuing in school. A second system exists, parallel to this education system, which combines general education with basic professional training. The first key career decision point is in Grade 4, when…

  3. [Infant mortality in Germany (2008-2012)--lower in the former German Democratic Republic?].

    PubMed

    Trotter, A; Schnakenburg, C v; Pohlandt, F

    2014-08-01

    German infant mortality is ranked near the median of European countries. In Germany infant mortality is significantly higher in the German Federal Republic compared with the former German Democratic Republic. This is often used as reason for a call for structural requirements and minimum caseload for the care for very low birth weight infants. Neonatal and infant mortality were calculated for the 16 German federal states with data from the German statistical federal office for the years 2008-2012. Considerable variations were found for the neonatal (1.34-3.61‰, total Germany 2.31‰) and the infant (2.38-5.20‰, 3.47‰) mortality. The rate of stillborn infants was 3.56‰. A lower neonatal mortality in the former German Democratic Republic (1.62‰ vs. 2.44‰, p<0.0001, Chi-squared test) could not be confirmed for preterm infants with birth weight less than 1 500 g. In the former German Democratic Republic stillbirth was significantly more frequent in preterm infants with birth weight 500-999 g (p<0.0001). Combined stillbirth and neonatal mortality showed no difference between the German Federal Republic and former German Democratic Republic (5.45‰ and 5.29‰, respectively, n.s.; infants less than 500 g birth weight were excluded). The average number of preterm infants per perinatal centre and federal state had no influence on state specific neonatal mortality. If stillborn infants were accounted for no difference was found between the German Federal Republic and the former German Democratic Republic regarding mortality. Comparing infant mortality of different countries has to account for stillborn infants. Considerable variation of neonatal mortality is persisting throughout Germany despite structural requirements and introduction of a minimum caseload since 2005. A lower infant mortality in the former German Democratic Republic and implications drawn from are not supported by the presented nationwide data from the German statistical federal office

  4. The Marketisation of Guidance Services in Germany, France and Britain.

    ERIC Educational Resources Information Center

    Rees, Teresa; Bartlett, Will; Watts, A. G.

    1999-01-01

    Compares developments in Britain, France, and Germany, focusing on the trends toward marketing adult career guidance services. Describes how Germany's centralized system and the quasi-market based system in France might apply in Britain. (JOW)

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

    PubMed Central

    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

  6. Three frequency false-color image of Oberpfaffenhofen supersite in Germany

    NASA Technical Reports Server (NTRS)

    1994-01-01

    This is a three-frequency, false color image of the Oberpfaffenhofen supersite, an area just south-west of Munich in southern Germany. This image was acquired by the Spaceborne Imaging Radar-C and X-Band Synthetic Aperture Radar (SIR-C/X-SAR) aboard the Shuttle Endeavour, April 11, 1994. The image is centered at 48.09 degrees north, 11.29 degrees east. The dark area on the left is Lake Ammersee. The two smaller lakes are the Woerthsee and the Pilsensee. On the bottom is the tip of the Starnbergersee. The city of Munich is located just beyond the right of the image. The forested areas have a reddish tint (L-Band). THe green areas seen near both the Ammersee and the Pilsensee lakes indicate marshy areas. The agricultural fields in the upper right hand corner appear mostly in blue and green (X-band and C-band). The white areas are mostly urban areas, while the smooth surfaces of the lakes appear very dark. The Jet Propulsion Laboratory alternative photo number is P-43930.

  7. Lyophilisation of influenza, rabies and Marburg lentiviral pseudotype viruses for the development and distribution of a neutralisation -assay-based diagnostic kit.

    PubMed

    Mather, Stuart T; Wright, Edward; Scott, Simon D; Temperton, Nigel J

    2014-12-15

    Pseudotype viruses (PVs) are chimeric, replication-deficient virions that mimic wild-type virus entry mechanisms and can be safely employed in neutralisation assays, bypassing the need for high biosafety requirements and performing comparably to established serological assays. However, PV supernatant necessitates -80°C long-term storage and cold-chain maintenance during transport, which limits the scope of dissemination and application throughout resource-limited laboratories. We therefore investigated the effects of lyophilisation on influenza, rabies and Marburg PV stability, with a view to developing a pseudotype virus neutralisation assay (PVNA) based kit suitable for affordable global distribution. Infectivity of each PV was calculated after lyophilisation and immediate reconstitution, as well as subsequent to incubation of freeze-dried pellets at varying temperatures, humidities and timepoints. Integrity of glycoprotein structure following treatment was also assessed by employing lyophilised PVs in downstream PVNAs. In the presence of 0.5M sucrose-PBS cryoprotectant, each freeze-dried pseudotype was stably stored for 4 weeks at up to 37°C and could be neutralised to the same potency as unlyophilised PVs when employed in PVNAs. These results confirm the viability of a freeze-dried PVNA-based kit, which could significantly facilitate low-cost serology for a wide portfolio of emerging infectious viruses. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Estimated burden of fungal infections in Germany.

    PubMed

    Ruhnke, Markus; Groll, Andreas H; Mayser, Peter; Ullmann, Andrew J; Mendling, Werner; Hof, Herbert; Denning, David W

    2015-10-01

    In the late 1980's, the incidence of invasive fungal diseases (IFDs) in Germany was estimated with 36.000 IFDs per year. The current number of fungal infections (FI) occurring each year in Germany is still not known. In the actual analysis, data on incidence of fungal infections in various patients groups at risk for FI were calculated and mostly estimated from various (mostly national) resources. According to the very heterogenous data resources robust data or statistics could not be obtained but preliminary estimations could be made and compared with data from other areas in the world using a deterministic model that has consistently been applied in many countries by the LIFE program ( www.LIFE-worldwide.org). In 2012, of the 80.52 million population (adults 64.47 million; 41.14 million female, 39.38 million male), 20% are children (0-14 years) and 16% of population are ≥65 years old. Using local data and literature estimates of the incidence or prevalence of fungal infections, about 9.6 million (12%) people in Germany suffer from a fungal infection each year. These figures are dominated (95%) by fungal skin disease and recurrent vulvo-vaginal candidosis. In general, considerable uncertainty surrounds the total numbers because IFDs do not belong to the list of reportable infectious diseases in Germany and most patients were not hospitalised because of the IFD but a distinct underlying disease. © 2015 Blackwell Verlag GmbH.

  9. [A critical review of applied criminology].

    PubMed

    Vollbach, Alexander

    2016-01-01

    By reporting on a recent decision of the Regional Court (LG) of Marburg (Germany) calling attention to applied criminology, a concept still insufficiently considered in the administration of criminal justice, the paper argues that professional action in the execution of the sentence represents nothing else but applied criminology. Based on this assumption, the paper discusses practical diagnosis and correctional planning. Beyond that, the paper deals with the future of criminology. In the opinion of the author an important aspect for the future of criminology will be if it will be able to remain in touch with the world in which we live, as an independent empirical science. Applied criminology and its methodology constitute the link between science and practice.

  10. Racialised Norms in Apprenticeship Systems in England and Germany

    ERIC Educational Resources Information Center

    Chadderton, Charlotte; Wischmann, Anke

    2014-01-01

    In this paper, we consider the issue of the under-representation of young people from minority ethnic/migrant backgrounds in apprenticeships in England and Germany. Whilst there are many studies on apprenticeships in England and Germany, few focus on under-representation or discrimination, even fewer on ethnic under-representation, and there are…

  11. Germany's Armed Forces in the Second World War: Manpower, Armaments, and Supply.

    ERIC Educational Resources Information Center

    Balsamo, Larry T.

    1991-01-01

    Discusses the state of Germany's armed forces in World War II. Describes Germany's progress from inferior weaponry and unprepared military at the beginning of the war to superior weapons and fighting. Stresses heavy German dependence on horse drawn supply. Credits Germany's defeat to human attrition accelerated by Hitler's operational leadership.…

  12. [Pharmacological aspects of pain research in Germany].

    PubMed

    Niederberger, E; Kuner, R; Geißlinger, G

    2015-10-01

    In spite of several approved analgesics, the therapy of pain still constitutes a challenge due to the fact that the drugs do not exert sufficient efficacy or are associated with severe side effects. Therefore, the development of new and improved painkillers is still of great importance. A number of highly qualified scientists in Germany are investigating signal transduction pathways in pain, effectivity of new drugs and the so far incompletely investigated mechanisms of well-known analgesics in preclinical and clinical studies. The highlights of pharmacological pain research in Germany are summarized in this article.

  13. Liver transplantation in Germany.

    PubMed

    Tacke, Frank; Kroy, Daniela C; Barreiros, Ana Paula; Neumann, Ulf P

    2016-08-01

    Liver transplantation (LT) is a well-accepted procedure for end-stage liver disease in Germany. In 2015, 1489 patients were admitted to the waiting list (including 1308 new admissions), with the leading etiologies being fibrosis and cirrhosis (n = 349), alcoholic liver disease (n = 302), and hepatobiliary malignancies (n = 220). Organ allocation in Germany is regulated within the Eurotransplant system based on urgency as expressed by the Model for End-Stage Liver Disease score. In 2015, only 894 LTs (n = 48 from living donors) were performed at 23 German transplant centers, reflecting a shortage of organs. Several factors may contribute to the low number of organ donations. The German transplant legislation only accepts donation after brain death (not cardiac death), whereas advances in neurosurgery and a more frequently requested "palliative care" approach render fewer patients suitable as potential donors. The legislation further requires the active consent of the donor or first-degree relatives before donation. Ongoing debates within the German transplant field address the optimal management of patients with alcoholic liver cirrhosis, hepatocellular carcinoma (HCC), and cholangiocarcinoma and measures to increase living donor transplantations. As a result of irregularities at mainly 4 German transplant centers that were exposed in 2012, guiding principles updated by the German authorities have since implemented strict rules (including internal and external auditing, the 8-eyes principle, mandatory repeated testing for alcohol consumption) to prohibit any manipulations in organ allocation. In conclusion, we will summarize important aspects on the management of LT in Germany, discuss legal and organizational aspects, and highlight challenges mainly related to the relative lack of organ donations, increasing numbers of extended criteria donors, and the peculiarities of the recipient patients. Liver Transplantation 22 1136-1142 2016 AASLD. © 2016 American

  14. Secondary Education in Germany.

    ERIC Educational Resources Information Center

    Jonen, Gerdi

    This booklet provides a brief description of secondary education in Germany. The publication is part of a series that seeks to make the public aware of the education systems and traditions in all signatory states to the European Cultural Convention and to outline the essential problems these systems presently are facing. This short booklet…

  15. Germany in Europe 1963.

    ERIC Educational Resources Information Center

    Stanford Univ., CA.

    The results of the 10-week National Defense Education Act (NDEA) Third-Level Institute for Secondary School Teachers of German, conducted by Stanford University in Bad Boll, Germany, are compiled in individual reports written in both German and English by the 25 participants. Emphasizing close contact with the residents in their working and home…

  16. Status of pre-processing of waste electrical and electronic equipment in Germany and its influence on the recovery of gold.

    PubMed

    Chancerel, Perrine; Bolland, Til; Rotter, Vera Susanne

    2011-03-01

    Waste electrical and electronic equipment (WEEE) contains gold in low but from an environmental and economic point of view relevant concentration. After collection, WEEE is pre-processed in order to generate appropriate material fractions that are sent to the subsequent end-processing stages (recovery, reuse or disposal). The goal of this research is to quantify the overall recovery rates of pre-processing technologies used in Germany for the reference year 2007. To achieve this goal, facilities operating in Germany were listed and classified according to the technology they apply. Information on their processing capacity was gathered by evaluating statistical databases. Based on a literature review of experimental results for gold recovery rates of different pre-processing technologies, the German overall recovery rate of gold at the pre-processing level was quantified depending on the characteristics of the treated WEEE. The results reveal that - depending on the equipment groups - pre-processing recovery rates of gold of 29 to 61% are achieved in Germany. Some practical recommendations to reduce the losses during pre-processing could be formulated. Defining mass-based recovery targets in the legislation does not set incentives to recover trace elements. Instead, the priorities for recycling could be defined based on other parameters like the environmental impacts of the materials. The implementation of measures to reduce the gold losses would also improve the recovery of several other non-ferrous metals like tin, nickel, and palladium.

  17. Tobacco Industry Influence on Science and Scientists in Germany

    PubMed Central

    Grüning, Thilo; Gilmore, Anna B.; McKee, Martin

    2006-01-01

    Using tobacco industry documents, we examined how and why the tobacco industry sought to influence science and scientists in Germany as a possible factor in explaining the German opposition to stricter tobacco regulation. Smoking and health research programs were organized both separately by individual tobacco companies and jointly through their German trade organization. An extensive network of scientists and scientific institutions with tobacco industry links was developed. Science was distorted in 5 ways: suppression, dilution, distraction, concealment, and manipulation. The extent of tobacco industry influence over the scientific establishment in Germany is profound. The industry introduced serious bias that probably influenced scientific and public opinion in Germany. This influence likely undermined efforts to control tobacco use. PMID:16317203

  18. Occurrence of Antibiotics in Surface and Groundwater of a Drinking Water Catchment Area in Germany.

    PubMed

    Burke, Victoria; Richter, Doreen; Greskowiak, Janek; Mehrtens, Anne; Schulz, Lena; Massmann, Gudrun

    2016-07-01

    The contamination of the aquatic environment with organic micropollutants, such as veterinary pharmaceuticals, has become an increasingly serious problem and has aroused attention in the course of the last decades. This study presents a screening for a series of veterinary antibiotics, potentially introduced by the application of liquid manure, in ground- and surface water of a drinking water catchment in Lower Saxony, Germany. Of the 26 compounds analyzed, eight, including sulfadiazine, sulfapyridine, sulfamethoxazole, trimethoprim, dehydrato-erythromycin, sulfadimidine, tylosin, and tetracycline were detected in surface water samples. Trimethoprim was detected in 11 out of 15 shallow groundwater samples, indicating its high environmental relevance. Column sorption experiments conducted on trimethoprim show a comparatively moderate sorption affinity to sandy aquifer material with a retardation coefficient of 5.7.

  19. STS-26 MS Lounge floats in life raft during JSC WETF exercises

    NASA Technical Reports Server (NTRS)

    1988-01-01

    STS-26 Discovery, Orbiter Vehicle (OV) 103, Mission Specialist (MS) John M. Lounge, wearing the newly designed launch and entry suit (LES), floats in single-occupant life raft in JSC Weightless Environment Training Facility (WETF) Bldg 29 pool. Lounge pulls cord on life raft and enlists the aid of a SCUBA-equipped diver. The simulation of the escape and rescue operations utilized the crew escape system (CES) pole method of egress from the Space Shuttle. Lounge is wearing gear like that each STS-26 crewmember and subsequent crews will carry onboard during launch.

  20. Vector-borne diseases in cats in Germany.

    PubMed

    Bergmann, Michèle; Hartmann, Katrin

    2017-10-17

    Vector-borne diseases (VBDs) are caused by a wide range of pathogens, which are transmitted by a variety of vectors, such as ticks and fleas. As a result of climate changes, more vector-borne diseases are becoming endemic in Germany, not only in dogs, but also in cats. For some of the pathogens prevalence data still need to be investigated in Germany. However, natural infections with Bartonella, Anaplasma, haemotropic Mycoplasma and Borrelia species have already been described in German cats. Clinical relevance of these pathogens is not fully understood, and it is still unknown, why most infected cats stay asymptomatic and which predisposing factors contribute to the development of clinical signs in cats. Moreover, there is a risk of zoonotic transmission for some of the pathogens, e.  g., for some Bartonella spp. infections that are associated with cat scratch disease in humans. Due to the increasing number of VBDs in cats in Germany, preventive measures, such as the use of acaricides and insecticides, should be performed on a regular base in order to reduce the risk of these infections.

  1. Single-Injection Vaccine Protects Nonhuman Primates against Infection with Marburg Virus and Three Species of Ebola Virus▿

    PubMed Central

    Geisbert, Thomas W.; Geisbert, Joan B.; Leung, Anders; Daddario-DiCaprio, Kathleen M.; Hensley, Lisa E.; Grolla, Allen; Feldmann, Heinz

    2009-01-01

    The filoviruses Marburg virus and Ebola virus cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (VSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Here, we performed a proof-of-concept study in order to determine the potential of having one single-injection vaccine capable of protecting nonhuman primates against Sudan ebolavirus (SEBOV), Zaire ebolavirus (ZEBOV), Cote d'Ivoire ebolavirus (CIEBOV), and Marburgvirus (MARV). In this study, 11 cynomolgus monkeys were vaccinated with a blended vaccine consisting of equal parts of the vaccine vectors VSVΔG/SEBOVGP, VSVΔG/ZEBOVGP, and VSVΔG/MARVGP. Four weeks later, three of these animals were challenged with MARV, three with CIEBOV, three with ZEBOV, and two with SEBOV. Three control animals were vaccinated with VSV vectors encoding a nonfilovirus GP and challenged with SEBOV, ZEBOV, and MARV, respectively, and five unvaccinated control animals were challenged with CIEBOV. Importantly, none of the macaques vaccinated with the blended vaccine succumbed to a filovirus challenge. As expected, an experimental control animal vaccinated with VSVΔG/ZEBOVGP and challenged with SEBOV succumbed, as did the positive controls challenged with SEBOV, ZEBOV, and MARV, respectively. All five control animals challenged with CIEBOV became severely ill, and three of the animals succumbed on days 12, 12, and 14, respectively. The two animals that survived CIEBOV infection were protected from subsequent challenge with either SEBOV or ZEBOV, suggesting that immunity to CIEBOV may be protective against other species of Ebola virus. In conclusion, we developed an immunization scheme based on a single-injection vaccine that protects nonhuman primates against lethal challenge with representative strains of all human pathogenic filovirus species

  2. Anatomy during the Third Reich--the Institute of Anatomy at the University of Marburg, as an example.

    PubMed

    Aumüller, G; Grundmann, K

    2002-05-01

    A complete documentation of German anatomical science and its representatives during the period of national socialism has not been published as yet--contrary to the situation in other medical disciplines. Instead of German anatomists, American anatomists have occasionally addressed this issue during their meetings and have reported on special aspects, such as the use of Nazi symbols in anatomical textbooks and atlases (Pernkopf 1952) and the use of corpses of justice victims for anatomical research and student education. Also, the genesis of the atrocious collection of "racial" skulls, initiated along with the SS-institution of the "Ahnenerbe" by the anatomist August Hirt of Strasbourg (who ordered more than 90 inmates from concentration camps to be murdered in the gas chamber built in the concentration camp of Natzweiler-Struthof close to Strasbourg, Alsace) has been described by Frederic Kasten and others. A broader view of the patterns of behaviour and political actions and fates of contemporary scientists, ranging from dismissal to clandestine opportunism, affirmative cooperation and fanatic activism can be obtained by the analysis of the activities in research, medical education and academic positions of the following members of the Institute of Anatomy at the Philipp-University in Marburg: Ernst Göppert, Eduard Jacobshagen, Ernst-Theodor Nauck, Adolf Dabelow, Helmut Becher and Alfred Benninghoff, whose activities and fates differ in several respects and allow more general deductions. Also, the individual fates of a number of prosecuted Jewish anatomists (Wassermann, München; Poll, Hamburg), of devoted and active members of the Nazi party (Clara, Leipzig; Blotevogel, Breslau) and of criminal fanatics (Hirt, Strasbourg; Kremer, Münster) are briefly discussed. The present contribution is an attempt to initiate a more detailed study of all German departments of anatomy during the Hitler regime and to generate a public discussion among the younger generation of

  3. Single-injection vaccine protects nonhuman primates against infection with marburg virus and three species of ebola virus.

    PubMed

    Geisbert, Thomas W; Geisbert, Joan B; Leung, Anders; Daddario-DiCaprio, Kathleen M; Hensley, Lisa E; Grolla, Allen; Feldmann, Heinz

    2009-07-01

    The filoviruses Marburg virus and Ebola virus cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (VSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Here, we performed a proof-of-concept study in order to determine the potential of having one single-injection vaccine capable of protecting nonhuman primates against Sudan ebolavirus (SEBOV), Zaire ebolavirus (ZEBOV), Cote d'Ivoire ebolavirus (CIEBOV), and Marburgvirus (MARV). In this study, 11 cynomolgus monkeys were vaccinated with a blended vaccine consisting of equal parts of the vaccine vectors VSVDeltaG/SEBOVGP, VSVDeltaG/ZEBOVGP, and VSVDeltaG/MARVGP. Four weeks later, three of these animals were challenged with MARV, three with CIEBOV, three with ZEBOV, and two with SEBOV. Three control animals were vaccinated with VSV vectors encoding a nonfilovirus GP and challenged with SEBOV, ZEBOV, and MARV, respectively, and five unvaccinated control animals were challenged with CIEBOV. Importantly, none of the macaques vaccinated with the blended vaccine succumbed to a filovirus challenge. As expected, an experimental control animal vaccinated with VSVDeltaG/ZEBOVGP and challenged with SEBOV succumbed, as did the positive controls challenged with SEBOV, ZEBOV, and MARV, respectively. All five control animals challenged with CIEBOV became severely ill, and three of the animals succumbed on days 12, 12, and 14, respectively. The two animals that survived CIEBOV infection were protected from subsequent challenge with either SEBOV or ZEBOV, suggesting that immunity to CIEBOV may be protective against other species of Ebola virus. In conclusion, we developed an immunization scheme based on a single-injection vaccine that protects nonhuman primates against lethal challenge with representative strains of all human pathogenic

  4. 26. Photocopy of photograph dated 1930; photographer unknown; original filed ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    26. Photocopy of photograph dated 1930; photographer unknown; original filed as MR2.9/SP8/p343 in Audio-Visual Collection of Minnesota Historical Society, St. Paul; THREE-QUARTER VIEW SHOWING WEST SIDE AND SOUTH FRONT SHORTLY AFTER COMPLETION; LOOKING NORTHEAST - Northwest Airways Hangar & Administration Building, 590 Bayfield Street, St. Paul Downtown Airport (Holman), Saint Paul, Ramsey County, MN

  5. A Single Amino Acid Change in the Marburg Virus Glycoprotein Arises during Serial Cell Culture Passages and Attenuates the Virus in a Macaque Model of Disease.

    PubMed

    Alfson, Kendra J; Avena, Laura E; Delgado, Jenny; Beadles, Michael W; Patterson, Jean L; Carrion, Ricardo; Griffiths, Anthony

    2018-01-01

    Marburg virus (MARV) causes disease with high case fatality rates, and there are no approved vaccines or therapies. Licensing of MARV countermeasures will likely require approval via the FDA's Animal Efficacy Rule, which requires well-characterized animal models that recapitulate human disease. This includes selection of the virus used for exposure and ensuring that it retains the properties of the original isolate. The consequences of amplification of MARV for challenge studies are unknown. Here, we serially passaged and characterized MARV through 13 passes from the original isolate. Surprisingly, the viral genome was very stable, except for a single nucleotide change that resulted in an amino acid substitution in the hydrophobic region of the signal peptide of the glycoprotein (GP). The particle/PFU ratio also decreased following passages, suggesting a role for the amino acid in viral infectivity. To determine if amplification introduces a phenotype in an animal model, cynomolgus macaques were exposed to either 100 or 0.01 PFU of low- and high-passage-number MARV. All animals succumbed when exposed to 100 PFU of either passage 3 or 13 viruses, although animals exposed to the high-passage-number virus survived longer. However, none of the passage 13 MARV-exposed animals succumbed to 0.01-PFU exposure compared to 75% of passage 3-exposed animals. This is consistent with other filovirus studies that show some particles that are unable to yield a plaque in cell culture can cause lethal disease in vivo . These results have important consequences for the design of experiments that investigate MARV pathogenesis and that test the efficacy of MARV countermeasures. IMPORTANCE Marburg virus (MARV) causes disease with a high case fatality rate, and there are no approved vaccines or therapies. Serial amplification of viruses in cell culture often results in accumulation of mutations, but the effect of such cell culture passage on MARV is unclear. Serial passages of MARV

  6. Orthopedics research output from China, USA, UK, Japan, Germany and France: A 10-year survey of the literature.

    PubMed

    Xin, Z; Jin, C; Zhengrong, G; Liehu, C; Weizong, W; Quan, L; Xiao, C; Jiacan, S

    2016-11-01

    In the past decade, researchers have made great progress in the field of Orthopedics. However, the research status of different countries is unclear. To summarize the number of published articles, we assessed the cumulative impact factors in top orthopedic journals. The aims of the study were to measure: 1) the quality and quantity of publications in orthopedics-related journals from China and other five counties, 2) the trend of the number of publications in orthopedics-related journals. The related journals were selected based on the 2014 scientific citation index (SCI) and articles were searched based on the PubMed database. To assess the quantity and quality of research output, the number of publications including clinical trials, randomized controlled trials, meta-analyses, case reports, reviews, citations, impact factors, number of articles in the top 10 journals and most popular journals were recorded. A total of 143,138 orthopedics articles were published from 2005 to 2014. The USA accounts for 24.9% (35,763/143,138) of the publications, followed by UK (7878/143,138 (5.5%)), Japan (7133/143,138 (5.0%)), Germany (5942/143,138 (4.2%)), China (4143/143,138 (2.9%)) and France (2748/143,138 (1.9%)). The ranking for accumulated impact factors as follows: USA, UK, Japan, Germany, France and China. The mean impact factor's order is USA, China, Germany, Japan, France, UK, and interestingly the mean impact factors in Japan is similar to the Germany in 2005-2014. The USA had the highest percentage of articles in the top 10 journals, while China owns the least. The USA had the highest number of average citations, while Japan had lowest number of average citations. According to this study, we can conclude that the USA has had been leading the orthopedics research in the past 10 years. Although China still falls behind, it has made considerable progress in the orthopedics research, not only in quantity but also quality. IV. Copyright © 2016. Published by Elsevier Masson

  7. Flood of June 26-29, 2006, Mohawk, Delaware, and Susquehanna River Basins, New York

    USGS Publications Warehouse

    Suro, Thomas P.; Firda, Gary D.; Szabo, Carolyn O.

    2009-01-01

    A stalled frontal system caused tropical moisture to be funneled northward into New York, causing severe flooding in the Mohawk, Delaware, and Susquehanna River basins during June 26-29, 2006. Rainfall totals for this multi-day event ranged from 2 to 3 inches to greater than 13 inches in southern New York. The storm and flooding claimed four lives in New York, destroyed or damaged thousands of homes and businesses, and closed hundreds of roads and highways. Thousands of people evacuated their homes as floodwaters reached new record elevations at many locations within the three basins. Twelve New York counties were declared Federal disaster areas, more than 15,500 residents applied for disaster assistance, and millions of dollars in damages resulted from the flooding. Disaster-recovery assistance for individuals and businesses adversely affected by the floods of June 2006 reached more than $227 million. The National Weather Service rainfall station at Slide Mountain recorded storm totals of more than 8 inches of rainfall, and the stations at Walton and Fishs Eddy, NY, recorded storm totals of greater than 13 inches of rainfall. The U.S. Geological Survey (USGS) stream-gaging stations at Mohawk River at Little Falls, West Branch Delaware River at Hale Eddy, and Susquehanna River at Vestal, NY, among others, recorded peak discharges of 35,000 ft3/s, 43,400 ft3/s, and 119,000 ft3/s respectively, with greater than 100-year recurrence intervals. The peak water-surface elevation 21.47 ft and the peak discharge 189,000 ft3/s recorded on June 28, 2006, at the Delaware River at Port Jervis stream-gaging station were the highest recorded since the flood of August 1955. At the Susquehanna River at Conklin, NY, stream-gaging station, which has been in operation since 1912, the peak water-surface elevation 25.02 ft and peak discharge 76,800 ft3/s recorded on June 28, 2006, exceeded the previous period-of-record maximums that were set during the flood of March 1936. Documented

  8. Paint removal activities in Germany

    NASA Astrophysics Data System (ADS)

    Holbein, R.; Arnolds-Mayer, G.

    1993-03-01

    To replace paint removing chemicals containing chlorinated hydrocarbons several alternative paint stripping methods have been developed or are under study in Germany: high pressure water stripping; plastic media blasting; use of alcalic and acid activated softeners; CO2 pellet blasting; and laser application.

  9. Using IRI and GSM TIP model results as environment for HF radio wave propagation model during the geomagnetic storm occurred on September 26-29, 2011

    NASA Astrophysics Data System (ADS)

    Kotova, D. S.; Klimenko, M. V.; Klimenko, V. V.; Zakharov, V. E.; Ratovsky, K. G.; Nosikov, I. A.; Zhao, B.

    2015-11-01

    This paper analyses the geomagnetic storm on September 26-29, 2011. We compare the calculation results obtained using the Global Self-consistent Model of the Thermosphere, Ionosphere and Protonosphere (GSM TIP) and IRI-2012 (Bilitza et al., 2014) model with ground-based ionosonde data of stations at different latitudes and longitudes. We examined physical mechanisms responsible for the formation of ionospheric effects during the main phase of geomagnetic storm that occurred at the rising phase of the 24th solar cycle. We used numerical results obtained from IRI-2012 and GSM TIP models as propagation environment for HF signals from an equatorial transmitter during quiet and disturbed conditions. We used the model of HF radio wave propagation developed in I. Kant Baltic Federal University (BFU) that is based on the geometrical optics approximation. We compared the obtained radio paths in quiet conditions and during the main and recovery storm phases and evaluated radio wave attenuation in different media models.

  10. Epidermolysis bullosa care in Germany.

    PubMed

    Bruckner-Tuderman, Leena

    2010-04-01

    Until 2003, no structures existed in Germany for special care of patients with rare diseases, such as epidermolysis bullosa (EB). At that point, the Federal Ministry of Education and Research announced a clinical research program-networks for rare diseases. The Network Epidermolysis Bullosa (EB Network), coordinated from the Department of Dermatology, University Medical Center Freiburg, has operated since October 2003 with the goal of improving diagnostics and clinical management, elucidating disease mechanisms, and development of novel therapies for EB (www.netzwerk-eb.de). Future goals of the EB Network include securing the clinical-diagnostic and IT structures established with grant support and focusing research on molecular disease mechanisms in EB and novel biologically valid therapies. Intensive collaborations with other networks for rare genetic diseases will generate durable structures in Germany and form a basis for future international consortia. Copyright 2010 Elsevier Inc. All rights reserved.

  11. Regional Climate Service in Northern Germany -The North German Climate Office

    NASA Astrophysics Data System (ADS)

    Meinke, I.; Von Storch, H.

    2012-12-01

    The North German Climate Office was established in 2006 at the Institute for Coastal Research at the Helmholtz-Zentrum Geesthacht, Germany as consequence of an increased public information need regarding coastal climate change and its impacts in Northern Germany. The service is characterized by an intensive dialogue between regional climate research and stakeholders in Northern Germany. About once a week scientists of the North German climate office are invited to contribute to public dialogue events. Also numerous direct inquiries are answered and expert interviews are conducted. From this dialogue process specific stakeholder information needs are localized and analysed to develop tailored information products. To provide easy and user specific access to research results interactive web tools are developed. One example is the North German climate atlas, an interactive web tool on possible future climate change in Northern Germany. Another interactive web tool is informing on present and future coastal protection needs in Northern Germany. Another aim of our information products is to assess and summarize the existing scientific knowledge on climate, climate change and impacts in Northern Germany. A mini IPCC-like regional assessment report has been published in 2010, which is summarizing, discussing and assessing the scientific knowledge on regional climate, climate change and impacts as well as possible adaptation strategies in the metropolitan region of Hamburg.

  12. Elimination of terrestrial rabies in Germany using oral vaccination of foxes.

    PubMed

    Müller, Thomas; Bätza, Hans-Joachim; Freuling, Conrad; Kliemt, Anke; Kliemt, Jeannette; Heuser, Rolf; Schlüter, Hartmut; Selhorst, Thomas; Vos, Adriaan; Mettenleiter, Thomas C

    2012-01-01

    Oral rabies vaccination (ORV) has become the method of choice in fox rabies control in Europe. During the past three decades fox-mediated rabies virtually disappeared from Western and Central Europe. Following Switzerland, Germany was the second European country to launch ORV field trials on its territory in 1983. This paper provides a historical overview on the emergence of fox rabies in Germany; describing the basic principles and milestones of the German rabies eradication programme and presenting results of two decades of efforts to control the disease in foxes. Also, setbacks as well as country-specific differences and particularities on Germany's long way to rabies elimination in comparison to other European countries are addressed. Since the first field trials in Germany the number of rabies cases steadily decreased from 10 484 in 1983 to three cases recorded in 2006. On February 3rd 2006 the last case of terrestrial rabies in Germany was detected in a fox near the town of Mainz, Rhineland-Palatinate. In 2008, ORV ceased after 25 years and Germany was officially declared as free from terrestrial rabies. The German rabies eradication programme did cost approximately 100 million euro of which 37 million euro were covered by the EU. For the future, efforts should focus on maintaining a rabies free status by implementing measures to prevent reintroduction of terrestrial rabies from endemic countries.

  13. STS-26 crewmembers pose for onboard portrait on middeck with 51L mementos

    NASA Image and Video Library

    1988-10-03

    STS026-08-007 (29 Sept-3 Oct 1988) --- An in-space crew portrait on the middeck of Discovery. Left to right are Astronauts David C. Hilmers, George D. Nelson, Frederick H. (Rick) Hauck, John M. (Mike) Lounge and Richard O. Covey (front). The crew portrait for STS 51-L, its flight insignia and the STS 26 flight insignia are at top edge of the frame. This photo was shown by the STS 26 astronaut crew during its Oct. 11, l988 post-flight press conference.

  14. Tularaemia in southwest Germany: Three cases of tick-borne transmission.

    PubMed

    Boone, I; Hassler, D; Nguyen, T; Splettstoesser, W D; Wagner-Wiening, C; Pfaff, G

    2015-07-01

    Tularaemia, caused by Francisella tularensis, is an endemic zoonosis frequently occurring in southwest Germany. Since 2005 there is an increase in the number of reported cases of tularaemia in Germany. We report on two cases of ulceroglandular tularaemia and one case of glandular tularaemia that occurred in the summer of 2012 and 2013 in two counties in the Federal State of Baden-Wuerttemberg. Bacteria were transmitted through tick bites, which to date has only rarely been reported in Germany. Inadequate treatment of the patients and an aggravation of clinical symptoms were caused by a delay between disease onset and the detection of the pathogen. Although contact to or consumption of infected hares are the most often reported transmission routes of tularaemia in Germany, tick-bites should also be taken into account. Health professionals should include Francisella tularensis in the differential diagnosis of patients with fever and/or ulcerative lymphadenopathy following a tick bite. Copyright © 2015 Elsevier GmbH. All rights reserved.

  15. The epidemiology of sickle cell disease in Germany following recent large-scale immigration.

    PubMed

    Kunz, Joachim B; Cario, Holger; Grosse, Regine; Jarisch, Andrea; Lobitz, Stephan; Kulozik, Andreas E

    2017-07-01

    The epidemiology of sickle cell disease (SCD) in Germany is currently changing fundamentally with ongoing immigration. Here, we address the challenges resulting from the increased frequency, that is, the morbidity, and mortality of SCD in this population. The number of immigrants with SCD was estimated based on the data of the German central registry of migrants (2007-2015) and published epidemiologic data. Additional data analysis was based on nationwide aggregated data from the diagnosis-related groups' (DRG) statistics of the German Federal Statistical Office. The total number of patients with SCD among migrants was estimated at 2,016 in 2007 and 3,216 in 2015, thus showing a 60% increase, which was particularly remarkable during 2014 and 2015. The countries of origin included those of West sub-Saharan Africa, followed by Syria, and other countries of the Middle East. In parallel, the number of SCD inpatient treatments increased from 780 in 2002 to 1,340 in 2015. Between 2012 and 2014, 42 patients with SCD died in hospital, mostly at an age of less than 5 years (n = 7) or over 30 years (n = 29). More than 3,000 patients with SCD are estimated to live among the immigrant population in Germany. In addition, the number of SCD patients of German nationality is not known. The increasing number of inpatient treatments and the death of young children from SCD indicate the need for a general newborn screening program and an increased awareness of this disease among medical practitioners in a country in which SCD used to be rare. © 2017 Wiley Periodicals, Inc.

  16. Transcatheter arterial embolisation in upper gastrointestinal bleeding in a sample of 29 patients in a gastrointestinal referral center in Germany.

    PubMed

    Heining-Kruz, S; Finkenzeller, T; Schreyer, A; Dietl, K H; Kullmann, F; Paetzel, C; Schedel, J

    2015-09-01

    This is a retrospective analysis of interventional embolisation performed with catheter angiography in 29 patients with upper gastrointestinal bleeding in the setting of a secondary care hospital. From April 2007 to February 2013, 29 patients with upper gastrointestinal bleeding underwent endovascular diagnostics and treatment. The diagnosis was established by endoscopy, computed tomography or clinically based on a significant decrease in hemoglobin. Transcatheter arterial embolisation was performed with coils, liquid embolic agents, and particles. The technical and clinical outcomes were assessed by postinterventional endoscopy, hemoglobin concentrations, number of necessary transfusions, or surgical interventions, as well as by post-interventional mortality within 28 days after the procedure. Selective angiographic embolisation in upper gastrointestinal bleeding was primarily successful technically and clinically in 22 of 29 patients. In 4/29 cases an angiographic reintervention was performed, which was successful in 3 cases. In 3 cases of primarily technically unsuccessful procedures reintervention was not attempted. No catheterisation-related complications were recorded. Peri-interventional mortality was 31%, but only 2 of these patients died due to uncontrolled massive bleeding, whereas the lethal outcome in the other 7 patients was due to their underlying diseases. Transcatheter arterial embolisation is an effective and rapid method in the management of upper gastrointestinal bleeding. Radiological endovascular interventions may considerably contribute to reduced mortality in GI bleeding by avoiding a potential surgical procedure following unsuccessful endoscopic treatment. The study underlines the importance of the combination of interventional endoscopy with interventional radiology in secondary care hospitals for patient outcome in complex and complicated upper gastrointestinal bleeding situations. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Modeling nitrogen fluxes in Germany - where does the nitrogen go?

    NASA Astrophysics Data System (ADS)

    Klement, Laura; Bach, Martin; Breuer, Lutz

    2016-04-01

    According to the latest inventory of the EU Water Framework Directive, 26.3% of German groundwater bodies are in a poor chemical state regarding nitrate. Additionally, the EU initiated infringement proceedings against Germany for not meeting the quality standards of the EU Nitrate Directive. Agriculture has been determined as the main source of nitrate pollution due to over-fertilization and regionally high density of livestock farming. The nitrogen balance surplus is commonly used as an indicator characterizing the potential of nitrate leaching into groundwater bodies and thus also serves as a foundation to introduce legislative restrictions or to monitor the success of mitigation measures. Currently, there is an ongoing discussion which measures are suitable for reducing the risk of nitrate leaching and also to what extent. However, there is still uncertainty about just how much the nitrogen surplus has to be reduced to meet the groundwater quality standards nationwide. Therefore, the aims of our study were firstly to determine the level of the nitrogen surplus that would be acceptable at the utmost and secondly whether the currently discussed target value of 30 kg N per hectare agricultural land for the soil surface nitrogen balance would be sufficient. The models MONERIS (Modeling Nutrient Emissions in River System) and MoRE (Modelling of Regionalized Emissions), the latter based on the first, are commonly used for estimating nitrogen loads into the river system in Germany at the mesoscale, as well as the effect of mitigation measures in the context of the EU directive 2008/105/EC (Environmental quality standards applicable to surface water). We used MoRE to calculate nitrate concentration for 2759 analytical units in Germany. Main factors are the surplus of the soil surface nitrogen balance, the percolation rate and an exponent representing the denitrification in the vadose zone. The modeled groundwater nitrate concentrations did not correspond to the regional

  18. The emigration of Germany's Jewish dermatologists in the period of National Socialism.

    PubMed

    Eppinger, S; Meurer, M; Scholz, A

    2003-09-01

    In the context of our investigation, we found information on 432 (76%) of the 569 Jewish dermatologists in Germany. There is evidence that 57 (10%) of the Jewish dermatologists were murdered in concentration camps, 61 (10.7%) died a natural death, 13 (2%) committed suicide, and 25 (4%) survived the Third Reich in Germany. After 1933, 276 (49%) Jewish dermatologists were able to leave Germany; the United States of America was the main destination and 107 (or 41%) emigrated there. A total of 34 (13%) Jewish dermatologists emigrated from Germany to Palestine and 16 to Latin America. Regarding emigration to other European countries, 20 of the Jewish dermatologists from Germany went to Great Britain (including Walter Freudenthal, 1893-1952, and Ernst Sklarz, 1894-1975), and 24 emigrated to other European countries, such as France (Rudolf Mayer, 1895-1962), Sweden (Carl Lennhoff, 1883-1963), and the Netherlands (Otto Schlein, 1895-1944).

  19. Labor, Business, and Change in Germany and the United States.

    ERIC Educational Resources Information Center

    Wever, Kirsten S., Ed.

    This book explores how two nations with widely divergent political economies, Germany and the United States (U.S.), embraced change in four contemporary settings. "Mutual Learning with Trade-Offs" (Kirsten Wever) discusses mutual learning and the distinguishing characteristics of the political economies of Germany and the U.S.…

  20. 29 CFR 1905.29 - Transmission of record.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-STEIGER OCCUPATIONAL SAFETY AND HEALTH ACT OF 1970 Hearings § 1905.29 Transmission of record. If... 29 Labor 5 2010-07-01 2010-07-01 false Transmission of record. 1905.29 Section 1905.29 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR...

  1. Effectiveness of Organ Donation Information Campaigns in Germany: A Facebook Based Online Survey

    PubMed Central

    Settmacher, Utz; Wurst, Christine; Dirsch, Olaf

    2015-01-01

    Background The German transplantation system is in a crisis due to a lack of donor organs. Information campaigns are one of the main approaches to increase organ donation rates. Since 2012, German health insurance funds are obliged by law to inform their members about organ donation. We raised the hypothesis: The willingness to sign a donor card rises due to the subsequent increase of specific knowledge by receiving the information material of the health insurance funds. Objective The objective of the study was to assess the influence of information campaigns on the specific knowledge and the willingness to donate organs. Methods We conducted an online survey based on recruitment via Facebook groups, advertisements using the snowball effect, and on mailing lists of medical faculties in Germany. Besides the demographic data, the willingness to hold an organ donor card was investigated. Specific knowledge regarding transplantation was explored using five factual questions resulting in a specific knowledge score. Results We recruited a total of 2484 participants, of which 32.7% (300/917) had received information material. Mean age was 29.9 (SD 11.0, median 26.0). There were 65.81% (1594/2422) of the participants that were female. The mean knowledge score was 3.28 of a possible 5.00 (SD 1.1, median 3.0). Holding a donor card was associated with specific knowledge (P<.001), but not with the general education level (P=.155). Receiving information material was related to holding a donor card (P<.001), but not to a relevant increase in specific knowledge (difference in mean knowledge score 3.20 to 3.48, P=.006). The specific knowledge score and the percentage of organ donor card holders showed a linear association (P<.001). Conclusions The information campaign was not associated with a relevant increase in specific knowledge, but with an increased rate in organ donor card holders. This effect is most likely related to the feeling of being informed, together with an easy

  2. Effectiveness of Organ Donation Information Campaigns in Germany: A Facebook Based Online Survey.

    PubMed

    Terbonssen, Tobias; Settmacher, Utz; Wurst, Christine; Dirsch, Olaf; Dahmen, Uta

    2015-07-28

    The German transplantation system is in a crisis due to a lack of donor organs. Information campaigns are one of the main approaches to increase organ donation rates. Since 2012, German health insurance funds are obliged by law to inform their members about organ donation. We raised the hypothesis: The willingness to sign a donor card rises due to the subsequent increase of specific knowledge by receiving the information material of the health insurance funds. The objective of the study was to assess the influence of information campaigns on the specific knowledge and the willingness to donate organs. We conducted an online survey based on recruitment via Facebook groups, advertisements using the snowball effect, and on mailing lists of medical faculties in Germany. Besides the demographic data, the willingness to hold an organ donor card was investigated. Specific knowledge regarding transplantation was explored using five factual questions resulting in a specific knowledge score. We recruited a total of 2484 participants, of which 32.7% (300/917) had received information material. Mean age was 29.9 (SD 11.0, median 26.0). There were 65.81% (1594/2422) of the participants that were female. The mean knowledge score was 3.28 of a possible 5.00 (SD 1.1, median 3.0). Holding a donor card was associated with specific knowledge (P<.001), but not with the general education level (P=.155). Receiving information material was related to holding a donor card (P<.001), but not to a relevant increase in specific knowledge (difference in mean knowledge score 3.20 to 3.48, P=.006). The specific knowledge score and the percentage of organ donor card holders showed a linear association (P<.001). The information campaign was not associated with a relevant increase in specific knowledge, but with an increased rate in organ donor card holders. This effect is most likely related to the feeling of being informed, together with an easy access to the organ donor card.

  3. Epidemiology in Germany-general development and personal experience.

    PubMed

    Wichmann, Heinz-Erich

    2017-08-01

    Did you ever hear about epidemiology in Germany? Starting from an epidemiological desert the discipline has grown remarkably, especially during the last 10-15 years: research institutes have been established, research funding has improved, multiple curriculae in Epidemiology and Public Health are offered. This increase has been quite steep, and now the epidemiological infrastructure is much better. Several medium-sized and even big population cohorts are ongoing, and the number and quality of publications from German epidemiologists has reached a respectable level. My own career in epidemiology started in the field of environmental health. After German reunification I concentrated for many years on environmental problems in East Germany and observed the health benefits after improvement of the situation. Later, I concentrated on population-based cohorts in newborns (GINI/LISA) and adults (KORA, German National Cohort), and on biobanking. This Essay describes the development in Germany after worldwar 2, illustrated by examples of research results and build-up of epidemiological infractructures worth mentioning.

  4. The Search for Specialists and Managers. Staff Shortage in Germany.

    ERIC Educational Resources Information Center

    Stahl, Klaus, Ed.

    1999-01-01

    Despite its high unemployment level, Germany is experiencing a shortage of specialists and managers. Germany's need for highly qualified information technology (IT) workers and engineers is particularly great. Approximately 10,000 posts for computer scientists and IT specialists remained vacant in 1998. Because of the shortage of such specialists,…

  5. Training and Further Training in the Federal Republic of Germany.

    ERIC Educational Resources Information Center

    Pakleppa, Hans

    The Federal Republic of Germany uses its development aid policy to support the growth of manpower resources in developing countries by means of a broad spectrum of training and further training programs of foreign specialists. In planning these programs and arranging scholarships, Germany tries to orient itself toward the educational policy…

  6. Space Radar Image of Oberpfaffenhofen, Germany

    NASA Image and Video Library

    1999-01-27

    This is a false-color, three-frequency image of the Oberpfaffenhofen supersite, southwest of Munich in southern Germany, which shows the differences in what the three radar bands can see on the ground.

  7. Presence and Persistence of Ebola or Marburg Virus in Patients and Survivors: A Rapid Systematic Review.

    PubMed

    Brainard, Julii; Pond, Katherine; Hooper, Lee; Edmunds, Kelly; Hunter, Paul

    2016-02-01

    The 2013-15 Ebola outbreak was unprecedented due to sustained transmission within urban environments and thousands of survivors. In 2014 the World Health Organization stated that there was insufficient evidence to give definitive guidance about which body fluids are infectious and when they pose a risk to humans. We report a rapid systematic review of published evidence on the presence of filoviruses in body fluids of infected people and survivors. Scientific articles were screened for information about filovirus in human body fluids. The aim was to find primary data that suggested high likelihood of actively infectious filovirus in human body fluids (viral RNA). Eligible infections were from Marburg virus (MARV or RAVV) and Zaire, Sudan, Taï Forest and Bundibugyo species of Ebola. Cause of infection had to be laboratory confirmed (in practice either tissue culture or RT-PCR tests), or evidenced by compatible clinical history with subsequent positivity for filovirus antibodies or inflammatory factors. Data were extracted and summarized narratively. 6831 unique articles were found, and after screening, 33 studies were eligible. For most body fluid types there were insufficient patients to draw strong conclusions, and prevalence of positivity was highly variable. Body fluids taken >16 days after onset were usually negative. In the six studies that used both assay methods RT-PCR tests for filovirus RNA gave positive results about 4 times more often than tissue culture. Filovirus was reported in most types of body fluid, but not in every sample from every otherwise confirmed patient. Apart from semen, most non-blood, RT-PCR positive samples are likely to be culture negative and so possibly of low infectious risk. Nevertheless, it is not apparent how relatively infectious many body fluids are during or after illness, even when culture-positive, not least because most test results come from more severe cases. Contact with blood and blood-stained body fluids remains the

  8. 77 FR 23508 - Brass Sheet and Strip From France, Germany, Italy, and Japan

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-19

    ...)] Brass Sheet and Strip From France, Germany, Italy, and Japan Determination On the basis of the record \\1... antidumping duty orders on brass sheet and strip from France, Germany, Italy, and Japan would be likely to... from France, Germany, Italy, and Japan: Investigation Nos. 731-TA-313, 314, 317, and 379 (Third Review...

  9. Jung's views of Nazi Germany: the first year and Jung's transition.

    PubMed

    Schoenl, William; Schoenl, Linda

    2016-09-01

    This article first considers Jung's response to the coming to power of the Nazis in Germany. It brings forth evidence that, besides wanting to preserve psychotherapy in Germany and maintain the international connection between the German and other communities of psychotherapists, he wanted to advance Jungian psychology - his psychology - in Germany. It also presents evidence that, although he occasionally made some anti-Semitic statements during this early period, he was not anti-Semitic in the way the Nazis were. The paper then argues that after Gustav Bally's criticisms in the Neue Zuercher Zeitung in February 1934, Jung entered into a transitional period that spring during which he became warier both of the Nazis and of making any statements that could be construed as being anti-Semitic. Schoenl and Peck (2012) have shown how Jung's views of Nazi Germany changed from 1933 to March 1936. This present article demonstrates very significant changes in Jung's views during the important early part of this period, that is from January 1933 - when Hitler became Chancellor of Germany - through to the spring of 1934. It draws on evidence from archival and other primary sources. © 2016, The Society of Analytical Psychology.

  10. Unprecedented 22,26-seco physalins from Physalis angulata and their anti-inflammatory potential.

    PubMed

    Sun, Cheng-Peng; Oppong, Mahmood Brobbey; Zhao, Feng; Chen, Li-Xia; Qiu, Feng

    2017-10-25

    Two novel physalins, including a 22,26-seco physalin, physalin X (1), and a 11,15-cyclo-9(10),14(17),22(26)-triseco physalin with an unprecedented aromatic ring, aromaphysalin B (2), were isolated from Physalis angulata L. Their structures were determined by IR, UV, HRESIMS, and 2D NMR spectra as well as theoretical calculations. Compounds 1 and 2 exhibited inhibitory activities on NO production with IC 50 values of 68.50 and 29.69 μM, respectively. A plausible biosynthetic pathway for 2 is also discussed.

  11. Bullying Involvement of Korean Children in Germany and in Korea

    ERIC Educational Resources Information Center

    Bae, Hwa-ok

    2016-01-01

    This study compared bullying involvement of Korean or Korean-German children living in Germany with children in Korea, and examined children's perceptions of school environment associated with bullying involvement of the children. This study included 105 Korean or Korean-German children living in the Bayern State of Germany as the study sample and…

  12. 29 CFR 29.7 - Apprenticeship agreement.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 1 2014-07-01 2013-07-01 true Apprenticeship agreement. 29.7 Section 29.7 Labor Office of... Apprenticeship agreement. The apprenticeship agreement must contain, explicitly or by reference: (a) Names and... of probation during which the apprenticeship agreement may be cancelled by either party to the...

  13. Terminal Decline in Well-Being Differs between Residents in East Germany and West Germany

    ERIC Educational Resources Information Center

    Vogel, Nina; Gerstorf, Denis; Ram, Nilam; Goebel, Jan; Wagner, Gert G.

    2017-01-01

    Lifespan research has long been interested in how contexts shape individual development. Using the separation and later reunification of Germany as a kind of natural experiment we examine whether and how living and dying in the former East or West German context has differentially shaped late-life development of well-being. We apply multi-level…

  14. 29 CFR 5.29 - Specific fringe benefits.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 1 2014-07-01 2013-07-01 true Specific fringe benefits. 5.29 Section 5.29 Labor Office of... SUBJECT TO THE CONTRACT WORK HOURS AND SAFETY STANDARDS ACT) Interpretation of the Fringe Benefits Provisions of the Davis-Bacon Act § 5.29 Specific fringe benefits. (a) The act lists all types of fringe...

  15. 76 FR 61825 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List 29 Mollusk...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-05

    ...We, the U.S. Fish and Wildlife Service announce a 90-day finding on a petition to list 29 mollusk species and subspecies as threatened or endangered, under the Endangered Species Act of 1973, as amended (Act). Based on our review, we find that the petition presents substantial scientific or commercial information indicating that listing 26 of the 29 species and subspecies may be warranted. Therefore, with the publication of this notice, we are initiating a review of the status of the 26 species and subspecies to determine if listing any of them is warranted. To ensure that the status review is comprehensive, we are requesting scientific and commercial data and other information regarding these 26 species and subspecies. Based on the status review, we will issue a 12-month finding on the petition, which will address whether the petitioned action is warranted, as provided in the Act.

  16. Innovative energy technologies and climate policy in Germany

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

    Schumacher, Katja; Sands, Ronald D.

    2006-12-01

    Due to the size and structure of its economy, Germany is one of the largest carbon emitters in the European Union. However, Germany is facing a major renewal and restructuring process in electricity generation. Within the next two decades, up to 50% of current electricity generation capacity may retire because of end-of-plant lifetime and the nuclear phase-out pact of 1998. Substantial opportunities therefore exist for deployment of advanced electricity generating technologies in both a projected baseline and in alternative carbon policy scenarios. We simulate the potential role of coal integrated gasification combined cycle (IGCC), natural gas combined cycle (NGCC), carbonmore » dioxide capture and storage (CCS), and wind power within a computable general equilibrium of Germany from the present through 2050. These advanced technologies and their role within a future German electricity system are the focus of this paper. We model the response of greenhouse gas emissions in Germany to various technology and carbon policy assumptions over the next few decades. In our baseline scenario, all of the advanced technologies except CCS provide substantial contributions to electricity generation. We also calculate the carbon price where each fossil technology, combined with CCS, becomes competitive. Constant carbon price experiments are used to characterize the model response to a carbon policy. This provides an estimate of the cost of meeting an emissions target, and the share of emissions reductions available from the electricity generation sector.« less

  17. Local modelling of land consumption in Germany with RegioClust

    NASA Astrophysics Data System (ADS)

    Hagenauer, Julian; Helbich, Marco

    2018-03-01

    Germany is experiencing extensive land consumption. This necessitates local models to understand actual and future land consumption patterns. This research examined land consumption rates on a municipality level in Germany for the period 2000-10 and predicted rates for 2010-20. For this purpose, RegioClust, an algorithm that combines hierarchical clustering and regression analysis to identify regions with similar relationships between land consumption and its drivers, was developed. The performance of RegioClust was compared against geographically weighted regression (GWR). Distinct spatially varying relationships across regions emerged, whereas population density is suggested as the central driver. Although both RegioClust and GWR predicted an increase in land consumption rates for east Germany for 2010-20, only RegioClust forecasts a decline for west Germany. In conclusion, both models predict for 2010-20 a rate of land consumption that suggests that the policy objective of reducing land consumption to 30 ha per day in 2020 will not be achieved. Policymakers are advised to take action and revise existing planning strategies to counteract this development.

  18. Heat waves in lowland Germany and their circulation-related conditions

    NASA Astrophysics Data System (ADS)

    Tomczyk, Arkadiusz M.; Sulikowska, Agnieszka

    2017-09-01

    The research study aimed at assessing multiannual variability of heat wave occurrence in the lowland part of Germany between 1966 and 2015 and determining the role of atmospheric circulation in their occurrence. The analysis was conducted with the use of two independent datasets, that is, the dataset of Germany's National Meteorological Service, Deutscher Wetterdienst, and American meteorological reanalysis database of the National Centre for Environmental Prediction/National Centre for Atmospheric Research. This article defines a hot day as a day with maximum temperature of >30 °C, and a heat wave as a sequence of at least three such days. The observed warming translated into an increase in a number of hot days and, consequently, an increase in the frequency of heat wave occurrence. In the analysed 50-year period, the smallest number of heat waves was observed between 1976 and 1985, and the largest number between 2006 and 2015 in the lowland part of Germany. The occurrence of heat waves in lowland Germany was related to anticyclonic circulation.

  19. [Surgical research in Germany. Organization, quality and international competitiveness].

    PubMed

    Menger, M D; Laschke, M W

    2012-04-01

    Surgical research in Germany is performed within surgical clinics by individual working groups or in surgical research divisions. Additionally, a few independent institutes and departments of surgical research have been established at medical faculties. The number of these institutions, however, is too small. To increase productivity in surgical research, structural changes are necessary, including additional establishment of further institutes and professorships. The quality of clinical research in surgery in Germany is critically discussed. International comparison shows that Germany has a low ranking with respect to the number of clinical studies published in leading surgical journals. However, there has been some improvement in the quality of clinical studies performed in surgical departments during the last 15 years. The establishment of the study center of the German Society of Surgery shows that excellent clinical studies with adequate numbers of patients can also be performed in Germany and can be published in leading journals. Accordingly, there is need to distribute the structures and the competence necessary to perform clinical studies in a standardized manner to all surgical departments involved in clinical research. The experimental surgical research in Germany is not adequately visible, although over the last 10 years the most relevant publications from institutions for surgical research have been placed in journals with a mean impact factor of 8. This may be due to the fact that 85% of these top publications are published in non-surgical journals. The aim for the future must therefore be to increase the impact factor and, thus, the attractiveness of surgical journals. This may be achieved by publishing the highest quality results from experimental surgical research not in non-surgical but in surgical journals.

  20. The health status of Russian-speaking immigrants in Germany.

    PubMed

    Tselmin, S; Korenblum, W; Reimann, M; Bornstein, S R; Schwarz, P E H

    2007-12-01

    Germany developed today into a country of immigration, which creates an additional burden for the social security system and results in a new challenge for the healthcare. In the last 17 years more than two million "Russia Germans" have been repatriated and about two hundred thousand Jewish refugees have resettled in Germany from the former Soviet Union. Nevertheless relevant data concerning migration-related public health care are very scare. Search of PubMed and Journals extracts combined with the own researches, analysing the health status indices of the Russian-speaking immigrants in Germany. Both repatriates of German origin and Jewish refugees demonstrated higher prevalence of impaired lipid metabolism in comparison with native population. 42 % of the 503,040 HBsAg (hepatitis B s-Antigen) carriers in Germany were migrants. The Jewish refugees demonstrated the highest rates of depression and anxiety and the highest levels of awakening cortisol. On the other side German resettlers showed lower cardiovascular as well as all-cause death rates compared to the native Germans. The development of adequate health care programmes to address migratory aspects as well as the establishment of quality standards will realistically enhance the capability of responding rapidly to migrant health aspects and help to tackle inequalities in health.