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Sample records for ten leading vaccine-candidate

  1. Differing Efficacies of Lead Group A Streptococcal Vaccine Candidates and Full-Length M Protein in Cutaneous and Invasive Disease Models

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    Tania Rivera-Hernandez

    2016-06-01

    Full Text Available Group A Streptococcus (GAS is an important human pathogen responsible for both superficial infections and invasive diseases. Autoimmune sequelae may occur upon repeated infection. For this reason, development of a vaccine against GAS represents a major challenge, since certain GAS components may trigger autoimmunity. We formulated three combination vaccines containing the following: (i streptolysin O (SLO, interleukin 8 (IL-8 protease (Streptococcus pyogenes cell envelope proteinase [SpyCEP], group A streptococcal C5a peptidase (SCPA, arginine deiminase (ADI, and trigger factor (TF; (ii the conserved M-protein-derived J8 peptide conjugated to ADI; and (iii group A carbohydrate lacking the N-acetylglucosamine side chain conjugated to ADI. We compared these combination vaccines to a “gold standard” for immunogenicity, full-length M1 protein. Vaccines were adjuvanted with alum, and mice were immunized on days 0, 21, and 28. On day 42, mice were challenged via cutaneous or subcutaneous routes. High-titer antigen-specific antibody responses with bactericidal activity were detected in mouse serum samples for all vaccine candidates. In comparison with sham-immunized mice, all vaccines afforded protection against cutaneous challenge. However, only full-length M1 protein provided protection in the subcutaneous invasive disease model.

  2. Ten Leading Causes of Death and Injury

    Science.gov (United States)

    ... Overdose Traumatic Brain Injury Violence Prevention Ten Leading Causes of Death and Injury Recommend on Facebook Tweet Share Compartir ... in Hospital Emergency Departments, United States – 2014 Leading Causes of Death Charts Causes of Death by Age Group 2016 [ ...

  3. Promising new vaccine candidates against Campylobacter in broilers.

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    Marine Meunier

    Full Text Available Campylobacter is the leading cause of human bacterial gastroenteritis in the European Union. Birds represent the main reservoir of the bacteria, and human campylobacteriosis mainly occurs after consuming and/or handling poultry meat. Reducing avian intestinal Campylobacter loads should impact the incidence of human diseases. At the primary production level, several measures have been identified to reach this goal, including vaccination of poultry. Despite many studies, however, no efficient vaccine is currently available. We have recently identified new vaccine candidates using the reverse vaccinology strategy. This study assessed the in vivo immune and protective potential of six newly-identified vaccine antigens. Among the candidates tested on Ross broiler chickens, four (YP_001000437.1, YP_001000562.1, YP_999817.1, and YP_999838.1 significantly reduced cecal Campylobacter loads by between 2 and 4.2 log10 CFU/g, with the concomitant development of a specific humoral immune response. In a second trial, cecal load reductions results were not statistically confirmed despite the induction of a strong immune response. These vaccine candidates need to be further investigated since they present promising features.

  4. Advanced Vaccine Candidates for Lassa Fever

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    Igor S. Lukashevich

    2012-10-01

    Full Text Available Lassa virus (LASV is the most prominent human pathogen of the Arenaviridae. The virus is transmitted to humans by a rodent reservoir, Mastomys natalensis, and is capable of causing lethal Lassa Fever (LF. LASV has the highest human impact of any of the viral hemorrhagic fevers (with the exception of Dengue Fever with an estimated several hundred thousand infections annually, resulting in thousands of deaths in Western Africa. The sizeable disease burden, numerous imported cases of LF in non-endemic countries, and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Presently there is no licensed vaccine against LF or approved treatment. Recently, several promising vaccine candidates have been developed which can potentially target different groups at risk. The purpose of this manuscript is to review the LASV pathogenesis and immune mechanisms involved in protection. The current status of pre-clinical development of the advanced vaccine candidates that have been tested in non-human primates will be discussed. Major scientific, manufacturing, and regulatory challenges will also be considered.

  5. Identification Of Protein Vaccine Candidates Using Comprehensive Proteomic Analysis Strategies

    National Research Council Canada - National Science Library

    Rohrbough, James G

    2007-01-01

    Presented in this dissertation are proteomic analysis studies focused on identifying proteins to be used as vaccine candidates against Coccidioidomycosis, a potentially fatal human pulmonary disease...

  6. Identification Of Protein Vaccine Candidates Using Comprehensive Proteomic Analysis Strategies

    Science.gov (United States)

    2007-12-01

    that fascinating fungus known as Coccidioides. I also want to thank the UA Mass Spectrometry Facility and the UA Proteomics Consortium, especially...W. & N. N. Kav. 2006. The proteome of the phytopathogenic fungus Sclerotinia sclerotiorum. Proteomics 6: 5995-6007. 127. de Godoy, L. M., J. V...IDENTIFICATION OF PROTEIN VACCINE CANDIDATES USING COMPREHENSIVE PROTEOMIC ANALYSIS STRATEGIES by James G. Rohrbough

  7. A novel live-attenuated vaccine candidate for mayaro Fever.

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    William J Weise

    2014-08-01

    Full Text Available Mayaro virus (MAYV is an emerging, mosquito-borne alphavirus that causes a dengue-like illness in many regions of South America, and which has the potential to urbanize. Because no specific treatment or vaccine is available for MAYV infection, we capitalized on an IRES-based approach to develop a live-attenuated MAYV vaccine candidate. Testing in infant, immunocompetent as well as interferon receptor-deficient mice demonstrated a high degree of attenuation, strong induction of neutralizing antibodies, and efficacy against lethal challenge. This vaccine strain was also unable to infect mosquito cells, a major safety feature for a live vaccine derived from a mosquito-borne virus. Further preclinical development of this vaccine candidate is warranted to protect against this important emerging disease.

  8. Generation of a parvovirus B19 vaccine candidate.

    Science.gov (United States)

    Chandramouli, Sumana; Medina-Selby, Angelica; Coit, Doris; Schaefer, Mary; Spencer, Terika; Brito, Luis A; Zhang, Pu; Otten, Gillis; Mandl, Christian W; Mason, Peter W; Dormitzer, Philip R; Settembre, Ethan C

    2013-08-20

    Parvovirus B19 is the causative agent of fifth disease in children, aplastic crisis in those with blood dyscrasias, and hydrops fetalis. Previous parvovirus B19 virus-like-particle (VLP) vaccine candidates were produced by co-infection of insect cells with two baculoviruses, one expressing wild-type VP1 and the other expressing VP2. In humans, the VLPs were immunogenic but reactogenic. We have developed new VLP-based parvovirus B19 vaccine candidates, produced by co-expressing VP2 and either wild-type VP1 or phospholipase-negative VP1 in a regulated ratio from a single plasmid in Saccharomyces cerevisiae. These VLPs are expressed efficiently, are very homogeneous, and can be highly purified. Although VP2 alone can form VLPs, in mouse immunizations, VP1 and the adjuvant MF59 are required to elicit a neutralizing response. Wild-type VLPs and those with phospholipase-negative VP1 are equivalently potent. The purity, homogeneity, yeast origin, and lack of phospholipase activity of these VLPs address potential causes of previously observed reactogenicity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Evaluation of Lethal Giant Larvae as a Schistosomiasis Vaccine Candidate

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    Yufan Cao

    2016-01-01

    Full Text Available Schistosomiasis is a neglected tropical disease of humans, and it is considered to be the second most devastating parasitic disease after malaria. Eggs produced by normally developed female worms are important in the transmission of the parasite, and they responsible for the pathogenesis of schistosomiasis. The tumor suppressor gene lethal giant larvae (lgl has an essential function in establishing apical-basal cell polarity, cell proliferation, differentiation, and tissue organization. In our earlier study, downregulation of the lgl gene induced a significant reduction in the egg hatching rate of Schistosoma japonicum (Sj eggs. In this study, the Sjlgl gene was used as a vaccine candidate against schistosomiasis, and vaccination achieved and maintained a stable reduction of the egg hatching rate, which is consistent with previous studies, in addition to reducing the worm burden and liver egg burden in some trials.

  10. Novel approaches to identify protective malaria vaccine candidates

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    Wan Ni eChia

    2014-11-01

    Full Text Available Efforts to develop vaccines against malaria have been the focus of substantial research activities for decades. Several categories of candidate vaccines are currently being developed for protection against malaria, based on antigens corresponding to the pre-erythrocytic, blood-stage or sexual stages of the parasite. Long lasting sterile protection from Plasmodium falciparum sporozoite challenge has been observed in human following vaccination with whole parasite formulations, clearly demonstrating that a protective immune response targeting predominantly the pre-erythrocytic stages can develop against malaria. However, most of vaccine candidates currently being investigated, which are mostly subunits vaccines, have not been able to induce substantial (>50% protection thus far. This is due to the fact that the antigens responsible for protection against the different parasite stages are still yet to be known and relevant correlates of protection have remained elusive. For a vaccine to be developed in a timely manner, novel approaches are required. In this article, we review the novel approaches that have been developed to identify the antigens for the development of an effective malaria vaccine.

  11. Identification of Novel Vaccine Candidates against Campylobacter through Reverse Vaccinology

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    Marine Meunier

    2016-01-01

    Full Text Available Campylobacteriosis is the most prevalent bacterial foodborne gastroenteritis affecting humans in the European Union. Human cases are mainly due to Campylobacter jejuni or Campylobacter coli, and contamination is associated with the handling and/or consumption of poultry meat. In fact, poultry constitutes the bacteria’s main reservoir. A promising way of decreasing the incidence of campylobacteriosis in humans would be to decrease avian colonization. Poultry vaccination is of potential for this purpose. However, despite many studies, there is currently no vaccine available on the market to reduce the intestinal Campylobacter load in chickens. It is essential to identify and characterize new vaccine antigens. This study applied the reverse vaccinology approach to detect new vaccine candidates. The main criteria used to select immune proteins were localization, antigenicity, and number of B-epitopes. Fourteen proteins were identified as potential vaccine antigens. In vitro and in vivo experiments now need to be performed to validate the immune and protective power of these newly identified antigens.

  12. Comparative Infectivity Determinations of Dengue Virus Vaccine Candidates in Rhesus Monkeys, Mosquitoes, and Cell Cultures

    Science.gov (United States)

    1993-01-28

    34 are required for the evaluation of these vaccine candidates. RE: DAMDI7-89-C-9175 Page 16 REFERENCES 1. Sabin AB, Sclesinger RW, 1945. Production of...AD-A261 892 CONTRACT NO: DAMD17-89-C-9 175 \\II\\IllI\\I\\I1\\\\~il\\ TITLE: COMPARATIVE INFECTIVITY DETERMINATIONS OF DENGUE VIRUS VACCINE CANDIDATES IN... Vaccine Candidates in Rhesus Monkeys, 63002A Mosquitoes, and Cell Cultures 3M263002D870 AC 6. AUTHOR(S) DA335475 Edmundo Kraiselburd 7. PERFORMING

  13. Identification of Novel Potential Vaccine Candidates against Tuberculosis Based on Reverse Vaccinology

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    Gloria P. Monterrubio-López

    2015-01-01

    Full Text Available Tuberculosis (TB is a chronic infectious disease, considered as the second leading cause of death worldwide, caused by Mycobacterium tuberculosis. The limited efficacy of the bacillus Calmette-Guérin (BCG vaccine against pulmonary TB and the emergence of multidrug-resistant TB warrants the need for more efficacious vaccines. Reverse vaccinology uses the entire proteome of a pathogen to select the best vaccine antigens by in silico approaches. M. tuberculosis H37Rv proteome was analyzed with NERVE (New Enhanced Reverse Vaccinology Environment prediction software to identify potential vaccine targets; these 331 proteins were further analyzed with VaxiJen for the determination of their antigenicity value. Only candidates with values ≥0.5 of antigenicity and 50% of adhesin probability and without homology with human proteins or transmembrane regions were selected, resulting in 73 antigens. These proteins were grouped by families in seven groups and analyzed by amino acid sequence alignments, selecting 16 representative proteins. For each candidate, a search of the literature and protein analysis with different bioinformatics tools, as well as a simulation of the immune response, was conducted. Finally, we selected six novel vaccine candidates, EsxL, PE26, PPE65, PE_PGRS49, PBP1, and Erp, from M. tuberculosis that can be used to improve or design new TB vaccines.

  14. Safety and immunogenicity of GMZ2 - a MSP3-GLURP fusion protein malaria vaccine candidate

    DEFF Research Database (Denmark)

    Esen, Meral; Kremsner, Peter G; Schleucher, Regina

    2009-01-01

    Malaria is a major public health problem in Sub-Saharan Africa. In highly endemic regions infants, children and pregnant women are mostly affected. An effective malaria vaccine would complement existing malaria control strategies because it can be integrated in existing immunization programs easily....... Here we present the results of the first phase Ia clinical trial of GMZ2 adjuvanted in aluminium hydroxide. GMZ2 is a malaria vaccine candidate, designed upon the rationale to induce immune responses against asexual blood stages of Plasmodium falciparum similar to those encountered in semi...... is a safe and immunogenic malaria vaccine candidate suitable for further clinical development....

  15. Efficacy of chimeric Pestivirus vaccine candidates against classical swine fever: protection and DIVA characteristics.

    Science.gov (United States)

    Eblé, P L; Geurts, Y; Quak, S; Moonen-Leusen, H W; Blome, S; Hofmann, M A; Koenen, F; Beer, M; Loeffen, W L A

    2013-03-23

    Currently no live DIVA (Differentiating Infected from Vaccinated Animals) vaccines against classical swine fever (CSF) are available. The aim of this study was to investigate whether chimeric pestivirus vaccine candidates (CP7_E2alf, Flc11 and Flc9) are able to protect pigs against clinical signs, and to reduce virus shedding and virus transmission, after a challenge with CSF virus (CSFV), 7 or 14 days after a single intramuscular vaccination. In these vaccine candidates, either the E2 or the E(rns) encoding genome region of a bovine viral diarrhoea virus strain were combined with a cDNA copy of CSFV or vice versa. Furthermore, currently available serological DIVA tests were evaluated. The vaccine candidates were compared to the C-strain. All vaccine candidates protected against clinical signs. No transmission to contact pigs was detected in the groups vaccinated with C-strain, CP7_E2alf and Flc11. Limited transmission occurred in the groups vaccinated with Flc9. All vaccine candidates would be suitable to stop on-going transmission of CSFV. For Flc11, no reliable differentiation was possible with the current E(rns)-based DIVA test. For CP7_E2alf, the distribution of the inhibition percentages was such that up to 5% false positive results may be obtained in a large vaccinated population. For Flc9 vaccinated pigs, the E2 ELISA performed very well, with an expected 0.04% false positive results in a large vaccinated population. Both CP7_E2alf and Flc9 are promising candidates to be used as live attenuated marker vaccines against CSF, with protection the best feature of CP7_E2alf, and the DIVA principle the best feature of Flc9. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. A full-length Plasmodium falciparum recombinant circumsporozoite protein expressed by Pseudomonas fluorescens platform as a malaria vaccine candidate.

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    Amy R Noe

    Full Text Available The circumsporozoite protein (CSP of Plasmodium falciparum is a major surface protein, which forms a dense coat on the sporozoite's surface. Preclinical research on CSP and clinical evaluation of a CSP fragment-based RTS, S/AS01 vaccine have demonstrated a modest degree of protection against P. falciparum, mediated in part by humoral immunity and in part by cell-mediated immunity. Given the partial protective efficacy of the RTS, S/AS01 vaccine in a recent Phase 3 trial, further improvement of CSP-based vaccines is crucial. In this report, we describe the preclinical development of a full-length, recombinant CSP (rCSP-based vaccine candidate against P. falciparum malaria suitable for current Good Manufacturing Practice (cGMP production. Utilizing a novel high-throughput Pseudomonas fluorescens expression platform, we demonstrated greater efficacy of full-length rCSP as compared to N-terminally truncated versions, rapidly down-selected a promising lead vaccine candidate, and developed a high-yield purification process to express immunologically active, intact antigen for clinical trial material production. The rCSP, when formulated with various adjuvants, induced antigen-specific antibody responses as measured by enzyme-linked immunosorbent assay (ELISA and immunofluorescence assay (IFA, as well as CD4+ T-cell responses as determined by ELISpot. The adjuvanted rCSP vaccine conferred protection in mice when challenged with transgenic P. berghei sporozoites containing the P. falciparum repeat region of CSP. Furthermore, heterologous prime/boost regimens with adjuvanted rCSP and an adenovirus type 35-vectored CSP (Ad35CS showed modest improvements in eliciting CSP-specific T-cell responses and anti-malarial protection, depending on the order of vaccine delivery. Collectively, these data support the importance of further clinical development of adjuvanted rCSP, either as a stand-alone product or as one of the components in a heterologous prime

  17. Characterization of Two Metal Binding Lipoproteins as Vaccine Candidates for Enterococcal Infections.

    Science.gov (United States)

    Romero-Saavedra, Felipe; Laverde, Diana; Budin-Verneuil, Aurélie; Muller, Cécile; Bernay, Benoit; Benachour, Abdellah; Hartke, Axel; Huebner, Johannes

    2015-01-01

    Enterococcus faecium and faecalis are Gram-positive opportunistic pathogens that have become leading causes of nosocomial infections over the last decades. Especially multidrug resistant enterococci have become a challenging clinical problem worldwide. Therefore, new treatment options are needed and the identification of alternative targets for vaccine development has emerged as a feasible alternative to fight the infections caused by these pathogens. We extrapolate the transcriptomic data from a mice peritonitis infection model in E. faecalis to identify putative up-regulated surface proteins under infection conditions in E. faecium. After the bionformatic analyses two metal binding lipoproteins were identified to have a high homology (>72%) between the two species, the manganese ABC transporter substrate-binding lipoprotein (PsaAfm,) and the zinc ABC transporter substrate-binding lipoprotein (AdcAfm). These candidate lipoproteins were overexpressed in Escherichia coli and purified. The recombinant proteins were used to produce rabbit polyclonal antibodies that were able to induce specific opsonic antibodies that mediated killing of the homologous strain E. faecium E155 as well as clinical strains E. faecium E1162, Enterococcus faecalis 12030, type 2 and type 5. Mice were passively immunized with the antibodies raised against recombinant lipoproteins, showing significant reduction of colony counts in mice livers after the bacterial challenge and demonstrating the efficacy of these metal binding lipoproteins as promising vaccine candidates to treat infections caused by these enterococcal pathogens. Overall, our results demonstrate that these two metal binding lipoproteins elicited specific, opsonic and protective antibodies, with an extensive cross-reactivity and serotype-independent coverage among these two important nocosomial pathogens. Pointing these two protein antigens as promising immunogens, that can be used as single components or as carrier proteins

  18. Reduced antibody responses against Plasmodium falciparum vaccine candidate antigens in the presence of Trichuris trichiura

    DEFF Research Database (Denmark)

    Esen, Meral; Mordmüller, Benjamin; de Salazar, Pablo Martinez

    2012-01-01

    BACKGROUND: Helminth infections are highly prevalent in the tropics and may have an effect on immune responses to vaccines due to their immunomodulatory effect. The prevalence of helminth infections in young children, the target group for malaria and most other vaccines, is high. Therefore we...... assessed the influence of helminth infection on vaccine-induced immune responses in a phase I clinical trial of the malaria vaccine candidate GMZ2. METHODS: Twenty Gabonese preschool-age children were vaccinated with GMZ2, a blood stage malaria vaccine candidate. Humoral immune response against the vaccine...... antigens and parasitological status were assessed. Vaccine-specific antibody concentrations and memory B-cell numbers were compared in worm infected and non-infected participants. RESULTS: Antibody response to GMZ2 was 3.4-fold (95% confidence interval: 1.6, 7.4) higher in Trichuris trichiura negative...

  19. Immunogenicity of mumps virus vaccine candidates matching circulating genotypes in the United States and China.

    Science.gov (United States)

    Zengel, James; Phan, Shannon I; Pickar, Adrian; Xu, Pei; He, Biao

    2017-07-13

    Mumps virus (MuV) causes acute infection in humans with characteristic swelling of the parotid gland. While vaccination has greatly reduced the incidence of MuV infection, there have been multiple large outbreaks of mumps virus (MuV) in highly vaccinated populations. The most common vaccine strain, Jeryl Lynn, belongs to genotype A, which is no longer a circulating genotype. We have developed two vaccine candidates that match the circulating genotypes in the United States (genotype G) and China (genotype F). We found that there was a significant decrease in the ability of the Jeryl Lynn vaccine to produce neutralizing antibody responses to non-matched viruses, when compared to either of our vaccine candidates. Our data suggests that an updated vaccine may allow for better immunity against the circulating MuV genotypes G and F. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Surface display of Clonorchis sinensis enolase on Bacillus subtilis spores potentializes an oral vaccine candidate.

    Science.gov (United States)

    Wang, Xiaoyun; Chen, Wenjun; Tian, Yanli; Mao, Qiang; Lv, Xiaoli; Shang, Mei; Li, Xuerong; Yu, Xinbing; Huang, Yan

    2014-03-10

    Clonorchis sinensis (C. sinensis) infections remain the common public health problem in freshwater fish consumption areas. New effective prevention strategies are still the urgent challenges to control this kind of foodborne infectious disease. The biochemical importance and biological relevance render C. sinensis enolase (Csenolase) as a potential vaccine candidate. In the present study, we constructed Escherichia coli/Bacillus subtilis shuttle genetic engineering system and investigated the potential of Csenolase as an oral vaccine candidate for C. sinensis prevention in different immunization routes. Our results showed that, compared with control groups, both recombinant Csenolase protein and nucleic acid could induce a mixed IgG1/IgG2a immune response when administrated subcutaneously (Psinensis infection. Csenolase derived oral vaccine conferred worm reduction rate and egg reduction rate at 60.07% (Psinensis prevention. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. The fimbrial protein FlfA from Gallibacterium anatis is a virulence factor and vaccine candidate

    DEFF Research Database (Denmark)

    Bager, Ragnhild Jørgensen; Nesta, Barbara; Pors, Susanne Elisabeth

    2013-01-01

    in the natural chicken host. Furthermore, protection against G. anatis 12656-12 could be induced by immunizing chickens with recombinant FlfA. Finally, in vitro expression of FlfA homologs was observed in a genetically diverse set of G. anatis strains, suggesting the potential of FlfA as a serotype-independent...... vaccine candidate This is the first study describing a fimbrial subunit protein of G. anatis with a clear potential as a vaccine antigen....

  2. Development of recombinant vaccine candidate molecule against Shigella infection.

    Science.gov (United States)

    Chitradevi, S T S; Kaur, G; Sivaramakrishna, U; Singh, D; Bansal, A

    2016-10-17

    Shigellosis is an acute bacillary diarrheal disease caused by the gram negative bacillus Shigella. The existence of multiple Shigella serotypes and their growing resistance to antibiotics stress the urgent need for the development of vaccine that is protective across all serotypes. Shigella's IpaB antigen is involved in translocon pore formation, promotes bacterial invasion and induces apoptosis in macrophages. S. Typhi GroEL (Hsp 60) is the immunodominant antigen inducing both arms of immunity and has been explored as adjuvant in this study. The present study evaluates the immunogenicity and protective efficacy of recombinant IpaB domain-GroEL fusion protein in mice against lethal Shigella infection. The IpaB domain and GroEL genes were fused using overlap extension PCR and cloned in pRSETA expression vector. Fused gene was expressed in Escherichia coli BL-21 cells and the resulting 90 KDa fusion protein was purified by affinity chromatography. Intranasal (i.n.) immunization of mice with fusion protein increased the IgG and IgA antibody titers as compared to the group immunized with IpaB and GroEL and control PBS immunized group. Also IgG1 and IgG2a antibodies induced in fusion protein immunized mice were higher than co-immunized group. Significant increase in lymphocyte proliferation and cytokine levels (IFN-γ, IL-4 and IL-10), indicates induction of both Th1 and Th2 immune responses in both immunized groups. Immunization with fusion protein protected 90-95% of mice whereas 80-85% survivability was observed in co-immunized group against lethal challenge with S. flexneri, S. boydii and S. sonnei. Passive immunization conferred 60-70% protection in mice against all these Shigella species. Organ burden and histopathology studies also revealed significant decrease in lung infection as compared to the co-immunized group. Since IpaB is the conserved dominant molecule in all Shigella species, this study will lead to an ideal platform for the development of safe

  3. Extended Preclinical Safety, Efficacy and Stability Testing of a Live-attenuated Chikungunya Vaccine Candidate.

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    Kenneth S Plante

    Full Text Available We recently described a new, live-attenuated vaccine candidate for chikungunya (CHIK fever, CHIKV/IRES. This vaccine was shown to be well attenuated, immunogenic and efficacious in protecting against CHIK virus (CHIKV challenge of mice and nonhuman primates. To further evaluate its preclinical safety, we compared CHIKV/IRES distribution and viral loads in interferon-α/β receptor-incompetent A129 mice to another CHIK vaccine candidate, 181/clone25, which proved highly immunogenic but mildly reactive in human Phase I/II clinical trials. Compared to wild-type CHIK virus, (wt-CHIKV, both vaccines generated lower viral loads in a wide variety of tissues and organs, including the brain and leg muscle, but CHIKV/IRES exhibited marked restrictions in dissemination and viral loads compared to 181/clone25, and was never found outside the blood, spleen and muscle. Unlike wt-CHIKV, which caused disrupted splenic architecture and hepatic lesions, histopathological lesions were not observed in animals infected with either vaccine strain. To examine the stability of attenuation, both vaccines were passaged 5 times intracranially in infant A129 mice, then assessed for changes in virulence by comparing parental and passaged viruses for footpad swelling, weight stability and survival after subcutaneous infection. Whereas strain 181/clone25 p5 underwent a significant increase in virulence as measured by weight loss (from 30% and mortality (from 0 to 100%, CHIKV/IRES underwent no detectible change in any measure of virulence (no significant weight loss and no mortality. These data indicate greater nonclinical safety of the CHIKV/IRES vaccine candidate compared to 181/clone25, further supporting its eligibility for human testing.

  4. Discovery of Novel Leptospirosis Vaccine Candidates Using Reverse and Structural Vaccinology

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    Alan John Alexander McBride

    2017-04-01

    Full Text Available Leptospira spp. are diderm (two membranes bacteria that infect mammals causing leptospirosis, a public health problem with global implications. Thousands of people die every year due to leptospirosis, especially in developing countries with tropical climates. Prophylaxis is difficult due to multiple factors, including the large number of asymptomatic hosts that transmit the bacteria, poor sanitation, increasing numbers of slum dwellers, and the lack of an effective vaccine. Several leptospiral recombinant antigens were evaluated as a replacement for the inactivated (bacterin vaccine; however, success has been limited. A prospective vaccine candidate is likely to be a surface-related protein that can stimulate the host immune response to clear leptospires from blood and organs. In this study, a comprehensive bioinformatics approach based on reverse and structural vaccinology was applied toward the discovery of novel leptospiral vaccine candidates. The Leptospira interrogans serovar Copenhageni strain L1-130 genome was mined in silico for the enhanced identification of conserved β-barrel (βb transmembrane proteins and outer membrane (OM lipoproteins. Orthologs of the prospective vaccine candidates were screened in the genomes of 20 additional Leptospira spp. Three-dimensional structural models, with a high degree of confidence, were created for each of the surface-exposed proteins. Major histocompatibility complex II (MHC-II epitopes were identified, and their locations were mapped on the structural models. A total of 18 βb transmembrane proteins and 8 OM lipoproteins were identified. These proteins were conserved among the pathogenic Leptospira spp. and were predicted to have epitopes for several variants of MHC-II receptors. A structural and functional analysis of the sequence of these surface proteins demonstrated that most βb transmembrane proteins seem to be TonB-dependent receptors associated with transportation. Other proteins

  5. SARS CTL vaccine candidates; HLA supertype-, genome-wide scanning and biochemical validation

    DEFF Research Database (Denmark)

    Sylvester-Hvid, C; Nielsen, M; Lamberth, K

    2004-01-01

    . Exact knowledge of how the immune system handles protein antigens would allow for the identification of such linear sequences directly from genomic/proteomic sequence information (Lauemoller et al., Rev Immunogenet 2001: 2: 477-91). The latter was recently established when a causative coronavirus (SARS...... of the HLA supertypes and identified almost 100 potential vaccine candidates. These should be further validated in SARS survivors and used for vaccine formulation. We suggest that immunobioinformatics may become a fast and valuable tool in rational vaccine design....

  6. SARS CTL vaccine candidates; HLA supertype-, genome-wide scanning and biochemical validation

    DEFF Research Database (Denmark)

    Sylvester-Hvid, C.; Nielsen, Morten; Lamberth, K.

    2004-01-01

    . Exact knowledge of how the immune system handles protein antigens would allow for the identification of such linear sequences directly, from genomic/proteomic sequence information (Lauemoller et al., Rev Immunogenet 2001: 2: 477-91). The latter was recently established when a causative coronavirus (SARS...... of the HLA supertypes and identified almost 100 potential vaccine candidates. These should be further validated in SARS survivors and used for vaccine formulation. We suggest that immunobioinformatics may become a fast and valuable tool in rational vaccine design....

  7. In vivo electroporation enhances the immunogenicity of an HIV-1 DNA vaccine candidate in healthy volunteers.

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    Sandhya Vasan

    Full Text Available DNA-based vaccines have been safe but weakly immunogenic in humans to date.We sought to determine the safety, tolerability, and immunogenicity of ADVAX, a multigenic HIV-1 DNA vaccine candidate, injected intramuscularly by in vivo electroporation (EP in a Phase-1, double-blind, randomized placebo-controlled trial in healthy volunteers. Eight volunteers each received 0.2 mg, 1 mg, or 4 mg ADVAX or saline placebo via EP, or 4 mg ADVAX via standard intramuscular injection at weeks 0 and 8. A third vaccination was administered to eleven volunteers at week 36. EP was safe, well-tolerated and considered acceptable for a prophylactic vaccine. EP delivery of ADVAX increased the magnitude of HIV-1-specific cell mediated immunity by up to 70-fold over IM injection, as measured by gamma interferon ELISpot. The number of antigens to which the response was detected improved with EP and increasing dosage. Intracellular cytokine staining analysis of ELISpot responders revealed both CD4+ and CD8+ T cell responses, with co-secretion of multiple cytokines.This is the first demonstration in healthy volunteers that EP is safe, tolerable, and effective in improving the magnitude, breadth and durability of cellular immune responses to a DNA vaccine candidate.ClinicalTrials.gov NCT00545987.

  8. Cell biological characterization of the malaria vaccine candidate trophozoite exported protein 1.

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    Caroline Kulangara

    Full Text Available In a genome-wide screen for alpha-helical coiled coil motifs aiming at structurally defined vaccine candidates we identified PFF0165c. This protein is exported in the trophozoite stage and was named accordingly Trophozoite exported protein 1 (Tex1. In an extensive preclinical evaluation of its coiled coil peptides Tex1 was identified as promising novel malaria vaccine candidate providing the rational for a comprehensive cell biological characterization of Tex1. Antibodies generated against an intrinsically unstructured N-terminal region of Tex1 and against a coiled coil domain were used to investigate cytological localization, solubility and expression profile. Co-localization experiments revealed that Tex1 is exported across the parasitophorous vacuole membrane and located to Maurer's clefts. Change in location is accompanied by a change in solubility: from a soluble state within the parasite to a membrane-associated state after export to Maurer's clefts. No classical export motifs such as PEXEL, signal sequence/anchor or transmembrane domain was identified for Tex1.

  9. Pilot scale production of highly efficacious and stable enterovirus 71 vaccine candidates.

    Directory of Open Access Journals (Sweden)

    Ai-Hsiang Chou

    Full Text Available BACKGROUND: Enterovirus 71 (EV71 has caused several epidemics of hand, foot and mouth diseases (HFMD in Asia and now is being recognized as an important neurotropic virus. Effective medications and prophylactic vaccine against EV71 infection are urgently needed. Based on the success of inactivated poliovirus vaccine, a prototype chemically inactivated EV71 vaccine candidate has been developed and currently in human phase 1 clinical trial. PRINCIPAL FINDING: In this report, we present the development of a serum-free cell-based EV71 vaccine. The optimization at each step of the manufacturing process was investigated, characterized and quantified. In the up-stream process development, different commercially available cell culture media either containing serum or serum-free was screened for cell growth and virus yield using the roller-bottle technology. VP-SFM serum-free medium was selected based on the Vero cell growth profile and EV71 virus production. After the up-stream processes (virus harvest, diafiltration and concentration, a combination of gel-filtration liquid chromatography and/or sucrose-gradient ultracentrifugation down-stream purification processes were investigated at a pilot scale of 40 liters each. Although the combination of chromatography and sucrose-gradient ultracentrifugation produced extremely pure EV71 infectious virus particles, the overall yield of vaccine was 7-10% as determined by a VP2-based quantitative ELISA. Using chromatography as the downstream purification, the virus yield was 30-43%. To retain the integrity of virus neutralization epitopes and the stability of the vaccine product, the best virus inactivation was found to be 0.025% formalin-treatment at 37 °C for 3 to 6 days. Furthermore, the formalin-inactivated virion vaccine candidate was found to be stable for >18 months at 4 °C and a microgram of viral proteins formulated with alum adjuvant could induce strong virus-neutralizing antibody responses in mice

  10. Pilot scale production of highly efficacious and stable enterovirus 71 vaccine candidates.

    Science.gov (United States)

    Chou, Ai-Hsiang; Liu, Chia-Chyi; Chang, Cheng-Peng; Guo, Meng-Shin; Hsieh, Shih-Yang; Yang, Wen-Hsueh; Chao, Hsin-Ju; Wu, Chien-Long; Huang, Ju-Lan; Lee, Min-Shi; Hu, Alan Yung-Chi; Lin, Sue-Chen; Huang, Yu-Yun; Hu, Mei-Hua; Chow, Yen-Hung; Chiang, Jen-Ron; Chang, Jui-Yuan; Chong, Pele

    2012-01-01

    Enterovirus 71 (EV71) has caused several epidemics of hand, foot and mouth diseases (HFMD) in Asia and now is being recognized as an important neurotropic virus. Effective medications and prophylactic vaccine against EV71 infection are urgently needed. Based on the success of inactivated poliovirus vaccine, a prototype chemically inactivated EV71 vaccine candidate has been developed and currently in human phase 1 clinical trial. In this report, we present the development of a serum-free cell-based EV71 vaccine. The optimization at each step of the manufacturing process was investigated, characterized and quantified. In the up-stream process development, different commercially available cell culture media either containing serum or serum-free was screened for cell growth and virus yield using the roller-bottle technology. VP-SFM serum-free medium was selected based on the Vero cell growth profile and EV71 virus production. After the up-stream processes (virus harvest, diafiltration and concentration), a combination of gel-filtration liquid chromatography and/or sucrose-gradient ultracentrifugation down-stream purification processes were investigated at a pilot scale of 40 liters each. Although the combination of chromatography and sucrose-gradient ultracentrifugation produced extremely pure EV71 infectious virus particles, the overall yield of vaccine was 7-10% as determined by a VP2-based quantitative ELISA. Using chromatography as the downstream purification, the virus yield was 30-43%. To retain the integrity of virus neutralization epitopes and the stability of the vaccine product, the best virus inactivation was found to be 0.025% formalin-treatment at 37 °C for 3 to 6 days. Furthermore, the formalin-inactivated virion vaccine candidate was found to be stable for >18 months at 4 °C and a microgram of viral proteins formulated with alum adjuvant could induce strong virus-neutralizing antibody responses in mice, rats, rabbits, and non-human primates. These

  11. A Rapid and Improved Method to Generate Recombinant Dengue Virus Vaccine Candidates.

    Science.gov (United States)

    Govindarajan, Dhanasekaran; Guan, Liming; Meschino, Steven; Fridman, Arthur; Bagchi, Ansu; Pak, Irene; ter Meulen, Jan; Casimiro, Danilo R; Bett, Andrew J

    2016-01-01

    Dengue is one of the most important mosquito-borne infections accounting for severe morbidity and mortality worldwide. Recently, the tetravalent chimeric live attenuated Dengue vaccine Dengvaxia® was approved for use in several dengue endemic countries. In general, live attenuated vaccines (LAV) are very efficacious and offer long-lasting immunity against virus-induced disease. Rationally designed LAVs can be generated through reverse genetics technology, a method of generating infectious recombinant viruses from full length cDNA contained in bacterial plasmids. In vitro transcribed (IVT) viral RNA from these infectious clones is transfected into susceptible cells to generate recombinant virus. However, the generation of full-length dengue virus cDNA clones can be difficult due to the genetic instability of viral sequences in bacterial plasmids. To circumvent the need for a single plasmid containing a full length cDNA, in vitro ligation of two or three cDNA fragments contained in separate plasmids can be used to generate a full-length dengue viral cDNA template. However, in vitro ligation of multiple fragments often yields low quality template for IVT reactions, resulting in inconsistent low yield RNA. These technical difficulties make recombinant virus recovery less efficient. In this study, we describe a simple, rapid and efficient method of using LONG-PCR to recover recombinant chimeric Yellow fever dengue (CYD) viruses as potential dengue vaccine candidates. Using this method, we were able to efficiently generate several viable recombinant viruses without introducing any artificial mutations into the viral genomes. We believe that the techniques reported here will enable rapid and efficient recovery of recombinant flaviviruses for evaluation as vaccine candidates and, be applicable to the recovery of other RNA viruses.

  12. A Rapid and Improved Method to Generate Recombinant Dengue Virus Vaccine Candidates.

    Directory of Open Access Journals (Sweden)

    Dhanasekaran Govindarajan

    Full Text Available Dengue is one of the most important mosquito-borne infections accounting for severe morbidity and mortality worldwide. Recently, the tetravalent chimeric live attenuated Dengue vaccine Dengvaxia® was approved for use in several dengue endemic countries. In general, live attenuated vaccines (LAV are very efficacious and offer long-lasting immunity against virus-induced disease. Rationally designed LAVs can be generated through reverse genetics technology, a method of generating infectious recombinant viruses from full length cDNA contained in bacterial plasmids. In vitro transcribed (IVT viral RNA from these infectious clones is transfected into susceptible cells to generate recombinant virus. However, the generation of full-length dengue virus cDNA clones can be difficult due to the genetic instability of viral sequences in bacterial plasmids. To circumvent the need for a single plasmid containing a full length cDNA, in vitro ligation of two or three cDNA fragments contained in separate plasmids can be used to generate a full-length dengue viral cDNA template. However, in vitro ligation of multiple fragments often yields low quality template for IVT reactions, resulting in inconsistent low yield RNA. These technical difficulties make recombinant virus recovery less efficient. In this study, we describe a simple, rapid and efficient method of using LONG-PCR to recover recombinant chimeric Yellow fever dengue (CYD viruses as potential dengue vaccine candidates. Using this method, we were able to efficiently generate several viable recombinant viruses without introducing any artificial mutations into the viral genomes. We believe that the techniques reported here will enable rapid and efficient recovery of recombinant flaviviruses for evaluation as vaccine candidates and, be applicable to the recovery of other RNA viruses.

  13. Top Down Tandem Mass Spectrometric Analysis of a Chemically Modified Rough-Type Lipopolysaccharide Vaccine Candidate

    Science.gov (United States)

    Oyler, Benjamin L.; Khan, Mohd M.; Smith, Donald F.; Harberts, Erin M.; Kilgour, David P. A.; Ernst, Robert K.; Cross, Alan S.; Goodlett, David R.

    2018-02-01

    Recent advances in lipopolysaccharide (LPS) biology have led to its use in drug discovery pipelines, including vaccine and vaccine adjuvant discovery. Desirable characteristics for LPS vaccine candidates include both the ability to produce a specific antibody titer in patients and a minimal host inflammatory response directed by the innate immune system. However, in-depth chemical characterization of most LPS extracts has not been performed; hence, biological activities of these extracts are unpredictable. Additionally, the most widely adopted workflow for LPS structure elucidation includes nonspecific chemical decomposition steps before analyses, making structures inferred and not necessarily biologically relevant. In this work, several different mass spectrometry workflows that have not been previously explored were employed to show proof-of-principle for top down LPS primary structure elucidation, specifically for a rough-type mutant (J5) E. coli-derived LPS component of a vaccine candidate. First, ion mobility filtered precursor ions were subjected to collision induced dissociation (CID) to define differences in native J5 LPS v. chemically detoxified J5 LPS (dLPS). Next, ultra-high mass resolving power, accurate mass spectrometry was employed for unequivocal precursor and product ion empirical formulae generation. Finally, MS3 analyses in an ion trap instrument showed that previous knowledge about dissociation of LPS components can be used to reconstruct and sequence LPS in a top down fashion. A structural rationale is also explained for differential inflammatory dose-response curves, in vitro, when HEK-Blue hTLR4 cells were administered increasing concentrations of native J5 LPS v. dLPS, which will be useful in future drug discovery efforts. [Figure not available: see fulltext.

  14. GapA, a potential vaccine candidate antigen against Streptococcus agalactiae in Nile tilapia (Oreochromis niloticus).

    Science.gov (United States)

    Zhang, Ze; Yu, Angen; Lan, Jiangfeng; Zhang, Hua; Hu, Minqiang; Cheng, Jiewei; Zhao, Lijuan; Lin, Li; Wei, Shun

    2017-04-01

    Streptococcosis due to the bacterium Streptococcus agalactiae (S. agalactiae) has resulted in enormous economic losses in aquaculture worldwide, especially in the tilapia culture industry. Previously, there were limited vaccines that could be employed against streptococcosis in tilapia. This study aimed to develop a vaccine candidate using the glyceraldehyde-phosphate dehydrogenase protein (GapA) of S. agalactiae encoded by the gapA gene. Tilapia were intraperitoneally injected with PBS, PBS + Freund's adjuvant, PBS + Montanide's adjuvant, GapA + Freund's adjuvant, GapA + Montanide's adjuvant, killed S. agalactiae whole cells (WC)+Freund's adjuvant, or killed S. agalactiae whole cells (WC)+ Montanide's adjuvant. They were then challenged with S. agalactiae, and the relative percentage survival (RPS) was monitored 14 days after the challenge. The highest RPSs were observed in the WC groups, with 76.7% in WC + Freund's adjuvant and 74.4% in WC + Montanide's adjuvant groups; these were followed by the GapA groups, with 63.3% in GapA + Freund's adjuvant and 45.6% in GapA + Montanide's adjuvant groups. The RPS of the PBS group was 0%, and those of PBS + Freund's adjuvant and PBS + Montanide's adjuvant groups were 6.7% and 3.3%, respectively. Additionally, the IgM antibody responses elicited in GapA groups and WC groups were significantly higher than those in PBS groups. Furthermore, the expressions of cytokine (IL-1β and TNF-α) mRNAs in the GapA groups and WC groups were significantly higher than those in the PBS groups. Taken together, these results reveal that the GapA protein is a promising vaccine candidate that could be used to prevent streptococcosis in tilapia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Evaluation of Novel Oral Vaccine Candidates and Validation of a Caprine Model of Johne's Disease

    Directory of Open Access Journals (Sweden)

    Murray E. Hines

    2014-03-01

    Full Text Available Johne’s disease (JD caused by Mycobacterium avium subspecies paratuberculosis (MAP is a major threat to the dairy industry and possibly some cases of Crohn’s disease in humans. A MAP vaccine that reduced of clinical disease and/or reduced fecal shedding would aid in the control of JD. The objectives of this study were 1 to evaluate the efficacy of 5 attenuated strains of MAP as vaccine candidates compared to a commercial control vaccine using the protocol proposed by the Johne’s Disease Integrated Program (JDIP Animal Model Standardization Committee (AMSC, and 2 to validate the AMSC Johne’s disease goat challenge model. Eighty goat kids were vaccinated orally twice at 8 and 10 weeks of age with an experimental vaccine or once subcutaneously at 8 weeks with Silirum® (Zoetis, or a sham control oral vaccine at 8 and 10 weeks. Kids were challenged orally with a total of approximately 1.44 X 10^9 CFU divided in 2 consecutive daily doses using MAP ATCC-700535 (K10-like bovine isolate. All kids were necropsied at 13 months post challenge. Results indicated that the AMSC goat challenge model is a highly efficient and valid model for JD challenge studies. None of the experimental or control vaccines evaluated prevented MAP infection or eliminated fecal shedding, although the 329 vaccine lowered the incidence of infection, fecal shedding, tissue colonization and reduced lesion scores, but less than the control vaccine. Based on our results the relative performance ranking of the experimental live-attenuated vaccines evaluated, the 329 vaccine was the best performer, followed by the 318 vaccine, then 316 vaccine, 315 vaccine and finally the 319 vaccine was the worst performer. The subcutaneously injected control vaccine outperformed the orally-delivered mutant vaccine candidates. Two vaccines (329 and 318 do reduce presence of JD gross and microscopic lesions, slow progression of disease, and one vaccine (329 reduced fecal shedding and tissue

  16. Evaluation of novel oral vaccine candidates and validation of a caprine model of Johne's disease

    Science.gov (United States)

    Hines, Murray E.; Turnquist, Sue E.; Ilha, Marcia R. S.; Rajeev, Sreekumari; Jones, Arthur L.; Whittington, Lisa; Bannantine, John P.; Barletta, Raúl G.; Gröhn, Yrjö T.; Katani, Robab; Talaat, Adel M.; Li, Lingling; Kapur, Vivek

    2014-01-01

    Johne's disease (JD) caused by Mycobacterium avium subspecies paratuberculosis (MAP) is a major threat to the dairy industry and possibly some cases of Crohn's disease in humans. A MAP vaccine that reduced of clinical disease and/or reduced fecal shedding would aid in the control of JD. The objectives of this study were (1) to evaluate the efficacy of 5 attenuated strains of MAP as vaccine candidates compared to a commercial control vaccine using the protocol proposed by the Johne's Disease Integrated Program (JDIP) Animal Model Standardization Committee (AMSC), and (2) to validate the AMSC Johne's disease goat challenge model. Eighty goat kids were vaccinated orally twice at 8 and 10 weeks of age with an experimental vaccine or once subcutaneously at 8 weeks with Silirum® (Zoetis), or a sham control oral vaccine at 8 and 10 weeks. Kids were challenged orally with a total of approximately 1.44 × 109 CFU divided in two consecutive daily doses using MAP ATCC-700535 (K10-like bovine isolate). All kids were necropsied at 13 months post-challenge. Results indicated that the AMSC goat challenge model is a highly efficient and valid model for JD challenge studies. None of the experimental or control vaccines evaluated prevented MAP infection or eliminated fecal shedding, although the 329 vaccine lowered the incidence of infection, fecal shedding, tissue colonization and reduced lesion scores, but less than the control vaccine. Based on our results the relative performance ranking of the experimental live-attenuated vaccines evaluated, the 329 vaccine was the best performer, followed by the 318 vaccine, then 316 vaccine, 315 vaccine and finally the 319 vaccine was the worst performer. The subcutaneously injected control vaccine outperformed the orally-delivered mutant vaccine candidates. Two vaccines (329 and 318) do reduce presence of JD gross and microscopic lesions, slow progression of disease, and one vaccine (329) reduced fecal shedding and tissue colonization. PMID

  17. Transcription status of vaccine candidate genes of Plasmodium falciparum during the hepatic phase of its life cycle.

    NARCIS (Netherlands)

    Bodescot, M.; Silvie, O.; Siau, A.; Refour, P.; Pino, P.; Franetich, J.F.; Hannoun, L.; Sauerwein, R.W.; Mazier, D.

    2004-01-01

    The CSP, EMP2/MESA, MSP2, MSP3, MSP5, RAP1, RAP2, RESA1, SERA1 and SSP2/TRAP genes of Plasmodium falciparum are vaccine candidates. The hepatic phase of the infection is of major interest due to the protection induced by immunization with radiation-attenuated sporozoites. We therefore performed

  18. Naturally acquired antibody responses to recombinant Pfs230 and Pfs48/45 transmission blocking vaccine candidates

    NARCIS (Netherlands)

    Jones, S; Grignard, L.; Nebie, I.; Chilongola, J.; Dodoo, D.; Sauerwein, R.W.; Theisen, M.; Roeffen, W.F.; Singh, S.K; Singh, R.K.; Kyei-Baafour, E.; Tetteh, K.; Drakeley, C.; Bousema, T.

    2015-01-01

    OBJECTIVES: Pfs48/45 and Pfs230 are Plasmodium falciparum sexual stage proteins and promising malaria transmission-blocking vaccine candidates. Antibody responses against these proteins may be naturally acquired and target antigens may be under selective pressure. This has consequences for the

  19. Biohazard Analysis of Select Biodefense Vaccine Candidates - Venezuelan Equine Encephalitis Virus Strain 3526 and Francisella Tularensis LVS

    International Nuclear Information System (INIS)

    Rao, V.

    2007-01-01

    Biohazard assessment of biodefense vaccine candidates forms the basis for a facility- and activity-specific risk assessment performed to determine the biosafety levels and general safety standards required for biological product development. As a part of our support to the US biodefense vaccine development program, we perform a systematic biohazard assessment of potential vaccine candidates with the primary objective to, (a) Identify and characterize hazard elements associated with the wild type and vaccine strains, (b) Provide biohazard information on the etiologic agent (vaccine candidate) to assess Phase 1 clinical trial facility sites, (c) Provide a baseline to conduct an agent and facility-specific risk assessment at clinical trial facilities interested in performing phase 1 clinical trial, (d) Provide comparative hazard profiles of the vaccine candidates wit MSDS for wild-type to identify and establish appropriate protective biosafety levels, and (e) Support determination of a hazard level to select personal protective equipment as required under the OSHA guidelines. This paper will describe the biohazard analysis of two vaccine candidates, Venezuelan Equine Encephalitis Virus Strain 3526 and Francisella tularensis LVS, a viral and bacterial agent, respectively. As part of the biohazard assessment we preformed a thorough review of published literature on medical pathology, epidemiology, pre-clinical investigational studies, and environmental data on the etiologic agent subtypes and the vaccine candidates. Using standard analytical procedures, the data were then analyzed relative to two intrinsic hazard parameters-health hazard and environmental hazard. Using a weight-of-evidence (WOE) approach, the potential hazards of etiologic agent wild subtypes and vaccine candidates were ranked under three main categories: Public Health Hazard, Environmental Hazard, and Overall Hazard. A WOE scoring system allows for both a determination of the intrinsic hazard of each

  20. Biohazard Analysis of Select Biodefense Vaccine Candidates - Venezuelan Equine Encephalitis Virus Strain 3526 and Francisella Tularensis LVS

    Energy Technology Data Exchange (ETDEWEB)

    Rao, V [National Security Programs, Computer Science Corporation, Alexandria (United States)

    2007-07-01

    Biohazard assessment of biodefense vaccine candidates forms the basis for a facility- and activity-specific risk assessment performed to determine the biosafety levels and general safety standards required for biological product development. As a part of our support to the US biodefense vaccine development program, we perform a systematic biohazard assessment of potential vaccine candidates with the primary objective to, (a) Identify and characterize hazard elements associated with the wild type and vaccine strains, (b) Provide biohazard information on the etiologic agent (vaccine candidate) to assess Phase 1 clinical trial facility sites, (c) Provide a baseline to conduct an agent and facility-specific risk assessment at clinical trial facilities interested in performing phase 1 clinical trial, (d) Provide comparative hazard profiles of the vaccine candidates wit MSDS for wild-type to identify and establish appropriate protective biosafety levels, and (e) Support determination of a hazard level to select personal protective equipment as required under the OSHA guidelines. This paper will describe the biohazard analysis of two vaccine candidates, Venezuelan Equine Encephalitis Virus Strain 3526 and Francisella tularensis LVS, a viral and bacterial agent, respectively. As part of the biohazard assessment we preformed a thorough review of published literature on medical pathology, epidemiology, pre-clinical investigational studies, and environmental data on the etiologic agent subtypes and the vaccine candidates. Using standard analytical procedures, the data were then analyzed relative to two intrinsic hazard parameters-health hazard and environmental hazard. Using a weight-of-evidence (WOE) approach, the potential hazards of etiologic agent wild subtypes and vaccine candidates were ranked under three main categories: Public Health Hazard, Environmental Hazard, and Overall Hazard. A WOE scoring system allows for both a determination of the intrinsic hazard of each

  1. Exoproteome and Secretome Derived Broad Spectrum Novel Drug and Vaccine Candidates in Vibrio cholerae Targeted by Piper betel Derived Compounds

    Science.gov (United States)

    Barh, Debmalya; Barve, Neha; Gupta, Krishnakant; Chandra, Sudha; Jain, Neha; Tiwari, Sandeep; Leon-Sicairos, Nidia; Canizalez-Roman, Adrian; Rodrigues dos Santos, Anderson; Hassan, Syed Shah; Almeida, Síntia; Thiago Jucá Ramos, Rommel; Augusto Carvalho de Abreu, Vinicius; Ribeiro Carneiro, Adriana; de Castro Soares, Siomar; Luiz de Paula Castro, Thiago; Miyoshi, Anderson; Silva, Artur; Kumar, Anil; Narayan Misra, Amarendra; Blum, Kenneth; Braverman, Eric R.; Azevedo, Vasco

    2013-01-01

    Vibrio cholerae is the causal organism of the cholera epidemic, which is mostly prevalent in developing and underdeveloped countries. However, incidences of cholera in developed countries are also alarming. Because of the emergence of new drug-resistant strains, even though several generic drugs and vaccines have been developed over time, Vibrio infections remain a global health problem that appeals for the development of novel drugs and vaccines against the pathogen. Here, applying comparative proteomic and reverse vaccinology approaches to the exoproteome and secretome of the pathogen, we have identified three candidate targets (ompU, uppP and yajC) for most of the pathogenic Vibrio strains. Two targets (uppP and yajC) are novel to Vibrio, and two targets (uppP and ompU) can be used to develop both drugs and vaccines (dual targets) against broad spectrum Vibrio serotypes. Using our novel computational approach, we have identified three peptide vaccine candidates that have high potential to induce both B- and T-cell-mediated immune responses from our identified two dual targets. These two targets were modeled and subjected to virtual screening against natural compounds derived from Piper betel. Seven compounds were identified first time from Piper betel to be highly effective to render the function of these targets to identify them as emerging potential drugs against Vibrio. Our preliminary validation suggests that these identified peptide vaccines and betel compounds are highly effective against Vibrio cholerae. Currently we are exhaustively validating these targets, candidate peptide vaccines, and betel derived lead compounds against a number of Vibrio species. PMID:23382822

  2. Exoproteome and secretome derived broad spectrum novel drug and vaccine candidates in Vibrio cholerae targeted by Piper betel derived compounds.

    Directory of Open Access Journals (Sweden)

    Debmalya Barh

    Full Text Available Vibrio cholerae is the causal organism of the cholera epidemic, which is mostly prevalent in developing and underdeveloped countries. However, incidences of cholera in developed countries are also alarming. Because of the emergence of new drug-resistant strains, even though several generic drugs and vaccines have been developed over time, Vibrio infections remain a global health problem that appeals for the development of novel drugs and vaccines against the pathogen. Here, applying comparative proteomic and reverse vaccinology approaches to the exoproteome and secretome of the pathogen, we have identified three candidate targets (ompU, uppP and yajC for most of the pathogenic Vibrio strains. Two targets (uppP and yajC are novel to Vibrio, and two targets (uppP and ompU can be used to develop both drugs and vaccines (dual targets against broad spectrum Vibrio serotypes. Using our novel computational approach, we have identified three peptide vaccine candidates that have high potential to induce both B- and T-cell-mediated immune responses from our identified two dual targets. These two targets were modeled and subjected to virtual screening against natural compounds derived from Piper betel. Seven compounds were identified first time from Piper betel to be highly effective to render the function of these targets to identify them as emerging potential drugs against Vibrio. Our preliminary validation suggests that these identified peptide vaccines and betel compounds are highly effective against Vibrio cholerae. Currently we are exhaustively validating these targets, candidate peptide vaccines, and betel derived lead compounds against a number of Vibrio species.

  3. Isolation and Characterization of Vaccine Candidate Genes Including CSP and MSP1 in Plasmodium yoelii.

    Science.gov (United States)

    Kim, Seon-Hee; Bae, Young-An; Seoh, Ju-Young; Yang, Hyun-Jong

    2017-06-01

    Malaria is an infectious disease affecting humans, which is transmitted by the bite of Anopheles mosquitoes harboring sporozoites of parasitic protozoans belonging to the genus Plasmodium . Despite past achievements to control the protozoan disease, malaria still remains a significant health threat up to now. In this study, we cloned and characterized the full-unit Plasmodium yoelii genes encoding merozoite surface protein 1 (MSP1), circumsporozoite protein (CSP), and Duffy-binding protein (DBP), each of which can be applied for investigations to obtain potent protective vaccines in the rodent malaria model, due to their specific expression patterns during the parasite life cycle. Recombinant fragments corresponding to the middle and C-terminal regions of PyMSP1 and PyCSP, respectively, displayed strong reactivity against P. yoelii -infected mice sera. Specific native antigens invoking strong humoral immune response during the primary and secondary infections of P. yoelii were also abundantly detected in experimental ICR mice. The low or negligible parasitemia observed in the secondary infected mice was likely to result from the neutralizing action of the protective antibodies. Identification of these antigenic proteins might provide the necessary information and means to characterize additional vaccine candidate antigens, selected solely on their ability to produce the protective antibodies.

  4. Attenuated Mycobacterium tuberculosis SO2 vaccine candidate is unable to induce cell death.

    Directory of Open Access Journals (Sweden)

    Adriana Aporta

    Full Text Available It has been proposed that Mycobacterium tuberculosis virulent strains inhibit apoptosis and trigger cell death by necrosis of host macrophages to evade innate immunity, while non-virulent strains induce typical apoptosis activating a protective host response. As part of the characterization of a novel tuberculosis vaccine candidate, the M. tuberculosis phoP mutant SO2, we sought to evaluate its potential to induce host cell death. The parental M. tuberculosis MT103 strain and the current vaccine against tuberculosis Bacillus Calmette-Guérin (BCG were used as comparators in mouse models in vitro and in vivo. Our data reveal that attenuated SO2 was unable to induce apoptotic events neither in mouse macrophages in vitro nor during lung infection in vivo. In contrast, virulent MT103 triggers typical apoptotic events with phosphatidylserine exposure, caspase-3 activation and nuclear condensation and fragmentation. BCG strain behaved like SO2 and did not induce apoptosis. A clonogenic survival assay confirmed that viability of BCG- or SO2-infected macrophages was unaffected. Our results discard apoptosis as the protective mechanism induced by SO2 vaccine and provide evidence for positive correlation between classical apoptosis induction and virulent strains, suggesting apoptosis as a possible virulence determinant during M. tuberculosis infection.

  5. Characterization of Brucella abortus mutant strain Δ22915, a potential vaccine candidate.

    Science.gov (United States)

    Bao, Yanqing; Tian, Mingxing; Li, Peng; Liu, Jiameng; Ding, Chan; Yu, Shengqing

    2017-04-04

    Brucellosis, caused by Brucella spp., is an important zoonosis worldwide. Vaccination is an effective strategy for protection against Brucella infection in livestock in developing countries and in wildlife in developed countries. However, current vaccine strains including S19 and RB51 are pathogenic to humans and pregnant animals, limiting their use. In this study, we constructed the Brucella abortus (B. abortus) S2308 mutant strain Δ22915, in which the putative lytic transglycosylase gene BAB_RS22915 was deleted. The biological properties of mutant strain Δ22915 were characterized and protection of mice against virulent S2308 challenge was evaluated. The mutant strain Δ22915 showed reduced survival within RAW264.7 cells and survival in vivo in mice. In addition, the mutant strain Δ22915 failed to escape fusion with lysosomes within host cells, and caused no observable pathological damage. RNA-seq analysis indicated that four genes associated with amino acid/nucleotide transport and metabolism were significantly upregulated in mutant strain Δ22915. Furthermore, inoculation of ∆22915 at 10 5 colony forming units induced effective host immune responses and long-term protection of BALB/c mice. Therefore, mutant strain ∆22915 could be used as a novel vaccine candidate in the future to protect animals against B. abortus infection.

  6. A plant-produced Pfs230 vaccine candidate blocks transmission of Plasmodium falciparum.

    Science.gov (United States)

    Farrance, Christine E; Rhee, Amy; Jones, R Mark; Musiychuk, Konstantin; Shamloul, Moneim; Sharma, Satish; Mett, Vadim; Chichester, Jessica A; Streatfield, Stephen J; Roeffen, Will; van de Vegte-Bolmer, Marga; Sauerwein, Robert W; Tsuboi, Takafumi; Muratova, Olga V; Wu, Yimin; Yusibov, Vidadi

    2011-08-01

    Plasmodium falciparum is transmitted to a new host after completing its sexual cycle within a mosquito. Developing vaccines against the parasite sexual stages is a critical component in the fight against malaria. We are targeting multiple proteins of P. falciparum which are found only on the surfaces of the sexual forms of the parasite and where antibodies against these proteins have been shown to block the progression of the parasite's life cycle in the mosquito and thus block transmission to the next human host. We have successfully produced a region of the Pfs230 antigen in our plant-based transient-expression system and evaluated this vaccine candidate in an animal model. This plant-produced protein, 230CMB, is expressed at approximately 800 mg/kg in fresh whole leaf tissue and is 100% soluble. Administration of 230CMB with >90% purity induces strong immune responses in rabbits with high titers of transmission-blocking antibodies, resulting in a greater than 99% reduction in oocyst counts in the presence of complement, as determined by a standard membrane feeding assay. Our data provide a clear perspective on the clinical development of a Pfs230-based transmission-blocking malaria vaccine.

  7. Evaluation of a Group A Streptococcus synthetic oligosaccharide as vaccine candidate.

    Science.gov (United States)

    Kabanova, Anna; Margarit, Immaculada; Berti, Francesco; Romano, Maria R; Grandi, Guido; Bensi, Giuliano; Chiarot, Emiliano; Proietti, Daniela; Swennen, Erwin; Cappelletti, Emilia; Fontani, Paola; Casini, Daniele; Adamo, Roberto; Pinto, Vittoria; Skibinski, David; Capo, Sabrina; Buffi, Giada; Gallotta, Marilena; Christ, William J; Campbell, A Stewart; Pena, John; Seeberger, Peter H; Rappuoli, Rino; Costantino, Paolo

    2010-12-10

    Bacterial infections caused by Group A Streptococcus (GAS) are a serious health care concern that currently cannot be prevented by vaccination. The GAS cell-wall polysaccharide (GAS-PS) is an attractive vaccine candidate due to its constant expression pattern on different bacterial strains and protective properties of anti-GAS-PS antibodies. Here we report for the first time the immunoprotective efficacy of glycoconjugates with synthetic GAS oligosaccharides as compared to those containing the native GAS-PS. A series of hexa- and dodecasaccharides based on the GAS-PS structure were prepared by chemical synthesis and conjugated to CRM(197). When tested in mice, the conjugates containing the synthetic oligosaccharides conferred levels of immunoprotection comparable to those elicited by the native conjugate. Antisera from immunized rabbits promoted phagocytosis of encapsulated GAS strains. Furthermore we discuss variables that might correlate with glycoconjugate immunogenicity and demonstrate the potential of the synthetic approach that benefits from increased antigen purity and facilitated manufacturing. Copyright © 2010 Elsevier Ltd. All rights reserved.

  8. Lipoprotein NMB0928 from Neisseria meningitidis serogroup B as a novel vaccine candidate.

    Science.gov (United States)

    Delgado, Maité; Yero, Daniel; Niebla, Olivia; González, Sonia; Climent, Yanet; Pérez, Yusleydis; Cobas, Karem; Caballero, Evelín; García, Darien; Pajón, Rolando

    2007-12-05

    Polysaccharide-based vaccines for serogroup B Neisseria meningitidis have failed to induce protective immunity. As a result, efforts to develop vaccines for serogroup B meningococcal disease have mostly focused on outer membrane proteins (OMP). Vaccine candidates based on meningococcal OMP have emerged in the form of outer membrane vesicles (OMVs) or, more recently, purified recombinant proteins, as alternative strategies for serogroup B vaccine development. In our group, the protein composition of the Cuban OMVs-based vaccine VA-MENGOC-BC was elucidated using two-dimensional gel electrophoresis and mass spectrometry. The proteomic map of this product allowed the identification of new putative protective proteins not previously reported as components of an antimeningococcal vaccine. In the present study, we have determined the immunogenicity and protective capacity of NMB0928, one of those proteins present in the OMVs. The antigen was obtained as a recombinant protein in Escherichia coli, purified and used to immunize mice. The antiserum produced against the protein was capable to recognize the natural protein in different meningococcal strains by whole-cell ELISA and Western blotting. After immunization, recombinant NMB0928 induced bactericidal antibodies, and when the protein was administered inserted into liposomes, the elicited antibodies were protective in the infant rat model. These results suggest that NMB0928 is a novel antigen worth to be included in a broadly protective meningococcal vaccine.

  9. Identification of synthetic vaccine candidates against SARS CoV infection

    International Nuclear Information System (INIS)

    Lien, Shu-Pei; Shih, Yi-Ping; Chen, Hsin-Wei; Tsai, Jy-Ping; Leng, Chih-Hsiang; Lin, Min-Han; Lin, Li-Hsiu; Liu, Hsin-Yu; Chou, Ai-Hsiang; Chang, Yu-Wen; Chen, Yi-Ming A.; Chong, Pele; Liu, Shih-Jen

    2007-01-01

    Three peptides, D1 (amino acid residues 175-201), D2 (a.a. 434-467), and TM (a.a. 1128-1159), corresponding to the spike protein (S) of severe acute respiratory syndrome corona virus (SARS CoV) were synthesized and their immunological functions were investigated in three different animals models (mice, guinea pigs, and rabbits). The peptides mixture formulated either with Freund's adjuvant or synthetic adjuvant Montanide ISA-51/oligodeoxy nucleotide CpG (ISA/CpG) could elicit antisera in immunized animals which were capable of inhibiting SARS/HIV pseudovirus entry into HepG2 cells. The neutralizing epitopes were identified using peptides to block the neutralizing effect of guinea pig antisera. The major neutralizing epitope was located on the D2 peptide, and the amino acid residue was fine mapped to 434-453. In BALB/c mice T-cell proliferation assay revealed that only D2 peptide contained T-cell epitope, the sequence of which corresponded to amino acid residue 434-448. The ISA/CpG formulation generated anti-D2 IgG titer comparable to those obtained from Freund's adjuvant formulation, but generated fewer antibodies against D1 or TM peptides. The highly immunogenic D2 peptide contains both neutralizing and Th cell epitopes. These results suggest that synthetic peptide D2 would be useful as a component of SARS vaccine candidates

  10. An assessment of enterotoxigenic Escherichia coli and Shigella vaccine candidates for infants and children.

    Science.gov (United States)

    Walker, Richard I

    2015-02-18

    Despite improvements to water quality, sanitation, and the implementation of current prevention and treatment interventions, diarrhea remains a major cause of illness and death, especially among children less than five years of age in the developing world. Rotavirus vaccines have already begun making a real impact on diarrhea, but several more enteric vaccines will be necessary to achieve broader reductions of illness and death. Among the many causes of diarrheal disease, enterotoxigenic Escherichia coli (ETEC) and Shigella are the two most important bacterial pathogens for which there are no currently licensed vaccines. Vaccines against these two pathogens could greatly reduce the impact of disease caused by these infections. This review describes the approaches to ETEC and Shigella vaccines that are currently under development, including a range of both cellular and subunit approaches for each pathogen. In addition, the review discusses strategies for maximizing the potential benefit of these vaccines, which includes the feasibility of co-administration, consolidation, and combination of vaccine candidates, as well as issues related to effective administration of enteric vaccines to infants. Recent impact studies indicate that ETEC and Shigella vaccines could significantly benefit global public health. Either vaccine, particularly if they could be combined together or with another enteric vaccine, would be an extremely valuable tool for saving lives and promoting the health of infants and children in the developing world, as well as potentially providing protection to travelers and military personnel visiting endemic areas. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. In silico analysis to identify vaccine candidates common to multiple serotypes of Shigella and evaluation of their immunogenicity

    KAUST Repository

    Pahil, Sapna

    2017-08-02

    Shigellosis or bacillary dysentery is an important cause of diarrhea, with the majority of the cases occurring in developing countries. Considering the high disease burden, increasing antibiotic resistance, serotype-specific immunity and the post-infectious sequelae associated with shigellosis, there is a pressing need of an effective vaccine against multiple serotypes of the pathogen. In the present study, we used bio-informatics approach to identify antigens shared among multiple serotypes of Shigella spp. This approach led to the identification of many immunogenic peptides. The five most promising peptides based on MHC binding efficiency were a putative lipoprotein (EL PGI I), a putative heat shock protein (EL PGI II), Spa32 (EL PGI III), IcsB (EL PGI IV) and a hypothetical protein (EL PGI V). These peptides were synthesized and the immunogenicity was evaluated in BALB/c mice by ELISA and cytokine assays. The putative heat shock protein (HSP) and the hypothetical protein elicited good humoral response, whereas putative lipoprotein, Spa32 and IcsB elicited good T-cell response as revealed by increased IFN-γ and TNF-α cytokine levels. The patient sera from confirmed cases of shigellosis were also evaluated for the presence of peptide specific antibodies with significant IgG and IgA antibodies against the HSP and the hypothetical protein, bestowing them as potential future vaccine candidates. The antigens reported in this study are novel and have not been tested as vaccine candidates against Shigella. This study offers time and cost-effective way of identifying unprecedented immunogenic antigens to be used as potential vaccine candidates. Moreover, this approach should easily be extendable to find new potential vaccine candidates for other pathogenic bacteria.

  12. Conjugating recombinant proteins to Pseudomonas aeruginosa ExoProtein A: a strategy for enhancing immunogenicity of malaria vaccine candidates

    OpenAIRE

    Qian, Feng; Wu, Yimin; Muratova, Olga; Zhou, Hong; Dobrescu, Gelu; Duggan, Peter; Lynn, Lambert; Song, Guanhong; Zhang, Yanling; Reiter, Karine; MacDonald, Nicholas; Narum, David L.; Long, Carole A.; Miller, Louis H.; Saul, Allan

    2007-01-01

    Conjugation of polysaccharides to carrier proteins has been a successful approach for producing safe and effective vaccines. In an attempt to increase the immunogenicity of two malarial vaccine candidate proteins of Plasmodium falciparum, apical membrane antigen 1 (AMA1) for blood stage vaccines and surface protein 25 (Pfs25) for mosquito stage vaccines, each was chemically conjugated to the mutant, nontoxic Pseudomonas aeruginosa ExoProtein A (rEPA). AMA1 is a large (66 kD) relatively good i...

  13. In silico analysis to identify vaccine candidates common to multiple serotypes of Shigella and evaluation of their immunogenicity

    KAUST Repository

    Pahil, Sapna; Taneja, Neelam; Ansari, Hifzur Rahman; Raghava, G. P. S.

    2017-01-01

    Shigellosis or bacillary dysentery is an important cause of diarrhea, with the majority of the cases occurring in developing countries. Considering the high disease burden, increasing antibiotic resistance, serotype-specific immunity and the post-infectious sequelae associated with shigellosis, there is a pressing need of an effective vaccine against multiple serotypes of the pathogen. In the present study, we used bio-informatics approach to identify antigens shared among multiple serotypes of Shigella spp. This approach led to the identification of many immunogenic peptides. The five most promising peptides based on MHC binding efficiency were a putative lipoprotein (EL PGI I), a putative heat shock protein (EL PGI II), Spa32 (EL PGI III), IcsB (EL PGI IV) and a hypothetical protein (EL PGI V). These peptides were synthesized and the immunogenicity was evaluated in BALB/c mice by ELISA and cytokine assays. The putative heat shock protein (HSP) and the hypothetical protein elicited good humoral response, whereas putative lipoprotein, Spa32 and IcsB elicited good T-cell response as revealed by increased IFN-γ and TNF-α cytokine levels. The patient sera from confirmed cases of shigellosis were also evaluated for the presence of peptide specific antibodies with significant IgG and IgA antibodies against the HSP and the hypothetical protein, bestowing them as potential future vaccine candidates. The antigens reported in this study are novel and have not been tested as vaccine candidates against Shigella. This study offers time and cost-effective way of identifying unprecedented immunogenic antigens to be used as potential vaccine candidates. Moreover, this approach should easily be extendable to find new potential vaccine candidates for other pathogenic bacteria.

  14. In silico analysis to identify vaccine candidates common to multiple serotypes of Shigella and evaluation of their immunogenicity.

    Science.gov (United States)

    Pahil, Sapna; Taneja, Neelam; Ansari, Hifzur Rahman; Raghava, G P S

    2017-01-01

    Shigellosis or bacillary dysentery is an important cause of diarrhea, with the majority of the cases occurring in developing countries. Considering the high disease burden, increasing antibiotic resistance, serotype-specific immunity and the post-infectious sequelae associated with shigellosis, there is a pressing need of an effective vaccine against multiple serotypes of the pathogen. In the present study, we used bio-informatics approach to identify antigens shared among multiple serotypes of Shigella spp. This approach led to the identification of many immunogenic peptides. The five most promising peptides based on MHC binding efficiency were a putative lipoprotein (EL PGI I), a putative heat shock protein (EL PGI II), Spa32 (EL PGI III), IcsB (EL PGI IV) and a hypothetical protein (EL PGI V). These peptides were synthesized and the immunogenicity was evaluated in BALB/c mice by ELISA and cytokine assays. The putative heat shock protein (HSP) and the hypothetical protein elicited good humoral response, whereas putative lipoprotein, Spa32 and IcsB elicited good T-cell response as revealed by increased IFN-γ and TNF-α cytokine levels. The patient sera from confirmed cases of shigellosis were also evaluated for the presence of peptide specific antibodies with significant IgG and IgA antibodies against the HSP and the hypothetical protein, bestowing them as potential future vaccine candidates. The antigens reported in this study are novel and have not been tested as vaccine candidates against Shigella. This study offers time and cost-effective way of identifying unprecedented immunogenic antigens to be used as potential vaccine candidates. Moreover, this approach should easily be extendable to find new potential vaccine candidates for other pathogenic bacteria.

  15. In silico analysis to identify vaccine candidates common to multiple serotypes of Shigella and evaluation of their immunogenicity.

    Directory of Open Access Journals (Sweden)

    Sapna Pahil

    Full Text Available Shigellosis or bacillary dysentery is an important cause of diarrhea, with the majority of the cases occurring in developing countries. Considering the high disease burden, increasing antibiotic resistance, serotype-specific immunity and the post-infectious sequelae associated with shigellosis, there is a pressing need of an effective vaccine against multiple serotypes of the pathogen. In the present study, we used bio-informatics approach to identify antigens shared among multiple serotypes of Shigella spp. This approach led to the identification of many immunogenic peptides. The five most promising peptides based on MHC binding efficiency were a putative lipoprotein (EL PGI I, a putative heat shock protein (EL PGI II, Spa32 (EL PGI III, IcsB (EL PGI IV and a hypothetical protein (EL PGI V. These peptides were synthesized and the immunogenicity was evaluated in BALB/c mice by ELISA and cytokine assays. The putative heat shock protein (HSP and the hypothetical protein elicited good humoral response, whereas putative lipoprotein, Spa32 and IcsB elicited good T-cell response as revealed by increased IFN-γ and TNF-α cytokine levels. The patient sera from confirmed cases of shigellosis were also evaluated for the presence of peptide specific antibodies with significant IgG and IgA antibodies against the HSP and the hypothetical protein, bestowing them as potential future vaccine candidates. The antigens reported in this study are novel and have not been tested as vaccine candidates against Shigella. This study offers time and cost-effective way of identifying unprecedented immunogenic antigens to be used as potential vaccine candidates. Moreover, this approach should easily be extendable to find new potential vaccine candidates for other pathogenic bacteria.

  16. A Large Size Chimeric Highly Immunogenic Peptide Presents Multistage Plasmodium Antigens as a Vaccine Candidate System against Malaria.

    Science.gov (United States)

    Lozano, José Manuel; Varela, Yahson; Silva, Yolanda; Ardila, Karen; Forero, Martha; Guasca, Laura; Guerrero, Yuly; Bermudez, Adriana; Alba, Patricia; Vanegas, Magnolia; Patarroyo, Manuel Elkin

    2017-11-01

    Rational strategies for obtaining malaria vaccine candidates should include not only a proper selection of target antigens for antibody stimulation, but also a versatile molecular design based on ordering the right pieces from the complex pathogen molecular puzzle towards more active and functional immunogens. Classical Plasmodium falciparum antigens regarded as vaccine candidates have been selected as model targets in this study. Among all possibilities we have chosen epitopes of Pf CSP, STARP; MSA1 and Pf 155/RESA from pre- and erythrocyte stages respectively for designing a large 82-residue chimeric immunogen. A number of options aimed at diminishing steric hindrance for synthetic procedures were assessed based on standard Fmoc chemistry such as building block orthogonal ligation; pseudo-proline and microwave-assisted procedures, therefore the large-chimeric target was produced, characterized and immunologically tested. Antigenicity and functional in vivo efficacy tests of the large-chimera formulations administered alone or as antigen mixtures have proven the stimulation of high antibody titers, showing strong correlation with protection and parasite clearance of vaccinated BALB/c mice after being lethally challenged with both P. berghei -ANKA and P. yoelii 17XL malaria strains. Besides, 3D structure features shown by the large-chimera encouraged as to propose using these rational designed large synthetic molecules as reliable vaccine candidate-presenting systems.

  17. A Large Size Chimeric Highly Immunogenic Peptide Presents Multistage Plasmodium Antigens as a Vaccine Candidate System against Malaria

    Directory of Open Access Journals (Sweden)

    José Manuel Lozano

    2017-11-01

    Full Text Available Rational strategies for obtaining malaria vaccine candidates should include not only a proper selection of target antigens for antibody stimulation, but also a versatile molecular design based on ordering the right pieces from the complex pathogen molecular puzzle towards more active and functional immunogens. Classical Plasmodium falciparum antigens regarded as vaccine candidates have been selected as model targets in this study. Among all possibilities we have chosen epitopes of PfCSP, STARP; MSA1 and Pf155/RESA from pre- and erythrocyte stages respectively for designing a large 82-residue chimeric immunogen. A number of options aimed at diminishing steric hindrance for synthetic procedures were assessed based on standard Fmoc chemistry such as building block orthogonal ligation; pseudo-proline and microwave-assisted procedures, therefore the large-chimeric target was produced, characterized and immunologically tested. Antigenicity and functional in vivo efficacy tests of the large-chimera formulations administered alone or as antigen mixtures have proven the stimulation of high antibody titers, showing strong correlation with protection and parasite clearance of vaccinated BALB/c mice after being lethally challenged with both P. berghei-ANKA and P. yoelii 17XL malaria strains. Besides, 3D structure features shown by the large-chimera encouraged as to propose using these rational designed large synthetic molecules as reliable vaccine candidate-presenting systems.

  18. Structure and interactions of a malarial vaccine candidate, AMA1, form the parasite plasmodium falciparum

    International Nuclear Information System (INIS)

    Miles, L.A.; Keizer, D.W.; Hodder, A.N.; Nair, M.; Hinds, M.G.; Norton, R.S.; Li, F.; Foley, M.; Coley, A.; Anders, R.F.

    2001-01-01

    Full text: Apical membrane antigen 1 (AMA1), a merozoite surface protein found in all species of Plasmodium and other apicomplexan parasites, is a strong candidate for inclusion in a malarial vaccine. Recombinant AMA1 protected against P. fragile in monkeys and P. chabaudi adami in mice. P. falciparum AMA1 which has a 62-kDa ectodomain consisting of three disulphide-stabilised domains, is a target of antibodies that inhibit merozoite invasion in vitro. Here we describe the solution structure of domain III (14 kDa), determined by NMR on 15 N- and 13 C/ 15 N-labelled samples. It has a well-defined disulphide-stabilised core interrupted by a disordered loop, and both the N- and C-terminal regions of the molecule are unstructured. The structured region includes all three disulphide bonds. Naturally-occurring mutations across 11 different P falciparum strains that are located far apart in the sequence cluster around the disulphide core in the 3D structure of domain III, suggesting that this region contains the major epitopes recognised by neutralising antibodies. Consistent with this, the disulphide-bond stabilised conformation of the ectodomain was essential for protection, as the antigen was not an effective vaccine after reduction and alkylation. Peptides have been found by phage display that bind to AMA1 and block merozoite invasion of erythrocytes. We have investigated their solution structures and interaction with full-length AMA1 ectodomain in an effort to understand the structure-function relationships of this important vaccine candidate

  19. A cell wall protein-based vaccine candidate induce protective immune response against Sporothrix schenckii infection.

    Science.gov (United States)

    Portuondo, Deivys Leandro; Batista-Duharte, Alexander; Ferreira, Lucas Souza; Martínez, Damiana Téllez; Polesi, Marisa Campos; Duarte, Roberta Aparecida; de Paula E Silva, Ana Carolina Alves; Marcos, Caroline Maria; Almeida, Ana Marisa Fusco de; Carlos, Iracilda Zeppone

    2016-02-01

    Sporotrichosis is a subcutaneous mycosis caused by several closely related thermo-dimorphic fungi of the Sporothrix schenckii species complex, affecting humans and other mammals. In the last few years, new strategies have been proposed for controlling sporotrichosis owning to concerns about its growing incidence in humans, cats, and dogs in Brazil, as well as the toxicity and limited efficacy of conventional antifungal drugs. In this study, we assessed the immunogenicity and protective properties of two aluminum hydroxide (AH)-adsorbed S. schenckii cell wall protein (ssCWP)-based vaccine formulations in a mouse model of systemic S. schenckii infection. Fractioning by SDS-PAGE revealed nine protein bands, two of which were functionally characterized: a 44kDa peptide hydrolase and a 47kDa enolase, which was predicted to be an adhesin. Sera from immunized mice recognized the 47kDa enolase and another unidentified 71kDa protein, whereas serum from S. schenckii-infected mice recognized both these proteins plus another unidentified 9.4kDa protein. Furthermore, opsonization with the anti-ssCWP sera led to markedly increased phagocytosis and was able to strongly inhibit the fungus' adhesion to fibroblasts. Immunization with the higher-dose AH-adjuvanted formulation led to increased ex vivo release of IL-12, IFN-γ, IL-4, and IL-17, whereas only IL-12 and IFN-γ were induced by the higher-dose non-adjuvanted formulation. Lastly, passive transference of the higher-dose AH-adjuvanted formulation's anti-ssCWP serum was able to afford in vivo protection in a subsequent challenge with S. schenckii, becoming a viable vaccine candidate for further testing. Copyright © 2015 Elsevier GmbH. All rights reserved.

  20. Immune response profiles of calves following vaccination with live BCG and inactivated Mycobacterium bovis vaccine candidates.

    Directory of Open Access Journals (Sweden)

    E M D L van der Heijden

    Full Text Available Conventional control and eradication strategies for bovine tuberculosis (BTB face tremendous difficulties in developing countries; countries with wildlife reservoirs, a complex wildlife-livestock-human interface or a lack of veterinary and veterinary public health surveillance. Vaccination of cattle and other species might in some cases provide the only suitable control strategy for BTB, while in others it may supplement existing test-and-slaughter schemes. However, the use of live BCG has several limitations and the global rise of HIV/AIDS infections has furthermore warranted the exploration of inactivated vaccine preparations. The aim of this study was to compare the immune response profiles in response to parenteral vaccination with live BCG and two inactivated vaccine candidates in cattle. Twenty-four mixed breed calves (Bos taurus aged 4-6 months, were allocated to one of four groups and vaccinated sub-cutaneously with live M. bovis BCG (Danish 1331, formalin-inactivated M. bovis BCG, heat-killed M. bovis or PBS/Montanide™ (control. Interferon-γ responsiveness and antibody production were measured prior to vaccination and at weekly intervals thereafter for twelve weeks. At nine weeks post-priming, animals were skin tested using tuberculins and MTBC specific protein cocktails and subsequently challenged through intranodular injection of live M. bovis BCG. The animals in the heat-killed M. bovis group demonstrated strong and sustained cell-mediated and humoral immune responses, significantly higher than the control group in response to vaccination, which may indicate a protective immune profile. Animals in this group showed reactivity to the skin test reagents, confirming good vaccine take. Lastly, although not statistically significant, recovery of BCG after challenge was lowest in the heat-killed M. bovis group. In conclusion, the parenteral heat-killed M. bovis vaccine proved to be clearly immunogenic in cattle in the present study

  1. Force Spectroscopy of the Plasmodium falciparum Vaccine Candidate Circumsporozoite Protein Suggests a Mechanically Pliable Repeat Region.

    Science.gov (United States)

    Patra, Aditya Prasad; Sharma, Shobhona; Ainavarapu, Sri Rama Koti

    2017-02-10

    The most effective vaccine candidate of malaria is based on the Plasmodium falciparum circumsporozoite protein (CSP), a major surface protein implicated in the structural strength, motility, and immune evasion properties of the infective sporozoites. It is suspected that reversible conformational changes of CSP are required for infection of the mammalian host, but the detailed structure and dynamic properties of CSP remain incompletely understood, limiting our understanding of its function in the infection. Here, we report the structural and mechanical properties of the CSP studied using single-molecule force spectroscopy on several constructs, one including the central region of CSP, which is rich in NANP amino acid repeats (CSP rep ), and a second consisting of a near full-length sequence without the signal and anchor hydrophobic domains (CSP ΔHP ). Our results show that the CSP rep is heterogeneous, with 40% of molecules requiring virtually no mechanical force to unfold (<10 piconewtons (pN)), suggesting that these molecules are mechanically compliant and perhaps act as entropic springs, whereas the remaining 60% are partially structured with low mechanical resistance (∼70 pN). CSP ΔHP having multiple force peaks suggests specifically folded domains, with two major populations possibly indicating the open and collapsed forms. Our findings suggest that the overall low mechanical resistance of the repeat region, exposed on the outer surface of the sporozoites, combined with the flexible full-length conformations of CSP, may provide the sporozoites not only with immune evasion properties, but also with lubricating capacity required during its navigation through the mosquito and vertebrate host tissues. We anticipate that these findings would further assist in the design and development of future malarial vaccines. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Limited variation in vaccine candidate Plasmodium falciparum Merozoite Surface Protein-6 over multiple transmission seasons

    Directory of Open Access Journals (Sweden)

    Branch OraLee H

    2010-05-01

    same community. By contrast, PfMSP6 was highly stable at the sequence level, with no SNPs detected in the 506 samples analysed. This limited diversity supports further investigation of PfMSP6 as a blood stage vaccine candidate, with the clear caveat that any such vaccine must either contain both alleles or generate cross-protective responses that react against both allele classes. Detailed immunoepidemiology studies are needed to establish the viability of these approaches before PfMSP6 advances further down the vaccine development pipeline.

  3. Conjugating recombinant proteins to Pseudomonas aeruginosa ExoProtein A: a strategy for enhancing immunogenicity of malaria vaccine candidates.

    Science.gov (United States)

    Qian, Feng; Wu, Yimin; Muratova, Olga; Zhou, Hong; Dobrescu, Gelu; Duggan, Peter; Lynn, Lambert; Song, Guanhong; Zhang, Yanling; Reiter, Karine; MacDonald, Nicholas; Narum, David L; Long, Carole A; Miller, Louis H; Saul, Allan; Mullen, Gregory E D

    2007-05-16

    Conjugation of polysaccharides to carrier proteins has been a successful approach for producing safe and effective vaccines. In an attempt to increase the immunogenicity of two malarial vaccine candidate proteins of Plasmodium falciparum, apical membrane antigen 1 (AMA1) to a blood stage vaccine candidate and surface protein 25 (Pfs25) a mosquito stage vaccine candidate, were each independently chemically conjugated to the mutant, nontoxic Pseudomonas aeruginosa ExoProtein A (rEPA). AMA1 is a large (66kD) relatively good immunogen in mice; Pfs25 is a poorly immunogenic protein when presented on alum to mice. Mice were immunized on days 0 and 28 with AMA1- or Pfs25-rEPA conjugates or unconjugated AMA1 or Pfs25, all formulated on Alhydrogel. Remarkably, sera from mice 14 days after the second immunization with Pfs25-rEPA conjugates displayed over a 1000-fold higher antibody titers as compared to unconjugated Pfs25. In contrast, AMA1 conjugated under the same conditions induced only a three-fold increase in antibody titers. When tested for functional activity, antibodies elicited by the AMA1-rEPA inhibited invasion of erythrocytes by blood-stage parasites and antibodies elicited by the Pfs25-rEPA conjugates blocked the development of the sexual stage parasites in the mosquito midgut. These results demonstrate that conjugation to rEPA induces a marked improvement in the antibody titer in mice for the poor immunogen (Pfs25) and for the larger protein (AMA1). These conjugates now need to be tested in humans to determine if mice are predictive of the response in humans.

  4. Comparative testing of six antigen-based malaria vaccine candidates directed toward merozoite-stage Plasmodium falciparum

    DEFF Research Database (Denmark)

    Arnot, David E; Cavanagh, David R; Remarque, Edmond J

    2008-01-01

    Immunogenicity testing of Plasmodium falciparum antigens being considered as malaria vaccine candidates was undertaken in rabbits. The antigens compared were recombinant baculovirus MSP-1(19) and five Pichia pastoris candidates, including two versions of MSP-1(19), AMA-1 (domains I and II), AMA-1......G concentrations. The two P. pastoris-produced MSP-1(19)-induced IgGs conferred the lowest growth inhibition. Comparative analysis of immunogenicity of vaccine antigens can be used to prioritize candidates before moving to expensive GMP production and clinical testing. The assays used have given discriminating...

  5. The meningococcal vaccine candidate neisserial surface protein A (NspA binds to factor H and enhances meningococcal resistance to complement.

    Directory of Open Access Journals (Sweden)

    Lisa A Lewis

    2010-07-01

    Full Text Available Complement forms an important arm of innate immunity against invasive meningococcal infections. Binding of the alternative complement pathway inhibitor factor H (fH to fH-binding protein (fHbp is one mechanism meningococci employ to limit complement activation on the bacterial surface. fHbp is a leading vaccine candidate against group B Neisseria meningitidis. Novel mechanisms that meningococci employ to bind fH could undermine the efficacy of fHbp-based vaccines. We observed that fHbp deletion mutants of some meningococcal strains showed residual fH binding suggesting the presence of a second receptor for fH. Ligand overlay immunoblotting using membrane fractions from one such strain showed that fH bound to a approximately 17 kD protein, identified by MALDI-TOF analysis as Neisserial surface protein A (NspA, a meningococcal vaccine candidate whose function has not been defined. Deleting nspA, in the background of fHbp deletion mutants, abrogated fH binding and mAbs against NspA blocked fH binding, confirming NspA as a fH binding molecule on intact bacteria. NspA expression levels vary among strains and expression correlated with the level of fH binding; over-expressing NspA enhanced fH binding to bacteria. Progressive truncation of the heptose (Hep I chain of lipooligosaccharide (LOS, or sialylation of lacto-N-neotetraose LOS both increased fH binding to NspA-expressing meningococci, while expression of capsule reduced fH binding to the strains tested. Similar to fHbp, binding of NspA to fH was human-specific and occurred through fH domains 6-7. Consistent with its ability to bind fH, deleting NspA increased C3 deposition and resulted in increased complement-dependent killing. Collectively, these data identify a key complement evasion mechanism with important implications for ongoing efforts to develop meningococcal vaccines that employ fHbp as one of its components.

  6. Identification of New Virulence Factors and Vaccine Candidates for Yersinia pestis

    Directory of Open Access Journals (Sweden)

    Jourdan A. Andersson

    2017-10-01

    -type CO92 in a pneumonic model. Further, evaluation of the attenuated T6SS mutant strains in vitro revealed significant alterations in phagocytosis, intracellular survival in murine macrophages, and their ability to induce cytotoxic effects on macrophages. The results reported here provide further evidence of the utility of the STM screening approach for the identification of novel virulence factors and to possibly target such genes for the development of novel live-attenuated vaccine candidates for plague.

  7. Identification of New Virulence Factors and Vaccine Candidates for Yersinia pestis.

    Science.gov (United States)

    Andersson, Jourdan A; Sha, Jian; Erova, Tatiana E; Fitts, Eric C; Ponnusamy, Duraisamy; Kozlova, Elena V; Kirtley, Michelle L; Chopra, Ashok K

    2017-01-01

    -challenge with wild-type CO92 in a pneumonic model. Further, evaluation of the attenuated T6SS mutant strains in vitro revealed significant alterations in phagocytosis, intracellular survival in murine macrophages, and their ability to induce cytotoxic effects on macrophages. The results reported here provide further evidence of the utility of the STM screening approach for the identification of novel virulence factors and to possibly target such genes for the development of novel live-attenuated vaccine candidates for plague.

  8. Immunoprotective efficacy of Acinetobacter baumannii outer membrane protein, FilF, predicted in silico as a potential vaccine candidate

    Directory of Open Access Journals (Sweden)

    Ravinder eSingh

    2016-02-01

    Full Text Available Acinetobacter baumannii is emerging as a serious nosocomial pathogen with multidrug resistance that has made it difficult to cure and development of efficacious treatment against this pathogen is direly needed. This has led to investigate vaccine approach to prevent and treat A. baumannii infections. In this work, an outer membrane putative pilus assembly protein, FilF, was predicted as vaccine candidate by in silico analysis of A. baumannii proteome and was found to be conserved among the A. baumannii strains. It was cloned and expressed in E. coli BL21(DE3 and purified by Ni-NTA chromatography. Immunization with FilF generated high antibody titer (>64000 and provided 50% protection against a standardized lethal dose (10*8 CFU of A. baumannii in murine pneumonia model. FilF immunization reduced the bacterial load in lungs by 2 and 4 log cycles, 12 and 24 h post infection as compared to adjuvant control; reduced the levels of pro-inflammatory cytokines TNF-α, IL-6, IL-33, IFN-γ and IL-1β significantly and histology of lung tissue supported the data by showing considerably reduced damage and infiltration of neutrophils in lungs. These results demonstrate the in vivo validation of immunoprotective efficacy of a protein predicted as a vaccine candidate by in silico proteomic analysis and open the possibilities for exploration of a large array of uncharacterized proteins.

  9. Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques.

    Science.gov (United States)

    Borggren, Marie; Vinner, Lasse; Andresen, Betina Skovgaard; Grevstad, Berit; Repits, Johanna; Melchers, Mark; Elvang, Tara Laura; Sanders, Rogier W; Martinon, Frédéric; Dereuddre-Bosquet, Nathalie; Bowles, Emma Joanne; Stewart-Jones, Guillaume; Biswas, Priscilla; Scarlatti, Gabriella; Jansson, Marianne; Heyndrickx, Leo; Grand, Roger Le; Fomsgaard, Anders

    2013-07-19

    HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb). We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques.

  10. Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques

    Directory of Open Access Journals (Sweden)

    Roger Le Grand

    2013-07-01

    Full Text Available HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb. We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques.

  11. Mechanism of protection induced by group A Streptococcus vaccine candidate J8-DT: contribution of B and T-cells towards protection.

    Directory of Open Access Journals (Sweden)

    Manisha Pandey

    Full Text Available Vaccination with J8-DT, a leading GAS vaccine candidate, results in protective immunity in mice. Analysis of immunologic correlates of protection indicated a role of J8-specific antibodies that were induced post-immunization. In the present study, several independent experimental approaches were employed to investigate the protective immunological mechanisms involved in J8-DT-mediated immunity. These approaches included the passive transfer of mouse or rabbit immune serum/antibodies in addition to selective depletion of T-cell subsets prior to bacterial challenge. Passive transfer of J8-DT antiserum/antibodies from mice and rabbits conferred significant resistance against challenge to mice. To exclude the possibility of involvement of other host immune factors, the studies were repeated in SCID mice, which highlighted the need for an ongoing immune response for long-lived protection. Depletion of CD4(+ and CD8(+ T-cell subsets confirmed that an active de novo immune response, involving CD4(+ T-helper cells, is required for continued synthesis of antibodies resulting in protection against GAS infection. Taken together these results indicate an involvement of CD4(+ T-cells in J8-DT-mediated protection possibly via an ability to maintain antibody levels. These results have considerable relevance to the development of a broad spectrum passive immunotherapy for GAS disease.

  12. Naturally acquired antibody responses to recombinant Pfs230 and Pfs48/45 transmission blocking vaccine candidates

    DEFF Research Database (Denmark)

    Jones, Sophie; Grignard, Lynn; Nebie, Issa

    2015-01-01

    for the future evaluation of vaccine immunogenicity and efficacy in populations naturally exposed to malaria. METHODS: We determined naturally acquired antibody responses to the recombinant proteins Pfs48/45-10C and Pfs230-230CMB in children from three malaria endemic settings in Ghana, Tanzania and Burkina Faso......OBJECTIVES: Pfs48/45 and Pfs230 are Plasmodium falciparum sexual stage proteins and promising malaria transmission-blocking vaccine candidates. Antibody responses against these proteins may be naturally acquired and target antigens may be under selective pressure. This has consequences....... We also examined genetic polymorphisms in the P. falciparum gene pfs48/45. RESULTS: Antibody prevalence was 1.1-18.2% for 10C and 6.7-18.9% for 230CMB. In Burkina Faso we observed evidence of an age-dependent acquisition pattern for both 10C (p assays...

  13. Naturally acquired antibody responses to recombinant Pfs230 and Pfs48/45 transmission blocking vaccine candidates.

    Science.gov (United States)

    Jones, Sophie; Grignard, Lynn; Nebie, Issa; Chilongola, Jaffu; Dodoo, Daniel; Sauerwein, Robert; Theisen, Michael; Roeffen, Will; Singh, Shrawan Kumar; Singh, Rajesh Kumar; Singh, Sanjay; Kyei-Baafour, Eric; Tetteh, Kevin; Drakeley, Chris; Bousema, Teun

    2015-07-01

    Pfs48/45 and Pfs230 are Plasmodium falciparum sexual stage proteins and promising malaria transmission-blocking vaccine candidates. Antibody responses against these proteins may be naturally acquired and target antigens may be under selective pressure. This has consequences for the future evaluation of vaccine immunogenicity and efficacy in populations naturally exposed to malaria. We determined naturally acquired antibody responses to the recombinant proteins Pfs48/45-10C and Pfs230-230CMB in children from three malaria endemic settings in Ghana, Tanzania and Burkina Faso. We also examined genetic polymorphisms in the P. falciparum gene pfs48/45. Antibody prevalence was 1.1-18.2% for 10C and 6.7-18.9% for 230CMB. In Burkina Faso we observed evidence of an age-dependent acquisition pattern for both 10C (p < 0.001) and 230CMB (p = 0.031). Membrane feeding assays on a separate dataset demonstrated an association between functional transmission reducing activity and antibody prevalence for both 10C (p = 0.017) and 230CMB (p = 0.049). 17 single nucleotide polymorphisms were found in pfs48/45 (from 126 samples), with 5 non-synonymous SNPs in the Pfs48/45 10C region. We conclude there are naturally acquired antibody responses to both vaccine candidates which have functional relevance by reducing the transmissibility of infected individuals. We identified genetic polymorphisms, in pfs48/45 which exhibited geographical specificity. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  14. Immunogenicity of a virosomally-formulated Plasmodium falciparum GLURP-MSP3 chimeric protein-based malaria vaccine candidate in comparison to adjuvanted formulations

    DEFF Research Database (Denmark)

    Tamborrini, Marco; Stoffel, Sabine A; Westerfeld, Nicole

    2011-01-01

    In clinical trials, immunopotentiating reconstituted influenza virosomes (IRIVs) have shown great potential as a versatile antigen delivery platform for synthetic peptides derived from Plasmodium falciparum antigens. This study describes the immunogenicity of a virosomally-formulated recombinant ...... fusion protein comprising domains of the two malaria vaccine candidate antigens MSP3 and GLURP....

  15. Oral administration of live Shigella vaccine candidates in rhesus monkeys show no evidence of competition for colonization and immunogenicity between different serotypes.

    Science.gov (United States)

    Ranallo, R T; Kaminski, R; Baqar, S; Dutta, M; Lugo-Roman, L A; Boren, T; Barnoy, S; Venkatesan, M M

    2014-03-26

    Live oral monovalent Shigella flexneri 2a vaccine candidates as well as bivalent formulations with Shigella sonnei were evaluated in a rhesus monkey model for colonization and immunogenicity. Freshly harvested suspensions of S. flexneri 2a vaccine candidates WRSf2G12 and WRSf2G15 as well as S. sonnei vaccine candidate WRSs3 were nasogastrically administered to groups of rhesus monkeys, Macaca mulatta, either in a monovalent form or when combined with each other. The animals were monitored daily for physical well-being, stools were subjected to quantitative colony immunoblot assays for bacterial excretion and blood and stools were evaluated for humoral and mucosal immune responses. No clinical symptoms were noted in any group of animals and the vaccine candidates were excreted robustly for 48-72h without significant changes in either the magnitude or duration of excretion when given as a monovalent or as bivalent mixtures. Similarly, immunological interferences were not apparent in the magnitude of humoral and mucosal immune responses observed toward Shigella-specific antigens when monkeys were fed monovalent or bivalent formulations. These results predict that a multivalent live oral vaccine of more than one serotype can have a favorable outcome for protection against shigellosis. Published by Elsevier Ltd.

  16. Enzymatic shaving of the tegument surface of live schistosomes for proteomic analysis: a rational approach to select vaccine candidates.

    Directory of Open Access Journals (Sweden)

    William Castro-Borges

    2011-03-01

    Full Text Available The membrane-associated and membrane-spanning constituents of the Schistosoma mansoni tegument surface, the parasite's principal interface with the host bloodstream, have recently been characterized using proteomic techniques. Biotinylation of live worms using membrane-impermeant probes revealed that only a small subset of the proteins was accessible to the reagents. Their position within the multilayered architecture of the surface has not been ascertained.An enzymatic shaving approach on live worms has now been used to release the most accessible components, for analysis by MS/MS. Treatment with trypsin, or phosphatidylinositol-specific phospholipase C (PiPLC, only minimally impaired membrane integrity. PiPLC-enriched proteins were distinguished from those released in parasite vomitus or by handling damage, using isobaric tagging. Trypsin released five membrane proteins, Sm200, Sm25 and three annexins, plus host CD44 and the complement factors C3 and C4. Nutrient transporters and ion channels were absent from the trypsin fraction, suggesting a deeper location in the surface complex; surprisingly, two BAR-domain containing proteins were released. Seven parasite and two host proteins were enriched by PiPLC treatment, the vaccine candidate Sm29 being the most prominent along with two orthologues of human CD59, potentially inhibitors of complement fixation. The enzymes carbonic anhydrase and APD-ribosyl cyclase were also enriched, plus Sm200 and alkaline phosphatase. Host GPI-anchored proteins CD48 and CD90, suggest 'surface painting' during worm peregrination in the portal system.Our findings suggest that the membranocalyx secreted over the tegument surface is not the inert barrier previously proposed, some tegument proteins being externally accessible to enzymes and thus potentially located within it. Furthermore, the detection of C3 and C4 indicates that the complement cascade is initiated, while two CD59 orthologues suggest a potential

  17. Meta-analysis of variables affecting mouse protection efficacy of whole organism Brucella vaccines and vaccine candidates

    Science.gov (United States)

    2013-01-01

    Background Vaccine protection investigation includes three processes: vaccination, pathogen challenge, and vaccine protection efficacy assessment. Many variables can affect the results of vaccine protection. Brucella, a genus of facultative intracellular bacteria, is the etiologic agent of brucellosis in humans and multiple animal species. Extensive research has been conducted in developing effective live attenuated Brucella vaccines. We hypothesized that some variables play a more important role than others in determining vaccine protective efficacy. Using Brucella vaccines and vaccine candidates as study models, this hypothesis was tested by meta-analysis of Brucella vaccine studies reported in the literature. Results Nineteen variables related to vaccine-induced protection of mice against infection with virulent brucellae were selected based on modeling investigation of the vaccine protection processes. The variable "vaccine protection efficacy" was set as a dependent variable while the other eighteen were set as independent variables. Discrete or continuous values were collected from papers for each variable of each data set. In total, 401 experimental groups were manually annotated from 74 peer-reviewed publications containing mouse protection data for live attenuated Brucella vaccines or vaccine candidates. Our ANOVA analysis indicated that nine variables contributed significantly (P-value Brucella vaccine protection efficacy: vaccine strain, vaccination host (mouse) strain, vaccination dose, vaccination route, challenge pathogen strain, challenge route, challenge-killing interval, colony forming units (CFUs) in mouse spleen, and CFU reduction compared to control group. The other 10 variables (e.g., mouse age, vaccination-challenge interval, and challenge dose) were not found to be statistically significant (P-value > 0.05). The protection level of RB51 was sacrificed when the values of several variables (e.g., vaccination route, vaccine viability, and

  18. Satisfactory safety and immunogenicity of MSP3 malaria vaccine candidate in Tanzanian children aged 12–24 months

    Directory of Open Access Journals (Sweden)

    Segeja Method D

    2009-07-01

    Full Text Available Abstract Background Development and deployment of an effective malaria vaccine would complement existing malaria control measures. A blood stage malaria vaccine candidate, Merozoite Surface Protein-3 (MSP3, produced as a long synthetic peptide, has been shown to be safe in non-immune and semi-immune adults. A phase Ib dose-escalating study was conducted to assess the vaccine's safety and immunogenicity in children aged 12 to 24 months in Korogwe, Tanzania (ClinicalTrials.gov number: NCT00469651. Methods This was a double-blind, randomized, controlled, dose escalation phase Ib trial, in which children were given one of two different doses of the MSP3 antigen (15 μg or 30 μg or a control vaccine (Engerix B. Children were randomly allocated either to the MSP3 candidate malaria vaccine or the control vaccine administered at a schedule of 0, 1, and 2 months. Immunization with lower and higher doses was staggered for safety reasons starting with the lower dose. The primary endpoint was safety and reactogenicity within 28 days post-vaccination. Blood samples were obtained at different time points to measure immunological responses. Results are presented up to 84 days post-vaccination. Results A total of 45 children were enrolled, 15 in each of the two MSP3 dose groups and 15 in the Engerix B group. There were no important differences in reactogenicity between the two MSP3 groups and Engerix B. Grade 3 adverse events were infrequent; only five were detected throughout the study, all of which were transient and resolved without sequelae. No serious adverse event reported was considered to be related to MSP3 vaccine. Both MSP3 dose regimens elicited strong cytophilic IgG responses (subclasses IgG1 and IgG3, the isotypes involved in the monocyte-dependant mechanism of Plasmodium falciparum parasite-killing. The titers reached are similar to those from African adults having reached a state of premunition. Furthermore, vaccination induced seroconversion in

  19. Polymorphism in liver-stage malaria vaccine candidate proteins: immune evasion and implications for vaccine design.

    Science.gov (United States)

    Flanagan, Katie L; Wilson, Kirsty L; Plebanski, Magdalena

    2016-01-01

    The pre-erythrocytic stage of infection by malaria parasites represents a key target for vaccines that aim to eradicate malaria. Two important broad immune evasion strategies that can interfere with vaccine efficacy include the induction of dendritic cell (DC) dysfunction and regulatory T cells (Tregs) by blood-stage malaria parasites, leading to inefficient priming of T cells targeting liver-stage infections. The parasite also uses 'surgical strike' strategies, whereby polymorphism in pre-erythrocytic antigens can interfere with host immunity. Specifically, we review how even single amino acid changes in T cell epitopes can lead to loss of binding to major histocompatibility complex (MHC), lack of cross-reactivity, or antagonism and immune interference, where simultaneous or sequential stimulation with related variants of the same T cell epitope can cause T cell anergy or the conversion of effector to immunosuppressive T cell phenotypes.

  20. Replacement of the Ectodomains of the Hemagglutinin-Neuraminidase and Fusion Glycoproteins of Recombinant Parainfluenza Virus Type 3 (PIV3) with Their Counterparts from PIV2 Yields Attenuated PIV2 Vaccine Candidates

    OpenAIRE

    Tao, Tao; Skiadopoulos, Mario H.; Davoodi, Fatemeh; Riggs, Jeffrey M.; Collins, Peter L.; Murphy, Brian R.

    2000-01-01

    We sought to develop a live attenuated parainfluenza virus type 2 (PIV2) vaccine strain for use in infants and young children, using reverse genetic techniques that previously were used to rapidly produce a live attenuated PIV1 vaccine candidate. The PIV1 vaccine candidate, designated rPIV3-1cp45, was generated by substituting the full-length HN and F proteins of PIV1 for those of PIV3 in the attenuated cp45 PIV3 vaccine candidate (T. Tao et al., J. Virol. 72:2955–2961, 1998; M. H. Skiadopoul...

  1. Generation of transgenic corn-derived Actinobacillus pleuropneumoniae ApxIIA fused with the cholera toxin B subunit as a vaccine candidate

    Science.gov (United States)

    Shin, Min-Kyoung; Jung, Myung Hwan; Lee, Won-Jung; Choi, Pil Son; Jang, Yong-Suk

    2011-01-01

    Corn, one of the most important forage crops worldwide, has proven to be a useful expression vehicle due to the availability of established transformation procedures for this well-studied plant. The exotoxin Apx, a major virulence factor, is recognized as a common antigen of Actinobacillus (A.) pleuropneumoniae, the causative agent of porcine pleuropneumonia. In this study, a cholera toxin B (CTB)-ApxIIA#5 fusion protein and full-size ApxIIA expressed in corn seed, as a subunit vaccine candidate, were observed to induce Apx-specific immune responses in mice. These results suggest that transgenic corn-derived ApxIIA and CTB-ApxIIA#5 proteins are potential vaccine candidates against A. pleuropneumoniae infection. PMID:22122907

  2. Antigen-Specific lgA B Memory Cell Responses to Shigella Antigens Elicited in Volunteers Immunized with Live Attenuated Shigella flexneri 2a Oral Vaccine Candidates

    Science.gov (United States)

    2011-01-01

    167. [10] E.V. Oaks, T.L. Hale, S.B. Formal, Serum immune response to Shigella protein antigens in rhesus monkeys and humans infected with Shigella ...cell responses to Shigella antigens elicited in volunteers immunized with live attenuated Shigella flexneri 2a oral vaccine candidates J.K. Simona,b... Shigella ;. B cell memory; Immunoglobulin lgA; Mucosal immunity Abstract We studied the induction of antigen-specific lgA memory B cells (BM) in

  3. A medically relevant capsular polysaccharide in Acinetobacter baumannii is a potential vaccine candidate.

    Science.gov (United States)

    Yang, Feng-Ling; Lou, Tze-Chi; Kuo, Shu-Chen; Wu, Wan-Ling; Chern, Jeffy; Lee, Yi-Tzu; Chen, Shui-Tsung; Zou, Wei; Lin, Nien-Tsung; Wu, Shih-Hsiung

    2017-03-07

    Concerns of Acinetobacter baumannii infection have increased due to the emergence of multi-drug resistance. In the present study, we determined the capsular polysaccharide (CPS) structure of A. baumannii SK44, a clinical isolate from Taiwan, to consist of pentasaccharide repeats. We found that CPS-induced antibody provided 55% protection against challenge in an animal model. The CPS-specific antibody reacted with the surface components of about 62% clinical isolates (342/554 strains) from cross-sectional and longitudinal studies by dot-immunoassay. Pulsed-field gel electrophoresis of positive strains showed the antibody covered different clonalites of A. baumannii clinical isolates. Meanwhile, using the CPS antibody as a probe, we found a number of outer membrane proteins bound to the antibody, including OmpA/motB, TonB-dependent receptor, and Omp38, indicating their association with CPS. These results might lead to the use of the capsular polysaccharide as a vaccine to prevent A. baumannii infection. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. A Semi-Synthetic Glycoconjugate Vaccine Candidate for Carbapenem-Resistant Klebsiella pneumoniae.

    Science.gov (United States)

    Seeberger, Peter H; Pereira, Claney L; Khan, Naeem; Xiao, Guozhi; Diago-Navarro, Elizabeth; Reppe, Katrin; Opitz, Bastian; Fries, Bettina C; Witzenrath, Martin

    2017-11-06

    Hospital-acquired infections are an increasingly serious health concern. Infections caused by carpabenem-resistant Klebsiella pneumoniae (CR-Kp) are especially problematic, with a 50 % average survival rate. CR-Kp are isolated from patients with ever greater frequency, 7 % within the EU but 62 % in Greece. At a time when antibiotics are becoming less effective, no vaccines to protect from this severe bacterial infection exist. Herein, we describe the convergent [3+3] synthesis of the hexasaccharide repeating unit from its capsular polysaccharide and related sequences. Immunization with the synthetic hexasaccharide 1 glycoconjugate resulted in high titers of cross-reactive antibodies against CR-Kp CPS in mice and rabbits. Whole-cell ELISA was used to establish the surface staining of CR-Kp strains. The antibodies raised were found to promote phagocytosis. Thus, this semi-synthetic glycoconjugate is a lead for the development of a vaccine against a rapidly progressing, deadly bacterium. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Preclinical Development and Production of Virus-Like Particles As Vaccine Candidates for Hepatitis C

    Directory of Open Access Journals (Sweden)

    Makutiro Ghislain Masavuli

    2017-12-01

    Full Text Available Hepatitis C Virus (HCV infects 2% of the world’s population and is the leading cause of liver disease and liver transplantation. It poses a serious and growing worldwide public health problem that will only be partially addressed with the introduction of new antiviral therapies. However, these treatments will not prevent re-infection particularly in high risk populations. The introduction of a HCV vaccine has been predicted, using simulation models in a high risk population, to have a significant effect on reducing the incidence of HCV. A vaccine with 50 to 80% efficacy targeted to high-risk intravenous drug users could dramatically reduce HCV incidence in this population. Virus like particles (VLPs are composed of viral structural proteins which self-assemble into non-infectious particles that lack genetic material and resemble native viruses. Thus, VLPs represent a safe and highly immunogenic vaccine delivery platform able to induce potent adaptive immune responses. Currently, many VLP-based vaccines have entered clinical trials, while licensed VLP vaccines for hepatitis B virus (HBV and human papilloma virus (HPV have been in use for many years. The HCV core, E1 and E2 proteins can self-assemble into immunogenic VLPs while inclusion of HCV antigens into heterogenous (chimeric VLPs is also a promising approach. These VLPs are produced using different expression systems such as bacterial, yeast, mammalian, plant, or insect cells. Here, this paper will review HCV VLP-based vaccines and their immunogenicity in animal models as well as the different expression systems used in their production.

  6. Recombinant outer membrane secretin PilQ(406-770) as a vaccine candidate for serogroup B Neisseria meningitidis.

    Science.gov (United States)

    Haghi, Fakhri; Peerayeh, Shahin Najar; Siadat, Seyed Davar; Zeighami, Habib

    2012-02-21

    Secretin PilQ is an antigenically conserved outer membrane protein which is present on most meningococci. This protein naturally expressed at high levels and is essential for meningococcal pilus expression at the cell surface. A 1095 bp fragment of C-terminal of secretin pilQ from serogroup B Neisseria meningitidis was cloned into prokaryotic expression vector pET-28a. Recombinant protein was overexpressed with IPTG and affinity-purified by Ni-NTA agarose. BALB/c mice were immunized subcutaneously with purified rPilQ(406-770) mixed with Freund's adjuvant. Serum antibody responses to serogroups A and B N. meningitidis whole cells or purified rPilQ(406-770) and functional activity of antibodies were determined by ELISA and SBA, respectively. The output of rPilQ(406-770) was approximately 50% of the total bacterial proteins. Serum IgG responses were significantly increased in immunized group with PilQ(406-770) mixed with Freund's adjuvant in comparison with control groups. Antisera produced against rPilQ(406-770) demonstrated strong surface reactivity to serogroups A and B N. meningitidis tested by whole-cell ELISA. Surface reactivity to serogroup B N. meningitidis was higher than serogroup A. The sera from PilQ(406-770) immunized animals were strongly bactericidal against serogroups A and B. These results suggest that rPilQ(406-770) is a potential vaccine candidate for serogroup B N. meningitidis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Development and evaluation of novel recombinant adenovirus-based vaccine candidates for infectious bronchitis virus and Mycoplasma gallisepticum in chickens.

    Science.gov (United States)

    Zhang, Dongchao; Long, Yuqing; Li, Meng; Gong, Jianfang; Li, Xiaohui; Lin, Jing; Meng, Jiali; Gao, Keke; Zhao, Ruili; Jin, Tianming

    2018-04-01

    Avian infectious bronchitis caused by the infectious bronchitis virus (IBV), and mycoplasmosis caused by Mycoplasma gallisepticum (MG) are two major respiratory diseases in chickens that have resulted in severe economic losses in the poultry industry. We constructed a recombinant adenovirus that simultaneously expresses the S1 spike glycoprotein of IBV and the TM-1 protein of MG (pBH-S1-TM-1-EGFP). For comparison, we constructed two recombinant adenoviruses (pBH-S1-EGFP and pBH-TM-1-EGFP) that express either the S1 spike glycoprotein or the TM-1 protein alone. The protective efficacy of these three vaccine constructs against challenge with IBV and/or MG was evaluated in specific pathogen free chickens. Groups of seven-day-old specific pathogen free chicks were immunized twice, two weeks apart, via the oculonasal route with the pBH-S1-TM-1-EGFP, pBH-S1-EGFP, or pBH-TM-1-EGFP vaccine candidates or the commercial attenuated infectious bronchitis vaccine strain H52 and MG vaccine strain F-36 (positive controls), and challenged with virulent IBV or MG two weeks later. Interestingly, by days 7 and 14 after the booster immunization, pBH-S1-TM-1-EGFP-induced antibody titre was significantly higher (P attenuated commercial IBV vaccine; however, there was no significant difference between the pBH-S1-TM-1-EGFP and attenuated commercial MG vaccine groups (P > 0.05). The clinical signs, the gross, and histopathological lesions scores of the adenovirus vaccine constructs were not significantly different from that of the attenuated commercial IBV or MG vaccines (positive controls) (P > 0.05). These results demonstrate the potential of the bivalent pBH-S1-TM-1-EGFP adenovirus construct as a combination vaccine against IB and mycoplasmosis.

  8. Protective efficacy of six immunogenic recombinant proteins of Vibrio anguillarum and evaluation them as vaccine candidate for flounder (Paralichthys olivaceus).

    Science.gov (United States)

    Xing, Jing; Xu, Hongsen; Wang, Yang; Tang, Xiaoqian; Sheng, Xiuzhen; Zhan, Wenbin

    2017-06-01

    Vibrio anguillarum is a severe bacterium that causes terminal haemorrhagic septicaemia in freshwater and marine fish. Virulence-associated proteins play an important role in bacterial pathogenicity and could be applied for immunoprophylaxis. In this study, six antigenic proteins from V. anguillarum were selected and the immune protective efficacy of their recombinant proteins was investigated. VirA, CheR, FlaC, OmpK, OmpR and Hsp33 were recombinantly produced and the reactions of recombinant proteins to flounder-anti-V. anguillarum antibodies (fV-ab) were detected, respectively. Then the recombinant proteins were injected to fish, after immunization, the percentages of surface membrane immunoglobulin-positive (sIg+) cell in lymphocytes, total antibodies, antibodies against V. anguillarum, antibodies against recombinant proteins and relative percent survival (RPS) were analyzed, respectively. The results showed that all the recombinant proteins could react to fV-ab, proliferate sIg + cells in lymphocytes and induce production of total antibodies, specific antibodies against V. anguillarum or the recombinant proteins; the RPS of rVirA, rCheR, rFlaC, rOmpK, rOmpR and rHsp33 against V. anguillarum was 70.27%, 27.03%, 16.22%, 62.16%, 45.95% and 81.08%, respectively. The results revealed that rHsp33, rVirA and rOmpK have good protections against V. anguillarum and could be vaccine candidates against V. anguillarum. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Safety and tolerability of a live oral Salmonella typhimurium vaccine candidate in SIV-infected nonhuman primates.

    Science.gov (United States)

    Ault, Alida; Tennant, Sharon M; Gorres, J Patrick; Eckhaus, Michael; Sandler, Netanya G; Roque, Annelys; Livio, Sofie; Bao, Saran; Foulds, Kathryn E; Kao, Shing-Fen; Roederer, Mario; Schmidlein, Patrick; Boyd, Mary Adetinuke; Pasetti, Marcela F; Douek, Daniel C; Estes, Jacob D; Nabel, Gary J; Levine, Myron M; Rao, Srinivas S

    2013-12-02

    Nontyphoidal Salmonella (NTS) serovars are a common cause of acute food-borne gastroenteritis worldwide and can cause invasive systemic disease in young infants, the elderly, and immunocompromised hosts, accompanied by high case fatality. Vaccination against invasive NTS disease is warranted where the disease incidence and mortality are high and multidrug resistance is prevalent, as in sub-Saharan Africa. Live-attenuated vaccines that mimic natural infection constitute one strategy to elicit protection. However, they must particularly be shown to be adequately attenuated for consideration of immunocompromised subjects. Accordingly, we examined the safety and tolerability of an oral live attenuated Salmonella typhimurium vaccine candidate, CVD 1921, in an established chronic simian immunodeficiency virus (SIV)-infected rhesus macaque model. We evaluated clinical parameters, histopathology, and measured differences in mucosal permeability to wild-type and vaccine strains. Compared to the wild-type S. typhimurium strain I77 in both SIV-infected and SIV-uninfected nonhuman primate hosts, this live-attenuated vaccine shows reduced shedding and systemic spread, exhibits limited pathological disease manifestations in the digestive tract, and induces low levels of cellular infiltration in tissues. Furthermore, wild-type S. typhimurium induces increased intestinal epithelial damage and permeability, with infiltration of neutrophils and macrophages in both SIV-infected and SIV-uninfected nonhuman primates compared to the vaccine strain. Based on shedding, systemic spread, and histopathology, the live-attenuated S. typhimurium strain CVD 1921 appears to be safe and well-tolerated in the nonhuman primate model, including chronically SIV-infected rhesus macaques. Copyright © 2013. Published by Elsevier Ltd.

  10. Prescreening of Nicotine Hapten Linkers in Vitro To Select Hapten-Conjugate Vaccine Candidates for Pharmacokinetic Evaluation in Vivo.

    Science.gov (United States)

    Arutla, Viswanath; Leal, Joseph; Liu, Xiaowei; Sokalingam, Sriram; Raleigh, Michael; Adaralegbe, Adejimi; Liu, Li; Pentel, Paul R; Hecht, Sidney M; Chang, Yung

    2017-05-08

    Since the demonstration of nicotine vaccines as a possible therapeutic intervention for the effects of tobacco smoke, extensive effort has been made to enhance nicotine specific immunity. Linker modifications of nicotine haptens have been a focal point for improving the immunogenicity of nicotine, in which the evaluation of these modifications usually relies on in vivo animal models, such as mice, rats or nonhuman primates. Here, we present two in vitro screening strategies to estimate and predict the immunogenic potential of our newly designed nicotine haptens. One utilizes a competition enzyme-linked immunoabsorbent assay (ELISA) to profile the interactions of nicotine haptens or hapten-protein conjugates with nicotine specific antibodies, both polyclonal and monoclonal. Another relies on computational modeling of the interactions between haptens and amino acid residues near the conjugation site of the carrier protein to infer linker-carrier protein conjugation effect on antinicotine antibody response. Using these two in vitro methods, we ranked the haptens with different linkers for their potential as viable vaccine candidates. The ELISA-based hapten ranking was in an agreement with the results obtained by in vivo nicotine pharmacokinetic analysis. A correlation was found between the average binding affinity (IC 50 ) of the haptens to an anti-Nic monoclonal antibody and the average brain nicotine concentration in the immunized mice. The computational modeling of hapten and carrier protein interactions helps exclude conjugates with strong linker-carrier conjugation effects and low in vivo efficacy. The simplicity of these in vitro screening strategies should facilitate the selection and development of more effective nicotine conjugate vaccines. In addition, these data highlight a previously under-appreciated contribution of linkers and hapten-protein conjugations to conjugate vaccine immunogenicity by virtue of their inclusion in the epitope that binds and

  11. Spatiotemporal exposome dynamics of soil lead and children's blood lead pre- and ten years post-Hurricane Katrina: Lead and other metals on public and private properties in the city of New Orleans, Louisiana, U.S.A.

    Science.gov (United States)

    Mielke, Howard W; Gonzales, Christopher R; Powell, Eric T; Mielke, Paul W

    2017-05-01

    Anthropogenic re-distribution of lead (Pb) principally through its use in gasoline additives and lead-based paints have transformed the urban exposome. This unique study tracks urban-scale soil Pb (SPb) and blood Pb (BPb) responses of children living in public and private communities in New Orleans before and ten years after Hurricane Katrina (29 August 2005). To compare and evaluate associations of pre- and ten years post-Katrina SPb and children's BPb on public and private residential census tracts in the core and outer areas of New Orleans, and to examine correlations between SPb and nine other soil metals. The Louisiana Healthy Housing and Childhood Lead Poisoning Prevention Program BPb (µg/dL) data from pre- (2000-2005) and post-Katrina (2010-2015) for ≤6-year-old children. Data from public and adjacent private residential census tracts within core and outer areas are stratified from a database that includes 916 and 922 SPb and 13,379 and 4830 BPb results, respectively, from pre- and post-Katrina New Orleans. Statistical analyses utilize Multi-Response Permutation Procedure and Spearman's Rho Correlation. Pre- to Post-Katrina median SPb decreases in public and private core census tracts were from 285 to 55mg/kg and 710-291mg/kg, respectively. In public and private outer census tracts the median SPb decreased from 109 to 56mg/kg and 88-55mg/kg. Children's BPb percent ≥5µg/dL on public and private core areas pre-Katrina was 63.2% and 67.5%, and declined post-Katrina to 7.6% and 20.2%, respectively. BPb decreases also occurred in outer areas. Soil Pb is strongly correlated with other metals. Post-Katrina re-building of public housing plus landscaping amends the exposome and reduces children's BPb. Most importantly, Hurricane Katrina revealed that decreasing the toxicants in the soil exposome is an effective intervention for decreasing children's BPb. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Serum-free microcarrier based production of replication deficient Influenza vaccine candidate virus lacking NS1 using Vero cells

    Directory of Open Access Journals (Sweden)

    Yan Mylene L

    2011-08-01

    Full Text Available Abstract Background Influenza virus is a major health concern that has huge impacts on the human society, and vaccination remains as one of the most effective ways to mitigate this disease. Comparing the two types of commercially available Influenza vaccine, the live attenuated virus vaccine is more cross-reactive and easier to administer than the traditional inactivated vaccines. One promising live attenuated Influenza vaccine that has completed Phase I clinical trial is deltaFLU, a deletion mutant lacking the viral Nonstructural Protein 1 (NS1 gene. As a consequence of this gene deletion, this mutant virus can only propagate effectively in cells with a deficient interferon-mediated antiviral response. To demonstrate the manufacturability of this vaccine candidate, a batch bioreactor production process using adherent Vero cells on microcarriers in commercially available animal-component free, serum-free media is described. Results Five commercially available animal-component free, serum-free media (SFM were evaluated for growth of Vero cells in agitated Cytodex 1 spinner flask microcarrier cultures. EX-CELL Vero SFM achieved the highest cell concentration of 2.6 × 10^6 cells/ml, whereas other SFM achieved about 1.2 × 10^6 cells/ml. Time points for infection between the late exponential and stationary phases of cell growth had no significant effect in the final virus titres. A virus yield of 7.6 Log10 TCID50/ml was achieved using trypsin concentration of 10 μg/ml and MOI of 0.001. The Influenza vaccine production process was scaled up to a 3 liter controlled stirred tank bioreactor to achieve a cell density of 2.7 × 10^6 cells/ml and virus titre of 8.3 Log10 TCID50/ml. Finally, the bioreactor system was tested for the production of the corresponding wild type H1N1 Influenza virus, which is conventionally used in the production of inactivated vaccine. High virus titres of up to 10 Log10 TCID50/ml were achieved. Conclusions We describe for the

  13. Characterization of Inherent Particles and Mechanism of Thermal Stress Induced Particle Formation in HSV-2 Viral Vaccine Candidate.

    Science.gov (United States)

    Li, Lillian; Kirkitadze, Marina; Bhandal, Kamaljit; Roque, Cristopher; Yang, Eric; Carpick, Bruce; Rahman, Nausheen

    2017-11-10

    Vaccine formulations may contain visible and/or subvisible particles, which can vary in both size and morphology. Extrinsic particles, which are particles not part of the product such as foreign contaminants, are generally considered undesirable and should be eliminated or controlled in injectable products. However, biological products, in particular vaccines, may also contain particles that are inherent to the product. Here we focus on the characterization of visible and subvisible particles in a live, replication-deficient viral vaccine candidate against HSV genital herpes in an early developmental stage. HSV-2 viral vaccine was characterized using a panel of analytical methods, including Fourier transform infrared spectroscopy (FTIR), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Western blot, liquid chromatography-mass spectrometry (LC-MS), light microscopy, transmission electron microscopy (TEM), micro-flow imaging (MFI), dynamic light scattering (DLS), right angle light scattering (RALS), and intrinsic fluorescence. Particles in HSV-2 vaccine typically ranged from hundreds of nanometers to hundreds of micrometers in size and were determined to be inherent to the product. The infectious titer did not correlate with any trend in subvisible particle concentration and size distribution as shown by DLS, MFI, and TEM under stressed conditions. This suggested that particle changes in the submicron range were related to HSV-2 virion structure and had direct impact on biological activity. It was also observed that subvisible and visible particles could induce aggregation in the viral product. The temperature induced aggregation was observed by RALS, intrinsic fluorescence, and DLS. The increase of subvisible particle size with temperature could be fitted to a two-step thermokinetic model. Visible and subvisible particles were found to be inherent to the HSV-2 viral vaccine product. The mechanism of protein aggregation was discussed and a two

  14. A Library of Plasmodium vivax Recombinant Merozoite Proteins Reveals New Vaccine Candidates and Protein-Protein Interactions

    Science.gov (United States)

    Hostetler, Jessica B.; Sharma, Sumana; Bartholdson, S. Josefin; Wright, Gavin J.; Fairhurst, Rick M.; Rayner, Julian C.

    2015-01-01

    Background A vaccine targeting Plasmodium vivax will be an essential component of any comprehensive malaria elimination program, but major gaps in our understanding of P. vivax biology, including the protein-protein interactions that mediate merozoite invasion of reticulocytes, hinder the search for candidate antigens. Only one ligand-receptor interaction has been identified, that between P. vivax Duffy Binding Protein (PvDBP) and the erythrocyte Duffy Antigen Receptor for Chemokines (DARC), and strain-specific immune responses to PvDBP make it a complex vaccine target. To broaden the repertoire of potential P. vivax merozoite-stage vaccine targets, we exploited a recent breakthrough in expressing full-length ectodomains of Plasmodium proteins in a functionally-active form in mammalian cells and initiated a large-scale study of P. vivax merozoite proteins that are potentially involved in reticulocyte binding and invasion. Methodology/Principal Findings We selected 39 P. vivax proteins that are predicted to localize to the merozoite surface or invasive secretory organelles, some of which show homology to P. falciparum vaccine candidates. Of these, we were able to express 37 full-length protein ectodomains in a mammalian expression system, which has been previously used to express P. falciparum invasion ligands such as PfRH5. To establish whether the expressed proteins were correctly folded, we assessed whether they were recognized by antibodies from Cambodian patients with acute vivax malaria. IgG from these samples showed at least a two-fold change in reactivity over naïve controls in 27 of 34 antigens tested, and the majority showed heat-labile IgG immunoreactivity, suggesting the presence of conformation-sensitive epitopes and native tertiary protein structures. Using a method specifically designed to detect low-affinity, extracellular protein-protein interactions, we confirmed a predicted interaction between P. vivax 6-cysteine proteins P12 and P41, further

  15. Bacillus subtilis spore with surface display of paramyosin from Clonorchis sinensis potentializes a promising oral vaccine candidate.

    Science.gov (United States)

    Sun, Hengchang; Lin, Zhipeng; Zhao, Lu; Chen, Tingjin; Shang, Mei; Jiang, Hongye; Tang, Zeli; Zhou, Xinyi; Shi, Mengchen; Zhou, Lina; Ren, Pengli; Qu, Honglin; Lin, Jinsi; Li, Xuerong; Xu, Jin; Huang, Yan; Yu, Xinbing

    2018-03-07

    Clonorchiasis caused by Clonorchis sinensis has become increasingly prevalent in recent years. Effective prevention strategies are urgently needed to control this food-borne infectious disease. Previous studies indicated that paramyosin of C. sinensis (CsPmy) is a potential vaccine candidate. We constructed a recombinant plasmid of PEB03-CotC-CsPmy, transformed it into Bacillus subtilis WB600 strain (B.s-CotC-CsPmy), and confirmed CsPmy expression on the spore surface by SDS-PAGE, Western blotting and immunofluorescence assay. The immune response and protective efficacy of the recombinant spore were investigated in BALB/c mice after intragastrical or intraperitoneal immunization. Additionally, biochemical enzyme activities in sera, the intestinal histopathology and gut microflora of spore-treated mice were investigated. CsPmy was successfully expressed on the spore surface and the fusion protein on the spore surface with thermostability. Specific IgG in sera and intestinal mucus were increased after intraperitoneal and intragastrical immunization. The sIgA level in intestinal mucus, feces and bile of B.s-CotC-CsPmy orally treated mice were also significantly raised. Furthermore, numerous IgA-secreting cells were detected in intestinal mucosa of intragastrically immunized mice. No inflammatory injury was observed in the intestinal tissues and there was no significant difference in levels of enzyme-indicated liver function among the groups. Additionally, the diversity and abundance of gut microbiota were not changed after oral immunization. Intragastric and intraperitoneal immunization of B.s-CotC-CsPmy spores in mice resulted in egg reduction rates of 48.3 and 51.2% after challenge infection, respectively. Liver fibrosis degree in B.s-CotC-CsPmy spores treated groups was also significantly reduced. CsPmy expressed on the spore surface maintained its immunogenicity. Both intragastrical and intraperitoneal immunization with B.s-CotC-CsPmy spores induced systemic and

  16. Evaluation of a genetically modified foot-and-mouth disease virus vaccine candidate generated by reverse genetics

    Science.gov (United States)

    2012-01-01

    . Thus, the full-length cDNA clone of FMDV can be a useful tool to develop genetically engineered FMDV vaccine candidates to help control porcinophilic FMD epidemics in China. PMID:22591597

  17. Recombinant α-actinin subunit antigens of Trichomonas vaginalis as potential vaccine candidates in protecting against trichomoniasis.

    Science.gov (United States)

    Xie, Yi-Ting; Gao, Jiang-Mei; Wu, Ya-Ping; Tang, Petrus; Hide, Geoff; Lai, De-Hua; Lun, Zhao-Rong

    2017-02-16

    stimulation with the corresponding antigens in vitro. Immunization with both ACT-F and ACT-T could confer partial to complete protection and trigger strong Th1/Th2 mixed humoral and cellular immune responses in the mouse host. This suggested that recombinant α-actinin subunit antigens may be promising vaccine candidates against trichomoniasis.

  18. Evaluation of a genetically modified foot-and-mouth disease virus vaccine candidate generated by reverse genetics

    Directory of Open Access Journals (Sweden)

    Li Pinghua

    2012-05-01

    wild O/HN/CHA/93 virus. Thus, the full-length cDNA clone of FMDV can be a useful tool to develop genetically engineered FMDV vaccine candidates to help control porcinophilic FMD epidemics in China.

  19. Pulmonary immunity and durable protection induced by the ID93/GLA-SE vaccine candidate against the hyper-virulent Korean Beijing Mycobacterium tuberculosis strain K.

    Science.gov (United States)

    Cha, Seung Bin; Kim, Woo Sik; Kim, Jong-Seok; Kim, Hongmin; Kwon, Kee Woong; Han, Seung Jung; Cho, Sang-Nae; Coler, Rhea N; Reed, Steven G; Shin, Sung Jae

    2016-04-27

    The majority of tuberculosis (TB) vaccine candidates advanced to clinical trials have been evaluated preclinically using laboratory-adapted strains. However, it has been proposed that challenge with clinical isolates in preclinical vaccine testing could provide further and more practical validation. Here, we tested the ID93/GLA-SE TB vaccine candidate against the clinical Mycobacterium tuberculosis (Mtb) strain K (Mtb K) belonging to the Beijing family, the most prevalent Mtb strain in South Korea. Mice immunized with ID93/GLA-SE exhibited a significant reduction in bacteria and reduced lung inflammation against Mtb K when compared to non-immunized controls. In addition, we analyzed the immune responses in the lungs of ID93/GLA-SE-immunized mice, and showed that ID93/GLA-SE was able to elicit sustained Th1-biased immune responses including antigen-specific multifunctional CD4(+) T cell co-producing IFN-γ, TNF-α, and IL-2 as well as a high magnitude of IFN-γ response for up to 10 weeks post-challenge. Notably, further investigation of T cell subsets in the lung following challenge showed remarkable generation of CD8(+) central memory T cells by ID93/GLA-SE-immunization. Our findings showed that ID93/GLA-SE vaccine confers a high level of robust protection against the hypervirulent Mtb Beijing infection which was characterized by pulmonary Th1-polarized T-cell immune responses. These findings may also provide relevant information for potential utility of this vaccine candidate in East-Asian countries where the Beijing genotype is highly prevalent. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Attenuation and efficacy of human parainfluenza virus type 1 (HPIV1 vaccine candidates containing stabilized mutations in the P/C and L genes

    Directory of Open Access Journals (Sweden)

    Skiadopoulos Mario H

    2007-07-01

    Full Text Available Abstract Background Two recombinant, live attenuated human parainfluenza virus type 1 (rHPIV1 mutant viruses have been developed, using a reverse genetics system, for evaluation as potential intranasal vaccine candidates. These rHPIV1 vaccine candidates have two non-temperature sensitive (non-ts attenuating (att mutations primarily in the P/C gene, namely CR84GHNT553A (two point mutations used together as a set and CΔ170 (a short deletion mutation, and two ts att mutations in the L gene, namely LY942A (a point mutation, and LΔ1710–11 (a short deletion, the last of which has not been previously described. The latter three mutations were specifically designed for increased genetic and phenotypic stability. These mutations were evaluated on the HPIV1 backbone, both individually and in combination, for attenuation, immunogenicity, and protective efficacy in African green monkeys (AGMs. Results The rHPIV1 mutant bearing the novel LΔ1710–11 mutation was highly ts and attenuated in AGMs and was immunogenic and efficacious against HPIV1 wt challenge. The rHPIV1-CR84G/Δ170HNT553ALY942A and rHPIV1-CR84G/Δ170HNT553ALΔ1710–11 vaccine candidates were highly ts, with shut-off temperatures of 38°C and 35°C, respectively, and were highly attenuated in AGMs. Immunization with rHPIV1-CR84G/Δ170HNT553ALY942A protected against HPIV1 wt challenge in both the upper and lower respiratory tracts. In contrast, rHPIV1-CR84G/Δ170HNT553ALΔ1710–11 was not protective in AGMs due to over-attenuation, but it is expected to replicate more efficiently and be more immunogenic in the natural human host. Conclusion The rHPIV1-CR84G/Δ170HNT553ALY942A and rHPIV1-CR84G/Δ170HNT553ALΔ1710–11 vaccine candidates are clearly highly attenuated in AGMs and clinical trials are planned to address safety and immunogenicity in humans.

  1. Humoral immune response to Plasmodium falciparum vaccine candidate GMZ2 and its components in populations naturally exposed to seasonal malaria in Ethiopia

    DEFF Research Database (Denmark)

    Mamo, Hassen; Esen, Meral; Ajua, Anthony

    2013-01-01

    for malaria infection microscopically and by the rapid diagnostic test (RDT). Sera were tested by using enzyme-linked immunosorbent assay (ELISA) for total immunoglobulin (Ig) G against P. falciparum blood-stage vaccine candidate GMZ2 and its subunits (Glutamate-rich protein (GLURP-R0), merozoite surface...... transmission in the two localities and/or genetic differences between the two populations in their response to the antigens. In both study sites, IgG subclass levels to GLURP-R0 were significantly higher than that to MSP3 for all corresponding subclasses in most individuals, indicating the higher relative...

  2. Lassa virus-like particles displaying all major immunological determinants as a vaccine candidate for Lassa hemorrhagic fever

    Directory of Open Access Journals (Sweden)

    Cashman Kathleen A

    2010-10-01

    virion, electron microscopy analysis demonstrated that LASV VLP appeared structurally similar to native virions, with pleiomorphic distribution in size and shape. LASV VLP that displayed GPC or GPC+NP were immunogenic in mice, and generated a significant IgG response to individual viral proteins over the course of three immunizations, in the absence of adjuvants. Furthermore, sera from convalescent Lassa fever patients recognized VLP in ELISA format, thus affirming the presence of native epitopes displayed by the recombinant pseudoparticles. Conclusions These results established that modular LASV VLP can be generated displaying high levels of immunogenic viral proteins, and that small laboratory scale mammalian expression systems are capable of producing multi-milligram quantities of pseudoparticles. These VLP are structurally and morphologically similar to native LASV virions, but lack replicative functions, and thus can be safely generated in low biosafety level settings. LASV VLP were immunogenic in mice in the absence of adjuvants, with mature IgG responses developing within a few weeks after the first immunization. These studies highlight the relevance of a VLP platform for designing an optimal vaccine candidate against Lassa hemorrhagic fever, and warrant further investigation in lethal challenge animal models to establish their protective potential.

  3. An optimized, fast-to-perform mouse lung infection model with the human pathogen Chlamydia trachomatis for in vivo screening of antibiotics, vaccine candidates and modified host-pathogen interactions.

    Science.gov (United States)

    Dutow, Pavel; Wask, Lea; Bothe, Miriam; Fehlhaber, Beate; Laudeley, Robert; Rheinheimer, Claudia; Yang, Zhangsheng; Zhong, Guangming; Glage, Silke; Klos, Andreas

    2016-03-01

    Chlamydia trachomatis causes sexually transmitted diseases with infertility, pelvic inflammatory disease and neonatal pneumonia as complications. The duration of urogenital mouse models with the strict mouse pathogen C. muridarum addressing vaginal shedding, pathological changes of the upper genital tract or infertility is rather long. Moreover, vaginal C. trachomatis application usually does not lead to the complications feared in women. A fast-to-perform mouse model is urgently needed to analyze new antibiotics, vaccine candidates, immune responses (in gene knockout animals) or mutants of C. trachomatis. To complement the valuable urogenital model with a much faster and quantifiable screening method, we established an optimized lung infection model for the human intracellular bacterium C. trachomatis serovar D (and L2) in immunocompetent C57BL/6J mice. We demonstrated its usefulness by sensitive determination of antibiotic effects characterizing advantages and limitations achievable by early or delayed short tetracycline treatment and single-dose azithromycin application. Moreover, we achieved partial acquired protection in reinfection with serovar D indicating usability for vaccine studies, and showed a different course of disease in absence of complement factor C3. Sensitive monitoring parameters were survival rate, body weight, clinical score, bacterial load, histological score, the granulocyte marker myeloperoxidase, IFN-γ, TNF-α, MCP-1 and IL-6. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Protection efficacy of the Brucella abortus ghost vaccine candidate lysed by the N-terminal 24-amino acid fragment (GI24) of the 36-amino acid peptide PMAP-36 (porcine myeloid antimicrobial peptide 36) in murine models.

    Science.gov (United States)

    Kwon, Ae Jeong; Moon, Ja Young; Kim, Won Kyong; Kim, Suk; Hur, Jin

    2016-11-01

    Brucella abortus cells were lysed by the N-terminal 24-amino acid fragment (GI24) of the 36-amino acid peptide PMAP-36 (porcine myeloid antimicrobial peptide 36). Next, the protection efficacy of the lysed fragment as a vaccine candidate was evaluated. Group A mice were immunized with sterile PBS, group B mice were intraperitoneally (ip) immunized with 3 × 10 8 colony-forming units (CFUs) of B. abortus strain RB51, group C mice were immunized ip with 3 × 10 8 cells of the B. abortus vaccine candidate, and group D mice were orally immunized with 3 × 10 9 cells of the B. abortus vaccine candidate. Brucella lipopolysaccharide (LPS)-specific serum IgG titers were considerably higher in groups C and D than in group A. The levels of interleukin (IL)-4, IL-10, tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) were significantly higher in groups B-D than in group A. After an ip challenge with B. abortus 544, only group C mice showed a significant level of protection as compared to group A. Overall, these results show that ip immunization with a vaccine candidate lysed by GI24 can effectively protect mice from systemic infection with virulent B. abortus.

  5. Immunization with the Malaria Diversity-Covering Blood-Stage Vaccine Candidate Plasmodium falciparum Apical Membrane Antigen 1 DiCo in Complex with Its Natural Ligand PfRon2 Does Not Improve the In Vitro Efficacy

    Directory of Open Access Journals (Sweden)

    Holger Spiegel

    2017-06-01

    Full Text Available The blood-stage malaria vaccine candidate Plasmodium falciparum apical membrane antigen 1 (PfAMA1 can induce strong parasite growth-inhibitory antibody responses in animals but has not achieved the anticipated efficacy in clinical trials. Possible explanations in humans are the insufficient potency of the elicited antibody responses, as well as the high degree of sequence polymorphisms found in the field. Several strategies have been developed to improve the cross-strain coverage of PfAMA1-based vaccines, whereas innovative concepts to increase the potency of PfAMA1-specific IgG responses have received little attention even though this may be an essential requirement for protective efficacy. A previous study has demonstrated that immunization with a complex of PyAMA1 and PyRON2, a ligand with an essential functional role in erythrocyte invasion, leads to protection from lethal Plasmodium yoelli challenge in an animal model and suggested to extend this strategy toward improved strain coverage by using multiple PfAMA1 alleles in combination with PfRon2L. As an alternative approach along this line, we decided to use PfRon2L in combination with three PfAMA1 diversity covering variants (DiCo to investigate the potential of this complex to induce more potent parasite growth inhibitory immune response in combination with better cross-strain-specific efficacy. Within the limits of the study design, the ability of the PfAMA1 DiCo-Mix to induce cross-strain-specific antibodies was not affected in all immunization groups, but the DiCo–PfRon2L complexes did not improve the potency of PfAMA1-specific IgG responses.

  6. Molecular characterization of thyroid hormone receptor beta from Schistosoma japonicum and assessment of its potential as a vaccine candidate antigen against schistosomiasis in BALB/c mice

    Directory of Open Access Journals (Sweden)

    Qiu Chunhui

    2012-08-01

    Full Text Available Abstract Background Thyroid hormones (TH modulate growth, development and differentiation and metabolic processes by interacting with thyroid hormone receptors (THRs. The purpose of this study was to identify a novel thyroid hormone receptor beta encoding gene of Schistosoma japonicum (SjTHRβ and to investigate its potential as a vaccine candidate antigen against schistosomiasis in BALB/c mice. Methods The full-length cDNA sequence of SjTHRβ, its gene organization, and its transcript levels were characterized, and the phylogenetic relationship between THR, RAR and RXR from other organisms were analysis, the ability of this protein binding to a conserved DNA core motif, and its potential as a vaccine candidate antigen against schistosomiasis in BALB/c mice were evaluated. Results The SjTHRβ cDNA was cloned, verified by 5’ and 3’ Rapid Amplification of cDNA Ends and shown to be polyadenylated at the 3’end, suggesting the transcript is full-length. SjTHRβ is homologous to THRs from other species and has a predicted conservative DNA binding domain and ligand binding domain that normally characterizes these receptors. A comparative quantitative PCR analysis showed that SjTHRβ was the highest expressed in 21d worms and the lowest in 7 d and 13 d schistosomula. The cDNA corresponding to DNA binding domain (SjTHRβ-DBD and ligand binding domain (SjTHRβ-LBD were cloned and subsequently expressed in E coli. The expressed proteins were used to immunize mice and generate specific serum against recombinant SjTHRβ (rSjTHRβ. Western blotting revealed that anti-rSjTHRβ-LBD serum recognized two protein bands in extracts from 21 d worm with molecular sizes of approximately 95 kDa and 72 kDa. Electrophoretic mobility shift assay (EMSA analysis showed that rSjTHRβ-DBD could bind to a conserved DNA core motif. Immunization of BALB/c mice with rSjTHRβ-LBD could induce partial protective efficacy(27.52% worm reduction and 29.50% liver eggs

  7. A multi-country study of dengue vaccination strategies with Dengvaxia and a future vaccine candidate in three dengue-endemic countries: Vietnam, Thailand, and Colombia.

    Science.gov (United States)

    Lee, Jung-Seok; Lourenço, José; Gupta, Sunetra; Farlow, Andrew

    2018-04-19

    The dengue vaccination era began when Dengvaxia (CYD-TDV) became available in 2016. In addition, several second-generation vaccine candidates are currently in phase 3 trials, suggesting that a broader availability of dengue vaccines may be possible in the near future. Advancing on the recent WHO-SAGE recommendations for the safe and effective use of CYD-TDV at the regional level on average, this study investigates the vaccination impacts and cost-effectiveness of CYD-TDV and of a hypothetical new vaccine candidate (NVC) in a country-specific manner for three endemic countries: Vietnam, Thailand, and Colombia. The vaccination impacts of CYD-TDV and NVC were derived by fitting the empirical seroprevalence rates of 9 year olds into an individual-based meta-population transmission model, previously used for the WHO-SAGE working group. The disability-adjusted life years were estimated by applying country-specific parametric values. The cost-effectiveness analyses of four intervention strategies in combination with routine and catch-up campaigns were compared for both vaccines to inform decision makers regarding the most suitable immunization program in each of the three countries. Both CYD-TDV and NVC could be cost-effective at the DALY threshold cost of $2000 depending upon vaccination costs. With CYD-TDV, targeting 9 year olds in routine vaccination programs and 10-29 year olds as a one-off catch-up campaign was the most cost-effective strategy in all three countries. With NVC, while the most cost-effective strategy was to vaccinate 9-29 and 9-18 year olds in Vietnam and Thailand respectively, vaccinating younger age cohorts between 1 and 5 years old in Colombia was more cost-effective than other strategies. Given that three countries will soon face decisions regarding whether and how to incorporate CYD-TDV or future dengue vaccines into their budget-constrained national immunization programs, the current study outcomes can be used to help decision makers

  8. Phase 1/2a Trial of Plasmodium vivax Malaria Vaccine Candidate VMP001/AS01B in Malaria-Naive Adults: Safety, Immunogenicity, and Efficacy.

    Directory of Open Access Journals (Sweden)

    Jason W Bennett

    2016-02-01

    Full Text Available A vaccine to prevent infection and disease caused by Plasmodium vivax is needed both to reduce the morbidity caused by this parasite and as a key component in efforts to eradicate malaria worldwide. Vivax malaria protein 1 (VMP001, a novel chimeric protein that incorporates the amino- and carboxy- terminal regions of the circumsporozoite protein (CSP and a truncated repeat region that contains repeat sequences from both the VK210 (type 1 and the VK247 (type 2 parasites, was developed as a vaccine candidate for global use.We conducted a first-in-human Phase 1 dose escalation vaccine study with controlled human malaria infection (CHMI of VMP001 formulated in the GSK Adjuvant System AS01B. A total of 30 volunteers divided into 3 groups (10 per group were given 3 intramuscular injections of 15 μg, 30 μg, or 60 μg respectively of VMP001, all formulated in 500 μL of AS01B at each immunization. All vaccinated volunteers participated in a P. vivax CHMI 14 days following the third immunization. Six non-vaccinated subjects served as infectivity controls.The vaccine was shown to be well tolerated and immunogenic. All volunteers generated robust humoral and cellular immune responses to the vaccine antigen. Vaccination did not induce sterile protection; however, a small but significant delay in time to parasitemia was seen in 59% of vaccinated subjects compared to the control group. An association was identified between levels of anti-type 1 repeat antibodies and prepatent period.This trial was the first to assess the efficacy of a P. vivax CSP vaccine candidate by CHMI. The association of type 1 repeat-specific antibody responses with delay in the prepatency period suggests that augmenting the immune responses to this domain may improve strain-specific vaccine efficacy. The availability of a P. vivax CHMI model will accelerate the process of P. vivax vaccine development, allowing better selection of candidate vaccines for advancement to field trials.

  9. Evidence for globally shared, cross-reacting polymorphic epitopes in the pregnancy-associated malaria vaccine candidate VAR2CSA

    DEFF Research Database (Denmark)

    Avril, Marion; Kulasekara, Bridget R; Gose, Severin O

    2008-01-01

    Pregnancy-associated malaria (PAM) is characterized by the placental sequestration of Plasmodium falciparum-infected erythrocytes (IEs) with the ability to bind to chondroitin sulfate A (CSA). VAR2CSA is a leading candidate for a pregnancy malaria vaccine, but its large size ( approximately 350 k...

  10. Trans-sialidase-based vaccine candidate protects against Trypanosoma cruzi infection, not only inducing an effector immune response but also affecting cells with regulatory/suppressor phenotype

    Science.gov (United States)

    Prochetto, Estefanía; Roldán, Carolina; Bontempi, Iván A.; Bertona, Daiana; Peverengo, Luz; Vicco, Miguel H.; Rodeles, Luz M.; Pérez, Ana R.; Marcipar, Iván S.; Cabrera, Gabriel

    2017-01-01

    Prophylactic and/or therapeutic vaccines have an important potential to control Trypanosoma cruzi (T. cruzi)infection. The involvement of regulatory/suppressor immune cells after an immunization treatment and T. cruzi infection has never been addressed. Here we show that a new trans-sialidase-based immunogen (TSf) was able to confer protection, correlating not only with beneficial changes in effector immune parameters, but also influencing populations of cells related to immune control. Regarding the effector response, mice immunized with TSf showed a TS-specific antibody response, significant delayed-type hypersensitivity (DTH) reactivity and increased production of IFN-γ by CD8+ splenocytes. After a challenge with T. cruzi, TSf-immunized mice showed 90% survival and low parasitemia as compared with 40% survival and high parasitemia in PBS-immunized mice. In relation to the regulatory/suppressor arm of the immune system, after T. cruzi infection TSf-immunized mice showed an increase in spleen CD4+ Foxp3+ regulatory T cells (Treg) as compared to PBS-inoculated and infected mice. Moreover, although T. cruzi infection elicited a notable increase in myeloid derived suppressor cells (MDSC) in the spleen of PBS-inoculated mice, TSf-immunized mice showed a significantly lower increase of MDSC. Results presented herein highlight the need of studying the immune response as a whole when a vaccine candidate is rationally tested. PMID:28938533

  11. High-yield production of a stable Vero cell-based vaccine candidate against the highly pathogenic avian influenza virus H5N1

    International Nuclear Information System (INIS)

    Zhou, Fangye; Zhou, Jian; Ma, Lei; Song, Shaohui; Zhang, Xinwen; Li, Weidong; Jiang, Shude; Wang, Yue; Liao, Guoyang

    2012-01-01

    Highlights: ► Vero cell-based HPAI H5N1 vaccine with stable high yield. ► Stable high yield derived from the YNVa H3N2 backbone. ► H5N1/YNVa has a similar safety and immunogenicity to H5N1delta. -- Abstract: Highly pathogenic avian influenza (HPAI) viruses pose a global pandemic threat, for which rapid large-scale vaccine production technology is critical for prevention and control. Because chickens are highly susceptible to HPAI viruses, the supply of chicken embryos for vaccine production might be depleted during a virus outbreak. Therefore, developing HPAI virus vaccines using other technologies is critical. Meeting vaccine demand using the Vero cell-based fermentation process has been hindered by low stability and yield. In this study, a Vero cell-based HPAI H5N1 vaccine candidate (H5N1/YNVa) with stable high yield was achieved by reassortment of the Vero-adapted (Va) high growth A/Yunnan/1/2005(H3N2) (YNVa) virus with the A/Anhui/1/2005(H5N1) attenuated influenza vaccine strain (H5N1delta) using the 6/2 method. The reassorted H5N1/YNVa vaccine maintained a high hemagglutination (HA) titer of 1024. Furthermore, H5N1/YNVa displayed low pathogenicity and uniform immunogenicity compared to that of the parent virus.

  12. Transcriptome Analysis of Human Peripheral Blood Mononuclear Cells Exposed to Lassa Virus and to the Attenuated Mopeia/Lassa Reassortant 29 (ML29), a Vaccine Candidate

    Science.gov (United States)

    Zapata, Juan Carlos; Carrion, Ricardo; Patterson, Jean L.; Crasta, Oswald; Zhang, Yan; Mani, Sachin; Jett, Marti; Poonia, Bhawna; Djavani, Mahmoud; White, David M.; Lukashevich, Igor S.; Salvato, Maria S.

    2013-01-01

    Lassa virus (LASV) is the causative agent of Lassa Fever and is responsible for several hundred thousand infections and thousands of deaths annually in West Africa. LASV and the non-pathogenic Mopeia virus (MOPV) are both rodent-borne African arenaviruses. A live attenuated reassortant of MOPV and LASV, designated ML29, protects rodents and primates from LASV challenge and appears to be more attenuated than MOPV. To gain better insight into LASV-induced pathology and mechanism of attenuation we performed gene expression profiling in human peripheral blood mononuclear cells (PBMC) exposed to LASV and the vaccine candidate ML29. PBMC from healthy human subjects were exposed to either LASV or ML29. Although most PBMC are non-permissive for virus replication, they remain susceptible to signal transduction by virus particles. Total RNA was extracted and global gene expression was evaluated during the first 24 hours using high-density microarrays. Results were validated using RT-PCR, flow cytometry and ELISA. LASV and ML29 elicited differential expression of interferon-stimulated genes (ISG), as well as genes involved in apoptosis, NF-kB signaling and the coagulation pathways. These genes could eventually serve as biomarkers to predict disease outcomes. The remarkable differential expression of thrombomodulin, a key regulator of inflammation and coagulation, suggests its involvement with vascular abnormalities and mortality in Lassa fever disease. PMID:24069471

  13. Transcriptome analysis of human peripheral blood mononuclear cells exposed to Lassa virus and to the attenuated Mopeia/Lassa reassortant 29 (ML29, a vaccine candidate.

    Directory of Open Access Journals (Sweden)

    Juan Carlos Zapata

    Full Text Available Lassa virus (LASV is the causative agent of Lassa Fever and is responsible for several hundred thousand infections and thousands of deaths annually in West Africa. LASV and the non-pathogenic Mopeia virus (MOPV are both rodent-borne African arenaviruses. A live attenuated reassortant of MOPV and LASV, designated ML29, protects rodents and primates from LASV challenge and appears to be more attenuated than MOPV. To gain better insight into LASV-induced pathology and mechanism of attenuation we performed gene expression profiling in human peripheral blood mononuclear cells (PBMC exposed to LASV and the vaccine candidate ML29. PBMC from healthy human subjects were exposed to either LASV or ML29. Although most PBMC are non-permissive for virus replication, they remain susceptible to signal transduction by virus particles. Total RNA was extracted and global gene expression was evaluated during the first 24 hours using high-density microarrays. Results were validated using RT-PCR, flow cytometry and ELISA. LASV and ML29 elicited differential expression of interferon-stimulated genes (ISG, as well as genes involved in apoptosis, NF-kB signaling and the coagulation pathways. These genes could eventually serve as biomarkers to predict disease outcomes. The remarkable differential expression of thrombomodulin, a key regulator of inflammation and coagulation, suggests its involvement with vascular abnormalities and mortality in Lassa fever disease.

  14. High-yield production of a stable Vero cell-based vaccine candidate against the highly pathogenic avian influenza virus H5N1

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Fangye; Zhou, Jian; Ma, Lei; Song, Shaohui; Zhang, Xinwen; Li, Weidong; Jiang, Shude [No. 5, Department of Bioproducts, Institute of Medical Biology, Chinese Academy of Medical Science and Pecking Union Medical College, Jiaoling Avenue 935, Kunming, Yunnan Province 650102, People' s Republic of China (China); Wang, Yue [National Institute for Viral Disease Control and Prevention, China Center for Disease Control and Prevention, Yingxin Lane 100, Xicheng District, Beijing 100052, People' s Republic of China (China); Liao, Guoyang [No. 5, Department of Bioproducts, Institute of Medical Biology, Chinese Academy of Medical Science and Pecking Union Medical College, Jiaoling Avenue 935, Kunming, Yunnan Province 650102, People' s Republic of China (China)

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer Vero cell-based HPAI H5N1 vaccine with stable high yield. Black-Right-Pointing-Pointer Stable high yield derived from the YNVa H3N2 backbone. Black-Right-Pointing-Pointer H5N1/YNVa has a similar safety and immunogenicity to H5N1delta. -- Abstract: Highly pathogenic avian influenza (HPAI) viruses pose a global pandemic threat, for which rapid large-scale vaccine production technology is critical for prevention and control. Because chickens are highly susceptible to HPAI viruses, the supply of chicken embryos for vaccine production might be depleted during a virus outbreak. Therefore, developing HPAI virus vaccines using other technologies is critical. Meeting vaccine demand using the Vero cell-based fermentation process has been hindered by low stability and yield. In this study, a Vero cell-based HPAI H5N1 vaccine candidate (H5N1/YNVa) with stable high yield was achieved by reassortment of the Vero-adapted (Va) high growth A/Yunnan/1/2005(H3N2) (YNVa) virus with the A/Anhui/1/2005(H5N1) attenuated influenza vaccine strain (H5N1delta) using the 6/2 method. The reassorted H5N1/YNVa vaccine maintained a high hemagglutination (HA) titer of 1024. Furthermore, H5N1/YNVa displayed low pathogenicity and uniform immunogenicity compared to that of the parent virus.

  15. Phase 1 trial of malaria transmission blocking vaccine candidates Pfs25 and Pvs25 formulated with montanide ISA 51.

    Directory of Open Access Journals (Sweden)

    Yimin Wu

    2008-07-01

    Full Text Available Pfs25 and Pvs25, surface proteins of mosquito stage of the malaria parasites P. falciparum and P. vivax, respectively, are leading candidates for vaccines preventing malaria transmission by mosquitoes. This single blinded, dose escalating, controlled Phase 1 study assessed the safety and immunogenicity of recombinant Pfs25 and Pvs25 formulated with Montanide ISA 51, a water-in-oil emulsion.The trial was conducted at The Johns Hopkins Center for Immunization Research, Washington DC, USA, between May 16, 2005-April 30, 2007. The trial was designed to enroll 72 healthy male and non-pregnant female volunteers into 1 group to receive adjuvant control and 6 groups to receive escalating doses of the vaccines. Due to unexpected reactogenicity, the vaccination was halted and only 36 volunteers were enrolled into 4 groups: 3 groups of 10 volunteers each were immunized with 5 microg of Pfs25/ISA 51, 5 microg of Pvs25/ISA 51, or 20 microg of Pvs25/ISA 51, respectively. A fourth group of 6 volunteers received adjuvant control (PBS/ISA 51. Frequent local reactogenicity was observed. Systemic adverse events included two cases of erythema nodosum considered to be probably related to the combination of the antigen and the adjuvant. Significant antibody responses were detected in volunteers who completed the lowest scheduled doses of Pfs25/ISA 51. Serum anti-Pfs25 levels correlated with transmission blocking activity.It is feasible to induce transmission blocking immunity in humans using the Pfs25/ISA 51 vaccine, but these vaccines are unexpectedly reactogenic for further development. This is the first report that the formulation is associated with systemic adverse events including erythema nodosum.ClinicalTrials.gov NCT00295581.

  16. Chimeric classical swine fever (CSF)-Japanese encephalitis (JE) viral replicon as a non-transmissible vaccine candidate against CSF and JE infections.

    Science.gov (United States)

    Yang, Zhenhua; Wu, Rui; Li, Robert W; Li, Ling; Xiong, Zhongliang; Zhao, Haizhong; Guo, Deyin; Pan, Zishu

    2012-04-01

    A trans-complemented chimeric CSF-JE virus replicon was constructed using an infectious cDNA clone of the CSF virus (CSFV) Alfort/187 strain. The CSFV E2 gene was deleted, and a fragment containing the region encoding a truncated envelope protein (tE, amino acid 292-402, domain III) of JE virus (JEV) was inserted into the resultant plasmid, pA187delE2, to generate the recombinant cDNA clone pA187delE2/JEV-tE. Porcine kidney 15 (PK15) cells that constitutively express the CSFV E2p7 proteins were then transfected with in vitro-transcribed RNA from pA187delE2/JEV-tE. As a result, the chimeric CSF-JE virus replicon particle (VRP), rv187delE2/JEV-tE, was rescued. In a mouse model, immunization with the chimeric CSF-JE VRP induced strong production of JEV-specific antibody and conferred protection against a lethal JEV challenge. Pigs immunized with CSF-JE VRP displayed strong anti-CSFV and anti-JEV antibody responses and protection against CSFV and JEV challenge infections. Our evidence suggests that E2-complemented CSF-JE VRP not only has potential as a live-attenuated non-transmissible vaccine candidate against CSF and JE but also serves as a potential DIVA (Differentiating Infected from Vaccinated Animals) vaccine for CSF in pigs. Together, our data suggest that the non-transmissible chimeric VRP expressing foreign antigenic proteins may represent a promising strategy for bivalent DIVA vaccine design. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Immunogenicity of a virosomally-formulated Plasmodium falciparum GLURP-MSP3 chimeric protein-based malaria vaccine candidate in comparison to adjuvanted formulations

    Directory of Open Access Journals (Sweden)

    Tamborrini Marco

    2011-12-01

    Full Text Available Abstract Background In clinical trials, immunopotentiating reconstituted influenza virosomes (IRIVs have shown great potential as a versatile antigen delivery platform for synthetic peptides derived from Plasmodium falciparum antigens. This study describes the immunogenicity of a virosomally-formulated recombinant fusion protein comprising domains of the two malaria vaccine candidate antigens MSP3 and GLURP. Methods The highly purified recombinant protein GMZ2 was coupled to phosphatidylethanolamine and the conjugates incorporated into the membrane of IRIVs. The immunogenicity of this adjuvant-free virosomal formulation was compared to GMZ2 formulated with the adjuvants Montanide ISA 720 and Alum in three mouse strains with different genetic backgrounds. Results Intramuscular injections of all three candidate vaccine formulations induced GMZ2-specific antibody responses in all mice tested. In general, the humoral immune response in outbred NMRI mice was stronger than that in inbred BALB/c and C57BL/6 mice. ELISA with the recombinant antigens demonstrated immunodominance of the GLURP component over the MSP3 component. However, compared to the Al(OH3-adjuvanted formulation the two other formulations elicited in NMRI mice a larger proportion of anti-MSP3 antibodies. Analyses of the induced GMZ2-specific IgG subclass profiles showed for all three formulations a predominance of the IgG1 isotype. Immune sera against all three formulations exhibited cross-reactivity with in vitro cultivated blood-stage parasites. Immunofluorescence and immunoblot competition experiments showed that both components of the hybrid protein induced IgG cross-reactive with the corresponding native proteins. Conclusion A virosomal formulation of the chimeric protein GMZ2 induced P. falciparum blood stage parasite cross-reactive IgG responses specific for both MSP3 and GLURP. GMZ2 thus represents a candidate component suitable for inclusion into a multi-valent virosomal

  18. Immunogenicity, protective efficacy, and non-replicative status of the HSV-2 vaccine candidate HSV529 in mice and guinea pigs.

    Science.gov (United States)

    Bernard, Marie-Clotilde; Barban, Véronique; Pradezynski, Fabrine; de Montfort, Aymeric; Ryall, Robert; Caillet, Catherine; Londono-Hayes, Patricia

    2015-01-01

    HSV-2 vaccine is needed to prevent genital disease, latent infection, and virus transmission. A replication-deficient mutant virus (dl5-29) has demonstrated promising efficacy in animal models of genital herpes. However, the immunogenicity, protective efficacy, and non-replicative status of the highly purified clinical vaccine candidate (HSV529) derived from dl5-29 have not been evaluated. Humoral and cellular immune responses were measured in mice and guinea pigs immunized with HSV529. Protection against acute and recurrent genital herpes, mortality, latent infection, and viral shedding after vaginal HSV-2 infection was determined in mice or in naïve and HSV-1 seropositive guinea pigs. HSV529 replication and pathogenicity were investigated in three sensitive models of virus replication: severe combined immunodeficient (SCID/Beige) mice inoculated by the intramuscular route, suckling mice inoculated by the intracranial route, and vaginally-inoculated guinea pigs. HSV529 immunization induced HSV-2-neutralizing antibody production in mice and guinea pigs. In mice, it induced production of specific HSV-2 antibodies and splenocytes secreting IFNγ or IL-5. Immunization effectively prevented HSV-2 infection in all three animal models by reducing mortality, acute genital disease severity and frequency, and viral shedding. It also reduced ganglionic viral latency and recurrent disease in naïve and HSV-1 seropositive guinea pigs. HSV529 replication/propagation was not detected in the muscles of SCID/Beige mice, in the brains of suckling mice, or in vaginal secretions of inoculated guinea pigs. These results confirm the non-replicative status, as well as its immunogenicity and efficacy in mice and guinea pigs, including HSV-1 seropositive guinea pigs. In mice, HSV529 produced Th1/Th2 characteristic immune response thought to be necessary for an effective vaccine. These results further support the clinical investigation of HSV529 in human subjects as a prophylactic vaccine.

  19. Formalin-inactivated EV71 vaccine candidate induced cross-neutralizing antibody against subgenotypes B1, B4, B5 and C4A in adult volunteers.

    Directory of Open Access Journals (Sweden)

    Ai-Hsiang Chou

    Full Text Available Enterovirus 71 (EV71 has caused several epidemics of hand, foot and mouth diseases (HFMD in Asia. No effective EV71 vaccine is available. A randomized and open-label phase I clinical study registered with ClinicalTrials.gov #NCT01268787, aims to evaluate the safety, reactogenicity and immunogenicity of a formalin-inactivated EV71 vaccine candidate (EV71vac at 5- and 10-µg doses. In this study we report the cross-neutralizing antibody responses from each volunteer against different subgenotypes of EV71 and CVA16.Sixty eligible healthy adults were recruited and vaccinated. Blood samples were obtained on day 0, 21 and 42 and tested against B1, B4, B5, C2, C4A, C4B and CVA16 for cross-neutralizing antibody responses.The immunogenicity of both 5- and 10- µg doses were found to be very similar. Approximately 45% of the participants had 4-fold increase in Nt, but there was no further increase in Nt after the second dose. EV71vac induced very strong cross-neutralizing antibody responses in >85% of volunteers without pre-existing Nt against subgenotype B1, B5 and C4A. EV71vac elicited weak cross-neutralizing antibody responses (∼20% of participants against a C4B and Coxsackie virus A16. Over 90% of vaccinated volunteers did not develop cross-neutralizing antibody responses (Nt<8 against a C2 strain. EV71vac can boost and significantly enhance the neutralizing antibody responses in volunteers who already had pre-vaccination antibodies against EV71 and/or CVA16.EV71vac is efficient in eliciting cross-neutralizing antibody responses against EV71 subgenotypes B1, B4, B5, and C4A, and provides the rationale for its evaluation in phase II clinical trials.ClinicalTrials.gov NCT01268787.

  20. Immunogenicity and Efficacy of Live L. tarentolae Expressing KMP11-NTGP96-GFP Fusion as a Vaccine Candidate against Experimental Visceral Leishmaniasis Caused by L. infantum

    Directory of Open Access Journals (Sweden)

    Vahid NASIRI

    2016-10-01

    Full Text Available Background: The aim of present study was to evaluate the protective efficacy of live recombinant L. tarentolae expressing KMP11-NTGP96-GFP fusion as candidates for live engineered recombinant vaccine against visceral leishmaniasis in BALB/c mice.Methods: KMP-11 and NT-GP96 genes cloned into the pJET1.2/blunt cloning vector and then into pEGFP-N1 expression vector. The KMP-11, NT-GP96 and GFP fused in pEGFP-N1 and subcloned into Leishmanian pLEXSY-neo vector. Finally this construct was transferred to L. tarentolae by electroporation. Tranfection was confirmed by SDS-PAGE, WESTERN blot, flowcytometry and RT-PCR. Protective efficacy of this construct was evaluated as a vaccine candidate against visceral leishmaniasis. Parasite burden, humoral and cellular immune responses were assessed before and at 4 weeks after challenge.Results: KMP- NT-Gp96-GFP Fusion was cloned successfully into pLEXSY -neo vector and this construct successfully transferred to L. tarentolae. Finding indicated that immunization with L. tarentolae tarentolae-KMP11-NTGP96-GFP provides significant protection against visceral leishmaniasis and was able to induce an increased expression of IFN-γ and IgG2a. Following challenge, a reduced parasite load in the spleen of the KMP11-NTGP96-GFP immunized group was detected.Conclusion: The present study is the first to use a combination of a Leishmania antigen with an immunologic antigen in live recombinant L. tarentolae and results suggest that L. tarentolae-KMP11-NTGP96-GFP could be considered as a potential tool in vaccination against visceral leishmaniasis and this vaccination strategy could provide a potent rout for future vaccine development. 

  1. A randomized trial assessing the safety and immunogenicity of AS01 and AS02 adjuvanted RTS,S malaria vaccine candidates in children in Gabon.

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    Bertrand Lell

    2009-10-01

    Full Text Available The malaria vaccine candidate antigen RTS,S includes parts of the pre-erythrocytic stage circumsporozoite protein fused to the Hepatitis B surface antigen. Two Adjuvant Systems are in development for this vaccine, an oil-in water emulsion--based formulation (AS02 and a formulation based on liposomes (AS01.In this Phase II, double-blind study (NCT00307021, 180 healthy Gabonese children aged 18 months to 4 years were randomized to receive either RTS,S/AS01(E or RTS,S/AS02(D, on a 0-1-2 month vaccination schedule. The children were followed-up daily for six days after each vaccination and monthly for 14 months. Blood samples were collected at 4 time-points. Both vaccines were well tolerated. Safety parameters were distributed similarly between the two groups. Both vaccines elicited a strong specific immune response after Doses 2 and 3 with a ratio of anti-CS GMT titers (AS02(D/AS01(E of 0.88 (95% CI: 0.68-1.15 post-Dose 3. After Doses 2 and 3 of experimental vaccines, anti-CS and anti-HBs antibody GMTs were higher in children who had been previously vaccinated with at least one dose of hepatitis B vaccine compared to those not previously vaccinated.RTS,S/AS01(E proved similarly as well tolerated and immunogenic as RTS,S/AS02(D, completing an essential step in the age de-escalation process within the RTS,S clinical development plan.ClinicalTrials.gov. NCT00307021.

  2. Histomorphometric characteristics of immune cells in small intestine of pigs perorally immunized with vaccine candidate F18ac+ nonenterotoxigenic E. coli strain

    Directory of Open Access Journals (Sweden)

    I. Valpotic

    2009-12-01

    Full Text Available Colidiarrhea and colienterotoxemia caused by F4+ and/or F18+ enterotoxigenic E. coli (ETEC strains are the most prevalent infections of suckling and weaned pigs. Here we tested the immunogenicity and protective effectiveness of attenuated F18ac+ non-ETEC vaccine candidate strain against challenge infection with F4ac+ ETEC strain by quantitative phenotypic analysis of small intestinal leukocyte subsets in weaned pigs. We also evaluated levamisole as an immune response modifier (IRM and its adjuvanticity when given in the combination with the experimental vaccine. The pigs were parenterally immunized with either levamisole (at days -2, -1 and 0 or with levamisole and perorally given F18ac+ non-ETEC strain (at day 0, and challenged with F4ac+ ETEC strain 7 days later. At day 13 the pigs were euthanatized and sampled for immunohistological/histomorphometrical analyses. Lymphoid CD3+, CD45RA+, CD45RC+, CD21+, IgA+ and myeloid SWC3+ cell subsets were identified in jejunal and ileal epithelium, lamina propria and Peyer’s patches using the avidin-biotin complex method, and their numbers were determined by computer-assisted histomorphometry. Quantitative immunophenotypic analyses showed that levamisole treated pigs had highly increased numbers of jejunal CD3+, CD45RC+ and SWC3+ cells (p<0.05 as compared to those recorded in nontreated control pigs. In the ileum of these pigs we have recorded that only CD21+ cells were significantly increased (p<0.01. The pigs that were treated with levamisole adjuvanted experimental vaccine had significantly increased numbers of all tested cell subsets in both segments of the small intestine. It was concluded that levamisole adjuvanted F18ac+ non-ETEC vaccine was a requirement for the elicitation of protective gut immunity in this model; nonspecific immunization with levamisole was less effective, but confirmed its potential as an IRM.

  3. Evaluation of vaccine candidate potential of deltaaroA, deltahtrA and deltaaroAdeltahtrA mutants of Salmonella enterica subspecies enterica serovar Abortusequi in guinea pigs.

    Science.gov (United States)

    Singh, Bhoj Raj; Chandra, Mudit; Hansda, Dhananjoy; Alam, Javed; Babu, Narayanan; Siddiqui, Mehtab Z; Agrawal, Ravi K; Sharma, Gautam

    2013-04-01

    Salmonella enterica subspecies enterica serovar Abortusequi (S. Abortusequi), a host adapted Salmonella causes abortions, still births and foal mortality in equids. Though known since more than 100 years, it is still a problem in many of the developing countries including India. There is dearth of really good vaccine affording immunity lasting at least for one full gestation. In search of a potential vaccine candidate, three defined deletion mutants (deltaaroA, deltahtrA and deltaaroAdeltahtrA) of S. Abortusequi were tested in guinea pig model for attenuation, safety, immunogenicity, humoral immune response, protective efficacy and persistence in host. The deltahtrA and deltaaroAdeltahtrA mutants were found to be safe on oral inoculation in doses as high as 4.2 x 10(9) cfu/animal. Also through subcutaneous inoculation deltaaroAdeltahtrA mutant did not induce any abortion in pregnant guinea pigs. All the three mutants did not induce any illness or death in 1-2 week-old baby guinea pigs except deltahtrA mutant which caused mortality on intraperitoneal inoculation. Inoculation with mutants protected against challenge and increased breeding efficiency of guinea pigs. After >4.5 months of mutant inoculation, guinea pigs were protected against abortifacient dose of wild type S. Abortusequi and mother guinea pigs also conferred resistance to their babies to the similar challenge. Early humoral immune response of S. Abortusequi mutants was characteristic. Faecal excretion of deltaaroA and htrA mutants was detected up to 45 days of inoculation in guinea pigs while deltaaroAdeltahtrA mutant could not be detected after 21 days of inoculation. The results indicated that the double deletion mutant (deltaaroAdeltahtrA) was the most effective and safe candidate for vaccination against S. Abortusequi through mucosal route of inoculation.

  4. Safety and Immunogenicity of a Tetravalent Dengue Vaccine Candidate in Healthy Children and Adults in Dengue-Endemic Regions: A Randomized, Placebo-Controlled Phase 2 Study.

    Science.gov (United States)

    Sirivichayakul, Chukiat; Barranco-Santana, Elizabeth A; Esquilin-Rivera, Inés; Oh, Helen M L; Raanan, Marsha; Sariol, Carlos A; Shek, Lynette P; Simasathien, Sriluck; Smith, Mary Kathryn; Velez, Ivan Dario; Wallace, Derek; Gordon, Gilad S; Stinchcomb, Dan T

    2016-05-15

    A safe, effective tetravalent dengue vaccine is a global health priority. The safety and immunogenicity of a live attenuated, recombinant tetravalent dengue vaccine candidate (TDV) were evaluated in healthy volunteers from dengue-endemic countries. This multicenter, double-blind, phase 2 study was conducted in Puerto Rico, Colombia, Singapore, and Thailand. During stage I, 148 volunteers aged 1.5-45 years were sequentially enrolled into 4 age-descending groups and randomized at a ratio of 2:1 to receive TDV or placebo. In stage II (group 5), 212 children aged 1.5-11 years were randomized at a ratio of 3:1 to receive TDV or placebo. Participants received a subcutaneous injection of TDV or placebo on days 0 and 90 and were followed for analysis of safety, seropositivity, and neutralizing antibodies to DENV-1-4. Injection site pain, itching, and erythema (mostly mild) were the only solicited adverse events more frequently reported with TDV than with placebo in all age groups. After 2 TDV doses, seropositivity was >95% in all 5 groups for DENV-1-3 and 72.7%-100% for DENV-4; geometric mean titers ranged from 582 to 1187 for DENV-1, from 582 to 1187 for DENV-2, from 196 to 630 for DENV-3, and from 41 to 210 for DENV-4 among the 5 groups. TDV was well tolerated and immunogenic in volunteers aged 1.5-45 years, irrespective of prevaccination dengue exposure. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mailjournals.permissions@oup.com.

  5. Immunogenicity, protective efficacy, and non-replicative status of the HSV-2 vaccine candidate HSV529 in mice and guinea pigs.

    Directory of Open Access Journals (Sweden)

    Marie-Clotilde Bernard

    Full Text Available HSV-2 vaccine is needed to prevent genital disease, latent infection, and virus transmission. A replication-deficient mutant virus (dl5-29 has demonstrated promising efficacy in animal models of genital herpes. However, the immunogenicity, protective efficacy, and non-replicative status of the highly purified clinical vaccine candidate (HSV529 derived from dl5-29 have not been evaluated. Humoral and cellular immune responses were measured in mice and guinea pigs immunized with HSV529. Protection against acute and recurrent genital herpes, mortality, latent infection, and viral shedding after vaginal HSV-2 infection was determined in mice or in naïve and HSV-1 seropositive guinea pigs. HSV529 replication and pathogenicity were investigated in three sensitive models of virus replication: severe combined immunodeficient (SCID/Beige mice inoculated by the intramuscular route, suckling mice inoculated by the intracranial route, and vaginally-inoculated guinea pigs. HSV529 immunization induced HSV-2-neutralizing antibody production in mice and guinea pigs. In mice, it induced production of specific HSV-2 antibodies and splenocytes secreting IFNγ or IL-5. Immunization effectively prevented HSV-2 infection in all three animal models by reducing mortality, acute genital disease severity and frequency, and viral shedding. It also reduced ganglionic viral latency and recurrent disease in naïve and HSV-1 seropositive guinea pigs. HSV529 replication/propagation was not detected in the muscles of SCID/Beige mice, in the brains of suckling mice, or in vaginal secretions of inoculated guinea pigs. These results confirm the non-replicative status, as well as its immunogenicity and efficacy in mice and guinea pigs, including HSV-1 seropositive guinea pigs. In mice, HSV529 produced Th1/Th2 characteristic immune response thought to be necessary for an effective vaccine. These results further support the clinical investigation of HSV529 in human subjects as a

  6. Evaluating Vaccine Candidates for Filariasis

    Science.gov (United States)

    2013-04-16

    causative agents of lymphatic filariasis, W. bancrofti, B. malayi, or B. timori, and that the worldwide prevalence of genital disease or lymphedema...St. Louis, Missouri: Saundeers Elsevier 71. Johnson MH, Orihel TC, Beaver PC. 1974. Dipetalonema viteae in the experimentally infected jird

  7. Deficiencies of effectiveness of intervention studies in veterinary medicine: a cross-sectional survey of ten leading veterinary and medical journals

    NARCIS (Netherlands)

    Di Girolamo, Nicola; Meursinge Reynders, Reint

    2016-01-01

    The validity of studies that assess the effectiveness of an intervention (EoI) depends on variables such as the type of study design, the quality of their methodology, and the participants enrolled. Five leading veterinary journals and 5 leading human medical journals were hand-searched for EoI

  8. The synthetic Plasmodium falciparum circumsporozoite peptide PfCS102 as a malaria vaccine candidate: a randomized controlled phase I trial.

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    Régine Audran

    Full Text Available BACKGROUND: Fully efficient vaccines against malaria pre-erythrocytic stage are still lacking. The objective of this dose/adjuvant-finding study was to evaluate the safety, reactogenicity and immunogenicity of a vaccine candidate based on a peptide spanning the C-terminal region of Plasmodium falciparum circumsporozoite protein (PfCS102 in malaria naive adults. METHODOLOGY AND PRINCIPAL FINDINGS: Thirty-six healthy malaria-naive adults were randomly distributed into three dose blocks (10, 30 and 100 microg and vaccinated with PfCS102 in combination with either Montanide ISA 720 or GSK proprietary Adjuvant System AS02A at days 0, 60, and 180. Primary end-point (safety and reactogenicity was based on the frequency of adverse events (AE and of abnormal biological safety tests; secondary-end point (immunogenicity on P. falciparum specific cell-mediated immunity and antibody response before and after immunization. The two adjuvant formulations were well tolerated and their safety profile was good. Most AEs were local and, when systemic, involved mainly fatigue and headache. Half the volunteers in AS02A groups experienced severe AEs (mainly erythema. After the third injection, 34 of 35 volunteers developed anti-PfCS102 and anti-sporozoite antibodies, and 28 of 35 demonstrated T-cell proliferative responses and IFN-gamma production. Five of 22 HLA-A2 and HLA-A3 volunteers displayed PfCS102 specific IFN-gamma secreting CD8(+ T cell responses. Responses were only marginally boosted after the 3(rd vaccination and remained stable for 6 months. For both adjuvants, the dose of 10 microg was less immunogenic in comparison to 30 and 100 microg that induced similar responses. AS02A formulations with 30 microg or 100 microg PfCS102 induced about 10-folds higher antibody and IFN-gamma responses than Montanide formulations. CONCLUSIONS/SIGNIFICANCE: PfCS102 peptide was safe and highly immunogenic, allowing the design of more advanced trials to test its potential

  9. Trypanosoma cruzi vaccine candidate antigens Tc24 and TSA-1 recall memory immune response associated with HLA-A and -B supertypes in Chagasic chronic patients from Mexico.

    Science.gov (United States)

    Villanueva-Lizama, Liliana E; Cruz-Chan, Julio V; Aguilar-Cetina, Amarú Del C; Herrera-Sanchez, Luis F; Rodriguez-Perez, Jose M; Rosado-Vallado, Miguel E; Ramirez-Sierra, Maria J; Ortega-Lopez, Jaime; Jones, Kathryn; Hotez, Peter; Bottazzi, Maria Elena; Dumonteil, Eric

    2018-01-01

    Trypanosoma cruzi antigens TSA-1 and Tc24 have shown promise as vaccine candidates in animal studies. We evaluated here the recall immune response these antigens induce in Chagasic patients, as a first step to test their immunogenicity in humans. We evaluated the in vitro cellular immune response after stimulation with recombinant TSA-1 (rTSA-1) or recombinant Tc24 (rTc24) in mononuclear cells of asymptomatic Chagasic chronic patients (n = 20) compared to healthy volunteers (n = 19) from Yucatan, Mexico. Proliferation assays, intracellular cytokine staining, cytometric bead arrays, and memory T cell immunophenotyping were performed by flow cytometry. Peripheral blood mononuclear cells (PBMC) from Chagasic patients showed significant proliferation after stimulation with rTc24 and presented a phenotype of T effector memory cells (CD45RA-CCR7-). These cells also produced IFN-γ and, to a lesser extent IL10, after stimulation with rTSA-1 and rTc24 proteins. Overall, both antigens recalled a broad immune response in some Chagasic patients, confirming that their immune system had been primed against these antigens during natural infection. Analysis of HLA-A and HLA-B allele diversity by PCR-sequencing indicated that HLA-A03 and HLA-B07 were the most frequent supertypes in this Mexican population. Also, there was a significant difference in the frequency of HLA-A01 and HLA-A02 supertypes between Chagasic patients and controls, while the other alleles were evenly distributed. Some aspects of the immune response, such as antigen-induced IFN-γ production by CD4+ and CD8+ T cells and CD8+ proliferation, showed significant association with specific HLA-A supertypes, depending on the antigen considered. In conclusion, our results confirm the ability of both TSA-1 and Tc24 recombinant proteins to recall an immune response induced by the native antigens during natural infection in at least some patients. Our data support the further development of these antigens as therapeutic

  10. Safety of the malaria vaccine candidate, RTS,S/AS01E in 5 to 17 month old Kenyan and Tanzanian Children.

    Directory of Open Access Journals (Sweden)

    John Lusingu

    2010-11-01

    Full Text Available The malaria vaccine candidate, RTS,S/AS01(E, showed promising protective efficacy in a trial of Kenyan and Tanzanian children aged 5 to 17 months. Here we report on the vaccine's safety and tolerability. The experimental design was a Phase 2b, two-centre, double-blind (observer- and participant-blind, randomised (1∶1 ratio controlled trial. Three doses of study or control (rabies vaccines were administered intramuscularly at 1 month intervals. Solicited adverse events (AEs were collected for 7 days after each vaccination. There was surveillance and reporting for unsolicited adverse events for 30 days after each vaccination. Serious adverse events (SAEs were recorded throughout the study period which lasted for 14 months after dose 1 in Korogwe, Tanzania and an average of 18 months post-dose 1 in Kilifi, Kenya. Blood samples for safety monitoring of haematological, renal and hepatic functions were taken at baseline, 3, 10 and 14 months after dose 1. A total of 894 children received RTS,S/AS01(E or rabies vaccine between March and August 2007. Overall, children vaccinated with RTS,S/AS01(E had fewer SAEs (51/447 than children in the control group (88/447. One SAE episode in a RTS,S/AS01(E recipient and nine episodes among eight rabies vaccine recipients met the criteria for severe malaria. Unsolicited AEs were reported in 78% of subjects in the RTS,S/AS01(E group and 74% of subjects in the rabies vaccine group. In both vaccine groups, gastroenteritis and pneumonia were the most frequently reported unsolicited AE. Fever was the most frequently observed solicited AE and was recorded after 11% of RTS,S/AS01(E doses compared to 31% of doses of rabies vaccine. The candidate vaccine RTS,S/AS01(E showed an acceptable safety profile in children living in a malaria-endemic area in East Africa. More data on the safety of RTS,S/AS01(E will become available from the Phase 3 programme.

  11. Deficiencies of effectiveness of intervention studies in veterinary medicine: a cross-sectional survey of ten leading veterinary and medical journals

    Science.gov (United States)

    Meursinge Reynders, Reint

    2016-01-01

    The validity of studies that assess the effectiveness of an intervention (EoI) depends on variables such as the type of study design, the quality of their methodology, and the participants enrolled. Five leading veterinary journals and 5 leading human medical journals were hand-searched for EoI studies for the year 2013. We assessed (1) the prevalence of randomized controlled trials (RCTs) among EoI studies, (2) the type of participants enrolled, and (3) the methodological quality of the selected studies. Of 1707 eligible articles, 590 were EoI articles and 435 RCTs. Random allocation to the intervention was performed in 52% (114/219; 95%CI:45.2–58.8%) of veterinary EoI articles, against 87% (321/371; 82.5–89.7%) of human EoI articles (adjusted OR:9.2; 3.4–24.8). Veterinary RCTs were smaller (median: 26 animals versus 465 humans) and less likely to enroll real patients, compared with human RCTs (OR:331; 45–2441). Only 2% of the veterinary RCTs, versus 77% of the human RCTs, reported power calculations, primary outcomes, random sequence generation, allocation concealment and estimation methods. Currently, internal and external validity of veterinary EoI studies is limited compared to human medical ones. To address these issues, veterinary interventional research needs to improve its methodology, increase the number of published RCTs and enroll real clinical patients. PMID:26835187

  12. Phase 1b randomized trial and follow-up study in Uganda of the blood-stage malaria vaccine candidate BK-SE36.

    Science.gov (United States)

    Palacpac, Nirianne Marie Q; Ntege, Edward; Yeka, Adoke; Balikagala, Betty; Suzuki, Nahoko; Shirai, Hiroki; Yagi, Masanori; Ito, Kazuya; Fukushima, Wakaba; Hirota, Yoshio; Nsereko, Christopher; Okada, Takuya; Kanoi, Bernard N; Tetsutani, Kohhei; Arisue, Nobuko; Itagaki, Sawako; Tougan, Takahiro; Ishii, Ken J; Ueda, Shigeharu; Egwang, Thomas G; Horii, Toshihiro

    2013-01-01

    Up to now a malaria vaccine remains elusive. The Plasmodium falciparum serine repeat antigen-5 formulated with aluminum hydroxyl gel (BK-SE36) is a blood-stage malaria vaccine candidate that has undergone phase 1a trial in malaria-naive Japanese adults. We have now assessed the safety and immunogenicity of BK-SE36 in a malaria endemic area in Northern Uganda. We performed a two-stage, randomized, single-blinded, placebo-controlled phase 1b trial (Current Controlled trials ISRCTN71619711). A computer-generated sequence randomized healthy subjects for 2 subcutaneous injections at 21-day intervals in Stage1 (21-40 year-olds) to 1-mL BK-SE36 (BKSE1.0) (n = 36) or saline (n = 20) and in Stage2 (6-20 year-olds) to BKSE1.0 (n = 33), 0.5-mL BK-SE36 (BKSE0.5) (n = 33), or saline (n = 18). Subjects and laboratory personnel were blinded. Safety and antibody responses 21-days post-second vaccination (Day42) were assessed. Post-trial, to compare the risk of malaria episodes 130-365 days post-second vaccination, Stage2 subjects were age-matched to 50 control individuals. Nearly all subjects who received BK-SE36 had induration (Stage1, n = 33, 92%; Stage2, n = 63, 96%) as a local adverse event. No serious adverse event related to BK-SE36 was reported. Pre-existing anti-SE36 antibody titers negatively correlated with vaccination-induced antibody response. At Day42, change in antibody titers was significant for seronegative adults (1.95-fold higher than baseline [95% CI, 1.56-2.43], p = 0.004) and 6-10 year-olds (5.71-fold [95% CI, 2.38-13.72], p = 0.002) vaccinated with BKSE1.0. Immunogenicity response to BKSE0.5 was low and not significant (1.55-fold [95% CI, 1.24-1.94], p = 0.75). In the ancillary analysis, cumulative incidence of first malaria episodes with ≥5000 parasites/µL was 7 cases/33 subjects in BKSE1.0 and 10 cases/33 subjects in BKSE0.5 vs. 29 cases/66 subjects in the control group. Risk ratio for BKSE1.0 was 0.48 (95% CI, 0

  13. Recombinant C-terminal 311 amino acids of HapS adhesin as a vaccine candidate for nontypeable Haemophilus influenzae: A study on immunoreactivity in Balb/C mouse.

    Science.gov (United States)

    Tabatabaee Bafroee, Akram Sadat; Siadat, Seyed Davar; Mousavi, Seyed Fazlollah; Aghasadeghi, Mohammad Reza; Khorsand, Hashem; Nejati, Mehdi; Sadat, Seyed Mehdi; Mahdavi, Mehdi

    2016-09-01

    Hap, an auto-transporter protein, is an antigenically conserved adhesion protein which is present on both typeable and nontypeable Haemophilus influenzae. This protein has central role in bacterial attachment to respiratory tract epithelial cells. A 1000bp C-terminal fragment of Hap passenger domain (HapS) from nontypeable Haemophilus influenzae was cloned into a prokaryotic expression vector, pET-24a. BALB/c mice were immunized subcutaneously with purified rC-HapS. Serum IgG responses to purified rC-HapS, serum IgG subclasses were determined by ELISA and functional activity of antibodies was examined by Serum Bactericidal Assay. The output of rC-HapS was approximately 62% of the total bacterial proteins. Serum IgG responses were significantly increased in immunized group with rC-HapS mixed with Freund's adjuvant in comparison with control groups. Analysis of the serum IgG subclasses showed that the IgG1 subclass was predominant after subcutaneous immunization in BALB/c mice (IgG2a/IgG1 HapS immunized animals were strongly bactericidal against nontypeable Haemophilus influenzae. These results suggest that rC-HapS may be a potential vaccine candidate for nontypeable Haemophilus influenzae. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. HIPs at Ten

    Science.gov (United States)

    Kuh, George; O'Donnell, Ken; Schneider, Carol Geary

    2017-01-01

    2017 is the anniversary of the introduction of what are now commonly known as high-impact practices (HIPs). Many of the specific activities pursued under the HIPs acronym have been around in some form for decades, such as study abroad, internships, and student-faculty research. It was about ten years ago that, after conferring HIPs at Ten with…

  15. Obtención y evaluación preliminar de un virus canarypox recombinante como candidato a vacuna antirrábica Development and preliminary assessment of a recombinant canarypox virus as an antirabic vaccine candidate

    Directory of Open Access Journals (Sweden)

    Flavia Zanetti

    2012-06-01

    Full Text Available En la Argentina, la rabia está circunscripta a algunas provincias del norte. La disponibilidad de nuevas vacunas que eliminen la manipulación del virus rábico y que permitan el control de la enfermedad es de importancia estratégica nacional y regional. Las vacunas basadas en poxvirus recombinantes se han utilizado con éxito como vacunas antirrábicas a nivel mundial. SI bien estos sistemas no están disponibles comercialmente, la plataforma de obtención de virus canarypox (CNPV recombinantes ya ha sido implementada en nuestro laboratorio. El objetivo de este trabajo fue obtener y evaluar un candidato a vacuna antirrábica basado en CNPV recombinantes que expresan la glicoproteína G (RG del virus rábico (RV. Se construyó un virus recombinante que expresa la secuencia codificante de RG (CNPV-RG. La inoculación de ratones con este virus indujo altos títulos de anticuerpos seroneutralizantes de RV (3,58 y 9,76 Ul/ml después de una o dos inmunizaciones, respectivamente y protegió al 78 % de los animales desafiados intracerebralmente con RV. Además, se determinó que el CNPV-RG posee una potencia relativa de 3,5 Ul/ml. Los resultados obtenidos constituyen la primera etapa en la evaluación del CNPV-RG como candidato a vacuna antirrábica. Se requerirán nuevos ensayos para confirmar su utilidad en especies de interés veterinario.In Argentina, rabies is limited to some northern provinces. Availability of new vaccines abolishing the handling of the rabies virus and allowing disease control has regional and national strategic importance. Vaccines based on recombinant poxviruses have been successfully used as antirabic vaccines worldwide. Although these systems are not commercially available, the platform to obtain recombinant canarypox viruses (CNPV has been previously set up in our laboratory. The aim of this work was the development and evaluation of an antirabic vaccine candidate based on recombinant CNPV expressing the rabies virus (RV

  16. Ten questions about systems biology

    DEFF Research Database (Denmark)

    Joyner, Michael J; Pedersen, Bente K

    2011-01-01

    In this paper we raise 'ten questions' broadly related to 'omics', the term systems biology, and why the new biology has failed to deliver major therapeutic advances for many common diseases, especially diabetes and cardiovascular disease. We argue that a fundamentally narrow and reductionist...... to understand how whole animals adapt to the real world. We argue that a lack of fluency in these concepts is a major stumbling block for what has been narrowly defined as 'systems biology' by some of its leading advocates. We also point out that it is a failure of regulation at multiple levels that causes many...

  17. Ten questions about systems biology

    DEFF Research Database (Denmark)

    Joyner, Michael J; Pedersen, Bente K

    2011-01-01

    to understand how whole animals adapt to the real world. We argue that a lack of fluency in these concepts is a major stumbling block for what has been narrowly defined as 'systems biology' by some of its leading advocates. We also point out that it is a failure of regulation at multiple levels that causes many......In this paper we raise 'ten questions' broadly related to 'omics', the term systems biology, and why the new biology has failed to deliver major therapeutic advances for many common diseases, especially diabetes and cardiovascular disease. We argue that a fundamentally narrow and reductionist...

  18. Chernobyl ten years after

    International Nuclear Information System (INIS)

    1996-01-01

    The accident in the fourth reactor plant in Chernobyl in Ukraine occurred ten years years ago, caused the death of 31 people while the health consequences have turned out to be difficult to assess. This review describes the accident, its consequences and effects to health, studies carried out at the present state as well as the comparison with the other accidents and disaster. (author)

  19. Tens bij bevallingen

    NARCIS (Netherlands)

    Tuin-Nuis, F.D.F.

    2000-01-01

    TENS (Transcutane Electrische Neuro Stimulatie) is een pijnverlichtingsmethode die berust op de Gate Control Theory van Melzack en Wall. Door middel van electrische pulsen via de huid zou de geleiding van nociceptieve signalen (pijnprikkels) worden beïnvloed en zou het lichaam endorfinen aanmaken:

  20. Affordances: Ten Years On

    Science.gov (United States)

    Brown, Jill P.; Stillman, Gloria

    2014-01-01

    Ten years ago the construct, affordance, was rising in prominence in scholarly literature. A proliferation of different uses and meanings was evident. Beginning with its origin in the work of Gibson, we traced its development and use in various scholarly fields. This paper revisits our original question with respect to its utility in mathematics…

  1. The Supersymmetric Top-Ten Lists

    OpenAIRE

    Haber, Howard E.

    1993-01-01

    Ten reasons are given why supersymmetry is the leading candidate for physics beyond the Standard Model. Ultimately, the experimental discovery of supersymmetric particles at future colliders will determine whether supersymmetry is relevant for TeV scale physics. The grand hope of supersymmetry enthusiasts is to connect TeV scale supersymmetry with Planck scale physics. The ten most pressing theoretical problems standing in the way of this goal are briefly described.

  2. Powers of ten

    CERN Document Server

    1979-01-01

    Powers of Ten is a 1977 short documentary film written and directed by Charles Eames and his wife, Ray. The film depicts the relative scale of the Universe in factors of ten (see also logarithmic scale and order of magnitude). The idea for the film appears to have come from the 1957 book Cosmic View by Kees Boeke. The film begins with an aerial image of a man reclining on a blanket; the view is that of one meter across. The viewpoint, accompanied by expository voiceover, then slowly zooms out to a view ten meters across ( or 101 m in standard form), revealing that the man is picnicking in a park with a female companion. The zoom-out continues, to a view of 100 meters (102 m), then 1 kilometer (103 m), and so on, increasing the perspective—the picnic is revealed to be taking place near Soldier Field on Chicago's waterfront—and continuing to zoom out to a field of view of 1024 meters, or the size of the observable universe. The camera then zooms back in to the picnic, and then to views of negative pow...

  3. The ten thousand Kims

    Science.gov (United States)

    Baek, Seung Ki; Minnhagen, Petter; Kim, Beom Jun

    2011-07-01

    In Korean culture, the names of family members are recorded in special family books. This makes it possible to follow the distribution of Korean family names far back in history. It is shown here that these name distributions are well described by a simple null model, the random group formation (RGF) model. This model makes it possible to predict how the name distributions change and these predictions are shown to be borne out. In particular, the RGF model predicts that for married women entering a collection of family books in a certain year, the occurrence of the most common family name 'Kim' should be directly proportional to the total number of married women with the same proportionality constant for all the years. This prediction is also borne out to a high degree. We speculate that it reflects some inherent social stability in the Korean culture. In addition, we obtain an estimate of the total population of the Korean culture down to the year 500 AD, based on the RGF model, and find about ten thousand Kims.

  4. The ten thousand Kims

    International Nuclear Information System (INIS)

    Baek, Seung Ki; Minnhagen, Petter; Kim, Beom Jun

    2011-01-01

    In Korean culture, the names of family members are recorded in special family books. This makes it possible to follow the distribution of Korean family names far back in history. It is shown here that these name distributions are well described by a simple null model, the random group formation (RGF) model. This model makes it possible to predict how the name distributions change and these predictions are shown to be borne out. In particular, the RGF model predicts that for married women entering a collection of family books in a certain year, the occurrence of the most common family name 'Kim' should be directly proportional to the total number of married women with the same proportionality constant for all the years. This prediction is also borne out to a high degree. We speculate that it reflects some inherent social stability in the Korean culture. In addition, we obtain an estimate of the total population of the Korean culture down to the year 500 AD, based on the RGF model, and find about ten thousand Kims.

  5. ABACC ten years applying safeguards

    International Nuclear Information System (INIS)

    Palacios, Elias

    2001-01-01

    The Argentinian-Brazilian Agency for Accounting and Control of nuclear special materials has been in operations for ten years. The rational behind the creation and the work performed by the Agency during the last decade is described. (author)

  6. Ten Lessons from Ten Years PPP Experience in Belgium

    NARCIS (Netherlands)

    Willems, T.; Verhoest, K.; Voets, J.; Coppens, T.; van Dooren, W.; van den Hurk, M.

    2017-01-01

    In 2004 Flanders, the northern region of Belgium launched a range of large public–private partnership (PPP) projects for a total value of 6 billion euros. Ten years later, PPP has become a well-embedded procurement method for long-term public infrastructure projects. This article makes a critical

  7. Daily atmospheric radionuclide observations and health impact estimation before and after the Fukushima-Daiichi nuclear accident: Five-year trends by Canadian monitoring stations - Ten-year trends of atmospheric lead-210 and the correlation to atmospheric mercury in the Canadian Arctic

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Weihua; Chen, Jing; Ungar, Kurt [Radiation Protection Bureau, Health Canada, 775 Brookfield Rd. Ottawa, K1A 1C1 (Canada)

    2014-07-01

    Mercury is a global threat to human and environmental health. Anthropogenic emissions of mercury have been larger than natural emissions since the start of the industrial age about 200 years ago. In the past decades, many studies have focused on monitoring and controlling anthropogenic emissions of mercury and their transport and transformation in the environment. In October 2013, the Minamata Convention on Mercury was formally adopted as international law. The new treaty aims to further cut mercury emissions and releases; it is the first global convention on environment and health. Coal burning for power generation and industrial use is one of the major sources of anthropogenic mercury emissions to the air. However, coal combustion processes produce significant quantities of dust containing not only mercury but also natural radionuclides that are released into the atmosphere. Like the case of mercury, those radionuclides can be transported over long distances, deposited on soil and oceans and accumulated in Arctic biota. Exposure to elevated levels of radiation is a health concern. This study analyses long-term trends of atmospheric lead-210 from Health Canada's radiological monitoring stations in the Arctic. Results are compared with ten-year records of atmospheric mercury reported by Environment Canada. A discussion is given on the correlation of long-range atmospheric transport of lead-210 and mercury from industrial sources, such as coal burning. It is expected that continuous decline of atmospheric mercury in the Arctic, especially with more and more countries signing the Minamata Convention, will result in a deceasing trend of atmospheric lead-210 from industrial sources as well. (authors)

  8. The Top Ten Algorithms in Data Mining

    CERN Document Server

    Wu, Xindong

    2009-01-01

    From classification and clustering to statistical learning, association analysis, and link mining, this book covers the most important topics in data mining research. It presents the ten most influential algorithms used in the data mining community today. Each chapter provides a detailed description of the algorithm, a discussion of available software implementation, advanced topics, and exercises. With a simple data set, examples illustrate how each algorithm works and highlight the overall performance of each algorithm in a real-world application. Featuring contributions from leading researc

  9. Audits reveal ten common environmental problems

    International Nuclear Information System (INIS)

    Buys, M.W.

    1992-01-01

    The old saying that open-quotes an ounce of prevention is worth a pound of cureclose quotes rings particularly true in environmental matters in the 1990s. Environmental problems can potentially lead to expensive fines, costly cleanups, negative public relations, and even criminal sanctions against members of the corporation. A recurring pattern of problems has been noted during the performance of environmental disposition, acquisition, and compliance assessments of many different operators in most of the producing states. The ten most common problems found in oilfield audits are discussed here in an effort to enhance the awareness of operators

  10. A Ten-Year Reflection

    Science.gov (United States)

    Phillip, Cyndi

    2016-01-01

    Five initiatives launched during Cyndi Phillip's term as American Association of School Librarians (AASL) President (2006-2007) continue to have an impact on school librarians ten years later. They include the rewriting of AASL's learning standards, introduction of the SKILLS Act, the presentation of the Crystal Apple Award to Scholastic Library…

  11. Ten per cent more grain

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1967-08-15

    At a low estimate, ten per cent of stored grain is lost every year to insect pests. In this article, based on a lecture given earlier this year in Switzerland, Dr. Harry E. Goresline, Food Radiation Specialist of the Food and Agriculture Organisation, now assisting the Joint FAO/IAEA Division of Atomic Energy in Food and Agriculture, explains how use of radiation can help to prevent losses and the research which has taken place to ensure its safety

  12. Differing patterns of selection and geospatial genetic diversity within two leading Plasmodium vivax candidate vaccine antigens.

    Directory of Open Access Journals (Sweden)

    Christian M Parobek

    2014-04-01

    Full Text Available Although Plasmodium vivax is a leading cause of malaria around the world, only a handful of vivax antigens are being studied for vaccine development. Here, we investigated genetic signatures of selection and geospatial genetic diversity of two leading vivax vaccine antigens--Plasmodium vivax merozoite surface protein 1 (pvmsp-1 and Plasmodium vivax circumsporozoite protein (pvcsp. Using scalable next-generation sequencing, we deep-sequenced amplicons of the 42 kDa region of pvmsp-1 (n = 44 and the complete gene of pvcsp (n = 47 from Cambodian isolates. These sequences were then compared with global parasite populations obtained from GenBank. Using a combination of statistical and phylogenetic methods to assess for selection and population structure, we found strong evidence of balancing selection in the 42 kDa region of pvmsp-1, which varied significantly over the length of the gene, consistent with immune-mediated selection. In pvcsp, the highly variable central repeat region also showed patterns consistent with immune selection, which were lacking outside the repeat. The patterns of selection seen in both genes differed from their P. falciparum orthologs. In addition, we found that, similar to merozoite antigens from P. falciparum malaria, genetic diversity of pvmsp-1 sequences showed no geographic clustering, while the non-merozoite antigen, pvcsp, showed strong geographic clustering. These findings suggest that while immune selection may act on both vivax vaccine candidate antigens, the geographic distribution of genetic variability differs greatly between these two genes. The selective forces driving this diversification could lead to antigen escape and vaccine failure. Better understanding the geographic distribution of genetic variability in vaccine candidate antigens will be key to designing and implementing efficacious vaccines.

  13. Ten Thousand Years of Solitude?

    International Nuclear Information System (INIS)

    Benford, G.; Pasqualetti, M.J.

    1991-03-01

    This report documents the authors work as an expert team advising the US Department of Energy on modes of inadvertent intrusion over the next 10,000 years into the Waste Isolation Pilot Project (WIPP) nuclear waste repository. Credible types of potential future accidental intrusion into the WIPP are estimated as a basis for creating warning markers to prevent inadvertent intrusion. A six-step process is used to structure possible scenarios for such intrusion, and it is concluded that the probability of inadvertent intrusion into the WIPP repository over the next ten thousand years lies between one and twenty-five percent. 3 figs., 5 tabs

  14. Ten Thousand Years of Solitude

    Energy Technology Data Exchange (ETDEWEB)

    Benford, G. (Los Alamos National Lab., NM (USA) California Univ., Irvine, CA (USA). Dept. of Physics); Kirkwood, C.W. (Los Alamos National Lab., NM (USA) Arizona State Univ., Tempe, AZ (USA). Coll. of Business Administration); Harry, O. (Los Alamos National Lab., NM (USA)); Pasqualetti, M.J. (Los Alamos National Lab., NM (USA) Arizona State Univ., Tempe, AZ (USA))

    1991-03-01

    This report documents the authors work as an expert team advising the US Department of Energy on modes of inadvertent intrusion over the next 10,000 years into the Waste Isolation Pilot Project (WIPP) nuclear waste repository. Credible types of potential future accidental intrusion into the WIPP are estimated as a basis for creating warning markers to prevent inadvertent intrusion. A six-step process is used to structure possible scenarios for such intrusion, and it is concluded that the probability of inadvertent intrusion into the WIPP repository over the next ten thousand years lies between one and twenty-five percent. 3 figs., 5 tabs.

  15. Ten questions on nuclear wastes

    International Nuclear Information System (INIS)

    Guillaumont, R.; Bacher, P.

    2004-01-01

    The authors give explanations and answers to ten issues related to nuclear wastes: when a radioactive material becomes a waste, how radioactive wastes are classified and particularly nuclear wastes in France, what are the risks associated with radioactive wastes, whether the present management of radioactive wastes is well controlled in France, which wastes are raising actual problems and what are the solutions, whether amounts and radio-toxicity of wastes can be reduced, whether all long life radionuclides or part of them can be transmuted, whether geologic storage of final wastes is inescapable, whether radioactive material can be warehoused over long durations, and how the information on radioactive waste management is organised

  16. LEADING WITH LEADING INDICATORS

    International Nuclear Information System (INIS)

    PREVETTE, S.S.

    2005-01-01

    This paper documents Fluor Hanford's use of Leading Indicators, management leadership, and statistical methodology in order to improve safe performance of work. By applying these methods, Fluor Hanford achieved a significant reduction in injury rates in 2003 and 2004, and the improvement continues today. The integration of data, leadership, and teamwork pays off with improved safety performance and credibility with the customer. The use of Statistical Process Control, Pareto Charts, and Systems Thinking and their effect on management decisions and employee involvement are discussed. Included are practical examples of choosing leading indicators. A statistically based color coded dashboard presentation system methodology is provided. These tools, management theories and methods, coupled with involved leadership and employee efforts, directly led to significant improvements in worker safety and health, and environmental protection and restoration at one of the nation's largest nuclear cleanup sites

  17. Ten years of nuclear power

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1964-08-15

    Ten years have elapsed since the world's first nuclear power station began to supply electricity in Russia, and this in turn marked the end of a twelve year stage following the first controlled nuclear chain reaction at Chicago. These periods mark major stages in the development of atomic energy from the realm of abstract ideas to that of everyday industrial application. They followed a period of fundamental research and laboratory work, culminating in Enrico Fermi's demonstration of a system whereby the forces of the atom could be brought under control. Then it was necessary to find ways and means of using the chain reaction for practical purposes and on an industrial scale. And after this had been shown in 1954 to be technically possible, it had still to be developed into an economic process. The nuclear power station has proved itself from the technical and engineering standpoint. The third phase of development has been to bring it to the stage of being economically competitive with alternative sources of energy, and it would appear that we are now reaching that goal - though more slowly than had been envisaged ten years ago

  18. Development and evaluation of a recombinant DNA vaccine candidate expressing porcine circovirus 2 structural protein Desenvolvimento e avaliação de um candidato à vacina de DNA recombinante expressando a proteína estrutural do circovírus suíno

    Directory of Open Access Journals (Sweden)

    Abelardo Silva Júnior

    2009-01-01

    Full Text Available Porcine circovirus 2 (PCV2 is generally associated with the porcine circovirosis syndrome, which is considered an important disease of swine and has potentially serious economic impact on the swine industry worldwide. This article describes the construction of a recombinant plasmid expressing the PCV2 structural protein and the evaluation of cellular and humoral immune responses produced by this recombinant vaccine in BALB/c mice. The vaccine candidate was obtained and analyzed in vivo, in an effort to determine the ability to induce a specific immune response in mice. DNA was extracted from a Brazilian PCV2 isolate and the gene coding for Cap protein was amplified by PCR and inserted into an expression plasmid. Groups of BALB/c mice were inoculated intra-muscularly and intradermally in a 15-day interval, with 100 µg and 50 µg of the vaccine construct, respectively. Another group was inoculated intramuscularly with 100 µg of empty plasmid, corresponding to the control group. Seroconversion and cellular response in BALB/c mice were compared and used for vaccine evaluation. Seroconversion was analyzed by ELISA. After a series of 3 immunizations the spleen cells of the immunized animals were used to perform lymphocyte proliferation assays. Seroconversion to PCV2 was detected by ELISA in the animals inoculated with the vaccine construct when compared with control groups. Lymphocyte proliferation assays showed a stronger cell proliferation in the inoculated animals compared with the control group. Thus, the vaccine candidate construct demonstrated to be able to induce both humoral and cellular responses in inoculated mice.O circovírus suíno 2 (PCV2 é geralmente associado à síndrome da circovirose suína, que é considerada uma importante doença de suínos e possui um sério impacto econômico na suinocultura mundial. Este trabalho descreve a construção de um plasmídeo recombinante que expressa a proteína estrutural do PCV2 e a avalia

  19. Ten out of ten for LHC decapole magnets

    CERN Multimedia

    2001-01-01

    CERN's Albert Ijspeert (left) and Avinash Puntambekar of the Indian CAT laboratory with the ten Indian decapole magnets on the test bench. Tests will be carried out by the LHC-MTA group. A batch of 10 superconducting decapole magnets for the LHC has just arrived at CERN from India. These will be used to correct for slight imperfections in the dipole magnets that will steer proton beams around CERN's new accelerator. All magnets have slight imperfections in the fields they produce, and in the LHC dipoles these will be corrected for using sextupoles and decapoles. The sextupoles were the first LHC magnets to be given the production green-light following successful tests of pre-series magnets last year (Bulletin 21/2000, 22 May 2000). Now it is the turn of pre-series decapoles to go on trial at CERN. Of the LHC's 1232 dipole magnets, half will use sextupole correctors only and the other half will use both sextupoles and decapoles. That means that a total of 616 pairs of decapoles are needed. Like the sextupole...

  20. Resolution 1540, ten years on

    International Nuclear Information System (INIS)

    Hautecouverture, Benjamin

    2014-06-01

    Adopted on the 28 April 2004 by the United Nations Security Council under Chapter VII of the UN Charter, Resolution 1540 is a composite tool that was hitherto unprecedented. To recap, States are bound to 'refrain from providing any form of support to non-State actors that attempt to develop, acquire, manufacture, possess, transport, transfer or use nuclear, chemical or biological weapons and their means of delivery' (par. 1), and to prohibit and prevent non-State actors from the aforementioned through 'appropriate and effective' (par. 2,3) legal, judiciary, and administrative means. A Committee was established to which States had to submit a first report outlining the steps 'they have taken or intend to take to implement this resolution' (par. 4). This Committee was initially established for two years and has been regularly renewed since, and its mandate was extended in 2011 for ten years. It is not a surveillance mechanism. Finally, with the aim of remedying difficulties that certain States may experience in implementing the Resolution, 'States in a position to do so' are invited to offer assistance (par. 7). The level of the application of Resolution 1540 was originally based on a delicate three-pronged balance of obligation, good will, and partnership. It is not a matter of designating certain States to the rest of the international community, whilst avoiding that the exercise be limited to the submission of national reports, instead aiming to initiate a dynamic. The wager was a risky one. Ten years on, 90% of UN member States have submitted one or several implementation reports. 170 States and 50 international and regional organisations have taken part in outreach and implementation support events. Whatever quantitative or qualitative conclusions that can be reached, we should continue to promote the Re-solution's universal adoption, and to ensure that the implementation of its provisions is undertaken in a lasting manner, taking account of the national

  1. Leishmaniasis vaccine candidates for development: a global overview.

    Science.gov (United States)

    Khamesipour, Ali; Rafati, Sima; Davoudi, Noushin; Maboudi, Fereidoun; Modabber, Farrokh

    2006-03-01

    A vaccine against different forms of leishmaniasis should be feasible considering the wealth of information on genetics and biology of the parasite, clinical and experimental immunology of leishmaniasis, and the availability of vaccines that can protect experimental animals against challenge with different Leishmania species. However, there is no vaccine against any form of leishmaniasis for general human use. One major factor is the lack of a conceived market for human leishmaniasis vaccines. Hence pharmaceutical industries involved in vaccine development are not interested in investing millions of dollars and a decade that is required for developing a new vaccine. Besides, leishmaniasis is a local/regional problem and not a global one. According to the estimates of the World Health Organization, 90 per cent of visceral leishmaniasis occurs in five countries (Bangladesh, Brazil, India, Nepal and Sudan). Those in need are amongst the poorest people in these countries. It should therefore be the objectives of these countries to develop a vaccine. Fortunately, both Brazil and India have designated the control of visceral leishmaniasis as a top priority for their respective Ministries of Health. The purpose of this review is to present only the vaccines in use and those in development for use in dogs or humans. This is not an exhaustive review of vaccine discovery or the principles of clinical immunology underlying vaccine development.

  2. Immunogenicity of novel mumps vaccine candidates generated by genetic modification.

    Science.gov (United States)

    Xu, Pei; Chen, Zhenhai; Phan, Shannon; Pickar, Adrian; He, Biao

    2014-03-01

    Mumps is a highly contagious human disease, characterized by lateral or bilateral nonsuppurative swelling of the parotid glands and neurological complications that can result in aseptic meningitis or encephalitis. A mumps vaccination program implemented since the 1960s reduced mumps incidence by more than 99% and kept the mumps case numbers as low as hundreds of cases per year in the United States before 2006. However, a large mumps outbreak occurred in vaccinated populations in 2006 and again in 2009 in the United States, raising concerns about the efficacy of the vaccination program. Previously, we have shown that clinical isolate-based recombinant mumps viruses lacking expression of either the V protein (rMuVΔV) or the SH protein (rMuVΔSH) are attenuated in a neurovirulence test using newborn rat brains (P. Xu et al., Virology 417:126-136, 2011, http://dx.doi.org/10.1016/j.virol.2011.05.003; P. Xu et al., J. Virol. 86:1768-1776, 2012, http://dx.doi.org/10.1128/JVI.06019-11) and may be good candidates for vaccine development. In this study, we examined immunity induced by rMuVΔSH and rMuVΔV in mice. Furthermore, we generated recombinant mumps viruses lacking expression of both the V protein and the SH protein (rMuVΔSHΔV). Analysis of rMuVΔSHΔV indicated that it was stable in tissue culture cell lines. Importantly, rMuVΔSHΔV was immunogenic in mice, indicating that it is a promising candidate for mumps vaccine development.

  3. A 52 Kilodalton Protein Vaccine Candidate for Francisella tularensis

    Science.gov (United States)

    2004-12-01

    du vaccin vivant F. tularensis (LVS). Soixante pourcent (60%) des souris vaccindes ont survdcu la dose ltale multiple alors que toutes les souris non...le lysat des cellules de cultures vivantes du vaccin vivant F. tularensis. Plusieurs composants de Francisella tularensis ont dt6 identifids par cet...antiserum. Le s6rum de souris provenant de souris vaccin6es avec F. tularensis non- vivant n’a pas identifid ces composants. A partir de ces prot6ines

  4. Production optimisation of a DNA vaccine candidate against ...

    African Journals Online (AJOL)

    Plasmid DNA (pDNA) vaccines are promising means to prevent and treat infectious diseases, such as leishmaniasis, but immunisation protocols require large amounts of supercoiled plasmid DNA (scpDNA). Although pDNA can be produced at a reasonable cost in bioreactors; this scale of production may not be the best ...

  5. Egg-Independent Influenza Vaccines and Vaccine Candidates

    Directory of Open Access Journals (Sweden)

    Ilaria Manini

    2017-07-01

    Full Text Available Vaccination remains the principal way to control seasonal infections and is the most effective method of reducing influenza-associated morbidity and mortality. Since the 1940s, the main method of producing influenza vaccines has been an egg-based production process. However, in the event of a pandemic, this method has a significant limitation, as the time lag from strain isolation to final dose formulation and validation is six months. Indeed, production in eggs is a relatively slow process and production yields are both unpredictable and highly variable from strain to strain. In particular, if the next influenza pandemic were to arise from an avian influenza virus, and thus reduce the egg-laying hen population, there would be a shortage of embryonated eggs available for vaccine manufacturing. Although the production of egg-derived vaccines will continue, new technological developments have generated a cell-culture-based influenza vaccine and other more recent platforms, such as synthetic influenza vaccines.

  6. Immunological Evaluation and Comparison of Different EV71 Vaccine Candidates

    Directory of Open Access Journals (Sweden)

    Ai-Hsiang Chou

    2012-01-01

    Full Text Available Enterovirus 71 (EV71 and coxsackievirus A16 (CVA16 are major causative agents of hand, foot, and mouth diseases (HFMDs, and EV71 is now recognized as an emerging neurotropic virus in Asia. Effective medications and/or prophylactic vaccines against HFMD are not available. The current results from mouse immunogenicity studies using in-house standardized RD cell virus neutralization assays indicate that (1 VP1 peptide (residues 211–225 formulated with Freund’s adjuvant (CFA/IFA elicited low virus neutralizing antibody response (1/32 titer; (2 recombinant virus-like particles produced from baculovirus formulated with CFA/IFA could elicit good virus neutralization titer (1/160; (3 individual recombinant EV71 antigens (VP1, VP2, and VP3 formulated with CFA/IFA, only VP1 elicited antibody response with 1/128 virus neutralization titer; and (4 the formalin-inactivated EV71 formulated in alum elicited antibodies that cross-neutralized different EV71 genotypes (1/640, but failed to neutralize CVA16. In contrast, rabbits antisera could cross-neutralize strongly against different genotypes of EV71 but weakly against CVA16, with average titers 1/6400 and 1/32, respectively. The VP1 amino acid sequence dissimilarity between CVA16 and EV71 could partially explain why mouse antibodies failed to cross-neutralize CVA16. Therefore, the best formulation for producing cost-effective HFMD vaccine is a combination of formalin-inactivated EV71 and CAV16 virions.

  7. Reverse Vaccinology: An Approach for Identifying Leptospiral Vaccine Candidates

    Directory of Open Access Journals (Sweden)

    Odir A. Dellagostin

    2017-01-01

    Full Text Available Leptospirosis is a major public health problem with an incidence of over one million human cases each year. It is a globally distributed, zoonotic disease and is associated with significant economic losses in farm animals. Leptospirosis is caused by pathogenic Leptospira spp. that can infect a wide range of domestic and wild animals. Given the inability to control the cycle of transmission among animals and humans, there is an urgent demand for a new vaccine. Inactivated whole-cell vaccines (bacterins are routinely used in livestock and domestic animals, however, protection is serovar-restricted and short-term only. To overcome these limitations, efforts have focused on the development of recombinant vaccines, with partial success. Reverse vaccinology (RV has been successfully applied to many infectious diseases. A growing number of leptospiral genome sequences are now available in public databases, providing an opportunity to search for prospective vaccine antigens using RV. Several promising leptospiral antigens were identified using this approach, although only a few have been characterized and evaluated in animal models. In this review, we summarize the use of RV for leptospirosis and discuss the need for potential improvements for the successful development of a new vaccine towards reducing the burden of human and animal leptospirosis.

  8. Compactified vacuum in ten dimensions

    International Nuclear Information System (INIS)

    Wurmser, D.

    1987-01-01

    Since the 1920's, theories which unify gravity with the other fundamental forces have called for more than the four observed dimensions of space-time. According to such a theory, the vacuum consists of flat four-dimensional space-time described by the Minkowski metric M 4 and a compactified space B. The dimensions of B are small, and the space can only be observed at distance scales smaller than the present experimental limit. These theories have had serious difficulties. The equations of gravity severely restrict the possible choices for the space B. The allowed spaces are complicated and difficult to study. The vacuum is furthermore unstable in the sense that a small perturbation causes the compactified dimensions to expand indefinitely. There is an addition a semi-classical argument which implies that the compactified vacuum by annihilated by virtual black holes. It follows that a universe with compactified extra dimensions could not have survived to the present. These results were derived by applying the equations of general relativity to spaces of more than four dimensions. The form of these equations was assumed to be unchanged by an increase in the number of dimensions. The authors illustrate the effect of such terms by considering the example B = S 6 where S 6 is the six-dimensional sphere. Only when the extra terms are included is this choice of the compactified space allowed. He explore the effect of a small perturbation on such a vacuum. The ten-dimensional spherically symmetric potential is examined, and I determine conditions under which the formation of virtual black holes is forbidden. The examples M 4 x S 6 is still plagued by the semi-classical instability, but this result does not hold in general. The requirement that virtual black holes be forbidden provides a test for any theory which predicts a compactified vacuum

  9. Radiology now. The ten day rule - principles and practice

    Energy Technology Data Exchange (ETDEWEB)

    Carmichael, J H.E. [Broadgreen Hospital, Liverpool (UK); Warrick, C K

    1978-11-01

    The ten day rule recommends that non-urgent diagnostic radiography of the abdomen in women of child-bearing capacity should be confined to the pre-ovulatory phase of the menstrual cycle. Arguments for and against this rule are reviewed. The attitudes and organization of radiographic practice in the UK differ from those in the USA. Assessment of the evidence for the hazards involved leads to the conclusion that the continued application of the ten day rule should be strongly recommended as an essential part of good radiological and radiographic practice.

  10. Lead poisoning

    Science.gov (United States)

    ... drinking water in homes containing pipes that were connected with lead solder . Although new building codes require ... lead in their bodies when they put lead objects in their mouths, especially if they swallow those ...

  11. Lead Poisoning

    Science.gov (United States)

    Lead is a metal that occurs naturally in the earth's crust. Lead can be found in all parts of our ... from human activities such as mining and manufacturing. Lead used to be in paint; older houses may ...

  12. Ten years of effective multilateralism?

    International Nuclear Information System (INIS)

    Hautecouverture, Benjamin

    2013-12-01

    successes of multilateralism and international law provide security assurances or do they mask the flaws of an insufficiently intrusive system? While the U.S. signaled their defiance under the guidance of John Bolton, European thinking settled on a conclusion with the air of a slogan: yes to multilateralism, providing it is effective. This was to be the cornerstone of the policies to undertake and the instruments to implement to forge a global role for the Union. Its originality is based simultaneously in realism and in a refusal to resort to force as the foremost means of action on the international stage. Another way of defining the 2003 Strategy is a skillful compromise between differing positions to banish the Iraqi 'cacophony' as quickly as possible. Ten years on, it is now time for 'impact assessments' and other 'scorecards' of public policies. In the midst of the Eurozone economic crisis, evaluating a strategy of 'effective multilateralism' is not easy. The Union's bi-annual reports on its implementation have recently begun to try to provide a quantitative analysis that is not entirely convincing (for instance, the number of ratifications of such-and-such an instrument with regard to the budget allocated by the EU to facilitate its universalization, over such-and-such a period). Fundamentally, the 2003 Strategy is essentially beyond this kind of analysis even if it can prove useful. The strength of the European approach consists in establishing a long-term willingness to maintain and strengthen collective security tools approved by the greatest possible number of States. Its weakness is to occasionally confront a strategic reality that is as contradictory as it is stubborn. Effective multilateralism is linked to voluntarism and vows. (author)

  13. Ten steps to successful software process improvement

    Science.gov (United States)

    Kandt, R. K.

    2003-01-01

    This paper identifies ten steps for managing change that address organizational and cultural issues. Four of these steps are critical, that if not done, will almost guarantee failure. This ten-step program emphasizes the alignment of business goals, change process goals, and the work performed by the employees of an organization.

  14. Clinical experience with TENS and TENS combined with nitrous oxide-oxygen. Report of 371 patients.

    OpenAIRE

    Quarnstrom, F. C.; Milgrom, P.

    1989-01-01

    Transcutaneous electrical nerve stimulation (TENS) alone or TENS combined with nitrous oxide-oxygen (N2O) was administered for restorative dentistry without local anesthesia to 371 adult patients. A total of 55% of TENS alone and 84% of TENS/N2O visits were rated successful. A total of 53% of TENS alone and 82% of TENS/N2O patients reported slight or no pain. In multivariable analyses, pain reports were related to the anesthesia technique and patient fear and unrelated to sex, race, age, toot...

  15. Lead poisoning

    Energy Technology Data Exchange (ETDEWEB)

    Beijers, J A

    1952-01-01

    Three cases of acute lead poisoning of cattle herds via ingestion are reported, and reference is made to several other incidents of lead in both humans and animals. The quantity of lead which was found in the livers of the dead cows varied from 6.5 to 19 mg/kg, while 1160 mg/kg of lead in the liver was found for a young cow which was poisoned experimentally with 5 gms of lead acetate per day; hence, there appears to be great variability in the amounts deposited that can lead to intoxication and death. No evidence was found for a lead seam around the teeth, prophyrinuria, or basophil granules in the erythrocytes during acute or chronic lead poisoning of cattle or horses examined. Reference is made to attempts of finding the boundary line between increased lead absorption and lead intoxication in humans, and an examination of 60 laborers in an offset-printing office containing a great deal of inhalable lead (0.16 to 1.9 mg/cu m air) is reviewed. Physical deviation, basophylic granulation of erythrocytes, increased lead content of the urine, and porphyrinuria only indicate an increased absorption of lead; the use of the term intoxication is justified if, in addition, there are complaints of lack of appetite, constipation, fatigue, abdominal pain, and emaciation.

  16. Lead Toxicity

    Science.gov (United States)

    ... o Do not use glazed ceramics, home remedies, cosmetics, or leaded-crystal glassware unless you know that they are lead safe. o If you live near an industry, mine, or waste site that may have contaminated ...

  17. Relational Leading

    DEFF Research Database (Denmark)

    Larsen, Mette Vinther; Rasmussen, Jørgen Gulddahl

    2015-01-01

    This first chapter presents the exploratory and curious approach to leading as relational processes – an approach that pervades the entire book. We explore leading from a perspective that emphasises the unpredictable challenges and triviality of everyday life, which we consider an interesting......, relevant and realistic way to examine leading. The chapter brings up a number of concepts and contexts as formulated by researchers within the field, and in this way seeks to construct a first understanding of relational leading....

  18. Lead Test

    Science.gov (United States)

    ... to do renovation and repair projects using lead-safe work practices to avoid creating more lead dust or ... in a dangerous area? Yes. If you are working in a potentially harmful environment with exposure to lead dust or fumes: Wash ...

  19. ALGORITHMS FOR TETRAHEDRAL NETWORK (TEN) GENERATION

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The Tetrahedral Network(TEN) is a powerful 3-D vector structure in GIS, which has a lot of advantages such as simple structure, fast topological relation processing and rapid visualization. The difficulty of TEN application is automatic creating data structure. Al though a raster algorithm has been introduced by some authors, the problems in accuracy, memory requirement, speed and integrity are still existent. In this paper, the raster algorithm is completed and a vector algorithm is presented after a 3-D data model and structure of TEN have been introducted. Finally, experiment, conclusion and future work are discussed.

  20. Vadose Zone Journal: The first ten years

    NARCIS (Netherlands)

    Vrugt, J.A.; Or, D.; Young, M.H.

    2013-01-01

    Celebrating ten years of publication, the authors introduce a special section commemorating the anniversary of Vadose Zone Journal and reviewing the journal’s role in an evolving understanding of vadose zone science.

  1. Ten key issues in modern flow chemistry.

    Science.gov (United States)

    Wegner, Jens; Ceylan, Sascha; Kirschning, Andreas

    2011-04-28

    Ten essentials of synthesis in the flow mode, a new enabling technology in organic chemistry, are highlighted as flashlighted providing an insight into current and future issues and developments in this field. © The Royal Society of Chemistry 2011

  2. Ten into four won't go

    International Nuclear Information System (INIS)

    Freedman, D.Z.; West, P.C.

    1989-01-01

    It is shown that nontrivial spontaneous compactification of ten-dimensional N = 1 supergravity with or without Yang-Mills matter is not possible unless maximal symmetry (i.e. Lorentz invariance) is violated in the four-dimensional spacetime

  3. Leading Democratically

    Science.gov (United States)

    Brookfield, Stephen

    2010-01-01

    Democracy is the most venerated of American ideas, the one for which wars are fought and people die. So most people would probably agree that leaders should be able to lead well in a democratic society. Yet, genuinely democratic leadership is a relative rarity. Leading democratically means viewing leadership as a function or process, rather than…

  4. Leading change.

    Science.gov (United States)

    2017-02-27

    In response to feedback from nursing, midwifery and other care staff who wanted to understand better how the Leading Change, Adding Value framework applies to them, NHS England has updated its webpage to include practice examples.

  5. ANALGETSKI UCINAK TRANSAKUTNE ELEKTRICNE NERVNE STIMULACIJE (TENS)

    OpenAIRE

    ĆURKOVIĆ, B.

    1984-01-01

    Transkutana električna nervna stimulacija. (TENS) danas je široko prihvaćen terapijski postupak za suzbijanje boli. Način njezina djelovanja nije još jasno definiran, premda se većina autora priklanja centralnom mehranizmu smanjenja boli. Rezultati, u literaturi, variraju od nesignifikantno boljeg učinka od placeba do 95°/o dobrog analgetskog djelovanja. U Zavodu za reumatske bolesti i rehabilitaciju Kliničkog bolničkog centra, Zagreb, evaluiran je učinak TENS-a u bolesnika s križ...

  6. Ecotoxicology: Lead

    Science.gov (United States)

    Scheuhammer, A.M.; Beyer, W.N.; Schmitt, C.J.; Jorgensen, Sven Erik; Fath, Brian D.

    2008-01-01

    Lead (Pb) is a naturally occurring metallic element; trace concentrations are found in all environmental media and in all living things. However, certain human activities, especially base metal mining and smelting; combustion of leaded gasoline; the use of Pb in hunting, target shooting, and recreational angling; the use of Pb-based paints; and the uncontrolled disposal of Pb-containing products such as old vehicle batteries and electronic devices have resulted in increased environmental levels of Pb, and have created risks for Pb exposure and toxicity in invertebrates, fish, and wildlife in some ecosystems.

  7. Ten recommendations for software engineering in research.

    Science.gov (United States)

    Hastings, Janna; Haug, Kenneth; Steinbeck, Christoph

    2014-01-01

    Research in the context of data-driven science requires a backbone of well-written software, but scientific researchers are typically not trained at length in software engineering, the principles for creating better software products. To address this gap, in particular for young researchers new to programming, we give ten recommendations to ensure the usability, sustainability and practicality of research software.

  8. Kaluza-Klein supergravity in ten dimensions

    International Nuclear Information System (INIS)

    Huq, M.; Namazie, M.A.

    1983-11-01

    We construct a massive version of N=2 supergravity in ten dimensions by compactification of the eleven dimensional, N=1 theory. This theory describes the usual N=2 massless super-multiplet, in addition to which there is an infinite tower of massive, charged N=2 supermultiplets. (author)

  9. Top-Ten IT Issues: 2009

    Science.gov (United States)

    Agee, Anne Scrivener; Yang, Catherine

    2009-01-01

    This article presents the top-ten IT-related issues in terms of strategic importance to the institution, as revealed by the tenth annual EDUCAUSE Current Issues Survey. These IT-related issues include: (1) Funding IT; (2) Administrative/ERP Information Systems; (3) Security; (4) Infrastructure/Cyberinfrastructure; (5) Teaching and Learning with…

  10. Ten years after the Jali Commission

    African Journals Online (AJOL)

    Ten years have lapsed since the Jali Commission's final report became publicly available, and it is therefore an .... as the 'core business' of the department. This was seen as .... the 2009/10–2013/14 DCS Strategic Plan did the department ...

  11. Czech, Slovak science ten years after split

    CERN Multimedia

    2003-01-01

    Ten years after the split of Czechoslovakia Czech and Slovak science are facing the same difficulties: shortage of money for research, poor salaries, obsolete equipment and brain drain, especially of the young, according to a feature in the Daily Lidove Noviny (1 page).

  12. Ten themes of viscous liquid dynamics

    DEFF Research Database (Denmark)

    Dyre, J. C.

    2007-01-01

    Ten ‘themes' of viscous liquid physics are discussed with a focus on how they point to a general description of equilibrium viscous liquid dynamics (i.e., fluctuations) at a given temperature. This description is based on standard time-dependent Ginzburg-Landau equations for the density fields...

  13. Top Ten Concerns for Trustees in 1988.

    Science.gov (United States)

    Meyerson, Joel W.

    1988-01-01

    Ten issues most likely to influence institutions this year include tuition policy and financing, capital renewal and replacement, charitable giving, scientific equipment and laboratories, endowment management and spending policy, research funding, corporate contributions, minority enrollment and hiring, debt financing and debt capacity, and cost…

  14. Giant multipole resonances: perspectives after ten years

    International Nuclear Information System (INIS)

    Bertrand, F.E.

    1980-01-01

    Nearly ten years ago evidence was published for the first of the so-called giant multipole resonances, the giant quadrupole resonance. During the ensuing years research in this field has spread to many nuclear physics laboratories throughout the world. The present status of electric giant multipole resonances is reviewed. 24 figures, 1 table

  15. VINKA, ten years on. Main scientific results

    International Nuclear Information System (INIS)

    1979-01-01

    The VINKA facility in the TRITON swimming-pool reactor at Fontenay-aux-Roses allows the irradiation of solids at low temperatures in order to study crystalline defects. After ten years of operation the main scientific results obtained in the fields of creep and growth (chapter I), point defects (chapter II), amorphisation (chapter III) and dechanneling of particles (chapter IV) are summarised [fr

  16. Leading men

    DEFF Research Database (Denmark)

    Bekker-Nielsen, Tønnes

    2016-01-01

    Through a systematic comparison of c. 50 careers leading to the koinarchate or high priesthood of Asia, Bithynia, Galatia, Lycia, Macedonia and coastal Pontus, as described in funeral or honorary inscriptions of individual koinarchs, it is possible to identify common denominators but also disting...

  17. Photocatalyzed removal of lead ion from lead-chelator solution

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Young Hyun; Na, Jung Won; Sung, Ki Woung [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1994-07-01

    The present study was undertaken to examine the influence of such chelating agents on the ease and speed of photocatalyzed metal removal and deposition. With excess EDTA, the free EDTA competes with Pb for oxidation, and at a ten fold excess, no lead oxidation (hence removal) occurs. With insufficient EDTA, the corresponding initial concentration of Pb-EDTA is decreased; after its destruction, the remaining Pb{sup 2+} is removed more slowly, at rates found with lead nitrate solution. The net result is that the maximum rate of lead deposition occurs at the stoichiometric ratio of 1:1 EDTA : Pb{sup 2+}.

  18. Who Leads China's Leading Universities?

    Science.gov (United States)

    Huang, Futao

    2017-01-01

    This study attempts to identify the major characteristics of two different groups of institutional leaders in China's leading universities. The study begins with a review of relevant literature and theory. Then, there is a brief introduction to the selection of party secretaries, deputy secretaries, presidents and vice presidents in leading…

  19. Fulfilling the atomic promise: Ten years history gives pointers for the future

    International Nuclear Information System (INIS)

    1967-01-01

    Ten years is a short period in human history, and a short period in the life of an international organization. Nevertheless the ten years now completed by the International Atomic Energy Agency has seen much work accomplished and has brought greater realization than ever before of the promise held out by the atom for peaceful benefits leading to the promotion of peace, health and prosperity throughout the world

  20. Data processing potential ten years from now

    International Nuclear Information System (INIS)

    Zajde, C.

    1982-01-01

    What today is still experimental will tomorrow be routine. Use of emission tomography, automatic determination of regions of interest, generalisation of Fourrier phase and amplitude analysis, parametric images these will become routine medical protocols. The next ten years will see a saturation in the field of research and a stabilisation in system development. Equipment renewal will be seen from the same angle as in the automotive industry - more for reasons of wear and tear than for reasons of technical advancement

  1. School Psychologists' Job Satisfaction: Ten Years Later

    OpenAIRE

    Worrell, Travis G.

    2004-01-01

    School Psychologistsâ Job Satisfaction: Ten Years Later (ABSTRACT) This study was designed to replicate nationwide surveys completed in 1982 and 1992. The purpose was to examine and describe the levels of job satisfaction and the relationship between the variables in a national sample of school psychologists belonging to the National Association of School Psychologists (NASP). The sample for this study consisted of respondents who reported being full-time school practitioners. ...

  2. Simplification of the helical TEN2 laser

    Science.gov (United States)

    Krahn, K.-H.

    1980-04-01

    The observation that the helical TEN2 laser can effectively be simplified by giving up the use of decoupling elements as well as by abolishing the segmentation of the electrode structure is examined. Although, as a consequence of this simplification, the operating pressure range was slightly decreased, the output power could be improved by roughly 30%, a result which is attributed to the new electrode geometry exhibiting lower inductance and lower damping losses.

  3. Modification of the 'ten-day rule'

    International Nuclear Information System (INIS)

    Klempfner, G.

    1985-01-01

    In a 1964 decision the National Health and Medical Research Council recommended that radiological examinations of the lower abdomen and pelvis of women of childbearing age should be confined to the 10-day interval following the onset of menstruation. Recent evidence suggests that the first four weeks from the first day of the last menstrual period is not a critically radiosensitive period and consequently strict adherence to the ten-day rule is no longer indicated

  4. Antimicrobial activity of Verbascum macrurum Ten. (Scrophulariaceae).

    Science.gov (United States)

    Guarino, C

    2002-01-01

    The Author presents the results regarding the antibacterial action of extracts of Verbascum macrurum Ten.. The leaves of this species, gathered on the slopes of Mt. Matese, were ground and four extracts were made as follows: with dicholoromethane, ethonol and water (70:30 v/v), water and methanol. The antibacterial activity of each of the samples was tested and it is demonstrated that the extract with the ethanol/water was the most activity one.

  5. EEG Correlates of Ten Positive Emotions.

    Science.gov (United States)

    Hu, Xin; Yu, Jianwen; Song, Mengdi; Yu, Chun; Wang, Fei; Sun, Pei; Wang, Daifa; Zhang, Dan

    2017-01-01

    Compared with the well documented neurophysiological findings on negative emotions, much less is known about positive emotions. In the present study, we explored the EEG correlates of ten different positive emotions (joy, gratitude, serenity, interest, hope, pride, amusement, inspiration, awe, and love). A group of 20 participants were invited to watch 30 short film clips with their EEGs simultaneously recorded. Distinct topographical patterns for different positive emotions were found for the correlation coefficients between the subjective ratings on the ten positive emotions per film clip and the corresponding EEG spectral powers in different frequency bands. Based on the similarities of the participants' ratings on the ten positive emotions, these emotions were further clustered into three representative clusters, as 'encouragement' for awe, gratitude, hope, inspiration, pride, 'playfulness' for amusement, joy, interest, and 'harmony' for love, serenity. Using the EEG spectral powers as features, both the binary classification on the higher and lower ratings on these positive emotions and the binary classification between the three positive emotion clusters, achieved accuracies of approximately 80% and above. To our knowledge, our study provides the first piece of evidence on the EEG correlates of different positive emotions.

  6. Ten steps to successful poster presentation.

    Science.gov (United States)

    Hardicre, Jayne; Devitt, Patric; Coad, Jane

    Receiving a letter confirming acceptance for you to present a poster at a conference can evoke mixed emotions. Joy, panic, fear and dread are among the many possible emotions and this is not exclusive to first time presenters. Developing an effective poster presentation is a skill that you can learn and can provide a rewarding way to present your work in a manner less intimidating than oral presentation (Shelledy, 2004). The key to successful poster presentation is meticulous, timely, well informed preparation. This article outlines ten steps to help guide you through the process to maximize your success.

  7. Novitäten im Breslauer Stadttheater

    OpenAIRE

    Zduniak, Maria

    2017-01-01

    Am Anfang des 20. Jahrhunderts zählte das Breslauer Stadttheater, obwohl mit nur einer kleinen Orchester-Besetzung ausgestattet, zu den bemerkenswerten europäischen Opernbühnen. Es war aufgeschlossen für musikalische Novitäten. Als Beweis dafür sind u.a. die Breslauer Premieren Salome (1906) von Richard Strauss, L\\'Orfeo (1913) von Claudio Monteverdi und die Uraufführung der Oper Eros und Psyche (1917) von Ludomir Różycki zu nennen.

  8. Ten financial management principles for survival.

    Science.gov (United States)

    Cleverley, W O

    1988-03-01

    Financial insolvency is the primary cause of hospital failure. Managers may analyze a hospital's financial statements to anticipate and prevent fiscal problems. Ten measures of fiscal status may be used to evaluate the following: operating profitability nonoperating income equity growth liquidity debt capacity age of facilities revenue generation replacement funds receivables survivability Based on data from the Financial Analysis Service, Catholic hospitals are doing better than other U.S. hospitals in some areas of financial preparedness. In most areas, however, all hospitals suffer by comparison with manufacturers. The 10 principles of solvent and successful operations can help hospitals improve financial resiliency.

  9. Ten essential skills for electrical engineers

    CERN Document Server

    Dorr, Barry

    2014-01-01

    Engineers know that, as in any other discipline, getting a good job requires practical, up-to-date skills. An engineering degree provides a broad set of fundamentals. Ten Essential Skills applies those fundamentals to practical tasks required by employers. Written in a user-friendly, no-nonsense format, the book reviews practical skills using the latest tools and techniques, and features a companion website with interview practice problems and advanced material for readers wishing to pursue additional skills. With this book, aspiring and current engineers may approach job interviews confident

  10. Optical spectroscopy of ten extragalactic radiosources

    International Nuclear Information System (INIS)

    Rawlings, S.; Riley, J.M.; Saunders, R.

    1989-01-01

    We present optical spectroscopy of ten objects associated with extra-galactic radiosources, using the University of Hawaii 2.2-m telescope. Redshifts are measured for four radiogalaxies (B20217 + 36A + B, 3C73, 0648 + 19A, 0648 + 19B) and for a galaxy which is probably associated with a double radio-source with highly unusual properties (0951 + 37); existing redshifts are confirmed for two radiogalaxies (4C39.04, 4C40.08); and a tentative redshift of z=2.87 measured for the quasar 3C82. (author)

  11. Ten new withanolides from Physalis peruviana.

    Science.gov (United States)

    Fang, Sheng-Tao; Liu, Ji-Kai; Li, Bo

    2012-01-01

    Ten new withanolides, including four perulactone-type withanolides, perulactones E-H (1-4), three 28-hydroxy-withanolides, withaperuvins I-K (5-7), and three other withanolides, withaperuvins L-N (8-10), together with six known compounds (11-16) were isolated from the aerial parts of Physalis peruviana. The structures of these compounds were elucidated on the basis of extensive spectroscopic analyses (1D and 2D NMR, IR, HR-MS) and chemical methods. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. TENS (transcutaneous electrical nerve stimulation) for labour pain.

    Science.gov (United States)

    Francis, Richard

    2012-05-01

    Because TENS is applied inconsistently and not always in line with optimal TENS application theory, this may explain why TENS for labour pain appears to be effective in some individuals and not in others. This article reviews TENS theory, advises upon optimal TENS application for labour pain and discusses some of the limitations of TENS research on labour pain. TENS application for labour pain may include TENS applied to either side of the lower spine, set to 200 mus pulse duration and 100 pulses per second. As pain increases, TENS intensity should be increased and as pain decreases, TENS intensity should be reduced to maintain a strong but pain free intensity of stimulation. This application may particularly reduce back pain during labour.

  13. Ten principles of good interdisciplinary team work.

    Science.gov (United States)

    Nancarrow, Susan A; Booth, Andrew; Ariss, Steven; Smith, Tony; Enderby, Pam; Roots, Alison

    2013-05-10

    Interdisciplinary team work is increasingly prevalent, supported by policies and practices that bring care closer to the patient and challenge traditional professional boundaries. To date, there has been a great deal of emphasis on the processes of team work, and in some cases, outcomes. This study draws on two sources of knowledge to identify the attributes of a good interdisciplinary team; a published systematic review of the literature on interdisciplinary team work, and the perceptions of over 253 staff from 11 community rehabilitation and intermediate care teams in the UK. These data sources were merged using qualitative content analysis to arrive at a framework that identifies characteristics and proposes ten competencies that support effective interdisciplinary team work. Ten characteristics underpinning effective interdisciplinary team work were identified: positive leadership and management attributes; communication strategies and structures; personal rewards, training and development; appropriate resources and procedures; appropriate skill mix; supportive team climate; individual characteristics that support interdisciplinary team work; clarity of vision; quality and outcomes of care; and respecting and understanding roles. We propose competency statements that an effective interdisciplinary team functioning at a high level should demonstrate.

  14. Ten years of the Spanish Virtual Observatory

    Science.gov (United States)

    Solano, E.

    2015-05-01

    The main objective of the Virtual Observatory (VO) is to guarantee an easy and efficient access and analysis of the information hosted in astronomical archives. The Spanish Virtual Observatory (SVO) is a project that was born in 2004 with the goal of promoting and coordinating the VO-related activities at national level. SVO is also the national contact point for the international VO initiatives, in particular the International Virtual Observatory Alliance (IVOA) and the Euro-VO project. The project, led by Centro de Astrobiología (INTA-CSIC), is structured around four major topics: a) VO compliance of astronomical archives, b) VO-science, c) VO- and data mining-tools, and d) Education and outreach. In this paper I will describe the most important results obtained by the Spanish Virtual Observatory in its first ten years of life as well as the future lines of work.

  15. Women in Astronomy II: Ten Years After

    Science.gov (United States)

    Sargent, Wallace

    2004-01-01

    The meeting "Women in Astronomy II: Ten Years After" took place at the California Institute of Technology in Pasadena, CA June 27-28, 2003. The meeting was sponsored by the Committee on the Status of Women of the American Astronomical Society and was attended by about 155 participants. The purpose of the meeting was: "To review the current status of women in astronomy, understand their work environment, assess development since the 1992 Baltimore conference, and recommend future actions that will improve the environment for all astronomers." A description of the meeting and its background can be found at http://www.aas.org/%7Ecswa/WIA2003.html. The proceedings are being edited by Profs. Meg Urry (Yale University) and Ran Bagenal (University of Colorado). The principal outcome of WIAII was a series of recommendations, "The Pasadena Recommendations", which have been approved by the AAS Council and which can be found at http://www.aas.org/%7Ecswa/.

  16. Spacelab - Ten years of international cooperation

    Science.gov (United States)

    Bignier, M.; Harrington, J. C.; Sander, M. J.

    1983-01-01

    The history, current status, and future plans of the Spacelab program are reviewed, with a focus on the cooperative relationship between ESA and NASA. The initial decision to undertake the program and the three agreements signed to begin its implementation are examined, and the division of responsibilities and financial contributions is discussed insofar as it affected the management structure. Consideration is given to the major facilities, the 50-mission operational cycle, communications, the currently scheduled activities (through 1985), the prospective later uses, and the ten dedicated discipline laboratories. The importance of continuous mutual support during the planning and development phases is stressed. The program so far is considered a success, in terms of the goals set by the participants and in terms of the resolution of the problems inherent in international technological endeavors.

  17. Ten years of x-ray holography

    International Nuclear Information System (INIS)

    Faigel, G.; Bortel, G.; Tegze, M.; Fadley, C.S.; Simionovici, A.S.

    2007-01-01

    With the appearance of nano-science the role of local methods has become more and more important. Hard x-ray holography based on the inside reference point concept is a local probe of the atomic order in solids. It gives the 3D real space image of atoms without the phase ambiguity inherent to diffraction methods. In this paper a brief description of the basics of hard x-ray holography is given. The last ten years' experimental and evaluation-related developments are reviewed. We also introduce different variants of the method, such as Bremsstrahlung and gamma ray holography (GRH). The power of the method is illustrated by examples. We outline new directions and future possibilities. (authors)

  18. Successful replantation in ten-digit amputation.

    Science.gov (United States)

    Kantarci, Umit; Cepel, Selim; Buldu, Halil

    2010-01-01

    Amputations involving ten digits are very rare because of different lengths of the digits. A 34-year-old man working in a printing house presented one hour after guillotine amputation involving all ten digits. Surgery was initiated 80 minutes after admission and took seven hours. Under axillary anesthesia, the operation was performed by two teams each consisting of two microsurgeons and two assistants. Replantation was completed without the use of any skin graft or flap. Fingertip examination showed poor arterial circulation in the second, third, and fourth digits of the left hand after 24 hours of replantation and surgical exploration was performed, during which anastomosis of the ulnar digital artery of the second digit was re-established and a Y-shaped vein graft was placed at the level of the third web to restore revascularization of the third and fourth digits. However, these interventions did not prevent the development of necrosis in the distal segment of the fourth digit which resulted in dry gangrene that required amputation. After 38 months of replantation, radiographic examination showed complete union in all fingers without malunion or damage to the joint surface and about 8 degrees of medial angulation in the proximal phalanx of the fourth digit of the right hand. The patient did not have difficulty in performing daily activities and had a considerably good pinching. Losses of active range of motion of the metacarpophalangeal and interphalangeal joints were within the rage of 10 to 30 degrees in both hands. In the assessment of sensation, static and dynamic two-point discrimination test results were 6.1 mm and 4.0 mm, respectively.

  19. The HADES project - ten years of civil engineering practice in a plastic clay formation

    International Nuclear Information System (INIS)

    De Bruyn, D.J.; Neerdael, B.A.

    1991-01-01

    Various civil engineering works and underground experiments have been performed during the last ten years in Belgium to assess the technical feasibility of building a repository for high level waste (HLW) disposal in a plastic clay formation; they lead to the conclusion that the construction of tunnels for this purpose may now be considered as technically and economically feasible. (author)

  20. Humanities and Social Sciences Books of Ten National Disciplinary Associations, 2000-2009

    Science.gov (United States)

    Wiberley, Stephen E., Jr.

    2016-01-01

    Books are the most important medium of communication in the humanities, a major medium in the social sciences, and a central component of academic library collections. This study examined humanities and social sciences books that won prizes from ten leading United States disciplinary associations between 2000 and 2009. The study extends earlier…

  1. MMM Fuchs HUIDIGE REGSONTWIKKELING TEN AANSIEN VAN ...

    African Journals Online (AJOL)

    fuchsmm

    consider the impact of the recent global economic downturn (the so-called 'credit crunch'), brought on by a subprime mortgage crisis and leading to an ... have devastating effects. Therefore, responsible lending and borrowing is crucial .... It permits court proceedings if 10 business days have passed 'since the credit provider ...

  2. Ten years for the public Web

    CERN Multimedia

    2003-01-01

    Ten years ago, CERN issued a statement declaring that a little known piece of software called the World Wide Web was in the public domain. Nowadays, the Web is an indispensable part of modern communications. The idea for the Web goes back to March 1989 when CERN Computer scientist Tim Berners-Lee wrote a proposal for a 'Distributed Information Management System' for the high-energy physics community. The Web was originaly conceived and developed to meet the demand for information sharing between scientists working all over the world. There were many obstacles in the 1980s to the effective exchange of information. There was, for example a great variety of computer and network systems, with hardly any common features. The main purpose of the web was to allow scientists to access information from any source in a consistent and simple way. By Christmas 1990, Berners-Lee's idea had become the World Wide Web, with its first server and browser running at CERN. Through 1991, the Web spread to other particle physics ...

  3. Comparative Genomics of Ten Solanaceous Plastomes

    Directory of Open Access Journals (Sweden)

    Harpreet Kaur

    2014-01-01

    Full Text Available Availability of complete plastid genomes of ten solanaceous species, Atropa belladonna, Capsicum annuum, Datura stramonium, Nicotiana sylvestris, Nicotiana tabacum, Nicotiana tomentosiformis, Nicotiana undulata, Solanum bulbocastanum, Solanum lycopersicum, and Solanum tuberosum provided us with an opportunity to conduct their in silico comparative analysis in depth. The size of complete chloroplast genomes and LSC and SSC regions of three species of Solanum is comparatively smaller than that of any other species studied till date (exception: SSC region of A. belladonna. AT content of coding regions was found to be less than noncoding regions. A duplicate copy of trnH gene in C. annuum and two alternative tRNA genes for proline in D. stramonium were observed for the first time in this analysis. Further, homology search revealed the presence of rps19 pseudogene and infA genes in A. belladonna and D. stramonium, a region identical to rps19 pseudogene in C. annum and orthologues of sprA gene in another six species. Among the eighteen intron-containing genes, 3 genes have two introns and 15 genes have one intron. The longest insertion was found in accD gene in C. annuum. Phylogenetic analysis using concatenated protein coding sequences gave two clades, one for Nicotiana species and another for Solanum, Capsicum, Atropa, and Datura.

  4. Ten steps to a cooler planet

    International Nuclear Information System (INIS)

    2001-01-01

    The overwhelming scientific consensus is that human activities, especially activities that produce greenhouse gases are accumulating in the atmosphere and are changing the intricate balance that has sustained life on earth for millions of years. The estimate is that in Canada about 35 per cent of the greenhouse gases released to the atmosphere come from personal sources. This booklet provides brief account of the ways that individuals contribute to green house gas emissions and provides some helpful hints on how to reduce this personal contribution to the climate change problem. The ten ways suggested are: (1) use public transport as much as possible, (2) buy smaller cars , (3) use the train instead of flying, make fewer long distance trips by combining business and vacation travel, (4) set the thermostat one degree lower and save 525 kg of carbon dioxide per year, (5) avoid overhousing by choosing a smaller house and by making every square foot count, (6) buy energy efficient appliances, (7) reduce water heater's energy consumption by insulating it, (8) reduce meat intake and buy locally produced food in season, (9) minimize garbage production by reusing and recycling, (10) use green power wherever available and contribute to the development of renewable energy sources

  5. Ten tips for authors of scientific articles.

    Science.gov (United States)

    Hong, Sung-Tae

    2014-08-01

    Writing a good quality scientific article takes experience and skill. I propose 'Ten Tips' that may help to improve the quality of manuscripts for scholarly journals. It is advisable to draft first version of manuscript and revise it repeatedly for consistency and accuracy of the writing. During the drafting and revising the following tips can be considered: 1) focus on design to have proper content, conclusion, points compliant with scope of the target journal, appropriate authors and contributors list, and relevant references from widely visible sources; 2) format the manuscript in accordance with instructions to authors of the target journal; 3) ensure consistency and logical flow of ideas and scientific facts; 4) provide scientific confidence; 5) make your story interesting for your readers; 6) write up short, simple and attractive sentences; 7) bear in mind that properly composed and reflective titles increase chances of attracting more readers; 8) do not forget that well-structured and readable abstracts improve citability of your publications; 9) when revising adhere to the rule of 'First and Last' - open your text with topic paragraph and close it with resolution paragraph; 10) use connecting words linking sentences within a paragraph by repeating relevant keywords.

  6. Choledochal cysts: our ten year experience.

    LENUS (Irish Health Repository)

    Cianci, F

    2012-04-01

    We present our experience in the management of choledochal cysts from 1999 to 2009. A retrospective review of all charts with a diagnosis of choledochal cysts in our institution in this ten-year period. Data was collated using Excel. A total of 17 patients were diagnosed with choledochal cyst: 9 females and 8 males. The average age at diagnosis was 28 months (range from 0 to 9 years). The most common presenting symptoms were obstructive jaundice 6 (35%) and abdominal pain and vomiting 4 (23%). Ultrasound (US) was the initial diagnostic test in all cases with 4 patients requiring further investigations. All patients underwent Roux-en-Y Hepaticojejunostomy. The average length of stay was 11 days. Patients were followed up with Liver Function Tests (LFTS) and US 4-6 weeks post-operatively. Three patients developed complications including post-op collection, high drain output requiring blood transfusion and adhesive bowel obstruction. Our overall experience with choledochal cyst patients has been a positive one with effective management and low complication rates.

  7. Chern-Simons gauge theory: Ten years after

    International Nuclear Information System (INIS)

    Labastida, J. M. F.

    1999-01-01

    A brief review on the progress made in the study of Chern-Simons gauge theory since its relation to knot theory was discovered ten years ago is presented. Emphasis is made on the analysis of the perturbative study of the theory and its connection to the theory of Vassiliev invariants. It is described how the study of the quantum field theory for three different gauge fixings leads to three different representations for Vassiliev invariants. Two of these gauge fixings lead to well known representations: the covariant Landau gauge corresponds to the configuration space integrals while the non-covariant light-cone gauge to the Kontsevich integral. The progress made in the analysis of the third gauge fixing, the non-covariant temporal gauge, is described in detail. In this case one obtains combinatorial expressions, instead of integral ones, for Vassiliev invariants. The approach based on this last gauge fixing seems very promising to obtain a full combinatorial formula. We collect the combinatorial expressions for all the Vassiliev invariants up to order four which have been obtained in this approach

  8. "Take ten minutes": a dedicated ten minute medication review reduces polypharmacy in the elderly.

    LENUS (Irish Health Repository)

    Walsh, E K

    2012-02-01

    Multiple and inappropriate medications are often the cause for poor health status in the elderly. Medication reviews can improve prescribing. This study aimed to determine if a ten minute medication review by a general practitioner could reduce polypharmacy and inappropriate prescribing in elderly patients. A prospective, randomised study was conducted. Patients over the age of 65 (n = 50) underwent a 10-minute medication review. Inappropriate medications, dosage errors, and discrepancies between prescribed versus actual medication being consumed were recorded. A questionnaire to assess satisfaction was completed following review. The mean number of medications taken by patients was reduced (p < 0.001). A medication was stopped in 35 (70%) patients. Inappropriate medications were detected in 27 (54%) patients and reduced (p < 0.001). Dose errors were detected in 16 (32%). A high level of patient satisfaction was reported. A ten minute medication review reduces polypharmacy, improves prescribing and is associated with high levels of patient satisfaction.

  9. "Take ten minutes": a dedicated ten minute medication review reduces polypharmacy in the elderly.

    LENUS (Irish Health Repository)

    Walsh, E K

    2010-09-01

    Multiple and inappropriate medications are often the cause for poor health status in the elderly. Medication reviews can improve prescribing. This study aimed to determine if a ten minute medication review by a general practitioner could reduce polypharmacy and inappropriate prescribing in elderly patients. A prospective, randomised study was conducted. Patients over the age of 65 (n = 50) underwent a 10-minute medication review. Inappropriate medications, dosage errors, and discrepancies between prescribed versus actual medication being consumed were recorded. A questionnaire to assess satisfaction was completed following review. The mean number of medications taken by patients was reduced (p < 0.001). A medication was stopped in 35 (70%) patients. Inappropriate medications were detected in 27 (54%) patients and reduced (p < 0.001). Dose errors were detected in 16 (32%). A high level of patient satisfaction was reported. A ten minute medication review reduces polypharmacy, improves prescribing and is associated with high levels of patient satisfaction.

  10. The five times ten things everyone should have had in their hands before they are ten and two years old.

    Science.gov (United States)

    Hut, R.; Poot, A.

    2017-12-01

    To train the young ones to become people that make stuff, I present the five times ten things we use a lot that everyone should have used before they are ten and two years old. I will bring at least two times ten of these things and show them live to you! And: I will bring a large paper for you to bring home with those five times ten things on it to put in the hands of your kids!

  11. The lead and lead-acid battery industries during 2002 and 2007 in China

    Energy Technology Data Exchange (ETDEWEB)

    Chen, H.Y.; Li, A.J.; Finlow, D.E. [Key Lab of Electrochemical Technology on Energy Storage and Power Generation in Guangdong Universities, School of Chemistry and Environment, South China Normal University, Guangzhou 510006 (China)

    2009-06-01

    In the past 15 years, the center of the international lead market has shifted to China. China has become the largest producer of raw and refined lead, plus the largest consumer. This paper reviews the status of the lead and lead-acid battery industries in China, including lead mining, lead refining, secondary lead production, the lead-acid battery industry, new opportunities for lead-acid batteries, and the environmental problems associated with lead and lead-acid batteries. The output of raw and refined lead has increased annually in China, and now accounts for more than 30% of the world total. As a result of a change in the Chinese government's policy regarding the export of lead, plus an increase in the price of lead, the profits of Chinese lead manufacturers were significantly reduced, the trade deficit of the Chinese lead industry increased, the operating rates of lead smelter enterprises greatly reduced, and some small enterprises were forced to shut down. At the present time, an increasing number of enterprises have begun to produce secondary lead, and the scale of production has expanded from tens of tons to tens of thousands of tons. In 2006, the output of secondary lead in China reached 700,000 tons, but outdated technology and equipment limited development of the secondary lead industry. Because of serious pollution problems, raw material shortages, and fierce price competition in the battery market, changes in the development of the lead-acid battery industry have been dramatic; approximately one thousand medium-sized and small lead-acid battery producers have been closed in the past 3 years. The output of large lead-acid battery enterprises has not been reduced, however, as a result of their manufacturing technology and equipment being comparable to those in other advanced industrial countries. In China, the flourishing development of electric bicycles, electric tricycles, and photovoltaic energy systems should provide ongoing opportunities for

  12. The lead and lead-acid battery industries during 2002 and 2007 in China

    International Nuclear Information System (INIS)

    Chen, H.Y.; Li, A.J.; Finlow, D.E.

    2009-01-01

    In the past 15 years, the center of the international lead market has shifted to China. China has become the largest producer of raw and refined lead, plus the largest consumer. This paper reviews the status of the lead and lead-acid battery industries in China, including lead mining, lead refining, secondary lead production, the lead-acid battery industry, new opportunities for lead-acid batteries, and the environmental problems associated with lead and lead-acid batteries. The output of raw and refined lead has increased annually in China, and now accounts for more than 30% of the world total. As a result of a change in the Chinese government's policy regarding the export of lead, plus an increase in the price of lead, the profits of Chinese lead manufacturers were significantly reduced, the trade deficit of the Chinese lead industry increased, the operating rates of lead smelter enterprises greatly reduced, and some small enterprises were forced to shut down. At the present time, an increasing number of enterprises have begun to produce secondary lead, and the scale of production has expanded from tens of tons to tens of thousands of tons. In 2006, the output of secondary lead in China reached 700,000 tons, but outdated technology and equipment limited development of the secondary lead industry. Because of serious pollution problems, raw material shortages, and fierce price competition in the battery market, changes in the development of the lead-acid battery industry have been dramatic; approximately one thousand medium-sized and small lead-acid battery producers have been closed in the past 3 years. The output of large lead-acid battery enterprises has not been reduced, however, as a result of their manufacturing technology and equipment being comparable to those in other advanced industrial countries. In China, the flourishing development of electric bicycles, electric tricycles, and photovoltaic energy systems should provide ongoing opportunities for the

  13. The TEN-T core network and the Fehmarnbelt region

    DEFF Research Database (Denmark)

    Guasco, Clement Nicolas

    This note is a snapshot picture, taken in early 2014, that places the Green STRING corridor project within the context of the TEN-T strategy and gives a summarized overview on the impact of this strategy in the region. Chapter 1 contains a summary of the TEN-T strategy today, chapter 2 presents...... the sources used for this note, chapter 3 presents all the relevant EU regulations with direct impact on the development of TEN-T corridors, chapter 4 gives practical examples of the challenges for the development of TEN-T corridors, chapter 5 pre-sents the national initiatives related to the TEN-T corridor...

  14. Ten years of energy policy in Catalonia

    International Nuclear Information System (INIS)

    Masalles Roman, I.; Marin Sanchez, J.M.; Gurgui Ferrer, A.; Figuerola Perez, E.

    1992-01-01

    Catalonia is located in the north-east corner of Spain, on the Mediterranean coast and bordering with France in the north. It is one of the most industrialized and developed regions of Spain, with a per capita income of 10879 ECU per year (1989), 21.9% higher than the Spanish average. It contributes to 20.3% of the Spanish GDP. Primary energy consumption was 16.5 M toe in 1989, covered by the following sources: 3.5% coal, 51.8% oil, 9.4% natural gas, 3.6% hydro, 30.8% nuclear, 0.1% electrical import/export balance and 0.8% waste residuals. Oil dependence is distorted by the existence of a major petrochemical industry that uses more than 2.6 Mtoe of oil derivatives for non-energy purposes. Final energy demand in 1989 was 8.8 Mtoe, 40.9% for industry, 36.9% for transportation and 22.3% for the domestic and services sector. In the 60's, Catalonia's socio-economic development was accompanied by a spectacular increase in the demand for primary energy: from slightly above 2.5 million toe in 1960 to 5.6 Mtoe ten years later. If this decade can be characterized by a steady increase in the total value of consumption, the 70's also constitute years of major changes in the field of energy on an international scale (the oil crisis) and in politics in the Spanish State. 6 refs., 3 figs., 6 tabs

  15. Shigella sonnei Vaccine Candidates WRSs2 and WRSs3 Are as Immunogenic as WRSS1, a Clinically Tested Vaccine Candidate, in a Primate Model of Infection

    Science.gov (United States)

    2011-01-01

    Experiments in rabbit ileal loops and in rhesus monkeys have shown that shigellae are initially taken up by antigen sampling microfold (M) cells that are...2011) – Table 1 Shigella antigen-specific immune responses and colonization in rhesus monkeys after nasogastric administration of WRSS1, WRSs2...the respective antigens. 3.3. Mucosal responses in rhesus monkeys The mucosal immune response to Shigella LPS, and Invaplex- 50 antigens are summarized

  16. Erkenntnisgewinnn durch Virtuelle Realitäten

    Directory of Open Access Journals (Sweden)

    Breiner, Tobias

    2009-11-01

    Full Text Available Virtual reality will gain a more and more important role in our everyday life. So it is very important to understand fully the impact and influence virtual reality will have on or view of the world. This article reveals that the interdependencies between the real space and the virtual space are much more subtle and profound then on first sight. Especially the value of several mathematical, physical and biological models and simulation methodologies will be reestimated by the use of virtual reality in the long term. As an example the article describes the historical chain from quaternions to quaoaring and how this may lead to a paradigm change in biology.

  17. Transcutaneous electrical nerve stimulation (TENS) for pain management in labour

    Science.gov (United States)

    Dowswell, Therese; Bedwell, Carol; Lavender, Tina; Neilson, James P

    2014-01-01

    Background Transcutaneous nerve stimulation (TENS) has been proposed as a means of reducing pain in labour. The TENS unit emits low-voltage electrical impulses which vary in frequency and intensity. During labour, TENS electrodes are generally placed on the lower back, although TENS may be used to stimulate acupuncture points or other parts of the body. The physiological mechanisms whereby TENS relieves pain are uncertain. TENS machines are frequently operated by women, which may increase a sense of control in labour. Objectives To assess the effects of TENS on pain in labour. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (30 April 2011) and reference lists of retrieved papers. Selection criteria Randomised controlled trials comparing women receiving TENS for pain management in labour versus routine care, alternative non-pharmacological methods of pain relief, or placebo devices. We included all types of TENS machines. Data collection and analysis Two review authors assessed for inclusion all trials identified by the search strategy, carried out data extraction and assessed risk of bias. We have recorded reasons for excluding studies. Main results Seventeen trials with 1466 women contribute data to the review. Thirteen examined TENS applied to the back, two to acupuncture points, and two to the cranium. Overall, there was little difference in pain ratings between TENS and control groups, although women receiving TENS to acupuncture points were less likely to report severe pain (average risk ratio 0.41, 95% confidence interval 0.31 to 0.54; measured in two studies). The majority of women using TENS said they would be willing to use it again in a future labour. Where TENS was used as an adjunct to epidural analgesia there was no evidence that it reduced pain. There was no consistent evidence that TENS had any impact on interventions and outcomes in labour. There was little information on outcomes for mothers and babies. No

  18. Transcutaneous electrical nerve stimulation (TENS) for pain relief in labour.

    Science.gov (United States)

    Dowswell, Therese; Bedwell, Carol; Lavender, Tina; Neilson, James P

    2009-04-15

    Transcutaneous nerve stimulation (TENS) has been proposed as a means of reducing pain in labour. The TENS unit emits low-voltage electrical impulses which vary in frequency and intensity. During labour, TENS electrodes are generally placed on the lower back, although TENS may be used to stimulate acupuncture points or other parts of the body. The physiological mechanisms whereby TENS relieves pain are uncertain. The TENS unit is frequently operated by women, which may increase sense of control in labour. To assess the effects of TENS on pain in labour. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (November 2008). Randomised controlled trials comparing women receiving TENS for pain relief in labour versus routine care, alternative pharmacological methods of pain relief, or placebo devices. We included all types of TENS machines. Two review authors assessed for inclusion all trials identified by the search strategy, carried out data extraction and assessed risk of bias. We have recorded reasons for excluding studies. The search identified 25 studies; we excluded six and included 19 studies including 1671 women. Fifteen examined TENS applied to the back, two to acupuncture points and two to the cranium. Overall, there was little difference in pain ratings between TENS and control groups, although women receiving TENS to acupuncture points were less likely to report severe pain (risk ratio 0.41, 95% confidence interval 0.32 to 0.55). The majority of women using TENS said they would be willing to use it again in a future labour. Where TENS was used as an adjunct to epidural analgesia there was no evidence that it reduced pain. There was no consistent evidence that TENS had any impact on interventions and outcomes in labour. There was little information on outcomes for mothers and babies. No adverse events were reported. There is only limited evidence that TENS reduces pain in labour and it does not seem to have any impact (either positive or

  19. Lead in some food crops and trees

    Energy Technology Data Exchange (ETDEWEB)

    Warren, H V; Delavault, R E

    1962-02-01

    An investigation has been made of the lead content of trees and some of the more common vegetables and cereals (maize, cabbage, potatoes, carrots, beets, onions, peas, hops, oats, rhubarb, lettuce, cauliflower, leeks, barley, rye, and wheat) grown in British Columbia and in Great Britain. The lead content of the lime, yew, willow, birch, oak, ash, hazel and cypress was determined. It was concluded that in areas where soils have an abnormally high lead content, food products may acquire up to ten times as much lead, or more, than those grown on normal soil.

  20. Flipped SU(6) from ten dimensions

    Energy Technology Data Exchange (ETDEWEB)

    Panagiotakopoulos, C. (Bartol Research Inst., Univ. of Delaware, Newark, DE (US))

    1990-06-20

    The authors study the compactification of the heterotic supersting on the only known three generation Calabi-Yau space with flux breakings leading to SU(6) {times} U(1) as the gauge group in four dimensions. We compute the massless spectrum and identify the discrete symmetries of the internal space that survive flux breaking. The possible four-dimensional models are classified according to their honest discrete symmetries. The allowed breaking chains of SU(6) {times} U(1) are listed. Model building with SU(6) {times} U(1) is discussed in general and a concrete realistic model is constructed which does not suffer from the gauge hierarchy problem, fast proton decay or any other obvious phenomenological disaster. A distinct experimental signature of this class of models is the presence in the low energy spectrum of vector-like quarks and antiquarks, outside the three known families, with masses of the order of the supersymmetry breaking scale.

  1. Transcutaneous electric nerve stimulation (TENS) in dentistry- A review.

    Science.gov (United States)

    Kasat, Vikrant; Gupta, Aditi; Ladda, Ruchi; Kathariya, Mitesh; Saluja, Harish; Farooqui, Anjum-Ara

    2014-12-01

    Transcutaneous electric nerve stimulation (TENS) is a non-pharmacological method which is widely used by medical and paramedical professionals for the management of acute and chronic pain in a variety of conditions. Similarly, it can be utilized for the management of pain during various dental procedures as well as pain due to various conditions affecting maxillofacial region. This review aims to provide an insight into clinical research evidence available for the analgesic and non analgesic uses of TENS in pediatric as well as adult patients related to the field of dentistry. Also, an attempt is made to briefly discuss history of therapeutic electricity, mechanism of action of TENS, components of TENs equipment, types, techniques of administration, advantages and contradictions of TENS. With this we hope to raise awareness among dental fraternity regarding its dental applications thereby increasing its use in dentistry. Key words:Dentistry, pain, TENS.

  2. Lead Farmers Approach in Disseminating Improved Tef Production ...

    African Journals Online (AJOL)

    Abate

    interview schedule and testing the tef variety on field plots of ten lead farmers ..... Product transporting from the farm ... partly explained by the fact that smallholder farmers cannot afford to purchase .... Agricultural Extension, Good Intentions.

  3. The origin of the future ten questions for the next ten years

    CERN Document Server

    Gribbin, John

    2006-01-01

    How did the universe begin? Where do galaxies come from? How do stars and planets form? Where do the material particles we are made of come from? How did life begin? Today we have only provisional answers to such questions. But scientific progress will improve these answers dramatically over the next ten years, predicts John Gribbin in this riveting book. He focuses on what we know—or think we know—about ten controversial, unanswered issues in the physical sciences and explains how current cutting-edge research may yield solutions in the very near future. With his trademark facility for engaging readers with or without a scientific background, the author explores ideas concerning the creation of the universe, the possibility of other forms of life, and the fate of the expanding cosmos. He examines “theories of everything,” including grand unified theories and string theory, and he discusses the Big Bang theory, the origin of structure and patterns of matter in the galaxies, and dark mass and dark ene...

  4. Increasing intensity of TENS prevents analgesic tolerance in rats

    Science.gov (United States)

    Sato, Karina L.; Sanada, Luciana S.; Rakel, Barbara A.; Sluka, Kathleen A.

    2012-01-01

    Transcutaneous electrical nerve stimulation (TENS) reduces hyperalgesia and pain. Both low frequency (LF) and high frequency (HF) TENS, delivered at the same intensity (90% motor threshold (MT)) daily, result in analgesic tolerance with repeated use by the 5th day of treatment. Thecurrentstudytestedif 1) increasingintensityby 10% per daypreventsthedevelopmentoftolerance to repeated TENS, and 2) iflowerintensity TENS (50 % MT) produces an equivalentreduction in hyperalgesia when compared to 90% MT TENS. Sprague-Dawley rats with unilateral knee joint inflammation (3% carrageenan) were separated according to the intensity of TENS used: Sham, 50% LF, 50% HF, 90% LF, 90% HF, and increased intensity by 10% per day (LF and HF). The reduced mechanical withdrawal threshold following the induction of inflammation was reversed by application of TENS applied at 90% MT and increasing intensity for the first 4 days. On the 5th day, the groups that received 90% MT intensity showed tolerance. Nevertheless, the group that received an increased intensity on each day still showed a reversal of the mechanical withdrawal threshold with TENS. These results show that the development of tolerance can be delayed by increasing intensity of TENS. PMID:22858165

  5. Ten Putative Contributors to the Obesity Epidemic

    Science.gov (United States)

    McAllister, Emily J.; Dhurandhar, Nikhil V.; Keith, Scott W.; Aronne, Louis J.; Barger, Jamie; Baskin, Monica; Benca, Ruth M.; Biggio, Joseph; Boggiano, Mary M.; Eisenmann, Joe C.; Elobeid, Mai; Fontaine, Kevin R.; Gluckman, Peter; Hanlon, Erin C.; Katzmarzyk, Peter; Pietrobelli, Angelo; Redden, David T.; Ruden, Douglas M.; Wang, Chenxi; Waterland, Robert A.; Wright, Suzanne M.; Allison, David B.

    2010-01-01

    The obesity epidemic is a global issue and shows no signs of abating, while the cause of this epidemic remains unclear. Marketing practices of energy-dense foods and institutionally-driven declines in physical activity are the alleged perpetrators for the epidemic, despite a lack of solid evidence to demonstrate their causal role. While both may contribute to obesity, we call attention to their unquestioned dominance in program funding and public efforts to reduce obesity, and propose several alternative putative contributors that would benefit from equal consideration and attention. Evidence for microorganisms, epigenetics, increasing maternal age, greater fecundity among people with higher adiposity, assortative mating, sleep debt, endocrine disruptors, pharmaceutical iatrogenesis, reduction in variability of ambient temperatures, and intrauterine and intergenerational effects, as contributing factors to the obesity epidemic are reviewed herein. While the evidence is strong for some contributors such as pharmaceutical-induced weight gain, it is still emerging for other reviewed factors. Considering the role of such putative etiological factors of obesity may lead to comprehensive, cause specific, and effective strategies for prevention and treatment of this global epidemic. PMID:19960394

  6. Ten years of Brazilian ballast water management

    Science.gov (United States)

    Castro, Maria Cecilia Trindade; Hall-Spencer, Jason M.; Poggian, Cecília Fonseca; Fileman, Timothy W.

    2018-03-01

    In 2005, Brazil addressed the environmental challenges posed by ballast water through a unilateral regulation, called the Maritime Standard N° 20 (NORMAM-20), applied to all shipping in her waters. This world-leading decision was the culmination of a process that started during the 1990‧s. Here, we summarize how these ballast water regulations were brought in and adopted and present the findings of 10 years of enforcement (2005-2015) in 39 ports along the Brazilian coast. We show that compliance with the Brazilian standard has increased significantly since the regulations were implemented (p < 0.001). After five years of implementation, non-compliance decreased probably reflecting an increase in awareness of the Brazilian Standard and a shift in the shipping industry commitment to minimize and control the spread of invasive species through ballast water. The Brazilian experience shows that very high levels (97%) of compliance with ballast water management regulations can be made to work in a region of global importance to the maritime industry. In the last decade, the rules governing ballast water in Brazil have evolved to address the demands from the maritime community and to provide updates such as imminent requirements for the use of ballast water management systems on board ships. These regulations are rarely cited when ballast water regulations are discussed internationally, yet there is much to learn from the proactive approach taken by Brazil such as what is feasible and enforceable.

  7. Transcutaneous electrical nerve stimulation (TENS) for chronic low back pain.

    Science.gov (United States)

    Milne, S; Welch, V; Brosseau, L; Saginur, M; Shea, B; Tugwell, P; Wells, G

    2001-01-01

    Low back pain (LBP) affects a large proportion of the population. Transcutaneous electrical nerve stimulation (TENS) was introduced more than 30 years ago as an alternative therapy to pharmacological treatments for chronic pain. However, despite its widespread use, the effectiveness of TENS is still controversial. The aim of this systematic review was to determine the efficacy of TENS in the treatment of chronic LBP. We searched MEDLINE, EMBASE, PEDro and the Cochrane Controlled Trials Register up to June 1, 2000. Only randomized controlled clinical trials of TENS for the treatment of patients with a clinical diagnosis of chronic LBP were included. Abstracts were excluded unless further data could be obtained from the authors. Two reviewers independently selected trials and extracted data using predetermined forms. Heterogeneity was tested with Cochran's Q test. A fixed effects model was used throughout for continuous variables, except where heterogeneity existed, in which case, a random effects model was used. Results are presented as weighted mean differences (WMD) with 95% confidence intervals (95% CI), where the difference between the treated and control groups was weighted by the inverse of the variance. Standardized mean differences (SMD) were calculated by dividing the difference between the treated and control by the baseline variance. SMD were used when different scales were used to measure the same concept. Dichotomous outcomes were analyzed with odds ratios. Five trials were included, with 170 subjects randomized to the placebo group receiving sham-TENS and 251 subjects receiving active TENS (153 for conventional mode, 98 for acupuncture-like TENS). The schedule of treatments varied greatly between studies ranging from one treatment/day for two consecutive days, to three treatments/day for four weeks. There were no statistically significant differences between the active TENS group when compared to the placebo TENS group for any outcome measures

  8. Granulocyte colony-stimulating factor in toxic epidermal necrolysis (TEN) and Chelsea & Westminster TEN management protocol [corrected].

    Science.gov (United States)

    de Sica-Chapman, A; Williams, G; Soni, N; Bunker, C B

    2010-04-01

    Toxic epidermal necrolysis (TEN) is a rare but life-threatening, allergic drug reaction. Skin blistering with epidermal and mucosal necrolysis with subsequent detachment from an inflamed underlying dermis is a hallmark of the condition. The pathogenesis of TEN is not well understood, accounting for controversies about its management and significant delay in initiating potentially beneficial therapy. There are no management protocols based on a robust evidence base. Prompt recognition of the diagnosis and consensus on early management initiatives are necessary in order to improve outcomes and survival in TEN. To date, TEN management has been directed at arresting the allergic reaction and treating the complications. We have identified a need for specific medical interventions to accelerate wound regeneration. This approach has not previously been adopted in the management of TEN. We observed that in two cases of severe TEN, dramatic re-epithelialization and recovery coincided with the introduction of granulocyte colony-stimulating factor (G-CSF) for neutropenia. We explain how addition of the G-CSF promotes recovery from TEN by enhanced bioregeneration of the damaged tissues through accelerated re-epithelialization. G-CSF has been used for severe neutropenia in TEN, but we recommend and explain why, as in our Chelsea and Westminster protocol, G-CSF should be considered in treating severe TEN irrespective of the severity of neutropenia.

  9. Firework injuries: a ten-year study.

    Science.gov (United States)

    Puri, Vinita; Mahendru, Sanjay; Rana, Roshani; Deshpande, Manish

    2009-09-01

    Fireworks are used worldwide to celebrate popular events (e.g. festivals, official celebrations, weddings). The festival of lights (Diwali) is celebrated with fireworks in India. During this period, many patients from all age groups present to hospital with injuries due to fireworks. Prevalence, period of occurrence, sex and age variation, adult supervision, causative fireworks, mode of lighting, age groups prone to injury, patterns of injury caused by individual fireworks, and the body parts injured were studied. One hundred and fifty-seven cases (92 retrospective, 65 prospective) with injury due to fireworks presenting to the Department of Plastic Surgery at KEM Hospital between 1997 and 2006 were studied. The prevalence of injuries has decreased steadily over the last 10 years (41 cases in 1997, 3 cases in 2006). The maximum number of injuries (35%) was seen in the age group 5-14 years; 92% of these children were unsupervised. The commonest cause of injury was firework misuse (41% of cases), followed by device failure (35%). Device failure was commonest with flares/fountains (ground firework emitting sparks upwards) and aerial devices. Flare/fountains caused most injury (39%), sparklers the least (0.6%). Flare/fountains, ground spinners, sparklers, and gunpowder (explosive material from cracker, obtained by tearing paper wrapper and obtaining chemicals) caused only soft tissue burns; stringbombs (high-intensity fire cracker made by wrapping chemicals with jute strings/coir in layers) and rockets (aerial device that zooms upwards and bursts) caused blast injuries, leading to soft tissue disruption and bony injuries. Emergency surgery was done if indicated: tendon and/or neurovascular repair, fracture fixation, flap cover or amputation. Superficial burns were treated with dressings. Certain wounds needed only thorough cleansing of the wound and primary suturing. We concluded that, over a 10-year period, the prevalence of firework injury decreased due to increased

  10. How the Big Ten West Was Won: Football Recruiting

    Directory of Open Access Journals (Sweden)

    Diehl Kevin A.

    2017-06-01

    Full Text Available The paper analyses the 2017 Big Ten West Division football cycle models recruiting. The top ten recruit scores [(Rivals.com * 100 + [100 (outside surrounding; 75 (surrounding] + extra credit walk-ons (100; 75] allow proper ranking: Iowa, Nebraska, Wisconsin, Northwestern, Illinois, Minnesota, and Purdue.

  11. Ten Things Every Professor Should Know about Assessment

    Science.gov (United States)

    Wolf, Kenneth; Dunlap, Joanna; Stevens, Ellen

    2012-01-01

    This article describes ten key assessment practices for advancing student learning that all professors should be familiar with and strategically incorporate in their classrooms and programs. Each practice or concept is explained with examples and guidance for putting it into practice. The ten are: learning outcomes, performance assessments,…

  12. Transcutaneous electrical nerve stimulation (TENS) for neuropathic pain in adults.

    Science.gov (United States)

    Gibson, William; Wand, Benedict M; O'Connell, Neil E

    2017-09-14

    Neuropathic pain, which is due to nerve disease or damage, represents a significant burden on people and society. It can be particularly unpleasant and achieving adequate symptom control can be difficult. Non-pharmacological methods of treatment are often employed by people with neuropathic pain and may include transcutaneous electrical nerve stimulation (TENS). This review supersedes one Cochrane Review 'Transcutaneous electrical nerve stimulation (TENS) for chronic pain' (Nnoaham 2014) and one withdrawn protocol 'Transcutaneous electrical nerve stimulation (TENS) for neuropathic pain in adults' (Claydon 2014). This review replaces the original protocol for neuropathic pain that was withdrawn. To determine the analgesic effectiveness of TENS versus placebo (sham) TENS, TENS versus usual care, TENS versus no treatment and TENS in addition to usual care versus usual care alone in the management of neuropathic pain in adults. We searched CENTRAL, MEDLINE, Embase, PsycINFO, AMED, CINAHL, Web of Science, PEDro, LILACS (up to September 2016) and various clinical trials registries. We also searched bibliographies of included studies for further relevant studies. We included randomised controlled trials where TENS was evaluated in the treatment of central or peripheral neuropathic pain. We included studies if they investigated the following: TENS versus placebo (sham) TENS, TENS versus usual care, TENS versus no treatment and TENS in addition to usual care versus usual care alone in the management of neuropathic pain in adults. Two review authors independently screened all database search results and identified papers requiring full-text assessment. Subsequently, two review authors independently applied inclusion/exclusion criteria to these studies. The same review authors then independently extracted data, assessed for risk of bias using the Cochrane standard tool and rated the quality of evidence using GRADE. We included 15 studies with 724 participants. We found a

  13. TRANSCUTANEOUS ELECTRICAL NERVE-STIMULATION (TENS) IN RAYNAUDS-PHENOMENON

    NARCIS (Netherlands)

    MULDER, P; DOMPELING, EC; VANSLOCHTERENVANDERBOOR, JC; KUIPERS, WD; SMIT, AJ

    Transcutaneous nerve stimulation (TENS) has been described as resulting in vasodilatation. The effect of 2 Hz TENS of the right hand during forty-five minutes on skin temperature and plethysmography of the third digit of both hands and feet and on transcutaneous oxygen tension (TcpO2) of the right

  14. Using TENS for pain control: the state of the evidence

    Science.gov (United States)

    Vance, Carol GT; Dailey, Dana L; Rakel, Barbara A; Sluka, Kathleen A

    2014-01-01

    Summary Transcutaneous electrical nerve stimulation (TENS) is a nonpharmacological intervention that activates a complex neuronal network to reduce pain by activating descending inhibitory systems in the central nervous system to reduce hyperalgesia. The evidence for TENS efficacy is conflicting and requires not only description but also critique. Population-specific systemic reviews and meta-analyses are emerging, indicating both HF and LF TENS being shown to provide analgesia, specifically when applied at a strong, nonpainful intensity. The purpose of this article is to provide a critical review of the latest basic science and clinical evidence for TENS. Additional research is necessary to determine if TENS has effects specific to mechanical stimuli and/or beyond reduction of pain and will improve activity levels, function and quality of life. PMID:24953072

  15. Lead levels - blood

    Science.gov (United States)

    Blood lead levels ... is used to screen people at risk for lead poisoning. This may include industrial workers and children ... also used to measure how well treatment for lead poisoning is working. Lead is common in the ...

  16. Lead Poisoning Prevention Tips

    Science.gov (United States)

    ... or removed safely. How are children exposed to lead? Lead-based paint and lead contaminated dust are ... What can be done to prevent exposure to lead? It is important to determine the construction year ...

  17. Effect of burst TENS and conventional TENS combined with cryotherapy on pressure pain threshold: randomised, controlled, clinical trial.

    Science.gov (United States)

    Macedo, L B; Josué, A M; Maia, P H B; Câmara, A E; Brasileiro, J S

    2015-06-01

    To assess the immediate effect of conventional and burst transcutaneous electrical nerve stimulation (TENS) in combination with cryotherapy on pain threshold and tolerance in healthy individuals. Randomised, controlled trial. University laboratory. One hundred and twelve healthy women. Volunteers were allocated at random to seven groups (n=16): (1) control, (2) placebo TENS, (3) conventional TENS, (4) burst TENS, (5) cryotherapy, (6) cryotherapy in combination with burst TENS, and (7) cryotherapy in combination with conventional TENS. Pain threshold and tolerance were measured by applying a pressure algometer at the lateral epicondyle of the humerus, before and after each intervention. The primary outcome measure was pressure pain threshold. A significant increase in pain threshold and tolerance at the 5% level of significance was recorded as follows: burst TENS {pain threshold: mean difference 1.3 [95% confidence interval (CI) 1.4 to 1.2]; pain tolerance: mean difference 3.8 (95% CI 3.9 to 3.7)}, cryotherapy [pain threshold: mean difference 1.3 (95% CI 1.4 to 1.2); pain tolerance: mean difference 1.9 (95% CI 1.8 to 2.0)] and cryotherapy in combination with burst TENS [pain threshold: mean difference 2.6 (95% CI 2.4 to 2.8); pain tolerance: mean difference 4.9 (95% CI 5.0 to 4.8)]. Cryotherapy in combination with burst TENS provided greater analgesia compared with the other groups (Pcryotherapy in combination with burst TENS to reduce induced pain, and suggest a potentiating effect when these techniques are combined. No such association was found between cryotherapy and conventional TENS. Copyright © 2014 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

  18. Ten-Competence: Life-Long Competence Development and Learning

    NARCIS (Netherlands)

    Koper, Rob; Specht, Marcus

    2006-01-01

    Koper, R., & Specht, M. (2008). Ten-Competence: Life-Long Competence Development and Learning. In M-A. Cicilia (Ed.), Competencies in Organizational e-learning: concepts and tools (pp. 234-252). Hershey: IGI-Global.

  19. Ten Things Parents Can Do to Prevent Suicide

    Science.gov (United States)

    ... Ribbon Commands Skip to main content Turn off Animations Turn on Animations Our Sponsors Log in | Register Menu Log in | ... teen at risk for suicide . Spend some time reading these ten ways you can help prevent a ...

  20. Simultaneous determination of ten compounds in two main ...

    African Journals Online (AJOL)

    Simultaneous determination of ten compounds in two main medicinal plant parts of Tibetan herb, Pterocephalus hookeri (CB Clarke) Höeck, by ultra-high performance liquid chromatography-photodiode array.

  1. Top Ten Challenges Facing the Next Secretary of Homeland Security

    National Research Council Canada - National Science Library

    2008-01-01

    In an effort to assist with the first Presidential administration transition of the Department of Homeland Security, the Homeland Security Advisory Council has identified ten key challenges that will...

  2. Critical Studies on Men in Ten European Countries

    DEFF Research Database (Denmark)

    Pringle, Keith; Hearn, Jeff (and 13 other network partners)

    2002-01-01

    This article is one the work of The European Research Network on Men in Europe project “The Social Problem and Societal Problematization of Men and Masculinities” (2000-2003), funded by the European Commission. The Network comprises women and men researchers with range of disciplinary backgrounds...... of statistical sources on men's practices in the ten countries, are presented. This is the second of four articles reviewing critical studies on men in the ten countries through different methods and approaches....

  3. Lead (Pb) Air Pollution

    Science.gov (United States)

    ... Regional Offices Labs and Research Centers Lead (Pb) Air Pollution Contact Us Share As a result of EPA's ... and protect aquatic and terrestrial ecosystems. Lead (Pb) Air Pollution Basic Information How does lead get in the ...

  4. Immunogenicity of a recombinant Rift Valley fever MP-12-NSm deletion vaccine candidate in calves.

    Science.gov (United States)

    Morrill, John C; Laughlin, Richard C; Lokugamage, Nandadeva; Wu, Jing; Pugh, Roberta; Kanani, Pooja; Adams, L Garry; Makino, Shinji; Peters, C J

    2013-10-09

    The safety and immunogenicity of an authentic recombinant (ar) of the live, attenuated MP-12 Rift Valley fever (RVF) vaccine virus with a large deletion of the NSm gene in the pre-Gn region of the M RNA segment (arMP-12ΔNSm21/384) was tested in 4-6 month old Bos taurus calves. Phase I of this study evaluated the neutralizing antibody response, measured by 80% plaque reduction neutralization (PRNT80), and clinical response of calves to doses of 1 × 10(1) through 1 × 10(7) plaque forming units (PFU) administered subcutaneously (s.c.). Phase II evaluated the clinical and neutralizing antibody response of calves inoculated s.c. or intramuscularly (i.m.) with 1 × 10(3), 1 × 10(4) or 1 × 10(5)PFU of arMP-12ΔNSm21/384. No significant adverse clinical events were observed in the animals in these studies. Of all specimens tested, only one vaccine viral isolate was recovered and that virus retained the introduced deletion. In the Phase I study, there was no statistically significant difference in the PRNT80 response between the dosage groups though the difference in IgG response between the 1 × 10(1)PFU group and the 1 × 10(5)PFU group was statistically significant (pPFU dose group showing the least response. The Phase II study also showed no statistically significant difference in PRNT80 response between the dosage groups though the difference in RVFV-specific IgG values was significantly increased (pPFU versus those inoculated s.c. with 1 × 10(3) or 1 × 10(5)PFU. Although the study groups were small, these data suggest that 1 × 10(4) or 1 × 10(5)PFU of arMP-12ΔNSm21/384 administered i.m. to calves will consistently stimulate a presumably protective PRNT80 response for at least 91 days post inoculation. Further studies of arMP-12ΔNSm21/384 are warranted to explore its suitability as an efficacious livestock vaccine. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Optimizing expression of the pregnancy malaria vaccine candidate, VAR2CSA in Pichia pastoris.

    Science.gov (United States)

    Avril, Marion; Hathaway, Marianne J; Cartwright, Megan M; Gose, Severin O; Narum, David L; Smith, Joseph D

    2009-06-29

    VAR2CSA is the main candidate for a vaccine against pregnancy-associated malaria, but vaccine development is complicated by the large size and complex disulfide bonding pattern of the protein. Recent X-ray crystallographic information suggests that domain boundaries of VAR2CSA Duffy binding-like (DBL) domains may be larger than previously predicted and include two additional cysteine residues. This study investigated whether longer constructs would improve VAR2CSA recombinant protein secretion from Pichia pastoris and if domain boundaries were applicable across different VAR2CSA alleles. VAR2CSA sequences were bioinformatically analysed to identify the predicted C11 and C12 cysteine residues at the C-termini of DBL domains and revised N- and C-termimal domain boundaries were predicted in VAR2CSA. Multiple construct boundaries were systematically evaluated for protein secretion in P. pastoris and secreted proteins were tested as immunogens. From a total of 42 different VAR2CSA constructs, 15 proteins (36%) were secreted. Longer construct boundaries, including the predicted C11 and C12 cysteine residues, generally improved expression of poorly or non-secreted domains and permitted expression of all six VAR2CSA DBL domains. However, protein secretion was still highly empiric and affected by subtle differences in domain boundaries and allelic variation between VAR2CSA sequences. Eleven of the secreted proteins were used to immunize rabbits. Antibodies reacted with CSA-binding infected erythrocytes, indicating that P. pastoris recombinant proteins possessed native protein epitopes. These findings strengthen emerging data for a revision of DBL domain boundaries in var-encoded proteins and may facilitate pregnancy malaria vaccine development.

  6. A randomized controlled Phase Ib trial of the malaria vaccine candidate GMZ2 in African children

    DEFF Research Database (Denmark)

    Bélard, Sabine; Issifou, Saadou; Hounkpatin, Aurore B

    2011-01-01

    GMZ2 is a fusion protein of Plasmodium falciparum merozoite surface protein 3 (MSP3) and glutamate rich protein (GLURP) that mediates an immune response against the blood stage of the parasite. Two previous phase I clinical trials, one in naïve European adults and one in malaria-exposed Gabonese ...... adults showed that GMZ2 was well tolerated and immunogenic. Here, we present data on safety and immunogenicity of GMZ2 in one to five year old Gabonese children, a target population for future malaria vaccine efficacy trials....

  7. A plant-produced Pfs230 vaccine candidate blocks transmission of Plasmodium falciparum

    NARCIS (Netherlands)

    Farrance, C.E.; Rhee, A.; Jones, R.M.; Musiychuk, K.; Shamloul, M.; Sharma, S.; Mett, V.; Chichester, J.A.; Streatfield, S.J.; Roeffen, W.F.G.; Vegte-Bolmer, M.G. van de; Sauerwein, R.W.; Tsuboi, T.; Muratova, O.V.; Wu, Y.; Yusibov, V.

    2011-01-01

    Plasmodium falciparum is transmitted to a new host after completing its sexual cycle within a mosquito. Developing vaccines against the parasite sexual stages is a critical component in the fight against malaria. We are targeting multiple proteins of P. falciparum which are found only on the

  8. Strategic evaluation of vaccine candidate antigens for the prevention of Visceral Leishmaniasis.

    Science.gov (United States)

    Duthie, Malcolm S; Favila, Michelle; Hofmeyer, Kimberley A; Tutterrow, Yeung L; Reed, Steven J; Laurance, John D; Picone, Alessandro; Guderian, Jeffrey; Bailor, H Remy; Vallur, Aarthy C; Liang, Hong; Mohamath, Raodoh; Vergara, Julie; Howard, Randall F; Coler, Rhea N; Reed, Steven G

    2016-05-27

    Infection with Leishmania parasites results in a range of clinical manifestations and outcomes, the most severe of which is visceral leishmaniasis (VL). Vaccination will likely provide the most effective long-term control strategy, as the large number of vectors and potential infectious reservoirs renders sustained interruption of Leishmania parasite transmission extremely difficult. Selection of the best vaccine is complicated because, although several vaccine antigen candidates have been proposed, they have emerged following production in different platforms. To consolidate the information that has been generated into a single vaccine platform, we expressed seven candidates as recombinant proteins in E. coli. After verifying that each recombinant protein could be recognized by VL patients, we evaluated their protective efficacy against experimental L. donovani infection of mice. Administration in formulation with the Th1-potentiating adjuvant GLA-SE indicated that each antigen could elicit antigen-specific Th1 responses that were protective. Considering the ability to reduce parasite burden along with additional factors such as sequence identity across Leishmania species, we then generated a chimeric fusion protein comprising a combination of the 8E, p21 and SMT proteins. This E. coli -expressed fusion protein was also demonstrated to protect against L. donovani infection. These data indicate a novel recombinant vaccine antigen with the potential for use in VL control programs. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  9. Identification and development of a promising novel mumps vaccine candidate strain.

    Science.gov (United States)

    Liang, Yan; Ma, Shaohui; Liu, Longding; Zhao, Hongling; Wang, Lichun; Jiang, Li; Xie, Zhongping; Dong, Chenghong; Li, Qihan

    2010-12-01

    Mumps epidemics are usually caused by airborne transmission of mumps virus (MuV) and have high morbidity in non-immunized children. Epidemiological studies in many regions of China show that the genotype F viral strain is the most prevalent. However, the genotype A strain is currently used to prepare vaccines. Regional epidemiological MuV data suggest a significant application for the development of live attenuated mumps vaccines targeting specific genotypes. This article reports the isolation and culture of a genotype F MuV candidate strain that could be used to prepare a live attenuated mumps vaccine. This strain is shown to have good immunological efficacy and stability in neurovirulence evaluations. This work should facilitate the implementation of mumps vaccination in mainland China by targeting the most prevalent MuV genotype, genotype F. Copyright © 2010 Institut Pasteur. Published by Elsevier SAS. All rights reserved.

  10. Optimizing expression of the pregnancy malaria vaccine candidate, VAR2CSA in Pichia pastoris

    Directory of Open Access Journals (Sweden)

    Narum David L

    2009-06-01

    Full Text Available Abstract Background VAR2CSA is the main candidate for a vaccine against pregnancy-associated malaria, but vaccine development is complicated by the large size and complex disulfide bonding pattern of the protein. Recent X-ray crystallographic information suggests that domain boundaries of VAR2CSA Duffy binding-like (DBL domains may be larger than previously predicted and include two additional cysteine residues. This study investigated whether longer constructs would improve VAR2CSA recombinant protein secretion from Pichia pastoris and if domain boundaries were applicable across different VAR2CSA alleles. Methods VAR2CSA sequences were bioinformatically analysed to identify the predicted C11 and C12 cysteine residues at the C-termini of DBL domains and revised N- and C-termimal domain boundaries were predicted in VAR2CSA. Multiple construct boundaries were systematically evaluated for protein secretion in P. pastoris and secreted proteins were tested as immunogens. Results From a total of 42 different VAR2CSA constructs, 15 proteins (36% were secreted. Longer construct boundaries, including the predicted C11 and C12 cysteine residues, generally improved expression of poorly or non-secreted domains and permitted expression of all six VAR2CSA DBL domains. However, protein secretion was still highly empiric and affected by subtle differences in domain boundaries and allelic variation between VAR2CSA sequences. Eleven of the secreted proteins were used to immunize rabbits. Antibodies reacted with CSA-binding infected erythrocytes, indicating that P. pastoris recombinant proteins possessed native protein epitopes. Conclusion These findings strengthen emerging data for a revision of DBL domain boundaries in var-encoded proteins and may facilitate pregnancy malaria vaccine development.

  11. Evaluation of a Ricin Vaccine Candidate for Human Toxicity Using an In Vitro Vascular Leak Model

    National Research Council Canada - National Science Library

    Porter, Aimee; Hale, Martha L; Pace, Amanda; Rosario, John-Michael; DaSilva, Luis

    2004-01-01

    Inhaling lethal doses of ricin (RT) causes pulmonary edema and results in death. In lower concentrations, ricin minimally causes tissue damage to the respiratory tract and lungs, which can incapacitate the individuals exposed to this toxin...

  12. Design of a Type-1 Diabetes Vaccine Candidate Using Edible Plants Expressing a Major Autoantigen

    Directory of Open Access Journals (Sweden)

    Edoardo Bertini

    2018-05-01

    Full Text Available Type-1 diabetes (T1D is a metabolic disease involving the autoimmune destruction of insulin-producing pancreatic beta cells. It is often diagnosed by the detection of autoantibodies, typically those recognizing insulin itself or the 65-kDa isoform of glutamic acid decarboxylase (GAD65. Oral insulin can be used to induce systemic immunological tolerance and thus prevent or delay the onset of T1D, suggesting that combination treatments with other autoantigens such as GAD65 could be even more successful. GAD65 has induced oral tolerance and prevented T1D in preclinical studies but it is difficult to produce in sufficient quantities for clinical testing. Here we combined edible plant systems, namely spinach (Spinacia oleracea cv Industra and red beet (Beta vulgaris cv Moulin Rouge, with the magnICON® expression system to develop a safe, cost-effective and environmentally sustainable platform for the large-scale production of GAD65. The superior red beet platform was extensively characterized in terms of recombinant protein yields and bioequivalence to wild-type plants, and the product was tested for its ability to resist simulated gastric digestion. Our results indicate that red beet plants are suitable for the production of a candidate oral vaccine based on GAD65 for the future preclinical and clinical testing of T1D immunotherapy approaches.

  13. Targeted modifications of foot-and-mouth disease virus; towards improved vaccine candidates

    DEFF Research Database (Denmark)

    Gullberg, Maria; Polacek, Charlotta; Bøtner, Anette

    these into susceptible cells it is possible to rescue specifically altered FMDVs. We have used this approach to generate modified viruses that have particular properties; these studies can assist in the development of improved and safer vaccines to protect against FMDV. For example, we have made changes to the leader (L...

  14. Immunogenicity of a Psoralen-Inactivated Dengue Virus Type 1 Vaccine Candidate in Mice

    Science.gov (United States)

    2010-02-01

    United States Naval Medical Research Center Detachment, Lima, Peru , 1 and United States Naval Medical Research Center, Silver Spring, Maryland2 R...and 28. The mice in group B mice received 10-ng vaccine doses on study clays 0, 14, and 28. The mice in group C received 10-ng vaccine doses on

  15. Development and efficacy of an attenuated Vibrio harveyi vaccine candidate with cross protectivity against Vibrio alginolyticus.

    Science.gov (United States)

    Hu, Yong-hua; Deng, Tian; Sun, Bo-guang; Sun, Li

    2012-06-01

    Vibrio harveyi is a Gram-negative bacterial pathogen that can infect a wide range of marine animals. In previous studies, we have reported a virulent V. harveyi strain, T4D. In the present study, an attenuated mutant of T4D, T4DM, was obtained by selection of rifampicin resistance. Compared to the wild type, T4DM was different in whole-cell protein profile and much slower in growth rate when cultured in stress conditions caused by iron depletion. Virulence analysis showed that compared to T4D, T4DM exhibited a dramatically increased median lethal dose, impaired tissue dissemination capacity, defective hemolytic activity, and significantly reduced resistance against the killing effect of host serum. To examine the potential of T4DM as a live attenuated vaccine, Japanese flounder (Paralichthys olivaceus) were vaccinated with T4DM via intraperitoneal injection or immersion. The results showed that at one and two months post-vaccination, fish administered with T4DM via both approaches, in particular that of immersion, were effectively protected against not only V. harveyi but also Vibrio alginolyticus, another important fish pathogen. Microbiological analysis showed that following immersion vaccination, T4DM was recovered from the internal organs of the vaccinated fish in a time-dependent manner within the first 6 days post-vaccination. Serum antibodies against V. harveyi and V. alginolyticus were detected in T4DM-vaccinated fish, and, compared to serum from control fish, serum from T4DM-vaccinated fish was significantly enhanced in bactericidal activity. These results indicate that T4DM is an attenuated strain with residual infectivity and that T4DM can induce effective cross-species protection against both V. harveyi and V. alginolyticus when used as a live immersion vaccine. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Live Zika virus chimeric vaccine candidate based on a yellow fever 17-D attenuated backbone

    OpenAIRE

    Nougairede, Antoine; Klitting, Raphaelle; Aubry, Fabien; Gilles, Magali; Touret, Franck; De Lamballerie, Xavier

    2018-01-01

    Zika virus (ZIKV) recently dispersed throughout the tropics and sub-tropics causing epidemics associated with congenital disease and neurological complications. There is currently no commercial vaccine for ZIKV. Here we describe the initial development of a chimeric virus containing the prM/E proteins of a ZIKV epidemic strain incorporated into a yellow fever 17-D attenuated backbone. Using the versatile and rapid ISA (Infectious Subgenomic Amplicons) reverse genetics method, we compared diff...

  17. Antigenicity and diagnostic potential of vaccine candidates in human Chagas disease.

    Directory of Open Access Journals (Sweden)

    Shivali Gupta

    Full Text Available Chagas disease, caused by Trypanosoma cruzi, is endemic in Latin America and an emerging infectious disease in the US and Europe. We have shown TcG1, TcG2, and TcG4 antigens elicit protective immunity to T. cruzi in mice and dogs. Herein, we investigated antigenicity of the recombinant proteins in humans to determine their potential utility for the development of next generation diagnostics for screening of T. cruzi infection and Chagas disease.Sera samples from inhabitants of the endemic areas of Argentina-Bolivia and Mexico-Guatemala were analyzed in 1(st-phase for anti-T. cruzi antibody response by traditional serology tests; and in 2(nd-phase for antibody response to the recombinant antigens (individually or mixed by an ELISA. We noted similar antibody response to candidate antigens in sera samples from inhabitants of Argentina and Mexico (n=175. The IgG antibodies to TcG1, TcG2, and TcG4 (individually and TcG(mix were present in 62-71%, 65-78% and 72-82%, and 89-93% of the subjects, respectively, identified to be seropositive by traditional serology. Recombinant TcG1- (93.6%, TcG2- (96%, TcG4- (94.6% and TcG(mix- (98% based ELISA exhibited significantly higher specificity compared to that noted for T. cruzi trypomastigote-based ELISA (77.8% in diagnosing T. cruzi-infection and avoiding cross-reactivity to Leishmania spp. No significant correlation was noted in the sera levels of antibody response and clinical severity of Chagas disease in seropositive subjects.Three candidate antigens were recognized by antibody response in chagasic patients from two distinct study sites and expressed in diverse strains of the circulating parasites. A multiplex ELISA detecting antibody response to three antigens was highly sensitive and specific in diagnosing T. cruzi infection in humans, suggesting that a diagnostic kit based on TcG1, TcG2 and TcG4 recombinant proteins will be useful in diverse situations.

  18. Subunit vaccine candidates against Aeromonas salmonicida in rainbow trout Oncorhynchus mykiss.

    Science.gov (United States)

    Marana, Moonika Haahr; Jørgensen, Louise von Gersdorff; Skov, Jakob; Chettri, Jiwan Kumar; Holm Mattsson, Andreas; Dalsgaard, Inger; Kania, Per Walter; Buchmann, Kurt

    2017-01-01

    Aeromonas salmonicida subsp. salmonicida is the etiological agent of furunculosis and a major fish health problem in salmonid aquaculture worldwide. Injection vaccination with commercial mineral oil-adjuvanted bacterin vaccines has been partly successful in preventing the disease but in Danish rainbow trout (Oncorhynchus mykiss, Walbaum) aquaculture furunculosis outbreaks still occur. In this study we tested the efficacy of experimental subunit vaccines against A. salmonicida infection in rainbow trout. We utilized in silico screening of the proteome of A. salmonicida subsp. salmonicida strain A449 and identified potential protective protein antigens that were tested by in vivo challenge trial. A total of 14 proteins were recombinantly expressed in Escherichia coli and prepared in 3 different subunit vaccine combinations to immunize 3 groups of rainbow trout by intraperitoneal (i.p.) injection. The fish were exposed to virulent A. salmonicida 7 weeks after immunization. To assess the efficacy of the subunit vaccines we evaluated the immune response in fish after immunization and challenge infection by measuring the antibody levels and monitoring the survival of fish in different groups. The survival of fish at 3 weeks after challenge infection showed that all 3 groups of fish immunized with 3 different protein combinations exhibited significantly lower mortalities (17-30%) compared to the control groups (48% and 56%). The ELISA results revealed significantly elevated antibody levels in fish against several protein antigens, which in some cases were positively correlated to the survival.

  19. Subunit vaccine candidates against Aeromonas salmonicida in rainbow trout Oncorhynchus mykiss

    DEFF Research Database (Denmark)

    Marana, Moonika Haahr; Jørgensen, Louise von Gersdorff; Skov, Jakob

    2017-01-01

    rainbow trout (Oncorhynchus mykiss, Walbaum) aquaculture furunculosis outbreaks still occur. In this study we tested the efficacy of experimental subunit vaccines against A. salmonicida infection in rainbow trout. We utilized in silico screening of the proteome of A. salmonicida subsp. salmonicida strain...... A449 and identified potential protective protein antigens that were tested by in vivo challenge trial. A total of 14 proteins were recombinantly expressed in Escherichia coli and prepared in 3 different subunit vaccine combinations to immunize 3 groups of rainbow trout by intraperitoneal (i...

  20. SARS CTL vaccine candidates; HLA supertype-, genome-wide scanning and biochemical validation

    DEFF Research Database (Denmark)

    Sylvester-Hvid, C.; Nielsen, Morten; Lamberth, K.

    2004-01-01

    . Exact knowledge of how the immune system handles protein antigens would allow for the identification of such linear sequences directly, from genomic/proteomic sequence information (Lauemoller et al., Rev Immunogenet 2001: 2: 477-91). The latter was recently established when a causative coronavirus (SARS...

  1. Conservation analysis of dengue virust-cell epitope-based vaccine candidates using peptide block entropy

    DEFF Research Database (Denmark)

    Olsen, Lars Rønn; Zhang, Guang Lan; Keskin, Derin B.

    2011-01-01

    residues. The block entropy analysis provides broad coverage of variant antigens. We applied the block entropy analysis method to the proteomes of the four serotypes of dengue virus (DENV) and found 1,551 blocks of 9-mer peptides, which cover 99% of available sequences with five or fewer unique peptides...

  2. In silico analysis for identifying potential vaccine candidates against Staphylococcus aureus

    OpenAIRE

    Delfani, Somayeh; Imani Fooladi, Abbas Ali; Mobarez, Ashraf Mohabati; Emaneini, Mohammad; Amani, Jafar; Sedighian, Hamid

    2015-01-01

    Purpose Staphylococcus aureus is one of the most important causes of nosocomial and community-acquired infections. The increasing incidence of multiple antibiotic-resistant S. aureus strains and the emergence of vancomycin resistant S. aureus strains have placed renewed interest on alternative means of prevention and control of infection. S. aureus produces a variety of virulence factors, so a multi-subunit vaccine will be more successful for preventing S. aureus infections than a mono-subuni...

  3. Construction and characterization of human rotavirus recombinant VP8* subunit parenteral vaccine candidates.

    Science.gov (United States)

    Wen, Xiaobo; Cao, Dianjun; Jones, Ronald W; Li, Jianping; Szu, Shousun; Hoshino, Yasutaka

    2012-09-21

    Two currently licensed live oral rotavirus vaccines (Rotarix® and RotaTeq®) are highly efficacious against severe rotavirus diarrhea. However, the efficacy of such vaccines in selected low-income African and Asian countries is much lower than that in middle or high-income countries. Additionally, these two vaccines have recently been associated with rare case of intussusception in vaccinated infants. We developed a novel recombinant subunit parenteral rotavirus vaccine which may be more effective in low-income countries and also avert the potential problem of intussusception. Truncated recombinant VP8* (ΔVP8*) protein of human rotavirus strain Wa P[8], DS-1 P[4] or 1076 P[6] expressed in Escherichia coli was highly soluble and was generated in high yield. Guinea pigs hyperimmunized intramuscularly with each of the ΔVP8* proteins (i.e., P[8], P[4] or P[6]) developed high levels of homotypic as well as variable levels of heterotypic neutralizing antibodies. Moreover, the selected ΔVP8* proteins when administered to mice at a clinically relevant dosage, route and schedule, elicited high levels of serum anti-VP8* IgG and/or neutralizing antibodies. Our data indicated that the ΔVP8* proteins may be a plausible additional candidate as new parenteral rotavirus vaccines. Published by Elsevier Ltd.

  4. Cryogenic current leads

    Energy Technology Data Exchange (ETDEWEB)

    Zizek, F.

    1982-01-01

    Theoretical, technical and design questions are examined of cryogenic current leads for SP of magnetic systems. Simplified mathematical models are presented for the current leads. To illustrate modeling, the calculation is made of the real current leads for 500 A and three variants of current leads for 1500 A for the enterprise ''Shkoda.''

  5. Lead - nutritional considerations

    Science.gov (United States)

    ... billion people had toxic (poisonous) blood lead levels. Food Sources Lead can be found in canned goods if there is lead solder in the ... to bottled water for drinking and cooking. Avoid canned goods from foreign ... cans goes into effect. If imported wine containers have a lead foil ...

  6. Supersymmetric gauged scale covariance in ten and lower dimensions

    International Nuclear Information System (INIS)

    Nishino, Hitoshi; Rajpoot, Subhash

    2004-01-01

    We present globally supersymmetric models of gauged scale covariance in ten, six, and four dimensions. This is an application of a recent similar gauging in three dimensions for a massive self-dual vector multiplet. In ten dimensions, we couple a single vector multiplet to another vector multiplet, where the latter gauges the scale covariance of the former. Due to scale covariance, the system does not have a Lagrangian formulation, but has only a set of field equations, like Type IIB supergravity in ten dimensions. As by-products, we construct similar models in six dimensions with N=(2,0) supersymmetry, and four dimensions with N=1 supersymmetry. We finally get a similar model with N=4 supersymmetry in four dimensions with consistent interactions that have never been known before. We expect a series of descendant theories in dimensions lower than ten by dimensional reductions. This result also indicates that similar mechanisms will work for other vector and scalar multiplets in space-time lower than ten dimensions

  7. Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN): could retinoids play a causative role?

    Science.gov (United States)

    Mawson, Anthony R; Eriator, Ike; Karre, Sridhar

    2015-01-12

    Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are overlapping manifestations on a spectrum of acute drug-induced conditions associated with severe blistering, skin peeling, and multi-organ damage. TEN is an eruption resembling severe scalding, with ≥30% skin detachment. SJS is a mild form of TEN, characterized histologically by epidermal keratinocyte apoptosis with dermo-epidermal separation and extensive small blisters with <10% body surface skin detachment. The syndrome can be induced by numerous medications and typically occurs 1-4 weeks after the initiation of therapy. Granulysin is found in the lesions of patients with SJS/TEN and plays a significant pathogenic role in the condition, but the overall mechanisms linking medications, granulysin, and disease manifestations remain obscure. This paper reviews evidence suggesting that the different medications implicated in SJS/TEN have the common property of interacting and synergizing with endogenous retinoids (vitamin A and its congeners), in many instances causing the latter to accumulate in and damage the liver, the main storage organ for vitamin A. It is hypothesized that liver damage leads to the spillage of toxic retinoid compounds into the circulation, resulting in an endogenous form of hypervitaminosis A and cytotoxicity with widespread apoptosis, mediated by granulysin and recognized as SJS/TEN. Subject to testing, the model suggests that symptom worsening could be arrested at onset by lowering the concentration of circulating retinoids and/or granulysin via phlebotomy or plasmapheresis or by pharmacological measures to limit their expression.

  8. Nonresponse Error in Mail Surveys: Top Ten Problems

    Directory of Open Access Journals (Sweden)

    Jeanette M. Daly

    2011-01-01

    Full Text Available Conducting mail surveys can result in nonresponse error, which occurs when the potential participant is unwilling to participate or impossible to contact. Nonresponse can result in a reduction in precision of the study and may bias results. The purpose of this paper is to describe and make readers aware of a top ten list of mailed survey problems affecting the response rate encountered over time with different research projects, while utilizing the Dillman Total Design Method. Ten nonresponse error problems were identified, such as inserter machine gets sequence out of order, capitalization in databases, and mailing discarded by postal service. These ten mishaps can potentiate nonresponse errors, but there are ways to minimize their frequency. Suggestions offered stem from our own experiences during research projects. Our goal is to increase researchers' knowledge of nonresponse error problems and to offer solutions which can decrease nonresponse error in future projects.

  9. Mid-term evaluation of ten National Research schools

    DEFF Research Database (Denmark)

    Gustafsson, Göran; Dahl, Hanne Marlene; Gustafsson, Christina

    the scheme was launched, the Research Council has issued three calls for proposals and allocated grants to a total of 22 national research schools. Five were started up in 2009, ten in 2013 and seven in 2015. A Nordic scientific programme committee was appointed in 2013, with responsibility for assessing...... grant applications, monitoring the progress of the FORSKERSKOLER scheme and serving as the evaluation panel for the mid-term evaluation in 2013 and in 2016/2017. The task of the evaluation panel has been to: 1) evaluate the quality of and progress achieved by the ten research schools which were awarded...... funding in 2012 and launched in 2013; and 2) to provide recommendations as to whether funding should be continued to cover the full eight-year period or terminated after five years. Continued funding is recommended for all ten schools to cover the full eight-year period, according to the proposed budget...

  10. Astrophysical parameters of ten poorly studied open star clusters

    International Nuclear Information System (INIS)

    Tadross, Ashraf Latif; El-Bendary, Reda; Osman, Anas; Ismail, Nader; Bakry, Abdel Aziz

    2012-01-01

    We present the fundamental parameters of ten open star clusters, nominated from Kronberger et al. who presented some newly discovered stellar groups on the basis of the Two Micron All Sky Survey photometry and Digitized Sky Survey visual images. Star counts and photometric parameters (radius, membership, distance, color excess, age, luminosity function, mass function, total mass, and dynamical relaxation time) have been determined for these ten clusters for the first time. In order to calibrate our procedures, the main parameters (distance, age, and color excess) have been re-estimated for another five clusters, which are also studied by Kronberger et al. (research papers)

  11. Time in powers of ten natural phenomena and their timescales

    CERN Document Server

    't Hooft, Gerard

    2014-01-01

    In this richly illustrated book, Nobel Laureate Gerard 't Hooft and Theoretical Physicist Stefan Vandoren describe the enormous diversity of natural phenomena that take place at different time scales. In the tradition of the bestseller Powers of Ten , the authors zoom in and out in time, each step with a factor of ten. Starting from one second, time scales are enlarged until processes are reached that take much longer than the age of the universe. After the largest possible eternities, the reader is treated to the shortest and fastest phenomena known. Then the authors increase with powers of t

  12. Von Blüten, Göttern und Gelehrten

    OpenAIRE

    Zotter, Astrid

    2013-01-01

    Der Sanskrittext Puṣpacintāmaṇi (PuCi) behandelt Blüten als Darbringungen (upacāra) im wichtigsten hinduistischen Verehrungsritual, der pūjā. In ca. 400 Strophen werden über 200 Namen von Blüten genannt und für verschiedene Gottheiten und pūjās als geeignete oder ungeeignete Gaben vorgeschrieben. Der Text ist eine Kompilation (Nibandha), in der die Inhalte aus 47 namentlich genannten Quellentexten referiert werden. Ziel der Dissertation ist es nicht nur, diesen Text, der 1966 zum ersten Ma...

  13. Reactor dosimetry calibrations in the Big Ten critical assembly

    International Nuclear Information System (INIS)

    Barr, D.W.; Hansen, G.E.

    1977-01-01

    Eleven irradiations of foil packs located in the central region of Big Ten were made for the Interlaboratory Reaction Rate Program. Each irradiation was at a nominal 10 15 fluence and the principal fluence monitor was the National Bureau of Standards' double fission chamber containing 235 U and 238 U deposits and located at the center of Big Ten. Secondary monitors consisted of three external fission chambers and two internal foil sets containing Au, In, and Al. Activities of one set were counted at the LASL and the other at the Hanford Engineering Developement Laboratory. The uncertainty in relative fluence for each irradiation was +-0.3%

  14. Fabrication of ten-fold photonic quasicrystalline structures

    Directory of Open Access Journals (Sweden)

    XiaoHong Sun

    2015-05-01

    Full Text Available Compared to periodic crystals, quasicrystals have higher point group symmetry and are more favorable in achieving complete band-gaps. In this report, a top-cut prism interferometer is designed to fabricate ten-fold photonic quasicrystalline structures. By optimizing the exposing conditions and material characteristics, appropriate quasicrystals have been obtained in the SU8 photoresist films. Atomic Force Microscopy and laser diffraction are used to characterize the fabricated structures. The measurement results show the consistence between the theoretical design and experiments. This will provide guidance for the large-area and fast production of ten-fold quasicrystalline structures with high quality.

  15. How green are the TEN-T core network corridors?

    DEFF Research Database (Denmark)

    Panagakos, George; Psaraftis, Harilaos N.

    defining this concept, identified the characteristics that distinguish a green corridor from an otherwise efficient one. The main thesis of this paper is that the „core network corridors‟ of the new TEN-T guidelines exhibit all these qualities and the vision of a green corridor network in Europe is close...... to reality. To support this thesis, and in continuation of the work of SuperGreen, the paper examines the proposed new „guidelines‟ for the development of the TEN-T after presenting a brief history of transport network development in Europe....

  16. Dosimetry results for Big Ten and related benchmarks

    International Nuclear Information System (INIS)

    Hansen, G.E.; Gilliam, D.M.

    1980-01-01

    Measured average reaction cross sections for the Big Ten central flux spectrum are given together with calculated values based on the U.S. Evaluated Nuclear Data File ENDF/B-IV. Central reactivity coefficients for 233 U, 235 U, 239 Pu, 6 Li and 10 B are given to check consistency of bias between measured and calculated reaction cross sections for these isotopes. Spectral indexes for the Los Alamos 233 U, 235 U and 239 Pu metal critical assemblies are updated, utilizing the Big Ten measurements and interassembly calibrations, and their implications for inelastic scattering are reiterated

  17. Lead inclusions in aluminium

    International Nuclear Information System (INIS)

    Johnson, E.; Johansen, A.; Sarholt-Kristensen, L.; Andersen, H.H.; Grabaek, L.; Bohr, J.

    1990-01-01

    Ion implantation at room temperature of lead into aluminum leads to spontaneous phase separation and formation of lead precipitates growing topotactically with the matrix. Unlike the highly pressurized (∼ 1-5 GPa) solid inclusions formed after noble gas implantations, the pressure in the lead precipitates is found to be less than 0.12 GPa. Recently the authors have observed the result that the lead inclusions in aluminum exhibit both superheating and supercooling. In this paper they review and elaborate on these results. Small implantation-induced lead precipitates embedded in an aluminum matrix were studied by x-ray diffraction

  18. VOLUMETRIC LEAD ASSAY

    International Nuclear Information System (INIS)

    Ebadian, M.A.; Dua, S.K.; Roelant, David; Kumar, Sachin

    2001-01-01

    This report describes a system for handling and radioassay of lead, consisting of a robot, a conveyor, and a gamma spectrometer. The report also presents a cost-benefit analysis of options: radioassay and recycling lead vs. disposal as waste

  19. CYSTINURIA - A TEN-YEAR FOLLOW-UP OF THE PATIENTS

    Directory of Open Access Journals (Sweden)

    Anđelka Slavković

    2001-09-01

    Full Text Available In the period from 1991 to 2001 there were four patients followed up who suffered from cystinuria and cystine calcinosis. The therapy consisting of the cystine dilution in the urine by a great taking-in of liquids and the urine alkalization was combined with alphamercaptopropione glycine and captoprile that bind cystine as well as a respective diet. Alphamercaptopropione glycine leads to the reduction of the already-formed calculus and their easier treatment in the case of a possible need for extracorporeal lithotripsy (ESWEL. During the ten-year follow-up of a small series of patients there were no complications related to the medicament treatment.

  20. Large scale exact quantum dynamics calculations: Ten thousand quantum states of acetonitrile

    Science.gov (United States)

    Halverson, Thomas; Poirier, Bill

    2015-03-01

    'Exact' quantum dynamics (EQD) calculations of the vibrational spectrum of acetonitrile (CH3CN) are performed, using two different methods: (1) phase-space-truncated momentum-symmetrized Gaussian basis and (2) correlated truncated harmonic oscillator basis. In both cases, a simple classical phase space picture is used to optimize the selection of individual basis functions-leading to drastic reductions in basis size, in comparison with existing methods. Massive parallelization is also employed. Together, these tools-implemented into a single, easy-to-use computer code-enable a calculation of tens of thousands of vibrational states of CH3CN to an accuracy of 0.001-10 cm-1.

  1. NA49: lead-lead collision

    CERN Multimedia

    1996-01-01

    This is an image of an actual lead ion collision taken from tracking detectors on the NA49 experiment, part of the heavy ion project at CERN. These collisions produce a very complicated array of hadrons as the heavy ions break up. It is hoped that one of these collisions will eventually create a new state of matter known as quark-gluon plasma.

  2. Uranium-lead systematics

    International Nuclear Information System (INIS)

    Wickman, F.E.

    1983-01-01

    The method of Levchenkov and Shukolyukov for calculating age and time disturbance of minerals without correction for original lead is generalized to include the cases when (1) original lead and radiogenic lead leach differently, and (2) the crystals studied consist of a core and a mantle. It is also shown that a straight line obtained from the solution of the equations is the locus of the isotopic composition of original lead. (Auth.)

  3. Atrioventricular Pacemaker Lead Reversal

    Directory of Open Access Journals (Sweden)

    Mehmet K Aktas, MD

    2007-01-01

    Full Text Available During cardiac surgery temporary epicardial atrial and ventricular leads are placed in case cardiac pacing is required postoperatively. We present the first reported series of patients with reversal of atrioventricular electrodes in the temporary pacemaker without any consequent deleterious hemodynamic effect. We review the electrocardiographic findings and discuss the findings that lead to the discovery of atrioventricular lead reversal.

  4. Lead Poisoning (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Lead Poisoning KidsHealth / For Parents / Lead Poisoning What's in ... Print en español La intoxicación por plomo About Lead Poisoning If you have young kids, it's important ...

  5. Frequency of diabetic retinopathy in patients after ten years of diagnosis of type 2 diabetes mellitus

    International Nuclear Information System (INIS)

    Shaikh, M.A.; Yakta, D.E.

    2010-01-01

    Background: Diabetic retinopathy is one of the most common and serious complications of type 2 diabetes mellitus and a leading cause of blindness not only in Pakistan but also worldwide. So we conducted this study to record the frequency of diabetic retinopathy in known diabetic patients ten years after diagnosis of type 2 diabetes mellitus. Methods: The study was conducted at Liaquat University of Medical and Health Sciences, Jamshoro, Pakistan for a period of 1 year from January 2008 to January 2010. The study group comprised of 200 patients of type 2 diabetes mellitus attending the medical clinic. All patients who were diagnosed as type 2 diabetes mellitus since ten years duration were included in the study. Retinopathy was graded into background, pre proliferative and proliferative retinopathy. Type 2 diabetes was diagnosed using the WHO criteria. Statistical analysis was carried out using the SPSS-11. Results: Diabetic retinopathy was found in 25.5% of the total Type 2 patients after ten years of diagnosis, and of these 4% of patients had proliferative retinopathy. Conclusion: Type 2 diabetic patients should be screened as early as possible to prevent permanent visual loss by timely management of diabetic retinopathy because diabetes is one of most common preventable cause of blindness in the world. (author)

  6. The Openhearted Audience: Ten Authors Talk about Writing for Children.

    Science.gov (United States)

    Haviland, Virginia, Ed.

    This book contains comments by ten authors of children's literature concerning the influences they feel account for the particular qualities that define their books and about creative writing and children's literature in general. In the first article, P. L. Travers stresses the importance of fairy tales, myths, and legends in shaping her work,…

  7. Quantum golden field theory - Ten theorems and various conjectures

    International Nuclear Information System (INIS)

    El Naschie, M.S.

    2008-01-01

    Ten theorems and few conjectures related to quantum field theory as applied to high energy physics are presented. The work connects classical quantum field theory with the golden mean renormalization groups of non-linear dynamics and E-Infinity theory

  8. Net Survey: "Top Ten Mistakes" in Academic Web Design.

    Science.gov (United States)

    Petrik, Paula

    2000-01-01

    Highlights the top ten mistakes in academic Web design: (1) bloated graphics; (2) scaling images; (3) dense text; (4) lack of contrast; (5) font size; (6) looping animations; (7) courseware authoring software; (8) scrolling/long pages; (9) excessive download; and (10) the nothing site. Includes resources. (CMK)

  9. Ten years into the marshes – Hapalemur alaotrensis conservation ...

    African Journals Online (AJOL)

    Natural resource management problems typically involve a multitude of stakeholders with diverse sets of needs and interests, and often conflicting worldviews in an ... during the past ten years at Lake Alaotra, discussing the plan of action and challenges for environmental education, ecotourism and alternative livelihoods.

  10. A critical comparison of ten disposable cup LCAs

    NARCIS (Netherlands)

    Harst, van der E.J.M.; Potting, J.

    2013-01-01

    Disposable cups can be made from conventional petro-plastics, bioplastics, or paperboard (coated with petro-plastics or bioplastics). This study compared ten life cycle assessment (LCA) studies of disposable cups with the aim to evaluate the robustness of their results. The selected studies have

  11. Socio-Demographic Determinants of Eclampsia in Calabar; A Ten ...

    African Journals Online (AJOL)

    A ten-year review of the socio-demographic determinants of eclampsia was ... had past histories of eclampsia, while in 7 (18.4%) cases history of change of ... no formal education and 34.25% were subsistence farmers living in the suburbs of ...

  12. Ten colour photometry of twelve Ap-stars

    International Nuclear Information System (INIS)

    Musielok, B.; Lange, D.; Schoeneich, W.; Hildebrandt, G.; Zelwanowa, E.; Hempelmann, A.; Salmanov, G.

    1980-01-01

    Ten-colour photoelectric observations are presented for twelve Ap-stars. Improved ephemeris for seven of them is given. Phase relations between the light curves and line intensity variations are discussed. The problem of the electromagnetic flux conctancy of IOTA Cas is approached from a qualitative point of view. (author)

  13. The Texas Ten Percent Plan's Impact on College Enrollment

    Science.gov (United States)

    Daugherty, Lindsay; Martorell, Paco; McFarlin, Isaac, Jr.

    2014-01-01

    The Texas Ten Percent Plan (TTP) provides students in the top 10 percent of their high-school class with automatic admission to any public university in the state, including the two flagship schools, the University of Texas at Austin and Texas A&M. Texas created the policy in 1997 after a federal appellate court ruled that the state's previous…

  14. Ten Strengths of How Teachers Do Cooperative Learning

    Science.gov (United States)

    Jaocbs, George M.

    2016-01-01

    Cooperative learning involves students in working together with peers to learn, to develop learning skills and to enjoy the learning process. This paper examines ten areas in which the author believes he and other teachers do cooperative learning well. These areas are: (1) keeping group size small, usually four or fewer; (2) encouraging students…

  15. Ten Indicators of Vitality in Smaller Academic Libraries

    Science.gov (United States)

    Pappas, David

    2009-01-01

    This paper provides a means of quickly ascertaining the relative health of smaller academic libraries by presenting a top ten list of vitality indicators. The list is based on an observational convenience sampling of thirty smaller academic libraries across the United States. The indicators making the list were those which appeared most often in…

  16. Ten questions about radiant heating and cooling systems

    DEFF Research Database (Denmark)

    Rhee, Kyu-Nam; Olesen, Bjarne W.; Kim, Kwang Woo

    2017-01-01

    to extend the applicability of the RHC system are providing the continuous impetus for research on RHC systems. This paper summarizes the important issues involved in the research on RHC system, whereby ten questions and answers concerning the RHC system are discussed, which will help researchers to conduct...

  17. Ten-year-olds' reflections on their life in preschool

    DEFF Research Database (Denmark)

    Broström, Stig

    2016-01-01

    What do children think of their time in preschool? In the present study, twelve ten-year-old children collected data from their classmates. The children tend to remember their friends, and reflect on what games they played and with whom. Only about one in three respondents even mentioned the day...

  18. Unified SU(4) color models in ten dimensions

    International Nuclear Information System (INIS)

    Hanlon, B.E.; Joshi, G.C.

    1992-01-01

    Some aspects of constructing unified models with SU(4) as the color group via a unifying group defined in ten dimensions are examined. Four dimensional theories are recovered using the Coset Space Dimensional Reduction scheme. Candidate models are considered in order to highlight some of the difficulties in constructing realistic four dimensional theories. 30 refs

  19. Technical descriptions of ten irrigation technologies for conserving energy

    Energy Technology Data Exchange (ETDEWEB)

    Harrer, B.J.; Wilfert, G.L.

    1983-05-01

    Technical description of ten technologies which were researched to save energy in irrigated agriculture are presented. These technologies are: well design and development ground water supply system optimization, column and pump redesign, variable-speed pumping, pipe network optimization, reduced-pressure center-pivot systems, low-energy precision application, automated gated-pipe system, computerized irrigation scheduling, and instrumented irrigation scheduling. (MHR)

  20. Reliability and validity of ten consumer activity trackers

    NARCIS (Netherlands)

    Kooiman, Thea; Dontje, Manon L.; Sprenger, Siska; Krijnen, Wim; van der Schans, Cees; de Groot, Martijn

    2015-01-01

    Background: Activity trackers can potentially stimulate users to increase their physical activity behavior. The aim of this study was to examine the reliability and validity of ten consumer activity trackers for measuring step count in both laboratory and free-living conditions. Method: Healthy

  1. Ten Questions about the Future of Art and Design Education.

    Science.gov (United States)

    Steers, John

    1997-01-01

    Asks ten questions about the future of art, crafts, and design education. Focuses on why art, crafts, and design education should be included in the curriculum; how the curriculum should be defined; and how art educators should respond to conflicting calls for cultural relativism and for cultural nationalism. (DSK)

  2. Eight to ten years follow-up after carotid endarterectomy

    DEFF Research Database (Denmark)

    Knudsen Rathenborg, Lisbet; Sillesen, H; Schroeder, T

    1990-01-01

    Follow-up information was obtained on 185 patients who consecutively underwent carotid endarterectomy eight to ten years previously. Doppler ultrasound examination was performed in 59 patients who were still alive and living within 100 miles of the hospital. Using lifetable analysis, the annual r...

  3. Does the Russian Economy Need Human Capital? Ten Doubts

    Science.gov (United States)

    Gimpelson, V. E.

    2016-01-01

    It is generally accepted that human capital is an important factor in economic growth, but its impact on growth depends on the demand for education and skills on the labor market. Demand for human capital is largely determined by the institutional environment that governs the basic conditions for economic activity. The author expresses ten doubts…

  4. Changes in users' Web search performance after ten years ...

    African Journals Online (AJOL)

    The changes in users' Web search performance using search engines over ten years was investigated in this study. Matched data obtained from samples in 2000 and 2010 were used for the comparative analysis. The patterns of Web search engine use suggested a dominance in using a particular search engine. Statistical ...

  5. Superconductivity in nanostructured lead

    Science.gov (United States)

    Lungu, Anca; Bleiweiss, Michael; Amirzadeh, Jafar; Saygi, Salih; Dimofte, Andreea; Yin, Ming; Iqbal, Zafar; Datta, Timir

    2001-01-01

    Three-dimensional nanoscale structures of lead were fabricated by electrodeposition of pure lead into artificial porous opal. The size of the metallic regions was comparable to the superconducting coherence length of bulk lead. Tc as high as 7.36 K was observed, also d Tc/d H was 2.7 times smaller than in bulk lead. Many of the characteristics of these differ from bulk lead, a type I superconductor. Irreversibility line and magnetic relaxation rates ( S) were also studied. S( T) displayed two maxima, with a peak value about 10 times smaller than that of typical high- Tc superconductors.

  6. Lead in the environment

    Science.gov (United States)

    Pattee, Oliver H.; Pain, Deborah J.; Hoffman, David J.; Rattner, Barnett A.; Burton, G. Allen; Cairns, John

    2003-01-01

    Anthropogenic uses of lead have probably altered its availability and environmental distribution more than any other toxic element. Consequently, lead concentrations in many living organisms may be approaching thresholds of toxicity for the adverse effects of lead. Such thresholds are difficult to define, as they vary with the chemical and physical form of lead, exposure regime, other elements present and also vary both within and between species. The technological capability to accurately quantify low lead concentrations has increased over the last decade, and physiological and behavioral effects have been measured in wildlife with tissue lead concentrations below those previously considered safe for humans.s.236 Consequently. lead criteria for the protection of wildlife and human health are frequently under review, and 'thresholds' of lead toxicity are being reconsidered. Proposed lead criteria for the protection of natural resources have been reviewed by Eisler. Uptake of lead by plants is limited by its generally low availability in soils and sediments, and toxicity may be limited by storage mechanisms and its apparently limited translocation within most plants. Lead does not generally accumulate within the foliar parts of plants, which limits its transfer to higher trophic levels. Although lead may concentrate in plant and animal tissues, no evidence of biomagnification exists. Acid deposition onto surface waters and soils with low buffering capacity may influence the availability of lead for uptake by plants and animals, and this may merit investigation at susceptible sites. The biological significance of chronic low-level lead exposure to wildlife is sometimes difficult to quantify. Animals living in urban environments or near point sources of lead emission are inevitably subject to greater exposure to lead and enhanced risk of lead poisoning. Increasingly strict controls on lead emissions in many countries have reduced exposure to lead from some sources

  7. ALICE: Simulated lead-lead collision

    CERN Multimedia

    2003-01-01

    This track is an example of simulated data modelled for the ALICE detector on the Large Hadron Collider (LHC) at CERN, which will begin taking data in 2008. ALICE will focus on the study of collisions between nuclei of lead, a heavy element that produces many different particles when collided. It is hoped that these collisions will produce a new state of matter known as the quark-gluon plasma, which existed billionths of a second after the Big Bang.

  8. Transcutaneous electric nerve stimulation (TENS) for cancer pain in adults.

    Science.gov (United States)

    Hurlow, Adam; Bennett, Michael I; Robb, Karen A; Johnson, Mark I; Simpson, Karen H; Oxberry, Stephen G

    2012-03-14

    Cancer-related pain is complex and multi-dimensional but the mainstay of cancer pain management has predominantly used a biomedical approach. There is a need for non-pharmacological and innovative approaches. Transcutaneous Electric Nerve Stimulation (TENS) may have a role in pain management but the effectiveness of TENS is currently unknown. This is an update of the original review published in Issue 3, 2008. The aim of this systematic review was to determine the effectiveness of TENS for cancer-related pain in adults. The initial review searched The Cochrane Library, MEDLINE, EMBASE, CINAHL, PsychINFO, AMED and PEDRO databases in April 2008. We performed an updated search of CENTRAL, MEDLINE, EMBASE, CINAHL and PEDRO databases in November 2011. We included only randomised controlled trials (RCTS) investigating the use of TENS for the management of cancer-related pain in adults. The search strategy identified a further two studies for possible inclusion. One of the review authors screened each abstract using a study eligibility tool. Where eligibility could not be determined, a second author assessed the full paper. One author used a standardised data extraction sheet to collect information on the studies and independently assess the quality of the studies using the validated five-point Oxford Quality Scale. The small sample sizes and differences in patient study populations of the three included studies (two from the original review and a third included in this update) prevented meta-analysis. For the original review the search strategy identified 37 possible published studies; we divided these between two pairs of review authors who decided on study selection; all four review authors discussed and agreed final scores. Only one additional RCT met the eligibility criteria (24 participants) for this updated review. Although this was a feasibility study, not designed to investigate intervention effect, it suggested that TENS may improve bone pain on movement in a

  9. Ten Tips for Parents to Help Their Children Avoid Teen Pregnancy

    Science.gov (United States)

    ... we do » Resource library » Ten tips for parents Ten Tips for Parents to Help Their Children Avoid Teen Pregnancy Publication Created with Sketch. Ten Tips for Parents to Help Their Children Avoid ...

  10. Secondary lead production

    Energy Technology Data Exchange (ETDEWEB)

    Hollis, R.G.

    1990-10-16

    This invention is concerned with the efficient recovery of soft lead from the paste component of used automobile lead-acid storage batteries. According to the invention, a scrap which contains lead oxide, lead sulfate, and antimony in an oxidized state is processed in the following steps to recover lead. A refractory lined reaction vessel is continuously charged with the scrap, along with a reductant effective for reducing lead oxide. The charged material is melted and agitated by means of a submerged lance at 900-1150{degree}C whereby some of the lead oxide of the scrap is reduced to form molten lead. A slag layer is then formed above the molten lead, and an amount of lead oxide is maintained in the slag layer. The molten lead, now containing under 0.5 wt % of antimony, is removed, and the antimony oxide in the scrap is concentrated as oxide in the slag layer. Preferred embodiments of the invention result in the production, in a single step, of a soft lead substantially free of antimony. The slag may be subsequently treated to reduce the antimony oxide and produce a valuable antimony-lead product. Further advantages of the process are that a wet battery paste may be used as the feed without prior drying, and the process can be conducted at a temperature 100-150{degree}C lower than in previously known methods. In addition, a smaller reactor can be employed which reduces both capital cost and fuel costs. The process of the invention is illustrated by descriptions of pilot plant tests. 1 fig.

  11. Lead-Free Piezoelectrics

    CERN Document Server

    Nahm, Sahn

    2012-01-01

    Ecological restrictions in many parts of the world are demanding the elimination of Pb from all consumer items. At this moment in the piezoelectric ceramics industry, there is no issue of more importance than the transition to lead-free materials. The goal of Lead-Free Piezoelectrics is to provide a comprehensive overview of the fundamentals and developments in the field of lead-free materials and products to leading researchers in the world. The text presents chapters on demonstrated applications of the lead-free materials, which will allow readers to conceptualize the present possibilities and will be useful for both students and professionals conducting research on ferroelectrics, piezoelectrics, smart materials, lead-free materials, and a variety of applications including sensors, actuators, ultrasonic transducers and energy harvesters.

  12. Lead Poison Detection

    Science.gov (United States)

    1976-01-01

    With NASA contracts, Whittaker Corporations Space Science division has developed an electro-optical instrument to mass screen for lead poisoning. Device is portable and detects protoporphyrin in whole blood. Free corpuscular porphyrins occur as an early effect of lead ingestion. Also detects lead in urine used to confirm blood tests. Test is inexpensive and can be applied by relatively unskilled personnel. Similar Whittaker fluorometry device called "drug screen" can measure morphine and quinine in urine much faster and cheaper than other methods.

  13. [THE TEN MOST CITED ARTICLES OF THE JOURNAL "NUTRICION HOSPITALARIA"].

    Science.gov (United States)

    Franco-López, Ángeles; González-Gallego, Javier; Sanz-Valero, Javier; Tuñón, María Jesús; García-De-Lorenzo, Abelardo; Culebras, Jesús M

    2015-12-01

    After 36 years of continued publication of the journal Nutrición Hospitalaria, a list with the ten most cited articles published in it is elaborated. The top ten most cited articles in the world literature and stratification according to language, English or Spanish, subject, or period of time published are also analyzed. Nutr Hosp is the most important Ibero latin American nutrition journal. Nutr Hosp published 369 items in 2014 gaining the fourth position among all the world's journals devoted to nutrition. Article publication in English, or simultaneously in Spanish and English and Open Access policy probably benefit the number of citations. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  14. Lead-210, polonium-210, and stable lead in the food-chain lichen, reindeer and man

    International Nuclear Information System (INIS)

    Persson, B.R.

    1972-01-01

    The measurements of stable lead and the natural fallout radionuclides lead-210 and polonium-210 in communities of lichen (Cladonia alpestris) in central Sweden from 1961 to 1970 indicate a quite constant level. The average lead-210 content per unit area in lichen carpets was found to be 15 +- 2 nCi m -2 , the average lead-210 activity concentration 6.7 +- 0.9 nCi per kg dry weight and the lead-210 specific activity 630 +- 60 nCi per g of stable lead. The polonium-210/lead-210 activity ratio was about 0.9 +- 0.1. The vertical distribution of lead-210 in the lichen carpet showed a maximum concentration in the top layer. The distribution was similar during 1967 and 1968 but the low amount of precipitation during 1968 and 1969 disturbed the distribution pattern in 1969 and 1970. The transfer of lead-210, polonium-210 and stable lead through the food chain: lichen, reindeer, and man was characterized. The absorbed dose rate in Lapps due to polonium-210 was estimated to be about 6 to 8 mrad per year in gonads and 8 to 20 mrad per year in bone tissues. This is about ten percent of their entire absorbed dose contribution from all natural radiation sources. (U.S.)

  15. TEN KEY CONCEPTS AND THE SUCCESS OF ROMANIAN ORGANIZATIONS

    Directory of Open Access Journals (Sweden)

    Ada Mirela TOMESCU

    2006-01-01

    Full Text Available This paper is focused on ten key concepts which influence the success of theorganizations at the beginning of XXI century. The great changes generatedby globalization determine firms to be more competitive. This means that wehave to focus on: mission, leadership, emotional intelligence, innovation,organizational culture, human resources, total quality management, ethics,conflict management, brand, and the value offered to the clients.

  16. Ventilation: Exploitation and maintenance. Ten years of experience

    International Nuclear Information System (INIS)

    Letertre, J.

    1990-01-01

    The evolution and the maintenance operations performed during the last ten years on the ventilation-air-conditioning system at the Hague plant are presented. The modifications operated in the ventilation-air-conditioning system were carried out in order to answer the safety requirements evolution due to the increase of the plant productivity. The choice and the results of the maintenance policies, defined as a function of the safety, quality and cost requirements, are presented [fr

  17. Noble gases in ten stone meteorites from Antarctica

    International Nuclear Information System (INIS)

    Weber, H.W.; Schultz, L.

    1980-01-01

    The concentrations and isotopic composition of noble gases have been determined in all ten stone meteorites recovered in Antarctica during 1976-1977 by a U.S.-Japanese expedition. From a comparison of spallogenic and radiogenic gas components it is concluded that the chondrites Mt. Baldr (a) and Mt. Baldr (b) belong to the same fall but that all other stone meteorites are individual finds. (orig.)

  18. Assisted reproductive technologies in South Dakota: the first ten years.

    Science.gov (United States)

    Brannian, John; Hansen, Keith

    2006-07-01

    One in six couples experience infertility. New assisted reproductive technologies such as in vitro fertilization (IVF) have helped thousands of couples worldwide to have a family. IVF has been available in South Dakota for the past ten years. Improvements in the clinic and laboratory have led to better live birth rates and lower incidences of multiple pregnancies. Advances in technology will help even more people overcome fertility problems in the near future.

  19. Equivalence of ten different discounted cash flow valuation methods

    OpenAIRE

    Fernandez, Pablo

    2004-01-01

    This paper shows that ten methods of company valuation using discounted cash flows (WACC; equity cash flow; capital cash flow; adjusted present value; residual income; EVA; business's risk-adjusted equity cash flow; business's risk-adjusted free cash flow; risk-free-adjusted equity cash flow; and risk-free-adjusted free cash flow) always give the same value when identical assumptions are used. This result is logical, since all the methods analyze the same reality using the same assumptions; t...

  20. Ten years campaign of Economical Heating: Successfull and educative

    International Nuclear Information System (INIS)

    Van den Brink, L.J.

    1992-01-01

    A review is given of the origin, the evolution and the results of the title campaign held by the natural gas and energy distribution companies in the Netherlands during the last ten years. The campaign is discussed against the background of the unique position of natural gas in the Netherlands within the context of the environmental protection activities of the energy distribution companies. 1 fig., 5 ills., 9 tabs

  1. Ten Challenges of the Amyloid Hypothesis of Alzheimer's Disease

    DEFF Research Database (Denmark)

    Kepp, Kasper Planeta

    2017-01-01

    The inability to effectively halt or cure Alzheimer's disease (AD), exacerbated by the recent failures of high-profile clinical trials, emphasizes the urgent need to understand the complex biochemistry of this major neurodegenerative disease. In this paper, ten central, current challenges...... as a background model of the disease, unify our understanding of the interplay between genetic and non-genetic risk factors, and combine into one framework both the familial and sporadic forms of the disease....

  2. Constructing unified models based on E8 in ten dimensions

    International Nuclear Information System (INIS)

    Kapetanakis, D.

    1992-01-01

    We examine the virtues and difficulties of the attempts to construct realistic four-dimensional models from a gauge theory based on E 8 and defined in ten dimensions. The four-dimensional theories are obtained using the coset space dimensional reduction scheme. Some of our points and in particular the proposed mechanism for supersymmetry breaking might be useful in other dimensional reduction schemes. (orig.)

  3. Modification of the 'ten-day rule'

    Energy Technology Data Exchange (ETDEWEB)

    Klempfner, G.

    1985-02-01

    In a 1964 decision the National Health and Medical Research Council recommended that radiological examinations of the lower abdomen and pelvis of women of childbearing age should be confined to the 10-day interval following the onset of menstruation. Recent evidence suggests that the first four weeks from the first day of the last menstrual period is not a critically radiosensitive period and consequently strict adherence to the ten-day rule is no longer indicated.

  4. Elliot Lake uranium mine reclamation, the first ten years

    International Nuclear Information System (INIS)

    Payne, R.A.

    2000-01-01

    In 1989, Rio Algom Limited finalized its plans for the closure and subsequent decommissioning of two of its then three operating mines in Elliot Lake as a result of market conditions. These two mines closed in August 1990. These mine closures had significant impacts. The principal mining operations of Rio Algom at that time were still in Elliot Lake and had been the very foundation of the company for about 40 years. The business impact on the Corporation was regarded as possibly severe. The resultant layoff of over 1,500 long-term, highly qualified, skilled and well-paid employees, a devastating blow to the affected employees and their families, would have a significant financial impact on the municipal economy, particularly as this announcement was seen as the first step in the early closure of all four operating mines in the region. At that time there was little precedence for such a high profile mine closure program and consequently the many unknowns relating to the mine decommissioning process, legislative requirements and society's expectations resulted in a perception of a significant yet ill-defined liability. In this atmosphere of understandable company, stakeholder and public concern, Rio Algom Limited embarked on what has turned out to be a long, rigorous, challenging yet ultimately reasonable and rewarding process of progressive reclamation of all its Elliot Lake mines, some ten in total (nine uranium, one copper). Over the past ten years, reclamation of all ten mines has been successfully completed, some $70 m plus has been expended in direct site reclamation works and the workforce has been reduced from over 2,500 to just 4. After ten years, the focus of attention is now on the long-term care, maintenance, monitoring and reporting required for the decommissioned mine sites, and the accomplishment of this in the best interests of all the stakeholders. (author)

  5. Ten inherited disorders in purebred dogs by functional breed groupings

    OpenAIRE

    Oberbauer, A. M.; Belanger, J. M.; Bellumori, T.; Bannasch, D. L.; Famula, T. R.

    2015-01-01

    Background Analysis of 88,635 dogs seen at the University of California, Davis Veterinary Medical Teaching Hospital from 1995 to 2010 identified ten inherited conditions having greater prevalence within the purebred dog population as compared to the mixed-breed dog population: aortic stenosis, atopy/allergic dermatitis, gastric dilatation volvulus (GDV), early onset cataracts, dilated cardiomyopathy, elbow dysplasia, epilepsy, hypothyroidism, intervertebral disk disease (IVDD), and hepatic po...

  6. A chemical reaction in the movie The Ten Commandments

    Directory of Open Access Journals (Sweden)

    López Pérez, José Pedro;

    2012-04-01

    Full Text Available The study of natural sciences in the second year of Secondary Education must be complemented with a visit to the laboratory, where experiments should be permormed. The curriculum emphasizes the initial basis of Chemistry and the study of reactions. In this paper we describe a laboratory experience, useful for understanding the concept of chemical change. Also, we present the hypothesis that a chemical reaction was used in the classic movie The Ten Commandments.

  7. Lead intoxication in dogs: risk assessment of feeding dogs trimmings of lead-shot game.

    Science.gov (United States)

    Høgåsen, Helga R; Ørnsrud, Robin; Knutsen, Helle K; Bernhoft, Aksel

    2016-07-25

    Expanding lead-based bullets, commonly used for hunting of big game, produce a scattering of lead particles in the carcass around the wound channel. Trimmings around this channel, which are sometimes fed to dogs, may contain lead particles. The aim of this study was to assess potential health effects of feeding dogs such trimmings. Lead ingestion most commonly causes gastrointestinal and neurological clinical signs, although renal, skeletal, haematological, cardiovascular and biochemical effects have also been reported. Experimental data indicate that a daily dose of around 1 mg lead as lead acetate/kg body weight for ten days may be considered as a Lowest Observed Effect Level in dogs. Acute toxicity documentation from the Centers for Disease Control and Prevention indicates 300 mg/kg body weight as the lowest dose of lead acetate causing death in dogs after oral ingestion. Our assessment suggests that dogs fed trimmings of lead-shot game may be affected by the amounts of lead present, and that even deadly exposure could occasionally occur. The intestinal absorption of lead from bullets was assumed to be 10-80 % of that of lead acetate, reflecting both the variability in particle size and uncertainty about the bioavailability of metallic lead in dogs. Despite data gaps, this study indicates that feeding dogs trimmings of lead-shot game may represent a risk of lead intoxication. More research is needed to assess the exact consequences, if lead-based bullets are still to be used. Meanwhile, we recommend that trimmings close to the wound channel should be made inaccessible to dogs, as well as to other domestic or wild animals.

  8. Ten-year scheme of network development - 2013 edition

    International Nuclear Information System (INIS)

    2013-01-01

    RTE, an independent subsidiary of EDF, is the French electricity transmission system operator. It is a public service company responsible for operating, maintaining and developing the high and extra high voltage network. It guarantees the reliability and proper operation of the power network. RTE transports electricity between electricity suppliers (French and European) and consumers, whether they are electricity distributors or industrial consumers directly connected to the transmission system. The mission of RTE is to balance the electricity supply and demand in real time. With the support of the government authorities, RTE prepares a ten-year scheme of network development in France; This document presents the main electricity transport infrastructures to foresee within the ten coming years and lists the network development investments which must be realised and implemented within 3 years. The document is updated each year and comes to complement at the national level the European ten year network development plan (TYNDP) and the European regional plans as provided for in the 2009/72/CE European directive

  9. Frictional amyloidosis in Oman - A study of ten cases

    Directory of Open Access Journals (Sweden)

    Mysore Venkataram

    2002-01-01

    Full Text Available Macular amyloidosis is an important cause for cutaneous pigmentation, the aetiology of which is poorly understood. Friction has recently been implicated the causation of early lesions, referred to as frictional amyloidosis. Confirmation of diagnosis by the detect on of amyloid using histochemical stains is inconsistent. Ten patients with pigmentation suggestive of macular amyloidosis were studied with detailed history, clinical examination, biopsy for histochemistry and electron microscopy. Nine out of ten patients had a history of prolonged friction with various objects such as bath sponges, brushes, towels, plant sticks and leaves. Amyloid was demonstrated by histochemical staining in only six out of ten cases. In the remaining four cases, amyloid was detected by electron microscopy. These consisted of aggregates of non-branching, extracellular, intertwining fibres measuring between 200-500 nm in length and between 20-25 nm in diameter. The study confirms the role of friction in the causation of this condition. Histochemical stains are not always successful in the detection of amyloid and electron microscopy is helpful for confirming its presence. The term frictional amyloidosis aptly describes the condition.

  10. Six to Ten Digits Multiplication Fun Learning Using Puppet Prototype

    Science.gov (United States)

    Islamiah Rosli, D.'oria; Ali, Azita; Peng, Lim Soo; Sujardi, Imam; Usodo, Budi; Adie Perdana, Fengky

    2017-01-01

    Logic and technical subjects require students to understand basic knowledge in mathematic. For instance, addition, minus, division and multiplication operations need to be mastered by students due to mathematic complexity as the learning mathematic grows higher. Weak foundation in mathematic also contribute to high failure rate in mathematic subjects in schools. In fact, students in primary schools are struggling to learn mathematic because they need to memorize formulas, multiplication or division operations. To date, this study will develop a puppet prototyping for learning mathematic for six to ten digits multiplication. Ten participants involved in the process of developing the prototype in this study. Students involved in the study were those from the intermediate class students whilst teachers were selected based on their vast knowledge and experiences and have more than five years of experience in teaching mathematic. Close participatory analysis will be used in the prototyping process as to fulfil the requirements of the students and teachers whom will use the puppet in learning six to ten digit multiplication in mathematic. Findings showed that, the students had a great time and fun learning experience in learning multiplication and they able to understand the concept of multiplication using puppet. Colour and materials of the puppet also help to attract student attention during learning. Additionally, students able to visualized and able to calculate accurate multiplication value and the puppet help them to recall in multiplying and adding the digits accordingly.

  11. 2012 Ten-year scheme of network development

    International Nuclear Information System (INIS)

    2012-01-01

    RTE, an independent subsidiary of EDF, is the French electricity transmission system operator. It is a public service company responsible for operating, maintaining and developing the high and extra high voltage network. It guarantees the reliability and proper operation of the power network. RTE transports electricity between electricity suppliers (French and European) and consumers, whether they are electricity distributors or industrial consumers directly connected to the transmission system. The mission of RTE is to balance the electricity supply and demand in real time. With the support of the government authorities, RTE prepares a ten-year scheme of network development in France; This document presents the main electricity transport infrastructures to foresee within the ten coming years and lists the network development investments which must be realised and implemented within 3 years. The document is updated each year and comes to complement at the national level the European ten year network development plan (TYNDP) and the European regional plans as provided for in the 2009/72/CE European directive

  12. Ten-year scheme of network development - 2011

    International Nuclear Information System (INIS)

    2011-01-01

    RTE, an independent subsidiary of EDF, is the French electricity transmission system operator. It is a public service company responsible for operating, maintaining and developing the high and extra high voltage network. It guarantees the reliability and proper operation of the power network. RTE transports electricity between electricity suppliers (French and European) and consumers, whether they are electricity distributors or industrial consumers directly connected to the transmission system. The mission of RTE is to balance the electricity supply and demand in real time. With the support of the government authorities, RTE prepares a ten-year scheme of network development in France; This document presents the main electricity transport infrastructures to foresee within the ten coming years and lists the network development investments which must be realised and implemented within 3 years. The document is updated each year and comes to complement at the national level the European ten year network development plan (TYNDP) and the European regional plans as provided for in the 2009/72/CE European directive

  13. Some hallways lead to other hallways and some lead to dead ends

    OpenAIRE

    Tam, Nancy Y.S

    2013-01-01

    Some Hallways Lead To Other Hallways And Some Lead To Dead Ends is a one-hour long synchronized audio tour for ten people. Listening to their assigned tracks played through headphones, the audience is mobilized through the SFU Woodward’s building. The aural content is comprised of choreographic instructions and my personal stories as a third culture kid in finding home. Appendix A is a research paper written for FPA 812, where I examine Henri Lefebvre’s ideas of space and how these ideas are ...

  14. Lead poisoning in dogs

    Energy Technology Data Exchange (ETDEWEB)

    Bond, E; Kubin, R

    1949-01-01

    Diagnosis was made from clinical observation and laboratory examination of nine cases. A successful treatment is described based on the similarity of the metabolism of lead and calcium, the lead being deposited in the bones where it is harmless, if it remains there. Details are given of the treatment.

  15. Developmental immunotoxicology of lead

    International Nuclear Information System (INIS)

    Dietert, Rodney R.; Lee, Ji-Eun; Hussain, Irshad; Piepenbrink, Michael

    2004-01-01

    The heavy metal, lead, is a known developmental immunotoxicant that has been shown to produce immune alterations in humans as well as other species. Unlike many compounds that exert adverse immune effects, lead exposure at low to moderate levels does not produce widespread loss of immune cells. In contrast, changes resulting from lead exposure are subtle at the immune cell population level but, nevertheless, can be functionally dramatic. A hallmark of lead-induced immunotoxicity is a pronounced shift in the balance in T helper cell function toward T helper 2 responses at the expense of T helper 1 functions. This bias alters the nature and range of immune responses that can be produced thereby influencing host susceptibility to various diseases. Immunotoxic responses to lead appear to differ across life stages not only quantitatively with regard to dose response, but also qualitatively in terms of the spectrum of immune alterations. Experimental studies in several lab animal species suggest the latter stages of gestation are a period of considerable sensitivity for lead-induced immunotoxicity. This review describes the basic characteristics of lead-induced immunotoxicity emphasizing experimental animal results. It also provides a framework for the consideration of toxicant exposure effects across life stages. The existence of and probable basis for developmental windows of immune hyper-susceptibility are presented. Finally, the potential for lead to serve as a perinatal risk factor for childhood asthma as well as other diseases is considered

  16. Leading Educational Change Wisely

    Science.gov (United States)

    Forrester, Gillian

    2011-01-01

    In this article, the author reviews Christopher Branson's book entitled "Leading Educational Change Wisely". The book provides an alternative and engaging perspective on leading educational change. Branson utilises "wisdom" as its central conceptual device to present a thought-provoking and philosophical account on how leaders are able to build a…

  17. Hypoalgesia in response to transcutaneous electrical nerve stimulation (TENS) depends on stimulation intensity.

    Science.gov (United States)

    Moran, Fidelma; Leonard, Tracey; Hawthorne, Stephanie; Hughes, Ciara M; McCrum-Gardner, Evie; Johnson, Mark I; Rakel, Barbara A; Sluka, Kathleen A; Walsh, Deirdre M

    2011-08-01

    Transcutaneous electrical nerve stimulation (TENS) is an electrophysical modality used for pain management. This study investigated the dose response of different TENS intensities on experimentally induced pressure pain. One hundred and thirty TENS naïve healthy individuals (18-64 years old; 65 males, 65 females) were randomly allocated to 5 groups (n = 26 per group): Strong Non Painful TENS; Sensory Threshold TENS; Below Sensory Threshold TENS; No Current Placebo TENS; and Transient Placebo TENS. Active TENS (80 Hz) was applied to the forearm for 30 minutes. Transient Placebo TENS was applied for 42 seconds after which the current amplitude automatically reset to 0 mA. Pressure pain thresholds (PPT) were recorded from 2 points on the hand and forearm before and after TENS to measure hypoalgesia. There were significant differences between groups at both the hand and forearm (ANOVA; P = .005 and .002). At 30 minutes, there was a significant hypoalgesic effect in the Strong Non Painful TENS group compared to: Below Sensory Threshold TENS, No Current Placebo TENS and Transient Placebo TENS groups (P TENS and No Current Placebo TENS groups at the hand (P = .001). There was no significant difference between Strong Non Painful TENS and Sensory Threshold TENS groups. The area under the curve for the changes in PPT significantly correlated with the current amplitude (r(2) = .33, P = .003). These data therefore show that there is a dose-response effect of TENS with the largest effect occurring with the highest current amplitudes. This study shows a dose response for the intensity of TENS for pain relief with the strongest intensities showing the greatest effect; thus, we suggest that TENS intensity should be titrated to achieve the strongest possible intensity to achieve maximum pain relief. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

  18. Lead-free piezoceramics.

    Science.gov (United States)

    Saito, Yasuyoshi; Takao, Hisaaki; Tani, Toshihiko; Nonoyama, Tatsuhiko; Takatori, Kazumasa; Homma, Takahiko; Nagaya, Toshiatsu; Nakamura, Masaya

    2004-11-04

    Lead has recently been expelled from many commercial applications and materials (for example, from solder, glass and pottery glaze) owing to concerns regarding its toxicity. Lead zirconium titanate (PZT) ceramics are high-performance piezoelectric materials, which are widely used in sensors, actuators and other electronic devices; they contain more than 60 weight per cent lead. Although there has been a concerted effort to develop lead-free piezoelectric ceramics, no effective alternative to PZT has yet been found. Here we report a lead-free piezoelectric ceramic with an electric-field-induced strain comparable to typical actuator-grade PZT. We achieved this through the combination of the discovery of a morphotropic phase boundary in an alkaline niobate-based perovskite solid solution, and the development of a processing route leading to highly textured polycrystals. The ceramic exhibits a piezoelectric constant d33 (the induced charge per unit force applied in the same direction) of above 300 picocoulombs per newton (pC N(-1)), and texturing the material leads to a peak d33 of 416 pC N(-1). The textured material also exhibits temperature-independent field-induced strain characteristics.

  19. Lead poisoning in dogs

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, M R; Lewis, G

    1963-08-03

    Within a short period, 14 cases of lead poisoning in the dogs have been encountered. A detailed record appears justified as no published reference can be found to this condition occurring in Britain and because reports from other countries stress the similarity of the clinical manifestations of lead poisoning to those of the common infections of the dog. Five of the 14 clinical cases of lead poisoning are described. The available literature is reviewed and the diagnosis and significance of the condition discussed. 19 references, 2 tables.

  20. Lead in Construction

    National Research Council Canada - National Science Library

    1993-01-01

    Although Occupational Safety and Health Administration (OSHA) regulations for occupational lead exposure have been in effect since 1971 for the construction and general industries, the agency regulations for general industry in 1978...

  1. Radiation shielding lead shield

    International Nuclear Information System (INIS)

    Dei, Shoichi.

    1991-01-01

    The present invention concerns lead shields for radiation shielding. Shield boxes are disposed so as to surround a pipeline through which radioactive liquids, mists or like other objects are passed. Flanges are formed to each of the end edges of the shield boxes and the shield boxes are connected to each other by the flanges. Upon installation, empty shield boxes not charged with lead particles and iron plate shields are secured at first at the periphery of the pipeline. Then, lead particles are charged into the shield boxes. This attains a state as if lead plate corresponding to the depth of the box is disposed. Accordingly, operations for installation, dismantling and restoration can be conducted in an empty state with reduced weight to facilitate the operations. (I.S.)

  2. Taste intensities of ten vegetables commonly consumed in the Netherlands.

    Science.gov (United States)

    van Stokkom, V L; Teo, P S; Mars, M; de Graaf, C; van Kooten, O; Stieger, M

    2016-09-01

    Bitterness has been suggested to be the main reason for the limited palatability of several vegetables. Vegetable acceptance has been associated with preparation method. However, the taste intensity of a variety of vegetables prepared by different methods has not been studied yet. The objective of this study is to assess the intensity of the five basic tastes and fattiness of ten vegetables commonly consumed in the Netherlands prepared by different methods using the modified Spectrum method. Intensities of sweetness, sourness, bitterness, umami, saltiness and fattiness were assessed for ten vegetables (cauliflower, broccoli, leek, carrot, onion, red bell pepper, French beans, tomato, cucumber and iceberg lettuce) by a panel (n=9) trained in a modified Spectrum method. Each vegetable was assessed prepared by different methods (raw, cooked, mashed and as a cold pressed juice). Spectrum based reference solutions were available with fixed reference points at 13.3mm (R1), 33.3mm (R2) and 66.7mm (R3) for each taste modality on a 100mm line scale. For saltiness, R1 and R3 differed (16.7mm and 56.7mm). Mean intensities of all taste modalities and fattiness for all vegetables were mostly below R1 (13.3mm). Significant differences (p<0.05) within vegetables between preparation methods were found. Sweetness was the most intensive taste, followed by sourness, bitterness, fattiness, umami and saltiness. In conclusion, all ten vegetables prepared by different methods showed low mean intensities of all taste modalities and fattiness. Preparation method affected taste and fattiness intensity and the effect differed by vegetable type. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Lead poisoning in mink

    Energy Technology Data Exchange (ETDEWEB)

    Purdy, J G

    1962-03-01

    This paper describes a case of lead poisoning in minks. The mink were housed in pens which had been painted with a bridge paint containing lead. They had chewed on the pen and ingested the paint. The animals that did not die were moved to new pens, and vitamin D and calcium gluconate were added to their diets. In three days, a marked improvement was seen in the food and water consumption, and convolutions became less frequent.

  4. Lead poisoning in dogs

    International Nuclear Information System (INIS)

    Zook, B.C.; Carpenter, J.L.; Leeds, E.B.

    1969-01-01

    Lead poisoning was diagnosed and studied in 60 dogs. It was found that lead poisoning is a common disease of young dogs, especially in the summer and fall, and is related to their chewing and eating habits resulting in the ingestion of paint, linoleum, or other lead-containing materials. The signs were characterized by gastrointestinal dysfunction (colic, vomiting, and diarrhea) and nervous disorders (convulsions, hysteria, nervousness, behavioral changes). The blood findings, which the authors consider nearly pathognomonic, consisted of numerous stippled and immature (especially nucleated) erythrocytes in the absence of severe anemia. Protein and casts were frequently found in the urine. Radiography sometimes revealed lead-containing particles in the gastro-intestinal tract, and lead lines were occasionally detected in the metaphysis of long bones in immature dogs. Treatment with calcium ethylenediamine-tetraacetic acid resulted in rapid and often dramatic recoveries in nearly all instances. Removal of lead from the gastrointestinal tract and treatment to relieve pronounced central nervous disorders was sometimes necessary. 40 references, 6 figures, 7 tables

  5. Magnesium Diboride Current Leads

    Science.gov (United States)

    Panek, John

    2010-01-01

    A recently discovered superconductor, magnesium diboride (MgB2), can be used to fabricate conducting leads used in cryogenic applications. Dis covered to be superconducting in 2001, MgB2 has the advantage of remaining superconducting at higher temperatures than the previously used material, NbTi. The purpose of these leads is to provide 2 A of electricity to motors located in a 1.3 K environment. The providing environment is a relatively warm 17 K. Requirements for these leads are to survive temperature fluctuations in the 5 K and 11 K heat sinks, and not conduct excessive heat into the 1.3 K environment. Test data showed that each lead in the assembly could conduct 5 A at 4 K, which, when scaled to 17 K, still provided more than the required 2 A. The lead assembly consists of 12 steelclad MgB2 wires, a tensioned Kevlar support, a thermal heat sink interface at 4 K, and base plates. The wires are soldered to heavy copper leads at the 17 K end, and to thin copper-clad NbTi leads at the 1.3 K end. The leads were designed, fabricated, and tested at the Forschungszentrum Karlsruhe - Institut foer Technische Physik before inclusion in Goddard's XRS (X-Ray Spectrometer) instrument onboard the Astro-E2 spacecraft. A key factor is that MgB2 remains superconducting up to 30 K, which means that it does not introduce joule heating as a resistive wire would. Because the required temperature ranges are 1.3-17 K, this provides a large margin of safety. Previous designs lost superconductivity at around 8 K. The disadvantage to MgB2 is that it is a brittle ceramic, and making thin wires from it is challenging. The solution was to encase the leads in thin steel tubes for strength. Previous designs were so brittle as to risk instrument survival. MgB2 leads can be used in any cryogenic application where small currents need to be conducted at below 30 K. Because previous designs would superconduct only at up to 8 K, this new design would be ideal for the 8-30 K range.

  6. Ten PM Note of Organophosphae Poisoning- Successful outcome of a Medical Audit with complete seven steps

    Directory of Open Access Journals (Sweden)

    M D Bhattarai

    2010-03-01

    Full Text Available Medical audit in general consists of seven steps like choosing topic, setting criterion and standard, collecting first data, comparing data with standard, introducing change, collecting second data and reflecting. Its three basic premise are improvement of patient care by using existing knowledge, team work with ongoing educational process and change management and promotion of blame-free culture maintaining confidentiality. Audit mostly relates to a particular practice and is therefore not generalisable. An audit of residents' late evening routine notes of organophosphate poisoning patients is reported here, as the change introduced appears relevant to the situation of developing countries. Organophosphate poisoning patients should be managed in intensive care unit with close monitoring, as inadvertent stoppage or slowing of atropine infusion may occur, particularly at night, leading to reappearance of poisoning manifestations, which may cause respiratory failure and death. If they are managed in wards, residents-on-duty can check the clinical and intravenous drip status in the late evening and communicate with nurses and relatives to be particularly vigilant. In the audit done, such regular ten pm notes of organophosphate poisoning about the clinical and drip status and communication by residents were increased from 15.5% in the first to 81.7% in the second data collection (p < 0.01 after the introduction of the change. The ten pm note is being continued for about two years now. Implementation of ten pm note of organophosphate poisoning patients admitted in medical wards is feasible and appears useful to improve the quality of health care delivery and learning of residents. Keywords: atrophine, audit, audit steps, organophosphate mortality, organophosphate poisoning.

  7. Extraskeletal mesenchymal chondrosarcoma: an imaging review of ten new patients

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, N.; Joyama, S.; Araki, N. [Osaka Medical Center for Cancer and Cardiovascular Disease, Department of Orthopedic Surgery, Osaka (Japan); Ueda, T.; Yoshikawa, H. [Osaka University Graduate School of Medicine, Department of Orthopedic Surgery, Osaka (Japan); Beppu, Y. [National Cancer Center Hospital, Department of Orthopedic Surgery, Tokyo (Japan); Tatezaki, S. [Chiba Cancer Center Hospital, Department of Orthopedic Surgery, Chiba (Japan); Matsumoto, S. [Cancer Institute Hospital, Japanese Foundation for Cancer Research Hospital, Department of Orthopedic Surgery, Tokyo (Japan); Nakanishi, K. [Osaka Seamen' s Insurance Hospital, Department of Radiology, Osaka (Japan); Tomita, Y. [Osaka University Graduate School of Medicine, Department of Pathology, Osaka (Japan)

    2005-12-01

    Extraskeletal mesenchymal chondrosarcoma (EMC) is a rare soft-tissue tumor that most arises in young adults. Because of its rarity, few imaging studies have been reported to date. The purpose of this study was to elucidate the imaging features of this tumor. We conducted a multi-institutional study in cooperation with five referral cancer centers in Japan. Imaging findings of ten new EMC cases, including conventional radiography, computed tomography (CT), and magnetic resonance imaging (MRI), performed at each institute, were reviewed along with clinical features. Ten patients with EMC, who had been treated at each hospital from 1990 to 2001, participated in this study. Soft-tissue masses with well-demarcated, dense and granular calcification were most frequently observed on plain radiographs and CT scans. T2-weighted MR images most clearly depicted a two-component structure composed of calcified and uncalcified areas, and enhanced MRI showed inhomogeneous enhancement in both areas. Although the sensitivity and specificity of these findings are unknown, they might be characteristic and have diagnostic value for this rare tumor. (orig.)

  8. The next ten years in neonatology: new directions in research

    Directory of Open Access Journals (Sweden)

    Vassilios Fanos

    2014-06-01

    Full Text Available This paper is a prelude to proceedings of the 10th International Workshop on Neonatology to be held in Cagliari, Italy from October 21st to 25th, 2014. These proceedings will be a significant milestone, highlighting the new frontiers of perinatal and neonatal research. Over the five days of this meeting, we aim to (1 examine the roots of the new directions in perinatal and neonatal research; (2 predict the trajectories of advancement in medical technologies, research, clinical care and teaching that will be the future of perinatology and neonatology. The discussion will be in four sections:back to the future: the placenta and perinatal programming;paradigm shift: the revolution of metabolomics in perinatalogy and neonatology;brave new world: the microbiome and microbiomics from perinatal to adult life;new inhabitants on the planet earth: adults who were born with extremely low birth weight. Proceedings of the 10th International Workshop on Neonatology · Cagliari (Italy · October 22nd-25th, 2014 · The last ten years, the next ten years in Neonatology Guest Editors: Vassilios Fanos, Michele Mussap, Gavino Faa, Apostolos Papageorgiou

  9. Assessment of clinical residents' needs for ten educational subjects

    Directory of Open Access Journals (Sweden)

    Mansour Razavi

    2002-04-01

    Full Text Available Background Fulfilling the learners' "real needs" will improve medical education. There are subjects that are necessary for any clinical residents not considering their field of specialty. Among the subjects ten seems to be the most important: research methodology and data analysis, computer-based programs, medical recording, cardiopulmonary and cerebral resuscitation, clinical teaching programs, communication skills, clinical ethics, laboratory examinations, reporting special diseases and death certification, and prescription. Purpose This cross-sectional study assessed educational needs of clinical residents for ten educational subjects. Methods A questionnaire prepared by board faculty members consisted of 10 close-ended questions, and one open­ ended question was distributed among 1307 residents from 22 clinical disciplines, who registered for preboard or promotion exam in June 2000. Results Among the subjects three were the most needed: computer-based programs 149 (60%, data collecting system 606 (49%, and clinical ethics 643 (46%. The prescription standard was the least required 177(13%. Conclusion Complementary training courses on these subjects can be an answer to the clinical residents needs. Keywords : research methodology, computer in medicine, cpr, clinical teaching methods, communication in medicine, medical ethics, laboratory ordering, disease coding system, death certificate, prescription writing

  10. Keys to success: Ten case studies of effective weatherization programs

    Energy Technology Data Exchange (ETDEWEB)

    Brown, M.A.; Berry, L.G.; Kolb, J.O.; White, D.L. [Oak Ridge National Lab., TN (United States); Kinney, L.F.; Wilson, T. [Synertech Systems Corp., Syracuse, NY (United States)

    1993-11-01

    In 1990, DOE initiated a nationwide evaluation of its Weatherization Program, with assistance from Oak Ridge National Laboratory and an advisory group of 40 weatherization professionals, program managers, and researchers. The evaluation is comprised of three impact studies covering the Program`s major market segments: Single-family homes, mobile homes, and dwellings in small (2 to 4-unit) multifamily buildings (the Single-Family Study), Single-family homes heated primarily with fuel oil (the Fuel-Oil Study), and Dwellings in buildings with five or more units (the Multifamily Study). The Single-Family Study, the subject of this report, is a critical part of this coordinated evaluation effort. Its focus on single-family dwellings, mobile homes, and dwellings in small multifamily buildings covers 83% of the income-eligible population and 96% of the dwellings weatherized during Program Year 1989. The first phase of the Single-Family Study involved the analysis of a massive data base of information collected from 368 local weatherization agencies and 543 electric and gas utilities. This analysis resulted in energy-saving and cost-effectiveness estimates for the Weatherization Program and the identification of a set of ten high-performing agencies located throughout the country. The second phase, which is the subject of this report, involves a ``process`` evaluation of these ten high performers, aimed at identifying those weatherization practices that explain their documented success.

  11. [Omalizumab: What have we learned after ten years of prescription?].

    Science.gov (United States)

    Pradère, P; Garcia, G; Humbert, M; Aubier, M; Taillé, C

    2016-02-01

    Omalizumab, an anti-immunoglobulin E monoclonal antibody, has now been used for ten years as an add-on therapy for severe adult atopic asthma, poorly controlled by high-doses inhaled steroids and long-acting beta-agonists. This innovative therapy has been the first biotherapy used on a large scale in severe asthma. It has shown clinical benefits, especially in the prevention of severe exacerbation, with a satisfactory safety profile. Despite its cost, it is an interesting alternative to continuous oral steroids, which cause more long-term side effects. After ten-years of prescription of omalizumab, we review here the mechanism of action, the benefits, the main side effects, the cost-effectiveness and also the alternative indications of this interesting molecule. We also consider the practicalities of using omalizumab, particularly the importance a rigorous assessment of its efficacy after 16 weeks of treatment, and possible future therapeutic indications. Omalizumab has proven its efficacy in large randomized studies but also in real life practice in severe allergic asthma. Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  12. Gas cooled leads

    International Nuclear Information System (INIS)

    Shutt, R.P.; Rehak, M.L.; Hornik, K.E.

    1993-01-01

    The intent of this paper is to cover as completely as possible and in sufficient detail the topics relevant to lead design. The first part identifies the problems associated with lead design, states the mathematical formulation, and shows the results of numerical and analytical solutions. The second part presents the results of a parametric study whose object is to determine the best choice for cooling method, material, and geometry. These findings axe applied in a third part to the design of high-current leads whose end temperatures are determined from the surrounding equipment. It is found that cooling method or improved heat transfer are not critical once good heat exchange is established. The range 5 5 but extends over a large of values. Mass flow needed to prevent thermal runaway varies linearly with current above a given threshold. Below that value, the mass flow is constant with current. Transient analysis shows no evidence of hysteresis. If cooling is interrupted, the mass flow needed to restore the lead to its initially cooled state grows exponentially with the time that the lead was left without cooling

  13. Flexibility in faculty work-life policies at medical schools in the Big Ten conference.

    Science.gov (United States)

    Welch, Julie L; Wiehe, Sarah E; Palmer-Smith, Victoria; Dankoski, Mary E

    2011-05-01

    Women lag behind men in several key academic indicators, such as advancement, retention, and securing leadership positions. Although reasons for these disparities are multifactorial, policies that do not support work-life integration contribute to the problem. The objective of this descriptive study was to compare the faculty work-life policies among medical schools in the Big Ten conference. Each institution's website was accessed in order to assess its work-life policies in the following areas: maternity leave, paternity leave, adoption leave, extension of probationary period, part-time appointments, part-time benefits (specifically health insurance), child care options, and lactation policy. Institutions were sent requests to validate the online data and supply additional information if needed. Each institution received an overall score and subscale scores for family leave policies and part-time issues. Data were verified by the human resources office at 8 of the 10 schools. Work-life policies varied among Big Ten schools, with total scores between 9.25 and 13.5 (possible score: 0-21; higher scores indicate greater flexibility). Subscores were not consistently high or low within schools. Comparing the flexibility of faculty work-life policies in relation to other schools will help raise awareness of these issues and promote more progressive policies among less progressive schools. Ultimately, flexible policies will lead to greater equity and institutional cultures that are conducive to recruiting, retaining, and advancing diverse faculty.

  14. Leading healthcare in complexity.

    Science.gov (United States)

    Cohn, Jeffrey

    2014-12-01

    Healthcare institutions and providers are in complexity. Networks of interconnections from relationships and technology create conditions in which interdependencies and non-linear dynamics lead to surprising, unpredictable outcomes. Previous effective approaches to leadership, focusing on top-down bureaucratic methods, are no longer effective. Leading in complexity requires leaders to accept the complexity, create an adaptive space in which innovation and creativity can flourish and then integrate the successful practices that emerge into the formal organizational structure. Several methods for doing adaptive space work will be discussed. Readers will be able to contrast traditional leadership approaches with leading in complexity. They will learn new behaviours that are required of complexity leaders, along with challenges they will face, often from other leaders within the organization.

  15. The Vixen Star Book user guide how to use the star book ten and the original star book

    CERN Document Server

    Chen, James

    2016-01-01

    This book is for anyone who owns, or is thinking of owning, a Vixen Star Book Ten telescope mount or its predecessor. A revolution in amateur astronomy has occurred in the past decade with the wide availability of high tech, computer-driven, Go-To telescopes. Vixen Optics is leading the way by offering the Star Book Ten system, with its unique star map graphics software. The Star Book Ten is the latest version of computer telescope control using star map graphics as a user interface, first introduced in the original Star Book first offered in 2003. The increasingly complicated nature of this software means that learning to optimize this program is not straightforward, and yet the resulting views when all features are correctly deployed can be phenomenal. After a short history of computerized Go-To telescopes for the consumer amateur astronomer market, Chen offers a treasury of technical information. His advice, tips, and solutions aid the user in getting the most out of the Star Book Ten system in observing s...

  16. [Analysis of body mass index in different sector workers for over ten years].

    Science.gov (United States)

    Perbellini, L; Zonzin, C; Baldo, M

    2010-01-01

    A critical review of the literature on obesity and overweight underlines that a low educational level, a low social-economic status, certain working conditions, the lack of physical activity in leisure time, together with the availability of food, are the main factors favouring increased prevalence of obesity. Certain jobs also contribute significantly to this problem. Automation, the use of machines for heavy works and sedentary activities favour body weight increase. Jobs that are a source of stress, such as work with night shift can cause metabolic disorders leading to an increased prevalence of obesity. The main aim of this article is to study the trend of body weight in different working area during ten years, comparing this parameter to different factors such as job, blood pressure, smoke, alcool and health diseases.

  17. Relational Perspectives on Leading

    DEFF Research Database (Denmark)

    Relational Perspectives on Leading discusses leadership from a relational and social constructionism perspective as practiced on an everyday basis between people. The book pursues a fast growing, practice-based approach - particularly within the Anglo-Saxon parts of the world - to organization...

  18. Learn about Lead

    Science.gov (United States)

    ... Search Main menu Environmental Topics Air Bed Bugs Chemicals and Toxics Environmental Information by Location Greener Living Health Land, ... it has some beneficial uses, it can be toxic to humans and animals causing of health ... some types of industrial facilities, and past use of lead-based paint ...

  19. Leading Causes of Blindness

    Science.gov (United States)

    ... have cataracts. They are the leading cause of blindness in the world. By age 80, more than half of all people in the United States either will have a cataract or have had cataract surgery. Common symptoms are: Blurry vision Colors that seem faded Glare Not being able to ...

  20. Lead User Innovation

    DEFF Research Database (Denmark)

    Brem, Alexander; Larsen, Henry

    2015-01-01

    covers the opposite view, where a company actively searches and involves lead users, however, with limited success also. Based on both cases, we analyze how, in these emerging processes of relating, meaning is co-created in a way that narrows the shared conceptual space for imagination and collaboration...

  1. Girls Leading Outward

    Science.gov (United States)

    Hamed, Heather; Reyes, Jazmin; Moceri, Dominic C.; Morana, Laura; Elias, Maurice J.

    2011-01-01

    The authors describe a program implemented in Red Bank Middle School in New Jersey to help at-risk, minority middle school girls realize their leadership potential. The GLO (Girls Leading Outward) program was developed by the Developing Safe and Civil Schools Project at Rutgers University and is facilitated by university students. Selected middle…

  2. Leading through Conflict

    Science.gov (United States)

    Gerzon, Mark

    2006-01-01

    This article talks about leading significant learning opportunities through conflict of ideas in a school system. Catalyzing school change can turn emotional differences of opinion into learning opportunities. Leaders who want to deal effectively with these challenging, often tense situations need to be more than good managers. They need to be…

  3. Lead Time Study,

    Science.gov (United States)

    1982-05-01

    1979, the number of titanium fabrications dropped from 16 to 4, primarily because of the sponge shortage and EPA and OSHA requirements. Non-military...East - Taiwan, Korea, Singapore, Malaysia and Hong Kong. In addition, a significant amount of ceramic parts, lead frames and high technology

  4. Lead pollution in Islamabad

    International Nuclear Information System (INIS)

    Mohammad, D.; Khatoon, N.; Ishaque, M.; Ahmed, I.

    1997-01-01

    Lead pollution of urban area emanating from the vehicular exhaust alone is being labeled as one of the worst form of environmental degradation attracting our attention for remediation. For factual assessment samples were collected from different areas of Islamabad. These samples consisted of tree scrapings / peelings, which were dried and ground before undertaking analysis for the lead content. The samples were digested with an acid mixture to remove the organic matter and analyzed using GFAAS technique. A total of 81 samples have been analyzed. The results sowed a lead content varying in the range of 8-474 Mu g g/sup -1/) and 23 samples with Pb content <50 Mu g g-1 (8.0-50.0 Mu g g/sup -1/). Most of the samples also contained some growth which consisted of bacterial, algae and fugal cells and the results have been explained on the basis of Pb absorption by these cells. The procedure followed in this study is recommended for evaluation of lead pollution in urban areas. (author)

  5. EFFECT OF LEAD ACETATE

    African Journals Online (AJOL)

    MICROSOFT

    increase in the production of poultry meat at a reasonable cost (Alam et al., ...... 36(4): 537-541. Taggart MA, Figuerola J, Green AJ, Mateo R, Deacon C, Osborn D, ... selenium, lead and copper levels in the livers and bones of five waterfowl ...

  6. Intoxication for lead

    International Nuclear Information System (INIS)

    Velez, Ruben Dario; Tamayo, Margarita Maria

    1999-01-01

    We present a case of a hospitalized girl with bronchopneumonia, who needed mechanic ventilation. Also she had a developmental delay and Burtons border in gums. Radiological studies showed dense transverse metaphiseal bands in long bones and hyperdensity in basal ganglia. We found high serum lead levels

  7. Lead Thickness Measurements

    International Nuclear Information System (INIS)

    Rucinski, R.

    1998-01-01

    The preshower lead thickness applied to the outside of D-Zero's superconducting solenoid vacuum shell was measured at the time of application. This engineering documents those thickness measurements. The lead was ordered in sheets 0.09375-inch and 0.0625-inch thick. The tolerance on thickness was specified to be +/- 0.003-inch. The sheets all were within that thickness tolerance. The nomenclature for each sheet was designated 1T, 1B, 2T, 2B where the numeral designates it's location in the wrap and 'T' or 'B' is short for 'top' or 'bottom' half of the solenoid. Micrometer measurements were taken at six locations around the perimeter of each sheet. The width,length, and weight of each piece was then measured. Using an assumed pure lead density of 0.40974 lb/in 3 , an average sheet thickness was calculated and compared to the perimeter thickness measurements. In every case, the calculated average thickness was a few mils thinner than the perimeter measurements. The ratio was constant, 0.98. This discrepancy is likely due to the assumed pure lead density. It is not felt that the perimeter is thicker than the center regions. The data suggests that the physical thickness of the sheets is uniform to +/- 0.0015-inch.

  8. Anatomy of lead poisoning

    African Journals Online (AJOL)

    ABEOLUGBENGAS

    Results: The primary form of lead toxicity is by oxidative stress mechanisms, apoptosis and necrosis involving ... néfastes sur la reproduction à l'avenir. Résultats:La forme ... prostate cancers, abnormal sexual ..... ensure this work is a success.

  9. Scientometry Leading us Astray

    Czech Academy of Sciences Publication Activity Database

    Haindl, Michal

    2010-01-01

    Roč. 2010, č. 82 (2010), s. 8-8 ISSN 0926-4981 Institutional research plan: CEZ:AV0Z10750506 Keywords : scientometry Subject RIV: BD - Theory of Information http://ercim-news.ercim.eu/en82/european-scene/ scientometry -leading-us-astray

  10. Total contribution of airborne lead to blood lead.

    OpenAIRE

    Manton, W I

    1985-01-01

    A nine year study of blood lead concentrations and isotope ratios carried out on a married couple shows that pulmonary deposition cannot account for all the airborne lead in blood; that lead from bone may comprise 70% of blood lead; and that during pregnancy blood lead may double due to mobilisation of lead from bone.

  11. Total contribution of airborne lead to blood lead.

    Science.gov (United States)

    Manton, W I

    1985-01-01

    A nine year study of blood lead concentrations and isotope ratios carried out on a married couple shows that pulmonary deposition cannot account for all the airborne lead in blood; that lead from bone may comprise 70% of blood lead; and that during pregnancy blood lead may double due to mobilisation of lead from bone. PMID:3970881

  12. Comparison of the refractive error changes among young children in ten years interval

    Directory of Open Access Journals (Sweden)

    Hai-Yan Li

    2013-07-01

    Full Text Available AIM: To compare the optometric examination results of myopic young children between those diagnosed in the period from 1998 to 2000 and those diagnosed in the period from 2008 to 2010; and to find out the causes of myopia and factors that worsen the condition, and suggest methods of its prevention and treatment.METHODS: This study was a retrospective case study. We randomly selected sample from out-patient department register of cases and divided them into two main groups, ‘ten year before group'(TYBG(1998/2000 year casesand ‘ten years later group'(2008/2010 year cases(TYLG. Each group was further subdivided into three sub-groups by age: under-six years old children group(CG, seven-twelve years old primary-school group(PSGand thirteen-eighteen years old middle-school group(MSG. The optometric examination results were statistically analyzed.RESULTS: The difference of the mean dioptre between the TYBG and TYLG was strongly statistically significant, also forward-lead trend of age when children suffered from myopia was found(P0.01. There was a significant increase of dioptre among PSG and MSG in TYLG compared to TYBG(PCONCLUSION: Our study shows that the age of getting myopia was forward lead, the dioptre increases by 1.00 degree and the prevalence of myopia is increasing gradually. This situation may due to the modern life style and changes of living standard of the population. Therefore, prevention of myopia should concentrate more on younger children at kindergarten and primary school stage students.

  13. Ten questions concerning green buildings and indoor air quality

    DEFF Research Database (Denmark)

    Steinemann, Anne; Wargocki, Pawel; Rismanchi, Behzad

    2017-01-01

    This paper investigates the concern that green buildings may promote energy efficiency and other aspects of sustainability, but not necessarily the health and well-being of occupants through better indoor air quality (IAQ). We ask ten questions to explore IAQ challenges for green buildings as well...... as opportunities to improve IAQ within green buildings and their programs. Our focus is on IAQ, while recognizing that many factors influence human health and the healthfulness of a building. We begin with an overview of green buildings, IAQ, and whether and how green building certifications address IAQ. Next, we...... examine evidence on whether green buildings have better IAQ than comparable conventional buildings. Then, we identify so-called green practices and green products that can have unintended and unfavorable effects on IAQ. Looking ahead, we offer both immediate and longer-term actions, and a set of research...

  14. Energy accounting of materials, products, processes and services. [Ten papers

    Energy Technology Data Exchange (ETDEWEB)

    Verbraeck, A [ed.

    1976-01-01

    Ten papers were presented, namely: Units in Energy Accounting--How Are They Defined, How Are They Measured, by Dr. Malcolm Slesser; Economics of Energy Analysis, by Dr. Thomas Veach Long II; Energy Considerations in Synthetic and Natural Fibers, by Mr. A. H. Woodhead; Energy Accounting in Food Products, by Mr. Gerald Leach; Energy Analysis of Transportation Systems, by Dr. E. J. Tuininga; Energy Accounting of Packaging Materials for Liquids and Their Transport viz Bottles and Pipes, by Mr. A. Bolzinger; Energy Accounting of Steel, by Dr. A. Decker; Energy Accounting of Aluminium, by Dr. D. Altenpohl, T. S. Daugherty, and W. Blum; Energy Requirement of Some Energy Sources, by Dr. P. F. Chapman and Dr. D. F. Hemming; Energy Analysis of Materials and Structures in the Building Industry, by Professor Dr. P. C. Kreijger. A panel discussion in response to a large number of questions was chaired by Professor Dr. W. van Gool. (MCW)

  15. Comparative toxicity of ten organic chemicals to four earthworm species

    Energy Technology Data Exchange (ETDEWEB)

    Neuhauser, E.F.; Durkin, P.R.; Malecki, M.R.; Anatra, M.

    1986-01-01

    Ten organic chemicals were tested for toxicity to four earthworm species: Allolobophora tuberculata, Eisenia fetida, Eudrilus eugeniae and Perionyx excavatus, using the European Economic Community's (EEC) earthworm artificial soil and contact testing procedure. The phenols were the most toxic chemicals tested, followed by the amine, substituted benzenes, halogenated aliphatic hydrocarbon, polycyclic aromatic hydrocarbon and phthalate as the least toxic chemical tested. Correlations among species within each type of test for a given chemical were extremely high, suggesting that the selection of earthworm test species does not markedly affect the assessment of a chemical's toxicity. The correlation between the two tests was low for all test species. The contact test LC50 for a given chemical cannot be directly correlated to an artificial soil test LC50 for the same earthworm species.

  16. Ten Challenges of the Amyloid Hypothesis of Alzheimer's Disease.

    Science.gov (United States)

    Kepp, Kasper Planeta

    2017-01-01

    The inability to effectively halt or cure Alzheimer's disease (AD), exacerbated by the recent failures of high-profile clinical trials, emphasizes the urgent need to understand the complex biochemistry of this major neurodegenerative disease. In this paper, ten central, current challenges of the major paradigm in the field, the amyloid hypothesis, are sharply formulated. These challenges together show that new approaches are necessary that address data heterogeneity, increase focus on the proteome level, use available human patient data more actively, account for the aging phenotype as a background model of the disease, unify our understanding of the interplay between genetic and non-genetic risk factors, and combine into one framework both the familial and sporadic forms of the disease.

  17. Northern part, Ten Mile and Taunton River basins

    Science.gov (United States)

    Williams, John R.; Willey, Richard E.

    1967-01-01

    The northern part of the Ten Mile and Taunton River basins is an area of about 195 square miles within Norfolk, Plymouth, and Bristol Counties in southeastern Massachusetts. The northern boundary of the area (plate 1) is the drainage divide separating these basins from that of the Charles, Neponset, and Weymouth River basins. The western boundary is, for the most part, the divide separating the basins from the Blackstone River basin. The eastern boundary is at the edge of the Brockton-Pembroke area (Petersen, 1962; Petersen and Shaw, 1961). The southern boundary in Seekonk is the northern limit of the East Providence quadrangle, for which a ground-water map was prepared by Allen and Gorman (1959); eastward, the southern boundaries of the city of Attleboro and the towns of Norton, Easton, and West Bridgewater form the southern boundary of the area.

  18. The General Factor of Personality: Ten Years After

    Directory of Open Access Journals (Sweden)

    Janek Musek

    2017-05-01

    Full Text Available According to the empirical and theoretical research in past ten years, the General Factor of Personality (GFP was interpreted as the highest-order (most general personality dimension, which occupies the apex of the structural hierarchy of personality traits. Thus, the GFP is the central concept in the new structural paradigm of personality (the Pyramidal Model of Personality. In the majority of the studies, the GFP was conceptualized as a general factor with substantial psychological (cognitive and behavioural content reflecting the general social and personal adjustment or effectiveness. The alternative explanations of the GFP emphasize the role of the semantic factors, response styles and other biases. This study reviews the main results of the GFP research including the nature, the biological bases, the strength and cultural universality of GFP, its relations to intelligence and other prominent psychological variables, and its predictive power and practical importance.

  19. Ten years of energy consumption in the tertiary sector

    International Nuclear Information System (INIS)

    Rabai, Yacine

    2012-11-01

    This document presents and comments data regarding electricity consumption by the tertiary sector over the last ten years in France. It notably outlines its strong increase compared to the other sectors (housing, industry, transport, agriculture). It comments the evolution of the energy mix of the tertiary sector (electricity with 47%, gas with 25% and oil with 19% are prevailing). It briefly comments the evolution of energy efficiency within this sector. It indicates and comments the shares of energy consumption, of high voltage electricity and gas consumption by the different sub-sectors (retail, automobile and motorcycle repair, public administration, health and social activity, real estate, specialised, scientific and technical activities, education, and so on)

  20. Instability Rules: The Ten Most Amazing Ideas of Modern Science

    Science.gov (United States)

    Flowers, Charles

    2002-03-01

    World-altering discoveries that reveal a universe of uncertainty and constant change Whether probing the farthest reaches of the vast universe or exploring the microscopic world of genetics and the subatomic world of quantum mechanics, Instability Rules is a remarkably informative and engaging look at ten milestone discoveries and their discoverers-a wide range of very human personalities whose insights have dramatically altered our most basic assumptions about human existence during the last century. The stories include Edwin Hubble and the expanding universe, Alfred Wegener and continental drift, Neils Bohr and quantum mechanics, Alan Turing and artificial intelligence, and James Watson and Francis Crick and DNA. Also covering discoveries of the twenty-first century that are already refining these and other ideas, Instability Rules is an exhilarating, sometimes amusing encounter with the defining scientific discoveries of our age.

  1. Comparison of radiology residency programs in ten countries

    International Nuclear Information System (INIS)

    Willatt, J.M.G.; Mason, A.C.

    2006-01-01

    The purpose of our study was to compare various aspects of radiology training schemes in ten countries. A questionnaire was sent to senior residents in the UK, USA, Canada, Australia, New Zealand, Italy, Egypt, India, Malaysia and Greece. The questions concerned length of training, required pre-training experience, the organization of the training scheme, teaching, resources, stages at which residents can independently perform and report examinations, fellowships, and progression to jobs. A wide variety of training, ranging from highly scheduled programs with detailed aims and objectives, to self-learning occurs across the world. Examinations and assessments are also variable. There are lessons to be learned from varying practices; more exchanges of ideas should be encouraged. In view of the ''internationalization'' of radiology services and the variation in training styles an international qualification for quality assurance purposes may be desirable. (orig.)

  2. Antioxidant capacities of ten edible North American plants.

    Science.gov (United States)

    Acuña, Ulyana Muñoz; Atha, Daniel E; Ma, Jun; Nee, Michael H; Kennelly, Edward J

    2002-02-01

    The EtOAc extract obtained from ten edible North American plants, Acorus calamus, Clintonia borealis, Gaultheria shallon, Juniperus osteosperma, Opuntia polyacantha, Prunus americana, Prunus virginiana, Sambucus cerulea, Sorbus americana and Vaccinium parvifolium, were tested in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical assay. High antioxidant activity was obtained from the extracts of three fruits, Gaultheria shallon, Sambucus cerulea and Prunus americana and one extracted rhizome, Acorus calamus. Catechin and epicatechin, potent polyphenolic antioxidants, were identified in the EtOAc extracts of Gaultheria shallon and Sambucus cerulea by reversed-phase thin-layer chromatography (TLC) and reversed-phase high-performance liquid chromatography (HPLC). Copyright 2002 John Wiley & Sons, Ltd.

  3. The Chooz power station: ten years of operation

    International Nuclear Information System (INIS)

    Teste du Bailler, Andre

    1977-01-01

    The switching into actual service of the Chooz plant, the first pressurized water reactor ever built in France, occurred on 3rd april 1967. Ten years later, one can establish a highly positive balance schedule of plant's operation whose availability is satisfactory, except the mechanical failure which occurred during the startup. The behavior of the equipment, in particular of the components of the primary loop, was satisfactory in its whole since it allowed the gradual increase in capacity by 15% with respect to the initial design. It allowed also the achievment of noticeable progress in the design of equipment intended for the new power stations. Interesting results have also been obtained in radioprotection, working conditions of the staff and environment protection fields. Finally, the training of the operating teams has been closely followed, whether it concerned the operators directly affected by plant operation or the trainees gathered in a school specially organized for this purpose and transferred since to a training Center [fr

  4. Inspection of Chooz power plant after ten years operation

    International Nuclear Information System (INIS)

    Saglio, Robert.

    1978-01-01

    This report is intended to discuss the results from the complete technical audit of the vessel effected in 1976 at the Ardennes reactor (CNA 305 MWe). This audit had a special character as far as this power plant has never been inspected before: the start-up had taken place in 1967 and was then prior to the development of French regulations (and even to the first version of the ASME code, Section XI). In that time, no inspection was expected; it has yet been possible to have a complete audit in ten days. The automatic start-up of focused ultrasonic testing so appeared to have reached the required reliability and a good sensitivity [fr

  5. Safe havens in Europe: Switzerland and the ten dwarfs

    Directory of Open Access Journals (Sweden)

    Martin Paldam

    2013-12-01

    Full Text Available Eleven safe havens exist in Europe providing offshore banking and low taxes. Ten of these states are very small while Switzerland is moderately small. All 11countries are richer than their large neighbors. It is shown that causality is from small to safe haven towealth, and that theoretically equilibriums are likely to exist where a certain regulation is substantially lower in a small country than in its big neighbor. This generates a large capital inflow to the safe havens. The pool of funds that may reach the safe havens is shown to be huge. It is far in excess of the absorptive capacity of the safe havens, but it still explains, why they are rich. Microstates offer a veil of anonymity to funds passing through, and Switzerland offers safe storage of funds.

  6. Mobile and Social: Ten Best Practices for Designing Mobile Applications

    Directory of Open Access Journals (Sweden)

    Liviu LICA

    2010-01-01

    Full Text Available This paper gives ten best practices for designing mobile applications that have social-networking functions. The need for such an approach is given by the rapid growth in impor-tance of both social networks and mobile applications. In order to make it easy to follow where the best practices come from, the paper starts with a look at why social networks are more than just a buzz word and at how the field of mobile applications is evolving. It also shows how and why the two fields go together so well. To further make the point, there is a case study of four interesting mobile applications that are textbooks examples of successful applications. The best practices are based on research done for this article and on the extensive knowledge of the author.

  7. Ten helical twist angles of B-DNA

    Energy Technology Data Exchange (ETDEWEB)

    Kabsch, W; Sander, C; Trifonov, E N

    1982-01-01

    On the assumption that the twist angles between adjacent base-pairs in the DNA molecule are additive a linear system of 40 equations was derived from experimental measurements of the total twist angles for different pieces of DNA of known sequences. This system of equations is found to be statistically consistent providing a solution for all ten possible twist angles of B-DNA by a least squares fitting procedure. Four of the calculated twist angles were not known before. The other six twist angles calculated are very close to the experimentally measured ones. The data used were obtained by the electrophoretic band-shift method, crystallography and nuclease digestion of DNA adsorbed to mica or Ca-phosphate surface. The validity of the principle of additivity of the twist angles implies that the angle between any particular two base-pairs is a function of only these base-pairs, independent of nearest neighbors.

  8. Ten per cent polarized optical emission from GRB 090102.

    Science.gov (United States)

    Steele, I A; Mundell, C G; Smith, R J; Kobayashi, S; Guidorzi, C

    2009-12-10

    The nature of the jets and the role of magnetic fields in gamma-ray bursts (GRBs) remains unclear. In a baryon-dominated jet only weak, tangled fields generated in situ through shocks would be present. In an alternative model, jets are threaded with large-scale magnetic fields that originate at the central engine and that accelerate and collimate the material. To distinguish between the models the degree of polarization in early-time emission must be measured; however, previous claims of gamma-ray polarization have been controversial. Here we report that the early optical emission from GRB 090102 was polarized at 10 +/- 1 per cent, indicating the presence of large-scale fields originating in the expanding fireball. If the degree of polarization and its position angle were variable on timescales shorter than our 60-second exposure, then the peak polarization may have been larger than ten per cent.

  9. Ten years of the uranium mines at Hamr na Jezere

    International Nuclear Information System (INIS)

    Stehlik, J.

    1976-01-01

    The ten-year long history of the uranium mine at Hamr na Jezere near Ceska Lipa (Czechoslovakia) is briefly discussed. The deposit is of the sedimentary-epigenetic origin and is located in complex hydrogeologic conditions in the so-called Lusatian Cretaceous system in the Bohemian Cretaceous Plateau. The deposit is characteristic of a considerable proportion of zirconium which forms complex minerals with uranium. The ore is exploited using two mining procedures. In areas with favourable geologic and hydrogeologic conditions it is the conventional mining method, in other parts chemical in-situ leaching is employed. The main demands placed on the two mining technologies include the undisturbed Turonian drinking water aquifer, minimum intrusion into the landscape and the treatment of radioactive waters before discharge into public water supplies. The importance of the Hamr deposit and the further development of the Uranium Mines Concern are indicated. (B.S.)

  10. Isoe - information system on occupational exposure. Ten years of experience

    International Nuclear Information System (INIS)

    2002-01-01

    The information System on Occupational Exposure (ISOE) was created in 1992 to provide a forum for radiation protection experts from both utilities and national regulatory authorities to discuss, promote and co-ordinate international co-operative undertakings in the area of worker protection at nuclear power plants. The ISOE System is jointly managed by the OECD Nuclear Energy Agency (NEA) and the International Atomic Energy Agency (IAEA). This report provides an overview of the experience gained from, and benefits provided by, the ISOE System over the past ten years. Active participation of a large number of utilities in ISOE has contributed to a reduction in occupational exposure at nuclear power plants worldwide. (authors)

  11. Systems Analysis of Ten Supply Chains for Whole Tree Chips

    Directory of Open Access Journals (Sweden)

    Helmer Belbo

    2014-09-01

    Full Text Available Whole trees from energy thinnings constitute one of many forest fuel sources, yet ten widely applied supply chains could be defined for this feedstock alone. These ten represent only a subset of the real possibilities, as felling method was held constant and only a single market (combustion of whole tree chips was considered. Stages included in-field, roadside landing, terminal, and conversion plant, and biomass states at each of these included loose whole trees, bundled whole trees or chipped material. Assumptions on prices, performances, and conversion rates were based on field trials and published literature in similar boreal forest conditions. The economic outcome was calculated on the basis of production, handling, treatment and storage costs and losses. Outcomes were tested for robustness on a range of object volumes (50–350 m3solid, extraction distances (50–550 m and transport distances (10–70 km using simulation across a set of discrete values. Transport was calculated for both a standard 19.5 m and an extended 24 m timber truck. Results showed that the most expensive chain (roadside bundling, roadside storage, terminal storage and delivery using a 19.5 m timber truck at 158 € td−1 was 23% more costly than the cheapest chain (roadside chipping and direct transport to conversion plant with container truck, at 128 € td−1. Outcomes vary at specific object volumes and transport distances, highlighting the need to verify assumptions, although standard deviations around mean supply costs for each chain were small (6%–9%. Losses at all stages were modelled, with the largest losses (23 € td−1 occurring in the chains including bundles. The study makes all methods and assumptions explicit and can assist the procurement manager in understanding the mechanisms at work.

  12. Ten major trends now emerging in the United States

    Energy Technology Data Exchange (ETDEWEB)

    Naisbitt, J.

    1978-01-01

    Using a special analytical procedure for tracking and assessing events reported in the nation's newspapers, the Center for Policy Process has identified ten emerging trends in the United States that are having a major impact on all our lives and on all businesses and industries--and especially on the electric utility industry. Although the trends may move in contradictory directions and have different degrees of significance, all have been carefully monitored for a considerable length of time. All are firmly established--and are not to be viewed as the momentary interests of certain radical elements of the population. The ten trends are: the fast-emerging clash between nuclear fuel and coal as an environmental health issue; displacement of racism and sexism by ''ageism'' as society's most prominent anti-discrimination preoccupation, and the complete elimination soon of mandatory retirement; in government and technology, the phenomenon of ''appropriate scale'' replacing economies of scale, emergence of single-issue political organizations; coming-of-age of the recycling ethic; emergence of ''access to capital'' as the new equity issue--the new rights issue; continuing shift from centralization to decentralization; movement of society in the dual directions of high technology/high touch; business' increasing involvement with the well-established accountability trend; and shift from a representative democracy to a participatory democracy--this profound change in American democracy actually began about a decade or so ago.

  13. The Top Ten Websites in Critical Care Medicine Education Today.

    Science.gov (United States)

    Wolbrink, Traci A; Rubin, Lucy; Burns, Jeffrey P; Markovitz, Barry

    2018-01-01

    The number of websites for the critical care provider is rapidly growing, including websites that are part of the Free Open Access Med(ical ed)ucation (FOAM) movement. With this rapidly expanding number of websites, critical appraisal is needed to identify quality websites. The last major review of critical care websites was published in 2011, and thus a new review of the websites relevant to the critical care clinician is necessary. A new assessment tool for evaluating critical care medicine education websites, the Critical Care Medical Education Website Quality Evaluation Tool (CCMEWQET), was modified from existing tools. A PubMed and Startpage search from 2007 to 2017 was conducted to identify websites relevant to critical care medicine education. These websites were scored based on the CCMEWQET. Ninety-seven websites relevant for critical care medicine education were identified and scored, and the top ten websites were described in detail. Common types of resources available on these websites included blog posts, podcasts, videos, online journal clubs, and interactive components such as quizzes. Almost one quarter of websites (n = 22) classified themselves as FOAM websites. The top ten websites most often included an editorial process, high-quality and appropriately attributed graphics and multimedia, scored much higher for comprehensiveness and ease of access, and included opportunities for interactive learning. Many excellent online resources for critical care medicine education currently exist, and the number is likely to continue to increase. Opportunities for improvement in many websites include more active engagement of learners, upgrading navigation abilities, incorporating an editorial process, and providing appropriate attribution for graphics and media.

  14. Safety and Health Topics: Lead

    Science.gov (United States)

    ... ammunition, pipes, cable covering, building material, solder, radiation shielding, collapsible tubes, and fishing weights. Lead is also ... lead linings in tanks and radiation protection, leaded glass, work involving soldering, and other work involving lead ...

  15. Lead poisoning: The invisible disease

    Science.gov (United States)

    Friend, Milton

    1989-01-01

    Lead poisoning is an intoxication resulting from absorption of hazardous levels of lead into body tissues. Lead pellets from shot shells, when ingested, are the most common source of lead poisoning in migratory birds. Other far less common sources include lead fishing sinkers, mine wastes, paint pigments, bullets, and other lead objects that are swallowed.

  16. Lead toxicity: current concerns.

    OpenAIRE

    Goyer, R A

    1993-01-01

    Over the 20-year period since the first issue of Environmental Health Perspectives was published, there has been considerable progress in the understanding of the potential toxicity of exposure to lead. Many of these advances have been reviewed in published symposia, conferences, and review papers in EHP. This brief review identifies major advances as well as a number of current concerns that present opportunities for prevention and intervention strategies. The major scientific advance has be...

  17. CMS lead tungstate crystals

    CERN Multimedia

    Laurent Guiraud

    2000-01-01

    These crystals are made from lead tungstate, a crystal that is as clear as glass yet with nearly four times the density. They have been produced in Russia to be used as scintillators in the electromagnetic calorimeter on the CMS experiment, part of the LHC project at CERN. When an electron, positron or photon passes through the calorimeter it will cause a cascade of particles that will then be absorbed by these scintillating crystals, allowing the particle's energy to be measured.

  18. Leading change: 3--implementation.

    Science.gov (United States)

    Kerridge, Joanna

    The potential for all staff to contribute to service improvement, irrespective of discipline, role or function, is outlined in the 2011 NHS leadership framework. This advocates developing the skills of the entire workforce to create a climate of continuous service improvement. As nurses are often required to take the lead in managing change in clinical practice, this final article in a three-part series focuses on implementing ande potentia reviewing change.

  19. Analysis of different atmospheric physical parameterizations in COAWST modeling system for the Tropical Storm Nock-ten application

    DEFF Research Database (Denmark)

    Ren, Danqin; Du, Jianting; Hua, Feng

    2016-01-01

    the storm center area. As a result, using Kain–Fritsch cumulus scheme, Goddard shortwave radiation scheme and RRTM longwave radiation scheme in WRF may lead to much larger wind intensity, significant wave height, current intensity, as well as lower SST and sea surface pressure. Thus......A coupled ocean–atmosphere–wave–sediment transport modeling system was applied to study the atmosphere and ocean dynamics during Tropical Storm Nock-ten. Different atmospheric physical parameterizations in WRF model were investigated through ten groups of numerical experiments. Results...... of atmosphere, ocean wave and current features were compared with storm observations, ERA-Interim data, NOAA sea surface temperature data, AVISO current data and HYCOM data, respectively. It was found that the storm track and intensity are sensitive to the cumulus and radiation schemes in WRF, especially around...

  20. The influence of transcutaneous electrical neurostimulation (TENS) on human cerebral blood flow velocities

    NARCIS (Netherlands)

    ter Laan, Mark; van Dijk, J. Marc C.; Elting, Jan-Willem J.; Fidler, Vaclav; Staal, Michiel J.

    It has been shown that transcutaneous electrical neurostimulation (TENS) reduces sympathetic tone. Spinal cord stimulation (SCS) has proven qualities to improve coronary, peripheral, and cerebral blood circulation. Therefore, we postulate that TENS and SCS affect the autonomic nervous system in

  1. Design and Evaluation on the Mobile Application of Transcutaneous Electrical Nerve Stimulation (TENS).

    Science.gov (United States)

    Cheng, Ching-Lung; Lee, Li-Hui; Cheng, Yu-Ting

    2017-01-01

    This study aims to design a transcutaneous electrical nerve stimulation Application (TENS App) according to the suggestions from potential users. To the best of our knowledge, this is the first App including meridian and acupoints for TENS. After its development, there are eight participants recruited for evaluating the usability. Despite two out of eight users reporting that the typical TENS system requires lower cost and has better functionality than TENS App, the results show that almost seventy percent of participants have a better perception of TENS App on price, functionality, convenience, operational ability, and quality. However, participants still reported concerns about the safety issue of adopting TENS App. Therefore, for people who are the first time or unfamiliar with TENS App, instructions from occupational or physical therapists are recommended. We conclude that by using TENS App, users can not only use the portable electrotherapy devices at anyplace, but also reduce their outpatient visits.

  2. Ten good reasons to practice ultrasound in critical care.

    Science.gov (United States)

    Lichtenstein, Daniel; van Hooland, Simon; Elbers, Paul; Malbrain, Manu L N G

    2014-01-01

    Over the past decade, critical care ultrasound has gained its place in the armamentarium of monitoring tools. A greater understanding of lung, abdominal, and vascular ultrasound plus easier access to portable machines have revolutionised the bedside assessment of our ICU patients. Because ultrasound is not only a diagnostic test, but can also be seen as a component of the physical exam, it has the potential to become the stethoscope of the 21st century. Critical care ultrasound is a combination of simple protocols, with lung ultrasound being a basic application, allowing assessment of urgent diagnoses in combination with therapeutic decisions. The LUCI (Lung Ultrasound in the Critically Ill) consists of the identification of ten signs: the bat sign (pleural line); lung sliding (seashore sign); the A-lines (horizontal artefact); the quad sign and sinusoid sign indicating pleural effusion; the fractal and tissue-like sign indicating lung consolidation; the B-lines and lung rockets indicating interstitial syndromes; abolished lung sliding with the stratosphere sign suggesting pneumothorax; and the lung point indicating pneumothorax. Two more signs, the lung pulse and the dynamic air bronchogram, are used to distinguish atelectasis from pneumonia. The BLUE protocol (Bedside Lung Ultrasound in Emergency) is a fast protocol (respiratory failure. With this protocol, it becomes possible to differentiate between pulmonary oedema, pulmonary embolism, pneumonia, chronic obstructive pulmonary disease, asthma, and pneumothorax, each showing specific ultrasound patterns and profiles. The FALLS protocol (Fluid Administration Limited by Lung Sonography) adapts the BLUE protocol to be used in patients with acute circulatory failure. It makes a sequential search for obstructive, cardiogenic, hypovolemic, and distributive shock using simple real-time echocardiography in combination with lung ultrasound, with the appearance of B-lines considered to be the endpoint for fluid therapy

  3. Ten-Year Network Development Plan - 2015 edition, executive summary

    International Nuclear Information System (INIS)

    2016-01-01

    Complying with the European and French laws, each year, RTE prepares and publicizes a Ten-Year Network Development Plan (NDP) to meet the expectations of its stakeholders and customers. The NDP lists the network development projects that RTE plans to complete and commission over a 3-year period and presents the main power transmission infrastructure work envisaged for the next Ten-years. Beyond, it outlines the possible network adaptation needs for a variety of energy transition scenarios. Over the next 10 years, the network investments will make it possible to: - Meet the goals of the Regional Climate Air Energy Plans, - Create 4 GW of extra offshore wind generation integration capacity and 10 GW of additional interconnection capacity, 2/3 more than the current capacity, - Enable the development of economically and demographically dynamic areas, with safe and high-standard electricity supply. In the coming decade, RTE plans: - 1,200 km of new underground and sub-sea DC links, along with their associated converter stations; - 600 km of existing equipment upgrades or new overhead 400 kV AC circuits substituting existing power lines. - and, at the same time, nearly 900 km of underground lines and just over 400 km of overhead 225 kV AC lines should be built. 400 projects are listed in this NDP: - 21% of the operations are on overhead lines (for 3/4 new lines or upgrade and for 1/4 dismantling of existing assets) - 27% concern new underground lines; - 52% on substation adaptations (about 20 new RTE substations and 100 new customer substations connected). Globally, nearly 80% of the network is developed underground or sub-sea. This edition of the Network Development plan is further enriched. In particular, it explains more thoroughly the link between the integration of renewable energy and the entailed development of the transmission network. It also provides a focus on smart grids. This edition relies on mid and long term scenarios describing the evolution of the

  4. Lead diffusion in monazite

    International Nuclear Information System (INIS)

    Gardes, E.

    2006-06-01

    Proper knowledge of the diffusion rates of lead in monazite is necessary to understand the U-Th-Pb age anomalies of this mineral, which is one of the most used in geochronology after zircon. Diffusion experiments were performed in NdPO 4 monocrystals and in Nd 0.66 Ca 0.17 Th 0.17 PO 4 polycrystals from Nd 0.66 Pb 0.17 Th 0.17 PO 4 thin films to investigate Pb 2+ + Th 4+ ↔ 2 Nd 3+ and Pb 2+ ↔ Ca 2+ exchanges. Diffusion annealings were run between 1200 and 1500 Celsius degrees, at room pressure, for durations ranging from one hour to one month. The diffusion profiles were analysed using TEM (transmission electronic microscopy) and RBS (Rutherford backscattering spectroscopy). The diffusivities extracted for Pb 2+ + Th 4+ ↔ 2 Nd 3+ exchange follow an Arrhenius law with parameters E equals 509 ± 24 kJ mol -1 and log(D 0 (m 2 s -1 )) equals -3.41 ± 0.77. Preliminary data for Pb 2+ ↔ Ca 2+ exchange are in agreement with this result. The extrapolation of our data to crustal temperatures yields very slow diffusivities. For instance, the time necessary for a 50 μm grain to lose all of its lead at 800 Celsius degrees is greater than the age of the Earth. From these results and other evidence from the literature, we conclude that most of the perturbations in U-Th-Pb ages of monazite cannot be attributed to lead diffusion, but rather to interactions with fluids. (author)

  5. lead glass brick

    CERN Multimedia

    When you look through the glass at a picture behind, the picture appears raised up because light is slowed down in the dense glass. It is this density (4.06 gcm-3) that makes lead glass attractive to physicists. The refractive index of the glass is 1.708 at 400nm (violet light), meaning that light travels in the glass at about 58% its normal speed. At CERN, the OPAL detector uses some 12000 blocks of glass like this to measure particle energies.

  6. Leading change: 2--planning.

    Science.gov (United States)

    Kerridge, Joanna

    National initiatives have outlined the importance of involving frontline staff in service improvement, and the ability to influence and manage change has been identified as an essential skill for delivering new models of care. Nurses often have to take the lead in managing change in clinical practice. The second in a three-part series is designed to help nurses at all levels develop the knowledge and skills to function as change agents within their organisations. This article focuses on planning the change and dealing with resistance.

  7. Leading Change, Adding Value.

    Science.gov (United States)

    Evans, Nick

    2016-09-12

    Essential facts Leading Change, Adding Value is NHS England's new nursing and midwifery framework. It is designed to build on Compassion in Practice (CiP), which was published 3 years ago and set out the 6Cs: compassion, care, commitment, courage, competence and communication. CiP established the values at the heart of nursing and midwifery, while the new framework sets out how staff can help transform the health and care sectors to meet the aims of the NHS England's Five Year Forward View.

  8. Turning lead into gold

    DEFF Research Database (Denmark)

    Jensen, Steffen Moltrup Ernø

    For years the field of entrepreneurship has been blinded by the alchemical promise of turning lead into gold, of finding the ones most likely to become the next Branson, Zuckerberg or Gates. The promise has been created in the midst of political and scientific agendas where certain individuals...... is not to accumulate state or market wealth, but for entrepreneurial skills to become tools towards the liberation of the individual from oppressive systems of control – essentially to add public value rather than economic value. In this presentation I will sketch an anarchist perspective on entrepreneurship, looking...

  9. Germination and early plant development of ten plant species ...

    Science.gov (United States)

    Ten agronomic plant species were exposed to different concentrations of nano titanium dioxide (nTiO2) or nano cerium oxide (nCeO2) (0, 250, 500 and 1000 mg/L) to examine potential effects on germination and early seedling development. We modified a standard test protocol developed for soluble chemicals (OPPTS 850.4200) to determine if such an approach might be useful for screening engineered nanomaterials (ENMs) and whether there were differences in response across a range of commercially important plant species to two common metal oxide ENMs. Eight of 10 species responded to nTiO2, and 5 species responded to nCeO2. Overall, it appeared that early root growth may be a more sensitive indicator of potential effects from ENM exposure than germination. The observed effects did not always relate to the exposure concentration, indicating that mass-based concentration may not fully explain developmental effects of these two ENMs. The results suggest that nTiO2 and nCeO2 have different effects on early plant growth of agronomic species, which may alter the timing of specific developmental events during their life cycle. In addition, standard germination tests, which are commonly used for toxicity screening of new materials, may not detect the subtle but potentially more important changes associated with early growth and development in terrestrial plants. Engineered nanoparticles (ENMs) have been recognized as valuable components of new technologies and are current

  10. Ten years of KRB Gundremmingen demonstration power station

    International Nuclear Information System (INIS)

    Facius, H. von; Ettemeyer, R.

    1976-01-01

    In August 1976 the first large nuclear power station in the Federal Republic, the KRB Gundremmingen plant with a net power of 237 MWe, has been in operation ten years. The construction of KRB as a demonstration plant was a major step forward on the way to the economic utilization of nuclear power for German utilities. Design and operation of the plant have decisively influenced the further development of the technology of light water reactors in the Federal Republic. Unlike the Kahl Experimental Nuclear Power Station (VAK), which was a test facility designed to generate experience and to train personnel, the decision to build KRB from the outset was conditional upon the fulfillment of economic criteria. Here are some of the aspects in which KRB has greatly influenced the development of nuclear power station technology: first application of internal steam-water separation instead of a steam drum with a water content of the steam of less than 1%; construction of a reactor buildung with all the necessary safety factors; solution of the corrosion and erosion problems linked with the use of a saturated steam turbine; special measures taken to prevent the turbine from speeding up due to post-evaporation effects after shutdown. Detailed comments are devoted to the subjects of availability, causes of failure and repair work. (orig.) [de

  11. Strategic Purchasing in Practice: Comparing Ten European Countries.

    Science.gov (United States)

    Klasa, Katarzyna; Greer, Scott L; van Ginneken, Ewout

    2018-02-05

    Strategic purchasing of health care services is widely recommended as a policy instrument. We conducted a review of literature of material drawn from the European Observatory on Health Systems and Policies Health Systems in Transition series, other European Observatory databases, and selected country-specific literature to augment the comparative analysis by providing the most recent healthcare trends in ten selected countries. There is little evidence of purchasing being strategic according to any of the established definitions. There is little or no literature suggesting that existing purchasing mechanisms in Europe deliver improved population health, citizen empowerment, stronger governance and stewardship, or develop purchaser organization and capacity. Strategic purchasing has not generally been implemented. Policymakers considering adopting strategic purchasing policies should be aware of this systemic implementation problem. Policymakers in systems with strategic purchasing built into policy should not assume that a purchasing system is strategic or that it is delivering any expected objectives. However, there are individual components of strategic purchasing that are worth pursuing and can provide benefits to health systems. Copyright © 2018. Published by Elsevier B.V.

  12. Ten years of born and infeld electrodynamics investigations

    Energy Technology Data Exchange (ETDEWEB)

    Vellozo, Sergio O. [Instituto Militar de Engenharia (IME), Rio de Janeiro, RJ (Brazil); Helayel Neto, Jose Abdala [Centro Brasileiro de Pesquisas Fisicas (CBPF), Rio de Janeiro, RJ (Brazil); Assis, Leonardo P. G. De [Stanford University (United States); Gaete, Patricio [U.S.M. (Chile)

    2013-07-01

    Full text: In this year, our group celebrates ten years of incursions in four-dimensional (3+1) Born and Infeld Electrodynamics (BIE). As is well known, BIE is a classical and nonlinear theory and it predicts a maximum finite value for the electric field, preventing the occurrence of classical singularities. It gives also finite energy for a point-like electric charge. In this period, our main effort was on BIE magnetic sector and the most significant results were: 1. the finite and well behaved magnetostatic field solution for a point-like electric charge at rest, 2. the intrinsic angular momentum (spin) as a self interaction among electric and magnetic field, 3. the cohesive resultant force, using the same natural and simple mechanism, giving stability to the electric charge. Another BIE incursion line stands for three-dimensional (2+1). We investigated the consequences of the space-time dimensionality on the existence of magnetostatic fields generated by electric charges at rest in an inertial frame, which were present in our four-dimensional version. A magnetostatic field associated with an electric charge at rest does not appear in this case. Interestingly, the addition of the topological term (Chern-Simons) to BIE yields the appearance of the magnetostatic field. Finally, we are looking for the hydrogen-like atom spectrum under the BI electrostatic potential, as well the muonic atom spectrum. (author)

  13. Coronary angiography in Qatar: the first ten years.

    Science.gov (United States)

    Chaikhouni, A; Gehani, A A; Horak, J; Hajar, H A

    1998-08-01

    Cardiac catheterization in Qatar was initiated in July 1982. In ten years, a total of 3900 procedures were performed at Hamad General Hospital. Computerized data registry has been maintained since 1982. Isolated coronary angiography was done in 2911 patients; of these, 2635 (90.5%) were men, and 276 (9.5%) were women, the average age of the patients was 47+/-9.2 years (range, twenty-five to eighty-eight). Patients' nationality was Qatari in 492 (17%), and other Arabs in 610 (21%), and 1512 (52%) were from the Asian subcontinent. Myocardial infarction was the most common indication (43%). Single-vessel disease was found in 638 (22%), two-vessel disease in 630 (22%), three-vessel disease in 950 (33%), and nonsignificant coronary artery disease in 693 (24%) patients. Morbidity related to the coronary angiography was reported in 147 (5%) patients, but there was no mortality related to the procedure. In 822 (28%) patients, the age was forty years or younger. The angiographic findings of these younger patients were compared with those of the older ones. Younger patients were usually men of Asian subcontinental origin with a recent myocardial infarction (MI). Often, they had normal coronary arteries or single-vessel disease. Patients of Asian subcontinent origin were usually young male patients with a recent MI, who receive streptokinase, and have single-vessel disease.

  14. WIPP: a perspective from ten years of operating success - 16189

    International Nuclear Information System (INIS)

    Gregory, Phillip C.

    2009-01-01

    The Waste Isolation Pilot Plant (WIPP), located 35 miles east of Carlsbad, New Mexico, USA is the first and, to the author's knowledge, only facility in the world for the permanent disposal of defense related transuranic (TRU) waste. Soon after plutonium was first synthesized in 1940 by a team of scientists at the University of California Berkeley Laboratory, the need to find a permanent repository for plutonium contaminated waste was recognized due to the more than 24,000 year half-life of Plutonium-239 ( 239 Pu). In 1957 the National Academy of Sciences published a report recommending deep geological burial in bedded salt as a possible solution. However, more than 50 years passed before the solution was achieved when in 1999 WIPP received the first shipment of TRU waste from Los Alamos National Laboratory. Ten years later, more than 7,600 shipments of TRU waste have been disposed of in rooms mined in an ancient salt bed more than 2,000 feet underground. This paper provides a brief history of WIPP with an overview of the technical, regulatory, and political hurdles that had to be overcome before the idea of a permanent disposal facility became reality. The paper focuses primarily on the safe, uneventful transportation program that has moved 100,000- plus containers of TRU waste from various U.S. Department of Energy (DOE) generator and/or storage sites across the Unites States to southeastern New Mexico. (author)

  15. Goiania, ten years later. Proceedings of an international conference

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-12-01

    Following the radiological accident that happened in Goiania, Brazil, in late 1987, the Brazilian National Nuclear Energy Commission (CNEN) was able to turn to the international community for assistance under the terms of the 1986 IAEA sponsored Convention on Assistance in the Case of a Nuclear Accident or Radiological Emergency; this marked the first time the convention was invoked. Additionally, to prevent the loss of useful information, CNEN and the IAEA designated a panel of international experts to investigate the causes and consequences of the accident and draw up a comprehensive report, `The Radiological Accident in Goiania`, which the IAEA published in 1988. Under its nuclear safety programme, it is the IAEA`s intention to follow up serious radiological accidents with review and analysis, to document the causes and circumstances and to disseminate conclusions, lessons to be learned and recommendations from which all States may benefit. A decade after the Goiania accident, the CNEN convened the international conference `Goiania, Ten Years Later` in co-operation with the IAEA. The purpose of this conference was to share with the local population and the international community the knowledge gained during this tragic event and in the following years. The conference attracted some 400 participants from 17 countries (Argentina, Austria, Brazil, Canada, Cuba, El Salvador, Estonia, Germany, Israel, Italy, Mexico, Peru, Russian Federation, Spain, Uruguay, United States of America and Venezuela). The present IAEA proceedings contain some 50 papers selected for publication by the editorial committee of the conference Refs, figs, tabs

  16. Goiania, ten years later. Proceedings of an international conference

    International Nuclear Information System (INIS)

    1998-12-01

    Following the radiological accident that happened in Goiania, Brazil, in late 1987, the Brazilian National Nuclear Energy Commission (CNEN) was able to turn to the international community for assistance under the terms of the 1986 IAEA sponsored Convention on Assistance in the Case of a Nuclear Accident or Radiological Emergency; this marked the first time the convention was invoked. Additionally, to prevent the loss of useful information, CNEN and the IAEA designated a panel of international experts to investigate the causes and consequences of the accident and draw up a comprehensive report, 'The Radiological Accident in Goiania', which the IAEA published in 1988. Under its nuclear safety programme, it is the IAEA's intention to follow up serious radiological accidents with review and analysis, to document the causes and circumstances and to disseminate conclusions, lessons to be learned and recommendations from which all States may benefit. A decade after the Goiania accident, the CNEN convened the international conference 'Goiania, Ten Years Later' in co-operation with the IAEA. The purpose of this conference was to share with the local population and the international community the knowledge gained during this tragic event and in the following years. The conference attracted some 400 participants from 17 countries (Argentina, Austria, Brazil, Canada, Cuba, El Salvador, Estonia, Germany, Israel, Italy, Mexico, Peru, Russian Federation, Spain, Uruguay, United States of America and Venezuela). The present IAEA proceedings contain some 50 papers selected for publication by the editorial committee of the conference

  17. [Dental care in pregnancy. Ten questions and answers].

    Science.gov (United States)

    Patcas, Raphael; Schmidlin, Patrick R; Zimmermann, Roland; Gnoinski, Wanda

    2012-01-01

    Dental care of pregnant patients is a demanding task. On one hand, clinicians are facing patients with an altered physiology that may cause a greater need for treatment. On the other hand, pregnancy in itself as well as the unborn child involves potential contraindications to dental interventions. It is therefore essential that dentists be knowledgeable of the ramifications pregnancy has on medical findings and therapy. Also, clinicians must be able to conduct their treatment based on well-grounded data to avoid any harm to the pregnant woman and her unborn child. This article focuses on facts specifically relevant to clinicians. Based on most current scientific data, we aim to answer the following ten questions: 1. What are the physiological changes during pregnancy? 2. What is the adequate lying position for a pregnant patient? 3. Is there a pregnancy-related gingivitis? 4. What is the association between periodontitis, pregnancy and preterm birth? 5. Are there oral manifestations of pregnancy-related therapies? 6. Are caries and erosions inevitable during pregnancy? 7. Should the intake of fluoride be advocated? 8. Is it permissible to x-ray pregnant patients? 9. Is orthodontics contraindicated during pregnancy and 10. Which medication should be administered with caution?

  18. A critical comparison of ten disposable cup LCAs

    Energy Technology Data Exchange (ETDEWEB)

    Harst, Eugenie van der, E-mail: eugenie.vanderharst@wur.nl [Environmental Systems Analysis Group, Wageningen University, P.O. Box 47, NL-6700 AA Wageningen (Netherlands); Potting, José, E-mail: jose.potting@wur.nl [Environmental Systems Analysis Group, Wageningen University, P.O. Box 47, NL-6700 AA Wageningen (Netherlands); Environmental Strategies Research (fms), KTH Royal Institute of Technology, SE-110 44 Stockholm (Sweden)

    2013-11-15

    Disposable cups can be made from conventional petro-plastics, bioplastics, or paperboard (coated with petro-plastics or bioplastics). This study compared ten life cycle assessment (LCA) studies of disposable cups with the aim to evaluate the robustness of their results. The selected studies have only one impact category in common, namely climate change with global warming potential (GWP) as its category indicator. Quantitative GWP results of the studies were closer examined. GWPs within and across each study show none of the cup materials to be consistently better than the others. Comparison of the absolute GWPs (after correction for the cup volume) also shows no consistent better or worse cup material. An evaluation of the methodological choices and the data sets used in the studies revealed their influence on the GWP. The differences in GWP can be attributed to a multitude of factors, i.e., cup material and weight, production processes, waste processes, allocation options, and data used. These factors basically represent different types of uncertainty. Sensitivity and scenario analyses provided only the influence of one factor at once. A systematic and simultaneous use of sensitivity and scenario analyses could, in a next research, result in more robust outcomes. -- Highlights: • Conflicting results from life cycle assessment (LCA) on disposable cups • GWP results of LCAs did not point to a best or worst cup material. • Differences in GWP results are due to methodological choices and data sets used. • Standardized LCA: transparency of LCA studies, but still different in approaches.

  19. Holistic System of Care: a ten-year perspective.

    Science.gov (United States)

    Nebelkopf, Ethan; Wright, Serena

    2011-01-01

    The Holistic System of Care for Native Americans in an Urban Environment is a community-focused intervention that provides behavioral health care, promotes health, and prevents disease. This approach is based on a community strategic planning process that honored Native American culture and relationships. Substance abuse, mental illness, homelessness, poverty, crime, physical illness, and violence are symptoms of historical trauma, family dysfunction, and spiritual imbalance. The holistic model links treatment, prevention, and recovery. The link between prevention and treatment is early intervention. Peer support is the link between treatment and recovery. Recovering individuals serve as role models linking recovery to prevention. Culture and spirituality build a strong and resilient foundation for recovery. This article documents the effectiveness of the holistic model over a ten-year period that it has been implemented at the Family & Child Guidance Clinic of the Native American Health Center in the San Francisco Bay Area. The holistic model has produced statistically significant reductions in substance abuse among adult Native American women, men, reentry, and homeless populations; reductions in substance abuse among Native American adolescents; reductions in HIV/AIDS high-risk behavior among Native American men, women, and adolescents; and decreases in acting out behavior among Native American severely emotionally disturbed children.

  20. Lateral patellar retinacular release: changes over the last ten years

    Directory of Open Access Journals (Sweden)

    Leonardo Pini Rosalem Marciano da Fonseca

    Full Text Available ABSTRACT Lateral retinacular release is a useful resource in knee surgery that can be used for disorders of the extensor mechanism. For many years, it was indiscriminately used in the treatment of the various patellofemoral joint alterations, with conflicting functional results. This study aimed to analyze the changes that have occurred in the indications and clinical effectiveness of lateral retinacular release by reviewing the relevant literature of the past ten years, comparing it to the classic literature on the subject. It was found that less extensive releases decompress the lateral patellar facet, helping with pain control, while decreasing the risks of medial subluxation. Nowadays, there is clear evidence for its indication in the lateral patellar hypercompression syndrome associated with anterior knee pain, as long as there is no related instability; furthermore, it will normally play an adjuvant role in extensor mechanism alignment surgeries for cases of recurrent patellar instability. The initial results for symptomatic patellofemoral osteoarthritis are promising when lateral release is combined with cartilage debridement; in total knee replacement, it is more commonly used for the correction of valgus deformity in order to improve the components’ congruency. Finally, distinguishing the different patellofemoral joint pathologies is seen as crucial in order to indicate this procedure. Further randomized control trials that compare surgical techniques with long-term results are still needed.

  1. Ten years of integrated care for the older in France

    Directory of Open Access Journals (Sweden)

    Dominique Somme

    2011-12-01

    Full Text Available Background: This paper analyzes progress made toward the integration of the French health care system for the older and chronically ill population. Policies: Over the last ten years, the French health care system has been principally influenced by two competing linkage models that failed to integrate social and health care services: local information and coordination centers, governed by the social field, and the gerontological health networks governed by the health field. In response to this fragmentation, Homes for the Integration and Autonomy for Alzheimer patients (MAIAs is currently being implemented at experimental sites in the French national Alzheimer plan, using an evidence-based model of integrated care. In addition, the state's reforms recently created regional health agencies (ARSs by merging seven strategic institutions to manage the overall delivery of care. Conclusion: The French health care system is moving from a linkage-based model to a more integrated care system. We draw some early lessons from these changes, including the importance of national leadership and governance and a change management strategy that uses both top-down and bottom-up approaches to implement these reforms.

  2. [Mobbing: ten-year evaluation experience in a University Hospital].

    Science.gov (United States)

    Monaco, Edoardo; Girardi, Paolo; Falaschi, Paolo; Ferracuti, Stefano; Martocchia, Antonio; Battaglia, Valentina; Capitanelli, Ilaria; Catarinozzi, Elena; Piccari, Ines; Rossi, Marina; Prestigiacomo, Claudio

    2017-11-01

    Bullying is a manifestation of occupational stress and can therefore be considered as a real "organizational pathology." Include the activities of the surgery dedicated to Mobbing, Unit of Occupational Medicine Sant'Andrea Hospital, which began operations in June 2001. In over ten years of operation (July 2012), the sample, consisting of 50.7% for men and 49.3% women, is heterogeneous in age. The schooling of the sample is medium-high as more than 82% have higher education level. The business sector is the service sector accounted for most (84%) than in industry (9%) and agriculture (2%). Of the 1545 patients seen, 1320 completed the diagnostic path, while 225 have stopped. 814 users have been certified for compatibility bullying (63% of cases) with a net reduction of the awards from 2007 onwards. Considerations are expressed about the possible intervention strategies: the presence of dedicated experts at the counters of listening and professionals as the trusted advisor, to which workers in distress can call on for advice and guidance on how to defend itself from, in accordance with the implemented for years at the Ministry of Health, the establishment of such figures as the manager rehability that in other European countries, are scheduled for some time in work organization. Copyright© by Aracne Editrice, Roma, Italy.

  3. Natural gas market assessment ten years after deregulation

    International Nuclear Information System (INIS)

    1996-11-01

    Changes which have taken place in the Canadian natural gas market in the ten years since the gas market was de-regulated, were reviewed. A 1985 agreement created conditions for a competitive natural gas market. However, the National Energy Board ensured that the pipeline transmission sector of the gas industry would continue to be regulated because of its natural monopoly characteristics. Open non-discriminatory access was to be provided to all shippers on inter-provincial gas pipelines. One objective of this report was to provide the Board with the means of assuring itself that the market was operating in such a way that Canadian requirements for natural gas were being met at fair market prices. The report also provided a review of the major changes in the gas producing and transmission sector, and reviewed developments in gas markets and sales practices. The overall assessment was that the natural gas industry was efficient and responsive to the demands of the marketplace. 5 tabs., 30 figs

  4. A critical comparison of ten disposable cup LCAs

    International Nuclear Information System (INIS)

    Harst, Eugenie van der; Potting, José

    2013-01-01

    Disposable cups can be made from conventional petro-plastics, bioplastics, or paperboard (coated with petro-plastics or bioplastics). This study compared ten life cycle assessment (LCA) studies of disposable cups with the aim to evaluate the robustness of their results. The selected studies have only one impact category in common, namely climate change with global warming potential (GWP) as its category indicator. Quantitative GWP results of the studies were closer examined. GWPs within and across each study show none of the cup materials to be consistently better than the others. Comparison of the absolute GWPs (after correction for the cup volume) also shows no consistent better or worse cup material. An evaluation of the methodological choices and the data sets used in the studies revealed their influence on the GWP. The differences in GWP can be attributed to a multitude of factors, i.e., cup material and weight, production processes, waste processes, allocation options, and data used. These factors basically represent different types of uncertainty. Sensitivity and scenario analyses provided only the influence of one factor at once. A systematic and simultaneous use of sensitivity and scenario analyses could, in a next research, result in more robust outcomes. -- Highlights: • Conflicting results from life cycle assessment (LCA) on disposable cups • GWP results of LCAs did not point to a best or worst cup material. • Differences in GWP results are due to methodological choices and data sets used. • Standardized LCA: transparency of LCA studies, but still different in approaches

  5. Treatment of severe tracheobronchomalacia: Ten-year experience.

    Science.gov (United States)

    de Trey, Lorraine A; Dudley, Julia; Ismail-Koch, Hasnaa; Durward, Andrew; Bellsham-Revell, Hannah; Blaney, Sean; Hore, Ian; Austin, Conal B; Morrison, Gavin A

    2016-04-01

    Paediatric tracheobronchomalacia is a rare but potentially serious condition. Severe tracheobronchomalacia requires intervention or operation. This is an evaluation of a ten-year experience at an institution. In this retrospective study all patients were included that required an intervention for severe tracheobronchomalacia from 2003 to 2012. Symptoms, aetiology, comorbidities, localisation of the malacia, age at diagnosis, therapeutic measures and associated complications were evaluated. Forty-four patients with severe tracheobronchomalacia underwent intervention/operation. The predominant aetiology was vascular compression in 48%. The majority of patients had complex comorbidities, most importantly cardiac pathology in 66%. The median age at diagnosis was 3 months. A total of 17 aortopexies, 21 tracheostomies and 25 stent placements were performed. The mean follow-up was 2.6 years. Severe complications occurred in 12 patients. The most common complications were stent obstruction/fracture and tracheostomy tube obstruction. The management of severe tracheobronchomalacia is complex and the population of patients is very heterogeneous. Therefore the treatment has to be adapted for each patient individually. The decision strategies are discussed in this article. The surgical techniques for placement and safe removal of expandable bare metallic stents employed in our institution are presented. A multidisciplinary team of ENT surgeons, Intensivists, Cardiologists and Cardiac surgeons is of great importance. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Use of interactive lecture demonstrations: A ten year study

    Directory of Open Access Journals (Sweden)

    Manjula D. Sharma

    2010-10-01

    Full Text Available The widely held constructivist view of learning advocates student engagement via interactivity. Within the physics education research community, several specific interactive strategies have been developed to enhance conceptual understanding. One such strategy, the Interactive Lecture Demonstration (ILD is designed for large lecture classes and, if measured using specific conceptual surveys, is purported to provide learning gains of up to 80%. This paper reports on learning gains for two different Projects over ten years. In Project 1, the ILDs were implemented from 1999 to 2001 with students who had successfully completed senior high school physics. The learning gains for students not exposed to the ILDs were in the range 13% to 16% while those for students exposed to the ILDs was 31% to 50%. In Project 2, the ILDs were implemented from 2007 to 2009 with students who had not studied senior high school physics. Since the use of ILDs in Project 1 had produced positive results, ethical considerations dictated that all students be exposed to ILDs. The learning gains were from 28% to 42%. On the one hand it is pleasing to note that there is an increase in learning gains, yet on the other, we note that the gains are nowhere near the claimed 80%. This paper also reports on teacher experiences of using the ILDs, in Project 2.

  7. 42 CFR 414.232 - Special payment rules for transcutaneous electrical nerve stimulators (TENS).

    Science.gov (United States)

    2010-10-01

    ... nerve stimulators (TENS). 414.232 Section 414.232 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... Special payment rules for transcutaneous electrical nerve stimulators (TENS). (a) General payment rule. Except as provided in paragraph (b) of this section, payment for TENS is made on a purchase basis with...

  8. Remediation of lead contaminated soil

    International Nuclear Information System (INIS)

    Urban, W.; Krishnamurthy, S.

    1992-01-01

    Lead contaminated soil in urban area is of major concern because of the potential health risk to children. Many studies have established a direct correlation between lead in soil and elevated blood lead levels in children. In Minneapolis, Minnesota, Mielke et al. (1983) reported that 50% of the Hmong children with lead poisioning were in areas where soil lead levels were between 500 and 1000 micrograms per gram (ug/g), and 40% of the children suffering from lead poisioning lived in areas where soil lead levels exceeded 1000 ug/g. In urban areas, lead pollution in soil has come from many different sources. The sources include lead paint, lead batteries and automobile exhaust. Olson and Skogerbee (1975) found the following lead compounds in soils where the primary source of pollution was from automobiles: lead sulfate, lead oxide, lead dioxide, lead sulfide, and metallic lead. The primary form of lead found was lead sulfate. Lead sulfate, lead tetraoxide, white lead, and other forms of lead have been used in the manufacture of paints for houses. At present, two remediation techniques, solidification and Bureau of Mines fluosilicic acid leaching, are available for lead-contaminated sites. The objective of the present investigation at the Risk Reduction Engineering Laboratory (RREL), Edison, was to try to solubilize the lead species by appropriate reagents and then recover the contaminants by precipitation as lead sulfate, using environmentally acceptable methods. The apparatus used for mixing was a LabMaster mixer, with variable speed and high-shear impeller. Previous work had used nitric acid for dissolving metallic lead. Owing to the environmental concerns, it was decided to use acetic acid in the presence of oxygen. The theoretical justification for this approach is the favorable redox potential for the reaction between metallic lead, acetic acid, and gaseous oxygen

  9. The optimum lead thickness for lead-activation detectors

    International Nuclear Information System (INIS)

    Si Fenni; Hu Qingyuan

    2009-01-01

    The optimum lead thickness for lead-activation detectors has been studied in this paper. First existence of the optimum lead thickness is explained theoretically. Then the optimum lead thickness is obtained by two methods, MCNP5 calculation and mathematical estimation. At last factors which affect the optimum lead thickness are discussed. It turns out that the optimum lead thickness is irrelevant to incident neutron energies. It is recommended 2.5 cm generally.

  10. Who will lead?

    Science.gov (United States)

    Gustafson, R P; Schlosser, J R

    1997-01-01

    A recent survey conducted by the UCLA Center for Health Services Management and the Physician Executive Practice of Heidrick & Struggles, an executive search firm, sheds light on the emerging physician executive's role. The goal of the research was to identify success factors as a means of evaluating and developing effective industry leaders. Respondents were asked to look at specific skills in relation to nine categories: Communication, leadership, interpersonal skills, self-motivation/management, organizational knowledge, organizational strategy, administrative skills, and thinking. Communication, leadership, and self-motivation/management emerged, in that order, as the three most important success factors for physician executives. An individual's general competencies, work styles, and ability to lead others through organizational restructuring defines his or her appropriateness for managerial positions in the health care industry.

  11. Testing for lead in toys at day care centers.

    Science.gov (United States)

    Sanders, Martha; Stolz, Julie; Chacon-Baker, Ashley

    2013-01-01

    Exposure to lead-based paint or material has been found to impact children's cognitive and behavioral development at blood lead levels far below current standards. The purpose of the project was to screen for lead in toy items in daycare centers in order to raise awareness of inside environmental lead exposures and minimize lead-based exposures for children. Occupational therapy students in a service learning class tested for lead in ten daycare or public centers using the XRF Thermo Scientific Niton XL3t, a method accepted by the Consumer Product Safety Commission (CPSC). A total of 460 items were tested over a two-month period for an average of 66 toys per setting. Fifty six (56) items tested > 100 ppm, which represented 12% of the entire sample. Items with high lead levels included selected toys constructed with lead-based paint, lead metals, plastics using lead as a color enhancer, and decorative objects. While the actual number of lead-based products is small, the cumulative exposure or habitual use may pose an unnecessary risk to children. Indoor exposures occurred for all day care centers regardless of socio-economic levels. Recommendations to minimize exposures are provided.

  12. Bylocks Drakskeppstrilogi – analogi och kulturmöten

    Directory of Open Access Journals (Sweden)

    Ingemansson, Mary

    2011-03-01

    Full Text Available In my thesis “It could just as well have happened today”: Maj Bylock's Drakskeppstrilogi and historical consciousness in ten- to twelve-year-olds, I provide a textual, thematic analysis of the three novels from 1997–1998. Further, in an empirical study I have documented the reading of Bylock's fictitious, historical trilogy about the Viking era as done by 11-year-old children, whose thematic work and development of a historical consciousness also have been part of the study. This article deals only with the textual analysis aspect, which purpose is to show what in the texts might produce a historical consciousness in children as well as how the characters are portrayed in order for children to identify with them. Two functions of the novels are studied: knowledge and analogy. The focus is on the main character Petite/Åsa and her development with a view to gender, ethnicity and class as seen from an intersectional perspective. I use postcolonial concepts such as diaspora and hybrid identity in order to describe cultural encounters brought on by migration. I portray female characters gaining a higher level of empowerment, a term used by Joanne Brown and Nancy St. Clair. Bylock claims that she is reflecting the present in her historical texts and that this is more straightforwardly achieved when the events are set several hundred years ago. As a result irrelevant details can be removed and the focus be placed on timeless, human phenomena, for instance cultural encounters. In the light of the above and ideas about how best to describe cultural encounters I analyse the cultural contexts in which the main character finds herself focusing on her transition from a girl into a woman and her quest for a multicultural identity. I elaborate on the concepts mentioned in the previous by describing two cultural encounters which provide an analogy with the present.

  13. Top ten most accessed AMOR articles in 2015/2016

    Directory of Open Access Journals (Sweden)

    Editorial Office

    2016-12-01

    Full Text Available In 2015/2016, Advances in Modern Oncology Research published a total of 67 articles over eight issues in two separate volumes. These published articles, consisting of editorials, reviews, case reports, and original research, have collectively accumulated 26,320 views as of December 2016. A total of 54 authors and 160 peer-reviewers from across the globe contributed to the journal in its first full year of publication. The journal’s top ten most accessed articles are:1. Indoles as anticancer agents (Vol. 1 Issue 1 2. Pharmacometrics and systems pharmacology of immune checkpoint inhibitor nivolumab in cancer translational medicine (Vol. 2 Issue 1 3. Hepatocellular carcinoma (HCC; aetiological considerations (Vol. 1 Issue 1 4. Oligoadenylate synthetase 1 (OAS1 expression in human breast and prostate cancer cases, and its regulation by sex steroid hormones (Vol. 2 Issue 2 5. Antiproliferative effects of cembranoid derivatives obtained from Red Sea soft coral Sarcophyton glaucum on human colorectal cancer cell lines (Vol. 1 Issue 1 6. Paraneoplastic pemphigus: A trait d’union between dermatology and oncology (Vol. 1 Issue 2 7. Cancer cell metastasis; perspectives from the focal adhesion (Vol. 1 Issue 1 8. Threshold-based parametric analysis of diffusion-weighted magnetic resonance imaging at 3.0 Tesla to identify men with prostate cancer (Vol. 1 Issue 2 9. Economic burden of patients with inoperable advanced breast cancer receiving early or late capecitabine or trastuzumab as second-line treatment: A population-based study (Vol. 1 Issue 2 10. Non-coding RNAs: New therapeutic targets and opportunities for hepatocellular carcinoma (Vol. 2 Issue 1

  14. In vitro activity of ten essential oils against Sarcoptes scabiei.

    Science.gov (United States)

    Fang, Fang; Candy, Kerdalidec; Melloul, Elise; Bernigaud, Charlotte; Chai, Ling; Darmon, Céline; Durand, Rémy; Botterel, Françoise; Chosidow, Olivier; Izri, Arezki; Huang, Weiyi; Guillot, Jacques

    2016-11-22

    The development of alternative approaches in ectoparasite management is currently required. Essential oils have been demonstrated to exhibit fumigant and topical toxicity to a number of arthropods. The aim of the present study was to assess the potential efficacy of ten essential oils against Sarcoptes scabiei. The major chemical components of the oils were identified by GC-MS analysis. Contact and fumigation bioassays were performed on Sarcoptes mites collected from experimentally infected pigs. For contact bioassays, essential oils were diluted with paraffin to get concentrations at 10, 5, and even 1% for the most efficient ones. The mites were inspected under a stereomicroscope 10, 20, 30, 40, 50, 60, 90, 120, 150, and 180min after contact. For fumigation bioassay, a filter paper was treated with 100 μL of the pure essential oil. The mites were inspected under a stereomicroscope for the first 5min, and then every 5min until 1h. Using contact bioassays, 1% clove and palmarosa oil killed all the mites within 20 and 50min, respectively. The oils efficacy order was: clove > palmarosa > geranium > tea tree > lavender > manuka > bitter orange > eucalyptus > Japanese cedar. In fumigation bioassays, the efficacy order was: tea tree > clove > eucalyptus > lavender > palmarosa > geranium > Japanese cedar > bitter orange > manuka. In both bioassays, cade oil showed no activity. Essential oils, especially tea tree, clove, palmarosa, and eucalyptus oils, are potential complementary or alternative products to treat S. scabiei infections in humans or animals, as well as to control the mites in the environment.

  15. In vitro activity of ten essential oils against Sarcoptes scabiei

    Directory of Open Access Journals (Sweden)

    Fang Fang

    2016-11-01

    Full Text Available Abstract Background The development of alternative approaches in ectoparasite management is currently required. Essential oils have been demonstrated to exhibit fumigant and topical toxicity to a number of arthropods. The aim of the present study was to assess the potential efficacy of ten essential oils against Sarcoptes scabiei. Methods The major chemical components of the oils were identified by GC-MS analysis. Contact and fumigation bioassays were performed on Sarcoptes mites collected from experimentally infected pigs. For contact bioassays, essential oils were diluted with paraffin to get concentrations at 10, 5, and even 1% for the most efficient ones. The mites were inspected under a stereomicroscope 10, 20, 30, 40, 50, 60, 90, 120, 150, and 180min after contact. For fumigation bioassay, a filter paper was treated with 100 μL of the pure essential oil. The mites were inspected under a stereomicroscope for the first 5min, and then every 5min until 1h. Results Using contact bioassays, 1% clove and palmarosa oil killed all the mites within 20 and 50min, respectively. The oils efficacy order was: clove > palmarosa > geranium > tea tree > lavender > manuka > bitter orange > eucalyptus > Japanese cedar. In fumigation bioassays, the efficacy order was: tea tree > clove > eucalyptus > lavender > palmarosa > geranium > Japanese cedar > bitter orange > manuka. In both bioassays, cade oil showed no activity. Conclusion Essential oils, especially tea tree, clove, palmarosa, and eucalyptus oils, are potential complementary or alternative products to treat S. scabiei infections in humans or animals, as well as to control the mites in the environment.

  16. The ten successful elements of an ambulatory care center.

    Science.gov (United States)

    Watkins, G

    1997-01-01

    Experts in healthcare predict that in the future, over 80% of all care will be provided either in the home or ambulatory care centers. How radiology facilities position themselves for this shifting market is critical to their long-term success, even though it appears there are endless opportunities for providing care in this atmosphere. The ten most critical elements that healthcare providers must address to ensure their preparedness are discussed. Location is critical, particularly since patients no longer want to travel to regional medical centers. The most aggressive providers are building local care centers to serve specific populations. Ambulatory care centers should project a high tech, high touch atmosphere. Patient comfort and the appeal of the overall environment must be considered. Centers need to focus on their customers' needs in multiple areas of care. A quick and easy registration process, providing dressing gowns in patient areas, clear billing functions--these are all important areas that centers should develop. Physicians practicing in the ambulatory care center are key to its overall success and can set the tone for all staff members. Staff members must be friendly and professional in their work with patients. The hours offered by the center must meet the needs of its client base, perhaps by offering evening and weekend appointments. Keeping appointments on schedule is critical if a center wants satisfied customers. It's important to identify the target before developing your marketing plan. Where do your referrals come from? Look to such sources as referring physicians, managed care plans and patients themselves. Careful billing is critical for survival in the ambulatory care world. Costs are important and systems that can track cost per exam are useful. Know your bottom line. Service remains the central focus of all successful ambulatory care center functions.

  17. Ten heuristics to evaluate the user experience of serious games

    Directory of Open Access Journals (Sweden)

    L. Fitchat

    2016-07-01

    Full Text Available The potential of serious games to promote effective learning has been establishedin the literature. However, designing effective serious games that strike a balancebetween being entertaining and at the same time instructional, remains elusive.This research turns to the field of human-computer interaction (HCI toinvestigate the aspects that are most influential to the player’s experiences withserious games. From this, HCI principles to evaluate the user experience ofserious games are identified and described. User experience (UX refers to howindividuals perceive and respond to using interactive systems such as seriousgames. Since UX is regarded as subjective in nature, this study was conductedusing interpretative phenomenological analysis, which focuses on idiographicinquiry. Semi-structured interviews were conducted with five participants afterthey were given time to play a serious game. The serious game, titledStoryTimes,aims to teach the user the multiplication tables by employing memory associationtechniques in a fun and innovative way.StoryTimeswas developed as part of thisresearch to investigate how HCI principles are applied during the developmentcycle of a serious game. The data from the interviews were analysed qualitativelyto determine which aspects of the serious game were regarded as the mostimportant from the participants’ point of view. The findings indicate that playersof serious games prefer mobile gaming platforms and have certain expectationsregarding how subject content is integrated into video games. It also reveals thedesign challenges associated with the attention spans and very diverse natures of individual players. These aspects were recast in the form of ten heuristics thatcould be applied when evaluating the UX of serious games. Designers of seriousgames can use these heuristics during the development process to create a learningenvironment that is both effective and fun.

  18. The management of radioactive waste. A description of ten countries

    Energy Technology Data Exchange (ETDEWEB)

    Lidskog, Rolf; Andersson, Ann-Catrin [Oerebro Univ. (Sweden). Man-Technology-Environment Research Centre

    2002-07-01

    The aim of this report is to provide a description of how the responsible authorities/companies in ten EDRAM countries (International Association for Environmentally Safe Disposal of Radioactive Materials) deal with the management of radioactive waste. The focus is on how the responsible organisation currently handles this issue, including technical, economic and socio-political aspects. The material used was primarily produced by the companies/authorities themselves. The report describes the development and situation in each country up to the end of 2001, or later if noted as such in the country report. The scope of this report does not permit an evaluation of how successful and effective the companies and authorities have been in implementing their plans and ambitions. The report does not include the views of other national stakeholders concerning radwaste management, or their opinions of the way that the authorities/companies handle the issue of radwaste. The description is based on a series of questions that were drawn up and discussed at the initial stage of the EDRAM co-operation. Technological aspects: 1. What technology is used? How is research and development promoted and executed? 2. Where is the waste to be put? What criteria does each country search for? 3. How is security to be maintained? Who can obtain a license for handling nuclear waste? Economic aspects: 1. In what way do the countries in question discuss the time aspects as regards delays and similar? 2. How are the economic and financial aspects of the process dealt with? Where does the money come from? Socio-political aspects: 4. What role do politicians play and to what extent is social acceptance a part of the process? What part does public opinion play? 5. How flexible is the decision-making process and can decisions be revised? 6. Does the public have confidence in the industry and the decision-makers? 7. What kind of institutional problems arise? With regard to public involvement in

  19. The management of radioactive waste. A description of ten countries

    International Nuclear Information System (INIS)

    Lidskog, Rolf; Andersson, Ann-Catrin

    2002-01-01

    The aim of this report is to provide a description of how the responsible authorities/companies in ten EDRAM countries (International Association for Environmentally Safe Disposal of Radioactive Materials) deal with the management of radioactive waste. The focus is on how the responsible organisation currently handles this issue, including technical, economic and socio-political aspects. The material used was primarily produced by the companies/authorities themselves. The report describes the development and situation in each country up to the end of 2001, or later if noted as such in the country report. The scope of this report does not permit an evaluation of how successful and effective the companies and authorities have been in implementing their plans and ambitions. The report does not include the views of other national stakeholders concerning radwaste management, or their opinions of the way that the authorities/companies handle the issue of radwaste. The description is based on a series of questions that were drawn up and discussed at the initial stage of the EDRAM co-operation. Technological aspects: 1. What technology is used? How is research and development promoted and executed? 2. Where is the waste to be put? What criteria does each country search for? 3. How is security to be maintained? Who can obtain a license for handling nuclear waste? Economic aspects: 1. In what way do the countries in question discuss the time aspects as regards delays and similar? 2. How are the economic and financial aspects of the process dealt with? Where does the money come from? Socio-political aspects: 4. What role do politicians play and to what extent is social acceptance a part of the process? What part does public opinion play? 5. How flexible is the decision-making process and can decisions be revised? 6. Does the public have confidence in the industry and the decision-makers? 7. What kind of institutional problems arise? With regard to public involvement in

  20. Environmental regulations: their impact on the battery and lead industries

    Science.gov (United States)

    Ainley, John R.

    This paper presents a general overview of the past and current position of the lead industry in relation to environmental legislation and its impact. The lead industry has watched environmental lead levels being steadily reduced down to levels that, ten years ago, would have been considered unachievable. Nevertheless, the industry has managed to survive the effect of the ever-increasing demands of environmental controls. During the last ten to twenty years, lead producers and users have had to assess their future positions, as the cost implications of environmental laws have had a significant impact on their bottom lines. Without doubt, this consideration most definitely affected the viability of many plants. The need to be aware of the existence of new and proposed legislation is of paramount importance, as the threat from the vast array of EEC legislation is ever apparent. Lead companies have all considered environmental legislation to have no more than a nuisance value, but it is of vital importance to the future of the industry that such legislation is approached in a positive and sensible way in order to demonstrate a full commitment to protecting both employees and the general environment. Lead must receive the credit that it so richly deserves.

  1. Lead and lead-based alloys as waste matrix materials

    International Nuclear Information System (INIS)

    Arustamov, A.E.; Ojovan, M.I.; Kachalov, M.B.

    1999-01-01

    Metals and alloys with relatively low melting temperatures such as lead and lead-based alloys are considered in Russia as prospective matrices for encapsulation of spent nuclear fuel in containers in preparation for final disposal in underground repositories. Now lead and lead-based alloys are being used for conditioning spent sealed radioactive sources at radioactive waste disposal facilities

  2. Is TENS purely a placebo effect? A controlled study on chronic low back pain.

    Science.gov (United States)

    Marchand, S; Charest, J; Li, J; Chenard, J R; Lavignolle, B; Laurencelle, L

    1993-07-01

    Although high-frequency low-intensity transcutaneous electric nerve stimulation (TENS) has been extensively used to relieve low back pain, experimental studies of its effectiveness have yielded contradictory findings mainly due to methodological problems in pain evaluation and placebo control. In the present study, separate visual analog scales (VAS) were used to measure the sensory-discriminative and motivational-affective components of low back pain. Forty-two subjects were randomly assigned to 1 of 3 groups: TENS, placebo-TENS, and no treatment (control). In order to measure the short-term effect of TENS, VAS pain ratings were taken before and after each treatment session. Also, to measure long-term effects, patients rated their pain at home every 2 h throughout a 3-day period before and 1 week, 3 months and 6 months after the treatment sessions. In comparing the pain evaluations made immediately before and after each treatment session, TENS and placebo-TENS significantly reduced both the intensity and unpleasantness of chronic low back pain. TENS was significantly more efficient than placebo-TENS in reducing pain intensity but not pain unpleasantness. TENS also produced a significant additive effect over repetitive treatment sessions for pain intensity and relative pain unpleasantness. This additive effect was not found for placebo-TENS. When evaluated at home, pain intensity was significantly reduced more by TENS than placebo-TENS 1 week after the end of treatment, but not 3 months and 6 months later. At home evaluation of pain unpleasantness in the TENS group was never different from the placebo-TENS group.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Lead concentrations and risk exposure assessment in surface soils ...

    African Journals Online (AJOL)

    This study investigated lead concentrations in < 250 μm and < 75 μm of deposited dust and< 2000 μm, < 250 μm, and < 75 μm of surface soils at undeveloped residential lands leased to auto-mechanic artisans for a minimum of ten years and estimated exposure risk for children that will reside on the polluted lands after the ...

  4. The sports results of leading pentathlonists during 2000-2010.

    OpenAIRE

    Pityn M.P.; Stetskovich S.R.

    2011-01-01

    The result sports changes of leading sportsmen of the world in modern pentathlon are considered in the paper. During the investigation process the competition rules changes were determined and what have affected on the sports result in the modern pentathlon. The winner results changes and top ten sportsmen of the world championships and the Olympic Games were characterized during 2000-2010. The rules changes influence of the competition holding on the results of competitive activity of high q...

  5. Lead poisoning in calves

    Energy Technology Data Exchange (ETDEWEB)

    Reeves, J E

    1964-01-01

    Over a three-year period a farmer lost seven calves in their second month of age. One year ago a tentative diagnosis of rabies was given and a brain was submitted to the Health of Animals Division for examination. No Negri bodies were found. The owner stated that the calves first appeared listless and later exhibited severe nervous signs. Deaths occurred in from one to 24 hours after onset of signs. Appetite and bowel movements were normal. There was no increase in temperature. The calf would lie quietly for an interval, then rise, run down the alley, press against a wall, and go into a convulsion. It acted as if it were in severe pain and during one of the intermittent convulsions, it jumped over a three-foot partition. This calf was sent to the Regional Veterinary Laboratory at Brighton for necropsy. The calf had been dead for 72 hours when submitted to the laboratory. The only gross findings were of mild pleurisy and hemorrhage on the kidney. A tentative diagnosis of lead poisoning was offered and specimens sent to the Division of Pharmacology and Toxicology, Ontario Veterinary College.

  6. Transcutaneous Electrical Nerve Stimulation (TENS) reduces pain, fatigue, and hyperalgesia while restoring central inhibition in primary fibromyalgia

    Science.gov (United States)

    Dailey, Dana L; Rakel, Barbara A; Vance, Carol GT; Liebano, Richard E; Anand, Amrit S; Bush, Heather M; Lee, Kyoung S; Lee, Jennifer E; Sluka, Kathleen A

    2014-01-01

    Because TENS works by reducing central excitability and activating central inhibition pathways, we tested the hypothesis that TENS would reduce pain and fatigue and improve function and hyperalgesia in people with fibromyalgia who have enhanced central excitability and reduced inhibition. The current study used a double-blinded randomized, placebo controlled cross-over design to test effects of a single treatment of TENS in people with fibromyalgia. Three treatments were assessed in random order: active TENS, placebo TENS, no TENS. The following measures were assessed before and after each TENS treatment: pain and fatigue at rest and movement, pressure pain thresholds (PPTs), 6 minute walk test (6MWT), range of motion (ROM), five time sit to stand test (FTSTS), and single leg stance (SLS). Conditioned pain modulation (CPM) was completed at end of testing. There was a significant decrease in pain and fatigue with movement for active TENS compared to placebo and no TENS. PPTs increased at site of TENS (spine) and outside site of TENS (leg) when compared to placebo TENS or no TENS. During Active TENS CPM was significantly stronger compared to placebo TENS and no TENS. No changes in functional tasks were observed with TENS. Thus, the current study suggests TENS has short-term efficacy in relieving symptoms of fibromyalgia while the stimulator is active. Future clinical trials should examine the effects of repeated daily delivery of TENS, similar to how TENS is used clinically, on pain, fatigue, function and quality of life in individuals with fibromyalgia. PMID:23900134

  7. Accessible mathematics ten instructional shifts that raise student achievement

    CERN Document Server

    Leinwand, Steven

    2009-01-01

    Accessible Mathematics is Steven Leinwand's latest important book for math teachers. He focuses on the crucial issue of classroom instruction. He scours the research and visits highly effective classrooms for practical examples of small adjustments to teaching that lead to deeper student learning in math. Some of his 10 classroom-tested teaching shifts may surprise you and others will validate your thinking. But all will improve students' performance. Read Accessible Mathematics, try its 10 suggestions, and discover how minor shifts in teaching can put learning into high gear.

  8. Ten years of ALARA experience in commercial nuclear pharmacy

    International Nuclear Information System (INIS)

    Coffey, J.L.; Seifert, K.L.; Green, R.L.; McAnany, P.J.

    2002-01-01

    The objective of this study was to review ten years of extremity exposure in a growing nuclear pharmacy company and determine those practices that have been most effective in keeping exposures ALARA. The focus of this study was specifically on extremity exposure since whole body exposures have not been as significant. Methods: More than 400 dispensing employees are monitored weekly for extremity exposure. Currently, these employees handle and dispense more than 9,000 Curies (333,000 GBq) of activity ready for use in nuclear medicine procedures each week. The quarterly and annual extremity exposure histories were examined and compared with the introduction of different initiatives to limit these exposures. Changes in the total activity per unit dose were considered as well as the introduction of different compounding practices during this time. An attempt was made to also determine specifically which activities contribute most to the extremity exposure of a dispenser. Procedural changes were reviewed as well as engineering controls such as new shielding materials and designs. Results: A significant conversion of cardiac doses occurred during the time period evaluated. Tc-99m heart agents became the preferred radiopharmaceutical replacing a significant portion of Tl-201 that had been used previously. Tl-201 is still used often in conjunction with a Tc-99m agent. The significance of the switch is the high percentage of dispensed doses for cardiac studies and the higher activities of the Tc-99m agents. A combination of procedural changes and engineering controls (primarily tungsten shielding devices) have been effective in preventing the extremity exposure increase one might expect based on higher activities dispensed per unit dose and the higher energy of Tc-99m compared to Tl-201. One procedural change, the mandatory use of tongs for handling unshielded syringes of radiopharmaceuticals, resulted in a 17% reduction in the average exposure to the extremities

  9. An assessment of ten ocean reanalyses in the polar regions

    Science.gov (United States)

    Uotila, Petteri

    2017-04-01

    Ocean reanalysis (ORA) combines observations either statistically or with a hydrodynamical model, to reconstruct historical changes in the ocean. Global and regional ORA products are increasingly used in polar research, but their quality remains to be systematically assessed. To address this, the Polar ORA Intercomparison Project (PORA-IP) has been established following on from the ORA-IP project (Balmaseda et al. 2015, with other papers in a special issue of Climate Dynamics). The PORA-IP is constituted under the COST EOS initiative with plans to review reanalyses products in both the Arctic and Antarctic, and is endorsed by YOPP - the Year of Polar Prediction project. Currently, the PORA-IP team consists of 21 researchers from 15 institutes and universities. The ORA-IP products with polar physics, such as sea ice, have been updated where necessary and collected in a public database. In addition to model output, available observational polar climatologies are collected and used in the assessments. Due to the extensive variety of products, this database should become a valuable resource outside the PORA-IP community. For a comprehensive evaluation of the ten ORA products (CGLORSv5, ECDA3.1, GECCO2, Glorys2v4, GloSea5_GO5, MOVEG2i, ORAP5, SODA3.3.1, TOPAZ4 and UR025.4) in the Arctic and Southern Oceans several specific diagnostics are assessed. The PORA-IP diagnostics target the following topics: hydrography; heat, salinity and freshwater content; ocean transports and surface currents; mixed layer depth; sea-ice concentration and thickness; and snow thickness over sea ice. Based on these diagnostics, ORA product biases against observed data and their mutual spread are quantified, and possible reasons for discrepancies discussed. So far, we have identified product outliers and evaluated the multi-model mean. We have identified the importance of the atmospheric forcing, air-ocean coupling protocol and sea-ice data assimilation for the product performance. Moreover, we

  10. Sclerotherapy of Plummer's disease - A critical ten year review

    International Nuclear Information System (INIS)

    Sandrock, D.; Humplik, B.I.; Munz, D.L.

    2002-01-01

    Aim: Since ten years sclerotherapy with ethanol is proposed for the treatment of Plummer's disease (unifocal autonomy). Hence, it was the aim of this study to evaluate critically all the sclerotherapies performed in our institution. Special attention should be given to the long-term results. Material and Methods: In the study enrolled were 47 consecutive patients with Plummer's disease, who were referred to sclerotherapy with ethanol since 1991 (10 men, 37 women, aged 24-79 years). The diagnosis of unifocal autonomy was proven in all patients by scintigraphy under TSH-suppressed conditions. 31 patients had latent, 16 manifest hyperthyroidism, 12 of these under antithyroid medication. All patients received ultrasound guided infiltrations of 0.5-2 ml 96 % ethanol into the autonomy. The procedure was repeated at intervals (individually between 1 week and 3 months) until there was A) sufficient success, B) partial success or C) the patient refused further infiltrations. Results: Overall, 407 infiltrations were performed. The number of infiltrations per patient reached from 1 to 63 (mean 7). The side effects included 2 cases of a (transient) paresis of the recurrent nerve and pain/discomfort in 32 %. The therapy was finished successfully (group A; normal TSH, normalisation of the scintigraphic pattern) in 17 patients, partially successfully (group B; change from manifest to latent hyperthyroidism and/or TSH > 0.1 mU/l, scintigram not completely normalized) in 12 patients, and without success (group C) in 16 patients - 2 changed to surgery, 4 to radioiodine therapy, 3 continued antithyroid medication and 4 refused therapy without further comments. Excluding 2 patients from group B (with 35 and 61 infiltrations, respectively) there was no significant difference between A, B, and C in the parameters uptake under suppression, volume of the autonomy, laboratory values, number of infiltrations, age or sex. Conclusion: The sclerotherapy with ethanol, consequently performed, is

  11. The experience of ABACC after ten years applying safeguards

    International Nuclear Information System (INIS)

    Feu Alvim, Carlos A.; Palacios, Elias; Esteves dos Santos, Jose M.; Oliveira, Antonio

    2001-01-01

    Full text: During the second half of this century, Argentina and Brazil shared a common ambition: to gain knowledge on and develop the technology required for attaining a full command of the nuclear fuel cycle. Until mid-1990's, neither of these countries had fully adhered to the Tlatelolco Treaty, nor had they signed the Non-Proliferation Treaty (NPT), as a way to protect themselves towards the development of such technology. The discriminatory nature of the NPT was the argument used to resist the international pressure for its signature. On the other hand, the text of the Tlatelolco Treaty involved special inspections to non-declared facilities that meant a threat of industrial espionage which Argentina and Brazil wanted to avoid. This position -maintained for almost two decades - led the international community to view these countries as competing for nuclear supremacy. As of 1985, both Argentina and Brazil, by means of joint declarations, expressed their decision to provide transparency to their nuclear programs. Consequently, they undertook several commitments concerning the exclusively peaceful purposes in their use of nuclear energy and in their respective nuclear programs. This process of joint declarations led to the signature of a Bilateral Agreement for the Exclusively Peaceful Uses of Nuclear Energy in July 1991. Through this agreement, they formally established their Common System of Accounting and Control of Nuclear Materials (SCCC) and created the Brazilian-Argentine Agency for Accounting and Control of Nuclear Materials (ABACC) in order to implement the established verification system. Also at that time, the decision was made to start negotiations with the International Atomic Energy Agency (IAEA) towards a joint agreement on safeguards based on the SCCC. In March 1994, the Quadripartite Agreement between Argentina, Brazil, the ABACC and the IAEA entered into force. The experience in the application of SCCC during its first ten years and the

  12. 2006 - 2016: Ten Years Of Tsunami In French Polynesia

    Science.gov (United States)

    Reymond, D.; Jamelot, A.; Hyvernaud, O.

    2016-12-01

    Located in South central Pacific and despite of its far field situation, the French Polynesia is very much concerned by the tsunamis generated along the major subduction zones located around the Pacific. At the time of writing, 10 tsunamis have been generated in the Pacific Ocean since 2006; all these events recorded in French Polynesia, produced different levels of warning, starting from a simple seismic warning with an information bulletin, up to an effective tsunami warning with evacuation of the coastal zone. These tsunamigenic events represent an invaluable opportunity of evolutions and tests of the tsunami warning system developed in French Polynesia: during the last ten years, the warning rules had evolved from a simple criterion of magnitudes up to the computation of the main seismic source parameters (location, slowness determinant (Newman & Okal, 1998) and focal geometry) using two independent methods: the first one uses an inversion of W-phases (Kanamori & Rivera, 2012) and the second one performs an inversion of long period surface waves (Clément & Reymond, 2014); the source parameters such estimated allow to compute in near real time the expected distributions of tsunami heights (with the help of a super-computer and parallelized codes of numerical simulations). Furthermore, two kinds of numerical modeling are used: the first one, very rapid (performed in about 5minutes of computation time) is based on the Green's law (Jamelot & Reymond, 2015), and a more detailed and precise one that uses classical numerical simulations through nested grids (about 45 minutes of computation time). Consequently, the criteria of tsunami warning are presently based on the expected tsunami heights in the different archipelagos and islands of French Polynesia. This major evolution allows to differentiate and use different levels of warning for the different archipelagos,working in tandem with the Civil Defense. We present the comparison of the historical observed tsunami

  13. [Ten years of destructive eyeball surgery in Lomé].

    Science.gov (United States)

    Vonor, K; Amedome, K M; Dzidzinyo, K; Ayena, K D; Santos, M K A; Maneh, N; Tete, Y; Balo, K P

    2015-01-01

    Destructive surgery of the eyeball comprises radical procedures - evisceration, enucleation, and exenteration - with various indications. The purpose of this study was to determine the features of these procedures in Lomé. We conducted a retrospective study reviewing records for all patients undergoing these procedures in 3 ophthalmic centers in Lomé in the decade from 2002 through 2011. Of 6240 eye operations, 76 involved one of these three procedures, for a frequency of 1.2%. Patients' mean age was 40.1 ± 26.9 years (range: 1 day to 91 years). The sex ratio (of men to women) was 1.2. The principal indications were staphyloma (38%), ocular and orbital tumors (30%), and phthisis bulbi (24%). Retinoblastoma was the leading type of ocular/orbital tumor (52%). Local anesthesia was performed in 64% of cases, and general anesthesia in 36%. Evisceration was practiced in 67% of cases, enucleation in 24%, and exenteration in 9%. An ocular prosthesis was placed in 46%. Staphyloma was the leading indication for destructive surgery. Given the damage of this type of procedure, primary prevention is important, including early and adequate management of ocular conditions.

  14. PENERAPAN MODEL BRAND EQUITY TEN PADA UPBJJ-UT BOGOR

    Directory of Open Access Journals (Sweden)

    Deni Surapto

    2015-04-01

    Full Text Available The objectives of the study are to (1 analyze the dimensions of awareness, associations, perceived quality/leadership, loyalty, and market behavior based upon the assessment of Open University students and the public, (2 evaluate the Open University brand equity model based on brand equity ten. The time period of research was during April-July 2012 and the location was in Open University Bogor campus. The population of this study consisted of high school students, employees and students of Open University Bogor, amounting to 693,950 people. Samples of 400 people were obtained. The data is collected using survey method, whereby interviews of the sample group is conducted using a closed form questionnaire based upon the Likert scale method. Based on the results from the analysis of the measures of awareness and brand recall, the Open University got the ranking of 11th and 7th among the other universities from 2% of the respondents respectively. It was ranked 1st on the measure of recognition and unaware by 5.5% of respondents. Based on the results from the analysis of the measure of association using Cochran test, it was found that the attributes of time and cost are associated with the brand of Open University. Results from the analysis of the measure of perceived quality regarding quality of services provided by Open University to its students show that registration services rated good while study material, online tutorials and exams were assessed as fair. Result from the analysis of the price premium loyalty measures indicate that students objected to an increase in tuition over Rp.25.000,-. Satisfaction measure indicates that the level of satisfaction of the Open University students is up to the extent of liking the brand, that is like and enjoy the study at Open University. This is indicated by the highest score received for the level of liking the brand which is 70%. Result from the analysis of the measure market behavior regarding market

  15. Drowning: a leading killer!

    Directory of Open Access Journals (Sweden)

    Nuno Domingos Garrido

    2016-10-01

    Full Text Available Drowning kills at least 372,000 people worldwide every year and is the 3rd leading cause of unintentional death, accounting for 7% of all deaths stemming from accidents (WHO, 2014. Conceptually, “drowning” is a complex and multi-faceted phenomenon, characterized as a chain of events (Bierens, 2006. Drowning is defined as the process of experiencing respiratory impairment from immersion or submersion in liquid. Research on drowning as a phenomenon presents several difficulties - most of all, that global data concerning the number of occurrences are not accurate. Nevertheless, detailed analysis of the registered incidents allows the identification of risk factors of drowning. An in-depth analysis of the risk factors is the basis for the creation of targeted and effective strategies to prevent drowning. Due to variability of situations which could lead to a drowning episode, experts suggest the adoption of a multi-layer prevention model, rather than opting for isolated measures, since no single measure can prevent all deaths and injuries caused by submersion. Among the preventive measures we would like to emphasize instruction in swimming and water safety. So, what does "knowing how to swim" really mean? Some authors define mastery of this competence as swimming a given distance, while others put the emphasis on how this/any given distance is swum (Stallman, Junge, & Blixt, 2008. It has long been realized that there is no contradiction between learning those competencies which make a person less susceptible to drowning and those competencies which prepare the path towards higher levels of performance and competition. Aquatic movement researchers and practitioners and drowning prevention researchers and practitioners, share in the responsibility for drowning prevention though they are often unaware of it. The question “What should be taught to children?” is too infrequently asked. There remains great variation in what is taught and programs

  16. Leading Your Leaders

    Science.gov (United States)

    Hale, Wayne N.

    2008-01-01

    life is good. More often when an unbelievably difficult test fails, we are left with a very long discussion of why and what was wrong in the design or execution of the test. Make sure that the test is well defined. Even then, it is important to explain to your leaders what inherent accuracy (or error) the test conditions or equipment have and what the assumptions or initial conditions were for the test. Test results without a good understanding of the test's accuracy or the pedigree of the test assumptions are worth very little. Finally, there is flight test data. Always limited, never at the edge of the envelope, it still shows how the real hardware works in a combined environment. Flight experience is dangerous because it typically doesn't show how close to the edge of the cliff the equipment is operating, but it does demonstrate how the hardware really works. A flight test is the ultimate test, again taken with the knowledge that it is probably not the extreme but something more like the middle of the environmental and systems performance. Good understanding of a problem and its solution always relies on a combination of all these methods. Be sure to lead your leaders by using all the tools you have at your disposal. At the end of the day, decisions in space flight always come down to a risk trade. Our business is not remotely safe, not in the sense that the public, the media, or our legislators use the term. Everything we do has a risk, cost, schedule, or performance trade-off. For your leaders to make an appropriate decision, you need to educate them, lead them, talk with them, and engage them in the discussion until full understanding takes place. It's your job. *

  17. Assessing the effects of transcutaneous electrical nerve stimulation (TENS) in post-thoracotomy analgesia.

    Science.gov (United States)

    Ferreira, Fabiana Cristina; Issy, Adriana Machado; Sakata, Rioko Kimiko

    2011-01-01

    Transcutaneous electrical nerve stimulation (TENS) is commonly used to treat musculoskeletal pain, but it may also be indicated for postoperative analgesia. The objective of this study was to evaluate the analgesic effects of TENS on post-thoracotomy. Thirty patients between 18 and 60 years of age undergoing thoracotomy for lung cancer resection on the second postoperative day were included in this study. Patients were divided into two groups (G1 and G2). G1 patients were treated with TENS; and in G2 (without TENS) electrodes were placed but the equipment was not turned on. TENS was maintained for one hour. The visual analogue scale was used to evaluate the analgesic effects on three moments: before TENS (M0), immediately after TENS (M1), and one hour later (M2), with the patient at rest, elevation of the upper limbs, change in decubitus, and coughing. The intensity of pain at rest was higher in G2 immediately after TENS, but not one hour after the procedure. There was no difference between both groups with elevation of the upper limbs, decubitus change, and coughing. With the use of TENS for one hour on the second post-thoracotomy day in patients who received fentanyl (50 μg) associated with bupivacaine (5 mL), a reduction in pain intensity was observed at rest immediately after TENS; with elevation of the upper limbs, change in decubitus, and coughing, a reduction in pain severity was not observed. Copyright © 2011 Elsevier Editora Ltda. All rights reserved.

  18. Research and realization of ten-print data quality control techniques for imperial scale automated fingerprint identification system

    Directory of Open Access Journals (Sweden)

    Qian Wang

    2017-01-01

    Full Text Available As the first individualization-information processing equipment put into practical service worldwide, Automated Fingerprint Identification System (AFIS has always been regarded as the first choice in individualization of criminal suspects or those who died in mass disasters. By integrating data within the existing regional large-scale AFIS database, many countries are constructing an ultra large state-of-the-art AFIS (or Imperial Scale AFIS system. Therefore, it is very important to develop a series of ten-print data quality controlling process for this system of this type, which would insure a substantial matching efficiency, as the pouring data come into this imperial scale being. As the image quality of ten-print data is closely relevant to AFIS matching proficiency, a lot of police departments have allocated huge amount of human and financial resources over this issue by carrying out manual verification works for years. Unfortunately, quality control method above is always proved to be inadequate because it is an astronomical task involved, in which it has always been problematic and less affiant for potential errors. Hence, we will implement quality control in the above procedure with supplementary-acquisition effect caused by the delay of feedback instructions sent from the human verification teams. In this article, a series of fingerprint image quality supervising techniques has been put forward, which makes it possible for computer programs to supervise the ten-print image quality in real-time and more accurate manner as substitute for traditional manual verifications. Besides its prominent advantages in the human and financial expenditures, it has also been proved to obviously improve the image quality of the AFIS ten-print database, which leads up to a dramatic improvement in the AFIS-matching accuracy as well.

  19. [Analysis of quality of life in patiens with low back pain after receiving transcutaneous electrical nerve stimulation (TENS)].

    Science.gov (United States)

    Zaniewska, Renata; Okurowska-Zawada, Bozena; Kułak, Wojciech; Domian, Karolina

    2012-01-01

    Low back pain (LBP) is one of the most common disorders affecting office employees working with a computer, which inevitably leads to lower quality of life. The aim of this study was to analyze the quality of life of patients with LBP after application of TENS (Transcutaneous Electrical Nervous Stimulation). The study group included 30 computer workers (26 females and 4 males) aged 30-60 years (45 +/- 12). The quality of life was assessed using the World Health Organization Quality of Life instrument-Abbreviated version (WHOQOL-Bref) before and after 10 applications of TENS. Outcomes were evaluated with a visual analog score (VAS) for pain and Schober's test to measure the ability of a patient to flex his or her lower back. The mean VAS value decreased significantly from 3.83 +/- 1.31 cm at baseline to 3.36 +/- 1.21 cm after treatment. Patients reported pain relief. The highest quality of life scores in terms of social relationships were found in the social category evaluating personal relationships, social support and sexual activity (15.91 +/- 2.07) and mental health (14.32 +/- 1.59). After treatment a significant increase in the flexion of lower back was observed in the majority of patients. No significant correlations between the quality of life and the intensity of pain and the flexion of lower back before and after treatment were found. TENS therapy is an effective technique for pain relief in patients with LBP. TENS can also be used with other methods of LBP treatment and may improve the patients' quality of life.

  20. Manurial properties of lead nitrate

    Energy Technology Data Exchange (ETDEWEB)

    Berry, R A

    1924-01-01

    Water culture, pot and field experiments were conducted in order to determine the toxic and stimulating limit of lead nitrate in solution. Oats and rye grass were evaluated for evidence of lead poisoning. Results indicate that except in solutions of fairly high concentration, soil adsorbs the lead and destroys the toxicity of soluble lead salts. There was evidence to show that the addition of lead salts increased the rate of nitrification in soil.

  1. Pierre Bourdieu, dez anos depois Pierre Bourdieu, ten years after

    Directory of Open Access Journals (Sweden)

    Cristina Carta Cardoso de Medeiros

    2013-03-01

    Full Text Available O presente texto procura discutir o legado deixado pelo sociólogo francês Pierre Bourdieu. Dez anos após sua morte, tem-se discutido, em nível internacional, a relevância deste autor, um dos mais influentes e citados teóricos do mundo. Para a identificação desta influência no Brasil, mais especificamente no campo educacional brasileiro, pesquisou-se nas teses e dissertações encontradas no banco de dados da CAPES, que referenciavam Bourdieu, de que forma estaria se dando a apropriação de seu quadro teórico de análise para construção de conhecimento no referido campo. Concluiu-se que o número de produções defendidas nos Programas de Pós-Graduação em Educação no Brasil, de 1965 a 2010, cresce de forma exponencial, demonstrando o quão profícua a utilização da teoria sociológica de Bourdieu tem se mostrado para explicar a realidade da Educação no Brasil na contemporaneidade. Encerra-se o artigo com uma reflexão sobre a consideração do status de Bourdieu como um clássico da Sociologia que, paradoxalmente, se mostra mais atual e vivo do que qualquer outro autor quando se trata de aplicar seu princípio maior, a saber, analisar o mundo social e suas lógicas, desvelando as formas de dominação e as misérias sociais.This paper's intent is to discuss the legacy left by the French sociologist Pierre Bourdieu. Ten years after his death, it has been discussed at an international level the relevance of this author, one of the most cited and influential theorists in the world. To identify such influence in Brazil, more specifically in the Brazilian educational field, we investigated theses and dissertations found in CAPES database, which referenced Bourdieu, to identify how those works use his theoretical framework of analysis for construction of knowledge in that field. It was concluded that the number of productions held in post-graduate programs in education in Brazil, from 1965 to 2010, grows exponentially

  2. Lead in teeth from lead-dosed goats: Microdistribution and relationship to the cumulative lead dose

    International Nuclear Information System (INIS)

    Bellis, David J.; Hetter, Katherine M.; Jones, Joseph; Amarasiriwardena, Dula; Parsons, Patrick J.

    2008-01-01

    Teeth are commonly used as a biomarker of long-term lead exposure. There appear to be few data, however, on the content or distribution of lead in teeth where data on specific lead intake (dose) are also available. This study describes the analysis of a convenience sample of teeth from animals that were dosed with lead for other purposes, i.e., a proficiency testing program for blood lead. Lead concentration of whole teeth obtained from 23 animals, as determined by atomic absorption spectrometry, varied from 0.6 to 80 μg g -1 . Linear regression of whole tooth lead (μg g -1 ) on the cumulative lead dose received by the animal (g) yielded a slope of 1.2, with r 2 =0.647 (p -1 , were found in circumpulpal dentine. Linear regression of circumpulpal lead (μg g -1 ) on cumulative lead dose (g) yielded a slope of 23 with r 2 =0.961 (p=0.0001). The data indicated that whole tooth lead, and especially circumpulpal lead, of dosed goats increased linearly with cumulative lead exposure. These data suggest that circumpulpal dentine is a better biomarker of cumulative lead exposure than is whole tooth lead, at least for lead-dosed goats

  3. Lead pollution sources and Impacts

    International Nuclear Information System (INIS)

    El-Haggar, S.M.; Saad, S.G.; Saleh, S.K.; El-Kady, M.A.

    1996-01-01

    Despite the medical awareness of lead toxicity, and despite legislation designed to reduce environmental contamination, lead is one of the most widely used heavy metals. Significant human exposure occurs from automobile exhaust fumes, cigarette smoking, lead-based paints and plumbing systems lead spread in the environment can take place in several ways, the most important of which is through the lead compounds released in automobile exhaust as a direct result of the addition of tetraethyl or tetraethyl lead to gasoline as octane boosting agents. Of special is the effect of lead pollution on children, which affects their behavioral and educational attributes considerably. The major channel through through which lead is absorbed is through inhalation of lead compounds in the atmosphere. Lead is a heavy metal characterized its malleability, ductility and poor conduction of electricity. So, it has a wide range of applications ranging from battery manufacturing to glazing ceramics. It is rarely found free in nature but is present in several minerals and compounds. The aim of this paper is to discuss natural and anthropogenic sources of lead together with its distribution and trends with emphasis on egypt. The effects of lead pollution on human health, vegetation and welfare are also presented. It could be concluded that, the excessive release of lead into the environment, especially through the atmosphere, can produce many detrimental and sometimes fatal effects on human, agriculture and zoological life. Besides, it is very plain that there is a serious problem of pollution lead in egypt and specially in cairo. 7 figs

  4. A controlled trial of transcutaneous electrical nerve stimulation (TENS) and exercise for chronic low back pain.

    Science.gov (United States)

    Deyo, R A; Walsh, N E; Martin, D C; Schoenfeld, L S; Ramamurthy, S

    1990-06-07

    A number of treatments are widely prescribed for chronic back pain, but few have been rigorously evaluated. We examined the effectiveness of transcutaneous electrical nerve stimulation (TENS), a program of stretching exercises, or a combination of both for low back pain. Patients with chronic low back pain (median duration, 4.1 years) were randomly assigned to receive daily treatment with TENS (n = 36), sham TENS (n = 36), TENS plus a program of exercises (n = 37), or sham TENS plus exercises (n = 36). After one month no clinically or statistically significant treatment effect of TENS was found on any of 11 indicators of outcome measuring pain, function, and back flexion; there was no interactive effect of TENS with exercise. Overall improvement in pain indicators was 47 percent with TENS and 42 percent with sham TENS (P not significant). The 95 percent confidence intervals for group differences excluded a major clinical benefit of TENS for most outcomes. By contrast, after one month patients in the exercise groups had significant improvement in self-rated pain scores, reduction in the frequency of pain, and greater levels of activity as compared with patients in the groups that did not exercise. The mean reported improvement in pain scores was 52 percent in the exercise groups and 37 percent in the nonexercise groups (P = 0.02). Two months after the active intervention, however, most patients had discontinued the exercises, and the initial improvements were gone. We conclude that for patients with chronic low back pain, treatment with TENS is no more effective than treatment with a placebo, and TENS adds no apparent benefit to that of exercise alone.

  5. Age Group Comparisons of TENS Response among Individuals with Chronic Axial Low Back Pain

    OpenAIRE

    Simon, Corey B.; Riley, Joseph L.; Fillingim, Roger B.; Bishop, Mark D.; George, Steven Z.

    2015-01-01

    Chronic low back pain (CLBP) is a highly prevalent and disabling musculoskeletal pain condition among older adults. Transcutaneous electrical nerve stimulation (TENS) is commonly used to treat CLBP, however, TENS response for older adults compared to younger adults is untested. In a dose-response study stratified by age, sixty participants with axial CLBP (20 young, 20 middle-aged, 20 older) received four 20-minute sessions of high frequency, high intensity TENS over a two to three-week perio...

  6. Age Group Comparisons of TENS Response Among Individuals With Chronic Axial Low Back Pain.

    Science.gov (United States)

    Simon, Corey B; Riley, Joseph L; Fillingim, Roger B; Bishop, Mark D; George, Steven Z

    2015-12-01

    Chronic low back pain (CLBP) is a highly prevalent and disabling musculoskeletal pain condition among older adults. Transcutaneous electrical nerve stimulation (TENS) is commonly used to treat CLBP, however response to TENS in older adults compared with younger adults is untested. In a dose-response study stratified by age, 60 participants with axial CLBP (20 young, 20 middle-aged, 20 older) received four 20-minute sessions of high-frequency high-intensity TENS over a 2- to 3-week period in a laboratory-controlled setting. Experimental measures of pain sensitivity (mechanical pressure pain detection threshold) and central pain excitability (phasic heat temporal summation and heat aftersensations) were assessed before and after TENS. Episodic or immediate axial CLBP relief was assessed after TENS via measures of resting pain, movement-evoked-pain, and self-reported disability. Cumulative or prolonged axial CLBP relief was assessed by comparing daily pain reports across sessions. Independent of age, individuals experienced episodic increase in the pressure pain detection threshold and reduction in aftersensation after TENS application. Similarly, all groups, on average, experienced episodic axial CLBP relief via improved resting pain, movement-evoked pain, and disability report. Under this design, no cumulative effect was observed as daily pain did not improve for any age group across the 4 sessions. However, older adults received higher TENS amplitude across all sessions to achieve TENS responses similar to those in younger adults. These findings suggest that older adults experience similar episodic axial CLBP relief to that of younger individuals after high-frequency, high-intensity TENS when higher dose parameters are used. This study examined age group differences in experimental and axial CLBP response to TENS, delivered under the current recommended parameters of strong, but tolerable amplitude. Older adults had comparable TENS response although at higher TENS

  7. Lead Contamination and Microbial Lead Tolerance in Soils at Major ...

    African Journals Online (AJOL)

    Devika

    ABSTRACT: Lead pollution and lead tolerance levels of microbes in soil at major road junctions in Benin. City were investigated. Results revealed that distance from the road junctions affected the concentrations of lead in soil, as well as the microbial population density and types of microbes present in the soil. The highest ...

  8. Lead Contamination and Microbial Lead Tolerance in Soils at Major ...

    African Journals Online (AJOL)

    Lead pollution and lead tolerance levels of microbes in soil at major road junctions in Benin City were investigated. Results revealed that distance from the road junctions affected the concentrations of lead in soil, as well as the microbial population density and types of microbes present in the soil. The highest concentrations ...

  9. Scientometric analysis of published papers in global ophthalmology in the past ten years.

    Science.gov (United States)

    Yu, Zheng-Lu; Hu, Xin-Yue; Wang, Ying-Na; Ma, Zheng

    2017-01-01

    To investigate the published papers of ophthalmology in past ten years and explore the development of ophthalmology. The data of this study retrieved from Science Citation Index Expanded and downloaded online in November 2017, including all the papers with publication year from 2007-2016 were analyzed. The papers were based on the Web of Science category and the journals were based on the Journal Citation Report category. The number of ophthalmology papers increased from 7450 to 9089 during 2007 to 2017. The average rate increased 2.2% annually. USA accounts for one thirds of the total and two thirds of the highly cited papers. In Asia, China, Japan and South Korea were in Top 10 by the number of ophthalmology papers. UK, Germany, Japan and Australia also had great impact in global ophthalmology. The hot spots included endothelial growth factor, optical coherence tomography and open-angle glaucoma. USA is in the leading position in global ophthalmology. Part of Asian countries play an important role in the development of ophthalmology, but the impact needs to be improved.

  10. Ten-year survival rates of teeth adjacent to treated and untreated posterior bounded edentulous spaces.

    Science.gov (United States)

    Aquilino, S A; Shugars, D A; Bader, J D; White, B A

    2001-05-01

    Failure to replace a single missing posterior tooth may lead to a variety of dental problems, which may ultimately result in tooth loss. However, little is known about the fate of the adjacent teeth if a missing posterior tooth is not replaced. This retrospective study evaluated the survival of teeth adjacent to treated and untreated posterior bounded edentulous spaces. Data were obtained from electronic treatment records from the Kaiser Permanente Dental Care Program, Portland, Ore. A final sample of 317 patients who met the study inclusion criteria was identified. Each bounded edentulous space was placed in 1 of 3 treatment categories: untreated, restored with a fixed partial denture, or restored with a removable partial denture. Subsequent treatment and the status of the teeth adjacent to the bounded edentulous space were followed through December 1999. Ten-year Kaplan-Meier survival estimates were generated for each treatment group, and differences in survival were evaluated with the log-rank chi-square test (alpha=.05). There was a significant difference in survival among the 3 treatment categories (P=.005). Spaces restored with a fixed partial denture had longer 10-year survival estimates (92%) than those that remained untreated (81%). Spaces restored with a removable partial denture had the poorest 10-year survival rate (56%). Under the conditions and selection bias associated with this retrospective study, the survival of teeth adjacent to a single posterior edentulous space was negatively associated with removable partial denture placement compared with no treatment or the use of a fixed partial denture.

  11. Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer

    Science.gov (United States)

    Milne, Roger L; Kuchenbaecker, Karoline B; Michailidou, Kyriaki; Beesley, Jonathan; Kar, Siddhartha; Lindström, Sara; Hui, Shirley; Lemaçon, Audrey; Soucy, Penny; Dennis, Joe; Jiang, Xia; Rostamianfar, Asha; Finucane, Hilary; Bolla, Manjeet K; McGuffog, Lesley; Wang, Qin; Aalfs, Cora M; Adams, Marcia; Adlard, Julian; Agata, Simona; Ahmed, Shahana; Ahsan, Habibul; Aittomäki, Kristiina; Al-Ejeh, Fares; Allen, Jamie; Ambrosone, Christine B; Amos, Christopher I; Andrulis, Irene L; Anton-Culver, Hoda; Antonenkova, Natalia N; Arndt, Volker; Arnold, Norbert; Aronson, Kristan J; Auber, Bernd; Auer, Paul L; Ausems, Margreet G E M; Azzollini, Jacopo; Bacot, François; Balmaña, Judith; Barile, Monica; Barjhoux, Laure; Barkardottir, Rosa B; Barrdahl, Myrto; Barnes, Daniel; Barrowdale, Daniel; Baynes, Caroline; Beckmann, Matthias W; Benitez, Javier; Bermisheva, Marina; Bernstein, Leslie; Bignon, Yves-Jean; Blazer, Kathleen R; Blok, Marinus J; Blomqvist, Carl; Blot, William; Bobolis, Kristie; Boeckx, Bram; Bogdanova, Natalia V; Bojesen, Anders; Bojesen, Stig E; Bonanni, Bernardo; Børresen-Dale, Anne-Lise; Bozsik, Aniko; Bradbury, Angela R; Brand, Judith S; Brauch, Hiltrud; Brenner, Hermann; Bressac-de Paillerets, Brigitte; Brewer, Carole; Brinton, Louise; Broberg, Per; Brooks-Wilson, Angela; Brunet, Joan; Brüning, Thomas; Burwinkel, Barbara; Buys, Saundra S; Byun, Jinyoung; Cai, Qiuyin; Caldés, Trinidad; Caligo, Maria A; Campbell, Ian; Canzian, Federico; Caron, Olivier; Carracedo, Angel; Carter, Brian D; Castelao, J Esteban; Castera, Laurent; Caux-Moncoutier, Virginie; Chan, Salina B; Chang-Claude, Jenny; Chanock, Stephen J; Chen, Xiaoqing; Cheng, Ting-Yuan David; Chiquette, Jocelyne; Christiansen, Hans; Claes, Kathleen B M; Clarke, Christine L; Conner, Thomas; Conroy, Don M; Cook, Jackie; Cordina-Duverger, Emilie; Cornelissen, Sten; Coupier, Isabelle; Cox, Angela; Cox, David G; Cross, Simon S; Cuk, Katarina; Cunningham, Julie M; Czene, Kamila; Daly, Mary B; Damiola, Francesca; Darabi, Hatef; Davidson, Rosemarie; De Leeneer, Kim; Devilee, Peter; Dicks, Ed; Diez, Orland; Ding, Yuan Chun; Ditsch, Nina; Doheny, Kimberly F; Domchek, Susan M; Dorfling, Cecilia M; Dörk, Thilo; dos-Santos-Silva, Isabel; Dubois, Stéphane; Dugué, Pierre-Antoine; Dumont, Martine; Dunning, Alison M; Durcan, Lorraine; Dwek, Miriam; Dworniczak, Bernd; Eccles, Diana; Eeles, Ros; Ehrencrona, Hans; Eilber, Ursula; Ejlertsen, Bent; Ekici, Arif B; Engel, Christoph; Eriksson, Mikael; Fachal, Laura; Faivre, Laurence; Fasching, Peter A; Faust, Ulrike; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Foulkes, William D; Friedman, Eitan; Fritschi, Lin; Frost, Debra; Gabrielson, Marike; Gaddam, Pragna; Gammon, Marilie D; Ganz, Patricia A; Gapstur, Susan M; Garber, Judy; Garcia-Barberan, Vanesa; García-Sáenz, José A; Gaudet, Mia M; Gauthier-Villars, Marion; Gehrig, Andrea; Georgoulias, Vassilios; Gerdes, Anne-Marie; Giles, Graham G; Glendon, Gord; Godwin, Andrew K; Goldberg, Mark S; Goldgar, David E; González-Neira, Anna; Goodfellow, Paul; Greene, Mark H; Grip, Mervi; Gronwald, Jacek; Grundy, Anne; Gschwantler-Kaulich, Daphne; Guénel, Pascal; Guo, Qi; Haeberle, Lothar; Hahnen, Eric; Haiman, Christopher A; Håkansson, Niclas; Hallberg, Emily; Hamann, Ute; Hamel, Nathalie; Hankinson, Susan; Hansen, Thomas V O; Harrington, Patricia; Hart, Steven N; Hartikainen, Jaana M; Healey, Catherine S; Hein, Alexander; Helbig, Sonja; Henderson, Alex; Heyworth, Jane; Hicks, Belynda; Hillemanns, Peter; Hodgson, Shirley; Hogervorst, Frans B; Hollestelle, Antoinette; Hooning, Maartje J; Hoover, Bob; Hopper, John L; Hu, Chunling; Huang, Guanmengqian; Hulick, Peter J; Humphreys, Keith; Hunter, David J; Imyanitov, Evgeny N; Isaacs, Claudine; Iwasaki, Motoki; Izatt, Louise; Jakubowska, Anna; James, Paul; Janavicius, Ramunas; Janni, Wolfgang; Jensen, Uffe Birk; John, Esther M; Johnson, Nichola; Jones, Kristine; Jones, Michael; Jukkola-Vuorinen, Arja; Kaaks, Rudolf; Kabisch, Maria; Kaczmarek, Katarzyna; Kang, Daehee; Kast, Karin; Keeman, Renske; Kerin, Michael J; Kets, Carolien M; Keupers, Machteld; Khan, Sofia; Khusnutdinova, Elza; Kiiski, Johanna I; Kim, Sung-Won; Knight, Julia A; Konstantopoulou, Irene; Kosma, Veli-Matti; Kristensen, Vessela N; Kruse, Torben A; Kwong, Ava; Lænkholm, Anne-Vibeke; Laitman, Yael; Lalloo, Fiona; Lambrechts, Diether; Landsman, Keren; Lasset, Christine; Lazaro, Conxi; Le Marchand, Loic; Lecarpentier, Julie; Lee, Andrew; Lee, Eunjung; Lee, Jong Won; Lee, Min Hyuk; Lejbkowicz, Flavio; Lesueur, Fabienne; Li, Jingmei; Lilyquist, Jenna; Lincoln, Anne; Lindblom, Annika; Lissowska, Jolanta; Lo, Wing-Yee; Loibl, Sibylle; Long, Jirong; Loud, Jennifer T; Lubinski, Jan; Luccarini, Craig; Lush, Michael; MacInnis, Robert J; Maishman, Tom; Makalic, Enes; Kostovska, Ivana Maleva; Malone, Kathleen E; Manoukian, Siranoush; Manson, JoAnn E; Margolin, Sara; Martens, John W M; Martinez, Maria Elena; Matsuo, Keitaro; Mavroudis, Dimitrios; Mazoyer, Sylvie; McLean, Catriona; Meijers-Heijboer, Hanne; Menéndez, Primitiva; Meyer, Jeffery; Miao, Hui; Miller, Austin; Miller, Nicola; Mitchell, Gillian; Montagna, Marco; Muir, Kenneth; Mulligan, Anna Marie; Mulot, Claire; Nadesan, Sue; Nathanson, Katherine L; Neuhausen, Susan L; Nevanlinna, Heli; Nevelsteen, Ines; Niederacher, Dieter; Nielsen, Sune F; Nordestgaard, Børge G; Norman, Aaron; Nussbaum, Robert L; Olah, Edith; Olopade, Olufunmilayo I; Olson, Janet E; Olswold, Curtis; Ong, Kai-ren; Oosterwijk, Jan C; Orr, Nick; Osorio, Ana; Pankratz, V Shane; Papi, Laura; Park-Simon, Tjoung-Won; Paulsson-Karlsson, Ylva; Lloyd, Rachel; Pedersen, Inge Søkilde; Peissel, Bernard; Peixoto, Ana; Perez, Jose I A; Peterlongo, Paolo; Peto, Julian; Pfeiler, Georg; Phelan, Catherine M; Pinchev, Mila; Plaseska-Karanfilska, Dijana; Poppe, Bruce; Porteous, Mary E; Prentice, Ross; Presneau, Nadege; Prokofieva, Darya; Pugh, Elizabeth; Pujana, Miquel Angel; Pylkäs, Katri; Rack, Brigitte; Radice, Paolo; Rahman, Nazneen; Rantala, Johanna; Rappaport-Fuerhauser, Christine; Rennert, Gad; Rennert, Hedy S; Rhenius, Valerie; Rhiem, Kerstin; Richardson, Andrea; Rodriguez, Gustavo C; Romero, Atocha; Romm, Jane; Rookus, Matti A; Rudolph, Anja; Ruediger, Thomas; Saloustros, Emmanouil; Sanders, Joyce; Sandler, Dale P; Sangrajrang, Suleeporn; Sawyer, Elinor J; Schmidt, Daniel F; Schoemaker, Minouk J; Schumacher, Fredrick; Schürmann, Peter; Schwentner, Lukas; Scott, Christopher; Scott, Rodney J; Seal, Sheila; Senter, Leigha; Seynaeve, Caroline; Shah, Mitul; Sharma, Priyanka; Shen, Chen-Yang; Sheng, Xin; Shimelis, Hermela; Shrubsole, Martha J; Shu, Xiao-Ou; Side, Lucy E; Singer, Christian F; Sohn, Christof; Southey, Melissa C; Spinelli, John J; Spurdle, Amanda B; Stegmaier, Christa; Stoppa-Lyonnet, Dominique; Sukiennicki, Grzegorz; Surowy, Harald; Sutter, Christian; Swerdlow, Anthony; Szabo, Csilla I; Tamimi, Rulla M; Tan, Yen Y; Taylor, Jack A; Tejada, Maria-Isabel; Tengström, Maria; Teo, Soo H; Terry, Mary B; Tessier, Daniel C; Teulé, Alex; Thöne, Kathrin; Thull, Darcy L; Tibiletti, Maria Grazia; Tihomirova, Laima; Tischkowitz, Marc; Toland, Amanda E; Tollenaar, Rob A E M; Tomlinson, Ian; Tong, Ling; Torres, Diana; Tranchant, Martine; Truong, Thérèse; Tucker, Kathy; Tung, Nadine; Tyrer, Jonathan; Ulmer, Hans-Ulrich; Vachon, Celine; van Asperen, Christi J; Van Den Berg, David; van den Ouweland, Ans M W; van Rensburg, Elizabeth J; Varesco, Liliana; Varon-Mateeva, Raymonda; Vega, Ana; Viel, Alessandra; Vijai, Joseph; Vincent, Daniel; Vollenweider, Jason; Walker, Lisa; Wang, Zhaoming; Wang-Gohrke, Shan; Wappenschmidt, Barbara; Weinberg, Clarice R; Weitzel, Jeffrey N; Wendt, Camilla; Wesseling, Jelle; Whittemore, Alice S; Wijnen, Juul T; Willett, Walter; Winqvist, Robert; Wolk, Alicja; Wu, Anna H; Xia, Lucy; Yang, Xiaohong R; Yannoukakos, Drakoulis; Zaffaroni, Daniela; Zheng, Wei; Zhu, Bin; Ziogas, Argyrios; Ziv, Elad; Zorn, Kristin K; Gago-Dominguez, Manuela; Mannermaa, Arto; Olsson, Håkan; Teixeira, Manuel R; Stone, Jennifer; Offit, Kenneth; Ottini, Laura; Park, Sue K; Thomassen, Mads; Hall, Per; Meindl, Alfons; Schmutzler, Rita K; Droit, Arnaud; Bader, Gary D; Pharoah, Paul D P; Couch, Fergus J; Easton, Douglas F; Kraft, Peter; Chenevix-Trench, Georgia; García-Closas, Montserrat; Schmidt, Marjanka K; Antoniou, Antonis C; Simard, Jacques

    2018-01-01

    Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease1. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10−8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 14% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer. PMID:29058716

  12. Work-life policies for faculty at the top ten medical schools.

    Science.gov (United States)

    Bristol, Mirar N; Abbuhl, Stephanie; Cappola, Anne R; Sonnad, Seema S

    2008-10-01

    There exists a growing consensus that career flexibility is critical to recruiting and retaining talented faculty, especially women faculty. This study was designed to determine both accessibility and content of work-life policies for faculty at leading medical schools in the United States. The sample includes the top ten medical schools in the United States published by U.S. News and World Report in August 2006. We followed a standardized protocol to collect seven work-life policies at each school: maternity leave, paternity leave, adoption leave, extension of the probationary period for family responsibilities, part-time faculty appointments, job sharing, and child care. A review of information provided on school websites was followed by e-mail or phone contact if needed. A rating system of 0-3 (low to high flexibility) developed by the authors was applied to these policies. Rating reflected flexibility and existing opinions in published literature. Policies were often difficult to access. Individual scores ranged from 7 to 15 out of a possible 21 points. Extension of the probationary period received the highest cumulative score across schools, and job sharing received the lowest cumulative score. For each policy, there were important differences among schools. Work-life policies showed considerable variation across schools. Policy information is difficult to access, often requiring multiple sources. Institutions that develop flexible work-life policies that are widely promoted, implemented, monitored, and reassessed are likely at an advantage in attracting and retaining faculty while advancing institutional excellence.

  13. The human CTC1/STN1/TEN1 complex regulates telomere maintenance in ALT cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Chenhui; Jia, Pingping; Chastain, Megan; Shiva, Olga; Chai, Weihang, E-mail: wchai@wsu.edu

    2017-06-15

    Maintaining functional telomeres is important for long-term proliferation of cells. About 15% of cancer cells are telomerase-negative and activate the alternative-lengthening of telomeres (ALT) pathway to maintain their telomeres. Recent studies have shown that the human CTC1/STN1/TEN1 complex (CST) plays a multi-faceted role in telomere maintenance in telomerase-expressing cancer cells. However, the role of CST in telomere maintenance in ALT cells is unclear. Here, we report that human CST forms a functional complex localizing in the ALT-associated PML bodies (APBs) in ALT cells throughout the cell cycle. Suppression of CST induces telomere instabilities including telomere fragility and elevates telomeric DNA recombination, leading to telomere dysfunction. In addition, CST deficiency significantly diminishes the abundance of extrachromosomal circular telomere DNA known as C-circles and t-circles. Suppression of CST also results in multinucleation in ALT cells and impairs cell proliferation. Our findings imply that the CST complex plays an important role in regulating telomere maintenance in ALT cells. - Highlights: • CST localizes at telomeres and ALT-associated PML bodies in ALT cells throughout the cell cycle. • CST is important for promoting telomeric DNA replication in ALT cells. • CST deficiency decreases ECTR formation and increases T-SCE. • CST deficiency impairs ALT cell proliferation and results in multinucleation.

  14. Screening of ten advanced chickpea lines for blight and wilt resistance

    International Nuclear Information System (INIS)

    Jamil, F.F.; Haq, I.; Sarwar, N.; Alam, S.S.; Khan, J.A.; Hanif, M.; Khan, I.A.; Sarwar, M.; Haq, M.A.

    2002-01-01

    Ten advanced chickpea lines developed at NIAB were screened for resistance to Ascochyta blight and Fusarium wilt diseases in different sets of experiments conducted under controlled environment. Inoculation of plants by spore suspension of virulent strains of Ascochyta rabiei revealed that one line (97313) was resistant tolerant, two lines (97305, 97392) were tolerant, six lines (97306, 97310, 97311, 97303, 97302, 97393) were tolerant/susceptible and one line (97301) was susceptible. Screening of the same lines against Fusarium wilt by water culture method showed that two lines (97301, 97313) were moderately resistant, four lines (97302, 97303, 97306, 97393) were tolerant and the remaining four lines were susceptible. Screening through phytotoxic culture filtrates revealed that two lines (97302, 97313) were less sensitive to culture filtrates of Ascochyta rabiei and Fusarium oxysporum than the resistant check (CM88). These lines were also analyzed spectrophotometrically for peroxidase enzyme activity. Maximum enzyme activity was detected after 48 hours of inoculation with A. rabiei in three lines (97305, 97311, 97313) and resistant check (CM88) while enzyme activity in the remaining lines reached its maximum after 72 hours of inoculation which was comparable to the susceptible check (Pb-1). These studies lead to the conclusion that one line (97313) exhibited resistance against both the diseases and can be used as a source of resistance for further improvement of chickpea germplasm. (author)

  15. TEN YEARS AFTER THE GLOBAL CRISES - EXPORTS RECOVERY AT REGIONAL LEVEL IN ROMANIA

    Directory of Open Access Journals (Sweden)

    Artur-Emilian SIMION

    2018-05-01

    Full Text Available After ten years of the global financial crises, which peak in Romania was 2009, the negative impact on exports and imports of Romania are still in place for some Romanian counties. The scale of the impact highlights the strong connections between the national economy and the economy of the other EU countries, which have suffered during the crisis because of falling demand for imports from Romania. The good export recovery is not a favorable thing for those counties who focused theirs exports on primary products, products based on natural resources and low-technology products. These exports lead to the decrease in foreign exchange earnings and implicitly the potential of endogenous growth at the county level, mainly due to deteriorating terms of trade. The paper is focused on Romanian exports recovery analysis, taking into account the impact of world financial crisis, which started in Romania in 2009. A special attention is paid to the recovery of exports at the regional level and to the importance of the structural changes of Romanian export, occurred in 2017 compared to 2008. Also, in this article are analyzed the concentration of exports at county level, the main partners on export, the share of the first 10 partners and evolution of export per capita at the counties level. The trade balance is used to classify the counties in: net exporters (export>import and net importers (import>export.

  16. Leaded gasoline - an environmental problem

    International Nuclear Information System (INIS)

    Petrushevska, Ljubica

    2001-01-01

    In the European countries it is a clear trend towards the increasing consumption of unleaded gasolines. Driving force of this trend is, on the one hand the high toxicity of lead compounds and on the other, the necessity of purification of exhaust gases by catalytic converters, for which the lead represent a catalyst poison. In Macedonia, the limit lead content in the leaded gasolines is relatively high (0,6 g/l), as well as the consumption of the leaded gasolines. Rapid and complete transition to unleaded gasolines can be realized by the concept of step by step reduction of lead in our gasolines. (Original)

  17. Experimental lead poisoning in chickens

    Energy Technology Data Exchange (ETDEWEB)

    Silven, L.

    1967-01-01

    Poisoning of water fowl due to the intake of lead shot is not rare in the USA. In order to study this kind of poisoning more closely domestic fowl were given varying amounts of lead shot and lead powder. This treatment did not provoke any symptoms of poisoning. Chemical analyses of different organs, muscles, skeleton and eggs yielded low lead values. It is concluded that the low toxicity of lead administered as lead shot to the domestic fowl is due to a low absorption rate from the gastro-intestinal tract.

  18. Decontamination and coating of lead

    International Nuclear Information System (INIS)

    Rankin, W.N.; Bush, S.P.; Lyon, C.E.; Walker, V.

    1988-01-01

    Technology is being developed to decontaminate lead used in shielding applications in contaminated environments for recycle as shieldings. Technology is also being developed to coat either decontaminated lead or new lead before it is used in contaminated environments. The surface of the coating is expected to be much easier to decontaminate than the original lead surface. If contamination becomes severely embedded in the coating and cannot be removed, it can be easily cut with a knife and removed from the lead. The used coating can be disposed of as radioactive (hot hazardous) waste. The lead can then be recoated for further use as a shielding material

  19. The Top Ten Astronomical 'breakthroughs' of the 20th century

    Directory of Open Access Journals (Sweden)

    Hughes, D. W.

    2007-10-01

    Full Text Available Astronomy was revolutionized in the 20th century. The electron was discovered in 1897 and this transformed spectroscopy and introduced plasma and magnetohydrodynamic physics and astro-chemistry. Einstein’s E = mc2, solved the problem of stellar energy generation and spawned the study of elemental nuclear synthesis. Large telescopes led to a boom in astronomical spectroscopic and photometric data collection, leading to such cornerstones as the Hertzprung-Russell diagram and the mass-luminosity relationship, and to the realization that the Universe contained a multitude of galaxies and was expanding. Radio astronomy was introduced and the advent of the space age saw the astronomical wavelength range expand into the ultraviolet, X-ray and gamma-ray regions, as well as the infrared and millimetre. We also startedwandering around roaming the Solar System instead of merely glimpsing its members from the bottom of our warm, turbulent atmosphere. Astronomical “breakthroughs” abounded. We have asked astronomers to select their “top ten” and these are listed and discussed in this paper.

  20. Microbial compositional changes in broiler chicken cecal contents from birds challenged with different Salmonella vaccine candidate strains.

    Science.gov (United States)

    Park, Si Hong; Kim, Sun Ae; Rubinelli, Peter M; Roto, Stephanie M; Ricke, Steven C

    2017-05-31

    Previously, we constructed and characterized the vaccine efficacy of Salmonella Typhimurium mutant strains in poultry with either inducible mviN expression (P BAD -mviN) or methionine auxotrophy (ΔΔmetRmetD). The aim of the present study was to assess potential impact of these Salmonella vaccine strains on the cecal microbiota using a next generation sequencing (NGS). The cecal microbial community obtained from unvaccinated (group 1) and vaccinated chickens (group 2, vaccinated with P BAD -mviN; group 3, vaccinated with wild type; group 4, vaccinated with ΔΔmetRmetD) were subjected to microbiome sequencing analysis with an Illumina MiSeq platform. The NGS microbiome analysis of chicken ceca revealed considerable changes in microbial composition in the presence of the different vaccine strains and exhibited detectable patterns of distinctive clustering among the respective groups (the R value of unweighted PCoA plot was 0.68). The present study indicates that different S. Typhimurium vaccine strains can differentially influence the microbiota of the ceca in terms of presence but not in the relative abundance of microbiota. Copyright © 2017 Elsevier Ltd. All rights reserved.