110 research outputs found

    MEMS 411: Piston Pong

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    This report documents the design process of our ”Piston Pong” device. Our device was designed to be an educational demonstration of pneumatics and energy transformations using work and fluids models. The concept is that a bike pump will pump air into a holding container. After enough pressure is built up inside, the air will be released from the holding tank to a pneumatic cylinder. The cylinder will be released, hitting and launching a ball into the air. Additionally, force and pressure sensors would allow the energy to be calculated to fully understand the energy transformation. Our priorities for this design were safety, educational value, the ability to launch a ball, and pressure and force measurements. Throughout the design process, our goals and design were altered to best meet these priorities. Our final prototype was able to safely launch a ball while measuring the energy introduced to the system via the bike pump. While we have a functioning program and pressure sensor, we were not able to measure the pressure within the holding tank due to concerns about maintaining the airtight system

    The Effect of Regulatory Sequence Elements upon the Initiation of DNA Replication of the Minute Virus of Mice

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    AbstractThe minute virus of mice (MVM) genome is a linear single-stranded length of approximately 5000 nucleotides of DNA with unique terminal palindromic sequences at both ends. The left (3′) hairpin is used to prime the initiation of DNA synthesis on parental single-strand DNA while the right (5′) hairpin or stem-plus-arms structure can also prime the initiation of DNA synthesis during synthesis of dimer and higher oligomers as well as synthesis of progeny single strands. Previous studies have shown that if viral duplex DNA was input into anin vitroDNA replication system using extracts from uninfected HeLa cells, the 5′ end of the molecule was able to form a hairpin and initiate DNA synthesis by DNA polymerase δ (Cossonset al.(1996),Virology216, 258–264). In this study, the effect of the deletion of knowncis-acting genetic elements upon the initiation of DNA replication was studied using a series of MVM mutants with deletions within the 5′ terminal region. Mutants containing deletions of elements A (nucleotides 4489–4636), B (nucleotides 4636–4695), and either one or both of the 65-bp repeats (nucleotides 4720–4785 and 4785–4849) were used as template in thein vitroDNA replication system. When element A was deleted, the efficiency of initiation decreased significantly. Subsequent removal of element B, leaving just the two 65-bp repeats, restored levels of initiation back to those seen in the wild-type genome. In the absence of either A or B both 65-bp repeats were necessary for efficient initiation, and removal of one of these repeats caused a decrease in efficiency. Thus, element B appeared to have a negative regulatory effect (in the absence of element A), and element A appeared to have a positive regulatory effect, at least in the presence of element B. These data demonstrate, for the first time, a complex interaction between thesecis-acting regulatory elements which can function as both positive or negative regulators in the initiation of MVM DNA replication

    'Be on the TEAM' Study (Teenagers Against Meningitis): protocol for a controlled clinical trial evaluating the impact of 4CMenB or MenB-fHbp vaccination on the pharyngeal carriage of meningococci in adolescents.

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    INTRODUCTION: Capsular group B Neisseria meningitidis (MenB) is the most common cause of invasive meningococcal disease (IMD) in many parts of the world. A MenB vaccine directed against the polysaccharide capsule remains elusive due to poor immunogenicity and safety concerns. The vaccines licensed for the prevention of MenB disease, 4CMenB (Bexsero) and MenB-fHbp (Trumenba), are serogroup B 'substitute' vaccines, comprised of subcapsular proteins and are designed to provide protection against most MenB disease-causing strains. In many high-income countries, such as the UK, adolescents are at increased risk of IMD and have the highest rates of meningococcal carriage. Beginning in the late 1990s, immunisation of this age group with the meningococcal group C conjugate vaccine reduced asymptomatic carriage and disrupted transmission of this organism, resulting in lower group C IMD incidence across all age groups. Whether vaccinating teenagers with the novel 'MenB' protein-based vaccines will prevent acquisition or reduce duration of carriage and generate herd protection was unknown at the time of vaccine introduction and could not be inferred from the effects of the conjugate vaccines. 4CMenB and MenB-fHbp may also impact on non-MenB disease-causing capsular groups as well as commensal Neisseria spp. This study will evaluate the impact of vaccination with 4CMenB or MenB-fHbp on oropharyngeal carriage of pathogenic meningococci in teenagers, and consequently the potential for these vaccines to provide broad community protection against MenB disease. METHODS AND ANALYSIS: The 'Be on the TEAM' (Teenagers Against Meningitis) Study is a pragmatic, partially randomised controlled trial of 24 000 students aged 16-19 years in their penultimate year of secondary school across the UK with regional allocation to a 0+6 month schedule of 4CMenB or MenB-fHbp or to a control group. Culture-confirmed oropharyngeal carriage will be assessed at baseline and at 12 months, following which the control group will be eligible for 4CMenB vaccination. The primary outcome is the carriage prevalence of potentially pathogenic meningococci (defined as those with genogroups B, C, W, Y or X), in each vaccine group compared separately to the control group at 12 months post-enrolment, that is, 12 months after the first vaccine dose and 6 months after the second vaccine dose. Secondary outcomes include impact on carriage of: genogroup B meningococci; hyperinvasive meningococci; all meningococci; those meningococci expressing vaccine antigens and; other Neisseria spp. A sample size of 8000 in each arm will provide 80% power to detect a 30% reduction in meningococcal carriage, assuming genogroup B, C, W, Y or X meningococci carriage of 3.43%, a design effect of 1.5, a retention rate of 80% and a significance level of 0.05. Study results will be available in 2021 and will inform the UK and international immunisation policy and future vaccine development. ETHICS AND DISSEMINATION: This study is approved by the National Health Service South Central Research Ethics Committee (18/SC/0055); the UK Health Research Authority (IRAS ID 239091) and the UK Medicines and Healthcare products Regulatory Agency. Publications arising from this study will be submitted to peer-reviewed journals. Study results will be disseminated in public forums, online, presented at local and international conferences and made available to the participating schools. TRIAL REGISTRATION NUMBERS: ISRCTN75858406; Pre-results, EudraCT 2017-004609-42

    Autosomal recessive cerebellar ataxia caused by mutations in the PEX2 gene

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    <p>Abstract</p> <p>Objective</p> <p>To expand the spectrum of genetic causes of autosomal recessive cerebellar ataxia (ARCA).</p> <p>Case report</p> <p>Two brothers are described who developed progressive cerebellar ataxia at 3 1/2 and 18 years, respectively. After ruling out known common genetic causes of ARCA, analysis of blood peroxisomal markers strongly suggested a peroxisomal biogenesis disorder. Sequencing of candidate <it>PEX </it>genes revealed a homozygous c.865_866insA mutation in the <it>PEX2 </it>gene leading to a frameshift 17 codons upstream of the stop codon. <it>PEX </it>gene mutations usually result in a severe neurological phenotype (Zellweger spectrum disorders).</p> <p>Conclusions</p> <p>Genetic screening of PEX2 and other PEX genes involved in peroxisomal biogenesis is warranted in children and adults with ARCA.</p

    Genomic approaches to understanding population divergence and speciation in birds

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    © 2016 American Ornithologists\u27 Union. The widespread application of high-throughput sequencing in studying evolutionary processes and patterns of diversification has led to many important discoveries. However, the barriers to utilizing these technologies and interpreting the resulting data can be daunting for first-time users. We provide an overview and a brief primer of relevant methods (e.g., whole-genome sequencing, reduced-representation sequencing, sequence-capture methods, and RNA sequencing), as well as important steps in the analysis pipelines (e.g., loci clustering, variant calling, whole-genome and transcriptome assembly). We also review a number of applications in which researchers have used these technologies to address questions related to avian systems. We highlight how genomic tools are advancing research by discussing their contributions to 3 important facets of avian evolutionary history. We focus on (1) general inferences about biogeography and biogeographic history, (2) patterns of gene flow and isolation upon secondary contact and hybridization, and (3) quantifying levels of genomic divergence between closely related taxa. We find that in many cases, high-throughput sequencing data confirms previous work from traditional molecular markers, although there are examples in which genome-wide genetic markers provide a different biological interpretation. We also discuss how these new data allow researchers to address entirely novel questions, and conclude by outlining a number of intellectual and methodological challenges as the genomics era moves forward

    Evolutionary consequences of feedbacks between within-host competition and disease control

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    Lay Summary: Competition often occurs among diverse parasites within a single host, but control efforts could change its strength. We examined how the interplay between competition and control could shape the evolution of parasite traits like drug resistance and disease severity

    H1N1 Antibody Persistence 1 Year After Immunization With an Adjuvanted or Whole-Virion Pandemic Vaccine and Immunogenicity and Reactogenicity of Subsequent Seasonal Influenza Vaccine: A Multicenter Follow-on Study

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    Background. We investigated antibody persistence in children 1 year after 2 doses of either an AS03B-adjuvanted split-virion or nonadjuvanted whole-virion monovalent pandemic influenza vaccine and assessed the immunogenicity and reactogenicity of a subsequent dose of trivalent influenza vaccine (TIV). Methods. Children previously immunized at age 6 months to 12 years in the original study were invited to participate. After a blood sample was obtained to assess persistence of antibody against swine influenza A/H1N1(2009) pandemic influenza, children received 1 dose of 2010/2011 TIV, reactogenicity data were collected for 7 days, and another blood sample was obtained 21 days after vaccination. Results. Of 323 children recruited, 302 received TIV. Antibody persistence (defined as microneutralization [MN] titer ≥1:40) 1 year after initial vaccination was significantly higher in the AS03B-adjuvanted compared with the whole-virion vaccine group, 100% (95% confidence interval [CI], 94.1%–100%) vs 32.4% (95% CI, 21.5%–44.8%) in children immunized <3 years old and 96.9% (95% CI, 91.3%–99.4%) vs 65.9% (95% CI, 55.3%–75.5%) in those 3–12 years old at immunization, respectively (P < .001 for both groups). All children receiving TIV had post-vaccination MN titers ≥1:40. Although TIV was well tolerated in all groups, reactogenicity in children <5 years old was slightly greater in those who originally received AS03B-adjuvanted vaccine. Conclusions. This study provides serological evidence that 2 doses of AS03B-adjuvanted pandemic influenza vaccine may be sufficient to maintain protection across 2 influenza seasons. Administration of TIV to children who previously received 2 doses of either pandemic influenza vaccine is safe and is immunogenic for the H1N1 strain

    Population genetic analysis of brazilian peach breeding germplasm.

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    ABSTRACT Peach has great economic and social importance in Brazil. Diverse sources of germplasm were used to introduce desirable traits in the Brazilian peach breeding pool, composed mainly by local selections and accessions selected from populations developed by the national breeding programs, adapted to subtropical climate, with low chill requirement, as well as accessions introduced from several countries. In this research, we used SSR markers, selected by their high level of polymorphism, to access genetic diversity and population structure of a set composed by 204 peach selected genotypes, based on contrasting phenotypes for valuable traits in peach breeding. A total of 80 alleles were obtained, giving an average of eight alleles per locus. In general, the average value of observed heterozygosity (0.46) was lower than the expected heterozygosity (0.63). STRUCTURE analysis assigned 162 accessions splitted into two subpopulations based mainly on their flesh type: melting (96) and non-melting (66) flesh cultivars. The remaining accessions (42) could not be assigned under the 80% membership coefficient criteria. Genetic variability was greater in melting subpopulation compared to non-melting. Additionally, 55% of the alleles present in the breeding varieties were also present in the founder varieties, indicating that founding clones are well represented in current peach cultivars and advanced selections developed. Overall, this study gives a first insight of the peach genetic variability available and evidence for population differentiation (structure) in this peach panel to be exploited and provides the basis for genome-wide association studies

    “MINHA VIDA, MINHA HISTÓRIA” - PROGRAMA PATRONATO MUNICIPAL DE FRANCISCO BELTRÃO-PR: CURSO PREPARATÓRIO PARA O EXAME NACIONAL PARA CERTIFICAÇÃO DE COMPETÊNCIAS DE JOVENS E ADULTOS - ENCCEJA

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    A discussão apresentada foi construída a partir das experiências da equipe multidisciplinar do Programa Patronato Municipal de Francisco Beltrão - PR. Um dos propósitos do Patronato é organizar atividades em prol da escolarização dos assistidos, sendo que o Curso Preparatório para o Exame Nacional para Certificação de Competências de Jovens e Adultos - ENCCEJA é uma destas, tendo como objetivo oportunizar a conclusão dos estudos do ensino fundamental séries finais ou ensino médio. As duas edições anteriores desta atividade (2017-2018), evidenciaram que o ENCCEJA se apresenta como uma possibilidade de reinserção dos assistidos na sociedade, bem como uma oportunidade para que os mesmos deem continuidade no processo de escolarização formal
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