1,720,957 research outputs found
Characterization of Alphavirus Replicon Based Vaccines and Adjuvants in a Neonatal Murine Model
Infectious diseases are the leading cause of childhood morbidity and mortality worldwide. Not only is there a lack of vaccines for many deadly diseases, early life immunization with the available vaccines is frequently ineffective and requires multiple doses to induce protective immune response. Additionally, the neonatal immune responses to infection and vaccination are biased towards TH2 at the cost of pro-inflammatory TH1 responses needed to combat intracellular pathogens. However, upon appropriate stimulation, the neonatal immune system can induce adult-like TH1 responses. We hypothesized that non-propagating Venezuelan equine encephalitis virus replicon (VEE)-based vaccine platforms (VRP) are good candidates for safe early life immunization, based on their ability to (1) target dendritic cells (DC) in the draining lymph node and (2) induction of robust innate immune response through intracellular amplification of replicon RNA. In the VRP expression vector, the same replicon particle functions to deliver the antigen and to serve as innate immune-stimulant. On the other hand, in the VRP as adjuvant (GVI3000), the replicon particle only provides the danger signal function, while the antigen is not expressed from the replicon particle, but co-delivered as purified protein or inactivated virions. By separating the antigen delivery function from the adjuvant function in the GVI3000, we were able to demonstrate the role of the adjuvant function in the VRP, and to start to understand how it mediates the changes in the quality and magnitude of the immune response in the neonate. In this thesis, using a neonatal mouse model, we showed that both platforms induced effective and protective immunity against two different infectious agents, influenza virus and dengue virus. Furthermore, VRP replicon particles served as useful tools to better understand the induction of the neonatal immune response. In summary, the VRP expression vector vaccines and adjuvants induced an adult-like adjuvant effect against dengue influenza antigens, and have the potential to improve the immunogenicity and protective efficacy of new and existing neonatal vaccines.Doctor of Philosoph
Genomic Sequencing of F+RNA as a Foundation for Development of Real-Time RT-PCR Assays
Male-specific RNA (F+RNA) coliphages, members of the family Leviviridae, have been studied for their potential as indicators of enteric virus pollution in environmental water samples. Additionally, they may also provide information on source-tracking, as levivirus genogroups have been associated with either human or animal fecal pollution. To identify conserved regions across the genome of the individual coliphage genogroups, long RT-PCR followed by cloning and sequencing of the PCR products was performed on 7 representative F+RNA coliphage strains including strains belonging to genogroups III, IV and the novel JS genogroup. A panel of genetically diverse strains was compiled and after plaque-purification, viral RNA was isolated. After polyadenylation of the 3'-end of the genome, genomic cDNA was generated using oligo-dT and Superscript reverse transcriptase. Using strain-specific primers targeting the partial replicase region, we generated ~1 kbp sequences of all 7 strains. Phylogenetic analysis including the prototype strains, confirmed the genetic grouping of F+RNA into 5 distinct genogroups and possibly two different subgroups withi ngenogroup III. The results of amplification of the 2.4 kbp fragments (31 kbp for alloleviviruses) of the 5'-end of each strain by poly-A tailing of the long cDNA using terminal transferase were inconclusive. In conclusion, this study is the first attempt to generate a comprehensive genomic sequence database of F+RNA coliphages. This database will serve as a valuable tool to find conserved regions across the genome that will be used to design robust genogroup-specific real-time RT-PCR assays for the sensitive detection and differentiation of F+RNA genogroups in environmental water samples.Master of Science in Public Healt
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
Author-wise bibliometric analysis based on entropy.</p
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