Thesis (M.Sc.)--York University, 2008. Graduate Programme in Chemistry. / Typescript. Includes bibliographical references (leaves 82-88). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:MR38748

This study is based on the notion that the most widely cited and used instrument for assessing volunteer motivations, the Volunteer Function Inventory (VFI), might not be sufficient in its aspiration to aid, streamline and benefit the recruitment and retention process within volunteer organizations. Understanding volunteers’ motivation is a crucial component in the process of securing future volunteer engagement in a world where their efforts are desperately needed. This study aims to explain motives and motivation behind volunteer efforts in extreme situations as well as to examine the dependability of the theoretical framework in relation to the forthcoming result, based on the following research questions: What motivated Swedish medical personnel to volunteer during the 2014 Ebola outbreak in West Africa? How could the motives and motivation of Swedish medical personnel be categorized in accordance with the Volunteer Function Inventory (VFI)? Is the Volunteer Function Inventory (VFI) a sufficient tool for analyzing the motives and motivation of Swedish medical personnel in the given case? The presented research questions will be answer through a qualitative theory-consuming study, based mainly on interviews. The interviews are, however, complimented by various written sources in the field of research. The result and subsequent analysis confirms the authors’ notion on the VFI and highlights certain deficits in the tool’s execution and its succeeding result. The result of the study shows that the respondents were motivated by a great variety of motivational elements, a variety that the VFI cannot properly account for. Essential information is therefore left unexposed by the VFI, leaving the volunteer organizations in an undesirable situation where they, in their pursuit to recruit and retain the volunteers, are forced to evaluate and accommodate candidates without knowing their complete motivational process. Therefore, the authors deem the tool as applicable but not sufficient. Concludingly, the authors call for additional and more distinct functions in the VFI; an instrument for assessing if the volunteers are intrinsically or extrinsically motivated as well as a sub-section within the tool for determining the presence and character of inhibiting factors affecting the volunteers motivation. / Att fastställa och möta en volontärarbetares motiv och motivation är en avgörande del i arbetet med att säkerställa ett framtida engagemang. I en värld med återkommande naturkatastrofer, väpnade konflikter och epidemier är betydelsen av volontärinsatser större än någonsin. Studien ämnar således undersöka om Volunteer Function Inventory (VFI) – det mest citerade och använda verktyget inom forskningsområdet för att undersöka och fastställa volontärarbetares motiv och motivation – är tillräckligt tillförlitligt i dess strävan att underlätta, effektivisera och gynna rekryterings- och retentionsprocessen inom volontärorganisationer. Undersökningen bygger på en kvalitativ teorikonsumerande studie vilken baseras på djupintervjuer med svensk sjukvårdspersonal kring deras volontärinsatser under ebolautbrottet i Västafrika 2014. Studiens resultat och efterföljande analys påvisar att VFI som verktyg uppvisar vissa brister i dess nuvarande utformning och i den data som genereras. Studien visar att respondenterna motiverades av en stor variation motivationsdrivande element som VFI inte kan redogöra för tillräckligt väl. Detta lämnar volontärorganisationer i en oönskad situation där de i sin strävan att rekrytera och behålla volontärarbetare tvingas utvärdera personer utan att känna till deras fullständiga motivationsbild. Sammanfattningsvis efterfrågar författarna fler och mer distinkta funktioner i VFI; ett instrument för att avgöra om volontärerna drivs av inre eller yttre motivation samt ett tillägg för att kunna fastställa förekomsten, och således karaktären, av motivationshämmande faktorer hos en volontärarbetare.

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Delivery of medicinal products to specific targets can be aided by utilizing different routes of administration. Particular routes may be advantageous when delivering products designed for therapeutic drug delivery, gene therapy, or vaccination. Vaccine candidates must remain stable, be delivered to their proper compartments, and promote sufficient immune responses to their delivered antigens, properties that can be modulated by formulation, adjuvants, and alternate routes of administration. Recently, the nasal passageway has been recognized as a promising route, as mucosally delivered vaccines have the advantage of inducing protection at both mucosal surfaces, a common site of infection, and systemically. Human adenovirus serotype 5 (Ad5) is a candidate vaccine vector capable of being delivered through several routes and inducing strong immune responses to its delivered transgene. The studies presented include vaccination strategies following different routes of administration with various formulation components to determine the ability of Ad5 to deliver its transgene and induce immune responses. The first study screens formulation candidates’ effects on an Ad5-based vaccine’s transduction in vitro, cellular and humoral immune responses in vivo, and efficacy upon challenge in mice. Screening formulation candidates in vitro can eliminate ineffective formulations, thereby limiting animal testing. An Ad5-based Ebola virus vaccine delivered in a combination of mannitol, sucrose, and the surfactant, pluronic F68, improves survival against lethal Ebola challenge in a mouse model compared to delivery in PBS alone. The second study tests the effect of an intravenously delivered Ad5-based vaccine complexed with anti-Ad5 neutralizing antibodies on cellular and humoral immune responses. Different antibody ratios complexed to the Ad5 vector are able to induce disparate cellular and humoral responses. Ratios initiating a strong humoral response towards the Ad5 vector correlate with a reduction of the humoral response against the transgene and few transgene targeted effector T cells. Accordingly, ratios leading to minor humoral responses to the Ad5 vector resulted in stronger humoral responses to the transgene and a strong effector memory T cell response. Taken together, these studies provide insight on how to achieve necessary immune responses in vaccine protocols by testing routes of administration, formulations, and surface modifications of the Ad5 vector. / text

Syfte och frågeställning: Att undersöka hur två svenska nyhetstidningar valt att skildra en nyhet under vald period. Detta görs genom att besvara följande frågeställning: På vilket sätt skildrar Dagens Nyheter och Svenska Dagbladet ebolaviruset i sina tidningsartiklar från 1 maj 2014 till och med den 31 oktober 2014? Metod och material: Kvantitativ innehållsanalys på samtliga artiklar publicerade i DN och SvD under perioden 1 maj 2014 till och med 31 oktober 2014 samt diskursanalys på sex artiklar. Huvudresultat: I studien framkom det en tydlig förändring i artiklarna under hela undersökningsperioden. Det förändrades från att vara diskussioner om en kris till att sedan diskuteras om olika åtgärder för att minska oroligheten bland invånarna.

The Ebola virus disease is one of the most dangerous diseases to develop into a major health concern in the modern era, largely because of the ZEBOV outbreak that has devastated West Africa from 2014 to 2016. The outbreak has compelled many countries and organizations to prioritize finding a vaccine for Ebola, which is key to preventing a similar outbreak on a global scale. As a result, studies on Ebola vaccines have increased in frequency since 2014. This thesis will focus on three vaccine candidates that could potentially be developed into a future vaccine for Ebola: chAd3, rVSV, and rAd5. Each of the vaccines has been the focus of several studies on both animals and humans, which have provided information and understanding of the vaccines’ characteristics in terms of reactogenicity and immunogenicity. All of the vaccines demonstrate safety and immunogenicity profiles that offer promise for the vaccines as future candidates, which at first makes them seem very similar to each other. However, they each differ substantially in their flaws and ability to generate an immunogenic response. More specifically, the chAd3 vaccine requires a boost of MVA to reach its full potential, the rVSV vaccine has expressed a higher level of reactogenicity and adverse effects than the other two vaccines, and the rAd5 vaccine’s efficacy is weakened by the presence of pre-existing immunity against Ad5 in the human population.

Bakgrund: Ebola upptäcktes för första gången 1976 i ett dubbelt utbrott i Sudan och Zaire i Afrika. Det pågående utbrottet av ebola virus sjukdom (EVD) startade i Guinea 2013 och har sedan dess spridits vidare till Liberia, Sierra Leone, Nigeria, Mali och Senegal. T.o.m. 4 mars 2015 har nästan 24 000 smittats och 10 000 avlidit vilket är mer än 50 gånger fler än i det tidigare största utbrottet i Uganda 2000. Viruset består av fem arter: Bundibugyo, Reston, Sudan, Tai Forest och Zaire. Vektorn för viruset är fortfarande okänd men förmodas vara flygande hundar (fruit bats) som själva är resistenta. Symtomen innefattar bl.a. feber, trötthet, kräkning, diarré, ledsmärtor och mukosala blödningar. Behandlingen består vanligen av vätskeersättning. Det finns varken godkänt vaccin eller läkemedel i dagsläget men flertalet studier pågår för att utveckla bl.a. antikropparna ZMapp och antiviral behandling med Brincidofovir. Syfte: Redogöra för tidigare och pågående utbrott av ebola och undersöka vilka faktorer som bidragit till att epidemin 2013-2015 inträffat och fått stora proportioner i Västafrika. Metod: Till det aktuella ämnet har den senaste informationen inhämtats via WHO och CDCs respektive hemsidor mellan 23/2-9/3 2015. Resultat: En kombination av faktorer har bidragit till att det pågående utbrottet blivit större än tidigare. Länderna som drabbats har inte varit förberedda, virusarten ebola Zaire har hög dödlighet, sjukvård och infrastruktur är svag och kulturen är djupt grundad i ett samhälle där utbildningen är låg. Befolkningen behöver respekteras och utbildas för att de aktivt ska kunna vara delaktiga i att stoppa smittspridningen av viruset. Ju mindre geografisk yta viruset är fördelat på desto lättare blir det att kontrollera och bekämpa det. Diskussion: Guinea, Liberia och Sierra Leone har alla drabbats extra hårt av pågående EVD utbrott och behöver nu få hjälp med återuppbyggnad av ett fungerande sjukvårdssystem som befolkningen kan lita på och med personal som kan arbeta under säkra förhållanden. Stort fokus bör också läggas på att implementera kulturen i de skyddsåtgärder som behövs för att förhindra ytterligare spridning och framtida utbrott. Ytterligare forskning krävs för att kunna erbjuda bättre behandling och profylax.

Sierra Leone had the highest number of cases of Ebola virus disease in history during the 2014 Ebola epidemic. The purpose of this quantitative, cross-sectional study was to examine the relationship between sociocultural and behavioral risk factors and Ebola status among women and men ages 15 to 49 years in Sierra Leone. The ecological model served as the theoretical framework. Secondary data were collected from the Sierra Leone Ebola Disease Survey. Results of chi-square tests revealed that attending a funeral (p = .001), touching a dead body at a funeral (p = .023), contact with a sick person (p = .001), touching bodily fluids (p = 0.001), gender (p = .035), traditional healer occupation (p = .001), and housewife/care taker occupation (p = .001) were significantly associated with Ebola infection status among the study population. Age, seeking traditional healer care, and preparation and consumption of primate meat were not associated with Ebola virus infection. Results of stepwise backward elimination logistic regression indicated the only significant predictor of Ebola infection was attending a funeral (adjusted R2 = .013 or 1.3%, p = .031). Findings may be used to promote awareness of funeral-related Ebola infection risk and avoiding traditional and religious practices that elevate infection risk during burial of the dead, which may be used to reduce or prevent future Ebola outbreaks in Sierra Leone.

On sait maintenant depuis quelques décennies que seule une petite fraction du génome est constituée de séquences codantes pour des protéines et que la majorité de l'ADN non codant, jadis considéré comme « poubelle », assure d'importantes fonctions biologiques. Avec ce nouveau paradigme, notre perception de l'expression et la régulation génique est passée d'une vision axée sur les protéines à une vision plus centrée sur les ARN, tant chez les procaryotes que chez les eucaryotes. L'avènement des techniques de séquençage à haut débit comme le RNA-Seq (séquençage ARN) a fortement contribué à la démystification de cette partie « non codante » de l'ARN. Outre le triumvirat de gènes d'ARNt, d'ARNr et d'ARNm, les génomes abritent de nombreux loci qui codent pour de petits ARN régulateurs non canoniques repartis dans de nombreuses classes. Les microARN (miARN) et les fragments dérivés des ARNt (tRFs) sont les deux classes de petits ARN non codants (ARNnc) les plus abondants et partageant des similarités dans leurs mécanismes. Bien que souvent éclipsés par les protéines, ils sont au cœur de la régulation post-transcriptionnelle et sont des acteurs émergents de la relation hôte-pathogène. Ces travaux de thèse s'inscrivent dans ce thème et traitent des relations hôtes-pathogènes sous l'angle des petits ARNnc à travers deux projets (#1 et #2) complémentaires qui ambitionnent d'apporter une lecture et des perspectives nouvelles. Dans le projet #1, nous avons travaillé avec le virus à ARN Ebola (EBOV), un agent pathogène connu pour provoquer une fièvre hémorragique mortelle, qui a été responsable de plusieurs épidémies en Afrique et demeure encore aujourd'hui une menace pour la santé publique mondiale. En combinant RNA-Seq, PCR quantitative et analyses computationnelles, nous avons obtenu le premier transcriptome détaillé des miRNA (miRNome) d'une lignée de cellules hépatiques humaines infectées par l'une des trois souches variantes de EBOV dont Mayinga, Makona et Reston. Lors de l'infection par EBOV, il y'a une expression différentielle de seulement 1/5 du miRNome de l'hôte au cours du temps avec une modulation spécifique des miR-122-5p, miR-148a-3p et miR-21-5p. Les données obtenues mettent en relief, au-delà des manifestations cliniques jusque-là connues, de nouvelles différences substantielles entre les souches vis-à-vis de leur effet sur le miRNome. Dans une seconde phase, avec la même approche, nous avons découvert, caractérisé et validé deux miARN viraux codés par les génomes EBOV (Mayinga et Makona). Ces deux miARN viraux peuvent potentiellement cibler des gènes impliqués dans le phénotype hémorragique, la régulation de la réplication virale et la modulation de la défense immunitaire de l'hôte. Le projet #2 s'inscrit dans un contexte où nous avions découvert fortuitement l'existence d'espèces d'ARN inférieures à 16 nt (appelés ici vsRNA pour very small RNA) qui s'avèrent fonctionnels chez les eucaryotes alors qu'ils étaient souvent retirés des jeux de données de séquençage, car considérés comme étant des « produits de dégradation ». Nous avons étendu notre analyse RNA-Seq aux bactéries pour caractériser les vsRNAs de Escherichia coli K-12 MG1655 et cinq autres souches bactériennes. L'étude est complétée par l'analyse des vésicules dérivées de la membrane externe (Outer Membrane Vesicles ; OMVs) produites par E. coli K-12 MG1655 en raison de leurs rôles déterminants pour améliorer des chances de survie, la régulation des interactions microbiennes et la promotion de la pathogenèse. Les résultats montrent l'existence de vsRNAs variés et très abondants avec les tRFs comme un biotype majeur, notamment ceux dérivés de l'ARNt isoleucine (Ile-tRF). En guise de preuve de concept de la fonctionnalité de ces vsRNAs de type tRFs, nous avons étudié en détail le très abondant et thermodynamiquement stable Ile-tRF. Nos analyses montrent qu'il est modulé sélectivement par le stress environnemental et peut être transféré via les OMVs (où il est particulièrement enrichi) aux cellules humaines HCT116 où il favorise l'expression des ARNm codant pour des membres de la famille des MAP-kinase. Notre étude est la toute première chez E. coli à rapporter l'existence de tRF abondants, trouvés dans des vésicules (OMVs) et assumant des fonctions potentielles chez l'hôte. L'Ile-tRF est également le premier tRF fonctionnel de 13 nt rapporté chez les bactéries. / For several decades now, it has been known that only a small fraction of the genome is made up of protein-coding sequences and that the majority of non-coding DNA, historically considered as "junk", carries out important biological functions. With this new paradigm, our perception of gene expression and regulation has shifted from a protein-centered view to a more RNA-centered view in both prokaryotes and eukaryotes. The advent of high-throughput sequencing techniques such as RNA sequencing (RNA-Seq), has strongly contributed to the demystification of this "non-coding" part of RNA. Besides the triumvirate of tRNA, rRNA, and mRNA genes, genomes harbor numerous loci that encode small non-canonical regulatory RNAs distributed in many classes. MicroRNAs (miRNAs) and tRNA-derived fragments (tRFs) are the two most abundant classes of small non-coding RNAs (ncRNAs) and share similarities in their mechanisms. Although often overshadowed by proteins, they are at the heart of post-transcriptional regulation and are emerging players in the host-pathogen relationship. This thesis addresses the host-pathogen relationship from the perspective of small ncRNAs through two complementary projects (#1 and #2) that aim to provide new insights and perspectives. In project #1, we worked with the Ebola RNA virus (EBOV), a pathogen known to cause a deadly hemorrhagic fever, which has been responsible for several epidemics in Africa and remains a global public health concern to this day. By combining RNA-Seq, quantitative PCR and computational analyses, we obtained the first detailed miRNA transcriptome (miRNome) of a human liver cell line infected with one of the three variant strains of EBOV including Mayinga, Makona and Reston. During EBOV infection, there is a differential expression of only 1/5 of the host miRNome over time with specific modulation of miR-122-5p, miR-148a-3p and miR-21-5p. The data obtained highlight, beyond the previously known clinical manifestations, substantial new differences between the strains with respect to their effect on the miRNome. In a second phase, using the same approach, we discovered, characterized and validated two viral miRNAs encoded by the EBOV genomes (Mayinga and Makona). These two viral miRNAs can potentially target genes involved in the hemorrhagic phenotype, the regulation of viral replication and the modulation of host immune defense. Project #2 was developed in a context where we had fortuitously discovered the existence of RNA species smaller than 16 nt (called here vsRNA for very small RNA) that were functional in eukaryotes but were often removed from sequencing datasets because they were considered as "degradation products". We have extended our RNA-Seq analysis to bacteria in order to characterize vsRNAs from Escherichia coli K-12 MG1655 and five other bacterial strains. The study is completed by the analysis of Outer Membrane Vesicles (OMVs) produced by E. coli K-12 MG1655 because of their critical roles in enhancing survival, regulating microbial interactions and promoting pathogenesis. The results show the existence of diverse and highly abundant vsRNAs with tRFs as a major biotype, especially those derived from isoleucine tRNA (Ile-tRF). As a proof of concept of the functionality of these tRF-like vsRNAs, we have studied in detail the highly abundant and thermodynamically stable Ile-tRF. Our analyses show that it is selectively modulated by environmental stress and can be transferred via OMVs (where it is particularly enriched) to human HCT116 cells where it promotes the expression of mRNAs encoding members of the MAP-kinase family. Our study is the first ever in E. coli to report the existence of abundant tRFs found in vesicles (OMVs) with potential functions in the host. Ile-tRF is also the first functional 13 nt tRF reported in bacteria.