Orientadora: Adolorata Aparecida Bianco Carvalho / Banca: Maria da Gloria Buzinaro / Banca: Luzia Helena Queiroz / Resumo: No Brasil, a potência das vacinas veterinárias contra a raiva é avaliada pelo teste NIH ("National Institutes of Health"), no qual o desempenho de uma vacina, medido pela DE50 em camundongos, é comparado ao desempenho de uma vacina de referência. São consideradas aprovadas as partidas com potência igual ou superior a 1,0 UI. O presente estudo comparou o desafio viral com vírus fixo CVS, utilizado como padrão no teste de potência NIH, a desafios com três amostras virais isoladas de bovinos naturalmente infectados. O objetivo foi verificar se as amostras de vírus de campo apresentariam virulência maior que a do CVS, o que poderia sugerir a inadequação do teste NIH para a avaliação das vacinas contra a raiva e, portanto, inferir que as vacinas aprovadas por esse teste poderiam não proteger suficientemente o rebanho. Apesar da grande variabilidade que o teste NIH pode apresentar, as três repetições desafiadas com CVS apresentaram semelhança em um intervalo de confiança de 95%, e nos desafios realizados com três amostras de vírus de campo a vacina utilizada protegeu mais do que nos desafios com CVS. Conclui-se que a virulência das amostras de vírus de campo utilizadas não foi maior que a virulência do CVS, em camundongos, e que o rigor do desafio padrão mostrou-se adequado para a avaliação da potência pelo teste NIH e, portanto, para o controle da qualidade de vacinas contra a raiva. / Abstract: The potency of veterinary rabies vaccines in Brazil is evaluated by the NIH (National Institutes of Health) potency test, in which the ability of a vaccine to induce protection in mice (ED50) is compared with a reference vaccine. The batches are approved when the potency is equal or superior to 1.0 IU. The present study compared CVS strain challenges (standard strain for the potency test) with challenges that used three wild isolates of natural occurrence in cattle. The aim was to verify if the wild strains could be more virulent than the CVS. If this occurred, the NIH potency test would prove inadequate to evaluate rabies vaccines. Therefore, one could infer that the approved vaccines might not provide sufficient herd protection. Despite the great variability of NIH test, all three repetitions that were challenged with CVS were similar at a 95% confidence-level; and when challenged with wild strains, the vaccine provided better protection than the one achieved at CVS challenge. In conclusion, wild strains virulence was not greater than CVS virulence in mice. The strictness of standard challenge proved to be adequate for potency evaluation by NIH test, and consequently, for the quality control evaluation of rabies vaccines. / Mestre

While it has been established that postural control is affected by executive function, research is lacking in identifying if specific executive function components are most responsible or if certain aspects of postural control are more affected than others (e.g., proprioception, vestibular, visual). The current study examined the role of inhibition, processing speed, and visuospatial ability in postural control under conditions affecting visual, proprioceptive, and vestibular sensory input. Cognitive assessments consisted of the Flanker Inhibitory Control and Attention Test, Digit Symbol Substitution Test, Clock Drawing Test, Trail Making Test – Part B, and simple reaction time. Standing Balance was used to assess postural sway. Analyses revealed that average balance was significantly associated with simple reaction time (r(88) = -0.31, p < .01) and the clock drawing test (r(88) = -0.25, p< .05). Further analyses revealed a significantly stronger relationship between pose #1 (eyes opened, firm) and average balance (r(88) = -0.845, p< 0.1) when compared to pose #2 (eyes closed, firm), and pose #3 (eyes opened, foam) and average balance r(88) = -0.8015, p< 0.1) when compared to pose #4 (eyes closed, foam). The significantly stronger relationship between these two measures demonstrates that visual input in both conditions #1 and #3 was associated with better postural control. The findings of this study demonstrate that reaction time and visuospatial abilities are associated with overall postural control in healthy older adults. Results suggest that reaction time should be more thoroughly researched to determine the extent of its influence on EF and physical function.

No description available.

ClinicalTrials.gov is a database designed to help clinical researchers make their research publicly available. The clinical trials registered on the database each include a brief summary, which is meant to be a short description that the public can easily understand. In September 2022, ClinicalTrials.gov published a "Plain Language Checklist for Lay Brief Summaries" on their website, which identifies plain language best practices intended to help investigators craft summaries that can be readily understood by the public. This thesis assesses the impact of the checklist on the language use in the brief summaries in the year following the checklist's publication. The analysis examines 62 brief summaries for Phase III and IV clinical trials posted on ClinicalTrials.gov between September 26, 2022, and September 26, 2023. It focuses particularly on summaries associated with rheumatoid arthritis, knee replacement, and conjunctivitis to gauge how well they complied with 4 of the 19 criteria on the Plain Language Checklist: keeping sentences and paragraphs short, aiming for a 6th to 8th grade reading level, writing out acronyms on the first use, and providing both percentages and natural frequencies. It also examines rhetorical moves made in the summaries to address the use of jargon, key term definitions, headings, formatted lists, direct research questions, descriptions of study type, sentence fragments, and the placement of the purpose statement to see how these moves affected the plain language. Although the summaries tended to comply with the paragraph length guidelines, they did not comply with the sentence length, reading level, or acronym guidelines. The variation in compliance could be attributed to researchers' lack of awareness of the guidelines, lack of time to devote to creating brief summaries, or being too immersed in the field to imagine the needs of a lay audience. It could also be attributed to the National Institute of Health not enforcing the guidelines or to researchers not viewing the guidelines as being relevant.

Cette thèse s'appuie sur la spectroscopie de NiH établie à la fin des années 1980 et au début des années 1990, principalement par le groupe du Pr. R. W. Field au MIT. Les mesures expérimentales ont amélioré de manière significative les travaux antérieurs, tant en spectroscopie en champ nul qu'en spectroscopie Zeeman. Le radical NiH est obtenu avec une source à décharge à température ambiante (310 K). Les radicaux formés dans la décharge sont excités par un laser continu à colorant et étudiés soit en spectroscopie d'excitation laser soit en fluorescence dispersée. Un circuit magnétique à aimants permanents (NdFeB) fournit un champ magnétique statique (0.4 – 0.9 T). En champ nul, les spectres de fluorescence par transformée de Fourier ont élargi les observations de l'état électronique fondamental jusqu'à 6000 cm-1, pour 58NiH et 60NiH. Les énergies sont modélisées avec un Hamiltonien effectif obtenu à partir du formalisme du modèle du 3d9 supermultiplet développé par le groupe de Field. Les mesures Zeeman se sont principalement concentrées sur l'étude des états Ω=3/2. Les facteurs de Landé effectifs ont été déterminés pour chaque niveau ro-vibrationnel pour les états de basse énergie et les états excités de 58NiH. L'inhabituelle dépendance en J des facteurs de Landé obtenus pour les états de basse énergie est expliquée par le modèle du supermultiplet, quantifiant alors l'ampleur des mélanges spin-orbite présents dans les états inférieurs. Les transitions étudiées ont un intérêt astrophysique depuis que plusieurs transitions d'hydrure métallique ont été observées dans les spectres d'étoiles froides et les taches solaires. / This thesis builds on the spectroscopy of NiH established in the late 1980s and early 1990s, principally by Pr. R. W. Field's group at MIT. Experimental measurements significantly extend earlier work, both in field-free and Zeeman spectroscopy. The NiH radical is obtained with a room-temperature metal-hydride discharge source (310 K). Radicals formed in the discharge are excited by a single-mode, continuous wave dye laser and can be conveniently studied either in laser excitation or in dispersed fluorescence. A magnetic circuit with permanent magnets (NdFeB) provides a static magnetic field (0.4 – 0.9 T). In the field-free regime, Fourier transform resolved fluorescence spectra have extended the range of observations up to 6000 cm-1 above v=0 of the electronic ground state, for 58NiH and 60NiH. Energies are modeled with an effective Hamiltonien matrix using the 3d9 supermultiplet formalism developed by Field's group. Zeeman measurements have focused mainly on the range of states studied by including transitions involving the Ω=3/2 excited states. Effective Landé factors have been determined for individual ro-vibrational levels of low-lying and excited states of 58NiH. The unusual J-dependence of the Landé factors obtained for low-lying states are explained by the 3d9 supermultiplet model, quantifying the extent of spin-orbit mixing present in the lower states. The transitions are of potential astrophysical interest since several transition metal hydrides have been observed in the spectra of cool stars and sunspots.

Cette thèse s'appuie sur la spectroscopie de NiH établie à la fin des années 1980 et au début des années 1990, principalement par le groupe du Pr. R. W. Field au MIT. Les mesures expérimentales ont amélioré de manière significative les travaux antérieurs, tant en spectroscopie en champ nul qu'en spectroscopie Zeeman. Le radical NiH est obtenu avec une source à décharge à température ambiante (310 K). Les radicaux formés dans la décharge sont excités par un laser continu à colorant et étudiés soit en spectroscopie d'excitation laser soit en fluorescence dispersée. Un circuit magnétique à aimants permanents (NdFeB) fournit un champ magnétique statique (0.4 - 0.9 T). En champ nul, les spectres de fluorescence par transformée de Fourier ont élargi les observations de l'état électronique fondamental jusqu'à 6000 cm-1, pour 58NiH et 60NiH. Les énergies sont modélisées avec un Hamiltonien effectif obtenu à partir du formalisme du modèle du 3d9 supermultiplet développé par le groupe de Field. Les mesures Zeeman se sont principalement concentrées sur l'étude des états Ω=3/2. Les facteurs de Landé effectifs ont été déterminés pour chaque niveau ro-vibrationnel pour les états de basse énergie et les états excités de 58NiH. L'inhabituelle dépendance en J des facteurs de Landé obtenus pour les états de basse énergie est expliquée par le modèle du supermultiplet, quantifiant alors l'ampleur des mélanges spin-orbite présents dans les états inférieurs. Les transitions étudiées ont un intérêt astrophysique depuis que plusieurs transitions d'hydrure métallique ont été observées dans les spectres d'étoiles froides et les taches solaires.

From fighting microbial infections to preparing for pandemics, Brett Finlay is discovering how the body's own defenses could boost our chances in the battle against infectious diseases.

Wounds in the mouth, occurring after oral surgery, take time to heal. No ointment can be added to help with the healing process because mouth saliva will constantly wash it away. In order to combat this problem, we propose engineering a normal flora microbe to grow at the site of injury and secrete a recombinant growth factor to promote healing of the damaged tissue. Our goal is to have the yeast Pichia pastoris produce human basic fibroblast growth factor (bFGF), which aids in cellular proliferation. P. pastoris is a good choice for this application because not only is it considered generally recognized as safe (GRAS) by the FDA, but it is a eukaryote that is able to perform posttranslational modifications and secrete large amounts of recombinant protein. Previous studies have shown that a strain of P. pastoris can be engineered to express bFGF from a methanol-sensitive promoter. The study also showed that the bFGF, which was purified from the yeast’s extracellular medium, was able to promote the growth of NIH/3T3 cells (mice fibroblasts). Because we needed the P. pastoris to express the bFGF in glucose –based tissue culture medium in the presence of mammalian cells, we expressed the bFGF from the constitutive promoter GAP promoter. Along with optimizing and characterizing expression of bFGF, we also investigated the effect of the recombinant protein on mammalian cell growth using both scratch ad MTS assays. In addition, the effects of the yeast being co-cultured with mammalian cells was studied. Our results provide a basis for how a recombinant protein can be clinically used to improve wound healing in the mouth using a yeast strain to produce and secrete a growth factor at the site of injury.

No description available.

Le thème central de ce travail est le développement expérimental d'une méthode spectroscopique intracavité laser visant à augmenter la sensibilité des expériences de fluorescence induite par laser (LIF) et analysée par spectrométrie par transformée de Fourier (FTS) haute résolution. Cette augmentation passe par la réalisation du couplage d'une cavité externe résonante avec la technique FTS. L'échantillon moléculaire est placé à l'intérieur de la cavité qui stocke l'énergie d'un laser à colorant mono-mode accordable en étant maintenue en permanence en résonance grâce à un système optoélectronique d'asservissement. L'accroissement de puissance intracavité permet alors l'observation de niveaux quantiques moléculaires inaccessibles par les méthodes LIF traditionnelles. Cette technique (ICLIF) est validée par l'étude du radical d'intérêt astrophysique NiH produit par une nouvelle source polyvalente à pulvérisation cathodique, développée en parallèle dans le cadre de ce travail.