<p>The interaction of human tumor viruses with host growth suppressive pathways is a fine balance between controlled latent infection and virus-induced oncogenesis. This dissertation elucidates how Epstein-Barr virus interacts with the host growth suppressive DNA damage response signaling pathways (DDR) in order to transform infected human B lymphocytes. </p><p> Here I report that the activation of the ATM/Chk2 branch of the DDR in hyper-proliferating infected B cells results in G1/S cell cycle arrest and limits viral-mediated transformation. Similar growth arrest was found in mitogen-driven proliferating of B cells that sets the DDR as a default growth suppressive mechanism in human B cells. Hence, the viral protein EBNA3C functions to attenuate the host DDR and to promote immortalization of a small portion of infected B cells. Additionally, the pharmacological inhibition of the DDR in vitro increases viral immortalization of memory B cells that facilitates the isolation of broadly neutralizing antibodies to various infectious agents. Overall, this work defines early EBV-infected hyper-proliferating B cells as a new stage in viral infection that determines subsequent viral-mediated tumorigenesis.</p> / Dissertation

A bas nombre de Reynolds, le concept de voilure battante apparaît comme une alternative auxconcepts conventionnels de voilure fixe et voilure tournante. Dans le cadre d'une applicationpratique (micro-drones ou MAVs), l'évaluation de l'adaptabilité d'un tel mode de sustentationrequiert la compréhension fine des principaux mécanismes aérodynamiques mis en jeu et de leurimpact sur les efforts résultants. Ces derniers se caractérisent par une instationnarité forte et descomportements complexes.Les travaux de cette thèse se concentrent sur l'étude du mouvement de vol battu à bas Reynolds (del'ordre de 1000), dans une configuration de vol stationnaire. Le modèle est constitué d'une ailerectangulaire à profil symétrique animé d'un mouvement couplé de battement et de tangage. Cemode de sustentation se caractérise par la génération à proximité de l'aile de structurestourbillonnaires plus ou moins persistantes influant fortement les efforts appliqués à l'aile.L'objectif consiste à analyser l'évolution des mécanismes instationnaires et des efforts en résultant.L'étude porte en particulier sur une analyse approfondie d'un cas de référence, comparé ensuite àd'autre résultats lors d'une étude paramétrique portant sur l'influences de l'allongement d'une part, etde la cinématique du mouvement d'autre part.Les moyens d'investigations adoptés pour mener cette étude sont à la fois numériques etexpérimentaux, L'analyse repose d'une part sur une approche numérique DNS utilisant unetechnique de maillage " chimère ", et d'autre part sur des mesures en bassin de type PIV 3D-3Crésolues en temps. La mesure directe des efforts instationnaires de faible niveau étant difficilementenvisageable, une part importante du travail a consisté à adapter une méthode d'évaluation desefforts par bilan de quantité de mouvement à partir des champs de vitesse PIV résolus en temps. Lespoints durs de cette approche, en particulier l'évaluation de la pression à partir des champs devitesse, font l'objet d'une attention particulière.

Master of Science in Biomedical Sciences / Department of Diagnostic Medicine/Pathobiology / Yunjeong Kim / Coronaviruses are pathogens that cause diverse diseases in humans and animals. The studies in this dissertation are focused on feline coronavirus (FCoV), ferret coronavirus (FRCoV) and mink coronavirus (MCoV). FCoV and FRCoV infections typically cause enteritis in cats and ferrets, respectively. However, a 100% fatal systemic disease called feline infectious peritonitis (FIP) can develop in some FCoV infected cats and a fatal systemic disease resembling FIP can develop in some FRCoV infected ferrets. MCoV causes enteritis which results in significant economic loss to mink farmers. No effective vaccine or treatment is available despite the increasing importance of these viral diseases. We have previously reported the synthesis of inhibitors against 3C-like protease (3CLpro) of FCoV and demonstrated the antiviral efficacy of a 3CLpro inhibitor for treating FIP. FRCoV and MCoV 3CLpro are closely related to FCoV 3CLpro. Therefore, we investigated the structure-function relationships of our 3CLpro inhibitors to identify the struc-tural requirements of inhibitors for FRCoV and MCoV. This is the first report of antiviral com-pounds against FRCoV and MCoV. We have previously conducted a field trial with a potent 3CLpro inhibitor, GC376, in cats with naturally occurring FIP. Comparison of the FCoV 3CLpro amino acid sequences from the pre- and post-treatment samples in one cat showed amino acid changes in 3CLpro. Hence, we generated recombinant 3CLpros carrying the amino acid changes and characterized the effects of these amino acid changes in FCoV 3CLpro on its susceptibility to GC376. We observed that these amino acid changes did not markedly affect the activity of GC376 in fluorescence resonance energy transfer (FRET) assay, explaining the absence of clinical drug resistance in this cat during the field trial.

The market for renewable energy sources, and solar cells in particular is growing year by year, as a result there is a large interest in research on new materials and new technologies for solar power applications. In this thesis the photovoltaic properties of cubic silicon carbide (3C-SiC) has been investigated. The research includes material growth using the sublimation epitaxy method, both n-type and p-type SiC have been investigated. 3C-SiC pn junctions have been produced and their electrical properties have been characterized, this is the first time 3C-SiC pn junctions have been studied in the research group. Photoresponse has been demonstrated from a 3C-SiC pn junction with Al and N used as p- and ntype dopants. This is the first demonstrated solar cell performance using 3C-SiC, to our knowledge.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-06-23T21:14:44Z No. of bitstreams: 1 NathaliaMattosNovaesDaRocha_DISSERT.pdf: 8902893 bytes, checksum: 548054835dc66d4ee903a6646b0226ac (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-06-28T18:39:22Z (GMT) No. of bitstreams: 1 NathaliaMattosNovaesDaRocha_DISSERT.pdf: 8902893 bytes, checksum: 548054835dc66d4ee903a6646b0226ac (MD5) / Made available in DSpace on 2016-06-28T18:39:22Z (GMT). No. of bitstreams: 1 NathaliaMattosNovaesDaRocha_DISSERT.pdf: 8902893 bytes, checksum: 548054835dc66d4ee903a6646b0226ac (MD5) Previous issue date: 2015-09-14 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / Descoberto em 1963, 3C 273 foi o segundo quasar identificado e catalogado no Terceiro Cat?logo de Cambridge para r?dio fontes, e o primeiro para o qual as linhas de emiss?o foram identificadas com uma sequ?ncia de hidrog?nio desviada para o vermelho. Ele ? o quasar mais brilhante da esfera celeste, o mais estudado, analisado, e com uma resultante abund?ncia de dados dispon?veis em uma vasta literatura. A an?lise precisa dos desvios das linhas espectrais de quasares, fornece informa??o suficiente para p?r em prova a varia??o das constantes fundamentais da natureza e similarmente da taxa de expans?o do universo. A an?lise da variabilidade das curvas de luz desses corpos, e a consequente precis?o das suas periodicidades, ? de suma import?ncia pois proporciona uma efic?cia nas observa??es deles, possibilita uma maior compreens?o dos seus fen?menos f?sicos, e torna fact?vel a realiza??o de observa??es espectrais em datas mais exatas (momentos nos quais suas curvas de luz apresentam picos acentuados e, por conseguinte, espectros mais ricos em informa??o). Na presente disserta??o, vinte e oito curvas de luz do quasar 3C 273 s?o estudadas, abrangendo todas as faixas do espectro eletromagn?tico (da emiss?o r?dio aos raios gama), totalizando na an?lise de quatro curvas de luz para cada faixa. Aplicamos o m?todo da Transformada Wavelet Cont?nua do tipo Morlet de ordem w = 06 e obtivemos resultados precisos e coerentes com a literatura. / Discovered in 1963, 3C 273 was the second quasar identified and cataloged in the Third Cambridge Catalog for radio sources, and the first one for which emission lines were identified with a hydrogen sequence redshifted. It is the brightest quasar of the celestial sphere, the most studied, analyzed, and with a resulting abundance of data available in a vast literature. The accurate analysis of the deviations of the spectral lines of quasars provides enough information to put in evidence the variation of fundamental constants of nature and similarly the universe expansion rate. The analysis of the variability of the light curves of these bodies, and the consequent accuracy of their periodicity, is of utmost importance as it provides an efficiency of their observations, enables a greater understanding of the physical phenomena, and makes it possible to conduct spectral observations on more accurate dates (when their light curves show pronounced peaks and therefore richer spectra information). In this master?s thesis twenty eight light curves from the quasar 3C 273 are studied, covering all the electromagnetic spectrum wavebands (radio emission to gamma rays), totaling in the analysis of four light curves for each waveband. We have applied the method of Continuous Wavelet Transform using the sixth-order (!0 = 6) Morlet wavelet function, and obtained excellent results in accordance with the literature.

No description available.

A bas nombre de Reynolds, le concept de voilure battante apparaît comme une alternative auxconcepts conventionnels de voilure fixe et voilure tournante. Dans le cadre d’une applicationpratique (micro-drones ou MAVs), l’évaluation de l’adaptabilité d’un tel mode de sustentationrequiert la compréhension fine des principaux mécanismes aérodynamiques mis en jeu et de leurimpact sur les efforts résultants. Ces derniers se caractérisent par une instationnarité forte et descomportements complexes.Les travaux de cette thèse se concentrent sur l'étude du mouvement de vol battu à bas Reynolds (del'ordre de 1000), dans une configuration de vol stationnaire. Le modèle est constitué d’une ailerectangulaire à profil symétrique animé d’un mouvement couplé de battement et de tangage. Cemode de sustentation se caractérise par la génération à proximité de l'aile de structurestourbillonnaires plus ou moins persistantes influant fortement les efforts appliqués à l’aile.L'objectif consiste à analyser l'évolution des mécanismes instationnaires et des efforts en résultant.L'étude porte en particulier sur une analyse approfondie d'un cas de référence, comparé ensuite àd'autre résultats lors d'une étude paramétrique portant sur l’influences de l'allongement d'une part, etde la cinématique du mouvement d'autre part.Les moyens d’investigations adoptés pour mener cette étude sont à la fois numériques etexpérimentaux, L’analyse repose d’une part sur une approche numérique DNS utilisant unetechnique de maillage « chimère », et d’autre part sur des mesures en bassin de type PIV 3D-3Crésolues en temps. La mesure directe des efforts instationnaires de faible niveau étant difficilementenvisageable, une part importante du travail a consisté à adapter une méthode d’évaluation desefforts par bilan de quantité de mouvement à partir des champs de vitesse PIV résolus en temps. Lespoints durs de cette approche, en particulier l’évaluation de la pression à partir des champs devitesse, font l’objet d’une attention particulière. / A low Reynolds number, flapping wings appears as an alternative to conventional concepts of fixed wings and rotary wings aircrafts. In the context of a practical application (micro air vehicles, MAVs), assessing the suitability of such mode of lift generation requires a detailed understanding of the key aerodynamic mechanisms involved and their impact on resulting forces. These are characterized by a strong unsteadiness and complex behaviors.This work focuses on the study of flapping flight at low Reynolds (around 1 000), in a hover configuration. The model consists of a rectangular wing with a symmetrical profile in a flapping motion. This mode is characterized by the generation of vortex structures more or less persistent that strongly influence the forces applied to the wing.The objective is to analyze the evolution of unsteady mechanisms and resulting forces. The study focuses in particular on a thorough analysis of e reference case, then compared to other results in a parametric study on the influence of aspect-ratio on the one hand, and on the kinematic of movement on the other.The means of investigation adopted for this study are both numerical and experimental. The analysis is based in part on a numerical approach using a DNS meshing technique “chimera”, and on experimental approach with 3C-3D TR-PIV measures. Direct measurement of unsteady low forces being difficult to consider, an important part of the work was to adapt a method for evaluating loads by applying momentum equation using PIV velocity fields. The bottleneck of this approach which is the evaluation of the pressure from the velocity fields is subject to special attention.

El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / SARS-CoV-2 main protease is a common target for inhibition assays due to its high conservation among coronaviruses. Since flavonoids show antiviral activity, several in silico works have proposed them as potential SARS-CoV-2 main protease inhibitors. Nonetheless, there is reason to doubt certain results given the lack of consideration for flavonoid promiscuity or main protease plasticity, usage of short library sizes, absence of control molecules and/or the limitation of the methodology to a single target site. Here, we report a virtual screening study where dorsilurin E, euchrenone a11, sanggenol O and CHEMBL2171598 are proposed to inhibit main protease through different pathways. Remarkably, novel structural mechanisms were observed after sanggenol O and CHEMBL2171598 bound to experimentally proven allosteric sites. The former drastically affected the active site, while the latter triggered a hinge movement which has been previously reported for an inactive SARS-CoV main protease mutant. The use of a curated database of 4.8 k flavonoids, combining two well-known docking software (AutoDock Vina and AutoDock4.2), molecular dynamics and MMPBSA, guaranteed an adequate analysis and robust interpretation. These criteria can be considered for future screening campaigns against SARS-CoV-2 main protease. / Consejo Nacional de Ciencia, Tecnología e Innovación Tecnológica / Revisión por pares

Proteases are important enzymes in the biotechnology due to their specific cleavage of substrates. HRV 3C, sortase A and TEV are some examples of cysteine proteases which become more of use lately in applications as removal of affinity tags (3C/TEV) and labelling of proteins (sortase). Here an investigation was made on the proteases by displaying them on two different prokaryotic hosts; E. coli and S. carnosus and to use these to cleave away affinity proteins (Affibody molecule) from other cells with an incorporated cleavage site. Constructs were cloned and incorporated into expressing strains which were then cultivated and induced. Analysis of surface expression was done by flow cytometer. Cleavage was made by cultivating combinations with cleavable bacteria and bacteria displaying proteases. A functional protease would lead to the presence of Affibody molecules in the supernatant. Flow cytomtery analysis was first made to inevstigate signal difference in Affibody binding by the addition of flurophores. Secondly SDS-PAGE was made on the centrifuged supernatant to investigate the presence of a product. Finally analysis of the bacteria was made by examining the reaction with soluble substrate and comparing activity with soluble enzyme. All of the enzymes were able to be displayed on the surface of bacteria with a clear separation from control. The cleavage analysis showed however varying results yet no clear evidence of product. Best flow cytometer results were seen for 3C but SDS-PAGE/MS did not show any cleaved product. For Sortase SDS-PAGE showed positive result but analysis with MS showed no product. TEV was concluded not to be funcional at all hence the failing to cleave soluble substrate  when condition seemed near optimal and faulty flow cytometer data. Even though the lack of success there is still many further studies that can be done on the proteases in order to prove its absence/presence  of activity.

The quasar 3C 279 was the target of an extensive multiwavelength monitoring campaign from 2006 January through April. An optical-IR-radio monitoring campaign by the Whole Earth Blazar Telescope (WEBT) collaboration was organized around target-of-opportunity X-ray and soft γ-ray observations with Chandra and INTEGRAL in 2006 mid-January, with additional X-ray coverage by RXTE and Swift XRT. In this paper we focus on the results of the WEBT campaign. The source exhibited substantial variability of optical flux and spectral shape, with a characteristic timescale of a few days. The variability patterns throughout the optical BVRI bands were very closely correlated with each other, while there was no obvious correlation between the optical and radio variability. After the ToO trigger, the optical flux underwent a remarkably clean quasi-exponential decay by about 1 mag, with a decay timescale of T d ∼ 12.8 days. In intriguing contrast to other (in particular, BL Lac type) blazars, we find a lag of shorter wavelength behind longer wavelength variability throughout the RVB wavelength ranges, with a time delay increasing with increasing frequency. Spectral hardening during flares appears delayed with respect to a rising optical flux. This, in combination with the very steep IR-optical continuum spectral index of α0 ∼ 1.5-2.0, may indicate a highly oblique magnetic field configuration near the base of the jet, leading to inefficient particle acceleration and a very steep electron injection spectrum. An alternative explanation through a slow (timescale of several days) acceleration mechanism would require an unusually low magnetic field of B ≲ 0.2 G, about an order of magnitude lower than inferred from previous analyses of simultaneous SEDs of 3C 279 and other flat-spectrum radio quasars with similar properties.