Made available in DSpace on 2018-06-27T18:56:12Z (GMT). No. of bitstreams: 2 Larissa Daiane Willrich de Melo.pdf: 1466861 bytes, checksum: 3695d65f6aa448f284f69ac1afd4510f (MD5) Larissa Daiane Willrich de Melo.pdf.jpg: 3370 bytes, checksum: 20955982b01b119bb6af06d3b4896dcc (MD5) Previous issue date: 2013-03-25 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Efforts to develop an effective vaccine against Herpes Simplex Virus-1 (HSV-1) has been intense enough, however, there is no effective vaccine yet. The using of nanocapsules (Ncs) for production of viral vaccines may contribute to the enhancement and effectiveness of the already developed vaccines models. The main properties of the nanostructured system, which may contribute to the improvement of the immune response generated by vaccine is the slow and gradual release of the encapsulated content, protection of the encapsulated molecule or protein and adjuvanticity, inherent in every Ncs. The objective of this study was to produce and characterize nanocapsules with aqueous core to encapsulate the SSIEFARL peptide from HSV-1. This peptide has hydrophilic characteristics which impossibility the encapsulation in conventional nanocapsules with oil core. For the standardization of the tunnel several adaptations where modified in the system previously developed by Lambert et al. Among these, the stirring of the suspension, temperature, amount of surfactant, amount of peptide and settling time were adapted. All protocols two aqueous suspensions were tested, one with the organic solvent ethanol in the aqueous phase or only water. The results showed that the production with magnetic stirring in the presence of ethanol in the aqueous phase lead to Ncs with better physicochemical characteristics. Empty Ncs presented an average of particle size of 285 nm (+ 19,4) and zeta potential of -40.1 mV (+ 1,7) and the Ncs containing SSIEFARL peptide presented the size of 315 nm (+ 20,7) and zeta potential of -35,5 mV (+ 2,4). Other condition of production tested was the water temperature added during the production. When water was used at 40 °C the physico-chemical parameters were better than when room temperature water was used. Additionally, we tested the stability of the suspensions after storage at room temperature or 4 °C. The Ncs were stable for longer periods of time under refrigeration. For the characterization of morphostructure, Ncs were analyzed by transmission electron microscopy (TEM). This analysis revealed that Ncs present as spherical structures, homogeneous and uniform as standards in nanostructure for biological application. The analysis of Ncs by confocal microscopy was applied to investigate the encapsulation. Three amounts of SSIEFARL-6 FAM peptide were used (20, 30 or 50 μL), and the 20 μL showed better encapsulation. The analysis of the release profile of the peptide from Ncs showed that of the suspension produced with 20 μL was more linear, demonstrating slow release for at least 24 h. These data indicate that the method of production under magnetic stirring with ethanol and 20 μL of peptide in the aqueous phase is more suitable for production of aqueous core Ncs. Furthermore, empty Ncs at low concentrations showed no cytotoxicity to lymphoid cells from BALB-c in cell culture. Thus, we suggest that this approach has promising potential for developing a vaccine against HSV-1. / Os esforços para o desenvolvimento de uma vacina eficaz contra o Herpes Simplex Vírus-1 (HSV-1) tem sido bastante intensos, entretanto, ainda não existe uma vacina eficaz. A utilização de nanocápsulas (Ncs) para a produção de vacinas anti-virais pode contribuir para o aprimoramento e eficácia dos modelos vacinas já desenvolvidos. As principais propriedades desse sistema nanoestruturado, que podem contribuir para a melhora da resposta imune gerada por uma vacina são liberação lenta e gradual do conteúdo encapsulado, a proteção da molécula ou proteína encapsulada e a adjuvanticidade, inerente a cada Ncs. Assim, o objetivo deste estudo foi produzir e caracterizar nanocápsulas de núcleo aquoso, capazes de encapsular o peptídeo SSIEFARL do HSV-1. Este peptídeo possui características hidrofílicas sendo impossível a encapsulação em nanocápsulas convencionais de núcleo oleoso. Para a padronização do encapsulamento, foram combinadas diversas adaptações ao sistema previamente desenvolvido por Lambert e colaboradores. Dentre essas, foram adaptados o modo de agitação das suspensões, temperatura, quantidade de tensoativo, quantidade de peptídeo e tempo de sedimentação. Em todos os métodos foram testados duas alterações na fase aquosa das suspensões, foram produzidas Ncs com solvente etanol, na fase aquosa e/ou sem. Como resultados foram observados que a produção com agitação magnética em presença de etanol na fase aquosa foi a que produziu NCs com melhores características físico-químicas. Foram obtidas Ncs brancas com tamanho de partícula médio de 285 nm (+ 19,4) e potencial zeta de -40,1 mV (+ 1,7) e Ncs contendo o peptídeo SSIEFARL com tamanho de 315 nm (+ 20,7) e potencial zeta de -35,5 mV (+2,4). Outra condição alterada foi a temperatura da água adicionada durante os processos de produção. Quando foi utilizada água na temperatura de 40 oC os parâmetros físico-químicos foram melhores do que quando foi utilizada água na temperatura ambiente (T.A). Além disso, foi testada a estabilidade das suspensões após armazenamento em temperatura ambiente e geladeira (4oC). As nanocápsulas se mantiveram estáveis por mais tempo em sob refrigeração. Para a caracterização morfoestrutural das Ncs produzidas, foi utilizada a microscopia eletrônica de transmissão (MET). Essa análise revelou que as Ncs apresentam-se como estruturas esféricas, homogêneas e uniformes, conforme padrões estabelecidos para esse tipo de nanoestrutura. A análise das Ncs por microscopia confocal foi utilizada para comprovação do encapsulamento do peptídeo SSIEFARL-6-Fam, assim como a melhor quantidade. Foram utilizadas três quantidades de peptídeo (20, 30 ou 50 L), sendo que a quantidade de 20 L foi a que apresentou melhores resultados. O gráfico do perfil de liberação da suspensão produzida com 20 μL mostrou-se mais linear, demonstrando liberação lenta por pelo menos 24 h. Estes dados apontam que a metodologia de produção sob agitação magnética com etanol e 20 μL de peptídeo na fase aquosa apresentaram os melhores resultados para produção de nanocápsulas de núcleo aquoso. Além disso, as nanocápsulas brancas em baixas concentrações não apresentaram citotoxicidade para células de órgãos linfóides de camundongos BALB-c em cultura de células. Com isso, podemos sugerir que esta metodologia possui potencial promissor para desenvolvimento de vacina contra o HSV-1.

Este projeto teve por objetivo a implementação de software para formulação de ração de frangos de corte utilizando Algoritmo Genético (AG). A geração da população inicial foi direcionada, impedindo a geração de indivíduos que possuíam características restritivas. Realizou-se três experimentos, sendo o primeiro para definição do tamanho da população, número de gerações e método de seleção de pais, o segundo para comparar a formulação de ração do AG com a do Simplex e o terceiro para verificar a variabilidade de resultados do AG. O experimento 1 foi realizado em delineamento inteiramente ao acaso, com tratamentos arranjados em esquema fatorial 2 x 5 x 19, sendo os fatores: métodos de seleção de pais (roleta e torneio de três), tamanho de população (200, 360, 500, 1.000 e 1.500 indivíduos) e número de geração (10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900 e 1.000), totalizando 190 tratamentos, com 20 repetições resultando em 3.800 observações. A cada observação registrou-se o fitness que foi submetido a análise de variância e quando significativa (P<0,05) aplicou-se o teste de Scott-Knott (5%). No experimento 2 foram formuladas três rações, sendo uma ração pelo método Simplex e duas pelo AG. As rações formuladas com AG utilizaram os parâmetros de tamanho de população, método de seleção de pais e número de gerações definidos no experimento 1. Os resultados obtidos pelo AG proporcionaram rações que apresentam uma diferença média no atendimento das necessidades nutricionais de 0,34% para a ração formulada pelo método roleta e de 0,16% pelo método torneio de três, sendo essas diferenças pequenas e que provavelmente não impactam sobre o desempenho animal e sobre as características de carcaça. A variação de resultados existente no AG, devido a sua característica heurística, foi testada no experimento 3 por intermédio de 100 execuções para cada método de seleção de pais, roleta e torneio de três, utilizando os mesmos parâmetros de tamanho de população e número de gerações das rações formuladas no experimento 2. Os resultados obtidos demonstram baixa dispersão nos dados. Conclui-se que o AG é uma estratégia de otimização eficiente para formulação de rações para frangos de corte, pois aproxima-se do atendimento exato da exigência nutricional, com variação pequena, e com mínimo custo. / The objective of the present project was to implement software for the formulation of broiler chicken feed using a Genetic Algorithm (GA). The generation of the initial population was directed, preventing the production of individuals with restrictive characteristics. A total of three experiments were carried out: the first one to define the population size, number of generations, and the method of parent selection; the second to compare ration formulation using the GA with that of the Simplex method, and the third to verify result variability using the GA. Experiment 1 was performed in a completely randomized design, with arranged treatments in a 2 x 5 x 19 factorial scheme, assessing the following factors: parent selection methods (roulette-wheel selection and tournament selection of three), population size (200, 360, 500, 1 000 and 1 500 individuals), and number of generations (10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900 and 1 000 ), totaling 190 treatments, with 20 repetitions each, resulting in 3 800 recordings. At each observation, the registered fitness was submitted to variance analysis, and if significant (P < 0.05), the Scott-Knott test (5%) was applied. In the second experiment, three rations were formulated: one by the Simplex method, and two employing the GA. The feeds formulated with the GA used the parameters of population size, parent selection method, and number of generations, defined in experiment 1. The results obtained by the GA provided feeds that exhibited a mean difference in nutritional requirements of 0.34% for the ration formulated by the roulette-wheel method and 0.16% for the tournament selection of three technique. These differences are considered small and may not impact on animal performance and carcass characteristics. The variation regarding the GA results, given its heuristic attribute, was tested in experiment 3 using 100 repetitions of each method of parent selection, employing the same parameters regarding population size and number of generations of the rations formulated in experiment 2. The obtained results demonstrate low data dispersion. In conclusion, the GA is an efficient optimization strategy for the formulation of broiler chicken feeds, since it approximates the exact fulfillment of the nutritional requirement, with small variation, and with minimum cost.

Orientadores: Aurelio Ribeiro Leite de Oliveira, Christiano Lyra Filho / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Eletrica e de Computação / Made available in DSpace on 2018-08-14T10:57:39Z (GMT). No. of bitstreams: 1 Cantane_DanielaRenata.pdf: 1253133 bytes, checksum: 870b16a2b9360f77ebd88f50491d181c (MD5) Previous issue date: 2009 / Resumo: A solução eficiente de sistemas lineares é fundamental em problemas de otimização linear e o primeiro método a obter êxito nesta classe de problemas foi o método Simplex. Com o objetivo de desenvolver alternativas eficientes para sua implementação, são apresentadas nesta tese técnicas de atualização da decomposição LU da base para aperfeiçoar a solução dos sistemas lineares oriundos do método Simplex, utilizando um reordenamento estático nas colunas da matriz. Uma simulação do método Simplex é implementada, realizando troca de bases obtidas pelo MINOS e verificando sua esparsidade. Somente os elementos afetados pela mudança de base são considerados para obter uma atualização da decomposição LU eficaz. As colunas da matriz são reordenadas de acordo com três estratégias: mínimo grau; forma bloco triangular e estratégia de Björck. Assim, obtém-se uma decomposição esparsa para qualquer base sem esforço computacional para obter a ordem das colunas, pois o reordenamento da matriz é estático e as colunas da base obedecem esta ordem. A forma bloco triangular obteve os melhores resultados, para os maiores problemas testados, em relação ao mínimo grau e a estratégia de Björck. Resultados computacionais para problemas da Netlib mostram a robustez e um bom desempenho computacional do método de atualização da decomposição LU proposto, pois não são necessárias refatorações periódicas da base como nos métodos de atualização tradicionais. O método proposto obteve uma redução do número de elementos não nulos da base em relação ao MINOS. Esta abordagem foi aplicada em problemas de corte de estoque e a atualização da decomposição LU proposta obteve uma redução do tempo computacional na solução destes problemas em relação ao GPLK. / Abstract: Finding efficient solution of linear systems is fundamental in the linear programming problems and the first method to obtain success for this class of problems was the Simplex method. With the objective to develop efficient alternatives to its implementation, techniques of the simplex basis LU factorization update are developed in this thesis to improve the solution of the Simplex method linear systems towards a matrix columns static reordering. A simulation of the Simplex method is implemented, carrying through the change of basis obtained from MINOS and verifying its sparsity. Only the factored columns actually modified by the change of the base are carried through to obtain an efficient LU factorization update. The matrix columns are reordered according to three strategies: minimum degree; block triangular form and the Björck strategy. Thus, sparse factorizations are obtained for any base without computational effort to obtain the order of columns, since the reordering of the matrix is static and base columns follow this ordering. The application of the block triangular form achieved the best results, for larger scale problems tested, in comparison to minimum degree method and the Björck strategy. Computational results for Netlib problems show the robustness of this approach and good computational performance, since there is no need of periodical factorizations as used in traditional updating methods. The proposed method obtained a reduction of the nonzero entries of the basis with respect to MINOS. This approach was applied in the cutting stock problems and the proposed method achieved a reduction of the computational time in the solution of such problems with respect to the GLPK. / Universidade Estadual de Campi / Automação / Doutor em Engenharia Elétrica

Métodos tipo simplex são a base dos principais softwares utilizados na resolução de problemas de otimização linear. A implementação computacional direta destes métodos, assim como são descritos na teoria, leva a resultados indesejáveis na resolução de problemas reais de grande porte. Assim, a utilização de técnicas computacionais adequadas é fundamental para uma implementação eficiente e estável. Neste trabalho, as principais técnicas são discutidas, com enfoque naquelas que buscam proporcionar a estabilidade numérica do método: utilização de tolerâncias, estabilização do teste da razão, mudança de escala e representação da matriz básica. Para este último tópico, são apresentadas duas técnicas, a Forma Produto da Inversa e a Decomposição LU. A análise das abordagens é feita baseando-se na resolução dos problemas da biblioteca Netlib / Simplex-type methods are the basis of the main linear optimization solvers. The straightforward implementation of these methods as they are presented in theory yield unexpected results in solving reallife large-scale problems. Hence, it is essencial to use suitable computational techniques for an efficient and stable implementation. In this thesis, we address the main techniques focusing on those which aim for numerical stability of the method: use of tolerances, stable ratio test, scaling and representation of the basis matrix. For the latter topic, we present two techniques, the Product Form of Inverse and the LU decomposition. The Netlib problems are solved using the approaches addressed and the results are analyzed

Submitted by Biblioteca da Faculdade de Farmácia (bff@ndc.uff.br) on 2018-01-11T13:56:55Z No. of bitstreams: 1 FIORELLA ZIBETTI.pdf: 1848554 bytes, checksum: a4058071f9ee8b5dc5ab5c3abb07a729 (MD5) / Made available in DSpace on 2018-01-11T13:56:55Z (GMT). No. of bitstreams: 1 FIORELLA ZIBETTI.pdf: 1848554 bytes, checksum: a4058071f9ee8b5dc5ab5c3abb07a729 (MD5) / O óleo essencial de Rosmarinus officinalis (OERo) possui atividade anti- herpética in vitro. Entretanto, os constituintes químicos estão sujeitos à degradação por oxidação ou volatilização. Desta forma, surge a necessidade de desenvolvimento de sistemas carreadores para este ativo vegetal. O presente trabalho teve como objetivo desenvolver nanoemulsões contendo OERo, comparando dois métodos de baixo aporte energético, titulação à frio e inversão de fases, quanto à estabilidade, teor do marcador químico, perfil de liberação in vitro, permeação e retenção cutânea in vitro e atividade anti-herpética in vitro. O OERo, utilizado nesse estudo, apresentou como constituinte majoritário o eucaliptol (27,9%), descrito na literatura por inibir o vírus Herpes simplex. As nanoemulsões e seus respectivos hidrogéis foram desenvolvidos e conservados em temperatura ambiente por 60 dias. Todas as formulações mantiveram-se estáveis durante o período estudado, apresentando tamanho de gotícula inferior a 200nm. Nenhum dos parâmetros avaliados apresentou diferença significativa entre os métodos utilizados, com exceção do teor, que foi menor em T0 nas nanoemulsões produzidas com aquecimento. Aas formulações apresentaram cerca de 60% de liberação do óleo em 150 minutos em ensaio in vitro. No estudo de permeação/retenção cutânea in vitro foi possível detectar o eucaliptol, por Cromatografia Líquida de Alta Eficiência, no meio de lavagem (~32%), estrato córneo (~12%) e meio receptor (~56%), não sendo observado na epiderme e derme. Para avaliação da atividade anti-herpética, as nanoemulsões apresentaram índice de inibição viral superior a 98,2% (HSV-1) e 99,5% (HSV- 2), apresentando maior especificidade pelo sorotipo 2. As diferentes metodologias não impactaram significativamente na atividade anti-herpética. Dessa forma, conclui-se que ambos os métodos são capazes de preparar nanoemulsões com características semelhantes e estudos in vivo serão necessários para melhor entendimento da atividade do óleo / The essential oil of Rosmarinus officinalis (OERo) has anti-herpetic activity in vitro. However, the chemical constituents are subject to degradation by oxidation or volatilization. Thus, indicating a need to develop carriers systems for this plant active.The aim of the present work was to develop nanoemulsions containing OERo, comparing two low energy methods, cold titration and phase inversion, in terms of stability, chemical marker content, in vitro release profile, in vitro skin permeation and retention, and anti-herpetic activity in vitro. The OERo used in this study presented as main constituent eucalyptol (27.9%), which was described in the literature for inhibiting the Herpes simplex virus. Nanoemulsions and their respective hydrogels were developed by two different methodologies and stored at room temperature for 60 days. All formulations remained stable during the study period, with particle size smaller than 200nm. None of the parameters evaluated showed a significant difference between the methods used, except for the chemical marker content, which was lower in T0 for the nanoemulsions prepared with heating. The in vitro release profile of the formulations showed 60% oil release in 150 minutes. In the in vitro skin permeation / retention study, it was possible to detect eucalyptol, by High Performance Liquid Chromatography, in washing liquid (~32%), stratum corneum (~12%) and receiving liquid (~56%), but none was detected in epidermis and dermis. In order to evaluate the anti-herpetic activity, the nanoemulsions showed a viral inhibition index higher than 98.2% (HSV-1) and 99.5% (HSV-2), presenting a better specificity for serotype 2. Despite the loss of volatile constituents of the oil by heating, the different methodologies did not significantly impact the antiherpetic activity. Thus, it could be concluded that both low-energy methods are able to prepare nanoemulsions with similar characteristics and it is necessary further studies to better understand the oil activity

No description available.

Spherical, Euclidean, and hyperbolic simplices can be characterized by the dihedral angles on their codimension-two faces. These characterizations analyze the Gram matrix, a matrix with entries given by cosines of dihedral angles. Hyperideal hyperbolic simplices are non-compact generalizations of hyperbolic simplices wherein the vertices lie outside hyperbolic space. We extend recent characterization results to include fully general hyperideal simplices. Our analysis utilizes the Gram matrix, however we use inversive distances instead of dihedral angles to accommodate fully general hyperideal simplices.For two-dimensional triangulations, an angle structure is an assignment of three face angles to each triangle. An angle structure permits a globally consistent scaling provided the faces can be simultaneously scaled so that any two contiguous faces assign the same length to their common edge. We show that a class of symmetric Euclidean angle structures permits globally consistent scalings. We develop a notion of virtual scaling to accommodate spherical and hyperbolic triangles of differing curvatures and show that a class of symmetric spherical and hyperbolic angle structures permit globally consistent virtual scalings.The double tetrahedron is a triangulation of the three-sphere obtained by gluing two congruent tetrahedra along their boundaries. The pentachoron is a triangulation of the three-sphere obtained from the boundary of the 4-simplex. As piecewise flat manifolds, the geometries of the double tetrahedron and pentachoron are determined by edge lengths that gives rise to a notion of a metric. We study notions of Einstein metrics on the double tetrahedron and pentachoron. Our analysis utilizes Regge's Einstein-Hilbert functional, a piecewise flat analogue of the Einstein-Hilbert (or total scalar curvature) functional on Riemannian manifolds.A notion of conformal structure on a two dimensional piecewise flat manifold is given by a set of edge constants wherein edge lengths are calculated from the edge constants and vertex based parameters. A conformal variation is a smooth one parameter family of the vertex parameters. The analysis of conformal variations often involves the study of degenerating triangles, where a face angle approaches zero. We show for a conformal variation that remains weighted Delaunay, if the conformal parameters are bounded then no triangle degenerations can occur.

No description available.

M.P.H., Faculty of Health Sciences, University of the Witwatersrand, 2009 / Background: Herpes Simplex Virus type 2 (HSV-2) is a common cause of genital ulcers worldwide and has emerged as a co-factor in human immunodeficiency virus (HIV) acquisition and transmission. A study was conducted to determine the prevalence of HSV-2, its correlates, the accuracy of reported history of genital ulcer disease (GUD) to predict HSV-2 infection and the extent of symptom recognition in a clinic population in Johannesburg. Methods: 210 women aged 18 years or older were interviewed and socio-demographic, sexual behaviour and clinical information collected. Serological testing for HSV-2 and HIV infections was performed, but only where sera were available for the latter. Factors associations with HSV-2 infection were assessed using logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI). The sensitivity, specificity, predictive values and likelihood ratios of a history of GUD were calculated. Results: The estimated sero prevalence of HSV-2 was 73% (95% CI 67% - 79%). Few participants, 13/206 (6%) participants had knowledge of genital herpes. Only 9/203 (4%) participants recognised lesions of genital herpes following education and counselling about HSV-2 infection. HSV-2 infection was associated with older age(>25 years of age) OR 2.6 (95% CI 1.4-5.0), spending more than 2 nights away from home, OR 6.0 (95% CI 1.0-62.7), having more than 2 sexual lifetime partners, OR 2.2 (95% CI 1.1-3.9), a history of an STI in the past 3 months ,OR 3.6 (95% CI 1.2-9.5) and HIV infection, OR3.3( 95%CI 1.4-7.9). A history of genital ulceration performed poorly as a predictor of HSV-2 seropositivity; the sensitivity was 7% and specificity was 96%. Conclusion: HSV-2 prevalence was high and few participants were aware of their infection. HVS-2 infection was associated with risky sexual behaviour .A history of genital ulcer disease was not sufficient as a diagnostic tool for HSV-2 infection. Public health interventions should focus on behavioural modification and increasing awareness of genital herpes. HSV-2 management should be incorporated into HIV care and STI protocols.

Finally, NF-kappaB and another transcriptional regulator p53 are usually tightly related in their control of cell survival. Opposite to NF-kappaB, p53 mediates cell death signals, usually activated under DNA damage and subsequently involved in cell growth control, DNA damage repair or apoptosis. It was found in this study, DNA damage and cell cycle arrest responses tended to participate with the anti-HSV-1 activity. Although in HEp-2 cells, TCS induced more DNA damage ratio and S and G2/M phase arrest proportion than HSV-1 infected cells, but more p53 was expressed and activated by phosphorylating at Ser 15 by TCS in HSV-1 infected HEp-2 cells than uninfected ones. In the same time the activation of BAX, which promotes the apoptotic function of p53, increased during TCS treatment when infected with HSV-1, the p53 therefore regulates apoptosis in HSV-1 infected cell during TCS treatment. / Firstly, we demonstrated that TCS reduced HSV-1 antigen and DNA content, The IC50 (half maximal inhibitory concentration) of TCS on HSV-1 replication was 2.5 +/- 0.23 mug/ml. The anti-HSV-1 effect of TCS was related to interfering with viral replication during 3 to 15 hours after infection which coincide with early to late viral replication period. TCS had no effect on HSV-1 attachment, penetration or immediate early gene expression. However, the expression of early gene, late gene and virion release were diminished. / Fourthly, the role of the nuclear factor-kappaB (NF-kappaB) in the anti-HSV-1 effect of TCS was explored. NF-kappaB initiates cell survival pathways. It is widely involved in viral infection and replication to make sure virus overcomes the host cells immune response. We found HSV-1 enhanced the activity of NF-kappaB in HEp-2 cells by triggering its translocation from cytoplasm to nuclear. However, during the anti-HSV-1 effect of TCS, TCS suppressed HSV-1-aroused NF-kappaB translocation in HEp-2 cells, the inhibition of NF-kappaB activity in HSV-1-infected cells by TCS treatment tend to abolish the anti-apoptosis effect developed by HSV-1, so that the host cells suffered more extracellular stress and showed more apoptosis ratio than uninfected ones. / Taken together, this study demonstrated TCS interfered with HSV-1 early to late infection period. TCS selectively induced more HSV-1 infected HEp-2 cells to apoptosis than uninfected ones, the selectivity of TCS was due to apoptotic signaling pathway switching from CD95 (Fas/Apo-1)-mediated type I to type II apoptotic pathway. Furthermore, during TCS induced-apoptosis in HSV-1 infected cells, TCS suppressed NF-kappaB activation that triggered by HSV-1 infection. At the meanwhile, p53 participated in the TCS-induced apoptosis regulation in infected cell. / TCS is toxic to cell because its RIP activity, killing of the viral host cells certainly inhibits virus expansion, only when it kills more infected cells, the material could be considered as an anti-viral agent. It was found TCS induced losing of cell viability and enhancing in apoptosis in HEp-2 cells and HSV-1 infected HEp-2 cells. The decrease of cell viability and increase of apoptosis ratio were enhanced when HEp-2 cells were infected with HSV-1 compared with uninfected ones. The 50% of effect concentration (EC50 ) in cytotoxicity and apoptosis were decreased from 24.64 +/- 1.17 mug/ml and 37.57 +/- 1.47 mug/ml in uninfected HEp-2 cells to 3.01 +/- 1.30 mug/ml and 3.89 +/- 1.31 mug/ml in HSV-1 infected HEp-2 cells respectively. / The reason of type I to type II apoptosis pathway transition might due to the activity change of death receptor on HEp-2 cells. The type I apoptotic pathway induced by TCS was related to CD95 (Fas/Apo-1) system activation and signaling pathway. When HEp-2 cells were infected with HSV-1, the CD95 (Fas/Apo-1) was suppressed by HSV-1 infection. As a result, TCS triggered a less CD95 (Fas/Apo-1) dependent type II apoptotic pathway in the infected cells. / Thirdly, TCS activated different apoptotic pathways, namely type I and type II apoptotic pathways, between uninfected and infected cells. The type I apoptotic pathway bypasses the dependence on the mitochondrial but quickly activates a large amount of caspase-8 at the CD95 (Fas/Apo-1) formed death inducing signaling complex (DISC), which amplifies the signal. By contrast, the formation of the DISC in the type II apoptotic pathway is strongly reduced. It depends on loss of the mitochondrial transmembrane potential (DeltaPsi m) and release of cytochrome c and capase-9 activation to mediate apoptosis signal transduction. We found in HSV-1 infected an uninfected HEp-2 cells, TCS induced the loss of DeltaPsim, this DeltaPsim losing was increased when HEp-2 cells were infected with HSV-1. Furthermore, when there were no HSV-1 infection, TCS induced caspase-dependent type I apoptosis pathway that quickly activated large amount of caspase-8 after TCS treatment. However, when infected with HSV-1, this pathway turned into mitochondrial dependent type II pathway involving caspase-9 response, whose apoptosis ratio was diminished by over expressed Bcl-2, which is a hallmark defining type I or type II apoptosis. / Trichosanthin (TCS) is a type I ribosome inactivating protein (RIP), it was found to inhibit human simplex virus type 1 (HSV-I) but the anti-HSV-I mechanism is unclear. HSV-1 is a widely distributed DNA virus, it causes large range of human diseases. During the lytic life cycle of HSV-1, highly regulated cascade of genes are expressed to interfere with host cell metabolism and immune response. In this context the anti-HSV-1 mechanism of TCS in human epithelial carcinoma HEp-2 cells was studied. / He, Dongxu. / Advisers: Wing Ho Yung; Siu Cheung Tam. / Source: Dissertation Abstracts International, Volume: 73-06, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 124-138). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.