Herpes simplex virus 1 (HSV-1) is a double-stranded DNA virus, often acquired during childhood, that currently infects more than 50% of the human population. The symptoms of infection are herpetic lesions that frequently appear throughout a host's life in response to stress in the orofacial or genital region. As a pathogen, HSV-1 replicates rapidly in epithelial cells, but it is also capable of infecting neurons where it can pursue a lytic or latent infection. Latency is a state of viral quiescence where the virus can persist indefinitely yet remain poised to reactivate. Latency is unique to herpesviruses and key to HSV's success, but the molecular mechanisms that govern this state are unclear. A virus-encoded E3-ubiquitin ligase, Infected Cell protein 0 (ICP0), is often correlated with latency establishment but is detected in opposition to the state of latency. During lytic infection, ICP0 has many biological roles but primarily catalyzes the addition of ubiquitin to target substrate, marking proteins for degradation or altering their function. This ubiquitination ability allows ICP0 to alter the intracellular environment making neurons conducive to lytic or latent HSV-1 infection. ICP0's neuron-specific targets, however, are unknown, representing a significant gap in knowledge. Through the studies presented in this dissertation, we identified some of the neuron-specific ubiquitination targets of ICP0 in neurons. We utilized primary adult sensory neurons of the dorsal root ganglia and HSV-1 viral strains KOS, wild-type virus encoding a fully functional ICP0, and HSV-1 n212, encoding a truncated ICP0 protein, to illuminate the mechanisms involved in establishing and maintaining HSV latency. By using adult primary neurons and functional HSV-1 strains with and without ICP0, we were able to show that ICP0 regulates host and viral proteins during the initial onset of neuronal infection. We also show that based on neuronal conditions set forth before HSV-1 initial infection, host proteins will influence HSV-1 viral proteins to repress viral gene expression, thereby promoting the establishment of latency. / Doctor of Philosophy / Herpes simplex virus (HSV-1) is a virus, often acquired during childhood, that more than 50% of people have. Those who are infected with HSV-1 often have cold sores that appear in response to stress on the face or on the genitals. As a virus, HSV-1 replicates around the eyes, nose, and mouth but can also infect neurons where it can continue to replicate or establish latency. Latency is when the virus is inside the neurons but is unnoticeable and can reappear in response to stress. The state of latency is unique to herpesviruses and key to the success of HSV-1, but scientists are unsure of how it works. A protein made by the virus, Infected Cell Protein 0 (ICP0), is often correlated with the state of latency but is often present when the virus is not latent. ICP0 does a lot to support HSV-1, but it primarily destroys proteins that prevent the virus from replicating. By destroying proteins that prevent HSV-1 replication, ICP0 can help the virus make more viruses. The proteins that are destroyed by ICP0 are currently unknown, which represents a significant gap in knowledge. Through the research conducted in this dissertation, we identified some of the proteins that ICP0 destroys in neurons. We utilized neurons from the dorsal root ganglia and HSV-1 viral strain KOS, which encoded a functional ICP0, and n212, which encodes a nonfunctional ICP0, to study the mechanisms used by the virus to infect neurons. By using HSV-1 viruses with and without ICP0, we were able to show what proteins ICP0 destroys during infection in neurons. We were also able to show that HSV-1's ability to establish latency is dependent on how the neurons handle the initial onset of infection. Overall, a combination of host and viral proteins coordinates the virus's ability to establish latency and persist within a host.

The development of microwave Gallium Arsenide Metal Semiconductor Field Effect Transistor (MESFET) devices has enabled the miniaturization of pagers, cellular phones, and other electronic devices. With these MESFET devices comes the need to model them. This thesis extracts a small signal equivalent circuit model from a Gallium Arsenide MESFET device. The approach taken in this thesis is to use measured S- parameters to extract a small signal equivalent circuit model by optimization. Small signal models and S-parameters are explained. The Simplex Method is used to optimize the small signal equivalent circuit model. A thorough analysis of the strengths and weaknesses of the Simplex method is performed. / Master of Science

Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) are major human pathogens. HSV establishes latency in the nervous system and reactivates to cause recurrent disease, resulting in transmission of progeny virions to naïve individuals. Though HSV-1 and HSV-2 share similar structure and genes, they have distinctive recurrence profiles. Generally, HSV-1 reactivation is associated with disease 'above the waist' and HSV-2 reactivation is associated with disease 'below the waist'. This phenomenon was described decades ago but still remains unexplained. The mechanism of HSV latent infection in the peripheral nervous system (PNS) has been extensively investigated, especially with in sensory neurons. Another component of the peripheral nervous system (PNS), autonomic neurons, were also known to be infected with HSV productively and latently, but largely ignored because of the assumption that there is no difference in the pathogenesis of HSV in the neurons and that both HSV-1 and HSV-2 behave in the same way in different types of neurons. However, autonomic neurons differ in physiological function compared to sensory neurons. Activation factors of autonomic neurons, such as emotional stress, trauma and hormonal fluctuation, are also known HSV reactivation triggering factors. Therefore, I hypothesized that autonomic neurons innervating the site of HSV infection are responsible the different reactivation frequencies of HSV-1 and HSV-2 after peripheral invasion. In this report, the role of autonomic neurons in HSV pathogenesis were examined using the female guinea pig reactivation model. Major findings of this report are that 1) parasympathetic ganglia innervating the ocular region support latent infection of HSV-1 selectively, thus contributing the more frequent HSV-1 reactivation, 2) mixed autonomic ganglia in the genital area support HSV-2 latent infection selectively, and 3) sympathetic neurons in the genital region supported productive and latent infection of HSV-1 and HSV-2 differently. All of the results in this report indicate that autonomic neurons play a distinctive role in HSV pathogenesis compared to the sensory neurons and are responsible for the different reactivation frequencies of HSV-1 and HSV-2. This report raises the importance of autonomic neurons in HSV pathogenesis and challenges the paradigm of HSV pathogenesis. / Ph. D.

Increasing concerns over the condition of our environment and its long term health have led to the development of greener combustion techniques for use in turbomachinery applications. Lean Direct Injection is an active area of research for how fuel is introduced and burned in the combustor section of a jet engine or land based liquid fuel turbine. Overall lean combustion results in lower NOx emmisions while direct injection insures shorter combustor lengths. Lean Direct Injection and other lean burning combustor designs are susceptible to thermoacoustic instabilities. The SARA or Synchronously Actuated Response Atomizer is a liquid fuel atomizer and supply system designed to allow for the active control of droplet size, cone angle, and mass flow rate. These three parameters have been shown to be important in controlling combustion quality and heat release. This research investigates the capabilities of the SARA design in a series of non-reacting tests. Static and Dynamic tests were performed on the SARA nozzle with a maximum actuation of 400 Hz. Also, a novel use of hot-film anemometry was developed to measure the dynamic flow rate fluctuations. / Master of Science

Os vírus são responsáveis por infecções de distribuição mundial com elevadas prevalência e morbimortalidade sendo, muitas das vezes, sem tratamento efetivo disponível. Existem medicamentos fitoterápicos com atividade antibacteriana ou antiviral comprovadas, porém seu uso na prática clínica ainda é limitado. O objetivo deste trabalho foi investigar a presença ou ausência de atividade antiviral in vitro de extratos brutos e fracionados de Cocos nucifera L. em cultura de células Vero infectadas com herpes simplex vírus tipo 1 (HSV-1). Foram escolhidas doses não tóxicas dos extratos aquoso e hidroetanólico da fibra do C. nucifera, de 4 frações derivadas daquele com diferentes solventes (hexano, acetato de etila, metanol e água) e de duas substâncias isoladas a partir desta fibra (Substâncias CN1A e CN342B). O HSV-1 foi adicionado à cultura de células Vero uma hora após estas serem incubadas com os dois extratos e seus derivados. As placas foram analisadas em microscópio óptico a cada 24 horas, sendo o material colhido quando o efeito citopático viral no controle negativo atingisse mais de 80% das células e congelado para posterior titulação viral por TCID50. Utilizamos o aciclovir como droga de referência para o HSV-1. A substância CN342B foi capaz de inibir a replicação do HSV-1, com efeito antiviral comparável ao do aciclovir, enquanto que os extratos brutos, as quatro frações e a substância CN1A não foram efetivas. Em conclusão, a substância CN342B isolada das fibras do C. nucifera foi eficaz contra o HSV-1 in vitro / Viruses are responsible for infections worldwide with high prevalence and morbimortality, often with no effective treatment available. There are herbal medicines with proven antibacterial and antiviral activities; however, their use in clinical practice is still limited. The aim of this study was to investigate the presence or absence of in vitro antiviral activity of aqueous and hydroethanolic extracts from Cocos nucifera L. husk fiber, in culture of Vero cells infected with herpes simplex virus (HSV)-1. Non-toxic dosages of aqueous and hydroethanolic extracts, as well as the hexane, ethyl-acetate, methanol and end-aqueous fractions were used. In addition, two isolated substances (CN1A and CN342B) were tested. HSV-1 was added to the cell culture after one hour of incubation with the extracts and fractions. The plates were analyzed in optical microscopes each 24 hours, and cells were harvested when the cytopathic effect in negative controls were above 80% of the cells. The cells were then frozen for viral titulation (TCID50). Acyclovir was the reference drug for HSV-1. Substance CN342B, but none of the other drugs, was able to reduce HSV-1 replication, similarly to acyclovir. In conclusion, the substance CN342B isolated from C. nucifera husk fibers was effective against HSV-1 in vitro

A substituição dos conservantes sintéticos em cosméticos por produtos naturais é uma tendência, direcionando as pesquisas para a busca de novas alternativas de compostos antimicrobianos naturais. Extratos de bambus asiáticos têm ampla aplicação na indústria cosmética, sendo muito utilizados em diversas formulações. No Brasil, a triagem química de espécies nativas de bambus para futuras aplicações na indústria ainda é incipiente. O objetivo do trabalho foi avaliar as atividades antioxidante e antimicrobiana de extratos e frações de folhas e colmos de A. simplex McClure & Smith. Extratos brutos de folhas e colmos foram obtidos por percolação com etanol 60%, liofilizados, e fracionados com solventes de polaridade crescente. A capacidade antioxidante foi quantificada pelo método de redução do radical DPPH, sendo a fração clorofórmica dos colmos a que apresentou melhor atividade (IC50= 24,02 µg/mL). A atividade antimicrobiana foi determinada pelo método de microdiluição frente Escherichia coli (ATCC 8739), Staphylococcus aureus (ATCC 6538), Pseudomonas aeruginosa (ATCC 9027), Candida albicans (ATCC 10231) e Apergillus brasilensis (ATCC 16404). Os extratos brutos e frações de folhas e colmos de A. simplex apresentaram baixa atividade antimicrobiana com concentração inibitória mínima (CIM) > 1mg/mL para todos os micro-organismos. O efeito sinérgico dos extratos com parabenos foi realizado utilizando o delineamento experimental centroide simplex para uma mistura de metilparabeno, propilparabeno e extrato. As misturas foram testadas frente aos micro-organismos utilizados no ensaio de atividade antimicrobiana. O sinergismo foi observado em maior intensidade em S. aureus e C. albicans. Adicionalmente, os resultados da quantificação de flavonoides e compostos fenólicos totais sugeriram que o sinergismo entre esses compostos e os parabenos poderia ser responsável pela atividade antimicrobiana. / The replacing synthetic preservatives in cosmetics with natural products, is a tendency, research to investigate new natural antimicrobial compounds. Although Asian bamboo extracts have wide application in the cosmetics industry and are widely used in various formulations, Brazilian native species were not yet been investigated for future industrial applications. Thus, the purpose of this study was to evaluate the antioxidant and antimicrobial activities of extracts and fractions from A. simplex McClure & Smith leaves and culms. Crude leaf and culm extracts were obtained by percolation with 60% ethanol, lyophilized and fractionated with increasing polarity solvents. Antioxidant capacity was measured by the DPPH radical scavenging method in which the culm chloroform fraction presented the highest activity (IC50=24.02 µg/mL). Antimicrobial activity was determined by the microdilution method against Escherichia coli (ATCC 8739), Staphylococcus aureus (ATCC 6538), Pseudomonas aeruginosa (ATCC 9027), Candida albicans (ATCC 10231) and Apergillus brasiliensis (ATCC 16404). All the extracts and fractions from A. simplex showed low antimicrobial activity with Minimal Inhibitory Concentration (MIC) > 1 mg/mL for all microorganisms. The synergistic effect of the extracts mixed with methyl and propyl parabens was tested using a simplex centroid design. The mixtures were tested against the same microorganisms used for extracts evaluation. A stronger synergic effect was observed for S. aureus and C. albicans. Additionaly, the quantification results of flavonoids and total phenolic compounds suggested that the synergism among these compounds and the parabenos could be responsible for the antimicrobial activity.

Os vírus são responsáveis por infecções de distribuição mundial com elevadas prevalência e morbimortalidade sendo, muitas das vezes, sem tratamento efetivo disponível. Existem medicamentos fitoterápicos com atividade antibacteriana ou antiviral comprovadas, porém seu uso na prática clínica ainda é limitado. O objetivo deste trabalho foi investigar a presença ou ausência de atividade antiviral in vitro de extratos brutos e fracionados de Cocos nucifera L. em cultura de células Vero infectadas com herpes simplex vírus tipo 1 (HSV-1). Foram escolhidas doses não tóxicas dos extratos aquoso e hidroetanólico da fibra do C. nucifera, de 4 frações derivadas daquele com diferentes solventes (hexano, acetato de etila, metanol e água) e de duas substâncias isoladas a partir desta fibra (Substâncias CN1A e CN342B). O HSV-1 foi adicionado à cultura de células Vero uma hora após estas serem incubadas com os dois extratos e seus derivados. As placas foram analisadas em microscópio óptico a cada 24 horas, sendo o material colhido quando o efeito citopático viral no controle negativo atingisse mais de 80% das células e congelado para posterior titulação viral por TCID50. Utilizamos o aciclovir como droga de referência para o HSV-1. A substância CN342B foi capaz de inibir a replicação do HSV-1, com efeito antiviral comparável ao do aciclovir, enquanto que os extratos brutos, as quatro frações e a substância CN1A não foram efetivas. Em conclusão, a substância CN342B isolada das fibras do C. nucifera foi eficaz contra o HSV-1 in vitro / Viruses are responsible for infections worldwide with high prevalence and morbimortality, often with no effective treatment available. There are herbal medicines with proven antibacterial and antiviral activities; however, their use in clinical practice is still limited. The aim of this study was to investigate the presence or absence of in vitro antiviral activity of aqueous and hydroethanolic extracts from Cocos nucifera L. husk fiber, in culture of Vero cells infected with herpes simplex virus (HSV)-1. Non-toxic dosages of aqueous and hydroethanolic extracts, as well as the hexane, ethyl-acetate, methanol and end-aqueous fractions were used. In addition, two isolated substances (CN1A and CN342B) were tested. HSV-1 was added to the cell culture after one hour of incubation with the extracts and fractions. The plates were analyzed in optical microscopes each 24 hours, and cells were harvested when the cytopathic effect in negative controls were above 80% of the cells. The cells were then frozen for viral titulation (TCID50). Acyclovir was the reference drug for HSV-1. Substance CN342B, but none of the other drugs, was able to reduce HSV-1 replication, similarly to acyclovir. In conclusion, the substance CN342B isolated from C. nucifera husk fibers was effective against HSV-1 in vitro

Três resíduos vegetais da agroindústria do dendê foram usados como substrato para o cultivo de distintas linhagens de fungos da podridão-branca (basidiomicetos). Foram avaliados o crescimento e produção de enzimas lignocelulolíticas por fermentação em estado sólido e submerso. Os extratos enzimáticos obtidos das fermentações foram utilizados no processo de hidrólise enzimática de bagaço de cana-de-açúcar e cacho vazio do dendê previamente pré-tratados. Um total de 54 linhagens de macrofungos foram cultivadas em três formulações de biomassa de dendê em placas Petri, onde foram escolhidas 5 linhagens com crescimento mais rápido e denso. Estas cinco linhagens de macrofungos foram cultivadas em fermentação em estado sólido e avaliados pelas atividades enzimáticas dos extratos obtidos. Nestes extratos, houve predominância das atividades de lacase, peroxidase, manganês peroxidase e protease. Das cinco linhagens foram selecionadas três linhagens com predominância nas atividades oxidativas nos cultivos em fermentação em estado sólido, para serem avaliadas em fermentação submersa (monocultivos) usando meio sintético suplementado com biomassa vegetal do dendê. As atividades enzimáticas das três espécies de basidiomicetos foram comparadas com cinco linhagens fúngicas usadas frequentemente na literatura. Houve diferenças significativas em função das atividades oxidativas (lacase e peroxidases) e hidrolíticas (FPase e β-glicosidases) entre as linhagens testadas. Estas diferenças foram usadas para estabelecer subgrupos, os quais foram avaliados através da interação em placa e cocultivos em fermentação submersa. As atividades enzimáticas dos extratos obtidos de monocultivos e cocultivos apresentaram diferenças com interações predominantemente positivas entre os três basidiomicetos e T. reesei ATCC® 60787. Os monocultivos e cocultivos foram comparados em função da liberação de glicose após da hidrólise enzimática de bagaço de cana-de-açúcar pré-tratado por autohidrólise. As hidrólises enzimáticas aplicando os extratos dos cocultivos obtiveram rendimento 44,7% superior quando comparadas com os monocultivos. Foi feita uma análise de misturas simplex lattice, usando como componentes os extratos dos monocultivos para a obtenção de um coquetel enzimático a fim de otimizar a liberação de glicose do bagaço de cana pré-tratado. Os resultados demostraram que os extratos com maiores atividades hidrolíticas estão correlacionadas com a maior liberação de glicose, e que os extratos com enzimas oxidativas podem melhorar o rendimento, tendo assim uma mistura ou coquetel caracterizado com enzimas hidrolíticas e oxidativas com potencial para obtenção de açúcares. Finalmente, este coquetel foi utilizado na hidrólise de cacho vazio de dendê pré-tratado fisicamente, biologicamente e biológica-físicamente (combinado) obtendo um rendimento máximo de 11,8 g.L-1 de glicose a partir de biomassa vegetal de dendê quando pré-tratada biológicafisicamente, o que correspondeu entre 40 - 60% do rendimento do rendimento obtido quando empregadas as enzimas comerciais Cellic® Ctec3 e Cellic® Ctec2. / Three vegetable residues from the palm oil industry were used as substrate for cultivation of different white rot fungi strains (basidiomycetes). The growth and production of lignocellulolytic enzymes were evaluated by solid and submerged fermentation. The enzymatic extracts obtained from fermentations were used in enzymatic hydrolysis process of pretreated sugarcane bagasse and oil palm empty bunch. Fifty-four macrofungal strains were cultivated in three formulations of oil palm biomass on Petri dishes, where 5 strains with faster and dense growth were chosen. These five macrofungal strains were cultivated in solid state fermentation and evaluated by the enzymatic activities of the extracts obtained. In these extracts, activities of laccase, peroxidase, manganese peroxidase and protease were found to be predominant. Three of the five strains were selected with predominance in oxidative activities on solid state fermentation cultures to be evaluated in submerged fermentation (monocultures) using synthetic medium supplemented with oil palm biomass. The enzymatic activities of the three basidiomycetes srtains were compared with five fungal strains frequently used in the literature. There were significant differences in function of the oxidative activities (laccase and peroxidases) and hydrolytic activities (PFase and β-glucosidases) among the tested strains. These differences were used to establish subgroups which were evaluated through the interaction in plates and cocultures in submerged fermentation. The enzymatic activities of the extracts obtained from monocultures and cocultures presented differences, with predominantly positive interactions between the three basidiomycetes and T. reesei ATCC® 60787. Monocultures and cocultures were compared as a function of the glucose release after the enzymatic hydrolysis of sugarcane bagasse pretreated by autohydrolysis. The enzymatic hydrolysis of the coculture extracts obtained higher percentages (maximum value 44.7%) when compared to monocultures. An analysis of simplex lattice mixtures was made using the monoculture extracts as components to obtain an enzymatic cocktail in order to optimize the glucose release of the pretreated sugarcane bagasse. The results showed that extracts with higher hydrolytic activities are correlated with the higher glucose release and extracts with oxidative enzymes can improve the sugar yield, thus having a mixture or cocktail characterized by hydrolytic and oxidative enzymes with the potential to obtain sugars. Finally, this cocktail was used in the hydrolysis of untreated, physically, biologically and biologically-physically (combined) pretreated oil palm empty bunch, obtaining a maximum yield of 11.8 gL-1 of glucose in the biomass of palm oil when pretreated biological-physically, which corresponded between 40-60% of the yield of the commercial enzymes Cellic® Ctec3 and Cellic® Ctec2.

Submitted by Erika Demachki (erikademachki@gmail.com) on 2014-08-28T21:24:23Z No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Vasconcelos, Eduardo Silva..pdf: 1832341 bytes, checksum: c00d3ca071a0f15e55eeef2079d52047 (MD5) / Made available in DSpace on 2014-08-28T21:24:23Z (GMT). No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Vasconcelos, Eduardo Silva..pdf: 1832341 bytes, checksum: c00d3ca071a0f15e55eeef2079d52047 (MD5) Previous issue date: 2013-04-12 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / This paper aims to describe the Simplex Method and Method of Resolution Graphics problems on Linear Programming, aiming at the teaching and learning of linear algebra in high school. And for this, presents some basic concepts in linear programming, it follows brie y on the Simplex Method and Method of Resolution Graphics and presents two resolutions of Linear Programming problems, a maximization and minimization another, both problems are solved by two methods cited. We understand the importance of this work is to present the Simplex Method eao Method Graphical resolution to high school students because we believe that together these two methods applied in teaching linear algebra could lead to increased motivation of students in learning mathematics. / Este trabalho tem o objetivo de descrever o Método Simplex e o Método de Resoluções Grá cas em problemas de Programação Linear, visando o ensino e a aprendizagem da álgebra linear no Ensino Médio. E, para tal, apresenta alguns conceitos básicos em Programação Linear, decorre sucintamente sobre o Método Simplex e o Método de Resolução Grá ca e apresenta duas resoluções de problemas de Programação Linear, uma de maximização e outra de minimização, ambos os problemas são resolvidos pelos dois métodos citados. Entendemos que a importância deste trabalho está em apresentar o Método Simplex e a o Método de Resolução Grá ca aos alunos do Ensino Médio pois, acreditamos que estes dois métodos juntamente aplicados no ensino de álgebra linear poderá levar a uma maior motivação destes alunos na aprendizagem da matemática.

Herpes simplex virusas sukelia recidyvuojančią burnos-veido ir lytinių organų infekciją. Latentinėje būklėje šis virusas glūdi sensoriniuose ganglijuose. Latencijos metu visi HSV genai yra supresuoti, išskyrus su latencija susijusį geną (LAT). Tyrimais nustatyta, kad tarp HSV LAT promotoriaus mutantų reaktyvacijos dažnis laboratorinių gyvūnėlių modeliuose yra mažesnis nei laukinių virusų. Nėra atlikta tyrimų, kurie nagrinėtų LAT promotoriaus sekų variaciją herpes simplex virusuose, išskirtuose iš žmonių klinikinių mėginių. Šio tyrimo tikslas buvo įvertinti herpes simplex viruso LAT promotoriaus sekų įvairovę molekulinės diagnostikos metodais bei palyginti su infekcijos klinikiniais požymiais. Tuo tikslu buvo sukurtas PGR metodas HSV LAT promotoriaus analizei atlikti. Buvo ištirta Lietuvos ir Švedijos klinikiniuose odos-gleivinių bei cerebrospinalinio skysčio mėginiuose rasto herpes simplex viruso promotoriaus DNR sekų įvairovė. Tyrimo metu rasta, kad 2 tipo herpes simplex virusas buvo pagrindinė lytinių organų HSV infekcijos priežastis tarp Lietuvos pacientų. Visuose veido srities bėrimuose rasta 1 tipo HSV. HSV LAT promotoriaus sekos ištirtos 145 klinikiniuose mėginiuose. Nustatyta, kad HSV LAT promotoriaus sekos yra gausios GC ir turi variabilias homopolimerinių nukleotidų sritis, kurios varijuoja tarp viruso padermių ir pačių padermių viduje. Ši variacija gali turėti įtakos baltymų sintezei, o drauge ir fenotipo pokyčiams. Nenustatytas ryšys tarp HSV LAT promotoriaus... [toliau žr. visą tekstą] / Herpes simplex virusas sukelia recidyvuojančią burnos-veido ir lytinių organų infekciją. Latentinėje būklėje šis virusas glūdi sensoriniuose ganglijuose. Latencijos metu visi HSV genai yra supresuoti, išskyrus su latencija susijusį geną (LAT). Tyrimais nustatyta, kad tarp HSV LAT promotoriaus mutantų reaktyvacijos dažnis laboratorinių gyvūnėlių modeliuose yra mažesnis nei laukinių virusų. Nėra atlikta tyrimų, kurie nagrinėtų LAT promotoriaus sekų variaciją herpes simplex virusuose, išskirtuose iš žmonių klinikinių mėginių. Šio tyrimo tikslas buvo įvertinti herpes simplex viruso LAT promotoriaus sekų įvairovę molekulinės diagnostikos metodais bei palyginti su infekcijos klinikiniais požymiais. Tuo tikslu buvo sukurtas PGR metodas HSV LAT promotoriaus analizei atlikti. Buvo ištirta Lietuvos ir Švedijos klinikiniuose odos-gleivinių bei cerebrospinalinio skysčio mėginiuose rasto herpes simplex viruso promotoriaus DNR sekų įvairovė. Tyrimo metu rasta, kad 2 tipo herpes simplex virusas buvo pagrindinė lytinių organų HSV infekcijos priežastis tarp Lietuvos pacientų. Visuose veido srities bėrimuose rasta 1 tipo HSV. HSV LAT promotoriaus sekos ištirtos 145 klinikiniuose mėginiuose. Nustatyta, kad HSV LAT promotoriaus sekos yra gausios GC ir turi variabilias homopolimerinių nukleotidų sritis, kurios varijuoja tarp viruso padermių ir pačių padermių viduje. Ši variacija gali turėti įtakos baltymų sintezei, o drauge ir fenotipo pokyčiams. Nenustatytas ryšys tarp HSV LAT promotoriaus... [to full text]