Fault management is a challenging task in all-optical wavelength division multiplexing (WDM) networks. However, fast fault localization for shared risk link groups (SRLGs) with multiple links is essential for building a fully survival and functional transparent all-optical mesh network. Monitoring trail (m-trail) technology is an effective approach to achieve the goal, whereby a set of m-trails are derived for unambiguous fault localization (UFL). However, an m-trail traverses through a link by utilizing a dedicated wavelength channel (WL), causing a significant amount of resource consumption. In addition, existing m-trail methods incur long and variable alarm dissemination delay. We introduce a novel framework of real-time fault localization in all-optical WDM mesh networks, called the monitoring-burst (m-burst), which aims at initiating a balanced trade-off between consumed monitoring resources and fault localization latency. The m-burst framework has a single monitoring node (MN) and requires one WL in each unidirectional link if the link is traversed by any m-trail. The MN launches short duration optical bursts periodically along each m-trail to probe the links of the m-trail. Bursts along different m-trails are kept non-overlapping through each unidirectional link by scheduling burst launching times from the MN and multiplexing multiple bursts, if any, traversing the link. Thus, the MN can unambiguously localize the failed links by identifying the lost bursts without incurring any alarm dissemination delay. We have proposed several novel m-trail allocation, burst launching time scheduling, and node switch fabric configuration schemes. Numerical results show that the schemes, when deployed in the m-burst framework, are able to localize single-link and multi-link SRLG faults unambiguously, with reasonable fault localization latency, by using at most one WL in each unidirectional link. To reduce the fault localization latency further, we also introduce a novel methodology called nested m-trails. At first, mesh networks are decomposed into cycles and trails. Each cycle (trail) is realized as an independent virtual ring (linear) network using a separate pair of WLs (one WL in each direction) in each undirected link traversed by the cycle (trail). Then, sets of m-trails, i.e., nested m-trails, derived in each virtual network are deployed independently in the m-burst framework for ring (linear) networks. As a result, the fault localization latency is reduced significantly. Moreover, the application of nested m-trails in adaptive probing also reduces the number of sequential probes significantly. Therefore, practical deployment of adaptive probing is now possible. However, the WL consumption of the nested m-trail technique is not limited by one WL per unidirectional link. Thus, further investigation is needed to reduce the WL consumption of the technique.

La thèse analyse la question de la stabilité du système financier international dans son ensemble et plus précisément comment améliorer sa résilience. Chaque chapitre se focalise sur un type d'acteur dans ce système complexe, à savoir les banques, les organismes de supervision et les régulateurs internationaux. Le premier chapitre introduit de nouvelles techniques d'optimisation pour accélérer le calcul de mesure de risque dans les banques et les institutions financières. Il propose également une étude théorique pour valider les algorithmes d'optimisation proposés. Le second vise à quantifier l'externalité négative générée par les activités d'une banque ou d'une d'institution financière. Finalement, le dernier chapitre concerne la coopération entre régulateurs nationaux en présence de coûts de coordination en proposant une analyse qui s'appuie sur la théorie des jeux. / We first investigate the computational complexity for estimating quantile based risk measures, such as the widespread Value at Risk for banks and Solvency II capital requirements for insurance companies, via nested Monte Carlo simulations. The estimator is a conditional expectation type estimate where two stage simulations are required to evaluate the risk measure: an outer simulation is used to generate risk factor scenarios that govern price movements and an inner simulation is used to evaluate the future portfolio value based on each of those scenarios. The second essay considers the financial stability from a macro perspective. Measuring negative externalities of banks is a major challenge for financial regulators. We propose a new risk management approach to enhance the financial stability and to increase the fairness of financial transactions. The basic idea is that a bank should assume as much risk as it creates. Any imbalance in the tails of the distribution of profit and losses is a sign of the bank's failure to internalize its externalities or the social costs associated with its activities. The aim of the third essay is to find a theoretical justification toward the mutual benefits for members of a bonking union in the context of a strategic interaction model. We use a unique contagion dynamic that marries the rich literature of game theory, contagion in pandemic crisis and the study of collaboration between regulators. The model is focused toward regulating asset classes, not individual banks. This special design addresses moral hazard issues that could result from government intervention in the case of crisis.

Made available in DSpace on 2016-06-02T20:21:21Z (GMT). No. of bitstreams: 1 2667.pdf: 1236621 bytes, checksum: 9702ce62be0433e7639201366d6444aa (MD5) Previous issue date: 2009-06-30 / Financiadora de Estudos e Projetos / Species of the fraterculus group are associated to the biggest damages to fruit crops due to the fact that they attack indiscriminately green and ripe fruits, making them pests of great economic importance. These species are hard to tell apart, even showing some potential criptic species. The understanding of the populational structure and biology of this species group is of paramount importance to strategies of management and control of these pests. Here, we investigate variation on the gene yolk em 37 individuals sampled throughout the species distribution in Brazil seeking to better understand the populational structure of this species group in Brazil. Our data indicated existence of recombination, which lead us to analyze three different regions in the gene, 5 , mid, and 3 . These regions show high levels of nucleotide diversity intra and interspecifically for all three gene regions investigated. The use of Nested Clade Phylogenetic Analysis independently used on these regions indicate two main results that occurred more than one throughout our analyses. The first is a range expansion from north-NE populations towards the south, mostly related to specimens of Anastrepha fraterculus. The second common event, detected eight times, is restricted gene flow with isolation by distance (IBD). Dating of such events indicated that they are temporarily congruent which might indicate that the lack of IBD in other levels of the analysis might be caused either by sampling limitations or an excess of local gene flow that tampers out as we move farther in space. Our results of the gene yolk have provided us with a better understanding of the levels of local variation of this marker of for the species that may help us determine the evolutionary processes that shaped the species group current distribution. / Espécies do grupo fraterculus estão relacionadas com os maiores danos a culturas de frutas carnosas por atacar frutos verdes e maduros indistintamente, o que as torna pragas de grande importância econômica. Contudo, estas espécies são de difícil distinção, com a existência potencial de diversas espécies crípticas. Dessa forma, o entendimento da biologia e, particularmente, da estrutura populacional desses insetos-praga tem grande importância para o desenvolvimento de novas estratégias de manejo. Neste trabalho, investigamos a variação no gene yolk em 37 indivíduos ao longo da distribuição do grupo no Brasil para conhecermos melhor o padrão estrutural das espécies do grupo fraterculus. Os dados indicam a existência de recombinação, de forma que analisamos a região amplificada separadamente por regiões distintas: 5 , mid e 3 . Análises de polimorfismos nestas regiões apontaram para altos valores de diversidade nucleotídicas intra e interespecíficas para as três regiões gênicas em questão, sendo estes valores maiores para a região 3 . A metodologia da Análise dos Clados Aninhados (NCPA) foi utilizada para inferências de possíveis relações entre a configuração das redes haplotípicas com o padrão de distribuição geográfica considerando estas três regiões distintas. Através do uso desta metodologia, observamos dois eventos principais que podem estar influenciando a distribuição das espécies do grupo fraterculus no território nacional. A primeira inferência refere-se à expansão populacional no sentido Centro-Sul do Brasil, referente preferencialmente à espécie Anastrepha fraterculus. O segundo evento de inferência indica fluxo gênico restrito com isolamento por distância ao longo da distribuição global dos espécimes amostrados. A datação destes eventos indica uma congruência temporal, o que pode indicar que a não ocorrência de fluxo gênico em clados inferiores possa estar associado a restrições amostrais, uma vez que nossa amostragem é de fato restrita. Além disso, em populações mais próximas, o fluxo gênico pode estar ocorrendo com freqüência suficiente para promover a homogeneização genética das populações. Os resultados obtidos mediante a análise das seqüências do gene yolk nos permitiu um melhor conhecimento àcerca dos níveis de variação referentes a esse marcador, bem como determinar os processos que possam estar envolvidos no padrão de distribuição atual das espécies do grupo fraterculus no território nacional.

abstract: The recent proposal of two-way relaying has attracted much attention due to its promising features for many practical scenarios. Hereby, two users communicate simultaneously in both directions to exchange their messages with the help of a relay node. This doctoral study investigates various aspects of two-way relaying. Specifically, the issue of asynchronism, lack of channel knowledge, transmission of correlated sources and multi-way relaying techniques involving multiple users are explored. With the motivation of developing enabling techniques for two-way relay (TWR) channels experiencing excessive synchronization errors, two conceptually-different schemes are proposed to accommodate any relative misalignment between the signals received at any node. By designing a practical transmission/detection mechanism based on orthogonal frequency division multiplexing (OFDM), the proposed schemes perform significantly better than existing competing solutions. In a related direction, differential modulation is implemented for asynchronous TWR systems that lack the channel state information (CSI) knowledge. The challenge in this problem compared to the conventional point-to-point counterpart arises not only from the asynchrony but also from the existence of an interfering signal. Extensive numerical examples, supported by analytical work, are given to demonstrate the advantages of the proposed schemes. Other important issues considered in this dissertation are related to the extension of the two-way relaying scheme to the multiple-user case, known as the multi-way relaying. First, a distributed source coding solution based on Slepian-Wolf coding is proposed to compress correlated messages close to the information theoretical limits in the context of multi-way relay (MWR) channels. Specifically, the syndrome approach based on low-density parity-check (LDPC) codes is implemented. A number of relaying strategies are considered for this problem offering a tradeoff between performance and complexity. The proposed solutions have shown significant improvements compared to the existing ones in terms of the achievable compression rates. On a different front, a novel approach to channel coding is proposed for the MWR channel based on the implementation of nested codes in a distributed manner. This approach ensures that each node decodes the messages of the other users without requiring complex operations at the relay, and at the same time, providing substantial benefits compared to the traditional routing solution. / Dissertation/Thesis / Doctoral Dissertation Electrical Engineering 2015

Submitted by Automação e Estatística (sst@bczm.ufrn.br) on 2018-07-03T15:17:42Z No. of bitstreams: 1 KerciaMonalineDeSouzaJoventino_DISSERT.pdf: 1519788 bytes, checksum: 901d657abfb5f3e00400db99cd1e6791 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2018-07-11T11:42:41Z (GMT) No. of bitstreams: 1 KerciaMonalineDeSouzaJoventino_DISSERT.pdf: 1519788 bytes, checksum: 901d657abfb5f3e00400db99cd1e6791 (MD5) / Made available in DSpace on 2018-07-11T11:42:41Z (GMT). No. of bitstreams: 1 KerciaMonalineDeSouzaJoventino_DISSERT.pdf: 1519788 bytes, checksum: 901d657abfb5f3e00400db99cd1e6791 (MD5) Previous issue date: 2017-03-20 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O citomegalovírus é uma importante complicação após o transplante renal. O uso de imunossupressores na prevenção de rejeição ao aloenxerto pode desencadear mudanças no comportamento do CMV, sendo importante o seguimento viral póstransplante, como medida preventiva para limitar o impacto clínico deste vírus. O objetivo do estudo foi monitorar a infecção por citomegalovírus em pacientes submetidos a transplante renal no Hospital Universitário Onofre Lopes, Natal, Rio Grande do Norte. No total foram incluídos 165 pacientes no período de fevereiro de 2013 a janeiro de 2016. Amostras de sangue periférico foram obtidas na 2ª, 4ª, 8ª, 12ª e 24ª semanas pós-transplante para detecção molecular do CMV pela nestedPCR e a quantificação da carga viral do CMV pela PCR em tempo real. Os transplantados renais apresentaram incidência de 59,4% de infecção ativa por CMV, correlacionada ao uso de everolimo (p=0,0008) e timoglobulina (p=0,0042). Quarenta e cinco pacientes apresentaram números de cópias superiores ao ponto de corte de 4600 cópias/mL, com sensibilidade de 67,2% e especificidade de 70,7%, associado a sinais e sintomas de infecção por CMV, tais como febre, distúrbio gastrointestinal, mialgia, leucopenia e trombocitopenia. Nossos resultados demonstraram uma alta incidência de infecção ativa por CMV, evidenciando a necessidade do diagnóstico precoce dessa infecção, além de que a PCR em tempo real pode ser utilizada para monitorar infecções sintomáticas por CMV em receptores de transplante renal. / Cytomegalovirus infection is an important complication after renal transplantation. The use of immunosuppressants in the prevention of rejection may trigger changes in the behavior of CMV, it is important to post-transplant viral follow-up, as preventive measure, to limit clinical impact of this vírus. The objective of this study was to monitor cytomegalovirus infection in patients who underwent renal transplant in the Onofre Lopes University Hospital (HUOL), Natal, Rio Grande do Norte. In total were included 165 patients in the period from 2013 to 2016. Samples of peripheral blood obtained on the 2nd, 4th, 8th, 12th and 24th weeks post-transplant to molecular detection of CMV by nested-PCR and quantification of CMV viral load by real-time PCR. Who renal transplants presented incidence of 59.4% of active CMV infection was, correlation with the use of everolimus (p = 0.0008) and thymoglobulin (p = 0.0042). Forty-five patients who presented copy numbers above the cut-off point (4600 copies/mL), with sensitivity of 67.2% and specificity of 70.7%, associated were clinical signs and symptoms of CMV infection, such as fever, gastrointestinal disturbance, myalgia, leukopenia and thrombocytopenia. Our results demonstrated a high incidence of active CMV infection, evidencing the necessity of the early diagnosis of this infection, in addition to real-time PCR can be using to monitor CMV symptomatic infections in renal transplant recipients.

Made available in DSpace on 2016-06-02T19:06:14Z (GMT). No. of bitstreams: 1 6202.pdf: 2303544 bytes, checksum: f49c225976e9069a96200021080e9dfa (MD5) Previous issue date: 2010-08-29 / The use of computer virtualization has grown rapidly in recent years, motivating the research for software and hardware improvements to optimize performance and reduce the bottlenecks inherent of virtualization. In the middle of this decade, the processors has added support for CPU virtualization, simplifying the design of virtual machine monitors, but the employed approach had performance limitations when combined with the virtualization of memory using shadow page tables. Adding support for nested paging hardware was the answer to this problem, providing performance closer to the native, ie, without the virtual abstraction. The multicore processors were the solution to keep the microprocessors' performance growth , as the monolithic architectures were close to their limit. The use of virtualization allows exploiting parallelism offered by them through the simultaneous execution of multiple virtual machines. This study evaluates the virtualization of memory subsystem and its interaction with the multicore architectures, to determine the set of features that maximize performance. We evaluated shadow and nested paging, comparing the use of conventional and large pages to map virtualized memory. We also analyzed the influence due to the presence of a level of cache shared among cores. The results showed that in the evaluated scenario the best performance was achieved by using nested paging using large pages to map memory, while the additional level of cache didn't bring any specific benefits to virtualization. / O uso de virtualização de computadores vem crescendo rapidamente nos últimos anos, motivando a pesquisa de melhorias em software e hardware que permitam aumento de desempenho e a redução dos gargalos inerentes à virtualização. Em meados desta década, os processadores adicionaram suporte a virtualização de CPU, simplificando o projeto dos monitores de máquinas virtuais, porém o modelo adotado apresentava restrições de desempenho quando combinado com a virtualização de memória utilizando tabelas de páginas de sombra. A inclusão de suporte a paginação aninhada em hardware foi a resposta a esse problema, oferecendo desempenho mais próximo ao nativo, isto é, sem a abstração virtual. Os processadores com múltiplos núcleos, também conhecidos como multi-core, foram a solução encontrada para manter o aumento de desempenho dos microprocessadores, visto que as arquiteturas monolíticas estavam próximo ao seu limite. A utilização de virtualização permite explorar o paralelismo oferecido por eles através da execução simultânea de múltiplas máquinas virtuais. O presente trabalho avalia o subsistema de virtualização de memória e sua interação com as arquiteturas multi-core, visando determinar o conjunto de características que maximizem o desempenho. Foram avaliadas as paginações de sombra e aninhada, comparando a utilização de páginas convencionais e grandes para o mapeamento da memória virtualizada. Também foi avaliada a influência decorrente da presença de um nível de memória cache compartilhado entre os núcleos de processamento. Os resultados mostraram que no cenário avaliado o melhor desempenho foi obtido através de utilização de paginação aninhada utilizando páginas grandes para o mapeamento da memória, enquanto que o nível adicional de memória cache não trouxe benefícios específicos à virtualização.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2016-08-03T12:26:28Z No. of bitstreams: 2 Dissertação - Francielly Pinheiro da Silva Borges - 2016.pdf: 3852166 bytes, checksum: 70bbe6c9a7c6c0aa1e10b9e7e9d49843 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2016-08-03T12:29:55Z (GMT) No. of bitstreams: 2 Dissertação - Francielly Pinheiro da Silva Borges - 2016.pdf: 3852166 bytes, checksum: 70bbe6c9a7c6c0aa1e10b9e7e9d49843 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2016-08-03T12:29:55Z (GMT). No. of bitstreams: 2 Dissertação - Francielly Pinheiro da Silva Borges - 2016.pdf: 3852166 bytes, checksum: 70bbe6c9a7c6c0aa1e10b9e7e9d49843 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2016-04-15 / Fundação de Amparo à Pesquisa do Estado de Goiás - FAPEG / The Human Cytomegalovirus (HCMV) is an important cause of morbi-mortality in recipients of allogeneic hematopoietic stem cell transplantation (AloHSCT). However, there is not a consensus on which protocol to use for monitoring the infection by HCMV and, data on the frequency and clinical manifestations of the infection in this group population are quite variable among the distinct transplant centers in the world. Thus, the main objective of the present study was to proceed the monitoring of active HCMV infection in patients undergoing AloHSCT by three different methodologies: antigenemia (AGM), nested-PCR (nPCR) and real-time PCR (qPCR) and determine viral load, correlating active infection with the clinical manifestations and prognosis of patients. For this, 21 patients undergoing AloHSCT were monitored (from pre-transplant period -5 days prior to transplantation- until one year after transplantation). For HCMV detection three methodologies were used: AGM, nPCR and qPCR, and for molecular detection a comparison was made between detection of HCMV in DNA extracted from pellet (buffy coat) and serum, in a paired manner. The results showed that the active HCMV infection was detected by at least one of three methodologies in 95.2% (20/21) of patients and 45% (9/20) of these were positive in pre-transplantation period, having been observed good agreement between the results of AGM and qPCR (kappa = 0.65). Of the 20 patients positive for active HCMV infection, 85% (17/20) were positive for the three methods and only 15% (3/20) were positive for AGM and qPCR, and negative by nPCR. Regarding the type of clinical sample, molecular techniques showed higher sensitivity to the pellet over the serum. The main alteration of patients was pancytopenia and the main complication was graft-versus-host disease. Six patients died during the study period, however, it was not possible to confirm if HCMV active infection was directly associated with the cause of death. The obtained data reveal a high positivity index and the occurrence of HCMV syndrome in patients submitted to aloHSCT. We hope that the results may assist in the therapeutical measures, as well as in the methodology of choice and the type of clinical sample for detection of active HCMV infection, in order to contribute for the inclusion of HCMV monitoring is included in the routine testing of patients. / O Citomegalovírus Humano (HCMV) constitui importante causa de morbi-mortalidade em receptores de transplantes de células progenitoras hematopoiéticas do tipo alogênico (AloTCPH). Entretanto, não existe ainda um consenso sobre que protocolo utilizar para o monitoramento da infecção por HCMV e, dados sobre a frequência e manifestações clínicas da infecção neste grupo populacional são bastante variáveis entre os diferentes centros de transplante em todo o mundo. Dessa forma, o principal objetivo do presente estudo foi realizar o monitoramento da infecção ativa por HCMV em pacientes submetidos ao AloTCPH por três metodologias distintas: antigenemia (AGM), nested-PCR (nPCR) e PCR em tempo real (qPCR), bem como determinar a carga viral, correlacionando a infecção ativa ao quadro clínico e prognóstico dos pacientes. Para tanto, foram monitorados (desde o período pré-transplante -5 dias antes do transplante- até um ano após o transplante) 21 pacientes submetidos ao AloTCPH. A pesquisa de HCMV foi realizada utilizando as metodologias de AGM, nPCR e qPCR, sendo que para as técnicas moleculares, houve comparação da detecção do HCMV em DNA extraído de pellet (creme leucocitário) e soro, de forma pareada. Os resultados mostraram que a infecção ativa pelo HCMV foi detectada por pelo menos uma das três metodologias em 95,2% (20/21) dos pacientes e 45% (9/20) destes foram positivos no período pré-transplante, tendo sido observada um boa concordância entre os resultados de AGM e qPCR (kappa = 0,65). Dos 20 pacientes positivos para infecção ativa por HCMV, 85% (17/20) foram positivos pelas três metodologias e 15% (3/20) foram positivos apenas por AGM e qPCR e negativos por nPCR. Em relação ao tipo de amostra clínica, as técnicas moleculares apresentaram maior sensibilidade em amostras de pellet, em comparação ao soro. A principal alteração apresentada pelos pacientes foi a pancitopenia e a principal intercorrência, a doença do enxerto contra o hospedeiro. Seis pacientes foram a óbito durante o período de estudo, entretanto, não foi possível confirmar se a infecção ativa por HCMV estava diretamente associada à causa mortis. Os dados obtidos revelam um elevado índice de positividade e síndrome de HCMV em pacientes submetidos ao AloTCPH. Esperamos que os resultados possam auxiliar na tomada de medidas terapêuticas, bem como na escolha da melhor metodologia assim como o tipo de amostra clínica para detecção da infecção ativa por HCMV de forma a contribuir para que a pesquisa de HCMV seja incluída na rotina de exames desses pacientes.

Magister Scientiae (Biodiversity and Conservation Biology) / Land-based abalone aquaculture in South Africa started in the early 1990s and is based on the local species Haliotis midae. This industry expanded with great success over the last decade. In 2006 abalone exhibiting typical clinical signs of tubercle mycosis was discovered for the first time in South African abalone culture facilities,posing a significant threat to the industry. Halioticida noduliformans, a fungus belonging to the Peronosporomycetes (formerly Oomycetes), has been identified as the causative agent of abalone tubercle mycosis (ATM). While diagnoses of this disease are currently done by gross observation and histopathology, these methods fail to be sensitive enough to identify the causative agent accurately and reliably.Molecular confirmation could provide for quicker more accurate diagnostic information. The aim of this study was to develop a DNA based molecular diagnostic test. Polymerase chain reaction (PCR) has been used to rapidly detect, characterise and identify a variety of organisms. Nucleotide sequences of the smalland large-subunit ribosomal ribonucleic acid (rRNA) and mitochondrial cytochrome oxidase subunit II (cox2) genes of H. noduliformans were compared with closely related Peronosporomycete gene sequences to identify potential PCR primer sites. H. noduliformans specific real-time quantitative PCR (Q-PCR) primer sets were designed and optimised for each of the selected genes. Results indicate that, although all tested primers sets could amplify fungal DNA, only the LSU and cox2 primer sets - v -demonstrated no cross-amplification with the closely related Peronosporomycete and non-fungal DNA tested in the present study. The H. noduliformans specific LSU primer set was chosen for further analysis and used for all subsequent real-time PCR assays. The lowest detection limit for the LSU primer set was evaluated by running Q-PCR on serial dilutions of known quantities of extracted H. noduliformans DNA.Serial dilutions were made in PCR grade water as well as in an abalone tissue matrix.The sensitivity of the Q-PCR reaction was determined to be 266 pg of H.noduliformans DNA per 25 μL reaction volume. However, inclusion of a nested PCR step, utilising universal fungal outer primers, followed by Q-PCR with the H.noduliformans LSU specific primers improved sensitivity to 0.266 pg of H.noduliformans DNA per 25 μL reaction volume. This equates to approximately 2.4spores per 25 μL reaction volume. DNA extraction protocols were optimised to ensure efficient and repeatable extraction of high quality fungal DNA from pure fungus and tissue samples spiked with known quantities of fungal DNA. PCR amplification efficiency and potential inhibition were examined for each extraction method. Results suggest that real-time PCR has great potential in monitoring and quantifying H. noduliformans on abalone culture facilities in South Africa.

Orientador: Sandra Cecilia Botelho Costa / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-07T12:27:03Z (GMT). No. of bitstreams: 1 Dieamant_DeboradeCampos_M.pdf: 2173566 bytes, checksum: ee57b8aa1f6592084b13483d2fc8d9ce (MD5) Previous issue date: 2006 / Resumo: A partir de 1960, com a evolução nos processos cirúrgicos para transplante, a infecção pelo HCMV começa a ser reconhecida como uma doença de importância clínica, sendo considerado o principal agente patogênico em hospedeiros com o sistema imunológico comprometido. Foi iniciada, em 1980, a utilização de medidas para o controle do vírus com agentes antivirais e intervenções imunológicas, e atualmente, os avanços para a compreensão dessa virose estão relacionados aos aspectos moleculares da infecção e controle clínico, principalmente nos grupos de risco. Sabendo-se da importância do diagnóstico precoce da infecção ativa e da identificação das linhagens de HCMV em pacientes transplantados por sua possível relação com a infectividade e apresentação clínica, este trabalho teve como objetivos principais: (1)Diagnosticar e monitorizar a infecção ativa por HCMV em receptores pediátricos de transplante de rim ou medula óssea em seguimento no Hospital de Clínicas da UNICAMP e no Centro Infantil Boldrini;(2)Determinar a prevalência dos subtipos gB de HCMV na população estudada;(3)Avaliar a relação de uma determinada linhagem com o quadro clínico, apresentado pelos pacientes estudados, durante a infecção ativa e doença por HCMV. Para o diagnóstico da infecção ativa por HCMV, foram analisadas amostras de sangue de 42 pacientes transplantados pediátricos, atendidos no Hospital de Clínicas da UNICAMP e Centro Infantil Boldrini, com idade entre 2 a 18 anos, sendo que 19 deles eram receptores de transplante renal e os outros 23, receptores de transplante de medula óssea. Foram utilizadas técnicas rápidas e precoces de diagnóstico: Antigenemia e Nested-PCR A identificação das diferentes cêpas do HCMV foi feita a partir do DNA de pacientes que apresentaram antigenemia e/ou 2 ¿Nested PCR¿ consecutivos positivos para a região IE do vírus. Para a genotipagem também foi utilizada a Nested-PCR para a amplificação da glicoproteína B seguida da análise de restrição com as enzimas Rsa I e Hinf I para que fosse possível a identificação da linhagem viral.A infecção ativa por HCMV foi diagnosticada em 20 (47,6%) dos 42 pacientes estudados, sendo 5/20 (21,7%) receptores de células tronco hemeatopoética e 15/20 (79%) receptores de transplante de rim. Deste pacientes que apresentaram infecção ativa pelo HCMV fizemos a genotipagem através de uma amostra positiva de sangue. Para os pacientes que apresentaram recorrência da infecção (5/20) a análise do genótipo viral foi feita nos dois períodos da infecção, caracterizando, em todos os casos, reatiavação viral. Como resultados da genotipagem tivemos uma prevalência do genótipo 1, encontrado em 45% (9/20) dos pacientes infectados pelo HCMV, sendo 7/15 receptores de rim e 2/5 receptores de células tronco hemetopoéticas. O Genótipo 2 também teve uma frequência considerável entre este pacientes apresentando uma prevalência de 25% (5/20) e sugeriu estar relacionado com um quadro clínico mais grave e reativação viral após tratamento. A mistura de linhagens também foi encontrada em 30% (6/20) dos pacientes estudados, gB1gB2 (3/6), gB1gB4 (2/6) e gB2gB3 (1/6). Os pacientes que apresentaram como linhagem viral a mistura de linhagens apresentaram melhor prognóstico da infecção ativa pelo HCMV. Os genótipos 3 e 4 não foram encontrados isoladamente em nenhuma amostra genotipada dos pacientes estudados / Abstract: Human cytomegalovirus (HCMV) remains the most important cause of serious viral infections in pediatric transplant recipients. In these patients, early diagnosis of active HCMV infection is important since the development of HCMV disease may be prevented. Ganciclovir has been established as an effective treatment agent for active infection by HCMV. HCMV disease can occur from infection acquired by the transplanted organ or from re-activation of latent infection. The risk is highest within 2 months of transplantation. Several risk factors for disease have been identified and include: HCMV-positive donor, HCMV-negative recipient, lack of anti-viral prophylaxis, and receipt of cadaveric kidney or type of bone marrow transplant. Intense immunosuppression has also been implicated. For discriminate patients with active infection from those without such infection, tests that include the pp65 antigenemia assay (AGM) and DNA detection methods are describle. The polymarase chain reaction (PCR) is a sensitive method for detection of HCMV DNA and active infection. The HCMV antigenemia assay is a rapid and quantitative method widely used as a guideline for starting treatment with ganciclovir. Genetic variability of functionally important genes among different virus strains may influence clinical manifestations of HCMV infections. These variabilities, mainly of the glycoprotein B (gB) gene of the viral envelope, appear to be of clinical relevance because they are assumed to play an essential role in the induction of immune response and in viral entry into host cells, and it has been considered as a potential marker for viral virulence. Based on the restriction analysis of PCR products (PCR-RFLP), the HCMV genotypes were determined previously, and it may possibly be helpful in predicting the clinical outcome of HCMV infection. The aim of this study were detect and monitoring active HCMV infection in pediatric patients recipients of renal or bone marrow transplantation using DNA detection and antigenemia tests and to study the prevalence of subtypes gB-HCMV in this patients and the clinical impact. Twenty patients (47.6%) were infected during the monitoring with N-PCR and/or AGM. Recurrent infection occurred in five out of 20 patients(25%). One of these patient (20%) had done bone marrow transplantation and four patients (80%) had renal transplant. The median time of the recurrent infection was 122 days (89-134). The patients that received ganciclovir prophylaxis had active HCMV infection and probable HCMV disease. Fourteen out of 20 patients (70%) developed probable HCMV disease. Three out of (21.4%) these patients were recipients of bone marrow transplantation and eleven (78.6%) were recipients of renal transplant. T he symptoms more frequent in these patients were fever, diarrhea and vomit. This symptoms associate with active HCMV infection were considered probable HCMV disease. Nested-PCR amplification and restriction enzyme digestion of the HCMV gene were performed in 20 patients with active HCMV infection and results in differentiation of four digestion patterns as previously demostrated (Chou and Dennison, 1991). The genotypes founds were: nine patients (45%) were compatible with the gB1 genotype; five (25%) were gB2 and six patients were mixture of gB types. In the patients that demostrated mixture of gB types, 3 (50%) were compatible with the gB1gB2; two (33.3%) were compatible with gB1gB4 and one (16.7%) were compatible with gB2 gB3. No found isolated gB3 and gB4 genotype in the patients studied. / Mestrado / Mestre em Farmacologia

In this thesis, we develop a SKU level market basket model and apply the model to investigate cross-category reference price effects. This research extends previous work on the category-level multivariate logit model (Russell and Petersen 2000). Our model is a generalization of the multivariate logit model which allows for both complementarity and substitution effects at the brand level. The modeling effort in this thesis allows us to use conditional probability distributions of individual items to construct the final joint-distribution of all possible basket selections. The resulting model is very flexible and accommodates a large variety of market structure patterns. The model structure implies that the changes in brand-level marketing variables directly affect category incidence (by altering category attractiveness) and indirectly determine market basket composition. Because the model can be written in a closed form manner, we can easily study the pattern of brand price competition by computing a matrix of cross-price elasticities. We use scanner panel data for the yogurt category to demonstrate the structural flexibility of the model. The results from this application reveal asymmetric competition consistent with price-tier competition literature. We use this model to investigate how consumers' responses to reference prices within a category spillover into their choices across multiple categories. The notion is that a consumer's subjective judgment of the fairness of the price levels in one category influences the choice decisions of related items in other categories. We begin with building within-category SKU-level model based on previous findings from single category reference price models (i.e., internal versus external reference prices, asymmetric response due to loss aversion, and heterogeneity in response across consumers). We then develop four alternative model specifications for cross-category spillover effects and test competing theories about those effects. Using scanner panel data for detergent and softener categories, we discover valuable implications for reference price effects. First, SKU-level reference price effects exist and improve forecasting ability. Second, those reference price effects influence category attractiveness, but do no spillover across categories. Finally, category-level reference dependent evaluation may exist but not be important in forecasting.