Made available in DSpace on 2015-12-06T23:47:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2006 / BV UNIFESP: Teses e dissertações

[pt] O objetivo deste trabalho é apresentar alguns resultados referentes ao estudo da sensibilidade da reposta impulsional de sistemas lineares, causais, a tempo discreto e monovariáveis a aproximações nos coeficientes das equações a diferenças finitas que os representam. São estudados primeiramente sistemas variantes no tempo representados por matrizes de estado nas formas canônicas diagonal e de Jordan, sendo analisado o caso invariante como uma particularização. Tais formas canônicas permitem obter diretamente a sensibilidade da resposta impulsional do sistema em relação aos autovalores, que são, no caso de invariância, os pólos do mesmo. A seguir são tratados sistemas variantes no tempo com equações de diferenças finitas de forma qualquer, explorando-se funções de dependência entre os diversos coeficientes. Todo o estudo é baseado em técnicas do domínio do tempo e álgebra matricial. A impossibilidade de se trabalhar de modo simples no domínio da freqüência com sistemas variantes, fez com que este não fosse utilizado nem nos casas particulares da classe mais geral dos sistemas variantes. / [en] The objective of this work is to present some results on the sensitivity of the weighting sequence (impulse response) of linear, causal, monovariable, discrete-time systems to approximations of the coefficients of the difference equations that model them. The first part of the work is devoted to systems represented in canonical representations diagonal and Jordan forms; the time-invariant case is studied as a particularization. These canonical forms allow the sensitivity to be determined as a function of the model eigenvalues and, in the time-invariant case, of the poles of the transfer function. The second part addresses systems represented in general forms. The whole work is based on time-domain techniques. Frequency-domain techniques were not used due to the fact that they are more difficult than in the time-invariant case.

Le titane et ses alliages sont très largement étudiés en raison de leur grande utilisation dans l'industrie chimique, les implants médicaux et les industries aérospatiales. Vu le rôle important dans la déformation plastique, le maclage a été largement étudié dans les métaux hexagonaux L'état de contrainte locale peut être modifié par maclage, ce qui influence les modes séquentiels de déformation tels que le glissement, le maclage et le maclage secondaire Ainsi, il existe une demande urgente pour comprendre le mécanisme associé à la déformation induite par maclage, utile pour le développement de modèles prédictifs qui peuvent décrire les événements ultérieurs induits par maclage, ainsi que leurs corrélations avec les microstructures. Dans ce travail, l'analyse cristallographique de la sélection de variantes de macles et des jonctions macle-macle (TTJ= twin-twin junction) est appliquée sur du titane commercialement pur. Un nouveau mécanisme de maclage séquentiel, où les macles {101̅2} sont stimulées par des jonctions macle {112̅1}-macle, est observée par EBSD quasi in situ. Un autre mécanisme de maclage séquentiel a été trouvé lorsque le maclage de compression {112̅2} contient une macle d'extension {101̅2} près des joints de grain à forte désorientation. L'accommodation est utilisée pour déterminer le variant de macle séquentiel lorsque le facteur de Schmid classique (SF) n'est pas suffisant. En outre, une analyse détaillée des 425 macles secondaires {101̅2} détectées dans les macles {11 2̅ 2} primaires révèle que les deux variants de macles qui présentent une désorientation spécifique par rapport aux grains parents sont les plus fréquentes. Il est possible de justifier la prévalence des macles secondaires avec un mécanisme de nucléation aidée par les dislocations prismatiques. Lorsqu'il est complété par une analyse SF généralisée, le critère peut prédire avec précision la sélection entre deux variants dans le groupe des macles secondaires les plus fréquentes. Lorsque plusieurs variants de macles sont actifs dans le même grain, des interactions macle-macle peuvent se produire. Les jonctions macle {112̅2}-macle peuvent être divisés en trois types selon la cristallographie des macles {112̅2}. Une analyse statistique de ces interfaces révèle qu'un seul type est le plus fréquent tandis que les autres types sont rarement activés. La fréquence des TTJ peut être évaluée en utilisant une analyse SF généralisée. Il en ressort que les interfaces macle-macle (TTB= twin-twin boundary) ne se forment que d’un côté de la macle. Concernant la formation de TTBs basée sur les interactions des dislocations de macle, les dislocations d'interface dans les TTBs observées ont une énergie de ligne inférieure à celles des TTB non observées. Une opération similaire est appliquée à l'analyse de {112̅1} TTJs / Titanium and its alloys have been extensively investigated due to their wide application in chemical industry, medical implants and aerospace industries. As a significant role in plastic deformation, twinning has been widely studied in hexagonal metals. The local stress state may be modified by twinning, which influences sequential plastic deformation modes such as slips, twinning and secondary twinning. Thus, there is also an urgent demand for understanding the mechanism associated with the twinning-induced deformation, which is useful for the development of predictive capabilities that can describe twinning and twinning-induced sequential events, and their correlations with microstructures. In this work, crystallographic analysis of twin variant selection and twin-twin junctions is applied in commercially pure titanium. A new sequential twinning mechanism that {101̅2} twins are stimulated by the {112̅1} twin-twin junctions (TTJs) is observed by quasi in-situ EBSD. Another sequential twinning mechanism that a {112̅2} compression twin adjoins a {10 1̅ 2} extension twin is found at high angle grain boundaries. Displacement gradient accommodation is used to determine the sequential twin variant while the classical Schmid factor (SF) is not sufficient. Besides, a detailed analysis of the detected 425 {101̅2} double twins inside primary {112̅2} twins reveals that the double twin variants that exhibit specific misorientation with respect to the parent grains are the most frequent. The prevalence of double twins is possible to justify with the prismatic-dislocation mediated nucleation mechanism. When complemented with an apparent SF analysis, the criterion can accurately predict the selection between two variants within the group of the popular double twins. When multiple twin variants are active in the same grain, twin-twin interactions may happen. {112̅2} TTJs can be divided into three types according to the crystallography of {112̅2} twins. A statistical analysis of {112̅2} TTJs reveals that one type is the most popular while other types are rarely activated. The frequency of TTJs can be evaluated by using an apparent SF analysis. The interesting finding is that twin-twin boundaries (TTBs) form in one side of the incoming twin as a TTJ forms. Corresponding to the formation of TTBs based on the interactions of twinning dislocations, interface dislocations in the observed TTBs have lower line energy than those in the un-observed TTBs. Similar operation is applied to the analysis of {112̅1} TTJs

Made available in DSpace on 2014-06-11T19:26:05Z (GMT). No. of bitstreams: 0 Previous issue date: 2005-08-29Bitstream added on 2014-06-13T20:33:44Z : No. of bitstreams: 1 ondei_ls_me_sjrp.pdf: 1659909 bytes, checksum: 0234670a460d2993f23cb77243c91e66 (MD5) / As hemoglobinas (Hb) variantes, originadas em sua maioria por simples substituições de aminoácidos, resultam de mudanças na seqüência de nucleotídeos. Atualmente, o número de Hb anormais identificadas tem aumentado devido à melhoria nas metodologias de análises, porém muitos laboratórios de rotina não estão preparados para a correta identificação dos mutantes. A Hb S é uma variante de Hb bem caracterizada que apresenta prevalência variável nas diferentes regiões do Brasil. No entanto, há uma variedade de Hb que apresenta padrão de migração eletroforética semelhante ao da Hb S em pH alcalino as quais são denominadas “Hb S-like”, podendo ser erroneamente diagnosticadas e com suas freqüências subestimadas. Neste trabalho foram estabelecidos os valores referenciais de Hb por HPLC em portadores de Hb S e determinados os perfis eletroforético e cromatográfico das Hb “S-like” dentre as amostras enviadas ao LHGDH. Foram encontradas as Hb Hasharon, Hb D-Los Angeles, Hb Korle-Bu, Hb Lepore, Hb D-Iran, Hb tipo G, Hb Queens, Hb Montgomery e Hb Q-Índia. Também foram encontrados casos de associação entre dois mutantes de cadeia beta. As eletroforeses em pH alcalino e pH ácido foram utilizadas para o rastreamento inicial das Hb variantes e as eletroforeses de cadeias polipeptídicas em ambos pH foram realizadas para a identificação da cadeia globínica alterada. As análises cromatográficas permitiram o direcionamento dos prováveis mutantes, sendo também possível a quantificação precisa das frações de variantes. Desta forma, a associação de metodologias laboratoriais clássicas de diagnóstico é fundamental para o levantamento das suspeitas fenotípicas. Os perfis da Hb S e das Hb “S-like” estabelecidos neste estudo auxiliarão no diagnóstico dessas Hb variantes em serviços de saúde. / The variants hemoglobin (Hb) originated mainly by simple amino acid substitutions, result of nucleotides sequences changes. Currently, the number of abnormal hemoglobin identified has increased due to improvement in the analysis methodologies, but many routine laboratories are not prepared for the correct mutants identification. The Hb S is a variant Hb well characterized that shows variable prevalence in different regions of Brazil. However, there is a diversity of Hb that present electrophoretic migration on alkaline pH similar to Hb S, named Hb S-like, which can be incorrectly diagnosed and with their frequencies underestimated. At the present study the reference ranges for Hb S obtained by HPLC were established, and the electrophoretic and cromatographic profile for Hb S like were determined. The Hb Hasharon, Hb D-Los Angeles, Hb Korle-Bu, Hb Lepore, Hb D-Iran, Hb tipo G, Hb Queens, Hb Montgomery e Hb Q-Índia were found. Cases of association between two mutants of beta chain were also found. The electrophoresis on alkaline pH and acid pH were utilized to the initial screen of these variants Hb and the globin chains electrophoresis in both pH were performed to identify the mutant globin chain. The chromatographic analysis permitted the identification of the likely variant hemoglobin and also facilitated the exact quantification of variants. Therefore, the association of the classical laboratory methods of diagnostic is fundamental for the identification of variant Hb suspect. The Hb S and Hb S-like profile determined in this study will help in the diagnostic of these variants Hb in healthy service.

Made available in DSpace on 2015-09-25T12:22:15Z (GMT). No. of bitstreams: 1 AlfredinaRosaOliveiraDoVale.pdf: 2309589 bytes, checksum: 64ba9fd0b60287525fad5aa22a3237dc (MD5) Previous issue date: 1999-07-20 / As far as textual production is concerned, this piece of research aims at describing the deviants as determinants of linguistic changes. Such deviants found in signs and notices (i.e. the conductive means of the collected messages), are exposed in public places in Campina Grande (PB). The main objective of this work is thus to identify, from the occurrences of these deviants, the possibilities to change the Brazilian spelling rules which may come to happen in the medium and/or long term. To carry out our research, we have based the study on two main theoretical moments: the first, a diachronic study from the 8th to the 10th century, divided in to six volumes HAUL, PAIVA, SPINA, MOREL PINTO, MARTINS and PIMENTEL PINTO entitled História da Língua Portuguesa. The second, a synchronic study, had two of PIMENTEL PINTO s works as a starting point: A língua escrita no Brasil (1986) and O português popular escrito (1990) and BAGNO s Preconceito lingüístico (1999). After detecting, selecting and categorizing the deviants (345 occurrences), we started the analysis, which we divided into two parts: the dismemberment of the diacritcs and the examination of the orthographic evidences in these changes. The analysis being concluded, a quantitative survey of the collected deviants was made in order to observe the incidence of these occurrences. The results so far seem to lead to a brief phonetic accommodation in the Brazilian Portuguese which will gradually abolish the general diacritic marks. As to spelling evidences, they are based on the metaplams of addition, subtraction, assimilation, and exchange. The latter is the most frequent case, which highlights the substitution of the grapheme s for the grapheme z , when it comes between two vowels. The results still show the frequent use of anglicism, or of its presence through the graphemes k and y . Thus, the analysis concludes that by being the act of writing signs and notices an uncommon situation to the ordinary man, it is this very fact that may justify the spontaneous occurrence of the deviant, stimulating linguistic changes which are considered non-acceptable at first but are accepted by the standard variant after a certain period of time. / Esta pesquisa, sob a perspectiva da produção textual, procura descrever os desvios como agentes determinadores de mudanças lingüísticas. Estes, localizados em porta-textos (o veículo condutor das mensagens coletadas), estão afixados em locais públicos de Campina Grande (PB). Identificar, a partir das incidências dos desvios, as possibilidades de mudanças no sistema ortográfico brasileiro, que poderão vir a ocorrer a médio e/ou longo prazo, é a meta principal deste trabalho. Para tal, apoiamo-nos em dois momentos teóricos: o primeiro, um estudo diacrônico, do Século XIII ao Século XX, distribuído em seis volumes HAUY, PAIVA, SPINA, MOREL PINTO, MARTINS e PIMENTEL PINTO intitulados História da Língua Portuguesa. O segundo, um estudo sincrônico, teve como ponto de partida duas obras de PIMENTEL PINTO: A Língua escrita no Brasil (1986) e O português popular escrito (1990). E, como ponto de chegada, a obra de BAGNO, intitulada Preconceito lingüístico (1999). Constatados os desvios (345 ocorrências), selecionados e categorizados, iniciamos a análise dividida em dois momentos: o desmembramento dos diacríticos e o exame das evidências (orto)gráficas em processo. Concluída a análise, foi feito um levantamento quantitativo dos desvios coletados, para observar-se a incidência das ocorrências. Os resultados obtidos acenam para uma breve acomodação fonética na língua portuguesa brasileira que, gradativamente, deverá abolir os diacríticos gerais. Quanto às evidências ortográficas, estas têm sua base nos metaplasmos de adição, subtração, assimilação e permuta. Este é o caso mais freqüente, destacando-se a substituição do grafema s pelo grafema z , quando aquele surge entre duas vogais. Os resultados ainda evidenciam o uso freqüente do anglicismo, ou da marca deste, através dos grafemas k e y . Assim, a análise conclui que sendo o ato de grafar uma situação rara para o homem comum, é esta realidade, possivelmente, que justifica o surgimento espontâneo do desvio, provocando alterações lingüísticas, execradas a princípio e aceitas posteriormente pela variante padrão.

La dégénérescence frontotemporale est une pathologie rare, plaçant au premier plan les désordres comportementaux. Après analyse des troubles psycho-comportementaux et de leurs méthodes actuelles d’évaluation, nous avons élaboré et validé un nouvel outil, appelé DAPHNE (pour Desinhibition-Apathie-Persévérations-Hyeroralité-Négligence-Empathie) spécialement conçu pour dépister et quantifier la sévérité et la progression des troubles du comportement dans la variante frontale de dégénérescence frontotemporale (vfDFT), en pratique clinique courante. Cette validation a été effectuée de manière prospective, auprès d’une population de patients présentant une vfDFT suivis pendant 2 ans et également d’une population contrôle afin d’établir sa spécificité. DAPHNE, adaptée des critères révisés de vfDFT, présente d’excellentes caractéristiques psychométriques. Explorant six domaines et dix symptômes comportementaux, avec un système de cotation innovant en 5 points, elle permet à la fois le screening mais également une appréciation quantitative et une aide au diagnostic. Parallèlement à cela, nous avons étudié les liens entre les différents troubles psycho-comportementaux, les fonctions cognitives proprement dites et la cognition sociale chez les patients vfDFT. Plus particulièrement, nous nous sommes intéressés à l’évaluation des troubles émotionnels des patients DFT. À l’aide d’une tâche originale TABEAU, portant sur l’étude de la sensibilité esthétique des patients DFT, nous avons observé des liens entre émotion et troubles du comportement (trouble de l’identification de certaines émotions et émoussement affectif etc.). Si le jugement esthétique est préservé en apparence, le patient est en difficulté sur le plan des processus cognitifs du fait de difficultés d’abstraction et en difficulté sur le plan des processus émotionnels. Ce travail montre quel spectateur est le patient DFT vis à vis de l’art et vient compléter les données de la littérature qui portaient jusque-là sur l’expression artistique. Ce type d’approche cognitive permet donc d’avancer dans la compréhension des interactions entre émotions et troubles du comportement, qui font toute la singularité de cette maladie. Pris dans leur ensemble, nos résultats soulignent l’intérêt majeur de l’étude fine du comportement en pratique quotidienne. À l’ère des biomarqueurs, la clinique garde une place de choix pour le diagnostic et la compréhension des maladies neurodégénératives. / Frontotemporal degeneration is a rare disease with early decline in social behavior and personal conduct. We have first presented behavioral disorders and their current evaluation methods. We developed and validated then a new tool, named DAPHNE (Disinhibition-Apathy-Perseverations-Hyerorality-Neglect-Empathy) specially designed to detect and quantify the severity and the progression of behavioral disorders in the behavioral variant of frontotemporal dementia (bvFTD), in clinical practice. This validation was performed prospectively, in patients with bvFTD with a follow-up of 2 years and also in AD, progressive supranuclear palsy and bipolar patients with cognitive disorders, in order to establish the specificity of this scale. DAPHNE, adapted from revised criteria of bvFTD, has excellent psychometric characteristics. Exploring six areas and ten behavioral symptoms, with an innovative scoring system in 5 points, it enables both the screening but also a quantitative assessment and a diagnostic support.As a second part of our works, we studied the links between the various psycho-behavioral disorders, cognitive functions and social cognition in bvFTD patients. Specifically, we focused on emotion assessment of FTD patients. Using an original task entitled TABEAU, based on the study of aesthetic sensibility of FTD patients, we observed the links between emotions and behavior disorders (such as trouble identifying certain emotions or emotional blunting). The aesthetic judgment seemed preserved. But the patient is in trouble in terms of cognitive processes due to abstraction problems and difficulties with emotional processes. This work shows what type of viewer is the FTD patient in front of a piece of art. It adds to the literature data that were previously based only on artistic expression. This cognitive approach improves the understanding of interactions between emotions and behavior disorders which make the singularity of this disease.Taken together, our results highlight the major interest of the detailed assessment of behavior in daily practice. In biomarkers’ era, clinical practice remains central in diagnosing and understanding of neurodegenerative diseases.

No description available.

Dermicidina (DCD) é um gene mapeado no cromossomo 12, lócus 12q13.1, e codifica uma proteína de 110 aminoácidos, que sofre um processamento proteolítico, gerando peptídeos ativos. O peptídeo C-terminal (DCD-1L) de 48 aminoácidos tem uma carga -2, e exerce função antibacteriana e antifúngica, e o peptídeo C-terminal splice variante, denominado DCD-SV de 59 aminoácidos, tem carga neutra, e suas propriedades ainda não foram estabelecidas. Neste trabalho são apresentados os resultados da expressão, purificação e sequenciamento da DCD nativa produzida em E. coli BL21 transformada com o vetor pAE-DCD. Na segunda parte são descritas as análises físico-químicas e bioquímicas da interação dos peptídeos sintéticos DCD-1L e DCD-SV com vesículas lipídicas gigantes e vesículas unilamelar grandes sintetizadas com palmitoil-oleoil-fosfatidilcolina. As preferenciais estruturais dos peptídeos foram investigadas por espectroscopia de Dicroísmo Circular. Nossos resultados sugerem que a DCD-SV tem alta propensão para adotar uma estrutura helicoidal permitindo sua inserção e oligomerização em membranas biomiméticas, e possível formação de canais de condutância molecular. / Dermicidin (DCD) is mapped a gene on chromosome 12, locus 12q1.13 whose 110 amino acids protein is proteolytically processed to N and C-terminal peptides. The 48-amino acid C-terminal peptide (DCD-1L) has -2 net charges and display antibacterial and antifungal properties and the 59-amino acid splice variant C-terminal peptide (DCD-SV) has neutral net charge; however, its structure and biological function are unknown. Here we show the results of expression, purification and amino acid sequencing of recombinant DCD protein produced in E.coli transformed with pAE-DCD vector. We also describe the results of physical-chemical and biochemical analyses showing the visible differences between the interactions of DCD-1LL and DCD-SV synthetic peptides with giant unilamellar vesicles and large unilamellar vesciles made of palmitoyl-oleoyl phosphatidylcholine, used as biomimetic membranes. The structural preferences of peptides were analyzed by circular dichroism spectroscopy. Our results suggest that DCD-SV peptide has higher propensity to adopt helicoidal structure enabling it to insert into mimetic membranes, undergo oligomerization and formation of conductance channel.

Mais de 95% de luz ultravioleta (UV) que atinge a superfície da Terra corresponde ao comprimento de onda da luz UVA (315-400 nm). A luz UVA induz no DNA danos pela absorção direta e indireta dos fótons, bem como por intermédio de cromóforos. Pacientes com Xeroderma Pigmentosum Variante (XP-V) possuem mutações na DNA polimerase η (pol eta), que promove a síntese translesão dos danos induzidos pela luz solar. Na ausência dessa polimerase há aumento da mutagênese, provável causa de câncer de pele em pacientes XP-V. O objetivo deste trabalho foi caracterizar os mecanismos de indução de danos no genoma e mutagênese por luz UVA, em células derivadas desses pacientes. Os resultados indicam que a exposição à luz UVA resultou em maior sensibilidade de células XP-V comparadas à linhagem controle. Os níveis de fosforilação da histona H2AX (gerando γH2AX - indicador de indução de danos no genoma) e detecção de danos diretos e indiretos no DNA apresentou um aumento significativo em células XP-V irradiadas com luz UVA. Curiosamente, na ausência de pol eta houve uma redução na capacidade de remoção das lesões formadas. Além disso, a irradiação com luz UVA causou forte bloqueio de replicação do DNA e parada do ciclo celular em fase S em células XP-V, desencadeando importantes respostas mediadas por ATR/Chk1. Surpreendentemente, o antioxidante N-acetilcisteína (NAC) resultou em diminuição da sensibilidade celular, dos níveis de γH2AX, da parada de forquilha de replicação e do ciclo celular, reduziu os efeitos citotóxicos da inibição de ATR, melhorou o reparo de lesões no DNA e preveniu a carbonilação de proteínas em células XP-V irradiadas com luz UVA. Investigamos também a indução de mutagênese nas células irradiadas com luz UVA, através de sequenciamento de exoma de clones celulares. Os dados indicaram um aumento significativo da mutagênese em células XP-V irradiadas comparadas a células controle, e pela avaliação dos tipos de mutações encontradas verificamos uma frequência bastante alta de transições C>T, provavelmente como consequência de replicação errônea de dímeros de pirimidina. Entretanto, também identificamos indução significativa de transversões C>A, provavelmente devido a lesões oxidadas no genoma. Curiosamente, ao compararmos células XP-V com células controle detectamos um aumento desse último tipo de mutação na ausência de pol eta, provavelmente devido a lesões endógenas, produzidas pela oxidação do DNA. Além disso, análises in silico mostraram que células XP-V irradiadas com UVA apresentaram assinatura mutacional similar ao observado para tumores de pele. Os dados claramente indicam que células XP-V são sensíveis a irradiação com UVA e que os danos promovidos no DNA, incluindo aqueles causados por estresse oxidativo, desencadeiam respostas celulares e mutagênese nesses pacientes. Assim, além de apontar que UVA pode gerar efeitos deletérios na pele de pacientes XP-V, nossos dados também contribuem para a compreensão de como esses comprimentos de onda podem atuar em células humanas em geral / More than 95% of ultraviolet-light (UV) that reaches the Earth surface corresponds to UVA wavelengths (315-400 nm). UVA-light induces DNA damage through direct and indirect absorption of photons, as well as, intermediated by chromophores and by oxidation mechanisms. Xeroderma Pigmentosum Variant (XP-V) patients are defective in DNA polymerase η (pol eta) that performs translesion synthesis of sunlight induced DNA damage. Absence of pol eta results in increased mutagenesis, which is probably responsible for high frequency of skin cancer in XP-V patients. The goal of this work was to characterize the mechanisms of UVA-induced genome DNA damage and mutagenesis in cells derived from these patients. The results indicate that UVA irradiation increased cell death of XP-V compared to control cell line. The phosphorylation of the histone H2AX (generating γH2AX, an indicator of genotoxic stress) and DNA damage was highly increased in UVA irradiated XP-V cells. Curiously, however, in the absence of pol eta, there was a reduction in the capacity of cells to remove DNA damage from genome. Moreover, UVA irradiation triggered strong DNA synthesis blockage and cell cycle arrest in S phase, resulting in important responses mediated by the ATR/Chk1 pathway in XP-V cells. Interestingly, the antioxidant N-acetyl cysteine (NAC) resulted in decreased cell sensitivity, γH2AX levels, fork stalling and cell cycle arrest, reduced the cytotoxic effect of ATR inhibition, improved DNA repair and prevented the protein carbonylation in XP-V cells irradiated with UVA. The mutagenesis by UVA-light was also investigated by exome DNA sequencing of cellular clones. The data indicated a significative increase of mutagenesis in XP-V irradiated cells compared to control cells, and the identification of mutation types indicated a high increase of C>T transitions, probably as result of error-prone replication of pyrimidine dimers. Nevertheless, the induction of C>A transversions were also detected, probably due to oxidized DNA damage. Curiously, when XP-V and control cells were compared, in the absence of irradiation, these transversions were also detected, maybe due to endogenous oxidation of DNA. In addition, in silico analyses showed that UVA-irradiated XP-V cells had a mutation signature similar to the observed for skin cancer. The data demonstrate XP-V cells are sensitive to UVA-light and DNA damage, including by oxidative stress, trigger cell responses and induce mutagenesis in these patients. Therefore, besides showing that UVA-irradiation may generate deleterious effects in the skin of XP-V patients, the data also contribute to understand how these light wavelengths may damage human cells in general

Introdução: A papilomatose recorrente respiratória (PRR) é uma doença benigna de enorme morbidade, com manifestações clínicas muito distintas, causada pelo papiloma vírus humano (HPV) dos tipos 6 e 11. Objetivo: Identificar os diferentes tipos de HPV e suas variantes relacionados com a PRR e estabelecer possível correlação clínica entre o tipo / variante viral e a agressividade da doença. Casuística e Métodos: Estudo prospectivo, realizado com 41 pacientes atendidos no Ambulatório de Laringologia do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, entre os anos de 2008 e 2015, que apresentaram quadro de PRR. Foi realizada genotipagem viral das biopsias laríngeas e os vírus presentes foram relacionados com a evolução clínica de cada paciente e a agressividade da doença, pelo escore de Derkay, número de cirurgias e traqueostomia. Resultados: Dos 41 pacientes avaliados, a maioria era do sexo masculino (68,29%), e maiores de 12 anos (63,41%). Os menores de 12 anos apresentaram número de cirurgias e escore de Derkay significativamente maiores do que os pacientes mais velhos. Foram identificados somente os HPV dos tipos 6 e 11, na frequência de 73,17% e 26,83%, respectivamente. A agressividade da doença não mostrou relação com o tipo ou a variante do vírus, mas sim com a idade de apresentação clínica da doença. Conclusão: Os tipos de HPV e as suas variantes não apresentaram comportamento clínico mais agressivo na PRR no grupo estudado. Em contrapartida, a idade foi determinante para a agressividade da doença. / Introduction: Recurrent respiratory papillomatosis (RRP) is a benign disease of enormous morbidity that presents very distincts clinical manifestations. It is usually caused by the human papillomavirus (HPV), mostly types 6 and 11. Purpose: To identify the different HPV types and variants related to RRP and to establish a possible correlation between HPV type/variant and viral disease aggressiveness. Casuistic and Methods: This prospective study included 41 patients followed at the Outpatient Clinic of Laryngology of the Medical School of Ribeirão Preto, University of São Paulo, between 2008 to 2015, due to RRP. Virus genotyping was performed on laryngeal biopsies by PCR, and this information was associated to each patient\'s data regarding aggressiveness of the disease and clinical evolution, by Derkay\'s score, number of surgeries and tracheostomy. Results: Most patients were male (68.29%) and older than 12 years-old (63.41%). Patients younger than 12 years had a significantly higher number of surgeries and Derkay score than older patients. In all samples, only HPV 6 and HPV 11 were detected, in a prevalence of 73.17% and 26.83%, respectively. The aggressiveness of the disease was not related to the type or variant of the virus, but to the age of patient when the clinical presentation of the disease occurred. Conclusions: HPV types and variant of HPV showed no more aggressive clinical behavior in recurrent respiratory papillomatosis in the studied group. In contrast, age was crucial to the aggressiveness of the disease.