In Parkinson's disease, severe damage to nigrostriatal neurons causes a depletion of the neurotransmitter dopamine (DA). Oxidative stress on the brain is thought to contribute to neuron cell death and to the onset of Parkinson's disease. Reactive oxygen radicals produced during oxidative stress have been implicated as an initiator of neuron destruction. Glutamate, an excitatory neurotransmitter, can initiate OH radical formation when present in excess. Oxidative stress on the brain caused by glutamate overflow may be monitored by trapping the OH radicals with salicylic acid to produce 2,3-dihydroxybenzoic acid (2,3-DHBA). Determination of this product is initially performed using capillary zone electrophoresis (CZE) coupled with UV detection to establish optimum separation conditions. These conditions were applied for rapid, efficient, and sensitive determination of 2,3-DHBA by CZE coupled with electrochemical detection. Quick and sensitive detection of 2,3-DHBA is essential in monitoring OH radical generation and identifying its role in Parkinson's disease. / Master of Science

Yes / Cutaneous science has seen considerable development in the last 25 years, in part due to the -Omics revolution, and the appreciation that this organ is hardwired into the body’s key neuroimmuno- endocrine axes. Moreover, there is greater appreciation of how stratification of skin disorders will permit more targeted and more effective treatments. Against this has been how the remarkable extension in the average human life-span, though in the West at least, this parallels worrying increases in lifestyle-associated conditions like diabetes, skin cancer etc. These demographic trends bring greater urgency to finding clinical solutions for numerous age-related deficits in skin function caused by extrinsic and intrinsic factors. Mechanisms for aging skin include the actions of reactive oxygen species (ROS), mtDNA mutations, and telomere shortening, as well as hormonal changes. We have also significantly improved our understanding of how to harness the skin’s considerable regenerative capacity e.g., via its remarkable investment of stem cell subpopulations. In this way we hope to develop new strategies to selectively target the skin’s capacity to undergo optimal wound repair and regeneration. Here, the unsung hero of the skin regenerative power may be the humble hair follicle, replete with its compliment of epithelial, mesenchymal, neural and other stem cells. This review introduces the topic of human skin aging, with a focus on how maintenance of function in this complex multi-cell type organ is key for retaining quality of life into old age.

Depuis une dizaine d'années, les polymères hyperbranchés sont apparus dans la littérature. Ils possèdent un grand nombre de branchements ainsi qu'un grand nombre de groupes terminaux. La structure globulaire des polymères hyperbranchés les empêche de former des enchevêtrements. Il en résulte un avantage décisif pour leur application sous forme de revêtement de surface: les polymères hyperbranchés ont une viscosité plus faible à l'état fondu que les polymères linéaires. Cela permet aisément de les étaler sous forme de films minces sans utiliser de solvant. De plus, les polymères hyperbranchés possèdent un grand nombre de groupes terminaux qui peuvent être fonctionnalisés avec des monomères photoréticulables. Le but du travail de thèse est d'obtenir de nouveaux revêtements de surface, à partir de polymères hyperbranchés ou de polymères fortement branchés, qui trouveront leur application dans l'industrie chimique. La thèse s'articule autour de trois chapitres de synthèse suivis d'un chapitre traitant de la photoréactivité des oligomères linéaires, fortement branchés, et hyperbranchés. La première approche de synthèse envisagée est la copolymérisation alternante radicalaire. Divers maléimides ont été engagés dans des copolymérisations radicalaires avec des allyléthers sans succès. Lorsque ces derniers sont remplacés par des vinyls éthers, une copolymérisation alternante est observée. Néanmoins, une importante irreproductibilité est constatée, certains batchs donnant lieu à une gélification. La seconde voie de synthèse étudiée est l'approche classique de polycondensation de monomères de type AB2 . Le monomère AB2 est obtenu par addition de Michael de la diéthanolamine sur l'acrylate de méthyle. La polycondensation est concomitante avec l'acrylation des fonctions alcools. La compétition entre ces deux réactions limite les masses molaires accessibles bien que les réactions de transestérification soient catalysées par des dérivés du Zr et que la stoechiométrie ait été variée. La troisième voie de synthèse se base aussi sur la réaction de Michael. Des oligomères fortement branchés sont obtenus à partir de 1,6-hexanedioldiacrylate et d'éthylènediamine. Leurs analogues linéaires sont synthétisés en remplaçant l'éthylènediamine par la propylamine. Lors de ces synthèses, il est apparu que les oligomères fortement branchés ont une viscosité supérieure à celle des oligomères linéaires! Les oligomères hyperbranchés et acrylés, les oligomères linéaires et leurs analogues fortement branchés ont été étudiés du point de vue de leur photoréticulation sous rayonnement UV. Contrairement à ce qui était attendu, ils se sont montrés moins réactifs que les produits les plus performants de Cytec-Surface Specialties. Lors de cette étude, l'effet bénéfique des mines tertiaires sur l'inhibition par l'oxygène est apparu plus complexe que décrit dans la littérature.

Work hypothesis: Different pea (Pisum sativum L.) morphotypes respond differently to various anthropogenic factors. This can be related with an alteration of plant metabolism and with changes of photosynthetic pigments and biochemical indexes. Work aim and the tasks: To investigate the effects of ozone and UV-B radiation on different pea (Pisum sativum L.) morphotypes under changing climatic conditions and to measure plant reaction to the effects of ozone and UV-B radiation. 1.To investigate the effects of ozone and UV-B radiation on the morphometric parameters of different pea morphotypes under changing climatic conditions; 2.To investigate the effects of ozone and UV-B radiation on the photosynthetic pigments of different pea morphotypes under changing climatic conditions; 3.To investigate the effects of ozone and UV-B radiation on the biochemical indexes of different pea morphotypes under changing climatic conditions. Novelty of the scientific work. For the first time the effects of the near-ground ozone and UV-B radiation on two different pea (Pisum sativum L.) morphotypes (leafy ‘Ilgiai‘ and semi-leafless ‘Profi‘) were investigated under changing climate conditions. The response of these plants to the effects of ozone and UV-B radiation was measured. Defended propositions The different pea morphotypes respond differently to the effect of anthropogenic factors; The morphometric parameters of the different pea morphotypes alters unequally when responding to the... [to full text] / Darbo hipotezė: Skirtingų morfotipų žirniai (Pisum sativum L.) nevienodai reaguoja į įvairius antropogeninius veiksnius. Tai gali būti susiję su augalų metabolizmo pakitimu, fotosintetinių pigmentų, bei biocheminių rodiklių kitimu. Darbo tikslas: Ištirti ozono ir UV-B spinduliuotės poveikį skirtingų morfotipų žirniams (Pisum sativum L.) kintančiomis klimato sąlygomis, bei nustatyti jų reakciją į ozono ir UV-B spinduliuotės poveikį. Uždaviniai: 1.Kintančiomis klimato sąlygomis ištirti ozono bei UV-B spinduliuotės poveikį, skirtingų morfotipų žirnių morfometriniams parametrams; 2.Kintančiomis klimato sąlygomis ištirti ozono ir UV-B spinduliuotės poveikį, skirtingų morfotipų žirnių fotosintetiniams pigmentams; 3.Kintančiomis klimato sąlygomis ištirti ozono poveikį, skirtingų morfotipų žirnių biocheminiams rodikliams. Mokslinis darbo naujumas. Pirmą kartą buvo ištirtas priežemio ozono ir UV-B spinduliuotės poveikis, kintančiomis klimato sąlygomis, skirtingų morfotipų sėjamajam žirniui (Pisum sativum L.) lapuotiems ‘Ilgiai‘ bei pusiau belapiams ‘Profi‘, bei nustatyta jų reakcija į ozono ir UV-B spinduliuotės poveikį. Ginamieji teiginiai Skirtingų morfotipų žirniai nevienodai reaguoja į antropogeninių veiksnių poveikį; Skirtingų morfotipų žirnių morfometriniai parametrai, nevienodai skirtingai kinta nuo poveikio laiko, bei poveikio stiprumo; Skirtingų morfotipų žirnių fotosintezės mechanizmai yra nevienodi, sąlygojantys apsaugą nuo fotooksidacinio streso; Skirtingų morfotipų žirnių... [toliau žr. visą tekstą]

Class of 2009 Abstract / OBJECTIVES: The purpose of the project was to identify two technologies from INAOE, Instituto Nacional de Astrofisica Optica y Electronica (INAOE) located in Puebla, Mexico, that were close to market and develop a feasibility study for those technologies in a 10 week time frame. METHODS: Open submission from INAOE researchers was allowed for two weeks. Following open submission a weighted criteria matrix was developed to identify the top eight technologies. Interviews were conducted with the top eight primary researchers and their laboratories over a one week period. Voting was conducted to determine the final two technologies. Research was conducted to analyze and identify the market, provide a business and financial model, and provide recommendations. RESULTS: Results are from the feasibility study of the silicon rich oxide UV sensor one of the two technologies selected. Market: Five markets were identified with combined annual production of approximately 3.5 million sensors per year and an annual expected growth rate of 9.1%. Average selling price of a commercially available UV sensor was approximately $35 per unit. Average selling price for the INOAE was estimated to be $18 per unit. Financial: A financial analysis for a start-up venture to sell and manufacture the sensor estimated gross sales in year 1 to be $2.7M, with a net profit $427K, and EBITDA $719K. The target market share of 2%, effective tax rate 40%, market risk premium 10%, discount rate (Wacc) 20.1%, and no debt was used. Start-up costs included a net investment of $279K. A licensing model $150K with 3% royalty fees from revenue was also considered. CONCLUSIONS: Research and information uncovered in the feasibility study supported a move to patent and license the UV sensor technology and move away from creating a new start-up. A thorough market analysis coupled with a conservative financial analysis allowed for the final decision. Five months from the start of the project, a licensing agreement was signed by INOAE and Impulsora Tack for a deal worth $500K, the first licensing agreement ever for the institute. Another first were patents for the technology, never before were any technologies patented by INOAE since its foundation in 1971. This project was made possible by a grant from the Brown Foundation.

No description available.

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Candidate: Denisa Mazouchová Supervizor: Mgr. Monika Kuchařová, Ph.D. Title of diploma thesis: Effect of ultraviolet radiation on the change the mechanical parameters of human skin This diploma thesis deals in theoretical part with the properties of human skin, the characteristics of the UV radiation and its effects on human skin. The practical part of the thesis focuses on the in vivo measurement of mechanical parameters of human skin after UV radiation. Mechanical characteristics of human skin were measured in 12 subjects before the application of UV radiation, immediately after application of UV and after 24 hours of rest skin. The experiment used a UV lamp with a wavelength of 370 nm emitted light. The monitored parameters were Hooke's and Newton's coefficients. Hooke's coefficient gives us the stiffness of the skin as a whole , Newton coefficient characterises its viscosity. For measurement of those parameters was used dynamic viscoelastomer. The experiment has been found out that no signifiant ganges of Hooke's and Newton's coefficients were not found immediately after the application of UV radiation of wavelength 370 nm, in 12 volunteers. Significant change occurred only in the...

O fascínio e a curiosidade da humanidade pela luz incentivaram a compreensão dos fenômenos que envolvem a interação matéria-energia, levando a um avanço tecnológico jamais visto antes. Com essa compreensão, atualmente é possível criar materiais com inúmeras finalidades; como na extensa área de micro e optoeletrônica; como na confecção de OLEDs e OPVs; no desenvolvimento de revestimentos inteligentes; marcadores biológicos; materiais para drug delivery; entre muitas outras aplicações. Seguindo essa perspectiva, a classe dos corantes rilênicos conhecida por naftalimidas possuem propriedades únicas que permitem a confecção dos mais diversos materiais. Desta maneira, o presente estudo sintetizou dois monômeros naftálicos inéditos derivados da 1,8-naftalimida e da 1,4,5,8-naftalenodiimida, os monômeros NI-AL e NDI-ALp. Além disso, também foram sintetizados dois copolímeros compostos por estireno-co-NI-AL e estireno-co-NDI-ALp. Para cada copolímero houve a variação da proporção estireno/comonômero, gerando, ao todo, dez copolímeros (seis de estireno-co-NI-AL e quatro de estireno-co-NDI-ALp). Os copolímeros foram analisados através de técnicas espectrométricas (1H RMN, FTIR, UV-Vis, Fluorescência, Reflectância) e cromatográficas (GPC). Os resultados indicaram que o copolímero de estireno-co-NI-AL sofre agregação devido às interações π-π, mas não há transferência de cargas entre os comonômeros. Já o copolímero estireno-co-NDI-ALp forma uma complexação no estado fundamental, deslocando a fluorescência da NDI-ALp para a região do verde e causando o surgimento de uma banda a 450 nm no espectro de UV-Vis. / The fascination and curiosity of humanity for light has stimulated the understanding of the interaction between energy and matter, leading to a technological advance never seen before. It is now possible to create materials with numerous purposes such as the extensive area of micro and optoelectronics, the manufacturing of OLEDs and OPVs, the development of intelligent coatings, biological markers, materials for drug delivery, among many others applications. Following this perspective, a class of rylene dyes known as naphthalimides have unique properties that allow the synthesis of numerous materials. In this study, two novel naphthalene allyl monomers derived from 1,8-naphthalimide and 1,4,5,8-naphthalenediimide have been synthesized, the monomers NI-AL and NDI-ALp. In addition, copolymers of styrene-co-NI-AL and styrene-co-NDI-ALp presenting different compositions were also synthesized. For each copolymer, the styrene: comonomer ratio varied, generating altogether tem copolymers (six of styrene-co-NI-AL and four of styrene-co-NDI-ALp). The copolymers were analyzed by spectrometric (1H NMR, FTIR, UV-Vis, Fluorescence) and chromatographic (GPC) techniques. The results indicated that the styrene-co-NIAL copolymer undergoes aggregation due to the π-π interactions, but there is no charge transfer between the comonomers. However, the styrene-co-NDI-ALp copolymer forms a complexation in the ground state, displacing the NDI-ALp fluorescence to the green region and causing the appearance of a band at 450 nm in the UV-Vis spectrum attributed to charge transfer complexes.

Les dommages de l’ADN interfèrent avec sa réplication et sa transcription. Ils sont en général éliminés par des mécanismes de réparation, en particulier par la réparation par excision de nucléotides (NER). Ils peuvent également être tolérés grâce à la synthèse translésionnelle (TLS). Au cours de mon travail de thèse, nous avons étudié l’implication de la voie NER et de l’ADN polymérase η (Polη) associée à la TLS dans la réponse aux lésions de l’ADN induites par les rayons ultraviolet (UV) et par une drogue chimiothérapeutique, la doxorubicine. Les principales lésions induites par les rayons UV sont les dimères de pyrimidine cyclobutane (CPDs) et les pyrimidines (6-4) pyrimidones (6-4PPs) qui sont éliminées par la NER. Les données obtenues sur la formation de régions d’ADN simple brin et celles du cycle cellulaire suggèrent que les lésions 6-4PPs sont tolérées par un mécanisme de réparation post-réplicative dans des cellules XP-C déficientes en NER (xeroderma pigmentosum du groupe C). Dans un second temps, mon objectif a été de déterminer la contribution de Polη dans la prise en charge des lésions induites par les rayons UV dans les cellules XP-C. En effet, il est connu que Polη est responsable de la réplication des CPDs, mais l’absence de Polη dans des cellules proficientes en NER ne les rend pas hypersensibles aux rayons UV. De plus, il a été suggéré que Polη soit impliquée dans la TLS des 6-4PPs. En réprimant par shARN l’expression du gène codant Polη dans les cellules XP-C, j’ai réussi à établir la première lignée stable de fibroblastes humains déficients à la fois en NER et en Polη (XP-C/PolηKD). Cette réduction fonctionnelle de l’expression de Polη dans les cellules XP-C irradiées à faible dose d’UV a entraîné un arrêt irréversible du cycle cellulaire, la génération de cassures simple- et double-brin de l’ADN et une mortalité cellulaire significative. Ces résultats montrent un rôle crucial de Polη dans la survie des cellules déficientes en NER après irradiation UV et suggèrent que Polη puisse participer aussi à la TLS des 6-4PPs.Par ailleurs, nous avons montré que les cellules déficientes en NER ou en Polη ont été sensibilisées par un traitement à la doxorubicine indiquant que la NER et Polη participent également de la prise en charge des lésions induites par cet agent. Donc au cours de mon travail de thèse, j’ai mis en évidence des interconnexions complexes entre Polη et la voie NER en réponses à différents agents génotoxiques. / DNA damages interfere with replication and transcription. They are normally eliminated by repair mechanisms, such as nucleotide excision repair (NER). They can also be tolerated by translesion DNA synthesis (TLS). During my PhD work, we studied the involvement of NER pathway and DNA polymerase η (Polη) associated with TLS in response to DNA damages induced by ultraviolet (UV) and a chemotherapeutic drug, doxorubicin.The main lesions induced by UV irradiation are cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidones (6-4PPs) which are removed by NER. Data on the formation of single-stranded DNA regions and those of the cell cycle suggest that 6-4PPs lesions are tolerated by a post-replication repair mechanism in XP-C cells (xeroderma pigmentosum group C, deficient in NER). In a second time, my goal was to determine the contribution of Polη in the tolerance of lesions induced by UV in XP-C cells. Indeed, it is known that Polη is responsible for the replication of CPDs, but in the absence of Polη, NER-proficient cells are not hypersensitive to UV rays. In addition, it was suggested that Polη is also involved in the TLS of 6-4PPs. By knocking down (KD) the expression of the gene encoding Polη in XP-C cells with a shRNA, we established the first stable line of human fibroblasts deficient in both NER and Polη (XP-C/PolηKD). This functional reduction in the expression of Polη in XP-C cells irradiated with low UVC dose resulted in an irreversible cell cycle arrest, the generation of single- and double-strand DNA breaks and significant cell death. These data demonstrate a crucial role for Polη in the survival of NER-deficient cells after UV irradiation and suggest that Polη can also participate in the TLS of 6-4PPs.In addition, we showed that cells deficient in NER or Polη are sensitized by treatment with doxorubicin indicating that NER and Polη also participate in the response of DNA damages induced by this agent.In conclusion, during my PhD work, we highlighted the complex interconnections between Polη and NER pathway in response to different genotoxic agents. / Os danos do DNA interferem com a sua replicação e transcrição. Eles são normalmente removidos por mecanismos de reparo, como o reparo por excisão de nucleotídeos (NER). Lesões não removidas também podem ser toleradas por processos específicos de síntese de translesão (TLS). Durante este trabalho de tese, estudamos a implicação da via NER e da DNA polimerase η (Polη), associada à TLS, na resposta aos danos no DNA provocados pela irradiação ultravioleta (UV) e por um agente quimioterápico, a doxorrubicina.As principais lesões provocadas pela luz UV são os dímeros de pirimidina ciclobutano (CPDs) e as pirimidinas (6-4) pirimidonas (6-4PPs) que são removidas pelo NER. Os resultados obtidos sobre a formação de regiões de DNA simples fita e os dados de ciclo celular indicam que as lesões 6-4PPs são toleradas por un mecanismo de reparo pós-replicativo em células XP-C deficientes em NER (xeroderma pigmentosum do grupo C). Em seguida, buscamos determinar a contribuição da Polη na tolerância de lesões UV em células XP-C. De fato, é conhecido que a Polη é responsável pela replicação dos CPDs, porém a ausência dessa em células proficientes em NER não as torna hypersensíveis à irradiação UV. Além disso, foi sugerido que Polη poderia estar envolvida na TLS dos 6-4PPs. A expressão do gene POLH, que codifica Polη, foi silenciada através de shRNA em células XP-C, sendo assim estabelecida a primeira linhagem estável de fibroblastos humanos deficientes em ambas proteínas XPC e Polη. Essa redução funcional da expressão de Polη em células XP-C provocou, em células irradiadas com doses baixas de luz UV, uma parada irreversível no ciclo celular, a formação de quebras no DNA (incluindo quebras simples e dupla fita) e morte celular. Esses resultados revelam um papel crucial da Polη na sobrevida das células deficientes em NER após irradiação UV e sugerem que Polη possa também participar da TLS de lesões tipo 6-4PP.Por outro lado, participei de trabalho no qual demonstramos que células deficientes em NER ou em Polη são sensibilizadas pelo tratamento com doxorrubicina, o que indica que o NER e a Polη participam da resposta aos danos induzidos por esse agente.Em conclusão, ao longo do meu trabalho de tese, eu coloquei em evidência interconexões complexas entre a Polη e o NER em resposta a diferentes agentes genotóxicos.