The amyloid beta peptide particularly the 40 and 42 amino acid residues are the responsible for plaque formation in Alzheimer's disease (AD) patients. Extra cellular plaque formation has been recognized after incessant investigations along with the formation of intracellular tau protein tangles as the hallmarks of AD. Furthermore, the plaque formation has been linked mostly as a cause of the disease and the tangles mostly as a consequence. Our investigation is focused on studying the formation of AD plaques. The amyloid beta (A[beta]) is a physiological peptide secreted from neurons under normal conditions, along with other soluble forms cleaved from the amyloid precursor protein (APP). These soluble forms of APP have neuroprotective and neurotrophic functions, while the A[beta] is considered an unwanted by-product of the APP processing. Under normal conditions there is an anabolic/catabolic equilibrium of the A[beta] peptide; therefore, it is believed that the formation of the plaque does not take place. On the other hand, the neurons' surface may play an important role in the adhesion mechanisms of the A[beta] peptide. Our experiments show that the neuron surfaces along with the media conditions may be the most important causes for progressive formation of plaques. We have incubated rigid supports (mica) and soft biomimetic substrates (lipid bilayers on top of a PEG cushion layer drafted onto a silica surface) with the three different conformations of the A[beta] peptide (monomeric, oligomeric and fibrils structures) to determine the adhesion mechanisms associated with in situ plaque formation. The soft biomimetic substrates have been assembled first by depositing and activating a thin film of silica (i.e., to create surface silanol groups). This film is then reacted with polyethylene glycol (PEG), which is a biocompatible polymer, to create a cushion-like layer that supports and allows the lipid bilayer to have high mobility. A lipid bilayer is then deposited on this soft support to reproduce a cell membrane using the Langmuir Blodgett deposition technique. The characterization of such biomimetic membranes has been studied by using Atomic Force Microscopy (AFM) in liquid environments. Our results show that these lipid bilayers are highly mobile. Additionally the structure and topography characteristics of the A[beta] conformations have been followed with atomic force microscopy (AFM). The kinetics and rates of adhesion have been measured with attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. Our results show the progress of the plaques' formation with time where simple monomers deposit on the substrates and allow the development of oligomeric species.

This dissertation shows the performance of adaptive waveforms when applied to two radar applications. One application is automatic target recognition (ATR) and the other application is range-Doppler ambiguity mitigation. The adaptive waveforms are implemented via a feedback loop from receiver to transmitter, such that previous radar measurements affect how the adaptive waveforms proceed. For the ATR application, adaptive transmitter can change the waveform's temporal structure to improve target recognition performance. For range-Doppler ambiguity mitigation application, adaptive transmitter can change the pulse repetition frequency (PRF) to mitigate range and Doppler ambiguity. In the ATR application, commercial electromagnetic software is used to create high-fidelity aircraft target signatures. Realistic waveform constraints are applied to show radar performance. The radar equation is incorporated into the waveform design technique and template-based classification is performed. Translation invariant feature is used for inaccurately known range scenario. The performance of adaptive waveforms is evaluated with not only a monostatic radar, but also widely separated MIMO radar. In MIMO radar, multiple transmit waveforms are used, but spectral leakage caused by constant-modulus constraint shows minimal interference effect. In the range-Doppler ambiguity mitigation application, particle-filter-based track-before-detect for a single target is extended to track and detect multiple low signal-to-noise ratio (SNR) targets, simultaneously. To mitigate ambiguity, multiple PRFs are used and improved PRF selection technique is implemented via predicted entropy computation when both blind and clutter zones are considered.

A broadband coupling approach applied to a single mode, sol-gel, planar integrated optical waveguide (IOW) was used to create a multichannel attenuated total reflection (ATR) spectrometer. Initial attempts to create an achromatic coupling element for sol-gel waveguides, based upon previous work applied to vacuum deposited glass devices, did not lead to an easily achievable design. Instead a simplified, non-achromatic approach based upon impinging an incident light beam with a large numerical aperture onto an incoupling prism was used. This simplified broadband coupling approach was used to create a sol-gel IOW-ATR spectrometer that transmitted light down to at least 400 nm, and produced a measurable bandwidth of ~ 250 nm; both phenomena are marked improvements upon the capabilities of previously reported devices. An experimental demonstration of this device proved it capable of measuring the visible spectrum of a thin film of horse heart cytochrome c adsorbed to the sol-gel surface at a submonolayer coverage. The broadband spectral capabilities of this sol-gel device were also used to experimentally validate a new method for determining the angular orientation of molecules bound to an arbitrary waveguide surface. In addition to the sol-gel IOW work, the simplified broadband coupling approach was applied to a previously reported multilayered electroactive waveguide device, which was used to collect electrically modulated, broadband spectra for thin films of cytochrome c, as well as a dicarboxyferrocene moiety. Both of these IOW-ATR spectrometers represent improved tools for probing the near-surface chemical environments of molecular assemblies.

The aim of the research is to examin the specialists from the Early Rehabilitation services (ERS) and the patients parents‘ attitude towards services for children quality, and introduce recommendations how to improve parents‘ and specialists‘ cooperation while accomplishing the services for children. Methodology. The anonymous questioning was made with 100 parents whose children were visiting specialists of Early Rehabilitation in 3 public medical institutions in Kaunas. The questionnaire used in the research was composed on the base of SERVQUAL methodology. One part of the questionnaire gave possibility to find parents‘ expectations towards servises for children quality, the next part satisfaction in services they get. The evaluation was made in differences which are in parents‘ expectations and satisfaction in the quality of servises they get in the aspect of dimensions (evidence, response, security, empathy). Linkert scale was used for answers. The statistical package SPSS version 13.0 for Windows was used to conduct data analysis. Results. In parent‘s opinion, services quality expectations got less point (mean score 2,80±0,44) than their satisfaction of the service provided (mean score 2,80±0,44) Therefore, the satisfaction of the service provided by ERS was beyond expectations. The largest quality gap was observed in the response, the smallest – in the dimensions of evidence. The parents‘ expectations were: to consult specialists of ERS at the desirable time... [to full text]

No description available.

Au cours de ma thèse au sein du laboratoire du Professeur Michelle Debatisse, je me suis intéressé aux mécanismes maintenant la stabilité du génome et contrôlant la dynamique de réplication dans les cellules de mammifères. J'ai étudié le rôle des kinases ATR (" Ataxia Telangectasia and Rad3 related ") et Chk1 (" Checkpoint Kinase 1 "), du point de contrôle intra-S (" checkpoint "), dans le contrôle de la dynamique de réplication. Cette première étude m'a amené à étudier la relation entre les dommages à l'ADN et la dynamique de réplication, dans des modèles cellulaires déficients pour des facteurs de la réponse aux dommages à l'ADN (DDR), appartenant soit au " checkpoint ", soit à la voie de réparation par recombinaison homologue (HR), tels que Rad51 et BRCA2. Je montre ici, que le ralentissement des fourches de réplication et l'augmentation de la densité d'événements d'initiation, observés dans des cellules déficientes pour Chk1 ou Rad51, sont la conséquence indirecte des lésions apparaissant spontanément dans de telles cellules. Le ralentissement des fourches dans ces cellules dépend d'une perturbation de la disponibilité en précurseurs de nucléotides qui dépend de la sur-expression et/ou de la re-localisation de la sous-unité p53R2 de la ribonucléotide réductase (RNR). De plus, contrairement à ce qui était proposé, je montre que Chk1 n'a pas de rôle actif dans la répression des origines latentes, mais que c'est la vitesse des fourches qui détermine l'espacement entre les origines actives, par un mécanisme de compensation découvert auparavant au laboratoire (Anglana, 2003 ; Courbet, 2008). L'ensemble de mes résultats permet de proposer un mécanisme général de communication entre la réplication et la réparation. Ce mécanisme confère un avantage aux cellules, puisque le ralentissement des fourches stabilise la machinerie de réplication qui voyage sur une matrice endommagée, et l'activation d'origines latentes procure une source de sauvetage pour les fourches bloquées.

Frankfurt (Main), Universiẗat, Diss., 2008.

Ewing Sarcoma (ES) is an aggressive pediatric solid tumor. Even though overall-survival for localized patients is approximately 70%, the overall-survival for high risk ES patients has not improved in the last 20 years. Therefore, there is a need for exploration of new therapeutic agents in ES. Recent evidence has demonstrated that ES cells behave like BRCA-deficient tumor types which renders them sensitive to PARP inhibitors in vitro and in vivo. However, a phase II study of the efficacy of single-agent PARP inhibition in patients with relapsed ES did not significantly improve outcome. As single-agent therapy is rarely expected to result in significant clinical responses, in this study, we plan to validate potential targeted combination therapies with PARP inhibitors in ES. Since ES appears to demonstrated BRCA-deficient biology with impaired homologous recombination, cells are expected to be sensitive to both PARP inhibitors and ATR inhibitors, drugs which have a role in regulating DNA damage and impairing homologous recombination. In breast cancer and ovarian cell lines with genetic BRCA-deficiency, PARP and ATR inhibitors have synergistic activity. We hypothesize that these inhibitors will also have synergistic anti-Ewing activity. Furthermore, we recognize that ES cells demonstrate remarkably quiet genomes suggesting that there is minimal ongoing DNA-damage when cells are growing unperturbed. Therefore, we also plan to test the effect of adding low-dose genotoxic chemotherapy to induce additional sensitivity to the combination of PARP and ATR inhibitors in ES. The specific aims of this study were to explore the possible anti-tumor effect of PARP inhibitors combined with ATR inhibitors in ES cell lines, and to explore whether low dose genotoxic chemotherapy with SN38 can potentiate the anti-tumor effect of combined PARP and ATR inhibition in ES cell lines. We studied the anti-Ewing Sarcoma effect of the combination of a PARP inhibitor, AZD2281, and an ATR inhibitor, AZD6738, across a range of doses with and without low doses of a DNA damaging agent, SN38 (irinotecan metabolite), in two ES cell lines. We analyzed synergy by determining the Combination Index (CI) and Fractional Inhibition (FA) of each combination. We found that the ATR inhibitor, AZD6738, was synergistic across large range of concentrations when combined with the PARP inhibitor, AZD2281, in ES cell lines. We also found that treatment of cells with low doses of SN38 increases ES cell sensitivity to treatment with the PARP inhibitor and ATR inhibitor combination. This study provides preclinical support for additional studies exploring these combinations in ES. Given the low number of pediatric patients with ES compared to adult cancer patients, there will be limited attempts in combining these agents in clinical trials. Therefore, the development of an in vivo trial testing the safety and efficacy of this combination in ES mouse models is proposed. / 2020-07-03T00:00:00Z

Submitted by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2016-01-06T18:54:10Z No. of bitstreams: 2 license_rdf: 22974 bytes, checksum: 99c771d9f0b9c46790009b9874d49253 (MD5) mayara_rodrigues_lessa.pdf: 2887620 bytes, checksum: 65d145401884724e28b09bbc9441aa53 (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2016-01-07T11:52:11Z (GMT) No. of bitstreams: 2 license_rdf: 22974 bytes, checksum: 99c771d9f0b9c46790009b9874d49253 (MD5) mayara_rodrigues_lessa.pdf: 2887620 bytes, checksum: 65d145401884724e28b09bbc9441aa53 (MD5) / Made available in DSpace on 2016-01-07T11:52:11Z (GMT). No. of bitstreams: 2 license_rdf: 22974 bytes, checksum: 99c771d9f0b9c46790009b9874d49253 (MD5) mayara_rodrigues_lessa.pdf: 2887620 bytes, checksum: 65d145401884724e28b09bbc9441aa53 (MD5) Previous issue date: 2014 / O caf? torrado e mo?do encontrado no mercado interno ? comercializado sob diferentes marcas, que trazem consigo uma heterogeneidade quanto ao aroma, sabor e at? o grau de torra??o. Esta diversidade de caracter?sticas est? associada a v?rios fatores, entre eles a origem dos gr?os de caf?. Considerando essas varia??es relatadas na literatura, o presente trabalho teve como objetivo realizar uma pesquisa da composi??o qu?mica e f?sico-qu?mica de caf?s comerciais em diferentes cidades da Regi?o Sudeste do Brasil. Cinquenta e oito pacotes de 250 gramas, de caf?s torrados e mo?dos acondicionados em embalagem do tipo almofada e/ou ? v?cuo foram adquiridos em diferentes cidades dos quatro Estados da Regi?o Sudeste do Brasil. Todos os produtos estavam dentro do prazo de validade e aproximadamente 58% das marcas apresentavam o selo de pureza da ABIC, enquanto 22% das marcas apresentavam o selo de qualidade da Associa??o Brasileira da Ind?stria de Caf?. As amostras foram levadas para o Laborat?rio de Tecnologia de Biomassas do Cerrado da Universidade Federal dos Vales do Jequitinhonha e Mucuri, onde foram realizadas as avalia??es de pH cujo resultado m?dio foi 5,95; acidez total titul?vel 15,03 ? 1,07(v/m)%; s?lidos sol?veis totais 1,15 ?Brix; ?ndice de colora??o com m?dia para os valores de L* de 28,87 ? 0,29, para os valores de a* de 8,99 ? 0,10 e para os valores de b* de 2,84 ? 0,21; os compostos fen?licos obtiveram uma m?dia de 4,1152 ? 0,4863 g.100g-1 e a m?dia dos flavonoides de 0,5042 ? 0,0291 g.100g-1. Os m?todos multivariados de an?lise, associados aos m?todos usando a espectroscopia na regi?o do infravermelho tem tido grandes avan?os com diversas aplica??es nas an?lises de alimentos. Com este intuito, utilizou-se a espectroscopia na regi?o do infravermelho para delinear os grupos funcionais mais representativos nas amostras de caf? analisadas com a inten??o de agrup?-las por similaridade atrav?s da estat?stica multivariada. Os resultados permitiram visualizar que poucos grupos foram formados utilizando as an?lises f?sico-qu?micas, para classificar as amostras. A An?lise das Componentes Principais foi capaz de acumular 61,98% de vari?ncia nas duas primeiras componentes e os grupos formados foram confirmados pela An?lise Hier?rquica por Agrupamento. Em rela??o aos espectros de infravermelho, as amostras foram mais agrupadas com a An?lise das Componentes Principais acumulando 41,76% da vari?ncia, os grupos das amostras foram confirmados pela An?lise Hier?rquica por Agrupamento. / Disserta??o (Mestrado) ? Programa de P?s-Gradua??o em Qu?mica, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2014. / ABSTRACT The roast and ground coffee found in the domestic market is sold under different brands that carry with them a heterogeneity for aroma, flavor and even the degree of roasting. This diversity of characteristics is associated with several factors, including the origin of the coffee beans. Considering these variations reported in the literature, the present study aimed to perform a search of the chemical and physico-chemical composition of commercial coffees in different cities in Southeastern Brazil. Fifty-eight packages of 250 grams of roasted and ground coffee packaged in packaging the type pad and / or vacuum were acquired in different cities of the four states of southeastern Brazil. All products were within the validity period and approximately 58% of brands had the seal of purity of ABIC, while 22% of brands had the seal of the Brazilian Association of Coffee Industry Samples were taken for Laboratory Technology Biomass of the Cerrado, Federal University of the Jequitinhonha and Mucuri, which were conducted evaluations of pH where the average yield around 5.95; titratable acidity 15.03 ? 1.07 (v / m)%; total soluble solids 1.15 ? Brix; staining index and the average for the values ??of L * was 28.87 ? 0.29 for the a * values ??was 8.99 ? 0.10 and b * values ??were 2.84 ? 0.21 ; phenolic compounds were obtained an average of 4.1152 ? 0.4863 g.100g-1 and the average of flavonoids was 0.5042 ? 0.0291 g.100g-1. The multivariate analysis methods, associated with methods using spectroscopy in the infrared region has taken great strides with several applications in food analysis. For this purpose, we used spectroscopy in the infrared region to delineate the most representative functional groups in coffee samples analyzed with the intention of grouping them by similarity using multivariate statistics. The results allowed us to visualize that few groups were formed using the physicochemical analyzes to classify the samples. The Principal Component Analysis was able to accumulate 61.98% of variance in the first two components and the groups formed were confirmed by Hierarchical Cluster Analysis. Regarding the infrared spectra of the samples were further grouped with the Principal Component Analysis accumulating 41.76% of the variance, the groups of samples were confirmed by Hierarchical Cluster Analysis.

As células a combustível de etanol direto (DEFCs, Direct Ethanol Fuel Cells) são baseadas na eletro-oxidação do etanol à baixa temperatura e necessitam catalisadores à base de metais nobres, devido à cinética mais lenta para as reações de oxi-redução. Entre os catalisadores, a platina e as ligas de platina são os mais utilizados. Materiais para suportar os catalisadores são necessários a fim de reduzir a carga do mesmo empregada. Um dos suportes de catalisadores mais versáteis é o carvão ativado, e um dos mais utilizados tem sido o carvão mineral Vulcan. Recentemente, estudos têm sido realizados sobre a madeira como material precursor de carvão ativado, devido à sua sustentabilidade e também porque os materiais carbonosos obtidos têm excelentes propriedades finais. No presente trabalho, estudou-se a reação de eletro-oxidação do etanol, de catalisadores à base de Pt e PtSn suportados em biocarvões obtidos a partir da madeira Eucalyptus grandis. No início desse trabalho não havia relatos na literatura sobre o uso de carvões ativados obtidos a partir de madeira de Eucalyptus grandis como precursor. Foram utilizados dois métodos de ativação nos suportes, ativação física com CO2 e ativação química com ZnCl2. Os suportes de catalisadores foram caracterizados por análise textural, análise elementar, análise termogravimétrica e por espectroscopia de infravermelho. As técnicas empregadas para a caracterização dos catalisadores foram espectrometria de retroespalhamento de Rutherford (RBS), difração de raios-X (DRX), análise termogravimétrica (TGA), microscopia eletrônica de transmissão (MET), voltametria cíclica (VC) e caracterização espectroeletroquímica (ATR-FTIR in-situ). Os biocarvões apresentaram áreas superficiais maiores e tamanhos de poros menores do que o carvão Vulcan, independente do tratamento. A natureza do suporte influenciou nas características morfológicas dos eletrocatalisadores preparados. Com base nos resultados obtidos os catalisadores suportados nos suportes com ativação química apresentaram os melhores resultados de densidade de corrente para eletro-oxidação do etanol, com exceção do catalisador PtSn suportado no biocarvão ativado fisicamente (PtSn/BCAF). Pode-se dizer que os biocarvões são adequados para aplicações em células de combustível, podendo substituir o uso de suportes baseados em carvões minerais. A eletro-oxidação do etanol nos eletrocataliadores de PtSn nos carvões ativados ocorre principalmente através da produção de acetaldeído e ácido acético. / Direct ethanol fuel cells (DEFC) are based on ethanol electrooxidation at low-temperature and they require noble metal based catalysts, due to the slower kinetic of redox reactions. Among the catalysts, platinum and its alloys have been the most widely used. Catalysts support materials have been employed with the intent to reduce loading catalyst. One of the most versatile catalyst supports is activated carbon, and one of the most widely used is the Vulcan®, a mineral carbon. Currently, different studies have been conducted concerning wood as activated carbon precursor, because of its sustainability and its properties, like suitable porous texture, surface area and surface chemistry. In this work, it was studied ethanol electrooxidation reaction on Pt and PSn catalysts supported on biocarbon. Biocarbons were obtained from Eucalyptus grandis. Literature reports the use of carbon materials as catalyst support, however focused on carbon fibers and carbon nanotubes, without any precedent on the use of activated carbon obtained from Eucalyptus grandis until the start of this work. The carbon supports were obtained by physical activation using CO2, and chemical activation with ZnCl2. Catalyst support characterization boarded elemental analysis, texture analysis, thermogravimetric analysis and infrared spectroscopy. Techniques employed for the catalyst characterization were Rutherford backscattering spectrometry (RBS), X-ray diffraction (XRD), thermogravimetric analysis (TGA), transmission electron microscopy (TEM), cyclic voltammetry (CV) and spectroelectrochemical characterization (ATR-FTIR in situ). Biocarbons presended the higher surface areas and smallest pore size than the Vulcan ones, independent of the treatment. The support nature influenced on the catalyst morphology. Results showed that the catalyst on the chemically activated supports presented the best current density for ethanol electro-oxidation, except for the PtSn on the physically activated biocarbon (PtSn/BCAF). Biocarbons resulted adequate for fuel cell applications and are capable of substituting the conventional supports based on mineral carbon. Ethanol electro-oxidation on PtSn catalysts takes place through the production of acetaldehyde and acetic acid reaction mechanism.