No presente trabalho, foi montado um sistema de eletrodifusão para o estudo dos efeitos da substituição de íons alcalinos, presentes no canal estrutural, por íons de hidrogênio (H POT. +), nas propriedades termoluminescentes e ópticas do quartzo. A corrente elétrica de eletrólise apresenta, na parte inicial de aquecimento, um ombro ou pico de corrente. Através da análise do comportamento deste pico e informações obtidas de dados de absorção óptica na região espectral do infravermelho, concluiu-se que o pico presente na curva inicial de eletrólise se deve ao complexo [AL POT. 3+/M POT. +]. As medidas de termoluminescência e absorção óptica na região espectral do visível e ultra-violeta foram feitas em amostras de quartzo eletrodifundidos e não eletrodifundidos e chegou-se à proposição de uma reação envolvendo os alcalinos presentes no canal. Nesta reação, os íons alcalinos fazem o papel de centros armadilhadores de íons de oxigênio O POT. produzidos pela radiação ionizante, e estabilizadores de vacâncias de oxigênio. O aquecimento, em tomo de 300 GRAUS C, provoca a desestabilização desses centros armadilhadores, liberando os íons alcalinos que reagem com os defeitos [ALO IND. 4] POT. 0 emitindo luz TL. Aproveitando a existência de canais estruturais, semelhantes ao quartzo, tentou-se eletrodifundir H POT + no berilo. Através de medidas de termoluminescência e corrente inicial de eletrólise, discute-se a possibilidade da existência do defeito [FE POT. 3+/M POT. +] no berilo. / A system of electrodiffusion was made in the laboratory to investigate effects of exchanging alkali ions, usually present in the structural channels by protons, in the optical and thermoluminescent properties of quartz. In the initial part of heating, the sweeping current presents a peak at about 350 GRAUS C. The analysis of the behaviour of this peak with additional data of optical absorption in the region of infrared, it was concluded that the peak at 350 GRAUS C of the current is due to [AL POT. 3+/M POT. +] system. Thermoluminescence and optical absorption spectra in the visible and ultraviolet light region for swept and unswept quartz were compared. Based on this comparison it was shown that, once irradiated to gama- or X-rays, alkali ions are removed from [AL POT. 3+/ M POT. +] and either couple to o ions or capture electron and become interstitial alkali atom, leaving, further, [ALO IND. 4] POT. 0 hole center. Heating at about 300 GRAUS C electrons from M POT 0 or M POT +O POT recombine with holes in [ALO IND. 4] POT. 0, emitting TL light, besides regrouping Al POT. 3+ and M POT. + to reform [Al POT. 3+/M POT. +] system by coulomb attraction. The electrodiffusion experiment was extended to beryl crystal, because beryl has also structural channels. To explain initial sweeping current behaviour as well as thermoluminescent property a mechanism involving [FE POT. 3+/M POT. +] system is proposed.

Motivados por trabalhos anteriores que analisaram diferentes comportamentos entre cristais e filmes policristalinos, relacionados com a cristalinidade e a concentração de impurezas, neste trabalho investigamos métodos de obtenção e processamento de filmes de haletos alcalinos dopados. Durante este trabalho foi montado um sistema de evaporação que disponibilizou a utilização de duas fontes de evaporação para a produção de amostras: resistiva e via feixe de elétrons. Apresentamos uma comparação entre resultados de caracterizações dos filmes produzidos e de monocristais existentes na literatura. A fim de se obter filmes dopados com impurezas mono e divalente e, também, duplamente dopados, alguns métodos alternativos de processamento foram investigados. A partir da comparação entre os sistemas KCl:(In +, Tl+ e Cu+) determinamos a dependência da cristalinidade em função do tamanho do íon dopante. O efeito da temperatura do substrato durante a evaporação foi investigado para o sistema KCl:Tl+, e comparado com resultados obtidos em filmes submetidos a tratamentos térmicos. Para a obtenção de filmes do sistema KCl:Yb2+:CN-, a preparação dos materiais precursores é um aspecto muito importante a ser considerado, a fim de se reproduzir nos filmes propriedades similares às dos monocristais. Nesse sentido, para evaporação foram utilizados o próprio cristal e pastilhas dos sais precursores obtidas a partir de técnicas de processamento cerâmico. A caracterização óptica dos filmes foi feita através de espectroscopia de absorção óptica e luminescência. A morfologia foi observada através de microscopia eletrônica de varredura e de força atômica, e a estrutura determinada por técnica de difração de raios X / The present work has been motivated by previous research on doped alkali halides films, that had been compared with single crystals, yielding different features, wich were related to crystallinity and impurity concentration. Preparation and processing techniques of doped alkali halides polycrystalline films have been investigated in this work. Two different evaporation sources have been used for samples production: resistive and via electron beam gun. Main results presented here are used to compare single crystals and films. In order to prepare single and double doped films, we have also tried several processing methods. From investigation of KCl:Tl+ system we have determined crystallinity dependency with impurity ion size. The KCl:Tl+ system has been used to verify the effect of substract temperature during evaporation. Results have been compared with films submited to thermal annealing. To obtain double doped KCI:Yb2+ :CN- films, we were very careful with preparation of precursor materials, since we intended to reproduce single crystals physical properties. Then, we have used single crystal itself for evaporation, besides pressed power pieces from precursor salts, obtained from ceramics processing technique. Optical absorption and photoluminescence have been carried out to perform optical characterization of evaporated films. Morphology has been observed by atomic force microscopy and scanning electron microscopy, and film structure has been observed by X-ray diffraction technique

Esta dissertação mostra a análise da interação de intersticiais pesados como oxigênio e nitrogênio em amostras policristalinas de nióbio e monocristalinas de nióbio e tânalo. Os dados experimentais foram obtidos através de medidas de atrito interno e freqüência de oscilação do pêndulo em função da temperatura, utilizando-se um pêndulo de torção invertido tipo Kê. Os resultados mostram estruturas de relaxação atribuídas à reorientação induzida por tensão de átomos intersticiais em torno de átomos da matriz metálica. Estas estruturas forma analisadas através de dois métodos: subtrações sucessivas e tempo de relaxação. A partir das medidas de atrito interno foram identificados os processos de relaxações Nb-O, Nb-N e Ta-O. Esses mesmos processos de relaxação foram confirmados por meio das medidas de freqüência de oscilação do pendulo usando um método proposto nesta dissertação, o qual relaciona o quadrado dessa freqüência medida e o inverso da temperatura. / This dissertation shows the analysis of heavy interstitials interaction, such as oxygen and nitrogen, in a policrystalline niobium sample and single crystal samples of niobium and tantalum. The experimental data were obtained by internal friction and oscillation frequency measurements as a function of temperature, using a Kê-type inverted torsion pendulum. The results show relaxation structures attributed to stress induced ordering of interstitial atoms around the mettalic matrix atoms. These structures were analysed by two methods: sucessive subtraction and relaxation time. From internal friction measurements, Nb-O, Nb-N and Ta-O relaxation processes were identified. These same relaxation processes were confirmed by oscillation frequency measurements, using a method proposed here, which relates squared frequency with inverse of temperature.

Para o desenvolvimento do tema, analisou-se a possibilidade de fixação de um conceito geral de invalidades, aplicável a todos os ramos do Direito. Tratou-se das especificidades das invalidades processuais, bem como de seu conceito e abrangência. Os principais critérios doutrinários para sistematização dos vícios dos atos processuais foram examinados como método auxiliar da elaboração da proposta de sistematização que compõe o objeto do presente estudo. A teoria das invalidades sofreu o impacto da acertada preocupação de que o processo não deve servir a seus próprios fins. Firmada essa concepção, nota-se uma dedicação à tarefa de realçar os limites deste aspecto instrumental, de modo a questionar a possibilidade de o exame da irrelevância do vício processual se dar pelo enfoque exclusivo de critérios exteriores à relação jurídica processual. Atualmente, a cláusula do devido processo legal incorpora a axiologia das garantias fundamentais do indivíduo, explicitando que são indispensáveis as garantias inerentes ao processo. A resolução da crise de direito material deve lançar efeitos sobre os vícios que acarretem transgressão de tais garantias, mas uma teoria das invalidades deve estar sustentada nos referenciais processuais, não podendo condicionar-se, exclusivamente, ao resultado final do processo, dado que lhe é externo. Assim, o enfoque classificatório adotado para sistematização dos vícios da sentença civil procura assentar-se sobre as regras e princípios do processo, notadamente porque se reconhece que o respeito ao direito material e ao direito processual equiparam-se em importância para que se obtenha uma decisão justa. A inexistência da sentença foi examinada sob os aspectos da decisão proferida em processo juridicamente inexistente ou pela ausência de seus elementos intrínsecos. Ao final, examinou-se a casuística relativa à sentença inválida, como aquela dada em processo com irregular constituição do juiz ou com defeito de fundamentação. / Aiming to develop the theme, the analysis on the possibility of setting a general concept of invalidities, applicable to all the areas of Law was analyzed. The specificities, concept and scope of procedural invalidities were addressed. The main juristic criteria used to systematize the defects of procedural acts were analyzed as an auxiliary method for preparing the systematization proposal that comprises the subject matter of this study. The theory of invalidities was impacted by the appropriate concern about the procedure not being used as means to suit its own purpose. After establishing this concept, there is the focus on underlining the limits of this instrumental aspect to question whether the possibility of the analysis on the irrelevance of the procedural defect is focused solely on criteria that is external to the procedural legal relationship. Currently, the section of the due process of law incorporates the axiology of individual fundamental guarantees, making explicit that the guarantees inherent to the procedure are fundamental. The solution for the crisis of substantive law should impact the defects that lead to the violation of such guarantees. However, the theory of invalidities should be grounded on procedural references, and not be exclusively dependent on the final result of the process, since such theory is external to it. Accordingly, the focus on classification adopted to systematize the defects of the civil judgment intends to have as base the rules and principles of the process, since it is known that the respect toward substantive law and procedural law are of equal importance in reaching a just decision. The inexistence of the judgment was reviewed based on the aspects of the decision granted in a process that does not exist in legal terms or by the absence of its intrinsic elements. Finally, there was the analysis of case histories related to the invalid judgment, such as the judgment of a procedure with irregular constitution of the court or with defect of reasons.

Yeung Sau-Man. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (leaves 139-172). / Abstracts in English and Chinese. / Title page --- p.i / Acknowledgements --- p.ii / Table of Content --- p.iv / List of Figures --- p.viii / List of Graphs --- p.x / List of Tables --- p.xi / Abbreviations --- p.xiv / Abstract --- p.xv / Chinese Abstract --- p.xvii / Chapter Chapter 1 --- General Introduction --- p.1 / Chapter 1.1 --- Diabetes Mellitus --- p.2 / Chapter 1.1.1 --- Type 1 diabetes mellitus --- p.3 / Chapter 1.1.2 --- Type 2 diabetes mellitus --- p.5 / Chapter 1.1.3 --- Maturity onset diabetes of the young (MODY) --- p.6 / Chapter 1.1.4 --- Gestational diabetes --- p.7 / Chapter 1.2 --- Effect of Diabetes on Pregnancy --- p.9 / Chapter 1.3 --- Suggested Causes of Diabetic Embryopathy --- p.10 / Chapter 1.3.1 --- Glucose --- p.10 / Chapter 1.3.2 --- Ketone bodies --- p.11 / Chapter 1.3.3 --- Somatomedin inhibitors --- p.12 / Chapter 1.3.4 --- TNF-α --- p.12 / Chapter 1.3.5 --- Oxidative stress --- p.13 / Chapter 1.4 --- Animal Model of Diabetes --- p.15 / Chapter 1.4.1 --- Chemically-induced --- p.15 / Chapter 1.4.2 --- Mutants --- p.17 / Chapter 1.5 --- Gene-teratogen Interaction under Diabetic Pregnancy --- p.19 / Chapter 1.6 --- Strategy of the Thesis --- p.21 / Chapter Chapter 2 --- General Materials and Methods --- p.24 / Chapter 2.1 --- Mouse Maintenance and Mating Method --- p.25 / Chapter 2.2 --- Induction of Diabetes --- p.25 / Chapter 2.3 --- Preparation of All-trans Retinoic Acid --- p.26 / Chapter 2.4 --- Dissection of Embryos --- p.26 / Chapter 2.5 --- DNA Extraction from Yolk Sac for Genotyping --- p.27 / Chapter 2.6 --- Genotyping of Embryos --- p.28 / Chapter 2.7 --- Preparation of RNA Probes for In Situ Hybridization --- p.29 / Chapter 2.7.1 --- Mini-scale preparation of plasmid DNA --- p.29 / Chapter 2.7.2 --- Linearization of plasmid DNA --- p.30 / Chapter 2.7.3 --- In vitro transcription --- p.31 / Chapter 2.8 --- Whole Mount In Situ Hybridization --- p.33 / Chapter 2.8.1 --- Fixation and dehydration of embryos --- p.33 / Chapter 2.8.2 --- Hybridization --- p.33 / Chapter 2.8.3 --- Post-hybridization wash --- p.34 / Chapter 2.8.4 --- Antibody wash and color development --- p.35 / Chapter 2.8.5 --- Embryo powder preparation --- p.36 / Chapter 2.8.6 --- Pre-absorption of antibody --- p.35 / Chapter 2.9 --- Whole Mount TUNEL Staining --- p.36 / Chapter Chapter 3 --- "Maternal Diabetes, Sp2H and RA Interaction" --- p.39 / Chapter 3.1 --- Introduction --- p.40 / Chapter 3.1.1 --- Neural tube defects --- p.41 / Chapter 3.1.2 --- Retinoic acid as environmental factor --- p.41 / Chapter 3.1.3 --- Sp2H as genetic factor --- p.44 / Chapter 3.1.4 --- Experimental design of this chapter --- p.46 / Chapter 3.2 --- Material and Methods --- p.47 / Chapter 3.2.1 --- Sp2H mice --- p.47 / Chapter 3.2.2 --- Mating and RA injection protocol --- p.47 / Chapter 3.2.3 --- Dissection of fetuses and analysis of neural tube development --- p.48 / Chapter 3.3 --- Results --- p.49 / Chapter 3.3.1 --- Maternal diabetes alone --- p.50 / Chapter 3.3.2 --- Sp2H mutation alone --- p.51 / Chapter 3.3.3 --- RA alone --- p.52 / Chapter 3.3.4 --- Maternal diabetes and RA interaction --- p.53 / Chapter 3.3.5 --- Sp2H mutation and RA interaction --- p.55 / Chapter 3.3.6 --- Sp2H mutation and maternal diabetes interaction --- p.57 / Chapter 3.3.7 --- "Maternal diabetes, Sp2H mutation and RA interaction" --- p.59 / Chapter 3.4 --- Discussion --- p.62 / Chapter 3.4.1 --- Maternal diabetes alone does not cause neural tube defects --- p.62 / Chapter 3.4.2 --- RA induces neural tube defects --- p.63 / Chapter 3.4.3 --- Interaction of maternal diabetes with RA in increasing the susceptibility to neural tube defects --- p.64 / Chapter 3.4.4 --- Embryos with Sp2H allele show increased susceptibility to neural tube defects when triggered by maternal diabetes and RA --- p.67 / Chapter Chapter 4 --- Molecular and Cellular Bases of Interaction --- p.71 / Chapter 4.1 --- Introduction --- p.72 / Chapter 4.1.1 --- Mechanism of diabetic embryopathy --- p.72 / Chapter 4.1.2 --- Mechanism of Sp2H mutation in development of neural tube defects --- p.74 / Chapter 4.1.3 --- Mechanism of RA teratogenicity --- p.75 / Chapter 4.1.4 --- "Possible common pathways shared by maternal diabetes, RA and Sp2H mutation" --- p.76 / Chapter 4.1.5 --- Experimental design of this chapter --- p.78 / Chapter 4.2 --- Materials and Methods --- p.80 / Chapter 4.2.1 --- Sample collection for studying Pax3 expression in Sp2H/+ And +/+ embryos in response to maternal diabetes or RA by whole mount in situ hybridization --- p.80 / Chapter 4.2.2 --- "Sample collection for studying the level of apoptosis in response to the interaction of maternal diabetes, Sp2H mutation and RA by whole mount TUNEL staining" --- p.82 / Chapter 4.3 --- Results --- p.86 / Chapter 4.3.1 --- Expression levels of Pax3 mRNA detected by whole mount in situ hybridization / Chapter 4.3.1.1 --- Expression of Pax3 in Sp2H/+/- and +/+ embryos --- p.86 / Chapter 4.3.1.2 --- Effect of maternal diabetes on Pax3 expression in Sp2H/+ and +/+ embryos --- p.87 / Chapter 4.3.1.3 --- Effect of RA on Pax3 expression in Sp2H /+ and +/+ embryos --- p.88 / Chapter 4.3.2 --- Level of apoptosis detected by whole mount TUNEL --- p.89 / Chapter 4.3.2.1 --- Effect of Sp2H allele on apoptosis --- p.94 / Chapter 4.3.2.2 --- Effect of maternal diabetes on apoptosis in Sp2H/+ and +/+ embryos --- p.95 / Chapter 4.3.2.3 --- Effect of RA on apoptosis in Sp2H/+ and +/+ embryos --- p.96 / Chapter 4.3.2.4 --- Effect of maternal diabetes and RA on apoptosis in Sp2H/+ and +/+ embryos --- p.97 / Chapter 4.4 --- Discussion --- p.99 / Chapter 4.4.1 --- Underexpression of Pax3 and increases in apoptosis under maternal diabetes --- p.99 / Chapter 4.4.2 --- "RA does not down regulate Pαx3, but increases apoptosis" --- p.102 / Chapter 4.4.3 --- Interaction of maternal diabetes and RA in increasing apoptosis --- p.104 / Chapter Chapter 5 --- "Maternal Diabetes, NOD and RA Interaction" --- p.108 / Chapter 5.1 --- Introduction --- p.109 / Chapter 5.1.1 --- Diabetic embryopathy in NOD mice --- p.109 / Chapter 5.1.2 --- Experimental design of this chapter --- p.110 / Chapter 5.2 --- Materials and Methods --- p.112 / Chapter 5.2.1 --- NOD mice --- p.112 / Chapter 5.2.2 --- Mating and RA Injection Protocol --- p.112 / Chapter 5.2.3 --- Sample Collection for the Study of Pax3 Expression --- p.113 / Chapter 5.3 --- Results --- p.115 / Chapter 5.3.1 --- Maternal diabetic alone --- p.116 / Chapter 5.3.2 --- NOD mutation alone --- p.117 / Chapter 5.3.3 --- RA alone --- p.118 / Chapter 5.3.4 --- Maternal diabetes and RA interaction --- p.119 / Chapter 5.3.5 --- NOD mutation and RA interaction --- p.121 / Chapter 5.3.6 --- NOD mutation and maternal diabetes interaction --- p.123 / Chapter 5.3.7 --- "Maternal diabetes, NOD mutation and RA interaction" --- p.125 / Chapter 5.3.8 --- Expression of Pax3 in embryos with different copies of NOD alleles --- p.128 / Chapter 5.4 --- Discussion --- p.130 / Chapter 5.4.1 --- Maternal diabetes interacts with NOD mutation to increase susceptibility to neural tube defects --- p.130 / Chapter 5.4.2 --- Interaction of maternal diabetes with NOD mutation is greatly exacerbated when exposed to RA --- p.131 / Chapter 5.4.3 --- Pax3 is not involved in the interaction --- p.133 / Chapter Chapter 6 --- Conclusion and Future Perspectives --- p.134 / References --- p.139 / Figures / Graphs

Chronic lymphocytic leukaemia (CLL) is the most common adult leukaemia, and despite recent introduction of targeted therapies, remains incurable. An important hallmark of CLL is severe immune deficiency, including the failure to mount effective anti-tumour immune responses. This can partly be explained by insufficient antigen presentation, but also by the existence of complex CLL-induced T-cell defects. Based on the cancer immuno-editing hypothesis that the immune system not only protects a host against tumour formation but can also be compromised to actively provide a pro-tumour microenvironment, modulating cancer-induced T-cell defects could restore the full anti-tumour response and result in more durable clinical responses. The immune checkpoint molecules PD-1 (expressed on activated immune effector cells) and PD-L1 (expressed on antigen-presenting and microenvironmental cells including tumour cells) have emerged as important mediators of T-cell suppression. Several studies suggest that PD-L1/PD-1 inhibitory signalling in CLL might be overcome by the immune modulatory drug lenalidomide. Furthermore, directly targeting PDL-1/PD-1 interactions produces significant responses in solid cancers. However, similar studies are notably absent in CLL, and the effect of PDL-1/PD-1 blockade on restoring cancer-induced immune dysfunction is not understood. Transgenic Eμ-TCL1 mice have been extensively validated as an adequate preclinical model of aggressive human CLL, and our group showed their suitability to mirror T-cell defects observed in human CLL. Using the Eμ-TCL1 model, this dissertation project substantially extends our previous characterization of CLL-induced T-cell dysfunction and evaluates the functional impact of PD-L1/PD-1 inhibitory signalling both in parallel with disease development and in different microenvironments. The findings to be described here demonstrate that developing CLL is associated with specific T-cell subset alterations, phenotypic changes, and functional defects that are very similar in peripheral blood and secondary lymphoid organs. In addition to PD-L1, PD-L2 is identified as a potential mediator of inhibitory signalling in CLL. CD8+ T cells in leukaemic mice are characterised as a functionally heterogeneous population, in which subsets of cells are able to exert effector functions despite PD-1 expression. In vivo lenalidomide treatment repairs selected phenotypic alterations and immune synapse formation, and a PD-L1 IgG blocking antibody effectively controls disease and reverses global T-cell defects even in cells expressing PD-1. In sum, this work provides a strong rationale to explore PD-L1/PD-1 targeting in CLL clinical trials, potentially in combination with novel agents.

Typescript (photocopy). / Digitized by Kansas Correctional Industries

O objetivo desta pesquisa foi avaliar a reparação de defeitos de furca classe II em cães tratados com o retalho deslocado coronariamente, sozinho ou em associação com a regeneração tecidual guiada e o enxerto de tecido reparativo de alvéolos utilizando uma análise imuno-histoquímica. Os defeitos foram criados nos 2os, 3os e 4os pré-molares direitos e esquerdos mandibulares em quatro cães sem raça definida. No lado teste de cada cão, após a instrumentação radicular, os defeitos foram enxertados com o tecido reparativo, removidos de locais de extração dental com cinco dias de reparação. As áreas cirúrgicas foram recobertas com membranas absorvíveis e o retalho deslocado coronariamente suturado. No lado controle, após a instrumentação radicular, o retalho também foi deslocado coronariamente e suturado. Após 45 dias os cães foram sacrificados. As análises imuno-histoquímicas para osteonectina, osteopontina e sialoproteína óssea foram feitas no plano vestíbulo-lingual das furcas dos 3os pré-molares. As marcações imuno-histoquímicas foram similares entre os grupos demonstrando que eles provavelmente estavam em um estágio reparativo semelhante. / The aim of this research was to evaluate the repair of class II furcation defects in dogs treated with the coronally positioned flap alone or in association with guided tissue regeneration and post extraction tissue graft using an immunohistochemical analysis. The defects were created on the lower jaw right and left 2nd, 3rd and 4th premolars on four mongrel dogs. On the test side of each dog, after root instrumentation, the defects were grafted with a alveolar socket reparative tissue removed from five days healing teeth extraction sites. The surgical areas were covered with absorbable membranes and a coronally positionated flap was sutured. At the control side, after root instrumentation the coronally positionated flap was sutured. After 45 days, the dogs were sacrificed. The immunohistochemical analyses for osteonectin, osteopontin and bone sialoprotein were done on the bucal-lingual plane extent of the 3rd premolars furcations. The immunohistochemical expressions were similar among the two groups showing that they probably were in a similar healing stage.

Thesis. 1977. Ph.D.--Massachusetts Institute of Technology. Dept. of Electrical Engineering and Computer Science. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND ENGINEERING. / Bibliography : p. 185-189. / by Robert J. Woodham. / Ph.D.

Thesis. 1976. M.S.--Massachusetts Institute of Technology. Dept. of Ocean Engineering. / Microfiche copy available in Archives and Engineering. / Includes bibliographical references. / M.S.