Thesis (Ph.D. (Nutrition))--North-West University, Potchefstroom Campus, 2009.

The oxidative dissolution of chalcopyrite in ferric media often produces incomplete copper recoveries. The incomplete recoveries have been attributed to inhibition caused by the formation of a metal deficient sulphide and the deposition of elemental sulphur and jarosite. Although these phases have been qualitatively identified on the surface of chalcopyrite, none have been quantitatively identified. The aim of the project was to quantitatively analyse the surface before and after oxidative dissolution, with X-ray photoelectron spectroscopy (XPS), and to use the phases identified as the basis for mechanisms of dissolution and inhibition. / XPS analysis was performed on chalcopyrite massive fractured under anaerobic atmosphere and chalcopyrite massive and concentrate oxidised in 0.1 M ferric sulphate (pH 1.9) and 0.2 M ferric chloride (pH 1.6) at 50, 65 and 80ºC. Quantitative XPS analysis of the chalcopyrite surfaces required the development of programs that accounted for the observed XPS spectra. The output of these programs was used to construct profiles of the chalcopyrite surfaces and the deposited phases. These surface profiles were correlated with copper recoveries determined for chalcopyrite concentrate dissolution under the same conditions. / The surface of chalcopyrite before oxidative dissolution reconstructs to form a `pyritic' disulphide phase. This phase is oxidised in ferric media to form thiosulphate via the incorporation of oxygen atoms from the hydration sphere. The thiosulphate reacts in the oxidising conditions of low pH to form elemental sulphur, sulphite and sulphate. The sulphate complexes with ferric to produce hydronium jarosite. This reaction occurs at the surface during the initial stages of dissolution and in the bulk solution during the latter stages. This precipitation of hydronium jarosite during the latter stages of dissolution corresponds to inhibition of the dissolution reaction. It is therefore concluded hydronium jarosite is responsible for inhibiting the oxidative dissolution of chalcopyrite in ferric media. / The identification of hydronium jarosite as the inhibiting phase is consistent with the industrial practice of removing `excess' iron from the ferric solution before oxidative dissolution. However, additional iron and sulphate are generated at the chalcopyrite surface during oxidative dissolution. These high iron and sulphate concentrations combine with the low pH and high temperatures favoured for the oxidative dissolution of chalcopyrite to produce ideal conditions for jarosite precipitation. Therefore, pH must be lowered further to prevent jarosite precipitation and enhance copper recoveries from chalcopyrite in ferric media.

[Truncated abstract] Hepatocellular carcinoma (HCC) is the major malignancy complicating chronic liver disease. New therapies for the prevention of HCC are required due to the limited success and high tumour recurrence rates of existing treatments. Emerging evidence suggests that HCC arise from the transformation of adult liver progenitor cells (LPCs), which have the capacity to differentiate into hepatocytes and biliary cells during liver regeneration. LPC activation precedes neoplasia in experimental hepatocarcinogenesis. LPCs share antigenic epitopes with HCCs, including α-fetoprotein (AFP) and M2- pyruvate kinase (M2PK). In animal models of hepatocarcinogenesis, attenuation of the LPC response reduces the incidence of HCC following prolonged liver injury via a tumour necrosis factor (TNF) dependent mechanism. As TNF is a pro-inflammatory cytokine, these data suggest that anti-inflammatory agents may be effective in inhibiting LPC activation and hepatocarcinogenesis. Cyclo-oxygenase-2 (COX-2) is an inducible enzyme that mediates the production of many prostaglandins during inflammation and carcinogenesis. Recent investigations show that the administration of selective COX-2 inhibitors (SC2Is) may reduce the incidence of a variety of tumours including breast, colon and skin. The broad aim of this thesis was to conduct a series of detailed studies on the effects of a SC2I on LPC activation and the hepatic pathologies associated with hepatocarcinogenesis in order to test the hypothesis that S2CIs may be a beneficial therapy that can reduce liver injury and pre-neoplastic changes in the choline-deficient, ethionine supplemented (CDE) murine model of hepatocarcinogenesis. Administration of a SC2I (SC-236) significantly inhibited a variety of hepatic cell populations that expand during the first month of the CDE mouse model of hepatocarcinogenesis (a choline deficient, ethionine supplemented diet). Numbers of M2PK-positive LPCs (which are more hepatocytic in morphology and are also COX-2 positive) and inflammatory cells were all significantly reduced by SC-236. In contrast, numbers of A6-positive LPCs (which are more biliary cell-like in morphology and do not express COX-2) were unchanged. ... In summary, these data suggest that COX-2 inhibitors such as SC-236 inhibit LPC activation and a variety of pre-neoplastic liver pathologies as a result of COX-2 dependent and independent mechanisms that may be mediated through inhibition of Akt phosphorylation and induction of apoptosis. Moreover, SC2Is may be useful as preventative treatment strategies for HCC in patients with chronic liver disease.

Made available in DSpace on 2016-08-03T12:30:38Z (GMT). No. of bitstreams: 1 HONORIO LIBRAS.pdf: 1623910 bytes, checksum: dd09347d9d87afcdb8a99eed892714c8 (MD5) Previous issue date: 2007-10-18 / The objective of this work is to understand how the communication, through the Internet, is used and built, considered the subjects of inclusion and integration of hearing deficiency people. The concepts about communication, inclusion and integration are analyzed; the hearing deficiency and its meaning for the individuals and the subject of the sites in the Internet that deals with this subject and the type of approach communicational used inside this universe are also analyzed. The message of the transmitter (via internet) - decoded by the receiver (hearing deficient) - supplies to the receiver an integration in the world mediation capable to supply an appropriate inclusion and to facilitated the use of Internet for the hearing deficient (receiver). The analysis of the answers of the applied questionnaires to the users and the transmitters of information of the sites, as well as the used theories, should show if there are difficulties in the construction of new messages in the field of Internet and in the use of the receivers. The way for inclusion and communicational integration will go through the transformation of those messages and for projects and actions to be developed in the construction of the sites in the Internet.(AU) / O objetivo deste trabalho é compreender como a comunicação, através da Internet, é utilizada e construída, consideradas as questões da inclusão e integração de pessoas com deficiência auditiva. Analisam-se os conceitos sobre comunicação, inclusão e integração; a deficiência auditiva e seu significado para os indivíduos; a questão dos sites que tratam do assunto na Internet e o tipo de abordagem comunicacional utilizada dentro deste universo. A mensagem do transmissor (via Internet) - decodificada pelo receptor (deficiente auditivo) fornece ao receptor uma integração no mundo midiático capaz de fornecer uma inclusão adequada e uso facilitado da Internet pelo deficiente auditivo (receptor/a). A análise das respostas dos questionários aplicados aos usuários e aos transmissores de informações dos sites e as teorias utilizadas mostrarão se há dificuldades na construção de novas mensagens no campo da Internet e na sua utilização pelos receptores. O caminho da inclusão e integração comunicacional passará pela transformação dessas mensagens e por projetos e ações a serem desenvolvidos na construção dos sites na Internet.

Submitted by Bruna Rodrigues (bruna92rodrigues@yahoo.com.br) on 2016-09-30T14:20:43Z No. of bitstreams: 1 DissKCB.pdf: 1409062 bytes, checksum: 55846fe1e74ddf61e1d5303cd056a9f0 (MD5) / Approved for entry into archive by Marina Freitas (marinapf@ufscar.br) on 2016-10-04T18:50:07Z (GMT) No. of bitstreams: 1 DissKCB.pdf: 1409062 bytes, checksum: 55846fe1e74ddf61e1d5303cd056a9f0 (MD5) / Approved for entry into archive by Marina Freitas (marinapf@ufscar.br) on 2016-10-04T18:50:16Z (GMT) No. of bitstreams: 1 DissKCB.pdf: 1409062 bytes, checksum: 55846fe1e74ddf61e1d5303cd056a9f0 (MD5) / Made available in DSpace on 2016-10-04T18:50:24Z (GMT). No. of bitstreams: 1 DissKCB.pdf: 1409062 bytes, checksum: 55846fe1e74ddf61e1d5303cd056a9f0 (MD5) Previous issue date: 2015-10-16 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Cardiorespiratory responses to peripheral baroreceptor activation are affected by sodium balance or anesthesia. In the present study, we investigated the baroreflex sensitivity and cardiorespiratory responses: to baroreceptor activation and deactivation with intravenous (iv) infusions of phenylephrine (phenyl) and sodium nitroprusside (NP) with or without angiotensinergic type 1 receptor (AT1) blocking; to baroreceptor activation with iv infusions of angiotensin II (ANG II), and cardiorespiratory responses: to cardiopulmonary receptor activation with iv infusions of fenilbiguanide: to chemoreceptor activation with iv infusions of sodium nitroprusside (KCN) in normovolemic, sodium depleted, and sodium repleted unanesthetized rats. Male Holtzman rats (280-320 g, n = 8 - 19) with a polyethylene tubing inserted into abdominal aorta through femoral artery to record mean arterial pressure (MAP) and heart rate (HR) and femoral vein to perform iv administration drugs were used. Respiratory frequency (fR), tidal volume (VT) and ventilation (VE) were recorded by whole-body plethysmography. Sodium depletion did not modify baseline MAP (102 ± 2, vs. normovolemic: 107 ± 2 mmHg), HR (382 ± 9, vs. normovolemic: 385 ± 7 bpm) or VE (468 ± 27, vs. normovolemic: 447 ± 26 ml/min/kg). Iv infusion of phenyl (5 μg/kg/ml, 0.011ml/s) in normovolemic, sodium depleted and repleted rats produced similar pressor (Δ +58  2, +59  2 and +60  3 mmHg, respectively) and bradycardic (Δ -97  10, -120  11 and -110  9 bpm, respectively) responses, however, sodium depleted rats showed an increased in VE (Δ +152  40, vs. normovolemic: +53 ± 26 ml/min/kg, p<0.05). After sodium repletion the VE returned to approximate value of normovolemic rats (Δ +125  50 ml/min/kg). In the other group of animal was made AT1 receptor blocking with iv bolus injections of losartan and was observed an attenuation of VE that was increased in sodium depleted rats (Δ +77 ± 33 ml/min/kg). 9 The bradicardic component gain also was increased in depleted rats (-1.9 ± 0.1, vs. normovolemic: -1.3 ± 0.1 bpm/mmHg, p<0.05) and returned to baselines values in sodium repleted rats (-1.5 ± 0.1 bpm/mmHg). Iv Infusion of NP (30 μg/kg/ml, 0.011ml/s) in normovolemic, sodium depleted and repleted rats produced similar hypotensive, tachycardic responses, similar VE and the tachycardic component gain. The iv infusion of fenilbiguanide (50 μg/kg/ml) induced similar hypotensive and bradicardic responses in normovolemic and sodium depleted rats, however increased VE in sodium depleted rats (Δ +281 ± 34, vs. normovolemic: +150 ± 50 ml/min/kg, p <0.05). Iv infusion of potassium cyanide (KCN, 40 μg/0.1ml per rat) did not change cardiorespiratory responses. Thus, the results suggest that sodium depletion with furosemide plus sodium-deficient diet increased bradicardic component of baroreflex and the neurondocrine changes produced by sodium depletion (like increased angiotensin II) may facilitate respiratory responses to baroreceptor activation with phenyl iv. / Respostas cardiorrespiratórias após ativação do barorreflexo são afetadas pelo balanço de sódio ou anestesia. No presente estudo, investigamos as respostas cardiorrespiratórias e a sensibilidade do barorreflexo: após ativação e desativação dos barorreceptores com infusões intravenosa (iv) de fenilefrina (fenil) e nitroprussiato de sódio (NP) com e sem o bloqueio de receptores angiotensinérgicos do tipo 1 (AT1); após ativação dos barorreceptores com infusão iv de angiotensina II (ANG II), e as respostas cardiorrespiratórias: após ativação de receptores cardiopulmonares com infusões iv de fenilbiguanida; após ativação quimiorreceptores com infusões iv de cianeto de postássio (KCN) em ratos não anestesiados normovolêmicos, depletados e repletos de sódio. Foram utilizados ratos Holtzman (280-320 g, n = 8 - 19) com um tubo de polietileno inserido na aorta abdominal através da artéria femoral para registrar a pressão arterial média (PAM) e frequência cardíaca (FC) e veia femoral para administração das drogas. A frequência respiratória (fR), volume corrente (VC) e ventilação (VE) foram determinadas por pletismografia de corpo inteiro. A depleção de sódio não modificou os valores basais de PAM (102 ± 2, vs. normovolêmicos: 107 ± 2 mmHg), FC (382 ± 9, vs. normovolêmicos: 385 ± 7 bpm) ou VE (468 ± 27, vs. normovolêmicos: 447 ± 26 ml/min/kg). A infusão iv de fenil (5 μg/kg, 0,011ml/s) produziu resposta pressora e bradicárdica semelhante em ratos normovolêmicos, depletados e repletos de sódio (Δ +58 ± 2, +59 ± 2 e +60 ± 3 mmHg, respectivamente) (Δ -97 ± 10, -120 ± 11 e -110 ± 9 bpm, respectivamente), no entanto, os ratos depletados de sódio mostraram um aumento na VE (Δ +152 ± 40, vs. normovolêmicos: +53 ± 26 ml/min/kg, p <0,05). Após a repleção de sódio, a VE retornou próximo ao valor dos ratos normovolêmicos (Δ +125 ± 50 ml/min/kg). Em outro grupo de animais, foi realizado bloqueio dos receptores AT1 com injeções iv em bolus de losartana e não foi observado este aumento da VE nos ratos depletados de sódio (Δ +77 ± 33 7 ml/min/kg). O ganho do componente bradicárdico também aumentou em ratos depletados (-1,9 ± 0,1, vs. normovolêmicos: -1,3 ± 0,1 bpm/mmHg, p <0,05) e retornou aos valores basais nos ratos repletos de sódio (-1,5 ± 0,1 bpm/mmHg). A infusão iv de NP (30 μg/kg, 0,011ml/s) promoveu respostas hipotensoras e taquicárdicas semelhantes nos ratos normovolêmicos, depletados e repletos de sódio assim como a VE e o ganho do componente taquicárdico não sofreram alterações significativas. A infusão iv de fenilbiguanida (50 μg/kg/ml) promoveu respostas hipotensoras e bradicárdicas semelhantes nos ratos normovolêmicos e depletados de sódio, porém aumentou a VE nos animais depletados de sódio (Δ +281 ± 34, vs. normovolêmicos: +150 ± 50 ml/min/kg, p <0,05). A infusão iv de cianeto de potássio (KCN, 40 μg/0,1ml por rato) não alterou as respostas cardiorrespiratórias. Sendo assim, os resultados sugerem que a depleção de sódio com furosemida seguido de dieta deficiente em sódio aumentou componente bradicárdico do barorreflexo e as mudanças neurondócrinas produzidas pela depleção de sódio (como aumento da ANG II) podem facilitar as respostas respiratórias à ativação dos barorreceptores

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-06-14T19:33:16Z No. of bitstreams: 1 alicebelleigolirezende.pdf: 4554252 bytes, checksum: 45624650ab925d7640e01b2b01e2a245 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-06-29T12:16:33Z (GMT) No. of bitstreams: 1 alicebelleigolirezende.pdf: 4554252 bytes, checksum: 45624650ab925d7640e01b2b01e2a245 (MD5) / Made available in DSpace on 2017-06-29T12:16:33Z (GMT). No. of bitstreams: 1 alicebelleigolirezende.pdf: 4554252 bytes, checksum: 45624650ab925d7640e01b2b01e2a245 (MD5) Previous issue date: 2011-08-30 / FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais / A aterosclerose é uma doença imune-inflamatória associada ao acúmulo de lípides na camada íntima das artérias. O baço desempenha uma importante função imunológica, mas a sua participação no desenvolvimento da aterosclerose permanece controversa. Considerando que a incidência de esplenectomias totais ainda é alta e que a doença aterosclerótica é prevalente, é de grande importância que se verifique se o tecido esplênico influencia no processo de aterosclerose. Neste trabalho, o impacto da esplenectomia no desenvolvimento da aterosclerose foi avaliado em camundongos deficientes em apoproteína E (apoE). Os animais foram divididos em dois grupos: grupo controle (CT), composto de camundongos deficientes em apoE submetidos a um procedimento cirúrgico simulado; e grupo esplenectomia total (ET), camundongos deficientes em apoE submetidos à esplenectomia total. Trinta dias após a cirurgia, os animais foram submetidos a uma dieta aterogênica enriquecida com 0,15% de colesterol. Após oito semanas, os animais foram eutanasiados e o sangue, o coração e a aorta foram submetidos à análise. Os níveis séricos de colesterol total e de anticorpos anti-LDL oxidada foram avaliados. As áreas de lesão aterosclerótica na raiz da aorta foram quantificadas por morfometria em cortes histológicos corados com hematoxilina-eosina. As lesões ateroscleróticas nas porções torácica e abdominal das aortas foram determinadas pela porcentagem da superfície luminal corada com Sudan IV em relação à área total do vaso. Os resultados mostraram que os níveis séricos de colesterol total não foram alterados pela esplenectomia e que os títulos de anticorpos IgG anti-LDL oxidada foram semelhantes entre os grupos. No entanto, foi observada uma maior porcentagem de lesões ateroscleróticas nas porções torácica e abdominal das aortas de animais esplenectomizados. Além disso, camundongos esplenectomizados apresentaram lesões ateroscleróticas na raiz da aorta significativamente maiores do que os animais controles. Estes dados indicam, em conjunto, que a esplenectomia está associada ao aumento das lesões ateroscleróticas em camundongos deficientes em apoE submetidos à dieta aterogênica, sugerindo um papel ateroprotetor do baço no modelo estudado. / Atherosclerosis is an inflammatory immune disease associated with lipid accumulation in the intima layer of arteries. The spleen plays an important immune function, but its influence in development of atherosclerosis remains unclear. Evaluation of the role of the spleen in atherosclerosis is justified due to the high frequency of total splenectomies and the high prevalence of atherosclerotic disease. In this work, the effect of splenectomy on the development of atherosclerosis in apolipoprotein E (apoE) deficient mice was investigated. ApoE deficient mice were divided into a sham-operated control group (CT) and a splenectomized group (SP). Thirty days after surgery, animals were fed a high fat western diet (with 0.15% cholesterol). After eight weeks, mice were euthanized and their blood, heart, and aorta were subjected to analysis. Total serum cholesterol and anti-oxidized LDL antibodies were measured. Atherosclerotic lesion areas in the aortic root were stained with hematoxylin-eosin and quantified by morfometry. The atherosclerotic lesions in the thoracic and abdominal portions of aorta were determined by assessing the percentage of the luminal surface area stained by Sudan IV. Levels of total serum cholesterol did not vary significantly after splenectomy. Anti-oxidized LDL IgG antibodies were similar between groups. However, compared to the control group, atherosclerotic area in the thoracic and abdominal portions of aorta were significantly increased in splenectomized mice. These data were confirmed by the larger lesions in the aortic root in splenectomized mice. These data indicate that splenectomy increases atherosclerotic lesions in apoE deficient mice fed an atherogenic diet, suggesting a atheroprotector role of the spleen.

The aim of this thesis is to describe the cognitive profile, including the developed and deficient cognitive functions, in a group of children and adolescents with specific learning disabilities. The theoretical part of the thesis introduces Reuven Feuerstein's work, especially his concepts of structural cognitive modifiability and mediated learning experience, the theory of cognitive deficits, cognitive map and Feuerstein's instrumental enrichment programme. The characteristics of traditional and dynamic assessment, basic differences between these diagnostic approaches and cognitive symptoms of specific learning disabilities are also described in the thesis. The results of the examination of twenty-eight DYS-centrum's clients with specific learning disabilities are qualitatively analyzed in the empirical part. We focus on their developed and deficient cognitive functions, their fulfilment of complex tasks, a preferred modality in which the tasks are presented, and differences between the results obtained through static and dynamic testing. The results collected from individual subjects are finally compared and visualized using figures and graphs which gives an overview of the studied phenomena throughout the whole research sample. We found all the clients of the research sample having following...

Mesoporous γ-Al2O3 is one of the most widely used catalyst supports for commercial catalytic applications. The performance of a catalyst strongly depends on the combination of textural, chemical and physical properties of the support. Pore size is essential since each catalytic system requires a unique pore size for optimal catalyst loading, diffusion and selectivity. In addition, high surface area and large pore volume usually result in higher catalyst loading, which increases the number of catalytic reaction sites and decreases reaction time. Therefore, determination of surface area and porosity of porous supports is critical for the successful design and optimization of a catalyst support. Moreover, it is important to produce supports with good thermal stability since pore collapsing due to sintering at high temperatures often results in catalyst deactivation. In addition, the ability to control the acidity of the catalyst enables us to design desirable acid sites to optimize product selectivity, activity, and stability in different catalytic applications. This dissertation presents a simple, one-pot, solvent-deficient method to synthesize thermally stable silica-doped alumina (SDA) without using templates. The XRD (X-ray diffraction), HTXRD (high temperature X-ray diffraction), SS NMR (solid state nuclear magnetic resonance), TEM (transmission electron microscopy), TGA(thermogravimetric analysis), and N2 adosorption techniques are used to characterize the structures of the synthesized SDAs and understand the origin of increased thermal stability. The obtained SDAs have a surface area of 160 m2/g, pore volume of 0.99 cm3/g, and a bimodal pore size distribution of 23 and 52 nm after calcination at 1100◦C. Compared to a commercial SDA, the surface area, pore volume, and pore diameter of synthesized SDAs are higher by 46%, 155%, and 94%, respectively. A split-plot fractional-factorial experimental design is also used to obtain a useful mathematical model for the control of textural properties of SDAs with a reduced cost and number of experiments. The proposed quantitative models can predict optimal conditions to produce SDAs with high surface areas greater than 250 m2/g, large pore volume greater than 1 cm3/g, and large (40-60 nm) or medium (16-19 nm) pore diameters. In my approach, I control acid sites formation by altering preparation variables in the synthesis method such as Si/Al ratio and calcination temperatures. The total acidity concentration (Brønsted and Lewis) of the synthesized SDAs are determined using ammonia temperatured program, pyridine fourier transform infrared spectroscopy (FTIR), and MAS NMR. The total acidity concentration is increased by introducing a higher mole ratio of Si to Al. In addition, the total acidity concentration is decreased by increasing calcination temperature while maintaining high surface area, large porosity, and thermal stability of γ-alumina support. I also present an optimized synthesis of various aluminum alkoxides (aluminum n-hexyloxide (AH), aluminum phenoxide (APh) and aluminum isopropoxide (AIP)) with high yields (90-95%). One mole of aluminum is reacted with excess alcohol in the presence of 0.1 mole % mercuric chloride catalyst. The synthesized aluminum alkoxides are used as starting materials to produce high surface area alumina catalyst supports. Aluminum alkoxides and nano aluminas are analyzed by 1H NMR, 13C NMR, 27Al NMR, gCOSY (2D nuclear magnetic resonance spectroscopy), IR (infrared spectroscopy), XRD, ICP (induced coupled plasma), and elemental analysis.

Les modèles animaux jouent un rôle crucial dans les recherches précliniques, mais il existe plusieurs limites. Les états physiologiques et immunologiques chez les murins et les primates non humains sont radicalement différents à ceux de l'homme, en particulier la restriction du CMH, qui ne peut éliminer l'influence de la spécificité de l'espèce dans les expériences précliniques. Le but du travail était de générer un niveau plus élevé de souris transgéniques «HLA humanisées» qui pourraient imiter les réponses immunitaires humaines avec plus de précision et de fiabilité; à viser d’appliquer pour l'évaluation préclinique de la transplantation humaine, à l'identification de nouveaux épitopes et à l'évaluation des vaccins et des médicaments candidats. Dans la première partie. Nous rapportons d’une nouvelles souris transgéniques HLA immunodéficientes «HUMAMICE». Des souris HLA-A2+/+/DR1+/+/H-2-β2m-/-/IAβ-/-/Rag2-/-/IL-2rγ-/-/Perf-/- ont été établies, lesquelles exprimaient des molécules HLA humaines au lieu de H-2 murines et ne présentaient pas de lymphocytes murins. Ce statut immunodéficient a été inversé en transférant les cellules hPBMC HLA appariées fonctionnelles pour produisant ensuite des souris ayant un statut immuno-compétent avec un système immunitaire humain fonctionnel. L'immunisation du vaccin HBsAg a permis d'obtenir une production robuste et reproductible d'anticorpsspécifiques. En conclusion, ces résultats indiquent que le modèle hPBMC-HUMAMICE représente un modèle prometteur pour disséquer les réponses immunitaires humaines aux maladies humaines. Dans la seconde partie de cette étude, les souris HLA-A11+/+/DR1+/+/H-2-β2m-/-/IAβ-/- ont été établies. Cette nouvelle souche de souris possède une caractéristique restreinte par HLA-A11 et une capacité normale à répondre aux antigènes. L'immunisation de souris avec un vaccin recombinant HBsAg contre le VHB ou une protéine recombinante du VIH-1 a entraîné la génération de lymphocytes T cytotoxiques producteurs d'IFN-y et d'anticorps spécifiques. En outre, nous avons identifié deux épitopes restreints par HLA-A11 de la protéine GP EBOV et quatre de la protéine MERS-CoV S. En fin, ce modèle de souris HLA-A11/DR1 pourra faciliter l'identification des épitopes de lymphocytes cytotoxiques et auxiliaires restreints par le HLA-A11 dominants en Chine. Le modèle constituer un nouvel outil technique prometteur pour comprendre les mécanismes immunologiques et les nouveaux vaccins pour les populations d’Asie de l’Est. Durant cette thèse, nous avons créé deux modèles de souris humanisées novateurs et prometteurs portant une restriction HLA humaine qui pourraient servir de modèles d'infection pathogène et étudier les tumeurs, les mécanismes de transplantation et l'invention et l'évaluation des vaccins et des médicaments. / Animal models play critical roles in pre-clinical researches, while there are still several limitations. The physiological and immunological states in murine and non-human primates are radically district from those of mankind, especially the MHC restriction, which cannot eliminate the influence of species specificity in pre-clinical experiments.The aim of our work was to generate a higher level of “humanized” transgenic mice which could mimic human immune responses with more accuracy and reliability; furthermore, to apply the novel models in the evaluation of human transplantation, the identification of new epitopes, and the evaluation of candidate vaccines and drugs.In the first part of the study, novel immuno-deficient HLA transgenic mice "HUMAMICE" (HLA-A2+/+/DR1+/+/ H-2-β2m-/-/IAβ-/-/Rag2-/-/IL-2rγ-/-/Perf-/- mice) were established, which expressed human HLA molecules instead of murine H-2 and present no murine lymphocytes. This immuno-deficient status was reversed by transferring the functional HLA-matched hPBMCs and then producing mice with an immuno-competent status with a functional human immune system, led to high lymphocytes engraftment rates without GvHD. Immunization of HBsAg vaccine resulted in robust and reproducible production of specific antibodies. Inconclusion, these results indicated that the hPBMCs-HUMAMICE model represents a promising model to dissect human immune responses towards human diseases.In the second part of this study, the Chinese/East Asian HLA dominated HLA-A11/DR1(HLA-A11+/+/DR1+/+/H-2-β2m-/-/IAβ-/-) transgenic mouse strain was established. This novel mouse strain possesses HLA-restricted characteristic and a normal ability to respond to antigens. Immunization of mice with a recombinant HBV vaccine or a recombinant HIV-1 protein resulted in the generation of IFN-γ-producing cytotoxic T lymphocytes and specific antibodies. Furthermore, we identified two HLA-A11 restricted epitopes of EBOV GP protein and four of MERS-CoV S protein. Above all, HLA-A11/DR1 mice could facilitate the identification of Chinese dominant HLA-restricted CTL and Th epitopes and provide a new promising technical tool to understand immunological mechanisms and new vaccines.Taken together, we created two novel and promising humanize mouse models carrying human HLA restriction which could apply as pathogen infection models, and study tumors, transplantation mechanism, and the invention and evaluation of vaccines and drugs.

Orientador: Paula da Cruz Landim / Banca: Claudia Renata Mont'Alvão Bastos Rodrigues / Banca: Dorival Campos Rossi / Resumo: Este estudo buscou por meio de pesquisas bibliográficas e da pesquisa experimental realizada com portadores de deficiência visual na entidade Olhos D'Alma de Jaboticabal - SP, analisar a usabilidade de produtos alimentícios enlatados. A relevância social volta-se ao portador de cegueira e de baixa visão, cujo foco é investigar quais as dificuldades encontradas durante a identificação e o uso. Foram abordados assuntos sobre o Sistema Braille, a composição estética e funcional da embalagem, o uso de materiais e a adequação à demanda; os riscos da ausência e da má informação e as contribuições que o design pode trazer ao deficiente visual, por meio de técnica e conhecimento e aspectos cognitivos da Semiótica e da teoria de Piaget A não obrigatoriedade da informação em Braille nos produtos exclui o cego, causando dependência durante o uso e a compra. O objetivo principal desta pesquisa foi comprovar, por meio da pesquisa experimental com 20 deficientes visuais, como são os reconhecimentos do produto, as dificuldades encontradas para identificá-los, devido à relevância do design visual, que limita outros sentidos de percepção / Abstract: This study it searched by means of bibliographical research and of the experimental research carried through with carriers of visual deficiency in the entity Eyes D'Alma de Jaboticabal, SP, to analyze the usability of tinned nourishing products. The social relevance turns it the carrier of blindness and low vision, whose focus is to investigate which the difficulties found during the identification and the use. They had been boarded subjects on the System Braille, the aesthetic and functional composition of the packing, the use of materials and the adequacy the demand; the risks of the absence and the bad information and the contributions that design can bring to the deficient appearance, by means of technique and knowledge and cognition aspects of the Semiotics and the theory of Piaget. The obligator ness of the information in Braille in the products does not exclude the blind person, causing the dependence during the use and the purchase. The main objective of this research is to prove, by means of the experimental research with 20 deficient appearances, as it is the recognition of the product, the found difficulties to identify them, due to relevance of design visual, that it limits other directions of perception / Mestre