Dissertations / Theses on the topic 'Mechanism of 2-methyl-1,3-dioxolane'

Deux nouvelles methodes de syntheses stereospecifiques de desoxy-2 c-glucosides possedant une fonction ester d'enol sont presentees : - l'addition conjuguee d'organocuprates cyanes sur des hexeno-1 pyrannuloses-3 peracetyles (l'anhydride acetique piegeant l'enolate intermediaire) permet d'obtenir des aryl-alpha -d-c-glycosides. Cette methode est detendue avec succes en serie furannose; - l'arylation de glycals catalysee par des sels de palladium fournit les composes voulus en une seule etape a partir de derives glucidiques commerciaux. L'etude de la configuration des c-glycosides obtenus est effectuee et de nombreuses donnees structurales sont exposees

Este trabalho destina-se ao estudo de modificações no espalhamento de Aharonov-Bohm para partículas relativísticas com spin 1/2, devido à não comutatividade do espaço, em 2+1 dimensões. As correções para o potencial de Aharonov-Bohm, sendo muito singulares, levam, em geral, ao aparecimento de divergências na expansão perturbativa em torno da teoria livre. Usando, então, como ponto de partida a solução exata da versão comutativa, determinamos, na aproximação de fluxo pequeno, a amplitude invariante, seção de choque diferencial e total, com as divergências eliminadas.
In this work we study modifications in the Aharonov-Bohm effect for relativistic spin 1/2 particles due the non-commutativity of space in 2+1 dimensions. The corrections for the Aharonov-Bohm potential originated from the non-commutativity of the underlying space are very singular, producing the appearance of divergences in the perturbative expansion around the free theory. Working with the pertubation around the exact solution of the commutative version of the problem, we determine then, in the small flux approximation, the invariant amplitude, and the corrections to the differential and total cross sections with all divergences eliminated.

Mean motion resonances (MMRs) play an important role in the formation and evolution of planetary systems and have significantly influenced the orbital properties and distribution of planets and minor planets in the solar system and in. exoplanetary systems. Most previous theoretical analyses have focused on the low- to moderate-eccentricity regime, but with new discoveries of high-eccentricity resonant minor planets and even exoplanets, there is increasing motivation to examine MMRs in the high-eccentricity regime. Here we report on a study of the high-eccentricity regime of MMRs in the circular planar restricted three-body problem. Numerical analyses of the 2: 1 and the 3: 2 interior resonances are carried out for a wide range of planet-to-star mass ratio mu, and for a wide range of eccentricity of the test particle. The surface-of-section technique is used to study the phase space structure near resonances. We find that new stable libration zones appear at higher eccentricity at libration centers that are. shifted from those at low eccentricities. We provide physically intuitive explanations for these transitions in phase space, and we present novel results on the mass and eccentricity dependence of the resonance widths. Our results show that MMRs have sizable libration zones at high eccentricities, comparable to those at lower eccentricities.

CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior
A substÃncia 1-(4-Nitrofenil)-3-fenilprop-2-en-1-ona (CG) Ã um derivado de chalcona, sintetizado a partir da reaÃÃo quÃmica entre a acetofenona e para-nitro benzaldeÃdo. Para avaliar o seu potencial anticÃncer foi realizado um estudo farmacolÃgico de suas propriedades antitumorais em vÃrios modelos biolÃgicos in vitro e in vivo. A CG apresentou potente atividade citotÃxica nas 5 linhagens tumorais testadas, inibindo a proliferaÃÃo das cÃlulas tumorais pelo ensaio do MTT e em cÃlulas mononucleares do sangue perifÃrico (PMCB) humano atravÃs do ensaio do Alamar blue. Todas as linhagens mostraram sensibilidade ao tratamento com a CG, e a CI50 variou de 1,18ÂM em HCT-8 a 3,32ÂM em SF-295. O composto apresentou fraca citotoxicidade (CI50 igual a 7,07ÂM) nas cÃlulas PBMC, com exposiÃÃo a CG em 72h, em relaÃÃo Ãs cÃlulas de HL-60, utilizada como modelo nos demais testes biolÃgicos. O tempo de encubaÃÃo com o composto foi de 24h na maioria dos experimentos. Adicionalmente, a CG nÃo induziu efeitos hemolÃticos. O ensaio de exclusÃo por azul de Tripan revelou diminuiÃÃo da viabilidade celular principalmente apÃs 24h na maior concentraÃÃo testada (4ÂM) com 58,4%. Para os testes de atividade antiproliferativa, LA/BE mostrou em sua morfologia cÃlulas em apoptose nas duas maiores concentraÃÃes, enquanto que o BrdU, apresentou incorporaÃÃo do mesmo nas concentraÃÃes testadas. A morfologia analisada por May-Grunwald-Giemsa mostrou reduÃÃo do volume celular, condensaÃÃo da cromatina e fragmentaÃÃo nuclear. Adicionalmente, a CG induziu apoptose em cÃlulas leucÃmicas HL-60, com participaÃÃo das vias intrÃnseca e maior estÃmulo da via extrÃnseca, de maneira concentraÃÃo-dependente, como observado na integridade da membrana citoplasmÃtica, aumento da fragmentaÃÃo do DNA e externalizaÃÃo da fosfatidilserina. Na anÃlise do ciclo celular, foi observado parada na fase G2/M, sendo ativada as caspases 3, 7, 8 e 9 (a Ãltima na maior concentraÃÃo e confirmada pelo teste do Western blot). NÃo houve ativaÃÃo do Citocromo c. A CG nÃo foi capaz de induzir processos genotÃxicos/ mutagÃnicos (testes do cometa e micronÃcleo in vitro). No ensaio de atividade antitumoral in vivo, observou-se inibiÃÃo tumoral nas doses testadas (25 e 50mg/Kg/dia, via oral) de 54,85 e 69,11% respectivamente. As doses de CG causaram tumefaÃÃo celular e o surgimento de focos inflamatÃrios no parÃnquima ou estroma hepÃtico/renal, necrose nefrotÃxica focal, esteatose microvesicular, pigmentos de hemossiderina, hiperplasia das cÃlulas de Kupffer, congestÃo da polpa vermelha e desorganizaÃÃo dos folÃculos linfÃides esplÃnicos. AlÃm disso, os Ãndices bioquÃmicos mostraram aumento do AST e diminuiÃÃo da urÃia (CG 25mg/Kg/dia), diminuiÃÃo do ALT (5-FU e CG 25mg/Kg/dia); as alteraÃÃes hematolÃgicas mostraram leucopenia e plaquetopenia (5-FU), aumento dos leucÃcitos totais (CG 50mg/Kg/dia), aumento de neutrÃfilos e linfÃcitos em todos os grupos tratados. Todos os resultados nos levam a enfatizar que a CG possui grande potencialidade como molÃcula promissora por suas propriedades anticÃncer.
The substance 1- (4-Nitrofenil)-3- fenilprop-2- en-1-ona (CG) is a chalcone derivative, synthesized from a chemical reaction between acetophenone and p-nitro benzaldehyde. To evaluate its anticancer potential a pharmacological study of its antitumor properties in selected biological models in vitro e in vivo. CG presented a powerful cytotoxic activity in the 5 tested tumor lines evaluated, inhibiting cell proliferation of the tumor lines in the MTT assay and human peripheral mononuclear blood cells (PMBC) through the Alamar Blue assay. All cell lines showed sensitivity to the treatment with the CG, and the IC50 varied from 1,18 ÂM in HCT-8 to 3,32 ÂM in SF-295. The sample presented weak cytotoxic effect (IC50 of 7,07 ÂM) in cells PMBC, with 72h exposure to CG, compared to HL-60 cells (leukemic cell line), used in the next biological tests. The sample was incubated with the cells during 24h for the majority of the experiments. Additionally, CG did not induce hemolytic effects. The Tripan Blue assay showed a decrease of the cellular viability especially after 24h of incubation of the higher tested concentration (4 ÂM) with 58,4%. In assays for antiproliferative activity, OA/BE showed in its morphology cells going under apoptosis in the two higher concentrations, whereas the BrdU assay, presented incorporation of the same in the tested concentrations. The morphology analyzed with the May-Grunwald-Giemsa stain showed a decrease of the cellular volume, chromatin condensation and nuclear fragmentation.CG induced apoptosis in HL-60 cells, with participation of the intrinsic pathway and major stimulation of the extrinsic pathway, in a concentration-dependent manner, as observed in the cytoplasmatic membrane integrity, increase of DNA fragmentation and outsourcing of phosphatidylserine. In the cellular cycle analysis, it was observed a stop in the G2/M phase, activating caspases 3, 7, 8 and 9 (the last one in the highest concentration and confirmed by the Western blot assay). It was not observed activation of Cytochrome c. CG was not capable to induce mutagenic/genotoxic processes (comet assay and micronucleus in vitro). In the in vivo antitumor activity assay, tumor inhibition was observed in the tested doses (25 and 50mg/Kg/day, oral intake) of 54,85 and 69,11%, respectively . The doses of CG caused cellular swelling and the arise of inflammatory focus in the parenchyma or hepatic/renal stroma, focal nephrotoxic necrosis, microvesicular steatosis, hemosiderin pigments, hyperplasia of Kupffer cells, congestion of the red pulp and disorganization of the splenic lymphoid follicles. Furthermore, the biochemical indices had shown increase of AST and reduction of urea (25mg/Kg/day of CG), reduction of ALT (25mg/Kg/day of 5-FU and CG); hematologic alterations showed leukopenia and thrombocytopenia (5-FU), increase of total leukocytes (50mg/Kg/day of CG), increase of neutrophils and lymphocytes in all treated groups. All results led us to emphasize that CG possesses great potential as a promising molecule for its anticancer properties.

The studies in this dissertation research were conducted to investigate the possible mode of action by which a brominated flame retardant, 2, 2-Bis (bromomethyl)-1, 3-propanediol (BMP) causes genotoxicity. Binding of BMP to DNA and BMP induced DNA strand breaks were investigated in SV-40 immortalized human uroepithelial cells (UROtsa) as an in vitro model for the bladder (a tissue that developed cancer after two year exposure to BMP in rodents). Results showed binding of [¹⁴C]-BMP equivalents to DNA increased with increased exposure time and concentration of [¹⁴C]-BMP. Comet analysis indicated BMP significantly increased the extent of DNA strand breaks at 1 and 3 h of incubation. However, strand breaks were repaired by 6 h of incubation. The DNA damaging effects of BMP at 1 h was concentration dependent. Compared with the parent compound, BMP-glucuronide (the predominant metabolite of BMP) bound less to DNA and produced less DNA strand breaks in UROtsa cells. Evidences that the BMP induced strand breaks were the result of an oxidative stress include: a concentration and time dependent increase in ROS generation; increased expression of Nrf2 and HSP70; complete attenuation of BMP induced DNA strand breaks by the antioxidant, NAC; and the presence of the oxidized base 8-OHguanine. UROtsa cells appear to be target cells for BMP because, as compared to rat hepatocytes (non-target cells), these cells lack the ability to detoxify BMP via glucuronidation and also because they are deficient in glutathione, a major intracellular antioxidant molecule. Both of these genotoxic events, DNA binding and oxidative DNA damage may, in part, contribute to BMP carcinogenicity observed in rodents. The relevance of current results to humans is remained to be established.

Neste trabalho realizamos dois estudos independentes sobre a termodinâmica de modelos de água e o dobramento de proteínas em rede.
On this work we develop two independent studies on lattice models for water thermodynamics and protein folding.

Thesis (M.S. in Mechanical Engineering)--Naval Postgraduate School, June 1990.
Thesis Advisor(s): Ligrani, Phillip M. ; Subramanian, Chelakara S. "June 1990." Description based on signature page. DTIC Identifier(s): Channel flow, Tollmien Schlichting waves, Klebanoff type waves, Stroubal number, Turbulence. Author(s) subject terms: Imposed oscillations, Tollmien-Schlichting waves, Klebanoff type waves, phase-averaged velocity, longitudinal velocity fluctuations, intermittency, center mode of secondary instability. Includes bibliographical references (p. 219-222). Also available online.

Neste trabalho realizo uma adaptação do método de Ma, Dasgupta e Hu para o estudo e caracterização das transições de fase quânticas, induzidas por um campo transverso, em cadeias XY de spins 1/2, unidimensionais e aperiódicas, no espírito da adaptação correspondente para cadeias XXZ. O presente trabalho determina de forma analítica uma série de expoentes críticos associados às transições ferro-paramagnéticas do sistema, e dá pistas quanto à natureza das estruturas presentes no estado fundamental. Os resultados são então testados pelo emprego da técnica de férmions livres, da análise de nite size scaling e, no limite de Ising, de resultados extraídos do mapeamento do problema em uma caminhada aleatória.
We employ an adaptation of the Ma, Dasgupta, Hu method in order to analyze the quantum phase transition, induced by a transversal magnetic eld, at spin-1/2 aperiodic XY chains, in analogy to the corresponding adaptation for XXZ chains. We derive analytical expressions for some cri tical exponents related with the ferro-paramagnetic transitions, and shed light onto the nature of the ground state structures. The main results obtained by this approach were tested by the free-fermion method, nite-size scaling analyses and, at the Ising limit of the model, by using results derived from a mapping to a random-walk problem.

Le captage du CO2 en postcombustion par absorption dans des solutions aqueuses d'amines est la technologie la plus mature pour réduire les émissions de gaz à effets de serre. Cependant, les amines utilisées sont susceptibles de réagir avec l'oxygène présent dans les fumées pour former de nouveaux composés qui peuvent être émis à l'atmosphère et avoir des conséquences sur l'environnement et la santé humaine.. L'objectif de cette thèse était donc d'identifier le maximum de produits de dégradation des amines grâce au développement de différentes techniques analytiques et d'échantillonnage, notamment pour l'analyse de la phase gaz. Ainsi plus de soixante produits issus de la dégradation de la monoéthanolamine (MEA) en pilote de captage du CO2 ont été identifiés. Une trentaine de ces produits sont nouveaux, ils sont souvent issus d'une même famille comme les pyrazines ou les oxazolines ou ils peuvent être caractérisés par l'allongement de la chaine carbonée (C2 entre deux hétéroatomes à C5).Des mécanismes basés sur des réactions d'alkylation/de désalkylation, la formation d'aldéhydes ou de cétones, l'amidification, l'aldolisation, la réaction d'Eschweiler Clarke, la formation de pyridines ont été proposés pour expliquer la formation de tous les nouveaux produits de dégradation et validés, dans la plupart des cas, en mélangeant les réactifs proposés dans le mécanisme. Finalement, il a été montré que la transposition de ces schémas réactionnels à trois autres amines (N-méthylaminoéthanolamine, 1-aminopropan-2-ol, 3-aminopropan-1-ol) a permis de prédire leurs produits de dégradation
The CO2 post-combustion capture with aqueous solutions of amines is the most mature technology to reduce greenhouse gases emissions. However chemical absorption is suffering from the degradation of amines mainly due to the presence of O2 in flue gases. Formed products, which could be rejected to atmosphere, may be detrimental to environment and human health. The aim of this thesis was to identify as many degradation products as possible thanks to the development of different sampling and analytical methods especially for gas phase analysis. Thus more than sixty products issued from monoethanolamaine (MEA) degradation were observed in pilot plant samples. Thirty of them are novel, they often belong to the same family as pyrazines or oxazolines, or they could be characterized by the increase of carbon chain lengths (C2 between two heteroatoms to C5).Mechanisms such as alkylation/dealkylation, aldehydes/ketones formation, amidification, aldolisation, Eschweiler Clarke, pyridines formation were proposed to explain the formation of novel products and were, most of the time, validated by mixing the reactants proposed in the mechanism. Finally, it has been shown that the transposition of these reactions to three other amines (N-methylaminoethanolamine, 1-aminopropan-2-ol, 3-aminopropan-1-ol) enabled us to predict their degradation products

AIDS, or acquired immunodeficiency syndrome, is caused by the human immunodeficiency virus (HIV). HIV is a retrovirus that is capable of rapid genetic mutation, which makes the virus and the disease difficult to treat. Several drug therapies are currently available, in the form of viral enzyme inhibitors. Other inhibitors of the viral entry and replication process are being investigated to enhance the drug therapy arsenal. Our research has focused on the development of HIV entry inhibitors. We are working towards the development of novel carbohydrate-based agents that are capable of binding the gp120 protein on the viral surface, such that viral entry into an uninfected host cell is prevented. In order for our research to progress, a qualitative method by which our synthetic compounds could be evaluated for gp120 binding was sought. We have developed a unique ELISA (enzyme-linked immunosorbent assay) that indicates whether or not a compound has binding affinity for the viral protein. A TIRF (total internal reflection fluorescence) microscopy method, has been developed as part of a collaborative effort with the laboratories of Professors Saavedra and O'Brien, to assess active compounds for quantitative equilibrium binding constants to gp120. We have synthesized several carbohydrate-based molecules targeted to one or more of the binding sites on the surface of gp120; the galactosylceramide site, the V3 loop, and the CD4 binding site. Utilizing both the ELISA and TIRF methods, we have succeeded in probing the binding profile of gp120. Circular dichroism studies have also been employed to evaluate the secondary structural characteristics of oligomeric carbohydrate materials. Molecules with helical properties have potential as CD4 binding site inhibitors. The long term goals of this project involve the synthesis and gp120 binding evaluation of novel carbohydrate-based materials to serve as entry inhibitors of the HIV replication process. A possible application of this project lies in the development of compounds capable of binding to more than one site on the protein. A variation of this goal involves the tethering of various compounds with specificities to different sites on gp120, for the purpose of inhibiting multiple binding sites on the protein.

Cardiovascular diseases are among the leading causes of death worldwide and particularly in the developed World. The search for new therapeutic approaches for improving the functions of the damaged heart is therefore a critical endeavour. Myocardial infarction, which can lead to heart failure, is associated with irreversible loss of functional cardiomyocytes. The loss of cardiomyocytes poses a major difficulty for treating the damaged heart since terminally differentiated cardiomyocytes have very limited regeneration potential. Currently, the only effective treatment for severe heart failure is heart transplantation but this option is limited by the acute shortage of donor hearts. The high incidence of heart diseases and the scarcity donor hearts underline the urgent need to find alternative therapeutic approaches for treating cardiovascular diseases. Pluripotent embryonic stem (ES) cells can differentiate into functional cardiomyocytes. Therefore the engraftment of ES cell-derived functional cardiomyocytes or cardiac progenitor cells into the damaged heart to regenerate healthy myocardial tissues may be used to treat damaged hearts. Stem cell-based therapy therefore holds a great potential as a very attractive alternative to heart transplant for treating heart failure and other cardiovascular diseases. A major obstacle to the realisation of stem cell-based therapy is the lack of donor cells and this in turn is due to the fact that, currently, the molecular mechanisms or the regulatory signal transduction mechanisms that are responsible for mediating ES cell differentiation into cardiomyocytes are not well understood. Overcoming this huge scientific challenge is absolutely necessary before the use of stem cell-derived cardiomyocytes to treat the damaged heart can become a reality. Therefore the aim of this thesis was to investigate the signal transduction pathways that are involved in the differentiation of stem cells into cardiomyocytes. The first objective was the establishment and use of cardiomyocyte differentiation models using H9c2 cells and P19 stem cells to accomplish the specific objectives of the thesis. The specific objectives of the thesis were, the investigation of the roles of (i) nitric oxide (ii) protein kinase C (PKC), (iii) p38 mitogen-activated protein kinase (p38 MAPK) (vi) phosphoinositide 3-kinase (PI3K) and (vi) nuclear factor-kappa B (NF-kB) signalling pathways in the differentiation of stem cells to cardiomyocytes and, more importantly, to identify where possible any points of convergence and potential cross-talk between pathways that may be critical for differentiation to occur. P19 cells were routinely cultured in alpha minimal essential medium (α-MEM) supplemented with 100 units/ml penicillin /100 μg/ml streptomycin and 10% foetal bovine serum (FBS). P19 cell differentiation was initiated by culturing the cells in microbiological plates in medium containing 0.8 % DMSO to form embryoid bodies (EB). This was followed by transfer of EBs to cell culture grade dishes after four days. H9c2 cells were cultured in Dulbecco’s Modified Eagle’s medium (DMEM) supplemented with 10% FBS. Differentiation was initiated by incubating the cells in medium containing 1% FBS. In both models, when drugs were employed, they were added to cells for one hour prior to initiating differentiation. Cell monolayers were monitored daily over a period of 12 or 14 days. H9c2 cells were monitored for morphological changes and P19 cells were monitored for beating cardiomyocytes. Lysates were generated in parallel for western blot analysis of changes in cardiac myosin heavy chain (MHC), ventricular myosin chain light chain 1(MLC-1v) or troponin I (cTnI) using specific monoclonal antibodies. H9c2 cells cultured in 1% serum underwent differentiation as shown by the timedependent formation of myotubes, accompanied by a parallel increase in expression of both MHC and MLC-1v. These changes were however not apparent until 4 to 6 days after growth arrest and increased with time, reaching a peak at day 12 to 14. P19 stem cells cultured in DMSO containing medium differentiated as shown by the timedependent appearance of beating cardiomyocytes and this was accompanied by the expression of cTnI. The differentiation of both P19 stem cells and H9c2 into cardiomyocytes was blocked by the PI3K inhibitor LY294002, PKC inhibitor BIM-I and the p38 MAPK inhibitor SB2035800. However when LY294002, BIM-I or SB2035800 were added after the initiation of DMSO-induced P19 stem cell differentiation, each inhibitor failed to block the cell differentiation into beating cardiomyocytes. The NF-kB activation inhibitor, CAPE, blocked H9c2 cell differentiation into cardiomyocytes. Fast nitric oxide releasing donors (SIN-1 and NOC-5) markedly delayed the onset of differentiation of H9c2 cells into cardiomyocytes while slow nitric oxide releasing donors (SNAP and NOC-18) were less effective in delaying the onset of differentiation or long term differentiation of H9c2 cells into cardiomyocytes. Akt (protein kinase B) is the key downstream target of PI3K. Our cross-talk data also showed that PKC inhibition and p38 MAPK inhibition respectively enhanced and reduced the activation of Akt, as determined by the phosphorylation of Akt at serine residue 473. In conclusion, PKC, PI3K, p38 MAPK and NF-kB are relevant for the differentiation of stem cells into cardiomyocytes. Our data also show that the PKC, PI3K and p38 MAPK signalling pathways are activated as very early events during the differentiation of stem cells into cardiomyocytes. Our data also suggest that PKC may negatively regulate Akt activation while p38 MAPK inhibition inhibits Akt activation. Our fast NO releasing donor data suggest that nitric oxide may negatively regulate H9c2 cell differentiation.

This study seeks to assess the level of women&rsquo
s participation and involvement in the promotion of effective governance during the African Peer Review Mechanism (APRM) implementation exercise in 2007, which was endorsed by the APRM Western Cape Province. The interest of the study arises from the concept of &lsquo
good governance&rsquo
and how the implementation of such a concept is carried out in the rendering of public services, specifically the role of women in rendering public service in the Western Cape Province, South Africa.

Made available in DSpace on 2014-07-29T15:18:22Z (GMT). No. of bitstreams: 1 Dissertacao parte 1 Pammila Japiassu.pdf: 6094546 bytes, checksum: 79242a16f08c8b4ca8b8d6b2112d1cda (MD5) Previous issue date: 2011-05-16
The historical glazed tiles facades are an important luso-brazilian cultural expression that must be conserved and preserved. The bonding loss of glazed tiles to laying mortars is one of the most critical pathologic manifestations of this kind of coating. However, despite this importance, there‟s still a lack of studies about the bonding mechanism between this historical components. Accordingly, this dissertation proposed to perform an experimental and exploratory research, which the main objective is to give some contribution to the understanding of the ancient tile‟s bonding mechanism to the aerial lime-based mortar of historical buildings facade. For this, were analyzed samples of facade historical ceramic coating, between the late XIX and early XX century, of Ovar‟s buildings, in Portugal. In order to reproduce the historical bonding mechanism, were also analyzed ceramic coating applied in laboratory studying mortars of rehabilitation. In the first stage, were analyzed the ceramic coating and the mortars historic of three cases, as well was performed the interface‟s study between this two materials. In the second stage, were produced ceramic coatings in laboratory using tiles (similar to the historical ones) and four types of mortars of rehabilitation, composed by aerial lime, metakaolin and sand, varying the content of pozolana in 0%, 5%, 10% e 15%, replacement of lime in volume. In this stage, were characterized the tile, the raw materials of the mortar, and mortar in the fresh and hardened. Finally, yet was studied the interface between the glazed tile and the mortar of rehabilitation, in order to compare this one to the historical one. It was observed in the analysis of the historical ceramic coatings that the values of bond strength and of extension of bond were more related to the agregates granulometry than to the binder/aggregate of the laying mortars. In the case of the ceramic coatings molded in laboratory, it was found the influence of the metakaolin content in the rehabilitation mortars in bond strength. It was also observed a possible influence of the shape of the tile‟s back surface in the bonding of ceramic coatings. By the analysis in the SEM was identified the morphology of the products of carbonation and possible pozzolanic reactions in the studied mortars, that contributing to the increased bond strength of these materials.
Os azulejos históricos em fachada são uma importante expressão cultural luso-brasileira, que deve ser conservada e preservada. A perda de aderência dos azulejos à argamassa de assentamento é uma das manifestações patológicas mais graves desse tipo de revestimento. No entanto, apesar dessa importância, ainda existe uma carência de estudos sobre o mecanismo de aderência entre esses componentes históricos. Nesse sentido, essa dissertação se propôs a realizar uma pesquisa exploratória e experimental, cujo objetivo principal é dar contribuição ao entendimento do mecanismo de aderência dos azulejos antigos à argamassa à base de cal aérea de fachada de edificações históricas. Para tanto, foram analisadas amostras de revestimentos cerâmicos históricos de fachada, entre o final século XIX e início do século XX, de edificações de Ovar, em Portugal. No intuito de reproduzir o mecanismo de aderência histórico, foram analisados também revestimentos cerâmicos aplicados em laboratório estudando argamassas de reabilitação. Na primeira etapa, foram caracterizados os azulejos e as argamassas históricas de três casos, bem como realizado o estudo interface entre esses dois materiais. Na segunda etapa, foram produzidos revestimentos cerâmicos em laboratório utilizando azulejos (similares aos históricos) e quatro tipos de argamassas de reabilitação, compostas por cal aérea, metacaulim e areia, variando o teor de pozolana em 0%, 5%, 10% e 15%, de substituição da cal em volume. Nesta etapa, foram caracterizados o azulejo, as matérias-primas da argamassa, assim como argamassa no estado fresco e endurecido. Por fim, ainda foi estudada a interface entre o azulejo e a argamassa de reabilitação, visando compará-la com a histórica. Observou-se na análise dos revestimentos cerâmicos históricos que os valores de resistência de aderência e de extensão de aderência estavam mais relacionados à granulometria dos agregados do que à relação aglomerante/agregado das argamassas de assentamento. No caso dos revestimentos cerâmicos moldados em laboratório, constatou-se a influência do teor de metacaulim nas argamassas reabilitação na resistência de aderência. Foi observada também uma possível influência da muratura do tardoz do azulejo na aderência dos revestimentos cerâmicos. Pelas análises no MEV foi identificada a morfologia de produtos de carbonatação e de possíveis reações pozolânicas nas argamassas estudadas, que contribuem para o aumento da resistência de aderência dessas.

Le système Rh est le système sanguin érythrocytaire le plus complexe et le plus poly morphe. Il est sous le contrôle de deux gènes homo logues RHD et RHCE et comporte 55 antigènes, parmi lesquels l’antigène D, porté par la protéine RhD, est le plus immunogène et présente un intérêt majeur en terme de Santé Publique. Actuellement, plusieurs centaines d’allèles variants sont répertoriés dans le gène RHD, qui se traduisent par une grande variabilité phénotypique de l’expression de l’antigène D. La plupart du temps, le typage sanguin des individus porteurs d’un variant de l’antigène D n’est souvent pas réalisable par des approches sérologiques, il faut alors avoir recours à des analyses moléculaires pour identifier les anomalies potentielles et déduire le phénotype correspondant. Néanmoins, l’interprétation de ces variants rares et de leurs conséquences sur l’expression de l’antigène demeurent souvent difficiles. Dans ce travail, nous nous sommes intéressés, plus spécifiquement à trois catégories de variants : les variants d’épissage, les variants synonymes et les variants faux-sens. Nous avons étudié l’impact moléculaire et cellulaire de ces variants en développant des approches de génétiques fonctionnelles et observé leurs effets respectifs sur l’altération de l’épissage et/ou sur l’expression de l’antigène D. Ces travaux ont per mis d’avoir une vision globale des différents mécanismes moléculaires impliqués dans la variabilité génétique du système Rh, en particulier sur l’interprétation des variants rares affectant les sites canoniques et les éléments régulateurs de l’épissage, par une approche minigène développée dans notre laboratoire. Puis, au-delà de l’intérêt fondamental de la caractérisation fonctionnelle de ces variants, en association avec les analyses sérologiques, elle présente un intérêt diagnostique dans l’interprétation fonctionnelle de certains phénotypes ambigus et ainsi guider le biologiste dans la prise en charge de la transfusion et de la grossesse
Rh system is the most complex and polymorphic blood group system. It’s driven by two homologous genes RHD and RHCE and contains 55 antigens, including the D antigen, carried by the RhD protein, is the most immunogenic and has a major interest in terms of public health. Currently, several hundred variants alleles are listed in the RHD gene, resulting in high phenotypic variability of the D antigen expression. In most cases, blood typing of individuals with a D variant is often not available by serological approaches, so molecular analyses should be used to identify potential defects and deduce the corresponding phenotype. Nevertheless, the interpretation of these rare variants and their consequences on the antigen expression often remain difficult. In this work, we are more specifically interested in three categories of variants: splicing variants, synonymous variants and missense variants. We studied the molecular and cellular impact of these variants by developing functional genetic approaches and observed their respective effects on the splicing alteration and/or on the D antigen expression. This work has provided an overview of the different molecular mechanisms involved in the genetic variability of the Rh system, in particular the interpretation of rare variants affecting the canonical splice sites and the splicing regulatory elements, using a minigene splicing assay developed in our laboratory. Then, beyond the fundamental interest of the functional characterization of these variants, in association with serological analyses, it presents a diagnostic interest in the functional interpretation of certain ambiguous phenotypes. Then, beyond the fundamental interest of the functional characterization of these variants, in association with serological analyses, it presents a diagnostic interest in the functional interpretation of certain ambiguous phenotypes and thus guide the biologist in the management of transfusion and pregnancy

Ce travail est consacre a la synthese, la caracterisation physico-chimique et l'application de films de polymeres conducteurs electroniques (pce) incluant des heteropolyanions (hpa). Ces entites minerales, connues pour leurs remarquables proprietes redox, sont immobilisees en tant qu'anion dopant lors de la synthese electrochimique des pce. Dans un premier temps, nous montrons qu'une electrode modifiee par un film de poly(3-methyl thiophene) dope par un hpa de structure de keggin xm#1#2o#4#0#n#- (x = p, si ; m = w, mo et n = 3, 4) presente l'electroactivite des deux partenaires. La reponse electrochimique associee a l'hpa n'est pas modifiee apres son immobilisation, pour peu que les conditions de l'electrosynthese du film soient optimisees (rapport monomere/hpa et valeur du potentiel impose). La geometrie particuliere de l'hpa n'induit pas une structure organisee dans le poly(3-methyl thiophene). Afin de remonter a une explication structurale du materiau, nous entreprenons, dans un second temps, l'etude d'un compose modele base sur un oligomere du thiophene (6t)#4#p#+/(pmo#1#2o#4#0)#p#- (6t represente l'hexamere du thiophene et 3 < p < 4). Malheureusement, la tres faible solubilite de ce sel ne permet pas des cristallisations adequates pour des etudes cristallographiques. Les films de pce/hpa peuvent realiser des electrocatalyses, a condition de choisir la bonne association. Dans ce sens, nous mettons en evidence qu'une electrode modifiee par un film de poly(n-methyl pyrrole) incluant un hpa mixte fepw#1#1o#3#9(h#2o)#4#- presente une remarquable stabilite electrochimique et activite electrocatalytique vis-a-vis de la reduction de no#2#-. Le mecanisme de reduction en phase immobilisee passe par un complexe fer-nitrosyl fepw#1#1o#3#9(no)#5#- qui assure la selectivite de cette catalyse chimique electroassistee. Cette electrode modifiee permet de la meme maniere la reduction catalytique du no dissous dans l'eau. Cette molecule, actuellement reconnue comme mediateur intercellulaire essentiel, peut etre detectee in vivo a partir d'une fibre de carbone modifiee par le depot catalytique precedent. Cette etude, realisee en collaboration avec r. Cespuglio (inserm, lyon) constitue un des rares exemples de detection fonctionnelle et en temps reel de cette molecule

O Vírus da Imunodeficiência Humana (HIV) é o agente etiológico da Síndrome da Imunodeficiência Adquirida (AIDS). A AIDS é uma doença de distribuição mundial, e estima-se que existam atualmente pelo menos 36,9 milhões de pessoas infectadas com o vírus. Durante o seu ciclo replicativo, o HIV promove diversas alterações na fisiologia da célula hospedeira a fim de promover sua sobrevivência e potencializar a replicação. A rápida progressão da infecção pelo HIV-1 em humanos e em modelos animais está intimamente ligada à função da proteína acessória Nef. Dentre as diversas ações de Nef está a regulação negativa de proteínas importantes na resposta imunológica, como o receptor CD4. Sabe-se que esta ação resulta da indução da degradação de CD4 em lisossomos, mas os mecanismos moleculares envolvidos ainda são totalmente elucidados. Nef forma um complexo tripartite com a cauda citosólica de CD4 e a proteína adaptadora 2 (AP-2), em vesículas revestidas por clatrina nascentes, induzindo a internalização e degradação lisossomal de CD4. Pesquisas anteriores demonstraram que o direcionamento de CD4 aos lisossomos por Nef envolve a entrada do receptor na via dos corpos multivesiculares (MVBs), por um mecanismo atípico, pois, embora não necessite da ubiquitinação de carga, depende da ação de proteínas que compõem os ESCRTs (Endosomal Sorting Complexes Required for Transport) e da ação de Alix, uma proteína acessória da maquinaria ESCRT. Já foi reportado que Nef interage com subunidades dos complexos AP-1, AP-2, AP-3 e Nef não parece interagir com subunidades de AP-4 e AP-5. Entretanto, o papel da interação de Nef com AP-1 e AP-3 na regulação negativa de CD4 ainda não está totalmente elucidado. Ademais, AP-1, AP-2 e AP-3 são potencialmente heterogêneos devido à existência de isoformas múltiplas das subunidades codificadas por diferentes genes. Todavia, existem poucos estudos para demonstrar se as diferentes combinações de isoformas dos APs são formadas e se possuem propriedades funcionais distintas. O presente trabalho procurou identificar e caracterizar fatores celulares envolvidos na regulação do tráfego intracelular de proteínas no processo de regulação negativa de CD4 induzido por Nef. Mais especificamente, este estudo buscou caracterizar a participação do complexo AP-1 na modulação negativa de CD4 por Nef de HIV-1, através do estudo funcional das duas isoformas de ?-adaptina, subunidades de AP-1. Utilizando a técnica de Pull-down demonstramos que Nef é capaz de interagir com ?2. Além disso, nossos dados de Imunoblot indicaram que a proteína ?2-adaptina, e não ?1-adaptina, é necessária no processo de degradação lisossomal de CD4 por Nef e que esta participação é conservada para degradação de CD4 por Nef de diferentes cepas virais. Ademais, por citometria de fluxo, o silenciamento de ?2, e não de ?1, compromete a diminuição dos níveis de CD4 por Nef da membrana plasmática. A análise por imunofluorêsncia indireta também revelou que a diminuição dos níveis de ?2 impede a redistribuição de CD4 por Nef para regiões perinucleares, acarretando no acúmulo de CD4, retirados por Nef da membrana plasmática, em endossomos primários. A depleção de ?1A, outra subunidade de AP-1, acarretou na diminuição dos níveis celulares de ?2 e ?1, bem como, no comprometimento da eficiente degradação de CD4 por Nef. Além disso, foi possível observar que, ao perturbar a maquinaria ESCRT via super-expressão de HRS (uma subunidade do complexo ESCRT-0), ocorreu um acumulo de ?2 em endossomos dilatados contendo HRS-GFP, nos quais também detectou-se CD4 que foi internalizado por Nef. Em conjunto, os resultados indicam que ?2-adaptina é uma importante molécula para o direcionamento de CD4 por Nef para a via ESCRT/MVB, mostrando ser uma proteína relevante no sistema endo-lisossomal. Ademais, os resultados indicaram que as isoformas ?-adaptinas não só possuem funções distintas, mas também parecem compor complexos AP-1 com diferentes funções celulares, já que apenas a variante AP-1 contendo ?2, mas não ?1, participa da regulação negativa de CD4 por Nef. Estes estudos contribuem para o melhor entendimento dos mecanismos moleculares envolvidos na atividade de Nef, que poderão também ajudar na melhor compreensão da patogênese do HIV e da síndrome relacionada. Em adição, este trabalho contribui para o entendimento de processos fundamentais da regulação do tráfego de proteínas transmembrana no sistema endo-lisossomal.
The Human Immunodeficiency Virus (HIV) is the etiologic agent of Acquired Immunodeficiency Syndrome (AIDS). AIDS is a disease which has a global distribution, and it is estimated that there are currently at least 36.9 million people infected with the virus. During the replication cycle, HIV promotes several changes in the physiology of the host cell to promote their survival and enhance replication. The fast progression of HIV-1 in humans and animal models is closely linked to the function of an accessory protein Nef. Among several actions of Nef, one is the most important is the down-regulation of proteins from the immune response, such as the CD4 receptor. It is known that this action causes CD4 degradation in lysosome, but the molecular mechanisms are still incompletely understood. Nef forms a tripartite complex with the cytosolic tail of the CD4 and adapter protein 2 (AP-2) in clathrin-coated vesicles, inducing CD4 internalization and lysosome degradation. Previous research has demonstrated that CD4 target to lysosomes by Nef involves targeting of this receptor to multivesicular bodies (MVBs) pathway by an atypical mechanism because, although not need charging ubiquitination, depends on the proteins from ESCRTs (Endosomal Sorting Complexes Required for Transport) machinery and the action of Alix, an accessory protein ESCRT machinery. It has been reported that Nef interacts with subunits of AP- 1, AP-2, AP-3 complexes and Nef does not appear to interact with AP-4 and AP-5 subunits. However, the role of Nef interaction with AP-1 or AP-3 in CD4 down-regulation is poorly understood. Furthermore, AP-1, AP-2 and AP-3 are potentially heterogeneous due to the existence of multiple subunits isoforms encoded by different genes. However, there are few studies to demonstrate if the different combinations of APs isoforms are form and if they have distinct functional properties. This study aim to identify and characterize cellular factors involved on CD4 down-modulation induced by Nef from HIV-1. More specifically, this study aimed to characterize the involvement of AP-1 complex in the down-regulation of CD4 by Nef HIV-1 through the functional study of the two isoforms of ?-adaptins, AP-1 subunits. By pull-down technique, we showed that Nef is able to interact with ?2. In addition, our data from immunoblots indicated that ?2- adaptin, not ?1-adaptin, is required in Nef-mediated targeting of CD4 to lysosomes and the ?2 participation in this process is conserved by Nef from different viral strains. Furthermore, by flow cytometry assay, ?2 depletion, but not ?1 depletion, compromises the reduction of surface CD4 levels induced by Nef. Immunofluorescence microscopy analysis also revealed that ?2 depletion impairs the redistribution of CD4 by Nef to juxtanuclear region, resulting in CD4 accumulation in primary endosomes. Knockdown of ?1A, another subunit of AP-1, resulted in decreased cellular levels of ?1 and ?2 and, compromising the efficient CD4 degradation by Nef. Moreover, upon artificially stabilizing ESCRT-I in early endosomes, via overexpression of HRS, internalized CD4 accumulates in enlarged HRS-GFP positive endosomes, where co-localize with ?2. Together, the results indicate that ?2-adaptin is a molecule that is essential for CD4 targeting by Nef to ESCRT/MVB pathway, being an important protein in the endo-lysosomal system. Furthermore, the results indicate that ?-adaptins isoforms not only have different functions, but also seem to compose AP-1 complex with distinct cell functions, and only the AP-1 variant comprising ?2, but not ?1, acts in the CD4 down-regulation induced by Nef. These studies contribute to a better understanding on the molecular mechanisms involved in Nef activities, which may also help to improve the understanding of the HIV pathogenesis and the related syndrome. In addition, this work contributes with the understanding of primordial process regulation on intracellular trafficking of transmembrane proteins.

碩士
國立臺灣大學
藥理學研究所
96
In the present study, the mechanism of antiplatelet activity of p95wu33a, a synthetic 1-( 5-methyl-2furyl )-3-phenyl-2-propen-1-one, was investigated. p95wu33a concentration-dependently inhibited platelet aggregation stimulated by collagen ( 10μg/ml ), AA ( 200μM ), U46619( 1μM ) and thrombin (0.1U/ml) with IC50 values of 0.23±0.02, 0.41±0.05,13.38±0.28 and 285.12±3.39 μM in washed human platelets, respectively. p95wu33a also inhibited collagen-induced P-selectin expression and thromboxane B2 formation. In addition, p95wu33a attenuated tyrosine phosphorylation of a number of signal proteins including PLCγ2、PI3K、Syk、Src、and LAT. Fibrinogen binding to activated glycoprotein GPIIb-IIIa is the final common pathway of platelet aggregation. However, p95wu33a did not affect fibrinogen binding to activated GPIIb-IIIa. This suggests that the inhibitory effect of p95wu33a is not through acting as a direct antagonist of GPIIb-IIIa. Sodium nitroprusside (SNP) markedly potentiated the platelet-inhibitory effect of p95wu33a. It was demonstrated that p95wu33a itself markedly increased guanosine 3’,5’-cyclic monophosphate (cGMP) level and Sodium nitroprusside potentiated the elevated cGMP by p95wu33a. The inhibitory effect of p95wu33a on collagen-induced platelet aggregation and cGMP content was markly enhanced in the presence of ODQ, an inhibitor of sGC. p95wu33a inhibited the biosynthesis of thromboxan B2 induced by arachidonic acid and collagen. However, it had no inhibitory on cytosolic phospholipase A2, suggesting that it dose not affect the endogenous cPLA2 activity, but impairs arachidonate - thromboxane A2 biosynthesis pathway. In Fura-2 loaded platelets, p95wu33a inhibited intracellular calcium mobilization triggered by collagen. Similar to other nucleotide-elevating agent, p95wu33a dose-dependently inhibited platelet adhesion to collagen. p95wu33a significantly reduced the ex vivo platelet aggregation of PRP in ICR mice, as it was intravenously administered at a dose of 10μg/g, whereas p95wu33a at the same dose cause a slight prolongation of tailing bleeding time. In conclusion, the promising antithrombotic profile of p95wu33a, PDE5 inhibitor and sGC activator, suggests that it is an attractive lead compound for developing antiplatelet agents.

碩士
輔仁大學
化學系
91
Abstract (1) When (E)-3-phenyl-1-[(phenylsulfonyl)imino]-2-propene(1) was treated with 2 equivalent methyl lithium(MeLi),five compounds-2, 3, 4, 5, and 6 were isolated. The formation of products 3 and 6 were studied. Compound 2 was treated with 2 equivalent MeLi to produce dianion 25.Dianion 25 underwent intramolecular reaction and reacted with water and deprotonation to generate anion 26 follwed by ring opening and proton absorption to form compound 3. The formation of 6 is via carbanion exchange from methyl carbanion to phenyl carbanion. When compound 6 reacted with phenyl carbanion, the 1,4-addition adduct, carbanion was generated. Carbanion underwent intramolecular addition and proton absorption to provide compound 9 which was oxidized to form compound 6. (2) When 1,7,7-tribromo-bicyclo[4.1.0]heptane (36) was treated with 2.5 equivalent MeLi, generated intermediate 41 which was trapped with 1,3-diphenylisobenzofuran (DPIBF) to form compound 40..Intermediate 41 was proved by compound 45 react with side product MeBr. Treatment of the compound 36 with 2.5 equivalent n-BuLi gave product 47 which is formed by intermediate 48 ring opening. We also found that compound 34 underwent ene-reaction fastly to give a dimeric product 48. But product 48 was unstabled to ring opening and reacted Oxygen in the air to give product 47.

Background & Aims: Oxidative stress and apoptosis are proposed mechanisms of cellular injury in studies of xenobiotic hepatotoxicity. The aim of this work is to find early signal markers of drug-induced injury of the liver by focusing on select antioxidant/oxidant and apoptotic genes. As well, to address the relationship between conventional liver dysfunction markers and the measured mRNA and protein expressions in the D-galactosamine/lipopolysaccharide and tert-butylhydroperoxide hepatotoxicity models. Furthermore, potential hepatoprotective capabilities of antioxidant polyphenols quercetin and curcumin were evaluated in relation to its modulation of the oxidative stress and apoptotic parameters in the given xenobiotic hepatotoxicity models. Methods: Biochemical markers testing the hepatic function included aminotransferases (ALT, AST) and bilirubin. Measurements of TBARS and conjugated dienes were used to assess lipoperoxidation. Plasma levels of catalase and reduced glutathione were used as indicators of the oxidative status of the cell. Real time PCR was used to analyse the mRNA expressions of the inducible nitric oxide synthase (NOS-2), heme oxygenase-1 (HO-1), superoxide dismutase (SOD-1), glutathione peroxidase (Gpx-1), caspase 3 (Casp3), BH3 interacting domain death agonist (Bid) and Bcl-2...

The cabbage seedpod weevil, Ceutorhynchus obstrictus (Marsham) (Coleoptera: Curculionidae), is an important pest of brassicaceous oilseed crops, especially canola (Brassica napus L. and Brassica rapa L.) in North America and Europe. Application of foliar insecticide is the only method currently employed to control C. obstrictus populations; because this approach is environmentally unsustainable, alternatives including host plant resistance have been explored. White mustard, Sinapis alba L., is resistant to C. obstrictus and was chosen as a potential source of resistance for B. napus oilseed. Interspecific crosses of S. alba x B. napus have produced several lines that are resistant to C. obstrictus feeding and oviposition and yield fewer, lighter-weight weevil larvae that take longer to develop. I investigated potential mechanisms of this resistance, including assessing differences in visual and olfactory cues among resistant and susceptible genotypes, and antixenosis and antibiosis. Determining effects of visual cues associated with host plant resistance required investigation of weevil vision. Deployment strategies for resistant germplasm were assessed to evaluate incorporation of susceptible refugia to promote long-term durability of resistance traits. Results reported in Chapter 2 indicate that the C. obstrictus visual system is apparently trichromatic and incorporates receptors with response maxima near 350, 450, and 550 nm. Modelling indicated that UV light alone reduced weevil responses but the interaction of yellow and UV light increased responses at a threshold reflectance level of UV. Results reported in Chapter 3 indicated that differences in yellow and UV reflectance among host plant flowers influence host selection in C. obstrictus. Results described in Chapter 4 determine differential attraction to the odours of S. alba and B. napus and among resistant and susceptible accessions. Inferences of the identities of glucosinolates found in varying amounts among susceptible and resistant genotypes suggested that 2-phenylethyl glucosinolate influenced attractiveness. Results described in Chapter 5 indicate differences in adult feeding and oviposition preferences among resistant and susceptible genotypes. Oocyte development, larval biomass and larval development time varied among weevils feeding on resistant and susceptible genotypes. Based on results of Chapter 4, 1-methoxy-3-indolylmethyl glucosinolate was implicated as contributing to antixenosis and antibiosis resistance. Results reported in Chapter 6 describe effects of mixed plots of resistant and susceptible genotypes on weevil spatial distribution and oviposition. These results are consistent with associational resistance and attributed to reduced apparency of susceptible plants in mixtures and antixenosis resistance associated with resistant germplasm.
Plant Science

博士
中山醫學大學
生化暨生物科技研究所
96
Cardiac hypertrophy is an adaptive response of heart under varied stresses. When stress has been accumulated, the transition from physiological hypertrophy to pathological hypertrophy results in promotion of heart failure. Our previous studies demonstrated upregulations of insulin-like growth factor II (IGF-II) and mannose 6-phosphate/IGF-II receptor (IGF2R) dose-dependently correlating with the progression of heart disease following complete abdominal aorta ligation, may play a critical role in angiotensin II (ANGII)-induced cardiomyocyte apoptosis. However, the detailed mechanisms of IGF2R in the promotion of heart failure in response to IGF-II remain unclear. Additionally, how igf2r gene up-regulation in response to pathological stresses is also poorly understood. Therefore, in the study I, we found a significant association of IGF2R overexpression with myocardial infarction and myocardial scars. Results of specifically activating IGF2R signaling through either inhibition of the IGF1R activity by IGF1R siRNA and AG1024 or using Leu27IGF-II analog, a ligand interact only with the IGF2R, revealed that IGF2R activated by IGF-II binding acted like a G protein-coupled receptor to activate PKC-α/CaMKII and calcineurin by association with Gαq, leading to pathological hypertrophy and mitochondria-dependent cell apoptosis in cardiomyocytes. Furthermore, we also found that IGF2R signaling activation disrupted the balance of MMP-9/TIMP-2 expressions and increased plasminogen activator (PAs) expression, resulting in the development of myocardial remodeling. In study II, we found the histone acetylation, but not the DNA methylation, is required for the induction of igf2r gene by ANGII. Moreover, when responding to ANGII, HSF-1, identified as a suppressor of igf2r gene under normal condition, slipped out of the HSF-binding element within the IGF2R promoter that contributes up-regulation of igf2r gene expression. Taken together, our study provides new insight into the gene regulation of IGF2R and the role of the IGF2R in the pathogenesis of cardiac disease. Suppression of IGF2R gene expression and its signaling pathways may be a good strategy to prevent the progression of heart failure. We also discovered a novel gene of IGF2R isoform, 2R-α, which transcripts 4656 nucleic acid mRNA examined by using the rapid amplification of cDNA ends (RACE) PCR and northern blots. After compared with IGF2R mRNA sequences, regardless of the same sequences from IGF2R’s exon 10 to exon 35, the 2R-α gene sequence unexpectedly comprise a partial fragment of intron 9 (645~806 bp) of IGF2R in its 5’ region and a partial fragment of intron 35 (1~455 bp) in its 3’ region. In addition, we found a new TATA box exists in the 5’ upstream region of 2R-α gene and its coding region starts at the 14 bp of exon 10, then stops in the 48bp of intron 35 that may encode a 1358 amino acids protein predicted by Open Reading Frame Finder. Furthermore, creating the antibody that recognized the 15 amino acidic sequence in N terminal：AYDESEDDTSDTTPC of predicted 2R-α protein sequences to confirm the translation of gene transcript into the 2R-α protein. Further to identify the role and function of this novel 2R-α gene in the future may provide a new concept of IGFs in regulating cell physiology and heart function.