Objective: CSL360 is a chimeric IgG1 mAb recognizing CD123+/CD131- LSCs responsible for acute myeloid leukemia (AML). The in vitro targeting properties of 111In-labeled CSL360 modified with nuclear localization sequence (NLS) were evaluated in AML cells. Methods: 111In-NLS-CSL360 was constructed and its binding affinity, cellular uptake and nuclear importation were analyzed on CD123+ cells. Cytotoxicity was evaluated by clonogenic assays on AML cells (CD123+/CD131-). Results: 111In-NLS-CSL360 exhibited preserved binding to CD123. High cellular and nuclear uptake was observed at 266 nM after 24 hour of incubation. Nuclear uptake of 111In-NLS-CSL360 (266 nM) was 2.0-fold higher than 111In-CSL360 (266 nM) after 24 hour of incubation. Clonogenic survival (CS) of AML cells was reduced to 27.5 ± 4.1%. The nuclear uptake and cytotoxicity were reduced when pre-exposed to unlabeled CSL360, indicating 111In-NLS-CSL360 was CD123-specific. Conclusion: 111In-NLS-CSL360 could be a promising radioimmunotherapeutic agent specific for LSCs.

Objective: The cytotoxic property of anti-EGFR-1 monoclonal-antibody nimotuzumab modified with nuclear localization sequence and radiolabeled with 111In was evaluated in trastuzumab-resistant breast cancer cells. Methods: 111In-nimotuzumab-NLS was constructed and its immunoreactivity was determined. Cellular and nuclear uptake was evaluated by cell fractionation. Finally, the cytotoxicity of conjugates (111In-nimotuzumab/111In-nimotuzumab-NLS) was studied by clonogenic assays. Results: The immunoreactivity of 111In-nimotuzumab-NLS was conserved. 111In-nimotuzumab-NLS exhibited 2-fold higher nuclear translocation as compared to 111In-nimotuzumab in MDA-MB-468 cells. Nuclear importation of 111In-nimotuzumab-NLS in MDA-MB-468 cells was 4-fold and 6-fold higher than moderate and low EGFR expressing cell lines, respectively. Clonogenic survival (CS) for MDA-MB-468 cells showed 111In-nimotuzumab-NLS to be 10-folds and 60-folds more potent than 111In-nimotuzumab and nimotuzumab, respectively. Moderate killing for TrR1 and MDA-MB-231 was observed. 111In-hEGF showed significantly higher cytotoxicity and 2-fold higher γ-H2AX foci integrated density/nuclear-area as compared to 111In-nimotuzumab-NLS. Preserved selectivity of 111In-nimotuzumab-NLS makes it an excellent drug for treating cancers.

Ethylene hydrogenation on Ni(111) / equilibrium geometry calculations for Ni2 dimer, Ni13 and Ni55 nanoclusters / and ethylene adsorption on Ni(100), Ni(111), Ni2, and Ni13 were studied quantum mechanically by means of energetic and kinetic differences. Ethylene hydrogenation on Ni(111) was simulated by use of DFT/B3LYP/6-31G** formalism. The reaction mechanism was mainly composed of three elementary steps. Firstly, ethylene adsorption on bare Ni(111) surface was performed. Second step and third step were the formation of ethane from adsorbed ethylene by use of two types of hydrogen atom, bulk and surface. During the hydrogenation reaction of ethylene on Ni(111), bulk hydrogen atom, representing for hydrogen atoms emerging from the bulk of Ni metal, was determined to be rather reactive than surface hydrogen atom, as suggested by experimental findings. Small Ni clusters, Ni2 and Ni13, were investigated by means of DFT/B3LYP/modified-6-31G**. Equilibrium geometry calculations resulted in Ni2 binding energy of 1.078eV/atom, showing good agreement with experimental value. Ni13 was found to have a structure of icosahedral, suggested experimentally, and binding energy of 2.70eV/atom. Ni55 was, also, studied by semi-empirical PM3 formalism, resulting in expected icosahedral structure. Finally, DFT/B3LYP/6-31G** investigation of ethylene adsorption was performed on Ni(111), Ni(100) and Ni13 surfaces which were selected according to their nickel atom coordination numbers of 9, 8 and 6, respectively. Comparison of adsorption energies of -18.00kcal/mol, -31.4kcal/mol and -43.42kcal/mol, respectively, indicated that the change in energies for ethylene adsorption on different nickel surfaces was directly proportional to coordination number of the nickel atoms constructing the surfaces.

ABSTRACT PREPARATION OF PLZT THIN FILMS BY CHEMICAL SOLUTION DEPOSITION AND THEIR CHARACTERIZATION Kaplan, Burkan M.S., Department of Metallurgical and Materials Engineering Supervisor: Prof. Dr. Macit &Ouml / zenbaS November 2005, 125 pages In this study, La3+ was substituted into lead zirconate titanate (PZT) system by Pb1-xLax(ZryTi1-y)1-x/4O3 nominal stochiometry and it was processed via chemical solution deposition on (111)-Pt/Ti/SiO2/Si-(100) substrate.PLZT solutions were prepared by mixing two solutions, one of which was obtained by dissolving lead acetate and lanthanum acetate hydrate in 2 methoxyethanol at high temperature. This solution was then mixed with the second solution containing zirconium propoxide and titanium isopropoxide. 40ml/0.4M solution was prepared and spin coated on Pt/Ti/SiO2/Si substrates at 3000 rpm for 30 seconds. After 4 coating cycles, film thickness was reached to 600 nm. A systematic study was carried out in different regions of PLZT phase diagram tetragonal, rhombohedral and on the morphotropic phase boundry (MPB) to obtain optimized results of ferroelectric, dielectric and optical properties of the material. During the period of the work, effect of parameters on these properties such as heat treatment conditions, chemical composition of the film, microstructure and thickness of the film was investigated. The films were characterized structurally and electrically. For structural properties, X-ray diffraction technique (XRD), energy dispersive spectrometry (EDS) and Scanning Electron Microscope (SEM) were used to observe phases and surface characterization. For electrical measurements, ferroelectric tester was used to obtain dielectric constant, loss tangent and hysteresis curves. Optical transmittance of the films was also investigated by UV-VIS Spectrophotometer and optical film constants were calculated by modified envelope method. It was observed that the optimum heat treatment conditions were achieved at 7500C for 3 hours. The highest ferroelectric and dielectric properties such as remanent polarization and dielectric constant were obtained using that temperature. The dielectric constant of the films was measured in the frequency range of 1kHz-1MHz and remained almost constant in this region. The change of dielectric constant and ferroelectric hysteresis loops were obtained as a function of Zr/Ti ratio and La content. The grain size as a function of sintering temperature and La content was investigated. It was seen that as the sintering temperature was increased, the grain size of the films increased. The same tendency was also observed when the La content was increased. Fatigue behavior of PLZT thin films was also investigated by Radiant Ferroelectric Tester at 50 kHz and &plusmn / 15V. Change of remanent polarization (Pr) as a function of cumulative switching cycles (N) was drawn with the log scale of x-axis. Furthermore, leakage current characteristics of the films were also obtained by the ferroelectric tester at &amp / #61617 / 15V. It has been observed that as the La content of the film was increased, leakage current of the PLZT films decreased. Keywords: PLZT, (111)-Pt/Ti/SiO2/Si-(100) substrate, Chemical Solution Deposition.

Made available in DSpace on 2014-10-09T12:46:45Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:56:46Z (GMT). No. of bitstreams: 1 08358.pdf: 3987174 bytes, checksum: bd5e0ea6705a189997deab3c68d85291 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP / FAPESP:99/08249-9

The world energy and product consumption keep increasing steadily over the years as the world population keeps growing and more countries become industrialized. As the world reserves deplete it becomes a necessity to find an alternative way to meet the population’s demand. Biomass conversion seems to be the future of a clean and sustainable world. Lignin is the second most abundant polymer in the biomass. Given the unique structure and chemical properties of lignin, a wide variety of bulk and fine chemicals can be obtained and be used for goods and biofuels production. Catalysis, with its selective bond cleavage and lower energy activation, is considered as a potential key solution in the process of lignin conversion into valuable chemicals. To gain insights into that catalytic system, we performed surface science experiments (X-ray Photoelectron Spectroscopy, Temperature Programmed Desorption and Reflection Absorption Infrared Spectroscopy) under Ultra-High Vacuum conditions (UHV). Due to lignin’s physical properties limitation under UHV conditions, lignin models with the same chemical structure such as phenol, anisole, 2-phenoxyethanol and veratrol were used to gain a better understanding of the reactivity of lignin itself. Dosing anisole and 2-phenoxyethanol on Pt(111) surprisingly gave benzene, carbon monoxide and hydrogen as the main desorbing products of decomposition. With the help of Density Functional Theory (DFT), we successfully explain the unexpected selectivity. In the present work, we show in particular that phenoxy PhO stands as a key intermediate. Although the UHV conditions do not allow the hydrogenation of phenoxy into phenol, i.e. the catalytic product, they reveal the key role of both hydrogen and carbonaceous species. Under UHV conditions, anisole and 2-phenoxyethanol are extensively dehydrogenated: it results in the formation of carbonaceous fragments, which can actually perform the deoxygenation of phenoxy into benzene. The reactivity of veratrol on Pt(111) hindered the formation of benzene and only gave carbon monoxide and hydrogen as the main desorbing products of decomposition. Although carbonaceous fragments were formed on the surface, the deoxygenation of the two oxygenated arm moieties does not occur without the total decomposition of the aromatic ring, hence the formation of coke. This detailed work opens the door to a rational design of metal-based catalysts and a route towards lignin valorization.

A presente dissertação tem por objetivo avaliar o papel do silêncio na formação contratual. Analisa-se, tendo-se como base os conceitos da proposta e da aceitação, assim como suas principais modalidades, as formas pelas quais pode se dar a declaração negocial. Inicia-se, com o objetivo de compará-los com o silêncio, pelo exame dos meios não silenciosos de declaração negocial, individualizando-se e analisando-se criticamente as formas expressa e tácita, assim como os comportamentos concludentes, elementos objetivos da última. Mediante o estudo dessas formas e das teorias tradicionais do silêncio, conclui-se que a adotada pelo vigente Código Civil é a Teoria do Silêncio Qualificado. A partir daí, analisa-se o silêncio como forma de declaração negocial e sua evolução no Direito brasileiro e comparado para alcançar-se o vigente diploma civil, o qual prevê que o silêncio importa anuência, em seu artigo 111. Conclui-se, tendo-se como base o acima exposto, que o silêncio é forma de declaração negocial autônoma, não se constituindo, pois, sinônimo ou subespécie da declaração expressa ou da tácita. Infere-se, igualmente e por isso mesmo, então, que o silêncio é forma de aceitação à proposta contratual, desde que presentes os elementos qualificadores – circunstâncias e usos – previstos no dispositivo legal respectivo e desde que observados outros elementos aplicáveis às relações de Direito civil e contratuais, especialmente. Analisam-se por fim, exemplificativamente, outros elementos de concreção a serem observados para valoração do silêncio, como a confiança negocial e os fins econômicos e sociais. / The purpose of the thesis is the assessment of the silence’s role in the contract formation. Taking into consideration the offer and acceptance meanings as well as their categories, their means of declaration are analyzed. Starting with the comparison to the silence as an objective, the tacit and express declarations are critically assessed. Based on the studies above mentioned it is possible to conclude that the theory regarding the silence adopted by the Brazilian Civil Code is the so-called Qualified Silence Theory. Therefore, the silence as a contractual declaration and its evolution in the Brazilian Civil Law is examined in order to reach the current article in the Brazilian Civil Code concerning this issue provision. The silence is an autonomous means of will declaration and it is not attached to the express or to the tacit one. This way, the conclusion regarding the silence’s role in the contract formation is that it is a way of expressing acceptance since special circumstances are present in the case, as stated in the article 111 of the Brazilian Civil Code, and once other elements applicable to the civil law and, specially, contractual relations are observed. e desde que observados outros elementos aplicáveis às relações de Direito civil e contratuais, especialmente Eventually, other concretion components – besides those provided in the referred article, which are the case’s circumstances and the common/usual practices – need to be taken into consideration in the silence analysis, such as the trust and the economical and social goals.

A presente dissertação tem por objetivo avaliar o papel do silêncio na formação contratual. Analisa-se, tendo-se como base os conceitos da proposta e da aceitação, assim como suas principais modalidades, as formas pelas quais pode se dar a declaração negocial. Inicia-se, com o objetivo de compará-los com o silêncio, pelo exame dos meios não silenciosos de declaração negocial, individualizando-se e analisando-se criticamente as formas expressa e tácita, assim como os comportamentos concludentes, elementos objetivos da última. Mediante o estudo dessas formas e das teorias tradicionais do silêncio, conclui-se que a adotada pelo vigente Código Civil é a Teoria do Silêncio Qualificado. A partir daí, analisa-se o silêncio como forma de declaração negocial e sua evolução no Direito brasileiro e comparado para alcançar-se o vigente diploma civil, o qual prevê que o silêncio importa anuência, em seu artigo 111. Conclui-se, tendo-se como base o acima exposto, que o silêncio é forma de declaração negocial autônoma, não se constituindo, pois, sinônimo ou subespécie da declaração expressa ou da tácita. Infere-se, igualmente e por isso mesmo, então, que o silêncio é forma de aceitação à proposta contratual, desde que presentes os elementos qualificadores – circunstâncias e usos – previstos no dispositivo legal respectivo e desde que observados outros elementos aplicáveis às relações de Direito civil e contratuais, especialmente. Analisam-se por fim, exemplificativamente, outros elementos de concreção a serem observados para valoração do silêncio, como a confiança negocial e os fins econômicos e sociais. / The purpose of the thesis is the assessment of the silence’s role in the contract formation. Taking into consideration the offer and acceptance meanings as well as their categories, their means of declaration are analyzed. Starting with the comparison to the silence as an objective, the tacit and express declarations are critically assessed. Based on the studies above mentioned it is possible to conclude that the theory regarding the silence adopted by the Brazilian Civil Code is the so-called Qualified Silence Theory. Therefore, the silence as a contractual declaration and its evolution in the Brazilian Civil Law is examined in order to reach the current article in the Brazilian Civil Code concerning this issue provision. The silence is an autonomous means of will declaration and it is not attached to the express or to the tacit one. This way, the conclusion regarding the silence’s role in the contract formation is that it is a way of expressing acceptance since special circumstances are present in the case, as stated in the article 111 of the Brazilian Civil Code, and once other elements applicable to the civil law and, specially, contractual relations are observed. e desde que observados outros elementos aplicáveis às relações de Direito civil e contratuais, especialmente Eventually, other concretion components – besides those provided in the referred article, which are the case’s circumstances and the common/usual practices – need to be taken into consideration in the silence analysis, such as the trust and the economical and social goals.

Made available in DSpace on 2014-10-09T12:55:02Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:05:57Z (GMT). No. of bitstreams: 0 / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP

A presente dissertação tem por objetivo avaliar o papel do silêncio na formação contratual. Analisa-se, tendo-se como base os conceitos da proposta e da aceitação, assim como suas principais modalidades, as formas pelas quais pode se dar a declaração negocial. Inicia-se, com o objetivo de compará-los com o silêncio, pelo exame dos meios não silenciosos de declaração negocial, individualizando-se e analisando-se criticamente as formas expressa e tácita, assim como os comportamentos concludentes, elementos objetivos da última. Mediante o estudo dessas formas e das teorias tradicionais do silêncio, conclui-se que a adotada pelo vigente Código Civil é a Teoria do Silêncio Qualificado. A partir daí, analisa-se o silêncio como forma de declaração negocial e sua evolução no Direito brasileiro e comparado para alcançar-se o vigente diploma civil, o qual prevê que o silêncio importa anuência, em seu artigo 111. Conclui-se, tendo-se como base o acima exposto, que o silêncio é forma de declaração negocial autônoma, não se constituindo, pois, sinônimo ou subespécie da declaração expressa ou da tácita. Infere-se, igualmente e por isso mesmo, então, que o silêncio é forma de aceitação à proposta contratual, desde que presentes os elementos qualificadores – circunstâncias e usos – previstos no dispositivo legal respectivo e desde que observados outros elementos aplicáveis às relações de Direito civil e contratuais, especialmente. Analisam-se por fim, exemplificativamente, outros elementos de concreção a serem observados para valoração do silêncio, como a confiança negocial e os fins econômicos e sociais. / The purpose of the thesis is the assessment of the silence’s role in the contract formation. Taking into consideration the offer and acceptance meanings as well as their categories, their means of declaration are analyzed. Starting with the comparison to the silence as an objective, the tacit and express declarations are critically assessed. Based on the studies above mentioned it is possible to conclude that the theory regarding the silence adopted by the Brazilian Civil Code is the so-called Qualified Silence Theory. Therefore, the silence as a contractual declaration and its evolution in the Brazilian Civil Law is examined in order to reach the current article in the Brazilian Civil Code concerning this issue provision. The silence is an autonomous means of will declaration and it is not attached to the express or to the tacit one. This way, the conclusion regarding the silence’s role in the contract formation is that it is a way of expressing acceptance since special circumstances are present in the case, as stated in the article 111 of the Brazilian Civil Code, and once other elements applicable to the civil law and, specially, contractual relations are observed. e desde que observados outros elementos aplicáveis às relações de Direito civil e contratuais, especialmente Eventually, other concretion components – besides those provided in the referred article, which are the case’s circumstances and the common/usual practices – need to be taken into consideration in the silence analysis, such as the trust and the economical and social goals.